Documenti di Didattica
Documenti di Professioni
Documenti di Cultura
Dear friends,
First of all let me thank all the readers of KJO for the suggestions and support they have given. In this issue we are covering some aspects of uveitis and community ophthalmology. Ocular sarcoidosis is an under diagnosed disease because of lack of clinical awareness. In the major review on ocular sarcoidosis all the aspects of the disease are well covered with special reference to investigative modalities. Many a times there is overlap of findings between sarcoidosis and tuberculosis the treatment of which are poles apart. This article will be of use to all general ophthalmologists who see uveitis cases. Also in the what is new section we are covering a new concept of biologics in non infectious uveitis. Biologics are biologic response modifiers which counteract the chemokines and their secretors T and B cells. Even though there are controversies in the use of biologic agents and they may not provide final answer in non infectious uveitis, this concept is worth reading. Despite experimental rationale, the lack of evidence from randomized controlled studies limits our understanding of when to commence therapy, which agent to choose and how long to continue treatment. Also the high cost and potential side effects of all biologic agents have limited their current use to uveitis refractory to immunosuppression1,2,3. Based upon indirect comparisons by Cochrane database, anakinra seemed less efficacious than etanercept, adalimumab and rituximab and etanercept seemed to cause fewer withdrawals due to adverse events than adalimumab, anakinra and infliximab in treatment of rheumatoid arthritis. Significant heterogeneity in
characteristics of trial populations imply that these finding must be interpreted with caution 4. Biologics may be used as an adjunctive therapy in some of the chronic cases of non infectious uveitis. Ocular surface squamous neoplasia is covered in the other major review. A detailed description of the histopathology is also mentioned. Seasonal variation of cataract surgery is not unknown in our country. The original article on this community ophthalmology aspect discusses some of the factors affecting seasonal variation of cataract surgery in India. The brief communication also discusses the training programmes for ophthalmologists in India. Deep lamellar keratoplasty is gaining in popularity in the recent past. It reduces some of the inherent complications of penetrating keratoplasty. The case series on DLK discusses the advantages of this technique. Community ophthalmology article discusses the current national scenario of eye banking and the scope of improvement. In the systemic diseases and eye this time retinal manifestations of cardiovascular diseases are discussed with excellent photographs. In ophthalmic instrumentation a head to head comparison of anterior segment OCT and UBM is given. We also have the regular brief reports and reviews and PG corner. We welcome feedback from the readers regarding the style and content of the journal. From the suggestions we have got after the last issue slight modifications are made. One last appeal is to all KSOS members. Please do contribute to the scientific content of the journal. We from the editorial board are trying to make more people write in the journal. Then only the standard of the journal will rise. The aim will be to make our journal the best regional journal in India. So please contribute.
Mahesh G
References:
1.Imri FR, Dick AD. Biologics in the treatment of uveitis. Curr Opin Ophthalmol. 2007;18(6):481-6. 2. Okada AA.The dream of biologics in uveitis. Arch Ophthalmol. 2010;128(5):632-5. 3. Ilowite NT. Update on biologics in juvenile idiopathic arthritis. Curr Opin Rheumatol. 2008;20(5):613-8 4. Singh JA, Christensen R, Wells GA, Suarez-Almazor ME, Buchbinder R, Lopez-Olivo MA, Tanjong Ghogomu E, Tugwell P. Biologics for rheumatoid arthritis: an overview of Cochrane reviews. Cochrane Database Syst Rev. 2009; 7(4):CD007848.
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Major Review
Common symptoms are vague, such as fatigue unchanged by sleep, lack of energy, weight loss, aches and pains, arthralgia, shortness of breath or skin lesions. The cutaneous symptoms vary which ranges from rashes and noduli (small bumps) to erythema nodosum or lupus pernio. It is often asymptomatic.
It has a worldwide prevalence. It affects adults between 20 and 40 years of age and is slightly more common in women than men.1 Sarcoidosis is 3 to 4 times more prevalent in US blacks than whites.1 HIV infection and sarcoidosis rarely coexist, presumably because their immunopathogenesis mechanisms diverge. A definite diagnosis of sarcoidosis can only be made by biopsy of the ocular tissues.2
Pathogenesis
The processes involved in the pathogenesis of sarcoidosis include accumulation of CD4 + lymphocytes at the affected site. The cytokines and factors secreted by these cells account for the influx of monocytes, alveolotis and non-caseating granuloma formation.3 Compartmentalization of the immune response is well recognized in sarcoidosis. At sites of granulomatous inflammation, there is a predominance of T-helper lymphocytes, which proliferate and secret large amounts of lymphokines, including interleukin (IL)-2, monocyte chemotactic factor (MCF) and migration inhibition factor (MIF). The concentration of lymphokines and monokines produced T sites of granulomatous inflammation is highest locally. As a result the traffic
Address for correspondence: Dr. Biswas Jyothirmay, Dept. of Uveitis, Sankara Netralaya, Chennai
of T-helper lymphocytes and monocytes is directed towards the granuloma formation.3 Exposure to an environmental or occupational antigen in a genetically susceptible individual is thought to trigger an immunologic response. The cells and cytokines that lead to granuloma formation have been an area of active study.4
intermediate uveitis, panuveitis with retinal vasculitis, and panuveitis with punched multifocal choroiditis.9
Anterior Segment
Anterior uveitis is usually bilateral and may be either acute or chronic. Acute iridocylitis are seen typically in young patients with acute sarcoidosis. Chronic granulomatous iridocylitis usually affects older patients.10 Patients may present with aqueous cells and/or aqueous flare. Mutton-fat keratic precipitates11 (KPs) are usually the signs for granulomatous anterior uveitis. KPs are coalescent precipitates forming small plaques that gradually become more translucent. Iris nodules11 may be seen at the pupillary margin (Koeppe nodules) and/ or in iris stroma (Busacca nodules). Seclusio pupillae
OCULAR SARCOIDOSIS
It usually presents with bilateral hilar lymphadenopathy, pulmonary infiltrates and eye involvement. 25% patients with sarcoidosis develop ocular symptoms1, 5 8-15 year age group has almost universal lung involvement, with the eye, skin, liver, and spleen involved in 30-40% of cases.6 Goto et al conducted an epidemiological survey in Japan and found that most frequent intraocular inflammatory disease identified was ocular sarcoidosis (13.3%).7 Children of 5 years of age and under are characterized by the triad of uveitis, arthropathy, and skin rash.6 As sarcoidosis can have protean manifestations, it can present acutely or chronically with both granulomatous and sometimes non-granulomatous uveitis. Investigations to rule out sarcoidosis should be performed in patients presenting with uveitis. The term ocular sarcoidosis should be applied both to isolate ocular disease as well as to ocular involvement in systemic disease.
and Occlusio pupillae are present in rare cases. Posterior synechiae1 is the adhesion between the posterior surface of iris and anterior surface of the lens. Tent-shaped peripheral anterior synechiae11 (PAS) is formed when protruding trabecular nodules retract the iris towards the trabeculum. Trabecular meshwork (TM) nodules11, giant iridociliary sarcoid tumors12 scleritis13, granulomatous tumor of the iris and ciliary body14, interstitial keratitis15, multilobular limbal corneal nodules16 are the rare signs of ocular sarcoidosis.
Posterior segment
Snowballs in the inferior anterior vitreous /string of pearls vitreous opacities11 are known signs of ocular sarcoidosis. They are very suggestive of a granulomatous process. Snowballs may also be seen in intermediate uveitis. Retinal perivasculitis is frequently found in ocular sarcoidosis. Perivasculitis11 is seen as segmental periphlebitis and vascular changes often locate at the equatorial or peripheral retina. Retinal haemorrhage appears when periphlebitis occludes the venous circulation. Branch retinal vein occlusion may occur as a rare vascular complication of sarcoidosis.17 If occlusion is extensive, neovascularisation and vitreous haemorrhage follows.
Figure 6: Periphlebitis
Figure 7: Periphlebitis
Figure 8: Snowballs Multiple chorioretinal peripheral exudates11 are seen in patchy exudates and are strongly suggestive of ocular sarcoidosis. When these exudates appear along the vein and if periphlebitis is extensive, they resemble candle wax drippings (taches de bougie). Retinal and pre-retinal granulomata are uncommon. The latter are typically discrete, grey-white and located inferior and anterior to equator (Lander sign).10 Acute sarcoid retinopathy is characterized by combination of vitreous haze, candlewax drippings, retinal and pre-retinal granulomata and retinal haemorrhages.10 Optic disc nodule(s)/granuloma(s) and/or solitary choroidal nodule are suggestive of sarcoid uveitis.18
Bilateral optic neuropathy occurs in cases of long term use of linezolid given for methicillin-resistant Staphylococcus aureus osteomyelitis.19 Panuveitis may be a sign of ocular sarcoidosis induced by Interferon-alpha which is used for the treatment of different viral, autoimmune and malignant diseases20 Posterior segment involvement is more common that has been reported.21 Choroidal white dots22, RPE detachments23, Birdshot chorioretinopathy24, acute posterior multifocal placoid pigment epitheliopathy24, bilateral optic neuropathy25, solitary choroidal mass26, giant nodular posterior scleritis27 are rare manifestation in sarcoidosis.
Neurosarcoidosis
Neurological involvement occurs in 5-6% of patients with sarcoidosis.36 Isolated sudden neurosensory hearing loss and uveitis in cases of neurosarcoidosis.37 Posterior segment involvement may be accompanied by disease of the central nervous system in 25% to 30%. 38 The neurological features includes babinski reflexes, spinal cord
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compression, myasthenia, cranial nerve paresis (V, VII, XI, and XII), hypothalamic- pituitary gland dysfunction, visual field loss and normal pressure hydrocephalus.3 Ocular involvement was characterized by anterior uveitis (in the initial stages), vitreous flare, bilateral disc edema, macular edema, streak hemorrhages, peripheral periphlebitis, nerve fibre bundle defects and candle-wax spots.39 Ocular sarcoidosis was accompanied by secondary glaucoma or optic nerve atrophy, the progression of neurosarcoidosis can lead to visual field defects.40
on the luminal surface of vascular endothelial cells but also in cells derived from the monocytemacrophage system. Increased serum ACE activity has been reported in pathologies involving a stimulation of the monocytic cell line, primarily granulomatous diseases. Sarcoidosis is the most frequent as macrophage products are produced by sarcoidal granulomas.41 ACE is elevated in ocular sarcoidosis and is significantly more elevated in children than in adults.11
Serum Lysozyme
Elevated serum lysozyme is seen in ocular sarcoidosis.11 Lysozyme is an enzyme that hydrolyses glycosidic bonds and is thus able to hydrolyse the cell wall peptidoglycans of some micro-organisms and thereby kill the organism. It is found in monocytes and macrophages. Serum ACE enzyme activity falls below detectable levels in patients taking ACE inhibitors and hence serum lysozyme test is recommended. Serum lysozyme is rarely used. In a study on 125 sarcoidosis cases ACE was elevated in 60% of patients43 and serum lysozyme in 76%43, because serum lysozyme is less specific for sarcoidosis than serum ACE, its diagnostic value may be limited. However, the sensitivity was high even when serum ACE levels were within normal limits and correlated well with clinical features in sarcoidosis.
Laboratory Investigations
Complete blood count with platelet count and measurement of serum calcium, creatine, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase levels should be carried out.41
Serum calcium
Hypercalcemia occurs in about 10% of the patients with sarcoidosis; hypercalciuria is about three times more frequent. These abnormalities of calcium metabolism are due to dysregulated production of 1, 25- (OH) 2-D3 (calcitriol) by activated macrophages trapped in pulmonary alveoli and granulomatous inflammation.44
pulmonary infiltrates Stage 3: Bilateral pulmonary infiltrates without BHL Stage 4: Pulmonary fibrosis
Vitamin D
The active hormone of Vitamin D (1, 25-dihydroxyvitamin-D) (1, 25-D) performs a vital function in immune diseases, including sarcoidosis. It causes hematopoetic stem cells to differentiate into monocytes, white blood cell and then it causes these to differentiate into macrophages and giant cells characteristic of sarcoid granuloma. Without this hormone there would be no formation of granuloma.44
HRCT Scan
It is used in cases where sarcoidosis was strongly suspected but the chest radiography was negative for BHL. Increasing age, presence of peripheral multifocal chorioretinitis and posterior synechiae were associated with an abnormal HRCT scan.46
Chest x-ray
Bilateral Hilar Lymphadenopathy (BHL) is the most frequent radiological finding in sarcoidosis.11 It is present in 5089% of cases.42 Other systemic condition that rarely causes BHL is lymphoma only, although symmetrical lymph node involvement is unusual, this is thought to be pathognomonic of sarcoidosis. Chest X-ray changes are divided into four stages45 Stage 0: Normal Chest X-ray Stage 1: Bilateral hilar lymphadenopathy (BHL) Stage 2: Bilateral hilar lymphadenopathy (BHL) and
Biopsy
It is the removal of tissue from a living subject to examine the presence or extent of a disease. The only confirmatory test is biopsy showing classic non-caseating granulomas. Granulomas are compact, centrally organized collections of macrophages and epithelioid cells encircled by lymphocytes.47 Macrophages, in the face of chronic cytokine stimulation, differentiate into epithelioid cells, gain secretory and bactericidal capability, lose some phagocytic capacity, and fuse to form multinucleated giant cells.41
Fundus fluorescein angiography helps to detect subtle vascular leakage. Optical coherence tomography (OCT) is used to detect the presence of cystoid macular edema, which is a risk factor. A granulomatous lesion of the optic nerve head was more visible in fluorescein angiography which shows hyperfluorescence. Multifocal choroidal lesions located in the posterior pole is only visible with indocyanine green (ICG) were demonstrated.48
TREATMENT
Sarcoidosis treatment suppresses the granulomatous process and its clinical, functional and radiographic consequences but it is not etiological. Systemic or topical corticosteroids are the mainstay for the treatment of systemic and ocular sarcoidosis.45 As a general rule, systemic
corticosteroids are the first-line treatment, given for at least 12 months.49 Corticosteroids can relieve symptoms, reduce inflammation, and improve the prognosis of ocular and pulmonary sarcoidosis.50 Most cases of ocular sarcoidosis, such as iridocyclitis, retinal periphlebitis, optic disc inflammation, vitritis and snowballs can be managed with topical or subconjunctival injections of corticosteroids. High doses of systemic steroids are effective in unusual manifestations of retinal vein occlusions, retinal and optic disc neovascularization and vitreous hemorrhage. Systemic corticosteroids starting with moderately high doses (40-60 mg/day) with slow tapering according to the clinical response is necessary.51 Bilateral choroiditis and papillitis subsides with the treatment of oral prednisolone.52 In addition to corticosteroids, topical cycloplegics, such as atropine or homatropine, may be used. Cytotoxic drugs like methrotrexate, cyclophosphamide and azathioprine may be used in refractory cases. An alternative option to corticosteroids proposed in case of contraindication or corticoresistant sarcoidosis is methotrexate. Although other drugs are only occasionally needed, the available therapeutical range is wide (azathioprine, infliximab, cyclophosphamide, 49 leflunomide, etc). The tumor necrosis factor alpha antagonist infliximab has been used successfully in cases of refractory sarcoidosis, whereas the use of etanercept in the treatment of sarcoidosis has been disappointing.18 Multi-systemic sarcoidosis and refractory retinal vasculitis experienced an excellent response with infliximab.53 Leflunomide is well tolerated in patients with chronic sarcoidosis. It appears to be as effective as methotrexate, with less toxicity. It should be considered as an alternative in chronic sarcoidosis patients (ocular and lung involvement) who cannot tolerate methotrexate.54 A lasting remission was found with the treatment by cyclosporine in
granulomatous tumor of the iris and ciliary body.14 Pars plana vitrectomy have beneficial effects on restoring vision, stabilizing vitreous inflammation, resolving preoperative cystoid macular edema and reducing systemic corticosteroid treatment in eyes with thick vitreous opacities associated with sarcoidosis that is resistant to corticosteroid treatment preoperatively.55 The visual prognosis of sarcoidosis is usually good.1 Poor visual outcome was seen in posterior segment involvement, significantly more frequent in multifocal choroiditis and panuveitis compared to anterior uveitis. Causes of visual loss were cataract, glaucoma, macular edema, vitreous haemorrhage and retinal detachment.56
Conclusion
Uveitis precedes systemic sarcoidosis in 30% of cases. In a study by Ganesh et al. in a series of 34 histologically confimed cases of systemic sarcoidosis, only 3 patients (8.8%) had ocular involvement and all of them had granulomatous anterior uveitis.57 Uveitis may be the presenting manifestation of sarcoidosis, especially in women. Bilateral panuveitis and chronic bilateral anterior uveitis are the most common clinical presentations.58 Sarcoid uveitis is common, mostly in a chronic form, and is prevalent in women past middle age. The onset is insidious. Complications are macular edema, cataract, and glaucoma, resulting in visual loss. The diagnosis is made according to characteristic ocular signs and systemic investigations. The diagnosis of sarcoidosis may be difficult, owing to the lack of definitive diagnostic criteria and a variety of presentations. Histologic confirmation may not always be possible or practical. However, a range of serological and radiological tests, when combined with physical and ophthalmic evaluation, can lead to the presumed diagnosis of sarcoidosis.59 Effective treatment consists primarily of long-term use of steroids.60
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References
