Recent A Advances : Cataract surgery and Age related M C t t dA l t d Macular l Degen g neration

Vaughan Tanner g Consultant Opht thalmic Surgeon

Reading Royal Berkshire Hospital Dunedin Hospital www.tann -eyes.co.uk nerner Windsor King Edward VII Hospital Princess Margaret Hospital

Age-relat cataract Ageg ted

Nuclear sclerosis Cortica lens opacity al

Posterior sub-capsular

Phacoemulsificatio cataract surgery on

Small incision phacoem mulsification has revolutionised cataract surgery t 1.8 mm Micro-incision Quicker rehabilitation n Less astigmatism Day case Local anaesthetic

Topical A Anaesthetic
Topical anaesthesia - my pre eferred technique Proxymetacaine and amethocai ine No injection N i j ti No orbital bruising No conjunctival bleeding Faster visual recovery General anaesthetic if very n nervous / young Sub-tenons anaesthesia if bl linker

Astigmatism g
On axis incision Li b l relaxing incisions Limbal l i i i i

Limbal Relax g Incisions xing

Partial thickness incisions in the cornea result in relaxation n of tissue and decrease in ast tigmatism Aim make cornea closer to a perfect sphere o Careful not t overcorrect C f l t to t

550 um

Acrysof Natural l
Recently released Currently use high risk eyes with signs of ARMD y g y g May start using as routi in all eyes if continued ine follow up is favourable

Modern Cataract Surgery so far : t

Predictable lens power r Topical anaesthesia Day case Blocked Bl k d UV li h light Blocked harmful blue l light Decreased astigmatism m

Still can t read w cant without specs Doc !

Can we replace ability to accommodate for byopia ? near and reverse presb Many patients can actu ually read quite well with standard distant f focus lens implants

Multifoca Lenses al
Try and use different parts of lens to focus for near and distan nce Introduce optical problems s Compromise both near and distant d But lenses improving

Alcon Restor - Multifocal ocal o

Accommodating IOL dating d

Increase effec ctive power by anterior m movement

Accommodating IOL
Problems : Post op fibrosis Minimal effect 0.8 dioptre Posterior Capsule O Opacity

Age Related Mac cular Degeneration

AMD is the major cause of bli indness in western world

Age and AMD

% of people
30 25 20 15 10 5 0 60-64 65-69 70-74 75-80

Dry AMD Wet AMD

2021 20 million > 70 in U UK 1/3 ARMD to some degree e 1/3 of them will have wet form assoc. with severe visual loss

Age

Impact of AMD on the Patient: D Patient

Reading Recognizing faces Driving Severe visual loss

eccentric fixation

Factors linked to AMD

Confirmed C fi d Under investigation U d i ti ti

- Age - AMD in one eye

- Nutrition - Smoking

Hypertension Cardiovascular disease Race Family history complex

Anatomy of the eye y y and retina

Sclera

Choroid Retina

Cornea

Macula (fovea)
Lens Iris Cilliary body Photoreceptors RPE Bruchs Membrane B h M b Chor roid Optic nerve

Ageing Retin - Drusen g g na

Hard Soft

Small well-defined spots Usually innocuous

Larger, ill-defined spots May enlarge and coalesce y g Increased risk of AMD

Main forms of AMD

DRY - Non-neovascular A NonAMD
Drusen and atrophy of RP PE Slow deterioration Untreatable

WET - Neovascular AMD D

New vessel from the choro oidal layer Rapid and severe drop in vision Treatable

Dry or Atro ophic AMD

Initially drusen and non-s specific RPE changes

Late RPE (geograp phic) atrophy

WET or Choroidal neo ovascularization (CNV)

Metamorphop is initial symptom psia Many lesions a not visible clinically y are y

Pinkish-yellow subretinal lesion with fluid

Subretinal blood or lipid

Diagnosis Diagnosis
Patient presentation
Vi l acuity tests Visual it t t - Distortion = urgent referral

