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Corneal

Transplantation

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DVD Contents

I. LAMELLAR KERATOPLASTY
1. Manual lamellar keratoplasty
2. Keratoglobus — Tuck it in (Tuck in lamellar keratoplasty)
3. Automated therapeutic lamellar keratoplasty
4. Deep anterior lamellar keratoplasty: Big bubble technique
5. Deep anterior lamellar keratoplasty: Double bubble technique
6. Deep anterior lamellar keratoplasty keratoconus
7. Deep anterior lamellar keratoplasty macular dystrophy
8. Large diameter lamellar keratoplasty

II. PENETRATING KERATOPLASTY


9. Autorotational and autorotational keratoplasty
10. Keratoplasty — The bond strengthened (Tuck in penetrating keratoplasty)
11. Corneal debulking for corneoiridic scar

III. THERAPEUTIC KERATOPLASTY


12. Corneoscleral graft for corneoscleral melting following pterygium surgery
13. Therapeutic keratoplasty in a perforated corneal ulcer following fungal keratitis
14. Patch graft for perforated corneal ulcer
15. Therapeutic penetrating keratoplasty in a case of infection following deep anterior lamellar keratoplasty

IV. POSTERIOR LAMELLAR KERATOPLASTY/ENDOTHELIAL KERATOPLASTY


16. Descemet’s membrane endothelial keratoplasty (DMEK)
17. Descemet’s stripping automated endothelial keratoplasty (DSAEK)
18. Sutureless Descemet’s stripping automated endothelial keratoplasty (Sutureless DSAEK)
19. Descemet’s stripping automated endothelial keratoplasty: triple procedure (DSAEK: triple procedure)

V. MULTILAYERED AMNIOTIC MEMBRANE GRAFTING IN NEUROTROPHIC KERATITIS

VI. PHOTOTHERAPEUTIC KERATECTOMY

VII. CULTIVATED LIMBAL STEM CELL TRANSPLANTATION


Corneal
Transplantation
Second Edition

Editor
Rasik B Vajpayee MS, FRCS (Edin), FRANZCO
Professor of Ophthalmology
Head, Cornea and Cataract Surgery
Centre for Eye Research Australia
University of Melbourne
Royal Victorian Eye and Ear Hospital
Melbourne, Australia

Associate Editors
Namrata Sharma MD, DNB, MNAMS Geoffrey C Tabin MD Hugh R Taylor AC, FRACS, FRACO, FACS
Associate Professor of Ophthalmology Professor of Ophthalmology and Visual Harold Mitchell Professor of Indigenous
Cornea and Refractive Surgery Services Sciences Eye Health
Dr Rajendra Prasad Centre for John A. Moran Eye Center Melbourne School of Population Health
Ophthalmic Sciences University of Utah University of Melbourne
All India Institute of Medical Sciences Salt Lake City Former Head Corneal Unit
New Delhi, India Utah Royal Victorian Eye and Ear Hospital
Melbourne, Australia

Foreword
Claes H Dohlman
Published by
Jitendar P Vij
Jaypee Brothers Medical Publishers (P) Ltd
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Corneal Transplantation

© 2010, Jaypee Brothers Medical Publishers (P) Ltd

All rights reserved. No part of this publication and DVD ROM should be reproduced, stored in a retrieval system, or transmitted in
any form or by any means: electronic, mechanical, photocopying, recording, or otherwise, without the prior written permission of
the editors and the publisher.

This book has been published in good faith that the material provided by contributors is original. Every effort is made to ensure
accuracy of material, but the publisher, printer and editors will not be held responsible for any inadvertent error(s). In case of any
dispute, all legal matters are to be settled under Delhi jurisdiction only.

First Edition : 2002


Second Edition : 2010

ISBN 978-81-8448-859-3

Typeset at JPBMP typesetting unit


Printed at Ajanta
Dedication

To my wife Madhu and Children Mihika and Shubhankar


— Rasik B Vajpayee

To my patients
— Namrata Sharma

To my wife, Jean and children Livia, Emilia,


Allessandra, Sara and Daniel with love and thanks
— Geoffrey C Tabin

To my students who have taught me so much


and their students who will learn so much
— Hugh R Taylor
Contributors

A Murchison MD Chandra Shekhar Kumar MD Gerrit RJ Melles MD


Department of Ophthalmology Fellow, Cataract, Cornea and Netherlands Institute for Innovative
University of Vermont Refractive Surgery Services Ocular Surgery
Burlington Dr Rajendra Prasad Centre for Consultancy for Research and
Vermont, USA Ophthalmic Sciences Development of Ophthalmic Surgical
All India Institute of Medical Sciences Techniques
Ahmad Kheirkhah MD New Delhi, India Rotterdam, The Netherlands
Ocular Surface Center and Ocular
Surface Research and Education Dimitri T Azar MD Graeme A Pollock BSc, MPH, PhD
Foundation BA Field Endowed Chair of Director
Miami, Florida Ophthalmologic Research Lions Eye Donation Service Melbourne
Professor and Department Head Melbourne, Australia
Amit Patel FRCOphth Department of Ophthalmology and
Villa Serena Hospital Visual Sciences Gurnarinder Singh MS
Department of Ophthalmology University of Illinois at Chicago Fellow, Cataract, Cornea and
Forli, Italy Chicago, IL 60612, USA Refractive Surgery Services
Fondazione Banca degli Occhi del Dr Rajendra Prasad Centre for
Veneto, Venice, Italy Eric Donnenfeld MD, FAAO, FACS Ophthalmic Sciences
Clinical Professor of Ophthalmology All India Institute of Medical Sciences
Ashok Kumar MD NYU Medical Center New Delhi, India
Fellow, Cataract, Cornea and Trustee Dartmouth Medical School
Refractive Surgery Services Harinder Singh Sethi MD, DNB,
Dr Rajendra Prasad Centre for Francis W Price Jr MD MNAMS, FRCS
Ophthalmic Sciences Price Vision Group, Indianapolis, USA Assistant Professor
All India Institute of Medical Sciences Department of Ophthalmology
New Delhi, India Fred Eggink OD Vardhman Mahavir Medical College
Netherlands Institute for Innovative and Safdarjung Hospital
Ben Connell BM BS, FRANZCO, MPH Ocular Surgery New Delhi, India
Corneal Unit Rotterdam, The Netherlands
Royal Victorian Eye and Ear Hospital Hossam Sheha MD, PhD
Melbourne, Australia Geetha Srinivasan MBBS, MS Ocular Surface Center and Ocular
Rajendra Prasad Centre for Surface Research and Education
Bhavna Chawla MS Ophthalmic Sciences Foundation
Assistant Professor of Ophthalmology All India Institute of Medical Sciences Miami, Florida
Dr Rajendra Prasad Centre for New Delhi, India
Ophthalmic Sciences Hugh R Taylor AC, MD, FRACS, FRACO,
All India Institute of Medical Sciences Geoffrey C Tabin MD FACS
New Delhi, India Professor of Ophthalmology and Visual Harold Mitchell Professor of
Sciences, University of Utah Indigenous Eye Health
Bilal Khan MD John A. Moran Eye Center Melbourne School of Population Health
Massachusetts Eye and Ear Infirmary Salt lake City, Utah, USA Salt Lake University of Melbourne
243 Charles Street City, Utah Former Head Corneal Unit
Boston, MA, USA Royal Victorian Eye and Ear Hospital
Gerald W Zaidman FAAO, FACS Melbourne, Australia
C Banu Cosar MD Director, Department of Ophthalmology
Associate Professor of Ophthalmology Westchester Medical Center Jacqueline Beltz MBBS (Hons), FRANZCO
Acibaden University Professor of Ophthalmology Corneal Services
Ophthalmology Clinic New York Medical College Royal Victorian Eye and Ear Hospital
Istanbul, Turkey Valhalla, NY, USA Melbourne, Australia
Jeewan S Titiyal MD Michael S Loughnan PhD, FRANZCO N Kloster MD
Professor of Ophthalmology Consultant, Cornea Clinic Department of Ophthalmology
Cataract, Cornea and Refractive Royal Victorian Eye and Ear Hospital University of Vermont
Surgery Services Melbourne, Victoria Burlington, Vermont, USA
Dr Rajendra Prasad Centre for Australia
Ophthalmic Sciences Peter R Laibson MD
All India Institute of Medical Sciences Mike Feilmeier MD Professor of Ophthalmology,
Corneal Transplantation

New Delhi, India University of Utah Thomas Jefferson University


John A Moran Eye Center School of Medicine
Jonathan G Crowston FRCOphth, Salt Lake City, Utah, USA Director Emeritus, Cornea Department
FRANZCO, PhD Wills Eye Institute
Professor of Ophthalmology Mohammad Anwar FRCS Edin, Philadelphia, Pennsylvania
Centre for Eye Research Australia FRCOphth
University of Melbourne Senior Consultant Ophthalmic Surgeon Prakash Chand Agarwal MD, FICO,
Australia Cornea and External Diseases FRCS
Magrabi Eye Hospital Fellow, Cataract, Cornea and Refractive
JW Dimming MD Dubai, UAE Surgery Services
Department of Ophthalmology Dr Rajendra Prasad Centre for
University of Vermont Mona H Dagher MD, FRCSC Ophthalmic Sciences
Burlington Fellow Cornea and Refractive Surgery All India Institute of Medical Sciences
Vermont, USA Massachusetts Eye and Ear Infirmary New Delhi, India
Harvard Medical School
Karl David Brown BSc (Hon), MPhil Boston Prashant Garg MS
Senior Research Assistant Centre MA, USA Director, Education and Dr G Chandra
for Eye Research Australia Sekhar Distinguished Chair of
32 Gisborne St. Monica Chaudhry BSc Education
East Melbourne, Australia Senior Technical Officer Consultant, Cornea and Anterior
Dr Rajendra Prasad Centre for Segment Services
Laurence Sullivan MBBS, FRANZCO Ophthalmic Sciences Medical Director, Ramayamma
Clinical Associate All India Institute of Medical Sciences International Eye Bank
Centre for Eye Research Australia New Delhi, India LV Prasad Eye Institute
Practice Principle Bayside Eye Hyderabad, India
Specialists and LaserSight Victoria M Vanathi MD
Australia Assistant Professor of Ophthalmology - Prashant Bhartiya MD, DNB, FRCS
Cornea Services Corneal Fellow, Royal Victorian Eye
Manotosh Ray MD, FRCSEd Dr Rajendra Prasad Centre for and Ear Hospital, Melbourne, Australia
Associate Consultant Ophthalmic Sciences Consultant Ophthalmologist
National University Hospital All India Institute for Medical Sciences Bombay Hospital, Indore, India
Singapore New Delhi, India
Clinical Teacher Rajesh Sinha MD,DNB, FRCS
National University of Singapore Mukesh Taneja MBBS, DO, DNB Cataract, Cornea and Refractive Surgery
Singapore Consultant, Cornea and Anterior Services
Segment Assistant Professor of Ophthalmology
Marianne O Price PhD, MBA LV Prasad Eye Institute Dr Rajendra Prasad Centre for
Cornea Research Foundation of Hyderabad, India Ophthalmic Sciences
America, Indianapolis, IN, USA All India Institute of Medical Sciences
Namrata Sharma MD, DNB, MNAMS New Delhi, India
Massimo Busin MD Associate Professor of Ophthalmology
Professor of Ophthalmology Cornea and Refractive Surgery Services Rajeev Sudan MD (AIIMS)
Director of Ophthalmology at Villa Dr Rajendra Prasad Centre for Medical Director
Serena Hospital, Forli, Italy Ophthalmic Sciences RR Eye Care and Laser Institute
University of Bonn (Germany) All India Institute of Medical Sciences CEO, Amar Eye Centre
Genova (Italy) and Catanzaro (Italy) New Delhi, India New Delhi, India

viii
Raj Maini BSc (Hons) BM FRCOphth Scheffer CG Tseng MD, PhD Victoria Casas MD
FRCSC FRANZCO Ocular Surface Center and Ocular Ocular Surface Center and Ocular
Consultant Ophthalmologist Surface Research and Education Surface Research and Education
Moorfield’s Eye Hospital Foundation, Miami, Florida Foundation
London Miami, Florida
S Louise Moffatt BSc
Rakesh Ahuja MBBS, MD Manager Viney Gupta MD

Contributors
UBC Fellowship (Canada), Harvard New Zealand National Eye Bank Associate Professor of Ophthalmology
Fellowship (Boston MA) Auckland, New Zealand Glaucoma Services
Long Island College Hospital, Dr Rajendra Prasad Centre for
Brooklyn, NY (USA) S McKeon MD Ophthalmic Sciences
Department of Ophthalmology All India Institute of Medical Sciences
Rasik B Vajpayee MS, FRCS (Edin), University of Vermont New Delhi, India
FRANZCO Burlington, Vermont, USA
Professor of Ophthalmology Virender Singh Sangwan MD
Head, Cornea and Cataract Surgery Sujata Das MS, FRCS Associate Director
Centre for Eye Research Australia Consultant, Cornea and Anterior LV Prasad Eye Institute
University of Melbourne Segment Service Head, Cornea and Anterior Segment
Royal Victorian Eye and Ear Hospital LV Prasad Eye Institute Ocular Immunology and Uveitis
Melbourne, Australia Bhubaneswar, Orissa, India Services
LV Prasad Eye Institute
Ritika Sachdev MS Sushil Vasudevan MS Hyderabad, India
Fellow, Cataract, Cornea and Refractive Senior Lecturer
Surgery Services Faculty of Medicine, University Vishal Jhanji MD
Dr Rajendra Prasad Centre for Teknologi MARA, Malaysia Assistant Professor of Ophthalmology
Ophthalmic Sciences Cornea and External Eye Diseases
All India Institute of Medical Sciences Tushar Agarwal MD Department of Ophthalmology and
New Delhi, India Assistant Professor of Ophthalmology Visual Sciences
Cataract, Cornea and Refractive Surgery The Chinese University of Hong Kong
Sameer Kaushal MD, DNB Services, Dr. Rajendra Prasad Centre 3/F Hong Kong Eye Hospital,
Associate Consultant for Ophthalmic Sciences 147K Argyle Street, Mongkok
Artemis Health Institute All India Institute of Medical Sciences Kowloon, Hong Kong
Sector 51, Gurgaon, India New Delhi, India
Vishal Gupta MD (AIIMS)
Samir A Melki MD, PhD Urmimala Ghatak MD Senior Consultant Ophthalmology
Director, Boston Eye Group and Laser Fellow, Cataract, Cornea and Refractive BCIMS
Center Surgery Services New Delhi, India
Assistant in Ophthalmology Dr Rajendra Prasad Centre for
Massachusetts Eye and Ear Infirmary Ophthalmic Sciences VK Raju MD, FRCS
Harvard Medical School All India Institute of Medical Sciences Ocular Surface Center and Ocular
New Delhi, India Surface Research and
Sandeep Jain MD Education Foundation
Assistant Professor Usha Gopinathan PhD Miami, Florida
Cornea Service Associate Executive Director
University of Illinois at Chicago LV Prasad Eye Institute Y Khalifa MD
Department of Ophthalmology and Technical and Scientific Director, RIEB University of Utah
Visual Sciences LV Prasad Eye Institute John A Moran Eye Center
Chicago, IL 60612, USA Hyderabad, India Salt Lake City, Utah, USA

ix
Foreword

It is my pleasure and an honor to be asked to write a foreword to the present text on corneal transplantation. The book presents
information that is not only updated and skillfully written, but also held in a format that should be very practical for ophthalmologists
throughout the world. With a minimum of effort, any ophthalmologist presented with a corneal problem that may need surgical
treatment should be able to rapidly find a sensible and still sufficiently detailed answer. Certainly the time is right for such a
systematic and lucid contribution. The professional standing of all the contributors certainly serves as a guarantee for success of
this timely textbook.

Claes H Dohlman MD
Professor of Ophthalmology
Harvard Medical School
Preface to the Second Edition

The first edition of “Corneal Transplantation” was published in year 2002 and techniques of corneal grafting surgery have undergone
almost revolutionary changes since then. There have been many significant and exciting developments in the technical aspects of
corneal transplantation as we have been progressively refining the relatively cumbersome use of penetrating keratoplasty to treat
all types of corneal diseases to the use of much more elegant and precise ‘Customized Component’ corneal transplantation surgery.
These customized lamellar corneal transplantation surgeries aim to replace only the diseased part of the cornea by selective
transplantation of the appropriate corresponding healthy donor lenticule. Surgical techniques like ‘Big Bubble’ DALK,
Microkeratome assisted ALTK and DSAEK have found favor with corneal surgeons over penetrating keratoplasty for corneal
disorders that affect only specific layers of cornea.
The present edition of the outstanding book has aimed to include all these developments and like the first edition, this version
too has been designed as a practical guide elucidating the many and varied aspects of modern corneal transplantation surgery. A
conscious effort has been made to keep the format very simple and easy to follow by using a straightforward ‘How to do’ kind of
approach.
This new edition includes a detailed description of all new techniques of lamellar corneal transplantation surgeries including
some very innovative techniques like “Tuck in” lamellar keratoplasty, Sutureless DSAEK Triple surgery, DMEK and “Double
Bubble” Deep Anterior lamellar keratoplasty. It also explains the various acronyms that seem to have populated modern corneal
surgery. The book carries a very wide range of and sound practical advice based on the experience of the world’s leaders in this
field who have described their surgical techniques and other aspects of corneal transplantation surgery in a lucid and well structured
manner.
A DVD of all these surgical techniques has been provided to help beginners to acquaint themselves with the state-of-the-art
techniques in corneal grafting surgery. We are indebted to all of our chapter authors for their hard work and hopes that this ‘User
Friendly’ book would be able accomplish its main objective of simplifying and spreading the knowledge of various aspects of
contemporary corneal transplantation surgery.

Rasik B Vajpayee
Namrata Sharma
Geoffrey C Tabin
Hugh R Taylor
Preface to the First Edition

Corneal Transplantation Surgery has undergone tremendous advancements over the last few decades. Innovative minds have been
contributing novel and original concepts in an ongoing pursuit, aimed towards achieving optimal long term success of this craft.
My journey in the field of corneal grafting surgery began during my residency at Gandhi Medical College, Bhopal. In those formative
years it was thrilling to observe surgeons replace diseased and scarred corneas with healthy donor tissue. After a formal training
in corneal surgery at Dr Rajendra Prasad Centre for Ophthalmic Sciences, I learnt the finer points of this craft at the Cornea
Service of Melbourne University Department of Ophthalmology in Australia. I would like to express my heartfelt gratitude to my
teachers Prof Santokh Singh, Prof MK Rathore, Dr Salil Kumar, Prof Madan Mohan, Prof VK Dada, Prof Hugh R Taylor and Prof
Peter R Laibson. These luminaries have helped me to shape my skills as an ophthalmologist and a corneal surgeon and have been
a source of inspiration in my academic endeavors including this book.
This book was conceived in Australia, when Dr Geoff Tabin and myself were working as corneal fellows with Prof Hugh
Taylor. Our interactions with him made us realize that the profile of corneal diseases and their management modalities in the
developing world differ somewhat from those of the developed nations. We felt that there was a need for a concise, user friendly
and practical book on corneal grafting surgery. The book was planned as an amalgamation of knowledge about the newer
technological advances of the developed world and the simpler alternatives appropriate and optimal for the developing countries.
Another principal purpose of this venture is to generate interest amongst ophthalmic surgeons of the developing countries in the
field of corneal grafting surgery, as corneal blindness is a major health issue here.
Bringing out a book on a subject like corneal transplantation is a kind of mammoth exercise and it is clear that work of such
enormity is the congregation of efforts of many individuals. I am grateful for the esprit de corps, collaboration, education and
altruism that my Australian, American and other International and Indian colleagues have bestowed on me over the years. Many
of them are contributing authors to this book. I am obliged to all the contributing authors for the time and effort they have put in
to share their expertise and knowledge with the readers. I am indebted to my co-editors Dr Namrata Sharma, Dr Geoff Tabin and
Prof Hugh R Taylor for their invaluable help and guidance at every step. I would also like to acknowledge my residents, and my
assistants Mr Rajkumar and Ms Meena Verma for providing useful inputs and assistance. And finally, I would like to thank my
wife Madhu and children Mihika and Shubhankar for their patience in allowing me to spend time to accomplish this work.
This book has been designed as a practical guide to the various aspects of corneal grafting surgery. It elucidates the basic
aspects in preoperative evaluation, investigations, established surgical procedures and the advanced techniques in special situations
as well as the newer technology in corneal grafting. Theoretical as well as research aspects of corneal grafting have been dealt in
a practical manner. An extensive and well-illustrated section provides up-to-date knowledge of complications in corneal
transplantation and their management. This should be of particular assistance to ophthalmologists practicing in remote areas and
involved in the postoperative care of the grafted patients.
Overall our book provides students, surgeons and practitioners a concise treatise on corneal transplantation that contains essential
information intended to help a beginner and can be consulted by the experienced corneal transplantation surgeons to acquaint
themselves with the state-of-the-art techniques in corneal grafting surgery.

—Rasik B Vajpayee
Preface to the First Edition

In the early 1990s Rasik Vajpayee and I were corneal fellows together under the guidance of Professor Hugh Taylor at the Royal
Victorian Eye and Ear Hospital in Melbourne, Australia. Dr Vajpayee had come from the busy corneal unit at the All India Institute
of Medical Sciences in Delhi and he was concerned about the difficulties of corneal surgery in the developing world. I trained at
Harvard Medical School and Brown University’s department of Ophthalmology in the United States of America and arrived with
a bias towards modern technology and no holds barred best possible care for every individual patient. Professor Taylor’s superb
corneal fellowship provided us with both a state of the art corneal fellowship experience and the opportunity to discuss wider
global issues surrounding the delivery of medical care both in the developed and developing world.
Dr Vajpayee returned to India where he quickly became one of the busiest and most influential corneal surgeons in the world.
He has an enormous surgical volume and innovative mind. He has developed numerous new techniques and has advanced the art
of corneal surgery in a myriad of areas. Along with his publications he experienced a meteoric rise through the academic ranks. Dr
Vajpayee is now a full Professor at the All India Institute of Medical Sciences and Director of Cornea services. In addition to
being involved with many aspects of cutting edge research and technology he has continued to be concerned about the difficulties
of delivering high quality corneal care in the developing world.
Dr Vajpayee and I spoke at the American Academy of Ophthalmology meeting one year ago. He felt that there was a need for
a practical book on modern corneal surgery that would transcend the boundaries of modern technology and the developing world.
He noted that there was no single book that would allow a rural surgeon in India to quickly learn what he needs to treat a specific
difficult corneal pathology that also provides in depth discussions and insights for the western fellowship trained corneal surgeon.
Professor Vajpayee’s enthusiasm was infectious. We discussed ideas and possible formats and drew up a list of topics. We then
discussed who in the world was currently at the absolute cutting edge in dealing with those specific problems. We enlisted the help
of Professor Taylor from Australia and Dr Namrata Sharma from India as co-editors and approached an all star cast of corneal
specialists from around the world.
We asked the authors to write succinct practical chapters geared towards patient care while still including sufficient academic
support for their views. In each chapter the authors delivered an excellent treatise on their topic of specific corneal expertise. We
hope this book will be a valuable resource for general ophthalmologists who are faced with a corneal crisis, residents and corneal
specialists alike. As we enter a new millennium, corneal disease and injury remains the second leading cause of blindness in the
world. We hope this book will provide a practical, yet comprehensive, guide to surgical corneal care.
I am indebted to all of our chapter authors and to my co-editors for their hard work. I am particularly grateful to Rasik B
Vajpayee for having the vision of this book and the enthusiasm to make it a reality. Happy reading!

—Geoffrey C Tabin

xv
Preface to the First Edition

I was very pleased when Rasik B Vajpayee first raised the possibility of writing a book on corneal transplantation. Dr Vajpayee,
in addition to being an expert surgeon is also one of the most industrious and productive members of a new generation of corneal
surgeons and is rapidly becoming a world leader.
He has assembled a most distinguished group of leading corneal surgeons from around the world to contribute to this very
important and impressive book.
There have been many significant and exciting developments in the technical aspects of corneal transplantation over recent
years and these have been beautifully set out in the chapters that follow. The precision and beauty of corneal transplantation still
amazes me after thirty years. With the large numbers of cases done around the world each year and the high success rate, corneal
transplantation must be without doubt the most successful example of transplantation in the whole of medicine. Although exquisite
surgical skill and attention to detail throughout the operation are extremely important in determining the successful outcome of
corneal transplantation, they are only part of the story.
Data from the Australian Corneal Transplant Registry show that the single most important factor affecting the long-term survival
of corneal grafts is the surgeon. This does not relate to the surgical skill and dexterity as much as it relates to meticulous postoperative
management. The key to the successful postoperative management of a corneal transplant is not how many patients are seen, or
whether they are seen exactly at the time of their appointment without having to wait, or whether they are first examined by an
ophthalmic assistant, the key is the meticulous attention to detail in the postoperative management especially the recognition of
early stages of low grade rejection and its appropriate management. Attention to detail is a key to success in ophthalmology, and
in no area is this more true than the postoperative management of corneal transplantation.
One of the great strengths of this book is the wide range of experience and opinion that is presented here. This book does not
give a simplistic cookbook recipe for the management of these sometimes complex and difficult cases, rather it gives the distilled
experience of the world’s leaders in this field in which they outline their approach and their justification for the decisions they
have taken. I trust you will find this book as interesting and as informative as I have and sustain the excitement I first felt when
this book was first discussed.

—Hugh R Taylor
Contents

SECTION I: EVOLUTION, PREOPERATIVE CONSIDERATIONS AND EYE BANKING

1. Evolution of Corneal Grafting Surgery ........................................................................................................ 1


Namrata Sharma, Chandra Shekhar Kumar
2. Indications and Outcome of Penetrating Keratoplasty ............................................................................... 4
Urmimala Ghatak, Rajesh Sinha, Namrata Sharma
3. Preoperative Evaluation ............................................................................................................................... 13
Namrata Sharma, Ritika Sachdev, Manotosh Ray, Rasik B Vajpayee
4. Eye Banking—A Practical Guide ................................................................................................................. 20
Graeme A Pollock, S Louise Moffatt
5. Medicolegal Aspects of Eye Banking ........................................................................................................... 38
M Vanathi, Gurnarinder Singh, Rakesh Ahuja
6. Setting Up Corneal Transplant Center ........................................................................................................ 43
Jacqueline Beltz, Rasik B Vajpayee
7. Setting Up an Eye Bank ................................................................................................................................ 48
Mukesh Taneja, Prashant Garg, Usha Gopinathan

SECTION II: PENETRATING KERATOPLASTY

8. Surgical Instruments for Penetrating Keratoplasty .................................................................................. 53


Prakash Chand Agarwal, Namrata Sharma, Vishal Gupta, Geoffrey C Tabin
9. Suture Materials and Needles ...................................................................................................................... 61
Rajeev Sudan, Sameer Kaushal
10. Technique of Penetrating Keratoplasty ....................................................................................................... 63
Namrata Sharma, Chandra Shekhar Kumar, Samir A Melki, Rasik B Vajpayee
11. Suturing Techniques in Penetrating Keratoplasty ..................................................................................... 73
C Banu Cosar, Peter R Laibson
12. Postoperative Care after Penetrating Keratoplasty ................................................................................... 78
Raj Maini, Urmimala Ghatak, Hugh R Taylor
13. Postkeratoplasty Contact Lens Fitting ........................................................................................................ 86
Rajesh Sinha, Jeewan S Titiyal

SECTION III: PENETRATING KERATOPLASTY: MANAGEMENT OF COMPLICATIONS

14. Complications of Penetrating Keratoplasty ............................................................................................... 95


Namrata Sharma, Urmimala Ghatak, Rasik B Vajpayee, Hugh R Taylor
15. Post Penetrating Keratoplasty Glaucoma ................................................................................................. 117
Viney Gupta, Sushil Vasudevan, Jonathan G Crowston
16. Corneal Graft Rejection ............................................................................................................................. 122
Ben Connell, Michael S Loughnan
17. Corneal Graft Astigmatism ........................................................................................................................ 128
Jacqueline Beltz, Vishal Jhanji, Laurence Sullivan, Rasik B Vajpayee
SECTION IV: LAMELLAR KERATOPLASTY

A: ANTERIOR LAMELLAR KERATOPLASTY TECHNIQUES

18. Surgical Instruments for Lamellar Keratoplasty ..................................................................................... 137


Namrata Sharma, Prakash Chand Agarwal, Rasik B Vajpayee
19. Epikeratoplasty ............................................................................................................................................ 140
Corneal Transplantation

Namrata Sharma, M Vanathi, Geetha Srinivasan


20. Manual Lamellar Keratoplasty .................................................................................................................. 145
Namrata Sharma, Chandra Shekhar Kumar, Rasik B Vajpayee
21. Automated Lamellar Therapeutic Keratoplasty ...................................................................................... 157
Namrata Sharma, Sameer Kaushal, Rasik B Vajpayee
22. New Lamellar Keratoplasty Techniques: Posterior Keratoplasty and
Deep Lamellar Keratoplasty ...................................................................................................................... 164
Sandeep Jain, Dimitri T Azar
23. Deep Anterior Lamellar Keratoplasty: Melles Technique ....................................................................... 170
Gerrit RJ Melles, Fred Eggink
24. Deep Anterior Lamellar Keratoplasty: Big Bubble Technique ............................................................... 185
Mohammad Anwar
25. Deep Anterior Lamellar Keratoplasty: Double Bubble Technique ........................................................ 194
Vishal Jhanji, Jacqueline Beltz, Namrata Sharma, Rasik B Vajpayee
26. “Tuck in” Lamellar Keratoplasty .............................................................................................................. 199
Jacqueline Beltz, Vishal Jhanji, Namrata Sharma, Rasik B Vajpayee

B: POSTERIOR LAMELLAR KERATOPLASTY TECHNIQUES

27. Descemet’s Stripping Automated Endothelial Keratoplasty ................................................................... 204


Marianne O Price, Francis W Price
28. Sutureless Descemet’s Stripping Automated Endothelial Keratoplasty ................................................ 214
Vishal Jhanji, Jacqueline Beltz, Namrata Sharma, Rasik B Vajpayee
29. Descemet’s Stripping Automated Endothelial Keratoplasty: Triple Procedure .................................... 220
Jacqueline Beltz, Vishal Jhanji, Rasik B Vajpayee
30. Descemet’s Membrane Endothelial Keratoplasty .................................................................................... 225
Amit Patel, Massimo Busin

SECTION V: SPECIFIC TECHNIQUES IN KERATOPLASTY


31. Penetrating Keratoplasty and Cataract Extraction: Triple Procedure ................................................. 229
Namrata Sharma, Ashok Kumar, Manotosh Ray, Prashant Bhartiya
32. Penetrating Keratoplasty for Aphakic and Pseudophakic Bullous Keratopathy ................................. 237
Sujata Das, Vishal Gupta
33. Pediatric Keratoplasty ................................................................................................................................ 245
Gerald W Zaidman
34. Therapeutic Keratoplasty ........................................................................................................................... 252
Eric Donnenfeld
35. “Tuck in” Penetrating Keratoplasty .......................................................................................................... 262
Namrata Sharma, Rasik B Vajpayee
xviii
36. Femtosecond Laser Assisted Keratoplasty ................................................................................................ 264
Chandra Shekhar Kumar, Namrata Sharma, Rasik B Vajpayee
37. Special Techniques of Corneal Grafting Surgery ..................................................................................... 268
Namrata Sharma, Rajesh Sinha, Manotosh Ray
38. Indication Specific Corneal Grafting Techniques .................................................................................... 274
Rasik B Vajpayee, M Vanathi, Harinder S Sethi

Contents
39. Autokeratoplasty ......................................................................................................................................... 281
Tushar Agarwal, Namrata Sharma, Rasik B Vajpayee
40. Limbal Stem Cell Transplantation ............................................................................................................. 285
Geoffrey C Tabin, MR Feilmeier, Y Khalifa, N Kloster, A Murchison, JW Dimming, S McKeon
41. Ex Vivo Cultured Limbal Stem Cell Transplantation .............................................................................. 295
Chandra Shekhar Kumar, Namrata Sharma, Virender Sangwan
42. Amniotic Membrane Transplantation ....................................................................................................... 305
Ahmad Kheirkhah, Hossam Sheha, Victoria Casas, VK Raju, Scheffer CG Tseng

SECTION VI: ALTERNATIVES TO PENETRATING KERATOPLASTY

43. Boston Keratoprosthesis ............................................................................................................................. 317


Mona Harissi-Dagher, Bilal Khan, Claes H Dohlman
44. Phototherapeutic Keratectomy .................................................................................................................. 329
Rajesh Sinha, Namrata Sharma, Jeewan S Titiyal
45. Optical Sector Iridectomy .......................................................................................................................... 335
M Vanathi, Rasik B Vajpayee, Namrata Sharma
46. Corneal Tattooing ........................................................................................................................................ 337
Sameer Kaushal, Harinder S Sethi, Namrata Sharma
47. Prosthetic Contact Lenses........................................................................................................................... 341
Monica Chaudhry
48. Amniotic Membrane Transplantation as an Alternative to Keratoplasty ............................................. 344
Bhavna Chawla, Rasik B Vajpayee
49. Gundersen Flap ........................................................................................................................................... 350
Prakash Chand Agarwal, Namrata Sharma, Rasik B Vajpayee
50. Future Developments .................................................................................................................................. 353
Vishal Jhanji, Karl David Brown, Rasik B Vajpayee, Hugh R Taylor

Index .............................................................................................................................................................. 357

xix
SECTION I: Evolution, Preoperative Considerations and
Eye Banking

Chapter 1: Evolution of Corneal Grafting Surgery


Evolution of Corneal Grafting Surgery
Namrata Sharma, Chandra Shekhar Kumar

Today, the keratoplasty is considered as the most frequently In the next 30 years grafting was performed using tissue from
performed and the most successful organ transplantation enucleated eyes of living donors. In 1908, Plange performed
technique worldwide. The success of this procedure has not been the first autokeratoplasty, where he replaced the scarred cornea
an overnight event. The history of today’s corneal grafting dates of a blind eye with a lamellar graft from the patient’s other eye
back to the nineteenth century when K Himly of Germany which, although blind had a normal cornea.
suggested replacing an opaque cornea of one animal with clear VP Filatov, a Russian ophthalmologist, is considered as the
cornea of another animal (1813). F Reisinger was the first to father of modern eye banking.4,5 He used an egg membrane to
suggest replacing opaque human cornea with transparent animal fixate the graft. This method was later practised widely. His work
cornea in 1824. He also coined the term ‘keratoplasty’. SLL also involved the usage of cadaver cornea as the donor material
Bigger performed the first successful penetrating allograft in and he highlighted the importance of protecting the intraocular
animals. Henry Power reported his experimental work on tissues while trephining the host tissue and advocated direct
animals and humans in 1872.1 He was the first to give importance suturing. In 1940s, corneal transplant surgery evolved
to proper graft placement, freedom from infection, usage of fresh dramatically with the availability of antibiotics and introduction
donor tissue and the minimal trauma to the endothelium. In 1886, of steroids in corneal surgery.
Von Hippel reported the first lamellar corneal grafting.2 The first In late 1950s, small fine needles were used for first time for
successful penetrating keratoplasty was performed almost a suturing. At the same time, Paufique and Charleux popularized
century ago by Edward Konrad Zirm (Fig. 1.1) on a patient lamellar corneal grafting. They also introduced limbal and
in the year 1906, who had sustained alkali burns.3 The donor eccentric grafts. Although, most of the corneal transplant surgery
was an 11-year-old boy whose eye was enucleated because of has evolved in the first-half of the 20th century, the greatest
penetrating scleral injury with retained intraocular foreign body. advances in corneal grafting have taken place in the past 30 years.
The understanding of corneal anatomy and physiology especially
with regard to the corneal endothelium, introduction of
microsurgical techniques, advances in corneal preservation, the
elucidation of the corneal immunology and the development of
usage of anti-inflammatory and immunosuppressive agents have
resulted in a high success rate of corneal grafting.
Corneal graft rejection is the greatest limiting factor in graft
survival and Edward Maumenee was the one to recognize this
clinical entity. The classic scientific description and experimental
models were elegantly designed by Khodadoust.
Ramon Castroviejo (Fig. 1.2) performed the world’s first
successful human cornea transplant. He devised numerous
instruments which were named after him, such as Castroviejo
Calipers, Forceps, Corneal Scissors, Corneoscleral Punch,
Cyclodialysis Spatula, Needle Holder, Tying Forceps, Suturing
Forceps. He was also a pioneer of various surgical techniques
in the field of keratoplasty. Castroviejo’s original suturing
technique used a continuous silk suture coursing across the
Figure 1.1: Edward Konrad Zirm external surface of a square graft, holding the graft in place using
1
Section I: Evolution, Preoperative Considerations and Eye Banking

Figure 1.3: Townley Paton

Figure 1.2: Ramon Castroviejo


advantages of lamellar keratoplasty such as extraocular
technique, less stringent criteria for donor tissue, less graft
intraocular pressure to support the graft against the suture. Many rejection and intraocular complications and yet offers a better
of his square grafts fared extremely well and provided good visual acuity in terms of contrast sensitivity. In 1974, Anwar
visual acuity for many years. described the use of big air bubble for deep dissection under
Richard Troutman designed a microscope and numerous direct visualization in the potential natural cleavage plane
microsurgical instruments. 6 He tackled the problem of between the Descemet’s membrane and the overlying stromal
astigmatism, invented surgical keratometer and the technique of layers.10 Archilla in 1980s, was first to use intrastromal air
wedge resection. injection and spatula dissection to facilitate access to Descemet’s
Townley Paton (Fig. 1.3) was first to set-up an eye bank in membrane without perforating it. 11 Sugita also described
New York in 1959. Later on, this led to setting up of Eye Bank hydrodelamination of the stroma from Descemet’s membrane.12
Association of America in 1961. This organization laid down Melles described the technique of deep anterior lamellar
the standards for obtaining, preservation, storage and usage of keratoplasty (DALK) in which deeper dissection was done with
donor tissue. The healthy functioning endothelium is the key to the help of viscoelastic injection through the lamellar stromal
success of a corneal graft. The specular microscope developed pocket.13 In 2002, Anwar and Teichmann described the “big
by Maurice has provided the means of studying donor and bubble” technique in which separation of Descemet’s membrane
transplanted endothelium. from the overlying stroma is achieved with injection of air.14
The preservation of donor cornea influences the outcome of Endothelial keratoplasty (EK) is an alternative to penetrating
surgery to a great extent. A preservation procedure besides keratoplasty in cases where corneal endothelium is diseased
ensuring the endothelium viability also enables safe alone. In 1998, Melles described a technique for posterior
transportation of material and increases the duration of storage, lamellar keratoplasty (PLK),15 and a year later, he successfully
so that an efficient use of donor cornea can be made. First implemented the technique for pseudophakic corneal edema. In
successful transplantation using a cryopreserved human donor 2001, Terry and Ousley reported successful results in patients
tissue was reported by East Cott in 1954. Capella and using similar procedure, which they named deep lamellar
Kaufman7,8 developed the basic method of cryopreservation in endothelial keratoplasty (DLEK).16 Price and Price made the
1965. The major break-through in corneal preservation came endothelial keratoplasty technique more popular and it was
with the introduction of MK medium by McCarey and known as Descemet’s stripping endothelial keratoplasty
Kaufman in 1974.9 This medium is quite reliable for storage of (DSEK). 17 In 2006, Gorovoy described the technique of
donor cornea for at least 3-4 days. This allowed the elective Descemet’s-stripping automated endothelial keratoplasty
planning for surgery and made corneal transplantation a (DSAEK) in which the manual stromal dissection was replaced
scheduled procedure rather than an emergency. by the microkeratome dissection.18 This method avoids all
In the last two decades, with the improvement in surgical manual lamellar dissections and has the potential to result in a
techniques and instrumentation lamellar keratoplasty has smoother interface.
undergone a revolution. The various types of lamellar In 2006, Tappin described the clinical transplantation of
keratoplasty include anterior and posterior lamellar keratoplasty 7.5 mm diameter Descemet’s membrane (DM) through an 8.0
depending on the level of pathology. With the advent of the mm scleral incision using a flat carrier device.19 In the same year
microkeratomes, automated lamellar therapeutic keratoplasty Melles described the first clinical results of DM transplantation
(ALTK) has given way to manual lamellar keratoplasty. through a self-sealing corneal incision and referred it to as
Deep lamellar keratoplasty was introduced to improve the Descemet’s membrane endothelial keratoplasty (DMEK).20
postoperative visual performance in cases with corneal pathology Further experimental studies are on to make cultured human
involving the stromal layers of the cornea. It provides all the endothelial cell transplantation successful.
2
Major contributions in the field of corneal transplantation
S.No. Year Name Contribution
1. 1813 K Himly Suggested replacing opaque cornea in one animal with clear cornea
from another animal.
2. 1824 F Reisinger Suggested replacing opaque human cornea with clear animal cornea
• Coined the term keratoplasty
3. 1837 SLL Bigger Successfully performed corneal allograft in animals

Chapter 1: Evolution of Corneal Grafting Surgery


4. 1872 Henry Power Experimental corneal grafting
5. 1880 Von Hippel • Introduced lamellar keratoplasty
• Invented circular trephine
6. 1906 Edward Konrad Zirm • Reported first successful penetrating keratoplasty in a
human
7. 1908 Plange • Autokeratoplasty
8. 1910-1950 VP Filatov • Father of keratoplasty
• Performed systematic study of keratoplasty
• Suggested using cadaver corneas as donor tissues
• Devised numerous instruments and surgical innovations
9. 1930-1950 R Castroviejo • Devised numerous instruments for microsurgery
10. 1950s Paufique and Charleux • Lamellar keratoplasty
• Limbal and Eccentric Grafts
11. 1944 RT Paton • Founded the first Eye Bank in USA
12. 1954 East Cott • Transplantation using cryopreserved cornea
13. 1960 E Maumenee • Recognition of “Graft Rejection” as a clinical entity
14. 1965 Troutman Surgical microscope and surgical keratometer
15. 1965 Capella and Kaufman • Cryopreservation
16. 1968 D Maurice • Developed Specular Microscope
17. 1974 B McCarey and H Kaufman • Developed Corneal Storage Media
18. 1985 Archila EA DALK with air assisted dissection
19. 1998 Melles GR Deep anterior lamellar keratoplasty
Posterior lamellar keratoplasty
20. 2001 Mark Terry Deep lamellar endothelial keratoplasty (DLEK)
21. 2006 Price and Gorovoy Descemet’s stripping endothelial keratoplasty (DSEK) and
Descemet’s stripping automated endothelial keratoplasty (DSAEK)
22. 2006 Melles GR Descemet’s membrane endothelial keratoplasty (DMEK)

REFERENCES 13. Melles GR, Lander F, Rietveld FJ, Remeijer L, Beekhuis WH,
Binder PS. A new surgical technique for deep stromal, anterior
1. Power H. IV International Congress of Ophthalmology. London lamellar keratoplasty. Br J Ophthalmol 1999;83(3):327-33.
1872;4:172. 14. Anwar M, Teichmann KD. Big-bubble technique to bare
2. Von Hippel A. Albrecht v. Graefes Arch Ophthalmol 1888;34:108. Descemet’s membrane in anterior lamellar keratoplasty. J Cataract
3. Zirm EK. Eine erfolgreiche totale keratoplastik. V. Graefes Arch Refract Surg 2002;28(3):398-403.
Ophthalmol 1906;64:580. 15. Melles GR, Eggink FA, Lander F, Pels E, Rietveld FJ, Beekhuis
4. Filatov VP. Transplantation of the cornea. Arch Ophthalmol WH, et al. A surgical technique for posterior lamellar keratoplasty.
1935;13:321-47. Cornea 1998;17:618-26.
5. Filatov VP, Bajenova MA. Culture of dried corneal tissue. Arch 16. Terry MA, Ousley PJ. Deep lamellar endothelial keratoplasty in
Ophthalmol and Rev Gen Ophthalmol 1937;1:385. the first United States patients: early clinical results. Cornea
6. Troutman RC. The operating microscope in ophthalmic surgery. 2001;20:239-43.
Trans Am Ophthalmol Soc 1965;63:335-48. 17. Price FW Jr, Price MO. Descemet’s stripping with endothelial
7. Capella JA, Kaufman HE, Robbine JE. Preservation of viable keratoplasty in 50 eyes: a refractive neutral corneal transplant. J
corneal tissue. Arch Ophthalmol 1965;74:669-73. Refract Surg 2005;21:339-45.
8. McCarey BE, Kaufman HE. Improved corneal storage. 18. Gorovoy MS. Descemet’s stripping and automated endothelial
Investigative Ophthalmol 1974;13:165-73. keratoplasty. Cornea 2006;25:886-89.
9. Lindstrom RL. Advances in corneal preservation. Trans Am 19. Tappin M. A method for true endothelial cell (Tencell) trans-
Ophthalmol Soc 1990;88:555-648. plantion using a custom made cannula for the treatment of
10. Anwar M. Dissection technique in lamellar keratoplasty. Br J endothelial cell failure. Eye 2007;21:775-79.
Ophthalmol 1972;56(9):711-13. 20. Melles GRJ, Ong TS, Ververs B, van der Wees J. Descemet’s
11. Archila EA. Deep lamellar keratoplasty dissection of host tissue membrane endothelial keratoplasty (DMEK). Cornea 2006;
with intrastromal air injection. Cornea 1984-1985;3(3):217-18. 25:987-90.
12. Sugita J, Kundo J. Deep anterior lamellar keratoplasty with
complete removal of pathological stroma for visual improvement.
Br J Ophthalmol 1997;81:184-88.
3
2
Section I: Evolution, Preoperative Considerations and Eye Banking

Indications and Outcome of


Penetrating Keratoplasty
Urmimala Ghatak, Rajesh Sinha, Namrata Sharma

Corneal transplantation surgery is performed for a variety of • Optical


reasons, the major being to achieve an improvement in vision. • Tectonic
Corneal transplantation is not performed just because a corneal • Therapeutic
problem exists. The transplanting surgeon must reasonably • Cosmetic
expect significant eventual improvement of the patient's
condition as a result of the surgical procedure. Improvement of Optical Keratoplasty
two or more lines in Snellen's visual acuity chart is taken as a The keratoplasty is performed with the main purpose of
significant improvement in vision after corneal grafting surgery.
improving the visual acuity. This is the most common indication
This may encompass one or more of the following:
of penetrating keratoplasty and comprises more than 90 percent
• Ability to see with acceptable optical correction of the total penetrating keratoplasties performed in majority of
• Restoration of binocularity
the countries.3 The indication for keratoplasty depends on the
• Elimination of corneal disease
visual requirement and the expected long-term benefit arising
• Improvement in function and life style out of surgery. A corneal pathology causing a reduction in visual
• Improvement in pain.
acuity to less than 6/18 is an acceptable norm for penetrating
corneal transplantation. The common indications of optical
INDICATIONS OF PENETRATING KERATOPLASTY
keratoplasty include aphakic bullous keratopathy (Fig. 2.2) and
Many reports have detailed the indications of penetrating pseudophakic bullous keratopathy (Figs 2.3A and B), corneal
keratoplasty (Table 2.1). Penetrating keratoplasty is today opacities following infectious keratitis (Fig. 2.4), trauma, graft
performed for a wide variety of conditions. These may be failure (Fig. 2.5), endothelial and stromal corneal dystrophies
unilateral or bilateral (Fig. 2.1). The indications can be divided (Figs 2.6 to 2.8), corneal degenerations and congenital corneal
into four categories:1-9 opacities.4 While keratoconus (Fig. 2.9), pseudophakic bullous

Figure 2.1: Bilateral corneal opacity Figure 2.2: Aphakic bullous keratopathy
4
Table 2.1: Clinical indications Contd...
of penetrating keratoplasty
Vitreocorneal touch
• Pseudophakic corneal edema Recurrent stromal dystrophy
• Aphakic corneal edema Trauma/rupture
• Stromal corneal dystrophies Glaucoma
Granular dystrophy • Other causes of corneal opacification/distortion
Lattice dystrophy Uveitis

Chapter 2: Indications and Outcome of Penetrating Keratoplasty


Macular dystrophy Detached Descemet's membrane
Central crystalline dystrophy of Schnyder Failed epikeratoplasty
Central cloudy dystrophy of Francois Post laser/postrefractive surgery
• Endothelial dystrophies Silicone oil keratopathy
Fuchs' endothelial dystrophy Epithelial downgrowth
Congenital hereditary endothelial dystrophy
Posterior polymorphous dystrophy
Iridocorneal endothelial syndrome
Chandler's syndrome
• Ectasias/thinning
Anterior keratoconus
Keratoglobus
Posterior keratoconus
• Congenital opacities
Peter's anomaly
Scleroconea
Congenital glaucoma/buphthalmos
Aniridia
• Viral/post-viral keratitis
Herpes simplex virus
Varicella zoster virus
Adenovirus-Epidemic keratoconjunctivitis
• Microbial/post-microbial keratitis Figure 2.3A: Pseudophakic bullous keratopathy
Bacterial
Infectious crystalline keratopathy
Fungal
Chlamydial keratitis
Trachoma
Parasitic
Acanthamoeba keratitis
• Nutritional deficiencies
Kearatomalacia
• Non-infectious ulcerative keratitis
Keratoconjunctivitis sicca
Sjögren's syndrome
Neuroparalytic/neurotrophic keratopathy
Exposure keratitis
Mooren's ulcer
• Corneal degenerations
Terrien's marginal degeneration
Calcific band keratopathy
• Chemical injuries Figure 2.3B: Penetrating keratoplasty
Alkaline with IOL exchange in PBK
Acid
• Mechanical trauma, nonsurgical
Traumatic opacity/irregular astigmatism keratopathy and Fuchs’ dystrophy are the most common
• Regraft related to allograft rejection indications for optical penetrating keratoplasty in western
• Regraft unrelated to allograft rejection world,10 in developing countries like India, corneal scarring,
Primary tissue failure caused by infection, trauma and malnutrition are the major
Pseudophakic corneal edema
indications of this surgery.11,12
With the advent of intraocular lenses, there was a rapid rise
Contd... in the numbers of cataract surgery.9 This resulted in plenty of
5
Section I: Evolution, Preoperative Considerations and Eye Banking

Figure 2.4: Healed keratitis Figure 2.7A: Lattice dystropy

Figure 2.5: Failed graft Figure 2.7B: Lattice dystropy (Retroillumination)

Figure 2.6: Macular dystrophy Figure 2.8: Fuchs' dystrophy with bullous keratopathy

cases of pseudophakic bullous keratopathy throughout the world. During 1970s and 1980s, when iris-fixated and rigid or semi-
Previously, regrafts, herpetic keratitis and keratoconus were the flexible, closed loop anterior chamber implants were commonly
common indications for optical penetrating keratoplasty. inserted; pseudophakic corneal edema became the leading

6
indication for corneal transplantation in many centers. These Tectonic/Reconstructive Keratoplasty
implants damage the corneal endothelium directly over a long
The prime purpose of tectonic/reconstructive keratoplasty is to
period. Presently, pseudophakic bullous keratopathy appears to
restore the altered corneal structure. Although improved visual
be decreasing, presumably because of improved implant design
acuity remains a relevant consideration, restoration or at least
and almost universal use of posterior chamber IOL.
preservation of ocular anatomy and physiology are the principal
indications for tectonic corneal grafts. This is required in eyes
with a thinning/ectasia in cornea, corneal perforation or loss of

Chapter 2: Indications and Outcome of Penetrating Keratoplasty


corneal tissue, keratoconus, keratoglobus (Figs 2.10A and B),
pellucid marginal degeneration (Fig. 2.11), corneal melting
associated with autoimmune disorders, corneal fistula (Fig. 2.12)
and post-traumatic loss of corneal tissue.13,14 A reconstructive
graft may also improve the patient's visual function and the
option for future optical graft remains viable.

Therapeutic Keratoplasty
Therapeutic keratoplasty is mainly indicated in cases of
infectious keratitis to eliminate the infectious load in eyes with
keratitis unresponsive to specific antimicrobial therapy15
(Fig. 2.13). These are commonly done in non-responding fungal
or Acanthamoeba keratitis. In these cases corneal transplantation
Figure 2.9: Keratoconus provides a form of surgical therapy as actively diseased tissue
is removed. Transplants that are done to preserve the globe

Figure 2.10A: Keratoglobus (diffuse illumination)

Figure 2.10B: Keratoglobus (slit) Figures 2.11A and B: Pellucid marginal degeneration
with hydrops 7
Section I: Evolution, Preoperative Considerations and Eye Banking

Figure 2.12: Corneal fistula Figure 2.14: Corneal perforation

Cosmetic Keratoplasty
The primary purpose in such cases is to restore the normal
appearance of the eye, which has limited or no visual potential
and this may be undertaken in case of unsightly corneal scars or
deposits. Patient must be cautioned that the grafts may not remain
clear in all cases and long-term medications are required as in
optical grafts. With the availability of painted soft contact lenses,
corneal tattooing, enucleation or evisceration with a skillfully
prepared prosthesis or cosmetic shields, cosmetic keratoplasty
has become a rare procedure.

REGIONAL DIFFERENCES AND CHANGING


INDICATIONS IN PENETRATING KERATOPLASTY

The leading indications for penetrating keratoplasty in


Figure 2.13: Non-healing corneal ulcer developing countries are corneal scarring including adherent
leucoma and active infectious keratitis.11,12 In a study by Sony
therapeutically often have the added advantages of improved et al, in India, leading indications for penetrating keratoplasty
visual clarity and subsequently, improved visual acuity. Other were corneal scarring (38.03%) followed by acute infectious
therapeutic indications may be edema, scarring, and various keratitis (28.38%), regrafting (11.5%), aphakic bullous
deposits in the cornea. Pain may be a significant factor in keratopathy (7.27%), pseudophakic bullous keratopathy (6.18%),
advanced corneal swelling with bullous epithelial changes. and corneal dystrophy (3.85%). Healed infectious keratitis
Penetrating keratoplasty is effective in reducing, and usually (19.83%) was the most common subcategory among the eyes
eliminating the pain of bullous keratopathy. Sometimes, with corneal scarring followed by traumatic corneal scars
therapeutic keratoplasty is necessitated for the visualization of (16.71%). Healed (19.83%) and active keratitis (28.38%)
fundus to perform the retinal procedure, e.g. pars plana together accounted for the majority of keratoplasties (48.21%).
vitrectomy, photocoagulation or repair of complicated retinal In cataract-related corneal edema (13.45%), aphakic bullous
detachment. The use of temporary keratoprosthesis to aid in keratopathy (7.27%) was almost as frequent as compared with
vitreoretinal surgery is another new indication for therapeutic pseudophakic bullous keratopathy (6.18%).16 This is unlike
keratoplasty. developed countries where the indications such as keratoconus,
Therapeutic keratoplasty is always considered as the last pseudophakic bullous keratopathy and Fuchs' dystrophy are more
option when all other treatment modalities have failed. Therefore, common.10
alternative treatments should always be tried, wherever Some interesting trends in the clinical indications for
applicable. Conjunctival flaps can be a successful alternative in penetrating keratoplasty have been observed in the developed
non-healing corneal ulcers. Small-perforated corneal ulcers countries over the last two decades.14 Before 1980, keratoconus
(Fig. 2.14) can be treated effectively with cyanoacrylate glue and aphakic corneal edema were the most common indications
and soft bandage contact lenses. and pseudophakic corneal edema was just emerging.4,7,8,12,17
8
The emergence of pseudophakic corneal edema as the most Table 2.2: Expected outcomes after
common indication correlated with the overwhelming increase penetrating keratoplasty
in the number of the cataract extractions and lens implantations Category 1 (Excellent prognosis > 90% success rate)
since mid-1970. • Keratoconus
Relative number of regrafts has increased as the number of • Lattice dystrophy
keratoplasties performed in the population has increased.10 The • Granular dystrophy
combined incidence of pseudophakic and aphakic corneal edema • Early Fuchs' dystrophy

Chapter 2: Indications and Outcome of Penetrating Keratoplasty


has been decreasing with the advances and improvements in Category 2 (Very good prognosis: 80-90% success rate)
• Pseudophakic bullous keratopathy
cataract surgery and intraocular implants.
• Aphakic bullous keratopathy
Pseudophakic bullous keratopathy remains the leading • Fuchs' dystrophy
indication for corneal transplantation in the United States • Herpetic keratitis
followed by regraft.17 Cosar et al report that the percentage of • Iridocorneal endothelial syndromes
PBK cases associated with PC IOLs has increased significantly, • Interstitial keratitis
whereas the percentage associated with AC IOLs has decreased. • Macular dystrophy
Further, the frequency of regraft had also increased Category 3 (Fair prognosis: 50-80% success rate)
• Keratoglobus
significantly.17
• Pellucid marginal degeneration
Keratoconus is the leading indication for penetrating • Congenital hereditary endothelial dystrophy
keratoplasty in New Zealand, accounting for a higher proportion • Corneal opacities in the pediatric group
than in any other published literature.18 This suggests that • Chemical injury (mild)
keratoconus leading to transplantation may have increased • Dry eye (mild)
prevalence in New Zealand.18 • Corneal perforations
• Active keratitis

PENETRATING KERATOPLASTY Category 4 (Poor prognosis: < 50% success rate)


• Ocular pemphigoid
OF THE FELLOW EYE • Stevens-Johnson syndrome
• Congenital glaucoma
An optimal visual recovery after corneal grafting surgery usually
• Anterior chamber cleavage syndrome
does not occur until 4 to 8 months. Prior to this, vision may in • Neuroparalytic/Neurotrophic disease
fact be worse than before surgery in some of the cases. • Multiple graft failures
Considering this fact, it is wise to wait for at least 6 months after
the corneal grafting surgery in one eye before performing corneal
sensations and the microenvironment of the eyelids, as well as
transplantation in the fellow eye.19,20 Following a corneal
the tear film is healthy. Examples include keratoconus, lattice
transplant in the second eye, the risk of rejection, to both eyes,
or granular stromal dystrophies, early central Fuchs' dystrophy
has been found to be lower, longer the time between the two
or other inactive central or paracentral scars. The prognosis in
transplantation procedures, with best survival if there was no
this group is excellent with over 90 percent success. The best
rejection for three years in the first eye prior to surgery on the
reported rates of keratoplasty success are for keratoconus. Keates
second.21
and Falkenstein22 reported 100 percent graft success and 81
percent patients had 20/40 or better visual acuity. A comparison
EXPECTED OUTCOMES AFTER
of 50 penetrating grafts to 50 lamellar grafts for keratoconus
PENETRATING KERATOPLASTY
showed 100 percent graft clarity with a mean best-corrected
A successful outcome of a corneal grafting surgery depends on visual acuity of 20/20 in the penetrating and 20/30 in the lamellar
many variables, indication for surgery being the most important grafts.23 Kirkness et al reported 97 percent graft clarity in cases
one. There are certain indications of penetrating keratoplasty, of keratoconus at 4 years follow-up.24
which have a relatively better prognosis. The definition of
success includes the presence of a clear graft along with Category 2 (Very Good Prognosis)
improvement in vision of two or more lines on a Snellen's visual This group includes corneal lesions which involve part or whole
acuity chart. This also implies visual rehabilitation with glasses of the corneal periphery with minimal vascularization (stromal
instead of contact lenses, attainment of binocularity, decreased vascularization in not more than 2 quadrants). For example,
glare and less pain. The expected outcome of the corneal graft pseudophakic bullous keratopathy, aphakic bullous keratopathy,
surgery may be classified into four major categories based on diffuse Fuchs' dystrophy, inactive herpetic keratitis, iridocorneal
the groups described by Buxton et al (Table 2.2).2 endothelial syndromes, interstitial keratitis and macular stromal
dystrophy. The prognosis in this group is very good with 80-90
Category 1 (Excellent Prognosis)
percent success rate. Polack25 et al reported 78 percent of clear
This group consists of corneas with central corneal disease and grafts done for aphakic bullous keratopathy at 1 year and Olson26
normal peripheral architecture. The limbal anatomy, corneal reported 89 percent of clear aphakic grafts. Pineros et al reported
9
results in Fuchs' dystrophy with 89 percent graft clarity and visual 0.87, 0.73, 0.60, and 0.46 at 1, 5, 10, and 15 years, respectively.
acuity of 20/40 or better in 64 percent of cases at 8 years of Reasons for graft failure included irreversible rejection (34%),
follow-up.27 corneal endothelial cell failure including cases of glaucoma
(24%), and infection (14%). Variables predicting graft failure
Category 3 (Fair Prognosis) in multivariate analysis included transplant center (Centres
The corneas in this group are characterized by extremes of performing more than 20 grafts per year showed increased
survival), location and volume of surgeon's case-load, graft era,
corneal thickness, involving a large part of the recipient zone
Section I: Evolution, Preoperative Considerations and Eye Banking

indication for graft, number of previous ipsilateral grafts, lens


adjacent to the limbus and Langerhans' cells, e.g. keratoglobus,
pellucid marginal degeneration, congenital hereditary endothelial status, corneal neovascularization at transplantation, a history
of ocular inflammation or raised intraocular pressure, graft
dystrophy, keratoplasty in young children, mild chemical injury
diameter (a graft size of more than 8.5 mm in diameter or a graft
and mild dry eye. This may also include certain active infectious
or inflammatory disease, corneal perforations, peripheral disparity of greater than 0.5 mm showing poorer prognosis), and
postoperative events including graft neovascularization and
descemetoceles, and active bacterial, fungal and herpetic
rejection. Best-corrected Snellen acuity of 6/12 or better was
keratitis. Prognosis in this group is fair with a success rate
varying from 50-80 percent. Waring and Laibson28 and Stulting29 achieved by 45 percent, and of less than 6/60 by 26 percent, of
grafted eyes at last follow-up. Most penetrating grafts were
reported 60 percent success in graft for congenital opacities.
performed for visual improvement.32
Dana et al evaluated the graft survival analysis in pediatric
keratoplasty and showed that 80 percent were clear at 1 year The UK Transplant Study noted the following to be
statistically significant risk factors for graft failure: Recipient
and 67 percent at 2 years.30
diagnosis being not keratoconus or other central corneal disease,
Category 4 (Poor Prognosis) larger grafts (trephine sum = 14.5 mm) and combined running
and interrupted sutures.33
In this group, there is absence of normal limbal stem cells and In the study done by Dandona et al12 the five-year survival
normal maturation of corneal epithelium. These cases are rate was highest if the corneal transplant was done for
characterized by severe fibrovascular replacement of the cornea, keratoconus and lowest if carried out for previous transplant
conjunctival ischemia, anterior chamber obliteration, loss of failure. The relative risk of transplant failure was higher if the
corneal sensations and advanced dry eye, e.g. ocular pemphigoid, preoperative diagnosis was previous transplant failure, aphakic
Stevens Johnson syndrome, congenital glaucoma, anterior bullous keratopathy, corneal clouding due to congenital
chamber cleavage syndromes, neuroparalytic or neurotrophic conditions and glaucoma or adherent leucoma. Patients with
disease, epithelial downgrowth and multiple graft failures. The lower socioeconomic status and patients less than 10 years of
prognosis in this group is very poor with a success rate of less age also had higher risk of transplant failure. This was also
than 50 percent. A penetrating corneal grafting surgery may not associated with vascularization of the host cornea before
be the preferred therapeutic option in this group; however, transplantation and the use of fair quality donor cornea for
surgery may be undertaken with guarded prognosis when the transplantation compared with excellent, very good or good
disease is bilateral or involves the patient’s only eye. quality donor cornea.
Various studies have evaluated different risk factors for the Hassan et al attempted to determine how donor health status
graft survival after penetrating keratoplasty. In the Collaborative affects the risk of infection after corneal transplant. 34
Corneal Transplant Study, the various factors, which have Postkeratoplasty endophthalmitis was associated with recent
influenced the survival of the graft, include:31 hospitalization and fatal cancer among donors. Endophthalmitis
• The indication for the graft (keratoconus showed the best appeared more likely with tissues transplanted longer than 5 days
survival) after donation. The prevalence of concordant microbial isolates
• The graft number in the ipsilateral eye from donors and recipients was greater among fungal
• Corneal vascularization at the time of the graft endophthalmitis than among bacterial endophthalmitis. In a
• The presence of anterior synechiae during surgery separate study,35 Hassan et al tracked the relative frequency and
• The history of previous increase in intraocular pressure explored possible risk factors of fungal compared with bacterial
• The presence of aphakia or pseudophakia endophthalmitis after corneal transplantation. They noted that
• The history of previous intraocular surgery concordant cultures of the residual donor corneoscleral rim or
• Recipient age less than 40 years of age preservation medium occurred significantly more often with
• Graft size less than 8 mm fungal than bacterial endophthalmitis. After the introduction of
• Time to preservation of donor cornea of greater than six Optisol-GS, the odds of bacterial relative to fungal
hours endophthalmitis decreased by 77 percent. After adjustment for
• Blood group ABO incompatibility. the preservation method and other eye-banking variables, the
Williams et al examined graft survival and visual outcome odds of fungal endophthalmitis were 3.4 times that of bacterial
after full-thickness corneal transplantation in the Australian endophthalmitis, when donor corneal preservation was 4 days
corneal graft registry. Probability of corneal graft survival was or longer.
10
In poor prognostic category such as aniridia, postoperative their present level of vision and whose lifestyles are not
complications include whorl keratopathy, persistent epithelial compromised should not be operated. In developing countries
defects, central subepithelial scarring, peripheral vascularization like India, because of very high chances of graft failure, patient
with pannus, and graft rejection.36 In a study by Kremer et al, with ambulatory vision in the eye with better vision should not
glaucoma was well-controlled medically but five of nine patients have surgery. In cases of advanced dry eye, grade IV chemical
(56%) with pre-existing glaucoma needed an increase in burns (Fig. 2.15), anterior staphyloma (Fig. 2.16) and severe
medication for intraocular pressure control. Graft rejection cases of Stevens-Johnson syndrome (Fig. 2.17), ocular cicatricial

Chapter 2: Indications and Outcome of Penetrating Keratoplasty


occurred in seven of 11 eyes (64%) and three of these eyes pemphigoid (Fig. 2.18), with no tear film, and bad ocular surface
required repeat transplantation.36 may jeopardize a successful penetrating keratoplasty.
Keratoprosthesis may be a better option for these patients.37
ALTERNATIVES AND CONTRAINDICATIONS TO Multiple graft failure is a relative contraindication for penetrating
PENETRATING KERATOPLASTY keratoplasty.
Cases of patients with inaccurate projection of rays and
While there are no absolute contraindications for penetrating underlying retinal detachment are also relative contraindications
keratoplasty except for the presence of no light perception, there for surgery. Patients with central corneal opacities and clear
are certain conditions of corneal opacification in which the paracentral areas may obtain useful ambulatory vision with
morphological and functional outcome is so poor that most optical iridectomy alone.38 Keratoplasty may also be deferred
surgeons would not prefer to perform a corneal grafting surgery in patients who have severely scarred corneas with anterior
in such cases. These eyes as such should not be operated but segment distortion due to trauma or infection in one eye and the
surgery may be undertaken especially if the disease is bilateral fellow eye has a visual acuity of 20/20. This topic is covered in
or involves patient’s only eye. Patients who are satisfied with details in section VI.

Figure 2.15: Grade IV chemical burns

Figure 2.16: Anterior staphyloma Figures 2.17A and B: Stevens-Johnson syndrome


11
18. Edwards M, Clover GM, Brookes N, et al. Indications for Corneal
Transplantation in New Zealand: 1991-1999. Cornea 2002;21:
152-55.
19. Buxton JN, Schuman M, Pecego J. Graft reactions after unilateral
and bilateral keratoplasty for keratoconus. Ophthalmology.
1981;88:771-73.
20. McNeill JI. Indications and outcomes. In: Cornea. Surgery of the
cornea and conjunctiva Eds. Krachmer JH, Mannis MJ, Holland
EJ. 1997 St. Louis, Missouri, Mosby Year Book, Inc.
Section I: Evolution, Preoperative Considerations and Eye Banking

21. Tuft SJ, Gregory WM, Davison CR. Bilateral penetrating


keratoplasty for keratoconus. Ophthalmology 1995;102:462-68.
22. Keates RH, Falkenstein S. Keratoplasty in keratoconus. Am J
Ophthalmol 1972;74:442-44.
23. Richard JM, Paton D, Gasset AR. A comparison of penetrating
keratoplasty and lamellar keratoplasty in the surgical management
of keratoconus. Am J Ophthalmol 1978;86:807-11.
24. Kirkness CM, Ficker LA, Steele AD, Rice NS. The success of
Figure 2.18: Ocular cicatricial pemphigoid penetrating keratoplasty for keratoconus. Eye 1990;4:673-88.
25. Polack FM. Keratoplasty in aphakic eyes with corneal edema:
results in 100 cases with 10-year follow-up. Ophthalmic Surg.
1980;11:701-7.
REFERENCES
26. Olson RJ, Mattingly TP, Waltman SR, Kaufman HE. Aphakic
1. Paytar D, Jones DB. Penetrating keratoplasty. Outcome keratoplasty: visual acuity and optical errors. Ophthalmology
monograph. Alcon monograph series 1(1), Alcon laboratories Fort 1980;87:680-86.
Worth, Texas 1976. 27. Pineros O, Cohen EJ, Rapuano CJ, Laibson PR. Long-term results
2. Buxton JN. Corneal surgery. In Collins JF, Editor: Handbook of after penetrating keratoplasty for Fuchs' endothelial dystrophy.
Clinical Ophthalmology, New York, Masson Publishers 1982. Arch Ophthalmol 1996;114:15-18.
3. Williams KA, Muehlberg SM, Lewis RF, et al. How successful 28. Waring GO 3rd, Laibson PR. Keratoplasty in infants and children.
is corneal transplantation? A report from the Australian Corneal Trans Am Acad Ophthalmol Otolaryngol 1977;83:283-96.
Graft Register. Eye 1995;9:219-27. 29. Stulting RD, Sumers KD, Cavanagh HD, Waring GO 3rd,
4. Hyman L, Wittpen J, Yang C. Indications and techniques of Gammon JA. Penetrating keratoplasty in children. Ophthalmology
penetrating keratoplasties 1985-1988. Cornea 1992;11:573. 1984;91:1222-30.
5. Mamalis N, Anderson CW, Kreisler KR, et al. Changing trends 30. Dana MR, Moyes AL, Gomes JA, Rosheim KM, Schaumberg
in the indications for penetrating keratoplasty. Arch Ophthalmol DA, Laibson PR, Holland EJ, Sugar A, Sugar J. The indications
1992;110:1409. for and outcome in pediatric keratoplasty. A multicenter study.
Ophthalmology 1995;102:1129-38.
6. The Australian Corneal Graft Registry: 1990-1992 report. Aust
31. Maguire MG, Stark WJ, Gottsch JD, Stulting RD, Sugar A, Fink
NJZ Ophthalmol 1993;21(2 suppl): 1.
NE, Schwartz A. Risk factors for corneal graft failure and rejection
7. Sharif KW, Casey TA. Changing indications for penetrating
in the collaborative corneal transplantation studies. Collaborative
keratoplasty, 1971-1990. Eye 1993;7:485.
Corneal Transplantation Studies Research Group. Ophthalmology
8. Haamann P, Jensen OM, Schimidt P. Changing indications for
1994;101:1536-47.
penetrating keratoplasty. Acta Ophthalmol (Copenh) 1994;72:443.
32. Williams KA, Lowe M, Bartlett C, Kelly TL, Coster DJ. All
9. Robin JB, et al. An update of the indications for penetrating
Contributors. Risk factors for human corneal graft failure within
keratoplasty, 1979-1983, Arch Ohthalmol 1986;104:87-89.
the Australian corneal graft registry. Transplantation 2008;
10. Patel NP, Kim T, Rapuano CJ, Cohen EJ, Laibson PR. Indications
86:1720-24.
for an outcomes of repeat penetrating keratoplasty 1989-1995
33. Bradley BA, Vail A, Gore SM, et al. Penetrating keratoplasty in
Ophthalmology 2000;107:719-24.
the United Kingdom:an imterim analysis of the corneal transplant
11. Dada T, Sharma N, Vajpayee RB. Indications for pediatric follow-up study. In:Terasaki PI, Cecka JM, eds. Clinical Transplants.
keratoplasty in India. Cornea 1999;18:296-98. Los Angeles: UCLA Tissue Typing Laboratory 1993;293-315.
12. Dandona L, Ragu K, Janarthanan M, et al. Indications for 34. Hassan SS, Wilhelmus KR, Dahl P, Davis GC, Roberts RT, Ross
penetrating keratoplasty in India. Indian J Ophthalmol KW, Varnum BH. Medical Review Subcommittee of the Eye Bank
1997;45:163-68. Association of America Infectious disease risk factors of corneal
13. Soong HK, Farzo AA, Katz D, et al. Lamellar corneal patch grafts graft donors. Arch Ophthalmol 2008;126:235-9.
in the management of corneal melting. Cornea 2000;19:126-34. 35. Hassan SS, Wilhelmus KR. Medical Review Subcommittee of
14. Taylor DM, Stern AL. Reconstructive keratoplasty in the the Eye Bank Association of America Eye-banking risk factors
management of conditions leading to corneal destructions. for fungal endophthalmitis compared with bacterial
Ophthalmology 1980;87:892-904. endophthalmitis after corneal transplantation. Am J Ophthalmol.
15. Killingsworth DW, Stern GA, Driebe WT, et al. The results of 2005;139:685-90.
therapeutic penetrating keratoplasty. Ophthalmology 1993;100: 36. Kremer I, Rajpal RK, Rapuano CJ, Cohen EJ, Laibson PR.
534-41. Results of penetrating keratoplasty in aniridia. Am J Ophthalmol
16. Sony P, Sharma N, Sen S, Vajpayee RB. Indications of penetrating 1993;15;115:317-20.
keratoplasty in northern India. Cornea 2005;24(8):989-91. 37. Dohlman CH, Doane MG. Some factors influencing outcome after
17. Cosar CB, Sridhar MS, Cohen EJ, et al. Indications for keratoprosthesis surgery. Cornea 1994;13:214.
penetrating keratoplasty and associated procedures, 1996-2000. 38. Vajpayee RB, Sharma N, Dada T, Pushker N. Optical sector
12 Cornea 2002;21:148-51. iridectomy in corneal opacities. Cornea 1999;18:262-64.
3

Chapter 3: Preoperative Evaluation


Preoperative Evaluation
Namrata Sharma, Ritika Sachdev, Manotosh Ray, Rasik B Vajpayee

The principal objective of the preoperative evaluation is to History taking should also document the use of antiglaucoma
identify the underlying corneal disease, to anticipate potential medications. Poor control of intraocular pressure after
intraoperative and postoperative problems during and after the keratoplasty decreases the chance of graft survival. Chronic
surgery and to prognosticate a case of keratoplasty. It is elevation of intraocular pressure may lead to decreased
imperative that a correct etiological diagnosis of corneal endothelial cell count.4,5
pathology and associated disorder if any, is established. An Changes in the quality of vision, as the day progresses should
attempt must be made to cure all associated conditions that can also be ascertained; for example in Fuchs' dystrophy, vision is
complicate a desired result of corneal transplantation surgery. often worse immediately upon awakening with gradual
Any active corneal disease must be identified preoperatively and improvement as the day progresses. When available, old records
if required, effective measures should be taken to prevent its should be looked for. These can caution the physician to the
adverse influence on a successfully performed corneal grafting possible occurrence of intra- and postoperative problems and
surgery. A proper patient selection and comprehensive confirm important information such as prior best-corrected visual
preoperative evaluation enhance the potential for a favorable acuity, intraocular pressure control and previous intraocular lens
outcome. powers. A history should be sought about prior ophthalmic
surgical procedures such as cataract extraction, filtering
OCULAR HISTORY procedures or Nd:YAG laser for posterior capsular opacification.
A candidate for regrafting carries a high risk of rejection.
A detailed history is taken to identify the related local or systemic
conditions for the corneal blindness. Patients are carefully
GENERAL HISTORY
screened for ocular injury, infectious keratitis, nutritional
deficiencies, history of previous surgery and for systemic The main question when obtaining the patient's history relates
diseases such as collagen vascular disease and Stevens-Johnson to the ability of the patient to undergo proposed operative
syndrome.1-3 procedure. In considering for local anesthesia, for example, the
Prognosis for successful outcome may be related to the ability of the patient to lie flat for the duration of the procedure
knowledge of the patient's preoperative history. Corneal grafts could be compromised by pulmonary or cardiac abnormalities
for herpetic scars develop recurrence of the disease and severe arthritis.6 Pre-existing medical problems such as
postoperatively and may require long-term systemic acyclovir hypertension and diabetes should be stabilized. Allergies to
therapy. medications such as antibiotics, systemic medications and
A history of good visual acuity prior to the development of anesthetics should be noted and reviewed to avoid subsequent
corneal opacity in the affected eye carries a better prognosis. A complications.
meticulous evaluation of the presence of any amblyopia related Patients taking aspirin, non-steroidal anti-inflammatory drugs
to duration of corneal opacity, anisometropia and strabismus is and other medications that interfere with blood coagulation may
mandatory. A patient with childhood onset of opacity presenting be discontinued for 48 hours before keratoplasty, especially, if
later during adulthood may signify the presence of amblyopia. the prothrombin times are in reasonably good range and the
Information should be obtained pertaining to the onset of the treatment can be resumed in the first postoperative day.
visual disturbance, whether a prior intraocular surgery or The patient's social and family support system also needs to
infection preceded it, or whether it simply deteriorated over time. be reviewed. Because consistent follow-up and proper use of
Previous retinal and macular pathology result in poor visual gain postoperative medications are required, patient rehabilitation and
despite a clear graft. compliance are important to the ultimate success of the graft.

13
OCULAR EXAMINATION Slit-lamp Biomicroscopy

Visual Acuity Conjunctiva and Cornea

Assessment of visual acuity is extremely important before the The tear film should be evaluated under slit-lamp for signs of
patient is taken for penetrating keratoplasty. This should include dry eye like decreased tear meniscus and floating debris.
recording of both uncorrected [UCVA] and best corrected visual Peripheral and tarsal conjunctiva are examined for the evidence
acuity [BCVA]. Standard Snellen's chart is commonly used to of scarring, symblepharon to detect the evidence of previous
Section I: Evolution, Preoperative Considerations and Eye Banking

record the visual acuity. Contact lens corrected visual acuity ocular surface disorder such as Stevens-Johnson syndrome,
should be recorded in cases of irregular astigmatism.7 ocular cicatricial pemphigoid or chemical burns. These patients
In case of poor visual acuity, it must be documented as are at increased risk of dry eyes, non-healing epithelial defects
counting fingers, hand movements or light perception. One of and postoperative infections as the normal external immune
the most important acuity factors involves the careful defense mechanism of IgA and lysozyme are compromised.
documentation of projection of rays, as this is an important Slit-lamp examination is also performed to assess the size,
indication of retinal and optic nerve function. In cases where shape, extent and severity of corneal opacity, degree and extent
there will be improvement of visual acuity after keratoplasty in of vascularization. The corneal sensation may be checked with
eyes with corneal edema, instilling topical glycerin after the fine tip of a cotton wisp 7 (Fig. 3.1).
anesthesia and waiting 20 to 30 minutes for corneal clearing may Consideration must be given to the condition of the host graft
improve acuity and facilitate retinal examinations. Pinhole visual bed, its corneal thickness or peripheral thinning in cases of
acuity, potential acuity meter and glare testing may have limited regrafts. The presence of corneal vascularization may dictate the
value in predicting best visual acuity due to severe light scattering type of suturing technique to be used in a particular case. The
from corneal pathology. In cases of small central scars, a stenopic underlying pathology and the diameter of the host cornea guide
slit visual acuity should be recorded after complete pupillary the diameter of host trephination and corresponding disparity in
dilatation. It is possible that some of these patients may the size of donor button. In cases with post-infectious scarring
significantly benefit from a simple optical iridectomy and hence with thinning and vascularization or corneal ectasias such as
a penetrating keratoplasty may be deferred.8 pellucid marginal degeneration, sizing and placement of the graft
Quantifying visual function in children is important to may require some decentring. Interrupted sutures may be
prognosticate the case. Occlusion of one eye, which is strongly preferred in corneas with excessive vascularization or in pediatric
objected by the child, can indicate a poorer acuity in the eyes due to their faster healing response seen after keratoplasty.
uncovered eye. Preferential looking test can also be performed
to assess visual acuity in children, which is based on the fact Anterior Segment and Iris
that infants prefer to fixate on the pattern rather than the The anterior chamber must be evaluated for the evidence of any
homogeneous stimuli. The infant is exposed to the stimulus and active inflammation. A transplant is best performed on an
the examiner observes the eye for fixation movements using uninflamed, quiet eye. Presence of a ciliary flush, keratic
Teller acuity cards or Cardiff acuity cards. In children > 2 years precipitates, anterior synechia and iridocorneal adhesions are
multiple picture test or Sheridan-Gardiner test can be performed signs of past or present inflammation. Iris should be examined
which is based on matching prototypes. for the presence of iridocorneal synechiae, rubeosis and also
Gross Ocular Examination fibrovascular membranes obscuring the pupil and location of

Eyes are examined with an emphasis on the external ocular


disorders. The lids are evaluated for ectropion, entropion,
lagophthalmos and trichiasis. A surgical correction of these
conditions prior to keratoplasty is advised. These conditions can
cause epithelial scarring and permanent deformity, and may
adversely affect the outcome of the corneal grafting surgery.
Because normal tear production is crucial to the graft re-
epithelization, one should note the tear film abnormalities during
the preoperative examinations. Any evidence for blepharitis
should be looked for and must be treated aggressively. The status
of the lacrimal sac and punctal positions is examined to rule out
any lacrimal system disorder. These anomalies must be corrected
before the patient is taken up for penetrating keratoplasty. If
significant dryness is present, partial or complete punctal
occlusion should be done preoperatively or at keratoplasty,
sometimes in combination with medial or lateral tarsorraphy Figure 3.1: Post-infectious corneal scarring with
14 particularly, if exposure keratitis is present. vascularization
peripheral iridectomies. Presence of extensive anterior synechiae keratoplasty despite successful graft. This may be of particular
may warrant use of special techniques like corneal debulking9 significance in cases of aphakic and pseudophakic bullous
and use of oversized grafts.10 The pupil should be examined for keratopathy with a history of intraoperative vitreous disturbances
size, shape and relative afferent pupillary defect. and postoperative iridocylitis. Knowledge of such conditions will
help to explain the prognosis to the patients. Direct and indirect
Lens ophthalmoscopy should be done under mydriasis and fundus
evaluated from the relatively clear areas, wherever possible.
The lens status must be determined for the presence of cataract,

Chapter 3: Preoperative Evaluation


aphakia and pseudophakia. Slit lamp microscopy is performed
INVESTIGATIONS
after dilatation of pupil to detect the lenticular opacities. The
lens may have weakened zonules and exhibit phacodonesis. Refraction
Pre-existing early cataract progresses very rapidly after
penetrating keratoplasty. Moreover, coexistent cataract and An accurate refraction is mandatory under mydriasis in all cases,
corneal opacities are common, especially when the patient is wherever possible. In cases such as keratoconus, where
older than 50 years. Therefore, it may be mandatory in such cases retinoscopy is impossible, keratometry may be checked and
to remove the cataract at the time of keratoplasty, even if it is patient refracted.
minimal.11 This can avoid the risk of endothelial damage during
subsequent cataract surgery. Tear Film Status
If the eye is aphakic, the status of the anterior hyaloid face The use of fluorescein and/or rose bengal and Schirmer testing
of vitreous, presence and extent of iris coloboma and pupillary gives the ophthalmologist an indication of the extent of dryness
status must be evaluated. Such eyes may additionally require and epitheliopathy.
anterior segment reconstruction including coreoplasty, anterior
vitrectomy and an anterior chamber or scleral fixated posterior Keratometry
chamber intraocular lens implantation.
Keratometry may be warranted in cases of corneal ectasias such
If pseudophakos is present, the type of IOL should be
as keratoconus, pellucid marginal degeneration and keratoglobus.
identified. If an anterior chamber IOL is present, it must be
identified as either an open looped or closed loop lens. Iris
Gonioscopy
supported closed loop anterior chamber lenses and open-looped
anterior chamber lens should be replaced especially if any Gonioscopy may be performed to examine the iridocorneal
pseudophacodonesis is suspected. adhesions, peripheral iridectomies and to locate the position of
the lens haptics if an anterior chamber lens is present.
Intraocular Pressure
Pachymetry
Intraocular pressure should be measured preoperatively.
Applanation tonometry may not be possible in corneas with Pachymetry should be performed to quantify corneal thickness
opacities and scarring. A MacKay Marg, pneumotonometer, using ultrasonic pachymeter or sonogauge especially in cases
scleral tonometer or Tono-pen may be required for more accurate of corneal thinning disorders such as keratoconus, keratoglobus
assessment in these patients. Raised intraocular pressure must and pellucid marginal degeneration. Not only central but also
be controlled either medically or surgically, before the patient paracentral and peripheral readings should be obtained in each
is planned for keratoplasty. Intraocular pressure should not be of the four meridians. Pachymetry is also mandatory in cases
higher than the low twenties on no more than two medications. where, automated therapeutic lamellar keratectomy is
If it is not, primary filtering or combined filtering and penetrating contemplated for proper selection of the microkeratome head
keratoplasty should be considered.4 Since, all keratoplasty to be used. Micheiletto et al have reported a very high risk of
patients require intraoperative viscoelastics to coat the perforation of the Descemet's membrane while performing the
endothelium, aid in control of bleeding and help prevent big bubble technique of deep anterior lamellar keratoplasty
synechia, therefore the eyes with pre-existing glaucoma should (DALK) in cases with preoperative pachymetry less than 250
be screened out. Further, the use of long-term topical steroids microns. 12 They hypothesized that the weakening of the
to prevent rejection may lead to steroid induced glaucoma.4,5 Descemet's membrane is related to end-stage keratoconus corneal
thinning and this ultrastructurally weakened Descemet's
Fundus Evaluation membrane is more likely to rupture during the DALK procedure.
If possible, a thorough evaluation of the retina and vitreous
Specular Microscopy and Confocal Microscopy
should be performed to ensure that the decreased vision is
secondary to corneal pathology only. Eyes with macular Specular microscopy and confocal microscopy may be
pathology, e.g. macular holes, macular degeneration and cystoid undertaken, wherever possible. Specular microscopic
macular edema are unlikely to improve after penetrating features help to diagnose early cases of Fuchs' dystrophy
15
(Figs 3.2A and B) and also help to differentiate various other degeneration and keratoglobus. Peripheral videokeratography
pathologies such as posterior polymorphous dystrophy and can also be done in cases of corneal opacities with cataract, which
iridocorneal syndromes. Endothelial cell counts and morphology helps to calculate the intraocular lens powers in a case of
may also be relevant in cases of superficial opacities where combined penetrating keratoplasty with cataract extraction and
lamellar grafts are contemplated and a normal endothelial reserve intraocular lens implantation.
is essential. Confocal microscopy, a more recent research tool
helps to study the status of the epithelium as well as the Slit Scanning and Scheimpflug Imaging
Section I: Evolution, Preoperative Considerations and Eye Banking

keratocytes. It non-invasively resolves the structural as well as


Slit scanning (Orbscan) and Scheimpflug (Pentacam) evaluation
functional interrelationships (Fig. 3.3). Confocal microscopy has of the anterior and posterior corneal surface as well as the corneal
been used in the detection and management of pathologic and
thickness may be useful in ectatic disorders of the cornea (Figs
infectious conditions, corneal dystrophies and ectasias and
3.5 to 3.7). Their role is however limited in opaque corneas and
assessment of the depth of corneal scarring prior to lamellar ultrasonic evaluation may be more useful in these cases.
keratoplasty procedures.
Yamaguchi T et al demonstrated that the postoperative BCVA
following DSAEK surgery correlated with irregularity of the
Laser Interferometry
anterior surface but not the posterior surface as evaluated using
More sophisticated testing with potential acuity meters and laser the Scheimpflug imaging system.13
interferometers may be helpful in evaluation of prognosis of
transplant surgery for patients with corneal opacities. Ultrasound Biomicroscopy
The original ultrasound biomicroscope (UBM) developed by
Videokeratography
Pavlin, Sherar and Foster is based on 50 to 100 MHz transducers,
Videokeratography (Fig. 3.4) should be performed in cases of
ectatic corneal disorders such as keratoconus, pellucid marginal

Figure 3.2A: Specular microscope Figure 3.3: Confocal microscopy

Figure 3.2B: Specular microscopic features of Fuchs'


dystrophy: extensive guttae are visible Figure 3.4: Videokeratography
16
Chapter 3: Preoperative Evaluation
Figure 3.5: ORBSCAN Quad map of a keratoconus patient: Note posterior elevation > 50 microns, anterior elevation coinciding
with area of posterior elevation and thinnest pachymetry. Asymmetric skewed bowtie pattern seen with Placido based topography

reconstruction may be undertaken in such cases. Ultrasound


biomicroscopic evaluation can be used to determine the presence
and extent of peripheral anterior synechiae, the status of the lens
or the intraocular implant and the capsular status in aphakes.
Madhavan et al have reported its role as a useful adjunct in the
preoperative planning and prognostication of patients requiring
penetrating keratoplasty.14 Lanzl et al demonstrated the role of
UBM in surgical planning for limbal dermoids. UBM is able to
assess the depth of involvement of opaque corneal lesions such
as limbal dermoids as it distinguishes the normal cornea from
the more sonolucent lesion.15 Because planning of the surgical
approach in these cases is facilitated by preoperative knowledge
about the depth of penetration of these opaque lesions, UBM
can be regarded as useful adjunct tool in their management.
Rutnin et al evaluated the role of UBM as a method of
Figure 3.6: The Scheimpflug imaging system- Pentacam
assessing anterior chamber intraocular lens (IOL) haptics before
combined penetrating keratoplasty and IOL exchange in eyes
incorporated into the B-mode clinical scanner. Higher frequency
with poor corneal clarity resulting from pseudophakic bullous
transducers permit increased resolution, but only at the expense
keratopathy.16 They concluded that UBM can evaluate the
of decreased tissue penetration depth. The commercially
presence and extent of fibrotic encasement of the haptics in cases
available UBM is most often configured with a 50 megahertz
with an opaque cornea and the extent of fibrotic encasement was
transducer, which provides a tissue resolution of approximately
found to be predictive of the surgical difficulty in removal of
50 microns and a penetration depth of 4-5 mm. This permits
the intraocular implant.
visualization of the anterior segment. The presence of a
corneoiridic scar may necessitate an ultrasound biomicroscopy
Ultrasonography
to assess the angle and the ciliary body (Figs 3.8 and 3.9A and
B). While performing keratoplasty, the corneal debulking by A and B-scan ultrasonography should be performed in all eyes
sequential lamellar separation8 and subsequent anterior segment with corneal opacity to rule out any coexistent posterior segment
17
Section I: Evolution, Preoperative Considerations and Eye Banking

Figure 3.7: Scheimpflug (Pentacam) map of a keratoconic cornea

Electrophysiological Tests
The use of electrophysiologic methods is helpful to assess the
retinal functions in eyes with corneal opacities. Bright-flash
electroretinogram (ERG) will give a response despite most media
opacities. However, ERG measures only gross retinal function.
The visual evoked response (VER) is a better indicator of optic
nerve function. Pattern stimuli can give a relatively precise
measure of visual function when the media are clear, but flash
stimuli must be used when the cornea is opaque. A decreased
amplitude and prolonged latency in VER indicates poor
prognosis.
Once, the evaluation is over, one must establish a diagnosis
and prognosticate the case very carefully. Several factors
Figure 3.8: Ultrasound biomicroscopy including age of the patient, status of the other eye, compliance
of the patients and need of binocularity play a role in decision-
pathology such as old retinal detachment in which case the making. The procedure should be clearly explained to the patient
keratoplasty may not be undertaken due to poor prognosis. and relatives. The risks of the procedure specifically regarding
Determination of the axial length using A-scan biometry is long follow-up time, chance of rejection, long-term use of
critical in IOL power calculation while performing the triple medications should be discussed. The patient should have a
procedure. realistic expectation for visual gain after the procedure.

18
3. Chang, SD, Pecego JG, Zadnik K, et al. Factors influencing graft
clarity. Cornea 1996;15:577-81.
4. Charlin R, Polack FM. The effect of elevated intraocular pressure
on the endothelium of corneal grafts. Cornea 1982;1:241.
5. Sekhar GC, Vyas P, Nagarajan R, et al. Post-penetrating
keratoplasty glaucoma. Indian J Ophthalmol 1993;41:181.
6. Altman AJ, Albert DM, Fournier GA. Cocaine's use in
ophthalmology: our 100-year heritage. Surv Ophthalmol

Chapter 3: Preoperative Evaluation


1985;29:300.
7. Vail A, Gore SM, Bradley BA, et al. Clinical and surgical factors
influencing corneal graft survival, visual acuity and astigmatism.
Corneal Transplant Follow-up Collaborators. Ophthalmology
1996;103:141-49.
8. Vajpayee RB, Sharma N, Dada T, Pushker N. Optical sector
iridectomy in corneal opacities. Cornea 1999;18:262-64.
9. Vajpayee RB, Angra SK, Honavar S, et al. Protection of the iris
by lamellar dissection of corneal layers. A technique in penetrating
keratoplasty. Cornea 1994;13:16-9.
10. Vajpayee RB, Dada T, Ray M, Tandon R, Sethi A, Turaka K.
Oversized corneal grafts for corneal opacities with iridocorneal
adhesions. Ophthalmology 2001;108:2026-28.
11. Flowers CW, McLeod SD, McDonell PJ. Evaluation of
intraocular lens power calculation formulas in the triple
procedure. J Cataract Refract Surg 1996;22:116.
12. Michieletto P, Balestrazzi A, Balestrazzi A, Mazzotta C,
Occhipinti I, Rossi T. Factors predicting unsuccessful big bubble
deep lamellar anterior keratoplasty. Ophthalmologica.
2006;220:379-82.
13. Yamaguchi T, Negishi K, Yamaguchi K, Murat D, Uchino Y,
Shimmura S, Tsubota K. Effect of anterior and posterior corneal
surface irregularity on vision after Descemet’s-stripping
endothelial keratoplasty. J Catarct Refract Surg. 2009;35:688-94.
Figures 3.9A and B: Ultrasound biomicroscopy 14. Madhavan C, Basti S, Naduvilath TJ, Sangwan VS. Use of
of corneoiridic scar ultrasound biomicroscopic evaluation in preoperative planning
of penetrating keratoplasty. Cornea. 2000;19:17-21.
15. Lanzl IM, Augsburger JJ, Hertle RW, Rapuano C, Correa-Melling
REFERENCES
Z, Santa Cruz C. Role of ultrasound biomicroscopy in surgical
1. Williams KA, Roder D, Esterman A. Factors predictive of corneal planning for limbal dermoids. Cornea. 1998;17:604-06.
graft survival. Report from Australian Corneal Graft Registry. 16. Rutnin SS, Pavlin CJ, Slomovic AR, Kwartz J, Rootman DS.
Ophthalmology 1992;99:403. Preoperative ultrasound biomicroscopy to assess ease of haptic
2. Price FW Jr, Whitson WE, John S, Gonzales JS. Risk factors for removal before penetrating keratoplasty combined with lens
corneal graft failure. J Refract Surg 1996;12:134-43. exchange. J Cataract Refract Surg 1997;23:239-43.

19
4
Section I: Evolution, Preoperative Considerations and Eye Banking

Eye Banking—A Practical Guide


Graeme A Pollock, S Louise Moffatt

The process of corneal transplantation begins with eye donation. The continued development, complexity, professionalism and
Corneal transplantation is not possible without the provision of evolution of the services provided by Eye Banks means that Eye
a viable, disease-free donor cornea. In no other area of Banking today is very different from that practiced only 10 to
ophthalmic surgery is the surgeon more dependent on a factor 20 years ago. This, coupled with increasing regulatory oversight,
over which they have little or no direct control. has consigned to history the concept of Eye Banking as a sole
An Eye Bank holds the dual responsibilities of ensuring the practitioner undertaking (often voluntary or part-time) who is
safety and efficacy of donor corneas, and ensuring fair and equipped with a only a telephone and refrigerator.
equitable distribution of transplantable corneas. In addition, Eye Such generational change has also created a new paradigm
Banks may provide other ancillary services including the supply for Eye Banks. No longer is the focus merely on the quantity of
of donated sclera for glaucoma, oculoplastic and retinal surgery, tissue provided. Instead, quality of tissue and quality of service
and more recently, human amniotic membrane for ocular surface has become a priority.
procedures.
It is also important to recognize that a fully functioning and Regulation and Quality Systems
effective Eye Bank is not a simple storage and supply unit. Eye
Banking has a rich history and traces its origins back to the Eye Banking services are provided in an environment of stringent
establishment of the Eye Bank for Sight Restoration in New York quality assurance standards, often with increasing government
in 1944. Over the ensuing 60 years Eye Banks have developed regulation or oversight. In Australia since 1995, the Therapeutic
professional practices that encompass all aspects of donation. Goods Administration has mandated the licensing of Eye Banks
Thus Eye Banking involves many activities that are not only under a code of Good Manufacturing Practice.1 During 2007
directed towards providing a service to the ophthalmologist and and 2008 a newly revised code and system of regulation and
their recipients but also directed towards to the eye donor and specific tissue standards will soon extend to New Zealand under
their family. Eye Banking activities include: a new regulatory body, the Australian and New Zealand
• Hospital development and professional in-service programs Therapeutic Products Authority.2 In the United States the Food
designed to maximize the appropriate identification of and Drug Administration (FDA) has published three rules to
suitable donors and referral to the Eye Bank ensure the safety of human cell and tissue products. The most
• Provision of trained professional staff to approach families recent rule, effective from May 2005, entitled “Current Good
to offer the option of donation Tissue Practices for Human Cell, Tissue and Cellular and Tissue-
• The meticulous screening of donors to assess donor risk, Based Establishments; Inspection and Enforcement,” (cGTP) is
including evaluation of donor medical history and risk factors aimed at preventing the introduction, transmission and spread
• The donation of eye tissue according to established and of communicable diseases. The FDA also continues to issue
recognized standards and procedures guidance documents to assist with compliance to these rules.3
• Evaluation of corneas by slit-lamp, specular or light The Commission of the European Union have issued two
biomicroscopy Directives on setting standards of quality and safety for the
• Fair and equitable distribution of tissue donation, procurement, testing, processing, preservation, storage
• Donor family support which may include access to and distribution of human tissues and cells, the first of which
bereavement counseling services, information on came into effect in April 2006. In addition, these Directives are
bereavement literature and associations and facilitation of accompanied by two detailed technical annexes.4 Member States
appropriate and anonymous correspondence between have the responsibility to put in place national measures to
recipients and donor families. implement the Commission Directives.

20
All of these regulations have as their basis the identification of a prospective donor’s available medical records, medical
and minimization of risk so as to ensure and improve the quality history or investigation of cause of death. Any relevant
and the safety of transplanted tissue. In each instance they cover information pertaining to the donor should be recorded. Within
standards and regulations pertaining to: donor selection, donation a hospital environment this should include a review of the death
and testing; traceability; organization and management; personnel certificate and cause of death (if available), a review of progress
and training; documentation and records, facilities, equipment notes noting temperature trends, admission and history notes,
and materials; procurement and preservation; packaging and medications, laboratory reports (especially microbiology,

Chapter 4: Eye Banking—A Practical Guide


labelling; and distribution, notification and recall systems. serology and hematology reports), and noting amount and time
Formulation of standards, establishment and compliance with of any transfusions. Donor screening should also consist of a
such quality systems approaches, whether government imposed verbal review with the appropriate treating physician. This is
or self-imposed, have been a central theme for Eye Banks over especially important to accurately assess the patient’s medical
this past decade. Inevitably it has required the introduction of and social conditions during the last admission and at the time
new expertise and training to manage the quality system. In many of death. The donor’s family doctor should also be interviewed
cases it has required the recruitment of additional staff and the as well as a donor’s family member or friend who is in a position
re-development of facilities. Naturally such adjustments in scope to answer questions about the donor’s medical and lifestyle
and complexity have effects on the administrative and history. This is especially important if the donation is outside of
infrastructure support systems of the Eye Bank and ultimately a hospital environment. However, donor family interview must
result in substantial increases in operating costs. not be considered in isolation to other history as its validity and
usefulness in providing information to exclude potentially
Donor Selection infectious tissues can be questionable.8,9 Donor review may also
While the technical aspects of Eye Banking must be robust to encompass consultation with forensic pathologists and coroners/
medical examiners if appropriate. An individual who is qualified
ensure the provision of safe tissue it is in the careful selection
either by profession, education or training to perform all of the
or exclusion of potential donors that is of utmost importance in
preventing the transmission of disease to the recipient. In addition above tasks and familiar with the potential surgical uses of the
tissue should perform donor screening.
donor selection must also take into account considerations
regarding the quality, or potential efficacy for purpose, of the
Disease Transmission from Donor Corneas
tissue.
Many of the standards that have been adopted by Eye Banks Fortunately, iatrogenic transmission of serious or fatal systemic
world-wide were initially developed by the Eye Bank Association disease from corneal transplantation appears to be a rare event.
of America5 who produced their first set of Medical Standards A review of the world literature reveals only 12 reports of disease
in 1980. A rigorous review process has ensured that these transmission since 1939 (excepting bacterial and fungal
Medical Standards continue to evolve as new knowledge, insights transmission).
and challenges develop. Other eye banking organizations, such Diseases that could potentially be transmitted by corneal
as the European Eye Bank Association,6 have also developed transplantation fall into three categories
minimum standards that are reviewed each year. The Eye Bank 1. Prion disease (Creutzfeldt-Jakob disease (CJD) and
Association of Australia and New Zealand (EBAANZ) have also associated variants).
produced comprehensive Medical Standards that are reviewed 2. Infections (bacterial, fungal and viral).
on a regular basis which take into account regional disease 3. Malignancies.
prevalence and risk assessment.7 However, each Eye Bank 4. Intrinsic eye disease or surgery.
jurisdiction should consider their own situation, disease
prevalence, donor profile and risk assessment, and consider their Prion Disease
contraindications accordingly.
Duffy et al.10 reported the possible transmission of CJD in 1974
and during the 1990’s two further possible cases were
Contraindications for the use of Donor Tissue
reported.11,12 However, the evidence for transmission in these
The EBAANZ contraindications for the use of Donor Tissue is later two cases is limited. In 1999, Hogan and colleagues13
reproduced in Table 4.1. These contraindications are designed reviewed known cases of transmission of CJD by tissues and
to reduce the potential for: concluded that the risk of transmission was very low. In addition,
1. Viral transmission of disease. they suggested that the review of a potential donor’s available
2. Transmission of bacterial or fungal infections. medical information for any evidence of a diagnosis or family
3. Transmission of malignant disease. history of CJD or evidence that human pituitary hormone had
4. Transplantation of corneal disorders, or of those corneas been administered was sufficient to guard against the extremely
which pose a risk to the success of the surgery. low potential risk of disease transmission.
To successfully implement these standards Eye Banks must Initial concern about the presence of variant CJD (vCJD) in
have consistent policies for the examination and documentation the United Kingdom and the theoretical possibility of
21
Table 4.1: Contraindications for the use of Donor Tissue for Penetrating Keratoplasty
[Eye Bank Association of Australia and New Zealand: Medical Standards 7]

1. General Exclusion: • Motor neurone disease (amyotrophic lateral sclerosis)


• Death of unknown cause • Multiple sclerosis
[May be acceptable if death certificate or autopsy report • Alzheimer’s disease
is only pending an unresolved differential cause of • Parkinson’s disease
death where all the alternatives are NOT
Section I: Evolution, Preoperative Considerations and Eye Banking

contraindications] 6. Neurodegenerative – High Risk:


• Death with neurologic disease of unknown diagnosis
2. Infectious Disease:
• Dementia or recent unexplained neurological
• AIDS or HIV seropositive symptoms, e.g. ataxia, myoclonus, memory loss
• Encephalitis – active, or of unknown origin • Recipients of human pituitary-derived growth hormone
• Endocarditis – active, or of unknown origin (PIT-HGH) from 1963 to 1985
• Hepatitis – active • Recipient of human-derived dura mater tissue at any
• HTLV-I or HTLV-II time
• Leprosy [Dementia resulting from cerebrovascular disease,
• Malaria brain tumour or trauma, or toxic- or metabolic-induced
dementia may be acceptable]
• Meningitis – active, or of unknown origin
[Recipients of synthetic growth hormone or dura mater
• Progressive multifocal leukoencephalopathy are acceptable]
• Reye’s syndrome
7. Eye Disorders, Infection and Surgery:
• Rubella – congenital
• Ocular/intraocular infection – active at time of death
• Smallpox
(e.g. endophthalmitis, keratitis, conjunctivitis, uveitis,
• Subacute sclerosing panencephalitis retinitis, choroiditis, iritis, vitreitis, scleritis)
• Syphilis – active • Malignant tumors of the eye and anterior segment (e.g.
• Tuberculosis – active retinoblastoma, melanoma, adenocarcinoma etc)
• Typhoid – active • Corneal disorders (e.g. keratoconus, keratoglobus,
[Bacterial disease may be acceptable if organ culture dystrophy)
storage is performed] • Corneal opacity, scarring, or pterygium, which involves
the central area of the corneal button
3. Infection:
• Corneal surgery e.g. radial keratotomy, refractive laser
• Septicemia (bacteremia, fungemia, viremia)
surgery (photorefractive keratectomy (PRK) or laser
[Bacteraemia may be acceptable if organ culture
in situ keratomileusis (LASIK)
storage is performed]
[Other eye disorders, e.g. cataract, glaucoma,
4. Malignancy: retinopathy acceptable]
• Hodgkin’s disease [Surgery/laser treatment for disorders other than
corneal acceptable]
• Leukemia
• Lymphoma 8. Infectious Disease – High Risk:Persons within
• Lymphomatoid granulomatosis previous 12 months who have:
• Lymphosarcoma • Performed intravenous drug use for non-medical
reasons
• Myeloma
• Been incarcerated in prison
• Myeloproliferative disease
• Engaged in prostitution or sex for money or drugs
• Polycythemia vera – primary
[Other cancers acceptable] • Tattoos or body piercings not performed in licensed
facility
5. Neurological Disorder: • Received human-derived blood-clotting factors
• Chronic idiopathic demyelinating polyneuropathy • Close contact with persons with viral hepatitis
• Creutzfeldt-Jakob disease (CJD) of any type – in • Had sex with persons known to have HIV or hepatitis
potential donor or immediate family member • Known exposure to blood from person with HIV or
• Guillain-Barre syndrome hepatitis
• Huntington’s chorea • Men who have had sex with other men

Contraindications for Lamellar Grafts


Criteria are the same as listed for penetrating keratoplasty except that tissue with local eye disease affecting the corneal
endothelium or previous ocular surgery that does not compromise the corneal stroma is acceptable for use.
Contraindications for use of Sclera
Criteria are the same as listed for penetrating keratoplasty except that tissue with local eye disease affecting the corneal
endothelium or previous ocular surgery that does not compromise the sclera is acceptable for use.
22
human-to-human transmission has tempered in recent years as paralytic or dumb rabies, flaccid paralysis develops and the
the numbers of new vCJD cases continue to fall. In 2006, there exclusion criteria of “death from central nervous system disease
were five deaths attributable to definite or possible vCJD and a of unestablished diagnosis” would today exclude such potential
total of 158 deaths (to the end of 2006), since being first donors from becoming actual donors.
identified in 1995.14 However, the amount and distribution of The possibility of iatrogenic transmission of hepatitis B virus
the infectious agent in people with vCJD is greater than in other (HBV) has long been recognized. Two cases of transmission from
forms of CJD perhaps increasing its potential for transmission. 1984 and 1985 were reported by Hoft et al.26 Both these cases

Chapter 4: Eye Banking—A Practical Guide


Unfortunately, diagnostic tests on lymphorecticular tissue took place before routine serological screening of donors for
samples have not proved reliable in detecting vCJD infection.15 hepatitis B surface antigen (HbsAg).
The emergence of vCJD has led Blood Banks in parts of the Hepatitis C virus has been detected in corneas27 and in the
world to exclude from donation those people who have visited media of organ cultured corneas of seropositive donors28
or resided in the United Kingdom for a cumulative period of although at the very low concentration of virus detected it
three months or more although such decisions were based on remains arguable whether transmission via corneal
theoretical risk reduction versus potential reduction in supply transplantation is likely. In one case of a donor being anti-HCV-
rather than actual risk reduction. Internationally, Eye Banks have negative but HCV RNA-positive, HCV infection occurred in
resisted such restrictions when the very low risk versus the eight of 30 recipients of organ and tissues but not in the single
benefits is taken into consideration.16 However, 2007 guidance recipient of a corneal transplant.29
from the FDA, Guidance for Industry: Eligibility Determination Similarly, the human immunodeficiency virus (HIV) has been
for Donors of Human Cells, Tissues, and Cellular and Tissue- shown to be present in a human cornea30 but such a presence
Based Products, determine to be ineligible to donate any person may not lead to transmission of the disease by corneal
who spent three months or more cumulatively in the UK from transplantation. There are three reports in the literature of HIV-
the beginning of 1980 through the end of 1996 and any person infected donors where the corneal recipients have not
who spent 5 years or more cumulatively in Europe from 1980 seroconverted.31-33 These negative reports suggest that the
until the present. Persons who received any transfusion of blood transmission of HIV through corneal transplantation may be
or blood components in the UK or France between 1980 and difficult.
the present are also excluded.17 There is a group of diseases listed as contraindications that
Interestingly, data on CJD and vCJD suggests the disease- are diseases of possible but unproved viral etiology. This includes
related prion protein (PrPSc) may not be distributed in human – subacute sclerosing panencephalitis, progressive multifocal
eye tissue as widely as previously thought. In three cases of leukoencephalopathy, Reye’s syndrome, acute leukemia, and
sporadic (or classical) CJD no PrPSc was detected in proximal active disseminated lymphomas such as Hodgkin’s disease.
optic nerve, sclera, retina, vitreous humor, lens, aqueous humor, Hematological malignancies, with decreased immunological
iris or cornea. In the one case of vCJD investigated PrPSc in the defense mechanisms, may also mask opportunistic viral or
eye was restricted to the optic nerve and retina.18 In addition, in bacterial infections.
a widely reported case of transplantation of ocular tissues from
a donor subsequently determined to have sporadic CJD (where Infections – Bacterial and Fungal
subsequently tissues were explanted with no known Septicemia is a contraindication in a prospective corneal donor
transmission), there was no evidence of PrPSc in the cornea.19
because of the risk of pathogenic organisms being harboured in
the conjunctiva, surviving the antibiotics used throughout the
Infections – Viral
retrieval and buttoning process, and eventually leading to an
During the 50 year history of Eye Banking corneas have endophthalmitis in the recipient’s eye. The only exception to this
transmitted three types of virus – Hepatitis B, herpes simplex is if the corneas are to be placed in organ culture for preservation.
and rabies. The microbiological surveillance during organ culture allows the
Nine cases of rabies transmission from six donors result- exclusion prior to transplantation of those corneas that may be
ing in eight deaths have been documented between 1979 and harbouring organisms.6
1996.20-25 In all cases rabies was not identified in the donor until Payne34 summarized 12 enucleations reported in the literature
transmission had occurred. In only one case was rabies in the due to bacteremic or fungemic donor-induced endophthalmitis,
donor detected promptly and subsequent intensive and a number of cases have appeared in the literature since.35,36
immunotherapy for the recipient prevented their death.25 The In addition, adverse event reporting by member Eye Banks to
problem arises that diagnosis in a potential donor can be difficult the Eye Banks Association of America indicate a rate of less
if the rabies does not present with its classical picture of than 0.1% of culture positive or clinically suspected microbial
hydrophobia and hyperaesthesia (furious rabies). In the Iran case endophthalmitis among corneal recipients (unpublished data).37
the donor is described as presenting only the prodromal While the rate is very low, and may not always lead ultimately
symptoms of fever, malaise, headache and gastrointestinal to the loss of the eye, an infection of this nature is a serious and
infections prior to death. However, even in the less common dangerous complication to the transplant’s success. For this
23
reason, if hypothermic storage is the method of choice, any Specular microscopy of donor corneas before and after
suspicion of bacteremia or fungemia must be thoroughly transplantation adds further weight to these follow-up study
investigated and if it cannot be positively excluded, even if it findings. Endothelial cell density of the cornea after
cannot be positively proved, then that tissue should not be transplantation is related to the endothelial cell density of the
considered for distribution. donor cornea and not to the donor’s age.44 Therefore a donor
cornea with normal endothelial cell density and morphology is
Malignancies suitable for transplantation regardless of age. However, the older
Section I: Evolution, Preoperative Considerations and Eye Banking

the donor the less likely that the density and morphology is going
There are two cases reported where a malignancy has been
transmitted. In the first case a retinoblastoma was transplanted to be suitable for transplantation.45,46 Armitage and Easty
reported for organ cultured corneas of the United Kingdom Eye
from the donor eye to the recipient eye.38 There is also a report
Bank that greater than 80 percent of corneas from donors less
of transmission of a disseminated adenocarcinoma from donor
to the recipient’s iris with confirmation of tumor markers with than 40 years of age were used, but in donors older than 80 years
of age the usage rate was 45 percent.47
PCR.39 It would be incorrect however to consider malignancies
in the donor as being high risk for transmission of disease. Non-
Lower Donor Age
hematological malignancy is not an exclusion for donation, and
a substantial percentage of the hundreds of thousands of corneal There is no clearly defined lower age limit for corneal donation.
transplants performed have used corneas from donors with The Eye Bank Association of Australia and New Zealand list
malignancies, without any evidence of transmission. However, the minimum age as 2 years. Problems relate to both the technical
the two isolated cases reported above, both relating to difficulties in using infant tissue and the complication of post-
malignancies in the donor eye, do demonstrate the importance operative myopia. The extreme thinness of the infant cornea
of a careful examination, including the posterior pole of the eye, means that it is likely to fold upon itself during handling. This,
to exclude the possibility of malignancy or other pathology in combined with the small diameter of the cornea, creates problems
the donated eye. during the donation surgery, trephining, and during placement
Although leukemia and lymphoproliferative disorders pose and suturing in the host bed. Koenig provides a review of these
the greatest theoretical risk of transmission, due to a possible problems.48 The myopic shift after keratoplasty with infant donor
viral etiology, no cases of transmission have been reported. corneas has been related to the steep curvature of these corneas.49
However, these latter disorders remain as a contraindication.
Donation of Eye Tissue
Intrinsic Eye Disease or Anterior Segment Surgery
Eye Donor Coordination
Local corneal disorders or surgery may pose a risk to the success
of corneal transplant surgery. Keratoconus in its early stages or Arguably, an Eye Bank’s most important work is done during
corneal dystrophies may go undetected. Incisional surgery to consent, the interaction with bereaved family members and with
correct myopia is detected through the appearance of radial and the process of gathering of accurate medical histories. All of this
arcuate lines upon slit lamp examination but detecting past involves multiple interactions with a variety of sources such as
photorefractive surgery in a donor cornea is difficult if not relatives, medical and nursing staff, pathologists and general
impossible by current Eye Bank examinations. Modern cataract practitioners. The skill is in the collection, assimilation and
extraction by phacoemulsufication and the replacement of the analysis of all this information while ensuring that the donor
host lens by an intraocular lens is not an absolute contraindication family is cared for and is fully informed of their choices and the
to donation. However, in these cases microscopy of the processes that donation entails. All of this must be done within
endothelium is required to exclude those corneas showing low an ethical and professional framework to reduce the risk of harm
cell density or abnormal morphology. to the donor family and to the prospective recipients of donated
tissue.
The form of the consent, or authority to proceed with the
Donor Age
donation, will of course vary depending on the jurisdiction’s
Clinical evidence shows that there is no influence of donor age legislation and social culture, but regardless of this the Donor
alone on corneal transplant survival.40,41 The most convincing Coordinator should ensure that all parties that need to be fully
evidence comes from the multi-centre outcome registries of the informed are fully informed. The extent of the donation (whole
United Kingdom42 and Australia.43 The United Kingdom follow- globe or just cornea, transplant and research purposes,) needs
up study followed 2,777 penetrating transplants over 4 years, to be identified and recorded. The investigations with regard to
while the 2004 Report of the Australian Corneal Graft Registry assessing medical risk or donor suitability must be conducted in
reported the outcome of 14, 649 transplants followed for periods a thorough and professional and considered manner that is
between one to 20 years. Both reported no influence of donor relative to the risk. These responsibilities extend to those
age on transplant outcome. instances where workplace partners have been primarily involved

24
in the consent and donor screening process (e.g. multiple tissue during the current admission. Equivalent amounts of colloid or
or organ donation); the Eye Donor Coordinator must still cross- crystalloid infused should also be considered. When blood loss
check and ensure that these processes have been suitably is known or suspected to have occurred, the potential eye donor
performed. was transfused or infused, and no adequate pre-transfusion/
infusion sample is available for infectious disease testing; then
Medical History Review an algorithm should be used to determine that there has not been
plasma dilution sufficient to affect test results. Examples of
It is important to establish the donor’s medical and lifestyle

Chapter 4: Eye Banking—A Practical Guide


appropriate algorithms are available.3,50
history prior to their death to assist in determining both the safety
and likely efficacy of the tissue. If a written Medical History of
Eye Donation Surgery
the donor’s last health care admission is readily available then
it should be thoroughly reviewed and details relevant to the Eye As with all surgery, there are many different possible approaches
Bank’s purposes recorded unambiguously. In particular the to donor surgery and donor eye preparation/dissection and
following details should be recorded – therefore this chapter will only deal with some of the salient
• Record cause of death and contributing factors points. The Procedures Manual of the Eye Bank Association of
• Record current and past medical history America does cover specific procedures written broadly enough
• Record the time of death as determined by cessation of the to provide a framework for the development of an Eye Bank’s
circulation of the blood, the important point here being a own procedures, yet specific enough to establish accepted
record of the beginning of the ischemic period baseline standards.51 In addition, an excellent introductory
• Record data to unambiguously identify the donor (as a handbook and atlas has also been published which provides good
minimum, name of patient and date of birth) illustrated step-by-step guides to Eye Bank surgical and
• In the instance of intended hypothermic storage of corneas, evaluation techniques.52
a review and interpretation of laboratory results (in particular The person performing the donor surgery must use their
blood cultures, temperature trends and white blood cell professional judgment and satisfy themselves that all reasonable
counts) must be performed to exclude or bacteremia or steps and normal surgical precautions have been taken to
fungemia in the donor at the time of death. Discussion with minimise contamination or damage to the tissue. These
the treating physician and gaining an insight into their clinical precautions should also extend to the safety of the surgeon and
impressions is often critical in making a decision on potential recipients of the tissue. Ideally the area should be one
bacteremic status. However, bacteremia can be considered of restricted access as a first step towards aseptic technique, have
suitable if normothermic (organ culture) of corneas is appropriate lighting, sharps and biohazard waste containers and
performed where significant infection of corneal tissue will generally be clean and organized. Personnel must be trained in
become evident as contamination in the storage medium. the procedures or in general surgical procedures.
In addition, as discussed in the contraindications for the use
of Donor Tissue section, it is important that the Eye Bank Preparation of the Donor
communicates with the treating doctor, the donor’s general If an enucleation is to be performed many Eye Banks may forego
practitioner, and a family member or friend in order to review
extensive donor preparation opting instead to decontaminate the
the donor’s medical and lifestyle history, and that these
globe within the Eye Bank laboratory prior to the removal of
discussions be appropriately recorded and evaluated. the cornea. This is usually performed in the laboratory by rinsing
the globe in a dilute povidone-iodine (PVP) solution (a 1 to 5%
Serology Testing
concentration resulting in 0.1 to 0.5% available iodine) for 1-2
As an absolute minimum, the donor must be serologically minutes. The PVP solution must not contain any detergents as
tested for Human Immunodeficiency Virus 1 and 2, Hepatitis this could harm the corneal epithelium, and this should be
B surface antigen and Hepatitis C virus. Depending on the checked beforehand. The PVP is then followed by a thorough
jurisdiction, additional tests (e.g. Syphilis and HTLV) may be rinse with a balanced saline solution. This is a very effective
mandated.3,4 means of decontamination53 if performed with appropriate
Plasma dilution may affect the validity of any post-infusion concentrations of PVP over a short period.54
serology so when reviewing the donor’s history it is important For those Eye Banks that perform in situ excision of corneas,
to record the amount and time of any transfusion or infusions similar solutions can be used to minimize ocular flora and reduce
(blood, colloid, crystalloid). As a rough guide a pre-transfusion/ contamination. This procedure is appropriate for donor
infusion sample should be obtained for testing if an adult donor preparation prior to both enucleation and excision. Here the
has received 4 or more units of whole blood (or equivalent) delivery of the solutions is also important as the eyes should
within 48 hours preceding cessation of circulatory function. For first be rinsed in a strong stream of balanced saline to remove
a child less than 12 years of age a pre-transfusion sample should all debris, mucus and foreign matter from the cornea and
be obtained if the child has received any blood transfusions conjunctival sack. This in itself will reduce microbial

25
contamination. A good stream of balanced saline is also required (other than a good medical history) to determine if there has been
after a period of PVP application to ensure good removal of the previous anterior segment surgery or if there is any pathology
PVP from the eye. The lids and the surrounding area can then of the eye not identified through the donor screening process.
be disinfected by a surgical skin preparation of PVP.
Slit-Lamp Evaluation
Enucleation, In Situ Excision and
The slit-lamp enables a more accurate observation of the cornea,
Corneoscleral Rim Sectioning revealing earlier stages of pathology that are visible grossly.
Section I: Evolution, Preoperative Considerations and Eye Banking

Enucleation or in situ excision can be performed in an operating Whole eyes can be examined by the slit-lamp within the container
theatre, a morgue, hospital room or funeral home. Prime used in retrieval, or excised corneas can be examined through
considerations are to minimize manipulation of tissues the bottom of the storage vial once the cornea and vial are
surrounding the eye in order to preserve donor appearance, to manipulated so that the cornea is endothelial side down. The
prevent touching or distortion of the cornea and thus minimize eye or cornea should be allowed to reach room temperature
any cell loss (epithelial and endothelial), and to reduce bacterial which makes the endothelium easier to visualize and more
contamination from both exogenous sources and from ocular normal in appearance.
flora. For in situ excision one must be especially aware of the The cornea should be methodically examined to ensure each
bacteriologic considerations, as no further decontamination of layer of the cornea is adequately assessed. The surrounding
the tissue is possible. limbal/scleral area should also be checked for evidence of
Corneoscleral rim excision after an enucleation is a similar surgical incisions (these may also be at the periphery of the clear
process to the in situ excision. Ideally the procedure is performed cornea) and for any sutures.
in a biological safety cabinet which provides a clean area for The epithelium is inspected for integrity and overall condition
the excision and at the same time protects the operator from specifically clarity, exposure, sloughing, defects, trauma, foreign
exposure to possible pathogens residing on the eye itself. The bodies and infiltrates. Haze is often localized and coincides with
dissection needs to be made through into and along the ante and postmortem exposure across the interpalpebral area.
suprachoroidal space. Perforation of the choroid would cause Swelling of the epithelium may cause some layers to detach
vitreous leakage, which may cause the collapse of the globe and (termed sloughing). Epithelial defects appear as clear depressed
anterior chamber, and compromise the cornea. In addition the areas within an otherwise hazy epithelium. The extent and
operator must be careful not to exert too much pressure on the position (central or peripheral) of any of these findings needs to
globe, as this will increase the potential for the scissors to cut be considered in any assessment of the suitability of the cornea
or catch on the choroid. During the procedure it is most important for transplantation.
that as little stress as possible is placed on the cornea as any The stroma is examined for overall clarity, amount of edema
stretching of the endothelial cell layer can critically damage it. and stromal folding. Major opacities are usually detected by the
preceding gross examination but using higher magnification and
Corneal Evaluation a thin slit can better identify the opacity as scarring (generally a
smooth gray appearance) or inflammatory infiltrates (generally
With the exception of tissue that would be potentially hazardous
whitish appearance with discrete borders). Stromal folding and
because of possible transmission of disease, there are no
haze are associated with corneal edema. The amount of corneal
absolutely defined criteria for the acceptance or rejection of a edema, and thus the severity and number of folds and the amount
cornea. The final decision regarding use rests with the surgeon
of haze will depend on time since donor death, temperature,
for each individual and unique case of donor to recipient
integrity of the epithelium, and the postmortem integrity and
transplantation and the transplant procedure to be undertaken. function of the endothelium. The thickest folds are a good
However, in reaching a decision on acceptance or rejection of
indicator of the overall severity of the edema. Striae, identifiable
tissue for clinical use the ophthalmologist must rely on the Eye
as fine gray/white lines, may also be in the stroma and are
Bank’s careful evaluation of the cornea. probably indicative of very localized disruptions of the stromal
lamellae.
Gross in situ Evaluation
Any detachment of Descemet’s membrane can be observed
Corneal evaluation begins with a gross examination of the as a separate membrane that seems to come from and be
corneas in situ. A simple penlight examination can reveal continuous with the endothelial side of the cornea. This finding
epithelial defects (drying, erosion, sloughing), corneal oedema alone is usually enough to consider the cornea unsuitable for
with associated haze and striations due to folding of Descemet’s any transplantation procedure requiring an intact endothelium.
membrane, abnormal corneal shape, blood or cloudiness in the A specular reflection of endothelial layer can be observed
anterior chamber, corneal scars or infiltrates, arcus senilis, and in a small area of the endothelial reflex. At high power
any signs of conjunctivitis and discharge. magnification an impression of cell density and the degree of
For in situ corneoscleral rim excisions a careful in situ cell uniformity in size and shape can be obtained. Guttae-like
examination is especially important. This is the only opportunity bodies (areas where no cells can be seen) may be observed in
26
the specular reflection. The exact nature of these areas is difficult decompensation.58 Corneal guttae have also been reported to
to determine. They may actually be guttae (bumps or reduce endothelial function.59,60 Inflammatory cells and bacteria
excrescences of Descemet’s membrane), they may be vacuolated can also be easily seen with endothelial microscopy and their
cells or they may be stress fractures (sometimes referred to as presence would lead to the exclusion of such corneas for
pseudo-guttae) due to trauma during the donation process. transplantation.
Regardless of their nature these conditions should be regarded
as a degenerative condition of the endothelium. The suitability Specular Microscopy

Chapter 4: Eye Banking—A Practical Guide


of the cornea for penetrating keratoplasty would depend on the Specular microscopy is mostly used by those Eye Banks using
relative number and location of these bodies. (Note: the term hypothermic storage of corneoscleral buttons. Plastic corneal
“pseudoguttae” is sometimes also used to refer to guttae that viewing chambers with optically clear lids (originally developed
appear at hypothermic storage temperatures but disappear at by Bourne61) are available from a number of manufacturers and
room temperature). allow for non-contact viewing of the specular image. Some Eye
Bank specular microscopes are also capable of producing
Endothelial Microscopy excellent endothelial images from corneas still contained within
The condition of the corneal endothelium is central to evaluating the storage media vial, thus further reducing handling of the
the suitability of corneal tissue for penetrating keratoplasty, as cornea. Today’s microscopes are also equipped with
it is primarily the layer responsible for the maintenance of corneal computerized morphometric analysis systems to analyze cell
turgor and transparency. Endothelial microscopy, whether it is density, average cell size and uniformity of cell shape.
through the technique of specular microscopy or transmitted A limitation with specular microscopy is that the area of
light/phase microscopy, allows for a reasonable determination the central corneal endothelium is much larger than can be
of endothelial cell density, cell pleomorphism and sampled by the specular microscope even with multiple
polymegathism and the identification of corneal guttae. These field examinations. Therefore the information gained from
changes reflect the current well being of the endothelium as well specular microscopy must be interpreted within the context of
as being indicative of its functional reserve.55 the slit-lamp evaluation.
Such objective information and has allowed the wide use of For the best observation of the corneal endothelium, the
older corneal tissue based on endothelial appearance rather than cornea must be at room temperature. Thus, the most convenient
arbitrarily excluding such tissue solely on the basis of donor age time to perform specular microscopy is after the placement of
(see section on Donor Age). In addition, endothelial microscopy the cornea in storage media, allowing sufficient time for the
has allowed for the use of corneas from donors that have had media to equilibrate with room temperature and for
anterior segment surgery. In both cases, if the corneas have deturgescence of the cornea. Corneas can also be observed after
passed the endothelial microscopy criteria and slit-lamp criteria, a period of 4ºC storage and subsequent warming to room
they should be considered for penetrating or endothelial temperature. The cycle of cooling, warming and re-cooling of a
keratoplasty (with the receiving ophthalmologist being fully donor cornea has been shown to have no adverse affects on the
informed). metabolic or morphometric status of the donor cornea.62
A low cell density may indicate that the cornea is unlikely However, it becomes more difficult to adequately visualize the
to be able to withstand the rigors of transplantation. Bourne and endothelium with specular microscopy after a period of storage.
O’Fallon56 elegantly showed that there was a loss of 23 percent Figure 4.1A shows the specular microscopic image of a
of the transplanted endothelial cells within the first week of relatively good endothelium from a 70-year-old donor. The cell
transplantation and others have demonstrated that this cell shape and size shows a small amount of variance, the cell density
loss may continue for up to at least 4 years.44 The critical at a calculated 2754 cell/mm2 is very good, and there are no
endothelial cell density below which any cornea undergoes guttae or evidence of inflammatory cells. This evidence,
decompensation is speculative although many clinicians estimate combined with a good slit-lamp appearance of the cornea,
it to be 300-500 cell/mm2. Based on the evidence of cell loss in suggests that this cornea would be suitable for use in a
the postoperative period and the estimated lower limit of a penetrating keratoplasty.
functional cell density, Eye Banks generally have a cut-off of
between 1500-2200 cells/ mm2 (depending on the Bank) below Light Microscopy
which they will no longer issue a cornea for penetrating or Eye Banks using normothermic (organ culture) storage methods
endothelial keratoplasty. In these instances the cornea may still use phase contrast microscopy and/or transmitted light
be suitable for anterior lamellar keratoplasty. microscopy often accompanied by intravital staining of the
In addition to a low cell density an abnormal endothelial endothelial layer (Figure 4.1B). This type of endothelial
appearance may indicate that the cornea is compromised or microscopy has the advantages of being able to assess the
functionally deficient. Corneas with considerable polymegathism endothelium after storage and close to the time of transplantation,
or pleomorphism have been reported to have a decreased and also enables visualization of a larger area of the central
functional reserve57 and an increased incidence of postoperative cornea compared to specular microscopy. Intravital staining,
27
donation and transplantation. This is the same aim as for solid
organ transplantation such as kidney transplantation. However,
while reliable kidney preservation time is still restricted to around
24 hours ischemic time, techniques developed over the past 30
years have enabled the extension of reliable corneal storage times
to approximately one month. Techniques designed to go beyond
this period of storage, such as cryopreservation, are still not
Section I: Evolution, Preoperative Considerations and Eye Banking

reliable enough for them to be routinely employed.64

Moist Chamber Storage


Filatov65 first described the use of moist chamber storage of
whole eyes. This is achieved by placing an enucleated eye in a
sealed chamber together with gauze, usually moistened by a
saline or antimicrobial solution, and then placed at 4ºC. Care
must be taken not to immerse the eye in solution as this will be
absorbed by the cornea and cause stromal edema. Although the
Figure 4.1A: Screen capture of image produced by a Konan moist chamber technique was used successfully and with
EKA-98 Eye Bank Keratoanalyzer system™ (specular confidence for over forty years (and is still employed in some
microscope and image analysis) countries), its main drawback is the limitation to around 24 hours
of storage. This is because the endothelium of a cornea stored
on the globe is subjected to the toxic build up of metabolic waste
and necrotic tissue in the stagnant aqueous humor.66 To overcome
this problem the idea evolved of removing the cornea and placing
it in a biologically defined environment.67

Hypothermic Corneal Storage


McCarey and Kaufman modified an existing tissue culture
medium, TC 199, by adding dextran as an osmotic agent to
compensate for the inactivity of the cornea’s normal water
removal mechanism at 4ºC.74 This extended reliable storage time
to 2-3 days and the media, M-K medium, quickly became the
storage system of choice for eye banks following publication of
several series of successful transplants.68,69 Over the years, the
M-K formulation has been improved by the addition of the more
stable HEPES buffer and the replacement of the penicillin-
streptomycin antibiotics to gentamicin which has a greater
Figure 4.1B: Light micrograph of endothelium of organ- spectrum against gram-negative bacteria.70 It remains a cheap,
cultured cornea. (X200 magnification) easy, simple and reliable form of corneal preservation.
In the mid-eighties, 2.5 percent chondroitin sulfate was added
to the basic M-K formulation. The resultant solution, K-Sol,
usually with trypan blue, also provides some information on successfully extended corneoscleral storage times to 7-10
number of endothelial cells still functioning. Sucrose or balanced days.71,72 However, one of the problems with media containing
salt solutions are often added which cause the intracellular space chondroitin sulfate is that the layers of the cornea can absorb
to swell, making the cell borders easier to discern for ease of some of its smaller molecular weight moieties, and the resultant
cell counting. The original technique is that described by osmotic flow of water causes the cornea to swell. An improved
Sperling.63 Such techniques can also be applied to corneas that solution, Dexsol, overcame this problem by the addition of
are hypothermically stored. dextran to the formula. Optisol, the latest commercially available
storage medium, further improves on Dexsol by maintaining
Storage
better endothelial cell morphology and thinness of the
Unlike tissues such as bone or heart valves that may be corneas.73,74
extensively processed and altered from their natural state, corneas While the original publications suggested that Optisol was
must be transplanted as a viable living tissue. Thus the aim of suitable for up to 14 days storage, in practice the maximum
all corneal storage techniques is simply to maintain this living storage time most Eye Banks feel happy within 7-10 days with
viable state while holding the cornea for the period between storage between 2 - 6ºC. The manufacturers have also published
28
that 48 hours room temperature storage (approximately 21ºC) Tissue swells during the culture period, becoming thickened
still provides adequate corneal preservation.81 Optisol is now and edematous (from 0.5 – 1 mm), but this is reversed during a
usually available as OptisolGS that contains both gentamicin and period of days in dextran-containing thinning medium prior to
streptomycin to give broad antimicrobial coverage75 (Figure distribution.87 Various studies have confirmed that there is a
4.2A). More recently other commercial hypothermic storage dramatically lower incidence of endothelial cell death compared
media have become available76,85 and there has been more to cold-stored corneas and that despite 10-15 percent endothelial
research on antimicrobial prophylaxis.77,78 loss during culture, the endothelium is able to eliminate dying

Chapter 4: Eye Banking—A Practical Guide


cells and repair itself.98 Cell loss is independent of donor age,
Normothermic (Organ Culture) Storage but slightly dependent on storage time and endothelial state
This alternative storage method, where corneas are incubated in before storage.94 The surface epithelial layers shed into the
nutrient medium at physiological temperature, retains active cell medium during increasing time in culture, which are quickly
metabolism and most closely resembles the corneal environment replaced by host cells postoperatively; however, fresher
in vivo. Corneas stored in this way can be reliably preserved for tissue may be indicated for patients with persistent epithelial
up to 30 days. Studies of organ-cultured corneas have defects.
demonstrated no significant difference in postsurgical endothelial Organ culture provides an in-built microbiological
cell density and graft survival when compared with surveillance system, since any culture containing microorganisms
hypothermically-stored corneas.79-81 not controlled by decontamination and antibiotics will become
Based originally on promising in vitro studies,82 the method contaminated, and the cornea not used for transplant. Such
was fully developed and extensively tested for clinical use in contamination is normally visually obvious by turbidity and
Minnesota, USA by Doughman et al, in 1974 83,84 and pH change, however, corneal cultures are quarantined until a
subsequently refined by groups in Denmark 64,85 and the sample of the medium taken at 3-7 days of storage is tested and
Netherlands,86,87 who overcame problems relating to reduction reported to show no growth of bacteria or fungi. After the
of tissue swelling, endothelial evaluation and effective antibiotic incubation period, corneas cleared for serology and microbiology
control of contamination. Organ culture storage has not been are evaluated by direct light microscopy of the endothelium
adopted in the USA, but has become the preferred storage before being transferred into ‘thinning’ medium containing 5
method in the UK,88,89 Europe90-92 and New Zealand.93 These percent dextran prior to transplantation. Prolonged presence of
reviews of organ culture provide comprehensive information on dextran in culture is thought to be toxic to the cornea, therefore
history, technique and clinical outcome. the maximum recommended time in thinning medium is 2-4
In the most common method, excised corneoscleral disks days.99,100
from decontaminated eyes are suspended in glass bottles Since endothelial evaluation is performed at the end of the
containing 100 ml of MEM medium with Earle’s salts storage period near to transplantation, the quality and likely
supplemented with 2-5 percent fetal bovine serum, L-glutamine efficacy of the tissue can be determined with greater assurance.
and the antimicrobial agents penicillin, streptomycin and This allows for reliable use of corneas from older donors and
amphotericin (Figure 4.2B). Culture bottles are closed and extended death-to-preservation time, with no significant
incubated in a dry (non-CO2) environment at a temperature impact on graft survival when compared with younger or fresher
between 31-37oC.94 Many studies have shown that corneal tissue.94
ultrastructure, endothelial cell morphology, density and viability Reported bacterial isolates101-104 are normally common
are well-maintained in organ-cultured corneas up to 48 days of ocular flora such as coagulase negative Staphylococci, Staph.
storage,47,95,96 although in practice most are distributed between aureus, Streptococcus, Pseudomonas and Corynebacterium,
10-28 days (average 16 days).97 some strains of which can be resistant to antibiotics. Fungal

Figure 4.2A: Excised cornea in hypothermic storage media Figure 4.2B: Excised cornea suspended by suture in
(Optisol GS) normothermic (organ culture) media
29
growth can include Candida species, Cryptococcus, Fusarium hypothermic storage and 0.7-5 percent for organ culture storage.
and Penicillium. Contamination related directly to systemic A recent single-centre study utilising both storage methods found
infection in the donor is rare, and so with this method the donor that the frequency of positive rim cultures was 9.8 percent for
pool can be expanded to include those with bacterial septicemia, hypothermic storage and 1.3 percent for organ culture storage,
a common reason for donor exclusion when hypothermic storage however, no cases of endophthalmitis resulted from either
is performed. technique.110
Compared to hypothermic storage, the organ culture
Section I: Evolution, Preoperative Considerations and Eye Banking

technique is more complex, requiring additional equipment, Current and Future Trends
testing and greater technical expertise. Although the set-up and
testing costs make it a more expensive method, efficiency Today, Eye Banking benefits from having well-established
benefits can be gained by increased certainty of cornea provision medical standards which are continually evaluated, reviewed and
and elimination of potentially unsafe tissue. It is a method best internationally promulgated, 1,2,7 improved corneal storage
suited to an established eye bank with skilled technical staff, and techniques, and comprehensive corneal evaluation through the
where donor rates are variable, or distribution required over wide combined use of slit-lamp and specular microscopy. These
geographical area. In addition to improved microbiological developments, combined with ongoing Eye Bank procurement
screening, the increased storage time allows the ability to provide programs have led to scheduled elective corneal transplant
ABO- or HLA-matched corneas for patients with high risk of surgery with safe, efficacious tissue.
rejection, and for optimizing allocation of particular corneas to The emergence of new lamellar transplant procedures such
specific patients. It more easily enables the operation of fully- as Deep Anterior Lamellar Keratoplasty (DALK) and Decemet’s
scheduled transplant booking systems, rather than those Stripping Automated Endothelial Keratoplasty (DSAEK)
organised at short notice, and enables transport over long presents some new opportunities for Eye Banking. Eye Banks
distances without the need for refrigerated conditions. need to consider and revise their acceptance criteria for eye
Regulatory concerns over the increased potential for donation and the analysis of possible anterior or posterior corneal
transmission of prion disease from the use of bovine serum have pathologies in regard to specific transplant procedures. The
to date proven unfounded, and all European Eye Banks now use reality of splitting a cornea and using the resultant lamellar tissues
serum derived from BSE-free cattle herds from Australia or New on multiple recipients111 creates new issues for the traceability
Zealand.86 Many Eye Banks compound and sterilize their own of tissue from donor to recipient and the subsequent challenges
organ culture media ‘in-house’, and although promising trials involved in reporting any adverse events that may be due to
of commercial and serum-free varieties have been reported in donor tissue. In addition, femtolaser technology is already
recent years, the long-term clinical efficacy of these is yet to be making available pre-cut corneal tissue for transplant purposes
determined.105,106 and the pre-cutting of DALK or DSAEK tissue by Eye Banks is
likely to be a natural extension of this technology.
Postoperative Infection Looking to the future, it may be possible for Eye Banks to
There is a low incidence of postoperative infection reported with enhance corneal epithelial and endothelial viability through the
any storage method, and relatively few of these cases can be manipulation of growth factors. Similar manipulation could
attributed directly to infection in the donor tissue.37 Application conceivably provide an opportunity to decontaminate the tissue
of antibiotic prophylaxis and the recipient’s ocular immune of infectious agents including bacteria, viruses and prions. Such
defense is generally effective. It can be assumed that, upon return tissue engineering techniques may also be able to modify the
to physiological temperature, the residual antibiotic effect is immune rejection and wound healing responses of donor corneas,
normally sufficient to control any organisms surviving or indeed provide the ability for in vitro “growth” of a cornea.
hypothermic storage. Confocal microscopy could provide an additional means of
Rim swabs of decontaminated eyes before storage do not evaluating the cornea prior to transplantation.
predict subsequent growth in corneal storage medium, so have Whatever the future holds, Eye Banks must continue to
been largely discontinued. Likewise, many reports have provide a service that ensures the safety and efficacy of donor
demonstrated the poor predictive value of testing the remaining tissue and ensures fair and equitable distribution of transplantable
donor rim after trephination in identifying cases of tissue. This must be achieved while at all times maintaining the
endophthalmitis due to the donor tissue.107-109 Reported figures dignity of the donor, the dignity of the donor’s family and the
of positive donor rims range widely from 12-39 percent for dignity of the prospective recipient.

30
APPENDIX

SUGGESTED PREPARATION OF THE DONOR color and expiry date. Ensure that the lids can be easily
removed by simply lifting.
Prior to Preparation • Aseptically drop the disposable drape onto the instruments.
• Review the donor’s medical notes. If excising also drop two no. 15 scalpel blades onto the field.
• Establish consent and extent of donation (corneas or globes). • Aseptically put on sterile gloves. The donor is now prepared
• Complete all legal requirements. for enucleation or excision.