1. Bonfioli AA and Orefice F (Jul-Sep 2005) Sarcoidosis. Semin Ophthalmol ; 20(3), 177-182 2. Papadaki TG, Kafkala C, Zacharopoulos IP et al (Oct 2006) Conjunctival non-caseating granulomas in a human immunodeficiency virus (HIV) positive patient attributed to sarcoidosis. Ocul Immunol Inflamm 14(5), 309-311 3. Foster and Vitale. Diagnosis and treatment of uveitis. (2002) 2nd Edition, 710-723 4. Margolis R and Lowder CY (Nov 2007) Sarcoidosis. Curr Opin Ophthalmol ; 18(6) : 470-475 5. Lowder CY, Char DH. (Mar 1984) Uveitis - A Review. West J Med: 140, 421-432 6. Hoover DL, Khan JA, Giangiacoma J (Jan-Feb 1986) Pediatric ocular sarcoidosis. Surv Ophthalmol ; 30(4), 215-228 7. Goto H, Mochizuki M, Yamaki K et al (JanFeb 2007) Epidemiological survey of intraocular inflammation in Japan. Jpn J Ophthalmol ; 51(1) : 41-44 8. L.S. Atmaca, Atmaca-Snmez P, Idil A et al. (April 2009) Ocular involvement in sarcoidosis. Ocul Immunol Inflamm ; 17, 91-94 9. Lee SY, Lee HG, Kim DS et al (Jun2009) Ocular sarcoidosis in a Korean population. J Korean Med Sci; 24(3) : 413-419 10. Dr. Nurchaliza H. Siregar. Uveitis in sarcoidosis. (2003) Digitized by USU digital library 11. Kawaguchi T, Hanada A, Horie S et al (Mar-Apr 2007) Evaluation of characteristic ocular signs and systemic investigations in ocular sarcoidosis patients. Jpn J Ophthalmol ; 51(2), 121-126 12. Finger PT, Narayana K, Iacob CE et al (Mar-Apr
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2007) Giant sarcoid tumor of the iris and ciliary body. Ocul Immunol Inflamm ; 15(2) : 121-125 13. Dunsun D, Akova YA, Bileziki B. (Jun 2004) Scleritis associated with sarcoidosis. Ocul Immunol Inflamm ; 12(2) : 143-148 14. Maca SM, Firbas U, Hauff W et al (Sep 2004) Semicircular tumor of the iris and uveitis as unilocal manifestation of sarcoidosis. Ocul Immunol Inflamm ; 12(3) : 237-240 15. Lennarson P and Barney NP (May-Jun 1995) Interstitial keratitis as presenting ophthalmic sign of sarcoidosis in a child. J Pediatr Ophthalmol Strabismus ; 32(3) : 194-196 16. Hegab SM, Al-Mutawa SA, Sheriff SM (Nov-Dec 1998) Sarcoidosis presenting as multilobular limbal corneal nodules. J Pediatr Ophthalmol Strabismus ; 35(6) : 323-326 17. Ohara K, Okubo A, Sasaki H et al (Jun 1995) Branch retinal vein occlusion in a child with ocular sarcoidosis. Am J Ophthalmol ; 119(6) : 806-807 18. Asukata Y, Ishihara M, Hasumi Y et al (MayJun 2008) Guidelines for the diagnosis of ocular sarcoidosis. Ocul Immunol Inflamm ; 16 : 77-81 19. Kiuchi K, Miyashiro M, Kitagawa C et al. (Jul 2009) Linezolid-associated optic neuropathy in a patient with ocular sarcoidosis. Jpn J Ophthalmol ; 53(4) : 420-424 20. Doycheva D, Deuter C, Stuebiger N et al (May 2009) Interferon-alpha associated presumed ocular sarcoidosis. Graefes Arch Clin Exp Ophthalmol ; 247(5) : 675-680 21. Khanna A, Sidhu U, Bajwa G et al (Sep 2007) Pattern of ocular manifestations in patients with sarcoidosis in developing countries. Acta Ophthalmol Scand ; 85(6) : 609-612 22. Dufay-Dupar B, Soubrane G, Ortonne N. (Nov
2006) Choroidal white dots and sarcoidosis. J Fr Ophthalmol ; 29(9) : e23 23. Salchow DJ and Weiss MJ (Aug 2006) Retinal pigment epithelial detachment in sarcoidosis. Ocul Immunol Inflammation ; 14(4) : 245-248 24. Machida S, Tanaka M, Murai K et al (Jul-Aug 2004) Choroidal circulatory disturbance in ocular sarcoidosis without the appearance of retinal lesions or loss of visual function. Jpn J Ophthalmol ; 48(4) : 392-396 25. Guilpain P, Andreu MA, Cassoux N et al (Oct 2004) Bilateral optic neuropathy revealing systemic sarcoidosis. Rev Med Interne ; 25(10) : 755-758 26. Tingey DP and Gonder JR (Feb 1992) Ocular sarcoidosis presenting as a solitary choroidal mass. Can J Ophthalmol ; 27(1) : 25-29 27. Perez Campagne E, Guez Crosier Y, Schalenbourg A et al (Oct 2007) Giant nodular posterior scleritis compatible with ocular sarcoidosis simulating choroidal melanoma. Arch Soc Esp Oftalmol ; 82 : 563-566 28. Braun M and Jonas JB (Nov 1996) Bandlike corneal degeneration as the initial sign of sarcoidosis. Klin Monatsbl Augenheilkd ; 209(5) : 328-329 29. Schilgen G, Sundamacher R, Pomjanski N et al (Apr 2006) Bilateral large conjunctival tumors as primary manifestation of sarcoidosis- successful treatment with steroid depot injections. Klin Monatsbl Augenheilkd ; 223(4) : 326-329 30. Caca I, Unlu K, Bykbayram H et al (Jan-Feb 2006) Conjunctival deposits as the first sign of systemic sarcoidosis in a pediatric patient. Eur J Ophthalmol ; 16(1) : 168-170 31. Yanardag H and Pamuk ON (Jul 2003) Lacrimal gland involvement in sarcoidosis. The clinical features of 9 patients. Swiss Med Wkly ; 133(27-28) :
: 388-391 32. Cornblath WT, Elner V, Rolfe M (Apr 1993) Extra ocular muscle involvement in sarcoidosis. Ophthalmology ; 100(4) : 501-505 33. Paul Henkind and Marvin B. Gottlieb (Oct 1973) Bilateral internal ophthalmoplegia in a patient with sarcoidosis. Br J Ophthalmol ; 57 : 792-796 34. Kim YJ and Kim YD (Dec 2006) A case of scar sarcoidosis of the eyelid. Korean J Ophthalmol ; 20(4) : 238-240 35. Koestinger A, Guexcrosier Y, Borruat FX (May 2006) Autoimmune retinal dysfunction in sarcoid chorioretinopathy. Klin Monatsbl Augenheilkd ; 223(5) : 428-430 36. Iizuka T and Sakal F (Sep 2002) Neurosarcoidosis. Nippon Rinsho; 60(9) : 1785-1793 37. Garcia Berrocal JR, Trinidad A, Vargas JA et al (Aug-Sep 1998) Sudden hearing loss and uveitis as a form of presentation of neurosarcoidosis. Acta Otorrinolaringol Esp ; 49(6) : 488-490 38. Obenauf CD, Shaw HE, Sydnor CF et al (1978) Sarcoidosis and its ocular manifestations. Am J Ophthalmol ; 86 : 648 39. R. G Turner, D. G. James, A. I Friedmann et al (Nov 1975) Neuro-ophthalmic sarcoidosis. Br J Ophthalmol ; 59 : 657-663 40. Hasumi Y, Ishihara M, Asukata Y et al (Sep 2007) Case of neurosarcoidosis with rapid visual field defect progression. Nippon Ganka Gakkai Zasshi ; 111(9) : 728-734 41. Iannuzzi M C, Benjamin A, Rybicki BA et al (Nov 2007) Review article on sarcoidosis. N Engl J Med; 357: 2153-2165. 42. Herbort P, Rao NA, Mochizuki M et al. (June 2009) International Criteria for the diagnosis of ocular sarcoidosis: results of the first International
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workshop on ocular sarcoidosis (IWOS). Ocul Immunol Inflamm ; 17: 160-169 43. Tutkun T I, Aydin-Akova Y, Gney-Tefekli E et al (July 2007) Referral patterns, demographic, clinical features and visual prognosis of Turkish patients with sarcoid uveitis. Ocul Immunol Inflamm ; 15: 337-343 44. Trevor G Marshall (July 2003). A review- Vitamin A and calcium in sarcoidosis. 45. Amro Al Astal. Review article on sarcoidosis. 46. Clement D, Postma G, Rothova A et al (Aug 2009) Intraocular sarcoidosis: association of clinical characteristics of uveitis with positive chest highresolution computed tomography findings. Br J Ophthalmol. 47. Violeta Mihailovic, Om P Sharma. (2005) Atlas of Sarcoidosis: pathogenesis, diagnosis and clinical features. 48. Marilita M Moschos and Yan Guex- Crosier (Dec 2008) Anterior segment granuloma and optic nerve involvement as the presenting signs of systemic sarcoidosis. Clin Ophthalmol ; 2(4) : 951-953 49. Nunes H, Uzunhan Y, Bonnet D et al (May 2008) Sarcoidosis treatment. Rev Prat ; 58(10) : 1099-1104 50. Miao JZ, Du DJ, Zeng P. (Jan 2003) The effect of therapeutic intervention with corticosteroids on outcome and prognosis of sarcoidosis. Zhonghua Jie He He Hu Xi Za Zhi ; 26(1) : 14-17 51. Kogure M (Jun 1994) Treatment of ocular
manifestation of sarcoidosis. Nippon Rinsho ; Vol: : 1654-1658 52. Cepilova Z, Porubska, Fabianov J. (Jan 2008) Sarcoidosis- a case report. Cesk Slok Oftalmol ; 64(1) : 34-37 53. Cruz BA, Reis DD, Araujo CA et al (Oct 2007) Refractory retinal vasculitis due to sarcoidosis successfully treated with infliximab. Rheumatol Int 27(12) : 1181-1183 54. Baughman RP and Lower EE (Mar 2004) Leflunomide for chronic sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis ; 21(1) : 43-48 55. Leki Y, Kiryu J, Kita M et al (Mar 2004) Pars plana vitrectomy for vitreous opacity associated with ocular sarcoidosis resistant to medical treatment. Ocul Immunol Inflamm ; 12(1) : 35-43 56. Lobo A, Barton K, Minassian D et al (Aug 2003) Visual loss in sarcoid-related uveitis. Clin Experiment Ophthalmol ; 31(4) : 310-316 57. Ganesh SK, Agarwal M. (Jan-Feb 2009) Clinical and investigative profile of biopsy proven sarcoid uveitis in India. Ocul Immunol Inflamm ; 16 :17-22 58. Adan A, Baget M, De Llobet JM et al (May 2004) Uveitis as initial manifestation of sarcoidosis: study of 31 patients. Med Clin (Barc) ; 122(19) : 748-752 59. Lauby YJ (May 2004) Presumed ocular sarcoidosis. Optometry ; 75(5) : 297-304 60. Uyama M (2002) Uveitis in sarcoidosis. Int Ophthalmol Clin ; 42(1) : 143-150
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Major Review
Noopur Gupta MS DNB, Shibal Bhartiya MS, Rajesh Sinha MD, Namrata Sharma MD,DNB
understanding of diagnosis and management as well the pathogenesis of ocular surface squamous neoplasia (OSSN). OSSN was a term proposed by Lee and Hirst1 to incorporate three broad categories: I. Benign dysplasia: Papilloma, Pseudotheliomatous hyperplasia, Benign hereditary intraepithelial dyskeratosis II.Preinvasive OSSN: Conjunctival/corneal carcinoma in situ III. Invasive OSSN: Squamous mucoepidermoid carcinoma carcinoma,
about 14% (4 -29%) of all oculo-orbital tumours. It is the third most common ocular tumor of the elderly, after melanoma and lymphoma. OSSN primarily occurs in older males (78.5%). It is predominantly seen in dark skinned Caucasians, the age of onset being significantly higher in latitudes closer to the equator than 30 degrees. The average age of occurrence has been noted to be 60 years, range 20 to 88 years.
3
that the average age of incidence of carcinoma in situ lesions is 5-9 years lower than invasive OSSN. This difference may represent the time taken for progression from intraepithelial neoplasm to invasive carcinoma. Patients of xeroderma pigmentosum develop OSSN at a younger age. Young patients of HIV are more prone to develop aggressive OSSN.
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Address for correspondence: Dr. Namrata Sharma, RP Center for Ophthalmic Sciences, New Delhi
Etiopathogenesis
1. Limbal transition zone/stem cell theory
OSSN may represent the abnormal maturation of corneal and conjunctival epithelium as a result of a combination of factors such as UV-B irradiation and HPV. Other risk factors include dust, wind, traumatic lid closure, chemical exposure like trifluridine, beryllium, arsenicals, petroleum products, cigarette smoke, vitamin A deficiency, and viruses like HSV type I.
without well defined borders .They usually straddle the limbus in the interpalpebral area but may be limited to the conjunctiva and less commonly ,the cornea.
MORPHOLOGICAL CLASSIFIACTION
1. Gelatinous 2. Leucoplakic 3 Pappiliform Circumscribed gelatinous lesions are the most common, the other two variants being nodular (Fig 2a) and diffuse (Fig 2b). The nodular type is fast growing with a propensity to metastasize to adjacent lymph nodes .The diffuse is the least common and in the early stages masquerades as persistent redness of the conjunctiva without associated papillae or follicles. These are slow growing, mimic chronic conjunctivitis and tumefaction occurs in the late stages only. Although it is difficult to differentiate between benign and malignant lesions clinically benign OSSN-pappilomatous type typically are exophytic, strawberry like with a stippled red appearance corresponding to its fibrovascular core. Corneal OSSN lesions typically are preinvasive, with an opalescent mottled ground glass sheet appearance. They have sharply defined fimbriated borders, are avascular, the convex leading edge spreads in an arc away from the limbus, and often white dots are present over the grey epithelium. The proposed etiology of these lesions varies from a denovo dysplasia to centripetal sliding of limbal dysplastic cells. These lesions are typically indolent, slow growing and remarkably prone to recurrence. OSSN typically presents as a growth on the ocular surface and gives rise to symptoms like foreign body sensation, redness or irritation and rarely, diminution of vision.
2. Ultraviolet-B light
UV-B light is known to cause DNA damage and formation of pyrimidine dimers .Failure or delay in repair can lead to neoplasia as in xeroderma pigmentosum. Also major risk factors like pale skin, pale iris, sunburn, sun exposure, and actinic solar keratosis can be attributed to UV-B irradiation. UV-B has also been shown to cause p53 gene mutation, which is associated with OSSN.4 Histological evidence of solar injury, which is recognised as a major risk factor for conjunctival OSSN, has been reported in 50-100% cases of OSSN.
Clinical Features
OSSN lesions mostly are slightly elevated, and have a pearly grey appearance with tufts of vessels commonly known as sentinel vessels (Fig 1) ,with or
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Differential Diagnosis
The differential diagnosis of OSSN includes
pannus, actinic disease, vitamin A deficiency, benign intraepithelial dyskeratosis, pinguecula, pyogenic granuloma, keratoacanthoma, malignant pseudoepitheliomatous melanoma and nevi. hyperplasia,
Histopathology
Papillomas demonstrate papillary fibrovascular fronds covered by acanthotic epithelium .This epithelium may show varying degrees of dysplasia, however, the cells have normal polarity and the basal layers are often unremarkable. Preinvasive OSSN are classified as mild, moderate or severe depending on the degree of involvement of the dysplastic epithelium(Fig 3). (i) Mild- CIN grade I: dysplasia confined to lower third of the epithelium (Fig 3a). (ii) Moderate-CIN grade II: dysplasia extends into the middle third. (iii) Severe-CIN grade III: full thickness dysplasia, also called carcinoma-in-situ (Fig 3b). Invasive OSSN show nests of infiltrating cells that have penetrated the epithelial basement membrane and spread into the conjunctival stroma. These cells can either be well differentiated (Fig 3d) and easily recognized as squamous, or poorly differentiated and difficult to distinguish (Fig 3c) .The latter are more uncommon and more aggressive. Two types of cells may be seen interspersed with squamous cells in these tumours: spindle cells and mucoepidermoid cells.9 reveals excessive mitochondria, tonofilaments and endoplasmic reticulm; decreased desmosomes, alteration/ absence of basement membrane and deposition of fibrillogranular material between the basement membrane and bowmans layer.
Electron
Microscopy:
Therapeutic modalities
Surgery
Surgical treatment has traditionally been the treatment of choice as a tissue diagnosis is essential before initiation of adjunctive therapy. Superficial excision remains the important initial
135
step in management as it is impossible to exclude invasive disease on clinical grounds or with impression cytology. Excision allows an immediate histopathological diagnosis, surgical debulking, and excludes life threatening invasive carcinoma. The disadvantage of primary excision alone is the high recurrence rate which ranges from 15% to 52%.Dissection of all abnormal tissue with a wide surgical margin of 4-5mm , with or without delineation with rose Bengal staining ,is usually sufficient. Conjunctival defect so created can be closed primarily (if less than three clock hours in diameter). Larger defects require tissue replacement transpositonal conjunctival flaps, free conj flaps from the other eye, or amniotic membrane grafts. Lamellar techniques may be indicated in lesions with deep invasion .Frozen section can be used to assess the adequacy of excision, and is accurate in delineating horizontal tumor spread. Bunns modification of Mohs technique of tumor margin surveillance may also be used .In this the free conjunctival edges are excised by 2mm if residual tumor is evident even after excision of a 2mm surgical margin.10 Enucleation, and rarely exenteration may be required in cases of intraocular or intraorbital spread. In all cases a no touch technique is used, and direct manipulation of the tumour is avoided to prevent tumour seeding.
is used to form an iceball extending 2mm for conjunctiva ,1mm for episcleral tissue and 0.5mm for the cornea. A slow duration freeze with a slow thaw, repeated two or three times (freeze-thawrefreeze) is recommended. It is important to include the limbal region during cryotherapy, and not apply the cryoprobe for more than three seconds. Both extensive surgical excision and cryotherapy can cause limbal stem cell insufficiency, requiring limbal autotransplantation.
Radiotherapy
Various sources such as strontium-90 (beta irradiation ) and radium (gamma radiation ) were used earlier .But given the high incidence of side effects and prolonged duration of treatment required means it is rarely used.
Chemotherapy
Topical chemotherapy is inexpensive, simple and reduces the risk of limbal stem cell deficiency, and obviates the need for clear tumor margins by treating the entire ocular surface, including the potentially dysplastic cells.11 However, the obvious limitation is the limited drug penetration in larger tumors, and a possibly deleterious effect on the nasopharyngeal epithelium on prolonged use.
Cryotherapy
This modality is often used in conjunction with surgery. It acts by directly destroying the tumor cells by thermal effect as well as by obliterating the microcirculation causing ischemic necrosis. Intraoperative cryotherapy is commonly used as adjunctive therapy as it is known to decrease the recurrence rate by destruction of any residual tumour tissue beyond the horizontal or deep surgical margin of the wound. It has the advantage of reaching both tumor cell islands and deeply infiltrated cells ,thus obviating the need for radical surgery .A nitrous oxide cryopobe tip (2.5 or 5mm)
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0.04% four times a day with one week on and one week off in alternating cycles for a maximum of 8 weeks. The one week on, one week off regimen prevents damage to more slowly dividing epithelial cells and limbal stem cells, allowing them to repair their DNA. Allowing time for complete epithelial healing before application of MMC is important in avoiding the more serious complications such as corneal epitheliopathy, scleral ulceration, uveitis, cataract, and glaucoma.
Recurrence
Recurrence rates of OSSN ranges from 15-52%, average reported being 30%. Recurrences are higher in case of inadequate excision margins, and occur usually within two years of surgery. These typically exhibit a more aggressive behavior because of the tissue disruption associated with the primary excision theoretically enhancing the ability of the tumor cells to enter the eye. The main predictors for recurrence include age, histological grade of the lesion, adequacy of margins at initial excision , ,corneal location , larger size (> 2 mm), and a high proliferation index ( Immunostaining with antibody to Ki-67, which is a nuclear antigen expressed in proliferating cells, allows evaluation of the growth fraction of normal and neoplastic cells yielding the proliferation index).16
specifically during the S phase of the cell cycle. It is converted to 5-F DUMP, which inhibits thymydilate kinase thus preventing DNA and RNA synthesis. Both MMC and 5FU are currently being used four times daily for 1-2 weeks in a pulsed fashion, the treatment being repeated after every 1-2 weeks. This one week on and one week off drug regimen has the added advantage of good efficacy and better tolerance.