Fundoscopy

Progression of Ne eovascular AMD: Normal Retina l

Photoreceptors

RPE Choroid
Copyright protected

Progression of Ne eovascular AMD: Formation of New Vessels f

Copyright Cop right protected

New abnormal blood vessels proliferate d and penetrate Br ruchs membrane

Vascular Endo othelial Growth Fac ctor

VEGF VEGF VEGF

New vessels penetrate p Bruchs membrane

Disciform scar

Possible subsequent course of CNV ent e

Fluorescein Angiography Angiography

Bright area of g fluorescence from abnormal leaking vessels

Classic occult Cl i or o lt CNV

Optical Coherence Tomography ( p T g p y (OCT) )

OCT of normal macula

Photoreceptors
Fovea

RPE / Choroid

100um

OCT of stage 4 macular hole (vision 6/60)

OCT of Wet ARMD

Current treatments for ARMD

D Dietary Supplements Di S l L Laser photocoagulation P Photodynamic therapy S Steroid Injection R Retinal Surgery A Growth Factor Anti Inj i njections

Dietary Su upplements
Large study USA (AREDS - published 2001 S) 5000 patients 5 y follow up p yr up High dose antioxidants and vitamin supplementation Vit E, Vit C Selenium, Zinc, b Caroten ne Current trials g lutein and omega 3

Trial Pre eparation

Vitamin C Vitamin E Beta Carotene Selenium Zinc 500mg 400 IU 15m mg 50ug 80 m mg

Best product Viteyes, Ocuv preservision vite Smokers version No beta c carotene Increasing evidence for Lute g ein
www.tanner-eyes.co.uk

Results of A AREDS trial Risk of visual los from ARMD in ss patients with high r characteristics risk

Targeted use e supplements s

Visual loss from ARMD in one eye D Bilateral soft drusen In these high risk group 25% reduction in ps severe visual loss Not all those with early ARMD

Downside of f supplements s
Cost 10 per month Skin tint - mild Gastric upset B Carotene and smoking

Argon laser ph hotocoagulation

Laser beam aimed at CNV

Damage caused to RPE and photoreceptors

Photodynam therapy mic with ver rteporfin

Photodynam Therapy mic

Step 1

Step 2

Surgical removal of sub-foveal CNV subWet ARMD Type 2 - Chorioretinitis

Removal of SRNVM of

Lucentis (ranibizumab Antibody Therapy b) - binds VEGF Interior o blood vessel showing of Lucentis bindin to VEGF-A ng

Wet A ARMD Choroidal Ch id l neov vascularisation l i ti

Oxidative stress Inflammatory mediators y and angiogenic cytokines

Block th Bl k the neovascular stimulus l ti l Inhibit growth of abnormal g blood vessels Eliminate edema and hemorrhage

Inappropriate vessel growth I i t l th

Exudation and hemorrhage

Discoid scar formation

Repair retinal scarring

VEGF A VEGF-A binds to dimeric VEG receptors GF

VEGFR binding site

VEGFR binding site

VEGF-A: Key mediator of y angiog genesis and vascular permeability

VEGF-A

Binding and activation of VEGF receptor Survival Proliferatio on

P P P

Migration

Endothelial cell P activation

VASCULAR PERMEABILITY

ANGIOGENESIS
Ferrara et al, Nat Med 2003; 9: 669

Ranibiz zumab

Ranibizumab binds all isoforms including 110, a plasmin-cleaved form of VEGF 1

110 121

145
VEGF

165

189

206

VEGF

206 189

165 145

121 110

Chen et al, J Mol Biol 1999; 293: 865 Dvorak et al, A J P h l 1995; 146: 1029 D k l Am Pathol 1995 146 Das et al, Prog Retinal Eye Res 2003; 22: 721 Ferrara et al, Biochem Biophys Res Commun 1989; 161: 851

VEGF-A Inhibition targ multiple components gets of A AMD

Oxidative stress Inflammatory mediators I fl t di t and angiogenic cytokines Inappropriate vessel I i t l growth Exudation d hemorrhage E d ti and h h Discoid scar formation Block th Bl k the neovascular stimulus l ti l

