KERALA JOURNAL OF OPHTHALMOLOGY

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1 KERALA JOURNAL OF OPHTHALMOLOGY VOL. XXI ISSUE 3 SEPTEMBER 2009 EDITOR Dr. Meena Chakrabarti EDITORIAL BOARD Dr. Rajiv Sukumaran (Kollam) (Associate Editor) Dr. Charles K. Skariah (Thrissur) Dr. Sonia Rani John (Trivandrum) Dr. Mini Jayachandran (Kollam) Dr. Mohammed Haneef (Alapuzha) Dr. Bindu Das (Kozhikode) Dr. Merine Paul (Thrissur) Dr. Leila Mohan (Kozhikode) Dr. Meenakshi Dhar (Kochi) Dr. Amitha Varghese (Thiruvalla) Dr. Sunil (Kasargode) Dr. Reena Rasheed (Trivandrum) Dr. Ashley Thomas (Kozhencherry) EX- OFFICIO MEMBERS Dr. R.R. Varma (President) Dr. Rajagopalan Nair (Past President) Dr. T.A. Alexander (Immediate Past President) Dr. Sahasranamam (Past Secretary) Dr. Sasi Kumar (Secretary) ADVISORS Dr. Shobhana Mohandas Dr. Thomas Cherian Dr. Sai Kumar S.J. Dr. Giridhar A. The Kerala Journal of Ophthalmology is the official scientific publication of the Kerala Society of Ophthalmic Surgeons and 4 issues are published every year. It welcomes original articles, interesting case reports, update articles, book reviews, journal abstracts and research papers in Ophthalmology. Dates of the upcoming conferences and CME s are also published. Original articles are accepted on condition that they have not been published in any other journal. SUBSCRIPTION RATE Annual : Rs. 600 (4 issues) Single Copy : Rs. 150 Subscription should be sent by demand draft in favour of Kerala Journal of Ophthalmology payable at Trivandrum addressed to the Editor, KJO ADDRESS FOR ALL CORRESPONDENCE: Dr. Meena Chakrabarti, Editor KJO, Chakrabarti Eye Care Centre, Kochulloor, Medical College PO, Trivandrum , Ph , Fax: , tvm_meenarup@sancharnet.in

2 KERALA SOCIETY OF OPHTHALMIC SURGEONS (Registered under Societies Registration XXI of No.387/2003) President Dr. R.R. Varma Ambikalayam, Warriam Road Kochi Ph: (R) Mob: General Secretary Dr. Sasikumar Ambadi, Adayath Lane, Ravipuram, Kochi Ph: (H) Mob: Treasurer Dr. Radha Ramanan LF Hospital, Angamaly Ernakulam Ph: (H) Mob: President Elect Dr. B.V. Bhat Asoka Hospital South Bazar Kannur Ph: Joint Secretary Dr. Arup Chakrabarti Chakrabarti Eye Care Centre Kochulloor, Trivandrum Ph: Mob: Immediate Past President Dr. P. Rajagopalan Nair Raj Bhavan Palakkad Ph: (R) Mob: Dr. T.A. Alexander Thottumughath, Kusumagiri Kakkanad, Kochi Ph: Dr. George Thomas T.C. 4/1040-1, Near Kowdiar Jn Trivandrum Ph: , Mobile: Dr. E.J. Mani Little Flower Hospital Angamali Ph: Vice President Dr. A. Giridhar Giridhar Eye Institute Ponneth Temple Road Kadavanthara, Kochi Ph: Web Site Editor Dr. Thomas George RIO, Red Cross Road Trivandrum Mob: Immediate Past Secretary Dr. Sahasranamam No. 30, Vinayaka Nagar Trivandrum Ph: (R) Mob: Managing Committee Members Dr. Anthrayose Kakkanat Dr. Meena Chakrabarti Executive Committee Members Dr. Suresh Babu Kasargode Dr. P.P. Kunhiraman Kannur Dr. Baburaj N.P. Kozhikode Dr. Mohammed Swadique Malappuram U Scientific Committee Chairman Dr. Sai Kumar S.J. Giridhar Eye Institute Kochi Ph: (H) Mob: Journal Editor Dr. Meena Chakrabarti Chakrabarti Eye Care Centre Kochulloor, Trivandrum Ph: Mob: Dr. Rajesh Radhakrishnan Palakkad Dr. Babu Krishnakumar Thrissur Dr. Davis Akkara Ernakulam Dr. C.K. Mathew Alapuzha Dr. Varghese Joseph Pathanamthitta Dr. Seshadrinathan Kottayam Dr. S Venugopal Kollam Dr. Biju John Trivandrum

3 KJO CONTENTS 241 EDITORIAL In the Grip of the Python: Medicine s Dependence on the Pharmaceutical Industry Dr. Meena Chakrabarti MAJOR REVIEW 243 Retinoblastoma Dr. Mahesh P. Shanmugham ORIGINAL ARTICLES Ocular Manifestations of Intracranial Space Occupying Lesions A Clinical Study Dr. K.V. Raju, Dr. Anju Abdul Khader Capsulo-Cortical Adhesions (CCA) and Phacoemulsification (PE) Dr. Arup Chakrabarti, Dr. Sonia Rani John, Dr.Valsa Stephen, Dr. Meena Chakrabarti Efficacy of Combining Intravitreal Bevacizumab Monotherapy (IVB) with Panretinal Photocoagulation (PRP) in Early Stages of Neovascular Glaucoma (NVG) Dr. Meena Chakrabarti, Dr. Arup Chakrabarti, Dr.Sonia Rani John Ophthalmic Manifestations in Children with Delayed Milestones A Clinical Study Dr. Reena A, Dr. Lekshmy S.R, Dr. Lekshmi H, Dr. Bindu K. Appukuttan An Outcome Analysis of Posterior Capsular Rent (PCR) In the Hands of A Senior Phaco Surgeon Dr. Arup Chakrabarti, Dr. Meena Chakrabarti, Dr. Sonia Rani John, Dr. Valsa Stephen MS DNB OPHTHALMIC SURGERY Lens Surgery in Marfan s Syndrome Dr. Somdutt Prasad OPHTHALMIC INSTRUMENATION The Eyesi: Ophthalmic Surgical Simulator Dr. Meena Chakrabarti, Dr. Sonia Rani John, Dr. Arup Chakrabarti OCULAR PHARMACOLOGY 285 Nepafenac Dr. Sonia Rani John, Dr. Meena Chakrabarti, Dr. Arup Chakrabarti 289 Recent Advances in The Back of the Eye Drug Delivery Dr. Meena Chakrabarti

4 KJO CONTENTS CURRENT CONCEPTS Care and Maintenance of Contact Lens An Overview Dr. Pravin Tellakula CASE REPORT A Case Report of Colobomatous RD Dr. Arya A.R, Dr. Biju John Vasoproliferative Tumour of The Retina A Case Report Dr. Tulefa Shafi, Dr. Natasha Radhakrishnan, Dr. Gopal S Pillai, Dr.Roshan George COMMUNITY OPHTHALMOLOGY Go Green for a Healthier Life Dr. Meena Chakrabarti PHOTO ESSAY Masquerade Syndrome Dr. Meena Chakrabarti CONSULTATION SECTION OPHTHALMIC HISTORY JOURNAL REVIEW BOOK REVIEW UPCOMING CME PG TEAR SHEET INSTRUCTION TO AUTHORS

5 EDITORIAL In the grip of the python: Medicine s Dependence on the Pharmaceutical Industry Everything has either a price, or it possesses dignity. 1 Professionals should be independent of the state or commerce 2. These are two off-quoted quotes, but there is a lingering doubt in our minds as to the threat of Commercialism and Professional integrity. Commercialism is such a threat to the professional ethics of individual physicians that commercialism is incompatible with medical professionalism. Personal financial choices by physicians at times violate professional responsibilities and the fundamental ethical pact with society. 3 The conflict between commercialism and professionalism is precisely about the appropriate and inappropriate (not legal vs illegal) ways that physicians should make money and contribute to society. 5 If medicine loses professionalism or the public perceives that physicians are not behaving as professionals, it is no wonder that medicine will surrender its influence and status in society. Can the medical profession and, specifically, peer-reviewed literature survive the challenges posed by the secular culture of commercialism and at the same time maintain the public trust? 5-7 For both academic institutions and individuals, receiving gifts, meals, books, or free continuing medical education creates the presumption of bias. The further acceptance of invitations to join speakers bureaus, to serve on boards, to consult on marketing issues, to receive payments for enrolling in clinical trials, and to participate in research studies with payment in stock pushes this presumption of bias into fact Other enticements, sometimes for spouses, sometimes at the request of the physicians themselves, are immoral, and some are illegal. Those who do not believe this bias exists are denying scientifically established patterns of human behavior and deceiving themselves. The rule of reciprocation, one of the strongest tenets of human social behavior, holds that we should try to repay what another person has provided to us. 3 The ability of physicians to remain neutral under the present barrage of industry largesse is questionable. Companies target academic key opinion leaders (a marketing term) to populate scientific advisory committees, join speakers bureaus that sometimes aggressively promote drugs or devices, and participate on manuscript writing committees that support industry marketing themes 16. Although key opinion leaders seem convinced of their own impartiality, Carl Elliott, a moral philosopher at the University of Minnesota and author of Better Than Well: American Medicine Meets the American Dream, 17 strongly disagrees with them, as do their own colleagues. 18 The practice of key opinion leaders consulting with multiple companies to present the appearance of objectivity is even more misleading 19,20,21

6 242 Kerala Journal of Ophthalmology Vol. XXI, No. 3 A generation of new physicians has grown up with the mistaken belief that professional values can be replaced with marketplace values and that medical care is just another economic service. Financial success has become the dominant standard of measurement or value even for most academic medical centers. 21 Young professionals are reminded that these commercial activities were previously considered unprofessional. 5 There is tremendous value in the cooperation between academia and industry, but the engagement should be at a distance, with both sides maintaining their own standards and ethical norms. 4 Although academic medicine and the health care industry seem intertwined at present, the profession needs to be reminded that the goals of the medical profession are very different from the goals of the commercial industry. We must seek ways to disentangle the two and not just use disclosure as the mechanism to cleanse the system; reader or buyer beware should not be the mantra of a profession There are serious questions about the reliability of some of the commercially funded trials, 24 raising very significant moral and ethical questions for some physicians and a dilemma for journals. In reality, it is the physicians who have permitted the pharmaceutical and biotech industries to manipulate medical science through these financial relationships. 19 Many researchers have delayed publication of their results by several months to allow for patent application, to protect their scientific lead, or to slow the dissemination of results that would hurt sales of their sponsor s product, 19 and in some instances scientists at top research universities have completely refused to share results with their colleagues. 30 The reporting of trial outcomes is also sometimes incomplete, biased, and inconsistent with protocols. 31 Published articles, as well as reviews that incorporate them, may therefore be unreliable and overestimate the benefits of an intervention; meta-analysis simply amplifies erroneous results and is much less powerful or valuable than assumed. To ensure transparency and avoid the overbearance of commercial industry, planned clinical trials must be registered and protocols should be made publicly available prior to trial completion. Many major journals will not permit submission of clinical studies that have not been registered Journals are hampered by this assault of commercialism on publishing. The only tools editors have in their efforts to enforce policies on full financial disclosure or to control excess commercialism and bias is the instigation of a full investigation following complaints by informed readers. When this happens, the journal is dedicated to clarifying the situation for the reader, albeit indirectly, by involving the relevant institutional review board because journals do not have formal investigative or enforcement functions. There is reason for hope, however, as resistance begins to mount against commercial influence in medicine, as evidenced by suggested changes in the relationship between academic medical centers and industry. 16, There are also new and influential parallel initiatives from academic medical centers themselves, and from think tanks addressing continuing medical education (the education environment is even more permissive in fostering biases than is publishing) Time will tell whether professionalism will rein over commercialism in medicine. Dr. Meena Chakrabarti MS DO DNB Editor, KJO

7 September 2009 Kerala Journal of Ophthalmology 243 MAJOR REVIEW Retinoblastoma Dr. P. Mahesh Shanmugam DO FRCSEd PhD Retinoblastoma occurs in approximately 1 in 14,000-34,000 live births. 1-3 No predisposition to race, sex or laterality of the eye is noted. The majority of cases of retinoblastoma are sporadic (no family history and no affected family members on ophthalmic examination). Retinoblastoma occurs as a result of loss of the tumor suppressor gene located on band 14, on the long arm of chromosome 13 (13q14). 4,5 In genetically transmitted disease, the abnormality results in the development of usually bilateral, multifocal tumors in relatively younger patients. This deletion also predisposes these children to other non-ocular tumors such as osteosarcoma in later stages of life. In contrast, sporadic tumors occur in older children and tends to be unifocal and unilateral. However, 10-20% of unilateral disease can also be genetically transmitted. The average age at diagnosis of retinoblastoma in American children is 18 months, and evidence indicates that Asian children present later than their western counterparts 1,6-8. Bilateral cases are diagnosed earlier than unilateral cases. 1,9 Clinical Features Fig. 1. Leukocoria Fig. 2. White, flat, translucent lesion in sensory retina The most common presentation of retinoblastoma is leukocoria (61-70 %) (Fig 1) and strabismus (22-48%) 1,10,11. On fundus examination retinoblastoma appears as a slightly white, flat, translucent lesion in the sensory retina (Fig 2). Moderately advanced lesions may present as unilateral or bilateral leukocoria (Fig 3). Head, Vitreoretinal and Ocular Oncology Services, Sankara Eye Hospitals, Bangalore Fig. 3. Advanced Leison Fig Common modes of presentation of retinoblastoma

8 244 Kerala Journal of Ophthalmology Vol. XXI, No. 3 Based on the growth pattern, the tumor can be classified into endophytic, exophytic, mixed (both endophytic and exophytic) and diffusely infiltrative tumors. Spontaneous regression of retinoblastoma occurs in about 1 percent of patients. It is often seen in eyes with phthisis bulbi and following an episode of severe inflammation. Local spread to the orbit, distant metastasis to brain, spinal cord, skull bones, distant bones, viscera and lymph nodes may occur in advanced retinoblastoma. On ocular ultrasonography retinoblastoma appears as an irregular mass lesion with high surface reflectivity and high internal reflectivity resulting in orbital shadowing all due to the presence of calcium. Computerized tomography and magnetic resonance imaging allow detection of extraocular disease, intracranial metastasis and pinealoblastoma. Retinoblastoma appears as an intraocular mass with calcium on CT scan; it appears as a hyperintense to vitreous lesion in T1 weighted image and hypointense to vitreous in T2 weighted images on MRI. (Fig 4) be well differentiated or poorly differentiated. Poorly differentiated retinoblastoma consists of small to medium-sized round cells with hyperchromatic nuclei and scanty cytoplasm. High mitotic figures are often observed. A well-differentiated tumor may show: (i) rosettes, or (ii) fleurettes. Seventy percent of retinoblastomas are known to contain rosettes. Rosettes are of two types: Flexner-Wintersteiner rosette Homer-Wright rosette In a Flexner-Wintersteiner rosette, columnar cells are arranged around a clear central lumen. The nuclei of the cells are arranged near the base of the tumor. The lumen contains hyaluronidase resistant glycosaminoglycans, which are found between photoreceptor and retinal pigment epithelium. In a Homer-Wright rosette, the cells are arranged radially around a central tangle of neural fibers. Fleurettes represent further differentiation and present as flower bouquet-like aggregates of tumor cells with bulbous eosinophilic processes projecting through the fenestrated membrane. They are seen in 6-10 percent of the retinoblastoma cases. Differentiation of the tumor does not have prognostic value. Management Fig. 4. MRI Scan in a child with unilateral retinoblastoma Rarely cytology by fine needle aspiration biopsy may be necessary to confirm the diagnosis. In advanced cases with extraocular disease, metastatic work-up that includes lumbar puncture, CT / MRI scan, bone marrow biopsy, bone scan and routine blood investigations will be necessary 12. Histopathology Retinoblastoma appears as a basophilic mass with lightly eosinophilic areas due to necrosis of tumor and/ or multiple dense basophilic foci (due to calcification) within areas of necrosis may be seen. The tumor may Management options in retinoblastoma include enucleation, in an eye without visual potential, if more than half the globe is involved by the tumor, or in the presence of glaucoma and anterior chamber involvement. Eyes with visual potential (unilateral/ bilateral cases) are managed conservatively with modalities that include cryotherapy, laser photocoagulation, transpupillary thermotherapy (TTT), thermochemotherapy, chemoreduction, plaque brachytherapy and external beam radiotherapy 1,13. International classification of retinoblastoma 14 : As early classifications were deemed insufficient in this era of chemoreduction of retinoblastoma, a new revised classification has been devised to offer prognosis of the affected eye. 14