Immunotherapy
Interferon alpha2b is a naturally occurring glycoprotein which binds to cell surface receptors affecting intracellular events resulting in anti tumor and anti viral properties. Its efficacy may be explained by this due to the oncogenic link between HPV and OSSN. It has been used for extensive, residual, recalcitrant , multifocal or diffuse lesions ;and for those that involve the visual axis where surgery is not the treatment of choice. Interferon alfa 2-b is an important treatment modality for recalcitrant OSSN, effective in both, primary tumors unresponsive to treatment, as well as recurrences. It is more toxic than MMC and usually takes a longer duration for complete resolution, so is not started as a first line of therapy and preserved for lesions non responsive to topical MMC. IFN-albha2b drops(1millionIU/ ml) is used four times a day until resolution, and a month thereafter. Subconjunctival injections have also been used.Median time for resolution has been reported as 54 days (range 28-188 days),with a mean follow up ranging from 2.9 to 18 months.13-15
Fig 2 a
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Fig 2 b
Fig 3 a MD-SCC
Fig 3 c PD-SCC
Fig 3 d WD-SCC
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specific anti-cancer treatment of these lesions with preservation of the limbal stem cells and ocular surface.
10.Buuns DR Tse.DT, Folberg R. Micro scopically controlled excision of conjunctival squamous cell carcinoma. Am J Ophthalmol 117;97-102, 1994. 11Chen C, Louis D, Dodd T, Muecke J Mitomycin C as an adjunct in the treatment of localized ocular surface squamous neoplasia.. Br J Ophthalmol. 2004 ;88(1):17-8. 12. Sepulveda R, Peer J, Midena E, Seregard S, Dua H, Singh ADTopical Chemotherapy for OSSN : Current Status. Br J Ophthalmol. 2009. [Epub ahead of print] 13. Holocombe DJ, Lee GA. Am.J. Topical interferon alfa-2b for the treatment of recalcitrant ocular surface squamous neoplasia. Ophthalmology. 2006 ;142(4):568-71. 14. Nemet AY, Sharma V, Benger R. Interferon alpha 2b treatment for residual ocular surface squamous neoplasia unresponsive to excision, cryotherapy and mitomycin-C.Clin Experiment Ophthalmol. 2006;34(4):375-7. 15.Galor A, Karp CL, Chhabra S, Barnes S, Alfonso EC. Topical Interferon Alpha 2b Eye Drops for Treatment of Ocular Surface Squamous Neoplasia: A Dose Comparison Study. Br J Ophthalmol. 2009. [Epub ahead of print]. 16. McKelvie PA, Daniell M, McNab A, Loughnan M, Santamaria JD. Squamous cell carcinoma of the conjunctiva: a series of 26 cases Br J Ophthalmol. 2002;86(2):168-73. 17. Basti S, Mascsai MS. Ocular surface squamous neoplasia: a review Cornea.2003;22:687-704. 18. Stone DU, Butt AL, Chodosh J Ocular surface squamous neoplasia: a standard of care survey. Cornea 24(3): 297-300, 2005.
References
1. Lee GA, Hirst LW. Ocular surface squamous Neoplasia Surv Ophthalmol 1995 39 429-50. 2. Lee GA, Hirst LW: Incidence of ocular surface epithelial dysplasia in metropolitan Brisbane. A 10year survey. Arch Ophthalmol 110:525-527, 1992. 3.Lee GA, Hirst LW Retrospective study of ocular surface squamous neoplasia Aust NZJ Ophthalmol. 1997 ;25:269-76. 4.Mahomed A, Chetty R Human immunodeficiency virus infection, Bci-2, p53 protein, and Ki-67 analysis in. OSSN. Arch Ophthalmol. 2002 ;120:554-8. 5. Sen S, Sharma A, Panda A Immunohistochemical localization of human papilloma virus in conjunctival neoplasias: a retrospective study. Indian J Ophthalmol. 2007;55(5):361-3. 6.Nolan GR, Hirst LW, Bancroft BJ The cytomorphology of ocular surface squamous neoplasia by using impression cytology. Cancer. 2001 25;93(1):60-5. 7. Tole DM, McKelvie PA, Daniell M. Reliability of impression cytology for the diagnosis of ocular surface squamous neoplasia employing the Biopore membrane. Br J Ophthalmol. 2001;85(9):1115-9. 8. McKelvie PA, Daniell M. Impression cytology following mitomycin C therapy for ocular surface squamous neoplasia Br J Ophthalmol 2001;85(9):115-9. 9 Freedman J, Rohm G.. Surgical management and histopathology of invasive tumours of the cornea Br.J Ophthalmol 63:632-635, 197.
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Original Article
Mrs. R. Jose MD, A.S. Rathore MD, V. Rajshekhar MS Sandeep Sachdeva MD DNB
Introduction
Eye care service in India has grown tremendously over the past three decade since the inception of the national programme in 1976. National Program for Control of Blindness [NPCB] with the implementation of Eleventh five year plan [2007-12] has become more comprehensive than ever before paving way for making available level appropriate eye care service to entire segment of population.1 The availability of expertise, infrastructure and technology is comparable to any of the developed nations in combating existing & future challenges of blindness such as diabetic retinopathy, glaucoma, retinopathy of prematurity, corneal blindness to name a few. On the parallel front, health sector in India is increasingly leading towards medical tourism. Major advances in the treatment of cataract across the globe have been availability of low cost high quality intra ocular lens [IOL] and newer techniques like small incision cataract surgery [SICS] & phacoemulsification.
Address for correspondence: Dr. Sandeep Sachdeva, Directorate General of Health Services, Govt. of India, New Delhi
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Background
Cataract surgery is a day-care elective procedure and can be successfully performed any time during the year without any risk of additional complications. However, there are various reasons including the beliefs prevalent amongst community to avoid surgery during the period of summer and monsoon i.e. timeframe corresponding to months of April to September. Thus from health system perspective this becomes a lean period as patients tend to flock during winter seasons. The principles of health economics indicate that such health practices results in under utilization of services and wastage of resources at one end and overcrowding, undue strain on health system, with a possibility of compromising quality of care and iatrogenic infection at other end. Ideally, from the health systems perspective cataract surgery performance should be spread evenly through out the year that would in-turn result in saving huge resources directly or indirectly. The objective of this paper was to analyze the proportion of cataract surgeries undertaken by respective States/UTs during the months of April to September and October to March. All States and UTs submit monthly performance report of cataract surgery to NPCB, New Delhi. The performance reports from various States/ UTs in India for the financial year 2008-09 was reconfirmed, analyzed and presented according to decreasing frequency [April to September] so as to gauge the scale of community acceptance for cataract surgery during reference period.
The findings reflect upon distinct developmental phases or transition amongst various States/UTs in the country as being witnessed in other spheres of life. The plausible complex, interlinked and
multi-factorial issues behind this diverse spectrum range from socio-economic factor as more than 60% of the sown area in the country is dependent on rainfall & the entire households are engaged in
Table 1: Proportion [%] of cataract surgeries reported by States/UTs in India for the year 2008-09 according to months
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agricultural practices, extreme weather conditions, & literacy status, cultural practices, intensity of social mobilization/information, education & communication [IEC] activities for dismantling wrong beliefs, creating demands for cataract surgeries and promotion of best practices, targetoriented approach for performance that is skewed at later months of financial year and/or other factors like governance or substantial presence or conspicuous absence of functional public-private partnership. Some of the studies in the western countries have attributed one of reason of lower uptake of elective cataract surgery during summer season [July to September] to vacation period of specialists. 3,4 This paper presents the snapshot for the year 2008-09 and as India evolves and traverses through time, we would be witnessing evenly spread of cataract surgeries through out the year especially the northern & central belt resulting in
References:
1. Jose R, Rathore AS, Rajshekar V, Sachdeva S. Salient features of the National Program for Control of Blindness during the XI th five-year plan period. Indian J Ophthalmol 2009;57: 339-40 2. Allen Foster, Clare Gilbert, Gordon Johnson. Changing Pattern in Global Blindness: 1998-2008. Community Eye Health J 2008; 21 [67]: 37-38 3. Alan M Leong, Eric J Crighton, Rahim Moineddin, Muhammad Mamdani, Ross EG Upshur. Time series analysis of age related cataract hospitalizations and phacoemulsification. BMC Ophthalmol 2006; 6:2 4. Pettinger N. Winter Pressures. Lazy days of summer. Health Serv J 1999, 109: 26-27
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Original Article
utcome of IOL Implantation for Congenital/Developmental Cataract in children less than 5 years
Vijaya Pai H. MS, Ajay Kamath N. MS
and wound dehiscence were noted in 1 eye each. Amblyopia was the another most common complication seen in 5 eyes , the others being irregular pupil in 2 eyes, IOL capture in 1 eye. 18 eyes were corrected to within + or 2 D spherical equivalent. Overcorrection was noted in 5 eyes (11.6%) and under correction in 11 eyes (25.5%). Owing to developments in surgical techniques biocompatible materials and intensive postoperative steroid regimen to reduce inflammation, IOL implantation in children less than 5 years has become relatively safe. However, more long-term studies are required to accurately calculate the power of IOLs to be implanted in infants and young children. Key words: Paediatric operative refraction cataract, post
Abstract:
AIM: To study the outcome of intraocular lens implantation for congenital/developmental cataract in children less than 5 years.
Methods: 43 eyes of 27 patients aged less than 5 years with congenital or developmental cataract, who underwent lens aspiration with IOL implantation between 1999 to 2006, were included in the study. The follow up period varied from 3 months to 6 years. Results: The most common early complication
(<3 months) was mild fibrinous membrane, seen in 7 eyes (16.3%) followed by posterior capsular opacity in 5 eyes (11.6%). Postoperative uveitis
Conclusion:
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Address for correspondence: Dr. Vijaya Pai H, Kasthurba Medical College, Manipal, Karnataka
Intraocular
lens
implantation
in
paediatric
cases has become an established procedure worldwide. With the evolution of new surgical instrumentation and techniques, complication rates have significantly reduced, making early surgery universally recommended for paediatric patients with cataracts.1 The efficacy and safety of this procedure, in short and intermediate terms have been documented in many studies.2 However, several questions have been raised especially with regard to IOL power calculation as the final refraction is variable and emmetropia cannot be guaranteed in adulthood, IOL design and material and management of posterior capsular opacity (PCO) and amblyopia.2
SURGICAL TECHNIQUE: A scleral tunnel of 6 mm was made in all cases, using an angled crescent blade. A viscoelastic was then injected into anterior chamber and an anterior continuous circular capsulorrhexis (CCC) done using 26 gauge prebent needle or Utrata forceps. Lens aspiration was then done using Irrigation - aspiration or Simcoe cannula. Then a primary posterior capsulorrhexis was performed followed by a limited anterior vitrectomy. A one-piece all PMMA IOL 5.5 mm x 12 mm was then inserted into the bag. The initial 5 eyes had heparinised infusion. The next 8 eyes had heparincoated IOLs. The remaining 30 eyes had only PMMA lenses. The wound was then sutured using 10-0 nylon. Subconjunctival dexamethasone and gentamicin was given at the end of the procedure.
Results: Early Postoperative Complications: (Within 3 Months): (Table 2) Mild fibrinous membrane
was seen in 7 eyes (16.3%). In 3 of these eyes, this mild fibrinous uveitis resolved rapidly and without sequelae with topical steroids. The other 4 eyes required YAG membranotomy for persisting membranes, which was done using and Nd: YAG laser with the patient under general anaesthesia. In one eye, YAG membranotomy had to be repeated and the same eye later underwent membranectomy with pupilloplasty. (Table 4) The next most common complication in early postoperative period was posterior capsule
opacification noted in 5 eyes (11.6%), which was treated with YAG capsulotomy. (Table 4) The other complications noted were severe postoperative uveitis in 1 eye (2.3%) and wound dehiscence post trauma in 1 eye (2.3%). Severe postoperative uveitis and grade IV cells in anterior chamber with posterior synechiae was noted in 1 eye, it resolved with frequent (hourly) antibioticsteroid combination eye drops and cycloplegics to break the posterior synechiae. Wound dehiscence following trauma to the eye, was noted in 1 eye and it required wound resuturing immediately. (Table 4)
encouraging and reliable data on the safety of IOL implantation in children <5 years, especially in short and medium term2, which is a witness to the continuous development of both techniques of surgery as well as biocompatible materials and intensive postoperative steroid regimen to reduce inflammation, prevent PCO formation and IOL decentration. As a result, there is increasing confidence about IOL implantation in children2. However any surgery will have its own share of complications.1 Posterior capsule opacification still remains a ubiquitous problem, although various options prevent it have been suggested such as primary posterior capsulotomy and anterior vitrectomy, pars plana posterior capsulotomy and posterior CCC with posterior optic capture, but none is foolproof. The incidence of PCO varies from 95.8% to 39% in various studies, both with and without posterior capsulotomy and anterior vitrectomy. Our study showed an incidence of PCO of 11.6%. Also the childs eye is known to exhibit increased postoperative inflammation. Postoperative uveitis can occur from mechanical, immunologiocal and complement activation or the toxic lens syndrome because of leaking of toxic chemicals from IOL. This fibrinoid uveitis can result in formation of posterior synechiae, pigment deposition on the IOL, or secondary membranes. Secondary membranes can be prevented by using heparin infusion (5 IU/ml) or heparin surface- modified IOLs and may require Nd: YAG laser for their treatment. Incidence of fibrinous membranes has varied from 28.2% to 7.6% in various studies and in our study, being 16.3%. Other postoperative complications include wound leak, iris prolapse, IOL capture, IOL dislocation, secondary glaucoma, CME and endophthalmitis.3,4 Normal phakic eyes elongate rapidly during the first 2 years of life. The axial growth continues at a slower pace until it stabilizes towards the end of the first decade. Corneal curvature decreases markedly during the first year of life and then changes
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Late Postoperative Complications: (After 3 Months): (Table 3) Amblyopia was the most
common complication noted in 5 eyes (11.6%), although amblyopia therapy was initiated from immediate postoperative period. Irregular pupil was noted in 2 eyes (4.7%) and IOL capture was noted in 1 eye (2.3%), for which an IOL exchange was done. No child had secondary glaucoma, cystoid macular edema, endophthalmitis and retinal detachment.
Discussion:
Several studies published earlier have shown
minimally thereafter. Lens growth, the third factor affecting overall refractive change in normal eyes, occurs throughout childhood. In the ideal phakic situation, these 3 variables change in concert over time so that the eye remains emmetropic. When the crystalline lens is surgically removed during the developmental years, a trend towards decreasing hyperopia (Myopic shift) should be inevitable as a result of on going axial elongation. However, it has been suggested that having an IOL in place may retard axial elongation, resulting in less myopic shift than if no IOL were used.5 Also, some studies have shown that rate of myopic shift decreases with age, and the variability among individuals decreases with age. Also, we will not know for sure what long-term refractive changes to expect in children until a generation or two have grown into adulthood. In the mean time, as more data with longer follow up are accumulated, we should be able to atleast improve our ability to select the appropriate IOL power for a growing childs eye.
Overall, the predictability of the refractive status of the eyes after IOL implantation was good, but a few patients showed major deviations from the refractive goal of the surgeon. There are several reasons why this may occur. The SRK-II formula is less accurate at the extremes of axial length values and a number of our patients fall into this category. A minor error in axial length measurement results in a much larger percentage error in shorter paediatric eyes. Ultrasound axial length measurements are calibrated for average eye length of 23.5mm, causing measurement errors in short eyes. Also, we used standard K1 K2 values due to a lack of hand held keratometer. In conclusion, the overall results of posterior chamber IOL implantation have been favourable. The advantage of relatively quick visual rehabilitation without problems associated with the use of glasses or contact lens wear can not be over estimated. However, long term follow up will be necessary to answer the safety of paediatric IOLs and accuracy of their power.
NO. OF EYES
15 17 11
UNILATERAL
3 5 3
BILATERAL
6 6 4
NO. OF EYES
7 5 1 1
PERCENTAGE %
16.3 11.6 2.3 2.3
NO. OF EYES
5 2 1 5 11
PERCENTAGE %
11.6 4.7 2.3 11.6 25.5
NO. OF EYES
4 1 1 2 1 1
NO. OF EYES
5 6 11 7 4 1 9 VK. Complications of paediatric cataract surgery and intraocular lens implantation: J Cataract Refract Surg 1999; 25: 1585-1588. 4. Steinert RF Surgical management of paediatric cataract. In - Cataract surgery and its complications. Philadelphia: WB Saunders, 1995. 5. Plager DA, Kipfer H, Sprunger DT, Sondhi N, Neely DE. Refractive changes in paediatric pseudophakia; 6 year follow up: J Cataract Refract Surg 2002; 28: 810-815.
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References:
1. Zwaan J, Mullaney PB, Awad A, et al. Paediatric intraocular lens implantation surgical results and complications in more than 300 patients: Ophthalmology 1998; 105:112-119. 2. Cassidy L, Rahi J, Nischal K, Russell-Eggitt I, Taylor D. Outcome of lens aspiration and intraocular lens implantation in children aged 5 years and under: Br J Ophthalmol 2001; 85: 540-542. 3. Sharma N, Pushker N, Dada T, Vajpayee RB, Dada
Original Article
linical outcome of Deep Anterior Lamellar Keratoplasty (DALK) using Big Bubble technique in a heterogenous group of corneal pathologies - 1 year prospective study
Aneeta Jabbar MS, Radharamanan MS, Thomas Cherian MS
Design:
non
comparative
Address for correspondence: Dr. Aneeta Jabbar Little Flower Hospital, Angamaly
Introduction
Lamellar Keratoplasty was once the treatment of choice for keratoconus, and anterior corneal pathologies. In an effort to offer the advantages of LKP (no risk of immune-mediated endothelial rejection) and PKP (superior visual results), epikera toplasty (EKP) was developed to flatten the cone with on lay donor tissue placed on top of undissected recipient corneal stroma. The optical results of lamellar keratoplasty can be improved by deep lamellar keratoplasty (DLK), where a deep dissection approaching or at the level of DM is achieved1. In this technique the patients cornea is dissected nearly to the level (DALKP) or to the level of Descemets membrane (MD-ALKP), after which a full-thickness donor corneal button (without endothelium or Descemets membrane) is sutured into the recipient bed. In DALK, most of the anterior layers of the cornea are removed, namely, epithelium, Bowmans membrane, and corneal stroma. The surgeon aims to cleave the cornea as close to Descemets membrane (DM) as possible, creating a smooth recipient bed for the donor tissue. Because the recipients own endothelium is retained, graft failure from endothelial rejection is not seen. The main disadvantage of DALK is of being both a technically more challenging and time-consuming procedure with a steep learning curve compared with PK, particularly when the host stroma is manually removed layer by layer until the DM is exposed.2 Recently Anwar and Teichmann 3 proposed a technique, which they called the bigbubble technique, where air is injected into the deep stroma with the aim of inducing separation by cleavage between posterior stroma and the DM, allowing the surgeon to gain a safe and direct access to this plane, with the advantages of shortening the surgical time, reducing the risk of perforation, and exposing a smooth, even surface of excellent optical quality with little tendency for interface scarring.