Chapter 4: Eye Banking—A Practical Guide


• Positively identify the donor, matching the consent with the
name on the deceased. SUGGESTED ENUCLEATION PROCEDURE

Clean Area Preparation


• Ensure all materials are within their “use by” date and all Follow the suggested preparation in Appendix.
sterile packs are intact.
• Unwrap a surgical gown and use the gown wrapping as a Clean Area and Draping
clean base for your work area.
• Put on the gown, surgical mask, cap and examination gloves. • Prepare two sterile containers (large enough to hold a globe)
by placing a 10 cm × 10 cm gauze swab on to the lids, and
In Situ Examination then use the Mosquito forceps to place two 5 cm × 5 cm gauze
swabs as cushioning in each container.
• Examine eyes for signs of infection, corneal damage or • Place a sterile drape onto the donor and isolate on the right
previous surgery—document if necessary eye.
• Elevate the donor’s head if deemed necessary (red, injected
(blood-shot), eyes are often an indication that the donor will
Surgery
bleed during an enucleation—this can be reduced by eleva-
tion—consider having a method of cautery on standby). • Insert the Eye Speculum.
• Perform a peritomy by using a pair of Toothed forceps and
Rinse and Swab Stevens scissors to incise the conjunctiva in a circle, as close
to the limbus as possible, and then push back Tenon’s capsule
• Gently open the eyelids (right eye by habit) and irrigate
by blunt dissecting with the scissors in each of the four
vigorously with a balanced sterile saline solution (such as
quadrants (Figs 4.3A and B).
Dulbecco’s phosphate buffered saline) removing all debris,
• Using the Muscle hook, isolate the lateral rectus muscle and
mucus and foreign matter from the cornea and conjunctival
clamp with a pair of Mosquito forceps. Cut the muscle distal
sack. Repeat on the left eye.
to the clamp with Strabismus scissors (Fig.4.3D). This
Irrigation at this time may prevent damage to the cornea during
provides a “handle” to manipulate the whole eye.
the skin preparation in the event that any foreign debris is under
• In turn, locate the other three rectus muscles and sever them
the eyelids. Irrigation will also reduce microbial contamination.
with Strabismus scissors close to the insertion point. Using
• Moisten the eye with a broad-spectrum antibiotic/antifungal
the mosquito forceps “handle”, rotate the eye and locate the
solution ophthalmic solution, close the lid and place the drops
superior and inferior oblique muscles, and sever these if they
onto the eyelashes. Repeat on left eye. A solution that does
have not already been cut with the rectus muscles (Fig. 4.3C).
not require refrigeration is a convenient advantage.
• Taking a pair of Enucleation scissors, insert them behind the
Antibiotic at this time will allow maximum time for the
eye with closed blades from the medial side of the globe,
antibiotic to be effective.
while applying a gentle, lifting pressure with the handle.
• With a 10 percent povidine-iodine swab, disinfect the lids
Open the blades and locate the optic nerve with a side-to-
and surrounding area using broad single sweeps starting
side action. Cut it whilst applying an upward pressure to
centrally and working out, covering the eyebrow, bridge of
the globe (Fig. 4.3E).
the nose and areas temporal to the eyelids. Pay close attention
• Once the optic nerve is severed, gently raise the globe away
to the eyelashes. Do not repeat a stroke over the same area.
from the socket, clearing away any residual orbital
Repeat on the left eye.
attachments with the enucleation scissors. Be careful not to
• Repeat the povidine-iodine skin preparation on each eye.
cut any eyelashes at this point (Fig. 4.3F).
The eyelashes may harbor contaminants. To allow adequate
• Place the free globe onto the gauze in one of the pots without
exposure time and coverage for the povidine-iodine preparation to
the cornea touching the sides. Do not irrigate it at this point.
be effective it should be recognized that a “one wipe” technique is
• Remove the speculum and shift the sterile drape to isolate
inadequate.
the left eye. Repeat the above procedure.
• Remove examination gloves and place in appropriate
biohazard container.
Restoration
Preparation of the Surgical Pack • Once both eyes are retrieved and in the sterile containers,
• Open the pack of sterile instruments on your work area with the sterile part of the procedure is complete, and they can
care taken to avoid reaching over the area or touching now be irrigated with enough balanced saline solution (e.g.
anything but the wrapper edges. Dulbecco’s phosphate buffered saline) to just moisten the globe
• If enucleating, place two sterile containers with loosened lids and just dampen the gauze. Place 15-20 drops of broad-
on the edges of the work area. If excising, use two containers spectrum ophthalmic antibiotic drops over each eye in their
of preservation media instead, after examining for clarity, containers to further minimize any bacterial contamination.
31
Section I: Evolution, Preoperative Considerations and Eye Banking

Figures 4.3A and B: Peritomy is performed close to the limbus and Tenon’s capsule is receded in each of the four quadrants

Figure 4.3C: The three recti muscles and the superior and Figure 4.3D: Lateral rectus is isolated and cut which provides
inferior oblique muscles are severed from the globe the handle to manipulate the whole eye

Figure 4.3E: Optic nerve is cut with side to side action with Figure 4.3F: The globe is raised away from the socket and
enucleation scissors by applying an upward pressure to the globe residual orbital attachments are cleared with enucleation scissors
32
• It is important to now restore the donor’s appearance, using • Using the fine Toothed forceps to steady the eye, take a
tight balls of cotton wool to fill the eye sockets, and a plastic no. 15 Scalpel blade and make an incision through the sclera
eye cap over this to ensure that when the upper lid is drawn 2 mm from the limbus, being careful not to penetrate the
over the lower one, the normal contour of the eye is underlying choroid (Fig. 4.4C).
maintained. Plastic eye conformers are available from funeral Perforation of the choroid would cause vitreous leakage,
director suppliers. which may cause the collapse of the globe and anterior
• Using alcohol swabs, the final part of the procedure is to wipe chamber. This can both compromise the cornea and make
off the povidone-iodine solution, ensuring that the donor is cosmetic restoration more difficult.
in a state suitable for viewing should the family have • Using Castroviejo’s corneoscleral scissors (left and right

Chapter 4: Eye Banking—A Practical Guide


requested it. In addition, the application of a moisturizer over medium blades), complete the incision around the eye,
the eyelids will improve the donor’s appearance and assist keeping the blades in the suprachoroidal space, and
keeping the eyelids comfortably shut. maintaining a 2-3 mm scleral rim (Fig 4.4D). The toothed
• A blood sample for serology can now be obtained. Suitable forceps should be used to steady and rotate the eye, and by
areas are subclavian vein, femoral vein or a cardiac puncture. using both the Left and Right scissors, difficult angles such as
• All disposable material is placed in a biohazard container that presented by the bridge of the nose can be avoided.
Trauma to the cornea during scissoring due to bending, loss of
and all sharps in a sharps container.
the anterior chamber or collapse of the globe through vitreous loss
can severely compromise its suitability for surgical use. Scleral rim
SUGGESTED CORNEAL EXCISION PROCEDURE width is important because some corneal trephines require a
minimum 2 mm rim while others require a rim not wider than 4
Preparation mm. Also cutting a rim less than 2 mm greatly increases the chance
of entering the anterior chamber during scissoring.
Follow the suggested preparation in Appendix. • Now the only attachments should be those at the scleral spur.
These adhesions are detached by using the toothed forceps
Clean Area and Draping to grasp the scleral rim, and the flat forceps to gently pull
• Prepare two preservation media containers by loosening the away the ciliary body and choroid (Figs 4.4E and F). It is
lids and placing 10 cm × 10 cm gauze swabs upon them. most important that as little stress as possible is placed on
• Place a sterile drape onto the donor and isolate on the right the cornea at this step, as any stretching of the endothelial
eye. cell layer can critically damage it. Aqueous fluid should
escape at this point.
Surgery • Lift the cap off the Corneal Preservation Media vial and place
the excised corneoscleral button into the media, endothelial
• Insert an Eye speculum.
side up.
• Perform a peritomy by using fine Toothed forceps and
• Remove the speculum, shift the eye drape to the left eye and
Stevens tenotomy scissors to incise the conjunctiva in a circle
repeat the procedure.
as close to the limbus as possible, and then push back Tenon’s
capsule by blunt dissecting with the scissors in each of the
Restoration
four quadrants (Figs 4.4A and B). The exposed sclera is
carefully scraped from the limbus outward with one of the • Upon completion, insert an eyecap into each eye, carefully
scalpel blades to remove all remaining conjunctival tissue. closing the lids.
The conjunctival tissue may contain microbial contami- • The remainder of the procedure is the same as for Enucleation
nants, which should not accompany the cornea into storage media. (above).
• Isolate the instruments and scalpel used to scrape the Removal of a corneoscleral button from an enucleated
conjunctiva to use only on the other eye so as not to re- eye follows the same surgical procedure as above although
introduce microbes into the globe. the procedure is usually performed within a sterile hood.

Figures 4.4A and B: Peritomy is performed close to the limbus and Tenon’s capsule is receded in each of the four quadrants
33
Section I: Evolution, Preoperative Considerations and Eye Banking

Figure 4.4C: An incision is made through the sclera 2 mm Figure 4.4D: The incision is completed around the eye with a
from the limbus with a no.15 scalpel blade Castroviejo’s corneoscleral scissors maintaining a 2-3 mm scleral
rim

Figures 4.4E and F: The adhesion from the scleral spur is detached by using toothed forceps
to grasp the scleral rim and the flat forceps to gently pull away ciliary body and choroid

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59. Bigar F, Schimmelpfennig B, Hurlzeler R. Cornea guttata in donor 82. Summerlin WT, Miller GE, Harris JE, Good RA. The organ-
material. Arch Ophthalmol 1978;96:653-55. cultured cornea: an in vitro study. Invest Ophthalmol 1973;12:
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77-85. organ cultured cornea. Arch Ophthalmol 1974;92: 516-23.
61. Bourne WM. Examination and photography of donor corneal 84. Doughman D, Lindstrom R, Skelnick D, Mindrup E, Nelson JD.
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62. Oak SS, Laing RA, Chiba HM, Tsubata K. Thermal cycling effects F (Editor). Corneal Surgery: Theory, Technique and Tissue. (2nd
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on the stored cornea. Invest Ophthalmol Vis Sci 1989;30: 1584- Edn) St Louis, Mosby 1993.
87. 85. Sperling S. Human corneal endothelium in organ culture. The
63. Sperling S. Early morphological changes in organ cultured human influence of temperature and medium of incubation. Acta
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64. Brunette I, Le Francois L, Tremblay M-C, Guertin MC. Corneal 86. Van der Want JJL, Pels E, Schuchard Y. Electron microscopy of
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96. dextran fraction (Dextran T500) in organ culture. Arch
65. Filatov VP. Transplantation of cornea from preserved cadaver Ophthalmol 1983;101: 1920-26.
eyes. Lancet 1937;1:1395. 87. Pels E, Schuchard Y. The effects of high molecular weight dextran
66. Bito LZ, Salvador EV. Intraocular fluid dynamics. II. Postmortem on the preservation of human corneas. Cornea 1985;3: 219-27.
changes in solute concentration. Exp Eye Res 1970;10: 273-87. 88. Armitage WJ, Moss SJ. Storage of corneas for transplantation.
67. McCarey BE, Kaufman HE. Improved corneal storage. Invest Chapter 20 in Current Ophthalmic Surgery DL Easty (Ed). Bailler
Ophthalmol 1974;13: 165-73. and Tindall, London 1990.
68. Bigar F, Kaufman HE, McCarey BE, Binder PS. Improved corneal 89. Tullo AB, Armitage WJ. Ocular tissue for transplantation – fresh,
storage for penetrating keratoplasties in man. Am J Ophthalmol chilled, warmed, frozen or pickled? (Editorial). Eye 2004;18: 865-
1975;79: 115-20. 66.
69. Aquavella JV, Van Horn DL, Haggerty CJ. Corneal preservation 90. Pels E, Schuchard Y. Organ culture preservation of human
using M-K Medium. Am J Ophthalmol 1975;80:791-99. corneas. Doc Ophthalmol 1983;56: 147-53.
70. Waltman SR, Palmberg PF. Human penetrating keratoplasty using 91. Pels E, Schuchard Y. Organ culture in the Netherlands:
modified M-K Medium. Ophthalmic Surg 1978;9: 48-50. preservation and endothelial evaluation. In Brightbill FS (Editor):
71. Kaufman HE, Varnell ED, Kaufman S, Beuerman RW, Barron Corneal Surgery, Theory, Technique and Tissue (2nd Edn).
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72. Keates RH, Rabin B. Extending corneal storage with 2.5 percent Danish Eye Bank System, where corneas await their patients. Acta
chondroitin sulfate (K-Sol). Ophthalmic Surg 1988;19: 817-20. Ophthalmol Scand. 2002;80: 572-78.
73. Lindstrom RL, Kaufman HE, Skelnik DL, et al. Optisol corneal 93. Patel HY, Brookes NH, Moffatt LS, Sherwin T, Ormonde S,
storage medium. Am J Ophthalmol 1992;114: 345-56. Clover GM, McGhee CNJ. The New Zealand National Eye Bank
74. Kaufman HE, Beuerman RW, Steinemann TL, Thompson HW, Study 1991-2003: A Review of the Source and Management of
Varnell ED. Optisol corneal storage medium. Arch Ophthalmol Corneal Tissue. Cornea 2005;24:576-82.
1991;109: 864-68. 94. Pels E, Houdijn Beekhuis W, Volker-Dieben HJ. Long-term tissue
75. Smith TM, Popplewell J, Nakamura T, Trousdale MD. Efficacy storage for keratoplasty. Ch 106 In Brightbill FS (Editor): Corneal
and safety of gentamicin and streptomycin in Optisol-GS, a Surgery, Theory, Technique and Tissue (2nd Edn). St Louis,
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76. Bourne WM, Nelson LR, Maguire LJ, et al. Comparison of Chen 95. Crewe JM, Armitage WJ. Integrity of epithelium and endothelium
Media and Optisol-GS for human corneal preservation at 4 in organ-cultured human corneas. Invest Ophthalmol Vis Sci
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77. Ritterband DC, Shah MK, Meskin SW, et al. Efficacy and safety 96. Borderie VM Kantelip B, Delbosc B. Morphology, histology and
of moxofloxacin as an additive in Optisol-GS preservation ultrastructure of human 31oC organ-cultured corneas. Cornea
medium for corneal donor tissue. Cornea 2006;25: 1084-89. 1995;14: 300-310.
78. Jeng BH. Preserving the cornea: corneal storage media. Curr Opin 97. European Eye Bank Association Directory. 14th Edition, January
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79. Doughman DJ. Prolonged donor cornea preservation in organ 98. Doughman DJ, Van Horn DL, Rodman W, et al. Human corneal
culture: long-term clinical evaluation. Trans Am Ophthalmol Soc endothelial layer repair during organ culture. Arch Ophthalmol
1980;78: 567-628. 1976;94: 1791-96.
80. Frueh BE, Bohnke M. Prospective, randomized clinical evaluation 99. Van der Want HJL, Pels E, Schuchard Y, Oleson B, Sperling S.
of Optisol vs Organ Culture corneal storage media. Arch Electron microscopy of cultured human corneas. Osmotic
Ophthalmol 2000;118: 757-60. dehydration and the use of a dextran fraction (dextran T500) in
81. Redmond RM, Armitage WJ, Whittle J, Moss SJ, Easty DL. organ culture. Arch Ophthalmol 1983;101: 1920-26.
Long-term survival of endothelium following transplantation 100. Borderie V, Baudrimont M, Lopez M, Carvajual S, Laroche L.
of corneas stored by organ culture. Br J Ophthalmol 1992;76: Evaluation of the deswelling period in dextran-containing medium
479-81. after corneal organ culture. Cornea 1997;16:215-23.

36
101. Borderie VM, Laroche L. Microbiologic study of organ-cultured 107. Wiffen SJ, Weston BC, Maguire LJ, Bourne WM. The value of
donor corneas. Transplantation 1998;66: 120-23. routine donor corneal rim cultures in penetrating keratoplasty.
102. Albon J, Armstrong M, Tullo A. Bacterial contamination of Arch Ophthalmol 1997;115: 719-24.
human organ-cultured corneas. Cornea 2001;20:260-63. 108. Everts RJ, Fowler WC, Chang DH, Reller LB. Corneoscleral rim
103. Hagenah M, Bohnke M, Engelmann K, Winter R. Incidence of cultures: lack of utility and implications for clinical decision-
bacterial and fungal contamination of donor corneas preserved making and infection prevention in the care of patients undergoing
by organ culture. Cornea 1995;14: 423-26. corneal transplantation. Cornea 2001;20: 586-89.
109. Rehany U, Balut G, Lefler E, Rumelt S. The prevalence and risk
104. Zanetti E, Bruni A, Mucignat G, Camposampiero D. Bacterial

Chapter 4: Eye Banking—A Practical Guide


factors for donor corneal button contamination and its association
contamination of human organ-cultured corneas. Cornea 2005;24:
with ocular infection after transplantation. Cornea 2004;23: 649-
603-07.
54.
105. Bednarz J, Doubilei V, Wollnick PCM, Engelmann K. Effect of
110. Fontana L, Errani PG, Zerbinati A, Musacchi Y, Di Pede B,
three different media on serum-free culture of donor corneas and Tassinari G. Frequency of positive donor rim cultures after
isolated human corneal endothelial cells. Br J Ophthalmol penetrating keratoplasty using hypothermic and organ-cultured
2001;85:1416-20. donor corneas. Cornea 2007;26: 552-56.
106. Stoiber J, Ruckhofer J, Lametschwandtner A, Muss W, Hitzl W, 111. Vajpayee RB, Sharma N, Jhanji V, Titiyal JS, Tandon R. One
Weikinger K, Grabner G. Eurosol versus fetal bovine serum- donor cornea for 3 recipients – A new concept for corneal
containing corneal storage medium. Cornea 2001;20:205-09. transplantation surgery. Arch Opthalmol 2007;125: 552-54.

37
5
Section I: Evolution, Preoperative Considerations and Eye Banking

Medicolegal Aspects of Eye Banking


M Vanathi, Gurnarinder Singh, Rakesh Ahuja

Laws have been enacted to allow Eye banks to effectively • The Department of Health in consultation with organ
perform the function of collection and distribution of eyes/ procurement organizations shall:
corneas from donors to recipients. There are a number of legal — Establish guidelines regarding efficient procedures
issues associated with Eye Donation and Eye Banking. In this facilitating the delivery of anatomical gift donations.
section, we reproduce key legal acts and documents that affect — Develop guidelines to assist hospitals in selection and
eye donation, eye banking and their operations. designation of tissue procurement providers (eye bank).
In countries like the USA, where organ transplantation and The quality of medical treatment is not affected if one is a
eye banking has been long established, legislation demands a known donor. Strict laws are in existence which protect the
special role in organ collection for hospitals as part of the potential donor. Legal guidelines must be followed before death
“Required Request Law.” In addition, the “Uniform Anatomical can be certified. The physician certifying a patient’s death is not
Gift Act” and “presumed consent” are in vogue which cover involved with the eye procurement or with the transplant. Also,
human organ transplantation. it does not prohibit reimbursement for reasonable costs
Eye banks in India were formerly regulated by the Bombay associated with the removal, storage or transportation of a human
Corneal Grafting Act, 1957 and thereafter, the Eyes Act 1982 body or part thereof pursuant to an anatomical gift executed
till 1994. At present, eye banks and transplantation of other pursuant to this Act.
human organs like heart, kidney, etc. are governed by the Indian The uniform anatomical gift act was made because the
Human Organ Transplantation Act, 1994 and in the process of following key problems that hinder organ donation were
enactment of this Act, the “Eyes Act of 1982” got repealed and identified:
the provisions of the Eyes Act were not even retained, thus • Failure of persons to sign written directives.
demoting the eye banks in India to collection centers attached • Failure of police and emergency personnel to locate written
to keratoplasty units. directives at accident sites.
• Uncertainty on the part of the public about circumstances
INTERNATIONAL LAWS ON EYE BANKING and timing of organ recovery.
• Failure on the part of medical personnel to recover organs
EYE BANKING LAWS IN USA on the basis of written directives.
• Failure to systematically approach family members
Uniform Anatomical Gift Act
concerning donation.
The Uniform Anatomical Gift Act was promulgated in 1968 by • Inefficiency on the part of some organ procurement agencies
the Federal Government of the United States of America. It in obtaining referrals of donors.
covers anatomical gifts including corneas. The Uniform Gift Act, • High wastage rates on the part of some organ procurement
USA says: agencies in failing to place donated organs.
• Each acute care general hospital, with the concurrence of • Failure to communicate the pronouncement of death to next
the hospital medical staff, shall develop a method for of kin.
identifying potential organ donors (within hospital wards). • Failure to obtain adequate informed consent from family
• The acute care general hospitals shall initiate a request (to members.
relatives of the deceased) and follow the designated
procedure of the option to donate organs, tissues or eyes. Persons Who may Execute an Anatomical Gift
The person initiating the request shall be an organ
procurement organization representative or a designated • Any individual of sound mind who has attained the age of
requestor. 18 may give all or any part of his or her body for any purpose.
38
Such a gift may be executed in any of the ways set out in “reasonably available” which is relevant to who can make
Section 5, and shall take effect upon the individual’s death an anatomical gift of a decedent’s body or parts.
without the need to obtain the consent of any survivor. An 5. Permits an anatomical gift by any member of a class where,
anatomical gift made by an agent of an individual, as there is more than one person in the class so long as no
authorized by the individual under the Powers of Attorney objections by other class members are known and, if an
for Health Care Law, as now or hereafter amended, is deemed objection is known, permits a majority of the members of
to be a gift by that individual and takes effect without the the class who are reasonably available to make the gift

Chapter 5: Medicolegal Aspects of Eye Banking


need to obtain the consent of any other person. without having to take account of a known objection by any
• If no gift has been executed under subsection (a), any of the class member who is not reasonably available.
following persons, may give all or any part of the decedent’s 6. Creates numerous default rules for the interpretation of a
body after or immediately before death: document of gift that lacks specificity regarding either the
– the decedent’s agent under a power of attorney for health persons to receive the gift or the purposes of the gift or both.
care which provides specific direction regarding organ 7. Encourages and establishes standards for donor registries.
donation, 8. Enables procurement organizations to gain access to
– the decedent’s spouse, adult sons or daughters, either of documents of gifts in donor registries, medical records, and
the decedent’s parents, any of the decedent’s adult the records of a state motor vehicle department.
brothers or sisters, any adult grandchild of the decedent, 9. Resolves the tension between a healthcare directive
the guardian of the decedent’s estate, the decedent’s requesting the withholding or withdrawal of life support
surrogate decision maker under the Health Care systems and anatomical gifts by permitting measures
Surrogate Act, any person authorized or under obligation necessary to ensure the medical suitability of organs for
to dispose of the body. intended transplantation or therapy to be administered.
If the donor has actual notice of opposition to the gift by the 10. Clarifies and expands the rules relating to cooperation and
decedent or any person in the highest priority class in which an coordination between procurement organizations and
available person can be found, then no gift of all or any part of coroners or medical examiners.
the decedent’s body shall be accepted. 11. Recognizes anatomical gifts made under the laws of other
jurisdictions.
Revised Uniform Anatomical Gift Act, 2006 12. Updates the [act] to allow for electronic records and
This revision retains the basic policy of the 1968 and 1987 signatures.
anatomical gift acts by retaining and strengthening the “opt-in”
system that honors the free choice of an individual to donate Presumed Consent Law
the individual’s organ (a process known in the organ transplant
Presumed Consent Law allows for the harvesting of human
community as “first person consent” or “donor designation”).
organs for transplantation. This law allows, upon brain death, a
This revision also preserves the right of other persons to make person’s organs to be made available automatically to be
an anatomical gift of a decedent’s organs if the decedent had
harvested for donation, unless he or she has declared an opposite
not made a gift during life. And, it strengthens the right of an
wish in writing or otherwise. Organs and tissue may be removed
individual not to donate the individual’s organs by signing a for transplantation or scientific purposes from cadavers of
refusal that also bars others from making a gift of the individual’s
persons who did not, while living, indicate their refusal of
organs after the individual’s death. This revision:
donation.
1. Honors the choice of an individual to be or not to be a donor Organ removal may be performed only after death has been
and strengthens the language barring others from overriding
determined by two licensed physicians. The physicians in
a donor’s decision to make an anatomical gift.
question must not be associated in any way with each other, with
2. Facilitates donations by expanding the list of those who may the transplant recipient, or with the transplant procedure. In the
make an anatomical gift for another individual during that
case of the death of a minor or mentally incompetent person,
individual’s lifetime to include health care agents and, under
organ donation must be approved by the patient’s family or legal
certain circumstances, parents or guardians. representative. The removal and transplantation of organs and
3. Empowers a minor eligible under other law to apply for a
tissues may be carried out only by a physician in a hospital.
driver’s license to be a donor.
Organs, parts of organs, or any bodily tissue, may not be used
4. Facilitates donations from a deceased individual who made for financial gain.
no lifetime choice by adding to the list of persons who can
make a gift of the deceased individual’s body or parts the EYE BANKING LAWS IN AUSTRALIA
following persons: the person who was acting as the
decedent’s agent under a power of attorney for health care In Victoria, Australia the relevant Act relating to the
at the time of the decedent’s death, the decedent’s adult donation of organs and tissues is the Human Tissue Act, 1982,
grandchildren, and an adult who exhibited special care and Human Tissue (Amendment) Act, 1987 and Coroners and
concern for the decedent and defines the meaning of Human Tissue Acts (Amendment) Act 2006.
39
The most immediately relevant aspects of this Act (and • That the death has been documented by the medical officer.
amendments) in regards to eye/corneal donation can be • That the donor had not objected to donation prior to death.
summarized as follows: • That the senior available next-of-kin has given consent.
• When the next-of-kin cannot be located following all
Consent of Next-of-Kin reasonable attempts to contact them have been made, the
Consent can be obtained from the donor’s spouse, adult son or designated officer may also authorize the removal of tissue.
daughter, either parent, adult brother or sister, or legal guardian— • That consent from the coroner has been obtained in cases
Section I: Evolution, Preoperative Considerations and Eye Banking

in that order of priority. where a referral is necessary.


Verbal consent by the senior available next-of-kin is sufficient
for donation to proceed. There is no requirement for written Retrieval of Eyes/Corneas
consent as long as it is appropriately documented in the It is no longer a requirement that the removal of eyes/corneas
deceased’s medical notes. be carried out by a medical practitioner. The Act now states:
Any person can take consent as long as they appropriately “medical practitioner or prescribed person or class of persons
document their status (the person taking consent) and from whom to remove skin or ocular tissue or both.”
consent was obtained and the time it was obtained.
There is no legal requirement to seek the consent of the next- EYE BANKING LAWS IN UK
of-kin if the wishes of the deceased are known. However, it is
the usual practice to approach the next-of-kin to determine if The retrieval and use of tissues for transplantation in the UK
they are aware of the deceased’s intention to be a donor. This was governed by Human Tissues Act, 1961. Now it has been
may have been indicated by family discussion, sticker on a replaced with Human Tissues Act, 2004. Consent is required
drivers licence, a signed donor card or registration on the before the removal of tissues can proceed for the purposes of
Victorian Organ Donor Registry. In respect to the family unit, it transplantation, research or medical education. Either the donor
is advised to seek consent from the senior available next-of-kin, must have made his/her wishes clear prior to death or the donor’s
regardless of whether the wishes of the deceased are known or relatives must confirm to the best of their knowledge that the
not. It is very unusual for the next-of-kin to go against the known donor had not during his/her life objected to donation (In
wishes of a deceased. Conversely, donation cannot proceed if practice, a donor’s relatives are always consulted). The Human
the deceased had objected to donation prior to death. Tissue Act, 2004 and the Human Tissue (Scotland) Act, 2006
Consent should be free and comprehending. Consent for the (HT Acts) require specific consent/authorization for the donation
eyes is preferable, but it is possible for only corneas to be and storage of tissue for transplantation and other specified
donated. It should be documented if the consent was for eyes or purposes, including research, education or training, quality
only corneas. assurance and clinical audit. If a person has expressed a wish to
be an eye donor, for example through the National Organ Donor
Certification of Death Register or in a will, that consent is paramount and cannot be
overridden by relatives. In the absence of prior consent given
For the purposes of donation after circulatory arrest, it is no
by a potential donor, consent may be given by a nominated
longer necessary that the medical practitioner be of at least five
representative of the donor or by a person in a qualifying
years standing to certify death. Any medical practitioner can now
relationship/nearest relative. There are some differences between
certify circulatory arrest death (but not brain death).
the two HT Acts and it is important that consent/authorization
A formal death certificate does not have to be completed in
is obtained according to the relevant legislation.
order for eye/corneal donation to proceed. However, death
While the primary purpose of eye donation will almost
should be adequately documented in the deceased’s notes by the
always be transplantation, there is also a need for ocular tissue
medical practitioner. If time and circumstances allow it is
both for research into human eye disease and for teaching
preferable for a Death Certificate to be completed.
purposes. Relatives should therefore be asked to confirm lack
of objection to these uses as well as to transplantation.
Coroner’s Consent
Relatives should be informed that not every cornea will be
In cases where a coronal inquiry is necessary, the removal of suitable for transplantation, but that suitability cannot be
tissue cannot proceed unless the coroner gives consent. The eye determined before the eyes have been collected. Corneas and
bank will obtain this consent but next-of-kin consent is first other parts of the eye that are unsuitable for transplantation may
required. nevertheless be suitable for research or education/training. If the
tissue is not going to be used, relatives should be informed that
Designated Officer Authorization the tissue will be disposed of in a lawful manner according to
This person could be a medical practitioner (e.g. admitting the HT Acts.
officer, medical administration), hospital administrator or a nurse Consent should also be obtained for a sample of the donor’s
appointed to this position. The role of Designated Officer is to blood to be taken for testing of viral and other microbiological
ensure: markers of transmissible disease. Relatives should be told that
40
they will be informed of any positive results that may have cases Indian law states that no removal of organs be done without
implications for their own health. the consent of relatives. Eyes/corneas can be removed by any
When an inquest is to be held in connection with the deceased registered medical practitioner possessing an MBBS degree even
or when the Coroner, or Procurator Fiscal in Scotland, requires from dead bodies laying in peoples homes or anywhere else.
a postmortem examination of the body, permission must be Strong punishment is specified for anyone removing organs
obtained from the Coroner/Procurator Fiscal before proceeding without consent or using them for any purpose other than
with eye collection, even though consent may have already been therapeutic purposes or for buying and selling organs. All organs

Chapter 5: Medicolegal Aspects of Eye Banking


obtained from the relatives. to be donated and distributed without charge.

Corneal Tissue Act, 1986 Authority for the Removal of Human Organs
Permits suitably trained National Health Service staff, who are Any donor may, in such manner and subject to such conditions
not medically qualified, to remove eyes from donors. Training as may be prescribed, authorize the removal, before his death,
courses are run by corneal transplant service (CTS) eye banks. of any human organ of his body for therapeutic purposes.
If any donor had, in writing and in the presence of two or
Human Organ Transplant Act, 1989 more witnesses (at least one of whom is a near relative of such
It prohibits commercial dealings in human organs. The general person), unequivocally authorized at any time before his death,
standards governing eye donation and retrieval are set out in this the removal of any human organ of his body, after his death, for
act. Guidance on the retrieval of human eyes used in therapeutic purposes, the person lawfully in possession of the
transplantation and research is issued by The Royal College of dead body of the donor shall, unless he has any reason to believe
Ophthalmologists. It has been now replaced by Human Tissues that the donor had subsequently revoked the authority aforesaid,
Act 2004. grant to a registered medical practitioner all reasonable facilities
for the removal for therapeutic purposes, of that human organ
EYE BANKING LAWS IN INDIA from the dead body of the donor.
Where no authority, was made by any person before his death
The main Act governing the donation of human organs in India
but no objection was also expressed by such person to any of
is the Transplantation of Human Organs Act, 1994 and also the
his human organs being used after his death for therapeutic
Transplantation of Human Organs Rules, 1995. This Act
purposes, the person lawfully in possession of the dead body of
legislated by the Government of India provides a legal
such person may, unless he has reason to believe that any near
framework for transplant of all human organs. Eye donation
relative of the deceased person has objection to any of the
comes within its scope.
deceased person’s human organs being used for therapeutic
In a bid to increase donor cornea collection, the National
purposes, authorize the removal of any human organ of the
Program for Control of Blindness has established Eye Banks in
deceased person for its use for therapeutic purposes.
medical colleges, and now also extends support to various eye
Where any human organ is to be removed from the body of
banks run by voluntary agencies. Eye bank Association of India
a deceased person, the registered medical practitioner shall
(EBAI) is the national level body focussed on relieving Corneal
Blindness. Amongst other goals, it aims at encouraging the satisfy himself, before such removal, by a personal examination
Government to create and enforce a uniform legal framework of the body from which any human organ is to be removed, that
for eye banking in the country. It has initiated action to persuade life is extinct in such body or, where, it appears to be a case of
the Government to amend the Human Organs Transplantation brainstem death.
Act, 1994 to include eye donation and eye banks in the
framework of the Act. Authority for Removal of Human Organs in Case of
Unclaimed Bodies in Hospital or Prison
The Indian Human Organs Transplantation Act, 1994 In the case of a dead body lying in a hospital or prison and not
It is an Act to provide for the regulation of removal, storage and claimed by any of the near relatives of the deceased person within
transplantation of human organs for therapeutic purposes. It forty-eight hours from the time of the death of the concerned
regulates the following actions: person, the authority for the removal of any human organ from
All hospitals or eye banks that collects eyes or other human the dead body which so remains unclaimed may be given, in the
organs have to be registered by the government after they meet prescribed form, by the person in charge, for the time being, of
certain service and medical standards. the management or control of the hospital or prison, or by an
A procedure for obtaining written consent of relatives of employee of such hospital or prison authorized in this behalf by
deceased persons has been laid down and has to be followed the person in charge of the management or control thereof.
before eyes or other organs are removed. No authority shall be given if the person empowered to give
In India even if a person when alive ‘wills’ that his organs such authority has reason to believe that any near relative of the
can be donated after death such a will is not valid. Even in such deceased person is likely to claim the dead body even though
41
such near relative has not come forward to claim the body of Punishment for commercial dealings in human organs.
the deceased person within the time. Whoever —
Where, the body of a person has been sent for postmortem a. Makes or receives any payment for the supply of, or for an
examination: offer to supply, any human organ.
• For medicolegal purposes by reason of the death of such b. Seeks to find a person willing to supply for payment any
person having been caused by accident or any other unnatural human organ.
cause; or c. Offers to supply any human organ for payment.
Section I: Evolution, Preoperative Considerations and Eye Banking

• For pathological purposes. d. Initiates or negotiates any arrangement involving the making
The person competent under this Act to give authority for of any payment for the supply of, or for an offer to supply,
the removal of any human organ from such dead body may, if any human organ.
he has reason to believe that such human organ will not be e. Takes part in the management or control of a body of persons,
required for the purpose for which such body has been sent for firm or company, whose activities consist of or include the
postmortem examination, authorize the removal, for therapeutic initiation or negotiation of any arrangement referred to in
purposes, of that human organ of the deceased person provided clause (d); or
that he is satisfied that the deceased person, had not expressed, f. Publishes or distributes or causes to be published or
before his death, any objection to any of his human organs being distributed any advertisement:
used, for therapeutic purposes after his death or, where, he had
– inviting persons to supply for payment of any human
granted an authority for the use of any of his human organs for
organ;
therapeutic purposes after his death, such authority had not been
– offering to supply any human organ for payment; or
revoked by him before his death. The doctor who removes the
– indicating that the advertiser is willing to initiate or
eyes for therapeutic purposes is protected against the charges of
negotiate any arrangement
mutilating the dead body or offending religious or emotional
These shall be punishable with imprisonment for a term
sentiments which are considered offences under Section 297 of
which shall not be less than two years but which may extend to
Indian Penal Code.
seven years and shall be liable to fine which shall not be less
Restrictions on Removal and than ten thousand rupees but may extend to twenty thousand
Transplantation of Human Organs rupees.

No human organ removed from the body of a donor before his


APPENDIX: THE TRANSPLANTATION OF
death shall be transplanted into a recipient unless the donor is a
near relative of the recipient.
HUMAN ORGANS RULES, 1995
Where any donor authorizes the removal of any of his human In exercise of the powers conferred by subsection (1) of Section 24 of
organs after his death or any person competent or empowered the Transplantation or Human Organs Act, 1994 (42 of 1994), the
to give authority for the removal of any human organ from the Central Government of India made rules, the relevant ones are quoted
body of any deceased person authorizes such removal, the human as under:
organ may be removed and transplanted into the body of any A registered medical practitioner shall, before removing a human
organ from the body of a person after his death satisfy himself—
recipient who may be in need of such human organ. National
• That the donor had, in the presence of two or more witnesses (at
Human Rights Commission in its office letter no, DO No. 11/5/ least one of whom is a near relative of such person), unequivocally
2001- PRP and Pdt 29-1-2004 circulated to all States/UTs to authorized before his death, the removal of the human organ of
check illegal trade in human organs has suggested certain his body, after his death, for therapeutic purposes and there is no
measures and also mentions that cadaver transplant program reason to believe that the donor had subsequently revoked the
should be promoted. authority aforesaid;
• That the person lawfully in possession of the dead body has signed
a certificate.
Offences and Penalties
A registered medical practitioner shall, before removing a human
Punishment for removal of human organ without authority. Any organ from the body of a person in the event of his brain-stem death,
person who renders his services to or at any hospital and who, satisfy himself—
• That a certificate has been signed by all the members of the Board
for purposes of transplantation, conducts, associates with, or
of medical experts
helps in any manner in, the removal of any human organ without • That in the case of brainstem death of a person of less than eighteen
authority, shall be punishable with imprisonment for a term which years of age, a certificate has been signed by all the members of
may extend to five years and with fine which may extend to ten the Board of medical experts and an authority has been signed by
thousand rupees. either of the parents of such person.

42
6

Chapter 6: Setting Up Corneal Transplant Center


Setting Up Corneal
Transplant Center
Jacqueline Beltz, Rasik B Vajpayee

INTRODUCTION Eye Bank

Corneal transplantation requires particular skill sets, specialized The role of an eye bank is to provide safe and viable corneal
equipment, and extensive coordination. For these reasons, tissue for transplantation. Tissue needs to be available, reliably
transplantation is only provided by top quality facilities. and safely transported, of good quality, and free of transmissible
A corneal transplant facility must offer top quality disease.
transplantation services, in all different types of corneal An onsite eye bank is most convenient, especially in
transplantation. It must employ specialized staff, right through developing countries, where same day transplantation may be
from reception staff to corneal surgeons (Fig. 6.1A). arranged once serology has cleared, without the need for
Many factors must be considered when setting up a corneal transport medium and storage. In the absence of an onsite eye
transplant facility. These include: bank, one should collaborate with as many eye banks as possible,
• Eyebank of choice and consider factors such as availability of tissue, culture medium
• Patient coordination and education used, transport issues and waiting time.
• Ward availability/staffing/education It is imperative to maintain up-to-date waiting lists, including
• Anesthetic availability all patients awaiting corneal transplantation. Priority should
• Specialty theatre nurses depend upon the need for the surgery and visual acuity in that
• Special equipment required and the other eye. The lists could be divided into the following
• Reception staff/Emergency department staff training/ categories:
education/availability • General list/Non-urgent cases
• Research • Priority list/Semi-urgent cases
• Wet Lab facilities • Top priority list/urgent cases
• Emergency list
Ideally, dates for elective, non urgent cases would be
specified at the time of booking tissue, however, emergency
cases, of course, would be organized more quickly.
If a lamellar surgical procedure, such as DSAEK or ALTK
has been planned, it is useful to cut the tissue one day prior to
the case, in order to save time in the corneal theater on the day
of surgery (Fig. 6.1B). This practice also allows for alternative
arrangements to be made should there be any technical problems
with the cutting of the tissue, and helps to avoid short notice
cancellations.

Patient Coordination and Education


Most corneal transplantation cases should be booked electively,
with confirmation of tissue availability 3-4 days prior to the
specified date. In more urgent cases, once a tissue is available,
Figure 6.1A: Operation theater in a corneal transplant center the patient will need to be notified of a time. They must fast for
43
Anesthetics Staff
Anesthetic staff involved with a corneal transplant facility should
be aware of the different types of corneal transplantation, and
their anesthetic requirements. Ideally, written guidelines would
be set by the anesthetic staff, outlining appropriate investigations
to be performed prior to each case, as this may help to avoid
delays at the time of surgery.
Section I: Evolution, Preoperative Considerations and Eye Banking

On booking a case, anesthetic preference should be


considered. If the patient is considered to be of high ansthetic
risk, preoperative assessment will be required by the anesthetist
prior to surgery. Relevant bloods and echocardiograph should
be considered. General or local anesthesia are appropriate for
most patients undergoing corneal transplantation.
It is most important to liaise with the anesthetist when
necessary, particularly for urgent cases.
Figure 6.1B: Pre-cutting tissue for DSAEK
OPERATING THEATER ISSUES
at least 6 hours preoperatively, and be aware of instructions
requiring particular medications, particularly diabetic
Specialty Theater Nurses
medications.
Patients should receive written information, in the form of a It is important to train Ophthalmic nurses in the different types
brochure, at the time of booking the case. This information of corneal transplantation, as they will be able to assist the
should include: surgeon with each case, and ensure appropriate instruments are
• Place of arrival available. A corneal transplant facility should include relevant
• What to wear/bring equipment, and a good selection of trephines and punches, as it
• Fasting instructions may be difficult to adequately predict use prior to the case. At
• Instructions relating to any special medications, e.g. diabetic/ the time of booking a case, make sure the type of transplant to
anticoagulant be performed, as well as any special equipment is clearly
• Risks and benefits of corneal transplantation specified.
• Theoretical risk associated with transplant material Provide the nursing staff with equipment lists for all types
• Possible day/time change at late notice due to unavailability of corneal transplantation. Examples of such lists are shown in
of tissue figures 1-5. In this way, you will always have what you need
• Need for lifelong follow-up following the transplant within reach, and each surgery may run more quickly and
• Postoperative instructions, including importance of drops efficiently.
• Symptoms of rejection/infection to look out for. Lasers in Corneal Surgery

Ward/Staff Education Femtosecond laser is now being used to perform many types of
specialized corneal transplant surgeries. It is ideal to have the
A corneal transplant facility should have the capacity to laser facility and the surgical facility in the same center, in order
accommodate patients overnight, both pre- and postoperatively, to avoid transport of patients mid-procedure. Due to financial
when required. Occasionally, particularly in developing and space constraints, however, this may not be possible for
countries, patients may need to remain as inpatients whilst many transplant facilities. Even if separate locations are
awaiting transplantation, and this may amount to many days on necessary, it may well still be possible to perform these
the ward. femtosecond-assisted procedures.
Ward staff should be aware of different types of corneal
transplantation, including the possibility of posturing Special Equipment
postoperatively. They should be aware that severe pain, A corneal transplant facility must be set-up with all of the
discomfort, nausea, or vomiting must be reported to the surgeon, commonly required instruments. Less frequently used
or on-call ophthalmologist or resident. On-call staff should instruments or materials may be ordered on a case-by-case basis.
understand that there is a low threshold for contacting the corneal Equipment in the clinic would approach that usually required
surgeon should problems arise. A corneal transplant facility must for an ophthalmology clinic. Medical photographic equipment
have an on-call ophthalmologist and also, if possible, a fellow such as slit lamp mounted photographic equipment, corneal
or resident at all times, so that problems may be easily reported topography, specular microscopy, and anterior segment ocular
and patients assessed. Once assessed, a corneal fellow or corneal coherence tomography is all required. A-scan measurements,
specialist should be notified of each presentation, to ensure such as by IOL master, will be required for cataract or triple
44 management of the patient has proceeded effectively. procedures.
Ideally, a transplant facility would be set-up for all types of equipment required will differ for different surgeons. For this
corneal transplantation, including Penetrating Keratoplasty reason, these lists are a guide only, and should be regularly
(PKP), Automated Lamellar Transplantation (ALTK), Big bubble updated and stored for each surgeon. In this way, an up to date
Deep Anterior Lamellar Keratoplasty (DALK), Manual Deep list of equipment required for all different transplant procedures
Lamellar Keratoplasty (DLK), Descemet Stripping Automated
Endothelial Keratoplasty (DSAEK), Tuck-in Lamellar
Table 6.3: Equipment required for Automated Lamellar
Keratoplasty (TILK), and Femtosecond Assisted Keratoplasty. Therapeutic Keratoplasty (ALTK) or Tuck-in Lamellar

Chapter 6: Setting Up Corneal Transplant Center


Provide the nursing staff with equipment lists for all types Therapeutic Keratoplasty (TILK) in addition to that already
of corneal transplantation (Tables 6.1 to 6.5), and specify the listed for PKP
exact type of transplant planned on the booking form. Exact Instruments Consumables
Artificial anterior chamber Tegaderm × 2
Table 6.1: Equipment required for penetrating Microkeratome console and tubing Microkeratome blade × 2
keratoplasty (PKP) ALTK lens applantor set Artificial AC tubing
DRAPES CONSUMABLES ALTK suction and cutting rings IV giving set
ALTK anterior chamber bell BSS 500 Ml
Sterile Eye Drape Gloves - Size X
ALTK lens applantor
Prep tray Disposable Gown
Cutting heads 200/250/300 um DONOR TISSUE
TRAYS and INSTRUMENTS Microscope Drape
Corneal Graft Tray 15 Degree blade
• Fine tooth forceps Teflon block Table 6.4: Equipment required for cutting tissue prior
e.g. Lim/Hoskins to automated lamellar transplantation procedures
• Right and Left hand Marking pen
corneal scissors Drapes Consumables
• Universal Corneal scissors Spears Sterile sheet Sterile Gown
• Westcott scissors Sterile gauze
• Vanass scissors Disposable pot
INSTRUMENTS Spears
– Straight
– Curved Fine tooth forcep x 2 IV giving set
• Needle Holder 10 Ml syringe x 1 Microkeratome console and tubing BSS 500 Ml
• Caliper 2 Ml syringe x 3 Microkeratome motor and cutting head Free standing
Trephines All types of IV pole
Viscoelastics Artificial anterior chamber and tubing 2 Ml syringe
• Eg Hessburg-Barron vacuum Nylon 10-0 suture with Cutting heads - 300 or 350 um Marking pen
trephine and punch, size sharp point needle
specified at start of case. Microkeratome blade Sterile pot
Operating microscope Tegaderm
Phaco Tray and Equipment if Subconjunctival
triple procedure Injections Pacchymeter Microscope drape
GRAFT MATERIAL Healon 0.4 Ml
• Check present • Example, Keflin,
dexamethasone,
lignocaine Table 6.5: Equipment required for Descemet Stripping
Automated Endothelial Keratoplasty (DSAEK), In addition
EQUIPMENT BSS 18 Ml to that already listed for PKP
Microscope with attached Fluorescein 2 percent
photographic and recording minim Drapes Consumables
devices None Bipolar leads
DVD recording device Rycroft cannula × 1 3.2 mm Keratome
INSTRUMENTS Crescent Blade
Busin Glide MVR Blade
Table 6.2: Equipment required for deep anterior lamellar Busin Forceps or End gripping IV giving set, IV Pole
keratoplasty (DALK) or deep lamellar keratoplasty (DLK) forceps
in addition to that on PKP list Descemet stripper BSS 500 Ml
• Air filter Descemet scorer Anterior chamber
• 2 MI Luer Lock syringe maintainer
• 26 g needle × 2 Bipolar cautery Vision Blue
• Crescent blade Miochol
• Lamellar dissectors DONOR TISSUE 8-0 Vicryl suture
• Vision blue Pre cut, preferably 1 day prior Steristrips × 1 packet
45
Check list for Booking a Case
• Tissue
– Book with eye bank
– Time of arrival
– Courier if necessary
– Place of delivery
– Storage once delivered
Section I: Evolution, Preoperative Considerations and Eye Banking

– Need to pre-cut tissue for lamellar procedures


• Theatre
– Book case
– Specify particular equipment required
• Notify specialty nursing staff
• Book ward bed
• Book anesthetist, and consider need for preoperative
assessment
Figure 6.2: Example of set-up for corneal transplantation • Fast and notify patient
• Preoperative photograph
may be kept by the transplant facility for each surgeon, thus • Book follow-up
helping each surgery to run smoothly and efficiently (Fig. 6.2).
Research
Follow-up It is essential that a corneal transplant facility will contribute to
A corneal transplant facility must have a clinic, and an emergency the progression of this rapidly expanding field. Research may
facility, in order to assess both pre- and postoperative patients. be laboratory based or clinically based. A corneal transplant
Referring practitioners would need to be aware of the presence facility should aim to publish new techniques, as well as results
of a transplant facility in their area. Services offered may be or modifications to pre-existing techniques. Make sure every
advertised to these referrers, by means of letter or pamphlet. An surgical case is recorded and catalogued for future video
example of a list of services offered by a corneal transplant production or education (Fig. 6.3).
facility may include:
• Inpatient or outpatient management of acute corneal disease Wet Lab
including: If possible, a corneal transplant facility should have a wet lab
– Infectious keratitis or skill development lab. Such a lab should have well functioning
– Neurotrophic keratitis operating microscopes, and appropriate instruments in order to
– Corneal melt practice the skills required for corneal transplant surgeries.
– Corneal perforation Residents and fellows should aim to frequently practice their
• In patient or outpatient management of chronic corneal
disease including:
– Corneal dystrophy
– Corneal ectasia
– Low vision due to previous corneal disease
• Follow-up and management of all corneal conditions
• Emergency assessment, management, and treatment of
corneal disease
Patients must be aware of the procedure to be followed
should an emergency develop, and the corneal fellow or specialist
should be contacted following on-call ophthalmologist or
resident assessment.
The major complications requiring immediate attention after
a corneal transplant are infectious keratitis and graft rejection.
A corneal transplant facility should develop management
protocols and make them available to corneal fellows for the
management of these cases.
A corneal transplant facility should aim to have photographs
of all patients preoperatively, and at each follow-up visit, to aid
in documentation of progression or improvement of disease. Figure 6.3: Recording device
46
skills on animal eyes prior to performing live surgeries. Suturing, identify any problems occurring. A computerized database should
in particular, must be practiced in the wet lab. Practice of the be arranged, such that data may be easily entered at the time of
various types of suturing is the best way to develop the skills of surgery or follow-up, and so additional time is not required to
intricate wrist movements and optimal hand-eye coordination that gather large quantities of data at the end of each year. It is
are required for a corneal transplant surgeon. important to specify the indication for each surgery, surgeons
Periodically, device companies may be invited to bring their involved, type of transplantation, date and time of
corneal transplant instruments and machines to the wet lab to transplantation, intra- or postoperative complications, and best

Chapter 6: Setting Up Corneal Transplant Center


encourage residents and corneal fellows to practice newer corrected visual acuities for each clinic visit. In this way, success
transplantation techniques, and to learn how to prepare donor or problems may be easily highlighted, and changes made to
tissues for such surgeries. address any issues arising.
Regular staff meetings should be held, involving all of the
Audit and Outcome Monitoring transplant facility staff, so that the facility may run effectively
An annual audit meeting should be arranged, involving all of as a single unit. In this way, any problems arising will be dealt
the corneal transplant facility staff, in order to monitor the with quickly and efficiently, in order to achieve the best possible
success of transplants performed at the facility, as well as to outcomes for as many patients as possible.

47
7
Section I: Evolution, Preoperative Considerations and Eye Banking

Setting Up an Eye Bank


Mukesh Taneja, Prashant Garg, Usha Gopinathan

INTRODUCTION Eye Bank (EB)

From all the evidence available, direct and indirect, an annual An Eye Bank is a non-profit community organization, usually a
performance of around 100,000 corneal transplants would have society or trust registered under the Registration of Societies Act
a salutary effect on the problem of reversible corneal blindness and run by a board of directors.1 A medical director, an eye bank
in India. Going by the experience of the eye banking systems manager, eye bank technicians and grief counselors manage the
worldwide, meeting this demand would require double that day-to-day affairs of an eye bank.
number of corneas to be harvested, i.e., 200,000 annually. Each The functions of eye banks are:
Eye Bank (EB) with adequate infrastructure and trained a. Educating the public about eye donation and eye banking
manpower can comfortably process 4000 corneas per year, which b. Carrying out eye donations
translates to 50 eye banks for the entire country. In a country
c. Preserving, processing and evaluating the donor corneas
like India, where the basic infrastructure and manpower exist,
d. Carrying out serological tests of eye donor’s blood sample
this should not be a problem-theoretically.
e. Distributing donor corneas to corneal surgeons according to
Each of these eye banks should be an autonomous
the waiting list
organisation, ideally with its own Board and governance structure
representing all the stakeholders in the community. All the major f. Initiating Hospital Cornea Retrieval Programme in
functions of an eye bank should be carried out, including public neighbouring hospitals and
awareness, tissue harvesting, tissue evaluation (including g. Fund raising for defraying the capital and recurring expenses.
serology and microbiology), tissue preservation and tissue
distribution. Equitable distribution is key to long term success, Eye Donation Center (EDC)
since this builds credibility in the community with all its Eye Donation Centers are suitable for places with population
subsequent benefits. The goal is to make safe and high quality between 2–4 lakhs where the annual target may be around 25
corneal tissue accessible to everyone who needs corneal eyes. It makes sense to save on infrastructure and manpower at
transplantation in the community in an equitable manner. such locations and the eyes retrieved can be handed over to the
Essentially, this means that all those who are in need of a corneal nearest eye bank, which maintains sufficient manpower and has
transplant for visual rehabilitation, irrespective of socio- the infrastructure to process, preserve and distribute corneas.
economic status, gender, religion, or choice of surgeon and The functions of an Eye Donation Center are:
institution, should have equal access to the eyes donated to eye
a. Tissue retrieval from the donor and
banks on a first-come first-served basis.
b. Transportation of tissues to the nearest eye bank for
There should be one eye bank for every 20 million people,
processing, evaluation and distribution.
each of which should be linked to 40 Eye Donation Centres
(EDC) — eye banking units that are involved only in harvesting Feasibility Study
corneas. In addition, each eye bank should develop a Hospital
Cornea Retrieval Programme (HCRP) in 10 major hospitals in One needs to conduct a feasibility study before setting up an
the immediate community. Half (2000) of the harvesting should eye bank which should cover the following aspects:2
be achieved by the Eye Bank directly through the HCRP and a. Existing eye banks/eye donation centers in the town/city/
the other half (2000) should be through the contribution of eye suburban area
donation centers, with 50 eyes (25 donors) from each EDC. b. Population of the town/city/suburban area

48
c. Hospitals located in the town/city/suburban area Table 7.1: Infrastructure requirement for EB and EDC
d. Distance of the hospitals from the EB/EDC
Infrastructure Physical
e. Financial viability
Eye Bank Eye Donation Center
If an EB or an EDC functions satisfactorily in the area of
your operation, it is worthwhile to extend your cooperation to Space 500 sft 300 sft
the existing center than trying to establish another one. You can Slit-Lamp 2,00,000 –
avoid unnecessary proliferation and fragmentation of EBs which Refrigerator 25,000 25,000

Chapter 7: Setting Up an Eye Bank


may be counterproductive. Ideally, in a large city or town one Four Wheeler 3,35,000 –
or two EBs should exist with all facilities to process, evaluate Two Wheeler – 35,000
and distribute corneas. Others should function as satellites of Laminar Flow 50,000 –
the EB functioning as EDCs only. The waiting lists of all EDCs hood (Fig. 7.1)
should be collated and maintained at the central community EB. 6 sets of 10,000 10,000
instruments
Distribution should be carried out according to the central
Telephone 6000(2) 3,000 (1)
waiting list only. Exception to this may occur in cases of
Furniture 1,00,000 15,000
emergency.
Serological 1,00,000 –
Some of the existing eye banks may not be functioning to
Equipment (Fig. 7.2)
the full potential that exists in their area. If the eye banks are
Autoclave 15,000 15,000
not achieving good results and exist for several years, then one
Specular 12,00,000 –
can think of setting up an EB/EDC despite their presence. Microscope (Fig. 7.3)
If no EBs/EDCs exist in your area of interest, the next aspect Total 20,41,000 1,03,000
to be examined is the population of the area.

Population and Total Potential for Eye Donation


Table 7.2: Human resource requirement for EB and EDC
According to the population of your area a decision whether an
Human Resources
EB or EDC should be established can be taken. If the population
Eye Banks Eye Donation Center
is less than 2 lakhs even an EDC may not be viable. One percent
of local death rate in the area, as an initial target for eye donation Panel of Statutory –
gives you rough figures for potential in your area. Ophthalmic
Surgeons
Hospital in Local Area and their Medical Director 1 Desired 1 Desired
Potential for Eye Donation Eye Bank 1 Desired 1 Desired
Manager
Information on hospitals located in your area of operation is Eye Bank 1 Statutory 1 Statutory
essential as tie-up with hospitals would ensure regular sourcing Technician
of corneas. Through such tie-ups Grief Counselors or Eye Social Worker- 1 Statutory 1 Statutory
Donation Counselors can be placed at hospital wards with cum-Health
Educator
substantial death rates. The distance of the hospitals from the
Driver-cum- 2 Statutory 1 Statutory
eye bank should be within 15 kms.
projectionist

Financial Viability
Once it is concluded that there is potential for either an Eye Bank
or Eye Donation Center, the next step is to take a look at the
requirements of setting up such a centre (Table 7.1). Substantial
funds for equipment and operations, especially manpower, are
required to set up and sustain the facilities.

Location of the Center


Ideally, an Eye Bank/Eye Donation Center should be an
independent setup, serving the community irrespective of caste,
creed or religion. In India, however, the eye banks / eye donation
centres are located in a general hospital or in an eye institute
(eye care center) as this allows the EB/EDC to use some of the
facilities of the host organization like telephones, reception,
laboratory and some basic manpower (Table 7.2). The most Figure 7.1: Laminar flow hood
49
4. Evaluation Lab and Shipping Area (approx 12’ × 10’)
Should have a sink, slit-lamp, work station, cabinets for
storage and refrigerator.
5. Technician’s Office (approx 10’ × 10’)
Where communication and record keeping is done.
6. Manager’s Office (approx 10’ × 10’)
Should have a work desk, phone, fax and cabinets.
Section I: Evolution, Preoperative Considerations and Eye Banking

Assistance for setting up an Eye Bank


or Eye Donation Center
The National Programme for Control of Blindness of the
Ministry of Health and Family Welfare provides assistance to
organisations that want to set up an eye banks.4

Figure 7.2: Serology laboratory Criteria for Eligibility


Besides the Central/State/District/mobile units and private
charitable hospitals and nursing homes, a voluntary organisation
is eligible to become an Eye Bank if it meets the following
criteria:
• The organization should be registered under the Human
Organs Transplantation Act.
• It should be non-governmental and should not be run for
profit to any individual or group of individuals.
• Its work and financial position should be satisfactory and
the payment of grant-in-aid should be recommended by a
State Government .
• It should have its own infrastructure to carry out the activities
of an Eye Bank.
• The organisation should have a good track record .
• It should be recognised/associated with the Eye Bank
Figure 7.3: Specular evaluation of donar eye Association of India (EBAI).

important advantage of such a policy is to gain credibility from Pattern of Assistance


the name of the host organization. If the host has an eye
• Non-recurring grant up to Rupees 5 lakhs for eye banks and
department, it has been the practice (though not mandatory) to
Rupees 50,000 for eye donation centers for items like
get an ophthalmologist as a medical director on honorary basis.
vehicles, refrigerator, emuclation set, containers for corneal
In such cases, the cornea retrieved by the eye bank is readily
sets, film projector with slides, etc .
utilized by the host hospital, if it specializes in corneal
• Recurring grant of Rupees 250 per eye collected for eye
transplantations. In case the host hospital cannot utilize the
donation centres and Rupees 500 per eye collected for eye
cornea, arrangements should be worked out for the distribution
banks for MK Media (Fig. 7.4), glassware and other
of the cornea to ensure timely utilization.
contingency expenditure.
Requirements for an Ideal Eye Bank Set Up
Procedure for Application
1. Instrument Cleaning Isolation Lab (approx 8’ × 10’)
An application should be submitted on the prescribed Performa
Limited access lab for authorised personnel where
through the Director, Health Services of State Governments or
instruments are washed and sterilized following corneal
be sent to the Ophthalmology Section, DGHS, Department of
excisions.
Health, New Delhi.
2. Serology isolation Lab (approx 12’ × 10’)
Limited access for authorised technician only, where blood For registration under the the Human Organs Transplantation
serum samples are tested. Act, the organization should apply to the state health department.
3. Tissue Processing Isolation Lab (approx 15’ × 10’)
Legal Formalities
Where tissues are evaluated, processed and prepared for
packing and distribution. Should have space for ultraviolet Legal formalities differ from state to state. But the common
50 and laminar flow hood. procedure is the registration of the eye bank/eye donation center
with the health department of the state government under the
Transplantation of Human Organ Act 1994.3 Once the system
of accreditation of eye banks comes into practice, the eye banks
will have to go through regular inspections and file reports as
required by the accreditation system. EBAI has started the
process of accreditation system in the state of Andhra Pradesh,
which gradually will be implemented throughout India.

Chapter 7: Setting Up an Eye Bank


REFERENCES

1. Rao GN. What is Eye Banking? Indian J Ophthalmol 1996;44:


1-2.
2. Guide lines and Project Report for setting up an Eye Bank or
Eye Donation Centre, EBAI: 2003.
3. Transplantation of Human Organ Act (HOTA), 1994.
Figure 7.4: MK media preparation
4. The ministry of Health and Family Welfare Notification regarding
amendment in HOTA, 2002.

51
SECTION II: Penetrating Keratoplasty

Chapter 8: Surgical Instruments for Penetrating Keratoplasty


Surgical Instruments for Penetrating
Keratoplasty
Prakash Chand Agarwal, Namrata Sharma, Vishal Gupta, Geoffrey C Tabin

The basic instruments for corneal grafting surgery include eye compression. The pediatric Barraquer eye speculum is open 11
speculum, corneal trephines, needle holders, and a Pierse-Hoskin mm of blade and the blade spread is 19 mm.
forceps. However in the recent past, the number of instruments
available for corneal grafting has increased considerably. Many
of the newer instruments are variations of the earlier designs.
Instruments specific for corneal transplantation surgery
can be divided into four categories:
• Instruments designed for optimal globe exposure.
• Instruments specifically designed to cut the recipient and the
donor cornea, such as trephines, punches and blocks.
• Instruments used to secure the donor cornea and to remove
and replace lens implants such as forceps, scissors and needle
holders.
• Instruments used to assist in the maintenance and Figure 8.1: Wire speculum
reconstruction of the anterior segment such as cannulae,
spatulas and hooks. Globe Supporting Rings
• Qualitative keratometers used intraoperatively to assess the
The Flieringa ring (Fig. 8.2) is made of stainless steel and is
corneal toricity.
useful for maintaining the architecture of the globe once the host
The suitability and selection of instruments for corneal
corneal button has been removed. Although, they are available
transplantation is based primarily on specific surgical technique,
in 11 sizes from 12 to 22 mm, the most commonly used sizes
surgeon’s preference and the expertise.
are the 17 and 18 mm. Use of globe supporting Flieringa rings
has been advocated in aphakic eyes especially where vitrectomy
INSTRUMENTS FOR GLOBE EXPOSURE
has been performed, pseudophakic eyes and pediatric eyes as
Eye Speculum the eyeball has a tendency to collapse in these cases after the
trephination. However, many surgeons do not choose to use these
The transplant surgeons must have several speculas available in rings as they may transmit unequal traction forces to the host
order to meet the needs of the various different anatomic cornea.1 This may distort the shape of the eyeball and cause an
configurations frequently encountered. The speculum should be oval cut during trephination and subsequent high astigmatism.
light in weight, have minimum extraneous parts and avoid undue Occasionally subconjunctival hemorrhage may also occur while
pressure over the globe which can increase intraocular pressure
or distort the cornea (which can result in increased postoperative
astigmatism). A wire lid speculum such as Barraquer eye
speculum (Fig. 8.1) or Kratz-Barraquer eye speculum is ideal
for most cases. Barraquer eye speculum has open 14 mm blades
and the blade spread is 20 mm. Eye specula used in children are
of small size and tend to offer slightly less resistance to Figure 8.2: Flieringa ring (Courtesy: Katena products)

53
suturing these rings to the conjunctiva. McNeill-Goldman ring CORNEAL TREPHINES
(Fig. 8.3) provides support with four stragically placed sutueres.
A trephine is a stainless, sharp, cylindrical blade, which when
The ring features medial and temporal openings for greater
used, creates a circular corneal incision (Fig. 8.4). An ideal
access to the surgical field and two lid retractors to prevent eyelid
trephine is one that produces a sharp vertical cut without causing
closure by the patient. It is available in three sizes—small,
too much damage to the corneal tissues. The most common
medium and large.
complication of corneal transplantation is postoperative
astigmatism. A poor quality trephine may contribute substantially
Section II: Penetrating Keratoplasty

to the occurrence of this problem. It is important to have an ideal


trephine that achieves the most accurate and reproducible cuts.
Some trephines are available with handles to get a firm grip while
cutting the corneal button (Fig. 8.6).

Types of Trephines
These may also be classified depending upon whether the host
cornea or the donor button has to be cut. There are various
trephines and trephination systems that are available for cutting
the recipient and donor cornea. Apart from this, the endothelial
Figure 8.3: McNeill-Goldman ring (Courtesy: Katena products)
punches are used to cut the donor cornea.
The various trephines are of following types:
• Conventional circular cutting trephines
Corneal Marking Instruments • Single point cutting trephines
Various instruments like the radial keratotomy marker and the • Combination trephines
Vajpayee corneal marker stained with gentian violet can be used • Non-contact trephines (Lasers)
to mark the donor cornea to aid in the optimal placement of the
Conventional Circular Trephines
sutures in keratoplasty (Fig. 8.4). Vajpayee corneal marker
consists of 20 radial arms which guide the placement of the single There are five types of circular trephines:
continous suture bites. Anis corneal marker (Fig. 8.5) with 8 • Hand held
marks is also commonly used to guide the initial sutures. • Mechanized
• Suction-fixation type
• Special-purpose type
• Skin biopsy punches
Hand-held trephines: Since the advent of micro-surgical
keratoplasty many modifications have occurred in the trephines
over a period of time.2-5 In the early era of corneal grafting,
trephines did not have disposable cutting edges and therefore,
required continual resharpening. This led to change in the
original circular shape over a period of time, thus distorting the
shape of the graft. Hand-held circular disposable trephines
remain the most commonly used trephines to cut both the
recipient and donor corneas, particularly in the developing
world. The hand-held trephines are available in sizes ranging
from 3 to 17 mm. The trephine is usually attached to a handle
for greater stability, leverage and control. The handle helps in
securing the trephine and confers a mechanical advantage over
Figure 8.4: Vajpayee corneal marker simply holding the trephine blade by hand. The trephine handle

Figure 8.5: Anis cornea marker (Courtesy: Katena products) Figure 8.6: Trephine Handle (Courtesy: Katena products)
54
may have a hollow core so as to allow observing the central mechanized trephines make the use of limbal suction ring to
cornea through the center of the trephines. In some trephines, assist in anterior chamber maintenance and protection during
there is a central obturator, which can be adjusted to select the trephination. Microkeratron (Hans Geuder, Heidelberg), a
depth of the corneal cut and hence an inadvertent entry into the commonly used mechanized trephine is used to trephine
anterior chamber can be avoided (Fig. 8.7). The handle of the recipient cornea and it permits variation of rotation speed and
obturator trephine offers a distinct advantage over the hollow has rapid braking within 0.1 second.
core in allowing a fairly accurate depth measurement. However, The disadvantages associated with motor driven trephines

Chapter 8: Surgical Instruments for Penetrating Keratoplasty


the obturator does not allow the surgeons to view the central include corkscrew edge effect in the corneal stroma. However,
cornea through the trephine during its use. This may result in less stromal disruption and a smoother interface has been
inaccurate centration during the trephination of the recipient’s reported with the use of a Microkeratron trephine (Hans Geuder,
cornea. Heidelberg) which moves at the rate of 800 rpm in comparison
The examples of hand-held trephines with obturator are the to the manual trephines.2
Castroviejo trephine and the Grieshaber-Franceschetti
Suction Fixation Corneal Trephines: These trephines have
trephine. The disadvantage of both the hollow core and the
been devised to obtain a perpendicular cut in the recipient
obturator type of handle is that each size trephine must be
cornea. These trephine systems essentially consist of an outer
matched to the handle size and hence different handles are
corneal suction ring for fixation and an inner circular cutting
required to accommodate different trephine sizes. Hence,
blade. Hessburg-Barron trephine is a prototype of this system
“Universal trephine” handle which accommodate various blade (Figs 8.8A to C). In Hessburg-Barron vacuum trephine a spring-
sizes was advocated. The advantage of this type of handle is that loaded disposable syringe creates the required negative pressure
this single instrument will secure trephine sizes used in majority and the suction fixation provides the stability and an opportunity
of cases. However, the disadvantage is that it is neither hollow to cut perpendicularly to the limbal plane and hence diminishes
for optimal visualization nor does it provide protection against the tilt of the trephine.6 The newer model of this trephine includes
inadvertent entry into the anterior chamber. the presence of a cross hair device for improved centration and
To overcome the problems of visualization associated with an outer ring of corneal marks at equal intervals to assist in suture
the obturator, certain trephine blades have been made long and placement. The Barron radial vacuum trephine is available in
can be easily grasped with the hand for a successful trephination diameters of 6.0 to 9.0 in 0.5 mm increments as well as diameter
both of the recipient cornea and the donor button. These of 7.75 mm. For each spoke (90 degrees) turned, the blade is
disposable trephines with long handle do not have provision lowered or raised approximately 0.06 mm. These trephine
for the obturator. These hand-held trephines are disposable and systems are used to trephine the host cornea. Its advantages are
made of razor blade and are see-through, easy to use and relatively low cost, consistency of the cut, control of depth,
economical. However, the cut may be uncontrolled and there may disposability and it is particularly useful for performing corneal
be difficulty in centration. Additionally, the slippage of the grafting surgery in extremely soft and perforated eyes.7 The
trephine may lead to an uneven cut. Hessburg-Barron trephine appears to improve the accuracy of
Mechanized Corneal Trephines: The cutting blade of this type the cut. However, this trephine has a tendency to undercut and
of trephine is driven by a motor present in the main body. A in the event of loss of suction during trephination, it can cause
circular trephine attached at the motor shaft end permits anterior an asymmetrical cut. The vacuum fixation ring may also lead to
chamber entry without damaging the intraocular structures. Some endothelial damage.8,9 The Barron Vacuum Punch features a
solid stainless steel blade which is permanently mounted in a
nylon housing. Four steel guide posts align with four
corresponding holes in the cutting block base, automatically
centering the blade over the donor cornea. The base of the punch
features a circular groove for aspirating the epithelial side of
the cornea, immobilizing it for cutting the button. The cutting
block well has four small holes which can be inked with a sterile
marking pen to identify the four quadrants of the cornea for
cardinal suture alignment in the recipient bed.
The Olson Calibrated Cornea Trephine System is a
precise, reproducible trephine that can be used to trephinate both
the donor and recipient corneas. The system consists of the
anterior chamber maintainer, the reusable blade holder (with
micrometer setting), and the suction ring. One revolution of the
micrometer is equivalent to 500 microns. The trephine should
Figure 8.7: Top—Obturator guided conventional circular be fully rotated at least three times to achieve a complete cut
trephine. Bottom—Conventional circular, disposable trephine for penetrating keratoplasty. If planning a partial depth incision,
55
select the desired depth by turning the micrometer, and tighten
the set screw. To cut the donor tissue the anterior chamber
maintainer is prepared. A small drop of viscoelastic is placed
on the endothelium of the donor tissue and the donor cornea is
centered onto the anterior chamber maintainer (epithelium-side
up). The trephine is centered on the patient’s cornea and releasing
the syringe activates the suction. While holding the suction ring,
Section II: Penetrating Keratoplasty

the top of the trephine is turned to complete the cut. Using a


different blade size, the recipient cornea can also be cut similarly.
After obtaining the donor button, it is placed in a graft
holder (Paton Spatula) (Fig. 8.9) over a viscoelastic and is kept
covered till the recipient dissection is complete. A trephine block
can be used to cut the donor cornea from endothelial side
(Fig. 8.10)
Special Purpose Trephines: These trephines are particularly
useful to perform a transplant in cases of optical zone lacerations
in the recipient cornea. This instrument helps in integrating two
Figure 8.8A: Hessburg-Barron trephine separate surgical procedures, that of initial repair and later
(Courtesy: Katena products) transplantation into one. The lacerated cornea is supported from
behind by protective plate, placed in anterior chamber and this
avoids injury to the lens and iris during trephining. An upper
plate is present above so that the cornea is securely placed
between the two plates. The trephine then descends along the
vertical shaft so that a circular cut is made without the underlying
damage to the iris or the lens.
Skin biopsy punches: The skin biopsy punches, which have
been used in dermatological practice, are especially useful in
harvesting of small patch grafts used for tectonic purposes in

Figure 8.9: Paton spatula

Figure 8.8B: Barron Punch (Courtesy: Katena products)

Figure 8.8C: Trephine Bottom view (Courtesy: Katena products) Figure 8.10: Teflon block (Courtesy: IOWA press)
56
cases of impending/frank perforation. These can be used for both the recipient as well as preserved donor cornea since it has an
donor and recipient corneas. The sizes of the most commonly artificial chamber maintainer system. It consists of two parts; a
used punches vary from 2.0 to 5.5 mm (Fig. 8.11). Additionally limbal suction ring system and a mechanical trephine fitted with
a Searcy chalazion trephine 2.5 or 3.0 mm in size may be used a suction ring. The suction ring helps fixating the trephine
to punch the patch grafts perpendicular to the cornea. A preset depth of cut is selected
and by rotation of the gear system, a cut of desired depth is
Single Point Cutting Corneal Trephines obtained. Once the desired depth is reached, there is no further

Chapter 8: Surgical Instruments for Penetrating Keratoplasty


descent of the blade despite continued knob rotations. The Hanna
The single point cutter trephines were designed to decrease
corneal torsion. In these trephines, fixation takes place at the vacuum trephine tends to produce less undercutting and smaller
epithelial diameter than the Hessburg-Barron trephine.6 Both the
limbus or on the sclera thereby reducing the corneal distortion.
systems produce greater final graft curvature than the hand-held
Leiberman single point cutter belongs to this class of trephines.
It is composed of two cones. The outer cone is held by the trephines although there was no significant difference in the final
keratometric results between the Hessburg-Barron trephine and
fixation hand and contains the suction ring. The inner cone
the Hanna’s trephine. Although better visual acuities were
revolves and carries a disposable razor blade knife and is capable
of making circular and oval perpendicular cuts with diameters reported in patients who underwent keratoplasty with the Hanna
trephine system compared with Hessburg-Barron trephine, the
of 2 mm to 8.5 mm. For 20º angle cuts, an interchangeable cutter
postoperative keratometric and refractive astigmatism were not
may be used for lamellar cuts. This trephine can be used only
on the eyeball for trephining donor and recipient corneas. As significantly different.10 Guided trephine system (GTS) is
another trephine system but with a different characteristic suction
compared to other available trephines, single point corneal
ring design. It uses a fixed glass obturator for corneal support
cutters do provide superior visibility under the microscope, the
least distortion and potential for reproducible controlled cutting. and the cornea is trephined in an applanated state and thus
enhances the perpendicularity of the corneal cuts.
Combination Corneal Trephines
Non-contact Trephines
Over the period of time, new trephines have come up, that
combine the best features of the previous trephines. Hanna They have got distinct advantages over other trephine systems
trephine system has got a circular razor-cutting blade and in providing complete visualization, better centration and
incorporates many of the salient features of single point cutting eliminating the corneal topographic distortion. Laser non-
trephines6 (Fig. 8.12). This assembly can be used to trephine contact trephination eliminates corneal topography distortion,
provides the visualization of the entire cornea and enhances
centration. Comparative studies between mechanical and laser
trephination with 193 nm reveal that there is no difference in
the immunologic reactions following penetrating keratoplasty.11
However, several concerns regarding endothelial injury,
mutagenicity and cost regarding use of these techniques remain.

GAUZE PIECE FIXATED EYEBALL

Gauze piece fixated eyeball can be used specially in developing


Figure 8.11: Skin biopsy punches countries where preservation techniques may not be available
and the eyeball is stored in a moist chamber at 4ºC.

EYE GLOBE FIXATION

Tudor Thomas Stand


The Tudor Thomas stand is used to fixate the whole eye globe
prior to trephination. The whole eye globe is positioned in the
Tudor Thomas stand and the trephination can be done both for
full thickness as well as lamellar grafts.

CUTTING BLOCKS

The various cutting blocks available for corneal grafting are


Paraffin block, Teflon block and Polycarbonate and nylon
Figure 8.12: Hanna's trephine (Courtesy: IOWA press) blocks.11,12
57
An ideal cutting block attempts to approximate the corneal
shape and reduces the tissue distortion. Previously, early models
of blocks used to consist of different concavities of simple radius
of curvature. But now, teflon blocks with different radius of
curvature are available. The available cutting blocks are as
follows:
• The Kaufmann corneal cutting block – This is the simplest
Section II: Penetrating Keratoplasty

design which consists of a teflon block with metal cover


(Fig. 8.10).
• The Brightbill polytef cutting block – This modern,
compound curved block approximates the central, mid-
peripheral and peripheral curvature of donor. The Brightbill
polytef-cutting block uses three wells, each with a different
radius of curvature and diameter. Two concentric inlays of
colored polytef are present. The outer black polytef zone has
a chord length of 12.5 mm and corresponds to the limbus
and a second white polytef inlay with an 8 mm chord length
corresponds to the central zone of the donor cornea.
Slippage of the moist donor cornea at the time of cutting
Figure 8.13: IOWA PK Press Corneal Punch
can cause oval graft. This can be prevented by repeated drying
of the well in which the donor is placed or by using a thin, slightly
moistened layer of cotton in the well.
Rothman-Gilbard Corneal Punch
Corneal Endothelial Punches
It uses a piston which is not spring loaded. The suction block
To cut a donor button from endothelial side corneal punches are has 8 evenly spaced suction holes which anchor the corneal
also available which use disposable trephine blades. The button firmly so that there is minimal movement during
advantage of corneal punch is that they yield sharp vertical cuts trephination. The button has eight precisely placed marks and
without beveling.8 can be sutured into the host bed by suturing every mark on the
button with the marks placed on the host bed.
Cottingham Corneal Punch There are four trephine assemblies, which use artificial
anterior chamber. These include Krumeich, Hanna, Olson and
It is a metal punch with a universal style handle. Additionally, it
Lieberman systems. This involves cutting the donor corneas
also has two replaceable base plugs.
from the epithelial side rather than the endothelial side. Pressure
Troutman Corneal Punch in the artificial anterior chamber is adjusted to the intraocular
pressure with the help of attachments of the infusion tubings.
It incorporates a centered block and a piston carrier with a central
piston. The piston accommodates blades of 7 to 9 mm. This relies CUTTING INSTRUMENTS
on the surgeon’s thumb to incise the cornea.
Blade Breaker
IOWA PK Press Corneal Punch
A disposable razor blade is broken and mounted on the tip of a
It incorporates a spring-loaded piston with an expandable edge metallic pencil handle. This is one of the best instruments
to accommodate 6 to 9.5 mm trephines to harvest various sizes available for cutting tissues in straight or curved lines. Blade
the donor graft from the endothelial side. It has a unique two- breaker is used to enter the anterior chamber in a controlled
color cutting block which aids in centration of the donor tissue. manner after a deep cut has been created in the recipient’s cornea
The recessed base assumes that the block is held centrally under by a trephine. Blunt side of the blade can sometimes be used
the trephine block (Fig. 8.13). for blunt dissection of adherent iris.

Lieberman Gravity-action Punch Diamond Knife


It is a guillotine-style punch with a heavy head, which uses the This is the sharpest cutting instrument and available in various
force of gravity rather than the surgeon’s hand to punch the sizes and shapes. It is the most durable instrument and useful
cornea. for stab incisions as well as to complete the trephine cuts.

58
Corneal Scissors is the prototype of this variety. It can be used for suture tying
and to bury the suture knots.
Ideally, all corneal scissors should have an immobile lower blade.
Troutman microscissor (Figs 8.14A and B) is the prototype,
Forceps with Special Functions
which has blades 5 mm in length and is curved on a radius of 5
mm. The lower handle, which controls the upper blade, has a • Double corneal forceps, Colibri style – It has two 2.75 mm
flexible spring. This is a very light and fine scissors and mainly long tips separated 1 mm with 0.4 mm Pierse tips. It is 72
used to complete the cutting of the trephine incision. The blades mm long and has a serrated handle.

Chapter 8: Surgical Instruments for Penetrating Keratoplasty


should be kept vertical and must be curved to follow the • Colibri-style Polack double corneal forceps – It is used
curvature of the trephine, while cutting the host cornea. It is often for the first corneal suture. The cut edge of the graft is gently
used to remove the irregular tags from the wound margin. grasped at the junction of the epithelium and stroma with
Corneal scissors are used to complete the trephination of the host fine toothed forceps (Fig. 8.17).
cornea after creation of the circular cut following anterior
chamber entry. Curved Vannas Scissors can also be used for the HOLDING INSTRUMENTS
same (Fig 8.15).
Needle holders used in ophthalmic microsurgery consists of two
handles, which are supported between index finger and thumb.
GRASPING INSTRUMENTS
Needle holder (Fig. 8.18), which is lightweight, with nonslip
Varieties of forceps are used for penetrating keratoplasty. curved handle and curved jaws is preferred for penetrating
However, they can be broadly classified into toothed, non- keratoplasty. The curvature of the jaw varies from a uniform
toothed or forceps used for special purposes. smooth to a hockey stick shape. The jaws should be atraumatic
to the steel needles but the grip should be firm. Barraquer’s
Toothed Forceps curved needle holder is an example.
• Pierse-Hoskin’s forceps It is a fine toothed tissue holding
forceps are used to hold the corneal tissue firmly. Pierse-
Hoskin’s forceps is the most frequently used tissue holding
forceps in corneal grafting surgery. It is a 2 × 1 fine toothed
lightweight instrument and extensively used for suture tying.
• Colibri forceps This is another example of tissue holding
forceps (Fig. 8.16).

Non-toothed Forceps Figure 8.15: Curved Vannas scissors


(Courtesy: Katena products)
The non-toothed forceps have flat edges that help in holding or
picking up structures like 10-0 nylon suture. McPherson forceps

Figure 8.16: Colibri forceps (Courtesy: Katena products)


Figure 8.14A: Right Troutman scissors
(Courtesy: Katena products)

Figure 8.14B: Left Troutman scissors


(Courtesy: Katena products) Figure 8.17: Polack forceps (Courtesy: Katena products)
59
observed ovality implies excessive curvature in the axis of
the shortest diameter of the oval. This is used for readjusting
and replacement of the sutures and helps to reduce
astigmatism intraoperatively and postoperatively.

ACKNOWLEDGMENTS

• Dutch Ophthelmic Research Center, DORC Middle East,


Section II: Penetrating Keratoplasty

Figure 8.18: Titanium Needle holder Dubai, UAE


(Courtesy: Katena products)
• Katena Products, Denville, NJ, USA.

REFERENCES
SPATULAS AND HOOKS
1. Vajpayee RB, Melki S. Three pearls to minimize penetrating
These are mainly used in the reconstruction of the anterior keratoplasty astigmatism. In: 101 pearls in Refractive, Cataract
chamber, the manipulation of the iris, and assistance in and Corneal Surgery 2001 Eds. Melki SA, Azar DT. SLACK Inc.,
intraocular lens placement. A double-ended iris repositer is useful Thorofare, New Jersey. Chapter 20:161-62.
for lysis of synechiae between the iris and lens capsule, dissection 2. Schanzlin DJ, Robin JB, Spence DJ. Clinical and ultrastructure
of iris from retrocorneal membranes and iris supported implants, analysis of variable speed corneal trephination. Ophthalmic Surg
lysis of broad based anterior synechiae, and sweeping the donor 1983;11:730.
tissue to undermine its edges below the host tissue. Intraocular 3. Drews RC. Corneal trephine. Trans Am Acad Ophthalmol
Otolaryngol 1974;78:223.
lens manipulators such as Sinskey and Lester hooks are very
4. Donaldson WBM, Haining WM. A new corneal trephine.
useful for placing and stabilizing an anterior chamber lens. Ophthalmic Surg 1979;10:55.
5. Smirmaul H, Casey TA. A clear view trephine and lamellar
QUALITATIVE KERATOMETERS dissector for corneal grafting. Am J Ophthalmol 1980;90:92.
6. Wiffen SJ, Maquire LJ, Bourne WM. Keratometric results of
The keratometers are very helpful to assess the degree of corneal penetrating keratoplasty with the Hessburg-Barron and Hanna
toricity at the end of the surgery. These can be of two types trephine systems using a standard double running suture
depending on whether they are attached to the microscope or technique. Cornea 1997;16:306.
they are hand-held. 7. Mader T, et al. Comparison of three corneal trephines for use in
• Keratometers with microscopic attachment – There are a theraeutic keratoplasties for large corneal perforations.
number of surgical keratometers like Smirmaul, Troutman Ophthalmic Surg 1995;26:209.
and Terry that are physically attached to the microscope and 8. Legeais JM, Parel JM, Simon G, Ren Q, Denham D. Endothelial
damage by the corneal Hessburg-Barron vacuum trephine.Refract
work by reflecting projected light off the surface of the cornea.
Corneal Surg 1993;9:255-8.
However, these are not portable and require a regular smooth 9. Denhem D, et al. Endothelial damage by the corneal hessburg-
refracting surface to reflect the image and are quite expensive. barron vacuum trephine. Refract Corneal Surg 1983;9:255.
• Handheld keratometer – Simpler, cost-effective and 10. Wilbanks GA, Cohen S, Chipman M, Rootman DS. Clinical
portable methods as Mandel intraoperative keratometer and outcomes following penetrating keratoplasty using the Barron-
Maloney keratometer are available which work by reflecting Hessburg and Hanna corneal trephination systems. Cornea
a circle from the corneal surface. Maloney keratometer is a 1996;15:589-98.
11. Seitz B, Langenbucher A, Diamantis A, Cursiefen C, Kuchle M,
titanium cone-shaped instrument, which is designed to reflect
Naumann GO. Immunological graft reactions after penetrating
the microscope light in rings on the cornea to detect
keratoplasty - A prospective randomized trial comparing corneal
astigmatism. In the absence of the expensive intraoperative excimer laser and motor trephination. Klin Monatsbl Augenheilkd
surgical keratometers, a safety pin can also be used to [German], 2001;218:710-9.
monitor the intraoperative astigmatism. The circle of the 12. Amsler M, Verry F. The removal of the graft for keratoplasty.
safety pin is reflected off the corneal surface and any Arch Ophthalmol (Paris) 8:150,1948.

60
9

Chapter 9: Suture Materials and Needles


Suture Materials and Needles
Rajeev Sudan, Sameer Kaushal

SUTURES strength that is maintained for many years. It has virtually no


tissue reaction and being the most inert material, is well accepted
Suture materials have an important bearing on anatomical and
by the tissues. Prolene resists microorganisms and tissue
functional success of penetrating keratoplasty. A judicious choice
enzymes. It is easy to remove when indicated, as it does not
of sutures, suture placement techniques and suture adjustment
adhere to the tissue. However, it is a stiff material and thus
can go a long way in reducing postoperative astigmatism.
difficult to handle. It is highly elastic and can stretch up to
Braided silk sutures were commonly used in penetrating
38 percent of its original length.5 Compared to nylon, it has a
keratoplasty before the advent of monofilament synthetic
longer life since it does not undergo hydrolytic degradation.
material. The braided silk sutures had the advantage of greater
Therefore unlike nylon, it does not produce the long term suture
tensile strength, extensibility, knot control, pliability and
relate complications due to loose or broken suture.3,4 Prolene is
resistance to shearability. However, it has been completely
rarely used as a single suture in keratoplasty but is used in
replaced by non-absorbable monofilament materials because of
combination in continuous interrupted pattern of suturing. Good
its rapid degradation and excessive tissue reactivity.
results have been reported with it because of its low tissue
reactivity, high tensile strength and non-absorbability.6 Prolene
Nylon
because of non-biodegradability is used for iris repair or scleral
Nylon is the suture of choice in keratoplasty because of low tissue fixation of posterior chamber lens.
reactivity. Its monofilament character permits a smooth passage
through corneal tissue and a lesser tissue reaction. It is easy to Polyester (Mersilene)
handle and is very pliable. It maintains its tensile strength for
more than 1 year allowing adequate time for wound healing. It is biodegradable material and thus allows long-term tension
Nylon requires a greater care while adjusting tension and tying maintenance in keratoplasty incision. Polyester is stronger as
the knot because of its high elasticity. A tight appearing suture compared to Nylon with lesser elasticity. It has a stretch factor
may have an inadequate tension and vice-versa. of only 1 percent.5 This helps in better control of intraoperative
Nylon because of its gradual hydrolytic degradation can wound tension. Thus, a better control of postoperative
result in breakage of suture as well as relaxation of wound astigmatism is possible by suture adjustment without the need
tension. The broken suture tip can produce irritation, for suture removal.
vascularization, graft injection and rejection. Thus, it is The suture is however stiff with difficulty in handling and
preferable to remove the sutures at an appropriate interval.1-4 requires precise tensioning. Moreover, its pale green color is
10/0 is the most frequently used size because of its ease of difficult to differentiate from the background of the operative
placement and tensile strength, though 9/0 and 11/0 is also field. Early experience has shown that it has higher tissue
sometimes employed. 11/0 suture is rarely employed alone reactivity. Case reports of necrotizing scleritis has been reported
because of its lack of strength. It is most commonly used as a with the use of polyester suture.7 It attracts particulate material
running suture in conjunction with 10/0-interrupted suture or as and thus, requires particle free field. The rate of infiltration,
double running suture. infection, neovascularization and handling complications such
as exposed knots, loose and tight sutures and wound leaks are
Polypropylene (Prolene) higher.8 It has been shown to have a five-fold increase in handling
It is a non-absorbable suture material, which has been used as related complications and a two-fold increase in tissue related
haptic material for intraocular lenses. It has an excellent tensile complications when compared to nylon.

61
NEEDLES which require the surgeon to be vigilant in the presence of
edematous tissues
A good surgical needle should be–
i. Strong enough to withstand mechanical deformation. Mini Curve Needles
ii. Long enough to be passed through the wound and retrieved
without the need to hold the point. Mini curve needles have their cord length and radius of curvature
iii. Sharp cutting edge. significantly smaller than the full curve needles. These needles
iv. Atraumatic. have the advantage of making shorter and deeper bites. However,
Section II: Penetrating Keratoplasty

The composition of the needle should provide enough they are difficult to handle because of smaller size and tight radii.
strength to withstand mechanical force but should yield enough
not to get fractured. Bicurve Needles
A brief nomenclature of the needles used in keratoplasty Bicurve needles also achieve short and deep bites but are easier
is as follows: to handle. The design has an average to flat radius of curvature
• Length: It is the total distance of the needle from point to from the swage to midportion and a much steeper or tighter
swage before bending. radius from midportion to needle point. The architecture permits
• Cord length: It is a straight-line distance from point to swage an easier handling and a rapid turn out after a deep bite.
after bending.
• Curvature: It is that portion of circle to which the needle is Compound Curve Needles
bent.
It is a further modification of a bicurve design. The needle has
• Diameter: It is the diameter of the original wire from which
an initial flat curve changing to a steeper curve with a sharp
the needle is made. It is measured in thousand of an inch or
straight point. The straight portion facilitates initial entrance and
mils (1 mil = 0.001 inch).
penetration to a depth and steep curve immediately behind the
• Regular cutting: Regular cutting needle has a cross-section
point and assures a rapid turnout.
of a triangle with the base down. It can easily traverse tougher
tissues such as full thickness scleral grafts and through and
REFERENCES
through corneal bites.
• Reverse cutting :It is a cross-section of a triangle with apex 1. Dana MR, et al. Suture erosion after penetrating keratoplasty.
down. Cornea 1995;14:243.
• Spatulated: Spatulated needle has a flattened reverse cutting 2. Sullivan LJ, Su C, Snibson G, Taylor HR. Sterile ocular
point without a third cutting edge on the bottom. Spatulated inflammatory reaction to monofilament suture material. Aust N
ZJ Ophthalmol 1994;22:175-81.
needles work better for intra-lamellar work such as lamellar
3. Landau D, Siganos CS, Mechoulam H, Solomon A, Frucht-Pery
keratoplasty, cataract incision closure, etc. J. Astigmatism after mersilene and nylon suture use for
• Tapered circular cross-section: This needle has the advantage penetrating keratoplasty. Cornea 2006;25:691-4.
of causing smaller tract in soft tissue and in conjunctiva. It 4. Bartels MC, van Rooij J, Geerards AJ, Mulder PG, Remeijer L.
is difficult to penetrate cornea and sclera with this needle. Comparison of complication rates and postoperative astigmatism
All keratoplasty needles are spatulated reverse cutting with between nylon and mersilene sutures for corneal transplants in
a smaller less traumatic point. patients with Fuchs endothelial dystrophy. Cornea 2006;25: 533-
9.
The different needles used in keratoplasty are:
5. Alcon Laboratories: Manufacturers’ specifications, Alcon
a. Full curve needles
Laboratories, Fort Worth, Tx, 1998.
b. Mini curve needles 6. Faggioni R, deCourten C. Short and long term advantages and
c. Bicurve needles disadvantages of prolene monofilament sutures in penetrating
d. Compound curve needles keratoplasty. Klin Monatsbi Augenheilk 1992;200: 395-7.
7. Stokes J, Wright M, Ramaesh K, Smith C, Dhillon B. Necrotizing
Full Curve Needles scleritis after intraocular surgery associated with the use of
polyester nonabsorbable sutures. J Cataract Refract Surg
These are most frequently used in keratoplasty as well as in most 2003;29:1827-30.
anterior segment surgeries. Their curvature ranges from 140 to 8. Bertram BA, et al. Complications of Mersilene sutures in
180o. These needles achieve long and somewhat shallow bites, penetrating keratoplasty. Refract Corneal Surg 1992;8:296-305.

62
10

Chapter 10: Technique of Penetrating Keratoplasty


Technique of Penetrating Keratoplasty
Namrata Sharma, Chandra Shekhar Kumar, Samir A Melki, Rasik B Vajpayee

Penetrating keratoplasty is the corneal transplant procedure in • Pupillary Management: In cases of phakic keratoplasty
which the full thickness diseased host corneal tissue is excised without combined cataract surgery, two drops of 2.5 percent
and replaced with healthy donor cornea. The objectives of pilocarpine may be instilled 5 minutes apart at the time of
penetrating keratoplasty are to: Honan balloon placement to constrict the pupil and to protect
• Establish a clear corneal visual axis. the crystalline lens. If a combined cataract procedure is
• Minimize refractive error. anticipated, the pupil is dilated as for cataract surgery: 2.5
• Provide tectonic support. percent phenylephrine and 1 percent cyclopentolate drops
• Alleviate pain. every 5 minutes for three times.
• Eliminate infection. • Donor Corneal Tissue Management: The surgeon should
Penetrating Keratoplasty is a major intraocular surgery and personally supervise the donor tissue and the history of donor.
requires a meticulous surgical preparation of the patient, Defects may include infiltrates, retained glass or other foreign
operation theater, instruments, etc. and precise practice of debris, scars/lacerations or other pathology. Some donor
planned surgical technique by the surgeon. corneas may have undergone refractive surgical procedures
like photorefractive keratotomy and LASIK. To be able to
PREOPERATIVE PREPARATION exclude use of such tissue, a videokeratography of the donor
eyeball may have to be performed.
• Infection Control: Use of topical preoperative anti-biotics
may help to reduce the incidence of graft infection and ANESTHESIA
endophthalmitis. Topical instillation of 0.3 percent
Ciprofloxacin or 0.3 percent Ofloxacin eye drops four times Penetrating keratoplasty can be performed safely under local or
daily 2-3 days prior to the surgery is advisable. The common general anesthesia.3,4 The patient’s age, cooperation during
source of infection after a penetrating keratoplasty is usually surgery influences the choice of anesthesia. General anesthesia
from the patient’s ocular and periocular flora. The is indicated in pediatric cases and in uncooperative adults with
preoperative lid preparation should include treatment of mental impairment, deafness, aphasia, language barrier, etc. It
blepharitis and painting the lid margin and surface with 5 is also indicated in perforated corneas and in inflamed eyes where
percent povidone-iodine solution. local anesthesia is difficult to obtain.
• Decrease in Corneal Neovascularization: Various Local anesthesia can be given by retrobulbar or peribulbar
modalities that have been tried to decrease the corneal blocks.3 Long lasting anesthetic agent such as bupivacaine alone
neovascularization include preoperative steroids, or combinations of bupivacaine with lidocaine should be used.4
electrocautery, argon laser photocoagulation and adrenaline A complete lid and extraocular muscle akinesia is essential to
soaked sponges.1,2 However, most of these techniques have eliminate intraoperative pressure elevations associated with
not yielded desired and consistent results in moderate to muscle contraction. A good hypotony should be achieved
severe vascularization and are no longer used. preoperative by means of intravenous mannitol or digital
• Intraocular Pressure Control: The lack of positive pressure massage or Honan balloon.
appears to play a significant role in reducing endothelial and
lens complications intraoperatively. A good hypotony should SURGICAL PREPARATION
be achieved preoperatively by means of intravenous
Painting and Draping
mannitol, digital massage or a Honan balloon. Honan balloon
may be applied for 30 minutes at 30 mm Hg of pressure. It The surgical field should be cleaned and draped appropriately
decreases posterior pressure during open sky phase of surgery with the aim of providing a sterile field. The skin of the
and the risk of vitreous loss and choroidal hemorrhage. periorbital area may be painted with 5 percent povidone-iodine. 63
Ideally an adhesive drape should be placed in such a manner so has been damaged or lost during the trephining maneuvers. That
that the lid margins as well as the eyelashes are kept out of the is why it is important to first procure a good quality donor button
surgical field. before trephining the host cornea.

Exposure and Insertion of Lid-speculum Graft Host Disparity

To be able to perform all the surgical maneuvers required for The selection of the graft size depends on the planned diameter
corneal transplantation surgery a good exposure of the eyeball of the host cut. There are various factors, which determine the
Section II: Penetrating Keratoplasty

is mandatory. Also, any inadvertent pressure exerted by the graft host disparity. Barron has highlighted certain facts about
speculum should be avoided as it may raise the IOP and cause the graft host disparity.6
globe distortion that can lead to oval or irregular trephination, • If the diameter of the recipient bed is larger than 9 mm or
poor suture alignment and increased postoperative astigmatism. smaller than 7 mm, the graft should be larger than the host
We frequently use Barraquer wire speculum as it is lightweight, by 1 mm.
easy to insert and exposes the globe adequately. However, in • If the diameter of the recipient is between 7 mm and 9 mm
certain cases it can raise positive vitreous pressure and it is ideal and the eye is aphakic, the graft should be larger than the
to use separate wire specula put under each lid and taped or tied host by 0.5 mm, however, if the eye is pseudophakic or
to the drapes. Some surgeons use lid-sutures to expose the globe. phakic, the graft should be 0.25 mm larger than the host.
Superior and inferior recti may be bridled to stabilize the • With the recipient bed of 7.5 mm, a 0.5 mm oversized graft
eye. Additionally, in cases with small palpebral fissure, lateral induces myopia of 4 diopters; with an 8.0 mm recipient bed,
canthotomy may be performed to increase the area of exposure. a 0.5 mm oversized graft induces 2.5 diopters of myopia.
• With a 7.5 mm bed, a 0.25 mm oversized graft does not
Placement of Scleral Fixation Ring usually induce any refractive error.
• A graft which is the same sized or smaller than the recipient
Patients of high myopia, pediatric age group, keratoconus, etc. opening decreases the myopia but can result in a flat cornea
have low ocular rigidity and can develop scleral collapse after which may not be amenable to contact lens fitting.
the trephination of recipient cornea. The resultant displacement • Most corneal surgeons use a 0.5 mm oversized graft for their
of iris, lens and vitreous can cause extrusion of lens and vitreous routine cases. In certain situations like keratoconus, the graft
loss. Even if there is no resultant complication, the collapse of host disparity is less, i.e. 0.25 mm to compensate for the
the recipient corneal rim makes suturing very difficult. Some associated myopia.
surgeons prefer to use scleral-supporting devices in such patients. Some surgeons prefer to use a 0.5 mm oversized donor graft
These scleral support rings include McNeill-Goldman scleral and for all the cases including those with keratoconus. Irrespective
blepharostat ring and Flieringa ring. The size and the placement of the diameter of the host cut, we use 1 mm oversized grafts in
of any such ring must be such that it does not interfere and hinder cases with severe corneoiridic scars7 and pediatric eyes.8
maneuvers required to perform the procedure of penetrating The donor cornea may be cut using one of the following
keratoplasty or distort the globe. The fixation ring diameter is methods:
sized to measure slightly less than the interpalpebral opening. • Harvesting the donor graft from the whole globe stored in a
The ring should be sutured with only enough force to rest gently moist chamber using hand-held or suction fixation trephines.
on but not to press the sclera. The scleral fixation ring is sutured • Harvesting donor graft from McCarey-Kaufman preserved
with interrupted 7-0 vicryl sutures with 50 percent of the corneoscleral button using hand-held trephines or endothelial
thickness of scleral bite. These sutures should be passed from punch systems.
periphery to the limbus. Fixating the ring just peripheral to the • Harvesting the donor cornea using artificial anterior chamber
limbus gives maximum scleral support. These rings can also be maintainer.
grasped during trephination to fixate the globe.
Many surgeons have however abandoned the use of fixation Harvesting the Donor Graft from the Whole Globe
rings as these may cause distortion of the globe, especially in Stored in a Moist Chamber Using Hand-held or
pediatric and aphakic patients where the scleral rigidity is low, Suction Fixation Trephines
resulting in ovalling of the trephined opening.5
In this technique, the donor graft is cut from the epithelial side
TREPHINATION OF DONOR CORNEA and the grafts are the same sized or 0.25 mm larger than the
intended recipient opening. Many surgeons who do not have
It is recommended that the donor corneal button be cut before access to the McCarey-Kaufman preserved corneoscleral buttons,
the recipient cornea. This helps to ensure that a good quality especially in developing countries, use the whole eye globe which
and optimally prepared donor button is available prior to is fixated in the gauze piece or on a Tudor Thomas stand.
trephination of the recipient cornea. At times it has happened The globe in a moist sterile gauze piece is held in the non-
that the donor button has been cut in an irregular manner and dominant hand, taking care that the cornea is perpendicular to

64
the gauze piece. If the eye is tilted, the cut may be misdirected. and through trephining of the donor button. The punched cut
Through a small stab incision in the limbus one may inject corneal button either stays in the well of the teflon block or
viscoelastic into the anterior chamber prior to trephination. Then may pass up into the barrel of the blade. If the donor button
using a sharp trephine in the dominant hand, the blade is placed has been sucked inside the trephine, a viscoelastic substance
centrally on the donor eye. Using counter pressure with one hand, like 2 percent methyl cellulose is gently squirted into the
the trephine is firmly placed into the cornea and rotated with barrel to dislodge the button. In order to confirm that the
the fingers while exerting pressure downwards. A release of donor button has been cut circumferentially all around, the

Chapter 10: Technique of Penetrating Keratoplasty


pressure will be noted when the anterior chamber is entered. peripheral skirt of the corneoscleral rim may be retracted over
Trephination must then stop immediately, otherwise the the barrel of the trephine.
endothelium will come in contact with the iris. The initial cut is The button is grasped with a forceps and placed epithelial
finished with the scissors, taking care not to shelve the edge. If surface down over the graft holder. The endothelium is
minimal pressure is used, an air bubble will spontaneously fill covered by viscoelastic to prevent desiccation.
the chamber and protect the endothelium from the iris and the • Using the corneal endothelial punch systems Corneal
lens. The cut is completed with the curved corneal scissors. endothelial punch system incorporating the use of a
The donor button is then picked with the Pierse Hoskins or disposable circular trephine is an ideal technique to harvest
a Colibri forceps and is placed endothelial side up on a drop of the graft from the donor button and most surgeons prefer to
balanced salt solution on a glass Petri dish. Viscoelastic/MK use these systems. However, use of these systems is not very
medium (if available) may be placed on the endothelial surface frequent in developing countries due to the cost factor.
to prevent it from drying while the recipient cornea is being Various corneal punches that can be used to harvest donor
trephined. The Petri dish is then covered and placed at a safe graft include Cottingham punch, Barron vacuum donor
and designated place. corneal punch, IOWA PK Press corneal punch and Rothman-
Gilbard corneal punch. These punches make a sharp vertical
Harvesting the Donor Graft from cut with relatively more accurate centration. These punches
Preserved Corneoscleral Button can use trephine blades of various diameters. The basic
method of punching is similar for all the trephine systems.
It has been observed that the corneal grafts cut from the
The corneoscleral donor button is placed endothelial side
endothelial side are smaller by 0.2 mm to those cut from the
epithelial side.6-9 Since most surgeons prefer to cut the graft up on a cutting block and a barrel mounted circular trephine
is brought down through the central part of system in a single
from the endothelial side, it is advisable to oversize the graft
motion cutting the donor button.
by 0.25-0.5 mm. Principally, depending on the availability of
the types of trephines, one of the two techniques may be used to The functioning of Barron vacuum donor cornea punch
is slightly different. This punch consists of nylon cutting
punch the preserved corneoscleral donor button, i.e. the hand-
block, seating ring and a blade. The cutting block has 4 holes
held trephines and the endothelial punch systems.
• Use of hand-held trephines This technique is used in most into which the steel guidepost of the blade fit to ensure that
the blade is perpendicular. The well of the cutting block has
developing countries, where the endothelial punches may not
a diameter of 19 mm and a radius of curvature of 25.4 mm,
be available due to increased expense.
The donor button is cut over a cutting block, which may except for the central 11 mm, which has a radius of curvature
of 10 mm. The well has a central positioning hole, as well
be made of Teflon, Nylon or Paraffin and has a concave
as four additional holes and a circular trough 12 mm in
depression, or a well in which the donor cornea is placed
with epithelial surface down.10 Various trephines have been diameter that are connected by a silicone tube to a 5 ml
syringe with a spring loaded plunger. The syringe creates
developed for cutting the donor cornea but a standard
suction that holds the cornea in place as it is cut and ensures
trephine consists of a disposable circular stainless steel blade
on a handle. The blade should be properly secured on the that the corneal button remains in the well, and not in the
blade, after the cut has been made. When inked with gentian
handle and the obturator fully retracted to avoid its contact
violet, the four holes in the well mark the cornea for accurate
with the endothelium. Donor cornea should be cut by
punching rather than rotating the blade.10,11 Rotation of the placement of the cardinal sutures.
blade results in more endothelial damage. The blade should
Trephining the Donor Cornea Using Artificial
always be held perpendicular to or centered on the cutting
Anterior Chamber Maintainer
block. The slipping of blade should be guarded against, as
it can result in oblique cutting of the cornea with resultant An Olson calibrated cornea trephine system is also used to cut
irregular or oval button with beveled or ragged edge. These the donor tissue. The system consists of an anterior chamber
irregularities can distort the wound and cause significant maintainer, a re-usable blade holder (with micrometer setting),
postoperative astigmatism. and a suction ring attached to a syringe. A small drop of
A uniform pressure should be applied over the blade with viscoelastic is placed on the top of the endothelium of the donor
the thumb and an audible click signifies the complete through tissue and the tissue is centered on to the anterior chamber
65
maintainer (epithelial side up). Air is used to create the anterior
chamber. The suction ring is placed on the donor cornea and is
activated by releasing the syringe. Following placement of the
trephine (which consists of the blade holder with the blade) on
the suction ring, the lever of the suction ring is pressed to lower
the blade onto the donor tissue and the trephine is turned to
complete the cut.
Section II: Penetrating Keratoplasty

Non-mechanical Laser Trephination


Nonmechanical laser trephination can also be performed from
the epithelial side on the donor. This avoids the mechanical
distortion during trephination resulting in smooth almost
perpendicular edges that are congruent in the donor and thus
potentially improves the optical performance after trans-
plantation.12 Figure 10.1: Vernier calipers used
for marking the geometric center
Trephination of the donor cornea is done using a 193 nm
excimer laser. A circular round metal aperture mask consisting
of eight orientation teeth (diameter 7.6 to 8.1 mm; central
opening 3 mm for centration) are positioned on a corneoscleral
button (16 mm diameter) fixed in an artificial anterior chamber
maintainer under microscopic control.13 The pressure within the
artificial chamber maintainer is adjusted to 20 mm Hg by
attaching it to an infusion system. Using an automated rotation
device for the artificial chamber (four rotations per minute),
approximately 11,000 laser pulses are necessary to perforate the
cornea focally. After perforation, the remaining stromal lamellae
and the Descemet’s membrane are cut with a curved corneal
microscissors.

MARKING THE HOST CORNEA

The centering of the graft is of utmost importance as any Figure 10.2: Geometric center of cornea marked
decentration may lead to increased risk of graft-rejection, and
high postoperative astigmatism as well as damage to the anterior
chamber angle.
The donor graft is usually centered on the host cornea or
over the pupillary axis.14 A decentered graft may be preferred
in certain situations.6 In a cornea with peripheral perforation, a
decentered graft which encompasses the area of perforation and
clears the pupil is preferred in comparison to a large, centered
graft.
If a previous decentered graft has failed, the previous
keratoplasty wound is ignored and the second graft is centered
on the geometric center of the cornea. The geometric center is
located by measuring the horizontal and vertical diameter of the
cornea with calipers (Fig. 10.1), halving each measurement and
finding the point at which the horizontal diameter line bisects
the vertical one. A centration mark is made on the anterior corneal Figure 10.3: Marks applied with suture marker using
gentian violet
surface with a surgical marking pen (Fig. 10.2).
After marking the geometric center of the cornea or the
center of the pupil, radial keratotomy markers [8 arms, 16 arms] antitorque and no torque15 The cornea should be thoroughly dried
may be used for creating impression marks guiding exact suture before putting the marker. The arms of the suture markers are
placement. We have designed a Vajpayee’s corneal marker which stained with gentian violet and the marker is pressed on the
has 20 radial arms and can be used to guide the placement of 20 corneal surface of the recipient (Fig. 10.3). While using such
bite single continuous sutures of various types such as torque, marker, care should be taken to ensure that the center of the
66
marker and the previously marked geometric center on the host
cornea coincide.

TREPHINATION OF THE RECIPIENT CORNEA

The size of the area on the diseased cornea to be trephined


depends upon many factors. These include diameter of the
patient’s cornea, extent of corneal disease and avoidance of use

Chapter 10: Technique of Penetrating Keratoplasty


of very small and very large grafts. The size of host cut guides
the diameter of the donor graft. Very small and very large host
cuts and corresponding diameters of donor graft may be
associated with occurrence of certain complications. While grafts
smaller than 6.5 mm can cause a high postkeratoplasty
astigmatism, a large sized host cut requiring placement of a
corresponding large donor button may carry a risk of
immunological rejection.17-19 We generally create a host cut Figure 10.4: Hand-held trephine used for trephination
ranging from 7 to 8 mm in routine cases. A larger host cut may
be needed in cases of infectious keratitis or in keratoconus. In
cases of keratoconus it is imperative that whole of the cone is
included in the host cut. Additionally, patients with poor
endothelial cell function such as Fuchs’ dystrophy or
pseudophakic or aphakic bullous keratopathy may benefit from
increased number of endothelial cells in a larger graft.
Based on the host corneal diameters and the induced myopia
after penetrating keratoplasty, the following recommendations
have been made. In patients with larger-than-average corneal
horizontal diameter (limbal white-to-white measurement ≥ 12.5
mm) an 8.25 or 8.5 mm host trephine be used and for patients
with a smaller-than-average corneal diameter (white-to-white
measurement ≤ 11.5 mm), a 7.5 or 7.75 mm trephine should be
used.
For cutting the recipient cornea the conventional hand-held Figure 10.5: Partial thickness mark given
trephines as well as the suction and automated trephines have by hand-held trephine
been used. Uniformity of the cuts varies with the trephine type
and an ideal trephine, which provides straight cuts without tissue
be thoroughly dried before trephining. The trephine is held
distortion, is not yet available. Graft curvatures are generally perpendicular to the cornea and positioned by aligning the center
greater with suction trephines than the hand-held ones. of this blade with the centration mark on the cornea and checking
the amount of cornea surrounding the blade (Fig. 10.4). The
Trephining with Hand-held Trephines
trephine is then rotated between the thumb and the forefinger
The “standard” trephine, i.e. Castroviejo trephine consists of a maintaining a downward pressure. Care is taken to avoid
circular blade on a handle. The circular blade can be used alone. applying undue external pressure on the eye with the trephine.
The handle has an internal obturator, which limits the depth of Some surgeons prefer to trephine almost to the full thickness
the cut. The obturator, however, can distort the cornea and cause whereas others recommend a guarded entry (Fig. 10.5). In the
an irregular, non-circular cut if it comes in contact with the former, the cut is perpendicular and allows easier removal of
corneal apex before the blade touches the cornea. This can the host cornea. In the latter, a partial thickness cut up to the
happen most frequently in patients of keratoconus. A disposable pre-Descemet’s membrane is made first. A full thickness cut is
open bladed trephine may be used as it trephines the recipient generally avoided as it may cause an uneven entry into the
without distorting the cornea and simultaneously allows anterior chamber, which may lead to its collapse; further pressure
visualization of the optical centration mark. applied may lead to damage of iris or lens or extrusion of the
The optical axis of the recipient’s cornea is marked by the lens. Once a partial thickness cut is made, anterior chamber entry
surgeon, using wherever possible the central point, as described is done with a blade, most conveniently at 11 o’clock position.
earlier. The blade of the trephine should always be examined The escape of the aqueous should be carefully noted to
under microscope to check for the regularity and sharpness of ensure a full-thickness incision. If the aqueous humor is not seen,
the edge before proceeding to trephination. The cornea should it is possible that the host’s Descemet’s membrane has been

67
Section II: Penetrating Keratoplasty

Figure 10.6A: Corneal scissors used to cut the cornea Figure 10.6B: Corneal scissors completes the excision of the
recipient bed

detached from the posterior stroma. This occurs most likely in


patients with bullous keratopathy and CHED and if inadvertently
left, may result in double anterior chamber postoperatively.
Viscoelastic substance, such as hydroxypropylmethyl
cellulose (2%) or sodium hyalunorate (1%), is injected from the
entry site to deepen the anterior chamber. This protects the iris
and the lens against any possible trauma with the scissors blade.
Corneal scissors used to complete the cut should have a longer
posterior blade and a blunt tip to protect iris and the lens
(Fig. 10.6A). The blade of the corneal scissors should be held
perpendicular to the cornea, so as to achieve a vertical cut. The
cornea is cut full thickness along the trephine cut by closing the
scissors as an upward pressure is applied. This is done to prevent
the scissors from plunging posteriorly and damaging the iris and
the lens. Some surgeons prefer to hold the scissors slightly Figure 10.7: Posterior ledge cut with Vannas scissors
obliquely to leave a small posterior ledge along the recipient
cut (Fig. 10.6B). It helps in avoiding inadvertent cutting of the Trephining the Recipient Cornea with
iris and the presence of a posterior ledge offers better apposition Suction Trephine
while suturing. The cornea must be stabilized with the forceps
once half of it has been cut. Any iris or vitreous attachment to Suction trephines like Barron radial vacuum trephine can also
the posterior surface is severed with the scissors before lifting be used for trephining the host corneas16 (Fig. 10.8). These fixate
the corneal button. the cornea by suction during trephination and are particularly
In perforated corneas, the anterior chamber is frequently useful in perforated corneas and result in less anterior chamber
shallow and entering the anterior chamber through the cut collapse and corneal distortion.20-22 These create a sharper,
obtained by the trephine may cause damage to the underlying deeper and more perpendicular incision than free blades.
iris and the lens. In such cases, the posterior blade of the scissors The Barron radial vacuum trephine is available in diameters
may be inserted through the site of the perforation and cuts can of 6.0 to 9.0 mm, in 0.5 mm increments, as well as a diameter
be made radially towards the trephine cut like the spokes of the of 7.75 mm. This trephine consists of a body and a blade
wheel. assembly. The body contains two plastic struts for holding and
If some posterior tags of the corneal tissue are inadvertently stabilizing the trephine and a circular vacuum chamber is
left at the edges of the trephined area, these are trimmed with a recessed slightly relative to the outer wall to account for the
curved corneal or Vannas scissors (Fig. 10.7). The anterior anterior corneal curvature. The vacuum chamber is connected
chamber is filled with a viscoelastic to maintain the dome and by a silicone tube to a 5 ml syringe with a spring-loaded plunger.
the orientation of the donor button for accurate placement of The blade assembly contains a blade, cross hairs for centering
the sutures and to prevent any endothelial decompensation. the trephine, and four plastic spokes for turning the blade. The

68
inner wall of the body and the outer wall of the blade assembly
are threaded so they fit together in a nut and bolt fashion. The
blade is lowered or raised by turning the spokes clockwise or
counterclockwise, respectively. For each spoke turned, the blade
is lowered or raised approximately 60 mm.
Before placement on the cornea, the trephine is examined
under the microscope and the edge of the blade is aligned with

Chapter 10: Technique of Penetrating Keratoplasty


the inner wall of the vacuum chamber. This position is called
the zero position. The blade is then retracted approximately 0.18
mm by turning the spokes 270 degrees (three spokes), which
prevents the blade from hitting the cornea and interfering with
suction as the trephine is placed on the eye.
The plunger of the syringe is pushed all the way, the cross
hairs of the trephine are aligned with the centration mark on the
cornea, the trephine is pressed evenly and the plunger is released Figure 10.8: Hessberg-Barron suction trephine used to
abruptly. If suction has been obtained, the plunger stops at about trephinate the recipient bed
the 4 ml mark on the syringe. If the plunger rebounds all the
way out, suction has not been obtained and the above process is edges, thus reducing the vertical tilt.12 Trephination is performed
repeated. After suction has been obtained, the position of the using 193 nm excimer laser along metal mask (diameter
trephine on the cornea is assessed by confirming that the cross 12.9 mm; central opening 7.5 to 8 mm; 8 orientation notches
hairs and centration mark are aligned and by checking the amount 0.15 to 0.3 mm) which is placed on the recipient cornea.
of cornea surrounding the outer wall of the vacuum chamber. Manually guided excimer laser is used. For focal corneal
The trephine is stabilized by gently holding the struts, and perforation on an average 7,000 laser pulses are required. To
the cornea is cut by turning the spokes clockwise. The suction complete trephination, the remaining deep stromal lamellae and
orients the trephine perpendicular to the cornea. As the blade is Descemet’s membrane are cut with a curved corneal
lowered, the trephine is steadied but its angle to the cornea should microscissors.13
not be forcible changed. The initial 270 degree (three-spoke)
turn lowers the blade to the zero position. Because of the anterior SUTURING OF DONOR CORNEA
corneal curvature, the cornea is cut slightly when the blade is
lowered to this position. The number of spokes to turn further Placement of the Donor Cornea on the Recipient
depends on the desired depth of cut and the corneal thickness:
The anterior chamber of the host is filled with a viscoelastic,
fewer for a shallow cut or a thin cornea and more for a deep cut
which helps to maintain dome of the donor button and its
or a thick cornea. It is preferred that the cornea be cut as close
orientation for accurate suture placement and further provides
to the Descemet’s membrane as possible, without entering the
endothelial protection. Balanced salt solution or air can be used
anterior chamber. The barrel of the trephine should be watched
for anterior chamber maintenance as well, but they are not so
as the blade is lowered because if the anterior chamber is
effective during the graft placement.
inadvertently entered, aqueous humor will appear in the barrel.
The donor cornea is brought into the field of microscope on
If this occurs, the plunger of the syringe is pushed in all the way,
a graft holder (Fig. 10.9). The edge of the button is placed on
which releases the suction and the trephine is removed from the
eye. After the cut has been made up to 90 percent depth, the
trephine is removed from the eye by pushing the plunger of the
syringe in all the way, which releases the suction. The anterior
surface of the cornea is dried to reveal the 16 radial impressions
made by the trephine, and each impression is marked with a
surgical marking pen containing gentian violet. Each impression
starts 0.2 mm from the edge of the cut and is 0.5 mm in length.
Subsequently, the anterior chamber may be entered with a
diamond blade and the cut is completed with corneoscleral
scissors.

Non-mechanical Trephination of the Recipient Cornea


Non-mechanical trephination of the recipient cornea is associated
with less deformation of the corneal tissue including the
distortion of the cut margins and smoother and congruent cut Figure 10.9: Paton spatula used to hold the graft
69
Section II: Penetrating Keratoplasty

Figure 10.10: First cardinal suture passed Figure 10.11: Second cardinal suture passed

the inferior limbus and the graft holder is slid down so that it Interrupted sutures are recommended in infants and children,
too rests on the limbus. It is then rotated slightly further so that highly vascularized corneas and in therapeutic keratoplasty. They
the anterior layers of the donor button can be grasped with a have the advantage of selective suture removal if need arises,
forceps. Alternatively, the corneal button can be flipped e.g. loose-suture, vascularized suture, suture abscess, etc.
completely over the corneal opening. Inversion of the corneal Interrupted sutures are placed in a manner similar to that used
button should be avoided by noting the orientation of the button for cardinal sutures. The needle should pass anterior to the
in the well or by the curvature of the button. The button is Descemet’s membrane. The suture length should be about 2 mm,
grasped with a “Polack” forceps and brought to the superior edge 1 mm on each side. Full-thickness suture should not be put as
of the recipient corneal opening and sutured to recipient cornea these cause more endothelial trauma and aqueous may leak
with 10-0 nylon suture on a spatulated side-cutting needle. through the suture tracts postoperatively. A total of 16 sutures
are usually placed with second four sutures equidistant between
Placement of the Cardinal Sutures the first four sutures and the second eight equidistant between
It is necessary to place four cardinal sutures first. The first suture the first eight sutures.19 More sutures may be required for larger
may be placed at 12 o’clock position followed by 6 o’clock grafts or in cases in with the recipient cornea is thin. If interrupted
suture (Fig. 10.10). The needle is passed between the two tips sutures are combined with a running suture, a total of 8,12 or
of Polack double corneal forceps exiting just anterior to 16 sutures are usually placed.
Descemet’s membrane. The needle is passed through the The knot ends are trimmed short and buried just beneath the
recipient cornea at the radial marks and should exit at 1 mm epithelium of recipient or the donor cornea. We generally prefer
from the edge. The suture is tied with a triple-throw, followed to bury the knots on the donor cornea as, if buried on the recipient
by two single throws. side, they may stimulate vascularization. However, some
The second suture is placed 180° from the first suture and is surgeons advocate that the knots should not buried on the donor
the most important suture in penetrating keratoplasty as it cornea as on removal they can create traction on the graft and
establishes equal distribution of the tissues (Fig. 10.11). Its result in dehiscence.
improper placement can cause severe postoperative astigmatism. If a single running suture technique is used a 10-0 nylon
The prior placement of radial marks can eliminate this problem. suture is placed after the cardinal sutures are in position and
The third and fourth sutures are placed through the marks 90° 20-24 bites are taken instead of 16. In double running suture
from the first two sutures. The first four sutures are known as technique, an 11-0 nylon suture may be placed between each
the cardinal sutures. The tension on the cardinal sutures should bite of a 16 bites 10-0 nylon suture. When a single running suture
be such that that a diamond-like shape appears after their is used torque, anti-torque or no torque suturing techniques can
placement. be used (Fig. 10.12). Each of these continuous suturing
techniques is amenable to suture adjustment in cases of
Placement of the Other Sutures astigmatism.

The rest of the sutures may be put as interrupted sutures, a single


Check for Wound Leakage
running suture or double running sutures. Long-term follow-up
shows no significant difference in astigmatism between the suture After the completion of the suturing, the wound is tested for water
techniques.23 tightness. This is done after drying the surface with a cellulose

70
may be manipulated towards the smallest diameter of the oval
so that a circular mire is obtained (Figs 10.13A and B).

INTRAOPERATIVE MEDICATIONS AND


POSTOPERATIVE REGIME

A subconjunctival injection of an antibiotic (gentamicin 20 mg)


and steroid (dexamethasone 4 mg) combination is given in

Chapter 10: Technique of Penetrating Keratoplasty


inferior fornix at the end of the surgery and the patient is given
Figure 10.12: Types of continuous suturing
pad and bandage for 24 hours. We follow the following
postoperative regime in various cases of penetrating keratoplasty
sponge pressing at the limbus and observing the wound for at our center.
leakage of aqueous humor. Topical fluorescein is a better method
of evaluation for wound leakage. Here the fluorescein is instilled Antibiotics
at the wound margins. In the presence of wound leak due to
Topical antibiotics such as 0.3 percent ofloxacin or 0.3 percent
dilution of the dye, fluorescein appears to be bright green and a
ciprofloxacin are used four times a day for 1 week
track of aqueous leak can be observed. If a wound leak is present,
postoperatively or until the epithelium is healed. Prolonged use
additional sutures should be applied appropriately.
of topical aminoglycosides is toxic to the epithelium and hence
should be avoided. Topical ofloxacin may be preferred as it has
Intraoperative Adjustment for Astigmatism
better penetration than ciprofloxacin and norfloxacin and also
An intraoperative keratoscope may be helpful in reducing better activity against alpha-hemolytic streptococci.13 Fortified
postoperative astigmatism by recognizing areas of steepness or antibiotics such as fortified tobramycin 1.3 percent or cefazolin
flatter meridian. A suture adjustment may be done until regular 5 percent may be given in cases where penetrating keratoplasty
mires are obtained. Intraoperative keratoscopes available include has been performed for uncontrolled infectious keratitis varying
those with microscope attachment such as Terry’s or those which in frequency from 30 minutes to 4 hourly which (if the infection
are based on the reflection of the mires from the corneal surface, is controlled) can be tapered over a 2 to 3 weeks period,
such as Maloney’s and Mandel’s keratometer. Alternatively, the postoperatively.
round end of a safety pin may be used and the reflex of the In fungal keratitis, 5 percent Natamycin drops may be used
circular image may be evaluated to adjust the suture placement postoperatively for several weeks.6
and hence correct for astigmatism intraoperatively. If the mires Oral acyclovir may be given (400 mg 5 times/day) in herpetic
are circular, generally minimal astigmatism is present; if however keratitis and continued for 1 to 3 weeks and then decreased to
the ovalling of the mires is present, the suture should be adjusted maintenance dose (400 mg BD) for several months.22, 23
in such a manner so as to achieve circular shape of the mires. In Systemic antibiotics such as ciprofloxacin 500 to 750 mg or
cases with interrupted sutures, the tight sutures (which are present ofloxacin 200-400 mg may be given twice daily perioperatively
along the shorter diameter of the oval) may be replaced by the and for 3-5 days after the surgery in the following conditions:
sutures which have optimal tension. Similarly, if a continuos • Pre-existing external eye infection
suture is used, the loop along the largest diameter of the oval • Prosthesis use in the fellow eye

Figure 10.13A: Pre-adjustment videokeratography Figure 10.13B: Post-adjustment videokeratography


map of a patient of the torque group map of a patient of the torque group
71
• Penetrating trauma 2. Nirankari VS, Baer JC. Corneal argon laser photocoagulation for
• Combined procedures especially with vitrectomy or neovascularization in penetrating keratoplasty. Ophthalmology
intraocular lenses. 1986;93(10):1304-9.
3. Feibel RM. Current concepts in retrobulbar anesthesia. Surv
Ophthalmol 1985;30:102.
Corticosteroids
4. Atkinson WS. Local anesthesia in ophthalmology. Am J
Topical corticosteroids such as 1 percent prednisolone acetate Ophthalmol 1948;31:1607.
or 0.1 percent dexamethasone sodium phosphate may be used 4 5. Vajpayee RB, Melki S. Three pearls to minimize penetrating
Section II: Penetrating Keratoplasty

keratoplasty astigmatism. In: 101 pearls in Refractive, Cataract


to 6 times a day in routine keratoplasty. These are then tapered
and Corneal Surgery 2001 Eds. Melki SA, Azar DT. SLACK Inc.,
over several months. They are used more frequently, i.e. in
Thorofare, New Jersey. Chapter 20: 161-62.
1 hourly or 2 hourly dosage in cases of – 6. Barron BA. Penetrating keratoplasty In: The cornea. Eds.
• High-risk keratoplasty Kaufman HE, Barron BA, McDonald MB. Chapter 34 805-46.
• Patient develops Butterworth-Heinemann 1998, Boston.
– Increased inflammation 7. Vajpayee RB, Dada T, Ray M, et al. Oversized corneal grafts for
– Keratic precipitates on graft corneal opacities with corneo-iridic scar. Ophthalmology 108,
– Increased corneal thickness. 2001.
8. Vajpayee RB, Ramu M, Panda A, et al. Oversized grafts in
Systemic corticosteroids, i.e. Prednisolone 1 mg/kg/day is
children. Ophthalmology 1999;106:829-32.
started 1 to 2 days before surgery and tapered over 2 to 3 weeks 9. Olson RJ. Variation in corneal graft size related to trephine
in high risk keratoplasties. technique. Arch Ophthalmol 1979;97:1323-5.
10. Brightbill FS, Polack FM, Slappey T. A comparison of two
Antiglaucoma Medications methods of cutting donor corneal buttons. Am J Ophthalmol
1973;75:500.
Prophylactic antiglaucoma medication such as timolol maleate
11. Tanne E. A new donor cutting block for penetrating keratoplasty.
0.5 percent twice a day should be given in following cases: Ophthalmic Surg 1981;12:271.
• Pre-existing glaucoma 12. Seitz B, Langenbucher A, Kus MM, et al. Nonmechanical corneal
• Penetrating keratoplasty combined with trephination with the excimer laser improves outcome after
– Cataract surgery penetrating keratoplasty. Ophthalmology 1999;106:1156-64.
– Vitrectomies 13. Langenbucher A, Seitz B, Kus MM, et al. Graft decentration in
– Lysis of synechiae penetrating keratoplasty: nonmechanical trephination with the
excimer laser (193 nm) versus the motor trephine. Ophthalmic
– Use of large amounts of hyaluronate
Surg Lasers 1998;29:106-13.
– Anterior segment reconstruction 14. Uozato H, Guyton DL. Centering corneal surgical procedures.
Am J Ophthalmol 1987;103:264-75.
Cycloplegics 15. Vajpayee RB, Sharma V, Sharma N, et al. Evaluation of
techniques of single continuous suturing in penetrating
Short-acting agents such as tropicamide 1 percent or
keratoplasty. Br J Ophthalmol 2001;85:134-8.
cyclopentolate 1 percent may be given for early postoperative 16. Verdier DD. Penetrating keratoplasty. In: Cornea surgery of the
pain and inflammation control. Strong agents such as atropine cornea and conjunctiva. Vol. III Eds. Krachmer JH, Mannis MJ,
should be avoided in cases of keratoconus because of reports of Holland EJ. Chapter 130; 1581-92. Mosby, St. Louis, 1997.
permanent pupillary dilatation (Urrets-Zavalia syndrome). Wide 17. Bourne WM, Davidson JA, O’Fallon WM. The effects of oversize
dilatation of the pupil in cases of posterior chamber IOL may donor button on postoperative intraocular pressure and corneal
increase the risk of formation of synechiae to the posterior curvature in aphakic penetrating keratoplasty. Ophthalmology
capsule and capture of the edge of the lens with iris. Wide 1982;89:242.
18. Wiffen SJ, Maguire LJ, Bourne WM. Keratometric results of
dilatation should also be avoided in cases where large grafts have
penetrating keratoplasty with the Hessburg-Barron and Hannah
been used as this may cause crowding at the angle and adherence trephine systems using a standard double running suture
to the posterior edge of the wound.6 technique. Cornea 1997;16:306.
19. Waring GO III. Management of pseudophakic corneal edema with
Lubricants reconstruction of anterior ocular segment. Arch Ophthalmol
1987;105:709.
In routine keratoplasties, preservative free lubricants may be
20. Cohen SW, Benko W. Automated motorized penetrating
given at 2 hourly to 4 times daily dosage. Epitheliotoxic drugs keratoplasty. Ann Ophthalmol 1977;14:1461.
such as beta-blockers, non-steroidal anti-inflammatory drugs and 21. Weiner M, alvis BY. Transplantation of cornea by means of a
topical aminoglycosides should be used with caution. mechanically obtained bevelled edge segment. Am J Ophthalmol.
1940;23:877.
REFERENCES 22. Denham D, et al. Endothelial damage by the corneal Hessburg-
Barron vacuum trephine. Refract Corneal Surg. 1993;9:255.
1. Lim KJ, Wee WR, Lee JH. Treatment of corneal neovas- 23. Filatov V. Comparison of suture-in and suture-out post-
cularization with argon laser. Korean J Ophthalmol 1993;7:25- keratoplasty astigmatism with single running or combined and
27. interrupted sutures. Am J Ophthalmol 1996;122:696.
72
11

Chapter 11: Suturing Techniques in Penetrating Keratoplasty


Suturing Techniques in
Penetrating Keratoplasty
C Banu Cosar, Peter R Laibson

INTRODUCTION In very young pediatric keratoplasty, interrupted sutures are


used almost exclusively. For older children some surgeons
Obtaining a clear graft in penetrating keratoplasty has become
advocate a running closure providing there is no asymmetric
almost expected. For most eyes undergoing penetrating
vascularization.12,13 Single interrupted sutures are also indicated
keratoplasty, the success rate for a clear graft exceeds 90
in vascularization in the host cornea. So that, partial suture
percent.1 However, postoperative astigmatism still remains a
removal may be performed earlier in these vascularized areas
problem that can prevent the functional success of clear graft.2
in the postoperative course. Multiple previous rejections,
There are many factors contributing to astigmatism after
inflammatory conditions that may predispose to localized
penetrating keratoplasty, including pre-existing corneal thinning
vascularization, rejection, or ulceration are other indications for
and vascularization, eccentric trephination of the donor or host,
single interrupted sutures.14
oversized grafts, pre-existing keratoconus, quality of wound
Interrupted sutures are placed with 10-0 nylon. Sixteen is
healing, and astigmatism of donor eye. Tension, length, depth
the average number of interrupted sutures placed for a typical
and configuration of corneal sutures have also been implicated
8 mm diameter graft. Twenty-four or 32 sutures may be necessary
as causative factors.3
in larger grafts. An 8-blade RK marker can be used as a guide
There are mainly four types of suturing techniques in
(Fig. 11.1). The first cardinal suture is placed at 12 O’clock
penetrating keratoplasty:
position. The second cardinal suture, placed 180 degrees away
1. Interrupted sutures
at 6 O’clock, is the most critical in terms of tissue alignment
2. Combined interrupted and continuous sutures
and subsequent astigmatism. It should be placed so that an equal
3. Single continuous suture
amount of tissue is distributed on either side. Then, cardinal
4. Double continuous sutures
sutures at 3 O’clock and 9 O’clock are placed followed by other
Many authors have compared the effectiveness of these
suturing techniques in terms of astigmatism, visual outcome, and
complications.4-10 However, it is dificult to corroborate the results
of these various studies because of the differences in techniques,
indications, timing of suture adjustment and removal, and follow-
up periods. However, all suturing techniques have been used
successfully to secure the wound and create a relatively smooth
corneal contour. Therefore, specific suturing technique is mainly
dictated by the expertise and preference of the surgeon, and by
the presence or absence of localized disease (Table 11.1).

SUTURING TECHNIQUES

Single Interrupted Suturing Technique

Interrupted sutures are commonly used by many corneal


surgeons11 because they are easy to place and permit partial or Figure 11.1: Eight-blade RK marks on the cornea to assist in
complete suture removal in one region of the graft if necessary. suture placement. The Flieringa ring is in place

73
Section II: Penetrating Keratoplasty

Figure 11.3: Penetrating keratoplasty with 16 interrupted sutures


Figure 11.2: Penetrating keratoplasty with 16 interrupted sutures. which are too tight. Note guttering of fluorescein at the host-
Note the smooth contour of the host-donor junction with the slit donor junction and whorl superficial punctate keratopathy of the
illumination donor cornea

sutures. The sutures should be placed as radially and as evenly interrupted suture so that the epithelial portion of the continuous
spaced as possible, with the ideal depth of each suture bite suture lies across the wound between the interrupted sutures. If
90 percent. They should neither be too loose or too tight suture bites are made halfway between the interrupted sutures,
(Figs 11.2 and 11.3). The knots can be buried either in the host the superficial segment will lie across the interrupted sutures,
tissue or the donor tissue. We prefer to bury the knots in the providing little additional wound support. The ideal depth of the
donor tissue to induce less vascularization in the graft.15 Some suture bites is 95 percent. 11-0 mersilene suture has also been
surgeons bury the knots in the host tissue so that after the knots reported to be an effective suture material in this technique for
are cut and the suture is pulled, there is less tension on the graft- either interrupted or the running suture.17,18
host junction, reducing the chance of dehiscence if the sutures
are removed during the early stages of postoperative wound Single Continuous Suturing Technique
healing.16 There are 3 types of single continuous suturing techniques –
namely, torque, antitorque and no torque (Fig. 11.5). The torque
Combined Continuous and Interrupted pattern rotates the corneal graft counterclockwise by
Suturing (CCIS) Technique 0.7 +/- 0.1 mm at the wound or 11 degrees; the antitorque pattern
rotates the corneal graft clockwise by 0.7 +/- 0.1 mm at the
This technique is most often performed using 12 interrupted 10-0
wound or 11 degrees; the no torque pattern, the bites of which
nylon sutures and a 12 bite continuous 10-0 or 11-0 nylon
running suture with bites of the continuous suture placed between form an isosceles triangle, produces no rotational effect.19 In the
antitorque suturing technique, the distortion occurs more in the
each of the interrupted sutures (Fig. 11.4). The needle pass of
deeper layers of cornea and does not contribute much to
the continuous suture bites should be made close to the
postoperative corneal astigmatism. However, with the torque
suturing technique, the oblique overlying suture segment causes
distortion of anterior corneal surface contributing to corneal
astigmatism postoperatively. In the no torque technique, since
the intrastromal bytes and the overlying sutures are at equal
inclination, they act as a splint and cause less corneal
distortion.19,20 Vajpayee RB et al evaluated these 3 single
continuous suturing techniques in penetrating keratoplasty and
found that the torque suturing technique showed the highest
astigmatism although the difference among the three was not
significant.20
A single continuous suture is technically more difficult than
interrupted sutures, because one irregular bite can impair the
integrity of the closure and cannot be removed without removing
the entire suture. The four cardinal sutures are placed in the
Figure 11.4: Combined technique, using 8 interrupted and 16- regular manner followed by a 24 bite continuous suture with 10-0
bite running 10-0 nylon sutures nylon with a 95 percent depth. The continuous suture is knotted
74
Chapter 11: Suturing Techniques in Penetrating Keratoplasty
Figure 11.5: Three types of single continuous suturing technique in penetrating keratoplasty

Figure 11.6: Twenty four-bite single Figure 11.7: Double continuous technique
continuous 10-0 nylon suture with 10-0 and 11-0 nylon sutures

temporarily at 12 O’clock while the four interrupted cardinal suture adjustment, early postoperative suture adjustment (< 2 wk)
sutures are carefully removed. The anterior chamber is inflated and late postoperative suture adjustment (>1 month) concluded
with BSS plus. The continuous suture is tightened and is then that early postoperative suture removal was more effective than
permanently knotted at 12 O’clock (Fig. 11.6). If the continuous late postoperative suture removal. The same study found that
suture is tightened when the eye is soft, “barrel topping” of the intraoperative suture adjustment may further reduce final
graft with a topographically flat donor cornea results.14 11-0 astigmatism and the necessity for postoperative suture
mersilene has also been reported to be an effective suture material manipulation.24 Whereas, another study compared early suture
for the single continuous suturing technique.21 removal (<18 months after surgery), late suture removal (>=18
months after surgery) and leaving the sutures in place, and
Double Continuous Suturing Technique concluded that final refractive error and net change in refractive
and keratometric astigmatism are not dependent on the timing
After the four cardinal sutures are placed, a 12 bite 10-0 nylon
of suture removal.25
suture is placed with bites at approximately 80 percent depth.
Suture adjustment or removal should be performed as early
The suture is then knotted superiorly and the knot is buried in
as possible to provide early visual rehabilitation. A previous study
the host cornea. A second continuous suture (either 10-0 or
tested the hypothesis that the cornea becomes fixed more than
11-0 nylon) is then placed. The bites should alternate between
1 year after PK, so that desirable refractive results will remain
each 10-0 bite for 360 degrees. The second 10 or 11-0 is placed
when all sutures are eventually removed. However, when the
approximately 50 to 60 percent the corneal depth (Fig. 11.7).
remaining sutures were removed 1 to 6 years after PK, corneal
astigmatism changed unpredictably and by large amounts.26
SUTURE ADJUSTMENT AND SUTURE REMOVAL
Topographical analysis using keratometry, photokeratoscopy,
The purpose of suture adjustment is to minimize postoperative or videoeratography, individually or in combination, are helpful
astigmatism. Postoperative suture adjustment is less effective in in planning suture adjustment.27 However, often there is a
reducing spherical refractive errors. Final suture removal may disagreement between the topographically determined steep axis
induce either hyperopization22 or corneal steepening.23 and sutures to be removed, and that determined by keratometry
Many studies have been performed previously to address the and refraction. Agreement between refraction, keratometry, and
ideal timing for suture removal. A study comparing intraoperative topography are associated with greater change in vector corrected
75
astigmatism. Disagreement between refraction, keratometry, and carefully advanced from the flat to the steep meridian,
topography is associated with less vector corrected astigmatism simultaneously flattening the steep meridian and steepening the
but patients in the disagreement group has a greater chance of flat meridian. Adjustment can be repeated more than once if
improvement than worsening following suture removal.28 desired. Acceptable astigmatism with sutures in allows the patient
Suture adjustment can take the form of removal of all sutures, to achieve early visual rehabilitation.
partial suture removal, or adjustment in the tension of a running The risk of breakage during the adjustment procedure should
suture. If corneal astigmatism is satisfactory with sutures in place, be considered seriously but is not common. Suture breakage can
Section II: Penetrating Keratoplasty

sutures should remain until there is some indication for removal, result in wound dehiscence and requires prompt repair in the
such as scarring, vascularization, suture breakage, loose operating room. Consequently, suture adjustment of the single
interrupted sutures, and pronounced inflammation, or infiltration continuous suture should not be attempted unless facilities are
around sutures.14 available to make the repair.
The suture removal or adjustment is performed at the slit
lamp with topical anesthesia guided by the computerized Double Continuous Sutures
topography, or keratometry or refraction, or by a combination
Double continuous suture technique may involve a 10-0 and an
of the three, as well as slit lamp evaluation. One drop of antibiotic 11-0 nylon suture or a double 10-0 running suture. The deeper,
is placed in the eye after removal or adjustment. The patient is
tighter 10-0 suture may be removed or adjusted. And the
given antibiotic drop four times a day and antibiotic ointment at
shallower 11-0 or 10-0 suture is left in place as a safety net.
bed time for 3 or 4 days.
The topographic changes induced by suture removal occur
immediately. However, continued shifting in corneal curvature CONCLUSION
takes place over the subsequent 4 to 6 weeks.29 Astigmatic errors All suturing techniques have been used successfully to secure
become stable, with less than 1 D of change between successive the wound and create a relatively smooth corneal contour. Suture
examinations within 6 months after suture removal.30 adjustment can be performed intraoperatively and
postoperatively. Sutures should be left in place once the suture
Single Interrupted Sutures
has been adjusted to achieve suitable topography.
The only adjustment possible with single interrupted sutures is
removal and therefore flattening. We start removing the sutures
REFERENCES
at 1 year after the surgery unless otherwise indicated. A very
tight suture can be removed as early as 6 weeks. In the case of 1. Price FW, Whitson WE, Collins KS, Marks RG. Five-year corneal
a suture that loosens or becomes undone in the first few weeks graft survival. Arch Ophthalmol 1993;111:799-805.
after keratoplasty, if there is a wound gape this suture can be 2. Hardten DR, Lindstrom RL. Surgical correction of refractive
errors after penetrating keratoplasty. Int Ophthalmol Clin 1997;
replaced under topical anesthesia. The suture at the steepest
37:1-31.
meridian indicated by computerized topography analysis is cut
3. Riddle HK, Parker DAS, Price FW. Management of post-
either with a razor blade fragment or a disposal 27-gauge needle. keratoplasty astigmatism. Curr Opin Ophthalmol 1998;9:15-28.
It is removed with a tying forceps or a jewelers forceps. A sudden 4. Karabatsas CH, Cook SD, Figueiredo FC, Diamond JP, Easty DL.
jerk is more effective at removing the interrupted suture than Combined interrupted and continuous versus single continuous
slower, less forceful pressure. adjustable suturing in penetrating keratoplasty: a prospective,
In pediatric keratoplasty, every other interrupted 10-0 nylon randomized study of induced astigmatism during the first
suture is removed in the early postoperative period, followed postoperative year. Ophthalmology 1998;105:1991-98.
by complete removal of sutures at a later date. All sutures in 5. Busin M, Monks T, al-Nawaiseh I. Different suturing techniques
patients less than a year are usually removed within 8 weeks. variously affect the regularity of postkeratoplasty astigmatism.
Ophthalmology 1998; 105(7):1200-05.
Combined Continuous and Interrupted Sutures 6. Murta JN, Amaro L, Tavares C, Mira JB. Astigmatism after
penetrating keratoplasty. Role of the suture technique. Doc
At approximately 2 to 3 months after PK, corneal topography is Ophthalmol 1994;87:331-36.
evaluated and a very tight interrupted suture can be removed. 7. Filatov V, Steinert RF, Talamo JH. Post-keratoplasty astigmatism
Usually this does not occur until six months from the time of with single running suture or interrupted sutures. Am J
surgery. A disadvantage of CCIS suture adjustment is that only Ophthalmol 1993;115:715-21.
the tight suture can be removed, therefore, only the steep axis 8. Assil KK, Zarnegar SR, Schanzlin DJ. Visual outcome after
can be flattened. Another disadvantage is that interrupted sutures penetrating keratoplasty with double continuous or combined
are very difficult to remove after several years. interrupted and continuous suture wound closure. Am J
Ophthalmol 1992;114:63-71.
Single Continuous Suture 9. Solano JM, Hodge DO, Bourne WM. Keratometric astigmatism
after suture removal in penetrating keratoplasty: double running
Adjustment of the single continuous suture can change corneal versus single running suture techniques. Cornea 2003;22(8):
topography and still support the wound. The suture is very 716-20.
76
10. Ramirez M, Hodge DO, Bourne WM. Keratometric results during 21. Touzeau O, Borderie VM, Allouch C, Scheer S, Laroche L.
the first year after keratoplasty: adjustable single running suture Effects of penetrating keratoplasty suture removal on corneal
technique versus double running suture technique. Ophthalmic topography and refraction. Cornea 1999;18:638-44.
Surg Lasers 2001;32:370-74. 22. Mathers WD, Gold JB, Kattan H, Lemp MA. Corneal steepening
11. Rapuano CJ, Luchs JI, Kim T. Anterior segment surgery and with final suture removal after penetrating keratoplasty. Cornea
complications. In: Krachmer JH, editor. Anterior segment: The 1991;10:221-23.
requisites in ophthalmology. St. Louis: Mosby, 2000;232-85. 23. Frueh BE, Brown SI, Feldman ST. 11-0 mersilene as running
12. Stulting RD. Penetrating keratoplasty in children. In: Brightbill suture for penetr ting keratoplasty. Am J Ophthalmol 1992;114:

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FS, editor. Corneal surgery: theory, technique, and tissue Mosby: 675-79.
St. Louis, 1993. 24. Shimazaki J, Shimmura S, Tsubota K. Intraoperative versus
13. Dana MR, Moyes AL, Gomes JAP, Rosheim KM, Schaumberg postoperative suture adjustment after penetrating keratoplasty.
DA, Laibson PR, Holland EJ, Sugar A, Sugar J. The indications Cornea 1998;17:590-94.
for and outcome in pediatric keratoplasty: a multicenter study. 25. Serdarevic ON, Renard GJ, Pouliquen Y. Randomized clinical
Ophthalmology 1995;102:1129-38. trial of penetrating keratoplasty. Before and after suture removal
14. Van Meter W, Katz DG. Keratoplasty suturing techniques. In: comparison of intraoperative and postoperative suture adjustment.
Krachmer JH, Mannis MJ, Holland EJ, editors. Cornea, Vol 2, Ophthalmology 1995;102:1497-503.
Surgery of the cornea and conjunctiva, ed.2. St. Louis: Mosby, 26. Davis EA, Azar DT, Jakobs FM, Stark WF. Refractive and
2005;1481-92. keratometric results after the triple procedure: experience with
15. Dana MR, Schaumberg DA, Kowal VO, Goren MB, Rapuano early and late suture removal. Ophthalmology 1998;105:624-30.
CJ, Laibson PR, Cohen EJ. Corneal neovascularization after 27. Mader TH, Yuan R, Lynn MJ, Stulting RD, Wilson LA, Waring
penetrating keratoplasty. Cornea 1995;14:604-09. GO. Changes in keratometric astigmatism after suture removal
16. Melles GRH, Binder PS. A comparison of wound healing in more than one year after penetrating keratoplasty. Ophthalmology
sutured and unsutured corneal wounds. Arch Ophthalmol 1980; 1993;100:119-26.
108:546-48. 28. Strelow S, Cohen EJ, Leavitt KG, Laibson PR. Corneal
17. Bigar F, Uffer S. The unsolved problem of transplant astigmatism. topography for selective suture removal after penetrating
Klin Montsbl Augenheilk 1992;200:401-03. keratoplasty. Am J Ophthalmol 1991;112:657-65.
18. Ramselaar JA, Beekhuis WH, Rijneveld WJ, van Andel MV, Dijk 29. Sarhan AR, Dua HS, Beach M. Effect of disagreement between
F, Jongebloed WL. Mersilene (polyester), a new suture for refractive, keratometric, and topographic determination of
penetrating keratoplasty. Doc Ophthalmol 1992;82:89-101. astigmatic axis on suture removal after penetrating keratoplasty.
19. Au YK, Mahjoub SB, Hart JC. Suture patterns and corneal graft Br J Ophthalmol 2000;84:837-41.
rotation in the cadaver eye. Ophthalmic Surg. 1990;21:472-74. 30. Goren MB, Dana MR, Rapuano CJ, Gomes JAP, Cohen EJ,
20. Vajpayee RB, Sharma V, Sharma N, Panda A, Taylor HR. Laibson PR. Corneal topography after selective suture removal
Evaluation of techniques of single continuous suturing in for astigmatism following keratoplasty. Ophthalmic Surg Lasers
penetrating keratoplasty. Br J Ophthalmol 2001;85:134-38. 1997;28:208-14.