9 September 2009 P. Mahesh Shanmugham : Retinoblastoma 245 GroupTumor characteristics A Small tumor ( 3mm) B Larger tumor ( 3mm) 3 mm from foveola 1.5 mm from disc Subretinal fluid 3mm from margin C D Focal seeding Subretinal and or vitreous seeds 3 mm from tumor Diffuse seeding Subretinal and or vitreous seeds 3 mm from tumor E Tumor >50 % globe Neovascular glaucoma Opaque media due to intraocular hemorrhage Postlaminar optic nerve invasion, choroid (>2 mm), sclera, orbit anterior chamber involvement Treatment of retinoblastoma 1, 15 Management of retinoblastoma confined to the eye: Eyes with visual potential (unilateral/bilateral cases) are managed conservatively. Primary or recurrent tumours anterior to equator, 4 mm in diameter and less than 3 mm thickness, confined to the retina are treated with triple freeze thaw cryotherapy. Tumors 3-4 mm in diameter, 2 mm thick confined to the retina are treated with 2 rows of deep laser burns around the tumor. Slightly larger tumors confined to the retina can be treated with transpupillary thermotherapy, which is increasing the tumor temperature by C above body temperature. Larger tumors or those with vitreous or subretinal seeds are treated with external beam radiation delivering cgy, 200 cgy fractions delivered over a 4-5 week period. Plaque brachytherapy with episcleral plaque applicators (Iodine or Ruthenium - 106) can be used to treat tumours 15 mm in diameter and 6-8 mm in height, at least 2 mm from optic disc and fovea with or without localized vitreous seeding. Plaque Fig. 5. Large tumor mass filling the globe therapy has the advantage of limited radiation to normal tissue, thereby limiting complications. Radiation in any form is associated with complications such as retinopathy, cataract and in bilateral germinal tumors, the increased risk of second malignant neoplasms in later years 16. The risk of second malignant neoplasms is highest when the child subjected to radiation less than 1 year of age. Hence it is preferable to avoid radiation and CT scan in retinoblastoma infants less than one year of age. Contemporary management of large tumors, tumors close to optic nerve (Fig 5) / fovea or those extending beyond the retina involves using chemoreduction. Triple drug chemoreduction using vincristine, etoposide and carboplatin are used in multiple cycles to chemoreduce the tumor and the residue is destroyed using focal treatments such as laser photocoagulation, cryotherapy etc., The tumor is replaced with chorioretinal atrophy and calcific residue with chemoreduction and local treatment. (Fig 6, 7) Current focus is on local chemotherapy and one of the avenues being explored in cannulation of the ophthalmic artery and melphalan infusion through the same. Fig. 6. Regressed retinoblastoma showing chalky white areas of calcification and chorioretinal atrophy

10 246 Kerala Journal of Ophthalmology Vol. XXI, No. 3 Fig. 7. Regressed retinoblastoma showing extensive chorio retinal atrophy and flecks of calcification Subconjunctival carboplatin chemotherapy is also used as an adjunct to systemic chemotherapy. This shift from radiation to chemoreduction is primarily aimed at reducing the increased risk of second malignant neoplasms associated with the use of radiation. Enucleation is indicated in retinoblastomas involving more than half the globe, presence of glaucoma and anterior chamber involvement. A long optic nerve stump ( 10 mm in length) should be obtained during enucleation. If post enucleation histopathological Fig. 9. Orbital recurrence of tumor following enucleation tumor, excision of the tumor followed by additional chemotherapy and radiation to the affected part. Intracranial involvement is treated with intrathecal chemotherapy in addition to CNS radiation and systemic chemotherapy. Prognosis The overall 5-year survival is around 90 percent in retinoblastoma. Patients with germinal mutations are more likely to die due to second nonocular tumors, which develop at a later age. Involvement of the cut end of the optic nerve indicates poor prognosis and possible intracranial metastatic disease if adequate (at least 10 mm) length of the optic nerve stump was obtained during enucleation. Tumor invasion into the ocular coats, extensive choroidal invasion and anterior chamber seeding are associated with an increased risk of subsequent metastatic disease. Extraocular, central nervous system involvement and hematogenous spread carry a poor prognosis. Fig. 8. Advanced tumor showing anterior segment involvement examination shows tumor invasion beyond lamina cribrosa, anterior segment involvement (Fig. 8) or extensive choroidal invasion, adjunctive chemotherapy is necessary to decrease risk of subsequent metastatic disease. Involvement of the cut-end of optic nerve with tumor has to be treated aggressively with adjunctive chemotherapy and radiation. Management of extraocular retinoblastoma: (Fig 9 showing orbital recurrence of retinoblastoma) Extraocular retinoblastoma is managed with a multimodal approach of chemoreduction to reduce the References 1. Shields JA, Shields CL. Retinoblastoma. Clinical and pathologic features. In: Intraocular tumours: A Text and Atlas. WB Saunders, Philadelphia, 1992, pp Senft S, al-kaff A, Bergqvist G, et al. Retinoblastoma. The Saudi Arabian experience. Ophthalmic Paediatr Genet 1988;9: Kock E, Naeser P. Retinoblastoma in Sweden A clinical and histopathological study. Acta Ophthalmol 1979:57: Francke U. Retinoblastoma and chromosome 13. Cytogenet Cell Genet 1976;16: Yunis JJ, Ramsay N. Retinoblastoma and subband deletion of chromosome 13. Am J Dis Child 1978; 132: Shanmugam MP, Biswas J, Gopal L, Sharma T, Nizamuddin SH. The clinical spectrum and treatment outcome of retinoblastoma in Indian children. J Pediatr

11 September 2009 P. Mahesh Shanmugham : Retinoblastoma 247 Ophthalmol Strabismus Mar-Apr;42(2):75-81; quiz Vemuganti G, Honavar S, John R. Clinicopathological profile of retinoblastoma in Asian Indians. Inv Ophthalmol Vis Sci 2000;41(S790);4. 8. Sahu S, Banavali SD, Pai SK, et al. Retinoblastoma: problems and perspectives from India. Pediatr Hematol Oncol 1998;15: Rubenfeld M, Abramson DH, Ellsworth RM, et al. Unilateral vs. bilateral retinoblastoma. Correlations between age at diagnosis and stage of ocular disease. Ophthalmology 1986;93: Kayembe L. Retinoblastoma: 21-year review. J Fr Ophthalmol 1986;9: Mathew L, Miale TD, Rao S, et al. Retrospective analysis of 58 children with retinoblastoma. Ophthalmic Paediatr Genet 1984; 4: Mohney BG, Robertson DM. Ancillary testing for metastasis in patients with newly diagnosed retinoblastoma. Am J Ophthalmol 1994;118: Epstein J, Shields CL, Shields JA. Trends in the management of retinoblastoma: evaluation of 1,196 consecutive eyes during J Pediatr Ophthalmol Strabismus. 2003;40: Shields CL, Shields JA. Basic understanding of current classification and management of Retinoblastoma. Curr Opin Ophtalmol 2006;17: Shields CL, Mashayekhi A, Demirci H, et al. Practical approach to management of retinoblastoma. Arch Ophthalmol. 2004;122: Abramson DH. Retinoblastoma in the 20th Century: Past Success and Future Challenges The Weisenfeld Lecture. Inv Ophthalmol Vis Sci. 2005;46:

12 248 Kerala Journal of Ophthalmology Vol. XXI, No. 3 ORIGINAL ARTICLE Ocular Manifestations of Intracranial Space Occupying Lesions A Clinical Study Dr. K.V. Raju MS, Dr. Anju Abdul Khader MS Abstract Aim To study the various ophthalmologic manifestations in intracranial space occupying lesions. To correlate the ocular manifestations and the site of the brain tumors. To study the visual field defects caused by space occupying lesions. Materials and methods The study included fifty CT/MRI proven cases of intracranial space occupying lesions who underwent detailed ocular, neurological and systemic examination. Results Female patients in the yrs age group were commonly affected. Headache was the common symptom [63.3 %] followed by defective vision.vii Cranial nerve was most commonly involved. Papilloedema was the most common fundus finding. Visual field defects correlated with the site of tumour. Most common histological subtype was neuroepithelial tumours. Cerebellopontine angle tumours were most common according to the site of tumour. Keywords. Ocular manifestations, intracranial space occupying lesions, visual field defects. Introduction Ocular features sometimes form an early manifestation of intracranial space occupying lesion, which helps us to diagnose the condition earlier and decrease the morbidity and mortality of the patient. How far the ophthalmologist s effort can be useful to the neurologist can be judged from the extensive distance the optic pathways cover in the brain from pole to pole, and from the fact that six of the twelve cranial nerves with their Regional Institute of Ophthalmology, Calicut Medical College nuclei are associated with the eyes besides the vagus and the sympathetic. This research work covers the assessment of the incidence of ophthalmologic manifestations in intracranial space occupying lesions, and to correlate the ocular manifestations and the site of the brain tumours as well as the study of the visual field defects caused by space occupying lesions. Aim of the Study To study the incidence of ophthalmologic

13 September 2009 Raju K.V. et al. - Ocular Manifestations of ICSOL 249 manifestations in intracranial space occupying lesions, to correlate the ocular manifestations and the site of the brain tumours and also to study the visual field defects caused by space occupying lesions. Methods The materials for the study were collected from the patients who attended Regional Institute of Ophthalmology, Calicut Medical College, during one year period [May May 2007]. Most of the patients were admitted in the Neurosurgery Department and the ophthalmologic evaluation was done in the preoperative period. Patients with CT or MRI proved intracranial space occupying lesions were taken up for the study. Those patients who were uncooperative on account of very young age, deteriorating general conditions or marked behavioural disorders were excluded from the study. Fifty patients with brain tumours and eye manifestations were included in the study. In each case clinical evaluation was done after obtaining a detailed history. Ophthalmologic assessment included routine ocular examination with special reference to ocular movements, corneal sensation, pupillary abnormalities and nystagmus. Ocular fundus was examined in detail and visual fields charted in all cases. A complete examination of the central nervous system which included examination of the higher functions, cranial nerves, motor system, sensory system and cerebellar signs were made. Observation and Discussion 1) Age distribution [Table :1] The age of patients ranged from years. The maximum incidence in the present study was in the age group between 40 to This is in accordance with other studies by Rao et al, which showed a 52 % incidence in the 3 rd & 4 th decade. Table 1: Age distribution. Age group Percentage <10 6 % 10 to 20 6 % 20 to % 30 to % 40 to % >50 16 % 2) Sex distribution: The present study showed a female preponderance of 60 %. 3) Area of involvement of brain tumors and histopathological types of brain tumors. [Table :2] In the present study according to the site of tumor most common was cerebellopontine angle tumors [20 %]. According to the histology the most common tumor found in our study was neuroepithelial tumors [34 %] like astrocytoma, oligodendroglioma, ependymoma etc. 4) Presenting symptoms:. In this series maximum no of patients presented with headache. Headache as initial symptom occurred in 30 % and along with other symptoms occurred in 63.3 %. S.Sood et al also made similar observation. Defective vision occurred during the course of the disease in 50 % of the patients. Seizures either generalized or focal occurred in 3.3 %. Behavioural and psychiatric changes were noted in patients with parietal, frontal & temporal lobe tumors. Other symptoms included vertigo, paresis, dysphasia, dementia, deafness, tinnitus ataxia, and diplopia etc. 5) Pupillary abnormalities Among the 50 patients examined 6[12 %] had abnormal pupillary reaction. All of them had afferent pupillary defect due to optic atrophy. Although Wernicke pupil has no significance according to the literature one patient in this study with left parietal meningioma and homonymous hemianopia showed the defect. 6) Papilloedema Uhthoffs [1914] study of bilateral papilloedema showed the etiology in 71 % as brain tumors, 12 % cerebral syphilis, 3.6 % cerebral oxycephaly, brain abscess and meningitis 2.2 % each. In this study 56 % of the patients had papilloedema during presentation. Posterior fossa tumors presented with papilledema earlier where as cortical & pituitary tumors presented late. Optic nerve fibres are compressed by elevated cerebrospinal fluid pressure in the subarachnoid space of the intraorbital portion of the optic nerve. Subsequent swelling of axons and leakage of water, protein, and other axoplasmic

14 250 Kerala Journal of Ophthalmology Vol. XXI, No. 3 Table 2 : Area of Involvement & Histopathological subtypes Area of lesion Histopathology Percentage Parietal lobe Meningioma-2 Malignant Ependymoma-1 14 % Glioblastoma multiforme-1 Astrocytoma-2 Epidermoid cyst-1 Fronto parietal Astrocytoma-1 6 % Meningioma-2 Frontal Meningioma-3 Glioblastoma multiforme-2 12 % Abscess-1 Fronto temporal Astrocytoma-1 Oligodendroglioma-1 6 % Glioblastoma multiforme-1 Temporal Pilocytic astrocytoma-1 4 % Caver. Haemangioma-1 CP angle tumour Acoustic neuroma-7 20 % Meningioma-1 Glioma-2 Parieto occipital Astrocytoma-1 Glioma-1 6 % Abscess-1 Perichiasmatic Pituitary tumours-3 Craniopharyngioma-5 18 % Tuberculum Sellae Meningioma-1 Cerebellum Medulloblastoma-1 4 % Glioma-1 Ventricle Colloid cyst-3 8 % Epidermoid-1 Corpus callosum Glioma-1 2 % contents into the extra cellular space causes venous obstructions, nerve fibre hypoxia and vascular telangiectasis of the disc as secondary events. Therefore, papilledema is primarily mechanical rather than a vascular phenomenon. Normally the disc edema takes 1-4 days to develop after the increase of CSF pressure. 7) Cranial nerves [Table:3] Expanding supratentorial mass lesions displaces cerebral tissues to compress the brainstem structures. During this process the nerves innervating the extraocular muscles are stretched resulting in false localizing sign. VI nerve may be stretched over the petrous tip between its point of emergence from the brainstem and its dural attachment to the clivus. This is due to the downward descent of the brainstem and may occur with posterior Table 3: Distribution of cranial nerve palsy Cranial Nerve Palsy Percentage IIIrd nerve 3.12 VI nerve VII nerve 31.2 VIII nerve IX, X nerves 6.25 V nerve 18.74