152
In this study, we report the clinical outcomes of the DALK big-bubble technique in unselected consecutive patients with anterior corneal pathologies.
Aim
To review clinical outcomes after DALK using Big Bubble technique in anterior corneal pathologies
Design
Prospective non comparative interventional case study
Setting
Cornea clinic Little Flower Hospital and Research Centre Angamaly
Inclusion criteria
Patients with anterior stromal pathologies who could be successively bared descemets membrane using big bubble method and who completed 12 months follow up
Exclusion criteria
Patients in which DM was bared by manual dissection, those who had intra operative perforation and converted into PK and patients with less than 12 months follow up
Surgical technique
All surgeries were performed by a single surgeon (AJ) The trephine size is 1mm larger than the diameter of the Fleischers ring in all cases of Keratoconus. Partial thickness trephination is performed up to 70-80% of the stromal depth. 27 G needle bent at 80 degrees 8 mm from the tip is attached to a
Outcome of DALK
TABLE 1 Patient Characteristics, Preoperative and Operative Data of Eyes Undergoing DALK Surgery Patient Characteristics
Age (mean SD) years Follow-up (mean SD) months Male/female Right/left eye Unilateral/bilateral
14 Eyes of 14 Patients
21.57 (9.24) 13.71 (1.73) 12 / 2 5/9 14 / 0 11 (78.57%) 02 (14.8%) 01 (7.14%) 1 (7.14%) 10 (71.42%) 3 (21.41%) 0 14 (100%)
Diagnosis
Keratoconus Non specific corneal opacity Corneal stromal dystrophy
Graft size
6.5 mm 8.0 mm 8.5 mm
Suturing method
Continuous Interrupted
5cc syringe. The needle is advanced carefully into the corneal stroma 5-6mm para- centrally with the bevel facing down wards and air is injected. There is an initial resistance followed by whitening of the corneal stroma as air enters within the corneal lamellae. A sudden easing of resistance indicates separation of the Descemets Membrane from the stroma. 40% of the superficial stroma is dissected with a crescent knife. The big bubble is now seen more clearly, with the whitish opacity outlining the edge of the bubble... Paracentesis is performed to release the aqueous and to lower the intraocular pressure. A blunt iris spatula is introduced into the space and the anterior stromal tissue is then incised with a sharp knife. The anterior stromal tissue is further split into smaller segments and excised
using a pair of blunt-tipped curved scissors. The clear Descemets membrane can be visualized now. The donor corneal button is punched out from the endothelial side. A fine tipped forceps is used to peel away the Descemets membrane from the donor tissue. After washing the interface, the donor tissue is placed on the stromal bed and secured into position using 10 -0 nylon, 16 interrupted sutures. Eye pad was removed the next day .After slit lamp evaluation, Applanation tonometry and Fundoscopy patients were started on broad spectrum antibiotics and Prednisolone acetate 1 % eye drops and lubricating drops. After 1 week, antibiotics were stopped and steroid drops were tapered stepwise. Selective suture removal for the
153
reduction of astigmatism started at 3 months after surgery. Otherwise, sutures were left in place for as long as 10 months to one year as long as they were not excessively tight, loose, exposed, or attracting blood vessels.
Results
14 eyes of 14 patients who underwent DALKP were included in this study. 12 were male and 2 were female. The mean follow-up for all patients was 13.71 1.73 months. The mean age of all patients was 21.57 9.24 years. Two (14.8%) eyes had superficial scar , one eye ( 7.1%) had Macular dystrophy and eleven eyes had moderate to severe Keratoconus ( (78.57% ) Baring of Descemets membrane (DM) during DALK using Big Bubble was achieved in 12 (85.71 %) eyes; some stroma was left during operation in the remaining 2 (14.8 %). eyes. DALK surgery was attempted in all eyes with anterior corneal pathologies and Keratoconus during the study period .Only in 14 eyes DM could be bared by the Big Bubble technique. Others were either converted into PK or baring of Descemets was achieved by manual dissection. Such cases were not included in the study. Of the 14 patients in whom DALK was successfully performed, status of contra lateral eye is waiting for same procedure in 38.5%, underwent penetrating keratoplasty in 7.1 %, is normal in 7.1 % and has good functional vision in 46.2% with RGP / Rose K lenses The quality of the graft was good in all the cases. Donor age ranged from 24 to 80 years. Preservation time ranged from 27 hours to 110 hours. Table 1 summarizes the characteristics and operative data of the patients in the study. In 64.3 % eyes the donor graft was oversized by 0.25mm and in 21.4 % eyes the donor graft was oversized by 0.5 mm. Preoperative vascularization was present in 15.4% eyes involving 2 quadrants.
Statistics
Parametric data are presented using mean (SD) values. Non-parametric data are presented with median values. Visual acuity data was analyzed by coding and then compared using two tailed tests.
154
Visual Outcome
Best-corrected visual acuity (BCVA) of 6/12 or better was present in 0 /14 (0 %) of the eyes preoperatively and 9 /13 (69.3 %) of the eyes postoperatively; 38.5 % of the eyes had a postoperative BCVA of 6/9 to 6/6.
Outcome of DALK
The mean preop and post op BCVA were compared and two tailed p value was < 0.0001. The mean of Pre op BCVA minus Post op BCVA equals 1.075 .with 95% confidence interval of this difference from 0.78 to1.37. BCVA( Best corrected visual acuity ) of 6/36 or better was present in 2 /13 eyes preoperatively and Uncorrected visual acuity of 6/36 or better in 12/13 eyes postoperatively. The mean UCVA preop and post op were compared using two tailed t tests and p value was < 0.0001. Five eyes had an uncorrected vision of 6/18 or better postoperatively (Table 2). One patient was having severe mental retardation and was unable to document visual outcome but as per the patients
refractive cylinder less than 3.0 D and 14.3% had a postoperative refractive cylinder of less than 4.5 D Selective suture removal for the reduction of astigmatism was started at an average of 3.5 months and complete suture removal was done at 6 to 8 months.
Complications (Table 3)
Over the follow-up period, none of the eyes had rejection episode. Two eyes had small DM perforations intraoperatively.. In these eyes, the indication for surgery was keratoconus . However, in both of these eyes who had micro punctures in the DM, it was possible
attendants he was happy after the surgery which can be due to the good functional vision.
Refractive outcome
The mean postoperative cylindrical refractive error was 2.05 D.. The mean spherical equivalent (SEQ) was 1.974; 64.3% of the eyes had a postoperative
to complete the surgery by carefully carrying out the lamellar dissection in a slightly anterior plane. One eye had a steep cone have given the surgeon an artificial feeling of security, and the perforations, when they occurred, were usually unexpected. In contrast, surgery was completed without perforations in few eyes with advanced
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keratoconus, which were thought to be at high risk of intra operative DM perforations. A double anterior chamber was noted in one of these eyes in the immediate postoperative period. This resolved with conservative management over a period of 2 weeks. Two patients had increased IOP in the follow up period which was managed medically. One of these patients had pre operative raise in IOP .Second
surgery leading a paradigm shift in the management of a variety of corneal disorders. Several of our patients who obtained good results would otherwise be considered poor candidates for PK because of high risk of graft rejection. Due to the young age. Several authors have reported a favorable visual outcome after DLKP 4,5,6. In our study following DALK 69.2% had UCVA 6/24 or better in the last follow
Complication Rate
(14.3 %) (0%) (7.1%) (7.1%)
2/14
(14.3 %)
patient was a steroid responder who did well after stopping Predinisolone acetate and maintaining on Loteprenolol. The two year old child included in this study had a loose suture on second follow up which was promptly removed .But she developed graft infiltrate which was resolved medically in three weeks time and the graft is clear except for a peripheral scar
Discussion
Lamellar keratoplasty has evolved over the last 150 years. However its ability as an optical procedure is limited by problems of interphase irregularity, scarring and residual pathological stroma. Deep Lamellar Keratoplasty or DLKP is an exciting new
156
up. All the patients had BCVA 6/12 or better The frequency of micro perforations (14.3% ) reported in this study compares well with that reported in other studies that used the same technique (8% to 13%).7 In our series of patients when ever the surgeon came across an IOP rise due to steroid response even if it was confronted in the early post operative period, a control over the situation was possible by either early tapering of steroids or switching over to less potent steroids without the fear of endothelial rejection. This can be considered as a greatest advantage of this novel technique .Recent results of comparison studies suggest that DLKP can be considered as a safe alternative to PKP in the treatment of different anterior corneal pathologic characteristics with stromal opacity and
Outcome of DALK
in keratoconus. 8,9,10 In addition to comparable results in terms of visual recovery, DLKP presents several advantages with respect to PKP, mainly linked to the preservation of corneal host endothelium, leading to a lower risk of endothelial rejection and late endothelial failure11 as well as a greater availability of donor corneas that do not need perfectly healthy endothelium and high endothelial cell density to be suitable for corneal grafting. Although our study lacks a post operative specular count the fair quality tissues used as grafts were not showing any clinical evidence of endothelial dysfunction and were maintaining clarity till final follow up.Also grafts with increased preservation time i.e.; about 110 hours were clear and compact till the last follow up .In a set up like ours excellent grade tissues are procured less frequently than good / fair quality tissues. Using DALK technique good/fair quality tissues can be better utilized preserving the excellent quality ones for pediatric as well as other high risk keratoplasties. Interface scarring leading to poor visual acuity represents one of the greatest reservations that has limited the applications of LKP in the past.12,13 The Big Bubble technique popularized by Anwar and Teichmann
3
published series that found the mean cylinder values of -4.D 15, 2.67,16 and 3.25 D4 after DALK. These values also compare well to series on PK with similar astigmatic outcome.11,17
Conclusion
Lamellar keratoplasty has many advantages over PKP. These include maintenance of globe integrity, the possibility of using older graft material, a significant reduction in quantity and duration of postoperative steroid therapy, nearly complete absence of graft rejection, and a low rate of acute and chronic endothelial cell loss. The full benefits of LKP will be realized only with long-term follow-up.
References
1 Sugita J, Kondo J. Deep lamellar keratoplasty with complete removal of pathological stroma for vision improvement. Br J Ophthalmol 1997;81:1848 2 Tsubota K, Kaido M, A new surgical technique
for deep lamellar keratoplasty with single running suture adjustment. Am J Ophthalmol1998;126:1 8. 3. Anwar M, Teichmann KD. Big-bubble technique to bare Descemets membrane in anterior lamellar keratoplasty. J Cataract Refract Surgery 2002;28:398 403. 4. Anwar M, Teichmann KD. Deep lamellar keratoplasty. Surgical techniques for anterior lamellar keratoplasty with and without baring of Descemets membrane. Cornea. 2002;21:374383. 5. Coombes AGA, Kirwan JF, Rostron CK. Deep lamellar keratoplasty with lympholised tissue in the management of keratoconus. Br J Ophthalmol. 2001;85:778791. 6. Bruce A. Noble, Ashish Agrawal, MS(Ophth), Deep Anterior Lamellar Keratoplasty (DALK) Visual Outcome and Complications for a Heterogeneous Group of Corneal Pathologies Cornea 2007;26:59 64
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reproducible of techniques consistently allowing one to reach the Descemets membrane. In the 14 eyes included in this study baring of Descemets membrane. was achieved by the big bubble technique. Surgery was successfully completed in 2 of the 14 eyes with DM micro perforation These eyes had some interphase haze but the final visual acuity is better than 6/18 in both. DALK techniques like big bubble 3 and femtosecond laser14 may offer the advantage of a smoother recipient bed that could reduce the risk of interface scarring. The mean postoperative cylindrical refractive error was 2.05 D. This finding is in line with those of other
7. Fogla R, Padmanabham P. Results of deep lamellar keratoplasty using the big-bubble technique in patients with keratoconus. Am J Ophthalmol 2006;141:254 259. 8. Olson RJ, Pingree M, Ridges R, et al. Penetrating keratoplasty for keratoconus: a long-term review of results and complications. J Cataract Refract Surgery 2000;26:987991. 9. Javadi MA, Motlagh BF, Jafarinasab MR, et al. Outcomes of penetrating keratoplasty in keratoconus. Cornea 2005;24: 941945. 10. Lim L, Pesudovos K, Coster DJ. Penetrating keratoplasty for keratoconus: visual outcome and success. Ophthalmology 2000;107:11251131 11. Watson SL, Tuft SJ, Dart JKG. Patterns of rejection after deep lamellar keratoplasty. Ophthalmology 2006;113:556560. 12. Tusbota K, Kaido M, Monden Y, et al. A new surgical technique for deep lamellar keratoplasty
with single running suture adjustment. Am J Ophthalmol 1998;126:18. 13. Timarchi F, Poppi E, Klersy C, et al. Deep lamellar keratoplasty. Ophthalmologica. 2001;215:389393. 14. Seitz B, Langenbucher A, Hofmann-Rummelt C, et al. Nonmechanical posterior lamellar keratoplasty using the femtosecond laser (femto-PLAK) for corneal endothelial decompensation. Am J Ophthalmol 2003;136: 769772. 15. Watson SL, Ramsay A, Dart JKG, et al. Comparison of deep lamellar and penetrating keratoplasty in patients with keratoconus. Ophthalmology.2004;111:16761682. 16. Timarchi F, Poppi E, Klersy C, et al. Deep lamellar keratoplasty. Ophthalmologica. 2001;215:389393. 17. Funnell CL, Ball J, Noble BA. Comparative cohort study of the outcomesof deep lamellar keratoplasty and penetrating keratoplasty for keratoconus. Eye. 2006;20:52732.
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Original Article
Conclusion
This pilot study suggests that high plasma glucose level is a confounding factor affecting accuracy of applanation readings in diabetic patients,especially in severe degrees of hyperglycaemia. Diabetic patients being a risk group for Primary OpenAngleGlaucoma are often subjected to applanation tonometry for glaucoma screening, diagnosis and follow up.Several studies have shown that hyperglycaemia can alter corneal thickness, which has a direct influence on tonometric accuracy.Thinking further; this could mean that hyperglycaemia may have a crucial confounding effect on applanation tonometry as well. This could lead to high incidence of false positives during glaucoma screening in diabetic patients.
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Address for correspondence: Dr. V.K. Lathika, Amala Institute of Medical Sciences, Thrissur
Aim
1) To determine whether variation in applanation tonometry readings in a study group with uncontrolled diabetes is statistically higher than the normal intraobserver variation in an age matched control group. 2) To analyze whether change in plasma glucose levels lead to the observed variation in tonometric readings in diabetic patients. 3) To correlate these tonometric variations in diabetic patients with the degree of hyperglycaemia.
We also had an age matched control group, who had no known ocular or systemic disease. Each patient was subjected to applanation tonometry by the same observer at two different sittings and the intraobserver variation in the control group was computed.
Exclusion critera1) patients with diagnosed glaucoma 2) Patients with ocular disease that could lead to secondary glaucoma
Results
The mean difference in applanation readings before and after glycaemic control in the study population was calculated (ATD-study 1.766).This was compared with the mean intraobserver variation in the normal control group.(ATD-control 0.9). The variation in the study group was statistically significantly higher (students t test-p<0.001) compared to the intraobserver variation in the normal control group. The next step was to determine whether the variation in applanation readings in the study group was influenced by the glycaemic changes in the study population.The paired t test showed that there was a statistically significant change in applanation ,with change in fasting plasma glucose levels (p<0.05). To analyse further,the pattern of distribution of applanation change in different degrees of
TABLE 1-Comparison of mean variation in applanation readings(ATD) in study and control groups
hyperglycaemia,the study population was grouped into three,based on fasting plasma glucose at the time of initial applanation recording.
Variation in tonometric value by more than 2 mm of Hg was found in no patient with mild hyperglycaemia.47%of patients with moderate hyperglycaemia and 69.2% of patients with severe hyperglycaemia showed a variation of more than 2 mm of Hg between applanation readings before and after control of diabetes.Analysis of this data using the Chi square test, showed a statistically significant association between variation in applanation readings and degree of hyperglycaemia.(p<0.001). TABLE-2
(FPG-fasting plasma glucose; ATD-Difference in applanation readings before and after control of diabetes.)
TABLE-3
ATD- 0 mm Hg 2 2 3
ATD- 1 mm Hg 17 5 0
ATD- 2mmHg 11 2 2
ATD- 3mmHg 0 5 5
Discussion
Diabetes has been proven to affect the biomechanical parameters of cornea like corneal hysteresis,corneal resistance factor and central corneal thickness.The Singapore Malay study ,a population based study among the
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Malays showed that diabetes and hyperglycaemia are associated with thicker central corneas.Most of these studies have attributed these effects to long term hyperglycaemia,as evidenced by HBA1c . The current study demonstrates a statistically significant fluctuation in applanation readings,which can be correlated well with short term fluctuations in fasting plasma glucose levels.Apart from the long term corneal changes in diabetic eyes,transitory hyperglycaemia could bring about osmotically mediated shifts in corneal hysteresis or central corneal thickness.The variations in applanation readings in the current study could be attributed to these changes. Very few studies have looked into the effects of transitory hyperglycaemia on applanation tonometry.The current study is in concurrence with a study by Ponnoosamy which concluded that the overall response of IOP correlated well with increase of plasma glucose. A drawback of our study is that pachymetry was not done,which would have provided the missing link between applanation changes and plasma glycaemic changes.
To conclude,this pilot study suggests that high plasma glucose level is a confounding factor affecting accuracy of applanation readings in diabetic patients,especially in severe degrees of hyperglycaemia. So, having the diabetic status controlled is desirable before taking applanation reading in a diabetic patient.This can minimise false positive errors while screening for glaucoma in diabetic patients. Acknowledgements-To Dr Rani Menon for her guidance,Dr Ajith T.A for his help in research work and Mrs Gini for the statistical analysis involved.
References
1. Toshiyuki Oshitari, Noya Fujimoto, Effect of Chronic hyperglycemia on intra ocular pressure in patients with diabetes Am J Ophthalmol 2007 ; 143: 365-367 2. Daniel H W Su et al Diabetes, Hyperglycemia and central corneal thickness Singapore Malay Eye study, Ophthalmology 2008; 115: 964-968 3. Shih CY , Graff Zivin JS et al , Clinical significance of central corneal thickness in the management of Glaucoma. Arch Ophthalmol 2004 ; 122: 1270-5 4. Mitchell P, Smith W , Chey T, Healey PR , Open angle Glaucoma in diabetes : The Blue Mountains Eye study. Ophthalmology 1997 ; 104 : 712-8 5. Sato T , Roy S. Effect of high glucose on Fibronectin expression and cell proliferation in trabecular meshwork cells. Invest Ophthalmol Vis Sci 2002 ; 43 : 170-75 6. Dielemans I , de Jong PTVM , Stolk R et al , Primary Open angle glaucoma Intraocular pressure in the general elderly population : The Rotterdam study. Ophthalmology 1996; 103: 1271-1275.