77
12
Section II: Penetrating Keratoplasty

Postoperative Care after


Penetrating Keratoplasty
Raj Maini, Urmimala Ghatak, Hugh R Taylor

The postoperative care of a corneal graft is probably more Increased pain, irritation, redness, decreased vision and
important in determining the long-term outcome of the graft than photophobia are important symptoms. Patients should seek
the surgery itself. A lack of careful attention to prevention of, referral immediately in the event that they experience any of these
early detection and prompt treatment of rejection episodes may and should be examined within twenty-four hours of symptom
lead to graft failure in an otherwise technically perfect graft. onset.
The postoperative care in penetrating keratoplasty (PK) is It is also important the patient avoids any situation that may
far more complex than that after cataract surgery. With the advent produce trauma to the eye, such as heavy lifting, eyelid
and increasing popularity of endothelial keratoplasty and deep squeezing, contact sports, etc.
anterior lamellar keratoplasty techniques for lower risk
indications, the postoperative care for the more complex patients STANDARD POSTOPERATIVE CARE
requiring full-thickness grafts becomes even more crucial.
Routine postsurgical care involves the use of topical This section covers postoperative care in uncomplicated corneal
antibiotics until epithelial defects are healed. The use of topical grafting in nonvascularized eyes, typically with keratoconus or
steroids to minimize postoperative inflammation, reduce immune corneal dystrophy (Fig. 12.1, Table 12.1).
sensitivity and chance of rejection must be carefully tailored.
Frequent clinical assessments in the early postoperative period Early Postoperative Management
are directed at prevention and early recognition of the myriad At the completion of surgery, subconjunctival corticosteroid and
of complications that can occur after PK. This can make the antibiotic of choice are usually administered. Though
difference between surgical success and failure. intracameral antibiotic injection is gaining popularity as this has
It is very important to instruct the patient regarding symptoms been shown to be safe and efficacious in cataract surgery2 there
of rejection, but even having done this, a significant proportion is a paucity of data in this regard for PK. The eye may be patched
of episodes of clinically evident rejection are picked up during for 24 hours with antibiotic ointment. We prefer to use
routine postsurgery visits.1 fluoroquinolone ointment.

Table 12.1: Follow-up schedule


1 week 1 month 3 months 6 months 1 year
• Visual acuity • Visual acuity • Visual acuity • Visual acuity • Visual acuity
• Graft clarity • Graft clarity • Graft clarity • Graft clarity • Graft clarity
• Status of corneal • Sutures • Sutures • Sutures • Sutures
epithelium • AC depth, • AC depth, • AC depth, • AC depth,
• Sutures: tight/loose/ inflammation inflammation inflammation inflammation
broken, infiltrates • Lens status • Lens status • Lens status • Lens status
• AC depth, inflammation • Fundus • Fundus • Fundus • Fundus
• Lens status • IOP • IOP • IOP • IOP
• Fundus • Corneal topography • Corneal topography • Corneal topography • Corneal topo-
• IOP +/- suture adjustment +/- suture adjustment +/- suture adjustment graphy +/- suture
• Selective suture • Selective suture adjustment
removal removal • Suture removal
• Refractive
correction
78
the leak persists for > 3 days, wound resuture should be
considered
• Pupil shape
• Corneal epithelial status
• Extreme anterior chamber shallowing or iris incarceration
in the wound—requires immediate surgical management
• Elevated intraocular pressure-treat medically in the first

Chapter 12: Postoperative Care after Penetrating Keratoplasty


instance
• Early signs of infection or endophthalmitis—this requires
aggressive medical and/or surgical management.
Topical medication should be commenced:
• Topical antibiotic: Fluoroquinolone eyedrops 4 times daily
until epithelium is healed—usually within 7-14 days
Figure 12.1: Routine one month postoperative appearance • Topical steroid: The use of topical corticosteroids is
of a penetrating keratoplasty universal, but the dose requirements may vary widely
between individual cases. Fluorometholone acetate 0.1
The oral carbonic anhydrase inhibitor acetazolamide may be
percent or Prednisolone acetate 1 percent are generally used
used to prevent a rise in intraocular pressure, especially if
4 to 6 times daily initially.
viscoelastic has been used. Topical carbonic anhydrase inhibitors,
Fluorometholone acetate 0.1 percent may be considered as
e.g. dorzolamide may controversially interfere with endothelial
first-line treatment because it has less epithelial toxicity than
function and should be avoided.
Prednisolone acetate 1 percent and is less likely to result in
Criteria for discharging the patient from hospital (in a
elevation of intraocular pressure. Recently Rimexolone 1 percent
daycare setting) include
• Stable vital signs has been touted as a potent topical anti-inflammatory agent
• Return to the preoperative mental state without the potential intraocular pressure problems encountered
• Absence of nausea with topical Dexamethasone. Other topical steroid preparations,
• Absence of unusual pain such as Prednisolone sodium phosphate are not potent enough
• Availability of an escort to produce adequate therapeutic effect.
• Review of postsurgical care with the patient and/or escort, In uncomplicated corneal grafts, the topical steroid medi-
including medication dosage cation may be gradually reduced as the inflammation within the
• Prearranged follow-up appointment eye diminishes. A typical regimen is outlined in Table 12.2.
• Written postoperative instructions. Intraocular pressure and the status of the lens must be
monitored carefully, for as long as the steroids are used.
First Postoperative Day
Postoperative Visits
The eye pad is removed at first dressing, but the eye should be
protected during sleep with a shield for the first 4-6 weeks and There are many postoperative care regimens; the key to them
the patient’s head should be slightly elevated (“higher than the all is a careful slit lamp examination. In addition to the signs
patient’s heart”). outlined above (day 1 assessment), the patient must be assessed
At this stage, it is mandatory to assess: for early signs of rejection: corneal stromal thickening, fine
• Visual acuity epithelial edema, aqueous flare and cell, but especially keratic
• Degree of pain precipitates (KP) (Figs 12.2 and 12.3). The presence of a few,
• Slit lamp examination fine keratic precipitates when there were none at previous visits
At slit lamp examination particular attention must be paid is indicative of early rejection and must be treated vigorously
to: with hourly topical steroid. Keratic precipitates can only be
• The presence of a wound leak-relative hypotony, unusual assumed to be ‘old pigmented KP’ if they do not resolve with
stromal swelling and a shallow anterior chamber should alert intensive treatment. If graft rejection does not improve with
you to the possibility of this. Assess the leak with the Seidel hourly topical steroids, topical cyclosporine A may be added.
test; treatment may require insertion of a therapeutic The use of pulsed high-dose systemic immunosuppression3,4 is
(bandage) contact lens or aqueous production inhibitors. If not universal.5

Table 12.2: Use of topical steroids in penetrating keratoplasty

Month 1 Month 2 Month 3 Month 4 Month 5 Month 6 Month 7

Fluorometholone acetate 0.1 percent Fluorometholone alcohol 0.1 percent


4-6 hrly 4x/day 3x/day 2x/day 4x/day 3x/day 2x/day
79
rosacea and blepharitis, which must be treated. Lubrication,
patching, a bandage contact lens, botulinum toxin, surgical ptosis
or tarsorraphy may be required.
Loose sutures may be secondary to poor surgical technique,
wound contraction, suture breakage or cheese wiring. They trap
mucous and can result in infection or stimulate graft rejection
or giant papillary conjunctivitis. They do not contribute to wound
Section II: Penetrating Keratoplasty

integrity and should be removed. Vascularization along suture


tracks indicates a healed wound and these sutures may also be
removed safely.
Patients who are grafted for corneal dystrophy must be
examined for recurrence of the dystrophy within the graft tissue;
fungal, viral and amebic infections may all recur within corneal
Figure 12.2: Early graft rejection manifesting an endothelial grafts and treatment should be directed towards the causative
(Khodadoust) rejection line agent.
A patient without signs or symptoms of complications should
be examined on a regular basis for 18-24 months (Table 12.3).
Progress of improvement and the course of complications should
be documented by detailed clinical drawings or anterior segment
photography at each visit.
Graft clarity and visual acuity should begin to improve in
the early postoperative period. Persistent graft edema from the
first dressing and continuing in the absence of inflammation may
indicate primary graft failure—this may be confirmed with
pachymetry and specular microscopy.
After suture removal, the patient will not require more
planned appointments. Patients should however, still be
instructed to consult an ophthalmologist promptly in the event
of any rejection symptoms. If a patient has had a rejection
episode, an argument can be made to continue long-term, low
Figure 12.3: Established graft rejection with graft thickening, dose topical steroid such as Fluorometholone alcohol 0.1 percent
keratic precipitates and neovascularization at the graft-host once or twice a day.
junction
The prescription of spectacles or contact lenses depends on
a number of factors. The patient’s visual needs are paramount,
but the healing process, the amount of astigmatism, the presence
Deturgescence of the graft in the short to medium term can of sutures and the stability of the refractive error may all be
be monitored using pachymetry. important factors. Refraction and computerized topographic
Fundoscopy should be undertaken within the first month after mapping with suture adjustment will aid visual rehabilitation in
surgery to assess the optic nerve (glaucomatous damage, the first year. Selective suture removal may be indicated where,
atrophy), macula (age-related degeneration, scarring) and interrupted sutures have been used. Temporary spectacles may
peripheral retina (retinal tears or detachment). be prescribed within a few months of surgery to aid with the
The presence of a non-healing corneal epithelial defect for rehabilitation process.
more than 14 days increases the risk of stromal ulceration with The final spectacles are prescribed when the sutures have
subsequent corneal stromal thinning, perforation or scarring. been removed and the refraction and corneal curvature have
These patients should be carefully assessed for ocular surface stabilized. Occasionally residual or irregular astigmatism may
disease and lid malposition, in particular dry eye, exposure, require rigid gas-permeable contact lens fitting.

Table 12.3: Postoperative penetrating keratoplasty outpatient schedule

Month 1 Month 2 Months 3-12 Months 13-24


Every 2 weeks Every 4 weeks Every 6 weeks Every 6-12 weeks until
all sutures are removed

80
CORNEAL GRAFTING IN OCULAR antibiotic and steroid if needed. Topical Cyclosporine 0.05
SURFACE DISEASES percent emulsion has been used in the management of posterior
blepharitis and ocular rosacea. 6 The value of systemic
This section includes management of keratoplasty in
tetracyclines in the treatment of rosacea should not be forgotten.
lagophthalmos, entropion, lid scarring, dry eye, chemical burns
and ocular cicatricial pemphigoid.
Postoperative Prevention of Epithelial Problems
Overview Careful clinical examination for lash, lid abnormalities and

Chapter 12: Postoperative Care after Penetrating Keratoplasty


abnormalities of the ocular surface is mandatory.
Penetrating keratoplasty in these conditions presents a
considerable management challenge, primarily aimed at
optimizing the health of the ocular surface. Trichiasis
The integrity of the corneal epithelium after keratoplasty is Epilation is temporary as lashes normally regrow within 2 to 3
vital for graft survival. The normal intact corneal epithelium weeks. Electrolysis works well only for removing a few lashes.
provides an optical interface with the tear film and a barrier to Cryotherapy is the treatment of choice to remove ingrowing
the external environment, noxious substances, and lashes.
microorganisms. The presence of an epithelial defect interferes
with vision and increases the risk of rejection, infection, thinning Dry Eye
and perforation. Epithelial defects occur frequently on the first
postoperative day in donor corneas stored in both McCarey- Punctal occlusion may be of benefit for patients with
Kaufman (MK) medium and organ culture medium. keratoconjunctivitis sicca to prevent epithelial ulceration
Toxic topical medication and preservatives may have an postkeratoplasty. Punctal occlusion increases tear retention and
adverse effect on epithelial wound healing because of the resultant increase in the tear volume to surface area (TVSA)
inhibition of epithelial migration, epithelial mitosis, or epithelial ratio. Options include temporary punctal occlusion using punctal
attachment to the underlying basement membrane; if these plugs or permanent punctal closure with laser, cautery or
problems are encountered the patient should be switched to diathermy.
unpreserved medication or commenced on these immediately Topical Cyclosporine 0.05 percent shows beneficial effects
postoperatively. in all categories of dry eye disease.7
Abnormalities of the tear film from decreased aqueous
Lagophthalmos
secretion, rapid evaporation, mucin deficiency, blepharitis, poor
lid position or movement and lagophthalmos can influence Surgical options to correct this include lateral tarsorrhaphy or
epithelial healing and wound healing. Some systemic medications lateral canthal sling procedures.
may exert an indirect effect on the corneal epithelium through The therapeutic effect of these procedures is attributable to
effects on tear secretion and epithelial cell wound healing. the decrease in exposed ocular surface area, which increases the
Local primary ocular surface disease, for example, Ocular TVSA ratio, protecting the epithelial surface and promotes
Cicatricial Pemphigoid, Stevens-Johnson syndrome or chemical spreading of the tear film.
burns may prevent normal epithelial wound healing secondary The ocular surface should be kept well lubricated with
to lid scarring, resulting in entropion and trichiasis. Disturbed artificial tears, if required more frequently than 4 to 6 times daily.
anatomy with symblepharon, ankyloblepharon and goblet cell Unpreserved solutions should be used to minimize epithelial
deficiency with resultant tear film abnormalities, or intrinsic toxicity. Unpreserved drops can be used every hour or more
epithelial abnormalities can also delay healing. frequently if needed. However, if required more than every two
Patients may present with inadvertent self-inflicted epithelial hours, punctal plugs should be considered. Carbomer gel based
damage through mechanical trauma with fingernails, mascara medication (e.g. Viscotears) and ointments without preservative
brushes, or curling irons and through the abuse of topical are retained in the conjunctival fornices for longer and may also
medication. be used four times a day and supplemented with unpreserved
It is critical for the survival of the donor corneal epithelium tears and/or punctal plugs.
that existing dry eye or local ocular surface disease, such as Patients with sensitivity to lanolin or wood should avoid
ocular pemphigoid, be recognized, treated and controlled before lanolin-containing ointment.
surgery. Topical antibiotics, antivirals, timolol and steroids may all
Aberrant lashes (trichiasis) should be eliminated either by exert a toxic effect on the epithelium and should not be used
electrolysis, or cryotherapy. Lid margin entropion or ectropion, indiscriminately.
lagophthalmos, and lid scarring should be surgically corrected Botulinum toxin ptosis is another treatment for persistent
prior to penetrating keratoplasty. epithelial defect: 7.5 units are injected into the orbital roof,
Blepharitis, whether from local or systemic disease, such as adjacent to levator palpebrae superioris. The ptosis develops in
rosacea, must be controlled with lid hygiene, topical lubrication, 2-3 days, resolves in 6-8 weeks and injections can be repeated.
81
Autologous serum tears containing vitamin A, epidermal Penetrating keratoplasty for non-inflammatory perforation or
growth factor and transforming growth factor-beta have been trauma requires antibiotic cover postoperatively to minimize the
shown to be of benefit in persistent epithelial defects;8 they can risk of infection and endophthalmitis.
be administered 4-6 times daily.
CORNEAL GRAFT IN INFECTED EYES
CORNEAL GRAFTING IN GLAUCOMA
Corneal blindness secondary to infective keratitis is a major
One of the major causes of corneal graft failure is inadequate problem in most parts of the world. Early diagnosis, better
Section II: Penetrating Keratoplasty

control of elevated intraocular pressure (IOP). Significant understanding of pathogenesis, and the availability of potent
endothelial cell loss occurs because of acute and greatly elevated antimicrobial drugs have improved the success rate for medical
intraocular pressure. control of corneal infections, particularly those of bacterial
This is encountered secondary to severe anterior chamber origin. However, virulent and resistant forms of some bacteria,
reaction and may require treatment with topical β-blockers, such fungi and Acanthamoeba can progress inexorably, even with
as timolol maleate 0.5 percent twice daily; α-blockers (e.g. maximal medical therapy, and these may necessitate penetrating
brimonidine) in those with relative contraindications to β- keratoplasty.
blockers may be considered.
Topical prostaglandin analogues are controversial and may Bacterial Keratitis
theoretically stimulate graft rejection, although this has not been
Postkeratoplasty, in the presence of active keratitis, antimicrobial
borne out in practice and these useful drugs are in widespread
treatment is directed against the offending microbe (Fig. 12.4).
use after PK. Dorzolamide may affect the donor endothelial If an etiologic diagnosis has not been established, antibiotic
function and result in prolonged graft edema and should be
coverage with combination therapy or with a broad-spectrum
avoided postkeratoplasty.
medication should be undertaken.
Miotics are known to dilate the ocular blood vessels and Where, the sensitivities are known, the topical antibiotic with
break down the blood-aqueous barrier inducing chronic
the least toxicity, to which the organism is most sensitive, should
iridocyclitis. Miotic use in aphakic patients is associated with
be administered frequently until sterilization is achieved.
increased risk of retinal tear and subsequent retinal detachment. In cases where, the organism and\or sensitivity is unknown,
Systemic carbonic anhydrase inhibitors (e.g. acetazolamide)
combination therapy (e.g. fortified cephazolin and tobramycin)
must be used with great caution in elderly keratoplasty patients
or a broad-spectrum antibiotic (such as a fluoroquinolone) should
as they may trigger a malaise symptom complex consisting of
be given. Cycloplegics are used to alleviate discomfort and
fatigue, depression, anorexia and weight loss; the diuretic effect minimize posterior synechiae, and antiglaucoma medication used
of this drug must also be considered in patients with
as required.
cardiovascular disease.
To minimize the risk of rejection, topical corticosteroids may
If seclusio pupillae develops secondary to posterior be used judiciously. If sensitivities are known, hourly or two-
synechiae, laser iridotomy may be needed to prevent or treat
hourly Fluorometholone acetate 0.1 percent or Prednisolone
pupil block.
acetate 1 percent can be used under sufficient antibiotic cover;
Anti-inflammatory therapy can result in steroid induced in the absence of confirmed sensitivities more cautious use of
glaucoma and topical medication should be carefully tailored to
topical medication is recommended, e.g. Fluorometholone
avoid this.
acetate 0.1 percent 4 times daily.

CORNEAL GRAFT IN INFLAMED EYES (HOT EYES)

Special precautions should be taken in cases of rheumatoid


arthritis, collagen diseases, perforation and trauma.
Postoperative care in these cases is often governed by how
well the ocular inflammation has been controlled preoperatively;
the chances of a successful outcome being inversely proportional
to the inflammatory status of the eye at surgery.
The presence of active systemic vasculitis has a bearing on
long-term outcome of grafting and should be monitored and
treated aggressively in the perioperative period; this may
necessitate the use of systemic as well as intensive topical
immunosuppression (see below—high risk keratoplasty).
Tight control of the systemic disease is necessary to
maximize graft survival and should be undertaken in conjunction
with a rheumatologist or immunologist. Figure 12.4: Microbial keratitis occurring in the graft
82
If perforation occurs, structural integrity can be maintained patients require frequent renal function monitoring. The HEDS
with tissue adhesive (cyanoacrylate or fibrin ‘glue’) until the study did not examine the effect of topical acyclovir as this
infection and inflammation has receded, when regrafting can be preparation is not available in the USA, it may have a role in
safely undertaken. prevention of recurrent disease in patients with a good fellow
eye.
Fungal Keratitis Valacyclovir 500 mg OD for one year has been found to have
equal efficacy as oral Acyclovir 400 mg BD in the prevention
Filamentous (Moulds) e.g. Aspergillus, Fusarium, the following

Chapter 12: Postoperative Care after Penetrating Keratoplasty


of recurrent lesions in immunocompetent individuals with ocular
regimens are currently recommended:
• Topical Natamycin 5 percent every hour initially herpes simplex virus (HSV) disease. 12 Prophylactic oral
Valacyclovir treatment is also at least as effective as oral
• Fluconazole 200-400 mg daily or topical preparation
Acyclovir in preventing recurrence in patients who underwent
1 percent
• Cyclosporine A (CsA) topically 4 times daily corneal transplantation for herpetic keratitis.13
Cyclosporine A—one drop 4 times daily may also be useful
Non-filamentous (Yeasts) e.g. Candida in controlling inflammation.
• Topical amphotericin B 0.075 – 0.15 percent every hour
initially REPEAT CORNEAL GRAFT/
• Cyclosporine A 4 times daily HIGH-RISK CORNEAL GRAFT
In patients not responding to conventional antifungal therapy,
Immunosuppression in High-risk Keratoplasty
Voriconazole (oral 200 mg BD, 2 hrly 1 percent topical eyedrops,
(Table 12.4)
intrastromal injection 50 micrograms/0.1 ml) may be used.9,10
Topical corticosteroids are used only under extremely special Two approaches can be taken to prevent immune mediated
conditions in which removal of the entire infected area has been rejection and ultimately failure (Fig. 12.5) in high-risk corneal
ensured. transplantation:
• Suppression of the host immune response.
Acanthamoeba Keratitis • Making the donor tissue less antigenic: Animal studies have
demonstrated reduced rejection rates for corneal allografts
• Topical amoebicidal drugs
after pretreatment with ultraviolet B irradiation14 and the use
• Polyhexamethyl biguanide (PHMB) 0.02 percent every 2
of anti CD4 receptor antibodies.15
hours
These are difficult cases and should be managed in
• Propamidine isethionate (Brolene) 0.1 percent every 2 hours
conjunction with an immunologist. The role of human leukocyte
• Chlorhexidine every 2 hours
antigen class I and II matching is at present unproven in most
• Neosporin every 2 hours
populations.
• Topical corticosteroids may be given judiciously
Options for immunosuppression (these may be used as single
• Systemic steroids and itraconozole may be required
agents or in combination) include:
• Oral nonsteroidal anti-inflammatory agent
• Cycloplegic Corticosteroids
• Topical anti-acanthamebal medication is often required for
many months to eradicate the infection. Topical: Topical steroids continue to be the primary immuno-
suppressive agents in the postoperative management of high-risk
Herpes Simplex keratoplasty:

Recurrence of herpes simplex infection in the graft may lead to


or mimic a rejection episode. It is often difficult to distinguish
between the two and treating a recurrence as a rejection with
intensive topical steroid will allow uncontrolled proliferation of
the virus. Therefore treatment should be aimed at both, balancing
the epithelial toxicity of the antiviral medication with the
deleterious effect of the steroid on the virus infection.
Acyclovir given orally 200 mg 4 times daily for 4/12, then
twice daily for 4/12 may prevent recurrences of epithelial
keratitis (the Herpetic Eye Disease study—HEDS—
demonstrated this effect while treatment continued).11 It has
therefore been suggested (especially for monocular patients) that
systemic acyclovir treatment may be required on an indefinite
basis for patients at high risk of recurrent epithelial HSK. Such Figure 12.5: Graft failure secondary to profound rejection

83
Table 12.4: Side effects of immunosuppressive agents in high-risk penetrating keratoplasty

Topical steroid Systemic steroids Topical CsA Systemic CsA Azathioprine


Glaucoma, cataract, Weight gain, Ocular discomfort, Hypertension, Anemia,
delayed wound Hypertension, Conjunctival injection, nephrotoxic, neurotoxic, thrombocyto-
healing, infectious hyperglycemia, Punctate keratopathy hepatotoxic, hirsutism, penia, leucopenia,
keratitis peptic ulcer, growth gingival hyperplasia, bone marrow
retardation, mental reactivation of latent suppression,
Section II: Penetrating Keratoplasty

changes, cataract, infections alopecia,


osteoporosis, gastrointestinal
susceptibility to toxicity
infections, avascular
hip necrosis

Topical Fluorometholone acetate 0.1 percent or Prednisolone • Used as a ‘steroid sparing’ agent in rejection for high-risk
acetate 1 percent every 2 hours is most commonly used. keratoplasty.
Systemic: Systemic steroids can be used as an adjunct to topical Renal, hepatic and bone marrow function must be monitored.
therapy in high-risk keratoplasty to minimize risk of rejection: Reversible leucopenia may occur in up to 20 percent of patients.
Methylprednisolone 125–250 mg intravenously at the time
of surgery followed by oral Prednisolone 1 mg/kg/day slowly Mycophenolate Mofetil
tapered in 3-6 months may be useful in high-risk cases.
• 2000-3000 mg daily.
Alternatively, Prednisolone 100 mg orally for 2-3 days, then • Suppresses lymphocyte proliferation in a similar manner to
tapered over two weeks maybe used.
azathioprine.
Severe or refractory rejection may also respond to systemic
Used successfully to treat refractory rejection in renal
immunosuppression. The role of pulsed intravenous transplantation, it has a low incidence of significant adverse
methylprednisolone for severe rejection is not proven and may
effects and is better tolerated than azathioprine.
only be of benefit if the patient presents early in the rejection
It may increasingly have a role in the management of
episode;3 some surgeons prefer to use short-term high dose oral rejection in high-risk keratoplasty.18
Prednisolone in these cases: A single intravenous dose of
Methylprednisolone 500 mg3 or oral Prednisolone 80 mg daily4 Tacrolimus
for 5-7 days may be considered.
Both are given in addition to hourly topical Fluorometholone This is a macrolide immunosuppressant that is a fungal
acetate 0.1 percent or Prednisolone acetate 1 percent. metabolite and suppresses both humoral and cellular immune
responses.
Cyclosporine A Liver transplantation studies have shown it may reduce the
need for adjunctive immunotherapy for treatment of rejection
Topical: Cyclosporine A 2 percent in castor oil or 1 percent in
episodes compared to cyclosporine based regimens.
artificial tears 4 times daily.
Renal function must be monitored and neurological adverse
At present, the penetration of this drug into the anterior effects have been documented (more so with intravenous
chamber or deeper corneal layers is not proven. Combined
preparations).
treatment with Cyclosporine 2 percent and topical corticosteroids
It may surpass cyclosporine as the ‘steroid sparing’ agent of
offered better rejection free graft survival rates over use of topical choice in the future. Recent studies have confirmed its efficacy
corticosteroids alone in a study evaluating results of pediatric
in the management of high-risk keratoplasty.19,20
keratoplasty.16
Topical tacrolimus 0.03 percent ointment seems to be a
Systemic: Some success has been achieved with the use of promising second-line immunosuppressant in management of
systemic cyclosporine in high-risk keratoplasty:17 high-risk grafts.21
• 4-5 mg/kg once or two divided doses daily
• Blood Cyclosporine A level should be between 100-300 REFERENCES
ng/ml. 1. Kamp MT, Finnk NE, Enger C, et al. Patient-reported symptoms
All patients using Cyclosporine A need close monitoring of associated with graft reactions in high-risk patients in the Colla-
blood pressure, renal function including serum creatinine and borative Corneal Transplantation Studies. Cornea 1995;14:43-8.
liver enzymes. 2. Barry P, Seal DV, Gettinby G, et al. ESCRS study of prophylaxis
of postoperative endophthalmitis after cataract surgery. J Cataract
Azathioprine Refract Surg 2006;32:407-10.
3. Hill JC, Maske R, Watson PG. The use of a single pulse of intra-
• 50 mg daily increasing to a maintenance dose of 75-100 mg venous methylprednisolone in the treatment of corneal graft
daily. rejection. A preliminary report. Eye 1991;5:420-24.
84
4. Hill JC, Maske R, Watson PG. Corticosteroids in corneal graft 13. Goldblum D, Bachmann C, Tappeiner C, Garweg J, Frueh BE.
rejection. Oral versus single pulse therapy. Ophthalmology Comparison of oral antiviral therapy with valacyclovir or
1991;98:329-33. acyclovir after penetrating keratoplasty for herpetic keratitis.Br J
5. Hudde T, Minassian DC, Larkin DFP. Randomized controlled trail Ophthalmol. 2008; 92(9):1201-05.
of corticosteroid regimens in endothelial corneal allograft 14. Niederkorn JY, Callanan D, Ross JR. Prevention of allospecific
rejection. Br J Ophthalmol 1999;83:1348-52. cytotoxic T lymphocyte and delayed-type hypersensitivity
6. Donnenfeld E, Pflugfelder SC.Topical ophthalmic cyclosporine: responses by ultraviolet irradiation of corneal allografts.
pharmacology and clinical uses. Surv Ophthalmol. 2009; Transplantation 1990;50:281-86.

Chapter 12: Postoperative Care after Penetrating Keratoplasty


54(3):321-38. 15. Pleyer U, Milani JK, Dukes A, et al. Effect of topically applied
7. Perry HD, Solomon R, Donnenfeld ED, Perry AR, Wittpenn JR, anti-CD4 monoclonal antibodies on orthotopic corneal allografts
Greenman HE, Savage HE. Evaluation of topical cyclosporine in a rat model. Invest Ophthalmol Vis Sci 1995;36:52-61.
for the treatment of dry eye disease. Arch Ophthalmol. 2008; 16. Cosar CB, Laibson PR, Cohen EJ, Rapuano CJ. Topical
126(8):1046-50. cyclosporine in pediatric keratoplasty. Eye Contact Lens.
8. Tsubota K, Goto E, Shimmura S, et al. Treatment of persistent 2003;29(2):103-37.
corneal epithelial defect by autologous serum application.
17. Hill JC. Systemic cyclosporine in high-risk keratoplasty: long
Ophthalmology 1999;106:1984-89.
term results. Eye 1995;9;422-28.
9. Lee SJ, Lee JJ, Kim SD. Topical and oral voriconazole in the
18. Reis A, Reinhard T, Voiculescu A, et al. Mycophenolate mofetil
treatment of fungal keratitis.Korean J Ophthalmol. 2009;
versus cyclosporine A in high-risk keratoplasty patients: a
23(1):46-8.
prospectively randomized clinical trial. Br J Ophthalmol
10. Prakash G, Sharma N, Goel M, Titiyal JS, Vajpayee RB.
Evaluation of intrastromal injection of voriconazole as a 1999;83:1268-71.
therapeutic adjunctive for the management of deep recalcitrant 19. Sloper CM, Powell RJ, Dua HS. Tacrolimus (FK506) in the
fungal keratitis.Am J Ophthalmol. 2008;146(1):56-59. management of high-risk corneal and limbal grafts.
11. Herpetic Eye Study Group. Oral acyclovir for herpes simplex Ophthalmology 2001;108:1838-44.
virus eye disease: effect on prevention of epithelial keratitis and 20. Joseph A, Raj D, Shanmuganathan V, et al. Tacrolimus
stromal keratitis. Arch Ophthalmol 2000;118:1030-36. immunosuppression in high-risk corneal grafts. Br. J. Ophthalmol
12. Miserocchi E, Modorati G, Galli L, Rama P. Efficacy of published online 6 Sep 2006.
valacyclovir vs. acyclovir for the prevention of recurrent herpes 21. Dhaliwal JS, Mason BF, Kaufman SC. Long-term use of topical
simplex virus eye disease: a pilot study. Am J Ophthalmol. 2007; tacrolimus (FK506) in high-risk penetrating keratoplasty.Cornea.
144(4):547-51. 2008;27(4):488-93.

85
13
Section II: Penetrating Keratoplasty

Postkeratoplasty Contact Lens Fitting


Rajesh Sinha, Jeewan S Titiyal

Contact lens can be used for either visual or therapeutic purposes Short-term Indications
after a successful penetrating keratoplasty.1-3 For optimal visual
Therapeutic contact lenses may be useful in the presence of
rehabilitation, contact lenses may be required when there is
epitheliopathy following keratoplasty. Most graft epithelial
marked postoperative astigmatism, anisometropia or aphakia. On
defects heal within 48-72 hours. Certain conditions where the
the other hand, bandage soft contact lenses are used to promote
epithelial defect persists beyond 72 hours, use of a bandage
surface healing in the presence of persistent epithelial defect.
contact lens may help to promote epithelial healing. It is also
Advances in microsurgical techniques and postoperative care
indicated in the presence of a persistent punctate epitheliopathy
have made it possible to achieve a high rate of clear graft in a
in the graft. Soft (hydrogel) contact lenses are the ones that are
number of clinical conditions. Despite all these advances, many
used in such conditions.
corneal surfaces remain irregular and have high degrees of
There are certain clinical conditions where in epithelial
astigmatism following penetrating keratoplasty.4 In most of the
healing is impaired. Patients being transplanted for Stevens-
studies, postoperative astigmatism ranges between 4 to 5
Johnson syndrome, alkali burns and herpetic neurotrophic ulcers
diopters. 5-7 Excessive astigmatism decreases potential
require cover for the epithelium as early as possible after surgery
uncorrected visual acuity, reduces best-corrected spectacle acuity,
to promote and maintain epithelialization.10 Again, therapeutic
and is associated with asthenopic symptoms when patients are
lenses may play a role in patients who have lagophthalmos. It is
given spectacles. The astigmatism can be caused by factors like
also indicated in certain lid or conjunctival deformities like
the configuration of trephine incisions, donor-recipient graft
keratinized conjunctiva, irregular lid margins, cobblestone
disparity, irregular and tight suturing and differences in thickness
papillae from vernal catarrh, that do not need plastic surgery
of donor and recipient wound edges creating a step.
before grafting but that may traumatize the epithelium of the fresh
Various approaches have been tried to reduce postoperative
graft.
irregular astigmatism, which includes suture adjustment, selective
Although trichiatic lashes should be removed before corneal
suture removal and occasionally refractive surgery. The non-
surgery, lash deviation, often in association with spastic
surgical approaches to the management of postkeratoplasty
entropion, may create problems in the postoperative period.
astigmatism can be spectacles, rigid gas permeable (RGP)
A bandage contact lens may be useful temporarily in such cases.
contact lens, soft toric contact lens, contact lens and spectacle
At times, therapeutic contact lens can be used to prevent
combination, piggyback and hybrid contact lenses. RGP contact
trauma to the graft by the lids, e.g. if there is slight graft override
lenses are usually the correction of choice for such patients
(misalignment) or if the edge of the graft is elevated by edema
because of the need to correct regular and irregular astigmatism
in the suture compression zone. Such lenses will allow defects
with due consideration to improved oxygen transmission.8
on the elevated portions of the graft to heal and may also prevent
dellen formation in the adjacent concave areas where wetting
INDICATIONS
by lid may not be proper.10 Finally, it has been seen on rare
Contact lenses of various types remain an important tool in the occasion that small wound leaks can be sealed by temporary
visual rehabilitation of patients after penetrating keratoplasty. placement of a therapeutic lens.
Around 10-25% of the postkeratoplasty patients require contact
Long-term Indications
lens for visual rehabilitation.1,6,9 Therapeutic contact lenses are
used for short-term to enhance graft resurfacing.10 Long-term Optical correction is the primary aim of long-term use of contact
use of these lenses is mainly for optical purposes. lenses following penetrating keratoplasty. The primary indication

86
for visual rehabilitation using contact lenses is high corneal the patients of keratoconus. These patients are often excellent
toricity, irregular astigmatism, anisometropia and uniocular rigid contact lens candidates, since they have often worn rigid
aphakia. lenses for many years previously under less optimal fitting
The increasing use of triple procedure (penetrating conditions, and they are usually rigid contact lens corrected in
keratoplasty, extracapsular cataract extraction and intraocular the non-grafted eye.12 Studies indicate that such postkeratoplasty
lens implantation) in dealing with combined corneal and lens patients can be fitted in the early postoperative period even in
pathology is based on providing visual correction without the the presence of sutures, that acuity and lens tolerance are good

Chapter 13: Postkeratoplasty Contact Lens Fitting


need of contact lens use. However, contact lenses do have a role and that prekeratoplasty experience is an important factor in the
when the graft has high or an irregular astigmatism. In some such rapid rehabilitation of these patients.
cases, rigid contact lens may be a better alternative to corrective
refractive surgery. CONTACT LENSES FITTING METHOD
Either rigid or soft contact lens may be employed for visual
Although lenses can be fitted when sutures are in place, rigid
purposes, depending on a variety of factors. The options from
lenses are usually fitted after suture removal, 12 to 18 months
which a physician has to decide are a rigid contact lens, a daily
postoperatively (Fig. 13.1). Prior to lens fitting, K readings and
wear or an extended wear soft contact lens, piggyback or hybrid
manifest refraction should be stable over a period of a couple
lenses. The indications for a specific lens type depend mainly
of months.
on the refractive status of the eye, the degree of corneal toricity
and the specific needs of the patient.
Prefitting Physiologic and
In an aphakic patient, with a graft of low toricity (< 2.5D),
Topographic Considerations
the physician may consider either a rigid contact lens or a soft
lens. In the presence of high corneal toricity or irregular The penetrating keratoplasty patient presents with an unusual
astigmatism, either a rigid lens or a piggyback system can be physiologic status. The patient’s donor button is entirely
employed. repopulated with host epithelium and keratocyte replacement has
In most of the phakic graft patients, contact lens correction begun by the time contact lens fitting is initiated. Unfortunately
can be achieved with rigid lenses or with daily wear soft lenses corneal innervation is permanently altered by penetrating
if corneal toricity is not excessive. If there is high toricity in the keratoplasty,13 and endothelial function may differ significantly
graft, rigid lens is the sole alternative. Most of the cases of from the preoperative status.14 Again, the impact of contact lens
keratoconus have high postoperative graft toricity and require wear on both corneal innervation,15 and endothelial function16
rigid contact lens for visual rehabilitation.9 has been well documented. For this reason, the physician has to
select a lens design that has a minimal impact on corneal
SOFT CONTACT LENSES physiology. In meeting this objective, ensuring adequate oxygen
transmissibility is a major priority. The rigid gas permeable
In the phakic or aphakic graft with low toricity, daily wear soft (RGP) lenses, owing to their high oxygen transmissibility, are
contact lenses can be used. The use of extended wear soft contact
an obvious choice (Fig. 13.2). To date, fluorosilicone-acrylates
lenses is more problematic as most studies have shown that the
are recommended because of their good oxygen transmission
corneal graft tolerates the extended wear contact lens poorly and characteristics.17
that its use in such patients is associated with corneal
vascularization. This increases the risk of graft rejection and
hence graft failure. On the contrary, some studies have shown
that extended wear contact lenses can be fitted in such patients
with long-term success.5,11 Regardless of the findings of various
studies, the indication for an extended wear lens in the graft
patients must be based not only on visual need but also on those
factors that may play a significant role in the success of the lens,
including lid function, tear quality and production, hygiene and
patient reliability. There has to be a serious commitment on part
of both patient and physician to monitor lens wear closely. Soft
contact lens especially extended wear has very limited use in
postkeratoplasty contact lens rehabilitation.

RIGID CONTACT LENSES

As mentioned earlier, rigid lenses play a significant role in visual


rehabilitation of phakic, aphakic and pseudophakic graft patients
with high corneal toricity.11,15-17 One such group comprises of Figure 13.1: Clear graft after suture removal

87
When a hydrogel lens is indicated, the physician should silicone-content lenses.17 With hydrogel lenses, high water lens
consider an extended wear variety worn on a daily basis. The options and ultrathin designs are usually contraindicated.20 The
limited oxygen profiles of hybrids and piggyback designs make use of prophylactic lid hygiene, ocular surface lubricants, and
each a less logical first choice. If these lens designs are indicated punctal occlusion should be considered if the patient remains
for other reasons, then a limited wearing time may be symptomatic. The potential for ocular surface erosion is
recommended. increased if an RGP lens is fitted on a highly irregular graft
Another factor of serious consideration in keratoplasty surface. Erosion is often the result of focal lens bearing and can
Section II: Penetrating Keratoplasty

patients is that of corneal neovascularization. be sometimes managed by altering lens design. If epithelial
If the patient’s pre-existing corneal disease is marked by erosion persists despite lens design alterations, the most prudent
severe inflammation, neovascularization may actually precede solution involves refitting into a hydrogel or piggyback design.
surgery. Often neovascularization develops as part of the In addition to these physiologic concerns of fitting the
postoperative healing phase. Aggressive corneal neovasculariza- penetrating keratoplasty patient, there are obvious topographic
tion can predispose an individual towards graft rejection.18 In considerations. Patients after penetrating keratoplasty often
contact lens patients, neovascularization has been associated with manifest a topographic profile that differs considerably from the
intracorneal hemorrhage and lipid leakage, both of which can normal cornea. This is often the result of many factors that
impair vision. Again, long-term use of contact lens itself can includes preoperative corneal pathology, donor-recipient
cause corneal vascularization. Although the exact mechanism of topographic discrepancies, surgical technique and wound healing.
contact lens induced corneal neovascularization is not known, With the corneal graft patient a significant discrepancy can exist
the importance of adequate oxygenation and minimal between the donor and recipient topographies. The resultant
inflammation is evident.19 In an effort to satisfy these needs, a cornea may manifest unusual asphericities, irregular optic zones
gas permeable lens design is often utilized. and a dramatically displaced apex. These topographic alterations
Hydrogel, hybrid and piggyback designs are less desirable result in postoperative visual disturbances which present as a
for the vascularized corneal graft, as they cover a large portion specific challenge to the contact lens fitter. Historically corneal
of the peripheral cornea. This additional coverage can result in topography measurements were limited to keratometry. In recent
a tight fit, hypoxia, and tear stagnation, inducing further years these measurements have been expanded to include
encroachment of the vessels. automated keratometry and photokeratoscopy.21 These days
Another important consideration regarding the physiologic computer assisted topographic analysis is advantageous to assess
status of the graft patient involves the corneal surface disease. the topography of regular and irregular corneas,22-29 monitor
In view of the significantly altered corneal topography, a contact lens induced corneal warpage,30 and as baseline measure-
keratoplasty patient often manifests an irregular tear film. This ments for fitting cosmetic, keratoconic and postsurgical contact
is most often observed at the graft host junction and at the site lenses.31-33 Recent software enhancements now allow the use of
of suture tracks. The compromised tear film may predispose these corneal topography to design rigid lenses.
individuals towards ocular surface disease, including keratitis
sicca, contact lens induced erosions and infectious keratitis. Contact Lens Options
No single material or design is most beneficial in managing
The aims of contact lens fitting after penetrating keratoplasty
the dry eye. While selecting an RGP lens it is wise to avoid high involve correction of residual refractive error, comfort
commensurate with a reasonable wearing time, and maintenance
of ocular health. It has long been accepted that such goals are to
be achieved by utilizing a variety of contact lens options and by
employing fitting techniques that are as much an art as a science.

Gas Permeable Lenses


Although lenses can be fitted when sutures are in place, rigid
lenses are usually fitted after suture removal, 12 to 18 months
postoperatively. Gas permeable lenses are preferable to standard
polymethylmethacrylate lenses. Enhanced oxygen trans-
missibility is desirable in the presence of a graft. Because of
astigmatism and ocular surface irregularity, it is often impossible
to achieve a perfect lens fit. Use of gas permeable materials
appears to improve the patient’s tolerance of lenses having areas
of corneal touch where the fit is fairly flat. Lens flexure and poor
wetting can be minor problems with gas permeable lenses, but
Figure 13.2: Rigid gas permeable contact lens after these can be alleviated through modifications in the lens design
penetrating keratoplasty and use of appropriate wetting agents and topical lubrication.
88
Goals Lens Materials
The goals in rigid contact lens fitting after keratoplasty are to Among the RGP materials fluorosilicone acrylate offers the
achieve adequate lens centration and movement, optimal visual greatest margin of safety. This material provides excellent oxygen
acuity, and good lens tolerance. Proper lens centration is difficult transmission, improved surface characteristics, and acceptable
to obtain, owing to asymmetry of the graft wound. Often there flexure resistance in comparison to other materials.
is a tendency for the lens to gravitate towards one aspect of the
wound, and lens also tends to ride high. Perfect centration is Lens Overall Diameter

Chapter 13: Postkeratoplasty Contact Lens Fitting


not necessary, but it is important to avoid decentration to the
Most clinicians agree that lenses with an overall diameter of at
extent that the lens passes over the limbus during blink-induced least 9.0 mm are indicated in graft patients.34 The earlier concept
movement. Lens contact with the limbus is usually associated
of a small (7.0 to 8.0 mm) lens fitted inside the graft-host junction
with discomfort (Fig. 13.3).
has been abandoned. Difficulties with lens position, poor
Lenses should be fit loosely enough to ensure 1 to 2 mm of comfort, and easy displacement have accounted for this designs
movement with each blink. Initially, there is often reflex tearing,
disfavor. Longer overall diameters of 9.5 to 11.0 mm are
so the lens movement must be evaluated after at least 30 minutes
necessary if the corneal apex is grossly decentered and the lens
of lens wear. Lens movement is necessary for tear exchange centration is a problem. These larger designs may also facilitate
under the lens, which in turn, is important not only for the
lid attachment. In general, flatter corneas are fit with larger lenses
delivery of oxygen that can pass through the lens but also for
and steeper corneas with smaller ones.
the removal of exfoliated material from under the lens.
Lens flexure or rocking can reduce acuity by several lines. Optic Zone
Sometimes lens flexure is diminished with a larger or thicker
lens. Lens rocking is often associated with edge lift, which can The optic zone diameter should be modified according to overall
be reduced through the use of either a steeper or a smaller lens. lens diameter. Ideally, optic zone diameter should be as large as
Lens fit as well as lens power affect visual acuity in the presence possible to facilitate lens centration and minimize glare, but not
of a graft. so large as to create harsh bearing or result in lens binding. The
The most important goal in contact lens fitting is to achieve optic zone diameter should equal the base curve when both are
good lens tolerance. The patient should be able to wear the lens expressed in millimeters. For example, a contact lens with a base
with reasonable comfort for 10 to 14 hours per day. Gas curve of 42.50D would have an optic zone of 7.95 mm.
permeable lenses with adequate centration and movement are
usually well-tolerated despite an imperfect fit over an irregular Base Curve and Peripheral Curve Systems
graft surface. Keratometry (K) provides a useful starting point for rigid lens
fitting but is of limited value in the final lens selection. After
Fitting Method keratoplasty, a wide range in curvature is present. The mires often
There are certain guidelines for selecting an initial trial lens, but are distorted making accurate measurement difficult. Routine
experience and trial and error are factors in the selection of keratometry measures only a small area of the central cornea.
subsequent trial lenses. Unfortunately, the graft topography is Because the shape of cornea near the graft-host junction is
often a challenge for the clinician who fits an RGP lens. To gain equally important in lens fitting, corneal topography, which
a better perspective on lens material and design considerations provides more information about surface topography than does
we will look at each variable. keratometry, is useful. Computerized videokeratoscopy software
programs have the capability to design initial RGP lens
parameters and simulate contact lens fluorescein patterns. Such
programs allow the physician to choose posterior lens curvature,
an overall and optic zone diameter, edge lift and power in some
instances.
Usually the first trial lens used is on or near flat K. Using
videokeratography, the average of the two flattest readings at a
point 1.5 mm superior to the visual axis can be used to select
the base curve of the initial trial lens. When astigmatism is greater
than 5 diopters, the selected initial trial lens is steeper than flat
K. The physician should modify base curve selection to facilitate
a divided support fit. In this strategy, the clinician strives for a
lens-cornea fitting relationship in which there is approximately
one-third surface area bearing and two-thirds surface area
clearance.35 Toric base curve options should be reserved for
Figure 13.3: Poorly fit contact lens patients whose grafts are highly astigmatic. Although many are
89
of the opinion that approximately 7D of postoperative manifest refraction expressed in minus cylinders. Sometimes, it
astigmatism is average,2 the irregular nature of this astigmatism is not possible to obtain excellent visual acuity with an over
precludes routine use of back toric designs. As aspheric lens refraction.
designs have long been recognized for their ability to Immediately after fitting a trial lens, slit lamp examination
accommodate atypical topographies, this option seems to be should be performed. A superior lens position with good lens
another logical choice. Recent work with a biaspheric back movement (1-2 mm) is the goal of fitting. A fluorescein pattern
surface design has proven beneficial for penetrating keratoplasty indicating a relatively flat fit is preferred. A tight lens fit should
Section II: Penetrating Keratoplasty

patients.36 be avoided in keratoplasty patient.


There is no clear consensus regarding the appropriate
peripheral curve system for fitting the penetrating keratoplasty Rose K Contact Lens
patient. As the central-peripheral corneal topography relationship
Rose K design of rigid gas permeable contact lens has been
is so dramatically altered in these patients, a traditional base successfully fitted in eyes with keratoconus38,39 and is now
curve-peripheral curve relationship may no longer be indicated.
becoming increasingly popular for postkeratoplasty fitting as well
There is one definite situation in which the peripheral curve
(Figs 13.4 and 13.5). The Rose K system has set optical zones
system is of paramount importance. This involves the patient to maximize vision while maintaining good corneal health.
with a plateau graft and difficulty with lens centration. In such
A separate set of post-graft trial lenses (Rose K2 post-graft) are
cases, an unusually steep peripheral curve system is indicated.
available for fitting Rose K contact lens after keratoplasty. Unlike
Such situation may require RGP design in which the secondary normal corneas, the post-graft cornea has irregularity on its
curve is steeper than the base curve.
surface and to achieve optimal alignment with the cornea, many
One recent study has reported the use of tetra-curve contact
curves are required on the back surface of the lens.
lens with an overall diameter of 12.0 mm in postkeratoplasty
patients.37 The lens was well-tolerated in all patients for more Rose K Post-graft Fitting Procedure
than 13 hours daily.
There are certain guidelines for fitting Rose K lens in
postkeratoplasty patients.
Lens Thickness

Whenever possible the thinnest design should be used to enhance Pre-fitting Examination
lens comfort, centration and optimum oxygen transmission.
A thorough history of the patients should be taken that should
Thicker lenses should be reserved for problem with flexure,
include the motivation of the patient towards using the contact
warpage, or frequent lens damage. lens. A detailed examination of the eye should be done in view
of the suitability for fitting contact lens.
Lens Power
Initial Base Curve Selection
Refraction with spheres over a trial lens of appropriate base curve
and diameter is necessary to determine which lens power to order. The initial base curve is 0.3 mm steeper than the average K
It is helpful, if a trial lens that approaches the correct power can reading. If the patient is already wearing an RGP contact lens, a
be used. Ideally, the lens power should be compatible with the base curve similar to the present lens may initially be tried.

Figures 13.4 and 13.5: Rose-K contact lens fitting over a corneal graft
90
Central Fit factor why it is relatively unacceptable is the potential for
neovascularization.24 Soft lenses are worn in an extended wear
Adequate time should be given for the lens to equilibrate on the
mode, the incidence of infectious keratitis can be expected to
eye and also to minimize watering in the eye. The central fit is
increase significantly.
evaluated by fluorescein pattern immediately after blink when
the lens is centered. A central pooling of 0.2-0.3 mm is acceptable Therapeutic Soft Contact Lens Fitting
in early flatter graft where the donor tissue is still flatter than
the host tissue but an alignment of 0.1 mm in older grafts is Bandage soft contact lenses are useful in management of

Chapter 13: Postkeratoplasty Contact Lens Fitting


aimed. An excessive amount of fluorescein may give a false postkeratoplasty epithelial defects and persistent superficial
picture. Similar situation can arise if there is excessive watering punctate keratitis. Patients with ocular surface diseases and
in the eye. neurotrophic keratitis prior to keratoplasty are predisposed to
nonhealing epithelial defects postoperatively. However, many
Peripheral Fit graft patients without these conditions also have significant
superficial punctate keratitis. This is caused by poor wetting due
Once a good central fit is achieved, the peripheral edge lift is to abnormal corneal topography near the wound and, in some
assessed. An even fluorescein band of 0.5-0.7 mm is aimed. cases, due to drug toxicity. When topical lubrication or patching
do not result in surface healing, bandage lenses are often
Size of the Lens beneficial. A variety of plano lenses with variable water content
The standard overall diameter in post-graft Rose K2 contact lens depending on the indication, can be used. Patients wearing
for initial trial is 10.4 mm. The purpose of using large diameter therapeutic lenses can be maintained on topical medications as
lenses is to achieve a better centration of the lens. needed for the underlying condition. Lens fit must be checked
after 1 hour, 1 day and 1 week of lens wear, and then monthly
Power to ensure that the lens moves 1-2 mm with the blink, the eye is
white and quite, and the graft is tolerating the lens.
Once the base curve has been determined, over refraction is done
to determine the correct power of the contact lens. Piggyback Lenses
When an RGP or hydrogel lens alone does not suffice, a
Soft Contact Lens Fitting
combination of the two may be indicated. The “piggyback”
Hydrogel Lenses involves using a hydrogel lens for surface smoothing and then
employing a rigid lens for visual restoration.
Soft contact lenses are fitted following keratoplasty more
frequently for therapeutic purposes to promote surface healing Materials
than for visual purposes.
The potential for oxygen debt is significant when one considers
Aphakia is one indication for corrective daily-wear and
the simultaneous use of a hydrogel and rigid contact lens.
extended-wear soft contact lens fitting. Extended wear soft
Therefore, high-oxygen transmission materials should routinely
contact lenses are used in elderly aphakic patients who are unable
be prescribed. During lens adaptation, the clinician should
to manipulate daily-wear lenses and who have only a low or
carefully monitor biomicroscopy and adjust wearing time
moderate amount of astigmatism. Another indication for hydrogel
accordingly.
lens is an atypical graft-recipient geometry with attending RGP
lens instability. Unfortunately, these cases may concomitantly
Design
manifest significant amount of astigmatism and require
adjunctive spectacle correction. The two major determinations in selection of hydrogel lens are
In prescribing for a corneal graft patient a balance between corneal topography and prescription. If the patient has a flat graft,
oxygen permeability and good surface characteristics is then a mid-plus range lens design is selected. This particular
important. For myopic correction this generally involves a thin carrier lens will accommodate the anticipated need for plus
design with low water content. For moderate and high plus power correction while providing for a steeper topography on
correction, an intermediate water content design is usually which to place the rigid lens. If the patient has a steep graft,
indicated. then an ultrathin mid-minus range lens design is indicated. This
The clinician may wish to consider a toric hydrogel lens to carrier lens will lessen the amount of minus power required in
cover for the astigmatism in keratoplasty patients. However, these the rigid lens while providing a flatter topography on which to
patients manifest significant amount of irregular astigmatism on fit the rigid lens. In either of these situations, the value of
corneal topographic analysis and may cause a problem in fitting incorporating some of the refractive power into the hydrogel lens
a back toric design. allows the use of a thinner and lighter rigid lens.
The primary reason why hydrogel lenses are not fitted in a The actual fitting of a “Piggyback” lens design begins with
corneal graft patient involves poor visual outcome. Another evaluation of the underlying hydrogel lens. The lens should be
91
allowed to equilibrate and then evaluated for centration and lens important among patients of penetrating keratoplasty, as the graft-
movement. Optimal to slightly excessive lens movement is host junction and suture tracks are highly prone to infection and
encouraged, as once the rigid lens is placed over the hydrogel the eye may be immunocompromised as a result of long-term
its movement is almost certainly diminished. Once, a satisfactory steroid usage. The significance of epithelial erosion, loose
hydrogel lens fit is obtained, over-keratometry is performed. The sutures, improper contact lens hygiene, bacterial invasion,
result of over-keratometry serves as a starting point for rigid lens compromised host immunity and delayed treatment is obvious
selection. The average of flat and steep over- keratometric value in establishing condition for potential infectious keratitis.
Section II: Penetrating Keratoplasty

is often a reasonable starting point for rigid lens selection. Final A keratoplasty patient fitted with hydrogel lenses is prone
base curve, overall diameter, optic zone, peripheral curve, power, to develop corneal neovascularization resulting in a high chance
and thickness determinations are best accomplished by diagnostic of graft rejection. Again, optical quality of hydrogel lenses is
fitting. High molecular weight fluorescein can be utilized to not as good as RGP. Moreover, as these lenses are used for
assess optical clearance of the rigid lens relative to its hydrogel extended wear, there is always the risk of infection.
carrier. Care must be taken to avoid a tightly fitted rigid lens, as The complications that can be associated with piggyback and
this often traps interfacial debris. hybrid designs are corneal edema, neovascularization, contact
lens adherence, acute red eye episodes, infectious keratitis and
Hybrid Lenses graft rejection. Another problem with hybrid designs is difficulty
Hybrid lenses were designed to combine the comfort and in inserting and removing the lens and a high percentage of lens
centering capabilities associated with hydrogel lenses with the separation. Because of the difficulty in removing the lens and
visual acuity offered by a rigid lens. The soft perm (SBH Corp. the presence of a junction between the optical centre and
Sunny vale, CA) lens is a hybrid lens made from a single button hydrogel skirt, the lens can tear relatively easily.
containing a co-polymerized hydrophilic skirt with an RGP Many contact lens designs may be employed for the
center molecularly bonded at the transition zone. refractive management of a graft patient. These include RGP,
The overall diameter of the lens is 14.3 mm and the rigid hydrogel, hybrid and piggyback lenses. The specific design
optical zone diameter is 8 mm. A single base curve is selected selected is dependent on a number of factors, which includes
from a diagnostic set of trial lenses based upon the mean central corneal graft physiologic status, corneal topography, refractive
keratometry reading. The greater the increased corneal toricity, error, desired wearing schedule and patient handling capabilities.
the steeper the base curve selected. Because the RGP center Each of these factors must be weighed independently to ensure
diameter is 8.0 mm, one typically fits steeper than the flattest K the greatest likelihood of contact lens success.
to achieve a parallel sagittal depth in relationship to the cornea.
The final base curve must be selected by diagnostic fitting, with REFERENCES
each trial lens allowed to equilibrate for a minimum of
1. Cohen EJ, Adams CP. Postkeratoplasty fitting for visual
15 minutes. Regardless of a good visual response and positive rehabilitation, in Dabezies OH jr (Ed): Contact Lenses: The
patients acceptance, adequate lens movement is essential. Once CLAO Guide to Basic Science and Clinical Practice. New York,
an optimal fit is achieved, an over refraction is performed to Grune and Stratton 1984; Chapter 52.
determine exact lens power. Certain clinicians believe that this 2. Genvert GI, Cohen EJ, Arentsen JJ, Laibson PR. Fitting gas
lens permits a more over-refraction free from the unstable, permeable lenses following penetrating keratoplasty. Am J
inconsistent vision that can be associated with RGP lenses that Ophthalmol 1985;99:511-14.
have been fit over corneas with irregular astigmatism.40 3. McDonald M, Baldone JA. Postkeratoplasty fitting to enhance
re-epithelialisation, in Dabezies OH jr (Ed): Contact Lenses: The
Complications CLAO Guide to Basic Science and Clinical Practice. New York:
Grune and Stratton 1984; Chapter 53.
Any keratoplasty patient fitted with contact lens has to be 4. Binder PS. The effect of total suture removal on Postkeratoplasty
monitored carefully for possible complications. A corneal graft astigmatism. Am J Ophthalmol 1988;105:637-45.
fitted with contact lens is prone to develop certain specific 5. Cayanaugh HD, Leveille AS. Extended wear contact lenses in
complications owing to altered corneal surface physiology and patients with corneal grafts and aphakia. Ophthalmology
topography. There is high risk of ocular surface erosion 1980;89:643-50.
particularly if an RGP lens has been fitted on a highly irregular 6. Jensen AD, Maumenee AE. Refractive error following
graft surface. Erosion is often the result of focal lens bearing keratoplasty. Trans Am Ophthalmol Soc 1970;72:123-31.
7. Troutman RC, Gaster RN. Surgical advantages and results of
and can sometimes be managed by altering lens design. Bad
keratoconus. Am J Ophthalmol 1980;90:131.
ocular surface and compromised tear film may further aggravate
8. Bennett ES, Weissman BA. Clinical Contact Lens Practice.
the existing situation. The use of ocular surface lubricants and Philadelphia, JB Lippincott Company 1991;Chapter 47, 9-10.
lid hygiene should be considered. Infectious keratitis is the most 9. Buxton JN. Contact Lenses in keratoconus. Contact Intraoc Lens
dreaded consequence of ocular surface disease. The propensity Med J 1978;4:74.
of certain bacteria to colonize epithelial defects in contact lens 10. Casey TA, Mayer DJ. Contact lenses and keratoplasty. Corneal
users is well documented.41 This consideration is especially Grafting. Philadelphia, WB Saunders 1984;281-88.
92
11. Dangel ME, Kracher GP, Stark WJ, et al. Aphakic extended wear 28. Wilson SE, Friedman RS, Klyce SD. Contact lens manipulation
contact lenses after penetrating keratoplasty. Am J Ophthalmol of corneal topography after penetrating keratoplasty, A preliminary
1983;95:156-60. study. CLAO J 1992;18:177-82.
12. Mannis MJ, Zadnik K, Deutch D. Rigid contact lens wear in the 29. Strelow S, Cohen EJ, Leavitt KG, et al. Corneal topography for
corneal transplant patient. CLAO J 1986;12:39-42. selective suture removal after penetrating keratoplasty. Am J
13. Ruben M, Colebrook E. Keratoconus, keratoplasty curvatures and Ophthalmol 1991;112:657-65.
lens wear. Br J Ophthalmol 1979;63:268. 30. Wilson SE, Lin D, Klyce SD, et al. Rigid lens decentration: A
14. Brown NAP, Bron AJ. Endothelium of the corneal graft. Trans risk factor for corneal warpage. CLAO J 1990;16:177-82.

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Ophthalmol Soc UK 1974;94:863. 31. Wasserman D, Itzkowitz J, Kamenar T, et al. Corneal topographic
15. Millodot M. Effect of the length of wear of contact lenses on
data: Its use in fitting aspheric contact lenses. CLAO J
corneal sensitivity. Acta Ophthalmol 1976;54:721.
1992;18:83-85.
16. Holden BA, Sweeny DF, Vannas A, et al. Contact lens induced
32. Rabinowitz YS, Garbus JJ, Garbus C, et al. Contact lens selection
polymegathism. Invest Ophthalmol Vis Sci 26(suppl.): 1985;275.
for keratoconus using a computer-assisted videokeratoscope.
17. Tomlinson A. Choice of materials—a material issue. Contact Lens
CLAO J 1991;17:88-93.
Spectrum 1990;5:27.
18. Lemp MA. The effect of extended wear aphakic hydrophilic 33. Lopatynsky M, Cohen EJ, Leavitt KG, et al. Corneal topography
contact lenses after penetrating keratoplasty. Am J Ophthalmol for rigid gas permeable lens fitting after penetrating keratoplasty.
1980;90:331. CLAO J 1993;19:41-44.
19. McMonnies CW. Etiology of contact lens induced corneal 34. Zadnik K. Post-surgical contact lens alternatives. Intern Contact
vascularisation. Int Contact Lens Clinics 1984;11:287. Lens Clinics 1988;15:211.
20. Helton DO, Walton LS. Hydrogel contact lens dehydration rates 35. Shovlin J, Kame R, Weissman B, DePaolis M. How to fit an
determined by thermogravimetric analysis. CLAO J 1991;17:59. irregular cornea. Rev Optom 1987;124:88.
21. Gormley D, Gerston M, Koplin RS, Lubkin V. Corneal modeling. 36. Weiner B. Contact lens correction of the post-penetrating
Cornea 1988;7:30. keratoplasty patient. Contact Lens Update 1989;8:61.
22. Dingledein SA, Klyce SD. The topography of normal corneas. 37. Eggink FAGJ, Nuijts RMMA. A new technique for rigid gas
Arch Ophthalmol 1989;107:512-18. permeable contact lens fitting following penetrating keratoplasty.
23. Dingledein SA, Klyce SD. Imaging of the cornea. Cornea Acta Ophthalmol Scand 2001;79:245-50.
1988;7:170-82. 38. Betts AM, Mitchell GL, Zadnik K. Visual performance and
24. Wilson SE, Klyce SD. Advances in the analysis of corneal
comfort with the Rose K lens for keratoconus. Optom Vis Sci.
topography. Surv Ophthalmol 1991;36:269-77.
2002;79(8):493-501.
25. Bogan ST, Waring GO, Ibrahim OA, et al. Classification of normal
39. Jain AK, Sukhija J. Rose K contact lens for keratoconus. Indian
corneal topography based on computer assisted videokerato-
graphy. Arch Ophthalmol 1990;108:945-49. J Ophthalmol. 2007;55(2):121-25.
26. Wilson SE, Lin D, Klyce SD. Corneal topography of keratoconus. 40. Binder PS, Kopecky L. Fitting the short-term contact lens after
Cornea 1991;10:2-8. keratoplasty. CLAO J 1992;18:170-72.
27. McMohan TT, Robin JB, Scarpulla KM, et al. The spectrum of 41. Reichert R, Stern G. Quantitative adherence of bacteria to human
topography found in keratoconus. CLAO J 1991;17:198-204. corneal epithelial cells. Arch Ophthalmol 1984;102:1394.

93
SECTION III: Penetrating Keratoplasty:
Management of Complications

14

Chapter 14: Complications of Penetrating Keratoplasty


Complications of Penetrating Keratoplasty
Namrata Sharma, Urmimala Ghatak, Rasik B Vajpayee, Hugh R Taylor

Significant technological advances in last few decades have superpinkie or a similar device can reduce vitreous as well as
increased the survival rate of corneal grafts after penetrating intraocular pressure. Hypotensive drugs such as systemic
keratoplasty. Numerous noteworthy advancements have been acetazolamide may be given preoperatively. Intravenous
made in the fields of corneal preservation, surgical techniques mannitol 1-2 g/kg body weight may be given 30 minutes before
and postoperative care. However, inspite of these advancements, surgery.
complications after corneal grafting surgery have not become Further the lid speculum should be checked for the possible
rare. While some of these complications like graft infection and increase in the vitreous pressure and preferably a speculum with
graft rejection threaten the graft survival, others like high post- separate specula for upper lid and lower lid should be used.
keratoplasty astigmatism prevents achievement of optimal visual
Management: If the vitreous face is ruptured, a partial anterior
acuity even with a clear graft. This chapter reviews the possible
vitrectomy should be performed with an automated vitrectomy
problems and complications that occur during penetrating
device. Some surgeons advocate the use of pars plana vitreous
keratoplasty so that they can be prevented or treated
aspiration with an 18-gauge needle attached to a 3-ml syringe
appropriately.
to tap the vitreous.1
The successful management of complications associated with
any surgery requires a combination of recognition, and
Scleral Perforation during Application
knowledge of important risk factors involved. The complications of Fixation Sutures
of penetrating keratoplasty may be broadly categorized into
intraoperative or postoperative. Postoperative complications can Sclera can be perforated while applying sutures beneath the
be early and late. Early postoperative complications are those superior and inferior recti, resulting in a retinal hole and possible
occurring within the first four weeks of surgery whilst the term retinal detachment. In case of a perforation, cryotherapy should
late is applied to changes occurring after this period. be done at the suspected area and the patient is kept under close
observation.
INTRAOPERATIVE COMPLICATIONS Flieringa rings and McNeill-Goldmann blepharostat are
used by some surgeons to prevent the scleral collapse, especially
Poor Anesthesia and Positive Vitreous Pressure indicated in cases of low scleral rigidity like in children and in
aphakic or pseudophakic patients. Sutures for the globe
A properly anesthetized and immobilized eye is a prerequisite
supporting rings are usually placed anterior to the pars plana.
for keratoplasty. Prior to the entry into the anterior chamber, the
Scleral perforation during their placement leads to damage of
eye must be soft with reduced vitreous volume and decreased
the ciliary body and clinically, hemorrhage may be observed at
intraocular pressure.
the angle in this region. This is, however, self-limiting and usually
The peribulbar or retrobulbar anesthesia increases the orbital
requires no treatment.
volume. Increased vitreous pressure may be encountered
especially if adequate measures have not been taken to obtain
Improper Trephination
adequate hypotony. Increased vitreous pressure can cause
problems especially during the performance of capsulorhexis, Reversed Host and Donor Trephines
cortex aspiration and intraocular lens implantation in a case
Corneal surgeons generally use a graft host disparity of 0.5 mm
where, triple procedure is being undertaken.
in keratoplasty. In a case where the trephines for the donor and
Prevention: Positive vitreous pressure can be prevented by the recipient get inadvertently reversed, the donor button
mechanical, medical or surgical methods. Digital pressure becomes smaller than the recipient size. This results in difficulty
applied to the globe or mechanical pressure applied by in suturing and hence, a water-tight closure of the surgical wound
95
may not be obtained. Further, it also causes rise in intraocular due to the unequal pull caused by the sutures used to fix these
pressure due to tightened sutures, which tend to collapse the devices. Many surgeons do not prefer to use these fixation rings
trabecular meshwork.2 This also causes hyperopia.3 because of the same reason.6
Management: If the host has not been trephined or only partially
Retained Descemet’s Membrane
trephined, without entering the anterior chamber and it has been
realized that the donor button has been cut inadvertently with This problem is usually encountered by the beginners and is
the smaller trephine, a trephine 0.25 mm smaller than used on particularly common in thick and edematous cornea seen in cases
Section III: Penetrating Keratoplasty: Management of Complications

the donor cornea may be used on the host, provided it completely of congenital hereditary endothelial dystrophy and interstitial
encompasses the lesion.4 keratitis. In these situations corneal stroma may be inadvertently
If the donor has been prepared and the host anterior chamber separated from the Descemet’s membrane during the removal
entry is complete, the smaller button may be used. If an of the recipient corneal button. This may also happen when the
intraocular lens is planned, the power of the lens may be adjusted corneal scissors may be inadvertently placed anterior to the
to account for 2-3 diopters of induced hyperopia. The best Descemet’s membrane. Since the Descemet’s membrane is
alternative is to transplant another donor button of appropriate transparent, visually it may not be possible to recognize this
size, if available. complication intraoperatively. The iris architecture should be
carefully inspected after trephination of such corneas and this
Eccentric Host Trephination tissue should be gently picked up with a forceps.7 Failure to grasp
the iris is a conclusive sign of presence of retained Descemet’s
Improper centration of the graft gives rise to a high postoperative
membrane. Postoperatively, anterior segment optical coherence
astigmatism.5 The trephine should be perpendicular to the cornea
tomography (OCT) may be used to demonstrate the presence of
to prevent sliding or lamellar dissection.
a retained Descement’s membrane as well as document
Prevention and management: Use of proper centration successful management of the same.8,9
techniques can eliminate this problem of eccentric trephination.
Management: If it is recognized intraoperatively, it should be
Adequate fixation with suction fixation trephines and use of sharp
removed. Viscoelastic is placed behind the Descemet’s
trephines can avoid most trephining problems. If the eccentric
membrane so that it is elevated and removed. Postoperatively
cut is less than one third of the stromal depth, the trephine can
the membrane appears as a sheet posterior to the graft (Figs
be replaced and the initial incision maybe ignored. If the cut is
14.2A and B) and opacifies with time so that it can be confused
deeper, it may be necessary to use a slightly larger trephine, so
with the retrocorneal membranes like epithelial or fibrous
that the resultant opening encompasses the previous eccentric
ingrowth. The usual consequence of stripped Descemet’s
cut and remains central (Fig. 14.1).
membrane is graft failure. However, an attempt should be made
Irregular/Oval Trephination to salvage the graft by making an opening with Nd:Yag laser,
i.e. Nd:Yag Descemetotomy. We have used 0.1 percent Trypan
Use of blunt trephines can cause slippage and irregular cuts while blue dye to stain this membrane to improve its visualization so
trephining the cornea. It is recommended that a new, disposable that tearing of the membrane, i.e. ‘Descemetorhexis’ can be
trephine be used for each cut. Ovalling of the cut after undertaken easily (Fig. 14.3)10 A repeat graft may be required
trephination may be seen with the use of scleral fixating rings in some of the cases.

Damaged Donor Button


For a full thickness corneal transplantation, it is important to
prepare the donor cornea before trephining the host cornea so
that in the event of damage or contamination to the donor,
surgeon may be prepared if another cornea is not available.
Surgeons, should avoid distilled water on trolley so that there is
no chance of water getting onto the endothelium and destroying
it completely.
Donor corneal tissue may be damaged inadvertently peri-
operatively. This can happen particularly during the trephination
of donor tissue and placement of the first 4 cardinal sutures.
Endothelial cell loss occurs more in phakic than in aphakic grafts
and is due to endothelialiris contact during surgery.11
Prevention: Every possible effort should be made to prevent
damage to the endothelium. Viscoelastics, which protect
Figure 14.1: Eccentric graft endothelium, such as Viscoat (Chondroitin sulfate 4%, Sodium
96
hyaluronate 3%, Alcon Labs) should be used to enhance the
protection of the endothelium and prevent the lenticular-iris touch
with the graft. At the same time, trephine with sharp edges should
be used to cut the graft tissue since blunt trephine may not cut
the corneal button completely and attempts to repunch will lead
to damage to endothelium.
Further, the donor cornea may be inadvertently dropped

Chapter 14: Complications of Penetrating Keratoplasty


during transfer to the recipient bed, jeopardizing the endothelium
and contaminating the donor material. Hence a graft holder
should always be used to transfer the donor cornea to the
recipient bed. Cases of graft loss have occurred and if no tissue
is available, the patient’s own cornea must be replaced and the
case may be rescheduled.12 In an aphakic eye, it is possible to
loose the graft in the vitreous.7 An oversized graft reduced the
risk of this disastrous hazard.
Figure 14.2A: Retained Descemet’s membrane

Inversion of the Graft


Inversion of the corneal button can occur rarely. In one instance,
the graft has been sutured with endothelial side facing upwards.13
Prevention and management: The epithelial and the endothelial
surfaces are easily identified by the orientation of the button in
the well, the curvature of the button and marks on the epithelial
surface, if the button has been previously marked. If such an
untoward event occurs, the graft should be immediately replaced.

Excessive Bleeding
This is a common occurrence especially when the keratoplasty
is being undertaken on inflamed or perforated eyes. The bleeding
occurs most commonly due to leaking from the iris vessels.
Minimal hemorrhage usually stops after the wound closure and
restoration of normal intraocular pressure. Excessive
manipulation of the iris should be avoided especially if there
Figure 14.2B: Trypan blue assisted descemetorhexis are long-standing peripheral anterior synechiae. Severe
intraocular hemorrhage may occur when explanting closed
looped anterior chamber lenses.14 When the haptics are pulled,
it may nip the iris and cause an iridodialysis, which may lead to
severe anterior chamber bleeding.
Prevention and management: Hemorrhage may be controlled
with cautery, compression with viscoelastic or tamponade with
sponges/swab sticks soaked with epinephrine 1:1000 dilution.7
Intracameral epinephrine should be avoided in aphakic eyes as
it leads to increased risk for cystoid macular edema. Care should
be taken to prevent seepage of blood into the vitreous, especially
in aphakic patients, as this absorbs very slowly.

Injury to Iris-lens Diaphragm


In patients with corneoiridic scars, injury to Iris and lens occurs
commonly while performing trephination if special precautions
are not taken. Use of our lamellar dissection technique can
effectively save the iris from undergoing severe damage during
trephination.14a Any inadvertent iris damage and iridodialysis
Figure 14.3: Graft after surgical removal of retained should be repaired with a 10-0 polypropylene suture as far as
Descemet’s membrane in a case of CHED possible.
97
In young patients with keratoconus and infants with low
scleral rigidity, the iris lens diaphragm may bulge forwards as
the anterior chamber is entered. Any extraneous pressure on the
globe by lid sutures or wire speculum should be checked. If the
patient is aphakic, it may be necessary to perform a vitrectomy
to allow the iris to fall posteriorly before placing the graft on
the recipient.
Section III: Penetrating Keratoplasty: Management of Complications

Injury to the lens and iris may also occur in thinned or


perforated corneas. This can be prevented by injecting the
viscoelastic into the anterior chamber before trephination through
a paracentesis. This can also be prevented by attempting a partial
depth trephination at first, followed by anterior chamber entry
and instillation of viscoelastic. The host bed can then be cut with
a curved corneal scissors. Hirst et al have recommended
combined use of viscoelastic for reformation of anterior chamber
Figure 14.4: Broken suture
along with cyanoacrylate adhesive prior to trephination to
prevent excision of the iris in the perforated globes.15
Damage to the anterior lens capsule that occurs during suture is not being used, and the continuous suture is cut or
trephination should be recognized immediately and extracapsular broken, another suture may be used as a splice added to its length
cataract extraction should be undertaken with placement of a and the ends should be retied.
posterior chamber intraocular lens.4
Problems with Suturing Graft to the Host
Posterior Capsular Tear and Vitreous Prolapse Improper suturing can cause unequal graft tissue distribution and
During combined procedure of penetrating keratoplasty with can lead to severe postkeratoplasty astigmatism. The second
extracapsular cataract extraction, the posterior capsule may be suture is the most important. The epithelium and the stroma
torn inadvertently during the aspiration of the lens matter. The should be firmly grasped and the first suture should be placed
incidence of posterior capsular tear with vitreous loss has been directly behind the forceps, which grasps the graft to prevent
reported to vary from 0 to 16 percent.16,17 any undue torque. The depth of the suture should be almost upto
the Descemet’s membrane to ensure optimal wound closure and
Management: Small capsular tears without vitreous loss are of prevent posterior wound gaping. The donor button may be
little significance and one can place posterior chamber rotated/spun in any direction before the application of the first
intraocular lens in the bag or in the sulcus. In case where the suture. The second suture should be placed exactly opposite first,
tear is large and associated with vitreous loss, an anterior as even a slight deviation will result in the torsion of the graft
vitrectomy should be performed. In the absence of any and consequently astigmatism.
contraindication, an open loop Kelman multiflex anterior
chamber intraocular lens may be implanted. This should be Iris Incarceration
combined with a peripheral iridectomy.
The iris can be picked up with the needle and inadvertently
Suture Related Complications sutured into the wound making the pupil eccentric. Incarceration
of uveal tissue in suture may lead to inadequate healing, low-
Broken/Loose/Tight Sutures grade uveitis and can enhance chances of graft rejection.
It is possible that some of the sutures appear loose or very tight Prevention and management: This is avoided by lifting the
at the end of surgery. A final assessment of such sutures should wound edge slightly before passing the suture through the host.
be made after the reformation of anterior chamber. Also if too Air, Healon GV or BSS may also be used to push the iris away
much tension is applied to the sutures, they will break. Failure effectively. If the iris incarceration occurs and the iris has been
to bury the knots is a common problem that can be encountered inadvertently sutured in the wound, the suture should be replaced.
following the suturing of the graft.
Shallow Anterior Chamber
Management: All broken, tight and loose interrupted sutures
should be replaced. Any suture which does not bury should be A shallow anterior chamber during penetrating keratoplasty may
immediately replaced. Caution is required, especially when using occur due to the presence of floppy iris, such as in cases of
a continuous suture (Fig. 14.4) The continuous suture may be corneo-iridic scars, positive vitreous pressure, and use of small
accidentally cut while attempting to remove the cardinal sutures. graft (Fig. 14.5).
The use of double-armed suture allows suturing in a direction All previously existing synechiae should be released,
opposite the first when needed. However, if the double-armed whenever possible. In cases such as corneo-iridic scar18 and
98
suprachoroidal space may result in expulsion of intraocular
contents through the recipient corneal opening.
The mechanism of suprachoroidal hemorrhage is sudden and
prolonged decompression of the globe resulting in rupture of
fragile choroidal vessels due to either traction on the vitreous
or elevated transmural pressure gradient. Various risk factors
involved are pre-existing glaucoma, hypertension, high myopia,

Chapter 14: Complications of Penetrating Keratoplasty


inflammation, sudden cough, previous surgery, previous traction
and Valsalva maneuver.21,22 Injection of excessive amount of
retrobulbar local anesthetic may also predispose hemorrhage by
sharply elevating episcleral venous pressure.21
The condition can be promptly diagnosed by progressive
bulging of the vitreous anteriorly along with direct observation
of the developing detached choroid.
Prevention and management: Suprachoroidal hemorrhage can
be prevented by preoperative lowering of intraocular pressure,
Figure 14.5: Shallow anterior chamber controlling hypertension and preventing any Valsalva maneuver
during surgery. Patient’s head can be slightly elevated.
Trephination should be performed gently so that the intraocular
pediatric cases19 where, shallow anterior chamber is anticipated, pressure is not markedly elevated by downward pressure with
over sized grafts should used to prevent the occurrence of a the trephine and then rapidly reduced when the anterior chamber
shallow anterior chamber. At the end of keratoplasty, the anterior is opened.
chamber should be formed with balanced salt solution to prevent However, if the intraoperative hemorrhage occurs, the
the occurrence of posterior synechiae and endothelial damage. emergency management includes occlusion of the host corneal
Failure to reform the anterior chamber usually signifies a wound opening and sealing of the eye to provide a good tamponade.
leak from poorly apposed corneal edges or irregular suturing and The management of expulsive hemorrhage depends on the
hence should be appropriately managed. immediate recognition and prompt action.
Air has higher surface tension than water and may actually If the hemorrhage occurs immediately or shortly after
seal and thereby hide a wound leak. Therefore, when checking entering the globe, a posterior sclerotomy via a stab incision
such a leak, BSS should replace air in the anterior chamber. A through the conjunctiva and sclera is performed. The
shallow anterior chamber may also occur due to the positive inferotemporal quadrant is the most readily accessible. Multiple
vitreous pressure in the absence of wound leak. Use of pars plana sclerotomies may be required. However, if the hemorrhage
vitreous aspiration with an 18-gauze needle attached to a 3-ml occurs during the open sky phase of keratoplasty, management
syringe has been advocated in such cases.12 is more difficult. A temporary keratoprosthesis, if available, or
Floppy iris should be managed by pupilloplasty. even a finger can be used for occlusion. Intravenous mannitol
should be started immediately and one or more sclerotomies
Wound Leak
made to facilitate drainage. Donor button is then sutured in place
Following completion of the suturing of the donor to the host, with 8-0 nylon as rapidly as possible. Visual prognosis is usually
one must always check for the presence of wound leaks. poor and depends on the extent of hemorrhage, concurrent
Fluorescein dye (Seidel’s test) can be applied to the surface of involvement of retina and efficiency of intraoperative
the cornea and tight manual pressure should be applied to the management.
globe. Alternatively, the wound may be dried with one Weck
sponge and the limbus may be gently pressed with another dry POSTOPERATIVE COMPLICATIONS
sponge, so that the presence of wound leak is easily detected. If
a wound leak is noted, additional sutures may be applied. If Early Postoperative Complications
suture tract leak is present, a 10-0 prolene suture should be placed Complications in the early postoperative period vary from minor
perpendicular to the suture tract. This is especially important in to true ophthalmic emergencies resulting in the loss of the eye.
pediatric keratoplasty where, there are more chances of wound Hence a meticulous follow-up, early diagnosis and a timely
leak due the presence of a less rigid cornea. intervention is mandatory to diagnose complication occurring
after corneal transplantation.
Suprachoroidal Hemorrhage
Shallow Anterior Chamber and Wound Leak
This is a rare and the most dreaded complication of penetrating
keratoplasty.20 The incidence of suprachoroidal hemorrhage A shallow anterior chamber along with low intraocular pressure
varies from 0.47 to 3.3 percent.4 Uncontrolled bleeding into on the first postoperative day usually signifies a wound leak.
99
However, intraocular pressure may be normal or even high in Iris Incarceration
some eyes. The site of leak can be identified by Siedel’s test.
Iris incarceration may occur due to collapse of anterior chamber
The test is performed by placing the concentrated fluorescein
or from wound leak. This may occur in cases where, penetrating
dye on the surface of the cornea. Under the cobalt blue filter,
keratoplasty has been undertaken in inflamed eyes and the iris
the concentrated fluorescien appears black. The leakage of the
is swollen and flaccid. It may also occur due to poorly placed
wound or a suture tract results in dilution of the fluorescein and
sutures which may incarcerate the iris, especially if the lens-iris
a change in color from black to bright green.
diaphragm herniates forwards. The presence of incarcerated iris
Section III: Penetrating Keratoplasty: Management of Complications

A prolonged shallow anterior chamber may result in


may incite postoperative inflammation. It closes the anterior
occurrence of secondary glaucoma and significant endothelial
chamber angle at the site of incarceration and can cause
cell loss, as there is more chance of contact between endothelium
glaucoma and graft failure. Large adhesions at the host-graft
and iris or lens. The graft survival is dependent on early diagnosis
junction may lead to localized edema of the graft and attract
and quick reformation of the anterior chamber. The likely causes
vascularization.
of wound leak are as mentioned in Table 14.1.
Management: Minimum incarceration due to wound leak can
Table 14.1: Common causes of wound leak be treated conservatively and efforts should be made to seal the
leakage. Argon laser iridoplasty may be undertaken to release
• Broken, loose or misplaced suture
• Suture track leak: full thickness suture the iris. However, if conservative management fails, surgical
• Suture through thin or necrotic tissue intervention is necessary. Iris tissue is separated from all
• Excessive gap between sutures attachments and swept out of the wound with an iris repositor.
• Unequal thickness of graft and host A viscoelastic material can be injected into the anterior chamber
by making a separate stab wound entry and the iris tissue may
Prevention and management: If the anterior chamber is flat and be rotated away from the wound gently using the viscoelastic
a wound suture tract leak or iris prolapse is present, immediate cannula. In case, the iris cannot be separated from the wound,
surgical repair is mandatory. the suture may be the culprit, in which case suture must be
If the anterior chamber remains formed in the presence of a replaced.
wound leak a pressure bandage or bandage contact lens may be
given which aids in reapposition of the wound, tamponades the Wound Dehiscence
leak and decreases the trauma from the lids in the wound. A wound dehiscence in the postoperative period may occur
Additionally, acetazolamide may be prescribed to decrease the immediately or may occur several years after penetrating
aqueous production. keratoplasty. Younger patients, especially males, should be made
If the wound does not seal in 24 hours, it must be resutured. aware that their eye, after keratoplasty, will always be vulnerable
In case of interrupted sutures, any loose or broken sutures should to injury. High-risk situations should be avoided if possible.
be replaced. An additional suture can be placed in the area of Older patients at particular risk should have adequate risk
leak. In case of a continuous suture, loosening the tight area and reduction strategies, social support, and supervision, in particular
tightening the area of the leak may redistribute the tension of to minimize the risk of falls.23 A wound dehiscence in the
the wound. In case of a broken continuous suture in the early immediate postoperative period usually occurs secondary to
postoperative period, a new segment of 10-0 nylon suture must technical problems such as a thin, necrotic recipient bed. It may
be added, making several bites across the wound. It is then tied also occur due to a postoperative rise in the intraocular pressure
to both the ends of the broken suture that have been withdrawn or after suture removal. The incidence of wound dehiscence after
a loop or two on either side to provide enough suture for tying. suture removal requiring repair has been reported to be 2.424
The new suture is passed for several bites before the original and 2.9 percent.25
suture is distributed for tying. Before tying the final knot, the Causes of wound dehiscence are as mentioned in Table 14.2.
tension should be gauged and the suture should be adjusted Spontaneous wound dehiscence may occur in the elderly or in
appropriately. If this attempt does not close the leak, the suture patients of keratoconus. Generally, all traumatic wound
is cut at the knot and a second knot is tied after tightening the dehiscence following penetrating keratoplasty occur at the donor-
suture from both the sides. If the surgeon feels difficulty in the recipient interface. Eyes with traumatic wound dehiscence have
above maneuver, interrupted sutures may be placed in the area worse visual outcome than those with dehiscence after suture
of leakage. removal. Patients should be cautioned about the risks and
Suture track leak caused by full thickness sutures usually
close spontaneously. An additional mattress suture may be
Table 14.2: Causes of wound dehiscence26-29
applied perpendicular to the suture which is causing the suture
track leak. Leak caused by suturing through necrotic tissue is • Trauma
very difficult to manage, as resuturing is nearly impossible. • Infectious keratitis
• Suture failure
Corneal gluing and bandage contact lenses may be tried in such
• Spontaneous wound separation
cases.
100
consequences of wound dehiscence. The suture may be left in
place longer in older patients or when corneal edema is the
indication for grafting.30
A full thickness wound dehiscence must be repaired
immediately. Wound dehiscence is the leading indication for
resuturing following penetrating keratoplasty.31 If iris prolapse
is present which is less than 24 hours duration and the iris tissue

Chapter 14: Complications of Penetrating Keratoplasty


appears healthy, it should be replaced back into the anterior
chamber. If the prolapsed tissue appears necrotic or if the
duration of iris prolapse is more than 24 hours, iris tissue
abscission should be done with scissors held flush to the wound.
Additional procedures, such as lensectomy, vitrectomy, IOL
explantation may be required, and in some cases, regrafting may
be necessary.

Suture-Related Problems Figure 14.6: Loose sutures


Various suture-related complications observed in keratoplasty
patient include exposed suture knot, broken, tight or loose
sutures, unraveled suture knot, suture related infectious or
immune infiltrates and suture induced vascularization (Figs 14.6
to 14.8).
Exposed suture knots are important causal factors for foreign
body sensation, photophobia, excess mucous production, giant
papillary conjunctivitis and stimulate local corneal vasculari-
zation thereby increasing the risk of rejection. An exposed suture
also acts as a nidus for microbial infection.
In a study by Christo et al, the incidence of broken or loose
sutures needing surgical repair was found in 8.3 percent of the
cases.23 Sutures should be placed with appropriate tension since
both tight as well as loose sutures are associated with problems.
Tight suture can cause persistent epithelial defect and induce
a high amount of astigmatism. In contrast, loose suture fails to
undergo epithelization and remains exposed. It acts as a nidus Figure 14.7: Suture infiltrates
for collection of collection of mucoid and tear debris and may
become a focus for infection.
Occasionally, a suture knot may unravel, which is more
common when the suture is not squarely tied, the ends of the
suture are trimmed too close to the knot or the knot is not buried
in the cornea. Corneal deturgescence, wound remodeling, scar
contraction and biodegradation caused by enzymatic factors and
ultraviolet light exposure of the suture occur during wound
healing. As the wound healing proceeds, the suture can loosen,
become exposed and may serve as a nidus for infection.23
Suture related infections are related to suture exposure, use
of soft bandage contact lens and topical steroids. Suture
abscesses are considered poor prognostic factor for the survival
of the clear graft since even when treated aggressively, they can
result in wound dehiscence, graft failure secondary to the
Figure 14.8: Suture induced vascularization
infection, corneal scarring and endophthalmitis.
Suture related immune infiltrates occur as a result of
immunological reaction to either suture material or to talc from in contact with the margins of upper and lower eyelid. In such
the surgical gloves, which adheres to the suture material. They situations, it is seen as a hypersensitivity reaction to
must be differentiated from infectious suture infiltrates Staphylococcus albus, which colonizes the lid margins,
(Table 14.3). They are seen in relation to sutures, which come particularly in the ocular surface disorders such as blepharitis.
101
Table 14.3: Comparison between features of immune Epithelial Defects
and infectious suture infiltrates
During the early postoperative course of penetrating keratoplasty,
Immune suture infiltrates Infectious suture infiltrates re-epithelization and maintenance of intact epithelium is essential
Usually multiple and small Solitary for the postoperative wound healing. Epithelial defect heals by
Occur on host side only May occur on host or graft side the sliding movement of the cells towards the center over the
basement membrane until the surface is confluent and the normal
Not associated with Epithelial defect common
overlying epithelial defect thickness of cornea is restored. Survival of a corneal graft is
Section III: Penetrating Keratoplasty: Management of Complications

critically dependent on an intact epithelial barrier. A persistent


corneal epithelial defect is a full thickness loss of cells that
Management: Any tight or loose suture in the immediate fails to show the expected rate of healing. Epithelial growth
postoperative period should be replaced. In case of exposed requires careful monitoring and persistent epithelial defect is
suture knot, suture rotation should be done. If the suture rotation considered if more than 2-4 days pass without progress of
is not possible, the suture with the exposed knot should be healing. Average time for complete epithelization of a corneal
replaced and the knot buried. graft is 4-6 days.32,33
Suture abscess should be treated energetically because of its The risk factors for a persistent epithelial defect are outlined
deleterious consequences. Suture roof should be debrided with in Table 14.4.
the help of a 26-gauge needle and the material should be sent Serious consequences follow if the epithelial defect does not
for microbiological examination and culture-sensitivity plating. heal. A persistent epithelial defect (Figs 14.9 and 14.10) can give
Some surgeons even advocate the removal of the affected suture rise to graft ulceration, stromal melting, perforation and even
followed by its microbiological examination and culture- graft failure.34
sensitivity plating. If the affected suture is a running suture,
removal is based upon whether additional sutures are present Prevention and Treatment
for support. The patient should be started on broad-spectrum Preoperative: Adequate protection of cornea by proper lid closure
fortified antibiotics until organism is identified and antibiotic must be ensured before penetrating keratoplasty. Significant
sensitivity is known. ectropion, entropion, lagophthalmos or other potential causes of
The frequency of topical corticosteroids may be temporarily corneal exposure should be corrected before undertaking a
reduced in the early stages of treatment. During this period, keratoplasty. Patients with significant loss of stem cells secondary
many surgeons have used systemic corticosteroids in order to to chemical burns, thermal burns, Stevens-Johnson syndrome or
protect against possible graft rejection, although the role of other ocular surface disease should be considered for an
systemic steroids in prevention of graft rejection is not clear. Autologous limbal conjunctival transplantation, keratoepithelio-
Once the infection is controlled, dose of topical corticosteroids plasty or stem cell transplantation. Dry eye conditions can be
may be increased cautiously. improved by medical treatment or by punctal occlusion.
The immune suture infiltrates are treated in a conservative
manner. The frequency of topical corticosteroids is increased to
Table 14.4: Risk factors for persistent epithelial defect
at least every 2 hours, if the graft epithelium is intact. If the graft
epithelium is not intact, oral corticosteroids may be used on a • Ocular surface diorders
short-term basis. If the infiltrates persist for more than few days, • Lid abnormalities: Ectropion, Entropion, Lagophthalmos
one may add cyclosporin-A drops topically. • Infection and inflammation (e.g. Herpes simplex virus
infection)
Descemet’s membrane detachment: We have to include this • Neurogenic
postoperative complication. • Iatrogenic: Tight sutures, drying of the ocular surface,
poorly apposed graft-host junction
Descemet’s membrane detachment: This may be a consequence
• Epitheliotoxic drugs: Gentamicin, Timolol maleate,
of improper graft handling at the time of trephination or suturing, Ciprofloxacin, Neomycin, Diclofenac sodium, Prednisolone
or result from trauma at host-graft junction during subsequent acetate, Dorzolamide
introduction and removal of instruments. • Damaged donor epithelium
Prevention: Gentle handling of donor tissue and careful • Basement membrane disorders
instrument manipulation may minimize incidence of this • Intrinsic epithelial disorder: Stem cell deficiency secondary
to chemical and thermal burns, Stevens-Johnson
complication.
syndrome, ocular cicatricial pemphigoid
Management: Options include intra-cameral injections of air or • Trauma
viscoelastic, transcorneal suturing, and even corneal • Poor nutrition: Vitamin A deficiency, protein-calorie
transplantation for persistent cases. Intracameral injection with malnutrition
either sulfur hexafluoride (SF6) or perfluoropropane (C3F8) gas • Metabolic eye disease such as diabetes in the donor as
is being increasingly used. well as the host
102
increased death enucleation time are associated with higher
incidence of epithelial defects.39 Fresh corneal tissue preferably
with short death enucleation time may be used in high-risk
patients. Intraoperatively, damage to the donor epithelium should
be avoided.
Any rough areas on the Teflon block should be inspected
for and slippage of the donor cornea during the trephination

Chapter 14: Complications of Penetrating Keratoplasty


should be avoided. Cornea must be kept moist to preserve donor
epithelial cells as much as possible. However, excessive
irrigation may be detrimental to the graft and should be avoided.
Use of viscoelastic substances over the donor cornea
intraoperatively to hydrate is a useful option. Any tight sutures
must be replaced and any misalignment of graft-host junctions
should be carefully avoided by meticulous surgery. A bandage
soft contact lens or even a temporary tarsorrhaphy at the end of
Figure 14.9: Epithelial defect following penetrating surgery may be considered in high-risk cases.
keratoplasty
Postoperative management: Eye patching for first 24 hours after
putting an antibiotic soaked collagen shield over the cornea may
help in epithelial healing. Most of the topical medications are
epitheliotoxic and therefore, their benefits must be weighed
against their possible adverse effects. Preservative free drops
such as 0.5 percent chloramphenicol minims and Predsol minims
may be used to prevent occurence of epitheliotoxicity. Use of
ointment form of Chloromphenicol is also recommended as it
provides lubrication. Frequent use of lubricants is necessary to
promote epithelial growth. In high-risk cases preservative-free
lubricants should be used.
Bandage soft contact lens is used if epithelial healing is not
complete by the first week of surgery. Bandage contact lens
protects the migrating epithelial cells underneath and hence
healing process is enhanced. Recently extended wear fluid
Figure 14.10: Fluorescein staining of epithelial defect ventilated gas-permeable scleral contact lenses have been tried.40
following penetrating keratoplasty
However, prolonged use of bandage contact lens is discouraged
because of the potential risk of infection and vascularization.
The incidence of persistent epithelial defects in herpetic
The frequency of the topical antibiotic drops should be increased
keratitis varies from 0-44 percent. In cases of penetrating
to 3 or 4 hourly when the bandage contact lens is used.
keratoplasty performed for herpes keratitis, use of perioperative
If the healing is not complete by the second postoperative
oral acyclovir (400 mg twice daily) may decrease the risk of
week, a temporary tarsorrhaphy is considered. 41 The
persistent epithelial defects associated with active herpes disease.
tarsorrhaphy should be performed in a manner that results in
In cases of persistent epithelial defects not amenable to treatment,
maximum coverage of epithelial defect. If the defect is located
the possibility of recrudescence of herpetic keratitis should
on the temporal cornea, a lateral tarsorrhaphy should be
always be considered in cases of previous herpetic scars. Surgical
performed and if it is nasal, a medial tarsorrhaphy should be
incision of the trigeminal nerve reactivates latent herpes
done. Temporary cyanoacrylate glue tarsorrhaphy has been
virus.35,36
described but there is a risk of glue migrating into the posterior
Herpes simplex keratitis may also develop after penetrating
aspect of the lids.41 Anterior chemodenervation of the levator
keratoplasty without prior history of herpetic keratitis in the
palpebrae superioris may be performed using 10-15 units of
host.37 The incidence of newly acquired herpetic keratitis after
botulinum toxin type A (Botox) injected transcutaneously,
penetrating keratoplasty has been reported to be 1.2 per 1000
thereby creating an iatrogenic ptosis and obviating the need for
person years in one study.38 The defect usually begins at the graft-
a surgical tarsorrhaphy.42
host junction and may not resemble a typical herpetic epithelial
Autologous serum can be used to enhance the healing of
keratitis.
epithelial defects. The various concentrations which have been
Intraoperative: In patients in whom problems with epithelization used range from 20 to 100 percent.43-45 Epidermal growth factor
are anticipated, the use of donor tissue with good donor is present in both tears and serum and has found to be helpful in
epithelium is warranted. Prolonged donor preservation time and healing of epithelial defects, possibly due to its anti-apoptotic
103
properties. Further, fibronectin and vitamin A are also present
in the serum which aid epithelization.
Umbilical cord serum has demonstrated faster healing of the
persistent corneal epithelial defects refractory to all medical
management compared to autologous serum.46
Amniotic membrane transplantation can also be done for
persistent epithelial defect after penetrating keratoplasty.47 The
Section III: Penetrating Keratoplasty: Management of Complications

amniotic membrane contains a thick basement membrane and


an avascular stromal matrix. The basement membrane facilitates
migration of the epithelial cells, reinforces adhesion of basal
epithelial cells and promotes epithelial differentiation. The
basement membrane is also important in preventing epithelial
apoptosis. Collectively, these actions explain why the amniotic
membrane effectively permits rapid re-epithelization.
The use of topical agents such as recombinant epidermal
growth factor and fibronectin for enhancement of epithelial Figure 14.11: Primary graft failure
healing has not been conclusively proven.48,49 Additional clinical
trials are required to determine the use of these agents in future.
• Surgical trauma
Multifocal phototherapeutic keratectomy (PTK) has also
• Herpes simplex virus infection.
been tried for persistent epithelial defect. A focal excimer laser
Unhealthy donor endothelium, inadequate tissue preservation
PTK with a 1.0 mm diameter and 150–200 pulse ablations at
and surgical trauma are the major causes of primary graft
the edge of the epithelial defect is performed.50 The excimer laser
failure.53 Primary graft failure has also been attributed to donor
is used to remove the elevated margin surrounding the epithelial
tissue contamination with herpes simplex virus.54,55 Edema
defect zone so that the epithelial cells can migrate easily.
usually develops within the first day after surgery and is
unresponsive to hypertonic saline or steroids. However, to make
Filamentary Keratitis
the diagnosis of primary graft failure, other causes of corneal
Filaments consist of abnormal collection of mucus and corneal edema, e.g. severe hypotony and intense inflammation must be
epithelial cells. The reported incidence of filamentary keratitis excluded. Hyposecretion of aqueous humor, which is common
after penetrating keratoplasty is 27 percent in one case series.51 after penetrating keratoplasty, may result in graft edema due to
Patients complain of redness and foreign body sensation. decreased supply of metabolites to the endothelium. The
Filaments are usually seen in the early postoperative period and endothelial function improves in these eyes, once the aqueous
develop at the graft-host junction along the suture tract. They production is restored and the cornea begins to clear. The
stain brilliantly with the rose-bengal stain. incidence of primary graft failure is less than 5 percent.53
The treatment consists of treating the underlying dry eye and Prevention: Primary graft failure can be minimized by proper
specific treatments for the corneal filaments. Proposed treatments
donor selection, good preservation and by avoiding endothelial
include nonpreserved lubricants, topical steroidal and
injury during donor processing and during the surgery. A major
nonsteroidal anti-inflammatory agents, and punctal plugs for goal of corneal preservation and transplantation is to maintain
aqueous-deficient dry eye as well as mechanical removal of
high postoperative endothelial count. Long-term graft survival
filaments, hypertonic saline, mucolytic agents, and bandage
depends on postoperative endothelial cell count and quality.
contact lenses for the filaments.52 Good technique is essential when removing the corneoscleral
rim from the donor globe. All corneas should be examined
Primary Graft Failure
preoperatively with slit lamp for any possible endothelial
Corneal grafts that have gross corneal edema with large broad damage. McCarey-Kaufman medium is used in most of the eye
folds immediately after keratoplasty and which is not followed banks in India, which can preserve the donor tissue up to 96
by a period of clear cornea is called primary graft failure hours. However, if the death-to-enucleation time is prolonged,
(Fig. 14.11). It is the faulty donor tissue that results in irreversible it can preserve the donor tissue only up to 2 hours. During
graft edema in the immediate postoperative period. The possible storage, endothelial cells are lost at variable degrees. Optimum
factors responsible for primary graft failure are listed below: results are obtained if the surgery is performed at the earliest,
• Prolonged death-enucleation time minimizing the donor preservation time.
• Poor donor endothelial count During the suturing of the corneal graft, most of the damage
• Aphakic and pseudophakic donor to the endothelium occurs at the beginning when the borders of
• Elderly donor the graft rub against the host corneal rim tissue. Endothelial loss
• Inadequate preservation can be avoided by using good viscoelastics at this stage. In our

104
experience, Viscoat (Alcon Labs, Fort Worth, TX) which consists be required in instance of acute IOP elevation. Weak mydriatics
of 4 percent chondroitin sulfate and 3 percent sodium to prevent posterior synechiae and topical steroids to control
hyaluronate was found to be endothelio-protective. During intraocular inflammations are recommended.
surgical manipulation, distortion of the donor corneal tissue The presence of uncontrollable elevated IOP or prolonged
should be minimized, and it is imperative that no surgical persistence of hemorrhage may necessitate surgical intervention
instruments come in contact with the endothelium. Endothelial in the form of clot irrigation and aspiration through limbal
cell damage may occur from excessive irrigation of the anterior incision. The use of thrombolytic agents, e.g. streptokinase, tissue

Chapter 14: Complications of Penetrating Keratoplasty


chamber. plasminogen activator to dissolve blood clots or ε-aminocaproic
acid to prevent rebleeds have not been adequately studied in
Management: Once the diagnosis of the primary graft failure is
penetrating keratoplasty.59
made, the regrafting should be performed as early as possible.
A repeat penetrating keratoplasty is the most definite therapeutic
High Intraocular Pressure and
modality, but some grafts may clear without additional surgery.
Pupillary-block Glaucoma
A case of primary graft failure should be preferably observed
for 3-4 weeks for the signs of graft clearing before proceeding Several factors can contribute to the early elevation of intraocular
with the second surgery.56 All cases should be investigated pressure after penetrating keratoplasty.60,61 The major factors
thoroughly to determine the possible factors responsible for involved are:
primary graft failure. • Residual viscoelastics in anterior chamber
• Uveitis
Graft Rejection • Hyphema
• Crowding of anterior chamber angle
It is a specific process in which a graft, having been clear for at
• Pupillary block.
least 2 weeks, suddenly succumbs to graft edema in conjunction
• Forward movement of lens iris diaphragm
with inflammatory signs due to some immunologic process57,58
(Fig. 14.12). This will be discussed in detail in Chapter 16. Prevention and management: Viscoelastic material, which is left
inside the anterior chamber, is one of the most common causes
Hyphema of early postoperative rise of intraocular pressure. Irrigation at
the end of surgery removes most of the viscoelastics and prevents
Postoperative occurrence of hyphema is rare after penetrating
postoperative pressure rise. However, excessive irrigation can
keratoplasty. Incidence of hyphema increases with intraoperative
manipulations like extensive synechiolysis, iridoplasty or cause endothelial damage and must be avoided.
Postoperative uveitis is controlled by intensive treatment with
iridotomy. Most of the postoperative hyphema clears
topical steroids such as 1 percent prednisolone acetate or 0.1
spontaneously without treatment. It may, however, be associated
with an elevated intraocular pressure that should be treated percent dexamethasone sodium phosphate given 2 hourly.
Systemic steroids, such as T prednisolone 1-2 mg/kg body weight
aggressively.
may be started. Further, short acting cycloplegics, such as 1
Management: If topical β-blockers alone is not adequate to percent tropicamide may be given.
control IOP, topical apraclonidine or systemic carbonic Crowding of anterior chamber angle gives rise to both
anhydrase inhibitor should be used. Systemic osmotic agents may immediate and long-term elevation of intraocular pressure. It is
more common in aphakic keratoplasty, when trabecular
meshwork collapses due to lack of lenticular support. Relatively
small size of donor button and tight sutures are the other
important factors. Use of slightly over-sized graft in aphakic
patients and avoidance of tight sutures by maintaining anterior
chamber depth through-out the procedure may prevent
postoperative rise of IOP in these cases.
The presence of a flat or shallow anterior chamber and a
securely closed wound, confirmed by Siedel’s test, suggest the
presence of pupillary block or choroidal detachment. The
pupillary block is usually associated with high IOP whereas, a
low intraocular pressure is recorded in cases of choroidal
detachment. The presence of posterior synechiae or vitreous
protruding through the pupil confirms the diagnosis of pupillary
block. Air should not be used to form the chamber, especially in
aphakes, as this may lead to pupillary-block glaucoma.
Figure 14.12: Corneal edema due to graft rejection Sometimes a diffuse wound leak results in anterior displacement

105
of lens-iris diaphragm, which plugs both leak and anterior
chamber angle. This again raises the IOP.
Treatment of pupillary block includes vigorous attempt to
dilate the pupil pharmacologically and concurrent use of
antiglaucoma medications. In situations where, the pupillary
block is unresponsive to the pharmacological dilatation, a
peripheral iridectomy should be considered. This may be
Section III: Penetrating Keratoplasty: Management of Complications

undertaken with the help of laser, if the peripheral cornea is clear


or a surgical iridectomy may be done, if the peripheral cornea is
hazy.

Low Intraocular Pressure


Low intraocular pressure after penetrating keratoplasty is not
uncommon. Following are the possible causative factors:
• Wound leak
• Iridocyclitis: Ciliary shock Figure 14.13: Recurrence of herpetic keratitis in a graft
• Cyclodialysis
• Choroidal detachment to distinguish the graft rejection and herpes simplex keratitis. It
• Retinal detachment. is relatively easier to diagnose herpes simplex keratitis when it
Postoperative wound leak is suspected when shallow anterior presents with classical dendritic or geographic form. However,
chamber coexists with low intraocular pressure. A positive stromal involvement which presents with graft edema and keratic
Siedel’s test confirms the diagnosis. Management of the wound precipitates, is almost impossible to distinguish from graft
leak has been discussed previously. rejection. The features which help to distinguish recrudescence
Postoperative iridocyclitis is also an important etiologic of epithelial herpetic keratitis from graft rejection include the
factor for low intraocular pressure. Iridocyclitis decreases the classical epithelial dendrite, focal involvement and propensity
aqueous humor produced by the ciliary body. Topical steroids of herpes to occur at the host-graft junction. In addition,
usually control the inflammation in 1-2 weeks and intraocular epithelium shows granular appearance. The characteristic feature
pressure returns to normal as the aqueous production resumes. of graft rejection – Khodadoust line is not seen in herpes keratitis.
A cyclodialysis is a separation of ciliary body from the scleral Management: Herpes simplex keratitis is treated with topical
spur. Inadvertent surgical manipulation can give rise to antiviral agents, e.g. acyclovir (3%) five times daily along with
cyclodialysis. Low intraocular pressure is due to excessive supportive therapy. Stromal keratitis is treated with topical
drainage of the aqueous into the supraciliary space. The condition corticosteroids along with topical antiviral agents, i.e.
is difficult to diagnose, as graft edema or hazy graft-host junction Prednisolone acetate 1 percent 2 to 4 hourly in combination with
prevents the visualization of the angle by gonioscopy. 3 percent acyclovir 5 times daily. Topical antivirals are
Fortunately, in majority of the cases resolution occurs epitheliotoxic and therefore, patients should be monitored
spontaneously. frequently.
Choroidal detachment as a cause of low IOP is suspected The recurrence of herpes simplex keratitis can be reduced
when a postoperative flat anterior chamber is associated with by prophylactic use of antivirals.62,63 Topical acyclovir (5 times
absence of wound leak. Ultrasonography B-scan confirms the daily) is given postoperatively for 2 weeks. Maintenance dose
diagnosis. Most choroidal detachments resolve spontaneously of acyclovir 400 mg BD has been shown to reduce allograft
without any sequelae. Commonly used treatment regimens for rejection and graft failure after PK in patients with herpes.
choroidal detachment include topical and systemic Vajpayee et al64 compared systemic vs topical acyclovir therapy
corticosteroids. If the anterior chamber angle is compromised for the prevention of recurrence of herpetic keratitis following
for more than 48-72 hrs and the choroidal detachment is penetrating keratoplasty (PK) and found that systemic acyclovir
persistent, surgical drainage of the suprachoroidal space with is more effective in prevention of recurrence of of herpetic
reformation of the anterior chamber is recommended. keratitis.
Valacyclovir 500 mg OD for one year has also been found
Herpes Simplex Keratitis
to be effective in the prevention of recurrent lesions in
Recurrence of herpes simplex keratitis in graft is not uncommon. immunocompetent individuals with ocular herpes simplex virus
The infection can recur any time between 1 and 15 years (HSV) disease.65 Prophylactic oral Valacyclovir treatment has
postoperatively37 (Fig. 14.13). There is a unique relationship of also been found to be as effective as oral Acyclovir in preventing
herpes simplex keratitis and graft rejection. The keratitis can recurrence in patients who undergo corneal transplantation for
incite graft rejection and vice versa. Sometimes it is very difficult herpetic keratitis.66

106
Microbial Keratitis and secured or knots are not buried, it can lead to loose, broken
sutures and exposed knots in the early postoperative period with
Postpenetrating keratoplasty microbial keratitis is characterized
increase risk of suture abscesses67,69 (Fig. 14.16). Corneal graft
by either infection within the graft or infection along the suture
sutures may erode through the overlying epithelium. Wound
tracts at the graft-host junction. The infections within the graft
remodeling, scar contracture and cheese-wiring of influenced
(Fig. 14.14) or at the graft-host junction can produce an
stroma may loosen and expose previously secure sutures. The
inflammatory reaction in the eye with the initiation of concurrent
superficial loop of an intrastromally embedded nylon suture tends
graft rejection and can cause graft faliure, melting of the graft

Chapter 14: Complications of Penetrating Keratoplasty


to undergo biodegradation earlier than does the deeper aspect
and even endophthalmitis with subsequent loss of vision. The
of the sutures. Loose sutures breach the epithelial surface and
incidence of microbial keratitis in corneal grafts ranges from 1.76
normal barrier and thus initiates the infection cascade providing
to 4.9 percent in western countries. In developing countries, it
a direct route for infection into the stroma. Broken and exposed
has been reported to be as high as 11.9 percent.67 Increased risk
end of a suture can accumulate mucus and foreign debris and
of graft infection is associated with preoperative herpes simplex
act as a “infectious wick”. The surgeon and the assistants should
keratitis and grafts performed for complications of previous
wash their gloves to avoid postoperative talc-related suture
infectious keratitis.67 Postoperative infectious keratitis may also
abscess. Suture fragments, cotton fibers or any debris trapped
be caused by intraoperative contamination, recurrent host disease
by the sutures must be removed meticulously as they serve as
or poorly preserved donor material (Fig. 14.15).
potential source of infection. Patients should be kept in close
Suture related problems and persistent epithelial defect are
follow-up and any loose suture must be removed as soon as
the most common risk factors predisposing to graft infection.68
possible and replaced if necessary.
It is important in reducing the risk of infection to ensure that all
Meticulous tissue processing in a sterile environment and
sutures are secure, knots are buried and sutures are nicely covered
optimum use of antibiotics in proper concentration reduce the
by epithelium postoperatively. If the sutures are not properly tied
risk factors related to faulty preservation. Any change in color
of preservative media is an indication of contamination and the
donor tissue must be discarded. Use of contact lens can incite
severe infection in the graft. The patients should be educated on
contact lens care and instructed to report early if there is pain,
irritation or foreign body sensation. Epithelial defect related
complications should be prevented. Pre-existing ocular diseases
should be treated preoperatively. Every attempt should be made
to improve ocular surface with tear substitutes, punctal
occlusions or lid surgery. Though topical corticosteroids suppress
ocular inflammation, they impair host defense mechanism and
promote bacterial super-infection. Corticosteroids are routinely
used in all keratoplasty patients to prevent graft rejection and
their risk in usage is well known. Caution must be practiced in
their use and dose should be tapered.
Figure 14.14: Graft infection following penetrating keratoplasty Management: About half of the infections occur within the first
six months of surgery, with the majority occurring within the

Figure 14.15: Infectious keratitis involving the entire graft Figure 14.16: Multiple suture abscesses in the graft
107
Table 14.5: Possible risk factors for antifungals may be added in cases of mycotic keratitis. In cases
postoperative graft infection unresponsive to medical management, therapeutic regraft should
• Faulty preservation
be under-taken at the earliest.70 If the infection is caused by
– Contamination of preservative media Acanthamoeba topical amoebicidal drugs including
– Long-term preservative media Polyhexamethyl biguanide (PHMB) 0.02 percent, Propamidine
– Lack of asepsis during tissue processing isethionate (Brolene) 0.1 percent, Chlorhexidine and Neosporin
• Faulty grafts must be used. The medical treatment must be continued several
Section III: Penetrating Keratoplasty: Management of Complications

– Suture related problems months after keratoplasty to reduce the risk of recurrence.
– Persistent epithelial defect
– Use of contact lens
Endophthalmitis
– Graft failure
– Wound dehiscence Endophthalmitis following keratoplasty though rare, but is a sight
• Pre-existing ocular disease threatening complication with incidence ranging from 0.1 to 0.7
– Dry eye syndrome percent.71-74 The rate of endophthalmitis was 0.200 percent in
– Herpes simplex keratitis
the 2000-2003 period, 0.453 percent in the 1990s, 0.376 percent
– Chemical burns
in the 1980s, and 0.142 percent during the 1970s. Furthermore,
• Cicatricial diseases: Stevens-Johnson syndrome
a downward trend in the incidence of endophthalmitis after 1992
• Topical steroids
has been observed compared with 1991 and earlier. 75
• Systemic diseases Endophthalmitis may occur in early or late postoperative period
– Diabetes mellitus
– Immunosuppression
after penetrating keratoplasty. Fortunately, the incidence is low.
Reported associations include contamination of donor material,
suture removal, wound dehiscence and vitreous incarceration.
first year. Gram-positive bacterial infections, especially
Early endophthalmitis can be attributed to contaminated
Staphylococcus species are more common than gram-negative
material.18 A study by Kloess et al76 revealed that contaminated
ones. Pneumococcus species and Staphylococcus aureus have
donor tissue is the major cause of post-keratoplasty
been found to be the commonest microorganisms in the
endophthalmitis. In this study, donor rim cultures were positive
developed world, whereas Staphylococcus epidermidis is the
in 56 percent of cases. In all but one cases of positive donor rim
most often detected microorganism in corneal graft infection in
cultures, the isolated organism was the same as that caused the
the developing world.68
endophthalmitis.
Fungal infections, although less common, are prevalent in
Both bacteria and fungi have been incriminated in
countries with warm and humid weather. Common causative
endophthalmitis following penetrating keratoplasty. In a study
organisms include Aspergillus and Candida.69 In majority of the
by Kunimoto et al isolates included 76.9 percent gram-positive
studies, the incidence of fungal keratitis varied from 0 to 14
cocci (Streptococcus sp. Being the most common and 23.1%)
percent. The high incidence of fungal keratitis in the series
gram-negative organisms (Proteus mirabilis, Serratia
reported by Harris and colleagues was attributed to possible
marcescens). Susceptibilities to organism-appropriate antibiotic
geographic variation and higher risk patients with significant
testing showed cefazolin 75.0 percent, ciprofloxacin 57.1 percent
ocular surface disorders or altered immune function. Fungal
and vancomycin 100.0 percent.77 Though antibiotic gentamicin
infections tend to recur more frequently than bacterial infections.
is present in preservative storage media like M-K medium, but
Acanthamoeba infection, on the other hand, is a rare but
the offending organisms have been found to be resistant in some
devastating infection with 30 percent chance of recurrence. The
studies.76,78 To minimize this serious complication, the donor
recurrence is manifested either by a peripheral stromal infiltration
tissue should be routinely screened and evaluated for microbial
or by a coarse elevated epithelial line. The latter should not be
contamination. All recipients should be treated with prophylactic
confused with an epithelial rejection line.
intraoperative subconjunctival and postoperative broad-spectrum
Diagnosis and treatment of microbial keratitis in a graft are
antibiotics. Suture removal requires strict asepsis and
analogous to the management of corneal ulcers in general.
continuation of topical antibiotics for several days after the
Corneal scrapings are obtained for smear and culture-sensitivity
procedure. Any wound dehiscence must be repaired as early as
and vigorous antimicrobial therapy should be started under
possible. Both bacteria and fungi have been isolated in cases of
hospitalization. Therapy can be modified on the basis of smear
the endophthalmitis following penetrating keratoplasty.
and culture reports and therapeutic response. The initial therapy
consists of either a fluoroquinolone 0.3 percent Ofloxacin eye Management: A full-fledged case of endophthalmitis is
deops or a combination therapy of concentration cefazolin 5 diagnosed by clinical signs and confirmed by ultrasound B-scan.
percent and concentration tobramycin 1.3 percent eye drops, in Management includes vitreous tap for smear and culture-
1 hourly dosage. Additional supportive therapy includes sensitivity and intensive topical, intravitreal and systemic
cycloplegics as well as antiglaucoma medications. Topical antibiotics as in any endophthalmitis patient.

108
Late Postoperative (Months, Years) by direct access through an epithelial defect. Administration of
topical corticosteroid serves to protect the organism from marked
Graft Rejection inflammatory response. The commonest organism causing ICK
This has been discussed previously and also been discussed in is Streptococcus viridans. Rarely other organisms such as
details in Chapter 16. Staphylococcus, Enterococcus, Hemophilus, fungal species like
Candida have been implicated. Fastidious bacteria which do not
Infectious Crystalline Keratopathy get a full nutrient supply and form a biofilm around them have

Chapter 14: Complications of Penetrating Keratoplasty


been particularly implicated.
Infectious Crystalline Keratopathy (ICK) is a chronic,
progressive corneal infection occurring mostly in the anterior Management: Management of ICK requires laboratory
lamella of the grafts without any clinically evident stromal evaluation including corneal scraping for smears and cultures.
inflammation. The clinical appearance of ICK includes Appropriate antibiotics can be formulated on the basis of
crystalline branching opacities in the anterior and mid stroma investigations. Often the lesion is too deep for material to be
due to intralamellar aggregates of gram-positive cocci occurring obtained by scrapings. A corneal biopsy may be necessary and
several months following penetrating keratoplasty79,80 (Figs can be performed by lamellar dissection over the lesion or with
14.17 and 14.18). The characteristic lesions are associated with a biopsy punch. Treatment of ICK begins with fortified antibiotic
persistent epithelial defect, use of topical corticosteroids, herpes regimen given in an intensive dosage schedule. Concentrated
simplex keratitis and contact lens use. The pathogenesis of ICK vancomycin and cefazolin (both 50 mg/ml) are most commonly
is not well understood. Bacteria are thought to gain access to used regimen. Therapy can be modified on the basis of culture
the corneal stroma via epithelial ingrowth into a suture track or report. Superficial lamellar keratectomy to remove or debride
infected tissue can be curative. Therapeutic ablation by excimer
laser is successful in very superficial ICK.81 Some cases have
shown poor response to antibiotics and eventually required
regrafting.82,83 Disruption of the intrastromal crystals using
Nd:YAG laser has hastened resolution of keratopathy
unresponsive to topical antibiotics.83a

Urrets-Zavalia Syndrome
This is an unexplained syndrome characterized by permanent
fixed dilated pupil after penetrating keratoplasty in patients with
keratoconus. The condition was described by Urrets-Zavalia.84
He also recognized iris atrophy and secondary glaucoma in these
patients. Typically, the mydriasis is unresponsive to miotics. This
syndrome has also been reported following deep lamellar
keratoplasty for keratoconus.85,86
Although the etiology is unknown, severe iris ischemia, as
Figure 14.17: Infectious crystalline keratopathy
demonstrated by anterior segment fluorescein angiography and
use of strong mydriatics are thought to be the possible
mechanisms. Peripherally painted contact lens with clear optic
zone may be helpful in these patients to prevent photophobia
and glare associated with the syndrome. This syndrome can be
avoided by monitoring the patient postoperatively by adequately
treating the raised intraocular pressure and by avoiding the use
of atropine postoperatively.

Corneal Membranes
Epithelial ingrowth: Corneal and conjunctival epithelium may
enter the anterior chamber through a gap at the host-graft
junction. Predisposing factors for epithelial ingrowth are87
• Poorly healed wound
• Fistulous tract
• Wound dehiscence with iris incarceration
• Trauma
Figure 14.18: Infectious crystalline keratopathy • Previous intraocular surgery
109
• Epithelial seeding in anterior chamber by
– full thickness suture
– surgical instrument
– foreign body.
Epithelial ingrowth progresses over the posterior surface of
cornea, anterior chamber angle and the iris in a sheet like fashion.
Ingrowth over the posterior surface of cornea results in
Section III: Penetrating Keratoplasty: Management of Complications

endothelial dysfunction, corneal edema and hazy graft. 87


Epithelial invasion into the anterior chamber angle, especially
trabecular meshwork hinders the aqueous drainage and ultimately
results in intractable glaucoma and severe vision loss. Epithelial
ingrowth over the iris causes pupillary distorsion, heterochromia,
iritis and rarely iris inclusion cyst. The epithelial ingrowth can
be distinguished from other retrocorneal membranes by applying
laser burns over the iris. In this case, the tissue ‘takes’ the laser,
identified by white, fluffy lesions. Other lesions do not take up Figure 14.19: Hurricane keratopathy
the laser.
Confocal microscopy imaging technique seems to be a useful
apposition. Stromal fibroblasts migrate into the anterior chamber
tool in the early diagnosis of epithelial ingrowth after penetrating
and cover the posterior surface of the graft. The pathology can
keratoplasty.88
be restricted to the peripheral part of the graft. If the ingrowth
Management: Meticulous surgery and a secure wound are is extensive the entire endothelium is destroyed and this results
necessary to prevent epithelial ingrowth. Treatment is extremely in graft failure.
difficult. Cryotherapy gives better result, but can lead to phthisis
Management: A repeat graft with larger donor button.
bulbi. Alternate treatment includes surgical extirpation of
involved ocular structure. In case of intractable rise of intraocular Hurricane (Whorl) keratopathy: “Hurricane keratopathy” is the
pressure, a glaucoma implant surgery may be tried. Use of name given to the whorl pattern, highlighted with fluorescein,
5-fluorouracil is a potentially effective treatment of epithelial seen in situations where, corneal epithelial cell turnover is
ingrowth, particularly in eyes with extensive involvement, in exaggerated (Fig. 14.19). The terms ‘vortex keratopathy’ and
which the risks of traditional ablative therapeutic modalities are ‘hurricane keratopathy’ describe two similar conditions affecting
considerable.89 the corneal surface. In the former, a vortex or whorl pattern is
seen on the corneal surface and is due to the deposition of
Fibrous Ingrowth substances such as pigment, iron or drugs in the epithelial cells.
In the latter, a similar pattern is presented by migrating epithelial
Also known as retrocorneal membrane is a gray or white fibrous
cells but, unlike the former, the pattern is rendered more visible
collagenous tissue invading between Descemet’s membrane and
by fluorescein staining. Both represent the migratory pattern of
endothelial cell layer. Predisposing factors include graft failure,
normal epithelial cells which is otherwise not visible due to the
prolonged vitreocorneal contact and severe postoperative
slow rate of epithelial turn-over and migration. The whorl pattern
inflammation. This may also occur due to poor wound apposition
has a clock-wise predisposition in the majority of cases and is
specially if a big ledge on the recipient bed is left behind. The
hypothesized to be due to the influence of ocular electro-
clinical course of fibrous ingrowth is variable and depends on
magnetic fields on the migrating epithelial cells.90,91
the extent of the factors promoting ingrowth. Frequently it runs
an insidious course with little discomfort and the membrane is Cataract
often noted as an incidental finding. Less commonly, patients
present with decreased visual acuity caused by fibrous membrane Cataract is a common cause of decreased visual acuity in a
or symptoms related to uveitis, glaucoma or rarely retinal patient with successful corneal grafting. Pre-existing senile
detachment. The diagnosis of fibrous ingrowth should be made cataract may progress rapidly after penetrating keratoplasty92
on the basis of preceding clinical features and distinguished from (Fig. 14.20). The incidence of cataract in various studies after
epithelial ingrowth by argon laser burns. Graft becomes hazy penetrating keratoplasty varies from 2592 to 80 percent.93
and edematous in penetrating keratoplasty when affected by Following three major mechanisms involved in
fibrous ingrowth. postkeratoplasty cataract.
1. Poor surgical technique
Management: A repeat graft is required to obtain a useful vision.
– Anterior capsular injury
Stromal ingrowth: Stromal ingrowth is a rare complication of – Excessive iris manipulation
penetrating keratoplasty due to improper posterior wound – Excessive irrigation

110
– Non-radial sutures
– Tight sutures
– Unequal distribution of tension in continuous suture
Surgical caveats to minimize postoperative astigmatism
• Central and vertical trephination
• Use of a sharp trephine
• Symmetric suture placement (especially second suture)

Chapter 14: Complications of Penetrating Keratoplasty


• Avoiding tight suture placement
• Suture adjustment (for continuous sutures) or selective
suture removal (for interrupted sutures)

Prevention: While cutting the recipient cornea the surgeon must


ensure that the trephine is centered properly and perpendicular
to iris plane. The cutting edge of the trephine can be checked
under microscope and a blunt trephine must be discarded. A blunt
Figure 14.20: Cataract after penetrating keratoplasty trephine causes slippage and irregular cuts. While suturing the
graft, the second suture is most important because it determines
the proper distribution of corneal tissue.94,95 The second suture
2. Altered lens metabolism should be exactly at the opposite meridian of first suture. Even
– Persistent inflammation a slight misplacement of the second suture can cause torsion of
– Hyphema the graft and subsequent severe astigmatism. A tight suture causes
3. Toxic peripheral flattening and central steepening of cornea. Placing
– Corticosteroids (topical and systemic) every second suture at the opposite meridian in the same
– Anticholinesterase direction ensures a radial suture. Nonradial sutures can distort
Prevention: To reduce lenticular injury a good viscoelastic can the graft and can cause postoperative astigmatism. Intraoperative
be used which prevents anterior capsular contact by maintaining use of keratometer facilitates the evaluation of astigmatism and
deep anterior chamber. Preoperative or intraoperative single dose it may be corrected accordingly by modifying the sutures.
of pilocarpine can provide a good mechanical barrier by There are controversies over the different suturing techniques
constricting the pupil. One should strongly consider combined and their long-term refractive outcome. Several suturing
cataract surgery and penetrating keratoplasty in patients with techniques such as interrupted, single running, double running
early senile cataractous changes. Postoperative inflammation or a combination of interrupted and running are used to secure
must be controlled and corticosteroids dose should be tapered a keratoplasty wound. A comparison of torque, anti-torque and
to minimum maintenance dose. no-torque techniques of single continuous suturing revealed
higher proportion of prolate corneal topography maps with anti-
Management: Cataract can be extracted through a separate torque suturing technique.96 The three techniques of single
incision after the wound is totally healed. Endothelium must be continuous suturing produced similar final astigmatic results.
protected by a good viscoelastic. Suture adjustment is an effective method of reducing post-
penetrating keratoplasty astigmatism.97 In general, the final
Astigmatism
outcome mostly depends on the expertise and efficiency of
Improvements in microsurgical techniques and instrumentation, operating surgeons. Interrupted sutures have the advantage of
surgical training, eye-banking procedures and management of selective suture removal on the basis of corneal topography. The
postoperative complications have enabled corneal surgeons to running sutures can be adjusted postoperatively to reduce the
expect a very high rate of clear grafts after penetrating astigmatism. Some surgeons advocate the combination of
keratoplasty. A physically successful graft may fail optically if interrupted and single running suture. As the running suture
postoperative astigmatism is too high. Average postkeratoplasty supports the wound, astigmatic error can be reduced by
astigmatism measured by keratometry ranges from 4 to 5 selectively removing the interrupted sutures even at early
diopters. High postoperative astigmatism is expected in eyes with postoperative days. Corneal topography performed 30-40 min
scarring due to corneal ulcer and keratoconus. Other cases are after suture removal can identify the next set of sutures requiring
solely related to surgical techniques of keratoplasty.94 Possible removal. This can be used as a guide to remove more sutures at
factors those give rise to high postoperative astigmatism are as the same visit, thereby expediting postkeratoplasty visual
follows: rehabilitation and reducing the number of follow-up visits.98 In
• Eccentric graft double running suture technique, ideally one 10-0 and other 11-0
• Mal-alignment of graft monofilament nylon are used. Early visual rehabilitation is
• Faulty suturing techniques achieved by removing the 10-0 suture about 3 months after
– Improper placement of second suture surgery. A stable refraction is usually possible with 11-0 suture
– Unequal depth in place.
111
Management: At times, even after suture adjustment or selective deleterious effect on the corneal endothelium also.103 High
suture removal, the residual astigmatism is quite high. These intraocular pressure is also responsible for occasional wound
patients require visual rehabilitation either by spectacles, contact dehiscence and ectasia. Factors related to early postoperative
lenses or astigmatic refractive surgery. Some patients may glaucoma had already been discussed. The following are the
tolerate spectacles with high cylinder, especially those operated major risk factors giving rise late postoperative glaucoma.
for keratoconus. Similarly monocular patients tolerate spectacles • Pre-existing glaucoma
better than those with binocular vision. If glasses are not tolerated • Aphakic and pseudophakic eye
Section III: Penetrating Keratoplasty: Management of Complications

or do not provide satisfactory visual acuity, the patients can be • Pigment dispersion syndrome
rehabilitated with contact lenses. Before fitting contact lenses • Prolonged severe inflammation
one must be sure that all suture knots are buried. The rigid gas • Tight and deep sutures
permeable lenses control astigmatism better with advantages. The • Peripheral anterior synechiae
patients using contact lenses must be monitored closely for • Epithelial and fibrous ingrowth
possible complications. A variety of surgical options are available • Long-term use of steroids.
for patients with high astigmatism who do not tolerate glasses Gradual flattening of anterior chamber, several months after
or contact lenses. Astigmatic keratotomies including relaxing aphakic keratoplasty has been described. Collapse of the
incisions, arcuate keratotomy, wedge resection, ‘T’-cuts can be trabecular meshwork may result from loss of anterior support,
performed in these eyes depending on the amount of residual because of incision on the Descemet’s membrane. Compression
astigmatism. Toric ablation by excimer laser remains a useful of the anterior chamber angle may be caused by conventional
option in postkeratoplasty astigmatism. Laser in situ technique of penetrating keratoplasty.103,104 This may lead to
keratomileusis (LASIK) after penetrating keratoplasty has been early postoperative IOP rise as well as subsequent chronic
used more commonly for the correction of myopia or myopic glaucoma resulting from peripheral anterior synechiae. A tightly
astigmatism and less so for hypermetropia or hyperopic sutured wound can contribute to crowding of anterior chamber
astigmatism. The primary goal after LASIK in such cases is angle and thus increases the intraocular pressure. Pigment
resolution of sufficient myopia and astigmatism to allow dispersion is more common with pseudophakic keratoplasty or
spectacle correction of the residual refractive error and decrease keratoplasty combined with cataract extraction and intraocular
anisometropia. All sutures should be removed prior to LASIK lens implantation. Postoperative use of corticosteroids may
and the interval between penetrating keratoplasty and LASIK elevate IOP in some patients.105 The incidence is further
should be a minimum of 1 year. Preoperative evaluation includes increased in patients with pre-existing glaucoma, diabetes
refraction, slit-lamp biomicroscopy, corneal topography, and mellitus and high myopia.106
specular microscopy. The technique of LASIK surgery after Prevention: The prevention of post-PK glaucoma begins with
penetrating keratoplasty is similar to the standard procedure.
adequate preoperative control of pre-existing glaucoma. Most
However, many variations have been described. These include
of the pre-existing glaucoma is controlled by antiglaucoma
maneuvers during surgery such as augmentation with arcuate cuts medication. However, if filtering surgery is necessary, it is better
on the stromal bed and topographically guided LASIK. Other
to perform along with penetrating keratoplasty. An over size graft
variations are relaxing incisions followed by LASIK surgery and
can minimize postoperative glaucoma in aphakic and
sequential treatment by LASIK, that is, raising of the flap as a pseudophakic keratoplasty. Smaller trephine size should be used
first stage procedure followed by ablation if required, 4 to 6
when possible.103 Intraoperative considerations include release
weeks later after relifting the flap in the second stage. The
of all synechiae, iridoplasty to make iris-diaphragm taut and
lamellar corneal flap alone may reduce postpenetrating sutures should not be too tight, too long or too deep. Inadvertent
keratoplasty astigmatism.99 Improvement in both uncorrected
overtightening of the suture can be avoided by maintaining a
visual acuity and spectacle-corrected visual acuity, as well as a
consistently deep anterior chamber throughout the procedure.
decrease in spherical equivalent, cylinder, and anisometropia, Postoperatively steroids with less IOP rising effects can be used
has been reported in various studies.100 Arcuate keratotomies
especially in high-risk cases.106
performed with the femtosecond laser have been found to be
effective in reducing postkeratoplasty astigmatism. 101 Management: Medical therapy should be tried first in all cases
Trans-scleral fixation of a toric IOL for aphakic patients with of established postkeratoplasty glaucoma. Medical therapy
high astigmatism following keratoplasty has been described. 102 involves use of systemic and topical anti-glaucoma medications,
The details of this are discussed in Chapter 15. topical β-adrenergic antagonists, like timolol 0.5 percent eye
drops twice daily, being the first choice. However, corneal
epithelial toxicity some-times prevents the use of topical β-
Glaucoma
blockers. Topical parasympathetic agents should be used very
Penetrating keratoplasty, using modern techniques of tight wound cautiously in eyes with severe peripheral anterior synechiae, as
closure, can be complicated by IOP elevation in both early and they tend to reduce uveoscleral outflow, which is a major
late postoperative periods. Sustained elevation of intraocular pathway of drainage in these eyes. Latanoprost is a better choice
pressure not only damages the optic nerve head but has a in such eyes.
112
Surgical therapy is indicated when either the optic nerve or risk of development of postoperative retinal detachment. A high
the graft is threatened by persistent elevation of IOP. Traditional cutting rate and a moderate suction are helpful in meticulous
filtering procedures have a high failure rate in postkeratoplasty removal of vitreous.
eyes. Use of antimetabolites such as mitomycin-C or 5- Early diagnosis gives a better prognosis, although surgical
fluorouracil to maintain the filtering bleb may be effective but reattachment rate after keratoplasty is poor. The main reason of
there is high risk of graft failure from epithelial toxicity. Selective failure is poor visualization of peripheral retina. The high-risk
laser trabeculoplasty may be considered a valuable therapeutic cases must be monitored closely with frequent indirect

Chapter 14: Complications of Penetrating Keratoplasty


method that limits invasive surgery for treatment of secondary ophthalmoscopy or ultrasound B-scan if indicated. Pre-existing
glaucoma after penetrating keratoplasty.107 Different glaucoma retinal detachment may be managed by placing a temporary
implants such as Molteno, Ahmed and Baerveldt108 implants can keratoprosthesis to allow visualization of retina and completing
be used to treat medically uncontrollable glaucoma. the keratoplasty after retinal procedure is over. Retinal
Cyclodestructive procedures may be used to control intraocular reattachment surgery requires tremendous manipulation of the
pressure in otherwise uncontrolled eyes, particularly with poor globe often result in graft failure.
visual potential. Diode laser trans-scleral cyclophotocoagulation
appears to be a safe and effective procedure in these eyes.109 Maculopathy
Cyclocryotherapy destroys the ciliary body by external
Macular edema: Macular edema is a common cause of non-
application of cryoprobe. Although the success rate is quite high,
improvement of vision in spite of clear graft after penetrating
the procedure is not without complications. Apart from pain, keratoplasty. Incidence of macular edema from keratoplasty itself
redness and chronic inflammation, there are chances of graft
is unknown because some of the macular edema may be pre-
failure and phthisis bulbi. Alternately Nd-YAG laser can be used
existing. Aphakic and pseudophakic bullous keratopathy, trauma
for cyclodestruction with relatively fewer complications. Further and virtually any previous intraocular surgery predispose to
details of this complications are discussed in Chapter 15.
macular edema. Anterior vitrectomy at the time of surgery greatly
increases the incidence. Similarly, the incidence is expectedly
Recurrence of Original Recipient Disorder
more in eyes undergoing combined cataract surgery and
Several corneal dystrophies are known to recur in the grafts penetrating keratoplasty.
usually decades after the keratoplasty. The probable mechanism
is migration of recipient keratocytes into the graft stroma. Initial Prevention and management: Prophylactic use of anti-
recurrence occurs at the graft periphery and smaller size grafts prostaglandin non-steroidal anti-inflammatory drugs such as
are most frequently involved. The following lesions are known indomethacin (both topical and systemic) can reduce the
to recur frequently in the grafts. incidence of macular edema. The treatment should be continued
• Stromal dystrophies for at least 2 weeks postoperatively. Chronic macular edema is
–Granular-100 percent at 4 years110 more difficult to treat than the acute one. Every attempt should
–Macular-5.2 percent111 be made to control the intraocular inflammations. Intravitreal
–Lattice-48 percent112 injection of triamcinolone acetonide may be an additional tool
• Reis-Buckler’s dystrophy in the treatment of therapy-resistant cystoid macular edema after
• Central crystalline dystrophy penetrating keratoplasty.113 Some macular edema may resolve
• Posterior polymorphous dystrophy. spontaneously. Macular edema and visual acuity continue to
improve for 1 to 2 years. However, overall prognosis remains
Management: Usual therapy is a repeat graft. Superficial unfavorable.
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15

Chapter 15: Post Penetrating Keratoplasty Glaucoma


Post Penetrating Keratoplasty Glaucoma
Viney Gupta, Sushil Vasudevan, Jonathan G Crowston

Secondary ocular hypertension after penetrating keratoplasy is Keratoplasty performed for tectonic reasons, especially grafts
not uncommon. However, with the introduction of less invasive performed for perforated corneal ulcers have also been found
surgical techniques for keratoplasty the incidence of post to lead to high rates of IOP elevation with glaucoma being the
keratoplasty rise of IOP has reduced. Intraocular pressure most common complication postoperatively.8,15,16 The longer the
elevation can have serious consequences after keratoplasty, in period between the perforation and therapeutic keratoplasty the
that it may lead to endothelial cell loss, early graft rejection, graft greater the likelihood of developing glaucoma. Eyes with
failure and over time optic nerve damage.1,2 Experimental corneo iridic scars (adherent leucomas) preoperatively have also
evidence indicates that corneal endothelium from grafted tissues been found to be at high risk of development of glaucoma post
is more susceptible to damage than healthy non grafted corneal keratoplasty.17
endothelium.3 Hence early detection of IOP elevation and its
control is important to promote graft survival. IOP elevation has Intraoperative
been associated with graft rejection episodes though a causal Using a donor transplant that is 0.5 mm larger than the recipient’s
association is not known.4 One large series found elevated IOP bed has been found to be less likely to cause IOP elevation than
to be the third most common cause of graft failure.5 In addition if same size donor graft was used especially in aphakic
to the corneal pathology IOP may, of course, also result in keratoplasties.18 Using same sized donor tissue as the recepient
progressive visual impairment due to optic nerve damage which results in compression of the corneolimbal angle thus
may go unrecognized especially in a failing graft. compromising the trabecular meshwork. Tighter sutures, longer
bites, larger trephine size, small total recepient corneal diameter
Incidence during surgery and increased peripheral corneal thickness,
The incidence of glaucoma following penetrating keratoplasty increase distortion of the angle leading to a raised IOP.7,19
ranges from 11 to 38 percent in phakic eyes and 42 to 89 percent
in aphakic eyes.6,7,8 The overall incidence of post keratoplasty
glaucoma may be as high as 30 percent.9

Factors Associated with IOP Elevation


in Eyes with Keratoplasty

Preoperative
The presence of glaucoma prior to the keratoplasty is an
important risk factor despite adequate control.10-13 Glaucoma
following keratoplasty is more common in aphakic eyes as
compared to phakic eyes.6 In pseudophakic eyes the rise in
pressure is more frequent than in phakic eyes, but less as
compared to aphakic eyes (Fig. 15.1).14 While keratoplasty in
patients with a keratoconus is less likely to be associated with a
raised intraocular pressure, the highest risk of glaucoma post
keratoplasty was reported for eyes with aphakic bullous
keratopathy.15 Figure 15.1: Post penetrating keretoplasty glaucoma

117
Other intraoperative factors that can cause raised IOP post Diagnosis
keratoplasty include the use of viscoelastics and additional
One of the indicators of raised IOP following keratoplasty is a
surgical procedures performed with the corneal grafting. thinning of corneal stroma. This is followed by epithelial edema
Mac Rae et al. demonstrated in primate studies, IOP elevation
and if not treated leads to progressive thickening of the stroma
as high as 67mm Hg, 90 minutes after intracameral injection of
due to endothelial damage.29,30
1 percent sodium hyaluronate.20 Hence it is recommended that IOP measurement is critical, though difficult in post
the viscoelastic agents will be replaced with balanced saline
keratoplasty eyes. Unrecognized IOP elevation can lead to
Section III: Penetrating Keratoplasty: Management of Complications

solution at the end of the surgery though an IOP elevation


progressive optic nerve damage. Biomechanical changes in the
> 50 mm Hg even after satisfactory removal of the viscoelastic cornea that may affect its flexural rigidity, can influence IOP
at the end of the procedure has also been reported in the early
measurement. Technical difficulties exist in measuring IOP with
postoperative period.21
Goldmann applanation tonometry due to irregular astigmatism
The risk of IOP elevation and glaucoma increases with and hence distorted mires. The OBF pneumotonometer, tonopen
additional procedures like lens extraction and IOL insertion or
and the dynamic contour tonometer are alternatives to Goldmann
even a secondary IOL implantation.22
applanation tonometry (GAT) for IOP measurement in eyes with
scarred corneas, postkeratoplasty. All the three instruments have
Postoperative
been found to give higher IOP reading than the GAT in
Shallow anterior chamber or the presence of an air bubble can postkeratoplasty eyes.31-33 While Rao et al.34 in their study on
trigger pupillary block glaucoma postoperatively. Pupil block 69 postkeratoplasty eyes found OBF pneumotonometer not to
glaucoma has also been reported to occur as a complication of be affected by CCT and a useful alternative to GAT, Browning
Descemets stripping automated endothelial keratoplasty.23,24 et al. found it to be most affected by CCT in eyes with other
Immediate postoperative wound leaks with shallow anterior corneal pathologies.33 The dynamic contour tonometer (DCT)
chambers can also lead to Malignant glaucoma.25 Both early and may give more realistic IOP readings in grafted eyes compared
delayed suprachoroidal hemorrhage is known to complicate a to GAT as the measurements take into account the corneal
penetrating keratoplasty.26,27 thickness variability, though there are no large studies using the
An IOP elevation postkeratoplasty may also accompany HSV DCT in grafted eyes.31
uveitis in eyes that have undergone keratoplasty for herpetic IOP measurement should be performed at all visits after
keratitis. This IOP elevation is related to the trabeculitis and is keratoplasty and optic disk assessed whenever possible if IOP
short lived.4 is elevated.35
Progressive angle closure due to development of fine
peripheral anterior synechiae can lead to postkeratoplasty Management
glaucoma and is one of the important causes of late IOP rise Medical
after corneal transplants (Fig. 15.2).28
Medical therapy remains the initial management of post
Epithelial and fibrous downgrowth though uncommon, can
lead to a refractory postkeratoplasty glaucoma. keratoplasty glaucoma unless surgically treatable cause like
pupillary block is found.
Finally, secondary ocular hypertension should be suspected
to be steroid induced in eyes on intensive steroid therapy Beta adrenergic blocking agents (Timolol, Levobunolol,
especially for graft rejection. Betaxolol) and alpha 2 adregenic agonist (Brimonidine) by
decreasing adequate aqueous humor production is useful in the
treatment of post keratoplasty glaucoma although there are
conflicting reports in the literature.36,37Adverse effects of beta
adregenic blockers such as superficial punctuate keratitis, corneal
anesthesia, dry eye and subconjuctival fibrosis may however
compromise graft function. Brimonidine is also to be used with
caution as it may cause allergic reactions, dry eyes and superficial
punctuate keratitis.
Prostaglandin analogues (Latanoprost Travaprost,
Bimatoprost) which decrease intraocular pressure by decreasing
uveal outflow may be used alone or in combination with beta
adregenic blocking agents or alpha 2 adregenic agonists.
Precautions should be taken as they have been reported to cause
cystoid macular edema in patients with a past history of uveitis
and patients with aphakia and pseudophakia.38 Wand et al. report
Figure 15.2: Ultrabiomicroscopy shows posterior synechiae recurrence of herpetic infections in patients’ with herpes simplex
118
keratitis. 39 Hence care needs to be taken in instituting trabeculectomy with mitomycin-C has been reported to be
prostaglandins in eyes grafted for HSV keratitis. between 67-91 percent and that of graft failure between
12-18 percent.45,46 An overall 70 percent success over a 3 year
Carbonic anhydrase inhibitors (Drozolomide, Brinzolomide, follow-up for IOP < 21 mm Hg is described for trabeculectomy
Acetazolamide) Topical therapy may be tried as a second or third with MMC in eyes with postkeratoplasty glaucoma.47 Hence
line agent however they are not recommended as they also trabeculectomy with MMC as a filtering surgery should be
suppress the carbonic anhydrase enzyme in the corneal preferred as first line surgical treatment. However, caution should
endothelium and may lead to graft decompensation.40

Chapter 15: Post Penetrating Keratoplasty Glaucoma


be taken in administering subconjunctival 5-Fluorouracil
Systemic carbonic anhydrase (acetazolamide) are useful in postoperatively to prevent bleb scarring in these eyes in view of
the treatment of immediate post operative pressure spikes but its epithelial corneal toxicity.
their long term therapy is limited by their side effects of nausea,
gastrointestinal disturbances, paresthesia, fatigue, depression, Glaucoma Drainage Devices
anorexia and weight loss. There have been reports however of
its limited efficacy.41 Glaucoma drainage devices may be considered in patients where
trabeculectomy with mitomycin-C is not an option and is likely
Miotics (Pilocarpine) are of little value in the presence of to fail, is contraindicated or in patients with a failed
peripheral anterior synechiae and is best avoided as they trabeculectomy with mitomycin-C. The average success of
breakdown the blood aqueous barrier and can cause graft glaucoma drainage devices to control glaucoma in patients
rejection.42 following keratoplasty in published series is 84.4 percent,
however a 10-51 percent incidence of graft failure is reported
Hyperosmotic agents (Mannitol) may be indicated for the to occur in different series with varying follow-up times.42,48,49
temporary relief of the high rise in intraocular pressure in the
early post operative period.41 Cyclodestructive Procedures
When using topical drugs to lower intraocular pressure
besides these specific side effects, effects of preservatives used Transceralal diode laser cyclophotocoagulation is the choice of
in these topical drops, which can cause corneal epithelial and cyclodestructive procedures. Graft failure following glaucoma
other surface toxicity should be taken into account.43 Hence if drainage devices and cyclodestructive procedures is about the
long-term therapy is indicated, preservative free topical same, however, there may be a higher incidence of permanent
medication should be considered. visual loss and hypotony with cyclodestructive procedures.35
Topical steroids are part and parcel of the treatment following Shah et al. in a series of 28 patients followed up from 18 to 38
penetrating keratoplasty. One should always consider the months found an incidence of 16 percent for graft failure after
possibility of steroid induced glaucoma, either decreasing the cyclodiode.50 The procedure needs to be repeated for the desired
dose/frequency of steroids or using less potent topical steroids IOP control. It is generally reserved if other interventions have
like fluorometholone are potential ways to decrease the IOP failed.
elevation associated with steroid use. Topical immunomodulators
Managing Pre-existing Glaucoma
like cyclosporine A in conjunction with topical glaucoma
medication can help lowering IOP in steroid responders. Preexisting glaucoma is a high risk factor for the development
of post keratoplasty glaucoma and also leads to higher incidence
Surgical of graft failure in patients undergoing glaucoma surgery
following keratoplasty.51-53 Hence patients with uncontrolled
Laser Iridotomy
glaucoma or those on maximal medical management should
Laser iridotomy may be performed if a component of pupillary ideally be treated with either trabeculectomy with antifibrotic
block is suspected in post keratoplasty glaucoma. or glaucoma drainage devices prior to keratoplasty or may be
combined with the planned corneal transplant.53 Staging the
Glaucoma Filtering Procedures trabeculectomy before the transplant however, has the risk of
bleb failure due to inflammation and progressive synechial
No glaucoma surgery has been found to be entirely suitable for
controlling intraocular pressure or preserving graft clarity formation after keratoplasty.54
however, is indicated when medical management has failed and
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Trabeculectomy with mitomycin-C has better success for role of glaucoma therapy in the need for repeat penetrating
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2. Chien AM, et al. Glaucoma in the immediate postoperative period
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4. Adams GG, Stevenson KE, Kirkness CM, Steele AD, Rice NS. 28. Lass JH, Pavan-Langston D. Timolol therapy in secondary angle-
Is raised intraocular pressure a bad prognostic sign in acute closure glaucoma post penetrating keratoplasty. Ophthalmology
corneal graft rejection? Eye 1995;1:412. 1979;86:51.
5. Williams KA, Muehlberg SM, Lewis RF, Coster DJ. How 29. Ytteborg J, Dohlman CH. Corneal edema and intraocular pressure
successful is corneal transplantation? A report from the Australian II. Clinical results, Arch Ophtahalmol 1965;74:477.
Corneal Graft Register. Eye 1995;9:219. 30. Olson RJ, Kaufman HE. Intraocular pressure and corneal thick-
6. Irvine AR, Kaufman HE. Intraocular pressure following ness after keratoplasty. Am J Ophthalmol 1978;86:97.
penetrating keratoplasty. Am J Ophthalmol 1979;68: 835. 31. Ismail AR, Lamont M, Perera S, Khan-Lim D, Mehta R, Macleod
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7. Karesh JW, Nirankari VS. Factors associated with glaucoma after JD, Anderson DF. Comparison of IOP measurement using GAT
penetrating keratoplasty, Am J Ophthalmol 1983;96:160. and DCT in patients with penetrating keratoplasties. Br J
8. GN Foulks. Glaucoma associated with penetrating keratoplasty. Ophthalmol 2007;91:980.
Ophthalmology 1987;94:871–74. 32. Geyer O, Mayron Y, Loewenstein A, Neudorfer M, Rothkoff L,
9. Kirkness CM, Moshegov C. Post-keratoplasty glaucoma. Eye Lazar M. Tono-Pen tonometry in normal and in post-keratoplasty
1988;2 Suppl:S19-26. eyes. Br J Ophthalmol 1992;76:538-40.
10. Foulks GN. Glaucoma associated with after penetrating kerato- 33. Browning AC, Bhan A, Rotchford AP, Shah S, Dua HS. The effect
plasty, Ophthalmology 1987;94:871.
of corneal thickness on intraocular pressure measurement in
11. Chien AM, et al. Glaucoma in the immediate postoperative period
patients with corneal pathology. Br J Ophthalmol 2004;88:1395.
after penetrating keratoplasty, Am J Ophthalmol 1993;115:711.
34. Rao VJ, Gnanaraj L, Mitchell KW, Figueiredo FC. Clinical
12. Goldberg DB, Schanzlin DJ, Brown SI. Incidence of increased
comparison of ocular blood flow tonometer, Tonopen, and
pressure after keratoplasty, Am J Ophthalmol 1981;92:372.
Goldmann applanation tonometer for measuring intraocular
13. Simmons RB, et al. Elevated intraocular pressure following
pressure in postkeratoplasty eyes. Cornea 2001;20:834.
penetrating keratoplasty. Trans Am Ophthalmol Soc 1989;87:79.
35. Ayyala RS. Penetrating keratoplasty and glaucoma. Surv
14. Zaidman GW, Goldman. A prospective study on implantation of
Ophthalmol 2000;45:91.
anterior chamber IOL during keratoplasty for pseudophakic and
aphakic bullous keratopathy. Ophthalmology 1990;97:757-62. 36. Nissenkorn I, Wood TO. Intraocular pressure following aphakic
15. Kirkness CM, Ficker LA. Risk factors for the development of transplata, Ann Ohpthalmol 1983;15:1168.
post-keratoplasty glaucoma. Cornea 1992;11:427. 37. Olson RJ, Kaufman HE, Zimmerman TJ. Effects of timolol and
16. Sukhija J, Jain AK. Outcome of therapeutic penetrating Daranide on elevated intraocular pressure after aphakic
keratoplasty in infectious keratitis. Ophthalmic Surg Lasers keratoplasty, Ann Ophthalmol 1979;11:1833.
Imaging 2005;36:303. 38. Ayyala RS, Cruz DA, Margo CE, et al. Cystoid macular edema
17. Sihota R, Sharma N, Panda A, Aggarwal HC, Singh R. Post- associated with latanoprost in aphakic and pseudophakic ayea,
penetrating keratoplasty glaucoma: risk factors, management and Am J Ophthalmol 1998;126:602.
visual outcome. Aust N Z J Ophthalmol 1998;26:305. 39. Wand A, Gilbert CM, Liesegang TJ. Latanoprost and herpes
18. ZimmermanTJ, Olson R, Waltman S, Kaufman H. Transplant size simplex keratitis, Am J Ophathalmol 1999;127:602.
and elevated intraocular pressure postkeratoplasty, Arch 40. Konowal A, Morrison JC, Brown SV, et al. Irreversible corneal
Ophthalmol 1978;96:2231. decompensation in patients treated with topical drozolomide, Am
19. Olson RJ, Kaufman HE. A mathematical description of causative J Ophthalmol 1999;127:403.
factors and prevention of elevated intraocular pressure after 41. Wood TO, West C, kaufmann HE. Control of intraocular pressure
keratoplasty, Invest Ophthalmol Vis Sci 1977;16:1085. in penetrating keratoplasty, Am J Ophthalmol 1972;74:724.
20. MacRae SM, Edelhauser HF, Hyndiuk RA, et al. The effects of 42. Beebe WE, Starita RJ, Fellman RL, et al. The use of Molteno
sodium hyaluronate, chondroitin sulfate and methylcellulose on implant and anterior chamber tube shunt to encircling band for
the corneal endothelium and intraocular pressure, Am J Ophthal- the treatment of glaucoma in keratoplasty patients,
mol 1983;95:332. Ophthalmology 1990;97:1414.
21. Barron BA, Busin M, Page C, Bergsma DR, Kaufman HE. 43. Fraunfelder FT. Drugs used primarily in Ophthalmology. In :
Comparison of the effects of Viscoat and Healon on postoperative Meyer SM (Ed) Drug induced ocular side effects and drug
intraocular pressure. Am J Ophthalmol 1985;100:377. interactions. Lea & Febiger. Philadelphia 1989.
22. Sekhar GC, Vyas P, Nagarajan R, Mandal AK, Gupta S. 44. Rand Allingham, et al. Glaucomas after Ocular Surgery. In R Rand
Postpenetrating Keratoplasty glaucoma. Ind J Ophthalmol Allingham,Karim Damji, Sharon Freedman, Sayoko Moroi,
1993;41:181. George Shafranov (Eds) Sheild’s Textbook of Glaucoma (2005)
23. Koenig SB, Covert DJ. Early results of small-incision Descemet’s 5th edition. Lipponcott Williams & Wilkins. Philadelphia.
stripping and automated endothelial keratoplasty. Ophthalmology 45. Ayyala RS, Pieroth L, Vinlas AF, et al. Comparison of mitomycin
2007;114:221.
C trabeculectomy, glaucoma drainage device implantation and
24. Cheng YY, Hendrikse F, Pels E, Wijdh RJ, van Cleynenbreugel
laser neodymium: YAG cyclophotocoagulation in the management
H, Eggink CA, van Rij G, Rijneveld WJ, Nuijts RM. Preliminary
of intractable glaucoma after penetrating keratoplasty,
results of femtosecond laser-assisted descemet stripping
Ophthalmology 1998;105:1550.
endothelial keratoplasty. Arch Ophthalmol 2008;126:1351.
46. Figueiredo RS, Araujo SV, Cohen EJ, et al. Management of
25. Greenlee EC, Kwon YH. Graft failure: III. Glaucoma escalation
after penetrating keratoplasty. Int Ophthalmol 2008;28:191. coexisting corneal disease and glaucoma by combined penetrating
26. Duncker GI, Rochels R. Delayed suprachoroidal hemorrhage after keratoplasty and trabeculectomy with mitomycin-C, Ophthalmic
penetrating keratoplasty. Int Ophthalmol. 1995-96;19:173. Surg Lasers 1996;27:903.
27. Price FW Jr, Whitson WE, Ahad KA, Tavakkoli H. 47. Ishioka M, Shimazaki J, Yamagami J, Fujishima H, Shimmura
Suprachoroidal hemorrhage in penetrating keratoplasty. S, Tsubota K. Trabeculectomy with mitomycin C for post-
Ophthalmic Surg 1994;25:521. keratoplasty glaucoma. Br J Ophthalmol. 2000;84:714-17.
120
48. Rapuano CJ, Schmidt CM, Cohen EJ, et al. Results of alloplastic 52. Reinhard T, Kallmann C, cephin A, et al. The influence of
tube shunt procedures before, during or after penetrating glaucoma history on graft survival after penetrating keratoplasty,
keratoplasty, Cornea 1995;14:26. Graefes Arc cli exp Ophthalmol 1997;235:26.
49. Binder PS Abel R, Kaufman HE. Cyclocryotherapy for glaucoma 53. Kirkness CM, Steele AD, Ficker LA, et al. Coexistent corneal
after post penetrating keratoplasty.Am J Ophthalmol 1975;79:489. disease and glaucoma managed by either drainage surgery and
50. Shah P, Lee GA, Kirwan JK, Bunce C, Bloom PA, Ficker LA, subsequent keratoplasty or combined drainage surgery and
Khaw PT. Cyclodiode photocoagulation for refractory glaucoma penetrating keratoplasty. Br J Ophthalmol 1992;76:146-52.
after penetrating keratoplasty Ophthalmology 2001;108:1986-91. 54. Lee RK, Fantes F. Surgical management of patients with

Chapter 15: Post Penetrating Keratoplasty Glaucoma


51. Chien AM,Schmidt CM, Cohen EJ, et al. Glaucoma in the combined glaucoma and corneal transplant surgery. Curr Opin
immediate postoperative period after penetrating keratoplasty, Am Ophthalmol 2003;14:95-9.
J Ophthalmol 1993;115:711.