15 September 2009 Raju K.V. et al. - Ocular Manifestations of ICSOL 251 fossa tumours. Bilateral palsy of VI nerve may be a false localizing sign. Cranial nerves were involved in 64 %. Cerebellopontine angle tumors were associated with cranial nerve involvement [5, 7, 8 cranial nerves involved in 100 % & 9, 10 cranial nerves involved in 6.25 %] 8) Hemiparesis Pyramidal tract involvement with some form of hemi paresis was seen in seven patients. 9) Cerebellar signs All cases of cerebellopontine angle tumors were associated with cerebellar signs. 10) Optic atrophy [Table:4] Optic atrophy was seen in 9 patients. 3 patients had primary optic atrophy [all cases were craniopharyngiomas]. Post-neuritic optic atrophy following papilledema was seen in rest of the cases. Table 4: Percentage of optic atrophy. Optic Atrophy Percentage Primary optic atrophy 2 Secondary optic atrophy 12 Total 18 11) Visual field defects [Table:5] Visual field testing helps in localizing and lateralizing the intracranial lesions. Most field defects of neurophthalmic significance are located in the central 30-degree field. 56 % of the patients in this study showed field defects. (a) Blind spot enlargement was the most common. (b) Bitemporal hemianopia - The partial decussation of nerve fibres in the optic chiasm accounts for the characteristic visual field defect. It was seen in 2 cases of craniopharyngioma and one tuberculum sellae meningioma. (c) Homonymous hemianopia occurs in optic tract lesions due to tumors in temporal, frontal, parietal & occipital lobes. It was seen in 6 cases -2 parietal lobe lesions, 2 frontoparietal & 2 temporal lobe lesions. (d) Homonymous superior quadrantanopia was seen in one case of temperofrontal meningioma due to involvement of the inferior fibres in the optic radiation. (e) Homonymous inferior quadrantanopia was seen in one case of parietal tumour due to involvement of superior fibres in the optic radiation passing through the parietal lobe. Frontal lobe tumors Patients with frontal lobe tumors showed behavioral abnormalities, dementia, seizures & urinary incontinence. Three out of the nine had convulsions. Gliomas were the most common tumors of the frontal lobe. 9 % of the frontal lobe tumors showed homonymous hemianopia and 50 % showed peripheral constriction of visual fields. Temporal lobe lesions Temporal lobe involvement was seen in 6 out of the 50 patients. 20 % of the cases showed superior quadrantanopia & 25 % showed homonymous hemianopia. Cerebellopontine angle tumours There were 10 cases with CP angle tumours. All of them had deafness, ataxia, impaired corneal sensation, papilledema and 7 th and 8 th nerve palsies. Other features Table 5: Distribution of visual field defects Field defect Percentage Cases Bitemporal hemianopia 7.14 Craniopharyngioma, tuberculus sellae meringroma Homonymous hemianopia Parietal astrocytoma, Parietal epidermoid Fronto parietal meningioma Tem parietal oligodendroglioma Tem.pilocystic astrocytoma Homo.superior quadrantanopia 3.57 Fronto temp.meningioma Haemangioblastoma cerebellum Homo.inferior quadrantanopia 3.57 Glioblastoma multiforme Parietal lobe Blind spot enlargement Peripheral constriction 28.57

16 252 Kerala Journal of Ophthalmology Vol. XXI, No. 3 include gaze induced nystagmus, brun s nystagmus, tinnitus and dysphasia. In the present study the incidence of raised ICT as evidenced by papilledema was seen in 80 % of cases. Papilledema occurred secondary to hydrocephalus as a result of aqueductal obstruction by the tumour. Papilledema may sometimes result due to increased protein secretion by the tumour. Optic atrophy is secondary to papilledema. In the present study nystagmus is seen in 20 % of cases of CP angle tumours. Conclusion Ocular manifestations occur very frequently in ICSOL,which in some cases helps us to diagnose the condition. Headache was the most common symptom followed by defective vision. Cranial nerve involvement was seen in many cases, most common of which was sixth nerve palsy. Papilledema was the most common fundus finding followed by optic atrophy. Visual field abnormality was seen in majority of cases out of which blindspot enlargement was most common followed by bitemporal hemianopia, homonymous hemianopia, superior and inferior quadrantanopia. Distribution of brain tumours showed CP angle tumours to be most common followed by parietal lobe, frontoparietal, frontal, frontotemporal, temporal and parieto-occipital lobe. This study emphasizes the importance of ocular manifestations in the localization, extent of the lesion, prognosis for vision and life of the patient, in the case of brain tumours. References 1. Rao KV, Subramanyam M, Rao BS. Papilledema. Indian Journal of Ophthalmology 1982; 30: Sood NK, Sharma M, Nada A, Dutt RC, Nagpal. Correlation between CT Scan and Automated Perimetry on Supratentorial Tumours. Neurology India. June 2002, 50; 2: Duanes Clinical Ophthalmology, Vol.2, Willaim Tasman, Edward A, Jaeger. 4. Duke-Elder, Sytem of Ophthalmology, Vol.XII, Neuroophthalmology, Hayreh SS. Pathogenesis of Edema of Optic Disc. BJO, 48: , Huber A, Eye Signs and Symptoms in brain tumours. Blodi FC. 3 rd Edition, St.Louis, C.V.Mosby, Smith JL. Homonymous Hemianopia: A review of 21 patients. Arch. Ophthalmol. 96; ; Miller NR. Walsh and Hoyt Clinical Neuroophthalmology 3 rd Edition, Vol.I&III Chamlin M et al. Ophthalmologic Changes Produced by Pituitary Tumours. Am. J. Ophthalmology 40: 353; Adler s Text Book of Physiology.

17 September 2009 Raju K.V. et al. - Ocular Manifestations of ICSOL 253 ORIGINAL ARTICLE Capsulo-Cortical Adhesions (CCA) and Phacoemulsification (PE) Dr. Arup Chakrabarti MS, Dr. Sonia R John DNB, Dr. Valsa T Stephen MS DNB, Dr. Meena Chakrabarti MS DNB One of the basic requirements of modern techniques of phacoemulsification is free rotation of the nucleus 1, 2, 3. A freely mobile nucleus 4 is a sign that it is totally separated from the capsular bag and subsequent maneuvers of the nucleus are likely to place minimal stress on the zonules. Rotation is achieved by cortical cleaving hydrodissection 5 which separates the nucleus from the capsular bag. Sometimes it may be difficult or impossible to rotate the nucleus despite meticulous cortical cleaving hydrodissection. If faulty technique of cortical cleaving hydrodissection has been ruled out, it is usually the presence of capsulo-cortical adhesions that makes nucleus rotation difficult. Capsulo-cortical adhesions are characterized by adhesions between the capsule and cortex (Figures 1a and 1b). These adhesions may be anterior, posterior, equatorial or any combinations of the above. Unlike in a cortical cataract, there is no definite area of Fig. 1a. Capsulo-cortical Adhesion on diffuse illumination Fig. 1b. Capsulo-cortical Adhesions on retroillumination Chakrabarti Eye Care Centre, Kochulloor, Trivandrum tvm_meenarup@sancharnet.in translucence visible between the capsule and the underlying opaque cortical layers in capsulo-cortical adhesions. Opacity exists in the outermost layers of the cortex that is adherent to the lens capsule. These adhesions can be assessed at the slitlamp as well as the operating microscope, to a certain extent. This prospective study was conducted to look into the peculiarities and difficulties faced by the surgeon while operating on cataracts with capsulo-cortical adhesions. The goal was to prepare a guideline for safe management of these cases. Patients and Methods 86 consecutive patients with capsulo-cortical adhesions scheduled for phacoemulsification (Group A) were included in this prospective study. The diagnosis of capsulo-cortical adhesion was made intraoperatively just before starting the surgery with the patient under the operating microscope after prepping and draping of the patient. The intraoperative findings were matched with the slitlamp examination findings documented in the casesheet during preoperative evaluation. All these patients had been preoperatively assessed at the slitlamp with a fully dilated pupil. Exclusion criteria included patients with prior ocular surgery, ocular disease, complicated cataract and nondilating pupils. 20 consecutive patients with routine uncomplicated cataract, scheduled for phacoemulsification were also included in the study as controls (Group B). The exclusion criteria,

18 254 Kerala Journal of Ophthalmology Vol. XXI, No. 3 Different types of CCAs seen on diffuse illumination (a), retro illumination (b) and slit beam illumination (c) observed between the lens and the posterior capsule. The shallowing of the anterior chamber was also considered as one of the endpoints of cortical cleaving hydrodissection. The capsular bag was decompressed by gently tapping on the anterior lens capsule with the hydrodissection cannula itself. The anterior chamber was refilled with viscoelastic and nucleus rotation was attempted with a Sinskey hook through the side port. If the nucleus did not rotate freely, no effort was made to attempt a forcible rotation. Additional multiquadrant hydrodissection was performed in two more sites that also included the area of capsulo-cortical adhesion. The cannula was also passed subcapsularly in an attempt to lyse the anterior capsulo-cortical adhesions by employing the concept of hydrofree dissection. Nucleus rotation was attempted again and the surgeon noted down the subjective difficulty encountered during nucleus rotation. If the nucleus did not rotate, another round of cortical cleaving hydrodissection was repeated once again at two different points. Subsequently, phacoemulsification was performed. A phacochop or stop and chop phacotechnique was employed using the Bausch and Lomb Millennium phaco unit. The surgeon looked out for any peculiarity or uniqueness in these cases. All cases were recorded in a DVD. Subsequently each of the recorded cases was analysed for a) the total duration of the actual surgical procedure, b) the total time required to perform rhexis and c) the total time required for cortical cleaving hydrodissection. surgical technique and protocols were the same in each group. Phacoemulsification was performed by a single surgeon (AC). All surgeries were performed under topical anesthesia with 2 % xylocaine jelly through the temporal clear corneal approach. The anterior capsule was stained with trypan blue dye (0.06 %) under an air bubble. Continuous curvilinear capsulorhexis was performed under 2 % hydroxypropyl methyl cellulose using a 26 gauge bent needle. A three-site cortical cleaving hydrodissection (3,9 and 6 o clock) was performed by injecting BSS through a 26-gauge cannula attached to a 2 ml syringe. The cannula tip was advanced under the anterior capsule approximately till the capsular fornix, the anterior capsule tented and BSS was gently injected until a complete fluid wave was Results 86 patients were noted to have capsulo-cortical adhesions at the start of the surgery. The average age Table 1: Patient Profile Group A Group B (N = 86) ( N = 20) Age (Years) Upper limit Lower limit Mean Sex Male Female Associated systemic disease Nil 19 (22.09 %) 53 (61.63 %) Diabetes Mellitus 5 (25 %) 10 (50 %)

19 September 2009 Arup Chakrabarti et al. - CCA and PE 255 of the patients was 67.1 years (range 46 years to 87 years). The sex distribution was even with 43 patients in each category (Table 1). 19 patients had no systemic illnesses with diabetes mellitus being the commonest systemic association Type of Cataract Group A Group B (No.86) (No. 20) 1. Anterior Subcapsular + Posterior Subcapsular 12 (13.95 %) 3 (15 %) 2. Anterior Subcapsular + Nuclear 4 (4.65 %) 2 (10 %) 3. Anterior Subcapsular + Posterior Subcapsular + White 6 (6.98 %) - 4. Anterior Subcapsular + Posterior Subcapsular+Nuclear 64(74.41 %)15 (75 %) (61.63 %) in those with concurrent systemic illness. The type of cataracts associated with capsulo-cortical adhesion are given in Table 2. The mean total duration of the surgical procedure as defined by the time from first incision till the application of the eye pad at the conclusion of surgery was minutes (range: minutes to minutes). The mean duration of time when the surgical steps were actually performed was minutes (range: minutes to 9.11 minutes). The mean time taken for rhexis was 1.39 minutes (range: 4.51 minutes to 0.46 seconds). The mean time taken for cortical cleaving hydrodissection was 2.13 minutes (3.35 minutes to 0.13 seconds) (Table 3). Group A Group B (N = 86) (N = 20) Elapsed Phaco Time (min) (5.1 to 0.52) (2.48 to 0.34) Absolute Phaco Time (min) (1.3 to 0.01) (0.24 to 0.03) Average Phaco Power (%) (70 to 40) (27 to 5) The capsulo-cortical adhesions encroaching into the pupillary area tended to render the red fundal glow (whenever present) a bit dull as opposed to rest of the central areas with a brighter red reflex. Trypan blue staining of the anterior capsule enhanced the visibility of the capsular tear at the zone of the adhesions. Some resistance was always encountered while performing the rhexis in the area of the capsulo-cortical adhesion. Nucleus rotation could be performed after the first sequence of cortical cleaving hydrodissection in 83 cases. However in 5 of these cases (5.81 %) the rotation was difficult and stressful though no untoward damage like zonular dialysis was noted. It could be completed only after the second sequence of cortical cleaving hydrodissection. In 3 cases (3.49 %) the nucleus could not be rotated. Milky turbid fluid (Figure 2) was noticed to originate from the area of the capsulo-cortical adhesions in 10 patients (11.63 %) at the stage of nucleus decompression during cortical cleaving hydrodissection. There were no significant intraoperative complications like posterior capsular rent or zonular dialysis in any of these patients. Visual recovery of 6/9 or better on the 5 th postoperative day was seen in 76 patients (88.37 %). Discussion Free and easy nucleus rotation is an important prerequisite in all the modern techniques of phacoemulsification.it considerably reduces the stress placed on the zonules and capsular bag during removal of the nucleus or nuclear fragments. Cortical cleaving hydrodissection is a step, which is aimed to completely separate the nucleus from its adhesions rendering it freely mobile within the capsular bag. This separation may be difficult or stressful and is at times impossible in the presence of capsulo-cortical adhesions (CCA). It is therefore important to be able to detect the presence of capsulo-cortical adhesions before the cortical cleaving hydrodissection step. A meticulous dilated slitlamp evaluation preoperatively helps to a great extent in diagnosing the presence of this condition. One should also look for this condition with the patient in extreme gaze. However one may miss the diagnosis of capsulo-cortical adhesion in the presence of a nondilating pupil or a dense cataract. Even if the condition is missed during the preoperative evaluation (for cataract surgery) a surgeon aware of this entity should be in a positon to make a diagnosis of capsulo-cortical adhesion intraoperatively. There were 13 cases (15.12 %) of capsulo-cortical adhesions which were undetected preoperatively and detected intraoperatively in the current study.