Inhibit I hibit growth of abnormal th f b l blood vessels Eliminate edema and hemorrhage Repair retinal scarring

Secondary Endpoint: y p
Mean change in V from baseline VA
ANCHOR Mean change from baseline (VA) m
12 8 4 0 -4 -8 -12
1 2 3 4 5 6 7 8 9 10 11 12

MARINA
12 8 4 0 -4 -8 -12
1 2 3 4 5 6 7 8 9 10 11 12

Ranibizumab 0.5 mg Ranibizumab 0.3 mg

PDT (n=143) Sham (n=238)

IntraIntra-vitreal injection al a

Lucentis treat tment regime

All sub types wet Recent visual loss and ac ctive leakage Some useful vision bet than 3/60 tter 3 injections one month a i j i h apart Then review VA and OC if further leak reCT inject

76 yr old male Vision Count Fingers Vision

Post 3 Lucentis Injections Vision 6/12 ections e

Lucentis treat tment regime

About 40% significant impr rovement, rest stabilise If catch early and treat urgen = save vision ntly Initial trials suggested mont thly injections for 2 years I tend to do six and then rev view About 40% only need 6 but require close f/up require prolonged treatment Rest very variable but may r NICE have indicated fundin should be available both ng eye Retinal vein occlusions and diabetes

Lucentis Junkies s
Major problem econom mics, patient convenience, on-going risk g g Radiation treatment offe exit strategy ers Offering places on national trial next year Delivered via vitrectomy procedure y

Epimacular Brach hytherapy for the Treatment of Ne T t t f Neovascular AMD l EPIR RAD

Radiation Dose to Ocular Structures

24.0 Gy
Center of Lesion

6 Gy at edges of 5.4mm lesion

Tissue Lens Retina Optic Nerve Effect Cataract Radiation Retinopathy Optic Neuropathy

2.4 Gy at 4
Optic Nerve Dose for Clinically Observable Damage 2 Gy 35-55 35 55 Gy >55 Gy

0.6 mGy
Delivered to Lens Dose Delivered by NeoVista Strontium 90 Device .00056 Gy 24 Gy 2.4 Gy

Reference: Finger PT, Berson A, Ng T, Szechter A. Ophthalmic plaque radiotherapy for age-re elated macular degeneration associated with subretinal neovascularization. Am J Ophthalmol. 1999 Feb;127(2):170-7. Adapted from Bardenstein, Cha and Rosenblatt ar

Why Use Bet Radiation? ta

Ionizing Radiation has Strong Inhibitory Effects
Anti angiogenic Anti-angiogenic (inhibits blood vessel growth) Anti-inflammatory (inhibits inflammation) Anti-fibrotic (inhibits scar formation)

Targeted Radiation Treats O Only the AMD Lesion

Rapid Energy Dispersion Means Less Exposure

Effective dose at lesion site, but little penetration to other parts of the eye Whole-body exposure for patient is less than that received from a routine chest x-ray

Proporti of Patients ion Losing 15 Letters g

100% 90 0% 91% 93%

Percent of Subjects

85%

Month 3 N =34

Month 6 N =34

Mon 9 nth N =31 =

Month 12 N =34

Month 18 N =30

Proporti of Patients ion Gainin 15 Letters ng

Percent of Subjects

53% 47% 39 9% 38% 37%

Month 3 N =34

Month 6 N =34

Mon 9 nth N =31 =

Month 12 N =34

Month 18 N =30

EPIRAD potentia to dramatically al decrease numb of lucentis ber injections

18 Months
73% of patients did not req quire additional tx* Mean gain of +6.6 ETDRS letters S 37% of patients gained 3-li ines or more

* Additional tx was administered per investigator discretion based upon evidence of lesion acti ivity

IOL-VIP -

LMI implant

Magnified cen ntral vision but retained p peripheral

Gene Th herapy Lebers C Congeni Amaurosis nital i

Retinal Retinal Implant

Thank Th k you