Conclusion
1)The mean difference in applanation tonometry readings before and after glycaemic control in the study group of diabetic patients was statistically significantly higher than the mean intraobserver variation observed in an age matched control group.(p< 0.001) 2)Changes in plasma glycaemic levels in the study population result in statistically significant changes in applanation tonometry readings .(p< 0.05) 3)The change in applanation readings has a statistically significant association (p<0.001)with increasing levels of hyperglycaemia.Higher the initial fasting plasma glucose level,greater is the variation in applanation reading
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Community Ophthalmology
Need = 100,000 Keratoplasty/year = 200,000 Cornea/year if we can enhance our utilization up to 50%.
n
Eye Bank Training Centre (EBTC) = 5 Eye Bank (EB) = 176 Eye Donation Centre (EDC) = 428 No. of active eye bank/EDC (>50 eyes/year) = 203 No. of active Eye Banks/EDC collects >100 eyes/ year = 46
163
Address for correspondence: Dr. Samar K. Basak, Disha Eye Hospital, Barrackpore, Kolkatta- 700 120
2002
19,352 7,562 39.1%
2003
20451 8,014 39.2%
2004
24,160 9,700 40.1%
2005
26,865 11,369 42.3%
2006
28,857 12,975 44.9%
2007
31,686 13617 42.9%
2008
34,506 13827 40%
Collection Utilization
HCRP Collection: in 2004 = 1034 (4.3%) HCRP Collection: in 2005 = 3094 (11.5%) HCRP Collection: in 2006 = 3437 (11.9%) HCRP Collection: in 2007 = 5054 (15.9%) HCRP Collection: in 2008 = 6551 (18.9%)
HCRP in PROVA EYE BANK, Disha Eye Hospitals, Barrackpore Collaboration with R G Kar Medical College & Hospital (2004-2008)
Voluntary Vs HCRP in PROVA Eye Bank (2003-08)
Collection 2003 2004 2005 2006 2007 2008 Voluntary 146 HCRP Total --- 146 134 126 22 164 144 128 110
156 290
Collection
614 658 610 1164 1483 1708 1456
Utilization
196 208 201 381 547 694 582
%
31.9% 31.6% 32.9% 32.7% 36.9% 40.6% 39.9%
Collection
130 150 156 290 554 622 542
Utilization
43 56 46 150 270 351 286
%
33.1% 38.3% 29.5% 51.7% 48.7% 56.6% 54.6%
Eye Banking
Organized sector Good networking Rigid Govt. regulations and National feeling Collection = 100,000 eyes/year Utilization rate = 65% or more Utilization = 35,000/year in USA alone = 40,000/ year to other countries
5 45 2000
5 Eye Bank Training Centre; 45 Eye Banks and 2000 Eye Donation Centre. The basic Equation is:
n
51% of Americans wish to donate their eyes 73.7% Licensed Drivers are registered for Eye/Organ donation
50 EB and EBTC will Network with 2000 EDC One EB/EBTC for 20 million population and linked with 40 EDC Each EB/EBTC will develop HCRP with 10 major hospitals. Each EB/EBTC can process 4000 Corneas/year Half (2000) through HCRP and Half (2000) via EDC. Each EDC will harvest 50 eye/year (25 person)
70.3% of urban people know something about eye donation Only 18.5% wish to donate their eyes But 87.5% of this willing persons family members do not wish to donate eyes/body.
57% do not want to donate their eyes 48% believe that they will born blind in next life
24.5% - undecided
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We, in PROVA Eye Bank, Disha Eye Hospitals, Barrackpore, have started our HCRP since September 2004 at RG Kar Medical College Hospital with collaboration of Health Deptt, Govt. of West Bengal. Since then there is a tremendous growth both in collection and utilization. In these 5 years we have collected 1786 eyes from HCRP and we utilized 942 eyes for different types of corneal grafting. That means, the collection is increased by 400% and the utilization is increased from 32% in 2000-03 to 52.7% in 2008-09 as compared to 2003-04. Initially, we used to perform only Penetrating Keratoplasty (PK). Now because of improved collection and quality of tissue we are performing newer Lamellar Keratoplasty (LK) procedures. Now, our waiting period for any keratoplasty has reduced
to 3-4 weeks as compared to 12-18 months in 2004. Like quantity, Quality issues are now important in Eye Banking for long term graft survival of the recipients. We need to utilize MK medium for better and longer storage of the donor cornea. And at the same time, we need 2-5 ml of donors blood for certain important serology tests which are of extreme importance for the safety of the recipient as well as the personnel who handle donor tissue. HCRP and MK medium storage of the donor cornea are the two important steps to improve the quality. That means, the utilization will be much better and it can increase up to 50% with present infrastructure. Let us put I in EYE BANKING: That is - Involvement, Inspiration and Innovation.
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Current Practice
temporary monocular or binocular loss of vision. It may be due to vascular, neurologic or ophthalmic causes. It commonly results from impaired blood supply to the afferent visual system, due to primary arterial occlusion or stenosis, secondary arterial occlusion as a result of embolism from a distant site (eg.internal carotid artery (ICA), aortic arch, or heart), vasospasm (eg.migraine), or systemic hypoperfusion.
Address for correspondence: Dr. Sandhya N, Giridhar Eye Institute, Cochin - 682 020
a cause. Three embolus subtypes may be identified: cholesterol, platelet-fibrin, and calcium. Cardiac emboli can arise from the left atrial appendage in patients with atrial fibrillation, severe mitral stenosis with stasis of blood in the left atrium, thrombus in the dyskinetic left ventricular apex following anterior wall myocardial infarction, dilated cardiomyopathy with severe left ventricular dysfunction and calcific aortic valve in the elderly. Rarely amaurosis fugax can occur from low central retinal artery perfusion pressure in patients with critical carotid stenosis with poor collateral flow from the circle of Willis. This can happen when there is transient hypotension. This may be associated with contralateral motor or sensory loss indicating concomitant hemispheric cerebral ischemia. Transient ischemic attacks from vertebrobasilar insufficiency can result in acute homonymous visual symptoms. Many patients mistakenly describe symptoms in the right or left eye. Interruption of blood supply to the visual cortex causes a sudden fogging or graying of vision occasionally with flashing lights or other positive phenomena that may mimic migraine. Opththalmic Artery Stenosis and Occlusion: Stenosis of the ophthalmic artery due to atheroma can produce isolated episodes of transient monocular visual loss, as a consequence of retinal and optic nerve hypoperfusion or embolism to the retinal arteries. Retinal arterial occlusion can occur rarely in association with retinal migraine, lupus erythematosis, temporal arteritis, hypercoagulable states like anticardiolipin antibodies, anticoagulant deficiency states(protein C, protein S and anti thrombin deficiency) and pregnancy. Impending branch or central retinal vein occlusion can produce prolonged visual obscurations. Sudden visual loss can occur in hypertensive
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crisis due to vasospasm of retinal arterioles and consequent retinal ischemia. Marked systemic hypertension causes sclerosis of retinal arterioles, splinter hemorrhages and focal infarcts of the nerve fiber layer (cottonwool spots) and leakage of lipid and fluid (hard exudate) into the macula. Acute hypertension may produce visual loss from ischemic swelling of the optic disc.
Neurologic
Retinal migraine
Ophthalmic
Papilledema and optic disc edema
Optic disc drusen Optic neuritis Intermittent angle-closure glaucoma Tear film dysfunction and dry eye
by a combination of anemia and hypotension, causing infarction of the retrobulbar optic nerve. This may follow major blood loss during major surgery, exsanguinating trauma or gastrointestinal blood loss. Fundus usually appears normal.
Neurologic
Migraine aura Occipital seizures Posterior reversible encephalopathy syndrome Head trauma
Is a common inflammatory disease of the optic nerve. In most patients demyelination is retrobulbar and hence fundus appears normal initially though disc pallor may develop later. They can develop episodic transient visual loss lasting minutes to hours with increase in body temperature(Uhthoff phenomenon). Episodes pose no threat to permanent vision. Vision returns to baseline when body temperature comes back to normal. This is due to transient conduction block within the optic nerve.
Ophthalmic
Papilledema and optic disc edema Optic disc drusen
Papilledema:
only one eye. Migraine phenomena remain visible in the dark or with the eye closed. After the visual symptoms recede headache develops in most patients. Cortical ischemic attacks are briefer in duration than migraine, occur in older patients and are not followed by headache. There may be associated signs of brainstem ischemia such as diplopia, vertigo, numbness, weakness or dysarthria.
several other ophthalmic diseases, although some of these produce visual blurring or visual distortion rather than actual loss of vision. Age-related macular degeneration can result in light-induced TVL due to increased photostress recovery time. The episodes are usually bilateral and affected patients have decreased acuity with obvious signs of macular degeneration on fundus examination. Intermittent angle-closure glaucoma can rarely present with isolated painless TVL although most patients have pain, vomiting, or other visual symptoms, such as halos, during episodes. TVL can rarely result from recurrent hyphaema, such as in the uveitis-glaucoma-hyphema syndrome that occasionally complicates cataract extraction with intraocular lens implantation. The patient reports a rapid reduction in vision over minutes, followed by gradual resolution over hours to days. There may be associated pain and erythropsia (red vision) and a microhyphema may be seen if the patient is examined during an attack. Corneal basement membrane dystrophy can also produce isolated TVL, but it is usually associated with pain. Signs of this disease can be detected on a careful anterior segment examination. Finally, dry eye and tear film dysfunction can result in TVL. The patient may report that their vision improves after blinking or after the application of artificial tears. Signs of dry eye may be present on examination.
adolescents and young adults. Calcium channel blockers may reduce the frequency of attacks in patients with presumed vasospasm.
TVL may occur with intraorbital mass lesions or foreign bodies and heat-evoked TVL(Uhthoffs phenomenon) may occur with demyelinating optic neuropathies.
Monocular
or binocular: Monocular TVL suggests a pre-chiasmal lesion, whereas binocular TVL suggests a chiasmal, retrochiasmal or bilateral pre-chiasmal lesions. An important caveat is that homonymous visual field loss is frequently mistaken for monocular visual loss on the side with the temporal field defect; it is therefore useful to ask if visual loss was noted in the other eye when the affected eye was covered during the episode.
Examination
A thorough examination is essential to document the current state of the afferent visual system and to detect signs that suggest a cause for the TVL. An
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ophthalmic examination, including an assessment of the orbits, anterior segment, and intraocular pressures, and funduscopy, is essential to find out the etiology (eg, asymptomatic retinal emboli or signs of the ocular ischemic syndrome due to atheromatous carotid stenosis)). Assessment of the pulse (for presence of atrial fibrillation) and blood pressure are also important. Cardiovascular exam may reveal features of valvular heart disease (like mitral stenosis and aortic stenosis which is most often calcific in the elderly), dilated and restrictive cardiomyopathy. Carotid bruit is audible when there is significant internal carotid artery stenosis unless there is total occlusion. Asymmetric pulses, bilateral subclavian and often carotid bruit in a young person may suggest a diagnosis of aortoarteritis.
Management is directed toward the underlying cause. In patients with a cardiac source of embolism, anticoagulation with warfarin and treatment of the underlying cardiac disease is indicated, whereas those with atherothrombotic disease should be commenced on antiplatelet therapy. Modifiable vascular risk factors should be addressed. In those with ICA stenosis, antiplatelet therapy with aspirin and clopidogrel should be initiated and modifiable vascular risk factors addressed(statins). Management of high-grade ICA (70% to 99%) stenosis in patients with isolated TVL remains controversial. Carotid stenting with distal protection device during the procedure might produce an equivalent long-term outcome as carotid endarterectomy and may be a safer option for poor surgical candidates. As TVL may be a warning symptom for impending anterior ischemic optic neuropathy in patients with giant cell arteritis and the patient may be otherwise asymptomatic, an erythrocyte sedimentation rate, C-reactive protein, platelet count, and fibrinogen level should be obtained urgently in all older patients with TVL. The diagnosis is confirmed by finding the characteristic histopathologic changes on temporal artery biopsy. The patient should be admitted for bed rest, as this may decrease the risk of infarction due to posturally-induced hypoperfusion, and commenced on high-dose intravenous steroids as soon as the diagnosis is suspected. One should not wait for the biopsy report to start steroids.
or those with vascular risk factors. The treatment approach for migraine involves avoidance of precipitating factors and the use of abortive treatments, such as the triptans, at the onset of attacks. Patients with frequent or disabling attacks may respond to prophylactic therapies, such as propranolol, amitriptyline, or topiramate. Attacks of transient monocular visual loss due to vasospasm may remit with calcium channel blockers. Occipital seizures can usually be adequately controlled with anticonvulsants. In patients with papilledema neuroimaging should be obtained urgently to exclude a structural cause, such as a mass lesion, obstructive hydrocephalus, or venous sinus thrombosis. Patients with normal imaging should undergo lumbar puncture for measurement of opening pressure and cerebrospinal fluid analysis. Treatment is directed towards the underlying cause. Optic disc drusen may be visible on funduscopy. B-scan ultrasonography or CT may be required to demonstrate their presence. Rarely, episodes of TVL can be harbinger for central retinal artery occlusion in these patients. No treatment is available. Uhthoffs phenomenon causing TVL is self limiting with good visual recovery. No specific treatment is required.
some causes of TVL, such and TIAs and GCA are true medical emergencies, the clinician should have a low threshold for urgent evaluation of patients who may have these conditions.
References
1. Mathew J. Thurtell, Janet C. Rucker. Transient Visual loss. International ophthalmology clinics, Neurophthalmology 2009;49:147-158. 2. Jonathan C. Horton. Disorders of the eye. Chapter28; section 4: 170-172. Harrisons-Principles of internal medicine (15th edition). 3. Miller NR. Embolic causes of transient monocular visual loss. Ophthalmol Clin North Am.1996;9:359380. 4. Biousse V, Touboul PJ, DAnglejan Chatillon J . Ophthalmologic manifestations of internal carotid artery dissection. Am J Ophthalmol.1998;126:565-577. 5. Savitz SI, Caplan LR. Vertibrobasilar disease. New Engl J Med.2005;352:2618-2626. 6. Biousse V,Trobe JD. Transient monocular visual loss. Am J Ophthalmol.2005;140:717-721. 7. Bruno A, Corbet JJ,Btiller J. Transient monocular visual loss patterns and associated vascular abnormalities. Stroke. 1990;21:34-39. 8. Hoya K,Morikawa E, Tamura A. Common carotid artery stenosis and amaurosis fugax. J Stroke Cerebrovasc Dis. 2008;17:1-4. 9. Burger SK, Saul RF, Selhorst JB. Transient monocular blindness caused by vasospasm. N Engl J Med. 1992;326:837-838. 10. Goadsby PJ. Recent advances in the diagnosis and management of migraine. BMJ.2006;332:25-29.
Summary
TVL is a sudden onset, temporary, monocular or binocular loss of vision that is often caused by a temporary disruption of blood supply to the eye or visual pathways. It can also result from a wide variety of other causes, including neurologic conditions, such as migraine, and ophthalmic conditions, such as optic disc edema. Diagnostic investigations should be tailored toward the suspected cause. As
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R
T
Tufela Shafi MS, Sandhya A. MS, Natasha Radhakrishnan MS, Gopal S Pillai MD
he human eye is unique in the sense that it is the only place where the blood vessels and optic nerve can be seen. Examination of the vessels and optic nerve can give a clue to an underlying systemic disorder; Hence it is rightly said that the eye is the window to the body. Like other systems, cardiovascular diseases also have an impact on the eye Below we present the fundus pictures of some patients, examination of whom gave us a clue that they had an underlying cardiovascular disorder.
Fig 1(a)
Fig 1(b)
Grade 4 hypertensive retinopathy with macular fan appearance in a 45 year old male who presented with severe headache.(Fig 1 a,b).On evaluation patient was found to have systemic hypertension.
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Address for correspondence: Dr. Gopal S. Pillai, Amrita Institute of Medical Sciences, Cochin
Focal arteriolar attenuation, Elschnigs spots and Siegrists streaks in a 40 year old male who had been diagnosed with accelerated hypertension following a bout of altered sensorium. (Fig 4 a,b,c,d)
Fig 2(a)
Fig 2(b)
Arterial attenuation with AV crossing changes and Hollenhorst plaque seen in the inferotemporal artery in this 60 year old hypertensive male who was admitted for CAD.(Fig 2 a,b)
Fig 5(a)
Fig 5(b)
Fig 3(a)
Fig 3(b)
Fig 5(c)
Fig 5(d)
Bilateral exudative retinal detachments seen in a 30 year pregnant old female who was diagnosed with PIH and presented with sudden onset visual loss in third trimester.(Fig 3 a and 3 b) The exudative detachments subsided and vision returned to normal after emergency caesarian section.
30 year old gentleman, with diagnosed malignant hypertension presented with acute severe decrease in vision in the left eye. Fundus examination showed disc edema in the left eye suggestive of hypertensive ischemic optic neuropathy. FFA showed disc leakage. (Fig 5a, b, c, d)
Fig 4(a)
Fig 4(b)
Fig 6(a)
Fig 6(b)
Fig 4(c)
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Fig 4(d)
Fig 6(c)
61 year old male who presented with sudden onset, painless loss of vision .On examination there was central retinal opacification with a well defined cherry red spot at the macula.FFA was done which confirmed the diagnosis of CRAO. Carotids Doppler showed evidence of plaques and occlusion. (Fig 6a, b, c)
Fig 8(c) 65 year old gentleman presented with sudden onset of dimunition of vision. Fundus examination of the right eye showed attenuation of the inferotemporal artery with corresponding opacification of the retina. FFA showed non filling of the artery in the early frames with complete filling in the later stages. Cause of embolism was evaluated to be a cardiac valvular defect (Fig 8a, b, c).
Fig 7(a)
Fig 7(b)
Fig 7(c)
71 yr old female who presented with sudden onset painless decrease in right eye vision .Patient gave a history of stroke 1 year back. On examination,patient had posterior pole retinal opacification with cherry red spot,gross arterial attenuation and multiple patches of RPE changes in the nasal retina .(Fig 7a). FFA was done which showed delayed arterial filling and macular ischemia(Fig 7b, c, d). Systemic evaluation showed aortic compression secondary to a sarcoma.