20 256 Kerala Journal of Ophthalmology Vol. XXI, No. 3 Cortical cleaving hydrodissection should be performed meticulously. The cannula tip should tent the anterior capsule and the fluid injection should be performed close to the capsular fornix. Mechanical lysis of the adhesion with the same cannula or a cyclodialysis spatula may be attempted. Signs of successful hydrodissection include a fluid wave across the posterior capsule, shallowing of the anterior chamber due to forward bulging of the nucleus, a prominent capsulorhexis edge and release of trapped fluid from the rhexis margin when the nucleus is tapped back. We routinely perform 3 - quadrant cortical cleaving hydrodissection even in our standard cases before attempting nucleus rotation. The same strategy was adopted in the study too, and this is more likely to lyse the adhesions than a one-point hydrodissection. This explains the high success rate of nucleus rotation in our study after the first sequence of cortical cleaving hydrodissection. No additional force is to be used to rotate the nucleus in the event of any difficulty and a repeat 3 quadrant cortical cleaving hydrodissection is called for. Sometimes, inspite of a good cortical cleaving hydrodissection, where the posterior fluid wave has been visualized and focal lysis of the capsulo-cortical adhesions has been performed, it may be difficult to rotate the nucleus. It could be due to the presence of equatorial adhesions and further multiquadrant hydrodissection should be done before attempting to rotate the nucleus. The milky fluid (Figure 2) seen to emanate from the area of capsulo-cortical adhesions (in 10 patients, %) while decompressing the capsular bag at that area seem interesting. The furry epinuclear surface (Figure 3) present focally at the area of the adhesions Fig. 2. Milky turbid fluid from the area of capsulo-cortical adhesions. Fig. 3. Furry epinuclear surface indicating the presence of capsulocortical adhesions were noted in many cases and could be a result of lysis of the fibrous adhesions between the anterior capsule and underlying cortex. Time required to perform rhexis as well as cortical cleaving hydrodissection was more in the patients with capsulo-cortical adhesions when compared to the control group. In conclusion, a thorough preoperative dilated slitlamp evaluation should be performed to detect capsulocortical adhesions. Intraoperative evaluation also helps to detect some cases of capsulo-cortical adhesions not detected by prior slitlamp examination. Before any attempt at nucleus rotation a 3-point cortical cleaving hydrodissection as well as focal and hydrofree dissection are strongly recommended. Reccomendations Detection of Capsulo cortical adhesions is important before hydrodissection Meticulous dilated slitlamp evaluation preoperatively is mandatory Capsulo cortical adhesions may be missed in non dilating pupil or dense cataract Can be diagnosed intraoperatively even if missed initially Meticulous cortical cleaving hydrodissection in presence of Capsulo cortical adhesions Fluid injection after tenting of anterior capsule, close to capsular fornix Mechanical lysis with cannula or cyclodialysis spatula Signs of successful hydrodissection Fluid wave across the posterior capsule Shallowing of anterior chamber Prominent capsulorhexis edge Release of trapped fluid from the rhexis margin when nucleus is tapped back. In presence of equatorial adhesions, further multiquadrant hydrodissection to be done before attempting nucleus rotation. Milky fluid emanating from area of adhesionscould be result of lysis of adhesions

21 September 2009 Arup Chakrabarti et al. - CCA and PE 257 Guidelines in Patients with Capsulo cortical adhesions CCA is a frequent phenomenon and often underdiagnosed Establish diagnosis preoperatively. (caution to be exercised in total cataract/small pupils) TB staining of the anterior capsule Meticulous cortical cleaving hydrodissection. Hydrofreedissection may be beneficial No forcible nucleus rotation Capsular tension ring/injector to be kept handy Conclusion Thorough preoperative dilated slitlamp evaluation mandatory Intraoperative evaluation to detect missed cases. Increased suspicion when lens milk visualized in preoperatively undiagnosed cases. A 3 point cortical cleaving hydrodissection and hydrofree dissection to be performed before attempting nucleus rotation. References 1. Gimbel HV. Divide and conquer nucleofractis phacoemulsification: development and variations. J Cataract Refract Surg 1991; 17: Shepherd JR. In situ fracture. J Cataract Refract Surg 1990; 16: Vasavada AR, Singh R. Step-by-step chop in situ and separation of very dense cataracts. J Cataract Refract Surg 1998; 24: Gimbel HV. Hydrodissection and hydrodelineation. Int Ophthalmol Clin 1994;34(2): Fine IH. Cortical cleaving hydrodissection. J Cataract Refract Surg 1992; 18:

22 258 Kerala Journal of Ophthalmology Vol. XXI, No. 3 ORIGINAL ARTICLE Efficacy of Combining Intravitreal Bevacizumab Monotherapy (IVB) with Panretinal Photocoagulation(PRP) In Early Stages of Neovascular Glaucoma (NVG) Dr. Meena Chakrabarti MS DO DNB, Dr. Arup Chakrabarti MS, Dr. Sonia Rani John DNB Anterior Segment neovascularisation results from several ocular and systemic diseases that predispose patients to retinal hypoxia and ischemia with subsequent release of angiogenesis factors such as vascular endothelial growth factor. Bevacizumab (Avastin), a recombinant antibody against vascular endothelial growth factor (VEGF), has been shown to effectively reduce neovascular activity and vascular permeability in ocular tissues. Administration of intravitreal Bevacizumab in the early stages of neovascular glaucoma (characterized by presence of neovascularisation of iris and angle, elevated IOP by the open angle mechanism) may dampen the neovascular trigger. When combined with panretinal photocoagulation (on the same day) control of the ischemic process is ensured and further progression to advanced secondary angle closure neovascular glaucoma may be prevented. Clinical Objective: To study the efficacy of combining intravitreal Bevacizumab (Avastin) injection with same day panretinal photocoagulation in eyes with early neovascular glaucoma (Stage II, Open angle mechanism prior to development of peripheral anterior synechiae and angle closure) Chakrabarti Eye Care Centre, Kochulloor, Trivandrum tvm_meenarup@sancharnet.in Primary Outcome Measures: Regression of neovascularisation of iris, and neovascularisation of the angle were the primary outcome measures that we studied. Brief Review of Pertinent Literature: 1. Oshima et al 1 reported a series of seven eyes with neovascularisation of iris (NVI) secondary to proliferative diabetic retinopathy. The NVI regressed in all patients at one week and repeated injections stabilized the recurrence in 2 eyes that was seen 2 months after the initial injection. IOP was controlled in 6 eyes throughout the follow up period with no inflammation and complications. 2. Tripathi et al 2 have shown that patients with NVG had significantly increased levels of VEGF in the aqueous humor. They discussed the possible role of ciliary epithelium, in addition to the retina, in the production of VEGF and the complementary functions of basic fibroblast growth factor and other growth factors. 3. Davidorf et al 3 described the regression of NVI and NVA in a patient with choroidal melanoma and diabetes (treated with TTT and PRP), following intravitreal injection of Bevacizumab.

23 September 2009 Meena Chakrabarti et al. - Combination therapy in NVG Mason et al 4 proposed the use of IVB for patients with NVG, recurrent hemorrhage from NVI and for those who despite PRP develop NVI. Tube drainage procedures may be avoided by giving intravitreal Bevacizumab injection as it causes regression of iris and angle neovasularisation and better IOP control medically. 5. Iliev et al 5 described six consecutive NVG patients with refractory symptomatic elevation of IOP who received intravitreal Bevacizumab injection. A marked regression of NVI, substantial IOP reduction in 3 eyes, and symptomatic relief in all eyes were observed in 48 hrs. 6. Grisanti et al 6 described the regression of NVI in 6 eyes with PDR and NVG following intracameral injection of Bevacizumab. As early as Day 1 decrease in leakage form the iris vessels was observed by iris fluorescein angiography. No inflammation or relapse was observed at 4 weeks. 7. Avery et al 7 demonstrated the regression of retinal and iris neovascualrisation due to PDR, following the administration of IVB. 8. Vatavuk et al 8 reported regression of iris and angle neovacularisation with reduction of IOP in an eye with NVG following CRAO. 9. Luis Amselemab 9 et al have demonstrated the efficacy of using Intravitreal Bevacizumab in patients with ocular ischemic syndrome and neovascular glaucoma. Although there was regression of NVI and no recurrence on follow up, no substantial IOP lowering effect or change in vision could be demonstrated. 10. Ehlers et al evaluated the efficacy of combining intravitreal Bevacizumab and panretinal photocoagulation in the treatment of neovascular glaucoma. Their results effectively showed that combination therapy resulted in more rapid decrease of IOP,increased frequency and rapidity of regression of neovascularisation. We conducted a prospective interventional study in 38 eyes with early stage II neovascular glaucoma that underwent one of the three modes of intervention. 1) Isolated PRP (15 eyes); (2) IVB Monotherapy (12 eyes) and combined IVB and PRP ( 11 eyes) a. Inclusion Criteria: i. Presence of peripupillary neovascularisation of iris and early neovascularisation of angle ii. iii. iv. Elevated Intraocular Pressure Good fundus view H/o Laser Photocoagulation (for PDR: Proliferative Diabetic Retinopathy/: Ischemic Central Retinal Vein Occlusion) more than 3 months prior to enrolment. v. Adequately controlled systemic co.morbid conditions. The randomization for enrolment into the various treatment groups was biased in that high risk patients with a history of prior thromboembolic episodes, or coronary artery disease were advised to enroll in the PRP group (Fig. 1). Likewise patients with higher baseline IOP were enrolled into the combination group. b. 38 eyes were studied and in bilateral cases (3 patients) one eye received panretinal photocoagulation and other eye received a combination of intravitreal Bevacizumab and panretinal photocoagulation. c. Patients were age and gender matched as both groups had patients with ages ranging from years. d. There was no control group and all patients underwent one of the three methods of intervention. e. Methods of collecting patients: Patients attending our out-patient department who satisfied our inclusion criteria were included in this study. Exclusion Criteria: 1. Florid NVI and presence of Peripheral anterior synechiae (PAS.) 2. Advanced NVG 3. Corneal Changes, Hyphema, Cataract with poor fundus view

24 260 Kerala Journal of Ophthalmology Vol. XXI, No Combined IVB + PRP group: included new cases with no prior laser who presented with early NVG and untreated retinopathy. PRP I was given on the same day as the intravitreal injection and the second sitting was given on the next day. Recurrence in this group were treated by repeat IVB injection (Fig. 2) Fig. 1. Bar diagram showing distribution of cases in each group based on associated co-morbid condition Fig. 2. Showing regression of NVE, NVI and decreased leakage in fluorescein angiography in a patient with NVG following Ischemic Central Retinal Vein Occlusion Therapeutic Intervention 1. PRP alone (15 eyes): underwent either primary PRP in 2 sittings if they were unlasered or fill in additional PRP if they had already undergone laser photocoagulation previously. They were followed up at weekly intervals and at each visit the best corrected visual acuity, slit lamp examination, applanation tonometry, gonioscopy and fundus examination were performed. The regression of NVI and the time to regression, presence or absence of recurrence were carefully noted. Repeat treatment for recurrence was by additional PRP or by combining PRP with IVB. 2. IVB monotherapy (12 eyes) who had undergone prior laser photocoagulation were included in this group. Recurrences were treated by fill in PRP or repeat IVB. We evaluated the patient for any systemic adverse effects especially thromboembolic episodes or acute coronary events. Local side effects evaluated were: vitreous hemorrhage, retinal detachment, endophthalmitis and recalcitrant glaucoma. The systemic adverse effects were evaluated by a detailed history and by consultation with the treating internist. Ocular side effects were assessed by post treatment ophthalmic examination and follow up. Outcome assessments: Outcomes were assessed in all patients by (VS) and (SRJ). At each follow up visit the following evaluations were performed. 1. Best corrected visual acuity 2. Non Contact Tonometry (Pulsair, Keeler) 3. Slit lamp examination of the anterior segment. 4. Gonioscopy 5. Indirect Ophthalmoscopy The parameters assessed were regression of NVI, by slit lamp biomicroscopy and gonioscopy for regression of NVA. The IOP was measured at each follow up visit and a dilated fundus examination was performed. All the patients were followed up at weekly intervals for a period of 12 weeks,at monthly intervals for 6 months, and 4 monthly for 1 year. All 38 patients adhered to the follow up schedule. The primary treatment outcome that we assessed was for the regression of NVI Table:1 compares the effect of intervention on the primary outcome ie time to regression of NVI under the three different interventions In the PRP group the mean time to regression of NVI was / in the PRP group, /-sd 14.5 days in the IVB Group, and 14.1+/-4.7days in the combination group.comparison of the time to NVI regression under the three different interventions was least in the combined group and was statistically

25 September 2009 Meena Chakrabarti et al. - Combination therapy in NVG 261 significant.(p=o.ooo ) using the Scheffe multiple comparisons test. Effect of intervention on the secondary outcome ie control of intraocular pressure is given in Table : 2a-c. The effect of intervention in controlling IOP was seen in all the 3 groups at 2 weeks and sustained at 12 weeks. However a further IOP lowering effect was seen at 12 weeks (p=0.002) in the combination group which was statistically significant using the paired t test. Discussion 1) Effect of intervention in causing regression of NVI and reducing the time to regression was most significant in the group which received combined PRP and IVB ( p = 0.000) 2) Effect of intervention in controlling the intraocular pressure was maximum in the group which received combined PRP and IVB at both 2 wks and 12 weeks post intervention ( p=0.000 & p= 0.002) 3) Recurrence occurred in 53.3 % of patients who received PRP alone and 20% in the combined group. 4) There was also a reduced need for repeat injection in the combination group when comparing the group that received IVB monotherapy versus combination group (3.5 injection Vs 1.8 injection) b) Limitation or Inherent Bias in the study design 1) The randomization for enrollment into the various study groups was biased with respect to co- morbid conditions. High risk patients with history of prior thrombo-embolic episodes or coronary artery disease received only pan retinal laser photocoagulation. This Table 1a Comparison of Time to NVI regression under three different interventions Type of intervention Mean Time SD N F Sig. Scheffe Multiple Comparisons (days) Pair Mean Diff p PRP (A) ** 0 A &B 55.94** 0 IVB (B) A & C 93.30** 0 IVB + PRP (C) B & C 37.36** 0 Effectiveness of intervention on IOP Table 2a Effectiveness of treatment on IOP in PRP group Stage Mean IOP SD N Group mean difference paired t p BT (A) A Vs B ** 0 post 2 wk (B) A Vs C ** post 12 wk (C ) B Vs C ** : significant at 0.01 level Table 2b Effectiveness of treatment on IOP in IVB group Stage Mean SD N Group mean difference paired t p BT (A) A Vs B ** 0 post 2 wk (B) A Vs C ** post 12 wk (C ) B Vs C ** : significant at 0.01 level Table 2c Effectiveness of treatment on IOP in IVB + PRP group Stage Mean SD N Group mean difference paired t p BT (A) A Vs B ** post 2 wk (B) A Vs C ** 0 post 12 wk (C ) B Vs C ** ** : significant at 0.01 level

26 262 Kerala Journal of Ophthalmology Vol. XXI, No. 3 Table 3: Comparison with another published study Author /Year No Grade Stage of PRP PRP+IVB Regression Time to NVI Regression P value IOP P of NVI NVG Gp of NVI Control value PRP PRP+IVB PRP PRP+IVB Ehlers JP et al 23 Not men- Not men days 12 day P< P=0.03 Retina 28(5) 2008 tioned tioned P( <0.0001) Present study 38 Gr II Open angle days 14.1days P= P= glaucoma stage II group also included patients with ocular ischemic syndrome. 2) Patients who received combined PRP + IVB were newly detected cases of vascular retinopathy presenting to our centre with early NVI and did not have a history of prior laser photocoagulation. The efficacy of combining intravitreal Bevacizumab monotherapy with pan retinal photocoagulation in early neovascular glaucoma prior to secondary angle closure glaucoma alone was studied. This may not be applicable to patients with 2 0 angle closure neovascular glaucoma where prior IVB injection is necessary in association with maximal medical therapy to control the ocular inflammation & quieten the eye before laser photocoagulation. Comparison of our results with a similar study was favourable with respect to regression of neovascularisation of iris and angle and adequate control of intraocular pressure. (Table : 3) Thus combining intravitreal bevacizumab injection panretinal laser photocoagulation can be considered as a first line therapy for patients with early stage of neovascular glaucoma References 1. Oshima Y, Sakaguchi.H et al. Regression of iris neovascularisation after intravitreal injection of Bevacizumab in patients with proliferative diabetic retinopathy. Am. J. Ophthalmol 2006; 142: Tripathi RC, Li.J, Tripathi BJ, Chalam KV et al. Increased levels of vascular endothelial growth factor in the aqueous of patients with neovascular glaucoma. Ophthalmology 1998; 105: Davidorf FH, Mouser JG et al. Rapid improvement of neovasularisation and of iris from a single Bevacizumab injection. Retina 2006; 26: Mason JO, Albert MA, Mays A et al. Regression of neovascular iris vessels by intravitreal injection of Bevacizumab. Retina 2006; 26: Iliev MF, Domig D, Wolf Schnurrbursch U et al. Intravitreal Bevacizumab injection in the treatment of neovascular glaucoma. Am.J. Ophthalmol 2006; 142: Grisanti.S. Biester S, Peters.S et al for the Tuebingen Bevacizumab study group. Intracameral Bevacizumab for iris rubeosis. Am. J.Ophthalmol 2006; 142:

27 September 2009 Meena Chakrabarti et al. - Combination therapy in NVG Avery RJ. Regression of Retinal and iris neovascualarisation after intravitreal Bevacizumab treatment. Retina 2006; 26: Vatavuk Z, Bencic.G et al. Intravitreal Bevacizumab for NVG following CRAO. Eur.J.Ophthalmol 2007; 17: Luis Amselemab, Javier Montero et al. Intravitreal Bevacizumab injection in Ocular Ischemic Syndrome Am.J.Ophthalmol 2007;Vol 144(1): Ehlers J, Lam, Samuel Micheal, William Tasman et al Combination Intravitreal Bevacizumab/Pan retinal Photocoagulation versus pan retinal photocoagulation alone in the treatment of neovascular glaucoma. Retina 2008; 28(5):

28 264 Kerala Journal of Ophthalmology Vol. XXI, No. 3 ORIGINAL ARTICLE Ophthalmic Manifestations in Children with Delayed Milestones- A Clinical Study Dr. Reena A. MS, Dr. Lekshmy S R MS, Dr. Lekshmi H MS, Dr. Bindu K. Appukuttan MS ABSTRACT A cross -sectional study of 150 children aged between 6 months and 3 years with delayed developmental milestones was conducted at Child Development Centre, Sri Avittam Thirunal Hospital and Regional Institute of Ophthalmology,Trivandrum over a period of 18 months.the study aimed at identifying the various ocular manifestations in children with developmental delay,the treatable causes of visual handicap among them and the associated antenatal and perinatal factors. A complete systemic examination in consultation with a paediatrician and a detailed ophthalmic evaluation including assessment of refraction was performed.the collected data was analysed by statistical methods. CONCLUSIONS :Ocular manifestations were present in 64 % of selected children. Refractive errors( 41.3 %), Stabismus (40 %) & Optic Atrophy(9.3 %)were identified as the major causes of visual impairment.the chief treatable causes were Refractive errors(41.3 %), Squint(40 %), Cataract (2.6 %) and Retinopathy of Prematurity(4 %).Visual impairment and ocular manifestations like squint and optic atrophy were more in children with global developmental delay.the importance of ophthalmological examination in children with developmental delay was highlighted in the study. Introduction Development delay is estimated to be present in about 10% of pediatric population. Development may be impaired due to a variety of factors like maternal, genetic, perinatal, post-natal and social factors. Visual development is a highly complex maturation process involving structural and functional changes in both the eye and the CNS.The burden of visual handicap in childhood especially in a child with developmental delay is of enormous importance because of the life long impact of the handicap on other areas of development. Early recognition of the problem may expedite treatment or other forms of management where the condition is not treatable. Developmental Regional Institute of Ophthalmology, Trivandrum delay may be associated with delayed visual maturation where infants fail to develop fixation for upto 6-12 months but may later develop normal visual behaviour. These children may have a totally normal eye but have poor fixation due to the delay in maturation of the visual system. In these cases, supportive treatment and reassurance is required until the visual attention becomes as expected. Aim of the Study To study the various ocular manifestations in children with delayed milestones. To find out the treatable causes of visual handicap in these children.

29 September 2009 Reena A. et al. - Ophthalmic manifestations in children with developmental delay 265 To study antenatal and postnatal factors in these children. To study type of developmental delay whether isolated or global delay. To highlight the importance of detailed ophthalmic examination in children with developmental delay. Materials and Methods Study Design StudySetting Sample size Study period : Cross Sectional Study : Child Development Centre, SAT Hospital, Medical College, Trivandrum, and Regional Institute of Ophthalmology, Trivandrum : 150 (calculated based on prevalance of Developmental Delay in South Kerala) : 18 months Study Population : Children between 6 months and 3 years with delayed developmental milestones language milestones or in all the four areas, ie, global developmental delay. In children <1year, visual acuity was assessed by CSM method of fixation pattern and by indirect methods like assessing the red reflex and resistance to occlusion. Candy Bead test was used to assess visual acuity in 1-2 year age group or alternatively by CSM method if needed. Sheridan Letter test was used in 2-3 year age group. Additional investigations including baseline blood investigations were done if indicated. Children detected to have ocular features were managed accordingly. Children who were found to have visual acuity inappropriate for age or who were not fixing and following despite normal ocular examination were followed up after 6 months to see if there was any improvement in visual acuity. Data collected was then subjected to thorough descriptive statistical analysis. Proportions of all relevant study variables were calculated; such as demographic variables, clinical variables such as antenatal illnesses in others, mode of delivery of the babies, neonatal illnesses, neonatal oxygen administration, types of developmental delay, refractive errors, squint, nystagmus, optic atrophy, delayed visual maturation, cortical visual impairment Retinopathy of Prematurity, papilloedema Methodology A cross- sectional study of 150 children between 6 months and 3 years of age with delayed developmental milestones attending Child Development Centre, SAT Hospital, Trivandrum and RIO, Trivandrum was conducted. Proforma was prepared for recording data of each patient separately. General examination including systemic examination in consultation with a pediatrician & ophthalmic examination consisting of visual acuity assessment, anterior segment examination, dilated fundus examination & retinoscopy were done. Developmental delay was assessed by Denver Development Screening Test. The milestones were assessed in terms of Personal Social, Gross Motor, Fine Motor and Language. Children who did not achieve milestones by the indicated ages were considered to have developmental delay. Delay may be present in either social, gross motor, fine motor or Results Sex Distribution Of the 150 children with developmental delay included in study, 83 were males and 67 females. Age Distribution Children < 3 years were included in study.among them 65 were between 6 months-1year,45 were between 1-2 years and 40 in 2-3 year age group. Consanguinity History of consanguinity was present only in 4 cases while the remaining 146 were nonconsanguinous. Antenatal Period Antenatal period was uneventful in 133 mothers, Pregnancy Induced Hypertension (PIH) was present in 5, fever with rashes in 5, 3 had history of trauma, 2 had Gestational Diabetes Mellitus and 2 had history of threatened abortion.

30 266 Kerala Journal of Ophthalmology Vol. XXI, No. 3 Delivery 125 were full term and 25 were preterm. Caesarian section was mode of delivery in 23,vacuum assisted in 2 while 125 had normal vaginal delivery. Table 1 Postnatal Period Post Natal Period YES NO Neonatal Jaundice Birth Asphyxia Oxygen administration Seizures Type of Developmental Delay Out of the 150 children, 53(36 %) showed global delay, 45(30 %) had only motor delay, 33(22 %) had delay in motor as well as language milestones, 14(9 %) had isolated language delay and 5 children (3 %) showed delay in motor & personal social milestones. Ocular Manifestations Table 2. Ocular Manifestations Number of Cases Percentage (%) Ocular manifestations Normal but poor VA Normal with good VA Of the total 150 children with developmental delay, 97 (64.6 %) had ocular manifestation, whereas 29 (19.4 %) had normal ocular examination and good visual acuity, whereas 24 (16 %) had normal ocular examination but were not fixing and following light or had poor visual acuity [Table 2]. Distribution of Ocular Manifestations The various ocular manifestations seen in children with developmental delay are refractive errors, squint, optic atrophy, delayed visual maturation, cortical visual impairment, retinopathy of prematurity, papilloedema, nystagmus, and cataract. (Fig. 1) Fig. 1. Aetiologic Classification Visual Acuity Assessment [Table 3] Table 3 Visual Acuity Assessment Visual Acuity Number of Cases By CSM method NFNF 25 GEF 1 UCF 24 CSF 16 CSF-MP 16 CSM 13 By Sheridan Letter Test 6/60-6/36 3 6/24-6/18 2 6/12-6/6 30 Refractive Errors Refractive Errors(seen in 41.3 %)) were the most common manifestation in these children on retinoscopy. 27 children had significant hypermetropia (>+3D) 18 had myopia and 17 showed astigmatism. Squint [Table 4] Table 4. Stabismus Exotropia 90(60 %) Esotropia 19(13 % ) Latent 39(26 % ) Hypertropia 2(1 % )

31 September 2009 Reena A. et al. - Ophthalmic manifestations in children with developmental delay 267 Delayed Visual Maturation 24 children who had visual acuity inappropriate for age or were not fixing or following light despite normal ocular examination were followed up after 6 months to look for any improvement.it was seen that 15 of them showed some improvement in visual acuity while it remained status quo or worsened in 9 cases. Vison and Delayed Milestones Severe visual impairment (< 6/60) and majority of ocular manifestations like squint and optic atrophy were seen more in children with global developmental delay. Fig. 2. Treatable Causes Table 5 Delayed Milestones and Ocular Manifestations POOR VISION SQUINT OPTIC ATROPHY GLOBAL MOTOR + SPEECH MOTOR MOTOR + SOCIAL 2 3 SPEECH 1 4 Treatable Causes of Visual Disability Among the various ocular manifestations, the various treatable causes identified were refractive errors (41.3 %), Squint (40 %), ROP (4 %) and cataract (2.6 %) (Fig 2) Discussion Of the total 150 children with developmental delay examined at CDC and RIO Trivandrum,97(64.6 %) had ocular manifestations.a study by Wu H J etal on 41 children with developmental delay showed ocular manifestations in 56.1%. Lagunju et al studied 149 cases of cerebral palsy alone and found ocular abnormalities in 28 %. Regarding the sex distribution, 55 % in this study were males and rest 45 % were females. In study by Wu H.J et al 68 % were males and rest females. Mean age range 1.58+/-0.9 years.in Wu H J et al study mean age range was 3.53+/-2.25 years. 3,6 Consanguinity was seen in only 2.7 %. Antenatal history was uneventful in 133 cases whereas 17 cases had either history of pregnancy induced hypertension, gestational diabetes, trauma, threatened abortion or maternal infections. History of pre-term delivery was present in only 25 cases.in a study by Chen et. al % had pre-term delivery and % had neonatal insults. In the post natal period, history of neonatal jaundice was present in 7 cases (4.7 %), birth asphyxia in 25 cases (16 %), oxygen delivery in 12 cases (8 %) and seizures in 19 cases (12.6 %). In a study by Nielson et. al, it was found that visual impairment was due to prenatal factors in 11 %, perinatal factors in 6 % and postnatal in 1.4 %. 7,4 On assessing developmental delay, 36 % of cases showed global delay, 30 % only motor delay, 22 % both motor and language delay, 9 % isolated language delay and 3 % showed delay in both motor and social milestones. In the study by Chen et. al, 51.2 % had global delay, 21.9 % had speech delay and had motor delay. 7 In this study ocular manifestations were seen in 64.6 % cases. On examining 150 children, refractive errors were seen in 62 cases (41.3 %), strabismus in 60 cases (40 %), optic atrophy in 14 cases (9.3 %), ROP in 6 cases (4 %), cortical visual impairment in 9 cases (6 %), nystagmus in 7 cases (4.6 %), cataract in 4 cases (2.6 %), papilloedema in 1 case and delayed visual maturation in 15 cases (10 %). In a study by Wu H J, Tsai et al, optic atrophy and strabismus were the two most common manifestations. Bankes et al studied 200 children with developmental delay & found refractive errors in 49 %,squint in 37 %, nystagmus in 7.5 % and other features like cataract,optic atrophy and retinopathy. 3,5 Refractive Errors(41.3 %) were the most common manifestation in this study of which 18 % had significant hypermetropia (> +3D) 12 % had myopia

32 268 Kerala Journal of Ophthalmology Vol. XXI, No. 3 and 11 % astigmatism. In a similar study by Nielson et al, 15.3 % had hyperopia>+3d, 10.8 % were myopic and 20.6 % had astigmatism. 4 On assessing Visual Acuity severe visual impairment (<6/60) was seen in 51 cases(34.6 %) Lagunju et al studied 149 Cerebral palsy cases and found that 61.9 % were completely blind.fazzi et al found that prevalence of reduced vision in children with CNS damage was about 86.7%. 6, 8 29 children (19.4 %) had normal ocular examination and good visual acuity while 24(16 %)had normal ocular examination but had poor vision or were not fixing or following light.these children were followed up after 6 months.on follow up,15 cases showed improvement in visual acuity whereas 9 cases showed no improvement. On analyzing the severity of developmental delay and ocular manifestations, it is found that poor vision (ie inability to fix and follow or unsteady fixation) was seen in 27 children with global delay and majority of ocular manifestations like squint (28 cases) and optic atrophy (12 cases) were seen in children with global developmental delay. In a study by Nielson et al, it was found that refractive errors and squint correlated with the level of IQ 4 Conclusions Of the 150 children with developmental delay examined at Regional Institute of Ophthalmology and Child Development Centre, SAT Hospital, Trivandrum,over a period of 18 months, 97 children (64.6 %) had ocular manifestations. Most common mode of presentation was that the child was not looking at objects. In this study, Refractive errors (41.3 %) was the major cause of visual impairment,followed by squint (40 %) and optic atrophy (9.3 %). 10% children showed delay in visual maturation. Visual impairment and ocular manifestations like Squint and Optic Atrophy were more in children with Global Developmental Delay. The major treatable causes were Refractive errors (41.3 %), Squint (40 %), Cataract (2.6 %) and Retinopathy of Prematurity (4 %). Consanguinity was present in 3 % cases. Antenatal risk factors were identified in 10 % cases. They were Pregnancy induced Hypertension (3 %),Fever with rash (3 %), Trauma (2 %), Gestational Diabetes (1 %) and Threatened abortion (1 %). There was history of Preterm delivery in 17 %, Birth Asphyxia in 16.7 %, Neonatal seizures in 12.6 %,history of Oxygen administration in 8 % and Neonatal jaundice in 4.7 % Global Developmental Delay was seen in 36 % children,whereas 30 % showed delay in motor development, 9 % showed delay in language and 22 % showed delay in both motor and language development. A full ophthalmic examination should be an essential part of evaluation of all children with developmental delay even when no gross ocular abnormalities are noticed by the attending Paediatrician. Early identification of such defects may prove crucial in institution of therapy in all cases which are amenable to treatment. Delayed visual maturation is closely associated with developmental delay. Occasionally infants fail to develop visual fixation for upto 6-12 months but develop normal visual behaviour at a later stage. Supportive treatment and reassurance is vital in such cases. References 1. O.P.Ghai,Essential Paediatrics-5 th edition Chap1 pg Uemura Y, Agucci Y, visual developmental delay, Ophthalmol pediatric Genet 1981; 1: Wu H.J Tsai R K,Dept of Ophthalmology,Kaohsing University, Taiwan, Kaohsing J Med Sci2000 Aug 16(8) Neilson LS, Skov L, Jensen H, University of Copenhagen, Acta Ophthalmol Scand 2007 Mar 85(12) Bankes et al Child health dev 1975 Sep-Oct; 1(5) Lagunju I.A et al Dept of Paediatrics University College Hospital, Nigeria Afr J Med Sci 2007 Mar; 36(1): Chan Gu. Chen IC, Chen CL, Wong MK,Chung CY, Dept of Rehabilitation Chang Gung Memorial hospital Taipei, Taiwan, ROC. Med J, 2002 Nov; 25(11) Spectrum of visual disorders in children with cerebral visual impairment. Fazzi E, Signorini SG, Bova SM,

33 September 2009 Reena A. et al. - Ophthalmic manifestations in children with developmental delay 269 La Piana. Dept of Child Neurology and psychiatry, IRCCS C. Mondino Institute of Neurology, University of Pavia, Italy. 9. Dev Med Child Neurol.1991 Feb ;33(2):181 Delayed visual maturation: ophthalmic and neurodevelopmental aspects. Tresidder J.Fielder AR,Nicholson J.University of Leicester. 10. Br J Ophthalmol Jan;66(1)46-52.Visual disorders associated with cerebral palsy.black P 11. Br J Ophthalmol May; 83(5): Risk factors for strabismus in children born before 32 weeks gestation. Pennefather PM, Clarke MP. Strong NP, Dutton J, Dept of ophthalmology, Royal Victoria Infirmary, Newcastle. 12. Trans Ophthalmol Soc UK.1985;104(Pt 6): Delayed visual maturation.fielder AR,Russell-EggittIR, Dodd KL, MellorDH. 13. Ocular Abnormalities associated with cerebral palsy after pre term birth. Pennefather PM, Tin W. Department of Ophthalmology, Royal Victoria Infirmary, New Castle 14. Peadiatric Ophthalmology and Strabismus-Kenneth W. Wright Chap 9, Pg Sondhi N. Archer S.M, Helveston E.M: Development of normal ocular alignment. J Pediatric ophthalmol Strabismus 25; , Teller D.Y, Mc Donald N, Visual Acuity in Infants and children the acuity card procedure. 17. Cole G. F.Jones RD, Delayed visual maturation. Arch Dis child 1984; 59: Lambert S.R, Kriss A, Taylor D, Delayed visual maturation Ophthalmol 1989;96: Fern K.D and Manney R.E Visual Acuity of pre school children : a review Am J Ophtalm, physio optics 63; , Paedriatic Ophthalmology Current aspects-kennith Wyaber and David Taylor 21. Visual Behaviours and Adaptations Associated with Cortical and Ocular Impairment in Children ; Jan, J.E; Groenveld, M; Journal of Visual Impairmnet and Blindness, April 1993, American Foundation for the Blind.