121
16
Section III: Penetrating Keratoplasty: Management of Complications

Corneal Graft Rejection


Ben Connell, Michael S Loughnan

Definition of Graft Failure Primary and Secondary Graft Failure


Corneal graft surgeons have debated for years: “What is the Graft failure is divided into two groups: primary (or early) and
definition of graft failure?” In one sense it is failure of the graft secondary (or late) failure. The timing distinction between these
to achieve the stated aim for performing the procedure. two is somewhat arbitrary, primary failure occurring in the first
There are 5 main indications for performing a corneal graft: postoperative weeks and secondary failure beyond this. A graft
to improve vision (visual), to achieve a therapeutic aim such as which never clears remaining thickened postoperatively, is
pain relief (therapeutic), to restore structural integrity to the termed a primary failure. This type of graft failure is rarely due
cornea (tectonic), to aid in the diagnosis of an underlying disease to an immunogenic mechanism and is usually due to poor eye
such as a microbial keratitis (diagnostic) and to improve cosmesis banking or surgical trauma with damage to the endothelial
(cosmetic). Frequently there is more than one aim, this is surface. The importance of good eye banking procedures to
especially the case with diagnostic and cosmetic grafts. For adequately screen out inappropriate donor material as well as
example, a corneal graft performed for a perforated leukoma in to adequately harvest and store donor buttons cannot be overly
an otherwise normal eye aims to achieve visual, tectonic and emphasized. Secondary graft failure occurs in a graft that has
cosmetic outcomes. functioned in the immediate postoperative period. Unless
Obviously it is reasonable then to judge the success or failure specifically stated graft failure refers to secondary graft failure.
of a graft on achieving these aims. For example, postoperative
unmanageable high astigmatism in an otherwise clear and Causes of Secondary Graft Failure
compact graft for keratoconus could be considered a failure. On Graft failure is due to any cause of endothelial cell loss to such
the other hand, stromal edema due to endothelial failure in a as aphakia, older style anterior chamber intraocular lenses,
macroscopically normal appearing eye where the indication was uncontrolled intraocular pressure or ongoing inflammation. The
cosmetic might not be considered failure. commonest cause of secondary graft failure is an immune
Despite this, when one uses the term graft failure it is usually mediated process termed allogenic graft rejection.2 Not all
in the sense of irreversible loss of graft clarity. This is usually, episodes of allogenic graft rejection however, progress to
although not always, due to graft edema secondary to endothelial secondary graft failure. Some resolve with endothelial function
cell loss. A cornea requires approximately 1000 cells/mm2 to returning and stromal edema improving. Allogenic graft rejection
remain clear and compact, although other factors such as will subsequently be referred to as graft rejection in this chapter.
intraocular pressure and some drugs do affect endothelial cell Primary graft failure is not considered further.
pumping capacity.
Endothelial cells maintain a clear and compact cornea in the Types of Graft Rejection
face of corneal stromal mucopolysaccharides through two The three transplanted tissue components in penetrating
enzymatic pumps:1 the most important an ATPase dependent and keratoplasty are epithelium, stroma and endothelium. Rejection
a less important carbonic anhydrase pump. As such corneal can be directed at any of these three layers in isolation or
endothelial cells are of prime importance in maintaining normal combination.3 Donor epithelium can persist for up to fifteen
corneal function. However, they are nonmitotic and therefore months post graft, hence rejection can occur at any time during
nonreplicatory in humans. As such the loss of sufficient this period.
endothelial cells as a result of an allogenic rejection episode can Stromal keratocytes persist indefinitely and are the antigenic
lead to irreversible graft edema. stimulus for stromal rejection. They are replaced gradually over

122
a period of years, (which explains why stromal dystrophies • Number of rejection episodes
eventually recur in the graft) but some keratocytes persist. Hence • Postoperative rise in intraocular pressure
stromal rejection can potentially occur for the life of the graft. The registry also demonstrated that the indication for the
Endothelial cells are non replicatory and persist indefinitely. graft influenced survival. Past or current HSV infection, other
Hence rejection can occur at any time against this layer. Allogenic infections such as acanthamoeba, bacteria, fungi and corneal
graft rejection refers to a cell-mediated immune reaction directed thinning all had negative effects on graft survival. Comparatively,
against the corneal allograft. It is directed against Major grafts performed for keratoconus and corneal dystrophies had a

Chapter 16: Corneal Graft Rejection


Histocompatability Complex (MHC) alloantigens present on better prognosis. Graft diameter also influenced survival with
donor cells. Endothelial graft rejection is the commonest type larger diameter grafts fairing worse.2
of rejection. Graft rejection generally refers to this unless
specifically stated. Topical Corticosteroids
Topical corticosteroids provide some prophylaxis against
Prevention of Graft Rejection rejection. Patterns of tailing topical corticosteroid drops in the
months post graft vary between surgeons. Their prophylactic
Careful Case Selection benefit is offset by their side effects of raised pressure, cataract
One of the most important lessons learnt over the past 50 years and inhibition of wound healing. Most don’t advocate lifelong
corticosteroids for noninflammatory indications such as
of grafting is when not to operate. Largely it has been
keratoconus, non HSV corneal scars or corneal dystrophies. They
demonstrated that there is little benefit with performing visual
grafts for unilateral disease.2 This is especially the case in high- should be considered where there is a history of inflammation
such as past HSV, other infections, corneal ulcer, thinning or
risk situations such as chemical burns and following herpes
previous graft failure. Essentially, long-term infrequent (once or
simplex keratitis. Even grafting for low-risk unilateral
keratoconus has marginal benefit. The patient needs to be twice daily) corticosteroid drops should be considered in patients
where there is a high risk of graft failure or where there has been
particularly motivated to wear a contact lens unilaterally to
more than one rejection episode.
achieve the full visual benefit.
Some surgeons have even performed auto-corneal Suture removal can often precipitate graft rejection. Frequent
topical corticosteroid should therefore be given for one week
transplants, taking the donor cornea from a blind second eye with
post removal. Our institution uses prednisolone acetate or
a normal cornea (e.g. optic nerve meningioma) and transplanting
it into the eye with corneal disease. This is not dissimilar to the dexamethasone acetate four times per day for a period of one
week.
strategy of anterior lamellar grafting where the host endothelium
is left in place. Anterior lamellar grafting is obviously only
Systemic Corticosteroid Sparing Immunosuppression
appropriate in the treatment of eyes with normal endothelial cell
function. While these strategies do minimize the risk of allograft There is only limited evidence of increased graft survival with
rejection, they do not avoid a myriad of other possible systemic cyclosporin A for high risk grafts.4 This finding has
complications that can compromise the success of such not been supported by other studies.5 Despite this systemic
procedures. immunosuppression, most commonly cyclosporin,6 could be
As such it is always important to address the question of considered in high-risk grafts, particularly where the
whether a patient really does require a corneal graft. Alternatively consequences of rejection and failure are high such as poor vision
no surgery or some other surgery such as lens extraction in Down in the other eye.
syndrome patients with a high degree of induced myopia may
Tissue Matching
be more appropriate.
The matching of MHC and blood group antigens has also been
Identifying High-risk Corneal Grafts examined in several major studies including the Collaborative
Corneal Transplantation Study (CCTS).7 This failed to establish
Risk factors for graft failure have been described by the any benefit from matching for Class 1 or Class 2 Antigens for
Australian Corneal Graft Registry.2 These were: high-risk grafts. Consequently, while matching of host and donor
• Inflammation before or at the time of grafting MHC antigens is widely practiced in other solid organ
• Recipient corneal neovascularization at the time of grafting, transplants, it is infrequently in ophthalmology. Most eye banks
with the magnitude of risk proportional to the number of are not set up for this facility.
quadrants vascularized Interestingly, the CCTS did demonstrate a significant
• History of raised intraocular pressure in the grafted eye reduction in the frequency of allograft rejection in high-risk cases
• Number of previously failed grafts where the ABO blood group was matched. Despite this, matching
Post graft events associated with graft failure were: for these antigens is not routinely performed in current clinical
• Donor vascularization practice.

123
Antiviral Prophylaxis where there is a
History of HSV Disease
Patients who have had a corneal graft with prior HSV corneal
infection represent a group at particular risk of developing
inflammation and subsequent rejection.
Much of rationale for prophylactic antiviral therapy post
corneal grafts has been derived from studies of HSV stromal
Section III: Penetrating Keratoplasty: Management of Complications

prophylaxis in populations with no history of corneal surgery.


The HEDS study8 demonstrated that acyclovir 400 mg twice
daily provided a 45 percent reduction in the recurrence of HSV
stromal disease. This benefit ceased when the acyclovir was
stopped.
The morbidity from systemic antivirals therapy is low. Most
patients with past HSV should therefore receive ongoing
prophylactic dose systemic antivirals. Figure 16.1: Epithelial rejection

Clinical Presentation

Symptoms
Graft rejection can present with any combination of the following
symptoms: blurred vision, a red eye, pain, discomfort, irritation
and/or photophobia. Many episodes however, are asymptomatic.9
Rejection typically occurs in the first postoperative year.10
Rejection has typically been classified into three types:
epithelial, stromal and endothelial.3 A clinical rejection episode
however, rarely fits discretely into one of these three entities. In
many there is overlap with the presentation taking components
from more than one type.

Signs
Epithelial rejection typically presents in the first year, on average
Figure 16.2: Subepithelial infiltrates
three months post surgery,10 as a raised line of epithelium,
staining with fluoroscein or rose bengal. The line advances across
the graft replacing donor with recipient epithelial cells leaving
damaged cells in its wake (Fig. 16.1).
Krachmer11 described graft rejection manifesting as anterior
stromal nummular inflammatory lesions in the donor, similar to
those seen in epidemic keratoconjunctivitis (Fig. 16.2). Stromal
rejection has been described in the New Zealand rabbit and is
seen infrequently in humans as an isolated clinic entity. Most
commonly it is associated with endothelial rejection. Stromal
rejection manifests as full thickness corneal haze and
circumcorneal hyperemia.
Endothelial rejection manifests as new keratic precipitates,
either in a line (Fig. 16.3) or diffusely arranged (Fig. 16.4). The
first entity described by Khodadoust3 is a line of keratic
precipitates across the endothelium representing the advancing
front of rejection. The line advances across the relatively healthy
donor endothelium, leaving a wake of damaged donor endothelial Figure 16.3: Khoudadoust endothelial rejection line
cells and stromal swelling.
Alternatively, endothelial rejection can present as increased
number of diffusely arranged keratic precipitates. A more diffuse Numbers of keratic precipitates should therefore be followed
stromal swelling ensues as endothelial cell density and function closely, since increased numbers are likely to represent recent
is diminished. inflammation and probable graft rejection. Keratic precipitates
124
Minimum Treatment for Allogenic Graft Rejection
The minimum treatment for a rejection episode is topical
corticosteroids drops. The corticosteroid should be combined
with a lipophillic base vehicle such as an acetate allowing high
corneal epithelial penetration. Examples are prednisolone acetate
1 percent, dexamethasone or fluoromethalone acetate.
In the appropriate patient, a prescription or bottle of

Chapter 16: Corneal Graft Rejection


corticosteroid drops should be supplied, suggesting they be
commenced empirically when presentation to an ophthalmologist
might be delayed.
The following is our institution’s protocol for treatment of
allogenic corneal graft rejection:
• Prednisolone acetate 1 percent or dexamethasone hourly day
and night for two days.
Where there is a clinical response the drops can be tapered
Figure 16.4: Diffuse keratic precipitates
in endothelial rejection according to the following regime:
• Continue hourly during the day (8 am to 10 pm) and less
with time become pigmented and develop sharper borders frequently overnight for two to five days
compared with the acute, fluffy edged precipitates associated • Where frequent overnight drop administration is logistically
with recent rejection. difficult and the rejection episode is resolving, overnight
Stromal swelling due to endothelial damage usually occurs drops can substituted with a corticosteroid ointment such as
with endothelial rejection although not in all cases.12 hydrocortisone acetate.
Modern portable, often handheld, pachymetry units allow • The drops should be tapered to four times daily over a period
corneal thickness to be measured accurately and quickly. Corneal of one month as the resolution process continues.
thickness can be used as a marker for endothelial function. Serial As discussed earlier, those at particular risk of further
pachymetry can be combined with slit lamp findings to improve rejection episodes should be considered for long-term infrequent
the diagnostic accuracy of early graft rejection. Minor increases (once or twice daily) corticosteroid drops.
in thickness with increased keratic precipitates suggest low grade A common issue is management where there appears to have
rejection. Corneal pachymetry can also be used to provide an been no resolution with initial therapy. Where poor compliance
objective measure of resolution after an episode of graft is suspected, admission should be considered. Once compliance
rejection. Use of corneal pachymetry however, is limited by the has been addressed, the question remains how long the frequent
expense of such units. topical corticosteroid drops should be continued. Some clinicians
Endothelial rejection is usually accompanied by anterior provide anecdotal reports of resolution with prolonged frequent
chamber inflammation, ranging from a minimal to marked topical corticosteroid where there appeared to be no resolution
reaction and rarely, hypopion. after one or two weeks. The morbidity of frequent topical
corticosteroids is low, particularly in the pseudophakic eye and
Treatment of Rejection where intraocular pressure (IOP) remains within the normal
range. The clinician should therefore have a low threshold for
Early Recognition continuing frequent topical corticosteroids. Where there is no
The principle of successful management of graft rejection is early immediate clinical improvement, they should be continued
presentation, diagnosis and prompt commencement of potent frequently for at least two to three weeks.
corticosteroid drops. Early treatment minimizes permanent Epithelial and stromal rejection are significant in that they
endothelial cell loss and therefore improves the probability of can progress to endothelial rejection. In isolation, they are less
graft clarity returning. significant. Both conditions should still be treated aggressively.
Early diagnosis occurs through clear pre- and postoperative
Role of Oral Corticosteroids and Steroid Sparing Agents
counselling regarding symptoms of graft rejection, emphasizing
the importance of prompt presentation should they arise. Patients Systemic corticosteroids such as oral prednisolone 1mg/kg daily
should be encouraged to have a low threshold for presenting. can be considered where the consequence of rejection
Acting promptly and presenting immediately to an progressing to failure is particularly significant, inflammation
ophthalmologist the same day as symptoms arise is extremely is severe or there is lack of response to initial therapy. For
important. Any potential graft recipient needs to understand that example, a patient experiencing a rejection episode in an “only
the risk of rejection is life-long. The ophthalmologist also needs eye” with previous grafts. The morbidity associated with
to understand the implications for this in terms of accessibility systemic corticosteroids needs to be considered and balanced
to their patient. against limited evidence for their efficacy.
125
Cyclosporin has relatively good T cell specificity. Topical Graft Failure
preparations are limited in their ability to penetrate the cornea.
The absence of inflammation is the main sign distinguishing graft
Our institution demonstrated no benefit in a randomized control
failure from rejection. Signs of inflammation can be subtle and
trial of cyclosporin for treatment of acute allogenic graft
easily missed. In some patients provisionally diagnosed with graft
rejection.
failure, stromal swelling resolves with treatment for rejection.
As a general principle, patients diagnosed with graft failure
Keratoconus and Allergic Eye Disease
should be given an empirical trial of rejection treatment. There
Section III: Penetrating Keratoplasty: Management of Complications

Patients undergoing keratoplasty for keratoconus with a history should be a low threshold for initiating graft rejection treatment,
of atopy rarely develop an aggressive sclerokeratitis up to ten particularly in the group with risk factors for rejection.
days post operatively.13 Sutures cheese wire through the graft,
attract mucous and the donor moves anteriorly rarely dehiscing Loose Sutures and Secondary Microbial Keratitis
completely. These patients generally require high dose oral
All loose sutures need to be removed immediately as they
prednisolone (1 mg/kg/day) and rarely oral cyclosporin.14 The
provide no tectonic function and if left, can precipitate graft
long-term prognosis for this condition is generally good once
the acute episode has resolved. rejection. Frequent topical corticosteroid should be used for at
least one week after removal of any suture as prophylaxis against
Rejection Post Lamellar Keratoplasty graft rejection. Where a loose suture is associated with
inflammation, the clinician should have a low threshold for
Anterior lamellar keratoplasty involves transplantation of a donor diagnosing early graft rejection and initiating frequent topical
anterior lenticule to a recipient posterior lamellar bed. The corticosteroids.
commonest indications are keratoconus and anterior stromal A loose suture associated with a stromal infiltrate or new
opacities or dystrophies, where there is a healthy recipient stromal tissue loss (even in the absence of a “typical” infiltrate)
endothelium. By maintaining the host’s own endothelium, the should be assumed due to microbial keratitis. The suture should
risk of immune mediated endothelial rejection is avoided, the be sent for microbiological culture, a corneal scrape performed
commonest and most significant type of rejection. Very good and hourly broad spectrum antibiotic drops initiated for at least
visual results have been demonstrated with this technique, almost 48 hours. In principle, frequent topical corticosteroids should
comparable to penetrating keratoplasty.15 Typical epithelial and be used since treating the inflammation takes precedence over
stromal rejection have both been demonstrated in anterior any small risk of promoting spread of the infection. Suture related
lamellar transplantation, often the former progressing to the infections are usually due to gram-positive cocci. These generally
latter.16 Treatment of these episodes is the same as for rejection don’t respond adversely to topical corticosteroids.
post penetrating keratoplasty. In the above series, five out of
seven patients responded to frequent corticosteroids drops with Microbial Keratitis
reversal of the rejection episode.
In posterior lamellar keratoplasty a posterior donor lenticule Chronic low grade infection such as infectious crystalline
is transplanted onto the recipient after descemet’s membrane and keratopathy or those caused by organisms such as Candida19 can
endothelium stripping or lamellar dissection. Relatively low also present in a similar manner or even cause graft rejection.
postoperative astigmatism, faster visual rehabilitation and The organism could be either acquired, or where the graft
tectonic benefits are making this a more popular procedure for indication was therapeutic, due to persistence. Inflammation in
patients with endothelial dysfunction. Both stromal and the graft in these scenarios could be due to infection. Such occult,
endothelial rejection has been reported with this procedure.17 chronic infections often respond badly to frequent corticosteroid
Pooled data from four centres, demonstrated 7.5 percent of 199 drops.
eyes developed a graft rejection episode within the first 2 years Treatment involves the competing needs of adequate
after posterior lamellar keratoplasty for this group containing corticosteroid administration to treat the rejection episode, and
Fuchs endothelial dystrophy and pseudophakic bullous resisting the use of high dose corticosteroids, which may
keratopathy patients.18 This rejection rate was significantly less potentiate the infection.
than the 13 percent, 2 year rate for a similar comparative group The primary clinical goal is to adequately treat the infection,
undergoing penetrating keratoplasty for the same indications. while protecting the graft long enough to minimize endothelial
This difference may however, be related to greater steroid use cell loss.
in the posterior lamellar group. In many patients in the lamellar
group, rejection episodes appeared related to cessation of topical HSV Keratitis
corticosteroids. All cases except one resolved with frequent This condition can be difficult to distinguish from allograft
corticosteroid drops. rejection. Keratic precipitates in HSV stromal disease are not
confined to the graft unlike endothelial rejection. Additionally
Differential Diagnosis of Graft Rejection
virus reactivation can precipitate rejection and vice versa.
The following diagnoses need to be considered: Activation of HSV epithelial disease should be confirmed with
126
laboratory testing. Polymerase chain reaction, where available REFERENCES
has a high sensitivity for HSV since small quantities of HSV
1. Bourne WM. Clinical estimation of corneal endothelial pump
antigen are amplified. Where a diagnosis of HSV has been made,
function. Trans Am Ophthalmol Soc 1998;96:229-39.
the viral replication process can be treated with a therapeutic 2. Williams KA, Hornsby NB, Bartlett CM, Holland HK, Esterman
dose of antiviral medication, such as acyclovir 400 mg orally A, Coster DJ. The Australian corneal graft registry 2004 Annual
fives times per day. report. Flinders Academic Commons. Snap printing 2004;8-7-
Graft inflammation where there is suspected or coexistent 2007. Ref Type: Electronic Citation

Chapter 16: Corneal Graft Rejection


HSV should still be treated aggressively with frequent topical 3. Khodadoust AA, Silverstein AM. Transplantation and rejection
corticosteroids. The concern regarding activation of epithelial of individual cell layers of the cornea. Invest Ophthalmol 1969;
8:180-95.
disease is less significant compared with ongoing graft
4. Hill JC. Systemic cyclosporine in high-risk keratoplasty. Short-
inflammation. Oral acyclovir penetrates the tear film well and versus long-term therapy. Ophthalmology 1994; 101(1):128-33.
is as efficacious as topical acyclovir. 5. Poon AC, Forbes JE, Dart JK et al. Systemic cyclosporin A in
high risk penetrating keratoplasties: a case-control study. Br J
Herpes Zoster Virus Inflammation Ophthalmol 2001;85:1464-69.
6. Barker NH, Henderson TR, Ross CA, Coster DJ, Williams KA.
Zoster related graft inflammation causes stromal swelling and
Current Australian practice in the prevention and management
increase anterior chamber inflammation. Similar to HSV of corneal allograft rejection. Clinical and Experimental
reaction, keratic precipitates should are not confined to the donor. Ophthalmology 2000;28:357-60.
7. The collaborative corneal transplantation studies (CCTS).
Epithelial Downgrowth Effectiveness of histocompatibility matching in high-risk corneal
transplantation. The Collaborative Corneal Transplantation
An advancing wave of epithelial downgrowth can spread across Studies Research Group. Arch Ophthalmol 1992;110:1392-1403.
the endothelial surface similar to the spread of an endothelial 8. Acyclovir for the prevention of recurrent herpes simplex virus
rejection line. When downgrowth spreads over the anterior eye disease. Herpetic Eye Disease Study Group. N Engl J Med
surface of the iris, the condition is distinguished from endothelial 1998;339:300-06.
rejection. Iris tissue blanching as a reaction to argon laser 9. Kamp MT, Fink NE, Enger C, Maguire MG, Stark WJ, Stulting
RD. Patient-reported symptoms associated with graft reactions
distinguishes this condition from fibrous downgrowth. Epithelial
in high-risk patients in the collaborative corneal transplantation
downgrowth has a poor prognosis, not responding to topical studies. Collaborative Corneal Transplantation Studies Research
corticosteroids. Group. Cornea 1995;14:43-48.
10. Alldredge OC, Krachmer JH. Clinical types of corneal transplant
Postsurgical Inflammation rejection. Their manifestations, frequency, preoperative correlates,
and treatment. Arch Ophthalmol 1981; 99:599-604.
Post graft patients having further surgery will usually develop
11. Krachmer JH, Alldredge OC. Subepithelial infiltrates: a probable
inflammation, often quite intense, depending on the type of sign of corneal transplant rejection. Arch Ophthalmol 1978;
surgery. For example, cyclodiode laser for glaucoma often results 96:2234-37.
in a strong postoperative inflammatory response. When used 12. McDonnell PJ, Enger C, Stark WJ, Stulting RD. Corneal thickness
postkeratoplasty, the inflammation can be difficult to distinguish changes after high-risk penetrating keratoplasty. Collaborative
from graft rejection. Similarly, other types of postkeratoplasty Corneal Transplantation Study Group. Arch Ophthalmol
surgery can precipitate graft rejection. The differential diagnosis 1993;111:1374-81.
13. Lyons CJ, Dart JK, Aclimandos WA, Lightman S, Buckley RJ.
of postoperative inflammation is therefore graft rejection.
Sclerokeratitis after keratoplasty in atopy. Ophthalmology 1990;
Inflammation of either cause needs to be treated with frequent 97:729-33.
topical corticosteroids. 14. Daniell MD, Dart JK, Lightman S. Use of cyclosporin in the
treatment of steroid resistant post-keratoplasty atopic
Prognosis sclerokeratitis. Br J Ophthalmol 2001;85:91-92.
15. Watson SL, Ramsay A, Dart JK, Bunce C, Craig E. Comparison
The most frequent complication of allograft rejection is failure.
of deep lamellar keratoplasty and penetrating keratoplasty in
Inflammation from endothelial rejection results in endothelial patients with keratoconus. Ophthalmology 2004;111:1676-82.
cell loss. Where endothelial reserve is sufficient and treatment 16. Watson SL, Tuft SJ, Dart JK. Patterns of rejection after deep
commenced promptly, rejection is reversed. Stromal swelling lamellar keratoplasty. Ophthalmology 2006;113:556-60.
resolves, graft clarity returns and a subjective improvement 17. Terry MA, Wall JM, Hoar KL, Ousley PJ. A prospective study of
ensues. Where pre morbid endothelial function was borderline endothelial cell loss during the 2 years after deep lamellar
at maintaining graft clarity, a relatively minor rejection episode endothelial keratoplasty. Ophthalmology 2007; 114:631-39.
18. Allan BDS, Terry MA, Price FW, Price MO, Griffin NB, Claesson
can result in graft failure, and its consequences: stromal
M. Corneal transplant rejection rate and severity after endothelial
thickening, descemet’s membrane folds, sub epithelial bullae and keratoplasty. Cornea. In press.
blurred vision. Where treatment for a rejection episode is 19. Morrison DA, Fahy GT, Brown LJ. Unsuspected infections
ineffective and the graft fails, there is no role for ongoing crystalline keratopathy masquerading as corneal graft rejection.
corticosteroids and they should be ceased. Br J Ophthalmol 1997;81:608.
127
17
Section III: Penetrating Keratoplasty: Management of Complications

Corneal Graft Astigmatism


Jacqueline Beltz, Vishal Jhanji, Laurence Sullivan, Rasik B Vajpayee

Penetrating Keratoplasty (PKP) may be performed for optical, Donor


therapeutic, tectonic, diagnostic, or cosmetic indications. Final • Size
clarity of the donor and refractive error, along with other optical • Thickness
considerations, may limit the visual outcome. Astigmatism of • Pre-existing astigmatism
greater than 5D has been found to reduce the uncorrected visual
acuity in up to 21 percent of cases of PKP.1 Modern techniques Intraoperative Factors
are allowing the corneal surgeon to successfully reduce this
• Wound edge profile
percentage. Corneal graft astigmatism may be regular or
• Trephination size
irregular, and management options will vary according to this • Tissue distribution
(Fig. 17.1).
• Suture related factors
• Other factors
CAUSES
Wound Edge Profile and Trephination Shape
Astigmatism following PKP may be due to a complex interaction
of one or more of the following factors: The use of lid specula, superior rectus suture, and sutured ring
supports for the globe, may all induce distortion of the host
Preoperative Factors cornea during trephination of the wound. This may induce
noncircular trephination or uneven wound profile.
Host
Tilting or movement of the host trephine blade during
• Ectasia/Other causes of thinning trephination may induce an elliptical rather than a circular wound.
• Scarring This may largely be overcome by the use of a suction trephine
• Vascularization system, such as the Hessberg-Barron, Hanna, or Krumeich.

Tissue Distribution
Uneven circumferential placement of the cardinal sutures will
lead to distortion of the graft. The second cardinal suture is
critical for determining tissue distribution, and extra care should
be taken to make sure all 4 cardinal sutures are perfect, as it is
difficult to redistribute the tissue later on.
Overriding of the donor over the host, due to unequal relative
depths of suture placement, or inequality in the thicknesses of
the donor and host will lead to unpredictable astigmatic outcome.
Larger donor size (> 7.50 mm) will induce less astigmatism
than smaller donor size, as any irregularity induced by suture
tension will be further away from the visual axis.
A mismatch between the donor and host size may lead to
distortion of the graft surface. Most surgeons oversize the donor
Figure 17.1: Corneal graft 4 weeks postoperatively. A 24-bite
button with respect to the host bed. Usually this oversizing is
continuous running 10/0 nylon suture is in situ by 0.25 to 0.5 mm.

128
The diameter of the donor button is usually equivalent to
the trephine size, whilst the host wound is usually slightly larger,
especially posteriorly. Tissue is drawn up into the barrel of the
trephine during trephination. This leads to a mushroom-top to
the donor, and undercutting of the host bed. The resulting
mismatch of the donor and host profiles may lead to posterior
wound gape, and distortion of the graft-host junction as sutures

Chapter 17: Corneal Graft Astigmatism


need to be tightened excessively to maintain a water-tight wound
edge. Techniques to overcome these problems include; partial-
thickness host trephination, with completion by blade or scissors
to produce a straight wound edge, deep sutures (95% depth),
and slight oversizing of the donor (by 0.25 to 0.5 mm).

Wound Profile Asymmetry


It is important to attempt to produce donor and host wound edges
with maximum congruence. Any departure from congruence has
the potential to induce distortion of the graft-host junction and Figure 17.2A: Donor trephination
increase astigmatism (Figs 17.2A to C).

Other Suture Related Factors


Variation in suture tension around the circumference of the graft
is one of the most important factors when considering astigmatic
outcome. A tight suture will induce focal steepening in the axis
of the suture, and may also induce wound gape 90 degrees away
from the suture, necessitating another tight suture to gain
apposition of the wound edges. Loose sutures are associated with
flattening in their meridia.
Differences between suture depth in the graft versus the host
may cause sectoral override of the graft over the host, and
subsequent flattening in that axis. As a general rule, suture depth
should be approximately 95% in both the graft and the host.
Some consideration must be given to relative changes in tissue
thickness postoperatively, particularly if there is edema of the
donor or host tissue. Figure 17.2B: Host trephination (full thickness)
Longer suture bites help to reduce astigmatic outcome as they
spread the tension over a larger proportion of the graft edge,
and therefore minimize the focal effects of each suture.

Other Factors
Tilted intraocular lenses, or pre-existing toric intraocular lenses
will induce unpredictable levels of astigmatism, and replacement Figure 17.2C: Donor button sited in the host bed
should be considered at the time of PKP in these patients.
Scleral-sutured posterior chamber intraocular lenses may single running, and combined interrupted and running suturing
distort the globe, also resulting in unpredictable astigmatic techniques provide comparable astigmatic outcomes, as long as
outcome. topography guided suture adjustment or removal are performed
during the postoperative period.2 For these reasons, we believe
SURGICAL TECHNIQUES FOR THE PREVENTION that suture technique may be left for each individual corneal
OF POST PKP ASTIGMATISM surgeon to consider, taking into account the risk profile of each
case.
Suturing Techniques
The aim of suturing a corneal graft is to obtain a watertight seal Continuous Sutures
with equal suture tension through 360 degrees, without inducing Some surgeons prefer a continuous suture technique, as they
distortion of the donor. It is now well-recognized that interrupted, believe this may distribute centrifugal forces more evenly around
129
Section III: Penetrating Keratoplasty: Management of Complications

Figure 17.3: Tomey TMS topography (computerised videokeratography) map of the corneal graft in Figures 17.1 and 17.4, 4 weeks
post -PK. The axis of astigmatism is at approximately 105°. However, the astigmatism is being “driven” by the steepening at
285° (the red area on the map). Arrows indicate the direction of manipulation of the suture (see above)

the circumference of the graft. Intraoperative suture adjustment Cheese-wiring or breakage of sutures may allow unopposed
using quantitative or qualitative keratoscopy is recommended suture tension from another part of the graft to distort the donor,
to minimize induced astigmatism, and some authors advocate again leading to poor astigmatic outcome.
the use of intraoperative topography.3
Continuous suture should be avoided for any high-risk case, Assessment of Post PKP Astigmatism
such as those for therapeutic or tectonic indications, as a broken
Often it is possible to detect tight sutures, and even the flat and
suture will not easily be able to be replaced.
steep axes of a graft at the slit-lamp. Manifest refraction,
retinoscopy, keratometry, placido ring keratoscopy, and
Interrupted Sutures computerized videokeratoscopy (CVK, corneal topography) are
Interrupted sutures should be of uniform length, and uniform all valuable techniques for the assessment of post PKP
tension. If one suture is tight it will cause steepening of the graft astigmatism.4
in the axis of the tight suture, with resulting astigmatism. Tight Placido ring keratoscopy is a qualitative measure of
or loose sutures should be replaced intraoperatively. One astigmatism. An elliptical reflex of the projected concentric
advantage of suturing a graft with interrupted sutures, particularly circular rings may be seen. The short axis of the ellipse indicates
a high-risk graft, is that suture complications, such as broken or the steep axis of the corneal astigmatism. Keratoscopy
loose sutures, may easily be addressed by replacing just the observations that indicate tight sutures include; peripheral
sutures involved, rather than by needing to re-suture the whole indentation of the keratoscope rings, individual keratoscope ring
graft. images between tight sutures, and decentration of the corneal
apex away from a tight suture.
CVK uses the same principles to give a quantitative
Postoperative Factors
assessment of astigmatism. It provides more detailed information,
Differential healing around the circumference of the graft will indicating the axis and magnitude of astigmatism, and also often
affect the final astigmatic outcome. This is particularly important indicating which interrupted suture, or sector of a continuous
in the case of sectoral vascularization or pathology. suture, is “driving” the astigmatism (Fig. 17.3).

130
MANAGEMENT OF POST PKP ASTIGMATISM Flow Chart 17.1: Management of Post PKP Astigmatism
(Flow Chart 17.1)

Nonsurgical Management of Post PKP Astigmatism

Spectacles and Contact Lenses


Spectacle correction of astigmatism is likely to be well-tolerated

Chapter 17: Corneal Graft Astigmatism


up to approximately 4 dioptres. Patients with pre-existing high
levels of astigmatism, particularly keratoconic patients, will often
tolerate a higher degree of spectacle correction. Above this level,
rigid gas-permeable contact lenses may be necessary for
satisfactory correction. Reverse-geometry (oblate) RGP lenses
may be necessary to ensure a satisfactory fit. Hard contact lens
fitting post keratoplasty is covered in more detail elsewhere in
this book.

Selective Suture Removal


Selective suture removal is a valuable technique, but is only
possible if interrupted sutures have been used. This may be
performed as early as day 1 postoperatively, particularly if a tight
suture is causing other problems, such as a wound leak. More
commonly, selective suture removal would not be considered
until 6 weeks postoperatively. The tight suture may be cut using
a 25 or 27 gauge needle at the slit lamp, and removed using
forceps under topical anesthetic. Selective suture removal should
be assessed by serial topography before and after the removal
of each suture, to properly assess and record the effects of each
intervention. Prophylactic anti-rejection and antibiotic therapy
is mandatory for at least a week following any suture
manipulations.

Adjustment of Continuous Suture


This may be considered between 3 and 6 weeks postoperatively, Figure 17.4A: Tying forceps are grasping the suture over the
when the corneal topography is relatively stable, but firm healing graft-host junction. The suture is “wiggled” tangentially to the graft-
of the wound is yet to occur. It may be performed at the slit- host junction to free it from the epithelium. Then the suture is
lamp or in the operating theatre. sequentially fed from the flat to the steep meridia

Requirements
• At least 4 diopters of astigmatism
• CVK/topography/keratoscopy/keratometry
• Topical anesthetic
• Slit-lamp ± lid speculum
• Suture-tying forceps.
Technique
• Instill topical anesthetic and insert lid speculum
• Break the epithelium and mobilize the suture with the forceps
at the graft/host junction around the entire circumference of
the graft (Figs 17.4A and B)
• Sequentially feed the suture around from the flat (blue) to
the steep (red) meridia (Fig. 17.5)
• Reassess and redo if necessary
• Aim for 1-2 D of overcorrection Figure 17.4B: Post-adjustment: fluorescein staining at the graft-
• Be prepared to re-tie or re-suture if the suture breaks host junction indicating where the suture has been grasped for
• Prescribe topical antibiotic and topical steroid for one week. adjustment
131
Section III: Penetrating Keratoplasty: Management of Complications

Figure 17.6: Astigmatic keratotomy for post-PK astigmatism

Figure 17.5: Difference CVK map showing topography before Manual Astigmatic Keratotomy (AK): Manual AK may be
and after suture adjustment. The suture was adjusted from the performed under the operating microscope or at the slit-lamp.
horizontal meridia towards the vertical meridia. The astigmatism
has changed (decreased) by approximately 8 diopters Requirements
• At least 4 diopters of astigmatism
• CVK/topography/keratoscopy/keratometry
• Topical anesthetic
There is little doubt that suture manipulation is effective in
• Operating microscope or slit lamp
ameliorating “suture-in” astigmatism and some evidence can lead
• Lid speculum
to a decrease in astigmatism, which may persist after suture • 12- or 16-spoke radial keratotomy corneal marker
removal.5,6
• Ultrasonic pachymeter
• Micrometer diamond knife
Surgical Management of Post PKP Astigmatism
Technique
Surgical correction of corneal astigmatism after suture removal
• Perform pachymetry 1mm inside graft-host junction at the
is achieved either by relaxation (to flatten the steep meridian)
steep axis of the cornea
or compression (to steepen the flat meridian) of the donor tissue.
• Set depth of micrometer diamond blade to 60-75% of the
A steep meridian may be flattened with a relaxing incision
thinnest pachymetry reading
(e.g. arcuate keratotomy). On the other hand, a flat meridian may
• Incise a 60° of arc, with the blade perpendicular to the graft
be steepened with compression sutures, wedge excision or both.
surface, and 1mm inside the graft-host junction.
Once an initial incision has been made, the astigmatism
Astigmatic Keratotomy (AK) – Manual and Femtosecond
should be reassessed, as the effect is unpredictable. A second
Astigmatic Keratotomy, or partial thickness incisions within the incision at 180° from the initial incision is sometimes required.
steep axis of the graft, the host, or the graft-host junction, may This may be performed immediately, although most surgeons
be considered once all sutures have been removed, and the would wait approximately one week to assess the full effect of
refraction and topography have stabilized (Fig. 17.6). Incisions the initial incision. If further astigmatic correction is required,
within the wound run the risk of wound dehiscence, and incisions the initial incisions may be deepened or extended, or additional
in the donor are performed more frequently. Even in the age of incisions performed at a smaller size.
refractive treatments such as LASIK, astigmatic keratotomy has Some authors have found improved, more predictable
been found to be a useful and safe technique for the management outcomes by employing the use of a Hanna arcitome. 10
of post PKP astigmatism.7 Compression sutures across the graft-host junction at 90° to the
AK surgery does not reduce the spherical equivalent incisions are sometimes used to augment the effect, and may be
refraction of a case, due to the fact that flattening of the steep selectively removed over the weeks following surgery to titrate
axis is most likely accompanied by a steepening of the flat axis the effect.11
at 90° to the original effect.7,8,9 If a significant myopic SEQ is Prophylactic anti-rejection and antibiotic therapy is
present, a refractive laser procedure, or AK followed by planned mandatory for at least a week following AK and sometimes
refractive laser procedure, may be more appropriate. longer, particularly if there is some wound gape at the incision

132
sites. Viscous lubricants, such as carbomer gel, are also useful Wedge Excision – Manual and Femtosecond-assisted
postoperatively, until the epithelium heals over the AK incision.
It is possible to treat extreme amounts of post PKP astigmatism
Femtosecond Assisted Astigmatic Keratotomy (AK): by means of a “wedge excision”.15 Wedge excision would be
Femtosecond laser has dramatically improved the precision of expected to correct a higher degree of astigmatism than AK.16,17
many corneal surgeries. Femtosecond works via photo-disruption Wedge excision was first published by Troutman in 1973,18
by ultrashort laser pulses, creating tiny cavitation bubbles in although this treatment would now be considered relatively rare.
precisely predicted areas of the cornea, providing perfectly In this technique, an arcuate wedge of graft tissue is excised

Chapter 17: Corneal Graft Astigmatism


accurate corneal incisions with predicted size, shape, depth, and from the donor margin in the flat axis. Excision of a 1mm wedge
location.12 An early trial evaluating the clinical benefit of of tissue is said to correct approximately 8D of astigmatism. The
managing post PKP astigmatism by femtosecond laser assisted disadvantages of this technique are the slow recovery of visual
arcuate keratotomy in 12 eyes has proved successful.13 Nubile acuity due to the need to leave the sutures in situ for some months
et al worked with the idea that femtosecond technology provides postoperatively, and the variable and unpredictable astigmatic
the possibility of precise creation of AKs of predicted shape, effect.
length, radius and depth, with minimal damage to surrounding Manual wedge excision
tissues.13 They used paired femtosecond assisted AKs, located Manual wedge excision should be performed under the operating
just inside the peripheral margin of the donor lenticule, at a depth microscope. Paracentesis of the anterior chamber may help to
of 90% of local stromal thickness. They found that mean decompress the wound and facilitate suture placement across the
subjective astigmatism decreased from 7.16 +/– 3.07D to wedge. Wedge excision must be performed very carefully to
2.23 +/– 1.55D at one month after AK surgery, without significant avoid inadvertent corneal perforation.
regression by the end of 6 months follow up.13 The wedge is achieved by freshening the graft host junction
Another group, Kymionis et al,14 report on a single case of with a 15° blade, almost down to the descemet membrane, and
reduction of irregular, non-orthogonal post PKP astigmatism by then a wedge of the donor tissue may be excised and the wound
femtosecond assisted AK. re-sutured, causing steepening at this location.
Final accuracy, as well as optimal size, location, depth, and
Femtosecond assisted wedge excision
radius, are yet to be confirmed for femtosecond assisted AK, Femtosecond technology has been reported as a successful
and further investigation is still required, particularly in the form method by which to create intersecting incisions in a wedge
of prospective, randomized controlled trials, before the final shape.15,19 Ghanem and Azar19 assessed feasibility in an animal
benefit of this treatment is really known. model prior to performing and publishing results of their
technique for a patient with high (20D) astigmatism. They
Compression Sutures achieved good results in the case, and suggest more controlled
Compression sutures may be placed across the graft-host junction and accurate results when wedge excision is created in this
to steepen the flat meridian. The sutures should be tied tightly, manner. The results of this technique have not been widely
as slight over correction is desirable in the early postoperative duplicated.
period.
Refractive Laser Surgery

Requirements As refractive treatments improve for the treatment of primary


ametropia, they are also becoming successful for the treatment
• At least 3-4 diopters of astigmatism of post PKP astigmatism. As with most astigmatic interventions
• Stable refraction post PKP, it is important to wait for at least one year post PKP,
• CVK/topography/keratoscopy and at least 3 months after last suture removal. Surface refractive
• Operating microscope treatments are most useful in the situation of combined myopia
• 10-0 monofilament nylon suture and astigmatism following grafting, where there is a residual
• Surgical instruments for suturing unwanted myopic spherical equivalent.
The flatter meridian is determined by topographic evaluation. Surface photorefractive keratotomy (PRK) has been reported
Under sterile conditions, using the operating microscope, 10-0 to cause a marked scarring response when performed for post
nylon sutures are placed in the flatter meridian at the graft-host PKP astigmatism, and is not recommended on it’s own.20,21 Some
junction. Alternate 9-0 and 10-0 nylon sutures may accentuate authors have had success with PRK combined with topical
the effect. The effect of compression sutures is titrated by mitomycin C (MMC).22,23 There are some reports of success of
subsequent keratographic assessment. The sutures may be left PRK with MMC post PKP.24
in place long term, or removed selectively depending upon Laser in situ keratomileusis (LASIK) has been reported to
residual astigmatism. Prophylactic anti-rejection and antibiotic be effective in reducing astigmatism and myopia following PKP
therapy is continued for at least a week. without regression.24,25

133
It is recommended by some to stage the LASIK 4. Rowsey JJ, Fowler WC, Terry MA, Scoper SV. Use of
procedure.26,27 That is, to perform the microkeratome cut, and keratoscopy, slit-lamp biomicroscopy, and retinoscopy in the
to wait 4-6 weeks for astigmatism to stabilize. Frequently, there management of astigmatism after penetrating keratoplasty. Refract
Corneal Surg 1991;7:33-41.
will be a significant change in refraction simply with the cutting
5. Chell PB, Hope-Ross MW, Shah P, McDonnell PJ. Long-term
of the LASIK flap, and the subsequent laser treatment will have
follow-up of a single continuous adjustable suture in penetrating
to be modified. keratoplasty. Eye 1996;10:133-37.
LASIK has not been found to hasten endothelial cell loss 6. Hirst LW, McCoombes JA, Reedy M. Postoperative suture
Section III: Penetrating Keratoplasty: Management of Complications

post PKP. 25 LASIK may be combined with astigmatic manipulation for control of corneal graft astigmatism. Aust N Z
keratotomy in the stromal bed in cases of very high astigmatism, J Ophthalmol 1998;26:3,211-14.
or in cases where inadequate tissue is available for a full 7. Poole TRG, Ficker LA. Astigmatic keratotomy for post-
ablation.28 Prophylactic anti-rejection and antibiotic therapy is keratoplasty astigmatism. J Cataract Refract Surg 2006;32:
mandatory for at least a week following LASIK, as with any 1175-79.
8. Hjortdal JO , Ehlers N. Transverse keratotomy in post penetrating
manipulations of the corneal graft.
keratoplasty astigmatism. Acta Ophthalmol Scand 1998;76:
138-41.
Cataract Extraction
9. Cohen KL, Tripoli NK, Noecker RJ. Prospective analysis of
Cataract extraction post PKP may be considered a possibility photokeratoscopy for AK to reduce post PKP astigmatism. Refract
for the management of post PKP astigmatism. Intraocular lens Corneal Surg 1989;5:388-93.
technology continues to improve at an astounding rate, and the 10. Hoffart L, Touzeau O, orderie V, Laroch L, Mechanized astigmatic
arcuate keratotomy with the Hanna arcitome for astigmatism after
options for post PKP lens implantation consequently are broad.
penetrating keratoplasty. J Cataract Refract Surg 2007;33:
Lens implants allow for the correction of a high degree of 862-68.
ametropia, as well as almost any degree of astigmatism. 11. Jacobi PC, Hartmann C, Severin M, Bartz-Schmidt KU. Relaxing
It is generally not recommended to implant a toric intraocular incisions with compression sutures for control of astigmatism after
lens at the time of concurrent corneal transplantation and cataract penetrating keratoplasty. Graefes Arch Clin Exp Ophthalmol
extraction procedure, as the astigmatic outcome would be 1994;232:527-32.
impossible to predict. If a triple procedure is planned, then a 12. Mian SI, Shtein RM. Femtosecond laser-assisted corneal surgery.
spherical lens should be used at the time. A toric lens, whether Curr Opin Ophthalmol 2007;18:295-99.
in-the-bag or a sulcus placed piggyback lens, may be an excellent 13. Nubile M, Carpineto P, Lanzini M, et al. Femtosecond laser
arcuate keratotomy for the correction of high astigmatism after
option for correction of post PKP astigmatism, but should not
keratoplasty. Ophthalmology 2009;116:1083-92.
be considered until all sutures are removed, and refraction is
14. Kymionis GD, Yoo SH, Ide T, Culbertson WW. Femtosecond-
stable (generally at least 3 months after removal of last suture). assisted astigmatic keratotomy for post-keratoplasty irregular
The potential problem arising from graft failure and consequent astigmatism. J Cataract Refract Surg 2009;35:11-13.
redo PKP and different astigmatic outcome must be mentioned 15. Ezra DG, Hay-Smith G, Mearza A, Falcon MG. Corneal wedge
in the consent process, as removal of the toric lens may, in those excision in the treatment of high astigmatism after penetrating
cases, be required. keratoplasty. Cornea 2007;26:819-25.
16. Krachmer JH, Fenzl RE. Surgical correction of high post
keratoplasty astigmatism. Arch Ophthalmol 1980;98:1400-02.
CONCLUSION
17. Rowsey JJ. Current concepts in astigmatism surgery. J Refract
Management of astigmatism is an essential part of the visual Surg 1986;2:85-94.
18. Troutman RC. Microsurgical control of corneal astigmatism in
rehabilitation of patients following corneal transplantation.
cataract and keratoplasty. Trans Am Acad Ophthalmol Otolaryngol
Management begins with preoperative assessment, and continues
1973:77:563-72.
through surgical techniques and postoperative management of 19. Ghanem RC, Azar DT. Femtosecond-laser arcuate wedge-shaped
the graft and its sutures. Modern techniques are continuing to resection to correct high residual astigmatism after penetrating
advance, allowing the corneal surgeon to offer PKP as a viable keratoplasty. J Cataract Refract Surg 2006;32:1145-49. (Ghanem
refractive procedure for patients with corneal disease. and Azar JCRS 2006)
20. Danjoux JP, Fraenkel G, Wai D, Conway M, Eckstein R, Lawless
M. Corneal scarring and irregular astigmatism following refractive
REFERENCES
surgery in a corneal transplant.. Aust N Z J Ophthalmol
1. Eisner G. Eye Surgery: An Introduction to Operative Techniques. 1998;26:47-49.
(2nd Edition) Springer–Verlag. Berlin 1990. 21. Chan WK, Hunt KE, Glasgow BJ, Mondino BJ Corneal scarring
2. Javadi MA, Naderi M, Zare M, et al. Comparison of the effect of after photorefractive keratectomy in a penetrating keratoplasty Am
three suturing techniques on Postkeratoplasty astigmatism in J Ophthalmol 1996;121:570-1.
keratoconus. Cornea 2006;25:1029-33. 22. Carones F, Vigo L, Scandole E, Vacchini L. Evaluation of the
3. Vinciguerra P, Epstein D, Albe E, et al. Corneal topography- prophylactic use of mitomycin-C to inhiit haze formation after
guided penetrating keratoplasty and suture adjustment. New photorefractive keratectomy. J Cataract Refract Surg 2002;
approach for astigmatism control. Cornea 2007;26:675-82. 28:2088-95.
134
23. Gambato C, Ghirlando A, Moretto E, et al. Mitomycin C 26. Alio JL, Javaloy J, Osman AA, et al. Laser in situ keratomileusis
modulation of corneal wound healing after photorefractive to correct post-keratoplasty astigmatism: 1-step versus 2-step
keratectomy in highly myopic eyes. Ophthalmology procedure. J Cataract Refract Surg 2004:30:2303-10.
2005;112:208-19. 27. Vajpayee RB, Dada T. LASIK after penetrating keratoplasty.
24. Chang DH, and Hardten DR. Refractive surgery after corneal Letter to the Editor. Ophthalmology 2000;107:1801-02.
28. Donnenfeld ED, Kornstein HS, Amin A, Speaker MD, Seedor
transplantation. Curr Opin Ophthalmol 2005;16:251-55.
JA, Sforza PD, Landrio LM, Perry HD Laser in situ
25. Barraquer C, Rodriquez-Barraquer T. Five-year results of laser
keratomileusis for correction of myopia and astigmatism after
in-situ keratomileusis (LASIK) after penetrating keratoplasty. penetrating keratoplasty. Ophthalmology 1999;106:1966-74;

Chapter 17: Corneal Graft Astigmatism


Cornea 2004;23:243-48. discussion 1974-5.

135
SECTION IV: Lamellar Keratoplasty
A: Anterior Lamellar Keratoplasty Techniques

18

Chapter 18: Surgical Instruments for Lamellar Keratoplasty


Surgical Instruments for
Lamellar Keratoplasty
Namrata Sharma, Prakash Chand Agarwal, Rasik B Vajpayee

INTRODUCTION There are other methods also described to harvest the partial
thickness donor lenticule. A simple technique harvesting the
The instruments required for lamellar keratoplasty are used to
donor lamellar lenticule from the corneoscleral rim using a three
dissect the donor cornea as well as the recipient bed.
point fixation has been used.1 Wong et al2 described another
Instruments for Donor Cornea Dissection method of obtaining the donor lamellar tissue. Two layers of
sterile fine-weave fabric were wrapped tightly around a glass
The instruments used to dissect donor cornea include various orbital implant. The corneoscleral button was sutured firmly at
artificial anterior chambers and clamps. Herein, the donor its scleral rim onto the fabric. The lamellar graft was then
corneo-scleral rim is fixed in the artificial anterior chamber (Fig. dissected in the regular fashion. During the dissection, the donor
18.1A) or in the King’s Clamp (Fig. 18.1B).
cornea and its supporting fabric-covered glass ball were easily
Trephines and lamellar dissectors can then be used to dissect
handled, and there was minimal risk of perforation of the
the lamellar disk.
posterior lamella of the donor cornea.

Lamellar Dissectors
In lamellar keratoplasty, a fine thin blade is necessary to split
the stroma in the correct plane. The instrument must be
lightweight, have a fine edge and have a curve that conforms to
the curvature of the cornea with a handle to allow for firm grip
for rotation. Various types of lamellar dissectors have been
designed according to different functions.
• Tooke’s knife—The pocket for the initiation of the lamellar
dissection may be performed with a Tooke’s knife. Its overall
length is 119 mm and it has a flat serrated handle. It has a 3
mm × 18 mm smooth blade at one end, which can be inserted
intralamellarly to create the pocket.
Figure 18.1A: Barron artificial anterior chamber • Paufique’s knife—It has a double-edged 1.5 × 3 mm sharp
(Courtesy: Katena Products)
angled blade simultaneously helps in outlining the graft,
making the pocket and in dissecting the lamellar planes
(Fig. 18.2).

Figure 18.1B: King’s clamp Figure 18.2: Paufique’s lamellar dissector


137
• Desmarre’s lamellar dissector—It is used in the open type 350 micrometer). The Moria ALTK artificial anterior chamber
of dissection, which has a curve in its vertical meridian and does require a donor scleral rim that is symmetrically greater
it is used to sweep across the fibers in a cutting and teasing than 16 mm (max 19 mm) in diameter to provide proper vacuum
motion (Fig. 18.3). A duckbill shape lamellar dissector is during the microkeratome pass. The surgical time is greatly
used for closed type of dissection, which is curved in the reduced as compared to manual dissection technique.
horizontal dimension.
Section IV: Lamellar Keratoplasty

Figure 18.3: Desmarre’s lamellar dissector

• Gill’s lamellar dissector—It has a 3 mm wide blade which


can be either straight or curved (Fig. 18.4).

Figure 18.6: Automated lamellar therapeutic


keratoplasty machine (Courtesy: Moria SA France)

Another machine available is the Amadeus II microkeratome


with an artificial anterior chamber (AAC; Ziemer Group). The
Figure 18.4: Gill’s straight lamellar dissector
assembly unit comes equipped with four interchangeable suction
units (with diameters of 8.5, 9.0, 9.5 and 10.0 mm) and a choice
• Guarded diamond knife—The micrometer adjusted,
of five blade holders (for a flap thickness of 200, 250, 350, 400
guarded diamond knife has made free hand, irregularly
or 450 µm). The AAC body has an inset type in which to place
shaped lamellar grafts easier and safer to accomplish.
the donor cornea. To obtain the ideal pressure inside the AAC,
• Cresent knife—This is another useful instrument for the
we create a direct link between the inset type and a
lamellar dissection. It has a 2.0 mm blade (Fig. 18.5).
phacoemulsification machine (Fig. 18.7). Once assembled, the
motor unit should cover the 16 mm diameter of the scleral rim.
This closing mechanism assures a watertight anterior chamber
— comparable to a human eye — for a stretched donor cornea;
the pressure inside the chamber is checked with a 65 mmHg
tonometer (Barraquer). The microkeratome cuts the button into
two parts. The posterior button can be used for DSAEK.

Figure 18.5: Crescent knife

With the continued development of lamellar keratoplasty


newer instruments are being designed to make the surgical
procedure easy and safe. The pioneers of DSAEK have
developed various instruments which have been rightly named
after them. With various available instruments lamellar surgeries
for different corneal pathology can be performed.

AUTOMATED LAMELLAR THERAPEUTIC


KERATOPLASTY MACHINE

We use the Moria Automated Lamellar Therapeutic Keratectomy


Figure 18.7: Amadeus II microkeratome
microkeratome system (Fig. 18.6, ALTK; Moria, Antony,
France). It utilizes the CBm microkeratome and an artificial
DSAEK SPATULA (STRIPPER)
chamber which is manually driven by the surgeon. Multiple
microkeratome heads may be used to achieve dissection of The DSAEK spatula is designed to strip the recipient’s
various thicknesses ranging from 130 to 350 (130, 150, 250, 300, Descemet’s membrane during the DSAEK procedure. The
138
DSAEK strippers (Fig. 18.8) are available in 45 and 90 degrees
angled models, in both irrigating and non-irrigating versions. The
angled tips facilitate the efficient dissection and removal of
Descemet’s membrane without inadvertent damage to the stroma.
The strippers are made of surgical steel.

Chapter 18: Surgical Instruments for Lamellar Keratoplasty


Figure 18.8: DSAEK spatula (stripper)

BUSIN GLIDE

The insertion can be done by the pull through technique using a


specially designed glide by called the Busin Glide (Fig. 18.9).
It allows insertion of the taco through 3.2 mm incision. It Figure 18.12: One corneal punch
facilitates the unfolding of the graft and simplifies centration of (Courtesy: Moria SA France)
the donor button in the anterior chamber. It helps to minimize
FORCEPS
intraoperative manipulation of the graft and the possibility of
endothelial loss. The tips of the forceps remain separated when the handles are
closed, to minimize injury to the folded donor tissue. The folded
graft is then easily released into the anterior chamber
(Fig. 18.13).
Figure 18.9: Busin glide (Courtesy: Moria SA France)

DSAEK BUSIN FORCEPS

It is a micro-incision forceps with 20 G diameter and distal action


(Fig. 18.10). It is designed to position the graft in the glide and
Figure 18.13: Forceps for donor insertion
to pull it from the glide into the anterior chamber. Its tips have
(Courtesy: Moria SA France)
been designed specifically to contact the periphery of the graft
such that the endothelial and the stromal surfaces remain CORNEAL MARKER
untouched in the optical zone. The size of the tips is perfectly
adapted to the glide to prevent endothelial cell damage during An 8.0 – 9.0 mm marker is available to mark the area of the
the pull-through maneuver (Fig. 18.11). recipient’s cornea to be stripped. The anterior surface can be
marked with gentian violet blue or surgical marker pen
(Fig. 18.14).

Figure 18.10: DSAEK busin forceps


(Courtesy: Moria SA France)
Figure 18.14: Corneal marker
(Courtesy: Moria SA France)

DSAEK ANTERIOR CHAMBER MAINTAINER


DSAEK Anterior Chamber Maintainer has a 20 G threaded tip,
supplied with silicone tubing and adaptor (Fig. 18.15).

Figure 18.11: Pulling the graft with DSAEK busin forceps


(Courtesy: Moria SA France) Figure 18.15: DSAEK anterior chamber maintainer
(Courtesy: Moria SA France)
ONE CORNEAL PUNCH
REFERENCES
A new corneal punch (Fig. 18.12) is available which is disposable
1. Vrabec M, Jordan J, Lawlor P. Lamellar keratoplasty performed
and has ultra-sharp razor trephine for straight walled cuts.
with a corneal scleral button. Ophthalmic Surg 1994;25:389-91.
The punch is a two piece device with a pre-load, recessed 2. Wong D, Chan W, Tan D. Harvesting a lamellar graft from a
blade. It is packaged sterile for single use in sizes from 8.0 to corneoscleral button: A new technique. Am J Ophthalmol
9.0 mm. 1997;123:688-89.
139
19
Section IV: Lamellar Keratoplasty

Epikeratoplasty
Namrata Sharma, M Vanathi, Geetha Srinivasan

The placement of a human donor lenticule or synthetic material procedure in preserving ocular structural integrity and can also
on the Bowman’s membrane in order to change the refractive aid in increasing visual acuity in patients with keratoglobus. It
power of the cornea is termed Epikeratoplasty. Werblin1 first is to be noted that epikeratoplasty in eyes with keratoglobus
described the concept of epikeratophakia in 1980. Kaufman and should be considered before corneal perforation, which may
Werblin2 developed epikeratophakia for the surgical correction result in loss of the eye.
of aphakia. Epikeratophakia differs from the Barraquer’s
technique as the refractive correction (donor lenticule) is placed SURGICAL TECHNIQUE
on the surface of the cornea. This “onlay lamellar keratoplasty”
The principle of epikeratoplasty technique involves placement
or “living contact lens” adheres to the Bowman’s membrane of
of a donor lenticule (homoplastic)/synthetic lenticule (alloplastic)
the host cornea. Studies were first conducted on non-human
with plano or refractive power on the surface of the Bowman’s
primate models and were later extended to human adult3 and
membrane to alter the anterior corneal curvature and the
pediatric aphakia,4 keratoconus5 and myopia.6
refractive power of the cornea or for tectonic purposes. The
Epikeratoplasty was a widely practiced lamellar refractive
lenticule edge is embedded and sutured into an annular
keratoplasty procedure for aphakia, 7,8 myopia 9 and
keratectomy/keratotomy in the host cornea. The host epithelium
keratoconus.10 However, problems of interface scarring and
grows over the donor lenticule and provides a smooth surface.
irregular astigmatism, predictability of results and decreased
best-corrected visual acuity dampened the initial enthusiasm for
Preparation of Recipient Cornea
the procedure. Epikeratoplasty still remains a surgical alternative
to penetrating keratoplasty in cases of keratoconus. De-epithelialization

INDICATIONS This can be done either with 4 percent cocaine soaked cellulose
sponge or a blunt spatula. We have used 4 percent xylocaine
Epikeratoplasty is performed for refractive and tectonic purposes.
soaked cellulose and have found it to be useful in de-
Epikeratoplasty has been used for the following indications.
epithelialization. Care is taken to avoid injuring the epithelium
• Aphakia7, 8,11 (children and adults)
peripheral to the proposed annular keratectomy and not to
• Myopia9,11
damage the Bowman’s membrane, to prevent subsequent stromal
• Keratoconus10-12
scarring.
• Terrien’s marginal degeneration13
• Pellucid marginal degeneration14 Annular Keratectomy
• Keratoglobus15,16
• Post-traumatic ectasia17 An annular keratectomy, which is 0.5 mm wide and 0.3 mm deep,
• Corneal melting.18 is made using two disposable trephines, 8 mm and 8.5 mm in
Although epikeratoplasty has been used for various diameter. If the diameter of the cone is very large, the trephines
indications, currently it is more commonly used for corneal to be used should be bigger, i.e. 8.5 mm or 9 mm in size.
ectasias due to keratoconus and trauma. Patients with spectacle Some surgeons do not make a keratectomy. Instead, they
corrected visual acuity of 6/60, with no apical scarring and create a simple keratotomy with a 8.5 mm trephine, followed
intolerant to contact lenses are suitable for epikeratoplasty. It is by a 1-3 mm lamellar dissection with a crescent knife, towards
not indicated in eyes with apical scarring or deep central scarring. the limbus. The incision should not be more than 0.3 mm deep,
In performing epikeratoplasty for keratoglobus, the donor as too deep an incision will cause excessive bending of the
corneoscleral button 1 mm larger than corneal diameter is to be lenticule after suturing and a regression effect with time. A
placed as an onlay graft. Epikeratoplasty is a safe and effective shallow incision permits the lenticule to function as a passive
140
overlay onto the host cornea with less mechanical effects in the in the recipient tissue (Figs 19.1 and 19.2). Equal tension of the
postoperative period. sutures and tucking of the edge of the lenticules should be
thoroughly checked. This helps the epithelium to grow over the
Procurement of the Donor Lenticules graft host junction effectively. Difficulty in placement of the
second cardinal suture may be a problem, sometimes. This can
A donor lenticule oversized by 0.5 mm to the annular
keratectomy is normally used. The donor lenticules used for be easily overcome by downwards pressure on the cone with a
vitreous sweep or an iris spatula by the assistant while the
epikeratoplasty can be obtained from Frozen lyophilized

Chapter 19: Epikeratoplasty


surgeon is tying the knot. A paracentesis may also help to soften
corneas or Manually dissected fresh corneas. The donor
lenticules are fashioned into a lens of required refractive power the globe and reduce the height of ectasia, thus enabling proper
suturing.
with an automated lathe. A corneal press19 was developed to
uniformly hydrate the donor lenticule before lathing in order to
Tectonic Epikeratoplasty
improve refractive results. These are then lyophilized20 and
preserved, frozen in sub-zero temperature, freeze-dried or preser- Tectonic epikeratoplasty (TEK)18 is a method in which a corneal
ved fresh21 in refrigerated tissue culture medium. The corneal button, preserved in glycerin is used as a seal over corneal
lenticule is rehydrated with balanced salt solution and gentamicin perforation. The graft is sutured to the recipient sclera, upon the
about 15 to 20 minutes before use. The disadvantage of use of sick melted cornea, with silk sutures, after 360 degree peritomy
frozen lyophilized corneas is the loss of keratocytes in the donor of the conjunctiva. The graft is left in place for a few weeks,
lenticule due to the freezing of the tissue, which renders the and by that time the cornea is completely healed.
keratocytes non-viable and subsequently delays epithelization.
The diameter and required power of the epikeratoplasty POSTOPERATIVE REGIMEN
lenticules is selected according to a nomogram that converts
This includes topical antibiotics such as 0.5 percent
spectacle power to power at corneal level. Refractive lenticules
chloramphenicol eyedrops and diluted steroids such as 1:10
thus fashioned are used for correction of refractive powers in
dexamethasone sodium phosphate eyedrops in a tapering dose
aphakia and myopia. However, for keratoconus plano lenses are
spread over 4 weeks. The operated eye should be patched until
used.
epithelization occurs. Selective suture removal may be done to
Manual Dissection of Donor Lenticule
We have used manually dissected donor lenticules from fresh
moist chamber stored eyes.22 This avoids loss of keratocytes in
the donor lenticule and leads to faster epithelialization and faster
recovery. The disadvantage in use of manully-dissected lenticule
is a shorter shelf life of moist chamber stored donor corneas.
The McCarey-Kaufman preserved corneoscleral rim is
placed in a King’s clamp over a wet gauze piece and tightly
clamped. A 9 mm Castroviejo’s trephine is set at a depth of
0.3 mm with the help of obturator and a 0.3 mm deep annular
cut is made. If the donor lenticule is harvested from the whole
globe, a Hessberg-Baron trephine may also be used to make the
keratotomy. A pocket is made at the incision’s site with a Figure 19.1: Traumatic corneal ectasia
Paufique’s knife and the closed technique of lamellar dissection
is used. Werblin et al have also advocated the creation of a
peripheral wing by dissecting the 0.2 mm annulus all around the
donor lenticules, so that it can fit into the peripheral superficial
keratectomy of the host bed.1,2 We trim the peripheral posterior
edge of the lenticule to create a peripheral wing which can be
effectively tucked into the keratectomy of the host bed.

Suturing
The edges of the lenticule or the wings of the lenticules are then
tucked into the peripheral annular lamellar dissection and sutured
with interrupted 10.0 monofilament nylon sutures. The bite on
the corneal side is about 0.5 mm and the host side is 1 mm. In
case of keratoconus, the sutures should be tight and applied with Figure 19.2: Postoperative epikeratoplasty in the same case
more tension, as this will flatten the cone. The knots are buried shown in Figure 19.1 141
control postoperative astigmatism, to prevent suture related
problems as loose vascularized sutures and suture abscesses.

ADVANTAGES AND DISADVANTAGES


Epikeratoplasty offers all the advantages of lamellar keratoplasty.
Epikeratoplasty does not require incision in the central host
cornea and is a relatively simple lamellar procedure, as
Section IV: Lamellar Keratoplasty

preparation of the host bed, is easy. Less astigmatism has also


been reported following epikeratoplasty. 17,22,23 Being an
extraocular surgical procedure, it avoids the potential vision
threatening complications of intraocular surgeries such as
glaucoma, wound dehiscence and endophthalmitis. Risk of
failure due to rejection episodes does not exist as the normal
Figure 19.3: Failed epikeratoplasty
host endothelium is retained. In the event of a complication, it
does not preclude or increase the risk of a future penetrating
Late complications include interface haze, epithelial
keratoplasty. The potential reversibility of the procedure permits
ingrowth, interface cysts28 and irregular astigmatism.
removal of the lenticule in case of postoperative complications.24
Interface haze is due to the combination of increased corneal
The disadvantages of epikeratoplasty procedure include poor
thickness, stress on the host endothelium, slow repopulation of
predictability in achieving emmetropia, poor quality of vision
the donor tissue with keratocytes and stromal irregularities
due to increased scatter of light and glare, and final visual
induced by tissue lathing and surgical procedure. Epithelial
outcome lesser than best corrected spectacle acuity. Further, it
Ingrowth29 and interface cyst formation between the lenticules
takes 6 to 16 months before optimal visual acuity is achieved.
and the recipient cornea, delays wound healing and contributes
This slow recovery of vision in cases, where preserved lenticules
to interface scarring. Interface haze gives rise to significant glare
is used may be unacceptable.
problems and reduces the quality of vision. Mild interface haze
COMPLICATIONS can be tackled with optical correction with contact lenses.
Significant haze necessitates surgical intervention in the form
Intraoperative Problems of replacement with a fresh donor lenticule, deep lamellar
Very few intraoperative complications are present, as this is keratectomy or penetrating keratoplasty.
mainly an extraocular procedure. Perforation during Irregular astigmatism30 may occur due to wrinkling of the
epikeratoplasty is rare, but has been reported.25 Bowman’s membrane from tight sutures, fractures and folds in
the Bowman’s membrane and steepening and ectasia of the
Postoperative Complications cornea. Selective suture removal during the postoperative period
These include the following: can help control and reduce irregular astigmatism.
Early postoperative complications include delayed Mooren’s Ulcer has also been described as a complication
epithelialization, dehiscence of the graft, microbial keratitis and following epikeratoplasty.31
kerotolysis of the lenticule. A relative hypesthesia has been observed in the
Persistent epithelial defect 7-13 is quite commonly epikeratoplasty lenticule as compared to the peripheral host
encountered following epikeratoplasty and has been attributed cornea, even 10 years after surgery.32
to the failure of the host epithelium to ascend over the sutured
Histopathological and Immunohistochemical
donor lenticules. These epithelial defects are encountered more
Changes in Epikeratoplasty Lenticules
when lyophilized and freeze dried donor lenticules are used as
compared to the fresh manually dissected lenticules, as the A study33 done to examine histopathological and immuno-
former has non-viable keratocytes which causes delayed histochemical changes in lenticules and host of corneal buttons
epithelization and the failure of epikeratoplasty (Fig. 19.3). These from patients who previously underwent epikeratoplasty for
defects should be treated with tear substitutes and bandage keratoconus found the keratoconus-like disruptions in the
contact lenses. Tarsorrhapy may be required in some cases. Bowman’s layer. Peripheral and posterior keratocyte
Persistent epithelial defect related problems lead to an overall repopulation of the lenticules was observed with the keratocyte
removal rate of 7.7 percent in major studies.7-12 Failure to re- repopulation in the anterior and midstromal regions of the
epithelize may lead to necrosis, infection and graft melting.26,27 lenticules being related to the time since epikeratoplasty. It is
Persistent epithelial defect can lead to stromal melting of therefore to be concluded that the epithelial cells and keratocytes
both the interfaces. In this event the lenticules has to be removed. that repopulated in the lenticules retain keratoconus-like
The stromal melt may be sterile27 or may have superadded biochemical abnormalities such as upregulation of Sp1 and
microbial keratitis. downregulation of alpha1-PI and alpha-2M.
142
OUTCOME: COMPARISON OF EPIKERATOPLASTY epikeratoplasty. Visual performance in epikeratoplasty procedure
AND PENETRATING KERATOPLASTY had the poorest results.
Lass et al40 report a reduction of the percentage of eyes with
Steinert and Wagoner 34 have compared the results of
corneal cylinder from 55 to 2 percent in the penetrating
epikeratoplasty (mean follow-up = 25 months; range, 19 to 31
keratoplasty group and from 36 to 0 percent in the
months) with penetrating keratoplasty for keratoconus (mean
epikeratoplasty group. Comparing baseline and final examination
follow-up = 33 months; range, 3 to 81 months) and indicate a
findings, they found, the change in the penetrating keratoplasty
similar level of postoperative spectacle visual acuity (20/32 vs

Chapter 19: Epikeratoplasty


group from 20/70 to 20/25 and the epikeratoplasty group from
20/27, respectively) and similar refractive and keratometric
20/40 to 20/30. Average keratometry decreased by 10.7 D for
results.
the former and 6.5 D for the latter.
Fronterre and Portesani35 in their comparison of epikerato-
plasty and penetrating keratoplasty for keratoconus observed that SYNTHETIC EPIKERATOPLASTY
the mean postoperative uncorrected visual acuity was 20/52 ±
0.25 with epikeratoplasty and a mean postoperative uncorrected With ongoing research in tissue adhesives and tissue growth
visual acuity was 20/63 ± 0.23 with penetrating keratoplasty in factors, the concept of a synthetic lenticule,41-46 which is
patients with keratoconus. In the epikeratoplasty group, astig- biocompatible with the host tissues, has been tried. This has the
matism (2.18 ± 1.48) and astigmatism reduction (– 4.16 ± 2.98) advantages of availability, stability and power design. However,
were comparable to the penetrating keratoplasty group the epithelialization is found to occur at a rate of 60 µm/hr and
(astigmatism; 3.16 ± 1.43 and astigmatism reduction; – 4.2 ± as the synthetic lenticule does not have a basement membrane
2.56). this delays epithelialization, which takes almost 14 days.
Waller et al36 in their analysis of long-term results of
epikeratoplasty for keratoconus patients with a mean follow-up Protein Coated Hydrogel
of 67 months (range = 35 to 101 months), found that each Epikeratoplasty Lenticules
maintained long-term stability of best corrected vision, refractive Chiron Vision investigated high water content hydrogels on
astigmatism, and keratometric astigmatism. The mean rabbit and cat eyes. They used surface coatings to enhance
uncorrected visual acuity improved from 20/660 to 20/134, epithelial cell migration and adhesion. The surface coatings were
whereas, the mean spectacle corrected acuity improved from collagen IV, collagen I, laminin and cell membrane components.
20/260 to 20/30. Refractive and keratometric astigmatism The edge of the synthetic epikeratoplasty lenticule (SEL) was
stabilized by 12 months (mean = 3.62 and 3.05 D, respectively), tucked in the edge of the trephine incision. The main problem
and decreased slightly during the longer period of follow-up was poor epithelial adhesion and random epithelial cell loss due
(mean = 2.94 and 2.17 D, respectively). to lack of permanent anchoring complexes.
We performed epikeratoplasty on 11 keratoconic corneas
using fresh or McCarey-Kaufman preserved, manually dissected Collagen Synthetic Epikeratoplasty Lenticules
donor lenticules and over a four-year follow-up found that 80
Collagen IV was co-polymerized with synthetic polymer
percent achieved a postoperative spectacle-corrected visual underwent biodegradation. Bovine type 1/3 collagen has been
acuity of 6/12 or better.22 Average postoperative keratometry was
tried has COL (collagen onlay). This was placed on the host
45.79 ± 2.07 D and a decrease of 4.60 ± 0.09 D was observed
tissue to mold and polymerize and stiffen to the consistency and
in refractive cylinder. Spherical equivalent showed a significant transparency of the hydrogel polymer. This allowed good
decrease in myopia of -4.35 ± 0.26 D. Mean time to stabilization
epithelial cell migration and adhesion. But the major
was 8 ± 2.3 weeks.
disadvantage was degradation with time.
Wagoner et al37 in a comparison of penetrating keratoplasty Future developments in tissue adhesives and growth factors
and epikeratoplasty for the surgical treatment of keratoconus
may cause a resurgence of this technique.
found that final median logMAR visual acuity for all patients,
irrespective of means of visual rehabilitation, was 0.30 (20/40) Things to Remember
for penetrating keratoplasty and 0.40 (20/50) for epikeratoplasty.
• Epikeratoplasty is onlay lamellar keratoplasty.
Goosey et al38 found the penetrating keratoplasty procedure
• Epikeratoplasty is mainly being used to treat corneal ectasias.
resulted in a higher percentage of eyes that had visual acuity of
• Epikeratoplasty is a reversible procedure.
20/20 than the epikeratoplasty. Both procedures resulted in
• Visual gain after epikeratoplasty is less than penetrating
significant corneal flattening, with the penetrating keratoplasty
keratoplasty.
group producing an average of 3 diopters more keratometric
• Persistent epithelial defect is a major complication.
reduction than the epikeratoplasty group one year
postoperatively.
REFERENCES
Carney and Lembach39 compared the visual performance of
keratoconus patients whose vision had been corrected with one 1. Werblin TP, Klyce SD. Epikeratophakia: the surgical correction
of the following: RGP lenses alone, penetrating keratoplasty or of aphakia: I. Lathing of corneal tissue. Curr Eye Res 1981;1:123.
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2. Werblin TP, Kaufman HE. Epikeratophakia: the surgical 27. Frangieh GT, Kenyon KR, Wagoner MD, Hanninen L, John T,
correction of aphakia: II. Preliminary results in non-human Steinert RF. Epithelial abnormalities and sterile ulceration of
primate model. Curr Eye Res 1981;1:131-37. epikeratoplasty grafts. Ophthalmology 1988;95:213-27.
3. Werblin TP, et al. Epikeratophakia: the surgical correction of 28. Zamir E, Solomon A. Interface corneal epithelial cyst following
aphakia: III. Preliminary results of a prospective clinical trial. epikeratoplasty. Arch Ophthalmol. 2003;121:1510.
Arch Ophthalmol 1981;99:1957-60. 29. Chen L, Chen J, Yang B, Liu Z, Feng C, Lin Y, Wang Z. [A
4. Morgan KS, et al. The use of epikeratophakia grafts in pediatric preliminary report of epikeratophakia for the treatment of Terrien’s
monocular aphakia. J Pediatr Ophthalmol Strabismus 1981;18:23- degeneration] Yan Ke Xue Bao. 1997;13:79-81.
Section IV: Lamellar Keratoplasty

29. 30. Lass JH, Stocker EG, Fritz ME, Collie DM. Epikeratoplasty. The
5. Kaufman HE, Werblin TP. Epikeratophakia for the treatment of surgical correction of aphakia, myopia, and keratoconus.
keratoconus. Am J Ophthalmol 1982;93:342-47. Ophthalmology 1987;94:912-25.
6. McDonald MB, et al. Epikeratophakia for myopia correction. 31. Teichmann KD. Mooren’s ulcer following epikeratoplasty for
Ophthalmology 1985;92:1417-22. keratoconus. Arch Ophthal 1998;116:1381-82.
7. McDonald MB, et al. The nationwide study of epikeratophakia 32. Kaminski SL, Biowski R, Lukas JR, Koyuncu D, Grabner G.
for aphakia in adults. Am J Ophthalmol 1987;103:358-65. Corneal sensitivity 10 years after epikeratoplasty. J Refract Surg.
8. Morgan KS, et al. The nationwide study of epikeratophakia for 2002;18:731-36.
aphakia in children. Am J Ophthalmol 1987;103:366-74. 33. Nakamura H, Riley F, Sakai H, Rademaker W, Yue BY, Edward
9. McDonald MB, et al. The nationwide study of epikeratophakia DP. Histopathological and immunohistochemical studies of
for myopia. Am J Ophthalmol 1987;103:375-83. lenticules after epikeratoplasty for keratoconus. Br J Ophthalmol.
10. McDonald MB, et al. Epikeratophakia for keratoconus. The 2005;89:841-6.
nationwide study. Arch Ophthalmol 1986;104:1294-1300. 34. Steinert RF, Wagoner MD. Long-term comparison of epikerato-
11. Wagoner MD, Steinert RF. Epikeratoplasty for adult and pediatric plasty and penetrating keratoplasty for keratoconus. Arch
aphakia, myopia, and keratoconus: the Massachusetts Eye and Ophthalmol 1988;106:493-96.
Ear Infirmary experience. Acta Ophthalmol Suppl 1989;192: 35. Fronterre A, Portesani GP. Comparison of epikeratoplasty and
38-46. penetrating keratoplasty for keratoconus. Refract Corneal Surg
12. Spitznas M, Eckert J, Frising M, Eter N. Long-term functional 1991;7:167-73.
and topographic results seven years after epikeratophakia for 36. Waller SG, Steinert RF, Wagoner MD. Long-term results of
keratoconus. Graefes Arch Clin Exp Ophthalmol 2002;240: epikeratoplasty for keratoconus. Cornea 1995;14:84-8.
639-43. 37. Wagoner MD, Smith SD, Rademaker WJ, Mahmood MA.
13. Chen L, Chen J, Yang B, Liu Z, Feng C, Lin Y, Wang Z. [A preli- Penetrating keratoplasty vs. epikeratoplasty for the surgical
minary report of epikeratophakia for the treatment of Terrien’s
treatment of keratoconus, J Refract Surg 2001;17:138-46.
degeneration]. Yan Ke Xue Bao: 1997;13:79-81.
38. Goosey JD, Prager TC, Goosey CB, Bird EF, Sanderson JC. A
14. Fronterre A, Portesani GP. Epikeratophakia for pellucid marginal
comparison of penetrating keratoplasty to epikeratoplasty in the
corneal degeneration. Cornea 1991;10:450.
surgical management of keratoconus. Am J Ophthalmol
15. Cameron JA. Keratoglobus. Cornea 1993;12:124-30.
1991;15;111:145-51.
16. Javadi MA, Kanavi MR, Ahmadi M, Yazdani S. Outcomes of
39. Carney LG, Lembach RG. Management of keratoconus:
epikeratoplasty for advanced keratoglobus. Cornea 2007;26:
comparative visual assessments. CLAO J 1991;17:52-8.
154-57.
40. Lass JH, Lembach RG, Park SB, Hom DL, Fritz ME, Svilar GM,
17. Vajpayee RB, Sharma N, Saxena R, Dada T. Epikeratoplasty for
Nuamah IF, Reinhart, WJ, Stocker EG, Keates RH, et al. Clinical
traumatic corneal ectasia. Cornea 1999;18:237-39.
management of keratoconus. A multicenter analysis.
18. Lifshitz T, Oshry T. Tectonic epikeratoplasty: A surgical procedure
Ophthalmology 1990;97:433-45.
for corneal melting. Ophthalmic Surg Lasers 2001;32:305-7.
41. Thompson KP, Hanna KD, Gipson IK, Gravagna P, Waring GO
19. Safir A, et al. The corneal press: Restoring donor corneas to
normal dimensions and hydration before cryolathing. Ophthalmic 3rd, Johnson-Wint B. Synthetic epikeratoplasty in rhesus monkeys
Surg 1983;14:327-31. with human type IV collagen. Cornea 1993;12:35-45.
20. Busin M, Spitznas M, Hochwin O. Evaluation of functional and 42. Robin JB, Picciano P, Kusleika RS, Salazar J, Benedict C.
morphologic parameters of the cornea after epikeratophakia using Preliminary evaluation of the use of mussel adhesive protein
prelathed, lyophilized tissue. Ophthalmology 1990;97;330-33. in experimental epikeratoplasty. Arch Ophthalmol 1988;106:973-
21. Zavala EY, Krumeich J, Binder PS. Clinical pathology of non- 77.
freeze lamellar refractive keratoplasty. Cornea 1988;7:327-30. 43. Thompson KP, Hanna K, Waring GO 3rd, Gipson I, Liu Y, Gailitis
22. Vajpayee RB, Sharma N. Epikeratoplasty for keratoconus using RP, Johnson-Wint B, Green K. Current status of synthetic
manually dissected fresh lenticules: 4-year follow-up. J Refract epikeratoplasty. Refract Corneal Surg 1991;7:240-48.
Surg 1997;13:659-62. 44. Colin J, Mader P, Volant A, Gravagna P, Dupont D, Eloy R,
23. Fronterre A, Portesani GP. Comparison of epikeratoplasty and Norquist RE, Rowsey J, McGee DA. [A trial use of lenses of
penetrating keratoplasty for keratoconus. Refract Corneal Surg human placental collagen in epikeratoplasty procedures].[Article
1991;7:167-73. in French]. J Fr Ophtalmol 1988;11:137-41.
24. Musco PS. Reversiblity of epikeratoplasty. J Refrac Surg 45. Rostran CK, et al. Experimental epikeratophakia with biological
1988;4:15-17. adhesive. Arch Ophthalmol: 1988;106:1103.
25. Teichmann KD. Management of perforations during epikerato- 46. Maury F, Honiger J, Pelaprat D, Baudrimont M, Borderie V,
plasty for keratoconus. J Cataract Refract Surg 1996;22:1143-46. Rostene W, Laroche L. In-vitro development of corneal epithelial
26. Binder PS, Zavala EY. Why do some epikeratoplasties fail? Arch cells on a new hydrogel for epikeratoplasty. J Mater Sci Mater
Ophthalmol 1987;105:63-69. Med. 1997;8:571-76.
144
20

Chapter 20: Manual Lamellar Keratoplasty


Manual Lamellar Keratoplasty
Namrata Sharma, Chandra Shekhar Kumar, Rasik B Vajpayee

Arthur Von Hippel performed the first successful lamellar cornea to remove host stromal pathology leaving the
keratoplasty (LK) for visual improvement in the last quarter of Descemet’s membrane and the endothelium intact and
the 19th century. The basic principle of LK is to replace only transplanting a complementary donor stromal button. DLK
that part of the cornea that is diseased and leave the recipient’s is mainly performed for Keratoconus and corneal scars.
normal anatomic layers intact. The idea is to do the least amount • Deep anterior lamellar keratoplasty: In this type of
of resection, with greatest amount of benefit thus leaving the keratoplasty the host dissection is done up to the level of
healthy endothelium and Descemet’s membrane as an the Descemet’s membrane and a full thickness graft which
immunologic barrier to rejection. is devoid of endothelium is sutured with 10-0 monofilamemt
Ever since its inception, this technique has evolved in the to the host.
recent years. The Anterior LK has evolved considerably in the
last few years with the precision of depth and smoothness INDICATIONS AND CONTRAINDICATIONS
achieved in the recipient bed, the refined automation and
The indications for lamellar keratoplasty can be divided into
sophisticated processing available for the donor tissue and
optical, therapeutic and tectonic. Optical lamellar keratoplasty
extension of indications for optical LK. Moreover, the
is performed for improving visual acuity mainly in cases of
application of Posterior LK for endothelial replacement leaving
superficial corneal scars and irregular/ectatic corneas Tectonic
the host’s healthy anterior stroma intact has been recently
lamellar keratoplasty is usually undertaken in cases of peripheral
investigated.1
corneal thinning/ectatic pathologies. The therapeutic lamellar
keratoplasty is performed in cases of recurrent pterygium and
TYPES OF LAMELLAR KERATOPLASTY
conjunctival intraepithelial neoplasia to remove and replace the
Various nomenclatures have been used for different types of affected corneal tissue and to arrest the pathologic process. The
lamellar keratoplasty. These include the following: major indications of lamellar keratoplasty in developed countries
• Inlay lamellar keratoplasty: In inlay lamellar keratoplasty in descending order of frequency include—corneal dystrophies,
a part of the anterior stromal lamellae of the patient’s cornea aniridia keratopathy, corneal scars and keratoconus.2 Whereas
is removed and replaced with healthy partial thickness donor in developing countries, the major indications include chemical
cornea, consisting of stroma, Bowman’s layer and epithelium. injuries, trachomatous keratopathy and dermoids.3
Inlay lamellar Keratoplasty is the conventional type of
Lamellar keratoplasty and is used to treat superficial corneal Indications for Lamellar Keratoplasty
scars. • Optical
• Onlay lamellar keratoplasty: In onlay lamellar keratoplasty Reis-Bücklers dystrophy4
a partial thickness donor cornea is placed on a de-epithlized Salzmann’s nodular dystrophy (Fig. 20.1)
recipient cornea in which a small peripheral keratectomy and/ Keratoconus5-8 (Fig. 20.2)
or peripheral lamellar dissection has been done. Granular dystrophy4-9 (Figs 20.3A and B)
Epikeratoplasty performed for keratoconus and keratoglobus Band shaped keratopathy10
is an example of on lay lamellar keratoplasty. Spheroidal degeneration10 (Fig. 20.4)
• Anterior lamellar keratoplasty: This term encompas-ses Trachomatous keratopathy3
both types of lamellar keratoplasty, i.e. the inlay lamellar Superficial scars secondary to infections and trauma11
keratoplasty and the onlay lamellar keratoplasty. Superficial corneal opacification caused by keratorefractive
• Deep lamellar keratoplasty (DLK): The term deep lamellar surgeries12
keratoplasty refers to a deep resection and or ablation of host Hurler’s syndrome10
145
• Tectonic
Dermoid10,13
Terrien’s marginal degeneration14,15
Mooren’s ulcer16 (Fig. 20.5)
Corneal melting17
Pellucid marginal degeneration18-20
Keratoglobus21
Section IV: Lamellar Keratoplasty

Acne keratitis with thinning


• Therapeutic
Recurrent pterygium10 (Fig. 20.6)
Conjunctival intraepithelial neoplasia22 (Fig. 20.7)
Epithelioma10
The criteria for lamellar keratoplasty include a reason-ably
healthy host ocular surface, optimum endothelial function, a
corneal opacity that spares the Descemet’s membrane or a grossly
distorted corneal surface that precludes a contact lens fitting.
Diseases, which either contraindicate lamellar keratoplasty
or are at high risk for failure, include:
• Herpes simplex keratitis
• Herpes zoster ophthalmicus
• Chemical or radiation injuries

Figures 20.3A and B: Granular dystrophy

Figure 20.1: Salzmann’s nodular degeneration

Figure 20.2: Keratoconus Figure 20.4: Spheroidal degeneration


146
LAMELLAR KERATOPLASTY VERSUS
PENETRATING KERATOPLASTY

Lamellar keratoplasty is an extraocular procedure that offers


intraocular safety especially in cases of one-eyed patients. The
intraocular complications of penetrating keratoplasty such as
endophthalmitis, expulsive hemorrhage, cataract and glaucoma
are avoided. Further there are less chances of graft rejection, as

Chapter 20: Manual Lamellar Keratoplasty


the endothelium is not transplanted. Lamellar keratoplasty is
undertaken in cases of moderate to advanced keratoconus.
Although penetrating keratoplasty gives superior visual results
in such cases,6-8 there is a greater likelihood for loss of graft
clarity than lamellar keratoplasty as a result of allograft reaction
episodes or intraoperative complications. Epstein compiled
Figure 20.5: Mooren’s ulcer
numerous studies on penetrating keratoplasty for keratoconus
and found that the mean weighted incidence of allograft rejection
was 18 percent.23 The Australian Corneal Registry analysis, over
a 6-year period with 3068 grafts (4% lamellar) found graft
rejection a major cause of graft failure after penetrating
keratoplasty at 33 percent.24 The 5-year graft survival was
actually better for lamellar keratoplasty (84%) than penetrating
keratoplasty (72%). The lower incidence of allograft rejection
and wound dehiscence seen with lamellar keratoplasty offers
young, monocular, poorly compliant, or high rejection risk
patients an excellent alternative to penetrating keratoplasty.10
Lamellar grafts can also replace large and eccentrically
displaced areas of corneal surface irregularity and thinning
without the risk for immune reactions to the endothelium. The
eccentric penetrating grafts adjacent to the limbus are associated
with increased risk of graft rejection.
Figure 20.6: Recurrent pterygium The criteria for the quality of the donor corneas in cases of
lamellar keratoplasty are less stringent.1,8,10 Corneal tissue that
would otherwise be rejected for penetrating keratoplasty may
be used. This is especially relevant to developing countries
where, there is paucity of good quality donor material or in
countries where the criteria for screening of donors are very
stringent. Donor corneas do not need to be fresh, since their
endothelium is not a concern as in penetrating keratoplasty. Two
or three days old whole eyes are acceptable. Glycerin preserved
or lyophilized tissue can also be used. However, in cases of large
diameter lamellar keratoplasty young donor corneas are
preferred, as one of the important functions of the large diameter
lamellar graft is to provide adequate stem cells. In general the
visual acuities following lamellar keratoplasty are inferior by one
line of Snellen visual acuity as compared to penetrating
keratoplasty. Moreover, manual lamellar keratoplasty is
technically difficult and time-consuming.
Figure 20.7: Conjunctival intraepithelial neoplasia
Lamellar Keratoplasty

Advantages
• Stevens-Johnson syndrome
• Ocular cicatricial pemphigoid • Extraocular procedure
• Neurotrophic keratopathy • Less potential for intraocular complications
• Lagophthalmos with exposure keratopathy • Less astigmatism
• Severe dry eye. • Less chances of graft rejection
147
• Less wound dehiscence Inlay LK is used for any corneal disorder that involves only
• Donor quality criteria less stringent the anterior layers of the cornea or for strengthening the cornea,
• Does not preclude a future penetrating keratoplasty. e.g. in corneal thinning disorders. In cases of stromal thinning,
descemetocele or peripheral degeneration, an inlay lamellar patch
Disadvantages graft can be fashioned to conform to stromal defect to reinforce
• Technically difficult the thinned area.
Whereas full thickness grafts are usually circular, lamellar
• Interface scarring
Section IV: Lamellar Keratoplasty

grafts may be of wide variety of shapes, sizes and depths. The


• Epithelial defects
• Less than optimal visual results. surgical points of importance during lamellar keratoplasty are
as follows:
PREOPERATIVE EVALUATION • The recipient cornea is dissected first, since the operation is
unpredictable in inexperienced hands and if the eye is
The work up of a patient scheduled to undergo lamellar perforated and the defect cannot be surgically repaired, a full
keratoplasty includes standard ocular examination and record thickness graft is necessary.
of history. Careful screening for the presence of any pre-existing • More than one donor eye must be at hand because of
ocular surface disease, which could impair the epithelization of difficulty of dissection.
the donor graft or reduce postoperative graft clarity in the event • The graft should be slightly larger (0.25 or 0.5 mm) than
of the recurrence of the host pathology, is mandatory. the recipient bed. Exceptions are peripheral grafts in
The preoperative assessment in cases of lamellar keratoplasty conditions of marginal thinning with large astigmatism in
includes the following: which a slightly smaller graft would help reduce the
• Visual acuity and refraction—This may be under-taken astigmatism by steepening the meridian.
with Snellen’s visual acuity charts. Refraction should be done • The grafts should be of uniform thickness and slightly thicker
wherever possible. than the recipient bed.
• Gross ocular examination—Tear film assessment should • The margin of the graft ideally should exactly match that of
be made and any abnormalities such as ectropion, entropion the recipient’s bed.
and trichiasis should be corrected.
• Slit lamp biomicroscopy—This should include assessment Graft-host Disparity
of the tear film status and the site, size and depth of opacity.
The endothelium should be assessed in particular, as a The size of the keratectomy bed and graft vary with disorder
healthy endothelium is a pre-requisite for anterior lamellar requiring surgery. In disorders causing opacification or
keratoplasty. irregularity of the central cornea, the keratectomy bed is usually
• Pachymetry—Ultrasonic pachymetry has allowed greater 8.0 to 9.0 mm in diameter.10 The graft diameter should be at
precision than slit lamp pachymetry for preoperative and least 0.25 to 0.5 mm larger to allow adequate wound apposition
intraoperative assessment of corneal thickness. The central between the graft and the keratectomy bed and optimum
paracentral and peripheral corneal pachymetry should be restoration of the corneal curvature. In keratoconus, the bed
done in 4 meridians. should at least 0.5 mm beyond the edge of the cone.10
• Computerized corneal maps—These maps with software
analysis such as these obtained on ORBSCAN (Bausch and Preparation of the Recipient Cornea
Lomb, St. Louis, MO, USA) have replaced keratometry. The patient is prepared and draped and the eye is immobilized
• Specular microscopy—This should be done whenever with the help of stay sutures. The dissection of the recipient
possible, especially when contemplating an anterior lamellar cornea consists of 2 steps, i.e. the trephination and the lamellar
keratoplasty. The evaluation of the host endothelial cell dissection of the marked area. The basic step of lamellar
integrity as well as the Descemet’s membrane is also an keratoplasty technique involves creation of partial thickness cut
important consideration. Poor endothelial cell function or in the recipient and the donor cornea followed by lamellar
previous breaks in Descemet’s membrane are contra- dissection through the initially trephined area. The keratotomy
indications for lamellar keratoplasty. In cases of marginal can be circular using a trephine or can be made with a blade or
endothelial reserve, the grafts may not be able to deturge micro-meter guided diamond knife in special situations. Recently,
sufficiently so that the epithelization is delayed or prevented. automated microkeratomes are also being used to perform a
smooth and regular lamellar dissection.
SURGICAL TECHNIQUE
Trephination with a Circular Trephine
In the standard lamellar keratoplasty, i.e. inlay lamellar
keratoplasty, the diseased portion of the anterior stromal lamellae The trephine is centered on the pupillary area and the cut is made
of the patient’s cornea is removed and replaced with a partial up to a depth of 0.2 to 0.4 mm, depending on the depth of the
thickness donor cornea consisting of stroma, Bowman’s layer, corneal pathology. Trephine may be eccentrically placed in cases
148 and in some cases epithelium. of corneal pathologies affecting the peripheral cornea such as
Mooren’s ulceration, pellucid marginal degeneration and Lamellar Dissection of the Recipient Bed
Terrien’s marginal degeneration. During trephination of the The depth of the lamellar dissection is determined by the position
recipient cornea in cases of keratoconus, the obturator of the of the opacities in the diseased cornea. It is advisable to dissect
trephine should be retracted into the shaft of the trephine or a beyond the anterior 1/3rd of the stroma as the lamellar
trephine without an obturator such as Barron radial vacuum arrangement in the posterior 2/3rd of the stroma is loose and
trephine or a blade without the handle may be used. The inner the dissection is easy, regular and smooth. The anterior stromal
trephine blade of the Hessburg-Barron trephine is advanced by fibers are short and closely intertwined with each other unlike

Chapter 20: Manual Lamellar Keratoplasty


a manual rotation mechanism. The four marks are present 90 posterior stromal fibers, which are longer and loosely arranged.
degrees apart and each 90 degrees of rotation advances the blade Hence, the deeper dissections are easier to perform as compared
by 60 µm. As the blade advances gradually, 360º rotation creates the more superficial dissections. The transition zone of these
a 240 µm deep cut. fibers is at the anterior one third and posterior two thirds of the
stroma.
Manual, Free Hand Dissection A Tooke’s knife can be used to create a pocket at the desired
In cases of corneas with irregular thickness, free hand dissection depth and the upper lip of the tissue to be excised is put on stretch
with a fine forceps (Fig. 20.8A). By a constant back and forth
is advocated. The area of keratectomy is outlined with a diamond
movement into the undissected tissue, a smooth plane can be
blade or a stainless steel blade, after marking the cornea with a
hand held trephine stained with gentian violet. Alternatively, a achieved using lamellar dissectors such a Gills or Desmarres’
(Fig. 20.8B). The dissector should be directed parallel to the
micrometer guided diamond blade may be used for free hand
bed of the stromal lamellae (Figs 20.8C and D) not downwards
dissection. The incision should be made perpendicular to the
corneal surface to provide a distinct edge to which the graft can to prevent inadvertent perforation/thinning of the recipient bed.
During the whole process of lamellar dissection, the host bed
be sutured. Following trephination the lamellar dissection can
should be kept dry as it aids in better visualization of the plane
be undertaken either under direct visualization or by creating
pockets. of dissection. Further, any inadvertent perforation during the
lamellar dissection is timely diagnosed due to the presence of
the aqueous leak and adequate measures may be taken
Automated Microkeratomes
immediately to prevent its extension and subsequent
Automated microkeratome assisted lamellar keratoplasty uses a complications (Fig. 20.8B). The host bed should be kept dry; it
microkeratome to excise the pathological part of the host cornea helps in better visualization of the plane of dissection and any
upto a desired depth. A lamellar donor lenticule obtained by inadvertent perforation can be diagnosed due to the presence of
lamellar dissection using an automated microkeratome and the aqueous leak. Following dissection of the host button, the
artificial chamber is sutured on to the recipient bed. dissected layer may be excised with the help of corneoscleral
scissors (Fig. 20.8C) and a smooth recipient bed is obtained (Fig.
Non-mechanical Excimer Laser Trephination 20.8D).
The closed type of dissection technique wherein, the lamellar
Excimer laser (193 nm) has been used to trephine and prepare dissection is undertaken with the help of a lamellar dissector
the donor lenticule as well as the recipient bed in experimental through the initially created pocket, should be avoided when
studies.24 dissecting the host. This is because the diseased host cornea may

Figure 20.8A: Creation of pocket at the desired depth (upper lip Figure 20.8B: Dissector is directed parallel to the bed of the
of the tissue which is excised is stretched with a fine forceps) stromal lamellae and not downwards
149
Section IV: Lamellar Keratoplasty

Figure 20.8C: The dissected layer is excised with Figure 20.8D: The dissected host bed after removal of
corneoscleral scissors diseased layer

be of unequal or disparate thickness and decreased visualization separating it from the overlying stroma. Using a spatula and
of the underlying host bed may cause inadvertent perforation. scissors, the overlying recipient cornea is removed and a full
Caution is mandatory for dissection of inferior peripheral thickness donor tissue is sutured into the Descemet’s membrane
120º in cases of keratoconus due to thinned out cornea at these bed. This technique was popularized by Archila et al26 and Price
locations. If another pass is required a small pocket is again made et al.27 However, the air dissection was relatively incomplete,
with the help of a Tooke’s knife and another layer of lamellar leaving the area with most stromal scarring or pathology
dissection done. In cases of deep lamellar dissections, the undissected in some cases and perforation occurred in few eyes.28
Descemet’s membrane can be easily identified. The stroma may
be irrigated with balanced salt solution so that it will cause stroma Hydrodelamination
to hydrate and appear fluffy, whereas the Descemet’s membrane
Sugita et al29 report use of hydrodelamination techniques to
appears clear.
facilitate deep intralamellar dissection. The host cornea is
When the dissection upto the edge of the trephine mark is trephined up to three-quarters depth using a Barron vacuum
completed, it should be extended a millimeter or two beyond
trephine. A small cut is then made on the remaining stromal
this mark which can be done with the help of a crescent knife.
fibers. The hydrodelamination is then done through this cut with
Such a maneuver ensures a vertical edge and forms a natural the saline using a 27 gauge cannula causing whitening of the
track for the needle when a corneal graft is sutured in place.
overlying stromal fibers. A 0.25 mm diameter spatula is then
In the Malbram’s “peeling technique”, which was
inserted rectilinearly into the stroma and it is moved in different
popularized for keratoconus, the lamellar dissection is done by directions. The Paufique knife or corneal scissors is slipped into
using a spatula or knife upto 2 to 3 mm horizontally, into the
this opening and the overlying stroma is peeled off. This exposes
desired plane.6 A 0.12 mm tissue forceps is used to apply anterior
the underlying Descemet’s membrane. Hydrodelamination can
traction to the elevated edge of the lamellar flap and lamellar also be used for thickening the thin host corneas, like in case of
dissectors are used to facilitate cutting. The lamellar flap is then
keratoconus and keratoglobus, making trephination and lamellar
grasped with tissue forceps and slowly but steadily pulled from
dissection safe.
the periphery to the center, until the entire flap has been removed.
Following the natural deep lamellar planes with a combination Viscoelastic Injection
of cutting and peeling a smooth surface and a clear lamellar bed
is obtained. Morris et al30 have used similar technique as Sugita et al but
they add a viscoelastic after hydrodelamination and perform
Modifications in Technique of Lamellar limbal paracentesis to prevent bulging of Descemet’s membrane
Dissection of Host Tissue during final resection of posterior fibers.
Various modifications of this basic technique have occurred to
Divide and Conquer Technique
facilitate deep recipient lamellar dissection in order to prevent
the risk of perforation and to improve the visualization. These This technique of lamellar keratoplasty has been deve-loped by
are as follows: Tsubota et al. 31 The technique facilitates deep lamellar
keratoplasty and prevents occurrence of high astigmatism. Their
Air Injection technique uses a 7.5 mm Barron suction trephine and leaves
In this technique, 1 cc of air is injected by a tuberculin syringe 100 µm of posterior stroma without trephination. Air and water
150
with a 26 gauge needle just above the Descemet’s membrane, are then used to demarcate and dissect this lamellar plane. From
the 12 o’clock position, the recipient cornea is divided in half
by lamellar dissection towards the 6 o’clock position. The same
procedure is then performed horizontally, thus creating four
quadrantic blocks. Each of these quadrantic blocks is then
dissected by a microblade and removed.

Harvesting of Donor Lenticule

Chapter 20: Manual Lamellar Keratoplasty


Donor lamellar tissue can be obtained from a whole eye, donor
corneal tissue, or pre-carved lyophilized tissue.

Whole Eye
The donor lamellar tissue can be obtained from the whole eye
that can be fixated in a gauze piece or in a Tudor Thomas stand
for stabilization while performing lamellar dissection (Fig. 20.9). Figure 20.9: Whole globe fixated in gauze piece
A suction fixated or a hand-held trephine may be used to obtain
the donor lenticule.

Corneoscleral Caps
When using the donor cornea, it is advisable that a larger rim of
the host should be left. The donor button may be tightly clamped
over some wetted cotton in a King’s clamp8 (Fig. 20.10) (See
Chapter 5). Simple modifications include three-point fixation
technique described by Vrabec et al32 or stabilizing the cap to
the fabric covered glass ball described by Wong et al.33

Pre-carved Lyophilized Tissue


The genesis of pre-carved lyophilized tissue is the desire for
readily available source of prepackaged, uniform thickness donor
tissue.34 A contact lens lathe was used earlier to reshape the
frozen corneal tissue, which was replaced by a corneal press.35 Figure 20.10: Donor corneoscleral rim clamped in
These lenticules were then frozen and cryolathed and stored in King’s clamp
McCarey-Kaufman medium for < 72 hr. However, the use of
frozen cryolenticules is associated by delayed visual recovery dissection is commenced, by making a line of cleavage with
which is attributed to the absence of active keratocytes. a Tooke’s knife to the approximate depth of the recipient
Additionally, the tissue can also be lyophilized so that this ‘freeze bed. The cut edge is then lifted with a Pierce Hoskin’s
dried’ tissue can be readily stored for up to 3 months and forceps. After the plane of cleavage has been found the
distribution to various places is facilitated.36 Lyophilized donor remainder of the dissection is performed with a Desmarres
lenticules are known to be immunogenic due to the absence of or a Gill’s lamellar dissector (Fig. 20.11). It is mandatory
active keratocytes. that the bed is kept dry so that the surgeon can see the plane
Similar to the recipient bed, the donor lamellar tissue can of dissection.
be dissected with a trephine or a manual dissection can be used • Closed technique – The closed technique provides a better
depending upon the host pathology. and smoother donor lenticule. The donor corneoscleral rim
There are four techniques employed in harvesting a graft is placed on a wet gauze piece and tightly clamped in a
from the donor tissue for lamellar keratoplasty. King’s clamp just as was described in the open technique.
• Open technique – In the open technique, the donor is The circular hand held or suction fixated trephine is placed
dissected with the lamellar button elevated. A desired circular on the corneoscleral button at the desired depth. The edge
partial thickness cut is made in the donor cornea with a hand- of the pocket is made with the help of a Tooke’s or a
held or a suction fixated trephine. When a circular trephine Paufique’s knife and a Gill’s lamellar dissector may be
is being used, the trephine’s obturator is set at the required inserted within this lamellar plane and the lamellar dissection
depth, usually 0.2-0.4 mm to match the recipient. The completed with gentle side-to-side movement without
trephine is then applied to the donor corneoscleral button, elevating the corneal edge. It is important to stay in the same
which has been tightly clamped on a wet gauze piece in a plane, and this is accomplished by pushing the dissector
King’s clamp, to make a stromal cut at this depth. The laterally but not downwards.
151
Section IV: Lamellar Keratoplasty

Figure 20.11: Lamellar dissection Figure 20.12A: Application of first two interrupted sutures
with a Gill’s lamellar dissector

• Use of microkeratomes – Automated microkeratome with


artificial chamber is also used to harvest the lamellar donor
corneal graft. These techniques shorten the surgical time and
cut a very smooth and regular graft.
• Full thickness graft – Some surgeons prefer to use a full
thickness graft punched from endothelial side just like in
penetrating keratoplasty. After harvesting the graft, the
endothelium is stripped from the posterior surface and the
graft is sutured. A peripheral rim of 2 mm tissue may be cut
from the edge of the endothelial side of the graft to obtain a
better apposition. We use full thickness grafts for very thin
host beds, like in cases of keratoconus, severely thinned
corneas due to chemical trauma and infections with only
superficial scarring. Figure 20.12B: Application of four cardinal sutures
Free hand dissection – If a non-circular graft is required, it is
dissected by free hand technique. This can be done by cutting
Good approximation of the margins is desired since imperfect
one side of the graft and suturing this side to an edge of the
apposition can result in astigmatism.
keratectomy bed. Another side of graft is than cut and this side
For optimal wound apposition at the host graft junction, some
is sutured in place. The sequence of cutting and suturing is
surgeons prefer to cut a peripheral rim of 2 mm tissue from the
repeated until the graft has been tailored to fit the keratectomy
edge of the endothelial side of the graft. This is then fitted into
bed. Alternatively a preset micrometer guided diamond blade
a 1 mm pocket, which is created lamellarly at the edge of the
may be used.
trephined host tissue with the help of a Crescent knife.
We use a simple technique to demarcate the host pathology
In some cases of large keratoconus and keratoglobus, a
and obtain a complementary donor lenticule. Using a Castroviejo
paracentesis and partial removal of the aqueous may be necessary
calipers, the diameter of the host pathology are measured in the
to soften the eye slightly, to enable adequate would closure. In
largest and smallest dimensions as well as in few other meridians.
these cases the lamellar graft has to compress the recipient bed
Then a gentian violet stained calipers is used to mark a
for the optimal reappostition and a tight suturing is advocated
complementary area on the donor cornea. This is then lamellarly
to achieve it.
dissected at the same depth as the host cornea.
Care must be taken to keep glove powder, cellulose sponge
material, lint or epithelial cells away from the interface. A
Suturing of the Graft
thorough wash of the interface should be done with BSS once
A running or interrupted suturing technique using 10-0 graft is anchored with three or four sutures and the graft should
monofilament nylon suture may be employed for lamellar be tightly secured to the host so that the epithelial ingrowth in
keratoplasty (Fig. 20.12A). We prefer to use interrupted sutures the graft host interface is prevented and a good apposition is
and 16 interrupted sutures are generally used (Fig. 20.12B). achieved (Fig. 20.13).
152
SUTURE REMOVAL

Interrupted sutures should be removed as soon as the vessels


bridge the host-graft junction or at 6 months postoperatively in
a non-vascularized cornea. Suture removal may be undertaken
earlier for any suture related problems such as loose sutures,
broken sutures and suture abscesses. Selective suture removal
may be done for the control of postkeratoplasty astigmatism

Chapter 20: Manual Lamellar Keratoplasty


beginning from 1st month onwards.

COMPLICATIONS OF LAMELLAR KERATOPLASTY

The complications of lamellar keratoplasty can be divided into


intraoperative and postoperative.

Intraoperative
Figure 20.13: Operated lamellar keratoplasty
Perforation of the Descemet’s Membrane
The most important intraoperative complication that can occur
during lamellar keratoplasty is perforation of the Descemet’s
Intraoperative Medications and membrane. This is diagnosed by the presence of the aqueous
Postoperative Regime fluid on the lamellar bed. Hence the lamellar bed should always
be kept dry during lamellar dissection. Perforation of the
A subconjunctival injection of an antibiotic (gentamicin 20 mg)
Descemet’s membrane can occur during trephination or
and steroid (dexamethasone 4 mg) combination is given in
keratotomy incision or at the time of deep lamellar dissection.
inferior fornix at the end of the surgery and the patient is given
a. During trephination—If perforation occurs during
pad and bandage for 24 hours. We follow the following
trephination, it is best managed with wound closure of the
postoperative regime in various cases of penetrating keratoplasty
keratotomy incision at the time of its occurrence. The surgery
at our center.
should be postponed for at least three months until the
Descemet’s membrane has healed. We use a mattress suture
Antibiotics
for a small inadvertent perforation caused during making of
Topical antibiotics such as 0.3 percent ofloxacin or 0.3 percent a circular cut in the host cornea (Fig. 20.14).
ciprofloxacin are used four times a day for 1 week post-
operatively or until the epithelium has covered the graft. Since
delayed epithelization is a problem in lamellar keratoplasty,
prolonged use of topical aminoglycosides is toxic to the
epithelium and hence should be avoided.

Corticosteroids
Topical corticosteroids such as 1 percent prednisolone acetate
or 0.1 percent dexamethasone sodium phosphate may be used
four times a day in routine lamellar keratoplasty. These are more
rapidly reduced than in penetrating keratoplasty. These are then
tapered by one month.

Lubricants
Adequate lubrication is the mainstay of the postoperative
management in lamellar keratoplasty. Preservative free lubricants
Figure 20.14: Mattress suture used for small inadvertent
may be given at 2 hourly dosage for at least one month which perforation at the keratectomy site
may be tapered to 4 times daily dosage. If re-epithelization of
the graft does not occur, bandage soft contact lens or a temporary b. During lamellar dissection—If the perforation occurs during
tarsorrhaphy may required. Epitheliotoxic drugs such as beta- lamellar dissection the management protocol is as follows:
blockers, non-steroidal anti-inflammatory drugs and topical i. If a small perforation occurs in the recipient bed during
aminoglycosides should be used with caution. the process of lamellar dissection, further lamellar

153
completely resolves after two to three weeks postoperatively
and are not visually significant. Occasionally, the Descemet’s
folds radiating from a tight suture may be seen. Such sutures
need to be replaced immediately.
• Delayed epithelization – Prolonged surgery with exposure
and drying of ocular surface is responsible for delayed
epithelization of the graft. This may also result from damage
Section IV: Lamellar Keratoplasty

to limbal conjunctival stem cells, which are the source of


corneal epithelium for the graft. These problems are seen
Figure 20.15: Autointralamellar patch for medium sized more with use of the lyophilized and cryo-preserved tissue
perforations. (A) Site of perforation, (B) Autointralamellar patch, as compared to the fresh lenticules. In high-risk cases, where
(C) Lamellar graft postoperative problems of delayed epithelization are
expected, relatively young and fresh donor tissue should be
dissection is halted. The anterior chamber is reformed used. In the immediate postoperative period, frequent
by injecting air through a paracentesis. A mattress suture preservative free lubricants should be prescribed. A bandage
may then be applied to the edges of the perforation in contact lens or a tarsorrhaphy may be used in cases where,
the recipient bed in order to close it. delayed epithelization is anticipated such as in ocular surface
ii. For small perforations another alternative technique may disorders.
be used. The dissection is halted at the site of the • Stromal melting – Persistent epithelial defects can also lead
perforation and begun from the keratectomy site 180º to the development of sterile corneal melting, particularly
away at a more superficial plane. The flap thus created in high-risk patients with pre-existing ocular surface disease.
as a result of the perforation acts as a valve which is self- Further, super-added infection in cases of persistent epithelial
sealing. defects can also lead to corneal melting.
iii. In cases of medium sized perforations the technique of • Microbial keratitis – Infections following lamellar
autointralamellar patch with lamellar keratoplasty may keratoplasty generally start from the graft-host interface and
be undertaken (Fig. 20.15). Dissection is halted at the then spread anteriorly towards the graft. Since these
site of the per-foration and a lamellar dissection is infections commence from the graft-host junction, a
commenced from the keratectomy site 180° away in a meticulous examination is mandatory to ensure their timely
different plane. A lamellar flap is thus created which is recognition and prompt management (Figs 20.16 and 20.17).
everted on to the site of the perforation and a suture is These infections may be difficult to diagnose as they may
applied from the edge of this everted flap to the commence as an infiltrate in the graft host interface and may
unbreached area of the host bed. A lamellar graft is then progress to the formation of an abscess. They are more
sutured to the host. difficult to treat, as they may not be amenable to topical
iv. In cases of very large perforations, the procedure of antibiotic therapy. Hence a prompt diagnosis and meticulous
lamellar keratoplasty may not be possible, and hence a management is warranted in such cases.
full thickness penetrating keratoplasty may be Corneal scrapings are obtained for culture and
undertaken. sensitivity of bacterial and fungal organisms. Intensive
fortified antibiotic therapy consisting of 5 percent cefazolin
Postoperative
Postoperative complications, which can lead to loss of graft
clarity include interface opacification caused by epithelial or
vascular tissue, delayed epithelization of the graft, folds in the
Descemet’s membrane and sterile corneal melting.
• Double anterior chamber – Double anterior chamber
following lamellar keratoplasty postoperatively occurs due
to the unrecognized inadvertent perforation of the host during
trephination, lamellar dissection or suturing. The double
chamber recognized in the immediate postoperative period
is best managed by draining the aqueous from both the
supernumerary chamber as well as the anterior chamber and
then reforming the anterior chamber by injecting air.
• Folds in the Descemet’s membrane – Folds in the
Descemet’s membrane may be observed especially in older
patients with keratoconus. These folds in younger patients Figure 20.16: Infection in a lamellar graft
154
dystrophy,38 macular dystrophy,39 Reis-Buckler’s dystrophy,
Hurler’s, pterygium and conjunctival intraepithelial neoplasia
(CIN). A penetrating keratoplasty may be performed in such
cases.
• Suboptimal visual acuity – Visual acuities achieved after
lamellar keratoplasty are generally inferior by one or more
line of Snellen visual acuity as compared to penetrating

Chapter 20: Manual Lamellar Keratoplasty


keratoplasty. The potential causes of suboptimal visual acuity
in these cases include the following:
— Irregular and uneven dissection of donor corneal tissue.
— Particulate debris trapped in lamellar surface.
— Irregular and uneven dissection of recipient bed.
— Mechanical folds in the posterior layer over the visual
axis induced from flattening of this layer with donor
Figure 20.17: Increased area of infiltration in lamellar corneal tissue.
keratoplasty in the same eye as in Figure 20.14
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of new techniques, which uses instruments such as automated
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156
21

Chapter 21: Automated Lamellar Therapeutic Keratoplasty


Automated Lamellar Therapeutic
Keratoplasty
Namrata Sharma, Sameer Kaushal, Rasik B Vajpayee

Lamellar keratoplasty with an automated microkeratome is a attainment of good visual acuity after ALTK, immuno-
modification of the manual lamellar keratoplasty. This technique compromized patients where, wound healing may be impaired,
uses a microkeratome to excise the pathological part of the host collagen vascular disorders and history of abnormal wound
cornea up to a particular depth and later a healthy donor cornea, healing, e.g. keloid formation are other contraindications of
which is also cut using an automated microkeratome and artificial ALTK.
chamber, is sutured in its place.1 This new lamellar grafting
eliminates several disadvantages associated with conventional Preoperative Evaluation
LK including difficult surgical manual technique. The automated
The preoperative evaluation of a patient undergoing ALTK is
microkeratome helps in achieving a regular, smooth recipient
similar to that of a routine manually dissected lamellar
bed and optimal recipient graft opposition. keratoplasty. Pachymetry is of special relevance as the depth of
the dissection is dictated by the depth of the pathology as well
Indications for Automated Lamellar
as the microkeratome head available. Ultrasound pachymetry
Therapeutic Keratoplasty
should be done for the central as well as peripheral areas of
The indications for automated lamellar therapeutic keratoplasty cornea to look for significant irregularity in corneal thickness.
(ALTK) include patients having diseases involving the anterior
to mid-stromal part of the cornea with normal endothelium.2,3 Surgical Technique
These include patients with superficial dystrophies, keratoconus,
Preparation of the Recipient Bed
superficial chemical burns, posttraumatic scars, postinfections
leucomas, trachoma, salzmann nodular degeneration, herpes and The recipient lamellar bed is prepared using a suction ring and
postexcimer surgery corneal haze.4-6 It has also been used for an automated microkeratome in a manner just as one does in
tectonic puposes in patients with significant corneal thinning and laser-in-situ keratomileusis (Figs 21.1 and 21.2). The suction ring
impending perforation.7 A modified microkeratome with a determines the size of the lenticule obtained. The suction ring is
redesigned head has also been evaluated for limbal stem cell available in sizes +2, +1, 0 and -1 producing smaller to larger
harvest and transplantation.8 lenticules respectively for the same keratometry. The automated
microkeratome is used as a cutting instrument. The advancement
Contraindications for Automated Lamellar of the microkeratome over the suction ring can be motor driven
Therapeutic Keratoplasty or manual. The microkeratome is available in various range of
The contraindications for ALTK include patients with endothelial heads such as 120, 180, 250 and 350 μm which can used
dysfunction, disorders of lids including ectropion, entropion, depending on the desired depth of the lamellar cut (Fig. 21.3).
trichiasis, lagophthalmos, dry eye, keratoconjunctivitis sicca, The goal is to cut a disk with the same diameter (or 0.5 mm
severe blepharitis, uncontrolled uveitis and glaucoma. Patients undersized) and thickness as the donor disk. Once the disk is
with deep set eyes or small palpaberal apertures also precludes removed, the recipient bed is washed with balanced salt solution
the use of microkeratome for preparation of host bed. Patients and dried with the sponge (Fig. 21.4).
with advanced keratoconus with severe ectasia and thinning are
also at increased risk of corneal perforation during preparation Preparation of the Donor Lenticule
of host bed ALTK should be avoided in these cases.2 Any The donor lenticule may be obtained from a corneoscleral rim.
posterior segment pathology of the eye that may preclude The corneoscleral rim should be at least 4 mm wide as the frill
157
Section IV: Lamellar Keratoplasty

Figure 21.1: Automated lamellar therapeutic keratoplasty


machine (Courtesy: Moria SA France)
Figure 21.4: Diameter of host cut measured after the
microkeratome cut

Figure 21.2: ALTK surgical trolley

Figure 21.5: Artificial anterior chamber

superficial sclera and maintains a tight fit on the metal base of


the chamber to avoid leakage. A second ring in an intermediate
position approximates the chamber on the former structure to
tighten the sclera from above. A third ring located superiorly is
adjusted to modify the height of the microkeratome plate. This
plate is a gearless track to guide the microkeratome head
translation at a constant height along the corneal pass (Fig. 21.5).
Depending on the height at which this plate is positioned,
more (lower position) or less (higher position) of the cornea is
exposed, resulting in a larger or smaller lenticule diameter,
respectively. The chamber is connected to the infusion system
with a reservoir of saline solution, placed 1.2 m above the
Figure 21.3: Host cut made with 250 μ microkeratome chamber level. An expansion air chamber is located within the
infusion line at the 10.0 cm of the connection to the chamber.
of the corneoscleral rim has to be positioned on the artificial The pressure should be more than 60 mm Hg and should be
anterior chamber maintainer. The artificial anterior chamber checked with a barraquer tonomter. Pressure as high as
consists of a stainless steel structure with 3 screw type safety 95 mm Hg has been suggested to ensure a donor lenticule with
rings. The lower ring sustains a metal device that covers the more consistent thickness.
158
Chapter 21: Automated Lamellar Therapeutic Keratoplasty
Figure 21.6: Microkeratome head applanation lenses Figure 21.8: Diameter adjusted the chamber
by use of applanation lens

Figure 21.7: Donor placed over the chamber Figure 21.9: Donor dissection done with 350 μ microkeratome

We use LSK microkeratome (Moria) to perform automated solution are placed on the cornea and keratectomy is performed
lamellar keratoplasty (Fig. 21.1). It consists of a single piece by passing the microkeratome head with its oscillating bade at a
metal head connected to a nitrogen-gas-driven hand piece. The relatively constant speed along the plate (Fig. 21.9). The diameter
blade oscillates at a rate of 15,000 oscillations/min with an of the flap which has been cut, is then measured (Fig. 21.10).
orientation of 25 degrees to the cut plane. The grooves on the Behrens et al report that the precision and accuracy of this system
base plate of the artificial anterior chamber are designed to fit varies according to the attempted thickness and diameter. Greater
into the microkeratome head, hence its pass along the cornea is precision is obtained if the diameter of the cut is < 8 mm or if
uniform (Fig. 21.6). the flaps are thinner.9
To reduce the number of air bubbles beneath the cornea, rims
are placed on the chamber base after the infusion is released Donor Recipient Apposition
(Fig. 21.7). Once the cornea is stabilized and centered and the
absence of air bubbles is confirmed, the infusion is closed, the The donor lenticule is placed on the recipient bed. Although some
superior metal support is placed and locked by turning the first surgeons leave the donor lenticule adhered to the recipient bed
ring clockwise, and the second ring is turned anticlockwise to without any sutures, we prefer to put at least 8 interrupted sutures
elevate the chamber height and tighten the scleral skirt between with 10-0 monofilament nylon. The eye is than patched for 24
the support and chamber. hours. Use of fibrin glue instead of sutures has also been
The applanation lens is then placed on the cornea to suggested for securing the donor lenticule over the host bed.10
determine the plate height for the desired diameter, turning the Postoperatively, the patient receives topical antibiotics, dilute
second ring counter clockwise or clockwise depending on the corticosteroids and preservative free artificial tears, which are
guiding circle marks on the lenses (Fig. 21.8). Drops of saline then subsequently tapered.
159
Section IV: Lamellar Keratoplasty

Figure 21.10: Diameter of the donor button measured Figure 21.11: Smooth interface after ALTK

Femtosecond Assisted Automated ring should be carefully chosen according to keratometry and
Lamellar Keratoplasty pachymetry to avoid this complication.
Incomplete pass of the microkeratome may result in partial
Femtosecond is the latest addition in the armamentarium
flap formation. This may result from resistance to the movement
available for lamellar corneal procedures. The main advantages
of the microkeratome or loss of suction. Patients with deep set
over a microkeratome is the better safety, reproducibility,
eyes and small palpaberal apertures are especially predisposed.
predictability, and flexibility of femtosecond laser. Use of
Another complication is significant discrepancy in the size
femtosecond laser for automated lamellar keratoplsty has been
and thickness of the host bed and donor lenticule. It has been
reported though larger studies are required to better understand
show that almost 85 percent of recipient beds have diameter
the full scope of utility provided by femtosecond laser.11
within 0.5 mm of the desired lenticule diameter but a few cases
may have too high or too low diameter due to improper choice
Advantages
of suction ring or abnormal keratometry. The donor cornea used
An automated microkeratome allows the surgeon to obtain may have significant edema during preparation of the lenticule.
corneal lenticules with parallel faces that are almost identical in The donor lenticule thus prepared will further reduce in thickness
the donor and the recipient corneas. These factors result in optical during the postoperative period.9
and refractive results that are better than those obtained with the There are several things surgeon should consider when using
manual techniques. The cut made by the microkeratome is this technique. It is important to obtain lenticules with same
regular and homogeneous producing a smooth surface diameter and thickness so that the fit is perfect and the future
(Fig. 21.11) without significant chatter lines as seen with epithelial ingrowth is avoided. Epithelial ingrowth can occur after
scanning electron microscope.12 This prevents the irregular significant trauma even after many years after surgery.14 The
astigmatism that occurs with a manual procedure because of the epithelium of the donor should be kept intact as far as possible.
horizontal adherence of the disk to the donor tissue. Further the The donor epithelium is replaced by the recipient epithelium
surgical time is shortened and fewer sutures are required for during the first week.
shorter periods of time, which reduces suture-related Other complications are similar to manual lamellar
complications. 13 The procedure may be combined with keratoplasty. Incidence and severity of interface haze is likely
phacoemulsification if a significant cataract is present. Removal to be less in ALTK due to a smoother interface. Though
of anterior diseased corneal tissue allows better visualization for endothelial rejection does not occur, possibility of stromal
phacoemulsification. rejection or epithelial rejection should always be kept in mind.15

Complications Outcome of ALTK


Complications associated with ALTK are usually microkeratome ALTK was undertaken in 48 eyes at our center for various
related. The most dreaded but uncommon complication is corneal indications which included cases such as keratoconus (Figs
perforation during recipient bed preparation.2 It usually occurs 21.12A and B), dystrophies (Figs 21.13A and B), Salzmann
in corneas with abnormal keratometry as with keratoconus or in nodular degeneration (Figs 21.14A and B), impacted corneal
corneas with irregular corneal thickness and localized areas of foreign bodies (Figs 21.15A and B), and healed bacterial (Figs
significant corneal thinning. Microkeratome head and suction 21.16A and B) and fungal keratitis (Figs 21.17A and B). The

160
Chapter 21: Automated Lamellar Therapeutic Keratoplasty
Figure 21.12A: Keratoconus Figure 21.12B: Postoperative ALTK 6 months
(Same case as in Figure 21.12A)

Figure 21.13A: Lattice dystrophy Figure 21.13B: Posteoperative ALTK


(Same case as in Figure 21.13A)

Figure 21.14A: Salzmann nodular degeneration Figure 21.14B: Postoperative ALTK 6 months
(Same case as in Figure 21.14A) 161
Section IV: Lamellar Keratoplasty

Figure 21.15A: Corneal foreign bodies Figure 21.15B: Postoperative ALTK 9 months
(Same case as in Figure 21.15A)

Figure 21.16A: Healed bacterial keratitis Figure 21.16B: Postoperative ALTK at 1 month
(Same case as in Figure 21.16A)

Figure 21.17A: Healed fungal keratitis Figure 21.17B: Postoperative ALTK 1 month
162 (Same case as in Figure 21.17A)
donor button size ranged from 8.5 to 10 mm (thickness 350 mm) 4. Tan DT, Ang LP. Modified automated lamellar therapeutic
and the host cut size ranged from 8 to 9.5 mm (thickness keratoplasty for keratoconus: a new technique. Cornea.
250 mm). Sixteen to twenty four interrupted sutures with 10-0 2006;25:1217-19.
5. Chen W, Qu J, Wang Q, Lu F, Barabino S. Automated lamellar
monofilament were applied (Fig. 21.4). The mean central corneal
keratoplasty for recurrent granular corneal dystrophy after
thickness was 503 mm. From a preoperative visual acuity of phototherapeutic keratectomy. J Refract Surg. 2005;21:288-93.
≤ 2/60 in all eyes, a postoperative visual acuity of ≥ 6/18 was 6. Tan DT, Ang LP. Automated lamellar therapeutic keratoplasty for
achieved in 32 out of 48 patients. Mean epithelialization time post-PRK corneal scarring and thinning. Am J Ophthalmol.