Fig 9(c) 68 year old known diabetic and hypertensive presented with blurring of vision in the left eye. Fundus examination showed a superior hemiretinal vein occlusion . The findings were confirmed on FFA. Systemically he had uncontrolled hypertension and high cholesterol levels. (Fig 9a, b, c)
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Fig 8(a)
Fig 8(b)
Fig 10(a)
Fig 10(b)
lipase deficiency with triglyceride levels >3000mg/ dl.This was later mutation proven with both mother and father testing positive for the recessive gene. With dietary modification, the baby had dramatic improvement with blood triglyceride levels coming back to normal and the fundus became normal again. (Fig 11a, b)
Fig 12(a) Fig 10(c) 35 year old hypertensive male presented with congestion of the right eye. Examination showed minimal proptosis, conjunctival and episcleral congestion and a raised intraocular pressure. Fundus examination showed central retinal vein occlusion. An MRA showed indirect carotico cavernous fistula. (Fig 10a, b, c)
Fig 12(b)
55 year old gentle man with hypercholesterolemia referred for fundus examination from internal medicine. Fundus examination showed minimal venous congestion with cholesterol deposits along the arteries. (Fig 12a, b)
Fig 13(b)
38 day old infant who was detected to have lipemia retinalis. On investigation the baby was found to have autosomal recessive congenital lipoprotein
55 year old patient on warfarin therapy for aortic valve thrombosis comes with sudden diminution of vision. On examination, there is central retinal artery occlusion with an embolus seen within the optic nerve vessel. (Fig 13a, b)
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What is New
B
The
treatment of non-infectious uveitis is a challenge to clinicians. The treatment involves suppressing the deleterious effects of inflammation caused by the patients own immune system. Corticosteroids are the mainstay of treatment for non-infectious uveitis. They have several advantages. They are rapidly effective, inexpensive, potent and work in almost all types of noninfectious uveitis. Their side effects prevent the use of corticosteroids in high doses for long-term control of inflammation. Conventional steroidsparing agents such as antimetabolites, alkylating agents and T-cell inhibitors have helped reduce the need for corticosteroids and improved quality of life. They have the risk of serious, life threatening adverse effects and may be of limited efficacy in some cases. Biologic therapy can be an alternative in patients who are refractory to treatment or who are intolerant of conventional immunotherapy.
Address for correspondence: Dr. Amala George, Dept. of Uveitis, Medical research Foundation, Sankara Nethralaya, Chennai
series have appeared in the literature regarding the control of the ocular inflammation in these patients. Most of the literature describing biologic treatment of uveitis is with the tumor necrosis factor inhibitors (infliximab, etanercept and adalimumab), followed by the IL-2 receptor (IL2-R) blocker daclizumab. Many of these studies were complicated by the fact that most patients with uveitis have been treated with more than 1 immunosuppressive agent, making it hard to determine the adverse effects of individual drugs. Some of the recent literature on biologics will be discussed in the following section.
serious adverse events, including 3 thromboses, 1 malignancy, 1 new onset of congestive heart failure, and 2 cases of drug-induced lupus. 75% of their patients, who received at least 3 injections of infliximab, also developed elevated antinuclear antibody titers. Of 23 patients who demonstrated initial success at 10 weeks, 15 completed 1 year in the study and 8 completed 2 years of therapy. Three patients developed a drug-related lupus-like illness. Two developed fatal solid malignancies. Some of the adverse events in this series, drug induced lupus, for example, are more frequent than reported in the rheumatologic literature. In an accompanying editorial Goldstein expresses the opinion that patients with isolated uveitis may be different from those with systemic disease5. It may be that patients with systemic inflammatory disease have TNF levels that are higher than in patients with localized inflammation such as uveitis. In rheumatoid arthritis, infliximab might therefore reduce TNF to a normal level, while in uveitis infliximab might result in an inappropriately low level of serum TNF. If this is true, uveitis associated with systemic diseases such as Behcet disease and sarcoidosis might be safer to treat with infliximab than idiopathic disease confined to the eye.
Infliximab
Infliximab is a chimeric monoclonal antibody that irreversibly and competitively inhibits both circulating and membrane-bound TNF-. Infliximab has been reported to be effective in the treatment of Behcets panuveitis, posterior uveitis, juvenile idiopathic arthritis (JIA) associated uveitis and retinal vasculitis1-3. Despite initial success with infliximab, some patients develop a decreasing response to the drug, possibly due to the development of antibodies to the murine portion of the chimeric molecule. Suhler and Smith et al recently reported their results with the use of infliximab in a recent prospective study with at least 2 years of follow-up4. It was effective in selected patients, with 60% of patients retained in the study per year. Their 1-year data, published in 2005 reported reasonable initial success, but an unexpectedly high incidence of adverse events2. Of their 23 patients, 7 developed
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Etanercept
Etanercept is a dimeric soluble form of the extra cellular ligand-binding protein linked p75 TNF receptor. It has the ability to bind to soluble TNF- and TNF- thereby blocking binding to cell surface TNF receptors. However, this interaction is unstable and dissociates rapidly which may then only neutralise TNF- transiently. Results have not been encouraging. There have been case reports of worsening of anterior uveitis and the development of scleritis in patients, even when the systemic inflammatory disease was under control6. One study reported that etanercept was not superior to placebo in preventing relapses of uveitis in previously controlled patients attempting
Biologic agents
to taper methotrexate7. Therefore while etanercept has shown efficacy in the treatment of systemic RA and JIA, is still controversial for ocular inflammatory disease
Adalimumab
Adalimumab is a fully human monoclonal antibody against TNF-. It is delivered by subcutaneous injections. A retrospective study for JIA uveitis revealed that adalimumab effectively controlled inflammation in approximately one-third of patients refractory to previous treatment with infliximab or etanercept8. A prospective study of adalimumab in 19 adults with various uveitis reported control of inflammation in 63 percent of patients and complete resolution of CME in 55 percent of eyes at one year of therapy9. One study showed that adalimumab could be an effective alternative for treatment of Behcets Disease -associated panuveitis in patients already well-controlled with infliximab 10.
four-weekly infusions increased uveitic recurrences were observed. After four years of intravenous infusions, some patients were could be switched to maintenance subcutaneous daclizumab therapy with good response. Ten of 15 patients in a subsequent study by Nussenblatt et al achieved at least a 50-percent reduction of concurrent immunosuppression with retained visual acuity, inflammatory control, and no significant side effects12. However, daclizumab failed to demonstrate effectiveness in Behcets Disease -associated uveitis in a randomized trial13.
INTERFERON THERAPY
Interferons (IFN) are cytokines produced in response to viral infections. These immunomodulatory substances disrupt viral replication, prevent tumour growth, act against tolerance inducers of autoimmune disease and have an antiproliferative and apoptotic effect on T-cells. Interferons are classified into type 1 (with alpha and beta subgroups) and type 2 interferons, based on their structure and biologic properties.
Interferon-
Interferons have been reported to be useful in the treatment of refractory ocular inflammation and associated macular edema, particularly in patients with Behcets Disease and multiple sclerosis14,15. However, relapse is frequently seen after discontinuation of therapy, and potentially serious complications may occur. Multiple cases of possible IFN-induced sarcoidosis with or without uveitis have been reported16.
Daclizumab
Daclizumab is a recombinant humanised immunoglobulin G monoclonal antibody that binds to the IL-2 receptors on activated T cells preventing their IL2- dependent activation. A study of intravenous daclizumab for the treatment of non-infectious uveitis demonstrated improvement of inflammation and visual acuity at one year in eight of 10 patients, which was maintained after four years of treatment11. When the infusions were reduced to six-weekly intervals from the initial
Other biologics
Other biologics under current study include efalizumab, rituximab, the IL-1 blocker anakinra17 and the T-cell costimulation inhibitor abatacept. Efalizumab blocks the pan-leukocyte surface marker CD11a and is under current study for non-infectious uveitis with macular edema. The B-cell antagonist
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rituximab18 is currently under study for treatment of scleritis and orbital inflammation. Vascular endothelial growth factor inhibitors, including bevacizumab and ranibizumab, widely
used to treat age-related macular degeneration and other retinal vascular diseases, have reported benefit in reducing uveitic CME in selected patients with otherwise well-controlled uveitis, at least transiently19,20.
ROUTE
DOSE
ADVERSE EFFECTS
ADALIMUMAB ETANERCEPT
SC SC
RITUXIMAB
IV
OTHERS INTERFERON
SC 3-6 IU/day, taper over 6 months. Flu like symptoms, bone marrow suppression, local injection site reactions Thrombotic events, Blood borne infection transmission
INTRAVENOUS IV IMMUNOGLOBULIN
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Biologic agents
Intravenous immunoglobulins are purified immunoglobulin G (IgG) products made from pooled human plasma. Intravenous immunoglobulin (IVIg) has been used successfully for treatment of refractory uveitis21. IVIg is not associated with systemic immunosuppression, reducing the risk of opportunistic infection. However, IVIg is extremely expensive and can cause severe side effects including thromboembolism, aseptic meningitis and bloodborne infections, and is usually reserved as a treatment of last resort.
and for three months after stopping medications. If there is significant exposure to the varicella virus discontinue the drug and administer varicella zoster immunoglobulin
Adalimumab: complete blood work up at start of therapy and whenever additional doses are given, routine monitoring 6 monthly. Most biologics are given with a second immunosuppressive agent so blood tests need to be ordered as per the protocol for the second agent. Use in Pregnancy and Lactation
In general, biologics should not be used in pregnant or lactating women unless the potential benefit justifies the risk to the fetus/ infant. This is not substantiated by longterm study. Thorough discussion with the patient of the risks and benefits, both ocular and obstetric, is required, and consultation with an obstetrician experienced in high-risk pregnancies is invaluable in these situations. In conclusion, biologics are potent new agents that may help in control of certain forms of uveitis that are refractory to more traditional immunosuppressive therapies. The types of uveitis most likely to benefit are those associated with systemic inflammatory conditions such as Behcets disease and JIA. Side effects are both serious and relatively common. Patients should be apprised of both the risks as well as the potential benefits of these agents. Their use in India may be limited due to the risk of reactivation of latent tuberculosis and because of the prohibitive cost and limited long-term safety data. Their use should be monitored by experienced uveitis specialists and rheumatologists.
Malignancy
Increased risk of solid tumours. Avoid TNF inhibitors in those with history of malignancy or treatment with history of previous use of alkylating agents.
Demyelinating disease
TNF inhibitors may cause or worsen demyelinating disease. Use with caution in patients with intermediate uveitis with neurological symptoms or family history of demyelinating disease. Avoid in persons with history of multiple sclerosis.
Vaccines
Avoid administering live vaccines concurrently
References:
1. Ohno S, Nakamura S, Hori S, et al. Efficacy, safety and pharmacokinetics of multiple
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administration of infliximab in Behets disease with refractory uveoretinitis. J Rheumatol 2004; 31:13628. 2. Suhler EB, Smith JR, Wertheim MS, et al. A prospective trial of infliximab therapy for refractory uveitis: preliminary safety and efficacy outcomes. Arch Ophthalmol 2005; 123:903-12. 3. Kahn P, Weiss M, Imundo LF, Levy DM. Favorable response to high-dose infliximab for refractory childhood uveitis. Ophthalmology 2006; 113:860-4 e2. 4. Suhler EB, Smith JR, Giles TR, et al. Infliximab therapy for refractory uveitis: 2-year results of a prospective trial. Arch Ophthalmol. 2009; 127(6):819-22. 5. Goldstein DA. Uncovering the risks of immunosuppressive therapy in patients with uveitis.Arch Ophthalmol. 2009;127(6):799-800. 6. Rosenbaum JT. Effect of etanercept on iritis in patients with ankylosing spondylitis. Arthritis Rheum 2004; 50:3736-7. 7. Foster CS, Tufail F, Waheed NK, et al. Efficacy of etanercept in preventing relapse of uveitis controlled by methotrexate. Arch Ophthalmol 2003; 121:437-40. 8. Tynjala P, Kotaniemi K, Lindahl P, et al. Adalimumab in juvenile idiopathic arthritisassociated chronic anterior uveitis. Rheumatology (Oxford) 2008; 47:339-44. 9. Diaz-Llopis M, Garcia-Delpech S, Salom D, et al. Adalimumab therapy for refractory uveitis: a pilot study. J Ocul Pharmacol Ther 2008; 24:351-61. 10. Mushtaq B, Saeed T, Situnayake RD, Murray PI. Adalimumab for sight-threatening uveitis in Behcets disease. Eye 2007;21:824-5 11. Nussenblatt RB, Thompson DJ, Li Z, et al. Humanized anti-interleukin-2 (IL-2) receptor alpha therapy: Long-term results in uveitis patients and preliminary safety and activity data for establishing parameters for subcutaneous administration. J Autoimmun 2003; 21:283-93.
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12. Nussenblatt RB, Peterson JS, Foster CS, et al. Initial evaluation of subcutaneous daclizumab treatments for noninfectious uveitis: a multicenter noncomparative in-terventional case series. Ophthalmology 2005;112:764-70 13. Buggage RR, Levy-Clarke G, Sen HN, et al. A double-masked, randomized study to investigate the safety and efficacy of daclizumab to treat the ocular complications related to Behets disease. Ocul Immunol Inflamm 2007;15:63-70 14. Gueudry J, Wechsler B, Terrada C, et al. Longterm efficacy and safety of low-dose interferon alpha2a therapy in severe uveitis associated with Behets disease. Am J Ophthalmol 2008; 146:837-44 15. Becker MD, Heiligenhaus A, Hudde T, et al. Interferon as a treatment for uveitis associated with multiple sclerosis. Br J Ophthalmol 2005;89:1254-7 16. Doycheva D, Deuter C, Stuebiger N, Zierhut M. Interferon-alpha-associated presumed ocular sarcoidosis. Graefes Arch Clin Exp Ophthalmol 2009;247(5):675-80 17. Teoh SC, Sharma S, Hogan A, et al. Tailoring biological treatment: Anakinra treatment of posterior uveitis associated with the CINCA syndrome. Br J Ophthalmol 2007; 91:263-4. 18. Tappeiner C, Heinz C, Specker C, Heiligenhaus A. Rituximab as a treatment option for refractory endogenous anterior uveitis. Ophthalmic Res 2007; 39:184-6. 19. Cordero Coma M, Sobrin L, Onal S, Christen W, Foster CS. Intravitreal bevacizumab for treatment of uveitic macular edema. Ophthalmology 2007; 114:1574-1579. 20. Mackensen F, Heinz C, Becker MD, Heiligenhaus A. Intravitreal bevacizumab (avastin) as a treatment for refractory macular edema in patients with uveitis: A pilot study. Retina 2008;28:41-5 21. Onal S, Foster CS, Ahmed AR. Efficacy of intravenous immunoglobulin treatment in refractory uveitis. Ocul Immunol Inflamm 2006;14:367-74.
Ophthalmic Instrumentation
biomicroscopy (UBM) (Figure 1) has been the gold standard for the objective and quantitative assessment of the anterior chamber especially the angle 1, 2 .The recent introduction of Anterior Segment Optical Coherence Tomography (AS OCT) (Figure 2) has offered another imaging option and thereby evoked a debate on the pros and cons of each system viz a viz the other.
Technological Basis
Introduced by Charles Pavlin and co workers 2-4, Ultrasound Biomicroscope (UBM) incorporates a high frequency ultrasound transducer used with a frequency of 35 50 MHz. The most frequently used device carries a polymeric, 50 Mhz transducer with a resolution of 50 microns. This high frequency is needed since the anterior segment has a depth of 4 5 mm and the structures are close to each other. The images obtained with the 50 Mhz probe are 5 mm wide but a 35 Mhz version covers the entire anterior segment. The lateral and axial physical resolution of the 50 MHz probe is 50 and 25 microns respectively and the depth of penetration is 4 5 mm. This technique can produce eight frames of
penetration is 6 mm. Like UBM, AS OCT generates eight frames of cross sectional images per second, but the limitations of its optical principles makes it suitable only for imaging through clear media.
The 1.3 micrometer light of AS OCT is unable to penetrate iris pigments adequately (except in albinos) and thereby cannot image structures and lesions behind the iris plane 6, namely the ciliary body and peripheral retina. This makes determination of presence of plateau iris configuration impossible. Plateau iris configuration is characterized by closure of the angle at the peripheral recess that is associated with relatively deep central anterior chamber. Plateau iris configuration is caused by anterior rotation of ciliary process and occasionally it may be caused by iridociliary cysts and / or iridociliary tumors neither of which can be visualized by AS OCT. Since the UBM can penetrate the iris, this imaging modality can show the etiology of plateau iris configuration (Figure 3) 7 8. Complications involving structures lying behind the iris such as choroidal detachment not clearly shown by the AS OCT are also best seen by the UBM.
Figure 3 UBM of an eye with a complete plateau iris configuration and showing a clear view of the ciliary body. Note the narrow image as captured by the UBM
While UBM is useful for assessing the blebs status in patients with previous filtration surgery 9 11, this approach is risky, can be stressful and not 100% safe. AS OCT due to its non contact method of analysis, is useful in assessment of anterior chamber angle and bleb status in eyes with history of trabeculectomy12. In eyes with positive Siedlels test due to unhealed incisions and / or conjunctival button holes, where the use of UBM is contraindicated, AS OCT due to its non contact mode of examination is safe and a superior choice. Similarly, AS OCT is safe in evaluating anterior chamber and angle details in eyes with compromised ocular or surface integrity like (1) Confirmed or suspected globe laceration or perforation (2) Recent intraocular surgery (3) Perforated corneal ulcer In these cases, AS OCTs non contact modality eliminates the risk of mechanical abrasion and further aggravation of the condition that may occur on assessment with UBM.
segment. The procedure requires some training to be performed and good co operation on the part of the patient, is at times messy and stressful to the patient, time consuming and causes discomfort to the patients due to placement of the eye cup. It is particularly difficult to perform in eyes with deep socket, in children and uncooperative adults. Due to the contact nature of the procedure it is not 100% safe to do the procedure in eyes with bleb post trabeculectomy and UBM is contra indicated in eyes with compromised structural or surface integrity. However, the UBM is very useful in evaluating plateau iris configuration and performing a host of dynamic procedures like (1) Indentation UBM gonioscopy (2) Changes in anterior segment morphology and angle configuration following Valsalva maneuver like thickening of the ciliary body, increase in iris thickness and narrowing of AC angle recess. The UBM like AS OCT is useful for objective analysis of the AC angle. However, due to its cost, size, time required and requirements of patient position and discomfort, UBM is not very useful as a screening tool in angle closure glaucoma. Unlike the AS OCT, the UBM can capture images through opaque media. In the UBM penetration of light through inherently scattering ocular structures such as the sclera and iris, enables imaging up to anterior layers of lens, zonules and anterior vitreous.
uncooperative adults. Since the procedure can be performed in a sitting position, we can study angle dynamics in physiological position. Due to the non contact nature of the procedure it is 100% safe to do the procedure in eyes with bleb post trabeculectomy and can be used with ease in eyes with compromised structural or surface integrity. The non contact mode of evaluation provides a pertinent advantage in the planning wound modulation following surgery. The AS OCT due its non contact mode of examination is helpful in evaluating in the following (1) Central corneal thickness of the eye (Figure 4) (2) Evaluation of tear film in individuals with dry eyes and epiphora (Figures 5 and 6) (3) Evaluating the positioning of the implantable contact lens in the eye (Figure 7)
Figure 7 The distance of the ICL from the crystalline lens as shown by the AS OCT
The UBM is not helpful in evaluating any of these three parameters in the eye.