34 270 Kerala Journal of Ophthalmology Vol. XXI, No. 3 ORIGINAL ARTICLE An Outcome Analysis of Posterior Capsular Rent (PCR) In The Hands of A Senior Phaco Surgeon Dr. Arup Chakrabarti MS, Dr. Meena Chakrabarti MS DNB, Dr. Sonia Rani John DNB, Dr. Valsa Stephen MS DO Introduction Posterior capsular rent is a common complication of cataract surgery including phacoemulsification. Though occurrence is higher with beginners, it can also occur in the hands of a senior phaco surgeon. This study analyses the predisposing risk factors, intraoperative events, mode of occurrence, management strategy and eventual outcome of Posterior capsular rent during phacoemulsification by a senior cataract surgeon. Materials and Methods This was a retrospective review of 8 consecutive patients who developed posterior capsular rent with or without vitreous disturbance during phacoemulsification over a period of 36 months from Dec 2005 to Dec Posterior capsular rent was defined as an unintended iatrogenic break in the posterior capsule occurring during any stage of phacoemulsification cataract surgery. Patients with zonular dialysis or preexisting posterior capsular rent were excluded from this study. Records of the patient and then surgical video tapes were reviewed to accumulate data concerning the nature, cause, surgical management and outcome of the surgery. All surgeries were done by a single surgeon using the Bausch and Lomb Millennium surgical unit. Preoperative work up and preparations were routine. All surgeries were done under topical or peribulbar Chakrabarti Eye Care Centre, Kochulloor, Trivandrum tvm_meenarup@sancharnet.in anesthesia. Direct chop or Stop and Chop were the standard phaco techniques employed. In the event of a posterior capsular rent, a stable anterior chamber was maintained and if vitreous presented, an automated anterior vitrectomy was performed by a dry or bimanual technique. Triamcinolone acetonide staining of the vitreous was used whenever appropriate. The data analyzed from the case sheets and videos were : patient profile, associated clinical features including predisposing risk factors if any, surgical details, and intraoperative events leading to posterior capsular rent, management of the posterior capsular rent as well as the postoperative outcome. Results Of the 8 patients who developed posterior capsular rent, 6 were females (75 %) and 2 were males (25 %). (Table 1). The mean age group was 72.4 yrs (Range yrs). 6 of the 8 patients (75 %) had hard cataract (Grade 4 nuclear sclerosis). One patient had an intumescent cataract, 1 had pseudoexfoliation and one had undergone parsplana vitrectomy. In 3 patients visibility was poor, due to poor mydriasis in 2 and corneal opacity in 1 (Table 2) (Fig. 1). In 6 patients, a clear corneal incision was used. In 2 patients a scleral tunnel incision and in 1 patient the incision had to be extended. In the post parsplana vitrectomy cataract, posterior capsular rent occurred during the end stage of phaco.

35 September 2009 A. Chakrabarti et al - Outcome of PCR 271 Table 1: Sex Distribution Male Female Total No % 25 % 75 % 100 % Table 2: Associated factors Associated Factors No Hard cataract 6 Intumescent cataract 1 Pseudoexfoliation 1 Post PPV 1 Corneal Opacity 1 Traumatic 1 Steps of Phaco No End stage of Phaco 6 I / A 2 Fig. 2. Triamcinolone assisted anterior vitrectomy Fig. 3. Dry Vitrectomy In the intumescent cataract, extension of the capsulorhexis resulted in posterior capsular rent. Thus, in a total of 6 cases posterior capsular rent occurred at the end stage of phacoemulsification. Two cases had an incomplete capsulorhexis with posterior capsular rent occurring during irrigation / aspiration (Table 3). In one case nucleus drop occurred requiring parsplana vitrectomy. Anterior vitrectomy was required in 5 cases. IOL could be inserted in the capsular bag in one case while 6 received PCIOL in the sulcus. 1 eye was left aphakic. Additional surgical procedures performed included triamcinolone acetonide (Fig 2) staining of the prolapsed vitreous to facilitate anterior vitrectomy in 4 cases, bimanual anterior vitrectomy in 5 dry Fig. 4 (a) Intraoperative still photographs of PC rent Fig 4b. Postoperative anterior segment photographs showing well centred PC I0L vitrectomy (Fig 3), residual cortex aspiration with 26 gauge cannula in 8 and posterior capsulorhexis in 2. Fig. 1. Preoperative Findings All patients were evaluated on the same day of surgery, at 1 week, 2 weeks and 2 months postoperatively. Refraction was done at the 2 nd week postoperatively. On the first postoperative review 4 patients had raised intraocular pressure which resolved in one week with routine single topical antiglaucoma medication. Only one patient required systemic antiglaucoma medication. 4 patients had moderate corneal edema and 2 had mild corneal edema which resolved by the second postoperative week. 75 % of the patients regained best corrected visual acuity of 6/12 or more of which 83 %

36 272 Kerala Journal of Ophthalmology Vol. XXI, No. 3 had vision of 6/9 or more Fig 4 a & b. One patient who had nucleus drop had a vision of less than 6/ 60 which could be attributed to the preexisting corneal opacity. Discussion Posterior capsular rent during phacoemulsification cataract surgery remains an important complication because it may lead to poor visual outcome. Posterior capsular rent though more common in beginners can also occur in the hands of the most experienced of surgeons. In our study, posterior capsular rent was seen to occur in association with certain risk factors especially with hard cataract, intumescent cataracts, in the presence of pseudoexfoliation and when there was poor visibility. In uncomplicated routine cases no posterior capsular rent occurred. Posterior capsular rent was found to occur during Irrigation Aspiration and end stage of phaco surgery in our study. Studies show that posterior capsular rent is rarer in the initial stages (capsulorhexis, hydrodissection) and mostly appears in the middle and final stages (phacoemulsification, Irrigation Aspiration, IOL implantation and posterior capsular polishing) 1,2 Gimbel et al 3 reported that posterior capsular rent arose most frequently during phacoemulsification. While Bast et al 4 reported 72 % occurred during Irrigation Aspiration. Taskapiliet al 5 reported that posterior capsular rent most frequently occurs during phacoemulsification in % followed by Irrigation Aspiration in 28.8 %. Corneal edema is the most frequent cause of reduced vision in the early postoperative period. This is generally temporary. Varying rates of corneal edema ranging from % had been reported 4, 5 6, 7. High postoperative IOP is another complication reported in patients with posterior capsular rent. Viscoelastic material remaining in the anterior chamber, preoperative glaucoma, trabecular blockage by dispersed lens particle and iris pigments and mechanical damage in the trabecular meshwork may lead to this postoperative event. In our study 50 % developed raised IOP compared to other studies which reported 4, 6, percent The most serious complication of posterior capsule rent is retinal detachment. Rates of up to 3.57 percent have been reported 4, 5, 6, 7. In our study no patient developed retinal detachment during the followup period. Cystoid macular edema is another complication of posterior capsular rent which can cause decreased visual acuity. Its incidence varies from 7.86 percent percent in different studies 6, 7, 8. In our study no patient developed cystoid macular edema. This may be due to proper management of posterior capsular rent minimizing the vitreous loss. There may have been cases of cystoid macular edema in our series which eventually resolved without being diagnosed clinically. With proper and timely management, the final visual acuity of our patients were comparable with those in other reports which cite 95 % of cases achieved 6 /12 or better visual acuity 3, 7,9, % of our patients had a visual acuity of 6/12 or more of which 83% had vision of 6/9 or more. Thus, when properly managed a torn posterior capsule is compatible with an excellent visual outcome. Early Recognition of Zonular or Posterior Capsular Rupture If a posterior capsular tear is not recognized in time, subsequent intraocular maneuvers required for phacoemulsification (viz. nuclear rotation, sculpting, cracking) and fluctuations in anterior chamber depth will quickly enlarge the size of the tear. The risks of vitreous loss and dropped nucleus increase, longer the rupture goes unrecognized. Early recognition of a posterior capsular tear and prompt prophylactic measures 5 will prevent expansion of the tear size 5,6. Signs of early posterior capsular tear or zonular dehiscence 6 include the following 10. Sudden deepening of the anterior chamber with momentary dilatation of the pupil. Sudden transitory appearance of a clear red reflex peripherally Newly apparent inability to rotate a previously mobile nucleus Excessive lateral mobility or displacement of the nucleus and loss of nucleus followability.

37 September 2009 A. Chakrabarti et al - Outcome of PCR 273 Excessive tipping of one pole of the nucleus Partial descent of the nucleus into the anterior vitreous space Early recognition of a posterior capsular rent and proper management ensures excellent visual outcomes. References 1. Corey RP, Olson RJ. Surgical outcomes of cataract extracts performed by residents using phacoemulsification. J Cataract refract Surg : Ota I, Miyake S, Miyake K dislocation of the lens nucleus into the vitreous cavity after hydrodissection. Am J Ophthalmol : Gimbel HV, Sun R, Ferensowicz et al. Intra Operative management of posterior capsular tears in phacoemulsification and intraocular lens implantation. Ophthalmology : Basti S, Garg P, Reddy MK. Posterior capsular dehisions during phacoemulsification and manual extra capsular extraction: comparison of outcomes J Cataract Refract Surg 2003; 29: Taskpili M, Engin G, Kaya G et al.single piece foldable acrylic intraocular lens implantation in the sulcus in eyes with posterior capsule tear during phacoemulsification. J Cataract Refract Surg 2005; 31: Brazitikos DP, Balidis MO, Tranos P et al Sulcus implantation three piece 6mm optic, hydrophobic, foldable acrylic intraocular lens in phacoemulsification complicated by posterior capsule tear. J Cataract Refract Surg 2002;28: Yap-E-Y, Heng W J, Visual outcome and complication after posterior capsule rupture during phacoemulsification surgery. Int Ophthalmol ;23: Cruz OA, Wallace GW, Gay CA et al. Visual results and complications of phacoemulsification with intraocular lens implantation performed by ophthalmology residents. Ophthalmology 1992: 99: Chan FM, Mathur R, Ku JJK et al. Short term outcomes in eyes with posterior capsule rupture during cataract surgery. J Cataract Refract Surg 2003;29: Blomquist PH, Rugwani RM. Visual outcomes after vitreous loss during cataract surgery performed by residents. J Cataract Refract Surg 2002;28:

38 274 Kerala Journal of Ophthalmology Vol. XXI, No. 3 OPHTHALMIC SURGERY Lens Surgery in Marfan s syndrome Dr. Somdutt Prasad MS FRCSEd FRCOphth FACS Introduction: Management of the subluxed lens in Marfan s syndrome presents one of the most challenging situations in contemporary lens surgery. Conventional approaches have included intracapsular lens extraction or a pars plana lensectomy with vitrectomy. Once the lens was removed, aphakia was corrected by glasses, contact lenses or an iris or angle supported anterior chamber IOL or a scleral sutured posterior chamber IOL. Marfan s syndrome patients are known to have an increased risk of glaucoma as well as retinal detachment (upto 11 % of patients with Marfan syndrome, and 8 38 % in those who have dislocation of the lens or have undergone lens surgery) 1. Accordingly, anterior chamber implants are best avoided in this setting and a surgical approach which preserves the capsular bag and avoids disruption of the vitreous, will, at least potentially, reduce the risk of retinal detachment subsequently. Considerations in the surgical approach: Ideally one wants to achieve lens extraction through a continuous capsulorrhexis with preservation of the capsular bag, re-center the bag and secure it using a scleral fixation device and place an in-the-bag IOL, without disrupting the vitreous body. The anticipated challenges in these cases include: i) Systemic considerations: These patients need a full systemic workup, as they have associated features of Marfan s which may increase the risk for an anaesthetic. They may have aortic arch or Arrowe Park Hospital, Wirral University Teaching Hospitals, NHS Foundation Trust, Wirral, United Kingdom, sprasad@rcsed.ac.uk ii) valve anamolies or indeed have had heart valve surgery already, in which case they may be on Warfarin. Biometry: Eyes with severely subluxed lenses need careful biometry to achieve a good refractive outcome. Remember that the refraction is influenced by the lens subluxation and may not correlate with the predicted IOL power. iii) Achieving a central curvilinear capsulorrhexis: This is difficult because the lens is unstable, the outward pull provided by the zonules is uneven and the young patients capsule is much more elastic than the adult, leading to a tendency for the tear to run out. iv) Preserving the capsular bag: Even when a satisfactory capsulorrhexis has been achieved, the game is not over. The bag of the Marfan s patient may sometimes be smaller than that of the normal eye leading to an increased risk of tear or rip during implantation of devices to support and recentre it 2. v) Achieve lens extraction, bag re-centration and fixation and IOL implantation without disrupting the anterior vitreous face. vi) Deploy techniques which reduce the risk of late complications: posterior capsular opacification and subluxation/dislocation of the IOL capsular bag complex. (1) Possible surgical strategies In any difficult surgical situation experts will often use different approaches to achieve the same end. For

39 September 2009 Somdutt Prasad et al. - Lens surgery in Marfan s syndrome 275 Fig. 1. The Modified Capsular Tension Ring or the Cionni Ring (mctr) Fig. 2. The Capsular Tension Segment or Ahmed Segment (CTS) subluxed lenses in Marfan s patients, possible strategies mainly follow one of two broad approaches. One may choose to sacrifice the capsular bag, clear the anterior chamber of all vitreous and then implant an intraocular lens. Lens extraction can be done by an anterior or pars plana approach if this strategy is chosen. A pars plana approach has the advantage of allowing a thorough vitrectomy along with a full internal search of the peripheral retina. Whilst a complete vitrectomy is appealing in this setting, as it would eliminate any future vitreo-retinal traction, it is technically quite difficult to induce a posterior vitreous separation in a young patient, and attempts to achieve this may actually induce retinal tears during surgery. Because of this a deep anterior vitrectomy may be preferable. An IOL can then be implanted in the anterior chamber. Anterior chamber IOLs, open loop 2,3 or iris fixated (Artisan) 5 are simple and efficient techniques, but risks include iritis, pigment dispersion, corectopia, glaucoma, and endothelial loss. Because of these potential problems many surgeons choose to implant a posterior chamber lens in the ciliary sulcus, fixated by trans scleral sutures 6. To avoid the risk of future suture breakage leading to subluxation or dislocation of the IOL and to achieve better centration, the elegant technique of sutureless intrascleral posterior chamber fixation has been developed 7,8. Techniques which preserve the capsular bag are intellectually more appealing, especially if the bag can be re-centred and secured with an in-the-bag IOL implanted. If all this can be achieved without disrupting the vitreous body, then (at least theoretically), the risk of complications like future retinal detachment can be reduced. A capsular tension ring (CTR) can be used to stabilise the capsular bag. However, CTR implantation in eyes with a subluxated lens does not correct capsular bag decentration 9. Lam and co authors overcame this obstacle by implanting a CTR and then suturing it and the capsular bag to the sclera to improve capsule centration 10. However passing sutures through the Fig. 3. Use of the mctr (a) a subluxed lens with temporal zonular loss (right in picture) has capsulorrhexis supported by two iris retractors. The bag is thus satbilised allowing completion of phacoemulsification. (b) The mctr with a double armed 9-0 prolene passed through its central islet is placed into the capsular bag, the anteriorly displaced central segment is positioned in front of the rhexis by a dialling hook, whilst a second instrument is poised to guide the trailing end in. (c) The CIF-4 (Ethicon) needles are passed behind the iris, but in front of the anterior capsule to emerge 1.5 mm behind the limbus under a previously prepared scleral flap. This secures the mctr and the Prolene knot is covered by the scleral flap. A secure in-the-bag IOL is then placed.