Chapter 21: Automated Lamellar Therapeutic Keratoplasty


was 3 days (range 1 - 10 days). No cases of interface scarring 2004;138:1067-69.
were seen after a follow-up of 6 months. However, the long- 7. Wiley LA, Joseph MA, Springs CL. Tectonic lamellar keratoplasty
term problems of interface scarring needs to be ascertained. utilizing a microkeratome and an artificial anterior chamber
Although we did not encounter any major complications, system. Cornea. 2002;21:661-63.
8. Chuck RS, Behrens A, McDonnell PJ. Microkeratome-based
there are risks of postoperative complications, which include
limbal harvester for limbal stem cell transplantation: preliminary
delays or defects in epithelization, epithelial ingrowth in the studies. Am J Ophthalmol. 2001;131:377-78.
interface, fibrosis and even vascularization.14 Edema or melting 9. Behrens A, Dolorico AMT, Kara DT, Novick LH, McDonnell PJ,
of the lenticule may also occur. Although an endothelial rejection Chao LC, et al. Precision and accuracy of an artificial anterior
will not occur, an epithelial and stromal rejection may occur.15 chamber system in obtaining corneal lenticules for lamellar
Finally the original disease may recur. Optical lamellar keratoplasty. J Cataract Refract Surg 2001;27:1679-87.
keratoplasty, performed with an automated microkeratome, is an 10. Chen W, Qu J, Lu F, Zhu RY. Sutureless lamellar keratoplasty
by microkeratome combined with fibrin tissue adhesive in rabbits.
easy, simple, and accurate technique. It produces good visual
Zhonghua Yan Ke Za Zhi. 2004;40:331-36.
results and is a good alternative to penetrating keratoplasty
11. Hoffart L, Proust H, Matonti F, Catanèse M, Conrath J, Ridings
especially in the treatment of anterior corneal pathology. B. Femtosecond-assisted anterior lamellar keratoplasty. J Fr
Ophtalmol. 2007;30:689-94.
REFERENCES 12. Victor G, Sousa SJ, Alves MR, Nosé W. Evaluation of a new
system for obtaining donor lamellar grafts. Cornea 2007;26(2):
1. Jimenez-Alfaro I, Perez-Santonja JJ, Telleria GG, Palcin B, Puy 151-53.
P. Therapeutic lamellar keratoplasty with an automated 13. Maia NC, Chamon W, Castelo Branco B. Evaluation of
microkeratome. J Cataract Surg 2001;27:1161-65. performance, efficacy and safety of semi-automated lamellar
2. Vajpayee RB, Vasudendra N, Titiyal JS, Tandon R, Sharma N, keratoplasty. Arq Bras Oftalmol 2006;69:795-804.
Sinha R. Automated lamellar therapeutic keratoplasty (ALTK) in 14. Wang TJ, Wang IJ, Hou YC, Hu FR. Giant epithelial ingrowth
the treatment of anterior to mid-stromal corneal pathologies. Acta induced by blunt injury after automated lamellar keratoplasty..
Ophthalmol Scand. 2006;84:771-73. Formos Med Assoc. 2005;104:279-81.
3. Jiménez-Alfaro I, Pérez-Santonja JJ, Gómez TellerÃ-a G, 15. Kawashima M, Mochizuki H, Kawakita T, Hatoh S, Shimazaki
Bueno PalacÃ-n JL, Puy P Therapeutic lamellar keratoplasty with J, Yamada M. J Med Case Reports. 2007 Apr 1;1:10. Presumed
an automated microkeratome. J Cataract Refract Surg. stromal graft rejection after automated lamellar therapeutic
2001;27:1161-65. keratoplasty: case report.

163
22
Section IV: Lamellar Keratoplasty

New Lamellar Keratoplasty Techniques:


Posterior Keratoplasty and
Deep Lamellar Keratoplasty
Sandeep Jain, Dimitri T Azar

Endothelial cell dysfunction is seen in conditions such as aphakic of 20/50 or better in 38 percent eyes that underwent LK for
and pseudophakic bullous keratopathy, graft failure and Fuchs’ corneal diseases such as dystrophies (Granular, Reis-Buckler’s),
dystrophy. Although penetrating keratoplasty (PK) is currently aniridic keratopathy, corneal scars and keratoconus.11 The major
the surgical method of choice for improving vision in such causes of poor postoperative visual acuity were graft-host
conditions, selective transplantation of only the posterior corneal interface haze and/or vascularization in 44 percent, graft surface
tissue (endothelium and posterior stroma) is an another alter- irregularities and/or astigmatism in 42 percent and persistent
native.1 This procedure, termed posterior keratoplasty, is useful epithelial defects in 21 percent. Interface scarring is almost
in selected patients with corneal decompensation due to diseased absent after microkeratome dissection in laser in situ
endothelium. Melles et al have previously reviewed the keratomileusis (LASIK). The use of a microkeratome for similar
techniques of posterior keratoplasty.2 Since, then the preliminary stromal dissection in posterior keratoplasty may result in reduced
results of posterior lamellar keratoplasty on sighted human eyes interface scarring. Haimovici et al described the use of a
have been reported by several investigators.3,4 Herein, we will microkeratome to cut donor and host lenticules for lamellar
review the surgical technique and results of posterior keratoplasty keratoplasty.13
on sighted human eyes.
Surgical Technique5
POSTERIOR LAMELLAR KERATOPLASTY
Donor Stromal Button Preparation
Surgical Technique The thickness of donor tissue in the corneal preservation media
is greater than normal physiological corneal thickness due to
Posterior keratoplasty may be done by two methods. In the first
edema. Tissue deturgescence is done prior to preparing the donor
method, a corneal flap is created using a microkeratome (as in
button to avoid a thinner donor stromal button than intended and
LASIK) and posterior stromal tissue is excised (by trephination).
resultant postoperative corneal flattening. A dedicated artificial
A donor button is similarly prepared (using a microkeratome and
anterior chamber (Bausch and Lomb, Rochester, NY or Storz,
artificial anterior chamber), transplanted and secured with
Heidelberg, Germany) is used to prepare the donor stromal
sutures. The host corneal flap is repositioned and sutured.5,6
button. A microkeratome (Automated Corneal Shaper or
In the second method, a deep stromal pocket is created across
Hansatome, Bausch and Lomb, Rochester, NY or Storz,
the cornea through a superior scleral incision. A custom-made
Heidelberg, Germany) is allowed to course across the donor
flat trephine is inserted into the stromal pocket to excise a
tissue without the stop to create an 8.5-9.5 mm diameter 160-
posterior lamellar disk. A ‘same size’ donor posterior disk is
180 μm thick anterior corneal cap (Fig. 22.1A). The anterior
transplanted, without suture fixation. The scleral incision is
corneal free cap is discarded. Next the donor cornea is placed
sutured. 7-9
on a Teflon or Kaufman trephine block with the endothelial side
MICROKERATOME-ASSISTED up, and a 6-8 mm trephine is used to punch the donor stromal
POSTERIOR KERATOPLASTY button (Fig. 22.1B).

Postoperative interface opacity due to stromal scarring is one Host Bed Preparation
of the major problems after lamellar keratoplasty using manual A hinged anterior corneal flap (8.5-9.5 mm in diameter and 160-
dissection. Soong et al have reported postoperative visual acuity 180 mm in thickness) is created using a microkeratome
164
(Fig. 22.1C). A 6-8 mm trephine is used to perform a full • Because only the posterior layers of the cornea are
thickness trephination to excise the diseased posterior layers transplanted, it may be possible to use infantile tissue of
(posterior stroma, Descemet’s membrane and endothelium) of excellent quality that may not be suitable for penetrating
the host central cornea (Fig. 22.1D). A viscoelastic substance is keratoplasty because of the risk of ectasia.
placed in the anterior chamber.
Advantages of creating a hinged corneal flap using a Transplantation
microkeratome: The donor stromal button is transplanted onto the host bed and

Chapter 22: New Lamellar Keratoplasty Techniques: Posterior Keratoplasty and Deep Lamellar Keratoplasty
• Interface scarring is minimal or almost absent after secured to the surrounding host cornea using interrupted non-
microkeratome dissection. The use of a microkeratome for absorbable (10-0 nylon) sutures or a running 8-bite antitorque
similar stromal dissection in posterior keratoplasty may 8-0 polygalactin suture (Fig. 22.1E). The hinged anterior corneal
reduce the interface scarring. flap is refloated over the donor stromal button and allowed to
• The incidence of postoperative epithelial defects and seal into place (Fig. 22.1F). Sutures (8-bite running or interrupted
abnormalities and epithelial rejection may be reduced as the 10-0 nylon) or a bandage contact lens may be used to secure the
hinged corneal flap is lined with patient’s own epithelium. corneal flap. Sutures are used to secure the donor stromal button
• The hinged corneal flap allows improved postoperative re- in order to avoid potential risks of aqueous leak (double anterior
apposition (as in LASIK procedure) and creates an optically chamber), and to allow better apposition of the graft.
smoother corneal surface. Postoperatively, argon laser may be used to cut the intrastromal
• The flap is amenable to relifting for suture removal and sutures. Selective suture cutting with the laser may be used to
excimer laser photorefractive keratectomy (PRK) done over reduce astigmatism without lifting the flap. Suture removal may
the posterior button may correct the residual refractive errors. also be done using a sharp blade or needle after flap elevation.

Outcome
We have reported the results of our technique of microkeratome-
assisted posterior keratoplasty performed in June 1996 in a
patient with pseudophakic bullous keratopathy.5 At 6 months
postoperative follow-up, the corneal topography revealed an
extremely flattened cornea, manifest refraction of +16 D sphere
and best spectacle corrected visual acuity of 20/50. At two-year
follow-up visit the uncorrected visual acuity was 20/100, and
the graft-host interface showed evidence of mild haze.
Preliminary results of the technique of posterior keratoplasty
in seven patients with aphakic bullous keratopathy, pseudophakic
bullous keratopathy, or Fuchs’ corneal dystrophy have been
reported by Busin et al (which they termed ‘endokeratoplasty).7
All patients underwent surgery using a 160 mm thick and 9.5
mm diameter with an automated microkeratome (Fig. 22.2A).
The underlying 6.5 mm button of deep stroma and endothelium
was excised (Fig. 22.2B). A 7.0 mm donor button was grafted
and anchored with a 8-bite continuous running suture. The flap
Figures 22.1A to F: Microkeratome-assisted posterior was then reposited and sutured with a 10-0 running nylon suture
keratoplasty technique. Schematic diagram showing donor
(Fig. 22.2C) The follow- up time ranged from 5-7 months. After
preparation (A and B), recipient bed preparation (C and D), and
transplantation (E and F): surgery all corneas were clear, and the surface re-epithelialized
A. Donor lenticule is excised using a microkeratome and a within 4 weeks. As early as 1 month after surgery useful
dedicated artificial chamber and discarded. uncorrected vision of at least 20/400 was achieved in each patient
B. Donor cornea is placed endothelial side up on a teflon block and the best spectacle-corrected visual acuity ranged between
and a trephine is used to punch a donor stromal button (red). 20/100 and 20/40. Patients with vision less than 20/60 had
C. Hinged anterior stromal flap is created in the host cornea
previous retinal detachment and cystoid macular edema. At
using a microkeratome and lifted.
D. A trephine is used to excise the posterior host stroma and 1 month following surgery, the refraction showed a myopic
endothelium. spherical equivalent between –1.00 D and –4.00 D. The mean
E. The donor stromal button (red) is transplanted onto the host keratometric readings ranged from 45.25 D to 48.50 D and the
bed (green) and secured using sutures (black). astigmatic error was within 4.00 D in all cases (Fig. 22.2D).
F. The host corneal flap is refloated over the transplanted donor
Epithelial interface ingrowth with extensive melting of the
button
(Copyright permission from Jain S, Azar DT. New lamellar corneal flap was observed in one patient 3 months after surgery
keratoplasty techniques: posterior keratoplasty and deep lamellar and was managed by removal of the flap and resuturing of the
keratoplasty. Curr Opin Ophthalmol. 2001;12(4):262-8.) donor button.
165
is made, and with a custom made spatula a stromal pocket is
dissected across the cornea at 60 percent depth, using the air-
to-endothelial interface as a reference plane for dissection depth.
A plastic strip is inserted into the pocket, and a corneoscleral
rim gently excised from the whole globe. The rim is mounted
endothelial side up onto a punch block and with a 7.0-7.5 mm
trephine, a full-thickness corneal button is excised. The button
Section IV: Lamellar Keratoplasty

is placed endothelial side down onto a custom-made spoon-


shaped glide covered with a viscoelastic substance. Then the
anterior lamella and the plastic strip are removed, so that a
posterior lamellar disc is in situ on the glide.
This technique of donor button preparation has been
modified by Terry et al.9 In place of the whole eyes, corneoscleral
rims are used. The donor corneoscleral rim is mounted in an
Figures 22.2A to D: Posterior lamellar keratoplasty artificial anterior chamber with Healon and Optisol-GS solution
(endokeratoplasty) (Chiron, Irvine, CA) after forming a deep lamellar pocket, the
A. Hinged flap retracted superiorly.
B. Exposure of the anterior chamber after removal of host button
tissue is removed from the artificial anterior chamber. A donor
(deep stroma and endothelium). punch is used to cut the central 7.5 mm diameter donor button.
C. Corneal flap sutured back into place after donor button is The endothelial donor disk is separated from the rest of the
transplanted anterior donor button and placed endothelial side down onto a
D. Corneal topography 1 month postoperatively shows regular healon-coated Ousley insertion spatula.
astigmatism of 3 diopters
(Copyright permission from Jain S, Azar DT. New lamellar
keratoplasty techniques: posterior keratoplasty and deep lamellar
Host Bed Preparation
keratoplasty. Curr Opin Ophthalmol 2001;12(4):262-8.) The anterior chamber is completely filled with air. The superior
conjunctiva is opened, and a 9.0 mm partial thickness scleral
A technique of endothelial lamellar keratoplasty in human incision is made (Fig. 22.3A). A stromal pocket is dissected
cadaver eyes using the microkeratome to create the host and across the cornea at 80 percent stromal depth, using the air-to-
donor tissues has also been reported.10 Battle et al later presented endothelium interface as reference plane for dissection depth
a modification of this technique of endothelial lamellar (Fig. 22.3B). A custom made, 7.0-7.5 mm diameter flat trephine
keratoplasty in which the donor button is prepared by sequential is inserted into the pocket to excise the posterior lamellar disk
ablation of epithelium and stroma of the donor cornea. Visual (Fig. 22.3C). Following perforation, remaining posterior corneal
acuity of 20/40 and 20/50 was reported twelve months after tissue is cut with the custom-made microscissors, and excised
endothelial lamellar keratoplasty in two patients with (Fig. 22.3D). This posterior disk is removed from the eye with
pseudophakic bullous keratopathy and Fuchs’ dystrophy. The use fine forceps (Fig. 22.3E).
of the excimer laser to create the donor button along with Terry et al have used a similar technique to prepare the host
intraoperative pachymetry improves the accuracy of matching bed.9 The scleral incision is made with a diamond knife parallel
donor and recipient tissue thickness. and 1.0 mm peripheral to the superior limbus. The depth is set
Postoperative shallow/flat anterior chamber occurs if the at 0.35 mm. The deep lamellar pocket is created over entire
donor stromal button is thinner than intended. The thickness of cornea, limbus-to-limbus, starting with a crescent blade and
donor tissue in the corneal preservation media is greater than followed by specialized instruments: a straight Devers dissector
the normal physiological corneal thickness because of edema. and a curved Devers dissector. Intralamellar trephination is
If the tissue deturgescence is not done before the donor button performed using the Terry trephine.
is prepared, thinner than intended donor stromal button may
result postoperatively, causing corneal flattening. Transplantation
The donor posterior disk is introduced into the recipient stromal
POSTERIOR LAMELLAR KERATOPLASTY
pocket (Fig. 22.3F), and the ‘same-size’ disk is slid into the
THROUGH A SCLEROCORNEAL
recipient posterior opening (Fig. 22.3G). The scleral incision is
POCKET INCISION
closed with 10-0 monofilament nylon sutures (Fig. 22.3H). An
Surgical Technique 7 air bubble, with a diameter of 75 percent of the graft diameter,
is left in place to temporarily support the donor tissue.
Donor Stromal Button Preparation
Outcome
Whole human eye bank eyes are mounted on a custom-made
eye holder. Through a paracentesis, the anterior chamber is The preliminary results of the surgical technique of posterior
166 completely filled with air. A 4.0 mm peripheral corneal incision lamellar keratoplasty (transplantation of posterior corneal tissue
The follow-up period was 6 months. At 6 months follow-up, best
spectacle corrected visual acuity was 20/40 with less than 2.00 D
of astigmatism. The keratometric power was 45.3 D and 43.3 D.
The pachymetry was 573 mm and 618 mm. Graft endothelial
cell count was 1,692 cells/mm2 and 2,631 cells/mm2.

DEEP LAMELLAR KERATOPLASTY

Chapter 22: New Lamellar Keratoplasty Techniques: Posterior Keratoplasty and Deep Lamellar Keratoplasty
Deep lamellar keratoplasty is a surgical technique of lamellar
keratoplasty for treating patients with corneal stromal disease
and normal endothelium.13 This surgical technique involves
Figures 22.3A to H: Diagrammatic representation of posterior resecting or ablating the host stromal pathology (leaving the
lamellar keratoplasty through sclerocorneal pocket incision Descemet’s membrane and endothelium intact), and transplanting
A. Partial thickness scleral incision. a complementary donor stromal button. Sugita et al reported
B. Stromal pocket dissection with a spatula across the cornea.
dramatic improvement of average visual acuity after deep stromal
C. Posterior corneal trephination to excise a posterior lamellar
disk. lamellar keratoplasty in 106 patients (20/200 preoperatively and
D. Stromal tissue cutting with a microscissors. 20/30 postoperatively) but noted that Descemet’s membrane was
E. Removal of the posterior disk from host cornea. punctured in 39 percent of eyes.14 Their technique involved an
F. Insertion of donor posterior disk on a glide. initial trephination of the cornea to three-quarters of its depth,
G. Removal of the spoon after positioning of the donor tissue. followed by lamellar keratectomy aided by hydrodelamination.
H. Suturing of scleral incision.
(Copyright permission from Jain S, Azar DT. New lamellar
Melles et al have performed deep stromal lamellar keratoplasty
keratoplasty techniques: posterior keratoplasty and deep lamellar in seven patients and observed astigmatism ranging from 1 to
keratoplasty. Curr Opin Ophthalmol. 2001;12(4):262-8.) 3.5 diopters.15 Their technique involved filling the anterior
chamber with air and lamellar dissection to create a stromal
pocket across the cornea just superficial to the Descemet’s
through a sclerocorneal pocket incision for corneal endothelial membrane using a custom made dissection blade.
disorders) has been reported by Melles et al. Patients with However, the most important limitations of deep LK are the
pseudophakic bullous keratopathy or Fuchs’ dystrophy were presence of residual irregular edges at the outer dissection border
included.7 In seven sighted human eyes, a deep stromal pocket close to Descemet’s membrane, and the risk of Descemet’s
was created at 80 percent depth across the cornea through a 9.0 microperforation. Several techniques have been used to
mm superior scleral incision. In order to obtain the appropriate overcome these limitations. Archila used an injection of 1 cc of
stromal dissection depth, the anterior chamber was filled with air into the corneal stroma to facilitate the dissection of lamellae
air, and the air-to-endothelial interface was used as a reference close to Descemet’s membrane.16 Tsubota et al used intrastromal
plane for dissection depth. A 7.0 or 7.5 mm diameter, posterior air and water injection coupled with a divide-and-conquer
lamellar disk was excised and replaced by a ‘same size’ donor technique to obtain better lamellar dissection.17 Sugita et al
posterior disk, without suture fixation. The scleral incision was injected saline solution in the deep stroma using a blunt 27-gauge
sutured. Six to twelve months after surgery, all transplants were needle, which produced whitening and swelling of collagen fibers
clear and in position. Best spectacle-corrected visual acuity was and facilitated deeper stromal dissection.14 Melles et al used a
limited by preexisting maculopathies in two eyes and varied from viscoelastic injection into a posterior stromal pocket to create a
20/80 to 20/20. The mean postoperative astigmatism was 1.54 “pseudo-anterior chamber” in order to protect the posterior
+/- 0.81 D, mean pachymetry was 0.49 μm +/- 0.09 μm, and the corneal tissues during trephination and to facilitate stromal
mean postoperative endothelial cell density was 2520 +/- 340 dissection.18 Manche et al have used a similar technique of deep
cells/mm2. Intraopertive complication included the occurrence lamellar dissection using a viscoelastic substance.19
of a microperforation during stromal pocket dissection in the We have reported technique of deep lamellar keratoplasty
eye. wherein a microkeratome is used to create a hinged anterior
Terry et al reported the preliminary results of their technique stromal flap in the host cornea, and the diseased stroma is
of posterior keratoplasty (which they termed ‘deep lamellar resected or ablated.12 A complementary donor stromal button,
endothelial keratoplasty) in two patients with pseudophakia and prepared using a microkeratome and an artificial anterior
Fuchs’ corneal dystrophy.9 A deep stromal pocket was created, chamber, is transplanted prior to repositioning of the flap. This
limbus-to-limbus over the cornea through a 9.0 mm superior technique may be useful in corneal stromal dystrophies and
scleral incision. The anterior chamber was filled with air, and stromal scarring secondary to traumatic, inflammatory or
the air-to-endothelial interface was used as a reference plane for infectious causes. It has the advantage of the preservation of the
dissection depth. A 7.5 mm diameter posterior lamellar disk was host epithelium and endothelium, which reduces the risk of graft
excised and replaced by a ‘same diameter’ endothelial donor rejection as well as reduced astigmatism and surface
disk, without suture fixation. The scleral incision was sutured. irregularities.
167
MICROKERATOME-ASSISTED lamellae covering the Descemet’s membrane are removed using
DEEP LAMELLAR KERATOPLASTY microscissors. If the corneal pathology is limited to the mid-
stroma, excimer laser ablation can be used to remove diseased
A microkeratome is used to dissect a hinged anterior corneal
cornea avoiding the posterior stromal manipulations.
flap, measuring 8.5-9.5 mm in diameter and 130-180 μm in
The donor stromal button is prepared using a dedicated
thickness (Fig. 22.4).12 The hinged anterior corneal flap is
artificial anterior chamber. A microkeratome is used to dissect a
temporarily elevated and the thickness of the residual stroma
110 mm anterior corneal cap. The microkeratome is allowed to
(host resection bed) is measured using a pachymeter. The
Section IV: Lamellar Keratoplasty

course across the donor tissue without the stop, thus an 8.5 mm
recipient hinged anterior corneal flap is elevated with a flat
anterior corneal free cap is created (which is discarded). The
spatula, exposing the underlying stroma. A 6 mm trephine is used
donor anterior corneal cap is made thinner than the recipient’s
to perform a partial thickness trephination. The depth of the
hinged corneal flap so that the remaining donor stroma is of
trephination is set at approximately 90 percent of the previously
sufficient thickness to allow for a second microkeratome pass
performed pachymetry. Lamellar keratectomy is then performed.
(which creates an 8.5 mm donor stromal lenticule). The thickness
Air, saline or viscoelastic material may be injected into the
of the donor stromal lenticule resected by the second
corneal stroma prior to trephination to facilitate lamellar
microkeratome pass is determined by choosing a plate similar
keratectomy. Lamellar dissection is initiated from the partial-
in depth to the thickness of the host resection bed. A 6 mm
thickness trephine incision using a spatulated dissector blade.
trephine is then used to punch the donor stromal lenticule to
Once the plane of dissection is established at the depth of
create the donor stromal button.
trephine incision, further dissection is performed with to-and-
The donor stromal button is then transplanted onto the host
fro movements of the spatula in order to split the corneal stroma
bed. The hinged anterior corneal flap is laid back over the donor
delimited by the trephine mark. This lamellar dissection removes
stromal button and allowed to seal into place. Sutures are placed
a layer of deep stromal corneal tissue. The remaining stromal
to secure the corneal flap. Alternatively a bandage contact lens
may be used.

REFERENCES
1. Rodriguez-Barrios R. The treatment of Fuchs’ dystrophy with
posterior lamellar keratoplasty. In: Pollack FM editor. First Inter-
American Symposium on Corneal and External Diseases of the
Eye. Springfield, Charles C Thomas, 1970;247-57.
2. Melles GR, Remeijer L, Geerards AJ, Beekhuis WH. The future
of lamellar keratoplasty. Curr Opin Ophthalmol 1999;10:253-59.
3. Melles GR, Eggink FA, Lander F, et al. A surgical technique for
posterior lamellar keratoplasty. Cornea 1998;17:618-26.
4. Melles GR, Lander F, Beekhuis WH, Remeijer L, Binder PS.
Posterior lamellar keratoplasty for a case of pseudophakic bullous
keratopathy. Am J Ophthalmol 1999;127:340-41.
5. Azar DT, Jain S, Sambursky R, Strauss L. Microkeratome-assisted
posterior keratoplasty. J Cataract Refract Surg 2001;27:353-56.
Figure 22.4: Microkeratome-assisted deep lamellar keratoplasty 6. Busin M, Arffa RC, Sebastiani A. Endokeratoplasty as an alter-
technique. Schematic diagram shown recipient bed preparation native to penetrating keratoplasty for the surgical treatment of
(Steps 1 and 2), donor preparation (Steps 3 and 4) and diseased endothelium: initial results. Ophthalmology
transplantation (Steps 5 and 6): 2000;107:2077-82.
Step 1: A hinged anterior stromal flap is created in the host cornea 7. Melles GR, Lander F, van Dooren BT, Pels E, Beekhuis WH.
using a microkeratome and lifted. Preliminary clinical results of posterior lamellar keratoplasty
Step 2: Partial-thickness trephination (90% depth) is followed by
through a sclerocorneal pocket incision. Ophthalmology
lamellar dissection to remove the diseased host stromal tissue
2000;107:1850-56.
overlying Descemet’s membrane.
8. Terry MA, Ousley PJ. Endothelial replacement without surface
Step 3: A donor lenticule is created using a microkeratome and
corneal incisions or sutures: topography of the deep lamellar
a dedicated artificial anterior chamber.
Step 4: A trephine is used to punch the donor stromal lenticule endothelial keratoplasty procedure. Cornea 2001;20:14-18.
to create a donor stromal button (red). 9. Terry MA, Ousley PJ. Deep lamellar endothelial keratoplasty in
Step 5: The donor stromal button (red) is transplanted onto the the first United States patients. Early clinical results. Cornea
host bed. 2001;20:239-43.
Step 6: The hinged anterior stromal flap is repositioned and 10. Jones DT, Culbertson WW. Endothelial lamellar keratoplasty
sutured. (ELK). Invest Ophthalmol Vis Sci. 1998;39:S76.
(Copyright permission from Jain S, Azar DT. New lamellar 11. Soong HK, Katz DG, Farjo AA, Sugar A, Meyer RF. Central
keratoplasty techniques: posterior keratoplasty and deep lamellar lamellar keratoplasty for optical indications. Cornea 1999;18:249-
keratoplasty. Curr Opin Ophthalmol 2001;12(4):262-8.) 56.

168
12. Azar DT, Jain S, Sambursky R. A new surgical technique of 16. Archila EA. Deep lamellar keratoplasty dissection of host tissue
microkeratome-assisted deep lamellar keratoplasty with a hinged with intrastromal air injection. Cornea 1984/1985;3:217-18.
flap. Arch Ophthalmol 2000;118:1112-15. 17. Tsubota K, Kaido M, Monden Y, Satake Y, Bissen-Miyajima H,
13. Haimovici R, Culbertson WW. Optical lamellar keratoplasty using Shimazaki J. A new surgical technique for deep lamellar
the Barraquer microkeratome. Refract Corneal Surg 1991;7:42- keratoplasty with single running suture adjustment. Am J
45. Ophthalmol 19981998126:1-8.
14. Sugita J, Kondo J. Deep lamellar keratoplasty with complete 18. Melles GR, Remeijer L, Geerards AJ, Beekhuis WH. A quick
removal of pathological stroma for vision improvement.Br J surgical technique for deep, anterior lamellar keratoplasty using

Chapter 22: New Lamellar Keratoplasty Techniques: Posterior Keratoplasty and Deep Lamellar Keratoplasty
Ophthalmol 1997;81:184-88. visco-dissection. Cornea 2000;19:427-32.
15. Melles GR, Lander F, Rietveld FJ, Remeijer L, Beekhuis WU, 19. Manche EE, Holland GN, Maloney RK. Deep lamellar
Binder PS. A new surgical technique for deep stromal, anterior keratoplasty using viscoelastic dissection. Arch Ophthalmol
lamellar keratoplasty. Br J Ophthalmol 1999;83:327-33. 1999;117:1561-65.

169
23
Section IV: Lamellar Keratoplasty

Deep Anterior Lamellar Keratoplasty:


Melles Technique
Gerrit RJ Melles, Fred Eggink

Anterior lamellar keratoplasty is a surgical procedure in which the dissection could be completed in the event of a micro-
a maximum of diseased corneal stroma is replaced by donor perforation, or aborted until a planned penetrating keratoplasty
tissue. Commonly, the anterior stroma is incised with a trephine can be performed.
that can be set to a depth not exceeding the corneal thickness,
and several stromal layers may be dissected until the desired OPTICAL VISUALIZATION OF DISSECTION
depth of the recipient bed is obtained. Lamellar dissections, for DEPTH DURING SURGERY
example in lamellar keratoplasty, are generally made by
To my knowledge, no surgical technique other than intraoperative
removing stromal tissue ‘layer for layer’, while the depth of the
slit-beam observation has been described to visualize the depth
dissection is judged by the changing tissue structure with deeper
of a corneal incision or a lamellar stromal dissection during
stromal beds.
surgery. To safely obtain deep dissections, a diamond knife
Compared to a penetrating keratoplasty, a lamellar procedure
equipped with a micrometer may be used to avoid corneal
has the advantage of avoiding most complications associated with
perforation, and the dissection may be extended from the bottom
‘open sky’ surgery, easier postoperative management, and less
of a keratotomy wound made at planned depth.
risk of allograft rejection and other long-term complications.
Despite these benefits, surgeons commonly perform a penetrating During surgery, the depth of corneal incisions and lamellar
keratoplasty for anterior corneal disorders, because the latter dissections relative to the corneal thickness may be visualized
technique is easier to perform, and lamellar transplants often by creating an optical interface at the posterior corneal surface.1
show decreased best corrected visual acuity due to irregular For this purpose, the anterior chamber may be filled with a liquid
astigmatism and/or scarring at the donor-to-recipient interface. or gas of which the refractive index differs from the cornea, for
Less scarring may occur with deeper, i.e. smoother example air. With a complete air fill of the anterior chamber,
keratectomies, and techniques such as air injection in, and the interface between the air and the corneal endothelium, i.e.
hydrodelamination or photoablation of the posterior stroma have the posterior corneal surface, was found to be useable a reference
been advocated to obtain a deep recipient stromal bed. plane in four ways.1,2
With all of these techniques, the stromal dissection depth First, the air bubble in the anterior chamber acted as a convex
relative to the corneal thickness cannot be optically visualized. mirror, so that a blade held against the anterior corneal surface
The posterior corneal surface is ‘invisible’ through an operating was reflected at the posterior corneal surface (‘Mirror effect’;
microscope, due to the small difference in the refractive index Figs 23.1A and 23.2). Because the corneal thickness was half
between corneal tissue and aqueous. Lamellar dissection the distance between the tip of the blade and its virtual image
techniques therefore bear the risk of inadvertent perforation, from the posterior corneal surface, it could be estimated how
when deeper dissections are intended. If perforation occurs, deep the blade had to be inserted into the stroma to obtain the
completion of the stromal dissection can be difficult, so that the desired incision depth. Because the cornea is very thin relative
donor button may have to be sutured into an imperfectly prepared to the surgical working distance, i.e. the surgical instrument was
recipient bed. When conversion of the procedure into a held very close to the reflective mirror plane, the minifying effect
penetrating keratoplasty is required, donor tissue with good of the convex ‘air bubble’ mirror may be negligible.
quality endothelium may not be available. Second, at the air-to-endothelium interface a semi-circular,
Anterior lamellar keratoplasty may become a more feasible specular light-reflex was created near the tip of the blade, by
and less complicated surgical procedure, if a stromal dissection the indentation of the tissue during the performance of an incision
could be made at a visually controlled depth during surgery, and (‘Indentation effect’; Figs 23.1B and 23.3A to F). The amount
170
Chapter 23: Deep Anterior Lamellar Keratoplasty: Melles Technique
Figure 23.2: ‘Mirror effect’. In an eye that has the anterior
chamber completely filled with air, two mirror images of the blade
are visible, one reflection from the anterior corneal surface (1)
and one from the posterior surface (2). The dotted line indicates
the approximate location of the plane of reflection, i.e. the
posterior surface. Thus, the estimated corneal thickness (arrows)
is half the distance between the blade tip and its reflection from
the posterior corneal surface (2). (Copyright permission from
Melles GRJ, Rietveld FJR, Beekhuis WH, Binder PS. A technique
to visualize corneal incision and lamellar dissection depth during
surgery. Cornea 1999;18:80-86)

of nonincised corneal tissue between the tip of the blade and


the light-reflex was seen as a dark band directly surrounding the
blade tip, i.e. the nonreflective tissue between the blade tip and
the air-to-endothelium interface.
The thickness of the dark band decreased with advancement
of the blade into the deeper stromal layers, so that the achieved
incision depth could be judged from comparing the thickness of
the nonreflective dark band (the nonincised tissue underneath
the tip of the blade) to the total corneal thickness. The distance
between the blade tip and the light-reflex, i.e. the amount of
nonincised corneal tissue relative to the corneal thickness was
used as a measure of relative incision depth. Thus, the
Figures 23.1A to C: Diagrammatic representation of three optical ‘indentation effect’ could be used to monitor the depth of the
effects used to visualize the corneal thickness and the relative blade while an incision or dissection was made.
depth of corneal incisions and dissections during surgery. (A)
Third, when the blade approached the posterior surface, small
‘Mirror effect’. When the anterior chamber is filled with air, both
the anterior and posterior corneal surfaces act as a convex mirror, folds in the posterior corneal tissue were seen (‘Folding effect’;
and two virtual images are produced when a blade is held against Figs 23.1C and 23.4). The number, width and motility of the
the cornea. Note that the corneal thickness is half the distance folds increased with deeper blade depth, and could be used as
between the tip of the blade and its reflection from the posterior indicators of how close the blade was to the posterior corneal
corneal surface. Compare to Figure 23.2. (B) ‘Indentation effect’. surface. The folds were accentuated by the air in the anterior
At the air-to-endothelium interface, a specular light-reflex is
chamber, and the number, width and motility of the folds was
created by the indentation of the stroma during the performance
of an incision. The nonincised posterior corneal tissue is seen found to indicate how close the blade tip was to Descemet’s
as a ‘dark band’ between the blade tip and the light-reflex. membrane. Hence, the ‘folding effect’ could be used to avoid
Compare to Figure 23.3. (C) ‘Folding effect’. As the blade perforation with deep incisions or dissections.
approaches the posterior corneal surface, small folds are Fourth, when a dissection is made to approximately
produced in the nonincised posterior corneal tissue in front of
95-98 percent corneal depth, the posterior layer obtains a ‘moon-
the blade. Compare to Figure 23.4 (Copyright permission from
Melles GRJ, Rietveld FJR, Beekhuis WH, Binder PS. A technique surface appearance’ (closely resembling abundant guttata, while
to visualize corneal incision and lamellar dissection depth during guttata are actually absent), possibly resulting from a reflection
surgery. Cornea 1999;18:80-86) of the endothelial cell layer.
171
Section IV: Lamellar Keratoplasty

Figures 23.3A to I: ‘Indentation effect’. Clinical, macroscopic, and light microscopic pictures of lamellar dissections made at an
intended depth of (A to C) 60 percent, (D to F) 80 percent, and (G to I) 99 percent. A ‘dark band’ is visible between the blade tip
(arrow) and the semicircular light-reflex at the air-to-endothelium interface (open arrow). Note how the amount of nonincised tissue
underneath the blade tip in A, D and G compares to the dissection depth in B/C, E/F and H/I. Thus, the achieved dissection depth
(thick arrows) can be estimated by the thickness of the dark band adjacent to the blade tip. See Figure 23.1B. (Copyright permission
from Melles GRJ, Rietveld FJR, Beekhuis WH, Binder PS. A technique to visualize corneal incision and lamellar dissection depth
during surgery. Cornea 1999;18:80-86)

To determine if these optical effects could be used to estimate A custom made dissection blade (DORC, Zuidland, NL) was
the achieved corneal depth during surgery, lamellar dissections introduced just within the superior limbus. The tip of the blade
were made in fresh porcine eyes obtained less than three hours was tilted slightly downward, to create a semicircular, specular
post-mortem. Each globe was placed in an eye-holder to light-reflex at the air-to-endothelium interface (Figs 23.1B and
immobilize the posterior globe and to control the intraocular 23.3A to I). When the tip of the blade appeared to have reached
pressure. The epithelium was gently removed with a cellulose the desired stromal depth, the blade was positioned parallel to
spounge. A self sealing side port was made at the 9 o’clock the posterior corneal surface, and a stromal dissection was made
limbus, and with a blunt cannula the aqueous was aspirated and across the cornea. Using the optical effects described above,
the anterior chamber was completely filled with air. dissections were made at an intended depth of 60 percent, 80
percent, or 99 percent of corneal thickness.

172
In conclusion, an air-to-endothelium optical interface can be
used to visualize the corneal thickness and the relative depth of
a dissection knife within the stroma during surgery, and with the
optical effects described dissections can be made to
approximately the desired corneal depth.

STRATEGY TO MINIMIZE INTERFACE HAZE

Chapter 23: Deep Anterior Lamellar Keratoplasty: Melles Technique


Interface haze has been described to occur frequently after
anterior lamellar keratoplasty. Opacification at the donor-to-recipient
interface may be one of the major drawbacks of the procedure,
since it may result in reduced best corrected visual acuity and
contrast sensitivity.3 To my knowledge, no histological reports
are available to define the cause(s) of interface haze after lamellar
keratoplasty.
In laser in situ keratomileusis (LASIK) the lamellar interface
Figure 23.4: ‘Folding effect’. Small folds in the posterior corneal usually shows minimal interface opacification, if any. Also, in
tissue are visible adjacent to the tip of a dissection blade that
automated lamellar keratoplasty (ALK), haze formation is most
approaches the posterior corneal surface (Copyright permission
from Melles GRJ, Rietveld FJR, Beekhuis WH, Binder PS. A often minimal at the interface between the donor and recipient
technique to visualize corneal incision and lamellar dissection tissues. These observations suggest that the presence of a lamellar
depth during surgery. Cornea 1999;18:80-86) interface by itself may not cause interface opacification, but that
the method of dissection is decisive. Apparently, microkeratome
dissection produces far less amounts of interface opacification
Relative lamellar stromal dissection depth averaged 58.3 in comparison to manual stromal dissection, probably because
percent (sd ± 9.4%) in eyes with lamellar dissections made at a smoother cut is obtained by the oscillating blade of a
60 percent intended depth; 81.1 percent (± 3.4%) in eyes with microkeratome than by manual dissection.
dissections made at 80 percent intended depth, and 94.4 percent Textbooks on lamellar keratoplasty advocate to dissect the
(± 1.5%) in eyes with dissections made at 99 percent intended recipient bed by lifting the anterior corneal lamella upward,
depth (Figs 23.3A to I). During surgery and in the light thereby stretching the interlamellar adhesions and cutting the
microscopy specimens, no microperforations were seen. adhesions with a various dissection blades. Blunt spatula
With the Student-t-test, only the intended dissection depth dissection is most often advocated for preparation of the donor
of 99 percent was not achieved (p=0.02). Because the variances tissue. To evaluate the smoothness of the stromal surfaces with
were not homogeneous across the three intended lamellar these dissection techniques, blunt corneal dissection and sharp
dissections depths (p=0.02), the Kruskal-Wallis test was dissection while lifting the anterior lamella was performed in a
performed, which showed an overall significant difference human eye bank eye model. The histologic appearance of the
between the three intended depths (p=0.002). For pairwise dissections was compared to that of a microkeratome and to sharp
comparisons the Mann-Whitney test was performed, which corneal dissection in a lamellar plane (without lifting the anterior
showed a significant difference between 60 percent and 80 lamella).
percent (p=0.008), and 80 percent and 99 percent (p=0.008) With light microscopy, blunt dissections showed abundant
intended lamellar dissection depths. torn stromal lamellae, with distortion of the parallel orientation
These data show that using the four optical effects described, of the stromal lamellae. Disrupted lamellae and an irregular
lamellar dissections can be made with a good predictability of stromal surface were also seen following sharp dissection while
achieved depth. No microperforations were noted in any of the lifting the anterior corneal lamella. Sharp dissection in a lamellar
stromal dissections. In a series of 25 human donor eyes, a plane better approached the smoothness of a microkeratome
microperforation rate of 12 percent was found with stromal dissection.
dissections made at 99 percent intended depth. In a series of 68 By using dissection techniques commonly advocated in
patient eyes, seven microperforations were encountered. textbooks, a relatively irregular stromal surface may be produced
Apparently, there is relatively low risk of perforation if the in both the donor and recipient tissues. As a result, apposition
depth of the blade is monitored optically while the dissection is of these stromal surfaces may distort the layered structure of the
made, even if extreme deep dissections are attempted. Depth stroma, and subsequent scarring at the interface may add to the
predictability of superficial dissections were not evaluated, since opacification seen clinically.
the ‘indentation effect’ used to estimate the blade depth is Absence of clinically significant interface opacification, i.e.
virtually absent with dissections to an intended depth of less than smoother interfaces in deep lamellar keratoplasty may be
50 percent. The optical effects described may therefore be of obtained by a combination of three factors. First, a custom made
limited use to monitor the depth of shallow corneal incisions. spatula was designed with ultrasharp edges, to create smooth
173
interface in the recipient. Second, an intended dissection depth At this point, the tip of the blade was slightly tilted downward
in the recipient at 95 percent of the stromal thickness may give to visualize the interface between the air bubble in the anterior
a smoother interface. Third, after stripping the Descemet’s chamber and the corneal endothelium; underneath the corneal
membrane from the donor button, the donor posterior stromal ‘dimple’, the air-to-endothelium interface was seen as a specular
interface will be smooth. light-reflex localized at the tip of the blade (Fig. 23.6A). Between
the blade tip and the light-reflex, a non-reflective, dark band was
MANUAL DEEP STROMAL DISSECTION THROUGH seen, representing the nonincised corneal tissue between the
Section IV: Lamellar Keratoplasty

A SCLERAL TUNNEL INCISION blade and the air-to-endothelium interface. Because the dark band
became thinner with advancement of the blade into the deeper
Using the techniques for visualizing stromal dissection depth as
stromal layers, the corneal depth of the blade could be judged
described earlier, deep anterior lamellar keratoplasty procedures
from the thickness of the dark band (Fig. 23.6B).
were performed in a series of 68 patients, after an Institutional
When the tip of the blade appeared to touch the
Review Board-approved informed consent was obtained from
air-to-endothelium light-reflex (Fig. 23.6C), i.e. the posterior
each patient (Fig. 23.5).4,5
corneal surface, the blade was positioned parallel to the posterior
In recipient eyes, a self-sealing side port was made at the
surface, for dissection of a stromal pocket across the cornea, just
9 o’clock limbus, to aspirate the aqueous using a blunt cannula,
anterior to the posterior corneal surface (Figs 23.5A and 23.7A).
and to completely fill the anterior chamber with air. At the
After a deep stromal pocket was created up to the limbus
12 o’clock limbus, the conjunctiva was opened and a superficial
over 360°, the air was removed from the anterior chamber, and
scleral incision was made, 5.0 mm in length, 1 mm outside the
a viscoelastic (Hydroxypropylmethylcellulose, Ocucoat, Storz,
limbus. With a custom made dissection blade (DORC, Zuidland,
Clearwater, FL, USA) was injected through the scleral incision
The Netherlands), a lamellar dissection was made to just within
into the stromal pocket (Figs 23.5B and 23.7B). Thus, the
the superior cornea.
posterior corneal lamella was separated from the overlying
anterior stroma, to avoid perforation of the posterior corneal
surface during trephination. Then, a Hessburg-Barron suction
trephine was centered over the anterior corneal surface
(Fig. 23.7C). The blade was turned downward until the stromal
pocket was just entered, i.e. until viscoelastic was seen to escape
from the pocket through the trephine incision. Remaining,
unincised stromal attachments of the anterior lamella were cut
with curved microscissors, the anterior corneal lamella was
removed, and the recipient bed was thoroughly irrigated to
remove all viscoelastic and debris (Figs 23.5C and 23.7D).
After removal of Descemet’s membrane, the donor button
was transferred to the recipient stromal bed, and the donor and
recipient corneal surfaces were marked with an eight incision
radial keratotomy marker (Fig. 23.7E). The button was sutured
into the recipient bed with two running, 10-0 monofilament nylon
sutures (Alcon, Gorinchem, The Netherlands) (Fig. 23.7F). The
tension of the sutures was adjusted until the anterior, donor
corneal surface reflected a spherical image of a Placido-disk held
about 3 cm above the recipient eye.
After deep lamellar dissection through scleral incision, only
few stromal lamellar are present between storma Descemet’s
membrane (Fig. 23.8).

Figures 23.5A to D: Diagrammatic representation of the deep, VISCODISSECTION OF DESCEMET’S


anterior lamellar keratoplasty technique. (A) After dissection of MEMBRANE FROM THE STROMA
a deep stromal pocket through a scleral incision, (B and C)
viscoelastic is injected into the pocket, and an anterior corneal Using the techniques for visualizing stromal dissection depth as
lamella is trephinated from the recipient cornea. (D) After stripping described earlier, deep anterior lamellar keratoplasty procedures
Descemet’s membrane, a full-thickness donor corneal button is were performed in a series of 8 patients, after an Institutional
sutured into the recipient stromal bed. Compare to Figures 23.2A-
Review Board-approved informed consent was obtained from
C and 23.3A-F (Copyright permission from Melles GRJ, Lander
F, Rietveld FJR, Remeijer L, Beekhius WH, Binder PS: A new each patient.6
surgical technique for deep stromal, anterior lamellar In recipient eyes, a self-sealing side port was made at the
keratoplasty. Br J Ophthalmol 1999;83:327-333) 9 o’clock limbus, to aspirate the aqueous using a blunt cannula,
174
filled with viscoelastic (Hydroxypropylmethylcellulose, Ocucoat,
Storz, Clearwater, FL, USA), was inserted into the stroma and
advanced towards the central cornea (Fig. 23.10A). The intended
depth of the needle was reached by advancing the needle toward
Descemet’s membrane, until the dark band inbetween the tip of
the needle and the specular light-reflex at the air-to-endothelium
interface, i.e. the unincised corneal tissue, had disappeared

Chapter 23: Deep Anterior Lamellar Keratoplasty: Melles Technique


(Figs 23.10A, 23.11A and B).
When the tip of the needle appeared to touch the light-reflex,
i.e. the posterior corneal surface, viscoelastic was injected into
the cornea, to separate Descemet’s membrane from the overlying
posterior stroma (Figs 23.10B and 23.11C). After a corneal
pocket filled with viscoelastic was created, approximately
9.0 mm in diameter, a 7.0 or 7.5 mm Hessburg-Barron suction
trephine was centered over the anterior corneal surface (Figs
23.10C and 23.11D). The trephine blade was turned downward
until the stromal pocket was just entered, i.e. until viscoelastic
was seen to escape from the pocket through the trephine incision.
Remaining, unincised stromal attachments were cut with curved
microscissors, the anterior corneal lamella was removed, and the
recipient bed was thoroughly irrigated to remove all viscoelastic
and debris (Figs 23.10D, 23.11E and F).
After removal of Descemet’s membrane, the donor button
was transferred to the recipient stromal bed, and the donor and
recipient corneal surfaces were marked with an eight incision
radial keratotomy marker. The button was sutured into the
recipient bed with two running, 10-0 monofilament nylon sutures
(Alcon, Gorinchem, The Netherlands). The tension of the sutures
was adjusted until the anterior corneal surface reflected a
spherical image of a Placido-disk held about 3 cm above the
recipient eye.

PREPARATION OF DONOR TISSUE

The posterior surface of the corneoscleral rim was


gently touched with a cellulose sponge (Fig. 23.14A), to damage
or remove the donor endothelium. Trypan blue 0.06 percent in
phosphate buffered sodium chloride (VisionBlue, DORC.
International, The Netherlands) was applied onto the rim to stain
Descemet’s membrane (Fig. 23.14B), and the posterior surface
of the rim was gently swabbed to completely remove the blue
Figures 23.6A to C: Demonstration of the surgical technique in
a human eye bank eye. (A) The anterior chamber has been filled stained Descemet’s membrane and the endothelium
with air. In-between the blade tip and the air-to-endothelial (Fig. 23.14C). Corneoscleral rims were mounted epithelial side
interface light-reflex, a dark band is visible. (B) Because the dark down onto a punch block, and a 0.25 mm oversized donor button
band reflects unincised posterior corneal tissue, the dark band was punched out with a punch trephine (Ophtec, Groningen, The
decreases in width when the blade is advanced into the deeper Netherlands).
stromal layers. (C) When the blade appears to touch the air-to-
endothelium interface, a stromal dissection level just anterior to
SUTURING TECHNIQUE
the posterior corneal surface is reached (Copyright permission
from Melles GRJ, Lander F, Rietveld FJR, Remeijer L, Beekhius For penetrating keratoplasty, multiple suturing techniques have
WH, Binder PS: A new surgical technique for deep stromal
been described. Most often a combination of eight interrupted
anterior lamellar keratoplasty. Br J Ophthalmol 1999;83:327-333)
10-0 nylon sutures and a running 11-0 suture is used, or a single
and to completely fill the anterior chamber with air. The or double running 10-0 nylon suture. The first technique may
air-to-endothelium interface was used to visualize the corneal have the advantage that the astigmatism can be closely monitored
thickness, as has been previously described. At the 12 o’clock by selective suture removal. In addition, suture loosening rarely
midperipheral cornea, a 30-gauge needle attached to a syringe requires secondary surgical intervention, since enough sutures
175
Section IV: Lamellar Keratoplasty

Figures 23.7A to F: Demonstration of the surgical technique in a human eye bank eye. (A) The pocket is dissected first across the
vertical meridian, and then extended sideways up to the limbus over 360 degrees, with the same spatula. Note that the anterior
chamber is completely filled with air, and that the dissection depth can be monitored by the width of the dark band (arrowheads) in-
between the spatula and the air-to-endothelium light-reflex. Note also the wrinkling of the posterior corneal tissue (arrow). (B) After
most air has been removed from the anterior chamber, the stromal pocket is filled with viscoelastic. Note the step-ladder configuration
of the relaxed posterior corneal tissue (arrow) that is pushed downward. (C) After trephination with a Hessburg-Barron trephine (D)
an anterior corneal lamella is excised. Note the smooth recipient bed (asterisk) with some residual posterior stroma overlying the
pupillary border (arrowheads). (E) After stripping Descemet’s membrane, a ‘full-thickness’ donor button (arrow) is placed onto the
recipient bed, and the donor and recipient corneal surfaces are marked with an eight incision radial keratotomy marker. (F) The
donor button sutured in place with two running sutures (Copyright permission from Melles GRJ, Lander F, Rietveld FJR, Remeijer
L, Beekhius WH, Binder PS: A new surgical technique for deep stromal anterior lamellar keratoplasty. Br J Ophthalmol 2000;19:427-
432)
176
Figure 23.8: Light microscopy of a deep lamellar dissection

Chapter 23: Deep Anterior Lamellar Keratoplasty: Melles Technique


through a scleral incision in a human eye bank eye. A deep
stromal dissection level is seen (98% corneal depth). Few stromal
lamellae are visible between the stromal dissection and
Descemet’s membrane (Hematoxylin-eosin, original
magnification × 35 and × 450)

Figures 23.10A to E: Diagrammatic representation of the visco-


dissection deep anterior lamellar keratoplasty technique. (A) After
insertion of a needle into the recipient cornea to just anterior to
Figure 23.9: Slit-lamp photograph six months after DALK. A clear
Descemet’s membrane, (B) viscoelastic is injected to separate
lamellar corneal transplant is visible, with a deep stromal
Descemet’s membrane from the posterior stroma, and (C+D) an
donor-to-recipient interface
anterior corneal lamella is trephinated and excised. (E) After
stripping its Descemet’s membrane, a ‘full-thickness’ donor button
are usually left for fixation of the transplant. Single or double is sutured into the recipient bed. Compare to Figures 23.11A-F
running sutures have the advantages that suture placement is (Copyright permission from Melles GRJ, Remeijer L, Geerards
easier and can be performed faster, and that the astigmatism may AJM, Beekhius WH: A quick surgical technique for deep lamellar
be monitored by suture adjustment. However, suture loosening keratoplasty using viscodissection. Cornea 2000;19:427-432).
may then require additional surgical intervention.
bury the knots at the 12 o’clock position, for unburied knots may
In contrast to penetrating keratoplasty, that requires the
cause continuing discomfort for the patient.
sutures to be in situ for at least one year, the sutures may be
Theoretically, a double running 8-bite 10-0 nylon anti-torc
removed at 4 to 6 months after lamellar keratoplasty. It may
suture may induce little astigmatism, because the forces exerted
therefore be considered to choose a suturing technique that
by each bite are counteracted by an opposing bite. If suture
requires the least surgical time, induces the least amount of
loosening occurs after surgery, the graft is usually fixated well
astigmatism, and provides sufficient fixation of the graft in the
by the remaining suture, and in our series secondary suture
event of inadvertent suture loosening. The suturing technique
placement has not been neccessary. Finally, in contrast to a 24-
that fits these criteria best may be a double running 8-bite 10-0
bite running 11-0 suture, removal of an 8-bite running 10-0 suture
nylon anti-torc suture (Figs 23.9 and 23.13).
is easily performed behind the slit lamp.
In deep anterior lamellar keratoplasty, placement of a double
running 8-bite 10-0 nylon anti-torc suture can be performed PERIOPERATIVE TOPICAL AND
quickly and easily, without the need for cardinal fixation sutures. SYSTEMIC THERAPY
After marking four corneal meridians with an eight radial marker,
the needle is placed obliquely in the donor button at an ink mark, A standard therapy regiment for penetrating keratoplasty patients
then inserted into the dissection plane present in the peripheral is gentamicin ointment at the evening before surgery, and after
recipient cornea, and moved upward. Care should be taken to surgery chloramphenicol 0.5 percent three times daily for one 177
Section IV: Lamellar Keratoplasty

Figures 23.11A to F: Preparation of the recipient bed in a human eye bank eye, using the viscodissection lamellar keratoplasty
technique. (A) The anterior chamber has been filled with air. In-between the blade tip and the specular light-reflex at the air-to-
endothelium interface (white open arrow), a dark band is visible, that reflects unincised posterior corneal tissue. (B) The dark band
decreases in width when the needle approaches Descemet’s membrane. (C) After injecting viscoelastic through the needle,
Descemet’s membrane is separated from the posterior stroma and displaced toward the iris. Note the typical reflex (asterisk) that
outlines the pocket (arrows) filled with viscoelastic. (D) After trephination, (E) Viscoelastic escapes from the pocket, and (F) an
anterior corneal lamella (L) is excised while leaving Descemet’s membrane in situ (DM) (Copyright permission from Melles GRJ,
Remeijer L, Geerards AJM, Beekhius WH: A quick surgical technique for deep lamellar keratoplasty using viscodissection. Cornea
2000;19:427-432).

178
Chapter 23: Deep Anterior Lamellar Keratoplasty: Melles Technique
Figures 23.12A and B: Light microscopy of the recipient bed
after viscodissection of Descemet’s membrane in a human eye
bank eye. (A) A dissection level just anterior to Descemet’s
membrane is seen, with complete removal of all stroma. (B) At
higher magnification, some residual stromal strands (arrowheads)
are visible over Descemet’s membrane (arrow); the dotted line
indicates the junction of Descemet’s membrane with the posterior
stroma (original magnification × 10 and × 450) (Copyright
permission from Melles GRJ, Remeijer L, Geerards AJM,
Beekhius WH: A quick surgical technique for deep lamellar
keratoplasty using viscodissection. Cornea 2000;19:427-432)

month, and dexamethasone 0.1 percent six times daily for one
month, tapering to one time daily at one year. In our series of
deep anterior lamellar keratoplasty patients, the same
perioperative therapy regimen was followed. Steroid therapy may
be tapered sooner, because the risk of endothelial allograft
rejection is eliminated.
In patients with recurrent herpetic keratitis acyclovir 400 mg
three times daily was given for six months or more. When
indicated, immunosuppressive therapy was prescribed.
Figures 23.13A and B: Slit lamp photographs three months
after visco-dissected deep anterior lamellar keratoplasty. (A) Note
RIGID GAS PERMEABLE CONTACT LENS FITTING
the characteristic lines in the recipient Descemet’s membrane.
Corneal surface irregularity and/or astigmatism may decrease (B) A clear lamellar transplant is visible, with the donor-to-recipient
interface at the level of Descemet’s membrane (Copyright
best spectacle corrected visual acuity after deep anterior lamellar permission from Melles GRJ, Remeijer L, Geerards AJM,
keratoplasty. The visual acuity may then be improved by fitting Beekhius WH: A quick surgical technique for deep lamellar
a rigid gas permeable (RGP) or soft toric contact lens, a contact keratoplasty using viscodissection. Cornea 2000;19:427-432).
lens and spectacle combination, a piggyback system (a
combination of soft and rigid contact lenses), or a hybrid lens. values may be used to gain a better insight into the entire donor-
A RGP lens may be the most effective, since this type of lens and-host corneal surface areas. A more detailed analysis of the
corrects high degrees of regular and irregular astigmatism and videotopography map may further facilitate the selection of the
has high oxygen permeability.7 base curve, and the entire fitting procedure.
For unoperated corneas, most contact lens fitting methods We hypothesized that the bearing of the contact lens may be
use keratometry values in combination with the fluorescein improved if the dioptric values over the transplant wound were
pattern for selection of the base curve of the initial trial lens. used for selection of the base curve, for two reasons. First, the
After keratoplasty, the central keratometry values may not be elevated wound ridge will always be in touch with the contact
representative for the entire corneal surface area, as in virgin lens, irrespective of the selected base curve (Fig. 23.15). Hence,
corneas. In fact, the radii within the central 3.2 mm optical zone the best possible contact lens bearing over the ridge may be
of a transplanted cornea often show no correlation with the radii expected to give a maximum of comfort in contact lens wearing.
in more peripheral areas of the same cornea. Because a good fit Second, the dioptric values over the wound ridge may be the
depends on the best possible overall support of the contact lens only true values displayed on the videotopography map, because
across the cornea, for transplanted corneas videotopography the algorithm will smoothen out the dioptric values over the
179
Section IV: Lamellar Keratoplasty

Figures 23.14A to C: Removal of the donor Descemet’s membrane as viewed from the endothelial side of a corneoscleral rim. (A)
The posterior surface of the rim is gently touched with a sponge, to damage the endothelium. (B) Trypan blue is applied to stain the
damaged endothelial cells and Descemet’s membrane. (C) The blue stained Descemet’s membrane is stripped from the posterior
stroma by gently swabbing the posterior surface with the sponge. A flap of Descemet’s membrane (asterisks) is visible; the arrowheads
point to the edge of the flap that is still attached to the posterior stroma (Copyright permission from Melles GRJ, Remeijer L,
Geerards AJM, Beekhius WH: A quick surgical technique for deep lamellar keratoplasty using viscodissection. Cornea 2000;19:427-
432).

Figure 23.15: The elevated wound edge (arrows) after deep


anterior lamellar keratoplasty may be the area for contact lens
bearing

central cornea and the wound edge, so that the central area is
displayed too flat. The peripheral cornea is almost never
displayed, because the irregular ring images in this area are
discarded by the software. We therefore decided to choose the
base curve radius of the first trial-lens according to the flattest
dioptric value displayed over the circular transplant wound on Figure 23.16: The ring segments of a topographical image. The
the absolute scale of the videotopography map. double running sutures are in situ. The only area where the
In virgin corneas, the central radius is used for selection of peripheral ring segments over the wound ridge are displayed is
at 2-3 o’clock region. This area was used to select the base
the contact lens base curve, so that the lens power equals the curve radius of the trial lens
spectacle correction calculated back to the corneal plane. With
our technique for lens fitting after deep anterior lamellar
keratoplasty, the base curve is chosen according to the largest the color map (Fig. 23.17) were used to determine the flattest
radius over the transplant wound. Hence, the base curve radius dioptric value displayed over the circular transplant wound. The
may not have any correlation with the central radius of the radius of the dioptric value was used to select the initial trial
transplanted cornea, i.e. the effective corneal power. As a result, lens with an identical base curve/radius.
a large shift in refractive error is induced due to the vault between Example: A 34-year-old female with bilateral keratoconus
the contact lens and the central cornea, i.e. the tear compartment became RGP contact lens intolerant because of corneal ectasia.
that creates a positive tear lens. Her left eye had a preoperative visual acuity of 0.25 with a
Thirteen (26%) patients were referred to the contact lens unit contact lens. Five months after deep anterior lamellar
of our hospital for contact lens fitting, 3.9 (± 1.31) months after keratoplasty, she was referred to the contact lens unit because
surgery. Seven patients had astigmatism of 4 diopters or more, of 4D of irregular astigmatism. Best spectacle corrected visual
and six had an anisometropia of 4D or more. Both the acuity of her left eye was 0.25 with Sph +0.5 C -4.0 x 160. Slit
videotopography (Alcon Eye Map, Alcon Laboratory inc. Fort lamp examination showed a well-centered, clear lamellar
Worth, TX, Software Version 5.50.03) ring map (Fig. 23.16) and transplant with the sutures in situ.
180
Chapter 23: Deep Anterior Lamellar Keratoplasty: Melles Technique
Figure 23.17: The green colored region with a refractive power of 43.69 D is the translation of the tangential measured points of
Figure 23.16. The Dioptric power is pointed out by the cursor. The base curve of the trial-lens is 7.60 mm

On the videotopography ring map and color map (Figs 23.16 (BSCVA) before contact lens fitting was 0.4 (± 0.1), and
and 23.17), the flattest dioptric value of 43.75 D (radius = 7.60 improved to 0.8 (± 0.1) after lens fitting (p < 0.001). None of
mm) over the transplant wound was displayed at three o’clock. the patients developed rejection periods or infiltrates. Progressive
Hence, an initial trial-lens was chosen with a base curve of graft vascularization did occur in one patient 10 months after
7.60 mm, i.e. a radius identical to the flattest area displayed over lens fitting, due to a loose suture. After suture removal, contact
the wound, with an optical zone diameter of 8.5 mm, Sph – 7.5 lens wear could be continued.
and a diameter of 12.0 mm (Fig. 23.18). The visual acuity with The most comfortable lens fit was obtained when the lens
the contact lens was 0.8. Daily wearing time of the contact lens had a slightly superior position and receives support from the
was 16 hours. upper lid, with good movement and a relatively flat fluorescein
The tetra-curved trial set we used consisted of lenses with pattern. During primary gaze, upward gaze and between blinks,
an optical zone of 8.5 millimeter. The first peripheral curve was the upper edge of the lens was retained under the upper lid. The
0.5 mm flatter than the base curve radius and had a diameter of bottom edge of the lens should be above the lower lid but the
10.5 mm. The second peripheral curve was 1.5 mm flatter than edge of the optical zone below the inferior pupillary margin under
the base curve and had an overall diameter of 12.0 mm. The primary gaze circumstances.
edge radius was 12.5 mm. All transitions were soft blended. In Compared to contact lens fitting in virgin corneas, the lens
all cases we used a very high Dk contact lens material such as edge was elevated more than normal to increase the tear
Boston XO (Polymer Technology Corp, Wilmington MA, USA) meniscus. This was acceptable because the upper lid does not
or FluoroPerm 151 (Paragon Vision Sciences, Mesa AZ, USA) have to pass over the lens edge. This concept of lens
to avoid corneal edema. performance, as if the corneal lens was attached to the upper lid
Mean best corrected spectacle correction before contact lens during blinking, may facilitate the tear-flow underneath the lens
fitting averaged Mean best spectacle corrected visual acuity during blinking and eye movements.
181
stromal bed cannot be completed due to inadvertent perforation,
donor tissue with good quality endothelium may not be available
to convert to a penetrating keratoplasty.
A three-step surgical technique is described earlier, to
perform a deep stromal, anterior lamellar keratoplasty procedure,
in which the depth of the dissection relative to the corneal
thickness can be visualized during surgery. The procedure can
Section IV: Lamellar Keratoplasty

be completed in the event of a microperforation, or can be


aborted to perform a planned penetrating keratoplasty. A
refinement of the surgical technique has also been described.
Instead of making a spatula dissection at a deep stromal level
through a scleral incision, a dissection with viscoelastic was
performed just above Descemet’s membrane, using a similar
method to achieve the intended level of dissection depth.
As a first step, a deep stromal, lamellar dissection is made
Figure 23.18: The fluorescein pattern shows bearing of the to a visually controlled depth. Injection of air into the anterior
contact lens over the elevated wound ridge
chamber may facilitate deep stromal dissection for four reasons.
First, because the air-to-endothelium interface reflects the
posterior corneal surface, its specular light-reflex may be used
In summary the principles of the fitting technique are:
as a reference plane for desired dissection depth. Second, small
• Large overall diameters with a minimum of 11.0 millimeters
folds in Descemet’s membrane can be seen during the perfor-
to avoid lens instability and decentration.
mance of deep stromal dissections. When the anterior chamber
• Use the circular wound edge as an alignment zone and have
is filled with air, these folds are accentuated, and the number,
trial lenses with an optical zone diameter of 8.5 millimeters.
width and motility of the folds seem to indicate how close to
• Good clearance in the periphery
Descemet’s membrane the dissection is made. Third,
• A high Dk contact lens material.
microperforations are easily noted during surgery, since a small
RESULTS air bubble is seen to escape from the anterior chamber into the
stromal pocket, and the break in Descemet’s membrane is sharply
outlined over the underlying air bubble. Fourth, in the event of
6 months 12 months
a micro-perforation, the break in Descemet’s membrane is self-
BCVA 0.7 ± 0.2 0.8 ± 0.1 sealing by the air in the anterior chamber, and the dissection may
Astigmatism 2.4 D ± 2.1 D 2.6 D ± 1.6 D be continued without loss of the intraocular pressure.
Pachymetry not done 0.66 ± 0.05 mm As a second step of the procedure, viscoelastic is injected
Endothelial cells not done 2240 ± 475 cells/mm2 into the stromal pocket to displace the entire posterior corneal
surface toward the iris, thereby creating an ‘pseudo-anterior
A micro-perforation occurred in 7 of the 68 (10%) eyes in
chamber’. Because the stromal pocket is made through a self
which manual dissection with a spatula was performed, and in 4
sealing scleral tunnel incision, the viscoelastic remains within
(50%) eyes in which viscodissection was performed. In these
the pocket when pressure is applied onto the anterior corneal
cases the procedure was converted into a penetrating
surface. Thus, a ‘normal’ intraocular pressure can be restored
keratoplasty. In one eye, the interface was later irrigated to
after the injection of viscoelastic into the stromal pocket, and
remove residual viscoelastic.
the anterior, diseased recipient corneal tissue may be excised
with routine trephination techniques, without damage to the
CONCLUSIONS AND RECOMMENDATIONS
posterior corneal surface.
Several lamellar keratoplasty dissection techniques have been In one of our patients, residual viscoelastic remained in the
described.8 One flaw of these techniques is that the depth of the stromal interface after surgery. After removal, the best corrected
stromal dissection cannot be visualized during surgery, and that visual increased from finger counting to 0.4 in the first
the procedures therefore bear the risk of perforation. Another postoperative week. It seems therefore important to completely
flaw is that the recipient bed is created by a ‘layer for layer’ remove all viscoelastic at the recipient stromal bed prior to
removal of corneal tissue. Once started, the procedure must be suturing the donor corneal button in place.
completed as a lamellar or penetrating keratoplasty, although As a third step, a donor button is transplanted into the
donor tissue requirements differ for each of these procedures. recipient bed using standard keratoplasty surgical instruments
In lamellar keratoplasty, a donor corneal lamella is generally and techniques. Since (almost) all stroma is removed, a full-
obtained from a fresh globe with unknown endothelial quality, thickness donor button can be sutured into the recipient opening.
or lyophilized corneal tissue. When the dissection of the recipient When the donor tissue thickness exceeds the depth of the
182
recipient bed, the donor button still fits because the peripheral structures. The recipient endothelium may be damaged by
recipient cornea is split while the dissection is made, and the inflating the anterior chamber with air, and/or performing a deep
excess thickness of the button only causes little separation of stromal dissection. In our ongoing clinical study, preoperative
the recipient, posterior stromal layers. and long-term postoperative endothelial cell counts are
A best corrected visual acuity of 0.7 at 6 months and 0.8 at performed to determine how endothelial cell loss with our
12 months compares favourably with reported series of lamellar technique compares to that after existing deep lamellar
keratoplasty, or penetrating keratoplasty. A postoperative keratoplasty techniques, for which a 13 percent cell loss at one

Chapter 23: Deep Anterior Lamellar Keratoplasty: Melles Technique


astigmatism of about 2.5 D also compares favourably with year has been reported.
reported series of lamellar keratoplasty, deep lamellar Since the 1960s, lamellar keratoplasty may have lost its
keratoplasty, or penetrating keratoplasty. One patient showed popularity due the imperfections of the existing surgical
high astigmatism after excentric trephination. A flaw of our study techniques rather than poor visual outcomes. Although better
is that it is a prospective, but not a comparative study, i.e. we microkeratomes have become available with the development
did not study the results of matched control penetrating of laser-assisted in situ keratomileusis (LASIK), microkeratome
keratoplasties. lamellar resections cannot be used for disorders with deep
Compared to deep lamellar keratoplasty techniques using stromal opacities, variable corneal thickness, and surface
manual dissection, the viscodissection technique may offer irregularities. Improvement of the manual technique for lamellar
several advantages. First, less surgical time is required for making keratoplasty could therefore potentially broaden the interest for
the dissection, since the pathological stroma over its full- the procedure again, to manage anterior corneal disorders.
thickness can be quickly separated from Descemet’s membrane
in the recipient. Second, the procedure can be performed using INSTRUMENTS
instrumentation commonly available for routine penetrating
For manual, deep stromal dissection, a spatula set was developed,
keratoplasty, without the need for special surgical instruments.
consisting of three spatulas, colorcoded like the Dutch flag.
Third, a smooth donor-to-recipient interface is created, which
A short, triangled spatula (RED) (Fig. 23.19A) is used to
may reduce the risk of interface scarring and improve the visual
dissect downward into the cornea, until the desired stromal depth
outcome. Fourth, an identical level of dissection depth is obtained
is reached. A half-length, curved spatula (WHITE) (Fig. 23.19B)
in both donor and recipient tissues, so that theoretically a perfect
with a rounded tip is used to make the dissection up to two-thirds
anatomical restoration is achieved.
across the cornea, and a third, full-length spatula (BLUE)
A disadvantage of the viscodissection technique is that there
(Fig. 23.19C) is used to complete the dissection across the cornea
is substantial risk of perforation of Descemet’s membrane during
over 360°.
injection of viscoelastic into the cornea, removal of the recipient
All spatulas have sharpened edges to create a smooth
anterior lamella, or suturing of the donor button. Although
interface, so that the risk of interface haze development is
Descemet’s membrane may easily withstand the intraocular
minimized. Since obtaining a smooth interface may be a crucial
pressure in the presence of a Descemetocèle, we found that a
step in lamellar keratoplasty, the spatulas may be used up to three
large area of exposed, denuded Descemet’s membrane is fragile,
surgeries.
and that a microperforation has a tendency to enlarge by itself
due to the elastic properties of Descemet’s membrane.
ACKNOWLEDGMENTS
In the current study, a perforation occurred in 7 out of 68
eyes (10%), using spatula dissection through a scleral tunnel. A During my corneal fellowship at the Rotterdam Eye Hospital, I
39.2 percent microperforation rate has been described for was given the opportunity to work on techniques for lamellar
conventional deep lamellar keratoplasty techniques. An keratoplasty. I am greatly indebted to the other corneal surgeons
advantage of the presently described technique may be that íf at our clinic, Houdijn Beekhuis, Lies Remeijer, and Annette
perforation occurs, it is likely to occur early in the surgery, Geerards, as well as the entire medical staff.
whereas inadvertent perforation usually occurs after preparation I would like to use this opportunity to sincerely thank Ger
of the recipient bed has almost been completed in conventional Vijfvinkel, president of DORC. International, for his continuous
lamellar keratoplasty techniques. The visco-dissection technique support throughout the study and his willingness to produce the
may be used for indications commonly managed with a neccessary instruments for this surgical technique. I also thank
penetrating keratoplasty, for example keratoconus and corneal his employees, in particular Frank Lander, the instrument maker
dystrophies. If dissection of Descemet’s membrane is successful, who manufactured the instruments.
these cases may benefit from the advantages of a lamellar Fred Eggink and Carla Nieuwendaal, I thank you for your
keratoplasty, whereas the procedure is easily converted to a enthusiasm over the years, for helping me out with the animal
penetrating keratoplasty in the event of perforation. experiments, and gathering the clinical data on the contact lenses.
Another disadvantage of our techniques may be that the I thank Bart van Dooren for processing the specular microscopy
anterior chamber has to be opened for an aqueous to air exchange and videotopography data.
prior to performing a corneal dissection. It therefore bears a risk I thank BIS/Eurotransplant and the Dutch Eye Bank at the
of intraocular infection and damage to the anterior chamber Academic Medical Center, Amsterdam for their continuous
183
cooperation with the ongoing projects, these projects were
sponsored by the “Rotterdamse Vereniging Blindenbelangen”
and “the STW, applied science division of the Ministry of
Economic Affairs.”

REFERENCES

1. Melles GRJ, ten Hoope GW, Rietveld FJR, Beekhuis WH, Binder
Section IV: Lamellar Keratoplasty

PS. Depth predictability of stromal pockets in the posterior


cornea. Cornea 1998;17:174-79.
2. Melles GRJ, Rietveld FJR, Beekhuis WH, Binder PS. A technique
to visualize corneal incision and lamellar dissection depth during
surgery. Cornea 1999;18:80-86.
3. Melles GRJ. How to minimize interface haze in lamellar
keratoplasty? In preparation.
4. Melles GRJ, Lander F, Rietveld FJR, Remeijer L, Beekhuis WH,
Binder PS. A new surgical technique for deep stromal, anterior
lamellar keratoplasty. Br J Ophthalmol 1999;83:327-33.
5. Nieuwendaal C, Lander F, Melles GRJ. Clinical results of deep,
anterior lamellar keratoplasty following manual dissection
through a scleral tunnel incision. In preparation.
6. Melles GRJ, Remeijer L, Geerards AJM, Beekhuis WH. A quick
surgical technique for deep lamellar keratoplasty using visco-
dissection. Cornea 2000;19:427-32.
7. Eggink FAGJ, Vreugdenhill W, Melles GRJ. Rigid gas permeable
contact lens fitting after deep lamellar keratoplasty. In preparation.
8. Melles GRJ, Remeijer L, Geerards AJM, Beekhuis WH. The
Figures 23.19A to C: Lamellar dissectors for future of lamellar keratoplasty. Curr Opinion Ophthalmol
deep lamellar keratoplasty 1999;10:253-59.

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24

Chapter 24: Deep Anterior Lamellar Keratoplasty: Big Bubble Technique


Deep Anterior Lamellar Keratoplasty:
Big Bubble Technique
Mohammad Anwar

HISTORICAL BACKGROUND INTRODUCTION

Von Walther was the first to propose Lamellar Keratoplasty in The current techniques for deep anterior lamellar keratoplasty
1830.1 After that in 18802 Von Hippel, Filatov in 19303 and are of two kinds:19-30
Paufique in 19404 advanced the technique. In 1963, McCulloh a. Deep stromal dissections achieved manually, microkeratome
reported that the donor endothelium in this technique is lost soon assisted or using femtosecond laser. A variable amount of
but DM remains intact which can be wrinkled.5 Malbran, in 1965, stroma is left behind, therefore, the interface between the
published his peeling technique in keratoconus in order to reduce donor and recipient is intrastromal. Stroma to stroma
interface granulations.6 Hollerman, in 1969, described deep interface may impede visual acuity by optical interference
dissection close to Descemet’s membrane (DM) in the recipient that is independent of clinically visible interface haze.
and he used full thickness donor button including DM and b. Planned exposure of DM by the Big Bubble Technique. This
endothelium.7 provides safe, speedy and consistent exposure of the smooth
Anwar, in 1974, published his technique in lamellar and shining surface of DM. On the donor side DM is peeled
keratoplasty.8 The following are the salient features of the article: off by non toothed forceps resulting in another uniform and
1. DM has been exposed for the first time under direct smooth surface. The apposition of the donor button to the
microscopic visual control. bare DM provides an interface of high quality. It is similar
2. For the first time the DM has been peeled off from the donor to the natural pre DM plane of a normal cornea. Thus, it does
button. not interfere with the visual acuity. The procedure is
standardized because the interface achieved is exactly the
3. The high quality interface created by bare DM and DM-free
same in every case. Once, the Big Bubble is achieved, it is
donor button has provided best visual results.
relatively safe and straight forward to bare DM even by an
Removal of the endothelium and DM from the donor avoids
average surgeon.
inflammatory reaction and possible wrinkling of the DM at the
interface. The other disadvantages of leaving the DM on the Indications
donor button are found in a histologic study by Morrison and
The Big Bubble Technique is only used for conditions where,
Swan.9
the endothelium is healthy and there is no sign of previous break
In 1984, Archila10 described intrastromal air injection and in DM. The goal is to bare DM. The indications are as follows:
the use of spatula to dissect down to DM. Similar technique was 1. Ectatic corneal disorders:
used by Price11 and Rostran.12 Suguita, in 1997, published his a. Keratoconus
experience with hydro delamination.13 Melles14-16 used a semi- b. Pellucid marginal degeneration (keratotorus).
sharp spatula to achieve deep lamellar dissection in a closed c. Keratoglobus
fashion using mirror reflection from the air in the anterior d. Keratectasia following refractive surgery.
chamber. 2. Stromal corneal opacities and scars sparing DM.
The most recent and important development in this field is 3. Corneal dystrophies involving anterior/deeper stroma.
“The Big Bubble” Technique,17,18 in which, air is injected deep
into the stroma generating a big air bubble between the DM and Contraindications
the stroma, thus, causing a large detachment of DM without using 1. Corneal conditions with diseased endothelium.
a surgical instrument. 2. Pre-existing rupture in DM.
185
3. Deep scars, however small, involving DM. 3. Superior rectus bridle suture to centralize the cornea in the
4. Macular corneal dystrophy is a relative contraindication operative field.
because of the fragile nature of DM. 4. Measure vertical diameter with calipers and choose an
appropriate size of the trephine blade, usually 8.25 mm
Advantages (range 7.5-10.0).
5. Mark the cornea with Anwar keratoplasty 16 blade ring
• The Big Bubble Technique is the safest and fastest way to
marker #79-735-1 (Duckworth and Kent Limited, Baldock
expose the DM.
Section IV: Lamellar Keratoplasty

Herts, England). This enables the trephine blade to be


• Once, the Big Bubble is formed, the exposure of the DM in
centered onto the pupil and provides aqui distant 16 radial
the surgical field is accomplished in 15-20 minutes. Suturing
marks for accurate suture placement. Other markers can also
and adjustment requires another quarter of an hour.
be used.
Therefore, the operating time is similar to that of the
6. Weck cell sponges are used to dry the perilimbal area for
penetrating keratoplasty.
efficient attachment of the suction trephine. Preference is
• The interface between the exposed DM and the smooth
given to Hanna trephine from Moria Limited, France.
posterior surface of the donor stroma is of high quality,
(Hessburg-Baron, GTS or manual trephine can also be used).
therefore, no optical interference is experienced at this site.
7. Partial trephination – about 300 μ deep – depending upon
• The procedure is repeatable.
the pachymetry (Fig. 24.1).
• A Big Bubble can be consistently achieved in about 90
8. Under direct visual control add more depth at the site chosen
percent of the cases.
for needle insertion, usually at 12 o’clock, by means of a
• The technique is standardized. The interface achieved is
super sharp metal blade. Avoid perforation.
exactly the same in every case and for every surgeon.
9. A 27/30 G needle is attached to an air-filled syringe. The
• The visual acuity is better in the Big Bubble Technique than
attachment must be firm and air-tight.
in those techniques where there is stroma to stroma interface.
10. Bend the needle by 30-40° of arc, 5 mm from its tip, the
• There is no late deterioration of visual acuity reported as
bevel facing down.
compared to techniques in which the interface is intrastromal.
11. The needle should be inserted deep into the stroma at about
80 percent of the depth through the trephination groove, then
Limitations
advance the needle into the corneal stroma staying parallel
• There is a steep learning curve. The Big Bubble can to the posterior corneal surface. The tip of the needle aims
successfully be achieved with practice. for the paracentral region. A small dab of viscoelastic fluid
• Long-term results are still awaited. on the corneal surface above the needle track aids visibility
• Statistical analysis of comparative studies between the Big by eliminating surface striations and also provides some
Bubble Technique, stroma-to-stroma procedure and magnification to allow better judgment as to the needle depth
penetrating keratoplasty are yet to be reported. (Fig. 24.2).
12. When the needle tip is well buried into the corneal stoma
Anesthetic Requirements for 3-4 mm, the plunger is depressed and air is injected with
DALKP using Big Bubble Technique can generally be performed some force. The stroma surrounding the tip becomes white
in 45-60 minutes. Local anesthesia is suitable (retro/peribulbar).
Topical anesthesia is a possibility but has not been tried. General
anesthesia is used for younger patients as it provides optimal
operating conditions eliminating sudden and jerky movements,
especially in the later stages when dealing with exposure of the
delicate DM.

Preoperative Topical Medications


1. Topical fluoroquinolone drops qid for two days.
2. No medications for pupil manipulation.

Surgical Technique

A. Recipient Dissection
1. Appropriately position the patient’s head to allow
perpendicular view of the cornea. Figure 24.1: Keratoconus, deep trephination, inner corneal
2. Use Barraquer wire speculum to open the eyelids. edge well retracted

186
Chapter 24: Deep Anterior Lamellar Keratoplasty: Big Bubble Technique
Figure 24.2: The needle is advanced deep into the stroma. A Figure 24.3: Formation of the Big Bubble outlined
dab of viscoelastic over the needle track improves visualization by a circular white band

and opaque and has irregular outline. Almost at the same


time the air also enters into the pre-Descemet’s plane and is
marked by a sudden and explosive appearance of a big air
bubble, which is outlined by a circular white band (Fig.
24.3). When the border of the bubble coincides with the
trephine incision, further injection of air is stopped,
otherwise the bubble may well extend beyond the
trephination groove and even cause a rupture at the
Schwalbe’s line and in this case the bubble is lost and a large
amount of air enters the anterior chamber. If no bubble is
formed the corneal disk becomes white and opaque with an
irregular outline. If the air begins to escape towards the
limbus and subconjunctival space, further injection is
stopped and the needle is withdrawn and a fresh area is
chosen for another attempt at air injection.
13. Keratectomy, anterior to the bubble, is performed with a Figure 24.4: Keratectomy anterior to the Bubble
crescent / 69 Beaver blade (Fig. 24.4). Circular white band
can now be seen even more clearly (Fig. 24.5)
14. Limbal paracentesis is done well away from the peripheral
edge of the big bubble and aqueous humor is drained (Fig.
24.6). It should not be done before the air injection, as air
can easily enter the anterior chamber through the
paracentesis opening. However, paracentesis 180 percent
away from the site of air injection avoids this complication.
15. The anterior wall of the bubble is pierced with a super sharp
30° metal blade to create an opening of 1 mm or slightly
larger (Fig. 24.7). Once, the withdrawal of the knife begins,
the air-bubble collapses and the stroma becomes translucent
(Fig. 24.8).
16. Barraquer wire spatula (Katena Products, Denville, NJ,
USA) or Anwar keratoplasty spatula [(#6-099-3 Duckworth
and Kent Ltd) shorter, more maneuverable, rigid, tapered,
0.5 mm at the base, 0.25 mm at the tip helps blunt dissection]
is introduced into the pre-Descemet’s plane through the
opening created by the super sharp blade. The spatula is Figure 24.5: View of the Bubble after keratectomy
187
advanced towards 6 o’clock position of the limbus
(Fig. 24.9). No resistance is felt during the maneuver.
17. Spatula is lifted anteriorly to tent up the residual stromal
layer. If it is in the correct plane, the air is sucked in behind
and along the sides of the spatula and the stroma.
18. The stroma over the spatula is split open by scraping it with
a super sharp knife. The blade is held at a right angle to the
Section IV: Lamellar Keratoplasty

spatula, tilted backwards, and its blades edge is moved


forward onto the spatula so it scrapes and splits the stroma
(along the length of the spatula). DM becomes visible
through the linear slit thus created.
19. The spatula is reintroduced into the pre-Descemet’s plane
and advanced towards 12 o’clock (Fig. 24.10) and the stroma
is again split with maneuver described as above (step 19).
20. More aqueous is drained through the paracentesis to soften
the globe again.
Figure 24.6: Paracentesis, away from the edge of the Bubble

Figure 24.7: Puncture of the Bubble with Figure 24.9: Scraping over the wire spatula
the tip of a super sharp blade with a super sharp blade

Figure 24.8: Collapse of the Bubble after Figure 24.10: Wire spatula advanced towards
the knife is withdrawn 12 o’clock and scraped over by the knife
188
21. By using 0.12 tissue forceps and a blunt tip corneal scissors,
the residual stroma is excised along the trephine cut in
clockwise (Figs 24.11 to 24.13) and counter clockwise
directions (Figs 24.14 and 24.15).
22. The entire surface of the brilliant DM in the surgical field
is now exposed (Fig. 24.16).

Chapter 24: Deep Anterior Lamellar Keratoplasty: Big Bubble Technique


Postkeratectomy Big Bubble
If the Big Bubble fails to form and there is no clear area left for
safe insertion of the needle, anterior keratectomy is done (at least
half thickness). A small nick is made in the residual stroma with
a super sharp blade and balance salt solution is forced into the
stroma through a blunt cannula. Air is injected through the
hydrated area using the same bent needle, the tip of the needle
is advanced into the stroma and it should stay anterior to tiny
air bubbles (if present from the initial air injection) deep in the
Figure 24.11

Figure 24.12 Figure 24.14

Figure 24.13 Figure 24.15

Figures 24.11 to 24.13: Removal of the left half of the residual Figures 24.14 and 24.15: Removal of the right half of the
stroma using Anwar clockwise scissors residual stroma using Anwar counter clockwise scissors
189
Section IV: Lamellar Keratoplasty

Figure 24.16: View of the completely exposed DM Figure 24.17: DM peeled off from the donor button

stoma. Extreme care is taken not to perforate or penetrate into the DM has been split between the banded and the non banded
the anterior chamber. Air is injected and the bubble should form. zones and the bubble has formed within the DM. The bubble
will not move freely in the anterior chamber.
The Hidden Big Bubble In one instance, two bubbles developed, one in the space
Occasionally, the air spreads very fast through the soft hydrated between the stroma and the DM (outlined by a circular white
bed which becomes completely opaque and it is difficult to band) and the other within the DM (with a clear outline).
identify if a bubble has been formed. The presence of the Big Paracentesis site is used to soften the globe frequently during
Bubble underneath the totally opaque stroma is indicated by: the later stages of the dissection of the DM. It can also be used
1. A circular white outline just inside the limbus. for reforming the anterior chamber with fluid, air or gas. The
2. Sudden increase in the anterior curvature of the stromal bed. latter is used to temponade a perforation. Unwanted air in the
To confirm the presence of the bubble underneath the opaque anterior chamber should be removed through the paracentesis,
tissue (a hidden big bubble) a second keratectomy is done so so that it does not interfere with the reflex image of the
that the bed becomes very thin allowing identification of the keratoscope required for suture adjustment.
white circular band around the big bubble. Small bubbles maybe
present in the anterior chamber and they are usually trapped B. Donor Dissection
peripheral to the big bubble. If small bubbles are not present, a
little bit of air can be injected into the anterior chamber to create 1. A required sized donor button is punched from endothelial
small bubbles and if they stay in the periphery it is an indication or epithelial side using Teflon punch blocks.
that a big bubble has been formed. On the other hand, if the 2. To peel off the DM, the graft margin is held with 0.12 tissue
small bubbles move into the center of the anterior chamber the forceps grasping as much of the stromal thickness as possible,
big bubble has not formed. without including the DM and the endothelium. A dry Weck
The presence of extra light reflexes deep in the anterior cell sponge is used to detach the DM from the peripheral
chamber is another indication of the presence of a big bubble. inner edge of the button by gently scraping it from the forceps
A small puncture is made near the 12 o’clock position of towards the center of the button. If the edge of the detached
the bubble and the air escapes. DM can then be exposed in the membrane is intact, it is held in a non toothed tying forceps
usual manner. and peeled off in one piece from the donor button
(Fig. 24.17). However, if a tear occurs in the detached edge
Augmentation of the Big Bubble of the DM, it is extended to the opposite edge by scraping it
with the smooth tip of Kelmen-McPherson forceps. The two
Sometimes the “Big Bubble” achieved is small in size, it can be halves of the split DM can be rolled off using the same
enlarged by re-injecting air into a hydrated adjoining area of the forceps in a stroking motion. If multiple tears occur in the
stromal bed. DM it has to be removed piece meal by using a dry Weck
cell sponge. Posterior stromal surface is smooth and uniform.
Intra-Descemet’s Membrane Big Bubble
Aggressive rubbing or scraping of the stroma could make it
Occasionally, the air bubble formed has a clear outline like that rough and irregular, and may interfere with the optical
of a water bubble, hence, the white band is not seen. In this case, performance.
190
• Disposable trephine blades – (Katena Products, Denville, NJ,
USA).
• Anwar convex teflon punching block, made by Moria SA,
Antony, France.
• A #69 Beaver blade (BD Company, Franklin Lakes, NJ,
USA).
• (Alcon Surgical ophthalmic knife 30º, Hemel Hampstead,

Chapter 24: Deep Anterior Lamellar Keratoplasty: Big Bubble Technique


Herts England).
• Anwar keratoplasty spatula (#6-099-3, Ductworth and Kent,
Baldock, Herts, UK) or Barraquer iris spatula (Katena
Products, Denville, NJ, USA).
• Sharp disposable hypodermic, 27 or 30-gauge needle and
5 cc syringe (both from BD Company, Franklin Lakes, NJ,
USA).
• Harms colibri forceps 1:12 (Katena Products, Denville, NJ,
USA).
Figure 24.18: Donor cornea placed on the recipient eye • Microsurgical needle holder K6-3830 (Katena Products,
Denville, NJ, USA).
• Anwar keratoplasty scissors #1-218 counter clockwise and
# 1-219 clockwise (Duckworth and Kent, Baldock, Herts,
UK).
• Anwar keratoplasty 16-blade ring marker and hook #9-735-
1 (Duckworth and Kent, Baldock, Herts, UK).
• 10-0 nylon suture on CU-1 needle ref. 8065198001 (Alcon
Surgical, Hemel Hampstead, Herts England).
• 4/0 silk suture (Alcon Surgical, Hemel Hampstead, Herts
England).
• Weck cell sponges/spears (Medtronic Solan, Jacksonville,
Fl, USA).
• Maloney keratometer (Katena Products, Denville, NJ, USA).
• Marking pen (Aculine Products, Inc. Hyannis, MA).
• Viscoelastic fluid (Pfizer Inc., NY, USA).
• Bandage contact lens (Johnson and Johnson, Jacksonville,
FL, USA).

Figure 24.19: Suturing and adjustment of the nylon sutures Postoperative Medications
• Topical combination of Dexamethasone and Chloram-
3. The donor button is sutured into the host with 10-0 nylon, phenicol three times daily for one week, other combinations
using running, interrupted or combination pattern, taking 16 may also be used.
or more bites. The suture is adjusted for astigmatism using • Topical Fluorometholone three times daily for one month
a qualitative keratoscope (Figs 24.18 and 24.19). and gradually tapered off in the next three/four months.
4. A bandage contact lens is placed and a combination of • Topical lubricants if necessary.
corticosteroid and antibiotic is instilled and the eye is patched
for about 24 hours. Follow-up Schedule
• First postoperative visit after five days, bandage contact lens
Surgical Instruments
is removed.
• Barraquer wire speculum – (Katena Products, Denville, NJ, • Follow-up visits after two weeks, one month, every three
USA). months and after one year.
• Suction trephine with depth control Hanna (Moria SA, • Removal of sutures usually after two years, if the astigmatism
Antony, France, Barron Vacuum punch, Katena, Denville NJ, is low, the sutures are left in situ for as long as possible to
USA, Guided Trephine System, Rhein Medical Inc, Tampa, allow wound healing in that position.
Fl., USA). • A loose suture/s must be removed or replaced if necessary.

191
Prevention of Complications • Astigmatism following this procedure is similar to that of
penetrating keratoplasty.
• A thorough slit lamp examination, to identify thin corneal
• Minimum use of postoperative steroids reduces (steroid
area/s, is necessary to avoid perforation with the trephine or
related) complications.
the injection needle.
• This technique is contraindicated in the presence of a scar
CONCLUSION
or a tear in the DM.
• Careful view of the depth of the groove is important while The “Big Bubble” Technique allows safe and consistent exposure
Section IV: Lamellar Keratoplasty

inserting the needle deep into the stroma. Advance the needle of Descemet’s membrane. The visual results achieved are
tip deep into the stroma parallel to the DM. A dab of comparable to those of penetrating keratoplasty. Long-term
viscoelastic/fluid on the corneal surface, right above the complications are greatly minimized. Corneal surgeons should
needle track, provides a magnification and eliminates surface be encouraged to use this technique in cases where the
striations. endothelium is healthy.
• The globe should be kept soft by intermittent release of the
aqueous, especially during the exposure of Descemet’s REFERENCES
membrane. Low intraocular pressure provides more space
1. Mühlbauer FX. Über Transplantation der Cornea, Gekrönte
for the insertion of the blade of the scissors between the final Preisschrift. Munich. Jos. Lindauer, 1840. Abstract in Zeis:
stromal layer and Descemet’s membrane. Schmidt CC (Ed): Jahrbücher der in und ausländischen
• The operative field should be kept moist to avoid thermal gesammten Medizin, Leipzig, Otto Wigand 1842;267-68.
damage to the endothelial cells from the light of the 2. von Hippel A. Eine neue Methode der Hornhauttransplantation.
microscope. Al-brecht v. Graefes Arch Ophthalmol 1888;34:108.
3. Filatov VP. Transplantation of the cornea. Arch Ophthalmol
Management of Complications 1935;13:321-23.
4. Paufique L, Charleux J. Lamellar keratoplasty. In: Casey T, ed.
• The most important and common intraoperative complication Corneal Grafting. New York, Appleton-Century-Crofts, 1972:121-
is a perforation in Descemet’s membrane. Near Descemet’s 76.
dissection can still be achieved which usually gives good 5. McCulloch C, Thompson GA, Basu PK. Lamellar keratoplasty
results. using full thickness donor material. Trans Am Ophthalmol Soc
1963;61:154-80.
• A small amount of stroma can be left over the site of
6. Malbran E. Lamellar keratoplasty in keratoconus. In: king JH,
perforation which helps to seal it. McTigue JW (Eds). The Cornea-World Congress. London/
• If the perforation is large, air tamponade in the anterior Washington DC. Butterworths. 1965;511-18.
chamber is extremely helpful. 7. Hallermann W Verschiendenes Über Keratoplastik. Klin Monatshl
• If a needle causes perforation, it usually occurs at the Augenheilkd 1959;135:252-59.
beginning of the technique. In this case, bubble formation 8. Anwar M. Technique in lamellar keratoplasty. Trans Ophthalmol
should not be attempted and the surgery needs to be Soc UK 1974;94:163-71.
completed by Near Descemet dissection technique. 9. Morrison JC, Swan KC. Full thickness lamellar keratoplasty:
A histologic study in human eyes. Ophthalmology 1982;89:
• A large rupture in DM can be managed with air or long acting
715-19.
gas temponade. Occasionally the break in DM is so large 10. Archila EA. Deep lamellar keratoplasty dissection of host tissue
that conversion to penetrating procedure may well be with intrastromal air injection. Cornea 1984-85;3:217-8.
necessary. A large bubble of gas/air could cause a pupil 11. Price FW, Jr. Air lamellar keratoplasty. Refract Corneal Surg
block.31 A prophylactic peripheral iridotomy is performed 1989;5:240-43.
and a mydriatic is instilled. The patient is positioned so as 12. Chau GK, Dilly SA, Sheard CE, Rostran CK. Deep lamellar
to provide efficient temponade depending upon the site of keratoplasty on air with lyophilized tissue. Br J Ophthalmol
1992;76:646-50.
the perforation.
13. Sugita J, Kondo J. Deep lamellar keratoplasty with complete
removal of pathologic stroma for vision improvement. Br J
Results Ophthalmol 1997;81:184-88.
• Baring of DM provides a perfect optical surface. Removal 14. Melles GRJ, Remeijer L, Geerards AJM, et al. A quick surgical
of DM from the donor gives a very smooth surface thus technique for deep, anterior lamellar keratoplasty using visco-
dissection. Cornea 2000;19:427-32.
eliminating the disadvantages of an intrastromal interface.
15. Melles GRJ, Remeijer L, Geerards A, et al. The future of lamellar
The visual results are comparable with those of penetrating keratoplasty. Curr Opin Ophthalmol 1999;10:253-59.
keratoplasty.32,33 16. Melles GRJ, Rietveld FJR, Beekhuis WH, et al. A technique to
• The endothelial cell loss resembles that of a normal cornea, visualize corneal incision and lamellar dissection depth during
a distinct advantage over PKP.23 surgery. Cornea 1999;18:80-86.

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17. Anwar M, Teichmann KD. Big Bubble Technique to bare 26. Coombes AGA, Kirwan JF, Rostran CK. Deep lamellar
Descemet’s membrane in anterior lamellar keratoplasty. J Cataract keratoplasty with lyophilized tissue in the management of
Refract Surg 2002:28: in press. keratoconus. Br J Ophthalmol 2001;85:788-91.
18. Anwar M, Teichmann KD. Deep lamellar keratoplasty. Surgical 27. Gasset AR. Lamellar keratoplasty in the treatment of
techniques for anterior lamellar keratoplasty with and without keratoconus:conoectomy. Ophthalmic Surg 1979;10:26-33.
baring of Descemet’s membrane. Cornea 2002;21:374-83. 28. Terry MA, Ousley PJ. A practical femtosecond laser procedure
19. Teichmann KD. Lamellar keratoplasty – a comeback? Middle East for DLEK endothelial transplantation. Cornea 2005;24:453-59.
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20. Amayem AF, Anwar M. Fluid lamellar keratoplasty in O. Excimer laser treatment in deep lamellar keratoplasty 100 mm
keratoconus. Ophthalmology 2000;107:76-80. over Descemet’s membrane. Ophthalmologe 2002;99:946-48.
21. Terry MA. The evolution of lamellar grafting techniques over 30. Melles GRJ, Lander F, Rietveld FJR, et al. A new surgical
twenty-five years. Cornea 2000;19:611-16. technique for stromal, anterior lamellar keratoplasty. Br J
22. Azar DT, Jain S, Sambursky R. A new surgical technique of Ophthalmol 1999;83:327-33.
microkeratome-assisted deep lamellar keratoplasty with a hinged 31. Urets-Zavalia A. Fixed, dilated pupil, iris atrophy, and secondary
flap. Arch Ophthalmol 2000;118:1112-15. glaucoma. A distinct clinical entity following penetrating
23. Morris E, Kirwan JF, Sugatha S, et al. Corneal endothelial keratoplasty for keratoconus. Am J Ophthalmol 1963;56:257-5.
specular microscopy following deep lamellar keratoplasty with 32. Mahmood MA, Wagoner MD. Penetrating keratoplasty for
lyophilized tissue. Eye 1998;126:1-8. keratoconus: long-term results in 38 eyes with and 202 eyes
24. Manche EE, Holland GN, Maloney RK. Deep lamellar without vernal keratoconjunctivitis. Middle East J Ophthalmol
keratoplasty using viscoelastic dissection. Arch Ophthalmol 1999;7:27-35.
1999;111:1561-65. 33. Mahmood MA, Wagnor MD. Penetrating keratoplasty in eyes
25. Anwar M. Dissection technique in lamellar keratoplasty. Br J with keratoconus and vernal keratoconjunctivitis. Cornea
Ophthalmol 1972;56:711-13. 2000;19:468-70.

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25
Section IV: Lamellar Keratoplasty

Deep Anterior Lamellar Keratoplasty:


Double Bubble Technique
Vishal Jhanji, Jacqueline Beltz, Namrata Sharma, Rasik B Vajpayee

INTRODUCTION is formed, there is a sudden peripheral movement of the air from


the center of the AC due to the inward bulging of DM. Being a
Deep anterior lamellar keratoplasty (DALK) is a technique of
dynamic sign, this sudden movement of the small bubble is easily
corneal transplantation that entails the replacement of diseased
appreciated by the surgeon. Also, the decompression of the AC
host corneal stroma without replacing the healthy endothelium.
prior to the injection of the small bubble reduces the resistance
The procedure eliminates the risk of corneal endothelial graft
offered by the cornea of an intact eye and allows space for the
rejection and other inherent complications related to full-
DM to bulge inward on formation of the big bubble.
thickness corneal transplantation surgery. Although DALK has
been described for various corneal stromal disorders, 1 Indications
keratoconus is by far the most common indication for DALK.2,3
Similar to “Big Bubble” DALK, “Double Bubble” DALK can
The classical technique for DALK involves the removal of
be successfully performed to treat corneal pathologies that do
host tissue layer by layer until the Descemet’s membrane (DM)
not involve the DM or endothelium. The indications for “Double
is exposed. Techniques such as intrastromal air injection or
Bubble” DALK are as follows:
segmental removal of host stroma help to improve the visibility
1. Keratoconus
of the DM. Melles et al were the first to inject air into the anterior
2. Corneal stromal dystrophies
chamber that creates a mirror reflex to guide surgical instruments
3. Corneal scars sparing the DM.
directly into the space between DM and the posterior stroma.4
Archila demonstrated the use of intrastromal air injection to
SURGICAL TECHNIQUE
facilitate the removal of diseased host corneal tissue.5 Anwar
et al modified the technique of air injection by performing about Preparation of the Patient
60-70 percent corneal trephination before injection the “Big
Bubble” of air into the corneal stroma.6 The “Big Bubble” The surgery should preferably be performed under general
technique is a novel method for achieving complete separation anesthesia. It is best to avoid a Leiberman speculum as it can
of DM from posterior stroma in DALK surgery. cause too much pressure on the globe and lead to bulging of the
In order to make this technique more successful and DM which may increase the chances of intraoperative perforation
reproducible, corneal surgeons have proposed some of the DM. A wire speculum should preferably be used in these
modifications to the standard surgical technique. Parathasarathy cases.
et al have reported a method of using a small air bubble in the
Corneal Trephination
anterior chamber to help determine if a successful big bubble
has been achieved.7 Foroutan et al have described the “shifting After marking the center of the cornea, a Hessburg Barron suction
bubble sign”.8 This is a description of a small bubble of air, trephine is used to perform partial-thickness trephination of the
injected into the AC after the injection of air into the cornea, host cornea to an approximate depth of 60-70 percent of the
moving to the center of the AC upon anterior decompression of minimum corneal thickness. Subsequently a self sealing
the big bubble. Inspite of all these modifications, it may be paracentesis wound is created with a 15 degree surgical blade,
difficult to ascertain the formation of the big bubble in the supra- just posterior to the limbus at 11 O’clock, and some aqueous
Descemet’s plane. In our technique of “Double Bubble” DALK humor is expressed out. A small amount of air (3 to 4 mm in
in which a small amount of air is injected into the AC before the diameter) is injected into the anterior chamber (AC) through
injection of air into the cornea stroma. As soon as a big bubble the same paracentesis wound using a Rycroft cannula
194
(Figs 25.1A and 25.2A). This is called as ‘first air bubble’ of Confirmation of the Big Bubble Formation
our “Double Bubble” technique.
At this stage the formation of the big bubble can be confirmed
by rotating the eye in all the quadrants. The big bubble formation
Injection of Air into the Corneal Stroma
can be confirmed by the confinement of the small bubbles to
Following this, a 27-gauge disposable needle, bent to 90 degrees, the periphery of the cornea. Since, the DM in the center bulges
is used to inject air into the corneal stroma to form the big bubble. into the AC, the small bubbles cannot migrate towards the center
The needle tip, with the bevel facing down, is inserted of the cornea. The next step involves debulking of the anterior

Chapter 25: Deep Anterior Lamellar Keratoplasty: Double Bubble Technique


tangentially into the paracentral corneal stromal tissue at a depth two-thirds of the corneal stroma central to the trephination mark
of 60-70 percent through the previously created partial using a crescent blade (Fig. 25.2C). This leaves a thin layer of
trephination wound (Fig. 25.1B). Under direct visual control, posterior corneal stroma above the big bubble and is easier to
the needle is advanced in the corneal stroma for about 2 mm excise to bare the DM without incurring too much stretch tension
and air is injected slowly until the bubble present in the AC on the DM. This debulking of the corneal stroma is helpful in
moves to the periphery (Fig. 25.2B). This sudden peripheral preventing the inadvertent occurrence of perforation of DM
movement of the air bubble in AC is an indication of formation while excising the overlying stromal tissue. Thereafter, the AC
of “Big Bubble” in the supra-Descemet space (Fig. 25.1C). This is decompressed again to reduce the tension over the DM and a
is the ‘second air bubble’ of our “Double Bubble” technique. 15 degree blade stained with gentian violet is used to create a
shelved opening into the potential space between the DM and
posterior stroma (Fig. 25.1D). Entry into this space is identified
by the sudden movement of the bubble from the periphery of
the AC back to the center of the AC of the host eye (Fig. 25.1E).
At this point, the incision is immediately discontinued and
2 percent hydroxypropyl methylcellulose is injected through the
opening into the potential space to keep the DM away from the
rest of the stroma (Fig. 25.1F). A pair of blunt-tipped curved
Vannas scissors is used to divide the thin layer of posterior
corneal stromal tissue into four quadrants (Fig. 25.1G), and each
quadrant is subsequently excised, baring the DM (Fig. 25.1H).

Preparation of the Donor Lenticule and Suturing


A 0.25 mm oversized donor lenticule is punched from the
endothelial side and its DM is removed after staining with
0.06 percent trypan blue dye. The hydroxypropyl methylcellulose
Figure 25.1A: A small amount of air (3 to 4 mm in diameter) was overlying the bare DM of the host cornea is washed away with
injected into the anterior chamber through the paracentesis balanced salt solution, and the donor lenticule is secured with
wound using a Rycroft cannula 10-0 monofilament nylon (Fig. 25.1I). As in penetrating
keratoplasty, standard suturing techniques can be used applying
interrupted, running, or combined interrupted-running sutures.

Figure 25.1B: Air was injected into the corneal stroma, until
peripheral movement of the small bubble of air within the anterior Figure 25.1C: Anterior two-thirds of the corneal stroma was
chamber was noted debulked leaving a thin layer of posterior corneal stroma
195
Section IV: Lamellar Keratoplasty

Figure 25.1D: A 15 degree blade stained with gentian violet was Figure 25.1G: A pair of blunt-tipped curved Vannas scissors
used to create a shelved opening into the potential space between was used to divide the thin layer of posterior corneal stromal
the Descemet’s membrane and posterior stroma tissue into four quadrants

Figure 25.1E: Entry of air bubble into the potential space was Figure 25.1H: Each quadrant was excised and Descemet’s
easily identified by the dynamic movement of the small bubble membrane was bared completely
from the periphery of the anterior chamber back to the center of
the anterior chamber

Figure 25.1F: The incision was discontinued and 2 percent Figure 25.1I: Donor lenticule was secured on to the host with
hydroxypropyl methylcellulose was injected through the opening sixteen10-0 monofilament nylon interrupted sutures
into the potential space
196
infiltrating the central corneal disk without an evident
bubble formation. This usually happens if the needle is
too superficial in the corneal stroma. In such cases, the
surgeon should stop injecting air in order to preserve
some clear areas of corneal tissue. The needle can be
withdrawn and the surgeon may repeat the procedure,
starting at another point on the perimeter of the trephine

Chapter 25: Deep Anterior Lamellar Keratoplasty: Double Bubble Technique


groove where the cornea is relatively clear. If the big
Figure 25.2A: Schematic diagram depicting the injection of small bubble fails to form even after 2-3 such attempts, an
bubble into the anterior chamber through the paracentesis wound anterior lamellar keratectomy can be carried out and
using a Rycroft cannula
repeat stromal air injection should be attempted through
the debulked corneal stroma.
b. Perforation of DM: Intraoperative perforation of the DM
is the most feared intraoperative complication during the
DALK. The management of DM perforation depends
upon the stage of the surgery at which the perforation
occurred, and also the size of the perforation. If the
cornea is perforated during initial trephination, the wound
can be sutured and the operation can either be postponed,
or a layer-by-layer dissection can be attempted. If a
Figure 25.2B: Schematic diagram depicting the injection of air
into the corneal stroma using a 27-gauge needle tip (bevel facing perforation occurs while the corneal stroma still covers
down) that was inserted into the paracentral corneal stromal DM, careful layer-by-layer dissection can be carried out
tissue at a depth of 60-70 percent and corneal stroma can be left over the area of the
perforation. Injection of air, a mixture of SF6 with air,
or a mixture of C3F8 with air into the anterior chamber
can be used for temporarily sealing microperforations.9
In case of a macroperforation, conversion to a full-
thickness penetrating keratoplasty may be inevitable. In
Figure 25.2C: Schematic diagram depicting the movement of such a situation, trypan blue dye may be used to highlight
the small bubble of air towards the periphery of the anterior the remnants of the ruptured DM in order to ensure the
chamber, and inward bulging of the Descemet’s membrane after complete removal of the DM.10
the air injection into the corneal stroma
2. Postoperative complications
a. Formation of double anterior chamber: The occurrence
of a microperforation intraoperatively may lead to the
Postoperative Follow-up formation of double anterior chamber in the post-
Postoperatively, the patients receive 0.5 percent antibiotic operative period. Although some cases may resolve
eyedrops three times a day for four weeks. Prednisolone spontaneously, non-resolution may necessitate the use of
acetate 1 percent eye drops are administered six times day and tamponading agents such as air, SF6 or C3F8. Injection
are tapered over the next one year. of any of these into the anterior chamber causes sealing
of the microperforation and causes the fluid to absorb
Suture Removal from the double anterior chamber. Injection of longer
acting agents such as SF6 and C3F8 may require a
Selective suture removal is performed for any suture-related peripheral iridotomy in order to prevent papillary block
problems and for control of astigmatism. However, all the sutures glaucoma.
should be removed only after one year of surgery as the wound b. Corneal stromal graft rejection: Although the risk of
of DALK is similar to that of PKP and can suffer dehiscence. endothelial rejection is eliminated after DALK, the risk
of immune-mediated stromal rejection remains.
Complications Presumed stromal graft rejection after lamellar
The complications of “Double Bubble” DALK are similar to that keratoplasty presents with diminished visual acuity and
the standard technique of Big Bubble DALK. Briefly, they can corneal stromal edema. The clinical features of stromal
be divided into the following categories: rejection after DALK are similar to those seen in
1. Intraoperative complications rejection after PKP. It is imperative to rule out herpetic
a. Failure of big bubble formation: Sometimes during the eye infection in such cases. Stromal graft rejections
injection of air into the corneal stroma , the air can keep respond well to intensive topical corticosteroid treatment.
197
SUMMARY 4. Melles GR, Remeijer L, Geerards AJ, Beekhuis WH. A quick
surgical technique for deep, anterior lamellar keratoplasty using
Our technique of “Double Bubble” DALK is a simple and visco-dissection. Cornea 2000;19:427-32.
effective surgery that helps in the recognition of the big bubble 5. Archila EA. Deep lamellar keratoplasty dissection of host tissue
with intrastromal air injection. Cornea 1984-1985;3:217-18.
during air injection into the corneal stroma. This further helps
6. Anwar M, Teichmann KD. Big-bubble technique to bare
in the successful performance of DALK in corneal stromal Descemet’s membrane in anterior lamellar keratoplasty. J Cataract
disorders sparing the Descemet’s membrane. Refract Surg 2002;28:398-403.
Section IV: Lamellar Keratoplasty

7. Parthasarathy A, Por YM, Tan DT. Using a “small bubble


technique” to aid in success in Anwar’s “big bubble technique”
REFERENCES
of deep lamellar keratoplasty with complete baring of Descemet’s
membrane. Br J Ophthalmol 2008;92:422.
1. Vajpayee RB, Tyagi J, Sharma N, Kumar N, Jhanji V, Titiyal JS.
8. Foroutan AR, Dastjerdi MH. Shifting-bubble sign in big-bubble
Deep anterior lamellar keratoplasty by big bubble technique for
technique in deep anterior lamellar keratoplasty. Cornea 2007;
treatment corneal stromal opacities. Am J Ophthalmol 2007;
26:117; author reply 117-18.
143:954-57.
9. Mannan R, Jhanji V, Sharma N, Titiyal JS, Vajpayee RB.
2. Noble BA, Agrawal A, Collins C, Saldana M, Brogden PR,
Intracameral C(3)F(8) injection for descemet membrane
Zuberbuhler B. Deep Anterior Lamellar Keratoplasty (DALK):
detachment after phacoemulsification in deep anterior lamellar
visual outcome and complications for a heterogeneous group of keratoplasty. Cornea 2007;26:636-38.
corneal pathologies. Cornea 2007;26:59-64. 10. Sharma N, Jhanji V, Titiyal JS, Amiel H, Vajpayee RB. Use of
3. Fontana L, Parente G, Tassinari G. Clinical outcomes after deep trypan blue dye during conversion of deep anterior lamellar
anterior lamellar keratoplasty using the big-bubble technique in keratoplasty to penetrating keratoplasty. J Cataract Refract Surg
patients with keratoconus. Am J Ophthalmol 2007;143:117-24. 2008;34:1242-45.

198
32

Chapter 32: Penetrating Keratoplasty for Aphakic and Pseudophakic Bullous Keratopathy
Penetrating Keratoplasty for Aphakic and
Pseudophakic Bullous Keratopathy
Sujata Das, Vishal Gupta

Bullous keratopathy is a major complication of cataract surgery. bullous keratopathy. Because of the optical advantages of IOL
Persistent corneal edema after cataract extraction is the leading over contact lenses or aphakic spectacles, eyes should remain
indication for penetrating keratoplasty (PKP) in the United pseudophakic after corneal transplant surgery.17-19 There is
States.1,2 The rate of corneal edema is low, thanks to modern consensus that iris plane, closed-loop anterior chamber IOL (AC-
cataract surgical techniques. However, the actual number of IOL) and dislocated IOL be removed and a careful anterior
afflicted patients is relatively high because a large number of segment reconstruction including vitrectomy, goniosynechiolysis,
cataract extractions are performed annually. Postoperative and iridoplasty (when indicated) be performed. 20-22 The
corneal edema may occur in the absence or presence of an indications of IOL exchange/removal during PKP are listed in
intraocular lens (IOL), and is accordingly termed aphakic bullous Table 32.1. At present, placement of a flexible open-loop AC-
keratopathy (ABK) or pseudophakic bullous keratopathy (PBK) IOL in the angle or suturing of a PC-IOL either to the iris or to
respectively (Fig. 32.1). the sclera is the method commonly used by most surgeons.
Aphakic bullous keratopathy is known to be the leading cause
of secondary corneal degeneration for over 100 years3 although PREOPERATIVE EVALUATION
it was described as corneal dystrophy or bullous keratitis in much
of the earlier literature.4 Past rates of ABK are difficult to History
determine. Comparative series in the period of early IOL use
Taking a careful history is a mandatory component. A detailed
give rates of 0 to 0.8 percent with intracapsular extraction and
history of the cause of vision loss is helpful in documenting
no IOL.5,6 Rates in eyes with vitreous loss during intracapsular
whether the visual loss is related solely to the corneal disease.
cataract extraction ranged from 0.9 to 11.3 percent before
The history should also include an assessment of the patient’s
vitrectomy techniques came into use.7
activities, employment, and the effect of visual loss on these.
The widespread use of IOLs was followed by a dramatic
The most crucial factor here is detailed information of the
increase in PBK, especially that associated with early
previous cataract surgery, including techniques used in cataract
prototypical lens models, beginning with the Ridley lens (1949-
removal, status of the posterior capsule and zonules, and
54), early anterior chamber lens (1952-86), and iris-supported
intraoperative and postoperative complications. The type, power,
pupillary lenses (1953-80). These early lenses were characterized
and configuration of the IOL should be obtained from the
by design flaws, manufacturing defects and inadequate quality
records. A history of general medical problems is helpful in
control.8,9 The rate of PBK was as high as 50 percent over five
planning the pre- and postoperative care and anesthesia.
years in some of the early European series of the 1950s and in
1960s.10,11 The incidence of PBK after posterior chamber IOL
Examination of Anterior Segment
(PC-IOL) implantation has been reported to be lower than the
rate associated with anterior chamber or iris-fixated intraocular Slit-lamp examination is an essential feature of the diagnostic
lens.12,13 evaluation. Careful attention should be paid to the status of the
In most cases of bullous keratopathy, PKP is the only lids, conjunctiva, and cornea. Measurement of central corneal
effective therapy. Survival of a donor cornea in bullous thickness may document stromal edema when, there is mild
keratopathy has been extensively studied.14-16 Although the short epithelial edema or Descemet’s folding. Serial pachymetry is
term graft survival rate is good, visual improvement is often poor. often helpful in documenting the progression of edema. Specular
Corneal transplant surgeons agree on certain goals in the microscopy of the corneal endothelium may be of some use in
surgical management of patients with pseudophakic and aphakic the evaluation of eyes with marginal vision and edema.
237
Table 32.1: Indications of IOL exchange/
removal during PKP
• An unstable IOL demonstrating dislocation or improper
sizing
• Poorly controlled glaucoma
• Recurrent hyphema
• UGH syndrome
• Metal clips or loops on the IOL
Section V: Specific Techniques in Keratoplasty

• Any closed-loop anterior chamber IOL (AC-IOL)


• Iris-supported IOLs with the optic in front of iris
• Chronic pain attributable to an AC-IOL

synechiae, and position, type, and stability of the IOL, vitreous


and capsule are important to observe preoperatively.
A high proportion of eyes with PBK have glaucoma. About
35 percent of the patients use antiglaucoma medication at the
time of keratoplasty.11 Intraocular pressure should be controlled
before keratoplasty is undertaken, if possible, or a combined
filtering or valve procedure should be done at the time of corneal
grafting.

Evaluation of IOL
In the pseudophakic patient who is about to undergo PKP, special
attention must be paid to the IOL and its relationship with the
surrounding structures. The iris should be examined for synechiae
to the IOL, suture to the IOL, erosions and dialysis. Extent and
location of peripheral anterior synechia should be documented.
If the view is inadequate, it can be evaluated by gonioscopy.
Gonioscopy not only provides the surgeon with information on
the condition of the angle but also on the site of IOL haptics (in
case of AC-IOL) and the environment surrounding them. In many
eyes with PBK, successful gonioscopy is not possible because
of the severity of the corneal edema. High-frequency ultrasound
biomicroscopy (UBM) now makes it possible to visualize the
anterior segment structure at high resolution even in the presence
of corneal opacity. It allows the surgeon to predict preoperatively
the degree of difficulty that will be encountered in explanting
the IOL.23

IOL Power Calculations


The IOL power calculations are derived from the modified
Sanders-Retzlaff-Kraff (SRK) formula that uses the axial length
measurements and the keratometry readings. There are various
methods by which the keratometry can be assessed.
• The surgeon’s average keratometry value can be used, which
Figures 32.1A to C: Pseudophakic bullous keratopathy (A) early
stage, (B) advanced stage with posterior chamber intraocular is the average for all previous postoperative keratometry
lens implant, (C) with anterior chamber intraocular lens implant values, following suture removal.
• Most surgeons use a value of 43.5 or 45.0 diopters.
• In cases where there is a large disparity between the average
postoperative keratometry value and keratometry readings
Documentation of the slit-lamp examination includes from the fellow eye, keratometry can be estimated as
variations in corneal thickness, extent and depth of 2 diopters greater than the measurements in the fellow eye
vascularization, and the location of opacities and edema. The to allow for the increased steepness from a slightly oversized
status of the anterior chamber, presence of peripheral anterior graft.
238
• For AC-IOL, horizontal limbal diameter, white to white, is unequal placement of the fixation sutures can cause irregularity
measured prior to the attachment to the Flieringa’s ring. One in the graft recipient bed and considerable graft astigmatism.
millimeter is then added to this measurement to determine Because of this problem, many corneal surgeons have
the size of the new AC-IOL.24,25 Power of the implanted IOL discontinued the use of Flieringa ring and instead simply place
may be determined from previous surgical records. The new a bridal suture beneath the superior and inferior rectus muscle.
AC-IOL power is achieved by subtracting 1.5 diopters from The recipient cornea should be inspected for any evidence
the previous AC-IOL, based on the assumption of an average of superficial corneal pannus, corneal neovascularization or

Chapter 32: Penetrating Keratoplasty for Aphakic and Pseudophakic Bullous Keratopathy
of 1 or 2 diopters of corneal steepening postoperatively. If corneal thinning. If corneal pannus is present, it should be
the original IOL is of iris plane style, 2.5 diopters are scraped off the superficial cornea using a surgical blade. It should
subtracted.26 be kept completely dry. If the epithelium is edematous and loose,
it should be removed with a cellulose sponge or blade at this
Retinal Evaluation time. In cases of ABK and PBK, the graft size is relatively large
in order to provide the maximum number of healthy endothelial
Preoperative detection of retinal detachment is of particular
cells. Using a hand-held disposable trephine or a Hessburg-Baron
concern in aphakic and pseudophakic eyes with opaque corneas,
particularly when, the original surgery is complicated by vitreous vacuum trephine, a partial thickness cut 80-90 percent deep
should be made in the recipient cornea. Corneal tissue is
loss or a dislocated nucleus. Indirect ophthalmoscopy must be
trephined with due care so as not to apply too much pressure on
performed, to the extent possible prior to keratoplasty. B-scan
ultrasonography can be performed rapidly as a screening the globe. The trephine should be perpendicular to the corneal
surface. Care should be taken to avoid uncontrolled entry into
procedure to rule out posterior segment pathology.
the anterior chamber especially in eyes with ABK because of
Cystoid macular edema (CME) is a major preoperative and
postoperative problem in eyes with ABK and PBK.27 It is a great the danger of collapse of the globe due to low scleral rigidity.
The anterior chamber is slowly entered with a microsharp blade.
problem in eyes with iris-supported and AC-IOLs that are
A 3 to 4 mm incision is made to allow easy entrance of the
inserted after intracapsular cataract extraction. In eyes with older
style IOL associated late-onset corneal edema is often associated corneal scissors, which cuts the rest of the host corneal disk. As
the cutting of the cornea is completed, attention should be
with late-onset of CME. Although fluorescein angiography
directed to its endothelial surface where, vitreous attachments
usually can not be performed in eyes with significant corneal
edema, fluroscein angioscopy using an indirect ophthalmoscope and iris adhesions may have to be cut before removal of the
corneal tissue. Once the recipient cornea has been removed from
and a blue filter often allows visualization of late cystoid pulling
the eye, several different approaches may be taken depending
in the macula. Many patients with CME after PBK experience
gradual improvement of their vision as the CME clears over a on the preoperative and intraoperative finding. These approaches
may be differentiated as follows:
period of two or more years.28 Macular function tests (Maddox
Rod test, 2-point discrimination test, Laser interferometry) may
Aphakia with Hyaloid Face Intact
be undertaken whenever possible. Visual evoked response (VER)
gives much needed information about the retinal and optic If the hyaloid face is intact and away from the cornea, the pupil
pathway integrity. may be constricted with pilocarpine. A decision to implant an
IOL depends on the status of the other eye, physical needs and
Surgical Technique activities of the patient and the inability to use contact lens. If
an intraocular lens is to be inserted into the eye, a small amount
The challenges in performing keratoplasty in cases of
of viscoelastic material is first placed over the pupil and on the
pseudophakic bullous keratopathy is not only to ensure minimal
postoperative astigmatism, but also to evaluate the stability of surface of the iris to help act as a cushion. A flexible open-loop
AC-IOL with three-point or quadriflex fixation lens is inserted,
IOL, and if IOL exchange or removal is contemplated, to
if indicated. The donor button is transferred to the recipient bed
facilitate atraumatic removal of the lens from fibrous encashment
in delicate uveal tissue, restoration of anterior segment anatomy, and sutured in place.
and implantation of an IOL which will remain stable and not
Aphakia with Loose Vitreous in Anterior Chamber
elicit intraocular inflammation.
The surgery can be performed either under local (peribulbar Vitreous manipulation at PKP may be a double-edged sword.
block) or general anesthesia. In some cases intravenous mannitol Failure to remove vitreous from the anterior chamber results in
(1-2 gm/kg body weight) can be administered immediately before vitreous incarceration in the wound, contact with the
the surgery over 20 to 30 minutes in order to deturgisate the endothelium, and a poor prognosis for graft clarity and macular
vitreous and make the iris diaphragm fall back. function. Open sky automated anterior vitrectomy should be
Aphakic eyes have very low scleral rigidity and are prone to performed in case of loose vitreous in the anterior chamber. This
scleral collapse during surgery. Either a single or double Flieringa reduces vitreous traction. Some surgeons have also advocated
ring may be fixed to the globe with sutures. Extreme care must the evacuation of fluid vitreous through the pars plana before
be taken in the placement of the scleral support ring because entering the anterior chamber. If formed vitreous is encountered
239
in the anterior chamber at the time of removal of the corneal the iris stroma, with short tags at the ends. The sutures are tied
button, care must be taken to cut any adhesion from the posterior tight enough to approximate the iris, but not so tight as to cause
surface of the cornea. Once the cornea has been removed, an button holing and cheese wiring of the tissue. If the pupil is
open-sky vitrectomy is performed. Attempts should be made to eccentric, one can perform sphincterotomies at the pupillary
free the pupil from vitreous adhesions and to remove any strands rough where interrupted sutures can be placed starting
of vitreous to the peripheral cornea. Vitrectomy should not be peripherally along the sphincterotomy defect. Purse string sutures
performed if the vitreous face is unbroken and does not protrude have been used along the pupillary margin to enable the creation
Section V: Specific Techniques in Keratoplasty

anteriorly because this increases the risk of cystoid macular of a central and circular pupil.30
edema and retinal detachment occurring after this procedure.29
IOL Implantation
Pseudophakia with Hyaloid Face Intact
Successful vision restoration in eyes with PBK is dependent, to
If the hyaloid is unbroken or the posterior capsule is intact, the a large extent, on the successful management of the IOL at the
style of the implant and its effect on the eye primarily determine time of surgery. The three available options for the management
the surgical approach. Whenever, the IOL has to be explanted, of IOL at the time of keratoplasty are to retain, remove without
anterior vitrectomy must be performed even if the hyaloid face replacement, or replace the lens. Earlier reports advocated the
is undisturbed. Depending on the style of IOL and duration of retention of the original IOL.31 However, this has not been
the surgery, frequently there are strong adhesions to the angle, corroborated by later investigations. The high rate of graft failure
iris, vitreous, capsular bag or cilliary sulcus. Explantation of associated with retained IOLs prompted the recommendation of
these lenses is extremely difficult and traumatic to the eye routine IOL removal at the time of PKP in these cases.32 Although
structure. Various forms of iris clips and loops must be opened this approach produced better graft clarity, it created problems
or cut before lysis of iris and vitreous adhesions that surround related to binocular vision in patients where the fellow eye was
the implant. The use of blunt and sharp dissection is required phakic or pseudophakic.33 This stimulated the introduction of
for removal of these lenses. Care must be taken to preserve as IOL exchange. An algorithm can be used in evaluating IOL
much of the iris as possible. In some cases, the AC-IOL optic exchange (Fig. 32.2). The various options for replacing the IOL
should be cut from the haptic near the optic junction and then at the time of PK and IOL exchange include the following:
carefully rotated free from the dense fibrous tissue in the angle • Flexible open-loop AC-IOL,
or cilliary sulcus. Anterior vitrectomy should be performed after • Iris-sutured PC-IOL (IS PC-IOL),
removal of the lens. IOLs are left in place when they are stable • PC-IOL in the cilliary sulcus,
and eye is quiet. • Scleral-fixated PC-IOL (SF PC-IOL).

Pseudophakia with Loose Vitreous in Anterior Chamber Flexible Open-loop AC-IOL


In patients with PBK and loose vitreous the course of action is
Experimental34 and clinical evidence35-38 indicates that Kelmann-
mainly determined by the type of implant and stability of the
style, one-piece, open-loop polymethylmethacrylate (PMMA)
lens. In most cases, the removal of IOL and anterior vitrectomy
AC-IOL performs more favorably than the closed-loop AC-IOL
is required. In general iris plane lenses and closed-loop AC-IOLs
and is associated with long-term graft survival. Open-loop AC-
are removed.
IOLs can give good postoperative results and functional vision
in cases of PBK and ABK.25 However, it is contraindicated in
Gonioplasty
cases of intractable glaucoma, peripheral anterior synechia (PAS)
Viscodissection of the angle may be done by injecting greater than three clock hours, and insufficient iris tissue.
viscoelastic. Iris adhesion to the cornea can be reduced by gently
stroking it radially towards the pupil with a Sinskey hook or
pulling it radially with smooth forceps.30 If large iridocorneal
adhesions are present which are not amenable to separation,
iridotomies may be undertaken on either side of the lesion to
prevent progression of the angle closure in the postoperative
period.

Pupilloplasty
Restoration of the pupil to a central, round configuration by
synechiolysis and iridoplasty serves several important functions.
These functions include prevention of glaucoma and allograft
rejection related to synechia formation, and improvement of the
support for an AC-IOL if it has to be used. When suturing the
iris with 10-0 polypropelene, it is important to bury the knots in Figure 32.2: Management options for IOL exchange
240
Advantages Disadvantages
• Technically easy, • Due to the large area of uveal contact with the IOL, there is
• Requires less iris manipulation, increased risk of suture-induced uveitis, iris atrophy, and
• Lack of suturing for IOL fixation, possible dislocation of the IOL,
• Precludes vitrectomy in many cases, • Insufficient iris from previous iridectomies or iris colobomas
• Less surgical intraoperative time, may not allow iris fixation,
• Can be used in nearly any eye, even in those with sector • Vitrectomy is required in all cases,

Chapter 32: Penetrating Keratoplasty for Aphakic and Pseudophakic Bullous Keratopathy
iridectomies or inflamed irides. • The iris sutures may also cause an ellipsoid dilation of the
pupil.
Disadvantages
• Possibility of progressive endothelial loss, Technique
• Potential for development of synechiae and secondary Fixation of the optic to the iris is preferred to haptic fixation to
glaucoma. ensure better fixation and centration. Either a planar or angled
haptic can be used to suture the optic to the iris. A double-armed
Technique 10-0 polypropelene (prolene) suture is passed through the
After trephination of the recipient, the pupil is constricted with positioning holes in a four-hole44 or two-hole lens.45 The lens
intracameral pilocarpine or acetylcholine hydrochloride as it implant is then held over the iris to determine the best position
minimizes the incidence of peripheral iris tuck. Viscoelastic is for its placement, avoiding any atrophic areas. The polypropelene
injected on the anterior surface of the iris and into the peripheral suture is then passed through the mid-peripheral iris. The PC-
iridocorneal angle. The AC-IOL is then grasped along the edge IOL is then slipped behind the iris with each haptic directed into
of the haptic or superior edge of the optic, and inserted using the cilliary sulcus. The sutures are then tied snuggly.43,46,47 The
the smallest angle of insertion to minimize the entrapment of suture knots are placed between the optic and the iris to reduce
the peripheral iris. The other haptic is grasped, flexed, lowered the areas of contact.
into the keratplasty opening and then released. The pupil should
be monitored to ensure that it is round without any oval PC-IOL in the Cilliary Sulcus
distortion; that would indicate the entrapment of peripheral iris.
In the past, IOL insertion at the time of penetrating keratoplasty
If entrapment of iris is suspected, the involved haptic can be
grasped with Kelman-McPherson forceps and gently pulled back for pseudophakic or aphakic bullous keratopathy after
intracapsular cataract extraction was limited to an AC-IOL or
from the angle, lifted slightly anteriorly, and reinserted until
suturing of PC-IOL to the iris or through the cilliary sulcus. A
displacement of the pupil is no longer visualized. Once
implanted, the haptic should be drawn towards the optic and complicated cataract surgery with AC-IOL placement may leave
posterior capsular remnants or a Soemmering’s ring. If sufficient
elevated with a lens hook to ensure that the foot plates have not
amounts of these tissues are available, implantation of the PC-
captured peripheral iris. Any bleeding is controlled by use of
sodium hyaluronate in the angle or compression with a sponge IOL into the cilliary sulcus with posterior support is possible
during penetrating keratoplasty and IOL exchange.48
soaked with epinephrine (1:1000). At least one peripheral
iridectomy should be done. Care must be taken to avoid placing
Advantages
the foot plates over iridectomies as prolapse through them to
the cilliary body may occur. • Technically less demanding,
Most authors have recommended that AC-IOLs should be • Less surgical time,
placed at 90° to the orientation of the explanted IOL, away from • IOL closer to nodal point,
goniosynechiae, damaged angle or peripheral iridectomies37,39 • Least complicated,
as it could otherwise erode, cause hemorrhage or become a • Avoids complications of AC-IOLs on the angle of the anterior
source of persistent inflammation. chamber.

Iris-sutured PC-IOL Technique


Suture-fixating a PC-IOL to the posterior aspect of the iris, The residual posterior capsule, the remnants of the anterior
through the limbal incision was first reported by Pearce.40 Several capsule and Soemmering’s ring should be carefully evaluated
other surgeons41-43 modified this technique combining it with by retracting the iris in all four quadrants with an iris retractor
penetrating keratoplasty in aphakic eyes with corneal edema. or Sinskey hook. Iris repositor, visco dissection, cyclodialysis
Graft survival ranged between 93 and 97.7 percent. spatula and/or Vannas scissors can be used to break the posterior
synechia. Very little capsular support is required for successful
Advantages PC-IOL implantation in the sulcus as capsular fibrosis occurs in
• Avoidance of the anterior chamber structure, a few months after the original cataract surgery. The IOLs can
• IOL closer to the nodal point of eye. be placed with the haptic over the region of greatest capsular 241
support after placing a high viscosity viscoelastic in the capsular themselves. The knots are buried beneath the episclera by gentle
remnant. rotation of the suture.

Scleral-fixated PC-IOL Ab Externo Approach


This technique involves suturing the haptics into the cilliary A straight transcorneal needle with a 10-0 polypropelene suture
sulcus, which then places the IOL in the anatomic position of penetrates the scleral bed parallel to the iris 1.5 mm posterior to
the lens. This procedure is indicated in cases of preoperative the surgical limbus. The needle tip is passed through the cilliary
Section V: Specific Techniques in Keratoplasty

glaucoma or PAS, and insufficient iris. sulcus posterior to the iris and is visualized in the pupillary space.
A 28-gauge needle is passed through the sclera 180° from the
Advantages straight transcorneal needle. The straight needle is threaded into
the barrel of the 28-gauge needle and then removed. It is then
• The posterior location limits endothelial damage,
passed back across the sulcus in the opposite direction parallel
• Lack of iris sutures allows full pupillary dilation.
to the initial pass but separated by a minimum of 2 mm on the
Disadvantages scleral bed.
A recent study by Sewelam et al 52 , reported
• Technically difficult, ultrabiomicroscopic (UBM) evaluation of 20 eyes, who had ab
• More intraoperative manipulation, externo approach transscleral fixation of PC-IOL. They observed
• Longer surgical time, 22 haptics (55%) were in the sulcus, 11 (27.5%) were, anterior
• Increased risk of vitreous hemorrhage, retinal detachment, to the sulcus, and 7 (17.5%) were, posterior to the sulcus. They
suture-wick, endophthalmitis, lens decentration and tilt.45,49-51 recommended use of the endoscopic technique for precise
localization of the entry of the needle in the sulcus.
Technique
Conjunctival peritomies measuring approximate 3 mm in Lamellar Keratoplasty
length are created at the 2 and 8 o’ clock positions or at the 4 Although PKP enjoys a high anatomic success rate, visual
and 10 o’ clock positions of the limbus to avoid cilliary blood rehabilitation is often slow due to delayed stromal wound healing,
vessels and the long posterior cilliary nerve at the horizontal surgically induced astigmatism, suture-related complications and
meridian. A bipolar cautery may be applied to the episcleral anisometropia associated with unexpected changes in the
vessels to control any bleeding. Scleral flaps can be constructed postoperative corneal power. In contrast, posterior lamellar
to cover the fixation sutures. corneal surgery allows for selective replacement of diseased host
The selection of an appropriate PC-IOL is critical to the endothelium. Posterior lamellar keratoplasty (PLK) for the
success of this technique. The recommended PC-IOL includes management of corneal endothelial disorders was first described
biconvex, large optic (6.5 to 7.0 mm) and one-piece all-PMMA in 199853-55 and since 2001, the technique has been made popular
construction. The eyelet-to-eyelet diameter is 12 to 12.5 mm, in the United States as deep lamellar endothelial keratoplasty
and the haptics are angled posteriorly to further minimize iris (DLEK).56 Instead of a full-thickness transplant, a 7.5 mm
contact. A 10-0 polypropelene suture with double-armed needles diameter posterior lamellar disk is transplanted through a 9 mm
is passed through the iris. The surgeon should ensure that both sutured scleral incision. In 2000, Melles et al modified this
ends of the suture pass the same side of the haptic to avoid any technique to a sutureless procedure in which a folded 9 mm
torque effect, which could result in IOL tilt. The transscleral diameter posterior lamellar disk is transplanted through a self-
fixation can be approached internally by the ab interno approach sealing 5 mm scleral tunnel incision. Despite the excellent
or externally by the ab externo procedure. postoperative result, visual acuity after DLEK rarely exceeded
20/30 due to presumed optical aberration at the graft-host
Ab Interno Approach
interface.57 Unlike DLEK, in Descemet’s stripping endothelial
This technique uses two polypropelene sutures on a short tapered keratoplasty (DSEK) the recipient endothelial layer can be
needle. The tip of the needle is held parallel to the iris and gently removed by stripping of the Descemet’s membrane
moved along the posterior surface of the iris until the cilliary (Descemetorhexis) followed by insertion of a folded donor
sulcus is entered approximately 0.75 mm back from the surgical lamellar donor disk.58 Price and Price employed mechanical
limbus. Both ends of the double-ended sutures are passed through stripping of the diseased host endothelium and replacement with
the cilliary sulcus approximately 3 mm apart. The IOL haptics a healthy homograft of the endothelium, Descemet’s membrane
gently placed into the cilliary sulcus while the fixation sutures and a thin layer of the donor’s stromal tissue harvested with an
are alternatively tightened to avoid further tangling of the sutures automated microkeratome (DSAEK). 59 Recently, Tappin
and to ensure symmetrical placement of the TS-PIOL. The IOL designed a carrier device for selective transplantation of the
is checked for adequate central fixation and tilt by gentle Descemet’s membrane through an 8 mm scleral incision; this is
retraction of the pupil. The sutures are then pulled taut and tied referred to as Descemet’s membrane endothelial keratoplasty

242
(DMEK).60 DMEK may have several advantages. As in DSEK 17. Polack FM. Results of keratoplasty for aphakic or pseudophakic
the surgical trauma to the recipient’s eye is minimized but DMEK corneal edema with intraocular lens implantation or exchange.
also provides a near normal restoration of the grafted cornea. Cornea 1988;7:239-43.
18. Binder PS. Secondary intraocular lens implantation during or after
The main advantages of PLK and its variants are that these
corneal transplantation. Am J Ophthalmol 1985;99:515-20.
techniques induce little postoperative astigmatism, eliminate 19. Arentsen JJ, Laibson PR. Surgical management of pseudophakic
suture-related complications and minimize the risk of wound corneal edema: complications and visual results following
dehiscence. However, from a technical viewpoint, it is penetrating keratoplasty. Ophthalmic Surg 1982;13:371-73.

Chapter 32: Penetrating Keratoplasty for Aphakic and Pseudophakic Bullous Keratopathy
challenging to create a dissection plane in a corneoscleral ring 20. Smith PW, Wong SK, Stark WJ, Gottsch JD, Terry AC, Bonham
that has already been excised. RD. Complications of semi-flexible closed-loop anterior chamber
intraocular lens. Arch Ophthalmol 1987;105:52-57.
21. Speaker MG, Lugo M, Laibson PR, Rubinfeld RS, Stein RM,
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1. Waring GO. 3rd. The 50-year epidemic of pseudophakic corneal pseudophakic bullous keratopathy. Management of the intraocular
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22. Sugar A, Meyer RF. PKP for PBK- we don’t have all the answers.
2. Lois N, Kowal VO, Cohen EJ, Rapuano CJ, Gault JA, Raber IM,
Cornea 1985-86;4:1-2.
Laibson PR. Indications for penetrating keratoplasty and
23. Rutnin SS, Pavlin CJ, Slomovic AR, Kwartz J, Rootman DS.
associated procedures, 1989-1995. Cornea 1997;16:623-29.
Preoperative ultrasound biomicroscopy to assess ease of haptic
3. Hess C. Klinische und experimintelle studie uber die entstehung
removal before penetrating keratoplasty combined with lens
der streifenformigen hornhauttraubung nach starextraktion.
exchange. J Cataract Refract Surg 1997;23:239-43.
Graefes Arch Clin Experiment Ophthalmol 1892 38:1.
24. Polack FM. Results of keratoplasty for aphkic or pseudophakic
4. Cogan DG. Experimental production of so-called bullous keratitis. corneal edema with intraocular lens implantation or exchange.
Arch Ophthalmol 1940;23:918. Cornea 1988;7:239-43.
5. Cataract surgery: interim results and complications of a 25. Zaidman GW, Goldman S. A prospective study on the
randomized controlled trial. Oxford Cataract Treatment and implantation of anterior chamber intraocular lenses during
Evaluation Team (OCTET). Br J Ophthalmol 1986;70:402-10. keratoplasty for pseudophakic and aphakic bullous keratopathy.
6. Jaffe NS, Eichenbaum DM, Clayman HM, Light DS. A Ophthalmology 1990;97:757-62.
comparison of 500 Binkhorst implants with 500 routine 26. Hunkeler JD. Longer haptic allows for better manipulation.
intracapsular cataract extractions. Am J Ophthalmol 1978;85:24- Ophthalmic Surg 1989;20:599.
27. 27. Brightbill FS, Dudley SS. Aphakic bullous keratopathy:
7. Vail DJ. After-results of vitreous loss. Am J Ophthalmol 1965; preoperative fluorescein angiographic screening for macular
59:573-86. edema. Contact Intraocul Lens Med J 1981;7:144-49.
8. Apple DJ, Mamalis N, Loftfield Km Googe JM, Noval LC, 28. Price FW Jr, Whitson WE. Natural history of cystoid macular
Kavka-Van Norman D, Brady SE, Olson RJ. Complications of edema in pseudophakic bullous keratopathy. J Cataract Refract
intraocular lenses: a historical and histopathological review. Surv Surg 1990;16:163-69.
Ophthalmol 1984;21:1-54. 29. Kramer SG. Cystoid macular edema after aphakic penetrating
9. Stark WJ, Whitney CE, Chandler JW, Worthen DM. Trends in keratoplasty. Ophthalmology 1981;88:782-87.
intraocular lens implantation in the United States. Arch 30. Waring GO. 3rd. Management of pseudophakic corneal edema
Ophthalmol 1986;104:1769-70. with reconstruction of the anterior ocular segment. Arch
10. DeVoe AG. Critical evaluation of current concepts in cataract Ophthalmol 1987;105:709-15.
surgery. The George K Smelser Lecture. Am J Ophthalmol 1976; 31. Speaker MG, Laibson PR, Cohen EJ, et al. Pseudophakic bullous
81:715-21. keratopathy. In: The Cornea. Cavanaugh HD (Ed). New York,
Raven Press, 1988.
11. Sugar A. An analysis of corneal endothelial and graft survival in
32. Waring GO 3rd, Welch SN, Cavanagh HD, Wilson LA. Results
pseudophakic bullous keratopathy. Trans Am Ophthalmol Soc
of penetrating keratoplasty in 123 eyes with pseudophakic or
1989;87:762-801.
aphakic corneal edema. Ophthalmology 1983;90:25-33.
12. Taylor DM, Atlas BF, Romanchuk KG, Stren AL. Pseudophakic
33. Alpar JJ. Long-term results of keratoplasty in eyes with intraocular
bullous keratopathy. Ophthalmology 1983;90:19-24.
lenses. Ophthalmic Surg 1986;17:650-54.
13. Fagadau WR, Maumenee AE, Stark WJ Jr, Datiles M. Posterior 34. Apple DJ, Hansen SO, Richards SC, Ellis GW, Kanka-Van
chamber intraocular lenses at the Wilmer Institute: a comparative Norman D, Tetz MR, Pfeffer BR, Park RB, Crandall AS, Olson
analysis of complication and visual results. Br J Ophthalmol 1984; RJ. Anterior chamber lenses. Part II: A laboratory study. J Cataract
68:13-18. Refract Surg 1987;13:175-89.
14. Waldock A, Cook SD. Corneal transplantation: how successful 35. Insler MS, Kook MS, Kaufman HE. Penetrating keratoplasty for
are we? Br J Ophthalmol 2000;84:813-15. pseudophakic bullous keratopathy associated with semiflexible,
15. Vail A, Gore SM, Bradey BA, Easty DL, Rogers CA. Corneal closed-loop anterior chamber intraocular lenses. Am J Ophthalmol
graft survival and visual outcome. A multicenter Study. Corneal 1989;107:252-56.
Transplant Follow-up Study Collaborators. Ophthalmology 1994; 36. Lass JH, DeSantis DM, Reinhart WJ, Hossain TS, Hom DL.
101:120-27. Clinical and morphometric results of penetrating keratoplasty with
16. Agrawal V, Vagh MM, Sangwan V, Rao GN. Penetrating one-piece anterior-chamber or suture-fixated posterior-chamber
keratoplasty for pseudophakic bullous keratopathy. Indian J lenses in the absence of lens capsule. Arch Ophthalmol 1990;
Ophthalmol 1994;75-80. 108:1427-31.
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37. Hassan TS Soong HK, Sugar A, Meyer RF. Implantation of 49. Rajpal RK, Carney MD, Weinberg RS. Complications of
Kelman-style, open-loop anterior chamber lenses during transscleral sutured posterior chamber intraocular lenses.
keratoplasty for aphakic and pseudophakic bullous keratopathy. Ophthalmology 1991;98(suppl):144.
A comparison with iris-sutured posterior chamber lenses. 50. Schecter RJ. Suture-wick endophthalmitis with sutured posterior
Ophthalmology 1991;98:875-80. chamber intraocular lenses. J Cataact Refract Surg 1990;16:755-
38. Lois N, Cohen EJ, Rapuano CJ, Liabson PR. Long-term graft 56.
survival in patients with flexible open-loop anterior-chamber 51. Heilskov T, Joondeph BC, Olsen KR, Blankenship GW. Late
intraocular lenses. Cornea 1997;16:387-92. endophthalmitis after transscleral fixation of a posterior chamber
Section V: Specific Techniques in Keratoplasty

39. Ritterband DC, Seedor JA, Speaker MG. Penetrating keratoplasty intraocular lens. Arch Ophthalmol 1989;107:1427.
for pseudophakic bullous keratopathy. Brightbill FS (Ed), In: 52. Sewelam A, Ismail AM, El Serogy H. Ultrasound biomicroscopy
Corneal Surgery. Theory, Technique and Tissue. 3rd Ed, St. Louis, of haptic position after transscleral fixation of posterior chamber
Mosby, 1999;292-301. intraocular lenses. J Cataract Refract Surg 2001;27:1418-22.
40. Pearce JL. New lightweight sutured posterior chamber lens 53. Melles GR, Eggink FA, Lander F, Pels E, Rietveld FJ, Beekhuis
implant. Trans Ophthalmol Soc UK 1976;96:6-10. WH, Binder PS. A surgical technique for posterior lamellar
41. Waring GO 3rd, Stulting RD, Street D. Penetrating keratoplasty keratoplasty. Cornea 1998;17:618-26.
54. Melles GR, Lander F, Beekhuis WH, Remeijer L, Binder PS.
for pseudophakic corneal edema with exchange of intraocular
Posterior lamellar keratoplasty for a case of pseudophakic bullous
lenses. Arch Ophthalmol 1987;105:58-62.
keratopathy. Am J Ophthalmol 1999;127:340-41.
42. Hall JR, Muenzler WS. Intraocular lens replacement in
55. Melles GRJ, Lander F, van Dooren BT, Pels E, Beekhuis WH.
pseudophakic bullous keratopathy. Trans Ophthalmol Soc UK
Preliminary clinical results of posterior lamellar keratoplasty
1985;104:541-45.
through a sclerocorneal pocket incision. Ophthalmology 2000;
43. Soong HK, Meyer RF, Sugar A. Posterior chamber IOL
107:1850-57.
implantation during keratoplasty for aphakic or pseudophakic
56. Terry MA, Ousley PJ. Deep lamellar endothelilal keratoplasty in
corneal edema. Cornea 1987;6:306-12.
the first United States patients: early clinical results. Cornea 2001;
44. Drews RC. Posterior chamber lens implantation during 20:239-43.
keratoplasty without posterior capsule support. Cornea 1987; 6: 57. Terry MA, Ousley PJ. Replacing the endothelium without corneal
38-40. surface incisions or sutures: the first United States clinical series
45. Price FW Jr, Whitson WE. Visual results of suture-fixated using the deep lamellar endothelial keratoplasty procedure.
posterior chamber lenses during penetrating keratoplasty. Ophthalmology 2003;110:755-64.
Ophthalmology 1989;96:1234-39. 58. Melles GR, Lander F, Rietveld FJ. Transplantation of Descemet’s
46. Morrison LK, Waltman SR. Management of pseudophakic membrane carrying viable endothelium through a small scleral
bullous keratopathy. Ophthalmic Surg 1989;20:205-10. incision. Cornea 2002;21:415-18.
47. Soong HK, Meyer RF, Sugar A. Techniques of posterior chamber 59. Price FW Jr, Price MO. Descemet’s stripping with endothelial
lens implantation without capsular support during penetrating keratoplasty in 200 eyes: early challenges and techniques to
keratoplasty: a review. Refract Corneal Surg 1989;5:249-55. enhance donor adherence. J Cataract Refract Surg 2006;32:411-
48. Donnenfeld ED, Ingraham HJ, Perry HD, Russell S, Foulks G. 18.
Soemmering’s ring support for posterior chamber intraocular lens 60. Tappin M. A method for true endothelial cell (Tencell)
implantation during penetrating keratoplasty. Changing trends in transplantation using a custom made cannula for the treatment
bullous keratopathy. Ophthalmology 1992;99:1229-33. of endothelial cell failure. Eye 2006 (in press).