A potential significant advantage of this technology is that it may be used in complete darkness. Any changes in ocular configuration that are induced by ambient lighting are thus eliminated. Therefore, the AS OCT is useful for dynamic evaluation of angle structures and their study in physiological conditions like - - Light and dark Accommodation
Since the AS OCT is unable to penetrate iris pigments adequately, it cannot image structures Figure 4 CCT shown by AS OCT in an eye with Keratoconus posterior to the iris3, namely the ciliary body and peripheral retina (Figure 8). There are also reports of difficulties in recognizing the scleral spur in a significant percentage of patients.13 While performing AS OCT, the upper and lower lids come in field of view thereby obstructing imaging of the superior and inferior angle. The examiner has to manually lift up the eyelids to get a proper Figures 5 & 6 Tear film as shown by AS OCT in patient with dry eye and epiphora
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imaging. Ideally both should be used in glaucoma evaluation, though in reality clinicians do not always have the luxury to have both imaging modalities. The two modalities differ in their ease of use with the UBM, unlike that of AS OCT necessitating longer training and reasonably good understanding of the anatomy of the anterior segment on the part of the examiner. However, the quality of images captured by the UBM, especially of the peripheral angle recess is slightly better than that of the AS OCT. UBM provides a detailed view of the structures Figure 8 Anterior Segment OCT image with defective outlining of the ciliary body. Note the wide image as imaged by the AS OCT behind the iris that cannot be viewed with the AS OCT. On the other hand, the non contact nature of the AS OCT provides a very patient friendly modality and makes easy imaging even of vulnerable eyes. Ultimately both modalities are useful for qualitative and quantitative assessment of the anterior chamber and angle of the eye and therefore it is for the individual physicians to choose the platform that suits their preferences and needs.
Conclusion
Though their indications do not overlap, UBM and AS OCT have their specific advantages and uniqueness in their role in anterior segment
UBM
High frequency ultrasound Supine Contact mode Yes Narrow Excellent Excellent More Less comfortable
AS OCT
Coherent light Upright and seated Non contact No Wide Poor Poor Fast More comfortable
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References:
1. Pavlin CJ, Harasiewicz K, Foster FS. Ultrasound biomicroscopy of anterior segment structures in normal and glaucomatous eyes. Am J Ophthalmol. 1992; 113:381 389. 2. Pavlin CJ, Harasiewicz K, Sherar MD, et al. Clinical use of ultrasound biomicroscopy. Ophthalmology. 1991; 98:287 295. 3. Pavlin CJ, Sherar MD, Foster FS: Subsurface ultrasound microscopic imaging of the intact eye. Ophthalmology. 1990; 97: 244 50 4. Pavlin CJ, Foster FS: Examination techniques. Pavlin CJ and Foster FS (eds) Ultrasound biomicroscopy of the eye. New York. Spring Verlag. 1995; 30 46 5. Huang D, Swanson EA, Lin CP, et al. Optical coherence tomography. Science 1991; 254:1178 1181. 6. Radhakrishnan S, Goldsmith J, Huang D, et al. Comparison of optical coherence tomography and ultrasound biomicroscopy for detection of narrow anterior chamber angles. Arch Ophthalmol. 2005; 123:1053 1059. 7. Ishikawa H, Schuman JS. Anterior segment imaging: ultrasound biomicroscopy. Ophthalmology Clin North Am. 2004; 17:7 20. 8. Ishikawa H, Liebmann JM, Ritch R. Quantitative assessment of the anterior segment using ultrasound biomicroscopy. Curr Opin Ophthalmology 2000; 11:133 139. 9. Yamamoto T, Sakuma T, Kitazawa Y. An ultrasound biomicroscopic study of filtering blebs after mitomycin C trabeculectomy. Ophthalmology. 1995; 102:1770 1776. 10. Rothman RF, Sidoti PA, Gentile RC, et al. Glaucoma drainage kink after pars plana insertion. Am J Ophthalmol 2001; 132:413 414. 11. Dansingani KK, Al-Khaier A, Russell-Eggitt IM, Nischal KK. Management of intracorneal bleb after trabeculectomy for congenital glaucoma. Cornea. 2005; 24:486 488. 12. Singh M, Chew PTK, Friedman DS, et al. imaging of trabeculectomy blebs using anterior segment optical coherence tomography. Ophthalmology. 2007; 114: 47 53. 13. Sakata LM, Aung HT, Aung T et al. Assessment of Scleral Spur in Anterior Segment Optical Coherence Tomography Images. Arch Ophthalmol 2008; 126: 181 5
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Brief Report
A
Choroideremia
is
a generalized choroidal dystrophy with X-linked inheritance and involvement of the mid peripheral receptors, mainly rods, similar to Retinitis Pigmentosa. These patients present with complaints of progressive night blindness and loss of peripheral vision. Being an X-linked disease, the carrier state is seen in females, and has a fundus appearance ranging between normal to very rarely a very advanced form of disease as seen in a male Choroideremia patient. We, report an eighteen year old girl who had presented to our General Ophthalmology clinic with asthenopic symptoms and referred to the retina department for opinion regarding abnormal looking fundus. Her vision unaided was 20/20 with normal near vision in both eyes. Fundus examination showed diffuse pigmentary mottling (Fig 1&2) with normal discs and vessels. The differential diagnoses under consideration were congenital syphilis, congenital rubella or a variant of Retinitis Pigmentosa. But the vessels and discs were normal and there was no history of night blindness. Also there were no other clinical signs to support
the diagnosis of congenital rubella or congenital syphilis. On further enquiry, she gave the history of her father having decreased vision since few years and was hence asked to report the next day with her father. On examination of the father, fundus showed diffuse chorio-retinal atrophy with an island of intact chorio-retinal tissue (Fig3&4) in the foveal area. He was suffering from night blindness and also gave similar history in his maternal uncle. The diagnosis in father was chorioderemia and the daughter was diagnosed to have the carrier state of the disease. Choroideremia is easy to diagnose in the full - blown stage in a male patient, when the clinical picture is characterized by history of night blindness and the retinal examination findings of generalized chorioretinal atrophy sparing the macular area with normal discs and vessels. But it can cause diagnostic difficulty in a carrier, if the relatives are not available for examination and in the absence of the history of similar eye disease in the male members of the family.
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A carrier of chorioderemia is often asymptomatic and can have fundus with normal appearance or with diffuse pigmentary mottling.[1] The vessels are of normal caliber and discs do not show any pallor. Electrophysiological studies are normal in asymptomatic carriers and is not useful in diagnosing the carrier state.[2] Focal area of choroidal atrophy may appear later in life and can progress. Rarely, this can lead to generalized chorioretinal atrophy causing visual dysfunction and fundus appearance similar to the male counterpart were the affected female could be the offspring of an affected father and a carrier mother.[3,4] In conclusion, Choroideremia carrier state is a diagnosis which is to be made with the help of examination of family members and proper elicitation of family history. Figure 3
Figure 4
References:
1. Goodman G, Ripps H, and Siegel IM . Sex-linked Figure 1 ocular disorders: trait expressivity in males and carrier females. Arch Ophthalmol. 1965; 73: 387398. 2. Sieving PA, Niffenegger JH, and Berson EL. Electroretinographic findings in selected pedigrees with chorioderemia. Am J Ophthalmol. 1986; 101:361-367. 3. Fraser GR, Friedman AI. Choroideremia in a female. Br Med J 1968; 2: 732-734. 4. Harris GS, Miller JR .Visual defects in a heterozygote. Figure 2
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Brief Report
ino Orbital Aspergillosis presenting as Choroidal Granuloma and Scleral Abscess a case report
Bindu N, MS, Nisha Namia
same the HPR of which was inflammatory lesion and fungal culture was positive for aspergillus. She was put on fluconazole, became asymptomatic and was on irregular follow up. She also report 2-3 similar episodes with pain and redness left eye with 6-8 months interval between each episode for which she consulted local doctor and had symptomatic relief. Her best corrected visual acuity in left eye was recorded to be 1mcf since 1 year. On examination her BCVA was 6/12 in right eye and light perception with inaccurate projection of rays in left eye. On left eye examination there was ptosis, dystopia with the eyeball pushed downward and medially by a firm to hard mass (1.5 x 1cm) in the lacrimal gland area (Fig.1 & 2). There was total ophthalmoplegia. Slit lamp examination showed exposure keratitis with signs of anterior uveitis. There was a scleral abscess which was discharging through the overlying conjunctiva about 1 x 1cm size in the supertemporal quadrant adjacent to the enlarged lacrimal gland. Fundus examination of left eye showed severe vitritis. There were multiple choroidal granulomas in the posterior
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Introduction
Aspergillus is a saprophytic ubiquitous fungi which exist in air, soil or skin and as common food molds. Patients may be exposed to infection by inhaling spores or ingesting contaminated food. Sino orbital aspergillosis is a rare but potentially blinding condition with high mortality rates. Aspergillosis presenting as choroidal granuloma or sclera abscess is rather rare.
Case Report
A 65 year old lady presented with history of pain, redness, defective vision and inability to open her left eye of 3 weeks duration. She also gave history of a swelling in the medial aspect of her left eye 3 years back. The CT scan taken at that time showed a small irregularly enhancing mass left ethmoid sinus with destruction of lateral wall and extension into left orbit. Her old medical records revealed she had undergone a left fronto ethmoidectomy for the
pole. Two were in the superotemporal quadrant corresponding to the site of scleral abscess about 2DD and 1DD size surrounded by shallow retinal detachment. Another granuloma about 1DD size was present in the superonasal quadrants (Fig.3). Haematological workup was normal except for a raised ESR (106). Clinical examination and investigations showed no evidence of immunosuppression and diabetes mellitus. CT scan showed 3x2.5x1.5cm lesion in the left orbit in the lateral, superior and posterior aspect of the eyeball involving extraconal and intraconal compartments and involving superior rectus, lateral rectus and levator palpebrae superioris muscles. Lesion was closely abutting the eyeball and optic nerve (Fig.4 & 5). Nonenhancing soft tissue density area with calcific foci was noted in the right sphenoid sinus extending to the spheno ethmoidal recess. Pus from the scleral abscess sent for microbiological evaluation came negative. Considering the clinical picture and previous history of aspergillosis she was put on intravenous Amphotericin B (1mg/kg body weight /day) and Natamycin eye drops since the day of admission. Lateral orbitotomy and debulking of the lesion was done after neurosurgery consultation (Fig.6). HPR came as inflammatory lesion suggestive of chronic dacryoadenitis (Fig.7). Culture revealed Aspergillus flavus species (Fig.8). Intravenous Amphotericin B was continued for 21 days. The patient responded well to treatment as evidenced by the disappearance of scleral abscess and decrease in the size of the choroidal granulomas. However, visual acuity and extraocular movements did not show much improvements. Patient was discharged after 21 days at her request and is under follow up in local hospital.
allergic
apsergillosis
or
aspergillomas
where
in destruction of the sinus mucosa and bone expansion may occur but with no invasion of tissue or bone. Invasive infections can either be localized or fulminant. Localized disease often starts in sinus and spreads to orbit through focal bony erosion or blood vessels. Fulminant form is characterized by multiple organ involvement1. Compared to mucormycosis which occurs only in immunocompromised, aspergillosis eventhough rarely affects healthy individuals as well. endogenous endophthalmitis, orbital Other apex ocular manifestations of aspergillosis included syndrome, infiltrative or ischemic optic neuropathy1. Eventhough very rare aspergillus iris granulomas has also been reported in literature2. Scleral involvement by aspergillus is very rare but has been reported following trauma or surgeries like pterygium excision, glaucoma surgery, cataract extraction and retinal detachment surgeries and is characterized by redness, ulceration, nodule or abscess formation. Abscess formation indicates intrascleral dissemination of the infectious process3. In this case scleral involvement could be attributed to the direct invasion by the organism from the adjacent structures. Choroidal and retinal involvement in aspergillosis usually occurs through haematogenous spread. It appears as multifocal yellow white lesions of the choroid with retinal necrosis and vitritis. With more severe infection, subretinal abscess and endophthalmitis may result4. In our patient with no evidence of any systemic involvement, choroidal granulomas especially in superotemporal quadrants without much retinal involvement could be due to the contiguous spread from the adjacent sclera. Correct diagnosis depends on a high degree of clinical suspicion and confirmation is by biopsy
Discussion
Sino orbital aspergillosis can either be invasive or non invasive. Non-invasive infections are either
196
Brief Report
demonstrating
dichotomously
branching
septate hyphae and positive cultures. There is no uniformly accepted completely effective treatment. Amphotericin B (0.5-1.5mg/kg body weight) still remains the gold standard1. Treatment of sino orbital asperigillosis include surgical debridement and Amphotericin B local irrigation followed by systemic antifungal usually intravenous amphotericin B alone or in combination with Flucytosine or Rifampicin4. The newer azole, voriconazole (6mg/ kg Q12H followed by 4mg/kg Q12H) is increasingly being used now a days5. Other drugs used in aspergillosis include Itraconazole and Capsofungin. Treatment should continue well past any remaining signs of disease and indefinite use considered in patients with ongoing immunosuppression1. Figure 2 Photograph of patient showing dystopia with extraocular movement restriction
Summary
In conclusion sino nasal aspergillosis occurring in immunocompetent and that too presenting as sclera abscess and choroidal granuloma is extremely rare. We are presenting this case for its extreme rarity. Eventhough our patient has responded to treatment, as orbital aspergillosis is well known for recurrences, she needs long term follow up may be life long. Figure 3 Fundus photograph showing choroidal granulomas
Figure 4 CT scan showing mass with destruction of lateral wall of (L) orbit
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Figure 5 CT scan showing lesion closely abutting (L) eye ball and optic nerve
References
1. Sivak JA, Callcott, Livesky N, Nugent RA et al. 687. 2. Varada Jain, Debraj Shome, Tina Dadu et al. Aspergillus iris granuloma: A case report with review of literature. Surv Ophthalmol 2009; 54(2); 286-291. 3. Ching-Hsiao, James JY Chen, Samuel CM, Huang et al. Intrascleral dissemination of infectious scleritis
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Br J Ophthalmol
4. Albert and Jakobiec. Principles and Practice of Ophthalmology. Saunders. Ed.2. Pg 1241, 48914894. 5. Muijsers RB, Goa KL, Scott LJ. Voriconazole: in the treatment of invasive aspergillosis. gov. Drugs 2002; 62(18): 2655-64.
Brief Communication
n-Service Training Of Eye Surgeons Under National Programme For Control Of Blindness [NPCB]
India has vast infrastructure for health care delivery managed by a complete gamut of functionaries ranging from grass root level workers at community level and at sub centre, primary care physicians at Primary/Secondary Health Centres and ophthalmologists with varying levels of specialization at District hospitals, Medical colleges and institutes of national importance. Educational objectives emerge from a clear identification of the tasks to be performed by each category of workers. Their classification into cognitive, psychomotor and attitudinal objectives ensures a balanced and wellrounded educational programme. The exponential rate of technological progress in recent past, as a consequence, caused an immeasurable increase in complexity of diagnostic and therapeutic intervention of health care personnel. However, the continuing influx of these newer technologies for curative, preventive,
promotive and rehabilitative purposes has resulted in constantly changing the definition of what constitutes competence. In general, competence implies the development and possession of sufficient cognitive [knowledge], psychomotor and affective [attitudes] skill and experience for a successful performance of ones professional life role to a prescribed standard. The level of cognitive domain from lowest to highest level includes factual knowledge, understanding, application, analysis, synthesis and judgement. The different abilities associated with each level of cognitive domain are depicted in Table 1.1 This brief provides an overview of in-service training of eye surgeons working in public sector in the country under National Programme for Control of Blindness [NPCB].
Address for correspondence: Dr. Sandeep Sachdeva, Directorate General of Health Services, Govt. of India, New Delhi
tertiary and secondary care institutions would play a major role in National Programme for Control of Blindness [NPCB] activities. They can play an effective role if they themselves have been exposed to the felt needs of the community and are keeping pace with changing technology. The in-service training programme for eye surgeon working in public sector [sub/ district hospital, medical college, Regional institute of Ophthalmology] lays emphasis on all the domains of theoretical, investigative procedures as well as hands on training in various sub or super specialty of ophthalmology. The inservice training programme under NPCB has been broadly divided into four category based on area and/or duration of training [Table 2].
book maintained. After successful completion of training, eye surgeon are required to submit to their respective office along with a copy to GOI; factual knowledge and skills gained, how they propose to utilize the knowledge gained; critical incident of the training along with any suggestions/deficiency noticed. Training institute also submit a report of each trainee on completion to NPCB, GOI.
Financial assistance
In the approved Eleventh plan, financial assistance is provided to all the training institutes by Government of India [GOI] upto a maximum of Rs. 55,000/- [fifty five thousand], 65,000/- [sixty five thousand], 70,000/- [seventy thousand] and Rs. 11,500/- [eleven thousand and five hundred] respectively per trainee towards travel/DA/ accommodation for participant and administrative charges/expert time/consumables for training institutes as per above training programme.2 An initial lump-sum is provided to these institutes to proceed with the training based on the instructions from GOI and recouped on submission of utilization/ audited statement. However, no funds are released to training institute, if they do not comply with technical and/or administrative guidelines of GOI.
Organization of training
Currently, 30 reputed institutes in public & NGO sector have been identified for imparting training under the programme in consultation with State authorities considering adequate case load, technical faculty, teaching & training infrastructure [including library, ophthalmology journals, & internet] and hostel accommodation. In a system of teaching and training that is based on the principle of adult learning, the onus of learning lies on the shoulder of trainee. However, each trainee is attached to one faculty [supervisor] in the training institute who further guides and coordinate related activities for the period of training. State authorities send nomination of participants to Government of India [GOI] for further recommendation to the training institute depending upon area of training and distance from work place. It is expected that services of such trained eye surgeon are utilized properly in health facilities which is equipped to provide level appropriate eye care services and minimum of three years are remaining for superannuation from government service. An eye-surgeon is re-entitled for training after three years of service. The training centres ensure that atleast 25 surgeries are performed by trainee & log
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Brief Communication
References:
1. PK Khosla, SP Garg, D Talwar, editors. In: Assessment Strategies in Ophthalmology: A panoramic view. 1st ed. New Delhi: RP Centre, AIIMS; 1993. 2. Guidelines for Training of eye surgeon under National Programme for Control of Blindness [NPCB] during Eleventh plan period. No. L. 11013/16/2007-Ophth/BC, Directorate General of Health Services, MOHFW, Nirman Bhawan, New Delhi; 3rd Dec 2008.
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Ophthalmic History
D
1. 2. 3.
Scottish ophthalmologist, Born -1837, Edinburgh; Died -3rd January, 1909, Gonday near Bombay, India.