40 276 Kerala Journal of Ophthalmology Vol. XXI, No. 3 capsular bag risks tearing it, and therefore may not be advisable. Cionni proposed the use of a modified (Fig.1) capsular tension ring (mctr), as this device avoided the need to pass sutures through the capsular bag 11. Ahmed introduced the capsular tension segment (CTS), this smaller device is much easier to manouvre into the bag and position as required 12 and avoids the risk of over stretching or tearing the unstable bag. (Fig.1) (2) Preferred surgical technique: For many surgeons today, the preferred approach is to go for a technique which preserves and re-centres the capsular bag, allowing in-the-bag implantation and fixation of the bag to the ciliary sulcus using a combination of a CTR and a CTS.(Fig.3 a - c) The first thing to note is that the work up to surgery in such a case has to be meticulous, involving liaison with all the physicians involved in the patients care and the anaesthetist, so that a safe general anaesthetic can be administered. Biometry presents some unique challenges in patients with Marfan s syndrome. One of the most important factors to consider when doing the biometry is which section the axial length measurement is taken through, i.e. the phakic or aphakic portion and then adjusting your instrument accordingly, to take into account the presence or absence of lens material. Depending on the extent of the subluxation you may need to consider dilating the patient in order to ensure you are definitely aiming the beam through the correct portion. If using the A-Scan ultrasound to measure axial length, you will be able to confirm the position of the probe by looking for the echo corresponding to the presence of the lens boundaries. Using a case of Marfan s as an illustrative example: A 13 year old had bilateral subluxed lenses had an undilated refraction of R:-30.00/+6.00x115 L: /+5.00x60. When dilated and using his aphakic portion his refraction was R:+8.00/+3.50x120 L:+9.00/+2.50x80 achieving the same level of vision with both prescriptions. His phakic axial length was RE:26.49, LE:26.01 and aphakic axial length RE:26.36, LE: As you would expect the measurement should be comparable regardless of which portion it s taken through, if the instrument is correctly programmed. The left eye was operated on using this measurement and has a deviated post-operative spherical equivalent of -0.68DS. The lens chosen should be a 3 piece lens with a 360 degree square edge, This reduces the risk of postopeartive posterior capsule opacification and the 3 piece designs allows for resturing into the scleral sulcus, should late breakage of the suture lead to IOL displacement in future years 13, 14. I prefer a B&L (Bausch & Lomb) L161AO which is a 3 piece lens with a 360 degree square edge and an aspheric design. The Sofport injection system, used for injecting this lens allows it to come out into the capsular bag in a fairly flat disposition, minimising the potential for destabilising an already unstable bag during IOL implantation. An illustrative case described below is used to demonstrate the steps in the technique. Surgery is usually done under a general anaesthetic. (3) Case Presentation A 12 year old boy with known Marfan s syndrome was referred by a paediatric ophthalmologist who had been seeing him from the age of two years. He had managed reasonably with spectacle correction, maintaining good vision in both eyes. More recently the subluxation in the right eye had progressed to the point that his vision was reduced to 6/24 (BCVA). On presentation his vision was 6/24 in the right eye ( DS / DC x 92 ½ and 6/9+3 in the left eye (-3.00 DS / DC x 95). In addition he was being bullied at school and children kept stealing his glasses. Systemic workup included aortic valve problems for which he was on Atenolol and antenatal hydronephrosis both of which were being managed by appropriate specialists. On examination the right lens was subluxed markedly with edge of the lens passing through the centre of the pupil and the left lens subluxed to a lesser extent. Rest of the eye examination was unremarkable with normal intraocular pressures, no vitreous in the anterior chamber and normal peripheral retinal examination. Axial length measurements through the phakic portion was RE: 25.50, LE:21.46 and through the aphakic portion RE:25.29, LE: Using the aphakic measurement we calculated a Diopter B&L (Bausch & Lomb) L161AO IOL for emmetropia when implanted into the capsular bag Figure 4a shows the pre-operative situation, with a subluxed and decentred lens. A fornix based conjunctival flap is made in the zone of maximum

41 September 2009 Somdutt Prasad et al. - Lens surgery in Marfan s syndrome 277 subluxation, followed by the creation of a partial thickness scleral flap with its base towards the fornix. The scleral dissection begins at the limbus and extends peripherally for about 3mm. It is 4 mm wide (Fig 4b). Two paracentecis incisions are made on either side of this scleral flap and flexible iris retractors are prepositioned to support the capsulorrhexis as it is later developed (Fig. 4c). Fig. 4a Fig. 4b The capsulorrhexis is begun close to the iris edge at 12 o clock as this is the centre of the lens (Fig 5a). Viscoat is used to fill the anterior chamber and tamponade the vitreous face. The capsulorrhexis is developed, taking care to keep a 3 mm distance from the lens equator (this facilitates later placement of CTR and CTS; an adequate anterior capsule is necessary to avoid the CTR or CTS flipping forward, out of the bag and into the anterior chamber later in the operation.). The tear is developed a few mm beyond the area where the iris retractor is poised to engage it, and once the tear is well clear, the iris retractor is used to engage the edge of the rhexis and gently draw the lens equator out to the periphery thus helping to re-centre the capsular bag. The rhexis is developed further and the second iris hook engaged and drawn centripetally further re-centres the capsular bag allowing the superior part of the capsule to come into view (Fig 5b). The rhexis can then be completed. Gentle hydrodissection, with small slow waves of fluid is then done. Fig. 5a Fig. 4c Fig. 5b A CTR is then inserted into the bag to stretch it (Fig 6a), and thus allow phacoemulsification without the bag flopping onto the probe, as is possible in a largely unsupported bag. Once lens matter has been removed a CTS with a 9-0 prolene on a double armed Ethicon CIF-4 needle passed through the central islet is guided into the capsular bag (Fig 6b). The IOL is then implanted into the capsular bag (Fig 6c) and the needles are passed in front of the anterior capsule but behind the iris to emerge about 1.5 mm behind the limbus under the previously designed scleral flap. The iris retractors are then released allowing the surgeon to judge the position of the capsular bag better. The suture is tightened (Fig 7) and incisions sutured after removing viscoelastic. Intracameral Cefuroxime was injected at the end for endophthalmitis prophylaxis. Fig. 6a Fig. 6c Fig. 6b Two weeks post operatively vision had recovered to 6/18 unaided, 6/12 with a pinhole and at six weeks Fig. 7

42 278 Kerala Journal of Ophthalmology Vol. XXI, No. 3 vision was 6/6 with minimal refraction (-1.00 DS / DC x 180). The IOL was well centred. He requested surgery for his other eye. (4) Surgical pearls i) Unstability of the anterior chamber must be avoided at all cost, mainly to avoid vitreous coming forward. Meticulous fluid viscoelastic exchange technique avoids the capsular bag diaphragm flopping forward and backward. This means that every time the phaco probe has to be removed from the eye, this is done by stopping aspiration, but with irrigation continuing, viscoelastic is injected through a side port to support the anterior chamber. Whilst viscoelstic is being injected, one gradually eases off the irrigation, and then the probe can be safely withdrawn whilst maintaining a deep anterior chamber, and preventing the capsular bag from coming forward. ii) iii) Instead of conjunctival dissection and a scleral flap, a 600 micron limbal incision is made with a guarded diamond blade in the region of maximal lens edge decentration. This incision is similar to a limbal relaxing incision. A crescent blade is then used to dissect a 4 mm (wide) x 3 mm deep (from limbus to periphery), partial thickness scleral pocket. This allows the prolene knot to be buried under sclera, with conjunctiva undisturbed. Moreover as the sides of the pocket are attached, there is no real risk of scleral flap contraction in the future. When the lens matter is soft (as in a young patient), most of the surgery is done through two paracentesis incisions (about 1mm each), with all the lens matter removed using bimanual irrigation-aspiration (no phacoemulsification). This allows for greater stability and reduces risk of vitreous disturbance. Only when all lens matter has been removed a 3 mm incision is made to enable placement of a CTS and then the IOL. Conclusion I have here presented the evolving techniques for lens surgery in Marfan s syndrome. Whilst some aspects are debatable, I believe that the combination of a CTR and a CTS fixated transclerally under a scleral pocket allows secure in-the bag IOL placement and potentially reduces the risk of future complications. Meticulous surgical technique is essential to avoid disrupting the capsular bag and disturbing the anterior vitreous face. When this is done excellent visual and anatomic outcomes are attained. At least potentially, this should reduce the risk of long term complications, time will tell if this potential is achieved. In a personal series of eleven consecutive Marfan s eyes operated on over the last two years, in the bag placement with a well centred bag and secure fixation of a capsular tension segment using a prolene suture was achieved in all cases with good visual outcomes. Reference: 1. Maumenee IH. The eye in the Marfan syndrome. Trans Am Ophthalmol Soc 1981;79: Bahar I, Kaiserman I, Rootman D. Cionni endocapsular ring implantation in Marfan s Syndrome. Br J Ophthalmol 2007;91; Wagoner MD, Cox TA, Ariyasu RG, et al. Intraocular lens implantation in the absence of capsular support; a report by the American Academy of Ophthalmology (Ophthalmic Technology Assessment). Ophthalmology 2003;110: Morrison D, Sternberg Jr P, Donahue S. Anterior chamber intraocular lens (ACIOL) placement after pars plana lensectomy in pediatric Marfan syndrome. J AAPOS 2005;9: Lifshitz T, Levy J, Klemperer I. Artisan aphakic intraocular lens in children with subluxated crystalline lenses. J Cataract Refract Surg 2004;30: Tsai YY, Tseng SH. Transscleral fixation of foldable intraocular lens after pars plana lensectomy in eyes with a subluxated lens. J Cataract Refract Surg 1999;25: Scharioth GB, Pavlidis MM. Sutureless intrascleral posterior chamber intraocular lens fixation. J Cataract Refract Surg 2007;33; Badon ACJ, Scharioth GB, Prasad S. Intrascleral Sutureless Posterior Chamber Intraocular Lens Fixation Using Scleral Tunnels. Techniques in Ophthalmology 2009 (in press) 9. Dietlein TS, Jacobi PC, Konen W, et al. Complications of endocapsular tension ring implantation in a child with Marfan s syndrome. J Cataract Refract Surg 2000;26: Lam DSC, Young AL, Leung ATS, et al. Scleral fixation of a capsular tension ring for severe ectopia lentis. J Cataract Refract Surg 2000;26:

43 September 2009 Somdutt Prasad et al. - Lens surgery in Marfan s syndrome Cionni RJ, Osher RH, Marques DM, et al. Modified capsular tension ring for patients with congenital loss of zonular support. J Cataract Refract Surg 2003;29: Hasanee K, Ahmed II. Capsular tension rings: update on endocapsular support devices. Opthalmol Clin North Am 2006;19; Buckley EG. Hanging by a thread: the long-term efficacy and safety of transscleral sutured intraocular lenses in children [an American Ophthalmological Society thesis]. Trans Am Ophthalmol Soc. 2007; 105: Por YM, Lavin MJ. Techniques of intraocular lens suspension in the absence of capsular/zonular support. Surv Ophthalmol. 2005;50: In a lighter vein MEMORY RRV I had previously written in this column that the most essential quality for a medical practitioner is patience. It is true, alright. But equally important is another one good memory for names and faces. At least some of your patients expect you to remember them when they come back to you six years after their previous visit. And are very gratified if you do. Some of them even feel insulted if you don t. In my school days we had our family doctor who used to manage anything from allergy to angina and pruritis to pregnancy. Every time one of the family members went to him, he used to ask about the others; their marriages; children s educational problems etc. And he never made a mistake. I always used to wonder how he managed to remember each one of his patients with their myriads of profiles and problems. Of course he had a good memory. But when I myself became a doctor, I happened to ask him as to his prodigious reminiscental capabilities he laughed and said: Oh! I make small notations on the edge of the prescription as to the job or class or wife s name etc. I tried to emulate him when I started practicing. But my memory was never as good; and I couldn t remember what my notations stood for. The problem is worst when you think you remember the face but can t put a name to it. And the patient talks on familiarly and has not brought the old prescription. When the time comes to write the prescription you use various techniques. One is to ask him/her what his/her FULL name is. If it is such small and simple name like Unni, you are in trouble. Or you ask him/her what the OFFICIAL name is. If the answer is It is the same one, again you are in trouble. May be you can ask what his/ her initials are. Most of them will say the name along with the initials. Again it won t help if he/she answers simply P.K. or C.T. With ladies I try another ruse. I ask what their husband s name is and prefix a Mrs. ; but you are in a fix if she demurely say Oh, doctor, but I am not married. So now a days I take the bull by the horns and say: Sorry, but I can t remember your name. With young boys or girls I may add, How you have grown up! I couldn t recognise you. Do not try this with older women Instead, say: You appear younger, I couldn t recognise you. Fortunately in my experience, men do not mind being asked the name visit after visit as much as the fairer sex. A couple of days back I asked a female patient her name and heard the familiar how can you forget me thing. But considering that she was clad in a burkha with a cloth mesh in front of her eyes, I felt vindicated.

44 280 Kerala Journal of Ophthalmology Vol. XXI, No. 3 OPHTHALMIC INSTRUMENTATION The Eyesi: Ophthalmic Surgical Simulator Dr. Meena Chakrabarti MS, Dr. Sonia Rani John DNB, Dr. Arup Chakrabarti MS In recent years, the medical community has benefited from technological advances that simulate surgical environments. Ophthalmologists now have access to commercially available virtual reality systems, including the Eyesi Ophthalmic Surgical Simulator (VRMagic, Mannheim, Germany). Fig (1) The ophthalmic training system is based at the Mayo Clinic s Multidisciplinary Simulation Center Fig. 1: The Eyesi: Ophthalmic Virtual Reality Surgical Simulator. Chakrabarti Eye Care Centre, Kochulloor, Trivandrum tvm_meenarup@sancharnet.in ( a 10,000-square foot clinical training facility dedicated to simulationbased clinical education and research. Gone are the days when residents first learned the basics of handling intraocular instruments and a surgical microscope in the OR or a variable wet lab environment. Instead, they now complete a structured curriculum that combines one-on-one instruction and independent study with the Eyesi simulator. Instructors create courses that residents repeat and practice until they achieve passing scores. The surgeons-in-training then advance to the Eyesi system s higher levels of difficulty until they master all of the simulator s training tasks. Residents are enthusiastic about the technology and its constant availability (24 hours a day, 7 days a week) (Fig 2). In studies, the Eyesi Ophthalmic Surgical Simulator demonstrated construct validity (the ability to reliably distinguish between novice and expert surgeons) for training tasks in the posterior and anterior segments 2, 3. The device s stereoscopic view and foot-pedal controls are excellent proxies for the real environment of cataract surgery. VRMagic originally developed the Eyesi system to simulate vitreoretinal surgery. Recently, however, the company added a training module for the anterior segment (Figure 1). In addition to simulating the use of forceps, precise navigational tasks, the capsulorhexis formation, and phacoemulsification, the Eyesi s anterior segment module evaluates the user s performance and measures instructor-defined, standardized surgical tasks in a virtual environment 1.