244
33

Chapter 33: Pediatric Keratoplasty


Pediatric Keratoplasty
Gerald W Zaidman

The field of penetrating keratoplasty has reached an exciting Even in a stable social situation, extensive preoperative
stage in its development. At one time, corneal transplantation in counseling is done. Before surgery is scheduled and after the
children was considered to have a very high chance of failure EUA is performed, parents are extensively counseled regarding
and even contraindicated. Because of advances in surgical the risks of surgery. The parents are reminded that they are about
technique and postoperative care, a clear transplant can now to begin a “marathon” of care. Infants are non-verbal and difficult
often be attained in an infant or a child. Therefore, penetrating to examine. In order to increase the chances of graft success,
keratoplasty is no longer contraindicated in pediatric patients. they must be examined very often. The parents are also informed
In fact, prompt penetrating keratoplasty is a necessary first step that eyes with more severe anterior segment pathology such as
in averting irreversible loss of visual function due to amblyopia. cataracts or glaucoma have a poorer surgical and visual
The visual results of pediatric penetrating keratoplasty, however, prognosis. They must know the difference between surgical
are often disappointing. Many unique difficulties encountered success (a clear graft) and visual development. The parents are
in the management of an infant or a child requiring corneal also informed about amblyopia and its treatment. Finally the
transplantation conspire to make these patients among the most parents are told that the goal is functional, ambulatory (i.e. better
challenging for the corneal surgeon. than counting fingers) vision and they should not expect perfect
vision.
PREOPERATIVE ASSESSMENT Once surgery is agreed upon, the timing of surgery must be
determined. Timing is slightly different in unilateral than bilateral
Many aspects of an infant or a child’s preoperative, intraoperative
cases because of the higher risk of amblyopia in unilateral cases.
and postoperative care differ from those of an adult undergoing
The timing of surgery is also influenced by glaucoma. Control
a corneal transplantation. The child and child’s parents are
of glaucoma is necessary before performing corneal transplant
usually very anxious when they present for the preoperative
surgery. If the untreated intraocular pressure is within a
evaluation. Also the difficulty in assessing the visual function
reasonable range (less than 30 mm Hg), it can usually be
of an infant or a young child, the child’s inability to cooperate
controlled medically. In these patients, therapy is begun with
with an eye examination and the great variability in outcome
Xalatan or other prostaglandins, Trusopt, a beta-blocker or oral
makes the physician’s decision regarding surgery more difficult.
Diamox. Alphagan is not used because of reports of pulmonary
The diagnosis is made after an office visit, family history,
side effects in infants. If medical control is unsuccessful, surgery
consultation with a pediatrician and pediatric ophthalmologist
is required. In these cases, a filtering procedure (trabeculectomy)
(to rule out systemic, genetic and metabolic disorders) and, most
is preferred rather than a valve because of the possible irritative
importantly, an exam under anesthesia (EUA). An EUA is done
effects of the tube on the corneal endothelium or crystalline lens.
on all children with congenital corneal opacities. This is the most
accurate way to do a slit lamp exam, check the intraocular
Indications
pressure, measure the corneal diameter and perform A-scan and
B-scan ultrasonography. At the same time, a refraction, VER, In North America, the most common cause of a congenital
ERG or ultrasound biomicroscopy can be done. corneal opacity is one of the anterior segment dysgeneses (Table
Before surgery one more factor is considered – the child’s 33.1).1,2 This is a group of disorders comprising Peter’s anomaly
social situation. A stable social situation is mandatory. These (Fig. 33.1) (Type I and II), sclerocornea, corneal dermoid
children will require many years of conscientious care; therefore (Figs 33.2A and B) and congenital anterior staphyloma. Peter’s
supportive and motivated parents or caregivers are a necessity. anomaly is the most common disease in this group.3 Type I, the
In an unstable social environment, surgery is doomed to fail and milder form, only involves the cornea and the iris. Type II is the
should not be undertaken. more severe form in which the lens is usually adherent to the
245
Section V: Specific Techniques in Keratoplasty

Figure 33.1: Peters’ anomaly Figure 33.2A: Limbal dermoid in Goldenhar's syndrome

Table 33.1: Indications for pediatric corneal transplants


Congenital
• Peter’s anomaly
• Sclerocornea
• Corneal dermoids
• Congenital glaucoma with corneal edema
• Congenital hereditary endothelial dystrophy
• Posterior polymorphous dystrophy
• Congenital hereditary stromal dystrophy*
• Mucopolysaccharoidosis*
Acquired, Non-traumatic
• Herpes simplex keratitis
• Keratoconus
• Bacterial keratitis
• Neurotrophic keratitis
• Interstitial keratitis*
Figure 33.2B: Preauricular tag in Goldenhar's syndrome
• Ophthalmia neonatorum*
• Fungal keratitis*
• Steven-Johnson syndrome*
Acquired, Traumatic
• Birth trauma
• Corneal or corneoscleral laceration
• Nonpenetrating injury with scar
*very rare causes of pediatric transplants

cornea, or is shrunken, dislocated or cataractous. Dysgeneses


makes up nearly 60 percent of congenital corneal opacities in
North America.1 The next most common cause is congenital
glaucoma, comprising 10 percent to 15 percent of the patients.
The third group, also consisting of approximately 15 percent of
the patients, is the congenital corneal dystrophies. This includes
Figure 33.3A: A case of CHED
congenital hereditary endothelial dystrophy (Figs 33.3A to C and
33.4A and B), congenital heredity stromal dystrophy, and
posterior polymorphous dystrophy. Finally trauma (Fig. 33.5), herpes keratitis, bacterial keratitis, trauma and keratoconus,
infection, metabolic and genetic disorders make up less than 10 which has been reported to occur as early as 6 years of age.
percent of the patients.
Timing of Surgery
In young children, congenital corneal opacities remain the
main cause of corneal transplant surgery. In older children Because of the small size of the neonatal eye and the significant
acquired conditions, both traumatic and non-traumatic, can be a risk of intraoperative complications, a penetrating keratoplasty
reason for transplant surgery. These most frequently include is not done before the child is two months of age. In an ideal
246
Chapter 33: Pediatric Keratoplasty
Figure 33.3B: Congenital hereditary endothelial dystrophy Figure 33.3C: Penetrating keratoplasty in
CHED seen in Figure 33.3B

Figure 33.4A: Congenital hereditary endothelial dystrophy Figure 33.4B: Penetrating keratoplasty in CHED seen in
Figure 33.4A

situation, the child is first seen in the office at 7-14 days of age. steepness and flaccidity makes it very difficult to manipulate in
The EUA is scheduled for 3-6 weeks of age. The corneal the operating room.
transplant is done at 8-12 weeks of age. With a bilateral opacity, Surgery starts by measuring the corneal diameter and sizing
surgery can be delayed slightly but in general the first eye is the incision. The donor cornea is generally ½ millimeter larger
also done between 2-3 months of age. In a bilateral case, the than the recipient. In cases of sclerocornea, the conjunctiva may
more severe eye is not necessarily done first. Because of the risk have to be recessed to the limbus. A scleral support (Flieringa)
of amblyopia and the need for the child to develop vision, the ring is sutured to the globe. The donor is removed from its
less severe eye is often done first. In bilateral cases, the second container, excised, and kept in Optisol until needed. A hand-held
eye is usually done 2-3 months after the first. Although this may trephine blade is used to make a partial thickness incision into
worsen the amblyopia between the two eyes, at least four weeks the patient’s cornea while stabilizing the globe with the ring. The
of postoperative care is required after the first eye to remove anterior chamber is very carefully entered with a microsharp
sutures, control glaucoma, avoid infection and validate parental (number 75) blade. The surgeon must be sure that a gush of
compliance. Once these have been accomplished, the second eye aqueous is seen – indicating that there is a space between the
is done. iris and the cornea. Most of these patients have synechiae (often
extensive) from the iris to the cornea and a shallow anterior
Surgical Technique chamber. Therefore, if the surgeon is not careful, he can find
Surgery is done under general anesthesia. The child is that he is dissecting above Descemet’s membrane or under
hyperventilated and intravenous Mannitol 20 percent is given the iris.
at the beginning of the case (the dose is weight related). The After the anterior chamber is entered, a high-viscosity
donor tissue always comes from a child between the ages of 4 viscoelastic (usually Viscoat) is injected between the iris and the
and 19 years. Corneal tissue under 4 is not used because its cornea. It is not necessary to fully reform the anterior chamber
247
at this time. A specially designed cyclodialysis spatula (made attached at one quadrant. A layer of viscoelastic is put on top of
by Storz) is used to separate some of the adhesions from the the patient’s cornea. The donor cornea is slid on top of the
cornea. The spatula is passed through the surgical opening and patient’s cornea (on the layer of viscoelastic) and sutured it to
into the angle and under the central cornea. This viscoelastic the limbal side of the incision with two 9-0 nylon sutures (at
and mechanical synechiolysis is a crucial step. It has to be done 6:00 and 12:00). Viscoelastic is placed under the host cornea
carefully and with sufficient magnification. After some of the and scissors are slid into the potential space between the host
adhesions are separated, Viscoat is again injected and the spatula cornea and the iris. The host cornea is then cut and slid out from
Section V: Specific Techniques in Keratoplasty

is reinserted. These two steps are alternated until the surgeon is under the donor cornea.
satisfied that all of the adhesions have been broken. During these There are some cases with “rapid and immediate bulging.”
maneuvers, bleeding can usually be controlled by Healon, topical Almost as soon as you start removing the cornea, the lens and
epinephrine drops (in a concentration of 1/10,000), gentle posterior segment begin to bulge forward. In these eyes, each
pressure or microcautery to the bleeding vessels. of the 4 quadrants of the patient’s cornea are opened one-by-
After the synechiolysis, the cornea can be excised. Excision one and tacked back down with a 7-0 silk suture. After that, some
of a cornea from an infant is a very difficult, delicate and precise viscoelastic is put on the surface of the cornea and the donor
maneuver. Because of the inherent instability of the infant eye, cornea is placed on the top of the viscoelastic. Two 9-0 nylon
the unpredictable variety of anomalies, the tendency for rapid sutures are passed through the donor 180° apart, at 6:00 and
and sudden scleral collapse (even in the presence of a Flieringa 12:00 o’clock. These sutures are then passed through the
ring) and the very high-positive vitreous pressure, surgeons remaining rim of the recipient cornea without tying them. Slowly,
should always “expect the unexpected.” These factors can rapidly each 7-0 silk suture is removed. As the 6:00 and 12:00 o’clock
lead to prolapse of the lens anterior to the iris with extrusion of silks are cut out, the 9-0 nylon above it is tied pulling the donor
the lens followed by vitreous loss and more serious into position. Then the host cornea is slid out from under the
complications. This can occur suddenly as the surgeon gently donor. Atropine 1 percent is then instilled and two more 9-0 nylon
lifts on the patient’s cornea or anytime during the synechiolysis. cardinal sutures are placed at 3:00 and 9:00 o’clock.
Therefore, the surgeon must be prepared to treat this potentially Using these maneuvers, it is possible to prevent lens prolapse
disastrous complication. There are several maneuvers available. in nearly all cases. Once the donor cornea is in position, the eye
First, the surgeon must be sure that the child is totally paralyzed is closed with multiple interrupted 10-0 sutures (nylon or prolene)
and hyperventilated. Another dose of Mannitol can be given removing the 9-0 nylon sutures. The anterior chamber is
intravenously. In most cases of “average bulging,” the surgeon deepened with either balanced salt solution or viscoelastic. All
can attempt rapid excision of the diseased cornea and rapid knots are trimmed and buried, the scleral ring is removed,
replacement of the donor. This can work, especially in older subconjunctival antibiotics and steroids are given, and the eye
infants and children and those with minimal anterior segment is covered with a patch and a shield. Before applying the pressure
pathology. In these patients, after removing the cornea, the donor patch and shield, a single drop of 0.5 percent atropine in healthy
tissue is quickly sutured in place with two 9-0 nylon sutures, full-term infants and 1 percent atropine in children should be
one at 12:00 o’clock and the other at 6:00 o’clock. A drop of 1 applied.
percent atropine can be used to pull the ciliary body posteriorly These maneuvers are only worthwhile if the lens is clear and
at this stage and then two more 9-0 nylon sutures are placed at not attached to the cornea. If the lens is cataractous, adherent to
3:00 and 9:00 o’clock. the cornea or abnormal in size or location, it is removed. If
In cases with “gradual severe bulging” of the lens possible, a standard extracapsular cataract extraction is done
approximately 270° of the cornea is excised leaving the cornea (Fig. 33.6). Generally, we prefer to keep the posterior capsule

Figure 33.5: Corneolenticular trauma Figure 33.6: Triple procedure in a pediatric patient
248
intact and plan on a second closed eye procedure to open it in same as adults but infants and young children are unable to
the future. If the posterior capsule breaks (or if the lens is small communicate as to whether they have pain, visual loss or other
or subluxed) then a generous anterior vitrectomy is performed. symptoms; hence they require frequent postoperative
If cataract surgery is required, heparin, 2500 units in 500 cc, examinations. The first postoperative examination is within 24
and epinephrine is added to the I/A bottle of BSS. The heparin hours after surgery. Postoperatively, the children are treated with
is used to decrease fibrin formation. The donor cornea is then Prednisolone Forte (1%) 10 to 12 times a day. A fluoroquinolone
sutured in position, the anterior chamber is deepened and the antibiotic is used 4 times a day and glaucoma therapy (if needed)

Chapter 33: Pediatric Keratoplasty


wound closed and the case ended as above. Finally, the new is continued. No systemic immunosuppressive therapy is used.
cornea may afford the surgeon the first view of the retina with Exams are done at least two to three times a week for the
the indirect ophthalmoscope. Retinoscopy or an A-scan can be first 3 to 4 weeks after surgery, then once or twice a week for 4
also be performed to measure the refractive error. weeks, once a week for the next month and then every two weeks
for 2 months and finally monthly. The monthly exams continue
CONCOMITANT PROCEDURES for the next year. The “marathon” does not only include office
visits. The child has an exam under anesthesia performed every
Iris Procedures 2 to 3 weeks. However, depending on the condition of the eye,
it can be as often as every five to seven days. These EUAs are
Peripheral Iridectomy
necessary in order to remove the sutures before they loosen and
This is indicated if there is posterior synechia or persistent to check the intraocular pressure. A loose suture in a pediatric
intraocular inflammation. This is also performed when graft is a recipe for disaster – loose sutures quickly (sometimes
lensectomy and vitrectomy are undertaken. overnight) lead to infection or graft rejection. Therefore they are
removed after they are noticed. The best way to recognize a loose
Tightening the Iris-diaphragm suture is if one sees mucous adherent to the suture—if this is
In some cases, creating a smaller pupil with 10-0 prolene suture noticed by the ophthalmologist or the parents, the child is sedated
on a noncutting needle will tighten the diaphragm and prevent and the suture removed.
the formation of synechia. In most young children with an uneventful postoperative
course, an average of three EUAs are required, usually every
Pupilloplasty three weeks. The steroid drops are slowly tapered, usually by
one drop every four weeks starting at the third month
This may be indicated when the pupil is disfigured. postoperative. Finally, the child is kept on at least once-a-day
steroid drops until one year postoperatively and then they are
Concomitant Retinal Surgery
stopped. If the graft begins to reject, the steroid drops are
If the eye requires a pars plana vitrectomy for a retinal increased until either the graft clears or it fails. If the cornea
detachment, use of an intraoperative keratoprosthesis for the fails, the drops are rapidly tapered and a regraft is done.
retinal surgery allows the retinal surgeon a better view than If all goes well with the first eye, the second eye is operated
through a new transplant. After the retinal surgeon completes on four to eight weeks after the first. During this time, the child
the retinal procedures, the keratoprosthesis is replaced with a is seen by a pediatric ophthalmologist. This co-management
donor cornea. continues indefinitely. As the months pass, the office exams
become less frequent. If the child is too uncooperative for
POSTOPERATIVE CARE subsequent office exams or if we cannot use either a
pneumotonometer or a tonopen to check the IOP, then a sedative,
Immediate such as chloral hydrate (75 mg/kg), is given orally in the office.
After surgery, premature infants and children with systemic Once the child falls asleep, the intraocular pressure is checked,
disease should be monitored carefully by the ophthalmologist, and a portable slit lamp is used to examine the eye.
pediatrician and anesthesiologist. These patients can be Finally, the parents are warned that the graft is at risk of
discharged on the first or second postoperative day if the vital rejection (Figs 33.7 and 33.8) whenever the child develops any
signs are normal, oral intake is normal and the eye is doing well. severe febrile illness or is to be vaccinated. At these times, the
Full-term infants and healthy older children are done as out- steroid drops are increased in frequency for a short time. Also
patients. vaccinations are delayed until one year after surgery. Then when
it is time to vaccinate the child, the steroid drops are increased
Early to four times a day for one week before and one week after the
vaccination.
In the first few weeks after surgery, the surgeon’s goals are to
make certain that the wound is secure and watertight, monitor
Alternatives to Penetrating Keratoplasty
and promote epithelization of the graft, monitor and control
intraocular pressure, rule out ocular infection and begin Some children with congenital corneal opacities can be treated
amblyopia therapy. Postoperative complications are usually the without a penetrating keratoplasty.4 These alternative operations 249
Section V: Specific Techniques in Keratoplasty

Figure 33.7: Graft rejection in pediatric keratoplasty (diffuse) Figure 33.8: Graft rejection in pediatric keratoplasty (slit)

consist of an optical iridectomy, rotating keratoplasty or lamellar keratometry measurement of 45 diopters and a vertex distance
keratoplasty. The first two can be used when the child has a of 10 mm.
peripheral opacity that just impinges on the visual axis. Surgically Distance Spectacle Power = 63.7 – (2.28 × Axial length in
enlarging the pupil (in an optical iridectomy) or moving the scar mm).
out of the way (rotating keratoplasty) can enable the child to The results from this formula can be modified by keratometry
see around the opacity. In some children, especially those with measurements. For an aphakic eye, an infant is generally
corneal dermoids or scars secondary to infectious keratitis, the prescribed a near correction that is approximately +2.50 D sphere
corneal opacity is not full thickness. In these cases, we first over the distance correction. Eventually the aphakic child should
remove the opacity with a lamellar dissection; if a relatively clear be put in a bifocal, with the top of the segment at the inferior
posterior cornea remains then a lamellar graft is placed on top border of the pupil. Contact lenses are also useful in visual
of the patient’s residual cornea. The main problem with any of rehabilitation of pediatric keratoplasty patients especially in
these procedures is that they can result in significant astigmatism. monocular aphakes. Silicone lenses offer the highest oxygen
Also, interface haze may be present after a lamellar graft. permeability of all lenses and are often well tolerated in aphakic
However, each procedure avoids a full thickness keratoplasty patients with normal corneas.
eliminating the risk of an endothelial graft rejection. Also the If the contralateral eye is normal, occlusion therapy should
postoperative regimen is less demanding than a full thickness be started as soon as the graft is partially clear and after
graft. correction of any refractive error. Optimally, this should not be
later than 3-4 postoperative weeks. Occlusion during the first 6
Optical Correction and Amblyopia Therapy months of life usually is limited to one fourth to three fourths of
Without effective optical correction and amblyopia therapy, a infant’s waking hours. If the child is older than 6 months, full
pediatric penetrating keratoplasty will be useless. The younger time occlusion therapy should be started. The vision in both eyes
the patient, the deeper the amblyopia, especially if the eye has a is monitored carefully to check for improvement of the
structural and refractive abnormality that limits vision. However, amblyopic eye or worsening of the normal eye.
amblyopia is more easily reversed in younger patients if it is
treated promptly and appropriately. Suture Removal
Correction of the refractive error is a vital part of amblyopia Typically all sutures can be removed safely according to the
therapy. At about the second to third postoperative week, the
following schedule. During the first year of life, sutures are
epithelium has usually healed and the graft has cleared
removed by 5-6 weeks after surgery, in one year olds by 2 to 3
sufficiently to perform cycloplegic retinoscopy. Retinoscopy may months postoperative; in 2 and 3 years olds at 3 to 4
be difficult and the refraction will change as the wound heals
postoperative months, and in 4 to 8 years olds by 5 to 6 months
and sutures are removed; but a correction of a moderate or large
postoperatively. Children older than that require removal of all
refractive error could be prescribed at this time. The refraction sutures before one year after surgery.
should be repeated periodically until a few months after all the
sutures have been removed. Thereafter, refraction should be
Results
repeated as needed. Refraction of an aphakic eye can be
confirmed if the axial length is known. The following formula In our experience, if this peri- and postoperative regimen is
is an approximation for an aphakic eye and assumes a followed children can have good surgical results. Graft clarity
250
is obtained in 70-75 percent of the young children with acquired 4. Fruech BE, Brown SI. Transplantation of congenitally opaque
corneal opacities (infections, trauma, etc.).5-9 In the milder form corneas. Br J Ophthalmol 1997;8:1064-9.
5. Dana MR, Moyes AL, Gomes JA, Rosheim KM, Schaumberg
of Peter’s anomaly, Peter’s anomaly type I, and in congenital
DA, Laibson PR, Holland EJ, Sugar A, Sugar J. The indications
corneal dystrophies, graft clarity is possible in 80-90 percent of
for and outcome in pediatric keratoplasty. A Multicenter Study.
children. The remainder of the children, even if they have a Ophthalmology 1995;102:1129-38.
translucent graft, have better visual potential than if they had 6. Dana MR, Schaumberg DA, Moyes AL, Gomes JA, Laibson PR,
their original opaque cornea.10-14 We recently reviewed our Holland EJ, Sugar A, Sugar J. Outcome of penetrating

Chapter 33: Pediatric Keratoplasty


experience with children with Peters anomaly Type I.15 We keratoplasty after ocular trauma in children. Arch Ophthalmol
followed our children for more than 3 years after their original 1995;113:1503-07.
7. Gollamudi SR, Traboulsi EI, Chamon W, Stark WJ, Maumenee
transplants and noted that nearly 90 percent had clear grafts;
IH. Visual outcome after surgery for Peters’ anomaly. Ophthalmic
additionally 54 percent of the children had obtained vision Genet 1994;15:31-5.
≥ 20/100. 8. Parmley VC, Stonecipher KG, Rowsey JJ. Peter’s anomaly: a
Children with sclerocornea, Peter’s anomaly Type II or review of 26 penetrating keratoplasties in infants. Ophthalmic
severe glaucoma do less well.5-8 However, also in these children Surgery 1993;24:31-35.
the visual potential is usually better with a cloudy keratoplasty 9. Cameron JA. Good visual result following early penetrating
than their original opaque cornea. keratoplasty for Peter’s anomaly. J Ped Ophthal Strabismus
1993;30:109-12.
Finally one must continually remind the parents that visual
10. Heon E, Barsoum-Homsy M, Cevrette L, Jacob JL, Milot J,
acuity is dependent both on the status of the graft and on Palemeno R, Musarella MA. Peters’ anomaly. The spectrum of
aggressive amblyopia therapy. The child must continue to see a associated ocular and systemic malformations. Ophthal Ped
pediatric ophthalmologist throughout the postoperative period Genetics 1992;13:137-43.
(and beyond) in order to develop and maintain the best possible 11. Tucker SM, Enzenauer RW, Levin AV, Morin JD, Hellmann J.
vision. Corneal diameter, axial length and intraocular pressure in
premature infants. Ophthalmology 1992;99:1296-300.
12. Cowden JW. Penetrating keratoplasty in infants and children.
REFERENCES Ophthalmology. 1990;97:324-9.
13. Brown SI, Salamon SM. Wound healing of grafts in congenitally
1. Dana MR, Schaumberg DA, Moyes AL, Gomes JA. Corneal opaque infant corneas. Am J Ophthalmol 1983;95:641-44.
transplantation in children with Peter’s anomaly and mesenchymal 14. Rahman W, Anwar S. An unusual case of keratoconus. JAPOS
dysgenesis. Arch Ophthalmol 1977;104:1580-86. 2006;43:373-75.
2. Developmental anomalies of size and shape. In: Cornea. 15. Zaidman, GW: Lamellar Keratoplasty for Anterior Corneal
Krachmer et al eds. St. Louis, Mosby, Chapter 1977;76:871-84. Scarring in Infants and Young Children. In Surgical Techniques
3. Zaidman GW, Juechter K. Peters’ anomaly associated with in Anterior and Posterior Lamellar Corneal Surgery. John, T. (ed).
protruding corneal pseudostaphyloma. Cornea 1998;17:163-68. Jaypee Brothers, New Delhi, India, 2005.

251
34
Section V: Specific Techniques in Keratoplasty

Therapeutic Keratoplasty
Eric Donnenfeld

Therapeutic keratoplasty is a surgical procedure the main purpose penetrating keratoplasty was performed for active ulcerative
of which is (1) to restore the structural integrity of the eye keratitis in 7 percent of these patients and for viral keratitis in 6
(tectonic keratoplasty) or (2) to resolve an infectious/ percent of patients. 13 Killingsworth et al 12 reviewed 80
inflammatory keratitis which is refractory to conventional consecutive therapeutic keratoplasties performed in Florida, over
medical therapy. Often, therapeutic keratoplasty is performed a 9-year period. Twenty-six therapeutic keratoplasties were
when both of these indications are present, such as in the performed for bacterial infections, 15 for fungal infections, 11
treatment of a corneal ulcer that has been unresponsive to for active herpetic keratitis, 4 for persistent epithelial defects
antibiotics, and has perforated. Therapeutic keratoplasties are following herpes simplex keratitis, 12 for dry eyes, 10 for
generally emergent or urgent procedures in which the survival nonherpetic persistent epithelial defects and 2 for Acanthamoeba
of the globe is in jeopardy. Thus, unlike optical penetrating keratitis. Similarly, a review in India of 100 cases by Sony and
keratoplasty, in which visual restoration is the primary goal, acute colleagues14 demonstrated that most therapeutic keratoplasties
visual rehabilitation remains of secondary importance in were performed for bacterial keratitis refractory to maximal
therapeutic keratoplasty. Visual rehabilitation if necessary can medical therapy, while fewer cases were for fungal keratitis
always be accomplished at a later date under more controlled unresponsive to maximal medical management. A recent series
circumstances. from Singapore showed that the most common infectious
organisms requiring a therapeutic keratoplasty were,
Pseudomonas aeruginosa (58.7%) and Fusarium species
INDICATIONS FOR THERAPEUTIC KERATOPLASTY
(32.3%).15 Eighty patients received a penetrating keratoplasty
Despite recent advances in the medical management of infectious and 12 underwent a lamellar keratoplasty. Mean transplant
keratitis, there remains a subgroup of bacteria, fungi, amoeba, diameter was 9.5 mm. One-year therapeutic survival for bacterial
parasites, and viruses that does not respond to antimicrobial and fungal keratitis was 76.6 and 72.4 percent, respectfully.
therapy. 1-7 Therapeutic keratoplasty is indicated when, When an acute ulceration threatens perforation, the patient
inflammatory or infectious corneal disease is progressing despite should be receiving systemic as well as topical therapy to reduce
maximal medical therapy, and the integrity of the globe is the likelihood of intraocular involvement. Subconjunctival
compromised. Medical therapy should be continued or altered, antibiotics do not appear to offer a signicant advantage over
if necessary, until there is no reasonable expectation that the aggressive topical therapy.16,17 Once, an acute infectious corneal
infection or inflammation can be controlled or until there is a perforation has occurred, topical antimicrobials should be
signicant risk of corneal perforation or scleral extension. Corneal continued, but the physician and patient should be aware of the
perforation dramatically increases the risk of endophthalmitis risk of intraocular toxicity.18-20 An attempt to seal the perforation
and reduces the survival of the keratoplasty, while infectious with cyanoacrylate adhesives can be considered.21-23 After the
scleritis should be avoided due to the severe morbidity of this integrity of the anterior chamber has been re-established, topical
disease.8-11 Noninvasive surgical treatment, such as conjunctival antimicrobial treatment can be reinstituted safely without the risk
flaps and tarsorrhaphies, can be attempted if indicated. of intraocular toxicity. Closing the perforation with cyanoacrylate
A therapeutic keratoplasty offers a surgical debridement of restores the integrity of the anterior chamber, opens the angle
an infectious process. The goal of therapeutic keratoplasty is to and prevents the formation of synechial angle closure glaucoma.
completely remove the infectious inoculum or to decrease the Sealing the perforation with cyanoacrylate may often be denitive
organisms in the cornea to a level at which exogenous anti- management, but if the perforation does progress to require
infective/anti-inflammatory agents and the patient’s endogenous therapeutic keratoplasty, the patient will have been temporized
host defense mechanisms can be effective.12 Robin et al13 with additional antimicrobials and hopefully the ulceration will
reviewed 497 penetrating keratoplasty buttons and noted that have been sterilized. When cyanoacrylate is applied, the patient
252
must be monitored closely because bacterial infections have been
shown to progress beneath the cyanoacrylate glue.24
When perforations or descemetoceles are treated with
therapeutic keratoplasties, outcomes are generally satisfactory.
Jonas et al examined a series of 60 cases of keratoplasty for these
indications, and found that 90 percent achieved some
improvement in preoperative visual acuity. Ten patients (17%)

Chapter 34: Therapeutic Keratoplasty


required repeat keratoplasties for recurrent corneal ulcers.25 In
a series of 20 patients who experienced a corneal perforation
graft transparency rate was 67 percent in 15 eyes that underwent
central penetrating keratoplasty and 85 percent of eyes had
improved visual acuity following their therapeutic keratoplasty.26

Therapeutic Keratoplasty for Bacterial Keratitis


Certain bacteria, notably Pseudomonas aeruginosa,27 can infect
the cornea and progress to corneal perforation over 24 to 48
hours. These bacteria may produce collagenase, which results
in rapid corneal thinning. Most bacterial infections, when,
managed expediently, respond to therapy, but due to delay in
patients seeking or obtaining medical treatment, the infections
may rapidly progress to corneal perforation.27,28 Bacterial
keratitis has been treated with both lamellar and penetrating
keratoplasty in an attempt to reduce the infectious organism count
in the cornea when medical treatment has not been successful.
Lamellar and penetrating grafts have also been used to prevent
and/or treat perforation. Malik and Singh 3 managed 36
Pseudomonas ulcers with lamellar and penetrating grafts. All
eight of the lamellar grafts became reinfected and one eye was
enucleated. Only four of the 28 penetrating therapeutic grafts
became reinfected. The authors concluded that penetrating grafts
are more efficient in treating active infection than lamellar grafts. Figures 34.1A and B: This 82-year-old female developed
Hill1 in 1986 presented 23 patients with deep, indolent ulceration microbial keratitis in the setting of pseudophakic bullous
keratopathy with epithelial bullae (A). Cultures grew Moraxella
and/or descemetocele that were treated with therapeutic spp. sensitive to the antimicrobials used, but the ulcer persisted
keratoplasty. Early surgery did not jeopardize thenal outcome with minimal improvement after four weeks (B). The patient
of the keratoplasty. The period of morbidity was shorter, and underwent successful penetrating keratoplasty with an
more rapid visual rehabilitation occurred with early keratoplasty, improvement of preoperative visual acuity
possibly secondary to the fact that corneal neovascularization
was prevented by earlier surgical management. Removal of the
infected cornea may necessitate a larger than customary unresponsive to conventional medical therapy. These infections
are generally opportunistic and indolent, but continue to progress
keratoplasty in order to debride the infected tissue. Cowden
despite aggressive treatment. This subgroup includes crystalline
et al29 presented 14 penetrating keratoplasty patients using
9.5 mm or larger diameter grafts (Figs 34.1A and B). Five of keratopathy (most commonly due to alpha-hemolytic
Streptococcus),12,31,32 but can be seen with a variety of bacteria
these patients had bacterial keratitis. They concluded that larger
as well as Candida and Mycobacterium fortuitum.2,12 These
diameter penetrating keratoplasties can salvage an eye that may
have otherwise been lost, with reasonable visual rehabilitation. infections are most commonly seen following corneal surgery,
and will relentlessly progress until a therapeutic keratoplasty is
Although visual prognosis is best when the surgery is performed
performed. Although greater than 50 percent of cases of
in a sterilized, minimally inflamed eye, perforation or threatened
perforation with uncontrolled progression of the disease and/or infectious crystalline keratopathy fail to respond to medical
management, as there is minimal inflammation in this disorder
a necrotic stroma all mandate early intervention. Lam and
therapeutic keratoplasty is generally successful.32
Cooper 30 presented 13 patients treated with therapeutic
keratoplasty for bacterial suppurative keratitis with satisfactory
Therapeutic Keratoplasty for Fungal Keratitis
long-term optical results.
A separate subgroup of bacterial keratitis, which may require The introduction of topical antifungal agents has reduced the
therapeutic keratoplasty, is bacterial infections that are need for therapeutic penetrating keratoplasty for fungal keratitis
253
and has also improved the prognosis and visual outcome of The mainstay for treatment after therapeutic keratoplasty has
patients with medically uncontrolled fungal ulcers. Forster and been corticosteroids to prevent allograft rejection and control
Rebell4 emphasized the importance of intensive antifungal postoperative inflammation. However, in the management of
treatment prior to therapeutic keratoplasty to help stabilize the mycotic keratitis, corticosteroids have been discouraged because
cornea and improve the prognosis. They reviewed 61 eyes with of the risks of exacerbating an existing infection or introducing
corneal fungal infections, of which 13 were considered treatment a superinfection. 40 In a prospective, nonrandomized
failures. Nine of the 13 patients with treatment failure underwent interventional case series of three patients, topical cyclosporin
Section V: Specific Techniques in Keratoplasty

therapeutic keratoplasty. Five of these nine patients achieved a A (tCSA) 0.5 percent has been shown to be a safe and useful
visual acuity of 20/70 or better. In all nine patients who adjunct in the treatment of therapeutic keratoplasties for fungal
underwent penetrating keratoplasty, the fungal disease process keratitis to avoid or reduce the use of corticosteroids. 41
was halted by the therapeutic keratoplasty.4 Polack et al33 had Furthermore, compared to corticosteroids, tCSA has been shown
reviewed 30 patients with keratomycosis. Of the 22 treated in vitro to have a statistically signicant suppressive effect on
surgically, penetrating keratoplasty was far superior to lamellar fungal growth.42,43 The most common fungal organisms isolated
keratoplasty. Pathological examination revealed that fungal preceding and during therapeutic keratoplasty include Fusarium,
elements appeared to penetrate Descemet’s membrane, causing Aspergillus, and Candida.4,15,44
a high recurrence rate in lamellar keratoplasty grafts. Forster34
observed that 17 of 29 corneas infected by fungi remained Therapeutic Keratoplasty
culture-positive at the time of keratoplasty, and 26 of the eyes for Acanthamoeba Keratitis
had viable hyphal elements on pathology (Fig. 34.2). 34
The respective roles of medical and surgical intervention in
Killingsworth et al12 obtained a 100 percent cure rate in 15 fungal
Acanthamoeba keratitis are controversial. Some patients
ulcers treated with therapeutic keratoplasty (Figs 34.3A and B).12
Postoperatively, fungal infection may inltrate the grafted
tissue.35-37
Xie and co-authors38 studied 108 eyes with fungal keratitis
in which therapeutic keratoplasty was performed. Eighty percent
of eyes remained clear during follow-up with no recurrence of
infection and visual acuity ranging from 20/100 to 20/20. A later
study by Xie and colleagues39 investigated the effectiveness of
lamellar keratoplasty in treating fungal keratitis. They achieved
therapeutically benecial results in 93 percent of eyes (51 of 55
operations performed) with a resulting visual acuity ranging from
20/63 to 20/20.39 In four cases there was a recurrence of the
fungal infection within 2 weeks, which was cured by a therapeutic
keratoplasty. The authors point out that corneal tissue used in
lamellar keratoplasty may be obtained more readily than healthy
tissue used in penetrating keratoplasty, and that lamellar
keratoplasty is a viable option for treating fungal keratitis.39

Figures 34.3A and B: (A) Shows an inactive scar from herpes


simplex interstitial keratitis, with cholesterol deposits within the
Figure 34.2: Recurrence of Candida albicans stroma. (B) Shows active herpetic stromal disease with prominent
in a corneal graft vascularization and significant inflammation
254
diagnosed early have been successfully treated with medication prophylaxis during the immediate postoperative period and
alone.45,46 Early penetrating keratoplasty has been advocated to during allograft rejection episodes while topical corticosteroids
remove the bulk of infection and reduce the risk of intractable are used may prevent recurrent herpetic disease.56 Ficker et al57
scleral contamination.47 In a report by Ficker et al,48 graft found that the combination of prophylactic antivirals and
survival for Acanthamoeba keratitis was poor with more than corticosteroids increased the success rate in inflamed eyes
50 percent incidence of recurrence in the graft. Cullen et al,49 in undergoing therapeutic keratoplasty for herpes simplex keratitis
a seven patient experience, concluded that early diagnosis helped to a rate comparable to that of quiescent eyes. The use of

Chapter 34: Therapeutic Keratoplasty


with successful medical treatment, but penetrating keratoplasty interrupted sutures, prompt removal of loose sutures, and the
continues to have a central role in the management of cases that previously noted antivirals and topical steroid treatment
are advanced or unresponsive to medical therapy. Cryotherapy combination reduced the recurrence of herpes simplex virus to
of the host cornea has also been suggested in conjunction with 15 percent. Killingsworth et al12 divided 15 patients who required
penetrating keratoplasty for cases unresponsive to medical therapeutic penetrating keratoplasty for herpes simplex keratitis
treatment. 50 In a series of 32 patients the most common into two groups. The first group included patients with severe
complication of therapeutic keratoplasty for Acanthamoeba stromal keratitis who did not respond to medical treatment and
keratitis was glaucoma with over half of these patients patients who progressed to perforation. The second group
developing graft failure and mydriatic, fixed pupils.51 The acute consisted of patients who developed corneal perforation
management of these active cases is to sterilize the infection as secondary to persistent epithelial defects with little or no active
rapidly as possible and to delay surgical management until the stromal inflammation. Only four of the 11 patients in the first
patient receives adequate antiamebic therapy.52 group achieved clear grafts, while all four patients in the second
group were successful.
Therapeutic Keratoplasty for Herpetic Keratitis
Herpes simplex viral disease of the cornea often requires surgical
intervention. Most commonly, this is done for signicant corneal
scarring and is performed under quiescent, controlled
circumstances. Adjunctive medical management has made
possible successful penetrating keratoplasty in the active stromal
stage of herpes simplex keratitis. Therapeutic keratoplasty can
be employed for signicant ulceration and/or perforation, or to
remove viral antigenic material responsible for repeated immune
inflammatory episodes (Fig. 34.4). Success of the keratoplasty
depends, as noted by Langston et al, 53 on the degree of
inflammation, presence of neovascularization, use of ne (10-0
nylon) sutures, and high doses of topical steroids in the
immediate postoperative period.
Adjunctive use of oral acyclovir has been shown to improve
prognosis as well (Figs 35.5A and B).54,55 Topical antiviral

Figures 34.5A and B: (A) shows a chronic, stable neurotrophic


Figure 34.4: A failed, infected graft in a patient who underwent ulcer. (B) Shows microbial keratitis occurring in the setting of a
penetrating keratoplasty for herpes zoster keratitis neurotrophic ulcer. Cultures grew Moraxella spp
255
The prognosis for therapeutic keratoplasty in herpes zoster common finding is breakdown of the epithelium and the loss of
keratitis is generally worse than for herpes simplex keratitis. corneal integrity. Exposure keratitis can occur due to a variety
Patients with herpetic corneal disease commonly have of lid abnormalities, including facial nerve paralysis, 71
neurotrophic corneas. However, the anesthesia tends to be more Parkinson’s disease, entropion, ectropion, lid notching, and lid
severe for herpes zoster than for herpes simplex. One of the most imbrication syndrome.72 The combination of fifth and seventh
important prognostic variables for herpes zoster therapeutic nerve dysfunction can be particularly dangerous.73
keratoplasty is the level of corneal sensation. Therapeutic Severe dry eye may also predispose to corneal perforation
Section V: Specific Techniques in Keratoplasty

keratoplasty in patients with herpes zoster keratitis perforations and therapeutic keratoplasty.74 The dry eye may affect the mucin,
often requires adjunctive therapy, such as conjunctival flaps or aqueous, or lipid component in the tear film, or any combination
tarsorrhaphies. Careful management of external and corneal of the above.75 Severe dry eye may be associated with systemic
disease can improve the outcomes in therapeutic keratoplasty conditions,76 such as collagen vascular disease, ocular cicatricial
for varicella-zoster keratitis. Tanure et al58 published results from pemphigoid,77 rosacea, Riley-Day syndrome,60 or Stevens-
a series of 15 keratoplasties performed for varicella-zoster Johnson syndrome.78,79 Localized causes of severe dry eye
keratopathy from 1989 through 1998 (12 with zoster and 3 with include radiation80 and chemical injuries.81 When a therapeutic
varicella), and found that 87 percent of grafts remained clear at keratoplasty is required and the patient has neurotrophic disease,
an average follow-up of 50 months. To reduce complications exposure keratitis, or severe dry eye, attention must be paid to
from neurotrophic keratopathy, four eyes received lateral the underlying condition.
tarsorrhaphies in conjunction with the keratoplasties, and
frequent lubrication was prescribed. PRE-SURGICAL EVALUATION

Antimicrobial Therapy
Therapeutic Keratoplasty for Persistent
Epithelial Defects and Sterile Melts Before therapeutic keratoplasty for infectious keratitis, the patient
should be treated with topical and systemic therapy directed
An additional subgroup, which may require therapeutic
towards the offending microbe. This treatment applies to
keratoplasty, is severe external disease resulting in a persistent
bacterial, fungal, herpetic, and parasitic infections. Regardless
epithelial defect that progresses to stromal loss. Killingsworth
of the infectious etiology, we always recommend topical
et al12 found that 26 of 80 patients (33%) in their series had
antibiotic therapy to prevent bacterial superinfection. In sterile
therapeutic keratoplasty for a persistent epithelial defect. This
corneal necrosis with corneal perforation, the preoperative
subgroup may often be secondarily infected. The underlying
antibiotic prophylaxis should be broad spectrum and nontoxic
disease process may be extremely varied, but all have in common
to help promote reepithelialization. In addition, we prefer an
the inability to maintain a normal ocular surface and tear film.
antibiotic that penetrates well into the cornea, aqueous, and
This category can be divided into three subclasses: neurotrophic
vitreous to achieve levels above the MIC90 of most pathogenic
disease, exposure keratitis, and dry eye.
bacteria. 88 We currently use a topical fourth-generation
Neurotrophic corneal perforation may be due to systemic
fluoroquinolone in conjunction with a systemic fluoroquinolone.
disease, trigeminal nerve dysfunction, or localized to the eye.
After the patient is hospitalized, we often place the patient on
Systemic diseases include Riley-Day59 syndrome (familial
intravenous vancomycin and tobramycin.
dysautonomia) and Wilson’s disease (hepatolenticular
degeneration).60 Trigeminal nerve dysfunction produces corneal
Donor Material
tissue damage by a poorly understood mechanism. The
pathogenesis may be related to neurologically controlled Exclusion criteria for therapeutic keratoplasties are similar to
mediators of the epithelium.61 Trigeminal dysfunction may occur those for optical penetrating keratoplasties. Most eye banks will
in 15 to 18 percent of patients following trigeminal respond to an emergent request, and either find a local donor or
ganglionectomies or inadvertent surgical trauma.62 Additional bring in a donor cornea from another eye bank. Under emergent
nonsurgical causes of trigeminal dysfunction include circumstances, the donor cornea may not be of the same quality
cerebrovascular accidents, multiple sclerosis, tumors, and as it is for an optical penetrating keratoplasty. Older donor
aneurysms. The most common cause of neurotrophic corneal corneas, that have decreased endothelial cell counts, or have been
disease is the herpes virus family.63 Neurotrophic keratitis in storage media too long to be used for optical penetrating
following herpes zoster ophthalmicus may be particularly keratoplasty, can be ideal for a therapeutic keratoplasty. When,
debilitating.64 Corneal anesthesia leading to perforation has been fresh tissue is not available, cryopreserved, glycerine-preserved
described following Acanthamoeba keratitis,48,65-67 anesthetic corneal tissue, or even sclera, can be acceptable.89-91 The surgeon
abuse,68 and penetrating keratoplasty.69,70 Corneal perforation should have a reasonable expectation of the size of keratoplasty
may be particularly devastating, as the patient is often unaware prior to entering the operating room. In many operating rooms,
of the severity of the disease process because of the lack of pain. small trephines less than 7.0 mm and trephines larger than
Exposure keratitis may predispose to corneal perforation and 8.5 mm may not be readily available. It is the surgeon’s
the need for a therapeutic keratoplasty. In exposure keratitis, the responsibility to make certain these devices are available if there
256
is any expectation that they are going to be needed. When the after pterygium surgery with adjunctive mitomycin or irradiation,
therapeutic keratoplasty is to be small, and off the visual axis, and peripheral inflammatory disorders such as Mooren’s
the donor cornea quality is not as important as when the visual ulceration. Small therapeutic grafts can be performed in a normal
axis is involved. Central therapeutic keratoplasties often become fashion with a corneal trephine straddling the limbus. Jonas and
optical penetrating keratoplasties, and the availability of good colleagues performed a series of 60 therapeutic keratoplasties
donor tissue in these cases is even more important. for patients with perforated or pre-descemetal corneal ulcers, and
found that sclerokeratoplasties were necessary in eight patients

Chapter 34: Therapeutic Keratoplasty


SURGICAL TECHNIQUE with paralimbal ulcers.25 With larger, eccentric therapeutic
keratoplasties, however, a round trephine will not adequately
At the time of therapeutic keratoplasty, the size of the graft
excise the affected tissue. In these severe cases, a freehand graft
should be carefully determined by placing the appropriate
is often required. The therapeutic patch graft can be excised with
trephine over the cornea and creating an indentation in the
a corneal trephine and then approximated into the corneal defect
epithelium. The goal of surgery is to excise all necrotic or
by serially excising tissue from the donor cornea until it ts into
infected tissue during the trephination. If possible, a 1 mm rim
the appropriate corneal scleral defect. Trephining a cornea in
of healthy corneal tissue should also be removed to leave a stable,
an eye with a flat anterior chamber or markedly decreased
noninfected recipient bed. We routinely suture a Flieringa ring
intraocular pressure can be challenging. Care should be taken
in place to provide scleral support. Once, the size of the recipient
bed has been determined, the donor cornea can be trephined and to avoid pressure on the eye if a perforation is present. We
is usually 0.25 to 0.5 mm larger than the host trephine. The donor recommend using an extremely sharp trephine and applying a
trephination is the same as for optical penetrating keratoplasty. minimal amount of pressure to the globe. Suction trephines, such
During trephination of the recipient bed, care should be taken as a Hessburg-Baron trephine,94 can be advantageous. We have
not to place pressure on the globe, which could lead to extrusion had success with a motorized trephine.
of the intraocular contents or an expulsive choroidal hemorrhage. Rarely, an undiagnosed infectious keratitis patient will be
Avoidance of pressure is particularly important in therapeutic brought to the operating room for a therapeutic keratoplasty. In
keratoplasty for corneal perforation. A self-retaining lid speculum a review by Cohen et al,95 two cases of Acanthamoeba keratitis
or lid sutures are very helpful to prevent pressure on the globe. were found on retrospective pathologic evaluation. At the time
The host trephination in a therapeutic keratoplasty for a corneal of keratoplasty, suppurative areas of the specimen should be
perforation can be difficult due to loss of scleral rigidity with aggressively cultured on multiple media. In addition to chocolate
decreased intraocular pressure. Femtosecond laser trephination agar, blood agar, Sabouraud’s, and thioglycolate, we frequently
for lamellar or therapeutic keratoplasty may offer the advantage culture specimens on Löwenstein-Jensen, brain-heart infusion,
of reduced pressure on the globe while stabalizing the corneal and blood agar with an Escherichia coli overlay, as indicated
perforation.92,93 Femtosecond laser trephinations may also be by the clinical findings. In undiagnosed infectious keratitis, we
customized to fit the corneal perforation. When cyanoacrylate also perform multiple scrapings and send a portion of the
adhesive has not successfully sealed a corneal perforation prior specimen for frozen-section pathological evaluation. Establishing
to therapeutic keratoplasty, it can often be attempted during the the diagnosis in the operating room allows us to alter
operation. A limbal incision or peripheral corneal stab incision intraoperative therapy, including the use of intravitreal
can be made to sweep iris with a cyclodialysis spatula from the antimicrobial injections, if we are suspicious of a concomitant
perforation under viscoelastic protection. When there is vitreous endophthalmitis. Establishing a diagnosis also allows the surgeon
in the perforation, an anterior vitrectomy can often be performed to modify the subconjunctival injections, soak a collagen shield
through the limbal incision. When there is significant chamber in an appropriate medication, and initiate directed postoperative
shallowing with vitreous pressure a pars plana vitrectomy can therapy.
be invaluable to deepen the anterior chamber and prevent Lamellar keratoplasty should gnerarally be avoided for
expulsion of the crystalline lens, If cyanoacrylate adhesive can therapeutic grafts in active infections, as there is an increased
be applied preoperatively or intraoperatively, the anterior risk of the infection spreading into the deeper tissue, particularly
chamber can be re-formed with viscoelastic, and the host in cases of fungal ulcerative keratitis.35 Fungi appear to have a
trephination can be performed under a more controlled tropism for Descemet’s membrane. When the deeper cornea is
environment. viable, however, we recommend an 80 percent depth trephination
The corneal trephination should be centered over the with approximately 1 mm of beveling of the incision to create a
infection or perforation to leave the maximal, noninfected tissue deep lip of tissue, which provides support for the therapeutic
between the ulceration and the recipient bed. The one exception keratoplasty and decreases the risk of postoperative wound leaks.
is the case of a small perforation or infection in which de- Suturing technique in any inflamed or infectious keratitis should
centering the therapeutic keratoplasty would provide a better almost always be interrupted. The sutures should be
optical result. Occasionally, the therapeutic transplantation is approximately 75 percent corneal depth and should not be full
located near the limbus. This possibility occurs most frequently thickness, as this increases the risk for a conduit of infectious
with limbal wound infections after cataract surgery, infections organisms from the cornea into the anterior chamber. The
257
interrupted sutures should be placed radially and farther into the POSTOPERATIVE MANAGEMENT OF THERAPEUTIC
recipient bed than for a noninflamed optical penetrating PENETRATING KERATOPLASTIES
keratoplasty. We use an increased number of sutures, but try to
The postoperative management of a therapeutic keratoplasty is
maintain only moderate suture tension. The goal of the longer
often as challenging as the operation. Several basic principles
interrupted sutures with moderate tension is to avoid “cheese-
should be followed:
wiring” of the sutures through a potentially necrotic host-bed.
1. Eradicate all remnants of infection, and prevent reinfection.
The interrupted sutures also allow early suture removal for
The therapeutic keratoplasty often provides a surgical
Section V: Specific Techniques in Keratoplasty

excessive sectoral inflammation, vascularization, or recurrent


excision of an infection. When there is a reasonable doubt,
infection.
however, anti-infectious therapy should be maintained until
At the time of keratoplasty, we recommend performing the
the corneal epithelium has healed. Duration of treatment
minimum intraocular surgery necessary. When possible, the
depends on the severity of the infection and the causative
crystalline lens should be left in place, as it provides a barrier
organism. In general, the more opportunistic infections, such
against vitreous seeding and infectious endophthalmitis.84 The
as Acanthamoeba and fungi, are the most resistant to therapy
anterior chamber should be irrigated aggressively with balanced
and require the longest postoperative antimicrobial treatment
salt solution and the iris should be inspected for infectious foci.
to prevent reinfection. This treatment may be as prolonged
Any iris lesions should be excised and cultured. When infection
as several months.
of the vitreous is suspected, particularly in aphakic eyes, the
2. Promote re-epithelialization of the cornea and wound
vitreous should be thoroughly cultured. When the organism is
healing. Avoid prolonged over-treatment of the cornea with
known, intravitreal injections of an appropriate antimicrobial are
toxic medications, such as fortied antibiotics, amphotericin
indicated. When the organism is in question, broad-spectrum
B, and antivirals. Systemic acyclovir appears to offer the
intravitreal injections are indicated. We currently use intravitreal
efficacy of topical antivirals without the risk of keratitis
vancomycin (1 mg in 0.1 ml) and ceftazidime (2.5 mg in 0.1
medicamentosa. We routinely maintain patients with a
ml) for suspected bacterial endophthalmitis.
therapeutic keratoplasty for herpes simplex keratitis on
At the time of surgery, any predisposing factors, that have
acyclovir 400 mg twice daily or valcyclovir 500 mg one a
contributed to the need for a therapeutic keratoplasty should be
day for 6 months after surgery. 55 When treating
addressed. As previously mentioned, many patients who require
epitheliopathy in therapeutic keratoplasties postoperatively,
a therapeutic keratoplasty have underlying external disease that
nonpreserved tears and lubricants are often useful. When
has been a signicant part of their disease process. After a
these agents are ineffective, a cyanoacrylate temporary
therapeutic keratoplasty, the donor cornea will be more anesthetic
tarsorrhaphy can often resolve a persistent epithelial defect.97
than preoperatively, and the tear film will be signicantly altered.
Milder medications should be substituted for toxic antibiotics
Failure to address the predisposing external disease problem, in
when indicated.
conjunction with the changes induced by the surgery, often leads
to severe postoperative complications, including persistent 3. Control inflammation with corticosteroids. The use of topical
epithelial defects, sterile corneal melts, infectious keratitis, corticosteroids following a therapeutic keratoplasty for an
wound leaks, and corneal neovascularization. All lid infectious organism is controversial. Most bacterial corneal
abnormalities should be corrected. Patients with mild dry eyes infections are responsive to antibiotics. Therefore, the
should have punctal occlusion. Patients with moderate to severe concomitant use of corticosteroids is justied in an inflamed
dry eye should undergo tarsorrhaphy. Patients with severe dry eye. In a therapeutic keratoplasty for herpetic keratitis, the
eyes or anesthetic corneas, in which postoperative wound healing corticosteroids can be given without signicant risk, as long
is jeopardized, should either have large tarsorrhaphies or should as the patient is managed with topical or oral antiviral
be offered a conjunctival flap at the time of therapeutic therapy. There is controversy regarding the use of
keratoplasty. A conjunctival flap is often a denitive procedure, corticosteroids after therapeutic keratoplasty involving
which is further indicated if the eye has limited visual prognosis. infections that do not respond readily to treatment, such as
A conjunctival flap is never indicated if there is active infection fungal or Acanthamoeba corneal ulceration. When there is
or perforation. any sign of active fungal or Acanthamoeba infection
Patients who have undergone previous penetrating following a therapeutic keratoplasty, corticosteroids should
keratoplasty may develop recurrence of the original disease or be avoided.20,98 When the eye has been treated extensively
have a neurotrophic cornea that leads to corneal melting. In these and a wide surgical debridement has been performed,
cases an anterior lameller keratoplasty can be considered. Any however, corticosteroids are indicated and can be used
reported 8 consecutive cases of ALK following PKP.96 Three of safely.12,99 For severe inflammation, the use of systemic
these cases were therapeutic and two were tectonic. All patients corticosteroids should be considered.
had an improvement in visual acuity although one patient 4. Intraocular pressure control. Postoperatively, the patient’s
required a repeat ALK for recurrence of the infectious process. intraocular pressure should be followed carefully. Glaucoma

258
is seen in approximately 50 percent of optical penetrating careful postoperative monitoring. Nevertheless, advances in
keratoplasties. Following therapeutic keratoplasty, the patient microsurgical technique, antimicrobial therapy, and control of
may develop anterior synechiae, iritis, and trabeculitis, which inflammation have resulted in an improved prognosis for
may further contribute to an elevated intraocular pressure. therapeutic keratoplasty.
The pupil should be dilated with cyclopentolate 1 percent
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Chapter 34: Therapeutic Keratoplasty


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70. Mathers WD, Jester JV, Lemp MA. Return of human corneal 86. Donlon JV. Succinylcholine and open eye injury. II.
sensitivity after penetrating keratoplasty. Arch Ophthalmol Anesthesiology 1986;64:525-26.
1988;106:210-11. 87. Liboniti MM, Leahy JJ, Ellison N. The use of succinylcholine
71. Foster CS. Corneal manifestations of neurologic disease. In and open eye injury. Anesthesiology 1985;62:637-40.
Smolin G, Thoft RA, editors: The cornea, Boston, Little Brown 88. Donnenfeld ED, Schrier A, Perry HD, et al. Penetration of
1994;488-89. topically applied ciprofloxacin, norfloxacin, and ofloxacin into

Chapter 34: Therapeutic Keratoplasty


72. Donnenfeld ED, Perry HD, Schrier A, et al. Lid imbrication the aqueous humor. Ophthalmology 1994;101:902-05.
syndrome. Ophthalmology 1994;101:763-66. 89. Capella JA, Kaufman, HE, Robbins JE. Preservation of viable
73. Donzis PB, Mondino BS. Management of non-infectious corneal corneal tissue. Arch Ophthalmol 1965;74:669.
ulcers. Surv Ophthalmol 1987;32:94-110. 90. Eastcott HHJ, Gross AG, Leigh AG, et al. Preservation of corneal
74. Pster RR, Murphy GG. Corneal ulceration and perforation grafts by freezing. Lancet 1954;1:327.
associated with Sjögren’s syndrome. Arch Ophthalmol 1980;
91. Mueller FO, Casey TA, Trevor-Roper PD. Use of deep frozen
98:89-94.
human cornea in full thickness grafts. Br Med J 1964;2:473.
75. Jones DB. Prospects in the management of tear deciency states.
92. Yoo SH, Kymionis GD, Koreishi A, et al. Femtosecond laser-
Trans Am Acad Ophthalmol Otolaryngol 1977;83:693-70.
assisted sutureless anterior lamellar keratoplasty Ophthalmology
76. Ralph RA. Conjunctival goblet cell density in normal subjects
2008;115:1303-7, 1307.
and in dry eye syndromes. Invest Ophthalmol 1975;14:299-302.
93. Farid M, Kim M, Steinert RF. Results of penetrating keratoplasty
77. Ormerod LD, Fong LP, Foster CS. Corneal infection in mucosal
performed with a femtosecond laser zigzag incision initial report
scarring disorder and Sjögren’s syndrome. Am J Ophthalmol
Ophthalmology 2007;114:2208-12.
1988;105:512-18.
78. Howard GM. Stevens-Johnson syndrome. Ocular prognosis and 94. Hessburg PC, Baron M. A disposable corneal trephine.
treatment. Am J Ophthalmol 1963;55:893. Ophthalmic Surg 1980;11:7830.
79. Potz A. Ocular involvement in erythema multiforme. Arch 95. Cohen EJ, Buchanan HN, Laughrea PA, et al. Diagnosis and
Ophthalmol 1950;43:244. management of Acanthamoeba keratitis. Am J Ophthalmol
80. Donnenfeld ED, Ingraham HJ, Abramson DH. Effects of ionizing 1985;100:389.
radiation on the conjunctiva, cornea and lens. In Medical 96. Ang M, Mehta JS, Arundhati A, Tan DT. Anterior Lamellar
radiology. Radiotherapy of intraocular and orbital tumors. Keratoplasty Over Penetrating Keratoplasty for Optical,
Germany, Springer-Verlag 1993;261-70. Therapeutic, and Tectonic Indications: A Case Series. Am J
81. Pster RR. The effect of chemical injury on the ocular surface. Ophthalmol 2008.
Ophthalmology 1983;90:601-09. 97. Donnenfeld ED, Perry HD, Nelson DB. Cyanoacrylate temporary
82. Das S, Samant M, Garg P, Vaddavalli PK, Vemuganti GK. Role tarsorrhaphy in the management of corneal epithelial defects.
of confocal microscopy in deep fungal keratitis Cornea. Ophthalmic Surg 1991;22:591-93.
2009;28(1):11-13. 98. Moore MB, McCulley JP. Acanthamoeba keratitis associated with
83. Heathcote JG, McCartney AC, Rice NS, et al. Endophthalmitis contact lenses. Six consecutive cases of successful management.
caused by exogenous nocardial infection in a patient with Br J Ophthalmol 1989;73:271.
Sjögren’s syndrome. Can J Ophthalmol 1990;25:29-33. 99. Stern GA, Buttrosski H. Use of corticosteroids in combination
84. Speaker MG, Menikoff JA. Prophylaxis of endophthalmitis with with antimicrobial drugs in the treatment of infectious corneal
topical povidone iodine. Ophthalmology 1991;98:1769-75. disease. Ophthalmology 1991;98:847-53.

261
36
Section V: Specific Techniques in Keratoplasty

Femtosecond Laser Assisted


Keratoplasty
Chandra Shekhar Kumar, Namrata Sharma, Rasik B Vajpayee

Since the first full-thickness corneal transplantation, performed Contiguous pulses are placed at a precise depth within the cornea.
by Zirn, in 1905, penetrating keratoplasty (PK) has grown to be The 1053 nm wavelength of light used by the laser is transparent
the most frequently performed tissue transplant in the world. The to the cornea, thus resecting only targeted tissue, while leaving
advent of the femtosecond laser as an ocular surgical tool offers surrounding tissue unaltered. With the energy and firing pattern
the potential for more finite control and precision in corneal controlled by computer, the laser is capable of cutting tissue at
surgery. With the use of proprietary software, femtosecond lasers various depths and patterns, producing minimal inflammation
are currently able to be programmed to create precise corneal or collateral tissue damage. Thermal damage to adjacent tissue
incisions in almost any plane while minimally distorting corneal in the cornea has been measured to be in the order of 1 mm.4
tissue.1-4 Over the past seven years, the femtosecond laser has The laser essentially vaporizes small volumes of tissue by
been used successfully in variety of corneal procedures, including photodisruption, producing a plasma, shock wave, cavitation, and
the preparation of laser in situ keratomileusis (LASIK) flaps, gas (CO2 and H2O) bubbles. Unlike lasers employing visible
the creation of channels for intracorneal rings, and the wavelengths, the ability of the femtosecond laser to cut corneal
preparation of donor and host tissue in anterior lamellar tissue is less hampered by optical haze, making it more useful
keratoplasty. in treating edematous or otherwise, opacified corneas. The laser
Theoretically, the femtosecond laser should increase the spots may be fired in a vertical pattern for trephination (side)
precision and practicality of such procedures because of the cuts or in a spiral or raster (zigzag) pattern to achieve lamellar
highly reproducible dimensions of the cuts made in donor and cuts.
host tissues.2 Such procedures may result in a better fit between The femtosecond laser creates a resection plane for a lamellar
the donor tissue and the recipient cornea, as well as the creation cut using a spot size of 2.5 mm, a pulse repetitionrate of 15–60
of a larger contact area at the donor–host junction. These features kHz, and a pulse width of 600–800 femtosecond (Fig. 36.1).
may result in faster and better wound healing, as well as reduced The laser energy utilized can be varied at the operator’s
suture-induced astigmatism, thereby promoting more rapid visual discretion. At the moment, three lasers are approved by the US
recovery. To allow for additional uses of the technology, the Food and Drug Administration for corneal surgery: Intralase
manufacturer recently increased the depth range of the device (Intralase Corp, Irvine, California, USA), Femtec (20/10
and developed software to enable a variety of incisions that are PerfectVision; GmbH, Heidelberg, Germany), and Femto LDV
both full and partial thickness. With appropriate parameter (Ziemer Ophthalmic Systems AG, Port, Switzerland).
selection, the corneal surgeon now can create a variety of shapes
for PK procedures. Corneal surgeons have utilized the FEMTOSECOND LASER ASSISTED
femtosecond lasers for various types of keratoplasty including PENETRATING KERATOPLASTY
anterior lamellar keratoplasty, penetrating keratoplasty and
The first human, shaped, full-thickness corneal procedure using
Descemet’s stripping endothelial keratoplasty.
the femtosecond laser was performed in Indianapolis, Indiana
in November 2005. Following this, the company opened up the
FEMTOSECOND LASER PRINCIPLES
clinical investigation of IntraLase Enabled Keratoplasty (IEK).
The femtosecond laser was commercially introduced in 2002 for The IEK software enables the femtosecond laser to perform
use in the creation of a corneal flap in laser in situ keratomileusis three-cut segments: a posterior side cut, a lamellar cut and an
(LASIK). The femtosecond laser is a focusable infrared laser, anterior side cut. Two or more of these cut segments can be
which utilizes pulses in the femtosecond (10_15 s) duration range. turned on or combined to create patterns for shaped keratoplasty,
264
Chapter 36: Femtosecond Laser Assisted Keratoplasty
Figure 36.1: Femtosecond laser creating a
resection plane for a lamellar cut

Figures 36.3A and B: Mushroom pattern — larger


diameter cut anteriorly

Figure 36.2: Top-hat configuration: Posterior lamella including


endothelium is more than anterior lamella- transplanting more
endothelium

including a top-hat pattern (larger diameter cut posteriorly) (Fig.


36.2), mushroom pattern (larger diameter cut anteriorly) (Figs
36.3A and B), zigzag (Figs 36.4A and B) and Christmas tree
pattern, tongue and groove (Fig. 36.5), etc. The shape and
diameter of shaped keratoplasty is dependent on a number of
clinical parameters, e.g. smaller diameter may be necessary with
a smaller recipient corneal diameter, top-hat pattern with larger
diameter cut posteriorly are suitable for endothelial
decompensation patients. Figures 36.4A and B: Zigzag pattern
The same laser parameters are used to cut the corneal tissue
for both the donor tissue and the recipient. To program the laser Complete preoperative work up- work up including keratometry,
accurately, recipient and donor corneal diameters and central and axial length, VKG, Orbscan, status of lens, posterior segment
peripheral thickness are needed. The laser pattern always starts evaluation should be done. Anterior segment Optical coherence
from the deepest portion of the cornea and then works its way tomography for measurement of central and peripheral corneal
anteriorly. If all three segments are enabled, the cut would start thickness is helpful in planning the cut dimensions.
from the posterior depth programmed into the laser, moving
toward the surface, then the lamellar cut would be performed Technique
followed by the anterior side cut. The software allows for a
maximum diameter of 9.5 mm, with the ability to vary the side Recipient Cornea Preparation
cut angle from 30 to 150°.
The recipient cornea is cut before the donor cornea is prepared.
In recipient, the femtosecond laser requires placement of a
Preoperative Work up
suction ring and applanation lens. The maximum graft diameter
Preoperatively patients should be investigated in the same line appropriate for each patient is determined at the time of surgery
as for the routine pentrating keratoplasty. Intraocular pressure based on caliper measurements of the horizontal corneal
(IOP) must be controlled adequately prior to surgery. Ocular diameter. An 8.0 mm diameter circle is indented on the anterior
surface diseases including rosacea, dry eyes, blepharitis, corneal surface without use of staining/ marking pen as oil-based
trichiasis, exposure keratopathy, ectropion, and entropion must ink may reduce the ability of the femtosecond laser to penetrate
be recognized and treated prior to penetrating keratoplasty. the cornea. 5 Using this mark as a reference, ultrasonic
265
pachymetry measurements are taken at the planned graft diameter keratoconic eyes was 20/30. The Fuchs eye also had a BSCVA
and used to determine the appropriate depth setting for the of 20/30, while the PBK eye was 20/60 with a visually significant
lamellar ring cut. In general, if the minimum peripheral posterior capsule membrane. At 3 months, four of the seven eyes
pachymetry measurement is at least 450.0 mm, the lamellar ring underwent partial suture removal in order to manage postsurgical
cut was set for 300.0 mm from the anterior surface.6 If the astigmatism. The mean induced astigmatism did not exceed 4D
minimum peripheral pachymetry measurement is less than 450.0 in this series.
mm, the lamellar ring cut depth is set between 200.0 mm and
Section V: Specific Techniques in Keratoplasty

250.0 mm. After a proper vacuum seal is obtained, the ANTERIOR LAMELLAR KERATOPLASTY (ALK)
applanation lens is applied to provide a uniform reference plane
Surgical advancements in recent years have led to renewed
for the laser, and the laser procedure is performed. After the laser
interest in ALK for appropriate corneal pathology. Benefits of
procedure, viscoelastic is injected into the anterior chamber and
ALK include less invasive (not intraocular) surgery and reduced
the patient’s cornea is removed with gentle manipulation.
risk of rejection. In comparison with microkeratome automated
The recipient cornea can be cut in the operation theater or if
anterior lamellar keratoplasty, Femtosecond ALK enables the
not possible partial cut of recipient cornea can be done at laser
surgeon to perform customized graft-thickness procedures.
center and then patient can be transferred to the operation
Combining Femtosecond ALK with anterior segment OCT
theater.5 An incomplete or nonintersecting incision is made in
findings provides us the ability to estimate the exact depth of
the recipient cornea to prevent the eye from opening while the
the corneal scarring and program the graft thickness in an
patient is moved to the operation theater and given a local
accurate way. In contrast to automated mechanical
injection. This incomplete or nonintersecting incision can be
microkeratomes only predetermined corneal graft thicknesses are
easily opened by blunt dissection during penetrating keratoplasty,
available to surgeons. In addition, the ability to create a vertical
and the incision could be precisely completed with the laser at
side cut with the Femtosecond laser could further improve the
the anterior and posterior surfaces.
fit at the graft-host junction.
The laser is programmed to excise a customized size button
Donor Graft Preparation
from the recipient eye to match the donor tissue. A spiral or raster
For donor graft preparation, the donor tissue is placed in an pattern may be used, although the raster pattern may provide
artificial anterior chamber. When, an entire donor globeis smoother residual stromal beds.9 After removal of the anterior
available, it is mounted directly under the laser. The center of corneal button, the donor cornea is sutured using a combination
the cornea is marked using a felt-tip pen and was aligned of interrupted and running sutures. Sutures may be removed up
underneath the laser’s applanation lens, without the use of a to 6 months after surgery, unless they are loose, or induce
suction ring. The laser procedure is performed and the donor neovascularization of the graft.
button is lifted gently from the host cornea. Sonia10 et al reported the technique of femtosecond laser–
The donor cornea then is fitted into place. The donor cornea assisted sutureless anterior lamellar keratoplasty for anterior
is sutured into place using either interrupted or a mixture of corneal pathology. In their procedure the host corneal button was
interrupted and continuous running sutures. If necessary, a removed and replaced with the donor lenticule on the dried
peripheral paracentesis is used to refill the anterior chamber recipient residual corneal stromal bed after they are cut with
because of the solid adhesion of the angulated margin of the graft Femtosecond laser. At the end of procedure bandage contact
to the bed. lense was applied. Up to 160 to 270 µm (thickness of the
lenticule adjusted in relation to depth of the lesions) lamellar
Postoperative Care
cut were made. They performed Femtosecond assisted lamellar
Postoperative care and medication for femtosecond keratoplasty keratoplasty in 12 eyes and found that 58.3 percent of showed
is similar to patient of convention keratoplasty and has been improvement of their uncorrected visual acuity (mean
mentioned in details in earlier chapters. improvement of 2.5 lines). In their series 50 percent of patients
developed dry eye but it improved with time. In their limited
Results follow-up (mean 12.7 months) they did not encounter other
complications like graft rejection, infection, or epithelial
Kim7 et al in their experimental study showed that femtosecond
ingrowth.
laser use for cutting the donor button is safe for the endothelium
at the graft center and has less harmful effects on the endothelium
Descemet’s Stripping Endothelial Keratoplasty
at the incision area than does conventional trephination. Buratto
and Bohm8 reported on 3-month results on their series of seven Femtosecond laser can be used in place of microkeratome for
eyes (five keratoconic, one with pseudophakic bullous kerato- preparation of posterior donor disk for Descemet’s stripping
pathy and one with Fuchs dystrophy) that underwent Intralase endothelial keratoplasty (DSAEK). It produces posterior stromal
Enabled Keratoplasty in 2006. At this visit, all eyes had good ablations that were, accurate in depth of ablation and circularity.11
central corneal pachymetry with good endothelial cell counts. Jones12 et al. compared the femtosecond laser (30 kHz) and the
The mean best-spectacle corrected visual acuity (BSCVA) in the manual microkeratome for cutting posterior lamella in
266
3. Steinert RF, Ignacio TS, Sarayba MA. “Top hat”–shaped
penetrating keratoplasty using the femtosecond laser. Am J
Ophthalmol 2007;143:689–91.
4. Jonas JB, Vossmerbaeumer U. Femtosecond laser penetrating
keratoplasty with conical incisions and positional spikes. J Refract
Surg 2004;20:397.
5. Ide T, Kymionis GD, Abbey AM, Yoo SH, Culbertson WW,
O’Brien TP. Effect of marking pens on femtosecond laser-assisted

Chapter 36: Femtosecond Laser Assisted Keratoplasty


flap creation. J Cataract Refract Surg. 2009;35(6):1087-90.
6. Price FW, Price MO, Jordan CS. Safety of incomplete incision
patterns in femtosecond laser–assisted penetrating keratoplasty.
J Cataract Refract Surg 2008;34:2099–103.
Figures 36.5: Tongue and groove pattern 7. Kim JH, Choi SK, Lee D. The comparison of femtosecond laser-
assisted penetrating keratoplasty with conventional surgery in
terms of endothelial safety: ex vivo study using porcine eyes.
Descemet’s stripping endothelial keratoplasty and found that the Cornea 2009;28(7):812-16.
both are equally effective in creating precut donor tissue, with 8. Buratto LB, Bohm E. The use of the femtosecond laser in
no detrimental effect on endothelial cell density. The penetrating keratoplasty. Am J Ophthalmol 2007; 143:737–42.
microkeratome creates a smoother stromal surface and thinner 9. Sarayba MA, Maguen E, Salz J, et al. Femtosecond laser keratome
endothelial disks. The femtosecond laser lamellar dissection creation of partial thickness donor corneal buttons for lamellar
depth is less deep, and the stromal surface is less smooth. keratoplasty. J Refract Surg 2007;23:58–65.
10. Yoo SH, Kymionis GD, Koreishi A. Femtosecond laser-assisted
Preliminary results of femtosecond laser assisted Descemet
sutureless anterior lamellar keratoplasty. Ophthalmology
stripping endothelial keratoplasty also showed average Best
2008;115(8):1303-07.
Spectacle corrected visual acuity to be lower as compared with 11. Mehta JS, Shilbayeh R, Por YM, Cajucom-Uy H, Beuerman RW,
recent DSAEK series.13 Larger series with longer follow-up may Tan DT. Femtosecond laser creation of donor cornea buttons for
be able to clear the exact role and use of Femtosecond laser in Descemet-stripping endothelial keratoplasty. J Cataract Refract
future. Surg 2008;34(11):1970-75.
12. Jones YJ, Goins KM, Sutphin JE, Mullins R, Skeie JM.
REFERENCES Comparison of the femtosecond laser (IntraLase) versus manual
microkeratome (Moria ALTK) in dissection of the donor in
1. Seitz B, Brunner H, Viestenz A, et al. Inverse mushroomshaped endothelial keratoplasty: initial study in eye bank eyes. Cornea
nonmechanical penetrating keratoplasty using a femtosecond 2008;27(1):88-93.
laser. Am J Ophthalmol 2005;139:941-44. 13. Cheng YY, Hendrikse F, Pels E, Wijdh RJ, van Cleynenbreugel
2. Ignacio TS, Nguyen TB, Chuck RS, Kurtz RM, Sarayba MA. H, Eggink CA, van Rij G, Rijneveld WJ, Nuijts RM. Preliminary
Top hat wound configuration for penetrating keratoplasty using results of femtosecond laser-assisted descemet stripping
the femtosecond laser: a laboratory model. Cornea 2006;25: endothelial keratoplasty. Arch Ophthalmol 2008;126(10):
336-40. 1351-56.

267
37
Section V: Specific Techniques in Keratoplasty

Special Techniques of
Corneal Grafting Surgery
Namrata Sharma, Rajesh Sinha, Manotosh Ray

Certain modifications in the conventional keratoplasty techniques lamellar patch is effective in reinforcing a thin, necrotic stroma
are required, as the conventional technique may not yield optimal with or without descemetocele. A full thickness patch graft is an
visual outcome in all cases of corneal opacities. Special easier alternative. Full thickness tectonic patch grafts are
techniques and modifications in the conventional corneal grafting particularly useful in eyes with long-standing uveal prolapse,
surgery are indicated for various situations. These include where additional structural support is required.
tectonic patch grafts for selected cases of corneal perforations, In an acutely inflamed eye such as corneal perforation or
keratolimbal grafts, sclerokeratoplasty and large diameter melting, it may be safer to perform a lamellar patch graft than a
lamellar keratoplasty. more invasive penetrating graft. The lamellar patch graft serves
as a interim procedure to stabilize the eye in such cases, so that
TECTONIC PATCH GRAFTS the vision restoring penetrating keratoplasty may be performed
at a later date, when the eye becomes quiet. Tectonic patch grafts,
Patch graft is a tectonic graft, which may be used to restore the
lamellar or full thickness are useful in the treatment of severe
integrity of the globe with minimal intraocular surgical
corneal melts, as they not only provide structural support, but
manipulation in an inflamed eye. This technique is performed
also help in the interim period until systemic immunosuppressive
in corneal lesions that are too large to be treated with tissue
medications halt the collagenolytic break down of the cornea.1
adhesives but small enough to preclude the conventionally sized
penetrating keratoplasty. Though a patch graft is usually preferred
Indications
in peripheral corneal lesions (Figs 37.1 and 37.2), the central
lesions may also be repaired with the patch grafts (Figs 37.3 Inflammatory diseases of the cornea result in collagenolytic
and 37.4). It may also be performed for central corneal lesions. destruction of the stroma leading to corneal melting and loss of
Depending on the thickness of the patch grafts, they can be vision. The use of a tectonic patch graft in these conditions aids
either full thickness or lamellar. Though technically difficult, in providing structural support to the cornea, thus stabilizing the

Figure 37.1: Perforated corneal ulcer Figure 37.2: Peripheral tectonic patch graft same patient as in
Figure 37.1
268
Chapter 37: Special Techniques of Corneal Grafting Surgery
Figure 37.3: Corneal perforation Figure 37.4: Patch graft, same patient as in Figure 37.1

globe.2, 3 The excision and removal of the involved necrotic areas Advantages Over Tissue Adhesives
eliminates the devitalized tissue, which is a source of
Tissue adhesives are not useful in eyes with corneal perforations
collagenolytic enzyme collagenase4-7 and the presence of the
larger than 2 mm. In a central corneal melt or perforation the
patch graft provides tectonic support to the globe.
tissue adhesives produce opaque tissue reaction and obscure the
Reconstructive lamellar patch graft is also indicated in
visual axis. Tissue adhesives promote corneal vascularization
corneal ectasia, descemetocele (Fig. 37.5) and following corneal
tend to attract new blood vessels in the cornea. Although these
dermoid excision.1
new blood vessels may aid in halting the melting process and
Scleral patch grafts are used in eyes with severe scleral
hasten healing, the risk of immune rejection in a subsequent full
thinning or melting as in scleromalacia perforans or after
thickness graft is enhanced.1
pterygium excision (Table 37.1).
Tectonic patch grafts on the other hand, provide better
structural support and stabilization of the globe in addition to
the removal of necrotic stroma, which is a source of collagenase.
The visual axis remains clear particularly, if care has been taken
to avoid the graft-host junction or suture placement in the center
of the cornea.

Surgical Technique
The various types of patch grafts can be lamellar patch grafts,
full thickness patch grafts and sclera patch grafts. Algorithms
have been described on the choice of patch grafts depending on
the size and severity of lesion.8-13

Lamellar Patch Graft


Figure 37.5: Descemetocele
Preoperative preparation for patch graft is similar to that of
Table 37.1: Indications of tectonic patch graft penetrating keratoplasty. Surgery is performed under general
anesthesia. The eyelids are separated with a Barraquer lid
Corneal Patch graft
• Corneal perforation not amenable to closure with tissue speculum.
adhesives or BCL Conjunctival peritomy or scleral dissection is occasionally
• Descemetocele with impending corneal perforation required in peripheral corneal lesions. The anterior chamber is
• Corneal perforation larger than 2 mm but smaller than formed with a viscoelastic substance injected through a self
5 mm
sealing paracentesis site. The dimensions of the perforation are
• Chronic non-healing corneal ulceration
• Traumatic irreparable corneal tissue loss measured. The host cut should encompass the entire involved
• Corneal ectasia area of the cornea and at least 1 mm clear area around the
• Postcorneal dermoid excision circumference of the perforation. The boundaries of the lamellar
Scleral Patch Graft bed are marked with a handheld disposable, sharp, obturator
• Scleromalacia perforans guided trephine blade up to the desired depth. Alternatively, a
• Following pterygium excision Hanna vacuum trephine may be set at a depth of 0.45 mm and
269
the recipient cornea is trephined which is centered at the
perforation site. The devitalized necrotic tissue is removed from
the recipient bed. Lamellar dissection is then facilitated by further
inflation of the anterior chamber with viscoelastics or air.
The lamellar dissection of the recipient bed is done by means
of a Tooke’s knife, or a crescent knife. The dissection is begun
peripherally at the trephine wound circumferentially proceeding
Section V: Specific Techniques in Keratoplasty

centrally towards the lesion. Preparation of a smooth recipient


bed is necessary to ensure proper apposition of the graft.
The lamellar donor patch is prepared from the donor cornea
after fixing it in a King’s clamp. The donor button should be of
the same size or 0.25 mm larger than that of the recipient size.
A complementary partial thickness lamellar graft is then
fashioned from the donor cornea. The donor graft is now secured
in place over the recipient bed with interrupted 10-0 nylon Figure 37.6: Scleral melting following pterygium surgery
sutures. Suture bites through the central visual axis should either
be avoided or should be intentionally placed shorter.

Full Thickness Patch Graft


The surgical technique is almost similar to that of penetrating
keratoplasty. After trephination, the anterior chamber is entered
with a sharp blade. Viscoelastic substances are injected into the
anterior chamber in order to push back the iris. The host cornea
is removed with a curved corneal scissors, holding it vertically
to avoid beveling. Any adherent iris tissue must be separated
gently and meticulously.
A full thickness donor graft oversized by 0.5 mm is prepared
and secured in place with interrupted 10-0 nylon sutures. Sutures
are buried and anterior chamber is formed with balanced salt
solutions and the wound is checked for any leakage.

Scleral Patch Graft Figure 37.7: Scleral patch graft

A scleral patch graft is occasionally indicated in cases of


localized scleral necrosis caused by scleromalacia or following
scleral thinning following recurrent pterygium surgery14 (Figs 2. Raziman MB, Sainz de la Maza M, Foster CS. Tectonic patch
graft in peripheral ulcerative keratitis. Cornea 1991;10:312-16.
37.6 and 37.7). Initially conjunctival peritomy is done in the
3. Taylor DM, Stern AL. Reconstructive keratoplasty in the
affected area. The scleral bed is prepared by removing the entire management of conditions leading to corneal destruction.
necrotic tissue and delineating a healthy scleral margin. A Ophthalmology 1980;87:892-904.
trephine mark, which includes the necrotic area, may help in the 4. Kenyon KR. Corneal perforations: discussion. Ophthalmology
scleral dissection. At least 1 mm healthy scleral area must be 1982;89:634-5.
included inside the trephine. Scleral incision may be deepened 5. Eiferman RA, Snyder JW. Antibacterial effect of cyanoacrylate
with a blade and dissection is performed manually. A full glue. Arch Ophthalmol 1983;101:955-60.
thickness same sized scleral graft is trephined from a donor globe 6. Kenyon KR, Berman MB, Hanninen LA. Tissue adhesive
prevents ulceration and inhibits inflammation of the thermal
and the graft is secured in place with 10-0 nylon sutures. The
burned rabbit cornea. Invest Ophthalmol Vis Sci. 1979;18:96.
graft is preferably covered, at least partially, with conjunctiva. 7. Kenyon KR. Decision-making in the therapy of external eye
Sangwan et al recommend that scleral grafting with overlying disease: non-infected corneal ulcers. Ophthalmology 1982;89:44-
conjunctival or amniotic membrane graft is an effective and 51.
simple measure for preserving globe integrity both structurally 8. Vanathi M, Sharma N, Titiyal JS, Tandon R, Vajpayee RB.
and functionally.15 Tectonic grafts for corneal thinning and perforations. Cornea.
2002;21:792-7.
REFERENCES 9. Orlin SE, Sulewski ME. Spontaneous corneal perforation in
pellucid marginal degeneration. CLAO J. 1998;24:186-7.
1. Soong HK, Farzo AA, Katz D, Meyer RF, Sugar A. Lamellar 10. Lam DS, Wah C, Lai JS. Short-term results of using corneoscleral
corneal patch grafts in the management of corneal melting. Cornea patch graft for the Ahmed glaucoma valve implant surgery. Yan
2000;19:126-34. Ke Xue Bao 1997;13:109-12.
270
11. Seino Jy, Anderson SF. Mooren’s Ulcer. Optom Vis Sci. keratolimbal grafts is the youngest possible donor. The pediatric
1998;75:783-90. donor tissue provides abundant limbal stem cells and results
12. Rumelt S, Rehany U. A donor corneal patch graft for an inrapid re-epithelization of the recipient cornea.10 Therefore, to
incompetent scleral flap following trabeculectomy. Ophthalmic
obtain appropriate tissue, the surgeons must communicate with
Surg Lasers 1996;27:878-80.
13. Vrabec MP, Jordan JJ. A surgical technique for the treatment of
eye banks regarding potential availability of donor tissue and
central corneal perforations. J Refract corneal Surg. 1994;10:365-7. educate the staff of the special requirements of the procedure.
14. Nguyen OD, Foster CS. Scleral patch graft in the management

Chapter 37: Special Techniques of Corneal Grafting Surgery


of necrotizing scleritis. Int Ophthalmol Clin. 1999;39:109-31. Surgical Technique
15. Sangwan VS, Jain V, Gupta P. Structural and functional outcome
Surgical technique is generally identical to penetrating
of scleral patch graft. Eye 2007;21:930-5.
keratoplasty. The donor corneal graft is obtained by eccentric
trephination from the endothelial side. A trephine of appropriate
CENTRAL KERATOLIMBAL GRAFT
size should include 40 percent of the circumference of donor
Management of patients with severe ocular surface disorder limbus. The donor disk endothelium is protected by viscoelastics
remains a considerable therapeutic challenge. Simple penetrating and kept separately.
keratoplasty may not be successful in the long-term in eyes with The recipient eye is prepared in the usual fashion. Eyelids
stem cell deficiency such as conjunctivalization, persistent are separated with speculum. Host corneal button is trephined
epithelial defect and irregular epithelium.1 A donor cornea used and removed from the recipient bed. The keratolimbal graft,
in routine keratoplasty does not replace the deficient corneal stem which is 0.5 mm oversized than the host, is then fitted centrally
cells. A number of ocular surface replacement procedures have into the trephination opening. The graft is sutured with
emerged in the recent past including conjunctival transplanta- interrupted or continuous 10-0 nylon sutures. The limbal edge
tion,2,3 limbal transplantation4,11 and keratoepithelioplasty.5,6 of the donor keratolimbal graft is generally positioned superiorly,
Central keratolimbal graft is relatively a recent concept, so that it remains covered by the upper lid. Suture knots are
where an eccentric donor corneal graft, including the superior buried and the wound is checked for leak (Figs 37.8 and 37.9).
or inferior limbal stem cells, is transplanted centrally in the host.
Eccentric trephination should include approximately 40 percent Postoperative Care
of a donor limbus. It is generally postulated that a keratolimbal Postoperative immune reactions are expected in these patients,
graft achieves sufficient epithelization in the event of limbal stem not only against the transplanted endothelial cells but also against
cell disease in the host. limbal cells. Therefore, standard treatment protocol should
include systemic cyclosporine-A, in addition to routine topical
Indications
steroids and antibiotics. Cyclosporine-A therapy is continued for
Common conditions known to produce severe ocular surface 6 months with frequent monitoring blood level at regular
disorder due to stem cell deficiency are chemical burns, aniridia intervals. Topical steroid should never be stopped and must be
and Stevens-Johnson syndrome. Less frequent causes include continued at least once or twice daily for indefinite period.
iatrogenic stem cell deficiency, 7 contact lens induced
keratopathy8 and corneal intra-epithelial neoplasia (Table 37.2).9 Outcome
Central keratolimbal graft may be performed in these ocular
There are varied reports of outcome in cases of single
conditions with variable success.
keratolimbal grafts. Shimmura et al suggest that a one-piece
keratolimbal graft does not seem to offer any advantage over a
Table 37.2: Indications of central keratolimbal graft
two-piece limbal and corneal graft in the treatment of severe
• Chemical burns ocular surface disorders involving the limbus and cornea.12 In
• Thermal burns other reports ambulatory vision for a period of more than 2 years
• Aniridia can be achieved by KLAL with or without PKP in eyes with
• Lattice dystrophy severe ocular surface disorders caused by total LSCD. Future
• Iatrogenic stem cell deficiency modifications of the surgical procedure and of the immune
• Corneal intraepithelial neoplasia suppressive protocols may improve survival of the allogeneic
• Contact lens induced keratopathy grafts and the final visual outcome.13,14

REFERENCES
Donor Tissue Selection
Most of the surgeons tend to avoid infant donors younger than 1. Daya SM, Bell RWD, Habib NE, Powel-Richards A, Dua HS.
Clinical and pathologic findings in human keratolimbal allograft
4 years for routine keratoplasty. This is because of difficulty of
rejection. Cornea 2000;19:443-50.
working with the tissue, which is flaccid in nature and has a 2. Vastine DW, Steward WB, Schawab IR. Reconstruction of
tendency to stretch postoperatively leading to highly periocular mucous membrane by autologous conjunctival
unpredictable results. However, tissue preference for central transplantation. Ophthalmology 1982;89:1072-81.
271
12. Shimmura S, Ando M, Shimazaki J, Tsubota K.Complications
with one-piece lamellar keratolimbal grafts for simultaneous
limbal and corneal pathologies. Cornea 2000;19:439-42.
13. Solomon A, Ellies P, Anderson DF, Touhami A, Grueterich M,
Espana EM, Ti SE, Goto E, Feuer WJ, Tseng SC. Long-term
outcome of keratolimbal allograft with or without penetrating
keratoplasty for total limbal stem cell deficiency. Ophthalmology
2002;109(6):1159-66.
Section V: Specific Techniques in Keratoplasty

14. Ilari L, Daya SM. Long-term outcomes of keratolimbal allograft


for the treatment of severe ocular surface disorders.
Ophthalmology 2002;109(7):1278-84.

SCLEROKERATOPLASTY

Sclerokeratoplasty was introduced by Barraquer1 and further


defined by Taylor2 and Stern as the “use of a corneoscleral graft
of varying size, shape and position, to end or improve those
treatment resistant diseases of the cornea, that result in
dissolution of tissue and the production of anatomic or structural
defects, that are incompatible with continued survival of the
globe”. The main goal of this surgical procedure is to extirpate
the diseased tissue which may be infective or neoplastic and
restore the structural integrity of the globe.
As compared to conventional penetrating keratoplasty it is
technically difficult to perform and carries a high risk of certain
complications. It has a high incidence of graft rejection,
secondary glaucoma and hypotony.3,4 The placement of a large
antigenic graft, superimposed on the limbal vasculature, greatly
increases the chance of severe allograft rejecion and the
development of an opaque graft.2,4,5
Figures 37.8 and 37.9: Keratolimbal graft in a case of limbal
The various indications of sclerokeratoplasty as described
stem cell deficiency in the literature include infective corneal ulcers with involvement
of the adjacent limbus or the sclera, total corneal melting due to
immunological disorders, squamous cell carcinoma, selected
cases of peripheral marginal degeneration and anterior
3. Kenyon KR, Wagoner MD, Hettinger ME. Conjunctival autograft staphyloma.1-17 It can be of two types depending on the type
transplantation for advanced and recurrent pterygium.
and thickness of the graft used, i.e. lamellopenetrating or
Ophthalmology 1985;92:1461-70.
4. Kenyon KR, Tseng SCG. Limbal autograft transplantation for lamellolamellar sclerokeratoplasty.
ocular surface disorders. Ophthalmology 1989;96:709-23. In lamellopenetrating sclerokeratoplasty the sclerocorneal
5. Thoft RA. Keratoepithelioplasty. AM J Ophthalmol 1984;97:1-6. dissection of the host is done so that a cut of 14 mm diameter is
6. Roat MI, Thoft RA. Ocular surface epithelial transplantation. Int made, which has a peripheral lamellar rim of 2 mm and a full
Ophthalmol Clin 1988;17:31-7. thickness trephination of 10 mm. The angle support sutures are
7. Schwartz GS, Holland EJ. Iatrogenic stem cell deficiecy. Cornea then applied to maintain the angle and its function. The
1998;17:629-33.
application of the angle support sutures considerably decrease
8. Jenkins C, Tufts, Lin C, et al. Limbal transplantation in the
the chances of postoperative glaucoma.
management of chronic contact lens associated epitheliopathy.
Eye 1993;7:629-33. A donor corneoscleral rim with a diameter of 14 mm is used.
9. Erie JC, Campbell RJ, Lisengang TJ. Conjunctival and corneal A lamellar dissection of sclera is done with a Paufique (or similar
intraepithelial and invasive neoplasia. Ophthalmology blade) knife to create a 360 degrees tunnel into the 2 mm clear
1986;93:176-83. peripheral cornea and the anterior chamber is entered with a
10. Croasdale CR, Schwartz GS, Malling JV, Holland EJ. sharp blade anterior to the limbus. The donor tissue is then
Keratolimbal allograft: recommendations for tissue procurement removed with Vannas scissors by extending the anterior limbal
and preparation by the eye banks, and standard technique. Cornea
incision. The host and the donor scleral surfaces are then apposed
1999;18:52-8.
11. Henderson TR, Coster DJ, Willams KA. The long-term outcome
with 10-0 monofilament interrupted sutures.
of limbal allografts: the search for surviving cells. Br J Apart from the complications associated with conventional
Ophthalmol 2001;85:604-9. penetrating keratoplasty increased chances of graft rejection,

272
postoperative glaucoma and persistent hypotony may occur with pellucid marginal degeneration. Acta Ophthalmol (Suppl.)
sclerokeratoplasty.3,4 (Cophen) 1989;192:17.
Lamellolamellar sclerokeratoplasty is the removal of a partial 6. Cobo M, Ortiz JR, Safran SG. Sclerokeratoplasty with
maintenance of the angle. Am J Ophthalmol 1992;113:533-7.
thickness of both sclera and cornea and its replacement with
7. Panda A. Lamellolamellar sclerokeratoplasty. Where do we stand
identical donor tissue.7 Depending on the host pathology a today? Eye 1999;13:221-5.
trephine up to 12 mm may be used. A 0.5 mm oversized graft is 8. Panda A, Sharma N, Angra SK, Singh R. Therapeutic
then sutured to the recipient bed with interrupted 10-0 sclerokeratoplasty versus therapeutic penetrating keratoplasty in

Chapter 37: Special Techniques of Corneal Grafting Surgery


monofilament nylon sutures. refractory corneal ulcers. Aust N Z J Ophthalmol 1999;27:15-9.
The complications which occur after lamellolamellar 9. Panda A, Sharma N, Angra SK, Singh R. Sclerokeratoplasty
sclerokeratoplasty are similar to those after conventional lamellar versus penetrating keratoplasty in anterior staphyloma.
keratoplasty. The chances of delayed epithelization are increased Ophthalmic Surg Lasers 1999;30:31-6.
10. Jonas JB, Rank RM, Budde WM. Tectonic sclerokeratoplasty and
as compared to conventional lamellar keratoplasty as the host
tectonic penetrating keratoplasty as treatment for perforated or
epithelium has to climb over a larger surface area. Further, predescemetal corneal ulcers. Am J Ophthalmol 2001;132:14-8.
interface haze may occur which may be minimal initially but 11. Reinhard T, Sundmacher R. Lamellar horseshoe
increases with the passage of time. sclerokeratoplasty and thermoplasty in keratoconus with
peripheral ectasia of the cornea. Klin Monatsbl Augenheilkd
REFERENCES 1994;205:305-8.
12. Suveges I. Sclerokeratoplasty in recurrent pterygium. Ger J
1. Barraquer J. Total penetrating keratoplasty. Proc R. Soc Med Ophthalmol 1992;1:114-6.
1961;54:1116. 13. Mendez EA, Daza MT. Sclerokeratoplasty in a case of corneal
2. Taylor DM, Stern AL. Reconstructive keratoplasty in the keloid. Cornea 1991;10:183-4.
management of conditions leading to corneal destruction. 14. Arora R, Panda A, Kumar H. Lamellar sclerokeratoplasty of
Ophthalmology 1980;87:892. epibulbar tumor in xeroderma pigmentosum. J Pediatr
3. Castroviejo R. Total penetrating keratoplasty: A preliminary Ophthalmol Strabismus 1990;27:80-3.
report. Am J Ophthalmol 1951;34:1697. 15. Bialasiewicz AA, Naumann GO. Tectonic keratoplasty in
4. Cherry PMH, Pashby RC, Tadros ML, Wolf A, Chipman ML, perforated corneal ulcer in Sjögren’s syndrome (report of 10 eyes
Basu PK, Dixon WS, Hunter WS, Thompson GA. An analysis in 8 patients). Klin Monatsbl Augenheilkd 1988;193:554-64.
of corneal transplantation. Graft Clarity. Ann Ophthalmol 16. Litricin O. Fibrous histiocytoma of the corneosclera. Arch
1979;11:461. Ophthalmol 1983;101:426-8.
5. Speaker MG, Arentsen JJ, Laibson PA. Long-term survival of 17. Tin MK. Sclerokeratoplasty in the treatment of progressive
large diameter penetrating keratoplasties for keratoconus and myopia. Vestn Oftalmol 1976;3:24-6.

273
38
Section V: Specific Techniques in Keratoplasty

Indication Specific
Corneal Grafting Techniques
Rasik B Vajpayee, M Vanathi, Harinder S Sethi

Certain corneal pathologies have morphological characteristics, thin layer of corneal tissue and hence improves the visibility,
which require the use of special techniques that are different from which may facilitate deeper dissections.
the conventional keratoplasty techniques. These include
conditions such as severe corneo-iridic scars, pellucid marginal Surgical Technique
degeneration, Terrien’s marginal degeneration, keratoglobus and
The technique of lamellar separation is identical to that of
Mooren’s ulcer. At our center we have developed some newer
standard penetrating keratoplasty in the initial stages. A trephine
techniques of corneal grafting surgery that yield optimal results of 7-7.5 mm is used to make the initial cut on the host cornea
in these conditions.
up to a depth of 75 percent of thickness. Lamellar dissection is
then undertaken using lamellar dissector and corneal scissors at
CORNEO-IRIDIC SCAR
the level of the posterior stroma. Corneal button is removed in
Corneal opacification along with iridocorneal adhesions is one two layers6 (Fig. 38.2). Following lamellar dissection, the
of the major indications for corneal grafting in developing superficial layer containing epithelium and major part of the
techniques (Fig. 38.1). The common causes of corneo-iridic scars stroma is removed. The deeper layer, which includes the posterior
are infectious keratitis, nutritional disorders, ocular trauma and stroma, Descemet’s membrane and the endothelium, is then
trachoma. The surgical principles of penetrating keratoplasty in dissected very gently from the adherent iris tissue (Fig. 38.3).
corneo-iridic scars are different from that of routine keratoplasty. Care should be taken to minimize the damage to the fragile iris.
The trephination of the host cornea in such cases leads to This layer is removed either in toto, if possible, or piecemeal.
mechanical damage to the iris and results in large surgical Peripheral anterior synechiae is almost universal in these cases.
colobomas or iridodialysis. Intraoperative bleeding and lenticular The synechiae is released by viscodissection with 2 percent
injury are the other possible complications.1,4 A technique has methylcellulose or with fine iris spatula. Some eyes may require
been developed by us to tackle these difficulties.2 The technique pupilloplasty. Anterior segment reconstruction is necessary to
of corneal debulking by lamellar dissection of corneal layers
and gentle separation of the adherent iris after partial trephination
is found to be useful in such cases.
The principle of lamellar separation technique is based on
the fact that the force required to remove an adherent cornea
from the underlying iris may result in iris tears, avulsions and
iridodialysis. Since the total mass of corneal tissue is greater than
that of iris, there is a greater chance of iris damage during iris
dissection. In this technique of lamellar dissection, host corneal
epithelium and the major portion of the iris stroma are removed
in the preliminary step and therefore, the bulk of the cornea is
significantly reduced. Debulking of the corneal tissue reduces
the amount of force required to separate the adherent iris from
the remaining corneal tissue. Thus the technique allows easier
separation of the deeper corneal layers from the adherent iris
with minimal manipulation. Debulking the cornea leaves a very Figure 38.1: Corneo-iridic scar
274
preoperative shallow anterior chamber which is common in such
eyes. Conventional 0.5 mm oversized graft is associated with
higher rates of peripheral anterior synechiae and secondary
glaucoma in eyes with corneo-iridic scar and shallow anterior
chamber.6
The corneoscleral rim donor cornea is placed on a Teflon
block and then punched from the endothelium side, so that it is

Chapter 38: Indication Specific Corneal Grafting Techniques


1 mm oversized in comparison to the host. The graft is sutured
to the host with interrupted 10-0 monofilament nylon sutures.
Figure 38.2: Superficial layer of corneo-iridic scar removed by Knots are buried in the suture track and wound is checked for
lamellar dissection
leak. Some viscoelastics may be left in the anterior chamber to
prevent the floppy iris from coming forward.
It is a well-known fact that the freshly separated iris has a
memory for its original preoperative position and thus prone to
formation of adhesions with the transplanted cornea. This risk
can greatly be reduced by using a 1 mm oversized corneal graft,
which also ensures a deep anterior chamber at the conclusion of
surgery.

REFERENCES
1. Arentsen JJ, Morgan B, Green WR. Changing indications for
keratoplasty. Am J Ophthalmol 1976;81:313-18.
2. Vajpayee RB, Angra SK, Honavar SG, Taherian K. Protection of
the iris by lamellar dissection of corneal layers. Cornea
Figure 38.3: Dissection of deeper corneal layer from 1994;13:16-19.
underlying adherent iris 3. Vajpayee RB, Ramu M, Panda A, Sharma N, Tabi GC, Anand
JR. Oversized grafts in children. Ophthalmology 1999;106:829-
32.
4. Morris RJ, Bates AK. Changing indications of keratoplasty. Eye
1989;3:455-9.
5. Foulks GN, Perry HD, Dohlmann CH. Oversize donor corneal
grafts in penetrating keratoplasty. Ophthalmology 1979;86:
490-94.
6. Paton RT. Symposium on corneal transplantation. Am J
Ophthalmol 1948;31:1265-404.

PELLUCID MARGINAL DEGENERATION

Pellucid marginal degeneration (PMD) is an ectatic disease that


affects the peripheral inferior cornea. A non-inflammatory band
of thinning 1 to 2 mm from the corneal limbus, usually extending
from the 4 o’clock to 8 o’clock positions is present. Normal
Figure 38.4: Oversized graft thickness cornea exists above and below this area of thinning
(Fig. 38.5). Surgery for pellucid marginal degeneration by
various methods has been advocated.1-6 These include the
reduce the risk of peripheral anterior synechiae due to floppy
following:
iris tissue.
We have also used 1 mm oversized corneal grafts in eyes
Conventional Large Diameter PK
with corneo-iridic scar and have found good results.3 (Fig. 38.4)
There are several theoretical advantages of using an oversized In this technique a large full thickness donor corneal button is
donor corneal buttons, including a decreased incidence of post- sutured to the recipient bed created by trephining a large (9 mm)
keratoplasty glaucoma, decreased hyperopia and increased host corneal tissue encompassing the area of corneal thinning.2
anterior chamber depth.3,5 Postoperative shallowing of anterior However, this technique is difficult to practice especially because
chamber and the occurrence of anterior synechiae may result in of inferior thinning. An attempt to effectively replace the
secondary glaucoma and other related problems leading to graft pathological cornea may compromise the trabecular meshwork
failure. These complications are more frequent in patients with and the limbus and carry a high risk of graft rejection. Moreover,

275
high postoperative astigmatism may occur particularly if the
abnormal cornea is incompletely excised.

Large Eccentric Penetrating Keratoplasty


In this technique of large eccentric penetrating keratoplasty, the
dissection of the host is extended to the limbus. This avoids the
occurrence of the graft host tissue disparity and prevents high
Section V: Specific Techniques in Keratoplasty

postoperative astigmatism. 3,4 However, this approach is


associated with an increased risk of graft rejection. Varley et al
reported 64 percent incidence of endothelial rejection in their
series of 12 eyes with mean follow-up of 3 years.4

Crescentic Lamellar Keratoplasty


This technique was described by Schanzlin et al in 1983.5 The
involved inferior crescentic lamellar dissection of the thinner Figure 38.5: Pellucid marginal degeneration
recipient cornea was undertaken followed by placement and
suturing of the matched corneoscleral button5 (Fig. 38.6).
Although optimal visual rehabilitation was achieved, the lamellar
surgery is technically difficult particularly in the recipient cornea
due to presence of thinning.

Simultaneous Crescentic Lamellar Keratoplasty (LK)


and Central Penetrating Keratoplasty (PK)
This technique involves the removal of lamellar recipient tissue
(upto 50% depth) from the thinner inferior cornea which is
supplemented with a partial thickness, semi-circular donor graft.
This is followed by central 7.5 mm full thickness penetrating
keratoplasty, which is performed at the same sitting.6
The advantage of this technique is that a single donor cornea
can be used for both the grafts and hence the donor tissue
requirement is reduced. Further, this also potentially reduces the Figure 38.6: Crescentic lamellar keratoplasty
antigenic load. The lamellar transplant restores normal thickness
to the inferior cornea and enables good edge-to-edge apposition “Tuck in” Lamellar Keratoplasty
with the full thickness graft. The central PK helps to correct the
residual irregular astigmatism. The visual rehabilitation is rapid We have developed this technique for cases of pellucid marginal
and against the rule astigmatic drift may be completely abolished. degeneration. In this technique an eccentric trephine mark of 10.5
mm is made on the cornea upto a depth of 0.3 mm so that it
Lamellar Crescentic Resection extends inferiorly eccentrically into the limbus whereas
superiorly the mark is on the corneal tissue. This is followed by
In this a full thickness crescent shaped area of inferior corneal the lamellar dissection of the recipient bed. A lamellar pocket is
thinning is removed. This is followed by suturing of full thickness created in the recipient from the edges of the dissected edge into
corneal edges to each other after undermining the base.7 Cameron the peripheral cornea upto the limbus which extends more so in
et al achieved VA of ≥ 20/40 in 4 out of 5 eyes during a follow- the periphery. A full thickness donor lenticule of 11.5 to 12 mm
up of 27-40 months (mean 31.8 months).7 diameter, with its endothelium removed is used. The peripheral
edges of the donor lenticule are trimmed so as to achieve
Epikeratoplasty
peripheral thinning. This is then placed on the recipient bed and
Fronterre et al treated 2 patients of PMD by bilateral the inferior edges are tucked under the peripheral rim of the host.
epikeratoplasty grafts of 9-12 mm.8 Marked reduction in corneal The rest of the cornea is apposed to its edges just as in
astigmatism was seen in both the cases and satisfactory best conventional lamellar keratoplasty. Undertaking paracentesis
corrected visual acuity was achieved after surgery either with beforehand may facilitate the procedure of tucking the edge of
spectacles or with contact lenses. the graft in the inferior peripheral lamellar pocket. This is

276
TERRIEN’S MARGINAL DEGENERATION

Terrien’s marginal degeneration (TMD) is a rare peripheral


corneal thinning disorder, which may take decades to progress
to perforation or irregular astigmatism. The earliest changes
typically occur in the superior limbus and consist of opacification
and superficial neovascularization. In more advanced cases, a
stromal thinning and a limbal gutter with progressive ectasia may

Chapter 38: Indication Specific Corneal Grafting Techniques


occur, causing against-the-rule astigmatism. Surgical treatment
is indicated in cases of progressive thinning or decreased visual
acuity due to irregular astigmatism. Various surgical options are
available.

Two-step Annular Tectonic Lamellar Keratoplasty


Two-step annular tectonic lamellar keratoplasty is undertaken
Figure 38.7: Central lamellar keratoplasty with inferior
for severe Terrien’s marginal degeneration where 360 degrees
peripheral intrastromal lamellar tuck
of cornea is involved.1 In this technique an annular shaped ectatic
lesion is defined and removed and donor tissues of the same size
and shape are sutured on the recipient bed with 10-0 nylon.
followed by the application of the 16-20 interrupted Annular lamellar grafts are performed 180 degree at a time in
monofilament nylon sutures. The sutures anchor the donor graft an effort to avoid extensive donor and host surgical manipulation.
into the host lamellar pocket (Fig. 38.7). This procedure allows corneal astigmatism to be controlled and
substantially improves the visual acuity. Annular lamellar
Deep Anterior Lamellar Keratoplasty keratoplasty serves as an efficient treatment of extensive
Deep anterior lamellar keratoplasty (DALK) involving removal peripheral circumferential stromal thinning.2
of the entire corneal stroma baring the Descemet’s membrane
Full Thickness Peripheral Grafting
and endothelium is a useful surgical alternative in the
management of PMD. The technique provides useful visual Although the use of full thickness peripheral grafts have been
rehabilitation in patients with PMD even in the presence of reported by several authors for Terrien’s marginal degeneration
previous corneal perforation.9 it is technically difficult and often astigmatically unpredictable.3,4

REFERENCES Dissection of the Ectatic Area Followed by Resuturing

1. Rasheed K, Rabinowitz YS. Surgical treatment of advanced Caldwell et al described incision of the ectatic area upto the
pellucid marginal degeneration. Ophthalmology 2000; Descemet’s membrane followed by subsequent approximation
107(1):1836-40. of the full thickness stroma on either side by suturing yielded
2. Parker DL, McDonnell PJ, Barraquer J, Green WR. Pellucid good results at 30 months follow-up.5
marginal corneal degeneration. Cornea 1986;5:115.
3. Speaker MG, Arenstren JJ, Laibson PR. Long-term survival of Limbus Based Lamellar Scleral Flap Covered by
large diameter penetrating keratoplasties for keratoconus and Fornix Based Conjunctival Flap
pellucid marginal degeneration. Acta Ophthalmol Suppl
1989;192:17-9. Anderson described the use of limbus based lamellar scleral flap
4. Varley GA, Macsai MS, Krachmer JH. The results of penetrating covered by a fornix based conjunctival flap to repair the
keratoplasty for pellucid marginal degeneration. Am J Ophthalmol perforation caused by Terrien’s marginal degeneration.6
1990;110:149.
5. Schanzlin DJ, Sarno EM, Robin JB. Crescentic lamellar Scleral Auto-transplantation with Lamellar
keratoplasty for pellucid marginal degeneration. Am J Ophthalmol Keratoplasty
1983;96:253-4.
6. Kremer I, Sperber LT, Laibson PR. Pellucid marginal Scleral autotransplantation with lamellar keratoplasty have also
degeneration treated by lamellar and penetrating keratoplasty. been described to treat Terrien’s marginal degeneration.7 Petit
Arch Ophthalmol 1993;111:169-70. achieved satisfactory results in 4 eyes with this disease using
7. Cameron JA. Results of crescentic resection for pellucid marginal corneoscleral lamellar grafts.9
corneal degeneration. Am J Ophthalmol 1992;113:296-302.
8. Fronterre A, Portesani GP. Epikeratoplasty for pellucid marginal Epikeratoplasty
degeneration. Cornea 1991;10:450.
9. Millar MJ, Maloof A. Deep lamellar keratoplasty for pellucid Chen et al10 have used the technique of epikeratoplasty in cases
marginal degeneration: review of management options for corneal of Terrien’s marginal degeneration and achieved an improvement
perforation. Cornea 2008;27:953-6. in best corrected visual acuity in 75 percent of their eyes.
277
Corneal/Scleral Horse-shoe Grafts 11. Eiferman RA, Dahringer VP. Surgery for peripheral corneal
thinning disorders. In: Cornea: Surgery of the cornea and
Eiferman advocated corneal/scleral horse-shoe grafts for conjunctiva; Vol III Eds. Krachmer JH, Mannis MJ, Holland EJ.
Terrien’s marginal degeneration.11 In this technique a caliper is Mosby St. Louis. Chap 1997;146:1789-98.
used to determine the proper length and width of the resection. 12. Liang LY, Liu ZG, Chen JQ, Huang T, Wang ZC, Zou WJ, Chen
The greater curve is outlined on the sclera with a 12 to 13 mm LS, Zhou SY, Lin AH. [Keratoplasty in the management of
trephine and the lesser curve is marked on the cornea with an Terrien’s marginal degeneration] Zhonghua Yan Ke Za Zhi.
8 mm trephine. Thus a partial thickness incision is achieved with 2008;44:116-21.
Section V: Specific Techniques in Keratoplasty

13. Cheng CL, Theng JT, Tan DT. Compressive C-shaped lamellar
the help of the trephines which are easily completed with the
keratoplasty: A surgical alternative for the management of severe
help of corneal scissors. A congruent graft is harvested from the astigmatism from peripheral corneal degeneration.
peripheral rim of the donor tissue using the same technique. Since Ophthalmology 2005;112:425-30.
the thickness as well as the consistency of the tissues match, the
surgery is technically simpler and better visual results are KERATOGLOBUS
obtained.
Keratoglobus is a bilateral, non-inflammatory, ectatic disorder
Keratoplasty with Foci Resection in which the entire cornea becomes thinned and takes on a
globular shape (Fig. 38.8). The cornea may be thinned to
Keratoplasty combined with foci resection has been described approximately one-third to one-fifth of the normal corneal
to be effective and safe in the treatment of TMD. This procedure thickness and the thinning is more pronounced in the peripheral
can preserve and improve the visual activity. Liang et el have cornea.
obtained improved visual acuity in 81.3% of eyes in their series.12 Surgical intervention should be considered when functional
vision cannot be obtained and should be delayed for as long as
Compressive C-shaped Lamellar Keratoplasty possible. A routine penetrating or central lamellar keratoplasty
is not possible in keratoglobus because of limbus to limbus
C-shaped lamellar keratoplasty using multiple trephines of
corneal thinning. Following special techniques have been used
different sizes, with deliberate undersizing of the donor graft for
by various surgeons to surgically treat keratoglobus.
a controlled compressive effect has also been described in the
management of TMD. 13 Compressive C-shaped lamellar
Epikeratoplasty
keratoplasty reduces severe corneal astigmatism in peripheral
corneal ectasia resulting in good visual and refractive outcomes Cameron et al had performed epikeratoplasty in 6 cases of
with early visual rehabilitation. keratoglobus associated with blue sclera. 1 Surgery was
performed for tectonic support and/or visual improvement and
REFERENCES was successful in 5 out of 6 cases upto a follow-up of 11-27
months. A lamellar graft or epikeratoplasty has the advantage
1. Hahn TW, Kim JH. Two-step annular tectonic lamellar of being an extraocular procedure with no risk of failure resulting
keratoplasty in Terrien’s marginal degeneration. Ophthalmic Surg from endothelial rejection. In these cases epikeratoplasty alone
1993;24:831-4.
may suffice or a smaller diameter penetrating keratoplasty may
2. Cârstocea B, Gafencu O, Apostol S. [Marginal ectasia of the
cornea resolved surgically]. Oftalmologia 1996;40:64-7. be considered as a second procedure. Epikeratoplasty is a safe
3. Binder PS, Zauala FY, Stainer GA. Noninfectious peripheral and effective procedure in preserving ocular integrity and
corneal ulceration. Mooren’s ulcer or Terrien’s marginal increasing visual acuity in patients with keratoglobus and should
degeneration. Ann Ophthalmol 1982;14:425.
4. Brown AC, Rao GN, Aquavella JV. Peripheral corneal grafts in
Terrien’s marginal degeneration. Ophthalmic Surg 1983;14:931.
5. Caldwell DR, et al. Primary surgical repair of severe peripheral
marginal ectasia in Terrien’s marginal degeneration. Am J
Ophthalmol 1984;97:332.
6. Anderson FG. Repair of marginal furrow perforation, Ophthalmic
Surg 1977;8:25.
7. Hinken MV. Marginal degeneration of the cornea. Arch
Ophthalmol 1964;72:29.
8. Christensen L. Corneoscleroplasty with scalpel. Trans Pac coast.
Otoophthalmol Soc Annu Meet 1964;45:323.
9. Petit TH. Corneoscleral free hand lamellar keratoplasty in
Terrien’s marginal degeneration of the cornea – long-term results.
Refract Corneal Surg 1991;7:28.
10. Chen L, et al. A preliminary report of epikeratophakia for the
treatment of Terrien’s degeneration. Yanke Xul Bao 1997;13:79-
81. Figure 38.8: Keratoglobus
278
be considered before corneal perforation, which may result in suturing of a corneoscleral ring graft over the periphery of the
loss of eye.2 cornea helps to achieve tectonic tissue support and stabilize eyes
with keratoglobus.
Corneoscleroplasty with Maintenance of the Angle
REFERENCES
Burk et al have described this procedure in a case of operated
penetrating keratoplasty for keratoconus who presented with 1. Cameron JA, Cotter JB, Risco JM, Alvarez H. Epikeratoplasty
decompensated keratoglobus.3 Clear grafts were obtained and for keratoglobus associated with blue sclera. Ophthalmology

Chapter 38: Indication Specific Corneal Grafting Techniques


the angles were open in both the eyes of a bilateral case. 1998;98:446-52.
2. Javadi MA, Kanavi MR, Ahmadi M, Yazdani S. Outcomes of
Tectonic Lamellar Keratoplasty followed by epikeratoplasty for advanced keratoglobus. Cornea 2007;26:154-
7.
Secondary Penetrating Keratoplasty
3. Burk RO, Joussen AM. Corneoscleroplasty with maintenance of
In this technique, the cornea is first trephined to the depth of the angle in two cases of extensive corneoscleral disease. Eye
the anterior stroma within the limbus. A lamellar dissection 2000;15:196-200.
4. Jones DH, Kirkness CM. A new surgical technique for
technique is then used to tunnel into the sclera under the limbus
keratoglobus—tectonic lamellar keratoplasty followed by
to preserve the stem cells. The host corneal epithelium is
secondary penetrating keratoplasty. Cornea 2001;20:885.
completely debrided, and a donor corneoscleral button, denuded 5. Kanellopoulos AJ, Pe LH. An alternative surgical procedure for
of its endothelium is laid on the top. the management of keratoglobus. Cornea 2005;24:1024-6.
The donor corneoscleral graft is then sutured into the
prefashioned scleral bed with interrupted sutures. Once in situ, MOOREN’S ULCER
the donor graft is debrided of epithelium and the host limbus is
sutured on to it, covering its scleral component. As a second stage Mooren’s ulcer is a chronic painful and devastating peripheral
procedure, 6 months later, a penetrating keratoplasty may be keratitis. The lesion begins with a steep undermined and
performed.4 occasionally infiltrated leading border and characteristically is
This technique restores the structural integrity of the globe confined to the periphery of the cornea in the early stages but
and retains the host limbal stem cells, reduces ectasia and may progress circumferentially and centripetally to involve the
provides visual rehabilitation. whole of cornea and occasionally the sclera.
A stepladder approach is recommended in cases of Mooren’s
“Tuck in” Lamellar Keratoplasty ulcer, which consists of topical corticosteroids, conjunctival
resection and systemic immunosuppressives.
We have developed this technique for cases of keratoglobus. In Surgery is indicated in cases of incomplete or absent response
this technique a trephine mark of 9 mm is made on the cornea to topical corticosteroids, excessive corneal thinning with
upto a depth of 0.3 mm. This is followed by the lamellar impending corneal perforation and frank peripheral perforations.
dissection of the recipient bed. A lamellar pocket is created in
the recipient from the edges of the dissected edge into the Limbal Conjunctival Resection
peripheral cornea upto the limbus. A full thickness donor
lenticule of 11.5 to 12 mm in diameter, with its endothelium If there is an incomplete or absent response to topical
removed is used. The peripheral edges of the donor lenticule corticosteroids conjunctival resection may be performed. The
are trimmed so as to achieve its peripheral thinning. This is then resection should extend 2-4 mm posteriorly and well beyond the
placed on the recipient bed and the edges are tucked under the affected area. This is the first surgical step in treatment of
peripheral rim of the host. Undertaking paracentesis beforehand Mooren’s ulcer.1
may facilitate the procedure of tucking the edge of the graft in
Cyanoacrylate Glue
the peripheral lamellar pocket. This is followed by the application
of the 16-20 interrupted monofilament nylon sutures. The sutures Perforations less than 1.5 mm can be easily plugged with the
anchor the donor graft into the host lamellar pocket. help of a tissue adhesive.2 It can also be used in combinations
with other surgical modalities such as conjunctival resection and
Annular Corneoscleral Ring superficial keratectomy where healing was achieved in 82.4
An alternative surgical technique for stabilizing peripheral percent of the cases.3
corneal thinning in keratoglobus corneas with severe ectasias has
Lamellar Keratoplasty
been elaborated by Kanellopoulos et al.5 A donor corneoscleral
ring with an outer diameter of 14.5 mm and an inner opening of Lamellar patch grafts can be used in cases of excessive corneal
7.0 mm, is placed around the limbus to support the mid- thinning with impending corneal perforation. Bessant et al treated
peripheral thinned cornea and 10-0 nylon interrupted sutures are ten cases of marginal corneal ulceration with perforation by
applied only at the limbus. Conjunctiva was draped over and lamellar keratoplasty and they were able to preserve the globe
sutured to the donor corneoscleral ring graft. The peripheral in all cases and achieved a visual acuity of ≥ 6/60 in 6 patients.4
279
A crescentic annular lamellar graft may also be undertaken in REFERENCES
cases of peripheral corneal thinning.
1. Brown SI, Mondino BJ. Therapy of Mooren’s ulcer. Am J
Ophthalmol 1984;98:1.
Penetrating Keratoplasty 2. Refozo MF, et al. Evaluation of adhesives for corneal surgery.
In cases of larger peripheral perforations, a partial annular Arch Ophthalmol 1968;80:645.
penetrating keratoplasty may be performed. Although penetrating 3. Agrawal V, Kumar A, Sangwan V, Rao GN. Cyanoacrylate
adhesive with conjunctival resection and superficial keratectomy
keratoplasty has been described in cases of Mooren’s ulcer, the
Section V: Specific Techniques in Keratoplasty

in Mooren’s ulcer. Indian J Ophthalmol 1996;44:23-7.


results are generally poor. Penetrating keratoplasty may be 4. Bessant DA, Dart JK. Lamellar keratoplasty in the management
complicated by recurrence and extension of the disease process of inflammatory corneal ulceration and perforation. Eye
into the donor tissue with resultant necrosis and sloughing. 1994;8:22-8.
5. Kinoshita S, Ohashi Y, Ohji M, Manabe R. Long-term results of
Keratoepithelioplasty keratoepithelioplasty in Mooren’s ulcer. Ophthalmology
1991;98:438-45.
This can be either used alone or in combination with 6. Martin NF, Stark WJ, Maumenee AE. Treatment of Mooren’s and
corneoscleral lamellar graft. In this procedure, the melting tissue Mooren’s like ulcer by lamellar keratectomy: report of 6 eyes and
in ulcerated areas is scraped off and several lenticules with intact literature review. Ophthalmic Surg 1987;18:564-9.
corneal epithelium of fresh donor eye are placed near the distal 7. Gong XM, Chen J, Feng CM, Du NZ. Mooren’s ulcer treatment
side of the ulcer and sutured to the bare sclera with with conjunctivo-scleral excision and lamellar scleral keratoplasty.
circumferential 10-0 nylon sutures. Kinoshita et al treated 20 Yan KE Xue Bao 1985;1:45-8.
8. Langlois J, Marx P, Brasseur G, Langlois JL. A case of Mooren’s
eyes of Mooren’s ulcer with keratoepithelioplasty alone or in
ulcer; treatment with keratoplasty and antimitotic agents. Bull Soc
combination with corneoscleral lamellar graft.5 Ninety percent Optalmol Fr 1980;80:389-93.
of the eyes showed complete remission after surgery. During the 9. Stilma JS. Conjunctival excision or lamellar scleral autografts in
follow-up period (mean 3.1 years), minor recurrences were found 38 Mooren’s ulcer from Sierre Lione. Br J Ophthalmol
in 25 percent eyes. 1983;67:475-8.
10. Dindeldein SA, Insler MS, Barron BA, Kaufman HE. Mooren’s
Other Surgical Procedures ulcer treated with periosteal graft. Ann Ophthalmol 1990;22:
56-7.
Lamellar keratectomy has been tried as it removes the corneal 11. Genvert G, Sakauye CM, Arentsen JJ. Treatment of marginal
antigenic stimulus to the autoimmune phenomenon that corneal ulceration with cryotherapy and conjunctival recession
causes corneal melting.6 Other procedures which have been or resection. Cornea 1984;3:256-61.
tried in Mooren’s ulcer with variable success include 12. Watson PG, Richardson E. Large corneal transplants in corneal
conjunctivo-scleral excision and lamellar scleral keratoplasty,7 destructive disease. Klin Monatsbl Augenheilkd 1994;205:
280-3.
keratoplasty and antimitotic agents,8 lamellar scleral autograft,9
13. Cowden JW, Copeland RA Jr, Schneider MS. Large diameter
periosteal autograft,10 cryocautery11 and large diameter corneal therapeutic penetrating keratoplasties. Refract Corneal Surg
grafts.12,13 1989;5:244-8.

280
39

Chapter 39: Autokeratoplasty


Autokeratoplasty
Tushar Agarwal, Namrata Sharma, Rasik B Vajpayee

Penetrating or Lamellar keratoplasty using allograft corneal Donor Eye


tissue is the standard approach for management of corneal
Important features to be looked for in eye being considered as a
opacification. However, this option is not always ideally suited
potential contralateral donor eye are:
all patients as there is shortage of optical grade corneas in many
1. Eye has no light perception (NLP)
parts of the world. This scarcity forces corneal surgeons to look
2. The cornea is clear and of normal size and shape. The cornea
at alternatives to use of allograft corneal tissue for use in visual
should be free from any synechiae. Examination by specular
rehabilitation of patients with corneal opacification.
reflection should be done to rule out any endothelial
Autokeratoplasty is a type of surgery which uses a patients’ own
abnormalities like guttae.
cornea for the purpose of restoration of vision.1 This is especially
3. Intraocular pressure should be assessed. Any long standing
applicable to those patients who are at a high risk for corneal
glaucoma can cause damage to the endothelial cells.
graft rejection.
Important investigations are:
Types of Autokeratoplasty 1. Specular Count: Endothelial cell count of 1000 cells/mm³
should be the cut off for considering an eye’s suitability for
Autokeratoplasty can be of two types:
corneal harvesting.
1. Contralateral Autokeratoplasty 2. Videokeratography: Videokeratography using a slit scan
based machine like orbscan is preferred to rule out any ectatic
In this type of surgery, a patient who has one eye primarily
disorders of the cornea.
affected with a corneal pathology and the contralateral affected
3. Visually Evoked Response: This is done to document that
eye is blind due to posterior segment or optic nerve pathology
this eye does not have any visual potential.
but has a normal cornea.1 In such a case, the corneas of the two
eyes can be switched surgically so as to provide a clear cornea Host Eye
to the eye with potential for vision.
Baseline investigations should be done as in any case being taken
2. Rotational Autokeratoplasty up for penetrating keratoplasty. Points to be noted specifically
In this type of autokeratoplasty, done in eyes with partial corneal in relation to contralateral autokeratoplasty are:
opacification, the cornea of the patient is surgically rotated, so 1. The corneal thickness should be assessed clinically and with
as to move the corneal opacity away from the pupillary axis.2-5 the use of ultrasonic pachymetry. The cornea should not be
extra ordinarily thin at any point. This would make it’s
apposition to the bed of the donor eye difficult.
CONTRALATERAL AUTOKERATOPLASTY
2. Iris and lens status has to examined carefully. The surgeon
Case Selection should be aware of any synechiae as they will need to be
broken during surgery. If the lens is cataractous then cataract
This type of surgery should be considered in any patient whose surgery is also planned along with autokeratoplasty. If the
one eye is affected by a corneal pathology and the other by a eye is pseudophakic, the IOL position and stability should
blinding posterior segment pathology. be assessed if it is visible. If the corneal opacity precludes
the examination then ultrasound biomicroscopy can be
Examination and Investigations done to determine the IOL position. If the posterior
For sake of clarity we term the eye with the diseased cornea as chamber IOL is found to be displaced anteriorly or there is
the host eye and the contralateral eye from which the clear cornea an anterior chamber IOL then IOL explantation can be
is to be harvested as the donor eye. planned.
281
The goals of examination and investigations are: Step Four (Donor Eye)
1. To ensure that the donor eye’s cornea is suitable for
The diseased cornea is sutured to the donor eye with four cardinal
harvesting
sutures.
2. Plan in advance the anterior segment surgical steps other then
keratoplasty required in the host eye.
Step Five (Host Eye)

Surgical Technique Suturing of the donor cornea to the host bed is completed with
Section V: Specific Techniques in Keratoplasty

sixteen 10-0 monofilament nylon sutures. Wound is checked for


The surgery should be undertaken in general anesthesia as any leaks and is supplemented with sutures if required. The
bilateral keratoplasty can take many hours to perform. It is surgical steps for the host eye are complete.
advisable to administer intravenous mannitol in a dose of 1 to
1.5 grams per kg to the patient, 45 minutes before surgery to Step Six (Donor Eye)
ensure minimize positive vitreous pressure during surgery.
The diseased cornea is securely sutured to the donor went. This
Both eyes of the patient are cleaned and draped. Two separate
may require a larger number and tighter than normal sutures as
instrument trolleys are prepared, one for each eye. The Operating
the corneal button is 0.25 millimeters undersized. Again, the
Room floor is organized to ensure that the surgeon can switch
wound is checked for any leaks and supplemented with sutures
between the two eyes anytime during the surgical procedure. To
as required.
understand the surgery better, surgical procedure is divided into
discrete surgical steps. The aim of these steps is to ensure that
Postoperative Management
the host eye is left open sky for minimum possible period of
time to minimize the risk of expulsive hemorrhage in the seeing Topical broad spectrum antibiotics, corticosteroids and
eye. preservative free lubricants are prescribed for both eyes.
Intraocular pressure is carefully monitored in both eye separately.
Step One (Host Eye)
ROTATIONAL AUTOKERATOPLASTY
A 7 to 8 millimeters trephine is used to cut a central button of
The principle of rotational autokeratoplasty is to surgically rotate
the host cornea. After freeing it completely from any attachments
a patient’s cornea that is affected by a localized corneal opacity,
to the corneal bed, it is set aside carefully in a graft holder. It is
so that the opacified part of the cornea is moved away from the
important to remember at this stage that this cornea is to be used
pupil.
to close the donor eye and so, it is handled carefully.
If any anterior segment reconstruction or anterior vitrectomy
Case Selection
is required it is performed at this time. Once the anterior segment
surgical procedures are completed, the diseased corneal button Selecting cases that are suitable for this type of surgery and
is temporarily sutured back to the host with the help of four planning the trephine size and its placement on the cornea are
cardinal sutures. The anterior chamber is formed with the major issues to be decided.
viscoelastic containing 0.9 percent Sodium Hyaluronate.
Mathematical Method
Step Two (Donor Eye) Bourne et al described the mathematical model for deciding the
suitability of the patient for this type of surgery and the trephine
The donor cornea trephined using a vacuum trephine which is size to be used.3
0.25 mm larger than that used for the trephination of the host To determine the suitability two measurements are taken.
cornea. One should make sure that the donor cornea is cut all at First the diameter of the largest circle of the clear cornea is
once so that minimal manipulation of the donor graft is required measured. Second, the shortest distance from the edge of the
with corneal scissors. Once the cut is completed, the donor circle to the geometric center of the cornea is assessed. This is
cornea is carefully set aside on a graft holder with the endothelial considered positive if the opacity involved the center of the
side up and covered with a viscoeleastic. The donor eye is cornea and negative in the opacity is within the largest area of
covered with a wet swab. the clear cornea.
The required trephine size is obtained with the following
Step Three (Host Eye) equation:
1.5 × diameter of the largest clear circle + shortest
The cardinal sutures are cut and the diseased cornea is removed distance from the circle to the corneal center
from the host. It is placed on a graft holder with the endothelial
side up and covered with a viscoeleastic as was done for the Computer Simulation
donor cornea. The donor cornea which has been prepared in step The cases can also be selected and the surgery planned on
two is placed on the host and tied with four cardinal sutures to the basis of preoperative computer simulation and digital
282 the host bed. imaging.6
A central photo of the cornea is captured using a digital photo operatively. The reference points from the limbus are marked
slit lamp (Fig. 39.1A). This image is imported into a on the cornea and it is trephined. The cornea is freed from any
commercially available image editing software like Photoshop. attachments to the host rim. Cataract surgery is performed if
Using the circle drawings tool, a circle approximating the pupil required (Fig. 39.1D). The cornea is placed in the rotated
is drawn over the cornea (Fig. 39.1B). This is done on a new, position as per the preoperative simulation (Fig. 39.1D). It is
transparent layer created on the original image. Then switching sutured to the eye in this position with interrupted 10-0
back to the original layer, a circle is drawn on the cornea to monofilament nylon sutures. Special care is required while

Chapter 39: Autokeratoplasty


simulate corneal trephination (Fig. 39.1B). The corneal area suturing the opaque parts as they are likely to be of uneven
within this circle is rotated on the image to simulate rotational thickness. Extra sutures can be place in this are is it seen that
autokeratoplasty (Fig. 39.1C). This step is repeated a number the host –graft apposition is not sufficiently secure at this point.
of times using varying sizes and position of the larger circle, The wound is check for leaks meticulously at the end of surgery.
which simulates the corneal trephine, to include maximum clear
cornea in the pupillary axis. The position of the rotated cornea Postoperative Management
that provides the maximum clearing of the pupil is chosen as
the final intended position of the cornea (Fig. 39.1C). The size Postoperatively the patient requires topical broad spectrum
of the larger circle (Trephine) and its distance from the limbus antibiotics topical steroids and preservative free lubricants.
is measured. The layers of the image can be fused at this stage Steroids can be tapered off after 4 weeks.
and printout be taken for reference during the surgery.
Advantages
Surgical Technique
The biggest advantages of autokeratoplasty is that the patient is
The surgery is performed under peribulbar anesthesia. The size totally free form the risk of graft rejection. This is a major benefit
and site of trephination has already been determined pre- for some patients who are at a high-risk of graft rejection

Figure 39.1A: Central photo of cornea is captured using digital Figure 39.1B: A circle is drawn on cornea to simulate corneal
photo slit-lamp which is then imported in commercially available trephination and another circle is drawn to simulate the pupil
imaging editing software

Figure 39.1C: Corneal area within the circle is rotated to Figure 39.1D: Cataract surgery, pupilloplasty and rotational
simulate rotational autokeratoplasty corneal transplantation done according to simulation
283
including those with previous failed grafts and vascularized rotational graft. Also the visual outcome is expected to be
corneas. Since no external donor is required, there is no waiting moderate in nature.
period for the patient for allograft tissue. The surgery can be An informed consent highlighting these points should be
scheduled at the convenience of the patient and the surgeon. obtained from the patient.
There is no risk of transmission of infections through donor
material as can be a possibility with allografts. Also, there is a CONCLUSION
decreased requirement for postoperative steroids as the tissue
Autokeratoplasty is a good alternative to allograft corneal
Section V: Specific Techniques in Keratoplasty

used belongs to the patient. This is especially helpful in patients


transplantation in cases suitable for these types of surgery. They
who are steroid responders. Finally, there is no risk associated
provide the benefits of zero risk of graft rejection and donor-
with the use of corneal preservative media.
transmitted infections, faster recovery, decreased dependence on
topical and systemic steroids and other immunosuppresives
Disadvantages
along. Along with these advantages, they provide the benefit of
However there are a few disadvantages for the patient. The elimination of dependence on the availability of donor corneal
opacity is not removed in cases with rotational autokeratoplasty tissue. There are some pitfalls like moderate visual recovery,
and merely shifted from one eye to the other in contralateral persistence of the corneal opacity and bilateral surgery in cases
keratoplasty. Some patients may not be willing to compromise of contralateral autokeratoplasty. If ideally suited cases are taken
on this issue. up for these surgeries, the risk benefit ratio may be skewed
Contralateral autokeratoplasty requires a bilateral towards the patients.
simultaneous keratoplasty. This requires general anesthesia which
may add an element of risk tot he procedure. These are higher REFERENCES
chances of astigmatism with rotational autokeratoplasty as tighter
sutures are required for fitting a same sized graft. Also, the 1. Price FW Jr, Hanna Si. Bilateral penetrating autokeratoplasty.
corneal thickness of the central and peripheral part of the cornea J Refract Surg 1995;11:494-96.
2. McDonnell PJ, Falcon MG. Rotational autokeratoplasty. Eye
that are being apposed are dissimilar. This may require additional
1989;3:576-80.
tightening of the sutures. 3. Bourne WM, Brubaker RF. A method for ipsilateral rotational
autokeratoplasty. Ophthalmology 1978;85:1312-16.
Patient Counseling 4. Verma N, Melengas S, Garap JA. Ipsilateral rotational auto-
keratoplasty for the management of corneal opacities. Aust NZJ
The treating physician should speak in detail with the patient
Ophthalmol 1999; 27:21-5.
regarding the procedure. The patient should be explained the
5. Murthy S, Bansal AK, Sridhar MS, Rao GN. Ipsilateral rotational
relative advantages and disadvantages of the procedure. It is autokeratoplasty: an alternative to penetrating keratoplasty in
important for the patient to have an understanding of the nonprogressive central corneal scars. Cornea 2001;20:455-57.
procedure and have realistic expectations regarding the 6. Bower KS, Mines MJ, Stutzman RD. Digital imaging to assist
procedure. The patient should be aware of that the opacity is preoperative planning for ipsilateral rotational auto-keratoplasty.
going to persist, although it may be covered by the eyelids in a J Telemed Telecare 2006;12:374-76.