Douglas Moray Cooper Lamb Argyll Robertson was one of the first surgeons to specialize entirely in the field of ophthalmology. He was born in 1837 in Edinburg. His father, John Argyll Robertson, was a general surgeon, with a special interest in surgery of the eye. Douglas Moray Cooper Lamb Argyll Robertson received his early education in Edinburgh, and then studied medicine at St. Andrews, from where he graduated in 1857, the year of his fathers death. He returned to Edinburgh to work as a house surgeon at the Royal Infirmary before departing for Berlin to study under the leading ophthalmologist of the day, Albrecht von Graefe (1828-1870). In this he was following on the work of his father who had been a lecturer in surgery at Edinburgh and had confined himself chiefly to ophthalmic surgery.
will soon rank as one of the most valuable in the ophthalmic pharmacopoeia. The same year, his former teacher von Graefe utilized its miotic effect to facilitate iridectomy. In 1867 he was appointed assistant ophthalmic surgeon to the Royal Infirmary of Edinburgh, and the following year described the phenomenon that bears his name. Argyll Robertsons syndrome = A frequent symptom of neurosyphilis, especially tabes dorsalis, and other diseases of the central nervous system, in which the pupil is small and responds slowly or not at all to light, but reaction to accommodation and convergence is retained. In 1870 he became full ophthalmic surgeon to the Royal Infirmary. Argyll Robertson in 1883 began teaching ophthalmology at the University of Edinburgh. In 1886 he became chairman of the Royal College of Surgeons in Edinburgh, honorary eye physician to Queen Victoria and King Edward VII. From 1893 to 1895 he was chairman of the ophthalmologic society of England In 1894 a patient who had lived in Old Calabar for the previous eight years consulted him. She complained of a tickling, irritating sensation under the skin of the eyelids, which she had noticed, was worse in warm surroundings. He observed a worm moving in a tortuous wriggling manner under the conjunctiva, the surface of which became slightly elevated as it moved along. He anaesthetized the conjunctiva, incised it and removed the worm intact. It was found to be a filarial larvae, which he presumed had got there through bathing in contaminated water. We know now that the vectors
are flies and that the adult worms migrate through the subcutaneous tissue causing fugitive Calabar swellings and sometimes beneath the conjunctiva hence the popular name eye worm. He remained in this office until 1897, when he retired from active hospital service and became a consultative ophthalmologist. In 1904, for health reasons, he moved to the Island of Jersey, and in 1908 made a journey to India. He caught fever in Gondal near Bombay, and died there. Argyll Robertson was a man of broad medical interests, always emphasizing the role of ophthalmology in a wider medical context. He published observations on the albuminuric retinopathy and lectured on the topic of The therapeutical contributions of ophthalmology to general medicine at his inauguration as president of the Ophthalmological Society Besides his professional standing Argyll Robertson seems to have impressed his contemporaries by his social appearance and party talents. This side of his personality was thus summarized in a biographical note: His handsome features and his tall, athletic frame made him the cynosure of all female eyes in his youth and in his later years, clad in a grey frockcoat and top hat, his dignified manner combined with his genial old-world courtesy made him conspicuous in any assembly and a magnificent ambassador of Scotland, firmly establishing that country in the social world of ophthalmology. He attributed his good health to golf and considered it the finest recreation in the world. Even though it was recreation, however, he brought to it the same skill he had as a surgical operator, winning the gold medal of the Royal and Ancient Club of St. Andrews five times.
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Spot Diagnosis
Answer to the last issue spot diagnosis was - Choroidal Folds The winners of the last spot diagnosis: Dr. Mihir Shah, Dr. Anitha Balachandran, Dr. Souda Kareem, Dr. Shanthi Sunil, Ms. Priya Ravi Collect your prize at the KJO stall in KSOS Drishti. 2010 at Kochi
205
Journal Review
Natural History of
group and each of 3 categories (HTG,NTG,PEXG). Progression of visual field damage was analyzed in 3 different ways Rate of progression (MD slope overtime), Progression versus Non-progression and time to progression. Median rates of progression were 0.40 dB/year overall (0.46 in HTG, 0.22 in NTG, -1.13 in PEXG.) Mean rates were considerably higher than medians (1.08dB/year overall, -1.31 in HTG, -0.36 in NTG and -3.13 in PEXG). There were large variations among patients with some showing low rates of progression but a considerable minority progressed rapidly. By 6 years overall 68% showed progression. In sub-group analysis 74% in HTG, 56% in NTG and 93% in PEXG group progressed, Median time to progression was 42.8 months. Time to progression differed significantly among diagnostic groups and was shortest in PEXG (19.5 months) and longer in HTG (44.8 months) and NTG (61.1.months). NTG had slowest rate of progression among all. Important conclusions of study are pseudoexfoliation is a strong risk factor for disease progression independent of IOP. Older age increases risk for development of glaucoma in patients with elevated IOP. Strengths of study are prospective study format, perimetric experience for patients before study baseline, frequent visual field testing and long follow up. Also there was no confounding effect from treatment of fellow eye because patients and not eyes were randomized to untreated control group. Large inter patient variability in rate of progression suggests individual progression rates cannot be predicted but must be determined with repeated visual field testing. Both median and mean rates are important to report as median rates
landmark randomized clinical trial to evaluate the effectiveness of lowering IOP in newly diagnosed and untreated glaucoma with early to moderate damage. It had an untreated control group and is the only such trial including patients with most common clinical presentations of open angle glaucoma:1. POAG (HTG + NTG) 2. PEXG Randomization of patients to untreated control arm provides a unique database to study natural history of glaucoma, knowledge of which would have definite clinical importance. It allows estimates of the amount of damage created by delayed access to clinical care and to decide on test intervals for glaucoma screening or follow up intervals for glaucoma suspects. The current article report includes those 118 patients (94%) who were followed for 6 years without treatment or progressed within 6 years among 126 patients randomized to untreated control group. Data analysis included until patient progressed. In patients with both eligible eyes, first eye to show progression was included in the analysis. If no eye progressed the eye with largest field defect at baseline (i.e, worse MD) was included. Visual field testing was performed with Humphrey Full Threshold algorithm using 30-2 test pattern. Fields were obtained every 3 months. Data analysis was performed for all patient
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Journal Review
are suitable to demonstrate difference between groups whereas means give an estimate of total loss of visual function overtime in patient cohort All patients in FMGT were of Caucasian origin, therefore results may not be applicable to patients with nonEuropean ethnicity. The results of current study provide a new and much needed benchmark to assess the success or lack of success of different treatment modalities for glaucoma.
started simultaneously without a period of refractive adaptation. Follow up visits were scheduled at 0.5, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9 and 12 months. VA testing and Orthoptic examination was done on all visits. Visits at 4.5 and 12 months included detailed ophthalmologic examination. End point of treatment with patching was equal BCVA bilaterally. Treatment continued thereafter with spectacles alone. Amblyopia resolution was defined as a difference of 1 line in BCVA between eyes. If BCVA deteriorated after cessation of patching by 2 lines, occlusion therapy was restarted. 2 children randomized to daily occlusion therapy dropped out leaving 38 children for evaluation. Median BCVA improved from 0.7 to 0.1 log MAR in daily occlusion group and from 0.9 to 0.1 log MAR in alternate day occlusion group. No statistically significant difference was found between two groups in magnitude of change in BCVA at follow up visits. One child in daily occlusion group and 2 children in alternate day patching group had recurrent amblyopia on discontinuation of therapy. Compliance was found to be 72% in daily patching group and 80% children in alternate day group (P value not significant). Amblyopia did not resolve in 3 children in daily patching group and 2 children in alternate day occlusion group inspite of good compliance. There was no change in median SE refracting error in amblyopic eyes with anisometropia in both groups. However, fellow eyes had a significant increase in median SE refractive error in both groups resulting in decrease of anisometropia. 13(72%) children in daily patching group and 15 (75%) children in alternate patching group had resolution of amblyopia, Median time to resolution of amblyopia was 3.6 months for children with daily occlusion and 3.8 months for children with alternate day patching. Good outcome in this study might be because of young age at entry (median age 4.3 years in both
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Randomized Evaluation of
Agervi P, Kugelberg U et al
groups) Median improvement in VA of 4.0 lines (median change 0.4 log unit) occurred in both groups from 0.5 to 4.5 months. Median improvement from 0.5 month to 1 year was 4 lines in daily patching group and 5.0 lines in alternate day patching group with no difference between groups. In conclusion current study showed no difference in median change in VA between spectacle plus alternate day patching of 8 hours from spectacle plus daily patching of 8 hours 6 days a week. However, because spectacles and patching were prescribed simultaneously without a period of refractive adaptation, improvement in VA in part may be secondary to wearing spectacles rather than patching therapy. So a better way of assessing efficacy of patching treatment may be after a period of refractive adaptation. Nevertheless, alternate day patching may be a way to adjust occlusion treatment especially in families in which daily occlusion may be problematic.
MAR chart, slit lamp examination and ultra sound pachymetry. Treatment was done under Topical anaesthesia and included 9 mm corneal deepithelization and instillation of riboflavin 0.1% with 20% dextran for 30 minutes. Subsequently UVA irradiation was applied to cornea for 30 minutes. A therapeutic contact lens was placed after surgery and kept for 7 days. Main variables analyzed were corneal transparency, central corneal thickness (CCT) and ocular pain intensity. Corneal transparency in all eyes was significantly better 1 month after treatment than preoperatively (P<.001). At 6 months, corneal transparency was better in 5 eyes, same in 7 eyes and worse in 2 eyes. VA was better in 8 eyes at 1 month an in 3 eyes at 6 months. Improvement in VA was significant at 1 month (P=.011) but not at 6 months (p=.133). A significant reduction in corneal thickness in all eyes by a mean of 124 m was observed at 1 month (P<.001) but by end of 6 months mean CCT was only 37 m less than preoperatively. All eyes had recurrence of microbullae and 11 had macrobullae. Pain scores at 1 month were significantly better (P=.007) but at end of 6 months, 13 out of 14 patients required a therapeutic contact lens to control pain. In an attempt to overcome limitations imposed by increased corneal thickness, many modifications in surgical technique have been proposed. Krueger etal propose intrastromal delivery of riboflavin with 2 pockets created by a femtosecond laser. Cornea can be dehydrated with 40% glucose before treatment. In present study 20% dextran was used for dehydration. Author concluded that an immediate improvement in corneal oedema ocular pain and corneal transparency was observed in all patients. However, beneficial effect seemed to fade with time. Further studies with technical improvements and modifications may be an important step towards finding the correct way to use the compaction principle of riboflavin/UVA CXL to postpone the need for corneal transplantation in patients with PBK.
Riboflavin and Ultraviolet-A in eyes with Psuedophakic Bullous Keratopathy. J Cataract Refract Surg.2010;36:273-276
Ramon C, Ghanem et al.
ullous keratopathy is a serious complication of intraocular procedures and a leading indication for keratoplasty worldwide. Recent studies suggest corneal collagen cross linking (CXL) with riboflavin 0.1% and ultraviolet A(UVA) can strengthen interfibre attachments resulting in stromal compaction and improvement in optical function. The aim of this study was to evaluate the safety and efficacy of UVA CXL in patients with painful pseudophakic bullous keratopathy (PBK). 14 consecutive patients (14 eyes) with PBK were prospectively enrolled for the study. The mean age of 8 women and 6 men was 71.14 years 11.70 (SD). They underwent VA assessment using log
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Book Review
Authors: Dr. Usha Kim,Dr Mahesh Kumar, Dr.K.G.Srinivasan Published by Aravind Eye Hospitals and Post graduate Institute of Ophtalmology, Madurai. 2009 This atlas which consists of 246 pages covers a wide spectrum of disorders of orbit and neuro ophthalmology. This book highlights the various radiological imaging methods used in investigating such diseases. It is divided into three major sections. Ocular disorders, orbital disorders and neuro ophthalmological disorders. The matter is presented in a very lucid manner in simple language. Each disease has been described to highlight the salient clinical, pathological and radiological features with accompanying photographs and references to access greater details. The pictures do enable one to understand the nature and location of the pathology. Overall this atlas will definitely be useful to postgraduate students as well as practicing ophthalmologists as a quick reference for orbital and neuro ophthalmological disorders.
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PG Corner
Area to be treated:
To micro aneurysms in CSME To the area of thickness in diffuse DME for grid Area of oedema in BRVO To the area of leak in CSCR To CNVM complex based on FFA with at least one burn all around including the area of hemorrhage and fluid.
Macula Laser
Points to remember:
Spot size: 50 100 microns. Power: Start from a lower power around 100
mw (this may vary depending on the machine).
Avoid perifoveal capillary network in cases of ischaemic maculopathy. Foveal avascular zone (500 microns) size should be kept in mind. Do not give heavy burns over dense hemorrhages.
Photodynamic Therapy
Diode range laser with a wavelength of 689 microns Dye used: Visudyne (Verteporfin). Lens: Goldman 3 mirror or any macula lens (magnification factor should be kept in mind). Greatest linear diameter and laser spot size has to be calculated from the mid phase of angiography. Laser spot size is 1000 microns more than the greatest linear diameter.
Light Dose: 50J per cm2 for full radiance and 25J
per cm2 for reduced fluence. Duration: 83 seconds. Power density: 600mW/cm2 for full fluence and 300mw/cm2 for reduced fluence Magnification factor of lenses: Volk area centralis 0.94, Ocular Mainster HM 0.80. Goldman 3 mirror 1.08, Volk equatorial 2.47, Volk supraquad 1.97, Ocular PRP 165- 1.90, Ocular Mainster UF 1.89.Volk transequator 1.44
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Nd YAG Hyaloidotomy
Laser used: Nd: YAG Contact Lens: Goldman 3 mirror Power: Start from lower power of 1-2 J. End Point: Rupture of hyaloid.
Spot size: 300-500 microns in slit lamp delivery Power: Starting from the lowest possible
reaction titrate. In extremely peripheral lesions LIO is preferable to get reaction to the anterior edge of break or lattice.
Wavelength used: 532 (Green) or 810 (Diode) No of shots per sitting: not to exceed 500
usually.
ROP Laser
Diode laser preferable since the wavelength is not absorbed by haemoglobin in Tunica Vasculosa Lentis which can result in cataract. Laser indirect ophthalmoscopic delivery
Instruction to Authors
he Kerala Journal of Ophthalmology (KJO) is a quarterly; peer reviewed one, devoted to dissemination of the latest in ophthalmology to the General Ophthalmologists as well as to specialists in the various subspecialties of this discipline. It invites submission of original work dealing with clinical and laboratory materials. Authors submitting materials to this journal are requested to adhere STRICTLY to the norms laid down below. The matter must be typed on one side of the paper. A margin of 1 must be left all around and the material must be double spaced. A page should contain not more than 25 lines. Two copies of the text in paper and one copy in a CD must be submitted to the Editor and the corresponding author is advised to keep another copy with him. The corresponding author must give it in writing in his covering letter that the same matter will not be submitted elsewhere if accepted. He must also enclose the copyright transfer of his work to this journal. The papers sent will be subjected to peer review. The accepted manuscripts become the permanent property of this journal. The author is informed that, if his work is returned to him for correction / clarification after peer review, he should effect the same and send the manuscript back to the Editor within one month. Each manuscript component mentioned here under must begin with a new page and the pages are to be numbered at the right tip corner starting from the Title page. 1. TITLE: The title of the work must be brief and precise. It should not exceed two lines and 40 characters (including comma, period) Author(s) full name (s) must be given along with his (their)
degree and the affiliations. Corresponding authors name, correct address (including e-mail and Fax, if available) and phone number must be mentioned at the bottom left hand corner of the first page. 2. ABSTRACT: The abstract is to be given in the beginning itself. It should not exceed 200 words. It must contain the aim, methodology, results and conclusion. For case report, summary / conclusion alone is to be given. KEY WORDS: (maximum five) in capitals are to be included at the end of Abstract. 3. INTRODUCTION: Describe the aim of the study, along with the hypotheses that were tested. Only necessary references are to be given. 4. METHOD: Give in detail the materials used and the methods employed. Describe the type of study. Pharmacological names only must be mentioned for the drugs used and, if proprietary name is used, then the manufacturers name must be given in parentheses. Except for standard, well-accepted abbreviations (including SI Units), all others must be introduced in parentheses when the full term is used for the first time in the article. 5. RESULTS: Giver only the results obtained by the study under discussion. State the statistics in the correct scientific form (P value, mean etc). Results based on assumptions must not be given. Indicate in the text the place where the tables have to be inserted. 6. DISCUSSION: The discussion should be to the point and relevant to the subject under discussion.
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This section can be combined with the previous one if the author desires. Avoid speculations. Use only standard abbreviations or the abbreviations already introduced. 7. ACKNOWLEDGEMENT: This is to be made only to those who were directly and scientifically involved with the preparation of the paper. Permitting authorities, technicians, photographers who assisted in the work need not be mentioned. 8. REFERENCES: The references should be given in numerical order in which they first appear in text and not in alphabetical order (Citation Order System). It should be numbered consecutively in the text. The references will not be checked by the Editor or by the Peer reviewer and hence the author is solely responsible for its completeness and the accuracy. Period should not be employed anywhere in the references. Personal communications, unpublished data and poster references, if mentioned, should be in the text itself and the source mentioned in parentheses. References should be in the following form: Journal reference: Author(s) full title, Journal name (as abbreviated in Index Medicus), volume number, pages and year. If there are more than three authors, then mention the first three authors and then et al. Book reference: Author(s) (& Editor, if any), title of book (and chapter), publisher, place of publication, page number (s) of the cited portion and year. 9. THE LEGEND: The legend for the illustrations (and tables, if necessary) must be given in a separate sheet of paper and should be typed double-spaced. Illustrations: The photos and figures should be prepared in glossy prints with good contrast and of the size 6 x 4. Only salient details should be included. On the back of the illustration, the figure number in text, title of the paper, the first authors name and the top side (marked with an arrow) must be specified. Except for arrows, no text is to
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be on the photos. It is the duty of the author(s) to get the patients written permission when the subject is identifiable in the photo. Submit two sets of illustrations. Illustrations from other Journals and books are usually not accepted. If used, it rests with the author(s) to get the copy right permission from the original author / publisher and this permission letter must be sent to the Editor at the time of submitting the manuscript. For Histological figures the stain and magnification used should be noted e.g.: H & E Stain x 70. 10. TABLE: It should be in double space. Each table must have an Arabic numeral (except for single table) and a title both in a single line. Each column in the table must have a short heading. If a table is large, then it must be continued in a second page, which also must have the table number and the title. Avoid vertical lines in the tables. Two sets must be submitted. 11. All manuscripts are subjected to editorial board review. 12. Other Categories of Manuscript a) Original Articles should generally not exceed 3,000 words or 12 double spaced pages. b) Review Articles: can be on topics of relevance to clinical practice, research methodology, community ophthalmology or investigative work, of relevance to visual science. These articles should include up to date review of existing literature, and summarize the current status / preferred practice for that particular topic. Brief reports are short communication of new instruments, new laboratory techniques or surgical techniques as well as interesting case reports with unique findings. These should not exceed 1000 words with a maximum of 2 illustrations. They should follow the format introduction, case, and discussion. No more than 8 references should be cited. Each brief report must begin with a 75-100 word summary that highlights the significance of the articles.