284
40

Chapter 40: Limbal Stem Cell Transplantation


Limbal Stem Cell Transplantation
Geoffrey C Tabin, MR Feilmeier, Y Khalifa, N Kloster, A Murchison,
JW Dimming, S McKeon

Severe ocular surface disease presents a significant challenge CONJUNCTIVAL DEFICIENCY


for the ophthalmologist. This chapter will review the ocular
Underlying disorders or damage to the conjunctiva can
surface anatomy, discuss the etiology and sequelae of
compromise the ocular surface. Disruption of the conjunctiva
conjunctival deficiency and limbal stem cell deficiency, and
can be due to a variety of causes such as conjunctivitis, trauma,
provide a stepwise approach to reconstruction of the ocular
surgery, conjunctival neoplasia, chemical or thermal burns,
surface.
Stevens-Johnson syndrome, epidermolysis bullosa, sarcoidosis
OCULAR SURFACE ANATOMY and scleroderma. Any disruption of the normally smooth
conjunctival surface can result in a deficiency of aqueous or
The health and clarity of the cornea is intimately related to the mucin, an unstable tear film, symblepharon formation, limbal
ocular surface. The ocular surface, which is both an anatomic stem cell deficiency or scarring. All of these sequelae can result
and functional unit, is comprised of the tear film and the in severe ocular surface disease and increased susceptibility to
epithelium of the cornea and conjunctiva. The integrity and further damage.
action of the eyelids provide protection and an adequate
dispersion of the tear film over the corneal surface. The tear film LIMBAL STEM CELL DEFICIENCY
is composed of three layers. The hydrophilic mucin layer,
Conjunctival disease may lead to further ocular surface
secreted by the unicellular goblet cells of the conjunctiva, allows
compromise and result in the deficiency of limbal stem cells.
the hydrophobic surface of the epithelium to retain moisture and
Limbal stem cell deficiency is also seen in chemical or thermal
stabilizes the precorneal tear film. The aqueous tears from the
injuries, aniridia, Stevens-Johnson syndrome, epithelial
accessory and main lacrimal glands provide water and proteins,
neoplasia, after multiple surgeries, and with ocular cicatricial
including protective secretory IgA. Finally, the meibomian
pemphigoid and contact lens-induced keratopathy. A major
secretions provide an oily surface that prevents evaporation of
sequel of limbal stem cell deficiency is conjunctivalization of
the underlying aqueous layers. Beneath the tears a stratified,
the cornea. In this process conjunctival cells invade and cover
nonkeratinized epithelium covers the entire cornea as well as
the cornea, resulting in a thickened, vascularized, and irregular
the bulbar and palpebral conjunctiva.
The normal conjunctival surface contains epithelial and
goblet cells. The location of stem cells for conjunctival goblet
and nongoblet epithelium is not known exactly, but recent studies
suggest the conjunctival fornices to be the most likely location
(Fig. 40.1).1,2 The corneal epithelium does not have goblet cells
and remains avascular. This layer of cells is in a constant state
of renewal from both anterior movement from basal layers and
centripetal and circumferential cellular migration from the
corneoscleral limbus. These limbal cells are responsible for the
renewal of the corneal epithelium. They are long-lived and
capable of asymmetric division, allowing one daughter cell to
remain a stem cell and the other to differentiate into a
proliferating corneal epithelial cell. These unique and important
cells have been termed “limbal stem cells” and are crucial to
the reconstruction of severe ocular surface disorders (Fig. 40.2). Figure 40.1: Anatomy of the limbus 285
Section V: Specific Techniques in Keratoplasty

Figure 40.2: Stages of stem cells

surface that may have chronic inflammation. Such an unstable Conjunctival autograft continues to be a valuable procedure,
corneal surface can lead to persistent epithelial defects, stromal especially for treatment of recurrent pterygia and fornix
ulceration and scarring, or even perforation. The end result is reconstruction.
often pain and severe loss of vision. The most significant progress in the treatment of severe
ocular surface disease was made with the discovery of limbal
TREATMENT OF SEVERE stem cells. Initially noted in 1971 by Davanger and Evensen,4
OCULAR SURFACE DISEASE stem cells are located at the limbus and are now known to be
long-lived, divide asymmetrically and have a long cell cycle time.
Most procedures to treat severe ocular surface disease have good
Based on a theory by Schermer,5 limbal basal (stem) cells are
short-term results, but early treatment with keratectomy and
thought to proliferate into basal corneal epithelium and then
keratoplasty carries a poor prognosis over time. A superficial
terminally differentiate into suprabasal corneal epithelium.
keratectomy will only result in the rapid re-invasion of the
Transplantation of limbal stem cells is now a highly successful
counjunctival epithelium. Keratoplasty may result in short-term
long-term treatment of severe ocular surface disease.6,7 There
improvement, but when the donor epithelium sloughs months
are several surgical techniques, which vary by donor and tissue
later the graft is destined to fail.
transplantation.
The optimal treatment for patients with limbal stem cell
deficiency and severe ocular surface disease aims at replacing
CLASSIFICATION OF EPITHELIAL
abnormal conjunctiva and/or limbal stem cells with epithelial
TRANSPLANTATION
and stem cell transplantation. Conjunctival transplantation for
severe ocular surface disease was first proposed to treat A variety of procedures have been described for the management
monocular chemical burns by Thoft in 1977.3 This procedure of severe ocular surface disease. All share the common goal of
used an autograft of bulbar conjunctiva from the fellow eye as transplanting a new source of ocular surface epithelium into a
donor tissue to re-establish an intact ocular surface in patients diseased eye. In 1996, Holland et al. 8 first proposed a
with ocular scarring. The procedure was based on the theory of classification system for epithelial transplantation that is widely
conjunctival transdifferentiation with the idea that conjunctival used today (Table 40.1). This classification is based on the
epithelium differentiated into cornea-like epithelium. primary type of epithelial tissue transplanted, the carrier tissue

Table 40.1: Classification of epithelial transplantation procedures for ocular surface disease
Procedure Abbreviation Donor Transplanted tissue
Conjunctival transplantation
Conjunctival autograft CAU Same/fellow eye Conjunctiva
Cadaveric conjunctival allograft c-CAL Cadaver Conjunctiva
Living-related conjunctival allograft lr-CAL Living relative Conjunctiva
Limbal transplantation
Conjunctival limbal autograft CLAU Fellow eye Limbus/conjunctiva
Cadaveric conjunctival limbal allograft c-CLAL Cadaver Limbus/conjunctiva
Living related conjunctival limbal allograft lr-CLAL Living relative Limbus/conjunctiva
Keratolimbal allograft KLAL Cadaver Limbus/cornea
Combined conjunctival and keratolimbal C-KLAL Living relative/Cadaver Limbus/Cornea/
allograft Cunjunctiva
Table modified from Holland et al (1996).8
286
used, and the source of the donor tissue. The epithelial tissues is an immune-privileged tissue possessing immunoregulatory
used for transplantation can be harvested from the conjunctiva, factors capable of reducing ocular surface inflammation and
cornea, and limbus. Conjunctival transplantation requires no promoting epithelial healing. This tissue serves as a substrate
carrier tissue because only conjunctiva is transferred. Limbal when underlying stromal tissue has been destroyed. Its epithelium
stem cell transplants utilize cornea or conjunctiva as carrier tissue produces growth factors and the basement membrane facilitates
because it is technically impossible to transplant limbal stem cells migration of epithelial cells and reinforces adhesion of basal
alone. Both conjunctival and limbal procedures are further epithelial cells. This enables the regrowth of normal epithelium

Chapter 40: Limbal Stem Cell Transplantation


divided according to the source of the donor tissue used. over the amniotic membrane and the ocular surface defect.
The source of the donor tissue for epithelial transplantation Amniotic membrane also reduces inflammation and suppresses
may be from self (autograft) or non-self (allograft). Autografts fibroblast proliferation. Immunosuppression is not required when
are harvested from the same or fellow eye. Allografts are only amniotic membrane is used given it does not express HLA
harvested from a cadaveric whole globe, cadaveric corneoscleral under normal circumstances.
rim, or a living relative. Conjunctival transplantation procedures Amniotic membrane was introduced in the 1940s for the use
can be either an autograft from the same or fellow eye in conjunctival epithelial defects and chemical injuries of the
(conjunctival autograft-CAU), or an allograft from a cadaveric conjunctiva and cornea. Since, amniotic membrane has been
or living-related donor. A cadaveric conjunctival allograft shown to be useful in the treatment of ocular surface disease
procedure is abbreviated c-CAL, while a living-related caused by conditions such as ocular cicatricial pemphigoid,
conjunctival allograft is abbreviated lr-CAL. Stevens-Johnson syndrome, chemical/thermal burns and
Limbal transplantation procedures are classified by the persistent epithelial defects, scleral thinning, and neurotrophic
source of the donor and the carrier tissue. For instance, a ulcers. Amniotic membrane can also be used in conjunctival
conjunctival limbal autograft (CLAU) is a limbal transplantation surface reconstruction for pterygium and symblepharon repair.
utilizing conjunctiva as a carrier of limbal stem cells from the Recent interests have focused on the use of AMT as a substrate
fellow eye. If cadaveric conjunctival and limbal tissue is used, for ex vivo expansion of limbal stem cells.
the procedure is called a cadaveric conjunctival limbal allograft Amniotic membrane is obtained shortly after elective
(c-CLAL). A living-related donor supplying the conjunctival and cesarean delivery and is tested for HIV, hepatitis B and C, and
limbal tissue is then considered a living-related conjunctival syphilis. Methods of preparation vary slightly, but generally the
limbal allograft (lr-CLAL). If peripheral cornea is used instead placenta is cleaned of blood clots under a lamellar flow hood
of conjunctiva as the carrier of limbal stem cells from a cadaver, using sterile saline. The amnion is separated from the rest of the
the procedure is named a keratolimbal allograft (KLAL). chorion by blunt dissection through the potential spaces between
Combined conjunctival-keratolimbal (C-KLAL) is a procedure the 2 tissues. It is then rinsed in 4 percent, 8 percent and 10
in which limbal tissue with a corneal carrier is harvested from percent dimethyl sulfoxide (DMSO) phosphate buffered saline
cadaveric tissue and limbal tissue with a conjunctival carrier is for 5 minutes at each successive concentration and flattened onto
harvested from a patients living relative are both transplanted a nitrocellulose paper with the epithelium/basement membrane
to the diseased eye. All of the above procedures, limbal and surface facing upward. The amniotic membrane is cut into
conjunctival, can benefit from amniotic membrane smaller pieces (e.g. 5 × 5 cm) and stored before transplantation
transplantation as an adjuvant treatment. Finally, a large-diameter at 80°C in a sterile vial containing a preserving medium. Prior
lamellar keratoplasty or eccentric penetrating keratolimbal to surgery the amniotic membrane is thawed and rinsed 3 times
keratoplasty can be performed as a means of introducing limbal in saline. In North America, amniotic membrane is available
stem cells at the time of keratoplasty.9 frozen and in media from the Tissue Bank International in
Most recently, significant research has focused on the Baltimore, MD and Biotissues in Miami, FL.
development of ex vivo stem cell expansion techniques. In this In general, prior to placing amniotic membrane, the ocular
procedure, limbal stem cells isolated from cadaveric eyes, living surface must be debrided to remove conjunctival or limbal
related eyes, or autologous eyes are harvested and grown in lesions or a corneal pannus if present. The membrane is then
culture on an amniotic membrane. The membrane and epithelial removed from the storage medium, peeled off the nitrocellulose
cells are then transferred to the recipient eye. Several recent filter paper and transferred to the recipient eye with the basement
studies have demonstrated the success of this promising membrane side upward. For corneal surface repairs the amniotic
technique. membrane covers the entire cornea, whereas for conjunctival
repairs the membrane is fitted to cover the defect. If the amniotic
AMNIOTIC MEMBRANE TRANSPLANTATION membrane is to be used for patching, then the stromal side faces
Amniotic membrane is the innermost layer of the fetal upward. The amniotic membrane is placed on the ocular surface
membranes and is a thin, semitransparent tissue. It has a stromal with the epithelial surface facing outward, and secured to the
matrix, a thick collagen layer and an overlying basement eye with 9-0 silk sutures, covering as much of the ocular surface
membrane with a single layer of epithelium. Amniotic membrane as possible.

287
EPITHELIAL TRANSPLANTATION PROCEDURES to the limbus. The thin conjunctival graft is cut free, rotated
across the cornea and placed over the pterygium excision site.
Several options must be considered by the clinician in the The graft is sewn without tension with interrupted 8-0 vicryl
management of patients with severe ocular surface disease. sutures. Finally, the eye is dressed with a steroid and antibiotic
Proper decision making requires accurate assessment of the ointment. The patient continues on steroid and antibiotic drops
patient’s condition. The first step is to determine whether the for one month.
disease is unilateral or bilateral. In unilateral disease an autograft
from the same or fellow eye can be used. Autograft procedures Conjunctival Limbal Autograft
Section V: Specific Techniques in Keratoplasty

have a better prognosis than allograft procedures because the


risk of graft rejection and the need for immunosuppression are When unilateral limbal deficiency is apparent with or without
eliminated. conjunctival involvement, a conjunctival limbal autograft should
be used. This procedure is most beneficial in patients with
concurrent conjunctival inflammation as the graft consists of both
Conjunctival Autograft
healthy conjunctiva and limbal cells. Unilateral limbal stem cell
If the disease involves the conjunctiva only, a conjunctival deficiency is most commonly seen after chemical injury, but can
autograft is indicated. In 1982, Thoft10 reported improvement also occur as a sequela of intraepithelial neoplasia or after
in the ocular surface in 16 of 17 eyes after conjunctival autograft. multiple eye surgeries. The clinical data clearly supports early
Vastine et al11 (1982) and Herman et al (1983)12 also reported intervention involving limbal autografting from the fellow eye
marked success with conjunctival autografts as 100 percent of in these cases.13-18
their patients (10 total) had improvement in their ocular surface. If a persistent epithelial defect does not improve despite
Reconstruction can be accomplished with transplantation of maximal supportive care, and is thought to be due to stem cell
healthy conjunctiva from an undamaged area of the same eye. deficiency, a limbal stem cell autograft is recommended.
For example, when elastotic degeneration of the bulbar Preparation of the recipient eye begins with a 360o conjunctival
conjunctiva results in the formation of pterygia, excision peritomy and careful dissection of all fibrovascular pannus and
followed by transplantation of healthy conjunctiva from the irregular epithelial tissue from the corneal surface. Further
superior bulbar conjunctiva is indicated. This technique is resection of the conjunctiva at the 12 and 6 o’clock meridians
essentially an autograft patch that replaces a focal defect in the will allow placement of the donor tissue. Hemostasis is
conjunctiva. A conjunctival autograft is also used to repair maintained with light wet field cautery. Next, the donor tissue is
defects after tumor excisions, to prevent extraocular muscle harvested. The dimensions of the donor site are marked with a
restriction and conjunctival or Tenon’s scarring, or to eliminate marking pen, which will include 3 clock hours at 6 and
the problem of symblepharon formation after chemical injuries 12 o’clock, approximately 1 mm of clear corneal tissue anteriorly,
which spare the limbus and cornea. The preferred technique for and 4-5 mm of bulbar conjunctiva posteriorly. Next, an incision
conjunctival autografting after pterygia excision is to perform is made in the clear cornea of the donor, 1mm anterior to the
surgery either under local or peribulbar anesthesia. If a peribulbar limbus, using a guarded diamond blade preset to 200 um (any
block is employed a 6-0 nylon suture is placed at the limbus at sharp blade will suffice). The cut must pass barely into the
both the six o’clock and twelve o’clock positions to aid exposure. corneal stroma. Next, Westcott scissors are used to dissect a
If local anesthesia is used the patient is asked to look in the limbal based conjunctival flap that is dissected forward to the
desired direction to yield maximal exposure and facilitate limbus. A Gill blade or crescent blade is used to bring the
surgery. Pterygia are carefully marked for conjunctival extension dissection forward into clear cornea until it meets the corneal
and removed to bare sclera with careful dissection of all scar incision made perpendicular to the surface. The harvested tissue
and Tenon’s capsule. A standard excision technique is utilized is removed en bloc and placed in storage medium. Two 90o
employing Westcott scissors and a disposable Beaver 57 blade. identical limbal conjunctival stem cell donor crescents are
The extent of the defect is carefully measured with calipers. Next, harvested from the 10:30 to 1:30 clock hours superiorly and 4:30
the eye is either retracted downward or the patient is asked to to 7:30 clock hours inferiorly. The adjacent conjunctiva of the
look down. donor eye is then undermined with blunt dissection, brought
Calipers are used to measure a length and width 1mm larger forward, and secured using a vicryl suture to cover the donor
than the defect created at the excision site. The planned excision site. This will improve postoperative patient comfort.
site is marked with ink, both to delineate the size of the graft Returning to the recipient eye, the grafts are placed superiorly
and to ensure that it is sewn in the proper orientation with the and inferiorly at the limbus and sewn securely in position with
top surface of the conjunctiva up. With the eye rotated two interrupted 10-0 nylon sutures at the anterior corners on the
downward, a 30-gauge needle is placed between conjunctiva and corneal side of the graft and interrupted 8-0 vicryl on the
Tenon’s capsule. One percent lidocaine with epinephrine is conjunctival side of the graft. Finally, it is recommended that
injected to help hydrodissect the conjunctiva free of Tenon’s. the entire corneal surface and all areas of debrided conjunctiva
Westcott scissors are then used to dissect a thin layer of are covered with an amniotic membrane graft. The amniotic
conjunctiva. The dissection starts superiorly and is brought down membrane is cut to the appropriate size and sewn in position
288
with interrupted 8-0 vicryl sutures. The amniotic membrane acts The proximity of the allograft transplant tissue to the highly
as a biological dressing, helping to decrease inflammation and vascular limbal area increases the likelihood of immunologic
to provide a surface for the spread of the new epithelial cells. It rejection, even if a well matched living related donor is used.
must be stressed that amniotic membrane alone does not provide The importance of systemic immunosuppression to maximize
new stem cells. Antibiotic and steroid combined drops are then graft survival and therapeutic success is clearly outlined in the
used four times per day for six weeks and then tapered literature.
accordingly. The combination of oral and topical immunosuppressive

Chapter 40: Limbal Stem Cell Transplantation


In most cases complete epithelialization is seen within the agents is necessary for long term graft survival in all patients
first week after successful autografting. Typically, the epithelium receiving allograft tissue. Both topical corticosteroids and
demonstrates sufficient adhesion and few recurrent erosions or cyclosporin A should be utilized postoperatively twice to four
persistent epithelial defects will be observed in the postoperative times per day. These medications should be used indefinitely in
period. Minimal eye trauma and eye-rubbing along with maximal patients receiving allograft tissue. An overview of systemic
ocular surface lubrication will promote rapid and optimal healing immunosuppression is provided in a following section.
of the ocular surface. If extensive goblet cell loss has taken place
or a dry eye is present, punctal occlusion should be performed Cadaveric Keratolimbal Allograft
at the time of the transplant.
If a suitable living donor is unavailable or the disease is primarily
Reduced vascularization improves the success rate of later
limbal without conjunctival involvement (as in aniridia), a
penetrating or lamellar keratoplasty. Specifically, Kenyon and cadaveric keratolimbal allograft should be considered.24-27
Tseng (1989)18 document success in a group of 21 patients that
Utilizing a donor corneal button as a carrier, limbal stem cells
underwent conjunctival limbal autografting. They reported rapid
are harvested from a cadaveric globe and the corneoscleral rim
surface healing in 19 cases, a stable ocular surface in 20 cases, is transplanted to the patient.
and improved visual acuity in 17 cases. Penetrating or lamellar
The technique involves first dissecting all fibrovascular
keratoplasty was successful in seven of seven patients after the
pannus from the host eye and performing a 360o peritomy
limbal transplantation procedure. that clears the limbus. Hemostasis is maintained using gentle
Serious complications in the donor eye are unusual,
wet-field cautery. The donor tissue is then prepared using a 9
particularly if high-risk patients are identified in the preoperative
mm trephine to punch a corneal button. Scissors are then used
examination and history. If the donor eye is partially to trim the scleral side of the donor to approximately 1.5 mm
compromised a stem cell deficit can occur after taking a limbal
posterior the limbus. The corneoscleral rim is then sectioned into
stem cell harvest. Reported complications in donor eyes
equal halves. Careful lamellar dissection of the posterior 1/2 to
(autograft or allograft) have included localized haze in a patient 2/3 of corneal and scleral tissue is performed using a crescent
with contact lens-induced keratopathy, pseudopterygium,
blade, careful to preserve the overlying conjunctiva. Some
filamentary keratitis, microperforation during surgery, abnormal
authors recommend using the donor rim from 2 cadaveric globes,
epithelium, and corneal depression. Additionally, pseudopterygia for a total of 3 halves, to maximize the number of stem cells
and vascular pannus formation are rarely observed at the corneal
transplanted. It is important that the donor tissue is the
harvest site.
appropriate thickness. If it is too thick, epithelialization will be
delayed. The allograft is then sewn into position with 2
Living-related Conjunctival Limbal Allograft
interrupted 10-0 nylon sutures at the anterior corners and
Bilateral limbal stem cell loss, as seen in Stevens-Johnson interrupted 8-0 vicryl sutures on the scleral side (Figs 40.3 and
syndrome, aniridia, cicitricial pemphigoid, or contact lens- 40.4) The entire cornea, including the graft, is covered with
induced keratopathy, presents a challenging situation. In bilateral amniotic membrane secured with vicryl sutures.
disease, living-related or cadaveric allograft procedures are This procedure is advantageous as it is available to all
necessary.19-23 patients and eliminates risk to the donor, yet it may not be as
Living-related conjunctival limbal autograft is a procedure beneficial in limbal stem cell deficiency with accompanying
in which limbal stem cells are harvested on a conjunctival carrier conjunctival disease. While the keratolimbal allograft is primarily
from a living relative of the recipient. The major disadvantage avascular, systemic immunosuppression is again employed as it
of using allograft tissue over autograft tissue is the introduction has been shown to improve outcomes. If the eye is quiet with an
of transplant rejection. In order to minimize the chance of graft intact epithelial surface at three months a penetrating or lamellar
rejection, an allograft from a well-matched living-related donor keratoplasty is performed for visual rehabilitation.
should be sought. Blood samples are obtained from the patient The literature has shown this technique to be very successful
and their first-degree relatives and the donor with the best ABO in appropriate candidates with bilateral LSCD. Preoperative
blood and HLA tissue match should be chosen. The surgical aqueous tear deficiency, keratinization of the ocular surface, and
procedure is then performed in the same manner as the previously uncontrolled severe inflammation has been shown to be poor
described autograft. prognostic factors to KLAL. In appropriate candidates, a stable

289
cadaveric globe is then processed as previously described and
placed in storage medium. The recipient eye is then prepared.
Lysis of all symblepharon and surface scarring is performed
followed by a 360 o conjunctival peritomy. A superficial
keratectomy is necessary to remove all abnormal epithelium and
fibrovascular pannus. Hemostasis is maintained using light wet
field cautery. It may be necessary to combine the efforts of an
Section V: Specific Techniques in Keratoplasty

oculoplastics specialist in the reconstruction of the lids and


fornices and prior arrangements should be made preoperatively
to optimize ocular surface rehabilitation if necessary.
The living-related conjunctival autografts are then positioned
and secured at the 6 o’clock and 12 o’clock positions using
interrupted 10-0 nylon and 8-0 vicryl sutures at the lateral and
posterior aspects of the grafts. The cadaveric tissue is then
Figure 40.3: Ocular surface disorder (preoperative) positioned and secured temporally and nasally using 10-0 nylon
and 8-0 vicryl sutures as previously described. The tissue should
be arranged so as to void gaps between the living donor tissue
and the cadaveric tissue. This will minimize conjunctivilization
of the ocular surface postoperatively.

LARGE-DIAMETER LAMELLAR KERATOPLASTY

More recently a single large-diameter lamellar keratoplasty9 that


incorporates limbal stem cells has been used in selected cases.
The advantage of this technique is that it can provide a stable
ocular surface and improved vision with a single procedure.
After the administration of peribulbar anesthesia and the
preparation of a sterile field, a 360o conjunctival peritomy is
performed and the conjunctiva is retracted posteriorly from the
limbus. Any symblepharon present over the cornea is released
simultaneously. A trephine, 12 or 13 mm in diameter set at a
Figure 40.4: Postoperative cadaveric keratolimbal allograft
depth of 300 mm, is used to remove the host button. The edge
of the lamellar button is held using Lim’s forceps, and lamellar
dissection is carried out with a Desmarre’s lamellar dissector.
ocular surface was achieved in 51 to 74 percent of recipients at The recipient bed is kept moist with viscoelastic while the donor
one year. 28-31 However, Solomon et al 24 demonstrated a button is being prepared.
significant decline in the percentage of patients maintaining a McCarey-Kaufman media-preserved corneoscleral tissue is
stable ocular surface over the first five years posttransplant (77 tightly clamped in a King’s clamp. Depending on the diameter
to 24%). Approximately 30-50 percent of patients receiving of the donor cornea, a trephine, 12 or 13 mm in diameter and
KLAL transplants will achieve improvement in visual acuity from set at a depth of 300 μm, is used to harvest the donor lamellar
baseline.13,21,31 graft. The trephine should encompass at least 1.5 mm of the
limbal frill 360o around the cornea, ensuring that limbal stem
Combined Conjunctival and Keratolimbal
cells are included in the graft. The lamellar button is dissected
Limbal Allograft (C-KLAL)
to a similar depth to the recipient with a Desmarre’s lamellar
Combination of conjunctival and keratolimbal autograft dissector. The graft is then sutured to the host with interrupted
techniques may be necessary in patients who have extensive radial 10-0 monofilament sutures (Figs 40.5 and 40.6)
ocular surface disease in which conjunctival loss contributes Vajpayee et al9 (2000) reports success with this technique
significantly to the pathology. Prime candidates for this in patients with severe ocular alkali burns. Successful
procedure are patients with severe cicatrizing disease such as epithelialization was achieved in 9 of 9 eyes. All patients noted
OCP, SJS, and bilateral chemical injuries. This procedure offers improvement in symptoms of watering, pain, and photophobia.
the advantage of replacement of both significant amounts of both Visual acuity improved significantly in 6 of 9 patients, and
stem cells and conjunctiva. corneal clarity improved in 7 of 9 eyes. No recurrence of corneal
The living-related tissue is harvested and previously vascularization or signs of rejection were seen in any eye during
described and placed in storage medium. The tissue from one the follow-up period in this report.

290
techniques, this concept may continue to evolve and provide
improved outcomes to patients with both ocular surface disease
secondary to limbal stem cell deficiency and stromal
opacification.

EX VIVO STEM CELL EXPANSION

Evolution of the surgical replacement of limbal stem cells using

Chapter 40: Limbal Stem Cell Transplantation


autologous and allograft tissue has greatly improved the
prognosis of patients with severe ocular surface disease due to
partial or total limbal stem cell deficiency. Despite surgical
advances, these methods have their limitations, including
potential risk to the donor, and require indefinite
immunosuppression to avoid limbal allograft rejection, which
Figure 40.5: Large-diameter lamellar keratoplasty
is associated with significant systemic risks and economic
burden.
Fortunately, recent innovation in tissue engineering and the
introduction of ex vivo limbal stem cell expansion has created
another option requiring significantly less donor tissue. Most
agree that this concept offers an improved surgical approach and
requires a very small amount of donor tissue, obviating the need
for immunosuppression, minimizing the risk to the donor site,
and increasing the possibility of obtaining an autologous donor
tissue from a small, uninvolved area of the limbus.
Potential sources of donor tissue include autologous tissue
from the contralateral healthy limbus or from an area of healthy
limbus in the diseased eye, 35-37 from an allograft limbus
source,35,38 or from a nonocular source that is induced into a
corneal epithelial morphology and expand this biopsy in cell
culture.39 A sufficient mount of tissue can be obtained from a
1 mm2 limbal biopsy. The tissue is treated with trypsin,
Figure 40.6: Large-diameter lamellar keratoplasty
(fluorescein staining)
suspended, and allowed to settle on the culture substrate of
choice. The specific detail of the different variations in culture
techniques is beyond the scope of this chapter.40-43
Allogenic Penetrating Limbo-keratoplasty
Most reported techniques involve culturing the harvested
Reinhard and associates reported the use and long-term outcomes cells on human amniotic membrane with some authors utilizing
of eccentrically trephinated limbo-keratoplasty in 48 patients intact amniotic membrane while others use denuded amniotic
with total limbal stem cell deficiency.32-33 The recipient cornea membrane. There are reports that amniotic membrane denuded
was prepared as normal for penetrating keratoplasty with a of epithelial cells provides a better substrate for limbal stem cell
central trephination varying between 7.7 mm and 10.0 mm. The expansion. 36 Other modifications involve culture media
donor cornea was prepared with eccentric trephination to include substitutions and additions, the use of mouse fibroblast cells in
limbal tissue in approximately 40 percent of the grafts co-culture, and airlifting prior to transplantation.44-45 To date,
circumferences. Graft fixation was performed using two there are no randomized, prospective clinical studies that
continuous 10-0 nylon sutures. Postoperatively, the patients were establish the superiority of one technique or variation of
given systemic immunosuppression with cyclosporin A and technique over another.
mycophenolate mofetil to reduce graft rejection. While the use of ex vivo cultivated limbal epithelium is in
Thirty percent of the grafts were clear 5 years post- its infancy, and long-term outcomes are largely unknown, short-
operatively. The authors demonstrated the importance of HLA term results of this technique appear promising. A recent report
matching in this procedure, as 65 percent of the grafts with 0-1 from Sangwan et al. demonstrates the short-term success of this
HLA mismatch were clear at 5 years, 41 percent of the grafts procedure.36 This study evaluated the outcomes of 88 eyes of
with 2-6 HLA mismatches were clear at 5 years, and 14 percent 86 patients that had severe or partial LSCD treated with
of the untyped grafts were clear at 5 years postoperatively. autologous cultivated limbal epithelial cell transplantation. Mean
With improvements in postoperative immunosuppressive follow-up in this study was 18.3 months. 73 percent of the
management and innovations in deep lamellar surgical patients in this study achieved a stable ocular surface.

291
POST-TRANSPLANT SYSTEMIC to many patients who previously had no treatment options. Over
IMMUNOSUPPRESSION the next decade, the advent of and ongoing work in ex vivo stem
cell expansion will bring many advances to the field and benefits
Allograft transplantation carries a higher risk of rejection given
to the recipients, including increased availability of stem cells
the vascular nature and the high concentration of Langerhans’
and autologous tissue throughout the world, improved surgical
cells and HLA-DR antigens at the limbus. Effective
outcomes for patients, and significantly less need for post-
immunosuppression is essential in allograft approaches to
operative immunosuppression in patients requiring stem cell
prevent immune destruction of the grafted tissue. Rejection can
Section V: Specific Techniques in Keratoplasty

transplantation.
be loosely organized into acute and chronic forms. Acute
In addition, newer and more innovative immunosuppressive
rejection is characterized by intense sectoral injection at the
limbus with edema and infiltration of the donor graft and punctate regimens from the organ transplant literature have not been
epithelial keratopathy of the cornea. Chronic rejection involves studied in depth and could possibly yield a lower risk of rejection
a mild but diffuse limbal injection, elevation of the perilimbal in allograft procedures with less toxicity. Harvesting techniques
tissues and punctate epitheliopathy. may one day be widely performed with femtosecond lasers.
Various immunosuppressive regimens have been reported, Finally, with the popularity of the keratoprosthesis expanding
and most authors recommend a combination of topical and and continued demonstration of safety and longevity, the clinician
systemic immunosuppression. Initially, all patients should receive may opt for a nontransplant approach for the treatment of limbal
topical immunosuppression postoperatively with cyclosporine stem cell deficiency.
0.05 percent and dexamethasone q.i.d. These topical medications
can eventually be tapered to twice daily. Many authors advocate CONCLUSION
continued use of these topical agents indefinitely.
Although several immunosuppressive regimens have been Severe ocular surface disease can be the sequela of numerous
described in the literature, it should be noted that there is no types of damage and a variety of disorders. Historically, severe
proven superiority of any single regimen over another. Most ocular surface disease has been a challenge to treat. Only 30
authors advocate the combination of several agents, which lowers years ago there was a poor prognosis for patients with severe
the necessary dose of each agent and decreases the associated ocular surface disease. With advances in microsurgical
and often dose-related side effects of these medications. The techniques, stem cell research and use of amniotic membranes,
addition of steroid-sparing agents such as cyclosporine and the current prognosis for patients is much improved. Current
azathioprine allows earlier tapering of oral prednisone to a dose work with limbal stem cell cultures offers the potential for even
that is associated with significantly less mortality. Because greater successes with decreased harvesting area and less need
systemic immunosuppression is necessary in many patients for for immunosuppressive agents. These great advances create
a minimum of 12-18 months, this is an important consideration. optimism that the next 30 years will show continued progress in
Perhaps the most commonly reported regimen consists of oral the treatment and prognosis for patients with severe ocular
prednisone, cyclosporine, and azathioprine (Imuran). Oral surface disease.
prednisone is started at a dose of 0.5-1.0 mg/kg/day and tapered
over the first 3 months to a dose of 5-10 mg per day. This is
APPENDIX A
supplemented with cyclosporine and azathioprine. Cyclosporine
A is started at 3 mg/kg/day and adjusted to a serum level of SYSTEMIC IMMUNOSUPPRESSIVE AGENTS
100-150 ng/dl. Azathioprine (Imuran) is initiated at a dose of
100 mg/day. Another option is systemic tacrolimus. Corticosteroids
It should be noted that immunosuppressive agents are
associated with many potential side effects and patients on Mechanism – Reduces size and lymphoid content of lymph nodes and
immunosuppressive therapy require special attention that is not spleen without effect on myeloid or erythroid stem cells in bone marrow.
routine in most ophthalmology practices. Careful monitoring for Interfere with cell cycle of activated lymphoid cells. Inhibit production
these side effects is essential and consultation with a specialist of inflammatory mediators. Inhibits cytokines that stimulate B-cell,
T-cell proliferation, T-cell activation. Diminishes chemotaxis of
trained in the use of these medications is recommended. An
monocytes and neutrophils. Inhibit IL-1 production by monocytes,
overview of each of these agents, including mechanism of action
decrease in IL-2 and IFN. Primary antibody response diminished. DTH
and side effect profiles is provided in Appendix A. inhibited.

FUTURE DIRECTIONS Indications – Autoimmune (autoimmune hemolytic anemia, ITP, IBD,


SLE), organ transplants, allergic reactions.
The future outlook continues to improve for patients suffering Adverse effects – Increased IOP, cataract formation, delayed wound
from severe ocular surface disease related to limbal stem cell healing, negative calcium balance (osteoporosis, avascular necrosis
deficiency. Over the past 30 years, significant progress has femoral head), Cushing-like syndrome, hypertension, edema, peptic
provided ocular surface rehabilitation, improved vision, and hope ulcers, increased glucose.
292
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human corneal epithelium in tissue culture. Invest Ophthalmol
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receptor-induced differentiation of T cells and blocks their activation. 2. Zieske JD. Perpetuation of stem cells in the eye. Eye 1994;8:163-
Inhibits gene transcription of IL-2, IL-3, IFN. Does not block effect of 69.
3. Thoft RA. Conjunctival transplantation. Arch Ophthalmol
these factors on primed T cells, or these cells interaction with antigen.
1977;95:1425-27.

Chapter 40: Limbal Stem Cell Transplantation


Inhibits mast cells. Spares T suppressor cells and B cells.
4. Davanger M, Evensen A. Role of the pericorneal papillary
Indications – Organ transplant, graft-versus-host syndrome after bone structure in renewal of corneal epithelium. Nature 1971;229:560-
marrow transplant, autoimmune disease (SLE, IBD, Psoriasis). 61.
5. Schermer S, Galvin S, Sun T-T. Differentiation-related expression
Adverse effects – Nephrotoxicity ≤ 75 percent (100% @ 10 mg/kg/ of a major 64K corneal keratin in vivo and in culture suggests
day), hyperglycemia, hyperlipidemia, osteoporosis, hirsutism, HTN, limbal location of corneal epithelial stem cells. J Cell Biol
hyperuricemia in renal patients, paresthesia, N/V, hepatotoxic, infection 1986;103:49-62.
from T cell suppression. 6. Pellegrini G, Traverso CE, Franzi AT, et al. Long-term restoration
of damaged corneal surfaces with autologous cultivated corneal
epithelium. Lancet 1997;349:990-93.
Tacrolimus (FK-506) 7. Holland EJ, Schwartz GS. Epithelial stem-cell transplantation for
severe ocular surface disease [editorial]. N Engl J Med
Mechanism – Macrolide antibiotic. Binds to FK-506 binding protein
1999;340:1752-53.
and inhibits the activation of T lymphocytes by interfering with 8. Holland EJ, Schwartz GS. The evolution of epithelial
calcineurin and blocking the transcription of lymphokines. transplantation for severe ocular surface disease and a proposed
Indications – Organ transplant classification system. Cornea 1996;15:549-56.
9. Vajpayee RB, Thomas S, Sharma N, Dada T, Tabin GC. Large-
Adverse effects – Nephrotoxicity (40%), hypertension, hyperglycemia, diameter lamellar keratoplasty in severe ocular alkali burns.
neurotoxicity (headache, tremor, parasthesias), lymphoma. Ophthalmology 2000;107:1765-68.
10. Thoft RA. Indications for conjunctival transplantation.
Ophthalmology 1982;89:335-39.
Antimetabolites 11. Vastine DW, Stewart WB, Schwab IR. Reconstruction of the
periocular mucous membrane by autologous conjunctival
Azathioprine (Imuran) transplantation. Ophthalmology 1982;89:1072-81.
12. Herman WK, Doughman DJ, Lindstrom RL. Conjunctival
Mechanism – Cleaved to 6-mercaptopurine, which competietively
autograft transplantation for unilateral ocular surface diseases.
inhibits de novo purine biosynthesis (T-cell, B-cell proliferation).
Ophthalmology 1983;90:1121-26.
Indications – Organ transplant, autoimmune disease (RA). 13. Tan DTH, Ficker LA, Buckley RJ. Limbal transplantation.
Ophthalmology 1996;103:29-36.
Adverse effects – Suppresses bone marrow (leucopenia, 14. Prabhasawat P, Kosrirukvongs P, Booranapong W, Vajaradul Y.
thrombocytopenia, anemia), GI toxicity (nausea, diarrhea), alopecia, Amniotic membrane transplantation for ocular surface
cholestasis and hepatotoxicity. reconstruction. J Med Assoc Thai 2001;84:705-18.
15. Yao Y, Zhang B, Zhou P, Jiang JK. Autologous limbal grafting
combined with deel lamellar keratoplasty in unilateral eye with
Mycophenolate Mofetil (Cellcept)
severe chemical or thermal burn at late stage. Ophthalmology
Mechanism – A prodrug that is hydrolyzes to mycophenolic acid. 2002;109:2011-17.
Selectively inhibits inosine monophosphate dehydrogenase and, as a 16. Ozdemir O, Tekeli O, Ornek K, Arslanpence A, Yalcindag NF.
Limbal autograft and allograft transplantations in patients with
result, the production of guanosine and the proliferation of B and T
corneal burns. Eye 2004;18:241-48.
cells. 17. Santos MS, Gomes JAP, Hofling-Lima AL, Rizzo LV, Romano
Indications – Organ transplant, inflammatory eye diseases A, Belfort R. Survival analysis of conjunctival limbal grafts and
amniotic membrane transplantation in eyes with total limbal stem
Adverse effects – GI toxicity (abdominal pain, diarrhea, vomiting), cell deficiency. Am J Ophthalmol 2005;140:223-30.
Myelosuppression (leucopenia, anemia, thrombocytopenia) 18. Kenyon KR, Tseng SCG. Limbal autograft transplantation for
ocular surface disorders. Ophthalmology 1989;96:709-23.
19. Daya SM. Living-related conjunctivo-limbal allograft (lr-CLAL)
Sirolimus (Rapamycin)
for the treatment of stem cell deficiency: an analysis of long-term
Mechanism – Macrolide immunosuppressant that prolongs the cell outcome [abstract]. Ophthalmology 1999;106:243.
cycle by inhibiting mammalian target of rapamycin, which regulates 20. Kwitko S, Raminho D, Barcaro S, et al. Allograft conjunctival
transplantation for bilateral ocular surface disorders.
the phosphorylation of several cell cycle-dependent kinases. This
Ophthalmology 1995;102:1020-25.
inhibits B cells, T cells, fibroblasts, and smooth muscle cells. 21. Tsai RJF, Tseng SCG. Human allograft limbal transplantation for
Indications – Organ transplant corneal surface reconstruction. Cornea 1994;13:389-400.
22. Rao SK, Rajagopal R, Sitalakshmi G, et al. Limbal allografting
Adverse effects – Hyperlipidemia, thrombocytopenia, leucopenia, from related live donors for corneal surface reconstruction.
hepatitis, pneumonitis, hemolytic uremic syndrome. Ophthalmology 1999;106:822-28.
293
23. Kenyon KR, Rapoza PA. Limbal allograft transplantation 35. Sangwan VS, Matalia HP, Vemuganti GK, et al. Early results of
for ocular surface disorders. Ophthalmology 1995; 102 penetrating keratoplasty after cultivated limbal epithelium
(suppl):101-2. transplantation. Arch Ophthalmol 2004;123:334-40.
24. Solomon A, Ellies P, Anderson D, et al. Long-term outcome of 36. Sangwan VS, Matalia HP, Vemuganti GK, et al. Clinical outcome
keratolimbal allograft with or without penetrating keratoplasty of autologous cultivated limbal epithelium transplantation. Indian
for total limbal stem cell deficiency. Ophthalmology J Ophthalmol 2005;54:29-34.
2002;109L1159-66. 37. Rama P, Bonini S, Lambiase A, et al. Autologous fibrin-cultured
25. Holland EJ, Djalilian AR, Schwartz GS. Management of aniridic limbal stem cells permanently restore the corneal surface in
keratopathy with keratolimbal allograft: A limbal stem cell patients with total limbal stem cell deficiency. Transplantation
Section V: Specific Techniques in Keratoplasty

transplantation technique. Ophthalmology 2003;110:125-30. 2001;72:1478-85.


26. Ilari L, Daya SM. Long-term outcomes of keratolimbal allograft 38. Schwab IR, Reyes M, Isseroff RR. Successful transplantation of
for the treatment of severe ocular surface disorders. bioengineered tissue replacements in patients with ocular surface
Ophthalmology 2002;109:1278-84. disease. Cornea 2000;19:421-26.
27. Croasdale CR, Schwartz GS, Malling JV, et al. Keratolimbal 39. Inatomi T, Nakamura T, Koizumi N, Sotozono C, Yokoi N,
allograft: recommendations for tissue procurement and Kinoshita S. Midterm results on ocular surface reconstruction
preparation by eye banks and standard surgical technique. Cornea using cultivated autologous oral mucosal epithelial
1999;18:52-58. transplantation. Am J Ophthalmol 2006;141:267-75.
28. Tseng SC, Prabhasawat P, Barton K, et al. Amniotic membrane 40. Pellegrini G, Traverso CE, Franzi AT, Zingirian M, Cancedda R,
transplantation with or without limbal allografts for corneal De Luca M. Long-term restoration of damaged corneal surfaces
surface reconstruction in patients with limbal stem cell deficiency. with autologous cultivated corneal epithelium. Lancet
Arch Ophthalmol 1998;116:431-41. 1997;349:990-93.
29. Tsubota K, Toda I, Saito H, et al. Reconstruction of the corneal 41. Tsai RJ, Li LM, Chen JK. Reconstruction of damaged corneas
epithelium by limbal allograft transplantation for severe ocular by transplantation of autologous limbal epithelial cells. N Engl J
surface disorders. Ophthalmology 1995;102:1486-95. Med 2000;343:86-93.
30. Tsubota K, Satake Y, Kaido M, et al. Treatment of Severe Ocular- 42. Meller D, Pires RT, Tseng SC. Ex vivo preservation and expansion
Surface Disorders with Corneal Epithelial Stem-Cell of human limbal epithelial stem cells on amniotic membrane
Transplantation. N Engl J Med 1999;340:1697-703. cultures. Br J Ophthalmol 2002;86:463-71.
31. Holland EJ. Epithelial transplantation for the management of 43. Koizumi N, Cooper LJ, Fullwood NJ, Nakamura T, Inoki K,
severe ocular surface disease. Trans Am Ophthalmol Soc Tsuzuki M, et al. An evaluation of cultivated corneal limbal
1996;19:677-743. epithelial cells, using cell-suspension culture. Invest Ophthalmol
32. Reinhard T, Sundmacher R, Spelsberg H, Althaus C. Homologous Vis Sci 2002;43:2114-21.
penetrating central limbo-keratoplasty (HPCLK) in bilateral 44. Koizumi N, Inatomi T, Suzuki T, et al. Cultivated corneal
limbal stem cell insufficiency. Acta Ophthalmologica epithelial stem cell transplantation in ocular surface disorders.
Scandinavica 1999;77:663-67. Ophthalmology 2001;108:1569-74.
33. Reinhard T, Spelsberg H, Henke L, et al. Long-term results of 45. Koizumi N, Inatomi T, Suzuki T, et al. Cultivated corneal
allogenic penetrating limbo-keratoplasty in total limbal stem cell epithelial transplantation for ocular surface reconstruction in acute
deficiency. Ophthalmology 2004;111:775-82. phase of Stevens-Johnson syndrome. Arch Ophthalmol
34. Lindberg KL, Brown ME, Chaves HV, et al. In vitro propagation 2001;119:298-300.
of human ocular surface epithelial cells for transplantation. Invest
Ophthalmol Vis Sci 1993;34:2672-79.

294
41

Chapter 41: Ex Vivo Cultured Limbal Stem Cell Transplantation


Ex Vivo Cultured Limbal Stem Cell
Transplantation
Chandra Shekhar Kumar, Namrata Sharma, Virender Sangwan

INTRODUCTION acuity, ocular discomfort and unstable ocular surface. Limbal


stem cell deficiency can be either partial or total. Depending on
Stem cells (SC) of the corneal epithelium have been found to be
etiology LSCD can be classified as primary or secondary.
located exclusively at the limbus—that is, the anatomical
junction between the cornea and the conjunctiva.1 Limbal Primary Limbal Stem-cell Deficiency
epithelial SC are the ultimate source of regeneration of the entire
corneal epithelium under both normal and injured states 2. The This is related to an insufficient stromal microenvironment to
basal cells of the limbal epithelium were hypothesized to be the support stem cell function. Examples of such a type of limbal
stem cells for the corneal epithelium by Schermer et al 3 in 1986. stem cell deficiency include aniridia, congenital erythrokerato-
This hypothesis was based on the finding that a 64-kd keratin dermia, keratitis associated with multiple endocrine deficiencies,
present in differentiated cells was found in all corneal epithelial neurotrophic (neural and ischaemic) keratopathy and chronic
cells except the limbal basal cells. Stem cells are capable of limbitis.7
unlimited mitosis, which extends through the life of the organism,
and are capable of asymmetric cell division, which means that Secondary Limbal Stem-cell Deficiency
one daughter cell remains a stem cell while the second proceeds This type of LSCD is more common and occurs due to extrinsic
toward terminal differentiation. The daughter cells derived from factors which may that may lead to destruction of the limbal stem
stem cell division that are committed to the differentiation cells. Examples of such a limbal stem cell deficiency include
pathway have been called transient amplifying (TA) cells. TA chemical (most common) or thermal injuries, Stevens-Johnson
cells divide more frequently than stem cells but have limited syndrome, ocular cicatricial pemphigoid (OCP), multiple
proliferative potential. After an unknown signal, TA cells lose surgeries or cryotherapies, contact lens wear, or severe microbial
the ability to undergo mitosis and become terminally keratitis7. In cases of vernal keratoconjunctivitis, chronic limbal
differentiated.4–6 Limbal stem cells play central role in corneal inflammation may have precipitate LSCD due to insufficient
epithelial regeneration and repair following injury. Limbal stem stromal support. In patients with long-standing VKC, we
cell acts as a barrier corneal and conjunctival epithelium. hypothesize that chronic limbal inflammation might have affected
the microenvironment of the stem cells, resulting in poor stromal
LOCATION OF LIMBAL STEM CELLS support, or there could have been direct damage to the stem cells
by the toxic products of eosinophils and other inflammatory cells
At the corneo-scleral limbus there is a gradual transition from
in the vicinity. 8
the stratified, non keratinised squamous epithelium of the cornea
to the stratified, nonkeratinised columnar epithelium with mucin- TYPES OF LSCD
secreting goblet cells of the conjunctiva. It has 7-10 layers of
cells, which have attachments similar to the corneal cells. The LSCD may be classified as partial or total. In partial or sectoral
architecture of the limbus demonstrates a palisade (of Vogt) deficiency there is localized deficiency of LESCs in a region of
arrangement. The limbal epithelial stem cells ( LESC) probably limbus but an intact population of LESCs in other areas. This
reside in the basal layer of the palisades of Vogt. results in sectoral ingrowth of conjunctival epithelium in areas
When limbal stem cells of a normal cornea get damaged then of LSCD. In total or diffuse stem cell deficiency there is
it may result in poor corneal epithelisation, persistent epithelial dysfunction or destruction of the entire limbal stem cell
defects, corneal vascularisation, corneal scaring and population resulting in conjunctivalization of the entire cornea.
conjunctivalisation of cornea, this can result in decrease in visual In cases where the conjunctival stem cells which are present in
295
the fornices are involved, keratinisation of the ocular surface Slit Lamp Examination
occurs such as in end stage OCP or SJS.
Clinical examination of a case of LSCD is of utmost importance.
One should specifically look for epithelial haze, conjunctiva-
ROLE OF CULTURED LIMBAL STEM CELL
lization of the cornea, vascularization and chronic inflammation
Successful limbal transplantation can achieve rapid surface which may present as recurrent erosions and persistent epithelial
healing, stable ocular surface without persistent epithelial defects, defects. In severe cases there may also be keratinisation of the
regression of corneal vascularisation and restoration of smooth entire ocular surface. All patients should be carefully examined
Section V: Specific Techniques in Keratoplasty

ocular surface with improvement in best corrected visual acuity on slit lamp documenting the severity of LSCD. Proper
and increased survival of a subsequent lamellar or a penetrating assessment of limbal palisades of vogt in the affected as well as
graft. donor eye should be done. Apart from it any ocular inflammation
The advantage of ex vivo expansion of limbal tissue is that should be ruled out before surgery as it affects the prognosis.
a smaller amount of tissue is harvested, which addresses the issue
of limited availability of limbal tissue in a diseased donor eye Impression Cytology
and at the same time poses less potential risk to a healthy donor Impression cytology is important diagnostic test to confirm the
eye. Another proposed advantage of cultured limbal stem cell LSCD.11 In impression cytology, an imprint of the superficial
transplantation over kerato-limbal allograft and live related cell layer is obtained by pressing a cellulose acetate filter paper
conjunctivo-limbal allograft is a reduced risk of allograft on the ocular surface. After topical anesthesia with 0.5 percent
rejection due to the absence of antigen-presenting Langerhan’s proparacaine eyedrops, the filter paper is gently pressed on the
cells in ex vivo cultured LEC grafts. ocular surface for 3 to 5 seconds. To increase the number of
cells that are harvested, the ocular surface is slightly dried by
DIAGNOSIS OF LSCD
keeping the eye open before sampling. The cells are then fixed
by an alcohol based fixative spray, gently sprinkled on the
Clinical Features
membrane surface from an adequate distance, and stored back
Limbal stem cell deficiency is characterized by epithelial haze, in its original package and is transported to the laboratory. Each
conjunctivalization of the cornea, vascularisation and chronic specimen is labelled to indicate its source along the ocular
inflammation which may present as recurrent erosions and circumference.
persistent epithelial defects. In severe cases there may also be The sample is stained with hematoxylin-eosin or PAS stain
keratinisation of the entire ocular surface. to demonstrate presence of goblet cells. Demonstration of goblet
cells containing conjunctival epithelium on the corneal surface
Histopathological diagnosis by impression cytology is diagnostic of limbal stem cell
Diagnosis of LSCD is made by identification of conjunctival cells deficiency. Immuno-staining for cytokeratin (CK3 and CK19)
over the cornea. Impression cytology helps to confirm the may also be done to assess the severity of LSCD.10
diagnosis of LSCD. Impression cytology specimen stained with
periodic acid Schiff stain may show the presence of goblet cells. Ultrasonic Pachymetry
However, the absence of goblet cells in the impression cytology Evaluation of corneal thickness in patients planned for limbal
may not correlate with the absence of limbal stem cell deficiency. stem cell transplantation is an integral part of the workup. It gives
Monoclonal antibody stain to cytokeratin may also help to an idea of the depth up to which the superficial keratectomy can
differentiate the conjuntival and corneal epithelium. Only CK3 be done to remove the fibrovascular tissue for preparation of
and CK19 have been demonstrated to discriminate, in humans, the recipient bed. Sometimes, especially in patients of post
between corneal and conjunctival epithelium. CK3 stains all chemical injury, the scarred cornea is so thin, that it may perforate
layers of normal human corneal epithelium but does not stain while removing the pannus or doing a keratectomy. Additionally,
the conjunctival one, whereas CK19 stains the conjunctival but one can also plan to do a lamellar keratoplasty or deep anterior
not the corneal epithelium.9 LSCD has been classified based on lamellar keratoplasty depending on the corneal thickness,
presence of cytokeratin 19 and absence of cytokeratin 3 on concomitantly with limbal stem cell transplantation.
impression cytology.10 Recent data demonstrates that deltaN P63
alpha20,74 and ABCG2 are presently the leading candidates for Posterior Segment Evaluation
stem cell markers.
Posterior segment evaluation should be done in all patients prior
to surgery. Indirect opthalmoscopy should be done in patent
INVESTIGATIONS where media clarity permits or else ultrasonography A and B
A meticulous history taking and a thorough examination is scan should be done carefully to assess the posterior segment in
mandatory for all cases. A careful slit lamp examination and patient where the corneal opacity preclude the evaluation of
investigations are required before planning any intervention. posterior segment.

296
Ultrabiomicroscopy
Ultrabiomicroscopy may be done to assess the angle area in cases
of severe corneal opacity as this may be damaged subsequent to
secondary glaucoma due to the chemical injury.

Tear Film Status


Tear film status must be assessed before planning for limbal stem

Chapter 41: Ex Vivo Cultured Limbal Stem Cell Transplantation


cell transplantation. It is reported that preoperative tear function
was a strong determinant for successful ocular surface
reconstruction in patients of Steven Johnson syndrome.12 It is
likely that these environmental factors affect the prognosis.

Adnexal Structures
Careful examination of adnexal structures and its correction prior
to the limbal stem cell transplantation is very important otherwise
it can adversely affect the prognosis of limbal stem cell surgery.
Conditions like entropion, cicatricial ectropion, lagopthalmos etc
should be carefully identified and corrected. Concurrent adnexal
abnormalities are associated with worse graft outcomes after stem
cell transplantation and can compromise epithelial healing if
uncorrected. Surgery for eyelid malposition and closure is
Figure 41.1
essential before and after transplantation for surface epithelial
integrity and often requires multiple procedures.13

TISSUE SCREENING

Ex vivo LEC culture carries a risk of transfer of bacteria, viruses,


and prions, both to the patient but also to the laboratory staff
processing the tissue. For these reasons consideration must be
given to the screening of tissue donors and the risk of cross
contamination of cultures. All tissue donors, whether autologous
or allogeneic, and human amniotic membrane should be screened
for human immunodeficiency virus 1 and 2, human T-cell
leukemia-lymphoma virus, hepatitis B and C, and syphilis before
use.

LIMBAL STEM CELL HARVESTING


Figure 41.2A: Biopsy taken from contralateral limbus
Depending on the severity and the laterality of affection, limbal
stem cell can be harvested either from same eye (Fig. 41.1), the
other eye (Figs 41.2A to F), and eye of live related donor or
cadaveric eye for ex-vivo expansion of limbal stem cells. In
patients with partial LSCD, limbal stem cell harvesting can be
done from the same eye,14,15 whereas in patient with unilateral
severe LSCD, harvesting can be done from other eye (if the
patient consents). In cases with bilateral severe LSCD, allogenic
limbal stem cells grown from either live related donor or cadaver
are used.

LIMBAL BIOPSY

Autologous Limbal Epithelial Cells


Harvesting of the autologous limbal epithelial cells is done under Figure 41.2B: Limbal explants shredded into small pieces and
local or general anesthesia depending on the age of the patient. implanted on deephithelized amniotic membrane
297
Cells for autologous cultures are obtained from a superficial
lamellar biopsy of the limbus which measures 2 to 3 mm in
tangential diameter and extends 1 mm posterior to the limbus
and 1 mm centrally into the clear cornea. Autologous biopsies
are obtained from regions of the cornea where limbal crypts were
visible either on slit-lamp biomicroscopy or by confocal
microscopy. The limbal biopsies should not include tennon’s
Section V: Specific Techniques in Keratoplasty

capsule and must include the palisades of Vogt. Autologous


limbal biopsies are transported to the tissue bank in phosphate
buffered saline and processed immediately.
Postoperatively, topical antibiotics are given four times a day
Figure 41.2C: Confluent growth obtained for 2 weeks and topical steroids are given in tapering doses for
4 to 6 weeks or until complete healing of the donor site occurs.15

Cadaveric Allogeneic Limbal Epithelial Cells


Allogeneic limbal epithelial cells are obtained from cadaveric
human corneas preserved under cold storage conditions in Eye
Bank. Age and the death enucleation time are important factors
in selecting the cadaveric eye for culture. Preferably, the donor
age should be less than 40 years and the death enucleation time
should be less than 6 hours.

Live Related Allogeneic Limbal Epithelial Cells


Harvesting from a live related donor is done in a similar way as
autologus stem cell harvesting.
Figure 41.2D: Grafted onto eye with
limbal stem cell deficiency
LIMBAL STEM CELL CULTURE TECHNIQUE

After obtaining the tissue is washed with phosphate-buffered


saline and incubated in Dispase II at 37°C for 30 minutes, and
the epithelial surface is gently scraped to separate the epithelium
from the underlying stroma. The separated epithelium is then
incubated and pipetted in trypsin-ethylenediaminetetraacetic acid
to obtain a single cell suspension. The trypsin is then neutralized
with corneal epithelium culture medium.

Culture Media
The composition of the culture medium is very important in cell
culture and especially so in the culture of epithelial cells. A
modified human corneal epithelial cell (HCE) culture medium,
Figure 41.2E: Post-LSCT stable corneal surface prepared using 9.7 g/l Modifi ed Eagle Medium (MEM) with
addition of 16.2 g/l Ham F12 serum, 0.01 mg/l epidermal growth
factor, 0.25 mg/l insulin, 0.1 mg/l cholera toxin, and
hydrocortisone. The medium is fi ltered with 0.22 mm membrane
filters using a vacuum pump. This is supplemented with
autologous serum or 10 percent fetal calf serum (FCS) at the
time of use.7
Animal products like fetal calf serum, 3T3 fibroblasts ware
commonly used in culture media. This raises the important safety
issue of possible transmission of animal viruses or prions. In
order to reduce this risk several authors have successfully
replaced the fetal calf serum in the culture medium with
autologous serum from the recipient. Nakamura et al evaluated
the use of autologous serum against fetal calf serum in vitro and
298 Figure 41.2F: Penetrating keratoplasty after 3-6 months in a non-comparative clinical study and concluded that they were
equivalent.16 Schwab et al reported switching to a serum free Confirmation of Growth
culture media once the cells had been isolated and cultures
This can be done various methods which includes direct
initiated.17
observation, whole mount stained preparation, histopathology,
There are two main methods of producing ex vivo cultured
immunohistochemistry, thymidine incorporation, and by flow
LECs for transplantation, the explants culture system and the
cytometry using markers for cell cycle.7,26
suspension culture system.18
TRANSPLANTATION PROCEDURE

Chapter 41: Ex Vivo Cultured Limbal Stem Cell Transplantation


Explant Culture System
The transplantation is done 10-14 days after limbal biopsy. A
This method employs amniotic membrane, which acts both as a
360-degree conjunctival peritomy is performed, and the
substrate and a carrier for the cultured cells. The amniotic
conjunctiva and Tenon’s layer are recessed. The abnormal
epithelial cells are killed by the process of cryopreservation, and
epithelium and any associated subepithelial fibrovascular tissue
are then removed by enzymatic digestion, chemical treatment,
are stripped from the corneal surface to prepare a stromal bed.
or physical scraping of the membrane prior to use.19-22 The limbal
Hemostasis is achieved using cautery with or without topical 10
tissue which is procured by biopsy is fragmented into 4 to 6
percent phenylephrine. The fibrovascular pannus is dissected off
pieces and are placed on the basement membrane surface of the
the corneal surface starting 2 to 3 mm away from the limbus.
amniotic membrane and allowed to adhere to it. Once attached,
Symblepharon is released and fornix is formed when required.
the biopsy and amniotic membrane are submerged in culture
In an attempt to prevent conjunctival ingrowth in the
medium. This contains nutrients and mitogens that stimulate
postoperative period some surgeons apply mitomycin C (0.04%
LECs to proliferate and migrate out of the biopsy and cover the
for 5 minutes) to the subconjunctival space followed by vigorous
surface of the amniotic membrane, which occurs over 14 to 28
irrigation.20,21,26,27
days. The medium is changed on alternate days for 10-14 days
and the cell growth is evaluated daily under phase contrast Amniotic membrane graft with cultivated stem cells is placed
microscope. over the bed with epithelial side facing externally. The graft is
This is the preferred technique for limbal stem cell secured 2 mm posterior to the limbus using a continuous 10/0
transplantation as it is easy to prepare and corneal epithelium Vicryl suture, and the conjunctiva is closed over the periphery
remains intact as enzymatic degradation is not done. of the graft using 7/0 Vicryl sutures. Subconjunctival gentamicin
The 3T3 explant co-culture system is a modification of this and dexamethasone is given. This is followed by the application
technique which uses an additional feeder layer of growth- of a bandage contact lens.
arrested 3T3 fibroblasts in the bottom of the cell culture well. Alternatively, with the advent of the firin glue, the amniotic
The 3T3 fibroblasts are primitive cells obtained from murine membrane with cultivated stem cells may be may be apposed to
source. They have a high proliferative capacity andgrowth arrest, the recipient cornea with the help of the glue (Figs 41.3 A to J).
either by irradiation or by treatment with mitomycin C stimulates
the production of the growth factors which promotes epithelial Contact Lens-Based Technique can be used wherein, limbal
growth. Hence the differentiation of corneal epithelial cells is stem cell are directly grown over extended wear contact lens.28
inhibited, which allows the expansion of the limbal epithelial The contact lens with layer of stem cells are put into eye after
stem cells. superficial fibrovascular tissue is removed. In this technique if
the contact lens is lost then another contact lens can be put. The
Suspension Culture System lens is kept in situ for about 22 days or till the corneal epithelial
cell regenerated. No suturing is required in this technique.
This method employs the enzymes dispase, which digests
Although encouraging results were recorded, high failure rates
basement membrane collagen and separates epithelial cells from
were observed with this method.
the stroma, and trypsin, which separates clumps of limbal
epithelial cells into a suspension of single cells. This suspension
ADJUNCTIVE PROCEDURES
is then seeded either onto amniotic membrane or onto a plastic
tissue culture dish that contains a feeder layer of growth arrested Depending on the thickness of the scarred cornea, either a
3T3 fibroblasts. Culture medium is added and the cells are lamellar keratoplasty (anterior or mid stromal involvement) or
incubated for 14 to 21 days. a deep anterior lamellar keratoplasty (involvement up to posterior
When confluent the epithelial sheet is transferred to the stroma) may be done along with cultivated stem cell
ocular surface using either contact lenses,23,24 paraffin gauze,23 transplantation.
collagen shields,24 or fibrin gel.25 Fibrin has been demonstrated
as a carrier to support the maintenance of stem cells.19 When POSTOPERATIVE TREATMENT
the suspension of single limbal epithelial cells is seeded onto
amniotic membrane, they are co-cultured with a layer of growth- The aim of the postoperative therapy is to control inflammation,
arrested 3T3 fibroblasts in the bottom of the dish and the amnion give prophylaxis against infection, protect the graft, and prevent
serves as a carrier. allograft rejection. Topical treatment is started after 24 hours
299
Section V: Specific Techniques in Keratoplasty

Figure 41.3E: Cell culture medium containing


Figure 41.3A: Healthy fellow eye
autologous serum

Figure 41.3B: Taking limbal biopsy Figure 41.3F: Total LSCD with fibrovascular pannus

Figure 41.3C: Patient’s blood for autologous serum extraction


and limbal biopsy samples in transport medium
Figure 41.3G: Excision of fibrovascular pannis

Figure 41.3D: Cell culture medium containing


300 autologous serum Figure 41.3H: Application of fibrin glue
medical and surgical treatments. Ten patients of them received
autologous grafts, and four received allogeneic grafts. Six of the
10 patients with autologous procedures and in all four allogeneic
transplants were reported to have successful outcome (defined
as restoration or improvement of vision, along with maintenance
of corneal re-epithelialization and absence or recurrence of
surface disease). There are several reports summary of some of

Chapter 41: Ex Vivo Cultured Limbal Stem Cell Transplantation


the recent ones are given in the Table 41.1, shows the success
to vary from 46 to 100 percent.14,15,17,21,23,25,32,33,35-38
In general patients treated for chemical or thermal corneal
burns had a higher success rate than for ocular pemphigoid and
Stevens-Johnson syndrome, because the ongoing limbal or
Figure 41.3I: Cultured limbal epithelial cells on amniotic conjunctival disease in these conditions creates a hostile
membrane brought to operative field environment for the transplanted cells.

COMPLICATIONS

The complications which can occur during limbal stem cell


transplantataion include intraoperative or postoperative.

Intraoperative Complications
These include damage of muscle during symblepharon release,
bleeding during superficial keratectomy and sometimes corneal
perforation, especially if the underlying cornea is thin and
scarred.

Figure 41.3J: Whole composite grafted on diseased cornea Postoperative Complications


Postoperatively there can be various complications which include
the following:
with preservative free steroid and antibiotic drops
(chloramphenicol 0.5%) 4 times per day for 8 weeks. Patients Microbial Keratitis
receiving allografts are started on a daily dose of oral
cyclosporine 3.5 mg/kg or oral steroids prednisolone 1 mg/kg. Microbial keratitis following cultivated stem cell culture has been
The oral prednisolone is tapered to stop over 4 weeks. The oral reported after allografts and not after autografts, especially
cyclosporine is continued for 6 months. patients who are immunosuppresed. 17,20,24 The standard
management protocol is followed which includes scrapping and
OUTCOME microbiological examination. Intensive topical antibiotics are
started along with cycloplegics to control the infection
The clinical use of ex vivo cultured limbal stem cells to treat
corneal limbal stem cells deficiency was first described by Rejection of the Limbal Graft
Pellegrini et al in 1997.23 Their long-term follow-up (more than
2 years of follow ups) showed the stability of regenerated corneal Acute rejection is associated with intense sector injection at the
epithelium and the striking improvement in patients’ comfort and limbus, edema, infiltration, punctuate epithelial keratopathy and
visual acuity. epithelial defects. In cases of low grade rejection there may be
Following ex-vivo cultured limbal stem cell transplantation, mild or diffuse perilimbal injection, elevated perilimbal area,
it takes about 6 weeks weeks for the ocular surface to punctatae epithelial keratopathy and irregularity of the
stabilize.14,15 epithelium.29
The parameters which describe a successful outcome include Classically, epithelial rejection is defined as an epithelial
re-establishment of a stable, transparent corneal epithelium, rejection line or diffuse punctate corneal epitheliopathy in
resolution of corneal conjunctivalization, resolution of persistent association with diffuse conjunctival inflammation.
epithelial defect, and regression of corneal vascularization.14
Other Complications
Many reports demonstrating the successful results of cultured
stem cell transplantation has been published. Schwab et al17 Late complications include recurrence of neovascularisation and
perfomed cultured limbal stem cell transplantation in fourteen symblepharon formation has been reported after the surgery.
patients with ocular surface disease unresponsive to standard Desquamation of cultured stem cells from the surface has also
301
Table 41.1: Summary of clinical studies of ex vivo cultivated limbal stem cell transplantation
Author/ year Type of LSCD Intervention No of Mean follow Overall success Improved BCVA Comments
eyes up (Months) rate from baseline
No./total (%)

Pelligrini et al/1997 23 Total-2 Autologus LSCT 2 24 Stable ocular surface Improvement


in BCVA
Schwab et al/200017 Total-7 Autologus LSCT-10 14 13 Stable ocular All patients
Partial-7 Allograft LSCT-4 surface in 6/10 of improved in
Section V: Specific Techniques in Keratoplasty

autografts and all BCVA. >20/200


4 of allografts in 12/14 patients
and > 20/30 in
7/14 patients
Tsai et al/200038 Total Autografts 6 15 All eyes had stable 83% BCVA
ocular surface improved from
20/112 to 20/45
Rama et al/200125 Unilateral severe Autologous LSCT 18 18.6 7/18 ( 38.9 %)
Koizumi et al/200121 Total Allografts-3 3 6 All eyes had stable BCVA improved Subconjunctival
ocular surface by 2 lines or tissue treatment
more in 10/13 with 0.04%
eyes. mitomycin C
Shimazaki et al/200232 Total-13 Allograft LSCT-13 13 NA 46.2% 3/8 eyes Corneal
developed partial perforation-4
conjunctival invasion eyes Infectious
2 eyes later keratitis-2 eyes
developed
epithelial defects
Sangwan et al/200515 Total- 14, Autologous LSCT-11 15 15.3 10/15 (67%) In 15 cases PKP
partial-1 Living related was done later
allograft LSCT- 3
nonrelated allograft
LSCT- 1
Sangwan et al/200514 Bilateral-4 Autologus LSCT 86 18.3
Unilateral-84
Daya et al/200537 Total-10 Allografts-10 10 28 Improvement in BCVA improve-
ocular surface -70% ment -40%
Nakamura et al/200633 Total-9 Allograft LSCT-7 9 14.6 Stable ocular surface Improvement
Autologus LSCT-2 at last follow-up in more than
2 lines of
preoperative
BCVA
Kawashima et al/200734 Total-6 Autologus-2 6 25 Stable ocular Improvement in All eyes
Allografts non surface at last BCVA in 4 out subsequently
related -3 follow-up if 6 eyes underwent
Allograft related -1 keratoplasty
for visual
rehabilitation
Shortt et al/200836 Autologus-3 10 13 60% (autografts Improvement
Allografts-7 33%, allografts in more than
71%) 2 lines of
preoperative
BCVA

been reported. Glaucoma in such patient is a complication which Fogla et al30 has done cultivated stem cell transplantation
at times is difficult to manage and sometimes trabeculectomy or with deep anterior lamellar keratoplasty for late cases of chemical
shunt surgery may be required for control of intraocular pressure. injury and reported gratifying results.
Sangwan et al report results of penetrating keratoplasty
Keratoplasty Following Ex-vivo Cultured performed after cultivated limbal epithelium transplantation
Limbal Stem Cell Transplantation following stabilization of the ocular surface in these cases.15 A
In cases of limbal LSCD, penetrating keratoplasty alone does 2-staged approach is preferred, wherein, in the first stage, ocular
not work. This is because of the presence of the transient surface reconstruction is done by cultivated limbal epithelium
amplifying cells which are transferred onto central corneal transplantation followed by the second stage of visual
surface during penetrating keratoplasty (PKP) which have limited rehabilitation by performing PKP. PKP is generally performed
life span and limited proliferative potential. Deep anterior 3 months after limbal stem cell transplantation.14,15
lamellar keratoplasty or penetrating keratoplasty may be done In a series of 15 cases reported by Sangwan et al, penetrating
following ex-vivo cultured limbal stem cell transplantation. keratoplasty was performed after cultivated limbal epithelium
302
transplantation after a mean follow-up of 7 months. The recipient 13. DeSousa JL, Daya S, Malhotra R. Adnexal surgery in patients
cornea was excised using a disposable handheld trephine, with undergoing ocular surface stem cell transplantation.
0.5 mm of graft host disparity. The graft was secured by 10-0 Ophthalmology 2009;116:235-42.
14. Sangwan VS, Matalia HP, Vemuganti GK, Fatima A, Ifthekar G,
nylon interrupted sutures. However, PKP in these conditions
Singh S, Nutheti R, Rao GN. Clinical outcome of autologous
warrants special mention of the difficulties encountered during cultivated limbal epithelium transplantation. Indian J Ophthalmol
the surgery. Because most of the cases follow chemical burns, 2006;54:29-34.
resulting in some collagenolysis, and had involve pannus 15. Sangwan VS, Matalia HP, Vemuganti GK, Ifthekar G, Fatima A,

Chapter 41: Ex Vivo Cultured Limbal Stem Cell Transplantation


resection with or without superficial keratectomy, a significant Singh S, Rao GN. Early results of penetrating keratoplasty after
disparity may be present in graft-host thickness, leading to cultivated limbal epithelium transplantation. Arch Ophthalmol
difficulty in graft host apposition. Many of the patients have a 2005;123:334-40.
16. Nakamura T, Inatomi T, Sotozono C, et al. Transplantation of
disorganized anterior segment with a complicated cataract and
autologous serum-derived cultivated corneal epithelial equivalents
require lensectomy and vitrectomy.15 Postoperatively, the ocular for the treatment of severe ocular surface disease. Ophthalmology
surface was stable and and 87 percent patients had an ambulatory 2006;113:1765-72.
BCVA of > 20/200 and 53 percent had BCVA of > 20/60.15 17. Schwab IR, Reyes M, Isseroff RR. Successful transplantation of
The specimens of excised buttons during keratoplasty are bioengineered tissue replacements in patients with ocular surface
also useful. Pauklin et al during penetrating keratoplasy disease. Cornea 2000;19:421-6.
demonstrated that in excised specimens of cases where cultivated 18. Vemuganti GK, Fatima A, Madhira SL, Basti S, Sangwan VS.
Limbal stem cells: application in ocular biomedicine. Int Rev Cell
stem cells had been transplanted, the lineage markers showed a
Mol Biol 2009;275:133-81.
corneal phenotype with decrease in the inflammatory markers.31 19. Grueterich M, Espana EM, Touhami A, et al. Phenotypic study
This confirms the potential of this method to reconstruct the of a case with successful transplantation of ex vivo expanded
corneal surface. human limbal epithelium for unilateral total limbal stem cell
deficiency. Ophthalmology 2002;109:1547-52.
REFERENCES 20. Koizumi N, Inatomi T, Suzuki T, et al. Cultivated corneal
epithelial stem cell transplantation in ocular surface disorders.
1. Schermer A, Galvin S, Sun TT. Differentiation-related expression Ophthalmology 2001;108:1569-74.
of a major 64K corneal keratin in vivo and in culture suggests 21. Koizumi N, Inatomi T, Suzuki T, et al. Cultivated corneal
limbal location of corneal epithelial stem cells. J Cell Biol epithelial transplantation for ocular surface reconstruction in acute
1986;103:49-62. phase of Stevens-Johnson syndrome. Arch Ophthalmol
2. Tseng SCG. Regulation and clinical implications of corneal 2001;119:298-300.
epithelial stem cells. Mol Biol Rep 1996;23:47-58. 22. Nakamura T, Inatomi T, Sotozono C, et al. Successful primary
3. Schermer A, Galvin S, Sun TT. Differentiation-related expression culture and autologous transplantation of corneal limbal epithelial
of a major 64 K corneal keratin in vivo and in culture suggests cells from minimal biopsy for unilateral severe ocular surface
limbal localization of corneal epithelial stem cells. J Cell Biol disease. Acta Ophthalmol Scand 2004;82:468-71.
1986;103:49-62. 23. Pellegrini G, Traverso CE, Franzi AT, et al. Long-term restoration
4. Zieske JD. Perpetuation of stem cells in the eye. Eye 1994;8: of damaged corneal surfaces with autologous cultivated corneal
163-69. epithelium. Lancet 1997;349:990-3.
5. Chung EH, DeGregorio PG, Wasson M, et al. Epithelial 24. Schwab IR. Cultured corneal epithelia for ocular surface disease.
regeneration after limbus-to-limbus debridement: expression of Trans Am Ophthalmol Soc 1999;97:891-986.
enolase in stem and transient amplifying cells. Invest Ophthalmol 25. Rama P, Bonini S, Lambiase A, et al. Autologous fibrincultured
Vis Sci 1995;36:1336-43. limbal stem cells permanently restore the corneal surface of
6. Pellegrini G, Dellambra E, Golisano O, et al. P63 identifies patients with total limbal stem cell deficiency. Transplantation
keratonocyte stem cells. Proc Natl Acad Sci USA 2001;98: 2001;72:1478-85.
3156-61. 26. Nakamura T, Inatomi T, Sotozono C, et al. Transplantation of
7. Burman S, Sangwan V. Cultivated limbal stem cell transplantation cultivated autologous oral mucosal epithelial cells in patients
for ocular surface reconstruction. Clin Ophthalmol 2008;2: with severe ocular surface disorders. Br J Ophthalmol 2004;
489-502. 88:1280-4.
8. Sangwan VS, Murthy SI, Vemuganti GK, Bansal AK, 27. Nakamura T, Inatomi T, Sotozono C, et al. Successful primary
Gangopadhyay N, Rao GN. Cultivated corneal epithelial culture and autologous transplantation of corneal limbal epithelial
transplantation for severe ocular surface disease in vernal cells from minimal biopsy for unilateral severe ocular surface
keratoconjunctivitis. Cornea 2005;24:426-30. disease. Acta Ophthalmol Scand 2004;82:468-71.
9. Elder MJ, Hiscott P, Dart JKG. Intermediate filament expression 28. Di Girolamo N, Chui J, Wakefield D, Coroneo MT. Cultured
by normal and diseased human corneal epithelium. Hum Pathol human ocular surface epithelium on therapeutic contact lenses.
1997;28:1348–54. Br J Ophthalmol 2007;91:459-64.
10. Donisi PM, Rama P, Fasolo A, Ponzin D. Analysis of limbal stem 29. Daya SM, Bell RW, Habib NE, Powell-Richards A, Dua HS.
cell deficiency by corneal impression cytology. Cornea 2003; Clinical and pathologic findings in human keratolimbal allograft
22:533-8. rejection. Cornea 2000;19:443-50.
11. Sangwan VS. Biosci Rep 2001;21:385-405. 30. Talbot M, Carrier P, Giasson CJ, Deschambeault A, Guérin SL,
12. Shimazaki J, Shimmura S, Fujishima H, Tsubota K. Association Auger FA, Bazin R, Germain L. Clinical and pathologic findings
of preoperative tear function with surgical outcome in severe in human keratolimbal allograft rejection. Cornea 2000;19:443-
Stevens-Johnson syndrome. Ophthalmology 2000;107:1518-23. 50. Mol Vis. 2006;12:65-75. 303
31. Pauklin M, Steuhl KP, Meller D. Characterization of the corneal 35. Lekhanont K, Choubtum L, Chuck RS, Sa-ngiampornpanit T,
surface in limbal stem cell deficiency and after transplantation Chuckpaiwong V, Vongthongsri A. A serum- and feeder-free
of cultivated limbal epithelium. Ophthalmology 2009;116: technique of culturing human corneal epithelial stem cells on
1048-56. amniotic membrane. Mol Vis. 2009;15:1294-302.
32. Shimazaki J, Aiba M, Goto E, Kato N, Shimmura S, Tsubota K. 36. Shortt AJ, Secker GA, Rajan MS, Meligonis G, Dart JK, Tuft SJ,
Transplantation of human limbal epithelium cultivated on Daniels JT. Ex vivo expansion and transplantation of limbal
amniotic membrane for the treatment of severe ocular surface epithelial stem cells. Ophthalmology 2008;115:1989-97.
disorders. Ophthalmology 2002;109:1285-90. 37. Daya SM, Watson A, Sharpe JR, Giledi O, Rowe A, Martin R,
Section V: Specific Techniques in Keratoplasty

33. Nakamura T, Inatomi T, Sotozono C, Ang LP, Koizumi N, Yokoi James SE. Outcomes and DNA analysis of ex vivo expanded stem
N, Kinoshita S. Transplantation of autologous serum-derived cell allograft for ocular surface reconstruction. Ophthalmology
cultivated corneal epithelial equivalents for the treatment of severe 2005;112:470-7.
ocular surface disease. Ophthalmology 2006;113:1765-72. 38. Tsai RJ, Li LM, Chen JK. Reconstruction of damaged corneas
34. Kawashima M, Kawakita T, Satake Y, Higa K, Shimazaki J. by transplantation of autologous limbal epithelial cells. N Engl J
Phenotypic study after cultivated limbal epithelial transplantation Med 2000;343:86-93.
for limbal stem cell deficiency. Arch Ophthalmol 2007;125:
1337-44.

304
42

Chapter 42: Amniotic Membrane Transplantation


Amniotic Membrane Transplantation
Ahmad Kheirkhah, Hossam Sheha, Victoria Casas, VK Raju, Scheffer CG Tseng

INTRODUCTION amniotic membrane during embryogenesis that has spawned


increasing interests over the past decade in ophthalmology.
Two modes of clinical uses:
Historically, AM had been used mostly as a “dressing” in
1. As a permanent graft
surgery of different parts of body, including the eye, starting from
• Persistent epithelial defects with different depths
the early 20th century. In 1940, de Rötth1 was the first to describe
• Sterile corneal stromal thinning, descemetocele and
the use of live placental membranes including both amnion and
perforation
chorion to repair conjunctival defects. His low success rate (1:6
• Infectious keratitis and scleritis
cases) was probably related to allograft rejection due to the
• Symptomatic bullous keratopathy
inclusion of the live, highly immunogenic chorionic membrane.
• Band keratopathy
Sorsby et al2,3 in 1946 and 1947 used chemically processed “dry”
• Partial limbal stem cell deficiency.
AM, termed “amnioplastin”, as a temporary patch for the
2. As an overlaid graft
treatment of acute ocular burns. Although a remarkable success
• Persistent or recurrent epithelial defect (Erosion)
was reported, for reasons still unclear, repetitive applications
• Acute chemical/thermal burns
were required in each treatment session, presumably due to its
• Acute Stevens-Johns syndrome with or without toxic
brittle and tenuous nature. Thereafter, the use of AM disappeared
epidermal necrolysis
from medical literature for several decades until Kim and Tseng4
• Chronic recalcitrant keratitis caused by neurotrophy,
reintroduced the use of cryopreserved AM for ophthalmic uses
HZO, HSV, or vernal keratoconjunctivitis
in 1995. Since then transplantation of cryopreserved AM has
• High-risk corneal grafts (to reduce complications)
been a widely accepted surgical procedure to promote epithelial
• Excimer laser ablation (PRK/PTK) (to prevent haze)
healing and to reduce inflammation, scarring and emerging
• Plastic indications as conformer (to prevent lid/lash
neovascularization on the ocular surface (for reviews see Tseng
mechanical insult to the cornea).
et al5 and Dua et al6). The experimental evidence explaining the
action mechanisms of cryopreserved AM in exerting anti-
Surgical Procedures inflammatory and anti-scarring actions is recently summarized.5
Although AM has been used in various ocular surface surgeries,
As a Permanent Graft this chapter will summarize only its applications for corneal
1. For corneal ulcers indications.
2. Following superficial keratectomy
3. For bullous and band keratopathy TWO MODES OF CLINICAL USES
4. For Partial limbal stem cell deficiency
The corneal indications for AMT can be categorized according
to the mode whether cryopreserved AM is used as a permanent
As an Overlaid Graft
graft or an overlaid graft.
1. To cover the entire ocular surface When used as a permanent graft, it is aimed to fill in the
2. To cover only the corneal surface corneal stromal defect and to restore the corneal stromal integrity.
3. ProKera™ Because of the preservation of the aforementioned remarkable
Human amniotic membrane (AM) is the innermost layer of biological actions, upon integration into the host tissue, the
the placental membrane. While the tough, semi-transparent nature resultant corneal stroma often regains clarity. Therefore, AMT
of amniotic membrane is valuable as a graft for ocular surface preserves better aesthetic appearance when compared to
reconstruction, it is the unique inherent biological action of tarsorrhaphy or conjunctival flap. Because the cryopreserved
305
amnion graft does not include live allogeneic cells, the patient Table 42.1: Corneal indications for permanent AM graft
does not require taking any topical or systemic immuno-
• Persistent corneal epithelial defects and ulcers
suppressive or anti-inflammatory medications after healing, and
• Descemetocele or perforation
will not face the risk of allograft rejection that may potentially
• Painful bullous keratopathy
occur in lamellar corneal transplantation. Therefore, it can
• Band keratopathy
overcome corneal tissue shortage. Even if additional surgeries
• Following superficial keratectomy to remove scar (before
are needed to improve vision, excimer laser ablation such as PTK
PTK is contemplated)
Section V: Specific Techniques in Keratoplasty

can be used to as the scarring is minimized. If corneal


• Partial limbal stem cell deficiency
transplantation is required, its success is promoted because the
recipient eye is less inflamed after AMT. The surgical time is
significantly reduced when sutures are not used, thus allowing
the surgery to be performed under topical anesthesia and Table 42.2: Corneal indications for temporary AM graft
facilitating the ease of postoperative care and patient’s recovery. • Persistent or recurrent epithelial defect (Erosion)
Corneal indications for AMT as a permanent graft are listed in • Acute chemical/thermal burns
Table 42.1. • Acute Stevens-Johnson syndrome with or without toxic
When AM is used as an overlaid graft (biological patch), it epidermal necrolysis
is aimed to reduce either acute or chronic ocular surface • Chronic recalcitrant keratitis caused by neurotrophy, HZO,
inflammation caused by various diseases and insults so as to HSV, or vernal keratoconjunctivitis
promote epithelial healing with minimal or no scarring. Corneal • High-risk corneal grafts (to reduce complications)
indications for AMT as an overlaid graft are mentioned in Table • Excimer laser ablation (PRK/PTK) (to prevent haze)
42.2. Many of these indications can now be managed by recently • Plastic indications as conformer (to prevent lid/lash
introduced ProKera™ (see below), a sutureless conformer ring mechanical insult to the cornea)
fastened with cryopreserved amnion graft (Figs 42.1A to C). • Implantation of keratoprosthesis

Figures 42.1A to C: Sutureless Amniotic Membrane Transplantation with ProKera™. ProKera™ is a dual ring system that
fastens a sheet of semi-transparent cryopreserved AM (A). The schematic drawing (B) and a slit-lamp photograph (C) depict its
appearance when inserted in the eye. During the insertion, the status of epithelialization can be monitored by fluorescein staining
without having ProKera™ removed
306
Because ProKera™ can deliver the aforementioned biological preservation of a better aesthetic appearance. Even if corneal
actions in the office, at the bedside or in the operating room, it transplantation is needed, its success is promoted if performed
further enhances the ease of patient care in many difficult corneal in an eye that received AMT to reduce inflammation. When
diseases. After epithelial healing is completed, the membrane is corneal ulcer is superficial (e.g., limited to the epithelium), AMT
dissolved and ProKera™ ring can be removed. using an overlaid graft is generally sufficient (Figs 42.2A to C).
However, when epithelial defects are accompanied by stromal
AS A PERMANENT GRAFT ulceration, a temporary overlaid AM graft is used together with

Chapter 42: Amniotic Membrane Transplantation


a permanent graft to provide as additional protection while
1. Persistent Epithelial Defects with Different Depths ensuring epithelialization (Figs 42.2D to F).8,9
A number of studies have shown that AMT has an average
Corneal ulcers are serious and urgent clinical problems that can success rate of 79 percent (ranging from 67 to 91%) and rapid
be complicated by microbial infections and threaten patient’s healing is usually completed in 1 to 4 weeks.8,10-18 Variable
vision. Corneal ulcers can be caused by various insults, e.g. success rates may be attributed to different underlying etiologies
exogenously from chemical burns, infection, radiation, or and concomitant or subsequent treatments in managing
surgeries, while endogenously from aging, diabetes mellitus, viral neurotrophic keratopathy. For example, AM rapidly dissolves
(herpes) infection, and autoimmune disorders, with the common (within one week) if there is severe exposure and dryness caused
denominator being neurotrophic keratopathy (for a review see by neurotrophic keratopathy. The corneal surface breakdown is
Solomon et al7). When all medical treatments fail and the likely to recur if severe neurotrophic keratopathy is left untreated.
ulceration persists, conventional surgical treatments include Therefore, it is advised to perform punctal occlusion before
lamellar or full-thickness corneal transplantation (patch graft), AMT, consider CL wear19 or temporary tarsorrhaphy at the time
tarsorrhaphy or conjunctival flap. Amniotic membrane of AMT, and add extended high DK contact lens or permanent
transplantation in these cases offers the following advantages: tarsorrhaphy after healing by AMT. It should be noted that AMT
avoidance of potential allograft rejection and postoperative alone is not sufficient to heal corneal epithelial defects caused
astigmatism of tectonic corneal grafts, ease and convenience of by total limbal stem cell deficiency or severe ischemia, e.g.
use, feasibility in the event of corneal tissue shortage, and chemical burns.

Figures 42.2A to F: Transplantation of Amniotic Membrane for Persistent Epithelial Defects. This eye developed superficial
persistent corneal epithelial defect associated with corneal stromal neovascularization at 3- and 8-o’clock positions (A). Fluorescein
staining showed a circumscribed defect (B). Overlaid graft with AMT using ProKera™ resulted in complete healing of the corneal
surface with resolution of peripheral corneal neovascularization (C).This eye showed persistent epithelial defect associated with
stromal ulceration at the donor-recipient junction (D and E). A temporary overlaid AM graft using ProKera™ was used together with
a permanent graft to provide as additional protection while ensuring epithelialization. Favorable outcome with complete healing of
the defect and resolution of the inflammation ensured (F)
307
2. Sterile Corneal Stromal Thinning, negative) in 7 patients. They used a single-layer of AM in 17
Descemetocele and Perforation patients, and a double-layer in 6 patients with corneal perforation
and anterior chamber collapse. After AMT, complete
For deeper stromal ulcers down to descemetocele, multiple layers
epithelialization was observed in 12 patients (75%) in the active
of AM can be used to restore the normal corneal thick-
group and in 7 patients (100%) in the inactive group. Treatment
ness.11,15,17,18,20 When there is frank perforation even up to 3
failure requiring tectonic penetrating keratoplasty was
mm in diameter, AMT may be used to seal the ulcer17 with or
experienced in 4 patients (25%) in the active group. Persistent
without additional tissue adhesive18,19 (Figs 42.3A and B).
Section V: Specific Techniques in Keratoplasty

fungal keratitis was noted in 2 patients in that group. They


Prabhasawat et al20 transplanted multiple layers of the AM for
concluded that AMT is effective in promoting epithelialization
corneal epithelial defect with stromal thinning (13 eyes) and
and preventing corneal perforations in acute fungal keratitis.
corneal perforations up to 1 mm (5 eyes). They achieved a
Experimental studies have shown that in eyes with herpes
success rate of 84.6 and 80 percent in these two groups,
simplex virus (HSV) necrotizing keratitis, AMT resulted in
respectively. Thirty-four eyes with descemetoceles or corneal
profound regression of corneal inflammation and neovas-
perforations less than 0.5 mm underwent 3-4 layers of AMT by
cularization and rapid closure of epithelial defects. 25,26
Solomon et al.8 A successful result was observed in 28 of 34
Heiligenhaus et al27 used AMT in management of seven patients
eyes (82.3%). Rodriguez-Ares et al17 used two layers of AM (for
with acute ulcerative and necrotising herpes simplex and zoster
perforations less than 0.5 mm, n = 6) and 3-4 layers (for
stromal keratitis. They noted improvement of stromal
perforations of 0.5-1.5 mm or >1.5 mm, 4 and 5 eyes,
inflammation within 16.4 + 2.5 days and the epithelial defects
respectively). The treatment was judged successful in 73 percent
healed within a mean of 17 + 2.7 days. In another study, Shi
(11/15) of eyes. Three of the 4 unsuccessful treatments were of
et al28 studied multilayer AMT combined with antiviral and
perforations 3 mm or more in diameter; of the 5 eyes with
corticosteroid medications for treatment of necrotizing herpes
perforations of more than 1.5 mm in diameter, only 2 were treated
simplex stromal keratitis. Corneal ulcer healed within 1-3 weeks
successfully. Hick et al18 performed single-layer AMT with fibrin
postoperatively and corneal stromal edema faded away within 1
glue in 14 eyes with corneal perforation up to 3 mm and on
month.
average 1.9 mm. Their success rate in sealing the perforation
When AMT is used for treating infectious corneal ulcers,
was 93 percent.
there may be a concern that AM may prevent penetration of
3. Infectious Keratitis and Scleritis
Corneal ulcers caused by bacterial, fungal or viral causes have
been successfully managed by AMT when the infection is
controlled (Figs 42.3C and D). Chen et al21 used AMT in 6 eyes
with Pseudomonas keratitis associated with prominent stromal
melting and extensive stromal loss. The lesion became sterile in
5 cases with rapid re-epithelialization within 9.4 + 2.1 days and
decreased inflammation. After controlling the infection with
proper antimicrobial treatment, Kim et al22 performed AMT in
21 eyes with infectious corneal ulcer caused by Staphylococcus
species (n = 4), Pseudomonas species (n = 5), Acanthamoeba
species (n = 3), fungi (n = 2), and herpes virus (n = 7). They
soaked the AM in anti-infective agents before transplantation.
Postoperatively, the corneal surface was healed successfully and
recurrences of microbial infection were not noted in any cases.
In 4 cases of infectious scleral ulcers with persistent scleral
melting, presenting with no sign of re-epithelialization and 3 Figures 42.3A to D: Transplantation of Amniotic Membrane
cases of corneoscleral ulcers with corneal perforation, caused for Descemetocele and Infectious Keratitis. This eye had
sterile corneal ulceration with descemetocele due to severe dry
by Pseudomonas (n = 4), fungi (n = 2), and atypical
eye in Stevens-Johnson syndrome (A). Multiple layers of AM
Mycobacterium (n = 1), Ma et al 23 performed AMT after were laid in the ulcer bed and a larger piece of AM was then laid
appropriate treatments with topical and systemic antibiotics. This down to cover both the ulcer and the healthy surface with the
procedure resulted in decreased melting and inflammation at the stromal side down, and sutured with a running 10-0 nylon suture
lesion site with re-epithelialization of the scleral lesions within to secure it onto the surrounding healthy tissue. This resulted in
15.7 ± 8.7 days. No recurrent infection was encountered. restoration of the normal corneal thickness (B). This eye
developed descemetocele after glaucoma drainage implantation
Chen et al24 performed AMT in 23 eyes with persistent
and pseudomonas infection (C), multi-layer AMT again resulted
corneal ulcers and perforations in acute fungal keratitis during in restoration of a normal corneal thickness and a non-inflamed
the active phase of the keratitis (fungal culture was still positive) and healed surface with improved vision without corneal
in 16 patients, and during the inactive phase (fungal culture transplantation (D)
308
antimicrobial agents. However, it has been found that AM after deficiency, which is characterized by conjunctivalization of the
impregnation with an antibiotic can slowly release it and act as cornea, i.e. the conjunctival epithelium migrates to cover the
a reservoir. In a study, Mencucci et al 29 showed the AM corneal surface, which is accompanied by vascularization,
fragments soaked in netilmicin inhibited bacterial growth; destruction of the basement membrane, chronic inflammation,
antibiotic uptake was dose-dependent and occurred rapidly. The and scarring of the cornea.42 Limbal stem cell deficiency can be
drug was released from the membrane, and the antibacterial caused by a number of corneal diseases such as chemical and
effect was present in the elution media at least 3 days after thermal burns, Stevens-Johnson syndrome, mucous membrane

Chapter 42: Amniotic Membrane Transplantation


treatment. They concluded that AM can absorb this antibiotic pemphigoid, severe microbial infections, radiation keratopathy,
and in the future may be used as a slow-releasing polymer to aniridia, etc. Conventional corneal transplantation invariably
deliver antibiotics as reported for collagen shields and other fails, as no stem cells are transplanted, and is frequently rejected
medical prosthetic devices. due to corneal vascularization and inflammation. In cases with
total limbal stem cell deficiency, transplantation of autologous
4. Symptomatic Bullous Keratopathy or allogeneic limbal epithelial stem cells is required.43,44 In eyes
with partial limbal stem cell deficiency, AMT alone can
Bullous keratopathy is a disorder caused by corneal endothelial
decompensation due to degeneration (Fuch’s endothelial successfully reconstruct human corneas.45-48 AMT restored 40
percent of rabbit corneas with limbal stem cell deficiency.4,49
dystrophy), surgical trauma, intractable glaucoma, or previous
These results suggest that AM helps expansion of residual limbal
corneal graft failure. For those who do not have a visual potential,
relief of pain and recurrent erosion will rely on several surgical stem cells in these corneas so as to avoid the need of limbal
stem cell transplantation (Figs 42.4E and F). That also explains
treatments including cauterization, anterior stromal puncture,
why AMT can be used to restore the donor eye undergoing
excimer laser photoablation, and conjunctival flap. AMT can
achieve a pain relief with an overall success rate of more than removal of the normal limbus and the recipient eyes receiving
conjunctival limbal autograft for unilateral total limbal stem cell
85 percent.30-34 The AM-covered corneal surface heals in 3
deficiency.50 Moreover, for bilateral total limbal stem cell
weeks with reduced inflammation and only less than 10 percent
eyes show recurrent surface breakdown (Figs 42.4A and B). deficiency, AMT has been used in conjunction with keratolimbal
allograft to facilitate re-epithelialization of cornea.45,51
Espana et al33 used AMT after epithelial debridement in 18
eyes with symptomatic bullous keratopathy. During a mean
AS AN OVERLAID GRAFT
follow-up of 25.1 months, pain relief was obtained in 88 percent
of patients. Corneal epithelial healing was complete in all except The main indication to use AM as an overlaid graft is to suppress
1 eye. During a mean follow-up of 14.1 months after AMT for inflammation on the ocular surface caused by various diseases
17 patient who had bullous keratopathy associated with and insults so as to promote epithelial healing with minimal or
intractable pain, Chansanti et al35 noted postoperative relief of no scarring. As shown in Table 42.2, clinical indications include
pain in 14 eyes (82.4%) and complete corneal epithelial healing intense ocular surface inflammation and epithelial erosion caused
in 15 eyes (88.2%). Sonmez et al36 performed anterior stromal by acute chemical and thermal burns52-60(Fig. 42.5), and acute
micropuncture and AMT in 5 eyes with painful bullous inflammatory and ulcerative stage of Stevens-Johnson syndrome
keratopathy. All showed an intact, smooth corneal epithelial with or without toxic epidermal necrolysis (TEN)61-63 (Fig. 42.6).
surface 1 month after the procedure, and no patients developed Conventional therapies for these diseases have a limited success.
recurrent bullae formation during an average follow-up period In contrast, early intervention by AMT (e.g. within the first week)
of 21 months. not only reduces inflammation and facilitates epithelial wound
healing, but also prevents the late cicatricial complications that
5. Band Keratopathy may lead to corneal blindness, cause motility restriction in the
Band keratopathy occurs in a number of corneal diseases conjunctiva, and lead to exposure, mechanical micro-trauma (by
characterized by chronic inflammation. Conventional treatments misdirected lashes and keratinization), and dryness in the lids
include chelation by EDTA and superficial keratectomy to and fornix.62 AMT alone is not sufficient for treating ischemia
remove superficial calcium deposit and corneal stromal tissue. in Grade IV chemical burns, and early treatments require
AMT after this procedure has achieved a success rate of more additional Tenonplasty.64
than 90 percent in relieving patient’s pain, establishing a stable In addition, cryopreserved AM can also be used as an
corneal epithelium, and in some eyes improved vision (Figs overlaid graft to treat chronic recalcitrant inflammation with or
42.4C and D).37-40 without persistent epithelial defect caused by several ocular
surface diseases including neurotrophic keratitis caused by
herpes zoster virus or herpes simplex virus25,65 and vernal
6. Partial Limbal Stem Cell Deficiency keratoconjunctivitis.66 When epithelial defects are accompanied
The epithelial stem cells are located exclusively at the limbus.41 by stromal ulceration, a temporary AM graft is used together
Destructive loss of the limbal epithelial stem cells and/or with a permanent graft to provide as additional protection while
dysfunction of the limbal stroma will lead to limbal stem cell ensuring epithelialization.8,9 Recently, AM has been shown to
309
As will be more detailed below, AM as an overlaid graft can
be delivered without sutures through a symblepharon conformer
termed “ProKera™” (see below). Besides the aforementioned
clinical effects, PMMA conformer ring of ProKera™ can be used
as a symblepharon ring and together with AM to reduce
conjunctival inflammation/swelling following reconstruction in
the orbit/socket, lids or the fornix.
Section V: Specific Techniques in Keratoplasty

Ex Vivo Expansion of Epithelial Stem Cells


In 1997, Pellegrini et al73 used tissue culture techniques to
cultivate epithelial cell sheets from a small limbus biopsy
obtained from the healthy eyes of two patients with unilateral
severe alkali injuries. The epithelial sheets were transplanted onto
the damaged fellow-eyes and the regenerated corneal epithelial
autograft remained stable over a 2-year period. This technique
of ex vivo expansion of limbal tissue has obvious advantages
where, there is limited availability of limbal tissue in a diseased
donor eye and poses less potential risk to a healthy donor eye.
There is also obviously no risk of allograft rejection and no need
for systemic immunosuppression.
Amniotic membrane substrate offers several favorable
Figures 42.4A to F: Transplantation of Amniotic Membrane advantages over Pellegrini’s original method as AM assists with
as a Permanent Graft to Restore Corneal Integrity. In this ex vivo expansion of limbal epithelial cells by providing:
eye with combined band keratopathy and bullous keratopathy • A natural, thick supporting substrate.
(A), the loose and calcified epithelium is removed by superficial • Easier transfer of tissue graft from the laboratory to the
keratectomy using a #64 blade, a superficial trephination (a operating room and onto the patient’s eye.
quarter turn) is followed by a lamellar pocket created 360 degrees
toward the limbus by a crescent blade, AM is inserted into this
• Unique biological actions of the amniotic membrane on
pocket and secured by a running 10-0 nylon suture resulting in a surrounding tissue.
non-inflamed, healed and stable corneal surface (B). In this eye, The validity of this method has now been proven in culture
band keratopathy caused erosion and pain (C). Superficial systems,74-76 laboratory animals,77,78 and human patients.79-81
keratectomy removes calcium deposit; a layer of AM is secured However, our recent studies indicated that there is a gradual
on the denuded surface with fibrin glue. This sutureless AMT
decline of limbal epithelial progenitor cells migrating out of the
results in a smooth and stable corneal surface with less scar
(D). In this eye, there is partial limbal stem cell deficiency in the limbal explant partly due to intrastromal invasion in this
inferior cornea (E); after removal of pannus, AMT helps the protocol.82 We believe there is a great need to optimize the ex
expansion of residual stem cells to achieve a smooth corneal vivo expansion protocol in the future.
surface without stem cell transplantation (F)

promote healing and reduce inflammation in high-risk eyes SURGICAL PROCEDURES


receiving penetrating or lamellar keratoplasties,65 to reduce Amniotic membrane transplantation is performed using standard
corneal haze induced by excimer laser ablation,67-71 and to surgical instruments and microsurgical equipment. In the United
improve implantation of keratoprosthesis72 (Table 42.2). States, AmnioGraft® distributed by Bio-Tissue, Inc. (Miami, FL)

Figures 42.5A to C: Amniotic Membrane Transplantation as an Overlaid Graft for Acute Chemical Burn. Chemical injury with
acid resulted in severe conjunctival inflammation and large corneal-limbal epithelial defect in this eye (A). AMT using ProKera™
was done at 1 day after the burn (B). Complete epithelialization of the cornea with resolution of the conjunctival inflammation were
obviously seen at 2 weeks after AMT (C)
310
As either biological overlaid or permanent graft, AMT is
conventionally performed by sutures. In this chapter, we will
focus on the new sutureless approach, which provides the
following advantages:
1. Shorter surgical time,
2. Feasibility of doing surgery under topical anesthesia,
3. Ease of postoperative care, and

Chapter 42: Amniotic Membrane Transplantation


4. Lack of suture-related complication, thus facilitating patient
care and reducing overall medical cost. These advantages
are demonstrated in our recent studies.84-87

As a Permanent Graft

Following Superficial Keratectomy


Topical anesthesia using 0.5 percent proparacaine hydrochloride,
0.5 percent tetracaine hydrochloride, or 2 percent xylocaine jelly
(AstraZeneca, Wimington, DE) is adequate if AMT is performed
without sutures using fibrin glue to secure AmnioGraft® to the
corneal surface. There are two commercially available fibrin
glues, i.e. Tisseel® and CoSeal® (Baxter Biologics, Inc.). The
former requires pre-warming in a thermal/stirrer provided
without costs by the manufacturer; the latter is ready for use
without warming. Both come with two components, thrombin
and fibrinogen.
AmnioGraft® (1.5 × 1.0 cm or 2.0 × 1.5 cm size) can be
used as a single layer to cover the defect produced by superficial
keratectomy (Fig. 42.8A). For large defects, the amniotic
Figures 42.6A to C: Amniotic Membrane Transplantation as
an Overlaid Graft for Acute Stevens-Johnson Syndrome. This membrane is placed over the cornea with stromal surface down
patient with acute manifestations of Stevens-Johnson syndrome (Fig. 42.8B). Half of the membrane is folded over the other half,
had severe conjunctival inflammation with corneal involvement exposing the stromal surface (Fig. 42.8C). Thrombin solution is
as epithelial defect in both eyes (A). AMT was used as an overlaid applied over the corneal surface (Fig. 42.8D) and fibrinogen
graft to cover the entire ocular surface of both eyes within the solution on the stromal surface of the membrane (Fig. 42.8E).
first week of presentation (B). The patient restored a completely
This half of the membrane is flipped back by two forceps
healed and non-inflamed ocular surface with a 20/20 vision in
both eyes (C) (Fig. 42.8F) and a muscle hook is used to stretch the membrane
over the cornea (Fig. 42.8G). The same procedure is done for
is the only cryopreserved AM approved by the US Food and other half of the membrane and excess membrane is trimmed
Drug Administration (FDA) as a graft for ocular surface off. For small defects, AmnioGraft® is trimmed to the size of
reconstruction. Because this cryopreservation method kills the defect. The membrane is placed outside of the defect with
allogeneic amniotic cells in AmnioGraft®,83 it eliminates the stromal side up. After application of thrombin and fibrinogen to
need for immunosuppression while maintaining the integrity of corneal surface and stromal surface of the membrane,
its cytokine-rich extracellular matrix. respectively, the membrane is placed over the defect with stromal
AmnioGraft® is distributed in a foil package in a frozen state. surface down and a muscle hook is used to stretch the membrane
After thawing at the room temperature, it can be retrieved over the cornea.
aseptically from the inner clear plastic pouch and the membrane
For Corneal Ulcers
is attached to one side of nitrocellulose paper (Fig. 42.7). Once
transferred to the operating field, the membrane can be easily For the corneal ulcers, AmnioGraft® (2.5 × 2.0 cm or 2.0 × 1.5
peeled off from the paper by two forceps grabbing the two cm size) can be used as a single layer or multiple layers to fill in
corners while the nurse peels the paper away. In general, the stromal defect of an ulcer, depending on the depth of the
AmnioGraft® is placed with the stromal side on the recipient stromal loss. The orientation of the bottom layers does not matter
bed; the side can be discerned by touching it with the tip of a and can be secured by fibrin glue, while the top layer meant for
dry MicroSponge™ (Alcon Surgical, Fort Worth, TX). The epithelialization is best to be placed with the stromal side down
stromal side, but not epithelial side, sticks to MicroSponge™ and secured tightly to the corneal surface with 10-0 nylon sutures,
(Fig. 42.7). either interrupted or running.

311
Section V: Specific Techniques in Keratoplasty

Figures 42.7A to D: Handling of Cryopreserved Amniotic Membrane. AmnioGraft® obtained from Bio-Tissuen, Inc., is stored in
a foil package in a frozen state. After thawing at the room temperature, it can be retrieved aseptically from the inner clear plastic
pouch and the membrane is attached to one side of nitrocellulose paper (A and B). Once transferred to the operating field, the
membrane can be easily peeled off from the paper by two forceps grabbing the two corners while the nurse peels the paper away
(C). In general, AmnioGraft® is placed with the stromal side on the recipient bed; the side can be discerned by touching it with the
tip of a dry MicroSponge™ (Alcon Surgical, Fort Worth, TX). The stromal side, but not epithelial side, sticks to MicroSponge™ (D)

For Bullous and Band Keratopathy sutures in a mattress fashion, parallel to the fornix, with solid
To ensure that epithelialization will take place on the top, but episcleral bites to seal the fornix border.
not underneath the membrane, a lamellar pocket can be prepared
with crescent blade to allow insertion of the membrane. For this As an Overlaid Graft
to be done, after removal of band keratopathy and bullous
To Cover the Entire Ocular Surface
epithelium, a very superficial trephination is performed on the
corneal surface, then a 2 mm wide lamellar pocket is created in To cover both corneal and conjunctival surfaces, especially for
360 degrees of cornea. Amniotic membrane is secured over the acute chemical/thermal burns or acute Stevens-Johnson
corneal surface and into the pocket by the fibrin glue. syndrome with or without toxic epidermal necrolysis, two large
pieces of AmnioGraft® (3.5 × 3.5 cm size) are needed to be
For Partial Limbal Stem Cell Deficiency secured to the skin surface of the upper lid margin by a 10-0
nylon suture in an interrupted or running manner, and then tugged
After removal of fibrovascular tissue from the corneal surface,
into the upper fornix with a muscle hook and secured there by
AMT is performed similar to the procedure mentioned for
passing a double-armed 4-0 black silk in a mattress fashion to
superficial keratectomy.
the skin surface with a bolster (Fig. 42.9)(see Meller et al53).
About Sutures: If fibrin glue is not used, the cryopreserved The remaining AM is spread to cover the upper bulbar
amnion graft can be secured by several interrupted 10-0 nylon conjunctiva and a part of the upper corneal surface. The other
sutures on peri-limbal bulbar conjunctiva and by 8-0 Vicryl piece is secured to the lower lid and the lower fornix in the similar
312
Chapter 42: Amniotic Membrane Transplantation
Figure 42.9: Amniotic Membrane as an Overlaid Graft to
Cover the Entire Ocular Surface. To cover both corneal and
conjunctival surfaces, two large pieces of AmnioGraft® (3.5 ×
3.5 cm size) are needed. One of these membranes is secured to
the skin surface of the upper lid margin by a 10-0 nylon suture in
an interrupted or running manner, and then tugged into the upper
fornix with a muscle hook and secured there by passing a double-
armed 4-0 black silk in a mattress fashion to the skin surface
with a bolster. The remaining AM is spread to cover the upper
bulbar conjunctiva and a part of the upper corneal surface. The
other piece is secured to the lower lid and the lower fornix in the
Figures 42.8A to H: Surgical Steps of Sutureless Transplanta- similar fashion, overlapped with the first AmnioGraft® on the
tion of Cryopreserved Amniotic Membrane as a Permanent corneal surface, and secured by a 10-0 nylon suture placed in
Graft to Cover the Corneal Surface with Fibrin Glue Following the same manner as described above
Superficial Keratectomy. After performing superficial
keratectomy (A), AmnioGraft® is laid on the cornea with the
stromal side facing down (B). Then, AM is flipped so that the done in the bedside or at the office without any need to the
stromal side is facing up (C). The thrombin solution is applied on
operation room facilities. There are two different diameters of
the corneal surface (D) and the fibrinogen solution on the stromal
side of the membrane (E). AmnioGraft® is then flipped back (F), ProKera™ available: 15 mm and 16 mm. Most adult patients
and a muscle hook is used to flatten and attach the membrane will tolerate a 16 mm device. For ProKera™ insertion, after using
onto the corneal surface (G). Excess amniotic membrane is topical anesthetic eye drops a lid speculum is used to open the
trimmed off (H) eye. Then, it is inserted into the upper fornix first, and then tucked
under the lower lid.

fashion, overlapped with the first AmnioGraft® on the corneal Postoperative Care
surface, and secured by a 10-0 nylon suture placed in the same
manner as described above. A temporary tarsorrhaphy is added Postoperative care varies depending on the clinical setting in
to minimize the lid fissure if there is an exposure concern due which AMT has been done. At the first postoperative day,
to large scleral show or infrequent blinking as a result of a medications such as prednisolone acetate 1 percent four times a
neurotrophic state. day and ofloxacin 0.3 percent three times a day are prescribed.
During postoperative course, the corneal epithelialization can
To Cover Only the Corneal Surface be assessed by fluorescein staining88 (Fig. 42.1C) and the
intraocular pressure can be monitored by Tonopen89 without
AmnioGraft® (2.5 × 2.0 cm size) is secured by a 10-0 nylon removing ProKera™ or AmnioGraft®. When used as an
suture at 2 to 3 mm from the limbus in a purse-string running
overlaid, the membrane does cut down the light transmission,
fashion for a total of 8 to10 episcleral bites to cover the corneal
leading to a blurry vision. Upon complete healing, e.g. 1-2 weeks,
surface as a biological bandage. ProKera™ or AmnioGraft® can be easily removed from the
ocular surface under a slit-lamp microscope with forceps.
ProKera™
Ofloxacin is then stopped and prednisolone eye drop is tapered
As mentioned previously, ProKera™ is a combination of a off at a weekly schedule from four times a day. For eyes with
PMMA conformer ring and amniotic membrane (Fig. 42.1). With severe neurotrophic keratopathy, a small permanent tarsorrhaphy
availability of this device, AMT as an overlaid graft could be to limit lid fissure may be necessary.
313
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transplantation in severely damaged rabbit corneas. Korean J (PRK)- amniotic membrane transplantation (AMT) on myopic
Ophthalmol 1995;9:32-46. regression with corneal opacity after PRK in high myopia. Invest.
50. Meallet MA, Espana EM, Grueterich M, Ti SE, Goto E, Tseng Ophthalmol. Vis. Sci. 39, S354. 1998. Ref Type: Abstract
SC. Amniotic membrane transplantation with conjunctival limbal 68. Kim JY, Wee WR, Choi YS, Lee JH. Clinical outcome of
autograft for total limbal stem cell deficiency. Ophthalmology photorefractive keratectomy (PRK) retreatment using amniotic
2003;110:1585-92. membrane. Ophthalmology 1998;162.
51. Tsubota K, Satake Y, Ohyama M, Toda I, Takano Y, Ono M, 69. Choi YS, Kim JY, Wee WR, Lee JH. Effect of the application of
Shinozaki N, Shimazaki J. Surgical reconstruction of the ocular human amniotic membrane on rabbit corneal wound healing after
surface in advanced ocular cicatricial pemphigoid and Stevens- excimer laser photorefractive keratectomy. Cornea 1998;17:389-
Johnson syndrome. Am J Ophthalmol 1996;122:38-52. 95.
52. Kim JS, Kim JC, Na BK, Jeong JM, Song CY. Amniotic 70. Park WC, Tseng SCG. Modulation of acute inflammation and
membrane patching promotes healing and inhibits protease keratocyte death by suturing, blood and amniotic membrane in
activity on wound healing following acute corneal alkali burns. PRK. Invest Ophthalmol Vis Sci 2000;41:2906-14.
Exp Eye Res 2000;70:329-37. 71. Wang MX, Gray TB, Parks WC, Prabhasawat P, Culbertson WW,
53. Meller D, Pires RTF, Mack RJS, Figueiredo F, Heiligenhaus A, Forster RK, Hanna K, Tseng SCG. Corneal haze and apoptosis is
Park WC, Prabhasawat P, John T, McLeod SD, Steuhl KP, Tseng reduced by amniotic membrane matrix in excimer laser
SCG. Amniotic membrane transplantation for acute chemical or photoablation in rabbits. J Cat Refract Surg 2001;27:310-19.
thermal burns. Ophthalmology 2000;107:980-90. 72. Kaminski SL, Lacombe E, Duchesne B, Fernandez V, Lamar P,
54. Sridhar MS, Bansal AK, Sangwan VS, Rao GN. Amniotic Lee W, Mannis F, Alfonso E, Parel J-M. Supradescemetic
membrane transplantation in acute chemical and thermal injury. keratoprosthesis (SD-Kpro): A novel design. Invest Ophthalmol
Am J Ophthalmol 2000;130:134-37. Vis Sci 2002;43:2993.

315
73. Pellegrini G, Traverso CE, Franzi AT, Zingirian M, Cancedda R, 81. Nakamura T, Koizumi N, Tsuzuki M, Inoki K, Sano Y, Sotozono
De Luca M. Long-term restoration of damaged corneal surface C, Kinoshita S. Successful regrafting of cultivated corneal
with autologous cultivated corneal epithelium. Lancet epithelium using amniotic membrane as a carrier in severe ocular
1997;349:990-93. surface disease. Cornea 2003;22:70-71.
74. Koizumi N, Fullwood NJ, Bairaktaris G, Inatomi T, Kinoshita S, 82. Li W, Hayashida Y, He H, Kuo CL, Tseng SC. The fate of limbal
Quantock AJ. Cultivation of corneal epithelial cells on intact and epithelial progenitor cells during explant culture on intact
denuded human amniotic membrane. Invest Ophthalmol Vis Sci amniotic membrane. Invest Ophthalmol Vis Sci 2007;48:605-13.
2000;41:2506-13. 83. Kruse FE, Joussen AM, Rohrschneider K, You L, Sinn B,
Section V: Specific Techniques in Keratoplasty

75. Meller D, Pires RTF, Tseng SCG. Ex vivo preservation and Baumann J, Volcker HE. Cryopreserved human amniotic
expansion of human limbal epithelial stem cells on amniotic membrane for ocular surface reconstruction. Graefe’s Arch Clin
membrane cultures. Br J Ophthalmol 2002;86:463-71. Exp Ophthalmol 2000;238:68-75.
76. Wang DY, Hsueh YJ, Yang VC, Chen JK. Propagation and
84. Kheirkhah A, Casas V, Blanco G, Li W, Hayashida Y, Chen YT,
phenotypic preservation of rabbit limbal epithelial cells on
Tseng SC. Amniotic membrane transplantation with fibrin glue
amniotic membrane. Invest Ophthalmol Vis Sci 2003;44:4698-
for conjunctivochalasis. Am J Ophthalmol 2007;144:311-13.
4704.
77. Koizumi N, Inatomi T, Quantock AJ, Fullwood NJ, Dota A, 85. Kheirkhah A, Casas V, Esquenazi S, Blanco G, Li W, Raju VK,
Kinoshita S. Amniotic membrane as a substrate for cultivating Tseng SC. New surgical approach for superior conjunctivo-
limbal corneal epithelial cells for autologous transplantation in chalasis. Cornea 2007;26:685-91.
rabbits. Cornea 2000;19:65-71. 86. Kheirkhah A, Casas V, Sheha H, Raju VK, Tseng SCG. Role of
78. Pan Z, Zhang W, Wu Y. An experimental study on treatment of conjunctival inflammation in surgical outcome after amniotic
limbal alkali burn by allograft transplantation with cultured stem membrane transplantation with or without fibrin glue for
cells on amniotic membrane. Zhonghua Yan Ke Za Zhi pterygium. Cornea 2007; In press.
2000;36:32-5, 3. 87. Casas V, Kheirkhah A, Blanco G, Tseng SCG. Scleral Approach
79. Tsai RJF, Li L-M, Chen J-K. Reconstruction of damaged corneas for scleral ischemia and melt. Cornea 2007; In press.
by transplantation of autologous limbal epithelial cells. N Eng J 88. Kobayashi A, Ijiri S, Sugiyama K, Di Pascuale MA, Tseng SC.
Med 2000;343:86-93. Detection of corneal epithelial defect through amniotic membrane
80. Shimazaki J, Aiba M, Goto E, Kato N, Shimmura S, Tsubota K. patch by fluorescein. Cornea 2005;24:359-60.
Transplantation of human limbal epithelium cultivated on 89. Yoshita T, Kobayashi A, Takahashi M, Sugiyama K. Reliability
amniotic membrane for the treatment of severe ocular surface of intraocular pressure by Tono-Pen XL over amniotic membrane
disorders. Ophthalmology 2002;109:1285-90. patch in human. J Glaucoma 2004;13:413-16.

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SECTION VI: Alternatives to Penetrating Keratoplasty

43

Chapter 43: Boston Keratoprosthesis


Boston Keratoprosthesis
Mona Harissi-Dagher, Bilal Khan, Claes H Dohlman

INTRODUCTION by a silver ring in a completely opaque cornea to restore vision.


He proposed the surgical procedure and designed the necessary
The restoration of vision in patients with corneal blindness has
instruments.
become increasingly successful with advances in standard
Later in 1853, Nussbaum performed experimental work with
penetrating keratoplasty progressing since the beginning of the
a glass stud in a rabbit eye and published human trials using a
twentieth century. While it is possible for grafts to remain clear
quartz crystal implanted into the cornea.9 Over the next 50 years,
for decades, graft failure for all diagnostic categories is not
Heusser,10 Dimmer,11 Salzer12 and Von Hippel13 continued further
insignificant. Although most episodes of rejection occur in the
efforts in design and insertion techniques. However, extremely
first or second year after penetrating keratoplasty, late endothelial
high incidences of early complications were associated with those
failure, without clinical evidence of a significant episode of
keratoprosthesis, which typically failed owing to tissue necrosis,
rejection, is the most significant cause of failure in grafts that
with subsequent leak, infection, and extrusion of the device.
last past 5 years.1-4 A subset of patients remains with severe
After 1906, when the first successful human-to-human
corneal opacities in which penetrating keratoplasty fails or carries
corneal graft was performed, attention was diverted away from
a poor prognosis, specifically, patients with a diagnosis of herpes
keratoprosthesis development until many years later when it was
simplex virus (HSV), Stevens-Johnsons Syndrome, ocular
realized that penetrating keratoplasties would not be successful
cictricial pemphigoid and chemical burns. Keratoprosthesis has
in all cases. In 1920, Verhoeff14 reported on a single case of
been carefully used in these severe corneal diseases in the past
insertion of a quartz button into a patient’s cornea. However, it
few decades with encouraging results.
had to be removed shortly afterward. Similarly in 1935, Filatov
The prognosis for subsequent graft failures is worse for
implanted a full penetrating glass device into an opacified cornea
all subgroups, especially in the multiple regraft failures
of a patient and covered it with a double conjunctival flap
category.5-7 Furthermore, generally accepted risk factors for graft
postoperatively achieving an ambulatory vision of 1/200.15
failure such as glaucoma, multiple surgeries, presence of
After 1950, keratoprosthesis research gained momentum.
inflammation, and severity of neovascularization are usually
During World War II, it was noticed that polymethylmethacrylate
more prevalent in subsequent grafts and tend to develop with
(PMMA) splinters imbedded in the corneas of pilots were well
time in initial grafts.2 At present, keratoprosthesis surgery appears
tolerated. This led to experiments by Wünsche,16 Stone and
to be a reasonable option for this regraft failure group of patients.
Herbert,17 Cardona18 and others showing that PMMA disks could
A considerable amount of research on the topic of
be retained in the cornea of rabbits. Soon, human applications
keratoprosthesis development has been conducted by several
followed, and many ophthalmologists attempted to refine their
groups of investigators. Recent advances aimed at preventing
and treating early complications after keratoprosthesis surgery
Table 43.1: Factors improving
have improved the outlook and prognosis of patients undergoing keratoprosthesis outcome
the surgery. Hence, there is now reason for more optimism with
• Design of device
this technique (Table 43.1).
• Identification of prognostic categories
HISTORY • Aggressive steroid regimens
• Tissue coverage (conjunctiva, eyelid skin, SCL)
The concept of an artificial cornea in the treatment of corneal • Glaucoma tube implant
blindness was first suggested in writing by the noted French • Nd:YAG laser membranectomy
surgeon, Pellier de Quengsy, in 1789, at the time of the French • Repair techniques
revolution.8 He suggested the implantation of a glass lens held • Meticulous, regular follow-up

317
procedure using these new inert plastics. Once again, however, In this chapter, we report our experience with the Boston
many of these cases were associated with severe complications, keratoprosthesis and the outcome after implantation of this
and the procedure lost favor with many surgeons. Some, device at the Cornea service of the Massachusetts Eye and Ear
nevertheless, persevered in developing their techniques and infirmary. For a number of years, we have used a PMMA
polished them over the years. keratoprosthesis of double-plated collar button design. Such a
The combined experience of surgeons preeminent in the general configuration has been suggested in the past, and has
development of keratoprosthesis surgery probably may have been modified by us as described in the following section.33-35
Section VI: Alternatives to Penetrating Keratoplasty

amounted to no more than about 4000 to 5000 cases during the Design and material are undoubtedly important, but it should
past half-century, a small number when compared with the be emphasized that the health of the surrounding tissue is vitally
number of penetrating keratoplasties carried out on a worldwide important as well.
basis. The results of many of these series have been published We do not have sufficient experience with other devices to
but they are difficult to interpret; this is mainly because visual do justice to them or to the experience of other surgeons, nor do
acuity was recorded as a single outcome at one point in time we claim superiority of our prosthesis or our technique over
without an indication of length of follow-up or duration of programs elsewhere. This chapter describes the Boston
retention of the keratoprosthesis. In addition, much focus and keratoprosthesis devices, surgical techniques and follow-up
attention has been centered on the design and materials of the routines with which we have become proficient.
keratoprosthesis, whereas follow-up of complications, such as
glaucoma, retroprosthetic membranes, melts, and vision- DESIGN AND MATERIAL
threatening retinal complications, have received less attention.
Our collar button-shaped device consists of two plates joined
Likewise, the necessity for close follow-up, and frequent
by a stem, which constitutes the optical portion and locked in
revisions were not emphasized in some of the reviews of the
by a titanium c-ring. It has undergone a number of important
literature. Long-term outcomes have been underreported, and the
design changes since the mid-1960s. The diameter of the front
incidence of eventual functional loss of vision remained
and back plates, the stem diameter, the absence or presence of
unknown. Furthermore, details of the preoperative diagnosis of
holes, and their diameter in the back plate have varied
patients undergoing surgery were not always included. This is
(Table 43.2). The double-plated devices we currently use come
crucial because there are definite subgroups of patients in whom
in two main designs (Fig. 43.1).36
keratoprosthesis carries a more favorable outlook than in others.
Type I, the simple collar button, is the most frequently used.
Despite these limitations, a considerable body of knowledge in
It is favored in eyes with reasonable blink and tear secretion
this complex field has accumulated.
mechanisms. The keratoprosthesis is made of PMMA, a
The current keratoprosthesis effort is maintained primarily
biologically inert and transparent material that has stood the test
in approximately a dozen centers worldwide and diverse
of time. The keratoprosthesis is machined as a front plate and a
approaches exist. One original principle inspired by Strampelli19
separate back plate, which is screwed onto the stem, clamping a
has been modified by a number of followers (Falcinelli et al,20
corneal graft. The current model has a titanium locking c-ring
Marchi et al,21 Temprano,22 Grabner et al,23 Liu et al,24 Hille,25
to prevent loosening of the back plate. The advantages of this
and others). This technique, called osteo-odonto-keratopros-
design include a short optical stem, which provides a good view
thesis, involves harvesting a tooth from the patient and preparing
with the slit lamp; a generous visual field; and good stability
a slice of osteodental lamina to be used as a skirt for a cylinder
because the wide plates prevent tilting of the device off the visual
of PMMA. In a second surgical session, it is then inserted into
axis. The design also facilitates repair should necrosis of tissue
the patient’s cornea and covered by lid skin or buccal mucosal
around the stem occur. Another noteworthy change in the design
graft. The procedure is somewhat invasive but has a reputation
is the addition of holes within the backplate, which, it is
for stability and low rate of infection.
postulated, allows for better access for nutrition form the aqueous
Pintucci et al,26 Girard et al,27 Legeais et al,28 and others
as well as rehydration of the corneal stroma adjacent to the stem.
have replaced the autologous tooth-derived skirt with
This helps to prevent necrosis of the surrounding tissue. The
“biocolonizable” porous plastic materials. In Russia, a large
profile of the keratoprosthesis was also redesigned both to
number of patients, especially with chemical burns, have been
implanted with devices of different designs with a PMMA optical Table 43.2: Keratoprosthesis design
core developed by Moroz and Yakimenko.29,30 Yet another
Type I Type II
approach exists using a hydrogel sheet with porous edges to serve
as an artificial cornea. Originally called the Chirila Front plate diameter 5.0 – 6.0 mm 7.0 mm
keratoprosthesis, the core-and-skirt device is now known as the Back plate diameter 7.0 – 8.5 mm 8.5 mm
Stem diameter 3.35 mm 3.35 mm
AlphaCor. It is implanted intrastromally and covered by a
Inter plate distance 0.6 mm 0.6 mm
conjunctival flap. The center of the device is exposed later.31 Holes (8) 1.3 mm 1.5 mm
Many small-scale efforts, some ingenious, such as the Seoul- Anterior-posterior length 3.7 mm 4.7 mm
type keratoprosthesis, are also currently under way.32 Visual field 60 degrees 40 degrees

318
INDICATIONS AND PROGNOSTIC CATEGORIES

Keratoprosthesis is a procedure in evolution, and because the


outcome of keratoprosthesis surgery differs markedly among
various corneal diseases, the indication for such surgery should
be categorized accordingly. In general, some criteria must be
fulfilled before qualifying for the procedure. First, end-stage
retinal, optic nerve disease or end-stage phthisis constitutes a

Chapter 43: Boston Keratoprosthesis


contraindication. Second, monocular status, young age, or poor
general health should be taken into consideration since they raise
more concern. In patients with bilateral involvement who have
little or no chance of success with a standard penetrating
keratoplasty, the only hope lies in a keratoprosthesis. Whether a
procedure is advisable is dependent not only on the affecting
condition but also on the experience and time commitment of
the surgeon. This said, guidelines can be suggested.
One of the principles that we have recognized is that among
diagnostic categories, there exists a prognostic hierarchy.37 This
begins with repeat graft failure patients, including those with a
diagnosis of HSV; these patients tend to fare best. Patients having
sustained chemical burns, in whom glaucoma is perhaps the most
important long-term complication, are more difficult. Finally, the
autoimmune and inflammatory diseases such as Stevens-Johnson
syndrome and ocular cicatricial pemphigoid have the worst
prognosis with any surgical intervention, including
keratoprosthesis surgery (Table 43.3).
The most risky category is Stevens-Johnson syndrome. These
patients are often young, occasionally monocular, but in
desperate need of a keratoprosthesis that must remain
Figures 43.1A and B: Designs of keratoprosthesis. (A) Type I, complication-free for many years. Stevens-Johnson patients
Collar button shaped device used in eyes with adequate tear should be approached with caution, as this is a difficult goal to
secretion and blink mechanism, (B) Type II, Device with an added
achieve. They have ongoing ocular inflammation increasing the
nub for through the lid placement in end-stage dry eyes
rate of complications postoperatively. Patients with ocular
cicatricial pemphigoid are usually older, a characteristic that
works in their favor because an eventual failure might be less
minimize a dellen effect and allow a contact lens to fit tragic than in a younger patient.38 They are nonetheless prone
comfortably over it. to postoperative skin retraction and glaucoma necessitating long-
Type II is reserved for end-stage dry eye conditions. It is term follow-up.
similar to keratoprosthesis type I except that it has a 2 mm long Chemical burn patients can have good results after
anterior nub designed to penetrate the skin. It is believed that if keratoprosthesis surgery. These patients seemingly have fragile
the prosthesis is allowed to protrude through the skin, safety is retinas making them susceptible to retinal detachment but this
enhanced and the extrusion rate is consequently reduced. should not be considered a contraindication to surgery. A
Optically, both types of devices are manufactured with a simultaneous glaucoma shunt procedure is often recommended
range of dioptric powers allowing selection to approximately fit because the incidence of long-term glaucoma is extremely high.39
the axial length of the patient’s eye. They are prepared for Contrary to the previous categories with history of
pseudophakia and aphakia in case the IOL or the natural lens is inflammation, keratoprostheses for graft failure with
removed.
Considerable modifications have been made over the years
Table 43.3: Keratoprosthesis prognostic
to various keratoprosthesis designs, but whether an ideal
categories from best to worst
keratoprosthesis can ever be designed that will integrate into the
human cornea without risk of extrusion or necrosis has yet to be 1. Noninflammatory conditions: graft failure, dystrophies
determined. In recent years, more attention has been directed at 2. Infectious: HSV, HZV, bacterial and fungal ulcers
the prevention and treatment of some of the complications 3. Chemical burns
common to virtually all types of keratoprosthesis surgery, helping 4. Autoimmune: Ocular cicatricial pemphigoid, Stevens-
Johnson syndrome, rheumatoid arthritis
in the retention of keratoprosthesis.
319
non-inflammatory edema, dystrophies, infection and trauma often A standard visual field test is rarely applicable in these cases;
do very well.40 Blink mechanism and tear secretion are usually alternatively gross projection of a strong light source is useful
normal. The frequency of postoperative uveitis or medically to assess. Testing central fixation, and particularly light
uncontrollable glaucoma is low, and good vision is restored projection nasally is often helpful. If nasal projection is lost, end-
rapidly, more rapidly than after a successful regraft. stage glaucoma must be suspected.
Because the long-term retention of visual acuity and the
integrity of the eye are critical end-points in assessing traditional Intraocular Pressure
Section VI: Alternatives to Penetrating Keratoplasty

grafts, the importance of the concept of Kaplan Meier survival/


Severe corneal damage often makes exact intraocular pressure
life table analysis in reviewing the success and failure of measurements impossible and precludes view of the optic nerve.
keratoprosthesis and its alternative procedures cannot be
Recording intraocular pressure can be fraught with error. Usually
overemphasized. Although keratoprosthesis retention has
in severe corneal pathology, pneumotonometry is more reliable
traditionally been a significant barrier to the long-term success that the applanation technique but both can give grossly
of such devices, today’s reality is much more encouraging
erroneous readings. Simple digital palpation, even if imprecise,
(Fig. 43.2).
is frequently the most dependable approach.

Patient Evaluation Blink Rate and Tear Secretion


History On examination, blink mechanism and tear secretion are
Taking a detailed history of the ocular condition, as well as any important factors in assessing keratoprosthesis prognosis.
important systemic disease is mandatory. This usually reveals Evaporative damage to the corneal tissue around a
the underlying cause of the corneal condition whether traumatic, keratoprosthesis can be detrimental especially if a soft contact
surgical or inflammatory in nature. Duration of symptoms, lens cannot be retained. Blink rate and completeness can be
laterality of the condition, its episodic or progressive course can estimated when the patient does not feel observed.
be elicited. Details and dates of previous surgery (keratoplasty, Lagophthalmos and frank chronic exposure are extremely
cataract extraction, glaucoma shunt, retina repair, etc.) should important to recognize. Tear secretion should be measured with
be solicited. History of glaucoma is particularly important in Schirmer’s test. Finally, tear break-up time may be valuable in
predicting outcome, especially following chemical burns. assessing the health of the ocular surface.

Visual Acuity Slit-lamp Examination

Visual acuity should be recorded in the standard fashion using a This step of the evaluation is the cornerstone of the patient
Snellen chart. Relative contributions of the cornea, cataract, evaluation. Eyelids should be inspected for marginal
retina, or optic nerve are difficult to ascribe in eyes so severely incongruities. Conjunctival inflammation, surface keratinization,
damaged that keratoprosthesis is a necessity. If the corneal and fornix foreshortening or symblephara should be noted. The
surface is highly irregular in the presence of only moderate corneal surface should be examined for irregularity, keratini-
stromal opacities, hard contact lens refraction can be revealing. zation, epithelial defects, and subepithelial vascularization.
Stromal opacity from scarring or edema, as well as, deep
vascularization should be evaluated. Anterior chamber depth and
reaction, and the status of the iris, pupil and lens (or intraocular
lens) all merit detailed notes. The fundus is often not observable
in keratoprosthesis candidates, but when possible, an effort
should be made to examine disk cupping and macular changes.
Disk cupping has high prognostic importance and may dictate
aqueous shunt implantation. Gross changes in the posterior pole,
such as massive age-related macular degeneration are vital to
observe. Special attention should be given to signs of
inflammation throughout the examination as its presence
influences the prognosis of keratoprosthesis surgery.

Special Examinations
Ultrasound examination is necessary in most cases. B-scan can
reveal a retinal detachment or massive debris behind an opaque
Figure 43.2: Graph demonstrating the retention of Boston
cornea or lens but it cannot measure glaucomatous optic nerve
Keratoprosthesis without surgical revision or replacements in non-
autoimmune and non-severe chemical burns. (Aquavella, Sippel cupping with precision. If a glaucoma shunt has been implanted
and Dohlman, unpublished) previously, B-scan can identify a fluid cleft over the shunt plate.
320
This indicates patency of the tube shunt, however, it does not complicated surgery, but also a closer life-long follow-up
rule out the presence of a dense capsule that has formed around regimen and more frequent revisions.
the plate obstructing flow and causing high intraocular pressure.
In addition, a B-scan can reveal the presence or absence of an BOSTON KERATOPROSTHESIS SURGERY
intraocular lens. A-scan measurement of the axial length of the
In this section, our surgical technique and postoperative
eye is also required for proper selection of a keratoprosthesis
regimens, the only approach we have personal experience with,
with the correct dioptric power in aphakic eyes.
will be described in some detail. This technique has been

Chapter 43: Boston Keratoprosthesis


In our experience, Electroretinography and Visual Evoked
developed over a number of years, with modifications and
Response have not been very helpful in keratoprosthesis
adjustments to improve the postoperative outcome.
preoperative evaluation. They can give falsely negative results,
leading to the conclusion that the situation is more hopeless than
Materials
it actually is.
In preparation for the operation, the following items must be
Documentation available:
1. Keratoprosthesis type I or II, with a suitable dioptric power
Pre- and postoperative external photography and detailed
for the axial length and intraocular lens status of the patient’s
drawings of the eyes help document baseline and allow
eye (Massachusetts Eye and ear Infirmary, Boston, MA)
assessment of progress and outcome of the surgery.
2. Donor cornea in storage solution, requested from the local
Eye Bank. In geographical areas where, availability and
Patient Selection
pricing precludes a fresh donor cornea, the patient’s own
If a standard corneal transplant has a good chance of giving cornea may be used.
longstanding vision, this would be the preferred technique. 3. Troutman punch device (Pilling Weck Surgical, Ft.
However, if one or more graft failures occur within months after Washington, PA)
surgery, bringing down vision to finger counting or less, a 4. Trephine blades 8.5 mm and 8.0 mm (Storz # E3096 L) as
keratoprosthesis may be considered. well as 3.0 mm punch (Accuderm Inc., Ft. Lauderdale, FL)
5. Hessberg-Barron vacuum trephine (Barron Precision
Keratoprosthesis Type I Instruments, 1LC, Grand Blanc, MI)
6. Trephine handle, universal (Storz # E3095)
Keratoprosthesis type I is indicated in the noninflammatory graft
7. Adhesive patch and spanner wrench to facilitate the
failure group where, blink and tear mechanisms are reasonably
keratoprosthesis assembly (included in the keratoprosthesis
normal and visual acuity is less than 20/400. As well, the status
package) (JG Machine Co, Woburn, MA)
of the fellow eye must be factored in. The opposite eye should
8. Irrigation/aspiration unit, vitrector and light pipe
have suboptimal vision, such as 20/100 or less. Furthermore, the
9. Standard keratoplasty instrument set
age of the patient is a consideration. If the long-term survival of
10. Fine bipolar cautery
the keratoprosthesis is questionable, it follows that elderly
11. Plano soft contact lens (Kontur lens, Kontur Kontact Lens
patients have a greater chance of trouble-free course than
Co., Richmond, CA, 16.0 mm diameter, 9.8 mm base curve)
younger patients.
12. Video (optional)
Patients with heavy exposure to evaporative forces may still
13. If needed, glaucoma valve shunt and Tutoplast (Ahmed shunt
be candidates for the procedure but would need extensive
S-2, New World Medical Inc., Rancho Cucamonga, CA).
tarsorraphy and other lid reconstruction in order to avoid
exposure of the surrounding tissues, limiting it to the PMMA
Preoperative Physical Evaluation
surface.
Experience with type I has shown that the prognosis for good Standard preoperative general medical assessment is done a few
outcome is better in eyes that have experienced little intraocular days before the surgery. The anesthesia can be general or local
inflammation in the past. Therefore, failed grafts, corneal (retrobulbar and lid block). Since the keratoprosthesis operation
opacities or edema, dystrophies, degenerations, post-surgical or usually takes longer than standard keratoplasty, we prefer general
traumatic, bacterial or fungal infections comprise a group with anesthesia when safe. Intravenous antibiotic at the start of surgery
good five-year prognosis in keratoprosthesis surgery.37 A history is recommended (Ancef 1.0 mg, if no allergy).
of herpetic keratitis may bring down the outlook somewhat.40
Type I
Keratoprosthesis Type II
Type I keratoprosthesis is incorporated into a fresh corneal graft
Keratoprosthesis type II is preferable in end-stage dry eyes, as or the patient’s cornea, which is then sutured into the host eye
observed in ocular cicatricial pemphigoid, Stevens-Johnson in the standard manner (Fig. 43.3). The donor cornea is usually
syndrome and chemical burns.38 This involves not only more trephined with an 8.5 diameter blade. With a 3.0 mm punch, a

321
procedure. In more extreme situations of exposure, radical lateral
and medial permanent tarsorraphies may have to be performed
to cover the entire ocular surface allowing only the plastic to be
exposed (Fig. 43.4).

Type II
The insertion of type II keratoprosthesis into an end-stage dry
Section VI: Alternatives to Penetrating Keratoplasty

eye is more complicated and time consuming. The


keratoprosthesis is implanted in such a way that the nub is
allowed to protrude through the closed lids, a principle
introduced by Cardona and Devoe.41 The fornices are cleaved
to allow for the implantation of the graft with a keratoprosthesis
type II. Then a central small notch is made in the upper lid. A
tight permanent tarsorhaphy is made on both sides of the
protruding nub. The rest of the surgery is similar to that described
Figure 43.3: Assembly of a type I keratoprosthesis above for type I. Implantation of a glaucoma shunt preferably
an Ahmed valve shunt is virtually essential in this category of
central hole is made, allowing the graft to be subsequently slid patients.39
over the keratoprosthesis stem. The back plate is then screwed
on and the graft-prosthesis is now ready to be transferred to the Postoperative Care
patient. The preliminary maneuvers are best carried out on a Follow-up visits should be individualized but typically patients
separate side table. are seen after 1 day, 1 week, 3 weeks, and then monthly during
Attention is then turned to the patient’s eye. With a trephine the first year. It is prudent to share the postoperative
0.5 mm smaller diameter than the prepared graft, usually 8.0 mm, responsibility with a glaucoma colleague (Fig. 43.5).
the patient’s cornea is trephined halfway through. Bleeding
vessels are cauterized. Occasionally, a glaucoma tube shunt is Type I
indicated, and the preferred moment for the insertion of the tube
Prophylactic antibiotic after surgery must be maintained
into the anterior chamber is before the eye is opened. With the
indefinitely. Excluding patients with autoimmune diseases or
tube in place, the trephine wound is perforated and the corneal
severe chemical burns, it seems adequate to treat patients with a
button is excised in the normal fashion. If the iris is in place, it
fourth generation fluoroquinolone initially four times a day, then
is usually not removed because this would allow excessive
rapidly decreasing to once daily for life. To be doubly sure in
scattered light to enter the eye and cause severe glare, entailing
preventing endophthalmitis, we give, in addition, Vancomycin
the need of tinted contact lens or dark sunglasses. The intraocular
14 mg/ml with benzalkonium once daily for life. Compliance
lens may or may not be removed or the natural lens is removed
should be stressed. Systemic antibiotics are recommended, such
by extracapsular extraction leaving the posterior capsule intact.
as cephalexin 500 mg two to three times a day for a week after
If vitreous is exposed, a deep core vitrectomy is advised.
the surgery, unless penicillin allergy dictates a substitute.
Preventing blood from reaching the vitreous is of utmost
Corticosteroid drops usually as prednisolone acetate 1
importance during these maneuvers.
percent are given four times a day for some time, occasionally
The graft-prosthesis combination is now placed into the
extended with lower doses for a year or two depending on the
trephinated opening and is sutured in place with 16 10-0 nylon
presence of postoperative inflammation and glaucoma.
sutures, with the knots buried after which a soft contact lens
The intraocular pressure is difficult to measure since
(Kontur 16.0 mm, 9.8 mm base curve) is applied. Antibiotic
essentially only finger palpation is possible. Disk appearance and
drops are administered at the end of the surgery.
visual field must be followed frequently. Topical glaucoma
In brief, after the assembly is sutured into place, a bandage
medications can penetrate into the eye despite the plastic barrier
contact lens is positioned over it to retard the effects of
albeit slower than normal. Oral carbonic anhydrase inhibitors
dehydration and minimize the dellen effect of the
have the usual effect.
keratoprosthesis, thus potentially preventing necrosis and corneal
In cases of herpes simplex, addition of systemic antivirals
melt of the donor tissue, an effect that can also be achieved by
(acyclovir 400 mg twice a day) is recommended on a permanent
an overlying conjunctival graft. The lens seems to diffuse the
basis.
osmotic forces evenly, allowing the surface epithelium to remain
well hydrated. We prefer to keep a soft contact lens on the eye
Type II
indefinitely, with occasional cleaning or replacement when lost.
In countries where, contact lenses are not readily available, it is Sustained postoperative prophylactic antibiotics are even more
advisable to perform a total conjunctival flap during the surgical important after type II than type I. We now use topical
322
Chapter 43: Boston Keratoprosthesis
Figures 43.4A to E: Surgical steps of Boston keratoprosthesis
surgery. (A) A 3 mm central opening is punched out in a large
corneal graft, (B) The stem of the mushroom shaped front plate
passes through the trephinated 3 mm central opening, (C) The
posterior plate then screws onto the exposed threads of the stem
tightly to sandwich the cornea between the front and back plates,
(D) and (E) A locking ring is added. The graft - keratoprosthesis
combination, seen from the posterior surface, is now ready to be
sutured in place like a standard transplant

vancomycin 1.4 percent in addition to the standard the first few months, depending on the degree of intraocular
fluoroquinolone no less than twice daily.42,43 The drops are reaction. Topically administered steroids do not reach the inside
administered on an indefinite basis to the crevice around the nub. of the eye, and systemic administration has a less favorable risk-
Since the institution of this prophylactic treatment, we have not benefit than subtenon delivery.
had any bacterial endophthalmitis among our patients which from In keratoprosthesis type II, oral carbonic anhydrase inhibitor
past experience tends to be secondary to Gram-positive is the only available medical treatment for elevated intraocular
organisms. pressure.
Corticosteroids in high doses are essential during the first Retraction of the skin away from the protruding nub can be
postoperative month to abate prolonged intraocular inflammation a setback. Therefore, during the last decade we occasionally have
common in patients requiring a type II keratoprosthesis. added medroxyprogesterone 1 percent suspension twice daily
Subtenon injection of 40 mg triamcinolone is recommended a to our regimen. This drug reduces wound necrosis and melt, most
few days after surgery and repeated every 2 to 3 weeks during likely due to suppression of collagenase synthesis. The clinical
323
Section VI: Alternatives to Penetrating Keratoplasty

Figures 43.5A to D: Successful implantation of type I and type II keratoprosthesis. (A) Eye with Lattice dystrophy and repeated
graft failures, (B) Same patient 10 years after keratoprosthesis type I insertion with a conjunctival flap. Vision is 20/20, (C) Example
of a keratoprosthesis type II in a patient who sustained a severe chemical burn, (D) Closer view of type II keratoprosthesis

Figures 43.6A and B: Keratoprosthesis complications. (A) Retroprosthetic membrane,


(B) Beginning skin retraction around the nub in type II

impression of this drug effect has been favorable.44 Topical loss of the eye (Table 43.4). During the last few decades,
tetracycline 1 percent suspension, a direct collagenase inhibitor, however, thanks to the work of several groups of surgeons and
has been less helpful. investigators, the picture has been much brighter. In most cases,
the severe complications are seen within the first year after
Complications surgery; however, the patient is never safe from potential
In past times, primarily tissue necrosis around the device, complications and requires frequent and close monitoring
extrusion, and/or endophthalmitis ended the effort, often with (Fig. 43.6).
324
and hypotony. A new keratoprosthesis in a new fresh graft should
be implanted and protected by a soft contact lens.
In type II keratoprosthesis, skin can retract away from the
nub secondary to evaporative damage of the skin edge and is
hard to avert. Medroxyprogesterone 1.0 percent suspension,
applied topically around the nub twice daily has a preventive
role. Skin revision is advisable when skin retracts to the edge of

Chapter 43: Boston Keratoprosthesis


the front plate. A new keratoprosthesis in a new fresh graft is
recommended if a leak occurs.45

Soft Contact Lens Loss


Addition of a soft contact lens after keratoprosthesis type I
surgery and its retention or replacement for an indefinite time
has added a remarkable benefit to the health of the tissue around
the device. Without a soft contact lens, evaporation and irregular
drying of corneal tissue around the double-plated
keratoprosthesis can be a disturbing problem. Drying, dellen
formation, epithelial defects, and stromal thinning can occur with
long-term undesirable consequences. However, the hydrophilic
soft contact lens worn around the clock has been found to be
highly protective. The lens seems to diffuse evaporative forces
well and to allow better hydration. 46 At times, inadvertent loss
of the lens requires replacement adding to the overall costs
(Figs 43.7 and 43.8).

Inflammation
In autoimmune diseases such as ocular cicatricial pemphigoid,
Figures 43.7A and B: Therapeutic effect of soft contact lenses Stevens-Johnson syndrome, graft-versus-host disease, a chronic
with Boston Keratoprosthesis: protection of the ocular surface low-grade intraocular inflammation complicates the course.
and promotion of healthy hydrated tissue. (A) Before SCL wear, Consequently, a retroprosthetic membrane, epiretinal membrane,
the ocular surface is dry, desiccated and thinned, (B) After SCL and angle closure glaucoma may supervene. Corticosteroids are
wear, the eye looks rehydrated, rejuvenated, and wet
the standard treatment to suppress such developments. In type I
keratoprosthesis, topical prednisolone drops are routine,
sometimes augmented by peribulbar/subtenon injections of
Table 43.4: Most significant keratoprosthesis triamcinonlone. Systemic steroids are used less commonly
complications because of less favorable risk-benefit ratio. After type II surgery,
1. Glaucoma drops cannot reach the anterior chamber, and therefore
2. Tissue necrosis - if unchecked: leak, infection, extrusion peribulbar/subtenon injections or systemic steroids are the only
a. Melts in type I (rare) means to influence intraocular events.
b. Skin retraction in type II
3. Postoperative uveitis Retroprosthetic Membrane
a. Retroprosthetic membrane
b. Vitreous opacities Intraocular inflammation postkeratoprosthesis surgery can be
c. Epiretinal membrane prolonged and severe in autoimmune eyes. This frequently leads
4. Retinal detachment to a retroprosthetic membrane with a severe decline in vision.
5. Endophthalmitis (now rare)
Repeated steroid injections (triamcinolone) are indicated at the
first sign of such a membrane formation. Once formed, it is
worthwhile to open the membrane with Nd:YAG laser before it
becomes too thick or vascularized.47 Laser pulses with energy
Tissue Necrosis and Melt
above 3.0 mJ are inadvisable because they can crack or
Tissue necrosis and subsequent melt are now rare with type I pockmark the plastic. If the membrane becomes thick, leathery
keratoprosthesis. Adding holes to the back plate has improved and particularly if vascularized, a closed vitrectomy under high
nutrition and hydration to the overlying corneal tissue. Prompt infusion pressure and membranectomy are required to restore
intervention is wise should the melt occur with a consequent leak vision.48
325
Section VI: Alternatives to Penetrating Keratoplasty

Figures 43.8A to D: Cosmetic advantage of soft contact lenses with Boston keratoprosthesis. (A) Successful implantation of
Boston Keratoprosthesis type I in a traumatized eye following three failed penetrating keratoplasties, (B) Same eye fitted with
Kontur Kontact lens Occluder Iris to diminish symptoms of glare and photophobia. Cosmetic appearance is less than optimal,
(C) Soft contact lens painted by Adventures in color to perfectly match the iris color of the normal left eye, (D) Cosmetic appearance
is improved, symptoms are reduced, and visual acuity is 20/50

Infectious Endophthalmitis accompanying pain, tenderness, or redness. Bacteria are usually


not isolated in these cases. Still, these patients might be treated
This is the ultimate disaster after keratoprothesis surgery. Vision
for suspected bacterial endophthalmitis. Within a few weeks, or
can be lost permanently within hours. Even in recent times,
months, the vitreous clears and the vision returns back to the
endophthalmitis might occur in Stevens-Johnson syndrome and
baseline level prior to the event. We speculate that it is a sterile
ocular cicatricial pemphigoid. In our experience, the infectious
immune reaction. Had the reaction been due to bacterial
agents have all been gram-positive organisms. However, bacterial
infection, most of the vision would have been wiped out.49
endophthalmitis has been nearly eliminated with adherence to
the regimen of antibiotic prophylaxis of vancomycin and a
fluoroquinolone.42,43 It is extremely important to impress upon Glaucoma
the patient that meticulous compliance for life is mandatory. With the drastic reduction in endophthalmitis, glaucoma is now
Should an endophthalmitis still occur, immediate tap and inject the most serious complication after keratoprosthesis surgery. Its
are crucial. An aqueous tap via the limbus for smear and culture pathogenesis is probably multifactorial, but gradual closure of
and an injection of 1.0 mg vancomycin, 0.4 mg amikacin, and the anterior chamber angle is the most likely cause of marked
0.4 mg dexamethasone are performed. The patient is hospitalized aggravation of intraocular pressure. It is therefore, vital to
for topical and intravenous antibiotics. A vitrectomy may be monitor the intraocular pressure and nerve damage
deemed necessary later. postoperatively. Tonometers are useless in this setting and digital
palpation of the globe is the main method available to ascertain
Sterile Uveitis – Vitritis
a rough estimate of intraocular pressure. Glaucoma drops are
A sudden massive vitritis has been observed in a few patients effective only in keratoprosthesis type I but not type II. Oral
with reduction of vision to hand motion. This vitritis carbonic anhydrase inhibitors have side effects and should be
masquerades as an infectious endophthalmitis with no used with caution in patients with Stevens-Johnson syndrome,
326
and completely avoided in patients with sulfa allergy. Since 4. Price FW Jr, Whitson WE, Collins KS, et al. Five-year corneal
medical control of glaucoma is often insufficient, an Ahmed graft survival. A large, single-center patient cohort. Arch
valve shunt is indicated at the time of the keratoprosthesis in Ophthalmol 1993;111:799-805.
5. Bersudsky V, Blum-Hareuveni T, Rehany U, et al. The profile of
autoimmune diseases, chemical burns, and in patients with pre-
repeated corneal transplantation. Ophthalmology 2001;108:461–
existing glaucoma.38,39 69.
6. Patel NP, Kim T, Rapuano CJ, et al. Indications for and outcomes
Retinal Detachment of repeat penetrating keratoplasty, 1989-1995. Ophthalmology

Chapter 43: Boston Keratoprosthesis


2000;107:719-24.
Retinal detachment is not a common complication. It can be
7. Dandona L, Naduvilath TJ, Janarthanan M, et al. Survival analysis
rhegmatogenous or tractional in nature. It is diagnosed by direct
and visual outcome in a large series of corneal transplants in India.
visualization or by B-scan ultrasonography. Three-port port Br J Ophthalmol 1997;81:726-31.
vitrectomy is performed and a long acting gas or sometimes 8. Pellier de Quengsy G. Precis ou cours d’operation sur la chirurgie
silicone tamponade is used. The prognosis is ominous. des yeux. Paris, Didot, 1789.
9. Nussbaum N. Cornea Artificialis, ein Substitut fur die
Transplantatio Cornea. Deutsche Klinik 1853;34:367.
CONCLUSION
10. Heusser J. Die Einheilung einer Cornea artificialis. Oesterr Ztschr
In conclusion, although standard penetrating keratoplasty has an Pract Med 1860;26:424.
excellent prognosis in the noninflamed virgin eye, the prognosis 11. Dimmer F. Zwei Falle von Celluoidplattern der Hornhaut. Klin
Monatsbl Augenheilkd 1891;29:104.
for repeat keratoplasties for graft failures, especially multiple
12. Salzer F. Uber den kunstlichen Hornhautersatz. Wiesbaden, 1898.
graft failures, is relatively poor, especially considering the time 13. von Hippel A. Uber die operative Behandlung totaler stationarer
necessary for a graft to reach a stage when it can provide good Hornhaut-Trubungen. Albrecht v. Graefes Arch Clin Ophthal
visual rehabilitation. On the other hand, the device retention and 1887;23:79.
vision rehabilitation achievable with a keratoprosthesis of the 14. Verhoeff FH, cited in Cardona H. Keratoprosthesis. Am J
keratoprosthesis type I compares favorably with repeat Ophthalmol 1962;54:284.
keratoplasty for multiple graft failures in nonimmune diseases.50 15. Filatov VP. Alloplastik bei vollstandig “hoffnungslosem”
Our present preference is the double-plated (collar button) Leukomen. Soiv Viest Opht 1936;9:400.
16. Wunsche G. Versuche zur totalen Keratoplastie und zur Cornea
PMMA device with its excellent optics, stability, wide visual field
Artificialis. Arztliche Forschung 1947;1:345.
and good retention. The surgery is carried out reasonably well 17. Stone W Jr, Hebert E. Experimental study of plastic material and
but postoperative follow-up is demanding. Complications may replacement of the cornea. Preliminary report. Am J Ophthalmol
arise but have become less common through prevention, early 1953;36:168.
recognition, and appropriate management. Successful outcome 18. Castroviejo R, Cardona H, DeVoe AG. The present status of
requires considerable patient compliance with antibiotics, prosthokeratoplasty. Trans Am Ophthalmol Soc. 1969;67:207-34.
glaucoma detection, and frequent follow-up. Temporary 19. Strampelli B. Osteo-Odontokeratoprosthesis. Ann Ottalmol Clin
Ocul 1963;89:1039-44.
postoperative tissue coverage, anti-inflammatory medicine,
20. Falcinelli G, Missiroli A, Pettiti V, et al. Osteo-
glaucoma shunts are among the factors that have improved
Odontokeratoprosthesis up to date. In: Acta XXV Concilium
keratoprosthesis survival. Although the management of Ophthalmologicum. Milano: Kugler and Ghedini, 1987.
keratoprosthesis patients requires a solid long-term commitment 21. Marchi V, Ricci R, Pecorella I, et al. Osteo-odonto-
from the patient and the surgeon, the potential reward in terms keratoprosthesis. Description of surgical technique with results
of the visual rehabilitation in an otherwise hopeless clinical in 85 patients. Cornea 1994;13:125-30.
situation can truly be gratifying. 22. Temprano J. Resultados a largo plazo de Osteo-odonto-
Concurrently, several clinical groups around the world have queratoprotesis y queratoprotesis tibial. An Inst Barraquer
1998;27(Suppl):53-65.
contributed substantially to the progress in keratoprosthesis
23. Stoiber J, Csaky D, Schedle A, et al. Histopathologic findings in
surgery during the last few decades. The approach will explanted osteo-odontokeratoprosthesis. Cornea 2002;21:400-4.
undoubtedly continue to spread owing to generally rapid 24. Liu C, Herold J, Sciscio A, et al. Osteo-odonto-keratoprosthesis
rehabilitation and improving long-term outcomes. surgery. Br J Ophthalmol 1999;83:127.
25. Hille K. Keratoprothesen. Klin Aspekt. Ophthalmologe
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328
44

Chapter 44: Phototherapeutic Keratectomy


Phototherapeutic Keratectomy
Rajesh Sinha, Namrata Sharma, Jeewan S Titiyal

INTRODUCTION However, even in a thicker and denser opacity, it may reduce


the density of opacity and may improve the visual status.
Phototherapeutic keratectomy (PTK) is a technique in which
2. Retention of at least 300 µm of corneal stroma: It is very
excimer laser is used to ablate the superficial corneal tissue in
essential to retain nearly 300 µm of corneal stroma so that
order to remove superficial corneal opacities. The superficial
the cornea sustains the intraocular pressure and does not give
corneal opacities and corneal surface irregularities can be ablated
rise to corneal ectasia.
sequentially so as to achieve a uniformly smooth corneal surface.
3. Superficial, homogeneous, diffuse opacities are easier to treat
The excimer laser uses 193 nm ultraviolet rays to disrupt
than focal, deep scars.
intermolecular bonds in the cornea by a process called
4. Realistic expectations: The patient should understand the fact
“photoablative decomposition”.1 This process is athermal and
that the visual outcome after the procedure may be
works with submicroscopic precision with minimal damage to
suboptimal. The understanding of this fact is very essential
adjacent tissues.2
to attain good patient satisfaction.
INDICATIONS
METHODS
1. Reiss Buckler dystrophy
2. Salzmann’s nodular degeneration Evaluation Parameters
3. Granular dystrophy Detailed history
4. Spheroidal degeneration Best corrected visual acuity
5. Band-shaped keratopathy Detailed slit lamp biomicroscopy
6. Corneal opacity after pterygium excision involving visual Posterior segment evaluation by indirect ophthalmoscopy
axis Ultrasonography, if posterior segment not visible
Keratometry and/ or videokeratography, if possible
AIM Nine points pachymetry, if possible
1. To improve visual acuity: Superficial corneal opacity Refraction, if possible
2. Delays lamellar and penetrating keratoplasty
As this procedure removes the superficial layers of cornea, Anesthesia
it either removes a corneal opacity or it may reduce the density The procedure is performed under topical anesthesia.
of a corneal opacity. In both the situation, there is improvement Proparacaine 0.5 percent is instilled every 5 minutes for 3 times
in the visual acuity of the patient. Hence, it may reduce the before the start of the procedure.
number of patients requiring lamellar keratoplasty or it may help
in delaying the need of lamellar or penetrating keratoplasty, Preparation of the Eye
thereby reducing the burden on eye banking facilities.
The procedure is performed with the patient in the supine
position. The eye and the periocular area are cleaned with
GUIDELINES FOR PATIENT SELECTION
povidone iodine 5 percent. The eye is draped and a speculum is
1. Depth of opacity < 100 µm: In order to achieve good clarity placed to retract the eyelids and expose the cornea and the ocular
of cornea, the depth of opacity should be less than 100 µm. surface.

329
Surgical Technique Step 2: Ablation of the Superficial Corneal Tissue
After removal of the corneal epithelium, the corneal surface is
Step 1: Removal of Corneal Epithelium
subjected to ablation by excimer laser (Fig. 44.4). The ablation
The corneal epithelium is usually removed manually with a diameter is usually kept at 6.0 mm. The amount of ablation
hockey stick spatula (Fig. 44.1). Sometimes the epithelium is depends upon the depth of the corneal opacity. It is usually kept
very tightly adherent to the underlying stroma, more so due to between 50 to 100 microns. Less than 50 microns ablation does
the superficial stromal scarring. In these conditions, it is difficult not produce the desired effect in most of the cases and greater
Section VI: Alternatives to Penetrating Keratoplasty

and time consuming to remove the corneal epithelium. In such than 100 microns of ablation results in formation of a
situations, one can use 20 percent alcohol in an alcohol well- subepithelial haze in the late postoperative period. In eyes with
placed over the cornea for 25 seconds to loosen the epithelial- irregular surface, coupling fluid (Fig. 44.5) may be used to spare
stromal adherence and strip off the epithelium easily (Fig. 44.2). the depressions and ablate the elevations so as to achieve a
Some surgeons have used excimer laser for removing the corneal smooth surface. In cases of Salzmann nodular degeneration,
epithelium3 in eyes with smooth epithelium and presence of manual keratectomy is performed to remove the nodule and
subepithelial opacities. ablation is performed using coupling fluid.
In certain conditions like Salzmann nodular degeneration, If the surgeon feels that the ablation is not enough and the
the nodules are also manually removed with the hockey stick opacity has not been removed adequately, retreatment can be
spatula or the lamellar dissector (Fig. 44.3). The surface after performed. However, care must be taken not to ablate beyond
this manual keratectomy is subjected to excimer laser ablation. 100 microns so as to prevent the occurrence of subepithelial haze.

Figure 44.1: Corneal epithelium being removed manually with Figure 44.3: Manual keratectomy to remove the nodules in
a hockey stick spatula Salzmann degeneration

Figure 44.2: Alcohol assisted corneal epithelial removal Figure 44.4: Corneal surface ablation by excimer laser
330
Chapter 44: Phototherapeutic Keratectomy
Figure 44.5: Coupling fluid being used for ablating the Figure 44.6: Bandage contact lens placed over the cornea
elevated areas after completion of ablation

During ablation, the patients are asked to fixate on coaxial Studies have shown an improvement of 47 to 78 percent in BCVA
red and green target lights within the delivery system positioned with PTK.6,8 In a series of 26 patients with anterior corneal
above the patient’s head and the eye-tracking system is kept on. pathology, Hersh et al have reported improved uncorrected and
However, if the opacity is too dense, and the patient is unable to best-corrected visual acuity in 20 eyes following excimer PTK.
maintain appropriate fixation, the eye-tracker is put off. Loss of 2 lines of BCVA occurred in 2 eyes and 2 eyes required
penetrating keratoplasty. The average refractive shift in this series
Step 3: Placement of Bandage Contact Lens was +1.4D.9 The Summit PRK Study group has reported results
of PTK for corneal visual loss in 232 eyes with one year follow-
Once, the ablation is complete, a therapeutic contact lens is
up. In a subgroup (103 eyes) in this study, BCVA improved in
placed on the eye (Fig. 44.6) and one drop of moxifloxacin 0.5
46 (45%) eyes and 9 (9%) eyes lost 2 or more lines. The average
percent eye drops is instilled in the eye.
improvement in BCVA was 1.6 lines and the mean refractive
shift was + 0.87D.10
Postoperative Evaluation and Treatment
Phototherapeutic keratectomy has been shown to be effective
The patient is examined immediately after the procedure. The and safe in improving visual acuity in clinical entities like
patient is prescribed moxifloxacin 0.5 percent eye drops TID Salzmann nodular degeneration11 (Figs 44.7 and 44.8), any
for 2 weeks, fluorometholone acetate 0.1 percent eye drops TID superficial corneal opacity12, Reiss-Buckler dystrophy13 (Figs
for 2 weeks and 0.5 percent carboxymethylcellulose eye drops 44.9 and 44.10), Granular dystrophy (Figs 44.11 and 44.12) and
QID for 6 months. Some surgeons start topical steroid only after recurrence of a granular dystrophy in a corneal graft,14 residual
complete epithelial healing. corneal opacity after pterygium surgery, band-shaped keratopathy
(Figs 44.13 and 44.14), anterior corneal dystrophies, and scars
Follow-up after injuries.15,16 It has been shown to be an effective procedure
to delay or avoid the requirement of penetrating or lamellar
The patients are followed up on Day 1, Day 5, Day 7, 1 month,
keratoplasty in corneal disorders.17,18 It is a minimally invasive
3 months and depending upon the requirement thereafter. The
technique that results in improvement of visual acuity
bandage contact lens is removed after complete epithelial
significantly in many clinical entities. Hence, the patient may
healing. Most of the patients show complete epithelial healing
not require a keratoplasty which is quite invasive and also carries
on Day 5 and nearly all by Day 7.
the risk of rejection and failure due to causes other than rejection
as well. However, in some situations, the visual improvement
OUTCOME
may not be as good as a keratoplasty. In such conditions a
Phototherapeutic keratectomy has been used in the management keratoplasty may be done later as a definitive procedure to
of many clinical entities and has been reported to be a safe and provide better visual recovery. In these cases, the PTK may act
effective procedure in selected superficial corneal scars that as an interim procedure to provide some visual improvement.
might otherwise need keratoplasty.4-7 The efficacy of PTK is In condition like band shaped keratopathy following a
evaluated by improvement in BCVA comparable with results of vitreoretinal surgery, the procedure makes the cornea clearer so
lamellar and penetrating keratoplasty in a similar situation.8 that a retinal evaluation can be performed properly.

331
Section VI: Alternatives to Penetrating Keratoplasty

Figure 44.7: Salzmann nodular degeneration Figure 44.8: Clear cornea in Salzmann nodular degeneration
after PTK

Figure 44.9: Reiss-Buckler dystrophy Figure 44.10: Clear cornea in Reiss-Buckler dystrophy after PTK

Figure 44.11: Granular dystrophy Figure 44.12: Clear cornea in granular dystrophy after PTK

332
Chapter 44: Phototherapeutic Keratectomy
Figure 44.13: Band-shaped keratopathy Figure 44.14: Clear cornea in band-shaped
keretopathy after PTK

COMPLICATIONS REFERENCES

1. Hyperopic shift: Due to the central corneal ablation there is 1. Wu WCS, Stark WJ, Green WR. Corneal wound healing after
some amount of flattening of the central cornea resulting in 193 nm excimer laser keratectomy. Arch Ophthalmol
hyperopic shift in the refractive staus.19 A shallow ablation 1991;109:1426-32.
depth (less than 100 microns), and use of a masking agent 2. Marshall J, Trokel SJ, Rothery S, Krueger RR. Long-term healing
decrease the hyperopic shift significantly. of the central cornea after photorefractive keratectomy using an
2. Corneal haze: Subepithelial corneal haze may be seen due excimer laser. Ophthalmology 1988;95:1411-21.
to deep stromal ablation. 3. Rao SK, Fogla R, Seethalakshmi G, Padmanabhan P. Excimer
laser phototherapeutic keratectomy: Indications, results and its
3. Glare: Night time glare and photic phenomenon may be seen
role in the Indian scenario. Indian J Ophthalmol 1999;47:167-
in some cases as in any other excimer laser refractive 72.
procedure.
4. Starr M, Donnenfeld E, Newton M, Tostanoski J, Muller J, Odrich
4. Myopic shift: Myopic shift after PTK is usually rare and it M. Excimer laser phototherapeutic keratectomy. Cornea
may be due to accumulation of plume in the central part of 1996;15:557-65.
the cornea and in some situations where the ablation is done 5. Gaster RN, Binder PS, Coalwell K, Berns M, McCord RL,
in the peripheral part of the cornea in order to remove a Burstein NL. Corneal surface ablation by 193 nm excimer laser
peripheral corneal opacity. and wound healing in rabbits. Invest Ophthalmol Vis Sci
5. Infection: Infectious keratitis may be seen rarely. The eye is 1989;30:90.
predisposed to infection by the ocular commensals due to 6. Steinert RF, Puliafito CA. Excimer laser phototherapeutic
presence of epithelial defect and use of therapeutic contact keratectomy for a corneal nodule. Refract Corneal Surg
1990;6:352.
lens.
7. Saini JS, Reddy MK, Jain AK, Ravindra MS, Jhaveria S,
6. Recurrence of the original pathology: Recurrence of a corneal
Raghuram L. Perspectives in eye banking. Ind J Ophthalmol
dystrophy like Reiss-Buckler or a granular dystrophy may
1996;44:47-55.
be seen. This may be treated by a reablation;13 however, some
8. Stark WJ, Charmon W, Kamp MT, Enger CL, Rencs EV, Gottsch
cases may require a keratoplasty. JD. Clinical follow-up of 193 nm ArF excimer laser
phototherapeutic keratectomy. Ophthalmology 1992:99:805-12.
CONCLUSION 9. Hersh PS, Burnstein Y, Carr J, Etwane G, Mayers M. Excimer
laser phototherapeutic keratectomy. Surgical strategies and clinical
Phototherapeutic keratectomy is a useful and satisfying
outcomes. Ophthalmology 1996;103:1210-22.
procedure provided its limitations are understood. It may provide
10. Maloney RK, Thompson V, Ghiselli G, Durrie D, Waring GO III,
visual improvement in many superficial corneal disorders. This
O’Connell M, and the Summit Phototherapeutic Keratectomy
may reduce the requirement of keratoplasty in some cases, Study Group. A prospective multicenter trial of excimer laser
thereby reducing the load on the eye bank. However, in some phototherapeutic keratectomy for corneal visual loss. Am J
conditions, the visual improvement may not be optimal. In these Ophthalmol 1996;122:149-60.
conditions, the procedure may provide some visual improvement 11. Das S, Langenbucher A, Pogorelov P, Link B, Seitz B. Long-
and a definitive keratoplasty may be performed at a later date. term outcome of excimer laser phototherapeutic keratectomy for

333
treatment of Salzmann’s nodular degeneration. J Cataract Refract 16. Kozobolis VP, Siganos DS, Meladakis GS, Pallikaris IG. Excimer
Surg 2005;31:1386-91. laser phototherapeutic keratectomy for corneal opacities and
12. Amano S, Oshika T, Tazawa Y, Tsuru T. Long-term follow-up of recurrent erosion. J Refract Surg 1996;12:S288-90.
excimer laser phototherapeutic keratectomy. Jpn J Ophthalmol 17. Nagy ZZ, Süveges I, Németh J, Füst A. Phototherapeutic use of
1999;43:513-16. excimer laser. Orv Hetil 1996;14:137:75-78.
13. el Aouni A, Briat B, Mayer F, Saragoussi JJ, Abenhaim A, 18. Forster W, Grewe S, Busse H. Clinical use of the excimer laser
Assouline M, David T, Pouliquen Y, Renard G. Reis-Buckler in treatment of surface corneal opacities—therapeutic strategy and
dystrophy: therapeutic photoablation with the excimer laser. J Fr case reports. Klin Monatsbl Augenheilkd 1993;202:126-29.
Section VI: Alternatives to Penetrating Keratoplasty

Ophtalmol 1998;21:23-27. 19. Dogru M, Katakami C, Yamanaka A. Refractive changes after


14. Heinz P, Wiegand W, Kroll P. Phototherapeutic keratectomy in excimer laser phototherapeutic keratectomy. J Cataract Refract
recurrences of granular corneal dystrophy after keratoplasty. Klin Surg. 2001;27:686-92.
Monatsbl Augenheilkd 1995;206:184-87.
15. Forster W, Atzler U, Ratkay I, Busse H. Therapeutic use of the
193 nm excimer laser in corneal pathologies. Graefes Arch Clin
Exp Ophthalmol 1997;235:296-305.

334
45

Chapter 45: Optical Sector Iridectomy


Optical Sector Iridectomy
M Vanathi, Rasik B Vajpayee, Namrata Sharma

Corneal opacities are the cause for 3 percent of corneal blindness not be useful. Hence, iridectomy should be placed in the lower
in India.1 More than half of the cases of corneal blindness is nasal and lower temporal quadrant.
treatable and curable. Penetrating keratoplasty is the procedure
of choice in such cases of moderate or severe corneal opacities INDICATIONS OF OPTICAL IRIDECTOMY
involving the central cornea. The penetrating keratoplasty
An optical sector iridectomy is ideally indicated in those cases
demands good quality donor material, surgical expertise and
where the corneal opacity is off center and encroaches on to the
optimal long-term follow-up to achieve ideal visual results. In
pupillary area.5-7 It has also been advocated in cases in which
developing countries there is a paucity of good quality donor
the scar is central and sufficient of the periphery of the cornea
material and patients with corneal blindness have to wait for
remains clear (Fig. 45.1).8 Optical iridectomy is especially
longer periods of time to undergo corneal transplantation. Also,
indicated in one eyed patients, in patients with corneal scars
a paucity of trained corneal specialists at the peripheral health
where the chances of graft failure are very high such as with
care centers precludes a proper long-term care of the grafted
ocular surface disorders and in cases of bilaterally blind patients
patients resulting in failure of many successful transplantation
who are awaiting their turn for keratoplasty.
surgeries. Moreover in developing countries poor socioeconomic
Optical iridectomy is an ideal alternative in cases of partial
status and lack of adequate transport facilities in remote areas
opacification of corneas where penetrating keratoplasty is
precludes a regular follow-up. All these factors do significantly
contraindicated or cannot be performed.9,10
reduce the chances of survival of a corneal graft. In such patients
if one graft fails, chances of a second graft being successful are
PREOPERATIVE EVALUATION
even more remote. Such a situation may be particularly disastrous
for one-eyed patients. Patient selection for iridectomy is of utmost importance to
If the corneal opacity is not total and if some area of the achieve a successful optical iridectomy. The patient must have
cornea is still transparent, an optical iridectomy in such cases an area of clear cornea and clear peripheral lens and objective
may help in providing good ambulatory vision.2,3 This vision
may not be equal to the vision achieved initially after a corneal
transplantation surgery, but it may last lifelong and enable these
patients to carry out their routine activities.

MECHANISM OF ACTION

Understanding mechanism of action of optical iridectomy is vital


if optimal results are to be achieved.4 Although the peripheral
part of the human optical system does not form as sharp an image
as the central part, the optical sector iridectomy aids in addition
of a peripheral bundle of rays so that a relatively clear vision is
produced by the peripheral rays superimposed on the blur
image of the central rays. Thus, one does not attain a visual
acuity of 6/6, but a significant improvement of vision does occur.
The best site for optical sector iridectomy is debated. The
superiorly placed iridectomy is covered by the upper lid and will Figure 45.1: A central corneal scar with clear periphery
335
estimation of optically achievable visual acuity based on the iridectomy improves visualization and may also aid in
clarity of the view of the fundus obtained with an performing phacoemulsification in case of presence of cataract.
ophthalmoscope through the area of proposed iridectomy is Postoperatively, all eyes are treated with topical antibiotic
essential. Patient with additional ocular problems such as and steroids given four times a day which is gradually tapered
nystagmus, macular degeneration or optical atrophy should be over four weeks. Topical cycloplegics may also be given in the
expected to achieve subnormal level of visual acuity and are not immediate postoperative period.
ideal for optical iridectomy. An estimation of the best-corrected
Section VI: Alternatives to Penetrating Keratoplasty

visual acuity with a stenopic slit, aids in optimal placement of RESULTS AND OUTCOME
the optical sector iridectomy.11 Further, if the media is hazy an
Optical sector iridectomy has been used to clear the visual axis
indirect ophthalmoscopy or ultrasound evaluation for posterior
in cases of Peter’s anomaly.6,7 Visual outcome following optical
segment evaluation should be done to rule out posterior segment
iridectomy for Peter’s anomaly was found to be equivalent to
pathology.
that of keratoplasty.6,13 We have evaluated visual outcome after
optical sector iridectomy in 17 patients of corneal opacities.8 In
SURGICAL TECHNIQUE
this study, an optical sector iridectomy8 was performed in the
A small fornixed base conjunctival flap is made at the previously lower nasal or temporal quadrant of 17 eyes with corneal scars
selected location with a conjunctival scissors and undermined. of which 16 achieved a visual acuity of 6/60 or better.
Mild cautery of the bleeding vessels is done. A 3.2 mm groove The complications, which can occur during optical sector
incision is made at the posterior limbus. A corneolimbal tunnel iridectomy, include postoperative hyphema, secondary glaucoma,
is dissected 0.5 mm into the clear cornea. The 3.2 mm keratome and injury to the lens and cataract formation.
blade is inserted in to the tunnel and advanced horizontally
parallel to the iris causing a linear horizontal cut through the REFERENCES
Descemet’s membrane into the anterior chamber. Care is taken
1. Eyebanks in India. Ophthalmology section. 1996 status of eye
to avoid injury to the iris tissue. A small amount of viscoelastic banks in India. New Delhi: Directorate General of Health
is injected to deepen the anterior chamber. Subsequently, the mid Services, Govt of India 1996;1-6.
periphery of the iris is caught with the forceps and pulled out of 2. Summers CG, Holland EJ. Neodymium: YAG pupilloplasty in
the incision gently and a complete iridectomy is facilitated using pediatric aphakia. J Pediatr Ophthalmol Strabismus 1991;28:155-
an iris forceps. Care is taken to avoid inadvertent injury to the 56.
lens. The anterior chamber is cleared of viscoelastic and formed 3. Weber SW, Crawford JS, Arndt JH, Parker JS. Visual acuity after
iridectomy or aspiration for congenital cataracts. Experimental
with BSS. The wound is sutured (Fig. 45.2).
and clinical studies. Can L Ophthalmol 1978;13:229-36.
Alternatively, another method can be used to perform optical
4. Drews LC, Drews RC. Optical iridectomy. Am J Ophthalmol
iridectomy, especially in cases of adherent leucomas.11,12 An 1964;71:789-96.
automated vitrector may be used to release the adherent leucoma 5. Costenbader FD, Albert DG. Conservation in the management of
and create an optical iridectomy at the start of surgery. The congenital cataract. Arch Ophthalmol 1957;58:426-30.
release of the iris adherence along with creation of an optical 6. Junemann A, Gusek GC, Nauman Go. Optical sector iridectomy:
An alternative to perforating keratoplasty in Peter’s anomaly. Klin
Monatsbl Augenheilkd 1996;209:117-24.
7. Zaidman GW, Rabinowitz Y, Forstot SL. Optical iridectomy for
corneal opacities in Peter’s anomaly. J Cataract Refract Surg
1998;24:719-22.
8. Vajpayee RB, Sharma N, Dada T, Pushker N. Optical sector
iridectomy in corneal opacities. Cornea 1999;18:262-64.
9. Sundaresh K, Jethani J, Vijayalakshmi P. Optical iridectomy in
children with corneal opacities. J AAPOS. 2008;12163-65. Epub
2007 Dec 26.
10. Vajpayee RB, Vanathi M, Tandon R, Sharma N, Titiyal JS.
Keratoplasty for keratomalacia in preschool children. Br J
Ophthalmol 2003;87:538-42.
11. Agarwal T, Jhanji V, Dutta P, Tandon R, Sharma N, Titiyal JS,
Vajpayee RB. J Cataract Refract Surg 2007;33:959-61.
12. Agarwal T, Jhanji V, Dutta P, Titiyal JS. Automated vitrector-
assisted optical iridectomy: Customized iridectomy. Eye
2009;23:1345-48.
Figure 45.2: Optical iridectomy of the 13. Zaidman GW. Optical iridectomy in corneal opacities. Cornea
same case as in Figure 45.1 2000;19:870.

336
46

Chapter 46: Corneal Tattooing


Corneal Tattooing
Sameer Kaushal, Harinder S Sethi, Namrata Sharma

Tattooing of the corneal opacity is one of the oldest procedures successfully used to cover iris defects due to trauma or surgery
described to conceal the corneal opacity. Galen (AD-131 - 210) when associated with disabling glare and diplopia. 3 It is
first described it, and used copper sulphate reduced with nutgall contraindicated in cases of corneal ectasia and thin cornea due
to conceal the unsightly leucomatous corneal opacities.1 Owing to the risk of inadvertent perforation. It should also be avoided
to tremendous progress in microsurgical reconstructive in cases of anterior staphyloma, phthisis bulbi, glaucoma and
procedures, corneal tattooing is presently indicated in only a adherent leucoma, due to the risk of inciting an iridocyclitis.4
selected group of patients.
METHODS OF TATTOOING
BASIC PRINCIPLE
The methods used to accomplish tattooing uses two principles—
Corneal tattooing involves impregnation of colored substances the chemical reduction method and the direct method.
in to the corneal stroma to imitate the patient’s iris and a central
pupil. It not only enhances the cosmesis of the eye, but it may Chemical Reduction Methods
also be used for optical purposes by converting a diffuse
Herein, a chemical reaction involves the precipitation of a
semitransparent nebula with irregular edges into an opaque
pigment, which occurs in the corneal tissues.5 Chemical tattoo
plaque with well-defined margins. 2 This eliminates the is easier and quicker but the results are less precise, fading of
undesirable effect of irregular scattering of the light. In such cases
the color more rapid and the chances of iridocyclitis higher with
the light is refracted regularly by the surrounding clear cornea
this technique. However, the area may be retattooed quickly and
into the macula, thus giving an undistorted image. Although, this simply.6
image has the disadvantage of small positive scotomata and a
These methods involve the chemical reduction of metallic
diminution of the intensity, it causes fewer disturbances to the
salts in the corneal tissues itself. This method was originally
patient as compared to an irregular distorted image due to a employed by Galen and was reintroduced by Paul Knapp in
nebulomacular corneal opacity. This principle has also been used
to treat the significant glare and monocular diplopia associated
with traumatic iris defects and aniridia.3

INDICATIONS AND CONTRAINDICATIONS

Corneal tattooing is done for cosmetic improvement in unsightly


corneal opacities and mature white cataracts when there is a high
chance of phithis with surgery. It has also been successfully used
for therapeutic purposes to block unwanted light entering the
eye with iris defects.3 For cosmetic improvement it may be
undertaken for old, firm and flat scars in quiet blind eyes,
especially in cases where iris print contact lens is either not
accepted by the patient or is uncomfortable. In selected cases
with corneal opacity an optical iridectomy may be used in
addition to tattooing as this confers an optical advantage
especially when tattooed area covers a major part of the pupillary
aperture (Figs 46.1, 46.2A and 46.2B).4 Tattooing has also been Figure 46.1: Corneal tattooing with optical iridectomy

337
1925. Knapp employed a solution of gold chloride, which was corneal bed for the pupil.11 Holth (1928) used a variety of
reduced by epinephrine or tannic acid.6 Although it produced solutions to achieve different colors of the corneal tattoo. He
satisfactory tattooing but the tattooed color was golden-brown suggested the use of 5 percent solution of fresh iron sulfate and
and not jet-black. 7 Kraut Baewer (1928) overcame this a fresh 5 percent solution of tannin to obtain black color, and
disadvantage by using platinum black, which produced dense water-soluble silver salts and hydrazine hydrate to imitate a
black colored tattoo.8 brown iris, lamp black and cobalt tannte to simulate a blue iris,
The platinum chloride remains the preferred chemical for while if a greenish tint was desired some burnt sienna was
Section VI: Alternatives to Penetrating Keratoplasty

corneal tattooing even in the recent times. The technique involves added.12
the removal of corneal epithelium over the opacified area and a With the chemical reduction techniques used for tattooing,
piece of blotting paper of same size, soaked in fresh 2 percent best results were obtained when epithelium alone was scrapped
solution of platinum chloride, is applied for two minutes to off, leaving the deeper tissues intact.
impregnate the subjacent tissues. On removal of the blotting
paper a few drops of fresh hydrazine hydrate 2 percent solution Direct Inoculation Methods
are poured for 25-30 seconds to reduce the platinum chloride. Direct introduction of the coloring agent into the corneal stroma
This causes precipitation of platinum black in situ making this is an older and a crude method of corneal tattooing. It is
area appear black in color. The eye is irrigated with saline, and technically more difficult, more time consuming and requires
a drop of parolein is instilled. Pad and bandage is applied over experienced handling of the needles. However, it produces more
the eye. The epithelium grows over the black deposit of platinum permanent results as compared to the chemical reduction
black in 4-5 days. However, with the passage of time, the methods.13 This is due to the fact that these dyes tend to be
epithelium may breakdown.9 phagocytosed by the keratocytes thus preventing leaching of the
dyes. When chemical reduction method is used, the metallic
Tattooing with Gold Chloride compounds are mainly deposited in the extracellular matrix of
cornea thus allowing early fading of the color.14
The cornea is anesthetized with 4 percent Xylocaine eyedrops.
The dye may be inoculated into the corneal stroma with the
If a central pupil is desired, the pupil is outlined with a trephine
help of various instruments such as 10/0 suture needle, hollow
of the required size and the epithelium is scraped off on this
needle, bundle of thin needles and blepharopigment needle. A
area. If a scar is to be obliterated the epithelium is scraped off
26-gauge hypodermic needle bent as a capsulotomy needle can
without going too far beyond the limits of the scar.
be also be used for the same purpose. This has the advantage of
A freshly prepared solution of 2 percent gold chloride is
easy availability and prevents inadvertent full thickness corneal
neutralized to a point of faint acidity with the soda bicarbonate
peforation. Tattooing with needles is a longer and more tedious
so that litmus paper turns only slightly pink. The applicator
procedure, which may require two or more sittings for
dipped in this solution is then firmly applied to the abraded
completion. The dye may also be inserted into a lamellar pocket
corneal area for a period of 3 to 7 minutes depending on the
made in the cornea in the area of opacity.15 This can be used in
color desired. The shorter the duration of application, the more
cases where the superficial stroma is clear.
brown and less black the ultimate color of the treated area will
With this method also there is corneal reaction but is
be.
comparatively less as compared to the chemical methods. Other
A freshly prepared solution of 2 percent tannic acid is
complications include under and over coloring, change in color
then dropped over this area to reduce the gold chloride. This
over time, migration of pigment, corneal perforation, uveitis and
will turn colored area to brown or black in about two minutes.
infection. Various coloring agents, which directly stain the
If tannic acid is unavailable, then a solution of epinephrine
cornea, are Indian ink, combination of Chinese ink and gold dust,
1:1000 may be used. Atropine is instilled and the eye patched.
uveal pigment from animal eyes, lamp black candle soot, animal
Corneal re-epithelialization occurs in 3 to 5 days. In most cases
charcoal, titanium dioxide (blue and white), ferric oxide (Fe2O3
there is only slight ocular reaction.
brown), iron oxide (Fe3O4 black). Use of iron compounds carries
a theoretical risk of toxicity though the compound used contain
Corneal Tattooing with Palladium Oxide ferric form which is nontoxic for ocular tissues.14
Vabutta and Toth reported a new method of the corneal tattooing
Corneal Needle Tattooing with Pigments
by using palladium oxide, which is reduced by vitamin C
solution. This is simpler than other methods and is said to give Lampblack or India ink may be used to produce black pupil.
the best cosmetic results. It produces a deep black color, which Both these agents may be autoclaved for sterility. The cornea is
lasts for many years.10 anesthetized and the area of pupil is trephined to mark it but the
Proper demarcation of the pupillary area and the colored area epithelium is not removed. A thick paste of black pigment is
corresponding to the iris is essential for a good cosmetic result. prepared by adding a few drops of sterile saline to the powder.
Anastas (1995) used excimer laser to create a perfectly circular A small amount of the black paste is placed on the anesthetized

338
cornea. Following this, a multiple tattoo needle is held at a slant for most of the patients especially where, the opacity also
of about 45 degrees and multiple punctures are made into the involves the subepithelial stroma.
corneal parenchyma in one small area. The pigment is irrigated
off, the effect noted and the process repeated until the whole THE PRESENT STATUS
area has been satisfactorily tattooed. The ultimate aim should
be to produce a slightly darker color to compensate for the slight The practice of corneal tattooing to conceal cosmetically bad
reduction in color with time. This may be done at one sitting if corneal opacities is rarely practiced in the current times. This is
due to the availability of cosmetic contact lenses to conceal

Chapter 46: Corneal Tattooing


the corneal area to be tattooed is small but usually two or more
sittings are required. This is followed by the instillation of the leucomatous corneal opacities. In addition, the current techniques
atropine and a patch is applied. Breaks in the conjunctival of penetrating and lamellar keratoplasty have been refined so as
mucosa should be avoided to prevent inadvertent staining of the to achieve good optical as well as cosmetic results which are
conjunctival surface. Pitz et al. have described the technique of far superior to tattooing.
tattooing based on dermatography using a three-edged spatula However, corneal tattooing may have some role in the third
needle (CSA-48oC) with a conventional 10-0 nylon suture. world countries where it may serve as a cheaper alternative to
Commercially available drawing inks in black, brown and blue the cosmetic contact lenses which may not be suitable for these
shade were used for coloring. patients due to tropical climates and poor socioeconomic and
hygienic status.
Corneal Tattooing with Pigments
(Lamellar Pocket Method) REFERENCES

This method is beneficial for cases with a clear superficial 1. Duke-Elder S. Disease of the outer eye (vol. VIII, part II). Henry
cornea. A partial thickness incision is made in the peripheral Krimptom Publishers, London NWS 20L, 1977, Mosby.
2. Duggan and Nanawati. Br J Ophthalmol 1936;20:419.
cornea which is extended to a lamellar intracorneal pocket in a
3. Beekhuis WH, Drost BH, van der Velden/Samderubun EM. A
plane anterior to the opacity. The pigment is made into a thick
new treatment for photophobia in post-traumatic aniridia: a case
paste after mixing with a few drops of saline and inserted into report. Cornea 1998;17:338-41.
the pocket. This technique has the advantage of requiring only 4. Knapp AA. Corneal graft or tattooing with iridectomy. US. Nav.
single sitting with more permanent results.16 Bull; 1944;42:1366.
Use of femtosecond laser has also been described as a tool 5. Forbes SB. New pigment for corneal tattooing. Am J Ophthalmol
to create lamellar flaps and pockets for corneal tattooing.16,17 A 1960;50:325.
free flap can be created with femtosecond laser which can be 6. Gifford SR, Steinberg A. Gold and silver impregnation of the
cornea for cosmetic purposes. Am J Ophthalmol 1927;10:240.
dipped in tattooing pigment and then repositioned on the corneal
7. Levis RJ. The new operation for coloring corneal opacities. Phil
bed.16 The versatility of the femtosecond laser can also be used Med Times 1946;3:1872-73.
to create a lamellar pocket where the pigment can be injected as 8. Pischel DK. Tattooing the cornea with gold and platinum chloride.
a paste. 17 The limitation of the femtosecond laser based Arch Ophthalmol 1930;3:176.
techniques include the high cost and the inability of the laser to 9. Taylor CB. The art of tinting opacities of the cornea. Br Med J
penetrate opaque cornea. This prevents the use of this technique 1872;2:214.

Figure 46.2A: Corneal tattooing for Figure 46.2B: Corneal tattooing (dispersion of pigment)
leucomatous corneal opacity

339
10. Vebutta A, Toth I. New operative method for corneal tattooing. 14. Mannis MJ, Eghbali K, Schwab IR. Keratopigmentation: a review
Szemeszet 1960;97:78. of corneal tattooing. Cornea 1999;18:633-7.
11. Anastas CN, McGhee CN, Webber SK, Bryce IG. Corneal 15. Burris TE, Holmes-Higgin DK, Silvestrini TA. Lamellar
tattooing revisited: excimer laser in the treatment of unsightly intrastromal corneal tattoo for treating iris defects (artificial iris)
leucomata. Aust N Z J Ophthalmol 1995;23:227-30. Cornea 1998;17:169-73.
16. Kymionis GD, Ide T, Galor A, Yoo SH. Femtosecond-assisted
12. Miller SJH. Parson’s diseases of the eye (Eighteenth edition).
anterior lamellar corneal staining-tattooing in a blind eye with
Churchill Livingstone, London 1990.
leukocoria. Cornea 2009;28:211-3.
13. Pitz S, Jahn R, Frisch L, Duis A, Pfeiffer N. Corneal tattooing:
Section VI: Alternatives to Penetrating Keratoplasty

17. Kim JH, Lee D, Hahn TW, Choi SK. New surgical strategy for
an alternative treatment for disfiguring corneal scars. Br J corneal tattooing using a femtosecond laser. Cornea 2009;
Ophthalmol 2002;86:397-99. 28:80-4.

340
47

Chapter 47: Prosthetic Contact Lenses


Prosthetic Contact Lenses
Monica Chaudhry

Prosthetic contact lenses provide an important therapeutic tool prosthetic lenses like CIBA Vision and CooperVision. Additional
in the treatment of diseased and disfigured eyes. For many local laboratories offer customized lens tinting, painting and
patients, a prosthetic contact lens is the most attractive option other services, which are preferred as one can custom modify
available to them. This article discusses general clinical fitting by ordering them.
considerations of prosthetic lenses and highlights the use of a Prosthetic lenses used in such cases are hydrogels made of
opaque hydrogel prosthetic lens with a decompensated cornea two main designs:
secondary to failed keratoplasties. 1. Iris painted center clear (Fig. 47.1)
Iris painted contact lenses are good cosmetic prostheses for 2. Iris painted center black/opaque (Fig. 47.2)
disfigured or blind eyes for which no evisceration or enucleation With a non-seeing eye, one has the possibility of using a clear
is indicated.1 Prosthetic contact lenses may be indicated over pupil or a black opaque pupil. If there is nothing to hide in the
clear corneas or heavily scarred corneas. It’s far less invasive pupil area then there is no need to use an opaque pupil in the
than the surgery required for enucleation and a prosthetic eye lens.
fitting, and it’s much more appealing than just wearing dark Custom hand-painted contact lenses are selected from the
sunglasses. catalog. Although there is a limited range of iris colors available
Besides providing superior cosmesis to enucleation, shades made available according to the Indian iris colors and
prosthetic contact lenses significantly improve the social diameters, yet they fit almost all the patients. By small
relationships and well-being of patients. Fitting prosthesis over modifications almost all eyes can achieve the desired cosmetic
a disfigured or an absolute (blind) eye could be a successful and anatomic result.
remedy for, enhancing the cosmetic appearance, and accelerating
the rehabilitation of patients with disfigured blind eyes.2 When Prefit Examination
a patient changes their appearance from disfigurement to
1. Detailed ophthalmologic examinations.
normalcy it can stimulate a positive change in self-confidence. 2. Corneal topography and keratometry of the fellow eye.
The improvement of physical characteristics can have a
3. The close-up photographs of healthy eyes of the subjects.
significant impact on their mind, personality and sense of self.
The essential measurements of the affected and the fellow
eye are:
Prosthetic Lens Options
1. HVID (Horizontal visible Iris diameter)
Prosthetic lenses are available in a limited range of colors, 2. Pupil diameter in bright, average and dim light conditions
designs in soft lens materials. Soft lenses are usually used 3. Visual acuity in each eye.
because they are able to fit a wider range of corneal conditions 4. Observe and note the following:
with excellent comfort and results. Very few companies offer – Iris color
– Any hyperemia of the conjunctiva/sclera
– Careful examination of the tears, cornea, limbus,
conjunctivas and lids using the slit lamp microscope
– Position and nature of scar tissue.

Prosthetic Fitting Procedure


The easiest way to create this type of prosthetic device is to work
Figure 47.1: Iris painted Figure 47.2: Iris painted from close-up pictures that have been taken of both eyes. Digital
clear pupil black pupil photographs work best and provide the truest colors making it
341
much easier to match eye color and any unique eye coloring
patterns. But one needs a good local laboratory to coordinate in
matching individual iris patterns and shades.
Prosthetic matching process: Setting proper expectations with
your patients is the first step. It’s important that they understand
that the results will be cosmetic and that there will be no visual
acuity or functional gain with these lenses.
Section VI: Alternatives to Penetrating Keratoplasty

It is preferable and useful to let patients watch the diagnostic


fitting so they can better appreciate the prosthetic matching
process. As far as possible maintain a library of the shades
available and let the patient feel the difference. Fine tuning of
the fitting and dimensions can be made on the trial lenses.
Fitting a prosthetic lens is much like fitting a regular soft
contact lens with a few extra considerations. While fitting
prosthetic contact lenses isn’t any more clinically demanding than
Figure 47.3A: Corneal opacity
most other contact lenses, what’s more difficult is working to
achieve a cosmetic match in eye color. The first choice is a single
standard opaque lens.
The steps include:
1. Evaluate clinical history and make sure that the underlying
condition is stable or resolved.
2. Keratometry readings and corneal topography may be
difficult to measure, so it may be helpful to take readings
of the fellow eye as a guide for diagnostic lens selection.
3. To determine the correct iris color, use a diagnostic lens.
Local brands usually give standard base curve and diameter
in 3 shades – Dark, Medium and Light brown. Go darker.
When selecting the darkness of the hue, go one step darker
than you think you probably should.
4. To determine the correct iris size, the visible horizontal iris
diameter HVID, should be measured in the undamaged eye.
5. To determine the correct pupil size, measure the undamaged Figure 47.3B: Cosmetic contact lens
pupil in normal to bright lighting with a millimeter ruler. Go
larger when determining pupil size; err on the size of larger. Problems in Fitting
A small pupil will stand out more than a larger pupil.
Sometimes fitting this soft lens may lead the issue of lens
6. Fitting and centration were examined by slitlamp
centration. If there has been any severe changes in the corneal
biomicroscopy. To achieve the best centration, stability, and
topography, peri-limbal scarring or chemosis there is a chance
movement, start with a clear trial lens to determine the base
that the lens may not center well. Additionally, the fit of the lens
curve needed. Select the optimal base curve as indicated by
periphery and edge may well be compromised. However, this
the keratometry readings and corneal topography of the
may not mean that fitting is impossible – one may have to warn
undamaged eye. Selecting the optimal base curve is vital to
the patient that wearing time might be limited and/or the white
preventing a lens with excessive movement, which is more
of the eye may become a little pink with lens wear. One has to
noticeable in patients with cosmetic needs. The normal fitting
accept some compromises in fitting compared to normal lenses
criteria apply for aspects such as Push-up-Test, lens
on normal eyes. If centration is poor, trying a larger total diameter
movement between blinks, excursion movements, etc.
could help. To assess the tolerance in terms of comfort a clear
However, compromises will have to be made in some cases.
soft lens with customized base curve can first be ordered and
One can only keep the eye under observation over time in
later on satisfaction the prosthetic lens can be dispensed in similar
order to assess if these compromises are adversely affecting
fitting curves.
the ocular tissues (Figs 47.3A to 47.4B).
7. Generally, such lenses fit slightly larger (0.5 mm) than normal
Pupil Size Problems
to get the best centration. If some sector of the underlying
cornea is showing, larger iris portion in 0.5 mm steps can This is always a difficult decision because the pupil size will
be ordered. not be correct when the fellow pupil is noticeably smaller or

342
expectations. Never promise more than you can deliver. Inform
patients in the initial visit that we can make an improvement,
but that we will not make a perfect match of God’s natural eye.

Follow-up
The gas exchange through prosthetic lenses is often limited due
to the qualities of necessary materials and manufacturing

Chapter 47: Prosthetic Contact Lenses


Figure 47.4A: Unilateral corneal opacity processes including placement of opaque backing. This does not
create a problem for clear corneas with good endothelial function
or for heavily scarred and vascularized corneas where oxygen
transmission is of limited concern. Prosthetic lens use on a
compromised cornea that has edema or bullae may be sufficient
to cause corneal decompensation.
Therefore, it is highly recommended that patients come in
for regular follow-up visits to help minimize possible
complications that arise from contact lens wear. It is also
Figure 47.4B: Prosthetic contact lens recommended that every prosthetic patient be evaluated
thoroughly with a post-wear biomicroscopy with sodium
fluorescein, as some eyes are not able to wear the lens. Also,
larger. Sometimes, this difference in pupil size can be noticeable some conditions may aggravate due to lens wear.
and is of concern to the patient. One should try to aim for a size
in average photopic conditions so that in bright light the lens’ Prosthetic Lens Care
pupil is slightly bigger and in dull conditions the lens’ pupil is Caring for prosthetic contact lenses is no different from normal
slightly smaller. If you have some trial lenses with different size contact lens maintenance routines.3 Because of the hand-crafted
pupils this is useful. The patient can take a mirror and look at nature of these lenses, they generally are not made to be
the effects in different light conditions while ignoring the color disposable. That means daily cleaning and disinfecting and
of the trial lenses. If in doubt err towards the larger size as in weekly enzyme cleansing routines to remove protein build-up
dull conditions any difference will be less obvious. Indian eyes are important to both preserving the coloring of the contact lenses
with dark brown irides are easily compromised in terms of pupil as well as preserving the health of the eye. Peroxide system of
size and color, as there is less contrast between the pupil and sterilization of lenses can sometimes lead to fading of iris shade.
iris colors. Regular replacement of such lenses is also important.
In case of pale iris, pay attention to the limbal ring, because
otherwise the lens will look artificial. It is easier again to fit REFERENCES
Indian eyes as the texture is more homogeneous compared to
1. Kanemoto M, Toshida H, Takahiro I, Murakami A. Prosthetic soft
lighter eyes.
contact lenses in Japan. Eye Contact Lens 2007;33:300-03.
To achieve success, you need to make the injured, damaged 2. Yildirim N, Basmak H, Sahin A. Prosthetic contact lenses:
or affected eye look as good as possible. Just don’t promise that adventure or miracle. Eye Contact Lens 2006;32:102-03.
the eye will look exactly like the other one –A very important 3. Bator KK, Salituro SM. Prosthetic soft contact lenses and you.
step in prosthetic lens fitting is setting appropriate patient Eye Contact Lens 2005;31:215-18.

343
48
Section VI: Alternatives to Penetrating Keratoplasty

Amniotic Membrane Transplantation


as an Alternative to Keratoplasty
Bhavna Chawla, Rasik B Vajpayee

INTRODUCTION preparations are a constraint in the widespread application of


AMT in the developing world. Amniotic membranes available
Alternative modalities of treatment that can have a keratoplasty-
for clinical use can be cryopreserved by the method described
sparing effect are of great value in a developing country like
by Tseng et al,8 which is now being used with some modifications
India due to shortage of donor corneal tissue. Such modalities
worldwide.7, 9
may be used to manage those cases of corneal blindness that
have recalcitrant ocular surface problems and are either
Cryopreserved Amniotic Membrane Preparation
unsuitable for a corneal transplantation surgery or have normal
vision in the other eye. Amniotic membrane transplantation A patient who is to undergo an elective cesarean section is
(AMT) is one such therapeutic option which is being increasingly selected. After obtaining a written and informed consent of the
employed in clinical practice. AMT was first used in donor, she is tested for viral infections like HIV, hepatitis B,
ophthalmology by De Rotth1 in 1940 as a conjunctival graft after hepatitis C and syphilis. Once, the placenta is obtained, the
symblepharon. After a gap of more than 50 years, there was a preparation of AM is done under laminar flow. An irrigating
renewed interest in this tissue when Kim and Tseng used AMT solution prepared with normal saline containing penicillin
for ocular surface reconstruction of severely damaged cornea in 50 IU/ml, Streptomycin 50 µg/ml, Gentamicin 200 µg/ml and
a rabbit model.2 Since then, AMT is becoming increasingly Amphotericin B 2.5 µg/ml is used to clean the placenta and the
popular for the treatment of several ocular surface disorders. membranes are gently peeled off. A thorough wash with the
Human amniotic membrane (AM) is the innermost layer of irrigating fluid is done to remove all blood clots from the
the placenta. It is composed of three layers: a single epithelial membranes comprising of chorion and amnion. The amnion
layer, thick basement membrane, and avascular stroma. The (smooth) is separated from the chorion (coarse) by blunt
basement membrane promotes epithelial cell migration, adhesion dissection. The chorion is discarded and both surfaces of the
and differentiation. It has been shown to contain collagen types amnion are thoroughly washed with the irrigating fluid till the
III and V. It also contains collagen types IV and VII similar to blood clots are completely removed. The AM is then placed on
corneal epithelial basement membrane as well as fibronectin and a sterile tray with the stromal side up. Autoclaved millipore paper
laminin. 3,4 Additionally, AM produces basic fibroblast, discs (0.45 µm pore size) are placed on the exposed stromal
hepatocyte and transforming growth factors which can stimulate surface of the AM. The disks when placed this way have the
epithelialization.5 Human AM is believed to have a very limited stromal side of the AM touching the paper. The AM is then cut
immunogenecity.6 The amnion surface epithelial cells do not into pieces and the extrafrill of membrane is wrapped around
express HLA A, B, C, or DR or beta2-microglobulin. Hence, the filter paper. A sample is sent for bacterial and fungal culture.
use of immunosuppressives following AMT is not required. The filter paper wrapped membranes are folded and transferred
Because of its anti-inflammatory effect, antifibroblastic activity, to sterile bottles containing Dulbecco’s modified Eagle’s medium
antimicrobial and anti-angiogenic properties, it is an ideal and glycerol (1:1 volume by volume). Bottles are labeled, sealed
material for ocular surface reconstruction. with parafilm, and stored at -70º C in the deep freezer. Once,
While fresh non-preserved AM has been used by some the bacterial and fungal culture reports are sterile and repeat
workers, the use of such tissue may be associated with a higher serology of donor 3 months later is negative, the membranes are
risk of blood borne infections.7 In the west, cryopreserved AM released for clinical use. Before use, it is thawed at room
is commercially available as Amniograft® (Biotissue Inc) and temperature for 10 minutes and rinsed thrice with normal saline
Prokera®. Factors such as cost and availability of commercial containing gentamicin.
344
Keratoplasty-sparing Indications for AMT Surgical technique: Symptomatic cases of bullous keratopathy
can be successfully treated by AM transplantation for alleviation
An AM graft can be used to treat various corneal diseases and
of symptoms. AM can be transplanted by any of the following
in some of these conditions, it may be an ideal alternative to a
two techniques:
corneal transplantation surgery. Ocular conditions in which it A. Inlay technique of AMT: In this technique, AM is used as
AMT can be used as an alternative to keratoplasty include:
a graft or ‘inlay’, whereby it acts as a scaffold for epithelial
1. Chronic symptomatic bullous keratopathy cells and allows migration of the surrounding epithelial cells

Chapter 48: Amniotic Membrane Transplantation as an Alternative to Keratoplasty


2. Neurotrophic ulcer on the membrane. This can be performed using the following
3. Mooren’s ulcer methods:
4. Impending corneal perforation, Corneal perforation 1. Under peribulbar anesthesia, the diseased epithelium is
removed up to 1-2 mm from the limbus by blunt scraping.
5. Selected cases of acute infectious keratitis not amenable to
medical therapy. A single layer of AM is placed on the corneal bed with
the epithelium-basement membrane side facing up and
is secured to the peripheral cornea using 10-0
AMT for Bullous Keratopathy
monofilament nylon sutures in either interrupted or
Symptomatic bullous keratopathy which occurs due to running fashion. The peripheral cornea is left uncovered
endothelial decompensation is a frequently encountered to promote epithelialization over the graft. The use of
condition in clinical practice and is one of the major indications sutures in anchoring AM to the corneal surface has its
for performing a penetrating keratoplasty. However, some of own drawbacks. Not only is the procedure time
these eyes carry a poor visual prognosis and may be treated with consuming and tedious, suture knots can incite corneal
modalities like a Gunderson flap, excimer laser PTK or AMT. irritation, with subsequent inflammation. Bioadhesive
AMT can be a safe, effective, and long-lasting treatment modality fibrin glue can successfully be employed as an alternative
for intractable pain associated with chronic bullous keratopathy to sutures to attach the AM to the ocular surface. After
in eyes with poor visual potential. epithelial debridement, a few drops of reconstituted
freeze dried Tisseel VH Fibrin sealant (Baxter AG,
Mechanism of action: In chronic bullous keratopathy, AMT can Vienna, Austria) are applied onto the corneal surface
be performed by an ‘inlay’ or ‘overlay’ technique (Fig. 48.1).
using the Duploject system consisting of two identical
When used as an ‘inlay’ material, the AM acts as a scaffold for
disposable syringes with a common plunger. The quick
epithelial cells and allows migration of the surrounding epithelial solidification method is used while reconstituting freeze
cells on the membrane. In the ‘overlay’ method, the AM is
dried Tisseel. A single layer of AM is placed evenly on
applied as a patch whereby it functions as a biological contact
the corneal surface with the epithelial side up and a
lens and epithelial healing takes place underneath the layer of waiting time of 4-5 minutes is given to ensure firm
AM. The fate of AM following transplantation and its integration
adhesion of the AM to the cornea. Excess frill of AM is
in the host cornea has not been entirely elucidated. It is possible
trimmed off and a bandage contact lens (BCL) is applied.
that the AM subsequently gets integrated into the corneal stroma 2. Alternatively, a lamellar pocket can be prepared to allow
and results in the formation of a stromal scar which mechanically
insertion of the amniotic membrane. In this technique,
limits entry of aqueous into the subepithelial space.
after removal of the bullous epithelium, a superficial
trephination 8-9 mm in diameter is performed on the
corneal surface. Then a 2 mm deep lamellar pocket is
created 360° toward the limbus using a crescent blade.
The denuded corneal surface is covered with AM and
the edges of the AM are introduced into the pocket and
secured to the corneal surface with the help of 10-0
monofilament nylon sutures or fibrin sealant. If fibrin
glue is used, the thrombin component of the fibrin glue
is applied to the defect area and the fibrinogen component
to the stromal surface. The membrane is applied to cover
the defect with stromal surface facing down and is tucked
in the lamellar pocket. In this method also,
epithelialization takes place on the top of the membrane.
A disadvantage with the inlay technique is that the
AM graft becomes trapped under the healed corneal
epithelium and may limit corneal transparency for several
Figure 48.1: Bullous keratopathy months or more affecting vision.
345
B. Overlay technique of AMT: In this technique, the AM AMT for Neurotrophic Ulcers
functions as a biological contact lens and epithelial healing
Neurotrophic keratitis is a condition of the corneal epithelium
takes place underneath the layer of AM. The AM is applied
in which corneal damage occurs secondary to involvement of
as a patch to cover the whole corneal surface including the
the trigeminal nerve. Causes include herpes simplex and herpes
limbus and sutured to the free conjunctival edges.
zoster infections, diabetes mellitus, leprosy, vit A deficiency,
1. Under peribulbar anesthesia, a 360° conjunctival
trauma, topical medications, and tumors and surgical procedures
peritomy is carried out followed by removal of the which damage the ophthalmic division of trigeminal nerve. AMT
Section VI: Alternatives to Penetrating Keratoplasty

diseased corneal epithelium. The AM with epithelium-


is effective in promoting epithelialization and improving visual
basement membrane side up is transplanted over the
acuity in refractory cases of neurotrophic ulcers.
cornea as a patch and sutured to the free conjunctival
edges using 10-0 nylon in either interrupted or running Mechanism of action: When used as a graft (inlay), the AM
fashion. promotes epithelialization over it. In deep ulcers, multiple layers
2. Alternatively, sutureless AMT can be performed using of AM can be used to increase the corneal thickness. A larger
PROKERA™ which is a commercially available device layer of AM can be applied as a patch in addition to the graft
created by clipping AM into a polycarbonate ring set. which helps in preventing surface exposure and dryness and
PROKERA™ can be inserted as an overlaid graft without functions like to tarsorrhaphy in these eyes.
the need for sutures. Surgical technique: The surgery is performed under peribulbar
Postoperative management: Topical ofloxacin 0.3 percent anesthesia. The base and margins of the ulcer are first scraped
eyedrops four times daily, topical prednisolone acetate 1 percent to remove all cellular debris. Depending on the depth of the ulcer,
four times a day and preservative free artificial tears 6 times daily single or multilayered AM can be used with or without additional
are prescribed for four weeks. BCL can be removed once membrane as a patch. The AM is oriented with the epithelium-
epithelialization is complete and prednisolone acetate can be basement membrane side up. Either ‘inlay’ or ‘overlay’ technique
tapered off. or both ‘inlay’ and ‘overlay’ technique can be used. The AM is
sutured with interrupted 10-0 monofilament nylon sutures to the
Outcome: Several studies have reported encouraging results with cornea for the ‘inlay’ technique and with 8-0 vicryl sutures to
the use of AMT in bullous keratopathy.10-20 In a study by Pires the sclera for the overlay technique. Postoperative medication
et al,14 AMT could relieve symptoms in 90 percent of patients consists of administration of topical ofloxacin 0.3 percent
with symptomatic bullous keratopathy and poor visual potential. eyedrops four times daily for two to three weeks, preservative-
The authors concluded that AMT could be considered as an free artificial tears 6 times daily and a lubricating gel at bed time.
alternative to conjunctival flaps in alleviating pain, promoting
Outcome: AMT has been reported to be effective in the
epithelial healing, and preserving cosmetic appearance in these management of neurotrophic keratitis. Chen et al21 performed
patients. Espana et al11 evaluated the long-term outcomes of
AMT in 16 eyes of 15 patients with neurotrophic corneal ulcers
epithelial debridement and AMT in symptomatic bullous
and vision equal to or worse than 20/200. They observed that
keratopathy. They observed that pain relief could be obtained 76.4 percent cases achieved rapid epithelialization and 2 eyes
in 88 percent and complete resolution of ocular discomfort in
gained vision better than 20/200. In another study on refractory
66 percent of eyes and concluded that AMT was a safe, effective,
neurotrophic corneal ulcers, 22 the efficacy of AMT was
and long-lasting treatment modality for intractable pain compared with that of conventional management (tarsorrhaphy
associated with chronic bullous keratopathy in eyes with poor
and bandage contact lens). At the end of 3 months follow-up,
visual potential. Other studies have also reported success with
66.67 percent cases in conventional management group and
AMT as a palliative treatment for bullous keratopathy.15-17 AMT 73.33 percent cases in AMT group showed complete
has also been found to be effective when combined with anterior
epithelialization and healing. Both groups showed an
stromal micropuncture for treatment of painful bullous
improvement in the best-corrected visual acuity and the median
keratopathy in eyes with poor visual potential.18 time for complete epithelialization was 21 days in both groups.
Apart from serving as palliative therapy and providing The authors concluded that both AMT and conventional
symptomatic relief, AMT is also effective in improving visual management are effective treatment modalities for refractory
acuity in patients with bullous keratopathy.12,19 Srinivas et al19 neurotrophic corneal ulcers.
evaluated the effectiveness of AMT in relieving pain and
discomfort in patients with painful bullous keratopathy and its AMT for Mooren’s Ulcer
role in improving vision in eyes with visual potential. They Mooren’s ulcer is a peripheral ulcerative keratitis of unknown
reported pain relief in 100 percent patients and an improvement etiology. The initial management of this condition is with the
in vision in 71.4 percent patients. In another prospective, non- use of topical corticosteroids. However, some cases may be
comparative interventional case series on the outcome of unresponsive to topical steroids and can progress relentlessly
cryopreserved AMT for the management of symptomatic bullous threatening the visual axis and structural integrity of the globe.
keratopathy,12 visual acuity improved in 79 percent patients AMT can be a valuable treatment modality in such cases and
346 following AMT. can obviate the need for a keratoplasty.
The surgical technique is the same as that for other ulcerative management of refractory cases, can be administered.23 The
conditions. A single or multilayered AMT can be used to fill the frequency of topical steroids is reduced once healing has taken
defect depending on the depth of ulceration, with additional AM place and thereafter tapered off over a few weeks.
as a patch (Fig. 48.2). Postoperatively, topical prednisolone
acetate 1 percent eyedrops two hourly, topical ofloxacin 0.3 AMT for Impending and Small Corneal Perforations
percent four times daily, preservative free lubricants two hourly AMT can be used as an effective alternative to keratoplasty in
and topical cycloplegics are administered. In addition, impending corneal perforations and small perforations. It results

Chapter 48: Amniotic Membrane Transplantation as an Alternative to Keratoplasty


immunosuppressives such as topical cyclosporine A 2 percent in rapid reconstruction of the ocular surface and can also give a
four times daily, reported to be safe and effective in the good functional result in the absence of donor corneal tissue. It
can provide a permanent cure or may temporarily help in
reducing inflammation to allow keratoplasty to be performed
under more favorable conditions.
Surgical technique: Multilayered AMT is employed for the
treatment of impending perforations and small perforations of
the cornea. The anterior chamber is formed with viscoelastics,
when required. Thereafter, debridement of the necrotic tissue is
carried out. Separate amniotic membranes are transplanted as a
filler for closing the corneal perforation with additional AM as
an ‘inlay’ for promoting epithelialization. A patch of AM is
applied over this which functions primarily as a biological
contact lens. Postoperative medication consists of topical
antibiotic eyedrops, artificial tears, cycloplegics and topical
corticosteroids, when indicated. Medication is continued for four
to six weeks and thereafter tapered according to the clinical
response. Fibrin glue can be used as an alternative to sutures in
the treatment of small corneal perforations (2-3 mm) with AMT.
The technique consists first of using a high-viscosity sodium
hyaluronate viscoelastic material to temporarily restore anterior
chamber depth followed by a debridement of the ulcer. The
perforation site is then filled with fibrin glue to corneal surface
level. The so-formed plug is secured with an AMT to avoid its
extrusion. An extended-wear bandage contact lens and topical
antibiotics are used postoperatively for 3 weeks.
Outcome: Hanada et al24 examined the efficacy of AMT in 11
eyes which included 4 eyes with corneal perforations and 5 eyes
with descemetocele. Following AMT, 8 (72.7%) eyes healed with
epithelialization. In another study by Soloman et al25 on the
clinical efficacy of AMT in the management of corneal
perforations and descemetoceles, 34 eyes of 33 consecutive
patients were studied. Main outcome measures included
formation of anterior chamber depth, epithelialization of the AM
grafts, and stability of the corneal stromal thickness. A successful
result was observed in 28 of 34 eyes (82.3%) thereby showing
that AMT is an effective method for managing nontraumatic
corneal perforations and descemetoceles.
Repair of small corneal perforations with fibrin glue and
AMT has resulted in a good outcome.26,27 Duchesne et al26
described the use of HFG and AMT in 3 patients with small
corneal perforations (< 2 mm) and were able to achieve rapid
epithelialization with long-term corneal stability. Hick et al27 also
evaluated the efficacy of AM with fibrin glue in corneal
perforations and found that grafts with fibrin sealant showed a
Figure 48.2: Mooren’s ulcer (A) and (B) Multilayered amniotic success rate of 92.9 percent as compared to 73.7 percent for
membrane graft (C)
amniotic grafts alone.
347
AMG for Intractable Infectious Keratitis perforations in acute fungal keratitis,30 AMT was performed
during the active phase of the keratitis in 16 patients and during
AMT can have a definite role in the management of selected
the inactive phase in 7 patients. During a mean follow-up time
cases of infectious keratitis caused by various etiological agents.
of 20.6 months, complete epithelialization was observed in
In acute cases of bacterial, viral or fungal keratitis not amenable
75 percent patients in the active group and in 100 percent patients
to medical therapy (Fig. 48.3), AMT helps in promoting
in the inactive group and an improvement in the final visual
epithelialization and limits the degree of stromal loss thus
acuity was noted in 17 cases.
preventing corneal perforations and the need for a subsequent
Section VI: Alternatives to Penetrating Keratoplasty

keratoplasty. Complications of Amniotic Membrane Transplantation


Surgical technique: Single or multilayered AMT can be used As with any other procedure, AMT is not devoid of compli-
depending on the depth of the ulcer. Following debridement of cations. These include hematoma formation in the postoperative
necrotic tissue, the AM can be applied as a graft with the period,31 retraction of the membrane, granuloma formation,
epithelium-basement membrane side up to provide a scaffold for premature degradation requiring repeat grafting and opacification
epithelialization. In cases of corneal perforations with anterior of the visual axis due to residual subepithelial membrane. Failure
chamber collapse, AM can be used as a filler to close the of the initial procedure or recurrences requiring retreatment may
perforation after reconstruction of the anterior chamber with also occur. Suture related problems can be encountered such as
viscoelastics. Additional AM can be applied as a patch which exposed sutures leading to corneal irritation and inflammation,
functions primarily as a biological contact lens providing or loose sutures which may need suture removal. The incidence
protection to the underlying epithelium. Postoperatively, of microbial infections following AMT has been reported to be
depending on the organism isolated, topical fortified antibiotics, 1.6 percent.32 Organisms include gram-positive pathogens,33 and
antiviral medication or antifungal therapy is administered. fungal keratitis due to Aspergillus species.34A case of sterile
Systemic medication is prescribed in cases with perforation and/ hypopyon has been reported following repeated AMT in a patient
or limbal involvement. In addition, topical cycloplegics, with nonhealing ulcer related to rheumatoid arthritis. 35
lubricants and IOP-lowering medication when required, are Calcification has been found to occur in some cases.36
administered as adjuvant therapy.
SUMMARY
Outcome: AMT has been found to be effective in the
management of acute microbial keratitis. Chen et al28 performed AMT is a safe, effective, and long-lasting therapeutic modality
AMT in cases of Pseudomonas keratitis with impending for patients with chronic bullous keratopathy. It can alleviate
perforation that were treated with fortified antibiotics for at least pain, promote corneal epithelialization, reduce conjunctival
one week and found that in 5/6 cases, AMT resulted in limiting inflammation and may also improve visual acuity in some cases,
the progression of lesions and stromal loss. In a series of 7 obviating the need for a keratoplasty. AMT has a valuable role
patients with herpes simplex virus or varicella zoster-induced in the management of neurotrophic corneal ulcers and Mooren’s
severe ulcerative keratitis, 5 eyes healed after the first AMT.29 ulcers which are refractory to conventional therapy. In cases with
AMT has also been reported to be beneficial in acute fungal impending and small corneal perforations, AMT leads to a rapid
keratitis in promoting epithelialization and preventing corneal reconstruction of the corneal surface and can give a good final
perforations. In a study on persistent corneal ulcers and functional result. Thus, it is a good alternative to avoid or delay
penetrating keratoplasty especially in acute cases in which graft
rejection risk is high. AMT has also been found to be effective
in limiting stromal loss and preventing corneal perforations and
the need for a therapeutic keratoplasty in selected cases of acute
infectious keratitis. To summarize, the ‘keratoplasty-sparing’ role
of AMT cannot be overemphasized. This is particularly relevant
in our scenario in the face of limited availability of donor corneal
tissue.

REFERENCES

1. DeRoth A. Plastic repair of conjunctival defects with fetal


membrane. Arch Ophthalmol 1940;23:522-25.
2. Kim JCI, Tseng SCG. Transplantation of preserved human
amniotic membrane for surface reconstruction in severely
damaged rabbit corneas. Cornea 1995;14:473-84.
3. Modesti A, Scarpa S, D’Orazi G. Localization of type IV and V
collagens in the stroma of human amnion. Prog Clin Biol Res.
Figure 48.3: Resolving keratitis 1989;296:459-63.
348
4. Fukuda K, Chikama T, Nakamura M, Nishida T. Differential 20. Chawla B, Tandon R. Sutureless amniotic membrane fixation with
distribution of subchains of the basement membrane components fibrin glue in symptomatic bullous keratopathy with poor visual
type IV collagen and laminin among the amniotic membrane, potential. Eur J Ophthalmol 2008;18:998-1001.
cornea and conunctiva. Cornea 1999;18:73-79. 21. Chen HC, Pires RT, Tseng SC. Amniotic membrane trans-
5. Sato H, Shimazaki J, Shinozaki N. Role of growth factors for plantation for severe neurotrophic corneal ulcers Br J Ophthalmol
ocular surface reconstruction after amniotic membrane 2000;84:826-33.
transplantation. Invest Ophthalmol Vis Sci. 1998;39:S428. 22. Khokhar S, Natung T, Sony P, Sharma N, Agarwal N, Vajpayee
6. Akle CA, Adinofli M, Welsh KI, Leibowitz S, McColl I. RB. Amniotic membrane transplantation in refractory

Chapter 48: Amniotic Membrane Transplantation as an Alternative to Keratoplasty


Immunogenicity of human amniotic epithelial cells after neurotrophic corneal ulcers: A randomized controlled clinical trial.
transplantation into volunteers. Lancet 1981;2:1003–05. Cornea 2005;25:654-60.
7. Dua HS, Azuara-Blanco A. Amniotic membrane transplantation. 23. Tandon R, Chawla B, Verma K, Sharma N, Titiyal JS. Outcome
Br J Ophthalmol 1999;83:748-52. of treatment of Mooren, ulcer with topical cyclosporine a 2
8. Tseng SC, Prabhasawat P, Barton K, Gray T, Meller D. Amniotic percent. Cornea 2008;27:859-61.
membrane transplantation with or without limbal allografts for 24. Hanada K, Shimazaki J, Shimmura S, Tsubota K. Multilayered
corneal surface reconstruction in patients with limbal stem cell amniotic membrane transplantation for severe ulceration of the
deficiency. Arch Ophthalmol 1998;116:431-41. cornea and sclera. Am J Ophthalmol 2001;131:324-31.
9. Madhavan HN, Priya K, Malathi J, Joseph PR. Preparation of 25. Solomon A, Meller D, Prabhasawat P, John T, Espana EM, Steuhl
amniotic membrane for ocular surface reconstruction. Ind J KP, Tseng SC. Amniotic membrane grafts for nontraumatic
Ophthalmol 2002;50:227-31. corneal perforations, descemetoceles, and deep ulcers.
10. Mejia LF, Santamaria JP, Acosta C. Symptomatic management Ophthalmology 2002;109:694-703.
of postoperative bullous keratopathy with nonpreserved human 26. Duchesne B, Tahi H, Galand A. Use of human fibrin glue and
amniotic membrane. Cornea 2002;21:342-45. amniotic membrane transplant in corneal perforation. Cornea
11. Espana EM, Grueterich M, Sandoval H, Soloman A, Alfonso E, 2001;20:230-32.
Karp CL, Fantes F, Tseng SC. Amniotic membrane transplantation 27. Hick S, Demers PE, Brunette I, La C, Mabon M, Duchesne B.
for bullous keratopathy in eyes with poor visual potential. J Amniotic membrane transplantation and fibrin glue in the
Cataract Refract Surg 2003;29:279-84. management of corneal ulcers and perforations: a review of 33
12. Georgiadis NS, Ziakas NG, Boboridis KG, Terzidou C, cases. Cornea 2005;24:369-77.
Mikropoulos DG. Cryopreserved amniotic membrane 28. Chen JH, Ma DH, Tsai RJ. Amniotic membrane transplantation
transplantation for the management of symptomatic bullous for pseudomonal keratitis with impending perforation. Chang
keratopathy. Clin Experiment Ophthalmol 2008;36:130-35. Gung Med J 2002;25:144-52.
13. Esquenazi S, Rand W, Velazquez G, Grunstein L. Novel 29. Heiligenhaus A, Li H, Hernandez Galindo EE, Koch JM, Steuhl
therapeutic approach in the management of band keratopathy KP, Meller D. Management of acute ulcerative and necrotizing
using amniotic membrane transplantation with fibrin glue. herpes simplex and zoster keratitis with amniotic membrane
Ophthalmic Surg Lasers Imaging 2008;39:418-21. transplantation. Br J Ophthalmol 2003;87:1215-19.
14. Pires RT, Tseng SC, Prabhasawat P, Puangsricharern V, Maskin 30. Chen HC, Tan HY, Hsiao CH, Huang SC, Lin KK, Ma DH.
SL, Kim JC, Tan DT. Amniotic membrane transplantation for Amniotic Membrane Transplantation for Persistent Corneal
symptomatic bullous keratopathy. Arch Ophthalmol. 1999; Ulcers and Perforations in Acute Fungal Keratitis. Cornea 2006;
117:1291-97. 25:564-72.
15. Chansanti O, Horatanaruang O. The results of amniotic membrane 31. Dua HS, Gomes JA, King AJ, Maharajan VS. The amniotic
transplantation for symptomatic bullous keratopathy. J Med Assoc membrane in ophthalmology. Surv Ophthalmol 2004;49:51-77.
Thai. 2005;88:S57-62. 32. Marangon FB, Alfonso EC, Miller D, Remonda NM, Marcus S,
16. Zemba M, Andrei S, Cucu B, Brãtulescu M, Stinghe A, Bobeico Tseng SC. Incidence of microbial infection after amniotic
V, Dobrescu N, Zugravu V, Furedi G. Amniotic membrane membrane transplantation. Cornea 2004;23:264-69.
transplantation in palliative treatment of bullous keratopathy. 33. Khokhar S, Sharma N, Kumar H, Soni A. Infection after use of
Oftalmologia 2006;50:51-53. nonpreserved human amniotic membrane for the reconstruction
17. Racine L, Demers PE, Thompson P. Amniotic membrane of the ocular surface. Cornea 2001;20:773-74.
transplantation for Patients with Painful Bullous Keratopathy 34. Das S, Ramamurthy B, Sangwan VS. Fungal keratitis following
Awaiting Penetrating Keratoplasty Invest Ophthalmol Vis Sci amniotic membrane transplantation. Int Ophthalmol 2007; Nov
2003;44: E-Abstract 1364. 6 (Epub ahead of print).
18. Sonmez B, Kim BT, Aldave AJ. Amniotic membrane 35. Gabler B, Lohmann CP. Hypopyon after repeated transplantation
transplantation with anterior stromal micropuncture for treatment of human amniotic membrane onto the corneal surface.
of painful bullous keratopathy in eyes with poor visual potential. Ophthalmology 2000;107:1344-46.
Cornea 2007;26:227-29. 36. Anderson SB, de Souza RF, Hoffmann-Rummelt C, Seitz B.
19. Srinivas S, Mavrikakis E, Jenkins C. Amniotic membrane Corneal calcification after amniotic membrane transplantation.
transplantation for painful bullous keratopathy. Eur J Ophthalmol Br J Ophthalmol 2003;87:587-91.
2007;17:7-10.

349
49
Section VI: Alternatives to Penetrating Keratoplasty

Gundersen Flap
Prakash Chand Agarwal, Namrata Sharma, Rasik B Vajpayee

Schoeler in Berlin described a conjunctival flap in 1877 but was formation, and inflammation subsides. Gundersen in his original
popularized by Kuhnt in 1884. Byers described flaps in cataract article hypothesized that a thin flap provides protection from
surgery, eviserations and corneo-scleral lacerations in 1912. In tears and irritants and provides blood factors from the
1927, Green advocated wound healing by conjunctivilization as conjunctival vessels (Fig. 49.2). Such vascular nutritive factors
beneficial for various corneal ulcerations, Mooren’s ulcers and provide for decrease in inflammation, early healing and wound
for corneal perforations. repair. It also provides some degree of tectonic support especially
In 1958, Gundersen described a technique of creating a thin if Tenon’s fascia is included in the flap. Flaps help to restore an
conjunctival flap devoid of the Tenon’s fascia.1 Such thin flaps intact epithelium, and improve tear film quality, thereby reducing
allow permanent coverage of the diseased cornea. Gundersen patient symptoms and the risk of phthisis. In bullous keratopathy,
flaps may be temporary procedure in acute cases followed by a the conjunctival flap creates an intact corneal surface over bare
suitable optical rehabilitation by a penetrating cornea transplant. exposed corneal nerve endings to alleviate corneal pain, whereas
It may be a permanent procedure in certain nonhealing chronic the formation of a semipermeable epithelium presents at least a
conditions. partial osmotic barrier at the tear film-epithelium interface. In
In addition to the total conjunctival flaps described by severe cases of herpetic stromal necrosis unresponsive to topical
Gundersen, partial flaps may be used to cover a particular sector and systemic antivirals, a conjunctival flap may often be the only
of the diseased cornea. Racquet flaps are created by rotating or effective means of controlling the inflammatory disease process,
swinging a flap of limbal conjunctiva onto the cornea. Thick flaps perhaps by providing a stable epithelial surface and introducing
including the Tenon’s fascia are used in certain conditions with vascularization and anti-inflammatory cellular components and
stromal loss (Fig. 49.1). Gundersen used thick flaps in bullous cytokines to the stromal bed to aid in controlling infective,
keratopathy. inflammatory, and melting processes.2 In noninfective destructive
The exact mechanism for the success of conjunctival flaps conditions of the cornea, such as neuroparalytic keratopathy,
remains unclear. In general prompt relief of pain is felt after flap neutrophil recruitment and liberation of collagenases are key
placement. Refractory ulcers and necrotic areas heal with scar factors in disease pathogenesis, and it has been postulated that

Figure 49.1: Thick flap including tennon’s fascia (Courtesy: Figure 49.2: Thin vascularized flap (Courtesy: Medical
Medical Photographic Imaging Centre, Royal Victorian Eye and Photographic Imaging Centre Royal Victorian Eye and Ear
Ear Hospital) Hospital)
350
vascularized structures ameliorate these destructive effects
through the introduction of anticollagenolytic substances from
the circulation.3 Gundersen flaps may also be removed after the
original infective or inflammatory process has resolved, and
reconstruction of the cornea by penetrating or lamellar
keratoplasty can be performed, although limbal stem cell loss
inherent in the procedure may subsequently result in an unstable

Chapter 49: Gundersen Flap


ocular surface, which may require limbal autograft surgery.4
The Gundersen flap does have some disadvantages such as
impairment of vision and inability to visualize the details of the
cornea and anterior chamber, more so with thicker flaps.
Monitoring of the disease process is impaired. Persistence of
infection under the flap can occur, and perforation under the flap
in herpetic stromal keratitis has been reported.5 Figure 49.3: Recurrence of original pathology may occur after
A relatively large area of healthy conjunctiva is also required, gundersen flap (Courtesy: Medical Photographic Imaging Centre
Royal Victorian Eye and Ear Hospital)
limiting its use in ocular surface disease with significant
conjunctival involvement or in severely damaged eyes with
previous retinal or glaucoma surgery. In addition, as mentioned
above, removal of limbal epithelium containing limbal stem cells 7. The superior edge of the flap is incised horizontally.
potentially precludes a stable ocular surface in cases in which 8. The blunt dissection is carried out by blunt scissors or moist
subsequent flap removal and keratoplasty to restore vision are cotton tip applicators. The flap is then pulled down to cover
planned. the conjunctiva.
9. The inferior edge of the flap is secured to the inferior limbus
Other Indications for the Conjunctival Flaps are with 10-0 nylon. The superior edge is secured to the superior
• Refractory infectious ulcers limbus or episcleral tissue using 10-0 nylon.
• Herpetic keratitis 10. Antibiotic ointment and pressure dressing is applied and
• Fungal keratitis sutured removed after 1 month.
• Bacterial
Complications of Conjunctival Flap
• Parasitic
• Ocular surface disorder with persistent epithelial defect • Button hole
• Neurotrophic ulcer • Flap retraction
• Peripheral ulcerative keratitis (PUK) • Epithelial cyst formation
• Mooren’s ulcer • Ptosis
• Exposure keratopathy • Recurrence with or without erosion
• Keratoconjunctivitis Sicca
• Tectonic support Modifications of the Technique
Interestingly, Gundersen advocated a lamellar keratectomy at the
SURGICAL TECHNIQUES time of surgery as being essential to the success of a Gundersen
1. Local anesthesia is achieved with retrobulbar or peribulbar flap for bullous keratopathy.6 Various reports have shown that
blocks. lamellar keratectomy may or may not be done.7,8 The original
2. All the corneal epithelium is scraped off with the help of a technique described by Gundersen in 1958, involved use of
blade or iris repositor. Any necrotic tissue is also removed. thinner flaps devoid of Tenon’s fascia. However, later
A superficial keratectomy may be done if deemed necessary. modifications have been done and surgeons have used thicker
Areas of dystrophic calcification and surface deposits and flaps in cases of corneal melting to prevent tissue lysis. It has
infiltrates were also debrided. several advantages over the traditional Gundersen conjunctival
3. A complete 360° peritomy is done and hemostasis is flap, such as generating lower rates of flap retraction, providing
achieved. more resistance to the tendency to lysis, and avoiding any
4. The superior rectus hook may be applied or superior corneal adhesion or scleral lysis after detaching the large, thick donor
traction suture may be secured. conjunctival flap. Gundersen flap can be combined with mucous
5. The area to be dissected may be marked. The vertical height membrane grafting as a modification.9
of the flap should be 15-18 mm above the superior limbus The use of the Gundersen flap has greatly declined in
and the horizontal extent should be 18-20 mm. developed countries with the advent of therapeutic penetrating
6. Conjunctiva is separated form Tenon’s fascia with keratoplasty, amniotic membrane transplants (AMTs) 10,11
subconjunctival injection of balanced salt solution, therapeutic extended wear bandage contact lenses (BCLs)12 and
lidnocaine (2%) with 1:100000 epinephrine. cultured epithelial transplantation techniques for ocular surface 351
reconstruction.13,14 These techniques represent significant REFERENCES
technological advances but are not without their limitations, not
1. Gundersen T. Conjunctival flaps in the treatment of corneal
least among which is their limited availability in underdeveloped
disease with reference to a new technique of application. AMA
areas, especially in relation to penetrating keratoplasty with a Arch Ophthalmol 1958;60:880-88.
lack of available corneal donor tissue. The Gundersen flap is 2. Gundersen T, Pearlson HR. Conjunctival flaps for corneal disease:
thus still a relevant but often overlooked procedure today. their usefulness and complications. Trans Am Ophthalmol Soc.
Gundersen flaps are mainly performed in cases with poor visual 1969;67:78-95.
Section VI: Alternatives to Penetrating Keratoplasty

potential. In selected cases, conjunctival flaps also have the 3. Berman MB. The role of alpha-macroglobulins in corneal
potential to improve visual acuity. Insler and Pechous15 have ulceration. Prog Clin Biol Res 1976;5:225-59.
4. Geria RC, Zarate J, Geria MA. Penetrating keratoplasty in eyes
reported visual improvement in 8 of 33 patients (24%) with
treated with conjunctival flaps. Cornea 2001;20:345-49.
conjunctival flaps performed as the only procedure. In acutely 5. Lesher MP, Lohman LE, Yeakley W, et al. Recurrence of herpetic
inflamed eyes, conjunctival flaps may also be used as a stromal keratitis after a conjunctival flap surgical procedure. Am
temporizing measure and on an emergent basis to maintain globe J Ophthalmol 1992;114:231-33.
integrity and allow for vision restoration in the future as stated 6. Gundersen T. Surgical treatment of bullous keratopathy. Arch
above.16 Ophthalmol 1960;64:260-67.
Therapeutic keratoplasty, AMT, BCLs, and cultured ocular 7. Gokhale NS. Penetrating keratoplasty after a total conjunctival
surface epithelial transplants have supplanted conjunctival flaps flap. Indian J Ophthalmol 2004;52:341-42.
8. Geria RC, Zarate J, Geria MA. Penetrating keratoplasty in eyes
in many cases. These newer procedures are not without their
treated with conjunctival flaps. Cornea 2001;20:345-49.
complications and limitations. Donor corneal tissue is usually 9. Cheng KC, Chang CH. Modified gunderson conjunctival flap
not freely available. AMT harvesting and preparation require combined with an oral mucosal graft to treat an intractable corneal
specialized equipment and technical expertise, there is a small lysis after chemical burn: a case report. Kaohsiung J Med Sci
but definite risk of infectious or prion disease transmission. 2006;22(5):247-51.
Extended wear BCLs are expensive, usually do not eliminate 10. Sippel KC, Ma JJ, Foster CS. Amniotic membrane surgery. Curr
medication requirements, and are associated with an increased Opin Ophthalmol 2001;12:269-81.
11. Fernandes M, Sridhar MS, Sangwan VS, et al. Amniotic
risk of microbial keratitis. The transplantation of cultured
membrane transplantation for ocular surface reconstruction.
epithelial equivalents is perhaps the most promising modality,
Cornea 2005;24:643-53.
but it is technically difficult, there are as yet no long-term results. 12. Arora R, Jain S, Monga S, et al. Efficacy of continuous wear
For these reasons, and particularly in developing countries PureVision contact lenses for therapeutic use. Cont Lens Anterior
where the burden of disease frequently exceeds the capacity in Eye 2004;27:39-43.
the health care delivery system, the Gundersen flap is still an 13. Kinoshita S, Koizumi N, Sotozono C, et al. Concept and clinical
important procedure and should be considered as a means of application of cultivated epithelial transplantation for ocular
stabilizing globe integrity in the management of cases of severe surface disorders. Ocul Surf 2004;2:21-33.
14. Ang LP, Nakamura T, Inatomi T, et al. Autologous serum-derived
ocular surface disease.
cultivated oral epithelial transplants for severe ocular surface
disease. Arch Ophthalmol 2006;124:1543-51.
15. Insler MS, Pechous B. Conjunctival flaps revisited. Ophthalmic
Surg 1987;18:455-58.
16. Geria RC, Zarate J, Geria MA. Penetrating keratoplasty in eyes
treated with conjunctival flaps. Cornea 2001;20:345-49.

352
50

Chapter 50: Future Developments


Future Developments
Vishal Jhanji, Karl David Brown, Rasik B Vajpayee, Hugh R Taylor

Corneal surgery has certainly come a long way since the first transplant surgery would replace only diseased tissues or
successful corneal transplantation which was performed by Dr ‘components’ in these situations.3
Eduard Zirm in 1905. In the succeeding 30 years, cornea Some of the recent innovations in component surgery of the
transplants were rare, and used only tissue from living donors. cornea include Descemet’s stripping automated endothelial
In those days, the cornea was removed from the donor, who was keratoplasty (DSAEK) for cases with endothelial dysfunction
often in the same operating room as the person receiving the and, automated anterior lamellar keratoplasty for the
donated tissue. We are fortunate to have been practicing in an management of corneal stromal dystrophies as well as
era with a well-established eye banking system, better transport keratoconus. Epithelial sheet transplantation can be successfully
media, binocular microscopes and novel surgical instruments. used in the treatment of ocular surface diseases such as Stevens-
Despite these significant advances in the field of corneal Johnsons syndrome, chemical injury and ocular cicatricial
transplantation, issues like management of a high-risk pemphigoid. All these surgical techniques have certain
keratoplasty and prevention of a graft failure still remain a major advantages over the conventional full-thickness corneal
concern today. This is especially relevant for high-risk cases like transplantation which may represent “overkill therapeutics” in
chemical injury, chronic inflammatory conditions and repeated these diseased states.4 Furthermore, the new techniques allow
grafts.1,2 In this chapter we will briefly discuss the ongoing the more appropriate utilization of the donor tissue so that one
developments in the field of corneal transplantation that aim to donor cornea can be used for more than one recipient. This is
increase the success of the surgery in addition to providing a especially useful in countries with shortage of donor corneal
better avenue for appropriate utilization of the existing resources. tissue.4
The main areas of focus for the development of corneal
transplantation include: Development of Artificial Cornea
1. Component surgery of the cornea
Keratoprosthesis (KPro), that involves the use of artificial
2. Development of artificial cornea materials to rebuild the damaged cornea, has been proposed as
3. Novel surgical techniques
an alternative to keratoplasty in high-risk cases.5-8 They are
4. Cultured corneal endothelial cells.
mainly designed to restore a functional level of vision. The
majority are made from plastic polymers and are designed
COMPONENT SURGERY OF THE CORNEA
to have a transparent central optic surrounded by a skirt to
The cornea consists of 3 cellular layers: epithelium, corneal provide stable anchorage through the integration into the host
stroma (comprising most of the corneal thickness), and the tissue. Some newer KPro designs now have modified anterior
single-layered endothelium. Each layer of the cornea is prone surfaces to promote epithelialization, as well methods to
to disease or injury that can cause irreversible opacification and inhibit downgrowth of epithelial cells into the stroma/implant
decreased visual acuity. interface.9-12
Although penetrating keratoplasty (PKP) has long been the Tissue engineered corneas have the same basic principle as
standard procedure for transplanting corneal tissue, all 3 layers keratoprosthesis. They are structured to provide the basic
of the cornea may not be needed in cases where, disease is limited anatomic and functional characteristics of a natural cornea.13
to certain layers only. For example, PKP may not be required in Although there is some argument as to the relative merits of
every cases of bullous keratopathy. Similarly, a full-thickness bioengineering versus artificial keratoprosthesis, it is also
corneal transplantation may increase the chances of endothelial feasible that hybrid materials that make use of both artificial and
graft rejection in a patient with keratoconus who could otherwise biologic material may enter the scene. Type I collagen, which is
benefit from an anterior lamellar keratoplasty. The ideal corneal the predominant extracellular matrix macromolecule found in
353
the human cornea, has been investigated by a number of groups do not have sufficient access to donor corneas for transplantation.
for its use as a scaffold for artificial cornea construction. Type I These reasons have led many researchers to test the possibility
collagen scaffolds have been used to cultivate human corneal of reliably culturing normal, corneal endothelial cells and then
stromal fibroblasts in vitro. In these cultures, the cell-scaffold transplanting them onto the recipient Descemet’s membrane.
interactions resulted in changes in the mechanical and Human corneal endothelial cells are maintained in an
permeability properties of the gels. The University of Ottawa arrested Gl-phase of division in vivo and do not normally
model is a hydrogel corneal substitute that has been implanted proliferate. Endothelial cells from older donors exhibit
Section VI: Alternatives to Penetrating Keratoplasty

successfully into a range of animal models.13 These hydrated proliferative capacity but in comparison with cells from younger
gels can be fabricated to the appropriate dimensions and donors, they enter the cell cycle more slowly. Several growth
curvatures, which allow for transmission of 90 percent or higher factors including fibroblast growth factor, epidermal growth
of white light. More recently, fibrillar recombinant human factor, and endothelial cell growth supplements have
collagens, types I (RHCI) and III (RHCIII), have been tested as demonstrated the ability to increase proliferation in cultured
corneal stromal matrix substitutes in pigs.14 The advantage of human corneal endothelium (Figs 50.1A and B). The feasibility
RHC is that it is produced synthetically in yeast and therefore of transplanting cultured animal or human corneal endothelial
avoids the risk of disease transmission from animal-extracted cells has been tested in the past in several models.23- 27 A recent
collagen and possible immune response. Currently, phase I model by Chen et al has indicated that it is possible to obtain a
human clinical trials have begun in Sweden where RHCIII healthy endothelial monolayer without the need for immortalized
corneal substitutes were, implanted as deep anterior lamellar
grafts. However, longer-term monitoring and testing in a larger
patient population is needed to determine whether or not they
will be useful as substitutes for donor tissue. In addition, further
modifications are likely needed to be useful to a wider range of
clinical indications.

Novel Surgical Techniques


Corneal surgeons around the world have been performing as well
as publishing novel techniques of corneal transplantation. These
techniques are aimed at management of challenging cases,
reducing intraoperative problems, as well as increasing the
chances of achieving a successful overall outcome. Many of these
surgical endeavors include fashioning of the corneal wound in
order to provide good integrity of the graft-host junction and to
induce rapid visual recovery.15,16
More recently, the femtosecond laser is being tested for
performing lamellar as well as full-thickness corneal
transplantation procedures. Use of the femtosecond laser to
create complex keratoplasty wound designs is a novel
technological advance to influence corneal transplantation. The
femtosecond laser-assisted penetrating grafts utilize stepped
incisions, with “top hat” or “mushroom” shapes, and Z-shaped
“zig-zag” incisions. These incisions have more wound surface
area to better resist rupture, plus the laser seems to induce a
fibrotic healing response along the vertical portion of the corneal
incision. All these features contribute to faster as well as better
visual recovery.17-21

CULTURED CORNEAL ENDOTHELIAL CELLS

The proposed use of cultured corneal endothelial cells in cases


with endothelial dysfunction has been a topic of discussion for
Figures 50.1A and B: Human corneal endothelial cells in vitro.
a few years.22 In about half of the cases requiring penetrating
Human corneal endothelial cells cultured from a primary cell
keratoplasty, such as bullous keratopathy and corneal suspension. Cells shown at day 33 of culture. (A) Endothelial
endotheliopathy, the endothelial cell layer is the only corneal cell sheet. (B) Central mass has morphology consistent with being
component that requires replacement. In addition, many countries a holoclone (a colony descended from a single stem cell).

354
cells. Preliminary functional data indicate that these transplanted 13. Griffith M, Jackson WB, Lagali N, Merrett K, Li F, Fagerholm
cells contribute to the dehydrated state of the stroma of recipient P. Artificial corneas: a regenerative medicine approach. Eye 2009
corneas.28 Future studies will determine whether any of these Jan 16. Epub 2009 Jan 16.
14. Fagerholm P, Lagali N, Carlsson DJ, Merret K, Griffith M.
gigantic efforts will be successful at the clinical level. The
Corneal regeneration following implantation of a biomimetic
ongoing studies provide a foundation for the further development tissue-engineered substitute. Clin Transl Sci (in press).
of methods to transplant corneal endothelial cells in vivo. 15. Kaushal S, Jhanji V, Sharma N, Tandon R, Titiyal JS, Vajpayee
RB. “Tuck In” Lamellar Keratoplasty (TILK) for corneal ectasias
SUMMARY

Chapter 50: Future Developments


involving corneal periphery. Br J Ophthalmol 2008;92:286-90.
16. Lee J, Winokur J, Hallak J, Azar DT. Femtosecond dovetail
With all these exciting and novel strategies being developed to
penetrating keratoplasty: surgical technique and case report. Br
combat various problems associated with corneal transplantation, J Ophthalmol 2009;93:861-63.
the future seems promising. 17. Farid M, Steinert RF, Gaster RN, Chamberlain W, Lin A.
Comparison of penetrating keratoplasty performed with a
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PR, Myers JS, Jin YP, Cohen EJ. Boston Keratoprosthesis
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8. Bradley JC, Hernandez EG, Schwab IR, Mannis MJ. Boston type in vitro. Part II: evaluation in the scanning electron microscope.
1 keratoprosthesis: the university of california davis experience. Cornea 1999;18:207-13.
Cornea 2009;28:321-27. 25. Gospodarowicz D, Greenburg G, Alvarado J. Transplantation of
9. Aldave AJ, Kamal KM, Vo RC, Yu F. The Boston type I cultured bovine corneal endothelial cells to species with
keratoprosthesis: improving outcomes and expanding indications. nonregenerative endothelium. The cat as an experimental model.
Ophthalmology 2009;116:640-51. Epub 2009 Feb 25. Arch Ophthalmol 1979;97:2163-69.
10. Ciolino JB, Dohlman CH. Biologic keratoprosthesis materials. 26. Jumblatt NM, Maurice DM, McCulley JP. Transplantation of
Int Ophthalmol Clin 2009 Winter;49:1-9. Review. tissue-cultured corneal endothelium. Invest Ophthalmol Vis Sci
11. Liu C, Hille K, Tan D, Hicks C, Herold J. Keratoprosthesis 1978;17:1135-41.
surgery. Dev Ophthalmol 2008;41:171-86. Review. 27. Aboalchamat B, Engelmann K, Bohnke M, et al. Morphological
12. Campillo-Fernandez AJ, Pastor S, Abad-Collado M, Bataille L, and functional analysis of immortalized human corneal
Gomez-Ribelles JL, Meseguer-Dueñas JM, Monleon-Pradas M, endothelial cells after transplantation. Exp Eye Res 1999;69:547-
Artola A, Alio JL, Ruiz-Moreno JM. Future design of a new 53.
keratoprosthesis. Physical and biological analysis of polymeric 28. Chen KH, Azar D, Joyce NC. Transplantation of adult human
substrates for epithelial cell growth. Biomacromolecules corneal endothelium ex vivo: a morphologic study. Cornea
2007;8:2429-36. 2001;20:731-37.

355
Index
Index

A surgical procedures 305 aphakia with loose vitreous 239


as a permanent graft 305 pseudophakia with hyaloid face
Ab externo approach 242 as an overlaid graft 305 intact 240
Ab interno approach 242 surgical procedures 310 pseudophakia with loose vitreous 240
Ablation 330 symptomatic bullous keratopathy 309 Artificial anterior chamber maintainer 65
Acanthamoeba keratitis 83,254 two modes of clinical uses 305 Artificial cornea 351
Adjunctive procedures 298 Anesthetics staff 44 Astigmatic keratotomy 132
Adnexal structures 297 Annular corneoscleral ring 279 Astigmatism 71, 111
Air injection 150 Annular keratectomy 140 Autokeratoplasty 281
Allogenic graft rejection 125 Anterior lamellar keratoplasty (ALK) 266 case selection 281
Allogenic penetrating limbo-keratoplasty 291 Anterior segment and iris 14 computer simulation 282
Amblyopia therapy 250 Anterior segment surgery 24 contralateral autokeratoplasty 281
Amniotic membrane transplantation Antibiotics 71,153 donor eye 281
287,305,348 Antiglaucoma medications 72 examination and investigations 281
AMT for Mooren’s ulcer 346 Antimetabolites 293 host eye 281
AMG for intractable infectious Antimicrobial therapy 256 mathematical method 282
keratitis 348 Antiviral prophylaxis 124 postoperative management 282, 283
AMT for impending and small Aphakia 239 advantages 283
corneal perforations Aphakic and pseudophakic bullous disadvantages 284
347 keratopathy 237 patient counseling 284
complications of amniotic evaluation of IOL 238 rotational autokeratoplasty 282
membrane examination of anterior segment 237 step five (host eye) 282
transplantation 348 flexible open-loop AC-IOL 240 step four (donor eye) 282
as a permanent graft 307,311 advantages 241 step one (host eye) 282
following superficial keratectomy disadvantages 241 step six (donor eye) 282
311 technique 241 step three (host eye) 282
for bullous and band gonioplasty 240 step two (donor eye) 282
keratopathy 312 history 237 surgical technique 282, 283
for corneal ulcers 311 IOL implantation 240 types of autokeratoplasty 281
for partial limbal stem cell IOL power calculations 238 contralateral autokeratoplasty 281
deficiency 312 iris-sutured PC-IOL 241 rotational autokeratoplasty 281
as an overlaid graft 309, 312 advantages 241 Autologous limbal epithelial cells 297
prokera™ 313 disadvantages 241 Automated lamellar therapeutic keratoplasty
to cover only corneal surface 313 technique 241 157
to cover entire ocular surface 312 lamellar keratoplasty 242 advantages 160
band keratopathy 309 PC-IOL in cilliary sulcus 241 complications 160
cryopreserved amniotic membrane advantages 241 contraindications 157
preparation 344 technique 241 donor recipient apposition 159
AMT for bullous keratopathy 345 preoperative evaluation 237 femtosecond assisted automated lamellar
AMT for neurotrophic ulcers 346 pupilloplasty 240 keratoplasty 160
keratoplasty-sparing indications for retinal evaluation 239 indications 157
AMT 345 scleral-fixated PC-IOL 242 machine 138
ex vivo expansion of epithelial stem ab externo approach 242 outcome of ALTK 160
cells 310 ab interno approach 242 preoperative evaluation 157
infectious keratitis and scleritis 308 advantages 242 surgical technique 157
partial limbal stem cell deficiency 309 disadvantages 242 preparation of the donor lenticule 157
persistent epithelial defects 307 technique 242 preparation of the recipient bed 157
postoperative care 313 surgical technique 239 Automated microkeratomes 149
sterile corneal stromal thinning 308 aphakia with hyaloid face intact 239 Azathioprine 84,293

357
B C high intraocular pressure and
pupillary-block
Bacterial keratitis 82,230,253 Cadaveric allogeneic limbal epithelial cells glaucoma 105
Band keratopathy 309 298 hyphema 105
Bandage contact lens 331 Cadaveric keratolimbal allograft 289 infectious crystalline keratopathy 109
Base curve 89 Calcineurin inhibitors 293 iris incarceration 100
Bicurve needles 62 Cardinal sutures 70 late postoperative 109
Big bubble technique 185 Cataract extraction 134 low intraocular pressure 106
advantages 186 Cataract extraction: triple procedure 229 maculopathy 113
Corneal Transplantation

anesthetic requirements 186 Cellcept 293 microbial keratitis 107


augmentation of big bubble 190 Central fit 91 prevention and treatment 102
contraindications 185 Central keratolimbal graft 271 primary graft failure 104
donor dissection 190 Central penetrating keratoplasty (PK) 276 recurrence of original recipient
Chemical burns 230 disorder 113
follow-up schedule 191
Chemical reduction methods 337 shallow anterior chamber and
hidden big bubble 190
Cilliary sulcus 241 wound leak 99
indications 185
Circular trephine 148 suture-related problems 101
intra-Descemet’s membrane big bubble
Clean area and draping 31 Urrets-Zavalia syndrome 109
190
Collagen synthetic epikeratoplasty lenticules vitreoretinal problems 113
limitations 186 143 wound dehiscence 100
management of complications 192 Combination corneal trephines 57 Component surgery of cornea 353
postkeratectomy big bubble 189 Combined conjunctival and keratolimbal Compound curve needles 62
postoperative medications 191 limbal allograft 290 Compression sutures 133
preoperative topical medications 186 Combined continuous and interrupted Compressive C-shaped lamellar keratoplasty
prevention of complications 192 suturing technique 278
recipient dissection 186 74 Computer simulation 282
results 192 Complications of penetrating keratoplasty 95 Concomitant retinal surgery 249
surgical instruments 191 intraoperative complications 95 Confocal microscopy 15
surgical technique 186 broken/loose/tight sutures 98 Conjunctiva and cornea 14
Blade breaker 58 damaged donor button 96 Conjunctival autograft 288
Bleeding 97 eccentric host trephination 96 Conjunctival deficiency 285
Blink rate 320 excessive bleeding 97 Conjunctival flap 351
Boston keratoprosthesis 317 improper trephination 95 Conjunctival limbal autograft 288
complications 324 injury to iris-lens diaphragm 97 Contact lens options 88
glaucoma 326 inversion of the graft 97 Contact lenses 131
infectious endophthalmitis 326 iris incarceration 98 Contact lenses fitting method 87
inflammation 325 irregular/oval trephination 96 Continuous suture 129, 131
retinal detachment 327 poor anesthesia and positive Contralateral autokeratoplasty 281
retroprosthetic membrane 325 vitreous pressure 95 Conventional circular trephines 54
soft contact lens loss 325 posterior capsular tear and vitreous Conventional large diameter PK 275
sterile uveitis – vitritis 326 prolapse 98 Corneal endothelial punches 58
problems with suturing graft to host Corneal epithelium 330
tissue necrosis and melt 325
98 Corneal evaluation 26
design and material 318
retained Descemet’s membrane 96 Corneal excision procedure 33
indications and prognostic categories
reversed host and donor trephines 95 Corneal graft 82
319
scleral perforation 95 infected eyes 82
materials 321
shallow anterior chamber 98 inflamed eyes (hot eyes) 82
patient evaluation 320 suprachoroidal hemorrhage 99 Corneal graft astigmatism 128
blink rate and tear secretion 320 suture related complications 98 assessment 130
documentation 321 wound leak 99 cataract extraction 134
history 320 postoperative complications 99 causes 128
intraocular pressure 320 astigmatism 111 compression sutures 133
slit-lamp examination 320 cataract 110 femtosecond-assisted 133
special examinations 320 corneal membranes 109 manual 133
visual acuity 320 disease transmission from donor requirements 133
patient selection 321 cornea 113 wedge excision 133
keratoprosthesis type I 321 early postoperative complications intraoperative factors 128
keratoprosthesis type II 321 99 other factors 129
postoperative care 322 endophthalmitis 108 other suture related factors 129
preoperative physical evaluation 321 epithelial defects 102 tissue distribution 128
surgery 321 fibrous ingrowth 110 wound edge profile and trephination
Broken/loose/tight sutures 98 filamentary keratitis 104 shape 128
Bullous and band keratopathy 312 glaucoma 112 wound profile asymmetry 129
Bullous keratopathy 345 graft rejection 105,109 management 131
Busin glide 139,216 herpes simplex keratitis 106 nonsurgical management 131

358
adjustment of continuous suture 131 surgical technique 269 Cutting blocks 57
selective suture removal 131 full thickness patch graft 270 Cutting instruments 58
spectacles and contact lenses 131 lamellar patch graft 269 Cyanoacrylate glue 279
postoperative factors 130 scleral patch graft 270 Cyclodestructive procedures 119
preoperative factors 128 surgical technique 271 Cycloplegics 72
donor 128 tectonic patch grafts 268 Cyclosporine 84,293
host 128 advantages over tissue adhesives 269
refractive laser surgery 133 indications 268 D
surgical management 132 Corneal marker 139

Index
astigmatic keratotomy 132 Corneal marking instruments 54 Deep anterior lamellar keratoplasty 185,277
femtosecond 132 Corneal membranes 109 Deep lamellar keratoplasty 167
manual 132 Corneal needle tattooing with pigments 338 De-epithelialization 140
surgical techniques for prevention 129 Corneal opacity in elderly patients 230 Descemet’s membrane 153,174,215
suturing techniques 129 Corneal perforations 347 Descemet’s membrane endothelial
continuous sutures 129 Corneal scissors 59 keratoplasty 225
interrupted sutures 130 Corneal stroma 195 donor preparation 226
Corneal graft rejection 122 Corneal surface 313 instruments required 225
causes of secondary graft failure 122 Corneal tattooing 337 postoperative regime 227
clinical presentation 124 basic principle 337 preoperative evaluation and indication
signs 124 indications and contraindications 337 225
symptoms 124 methods of tattooing 337 recipient preparation 226
definition of graft failure 122 chemical reduction methods 337 surgical technique 226
differential diagnosis 126 corneal needle tattooing with Descemet’s stripping automated endothelial
epithelial downgrowth 127 pigments 338 keratoplasty 204,220
graft failure 126 corneal tattooing with palladium combined procedures 209
herpes zoster virus inflammation 127 oxide 338 evolution of EK 204
HSV keratitis 126 corneal tattooing with pigments 339 future directions 211
loose sutures and secondary microbial direct inoculation methods 338 indications 205
keratitis 126 tattooing with gold chloride 338 instrumentation 205
microbial keratitis 126 present status 339 outcomes 210
postsurgical inflammation 127 Corneal tissue act 41 refractive outcomes 210
prevention of graft rejection 123 Corneal transplant center 43 visual outcomes 210
antiviral prophylaxis 124 anesthetics staff 44 postoperative care and complications 210
careful case selection 123 audit and outcome monitoring 47 surgical technique 206
identifying high-risk corneal grafts check list for booking a case 46 graft insertion and attachment 208
123 eye bank 43 manual donor dissection 206
systemic corticosteroid sparing follow-up 46 microkeratome donor dissection
immunosuppression lasers in corneal surgery 44 206
123 operating theater issues 44 recipient preparation 207
tissue matching 123 patient coordination and education 43 Descemet’s stripping endothelial
topical corticosteroids 123 research 46 keratoplasty 266
primary and secondary graft failure 122 special equipment 44 Descemetocele 308
prognosis 127 specialty theater nurses 44 Diamond knife 58
rejection post lamellar keratoplasty 126 ward/staff education 44 Direct inoculation methods 338
treatment of rejection 125 wet lab 46 Disease transmission from donor cornea
early recognition 125 Corneal trephination 194 21,113
keratoconus and allergic eye disease Corneal trephines 54 Divide and Conquer technique 150
126 Corneal ulcers 309 Donor button 96
minimum treatment for allogenic Corneal/scleral horse-shoe grafts 278 Donor cornea 69
graft rejection 125 Corneo-iridic scar 274 dissection 137
role of oral corticosteroids and Corneoscleral button 65 recipient 69
steroid sparing agents Corneoscleral caps 151 trephination 232
125 Corneoscleral rim sectioning 26 Donor dissection 190
types of graft rejection 122 Corneoscleroplasty with maintenance of Donor eye 281
Corneal graft/ high-risk corneal graft 83 angle 279 Donor graft preparation 266
Corneal grafting 1 Coroner’s consent 40 Donor lenticule and suturing 195
glaucoma 82 Corticosteroids 72,83,153,292 Donor material 256
ocular surface diseases 81 Cosmetic keratoplasty 8 Donor preparation 226
Corneal grafting surgery 1, 268 Cottingham corneal punch 58 Donor recipient apposition 159
central keratolimbal graft 271 Crescentic lamellar keratoplasty 276 Donor selection 21
donor tissue selection 271 Cryopreserved amniotic membrane Donor stromal button preparation 164,166
indications 271 preparation 344 Donor tissue 21,175
outcome 271 Culture media 298 preparation 215,262
postoperative care 271 Cultured corneal endothelial cells 354 selection 271
sclerokeratoplasty 272 Cultured limbal stem cell 296 Donor–recipient apposition 262
359
Double bubble technique 194 adjunctive procedures 298 slit-lamp evaluation 26
complications 197 adnexal structures 297 specular microscopy 27
confirmation of big bubble formation autologous limbal epithelial cells 297 current and future trends 30
195 cadaveric allogeneic limbal epithelial disease transmission from donor corneas
corneal trephination 194 cells 298 21
indications 194 clinical features 296 bacterial 23
injection of air into corneal stroma 195 complications 301 fungal 23
postoperative follow-up 197 culture media 298 infections 23
preparation of donor lenticule and explant culture system 299 intrinsic eye disease 24
Corneal Transplantation

suturing 195 suspension culture system 299 malignancies 24


preparation of patient 194 diagnosis of LSCD 296 prion disease 21
surgical technique 194 histopathological diagnosis 296 viral 23
suture removal 197 impression cytology 296 donation of eye tissue 24
Double continuous suturing technique 75 intraoperative complications 301 corneoscleral rim sectioning 26
Dry eye 81 investigations 296 enucleation 26
DSAEK anterior chamber maintainer 139 keratoplasty 302 eye donation surgery 25
DSAEK busin forceps 139 limbal biopsy 297 eye donor coordination 24
DSAEK spatula (stripper) 138 limbal stem cell culture technique 298 in situ excision 26
limbal stem cell harvesting 298 medical history review 25
E live related allogeneic limbal epithelial preparation of donor 25
cells 298 serology testing 25
Early postoperative complications 99 location of limbal stem cells 295 donor age 24
Early postoperative management 78 microbial keratitis 299 lower donor age 24
Eccentric host trephination 96 rejection of limbal graft 299 donor selection 21
Electrophysiological tests 18 other complications 299 postoperative infection 30
Endophthalmitis 108 outcome 301 practical guide 20
Endothelial microscopy 27 posterior segment evaluation 296 regulation and quality systems 20
Enucleation 26,31 postoperative complications 301 storage 28
Epikeratoplasty 140,276 postoperative treatment 299 hypothermic corneal storage 28
advantages and disadvantages 142 primary limbal stem cell deficiency 295 moist chamber storage 28
comparison of epikeratoplasty and role of cultured limbal stem cell 296 normothermic (organ culture)
penetrating secondary limbal stem cell deficiency 295 storage 29
keratoplasty 143 slit-lamp examination 296 suggested corneal excision procedure 33
complications 142 tear film status 297 clean area and draping 33
histopathological and tissue screening 297 preparation 33
immunohistochemical transplantation procedure 299 restoration 33
changes 142 types of LSCD 296 surgery 33
intraoperative problems 142 ultrabiomicroscopy 297 suggested enucleation procedure 31
postoperative complications 142 ultrasonic pachymetry 296 clean area and draping 31
indications 140 Ex vivo expansion of epithelial stem cells 310 preparation 31
lenticules 142 Ex vivo stem cell expansion 291 restoration 31
outcome 143 Explant culture system 299 surgery 31
postoperative regimen 141 Extracapsular cataract extraction 232 suggested preparation of donor 31
preparation of recipient cornea 140 Eye bank 43,48,50 clean area 31
annular keratectomy 140 assistance 50 in situ examination 31
de-epithelialization 140 criteria for eligibility 50 preparation of surgical pack 31
procurement of donor lenticules 141 eye donation center (EDC) 48 prior to preparation 31
manual dissection of donor lenticule feasibility study 48 rinse and swab 31
141 financial viability 49 Eye banking laws 38
surgical technique 140 hospital in local area and their potential Eye donation center 48,50
suturing 141 49 Eye donation surgery 25
synthetic epikeratoplasty 143 legal formalities 50 Eye donor coordination 24
collagen synthetic epikeratoplasty location of center 49 Eye globe fixation 57
lenticules 143 pattern of assistance 50 Eye speculum 53
protein coated hydrogel population and total potential 49 Eye tissue 24
epikeratoplasty procedure for application 50
lenticules 143 requirements for an ideal eye bank set F
things to remember 143 up 50
tectonic epikeratoplasty 141 Eye banking 20 Femtosecond assisted automated lamellar
Epithelial defects 102,307 contraindications for use of donor tissue keratoplasty 160
Epithelial downgrowth 127 21 Femtosecond laser assisted keratoplasty
Epithelial problems 81 corneal evaluation 26 264
Epithelial transplantation procedures 288 endothelial microscopy 27 anterior lamellar keratoplasty 266
Ex vivo cultured limbal stem cell gross in situ evaluation 26 Descemet’s stripping endothelial
transplantation 295 light microscopy 27 keratoplasty 266

360
femtosecond laser assisted penetrating HSV disease 124 Inflammation 325
keratoplasty 264 HSV keratitis 126 Initial base curve selection 90
femtosecond laser principles 264 Human organ transplant act, 1989 41 Interface fluid 217
postoperative care 266 Hyaloid face intact 239 Interface haze 173
preoperative work up 265 Hybrid lenses 92 International laws on eye banking 38
results 266 Hydrodelamination 150 Interrupted sutures 130
technique 265 Hydrogel lenses 91 Intractable infectious keratitis 348
donor graft preparation 266 Hyphema 105 Intra-Descemet’s membrane big bubble 190
recipient cornea preparation 265 Hypothermic corneal storage 28 Intraocular lens power calculations 231

Index
Fibrous ingrowth 110 Intraocular pressure 15,320
Filamentary keratitis 104 I Intraoperative problems 142
Flexible open-loop AC-IOL 240 Intrinsic eye disease 24
Forceps 59,139 Ideal eye bank set up 50 IOL implantation 240
Fuchs’ dystrophy 229 Immunosuppression 83 IOL power calculations 238
Full curve needles 62 Impression cytology 296 IOWA PK press corneal punch 58
Full thickness patch graft 270 Improper trephination 95 Iris 97
Full thickness peripheral grafting 277 Imuran 293 diaphragm 249
Fundus evaluation 15 In situ examination 31 incarceration 98
Fungal keratitis 83,253 In situ excision 26 lens diaphragm 97
Future developments 353 Indian human organs transplantation act, procedures 249
component surgery of cornea 353 1994 41 sutured PC-IOL 241
development of artificial cornea 353 Indication specific corneal grafting Irregular/oval trephination 96
novel surgical techniques 354 techniques 274
cultured corneal endothelial cells 354 annular corneoscleral ring 279 K
compressive C-shaped lamellar
G keratoplasty 278 Keratoconus and allergic eye disease 126
conventional large diameter 275 Keratoepithelioplasty 280
Gas permeable lenses 88 corneal/scleral horse-shoe grafts 278 Keratoglobus 278
Gauze piece fixated eyeball 57 corneo-iridic scar 274 Keratometry 15
Glaucoma 112,119,326 corneoscleroplasty with maintenance of Keratoplasty with foci resection 278
Glaucoma drainage devices 119 angle 279 Keratoplasty-sparing indications for AMT 345
Glaucoma filtering procedures 119 crescentic lamellar keratoplasty 276 Keratoprosthesis 321
Globe exposure 53 cyanoacrylate glue 279
Globe supporting rings 53 deep anterior lamellar keratoplasty 277 L
Gold chloride 338 epikeratoplasty 276,278
Gonioplasty 240 full thickness peripheral grafting 277 Lagophthalmos 81
Gonioscopy 15 dissection of ectatic area 277 Lamellar crescentic resection 276
Graft failure 122,126 keratoepithelioplasty 280 Lamellar dissection 149
Graft host disparity 64 keratoglobus 278 host tissue 150
Graft insertion and attachment 208 keratoplasty with foci resection 278 recipient bed 149
Graft rejection 105,109,122,126 lamellar crescentic resection 276 Lamellar dissectors 137
Graft-host disparity 148 lamellar keratoplasty 279 Lamellar keratoplasty versus penetrating
Grasping instruments 59 large eccentric penetrating keratoplasty keratoplasty 147
Gross ocular examination 14 276 Lamellar patch graft 269
Gundersen flap 350 limbal conjunctival resection 279 Lamellar pocket method 339
complications of conjunctival flap 351 limbus based lamellar scleral flap 277 Large eccentric penetrating keratoplasty 276
modifications of technique 351 Mooren’s ulcer 279 Large-diameter lamellar keratoplasty 290
other indications 351 pellucid marginal degeneration 275 Laser interferometry 16
surgical techniques 351 penetrating keratoplasty 280 Laser iridotomy 119
scleral auto-transplantation 277 Lasers in corneal surgery 44
H simultaneous crescentic lamellar Lens materials 89
keratoplasty 276 Lens overall diameter 89
Hand-held trephines 67 surgical technique 274 Lens power 90
Herpes simplex 83 tectonic lamellar keratoplasty 279 Lens thickness 90
Herpes simplex keratitis 106 Terrien’s marginal degeneration 277 Lid-speculum 64
Herpes zoster virus inflammation 127 tuck in lamellar keratoplasty 276,279 Lieberman gravity-action punch 58
Herpetic keratitis 230,255 two-step annular tectonic lamellar Light microscopy 27
Hidden big bubble 190 keratoplasty 277 Limbal conjunctival resection 279
High intraocular pressure 105 Infections 23 Limbal graft 299
High-risk corneal grafts 123 bacterial 23 Limbal stem cell 295
High-risk keratoplasty 83 fungal 23 culture technique 298
Holding instruments 59 viral 23 deficiency 285
Host bed preparation 164 Infectious crystalline keratopathy 109 harvesting 297
Host cornea 66 Infectious endophthalmitis 326 transplantation 285
Host eye 281 Infectious keratitis and scleritis 308 Limbal stem cell transplantation 285
361
allogenic penetrating limbo-keratoplasty intraoperative medications and rigid gas permeable contact lens fitting
291 postoperative regime 179
amniotic membrane transplantation 287 153 strategy to minimize interface haze 173
antimetabolites 293 antibiotics 153 suturing technique 175
azathioprine (imuran) 293 corticosteroids 153 viscodissection of Descemet’s
mycophenolate mofetil (cellcept) lubricants 153 membrane 174
293 lamellar keratoplasty 147 Microbial keratitis 107,126,299
sirolimus (rapamycin) 293 advantages 147 Microkeratome donor dissection 206
calcineurin inhibitors 293 disadvantages 148 Microkeratome-assisted deep lamellar
Corneal Transplantation

cyclosporine A (CSA, sandimmune) lamellar keratoplasty versus penetrating keratoplasty 168


293 keratoplasty 147 Microkeratome-assisted posterior
classification of epithelial modifications in technique 150 keratoplasty 164
transplantation 286 air injection 150 outcome 165
conjunctival autograft 288 divide and Conquer technique 150 surgical technique5 164
conjunctival deficiency 285 hydrodelamination 150 donor stromal button preparation
conjunctival limbal autograft 288 viscoelastic injection 150 164
cadaveric keratolimbal allograft 289 postoperative 154 host bed preparation 164
limbal allograft 290 preoperative evaluation 148 transplantation 165
living-related conjunctival limbal preparation of recipient cornea 148 Mini curve needles 62
allograft 289 automated microkeratomes 149 Moist chamber storage 28
corticosteroids 292 lamellar dissection of recipient bed Mooren’s ulcer 279,346
epithelial transplantation procedures 288 149 Mycophenolate mofetil 84,293
ex vivo stem cell expansion 291 manual, free hand dissection 149
large-diameter lamellar keratoplasty 290 non-mechanical excimer laser N
limbal stem cell deficiency 285 trephination 149
ocular surface anatomy 285 trephination with a circular trephine Needles 62
post-transplant systemic 148 bicurve needles 62
immunosuppression surgical technique 148 compound curve needles 62
292 suture removal 153 full curve needles 62
systemic immunosuppressive agents 292 suturing of graft 152 mini curve needles 62
tacrolimus 293 types of lamellar keratoplasty 145 Neurotrophic ulcers 346
treatment of severe ocular surface Manual, free hand dissection 149 New lamellar keratoplasty techniques 164
disease 286 Medicolegal aspects of eye banking 38 posterior keratoplasty and deep lamellar
Limbus based lamellar scleral flap covered Australia 39 keratoplasty 164
by fornix based certification of death 40 posterior lamellar keratoplasty 164
conjunctival flap consent of next-of-kin 40 surgical technique 164
277 Coroner’s consent 40 Non-contact trephines 57
Live related allogeneic limbal epithelial cells designated officer authorization 40 Non-mechanical excimer laser trephination
298 retrieval of eyes/corneas 40 149
Living-related conjunctival limbal allograft India 41 Non-mechanical laser trephination 66
289 authority for removal 41 Non-mechanical trephination of recipient
Loose sutures 126 Indian human organs transplantation cornea 69
Low intraocular pressure 106 act, 1994 41 Nonsurgical management of post PKP
Lower donor age 24 offences and penalties 42 astigmatism 131
Lubricants 72,153 restrictions on removal and Non-toothed forceps 59
transplantation 42 Normothermic (organ culture) storage 29
M international laws on eye banking 38 Novel surgical techniques 354
transplantation of human organs rules, Nylon 61
Maculopathy 113 1995 42
Manual deep stromal dissection 174 UK 40 O
Manual dissection of donor lenticule 141 corneal tissue act, 1986 41
Manual donor dissection 206 human organ transplant act, 1989 41 Ocular examination 14
Manual lamellar keratoplasty 145 USA 38 Ocular history 13
complications of lamellar keratoplasty presumed consent law 39 Ocular surface 310
153 revised uniform anatomical gift act, Ocular surface anatomy 285
graft-host disparity 148 2006 39 Ocular surface disease 286
harvesting of donor lenticule 151 uniform anatomical gift act 38 One corneal punch 139
corneoscleral caps 151 Melles technique 170 Operating theater issues 44
pre-carved lyophilized tissue 151 instruments 183 Optic zone 89
whole eye 151 manual deep stromal dissection 174 Optical correction 250
indications and contraindications 145 optical visualization 170 Optical iridectomy 335
indications for lamellar keratoplasty 145 perioperative topical and systemic Optical keratoplasty 4
intraoperative 153 therapy 177 Optical sector iridectomy 335
perforation of Descemet’s preparation of donor tissue 175 indications of optical iridectomy 335
membrane 153 results 182 mechanism of action 335
362
preoperative evaluation 335 complications 333 rose k contact lens 90
results and outcome 336 evaluation parameters 329 rose k post-graft fitting procedure 90
surgical technique 336 follow-up 331 size of the lens 91
Optical visualization 170 guidelines for patient selection 329 soft contact lens fitting 91
Oral corticosteroids and steroid sparing indications 329 therapeutic soft contact lens fitting
agents 125 methods 329 91
Overlaid graft 305,309,312 outcome 331 indications 86
postoperative evaluation and treatment long-term indications 86
P 331 short-term indications 86

Index
preparation of eye 329 rigid contact lenses 87
Pachymetry 15 surgical technique 330 soft contact lenses 87
Painting and draping 63 ablation of superficial corneal tissue Postoperative care after penetrating
Palladium oxide 338 330 keratoplasty 78
Partial limbal stem cell deficiency 309,312 placement of bandage contact lens corneal graft in infected eyes 82
Patient coordination and education 43 331 acanthamoeba keratitis 83
Patient counseling 284 removal of corneal epithelium 330 bacterial keratitis 82
Patient evaluation 320 Piggyback lenses 91 fungal keratitis 83
Patient preparation 222 Polyester (mersilene) 61 herpes simplex 83
Patient selection 321 Polypropylene (prolene) 61 corneal graft in inflamed eyes (hot eyes)
Pediatric keratoplasty 245 Post penetrating keratoplasty glaucoma 117 82
alternatives to penetrating keratoplasty diagnosis 118 corneal grafting in glaucoma 82
249 factors associated with IOP elevation 117 corneal grafting in ocular surface
concomitant procedures 249 intraoperative 117 diseases 81
concomitant retinal surgery 249 postoperative 118 dry eye 81
early 249 preoperative 117 lagophthalmos 81
immediate 249 incidence 117 postoperative prevention 81
indications 245 management 118 trichiasis 81
iris procedures 249 cyclodestructive procedures 119 repeat corneal graft/high-risk corneal
peripheral iridectomy 249 glaucoma drainage devices 119 graft 83
pupilloplasty 249 glaucoma filtering procedures 119 azathioprine 84
tightening iris-diaphragm 249 laser iridotomy 119 corticosteroids 83
optical correction and amblyopia managing pre-existing glaucoma 119 cyclosporine A 84
therapy 250 medical 118 immunosuppression in high-risk
postoperative care 249 surgical 119 keratoplasty 83
preoperative assessment 245 Post PKP astigmatism 129 mycophenolate mofetil 84
results 250 Posterior capsular tear and vitreous tacrolimus 84
surgical technique 247 prolapse 98 standard postoperative care 78
suture removal 250 Posterior lamellar keratoplasty 164 early postoperative management 78
timing of surgery 246 Posterior segment evaluation 296 first postoperative day 79
Pellucid marginal degeneration 275 Postkeratectomy big bubble 189 postoperative visits 79
Penetrating keratoplasty 4 Postkeratoplasty contact lens fitting 86 Postoperative complications 99,142,
alternatives and contraindications 11 contact lenses fitting method 87 217,301
expected outcomes 9 base curve and peripheral curve Postoperative evaluation and treatment 331
excellent prognosis 9 systems 89 Postoperative factors 130
fair prognosis 10 central fit 91 Postoperative follow-up 197
poor prognosis 10 complications 92 Postoperative infection 30
very good prognosis 9 contact lens options 88 Postoperative management 217,282
fellow eye 9 design 91 Postoperative medications 191
indications 4 gas permeable lenses 88 Postoperative regime 141, 227,263
cosmetic keratoplasty 8 goals 89 Postoperative treatment 223,299
optical keratoplasty 4 hybrid lenses 92 Postoperative visits 79
tectonic/reconstructive keratoplasty 7 hydrogel lenses 91 Postsurgical inflammation 127
therapeutic keratoplasty 7 initial base curve selection 90 Post-transplant systemic immunosuppression
regional differences and changing lens materials 89 292
indications 8 lens overall diameter 89 Power 91
Perioperative topical and systemic therapy lens power 90 Pre-carved lyophilized tissue 151
177 lens thickness 90 Prefit examination 341
Peripheral curve systems 89 materials 91 Pre-fitting examination 90
Peripheral fit 91 optic zone 89 Prefitting physiologic and topographic
Peripheral iridectomy 249 peripheral fit 91 considerations 87
Permanent graft 305,307,311 physiologic and topographic Preoperative assessment 245
Phacoemulsification 234 considerations 87 Preoperative considerations 214
Phototherapeutic keratectomy 329 piggyback lenses 91 Preoperative evaluation 13,148,157,231,
aim 329 power 91 237,335
anesthesia 329 pre-fitting examination 90 general history 13

363
investigations 15 Recipient cornea 140,148,232,265 Slit-lamp 14
confocal microscopy 15 preparation 265 biomicroscopy 14
electrophysiological tests 18 trephination 232 evaluation 26
gonioscopy 15 Recipient dissection 186 examination 296,320
indication 225 Recipient preparation 207,215,226,262 Soft contact lens 87,91,325
keratometry 15 Refraction 15 fitting 91
laser interferometry 16 Refractive laser surgery 133 loss 323
pachymetry 15 Refractive outcomes 210 Spatulas and hooks 60
refraction 15 Rejection post lamellar keratoplasty 126 Specialty theater nurses 44
Corneal Transplantation

slit scanning and Scheimpflug Removal and transplantation of human Spectacles 131
imaging 16 organs 42 Specular microscopy 15,27
specular microscopy 15 Restoration 31,33 Standard postoperative care 78
tear film status 15 Retained descemet’s membrane 96 Sterile corneal stromal thinning 308
ultrasonography 17 Retinal detachment 327 Sterile melts 256
ultrasound biomicroscopy 16 Retinal evaluation 239 Sterile uveitis – vitritis 326
videokeratography 16 Retrieval of eyes/corneas 40 Storage 28
ocular examination 14 Retroprosthetic membrane 323 Stroma 174
anterior segment and iris 14 Reversed host and donor trephines 95 Stromal fenestrations 216
conjunctiva and cornea 14 Revised uniform anatomical gift act, 2006 39 Suction fixation trephines 64
fundus evaluation 15 Rigid contact lenses 87 Suction trephine 68
gross ocular examination 14 Rigid gas permeable contact lens fitting 179 Superficial corneal tissue 330
intraocular pressure 15 Rinse and swab 31 Superficial keratectomy 311
lens 15 Rose K contact lens 90 Suprachoroidal hemorrhage 99
slit-lamp biomicroscopy 14 Rose K post-graft fitting procedure 90 Surgical instruments for lamellar
visual acuity 14 Rotational autokeratoplasty 281 keratoplasty 137
ocular history 13 Rothman-Gilbard corneal punch 58 automated lamellar therapeutic
Preoperative factors 128 keratoplasty machine
Preoperative management 231 138
S
Preoperative physical evaluation 319 busin glide 139
Preoperative preparation 63 Sandimmune 293 corneal marker 139
Preoperative topical medications 186 Scheimpflug imaging 16 DSAEK anterior chamber maintainer 139
Preoperative work up 220,265 Scleral auto-transplantation with lamellar DSAEK busin forceps 139
Primary and secondary graft failure 122 keratoplasty 277 DSAEK spatula (stripper) 138
Primary graft failure 104 Scleral fixation ring 64 forceps 139
Primary limbal stem cell deficiency 295 Scleral patch graft 270 instruments for donor cornea dissection
Prion disease 21 137
Scleral perforation during application of
Prokera™ 313 lamellar dissectors 137
fixation sutures 95
Prosthetic contact lenses 341 one corneal punch 139
Scleral tunnel incision 174
follow-up 343 Surgical instruments for penetrating
Scleral-fixated PC-IOL 242
prefit examination 341 keratoplasty 53
Sclerocorneal pocket incision 166
problems in fitting 342 corneal trephines 54
outcome 166
prosthetic fitting procedure 341 combination corneal trephines 57
surgical technique 166
prosthetic lens care 343 conventional circular trephines 54
donor stromal button preparation
prosthetic lens options 341 non-contact trephines 57
166
pupil size problems 342 single point cutting corneal
Prosthetic fitting procedure 341 host bed preparation 166
trephines 57
Prosthetic lens care 343 transplantation 166
types of trephines 54
Prosthetic lens options 341 Sclerokeratoplasty 272
cutting blocks 57
Protein coated hydrogel epikeratoplasty Secondary graft failure 122
corneal endothelial punches 58
lenticules 143 Secondary limbal stem cell deficiency 295 Cottingham corneal punch 58
Pseudophakia 240 Secondary microbial keratitis 126 Lieberman gravity-action punch 58
with hyaloid face intact 240 Selective suture removal 131 Rothman-Gilbard corneal punch 58
with loose vitreous in anterior chamber Serology testing 25 Troutman corneal punch 58
240 Shallow anterior chamber 98 cutting instruments 58
Pupil size problems 342 Shallow anterior chamber and wound leak 99 blade breaker 58
Pupillary-block glaucoma 105 Simultaneous crescentic lamellar keratoplasty corneal scissors 59
Pupilloplasty 240,249 (LK) 276 diamond knife 58
Simultaneous extracapsular cataract extraction eye globe fixation 57
Q with corneal trans- Tudor Thomas stand 57
plantation 232 gauze piece fixated eyeball 57
Qualitative keratometers 60 Single continuous suturing technique 74 grasping instruments 59
Single interrupted suturing technique 73 forceps with special functions 59
R Single point cutting corneal trephines 57 non-toothed forceps 59
Sirolimus (rapamycin) 293 toothed forceps 59
Recipient bed 157 Slit scanning 16 holding instruments 59
364
instruments for globe exposure 53 check for wound leakage 70 Topical corticosteroids 123
corneal marking instruments 54 intraoperative adjustment for Transplantation of human organs rules, 1995
eye speculum 53 astigmatism 71 42
globe supporting rings 53 placement of cardinal sutures 70 Trauma 230
qualitative keratometers 60 placement of donor cornea 69 Trephination 64
spatulas and hooks 60 placement of other sutures 70 Trephination shape 128
Surgical wounds 215 trephination of donor cornea 64 Trephines 54
Suspension culture system 299 graft host disparity 64 Trichiasis 81
Suture 61,75 harvesting donor graft 64 Triple procedure 220

Index
adjustment 75 non-mechanical laser trephination 66 anesthesia 221
materials and needles 61 trephining donor cornea 65 bacterial keratitis 230
nylon 61 trephination of recipient cornea 67 chemical burns 230
polyester (mersilene) 61 non-mechanical trephination 69 combined versus single staged
polypropylene (prolene) 61 trephining recipient cornea 68 procedures 229
related complications 98 trephining with hand-held trephines complications and their management 223
removal 75,153,197,250,263 67 considerations for selection of
tension 234 Suturing techniques in penetrating intraocular lens 220
Sutureless Descemet’s stripping automated keratoplasty 73 corneal opacity in elderly patients 230
endothelial suture adjustment and suture removal 75 Fuchs’ dystrophy 229
keratoplasty 214 combined continuous and interrupted herpetic keratitis: selective cases 230
anesthesia 214 sutures 76 indications 220, 29
complications 217 double continuous sutures 76 intraocular lens power calculations 231
intraoperative complications 217 single continuous suture 76 outcome 224,234
donor tissue preparation 215 suturing techniques 73 patient preparation 222
indications 214 combined continuous and phacoemulsification 234
postoperative complications 217 interrupted suturing postoperative care 235
postoperative management 217 technique 74 postoperative treatment 223
preoperative considerations 214 double continuous suturing preoperative evaluation 231
preparation of patient 214 technique 75 preoperative management 231
recipient preparation 215 single continuous suturing preoperative work up 220
centration of donor lenticule 217 technique 74 preparation of donor lenticule 221
creation of stromal fenestrations 216 single interrupted suturing technique presurgical preparation 221
creation of surgical wounds 215 73 simultaneous extracapsular cataract
drainage of interface fluid 217 Tectonic epikeratoplasty 141,279 extraction 232
insertion of donor lenticule 216 Tectonic patch grafts 268 adjustment of suture tension 234
stripping of Descemet’s membrane Tectonic/reconstructive keratoplasty 7 donor cornea trephination 232
215 Temporary graft 235 extracapsular cataract extraction 232
surgical technique 214 Temporary keratoprosthesis 235 recipient cornea trephination 232
Suture-related problems 101 Terrien’s marginal degeneration 277 suturing the graft 234
Symptomatic bullous keratopathy 307 Therapeutic keratoplasty 252 surgical technique 231
Synthetic epikeratoplasty 143 acanthamoeba keratitis 254 temporary graft 235
Systemic immunosuppressive agents 292 antimicrobial therapy 256 temporary keratoprosthesis T 235
bacterial keratitis 253 trauma 230
T donor material 256 Troutman corneal punch 58
Tacrolimus 84,293 fungal keratitis 253 Tuck in lamellar keratoplasty 199,276,279
Tattooing 337 herpetic keratitis 255 fixation of graft 201
Tear film status 15,297 indications for therapeutic keratoplasty indications 199
Tear secretion 320 252 modifications 202
Technique of penetrating keratoplasty 63 persistent epithelial defects and sterile postoperative care 202
intraoperative medications and melts 256 preparation of the graft 199
postoperative regime postoperative management 258 anterior approach 199
71 pre-surgical evaluation 256 posterior approach 201
antibiotics 71 surgical technique 257 preparation of host bed 199
antiglaucoma medications 72 visual prognosis for therapeutic technique 199
corticosteroids 72 keratoplasty 259 Tuck in penetrating keratoplasty 262
cycloplegics 72 Therapeutic keratoplasty 7,252 donor tissue preparation 262
lubricants 72 Therapeutic penetrating keratoplasties 258 donor–recipient apposition 262
marking host cornea 66 Therapeutic soft contact lens fitting 91 postoperative regime 263
preoperative preparation 63 Tissue 123 recipient preparation 262
surgical preparation 63 adhesives 269 results 263
exposure and insertion of lid- distribution 128 surgical technique 262
speculum 64 matching 123 suture removal 263
painting and draping 63 necrosis and melt 325 Tudor Thomas stand 57
placement of scleral fixation ring 64 screening 297 Two-step annular tectonic lamellar
suturing of donor cornea 69 Toothed forceps 59 keratoplasty 277
365
U V W
Ultrabiomicroscopy 297 Videokeratography 16 Ward/staff education 44
Ultrasonic pachymetry 296 Viscodissection 174 Wedge excision 133
Viscoelastic injection 150
Ultrasonography 17 femtosecond-assisted 133
Visual acuity 14,320
Ultrasound biomicroscopy 16 Visual outcomes 210 manual 133
Uniform anatomical gift act 38 Visual prognosis 259 Wet lab 46
Urrets-Zavalia syndrome 109 Vitreoretinal problems 113 Whole eye 151
Corneal Transplantation

366

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