45 September 2009 Meena Chakrabarti et al. - The Eyesi: Ophthalmic Surgical Simulator 281 Using the anterior segment training module and the built-in forceps tool, residents learn how to manipulate instruments in the eye, pivot them at the wound, and avoid inadvertently injuring the cornea or crystalline lens. The simulator s scoring system rewards users for the efficiency of their intraocular manipulations and the precision with which they complete their tasks. The capsulorhexis training module is actually more challenging than the real thing, an acceptable and desirable quality for a surgical training system. The posterior segment training modules simulate the manipulation of forceps, the precise movement of instruments in the posterior segment, antitremor training/control, and procedures such as vitrectomy, epiretinal membrane peeling, and internal limiting membrane peeling. The Eyesi s retinal simulations can suspend reality quite effectively. For example, inexperienced surgeons become so engrossed in virtually peeling an epiretinal membrane that they actually start sweating. Hands-on experience in traditional surgical wet labs is still the gold standard for training residents to perform corneal and scleral suturing techniques. Currently available surgical simulators do not attempt to replace the experience of working with real cadaveric eyes. Instead, the simulator provides a realistic, repeatable, and measurable intraocular surgical environment that is difficult to duplicate in the traditional wet lab setting. The Eyesi s on/off setup eliminates the significant time and effort typically involved in preparing and dismantling a wet lab. In addition, the surgical simulator measures and documents the user s efforts and performance. Depending on which module is used during a training session, the system tracks and scores up to 74 different performance variables (Table 1). The Eyesi s screen displays the data for each trial, which can also be summarized and graphed at the end of each simulated surgical session or exported to a spreadsheet program for statistical analysis. By allowing residents to repeatedly perform standardized tasks and measuring their performance in a realistic environment, the Eyesi system helps us train surgeons to perform cataract surgery safely and competently without putting patients at risk. Surgical training content for EYESi is organized in software modules. Training is available for cataract and vitreoretinal surgery. The ever expanding menu of surgical modules now offers procedures like Capsulorhexis and Phaco-emulsification or Posterior Hyaloid Detachment and ILM Peeling. Each training module includes various tasks with increasing difficulty levels. As EYESi is designed to integrate into a residency program curriculum the system allows for customisation. Therefore medical educators can create courses from the assorted modules and levels of complexity that exist within the surgical training modules. The ability to define training content ensures medical educators can set up individual curricula to meet the needs of the trainee relative to the trainee s current Fig. 2. An Eyesi training session in progress. stage of skill and experience. Thus dedicated courses can use easy or difficult levels from the selected training modules so that both novices and advanced trainees can refine their skill level. EYESi provides the medical educator with detailed user and group management so that a course can be assigned to an individual trainee or groups of trainees. After courses are build and integrated into the residency curriculum a medical educator would logically want to monitor each trainee s development. EYESi offers detailed performance evaluation and all data for a trainee can be exported via USB as user friendly spread sheets or graphs. To further support medical educators EYESi offers a recorder playback functionality so that an instructor

46 282 Kerala Journal of Ophthalmology Vol. XXI, No. 3 explore the effects of parameter changes. In practical terms this means a trainee can cause unwanted events like surge and chatter and learn how phaco parameter adjustments can eliminate these occurrences. Fig. 3. The Cataract Module can review any given simulation session and provide feedback to the trainee. All videos and screenshots can easily be exported via USB for later use. An identical curriculum can be used over time to measure the learning curve or to compare skill levels of students. EYESi cataract For training of anterior segment surgery the EYESi platform is equipped with a cataract surgery interface which includes a head with a cataract eye interface, the cataract instrument set, footpedals and the corresponding system software. The simulation can be configured easily for superior or temporal access to the patient s eye; the cataract eye is prepared for corresponding incisions. According to many instructors and trainees, mastery of the capsulorhexis and phaco-emulsification are amongst the most difficult steps in cataract surgery. In a capsulorhexis the main difficulty lies in controlling the delicate capsule tissue to tear in the desired manner. Furthermore the trainee must learn this complex manual skill within a confined space of the anterior chamber. EYESi cataract offers extensive training of the capsulorhexis. It even allows for the training of complications so that trainees master what to do when the rhexis runs outwards. In learning to perform phacoemulsification the challenge rests in understanding and controlling the complex physics of the phaco device. The phaco training modules offer a safe environment to experiement with phaco machine settings and to A step-by-step approach to the Divide and Conquer technique allows for stress free and lasting acquisition of the required surgical skills. EYESi also enables a trainee to now pool all the manual skills together that make up modern phaco techniques as the simulation requires coaxial use of instruments, use of the microscope foot pedal, and modulation of the desired phaco parameters with a phaco foot pedal. Table: 1 Performance variables tracked and scored by the Eyesi System 1. Educational open forceps insertion and removal 2. Nonhorizontal instrument insertion and removal 3. Interacting out of focus and light cone 4. Average radius of capsulorhexis 5. Decentration and overall irregularity of capsulorhexis 6. Deviation of capsulorhexis radius from target value 7. Instrument insertions 8. Remaining aqueous humor 9. Efficiency Time (after first interaction) 10. Ultrasonic energy 11. Viscoelastic injection 12. Injury Incision stress 13. Injured cornea and lens area 14. Lens displacement 15. Damaged zonular fibers 16. Iris contact 17. Anterior chamber pressure too low 18. Ultrasonic leakage 19. Emulsification of adjacent cortex 20. Cornea and capsule damaged by ultrasonic energy 21. Anterior and posterior capsule torn 22. Target Remaining objects 22. Progress 23. Capsulorhexis completed 24. Lens cracked/removed Most medical educators and trainees know that learning to see through a microscope with both hands and both feet working all at the same time in a deliberate and harmonious manner takes considerable practice. EYESi provides a better way to train for anterior segment surgery as risk is removed when a patient is eliminated from the training loop and a trainees can safely practice critical parts of cataract surgery to mastery.

47 September 2009 Meena Chakrabarti et al. - The Eyesi: Ophthalmic Surgical Simulator 283 EYESi vitreoretinal For training of posterior segment surgery the EYESi platform is equipped with the vitreoretinal surgery interface which consists of a head with the vitreoretinal eye interface, a vitreoretinal instrument set, foot pedals and the corresponding system software. medical educators to use the system as a complete training platform. EYESi s system software enables medical educators to seamlessly integrate their own courseware into the platform. Through the secure administration functions individual courses can be compiled and complemented with academic text, still images and high resolution digital video footage. Powerpoint presentations can be imported and presented on the graphical user interface of the EYESi simulator. This allows trainees to study medical background information and then observe demonstrations depicting how their mentors perform Fig. 4. A vitreoretinal training session in progress. Most everyday realities of microsurgery in the complex vitreoretinal environment are represented in EYESi. The EYESi microscope renders a stereoscopic view identical to the real OR microscope. The trainee is required to establish suitable visualization via the microscope foot pedal s zoom, focus, and X/Y controls. Experienced retina surgeons know observing the retina requires a BIOM/ SDI hardware so this too is integrated into the microscope setup. Assorted training modules are available for EYESi vitreoretinal. Training sessions include tasks like inducing posterior hyaloid detachment and performing peripheral vitrectomies, peeling the internal limiting membrane (ILM) or the removal of epiretinal membranes. To aid trainees in refining precise manual dexterity skills associated with vitreoretinal surgery EYESi provides a virtual surgical instrument tray. In the course of performing virtual surgery a trainee will use an illumination probe in their non-dominate hand. As in real retinal surgery EYESi realistically enables the surgeon s dominant hand to alternate between instruments such as vitrector, endolaser, forceps, scissors etc. Trainees acquire expert status during training in a variety of ways. EYESi therefore was developed to allow Fig. 5. Macular translocation. any given procedure. If the goal is teaching the capsulorhexis a trainee can read about the task, observe how the task is done, and then complete the task in virtual reality till mastery of the skill is known to have been obtained. With the option to combine the practical surgical training with multimedia presentations of medical knowledge EYESi represents the modern way of teaching surgical skills. Conclusion Keeping up to date with the rapid advances and complexity of modern intraocular surgery is a challenging but ultimately satisfying and rewarding endeavor. Surgical simulators based in virtual reality allow residents to develop and hone their surgical skills so that they provide patients with the safest and highestquality surgical outcomes possible. Currently, a barrier to the Eyesi s broad adoption appears to be the system s cost (between $100,000 and $200,000, depending on optional features and the date of purchase)

48 284 Kerala Journal of Ophthalmology Vol. XXI, No. 3 References 1. EYESi Ophthalmosurgical Simulator user guide. Mannheim, Germany: VRMagic; Rossi JV, Verma D, Fujii GY, et al. Virtual vitreoretinal surgical simulator as a training tool. Retina. 2004;24: Mahr M, Hodge D. EYESI Ophthalmic Surgical Simulator anterior segment anti-tremor and forceps training module construct validity: attending versus resident performance. J Cataract Refract Surg. In press. To view a video of a simulated capsulorhexis rescue performed on the Eyesi Ophthalmic Surgical Simulator, visit the ESCRS s Video on Demand Web site at or aspx# VRMagic s Web site at eyesi/videos/escrs%20mahr.zip

49 September 2009 SR John et al. - Nepafenac 285 OCULAR PHARMACOLOGY Nepafenac Dr. Sonia Rani John DNB, Dr. Meena Chakrabarti MS, Dr. Arup Chakrabarti MS Ocular inflammation is a common result of cataract surgery, producing pain and photophobia in many patients and potentially leading to serious complications including increased intraocular pressure, posterior capsule opacification, cystoid macular oedema and decreased visual acuity. Steroidal agents have been the standard treatment for ocular inflammation in the past while the use of topical NSAIDS has increased over the past two decades. Clinical evidence suggests that the combined use of NSAIDS and steroids is synergistic 1. In fact it has become the standard of care to use a regimen of NSAIDS and steroids before and after cataract surgery 2. Prostaglandins are involved in human intraocular inflammation and released in response to ocular trauma, including surgery. When present following trauma, intraocular surgery, or in association with uveitis, they may contribute to disruption of blood ocular barriers and the generation of macular edema. During cataract surgery, arachidonic acid is released from phospholipids of cell membranes to provide the precursor for prostaglandin synthesis. Corticosteroids affect the cascade by attenuating the expression of inflammatory mediators that initiate activation of phospholipase and the release of arachidonic acid thus limiting prostaglandin production. NSAIDs exert their effects further downstream of the cascade, directly inhibiting cylco-oxygenase and the production of prostaglandins. There are 2 main settings of ocular surgery in which ophthalmologists use topical NSAIDS. One is refractive Chakrabarti Eye Care Centre, Kochulloor, Trivandrum tvm_meenarup@sancharnet.in surgery and the other is cataract or other intraocular surgeries. With refractive surgery, NSAID drops are particularly effective in reducing discomfort both during and after the procedure. To a lesser extent, they also reduce inflammation in the eye related to refractive surgery, particularly in the cornea and conjunctiva. With cataract and intraocular surgery, topical NSAIDS offer several benefits. The goals of topical prophylactic nonsteroidal anti inflammatory drug treatment include the prevention of intraoperative miosis 3, management of postoperative inflammation 3, prevention or treatment of CME 3,4 and reduction of ocular pain 5. They lessen the patient s discomfort during the procedure, which is especially important when using topical anesthesia in cataract surgery. NSAID also help maintain pupillary dilation during cataract surgery, which has been shown to lower the rate of complications. They help in controlling inflammation in the first few days after surgery, as measured by the presence of cells and flare in the anterior chamber. Finally, NSAIDs inhibit the development of cystoid macular oedema (CME), which usually occurs 4 to 6 weeks after cataract surgery. Even after a perfect cataract surgery with the most modern techniques and the best instrumentation, as many as 12 % of patients may develop some CME and the use of an NSAID may significantly reduce this complication. Four topical ocular NSAIDS are currently approved by the U.S Food and Drug Administration (FDA) for the treatment of postoperative inflammation after cataract surgery. They are Acular (ketorolac 0.5 %), Xibrom (bromfenac 0.09 %), Voltaren (diclofenac 0.1 %) and Nevanac (nepafenac 0.1 %).

50 286 Kerala Journal of Ophthalmology Vol. XXI, No. 3 Nepafenac (Nevanac, Alcon Laboratories) is a novel topical nonsteroidal anti-inflammatory drug, which is the only prodrug NSAID, having less anti-inflammatory activity without conversion to its more active state 6. Each ml of Nevanac (0.1 %) suspension contains 1 mg of nepafenac. Nepafenac is designated chemically as 2 amino 3-benzoylbenzene acetamide with an empirical formula of C 15 H 14 N 2 O 2. Nevanac Ophthalmic suspension is the first and only topical NSAID structured as a prodrug. This unique design allows for target specific activity, because its efficacy is maximized at the intraocular sites of most concern to ophthalmologists. Once Nevanac penetrates the eye, intraocular hydrolysis converts the nepafenac molecule into a potent cyclooxygenase inhibitor called amfenac, an active drug that has strong antiinflammatory capabilities. Unlike conventional NSAIDs, the active forms of which tend to accumulate on the ocular surface and decrease in activity and concentration as they penetrate the eye, Nevanac is specially designed to maximize intra ocular efficacy. Its unique prodrug structure allows Nevanac to achieve optimal distribution through the cornea into the iris / ciliary body and retina / choroid, providing superior inflammation suppression. At the same time, this rapid and targeted distribution may minimize tolerability issues commonly noted with conventional NSAID therapies, because the drug doesn t overload the ocular surface. Nevanac uniformly inhibits all prostaglandins of the iris / ciliary body, retina, PGE 2 synthesis, and the breakdown of the blood aqueous barrier. Compared with conventional NSAIDs such as diclofenac, nepafenac 0.1 % is superior in blocking the production of prostaglandins in an uniform manner 7. Studies 8 show that nepafenac 0.1 % inhibits 95 % of prostaglandin formation by the iris / ciliary body within 80 minutes after topical dosing, compared with diclofenac s 53 % 9. This fact has important clinical implications in terms of potential differences in efficacy between Nevanac and conventional NSAID therapies. It is believed that CME is caused by surgically induced prostaglandin formation in the aqueous and vitreous and / or by the breakdown of the blood aqueous and blood retinal barriers. Even mild CME damages the retinal pigment epithelium. Such damage is irreversible, because these cells do not regenerate. Therefore, any retinal swelling can have a lasting negative impact on a patient s vision. Due to their mechanism of action, NSAIDs have been shown to be a good line of defense against CME. Obviously, it is key that the NSAID selected reaches the target tissues to provide therapeutic anti-inflammatory activity and thus prevent the processes described. The target- specific activity of Nevanac hold great potential for the superior prevention of post-cataract complication such as CME. Because the highest concentration of Amfenac occurs in the choroid and retina, the agent not only decreases inflammation in the anterior chamber, but should also lower the patient s risk of developing CME. Studies 10,11 have shown that nepafenac 0.1 % inhibits prostaglandin formation in the vitreous, whereas conventional NSAID such as diclofenac and ketorolac fail to do so. A study 12 evaluating the suppression of prostaglandin synthesis of nepafenac 0.1 % versus diclofenac in the iris/ ciliary body and the retina / choroid showed that a single topical dose of nepafenac 0.1 % significantly inhibited prostaglandin synthesis in the iris/ciliary body and retina choroid. Efficacy was sustained for 6 hours in the iris / ciliary body and for 4 hours in the retina/ choroids. In contrast, for diclofenac peak suppression of prostaglandin activity in the iris/ciliary body was sustained for 20 minutes, with only minimal inhibition of prostaglandin synthesis observed with diclofenac in the retina / choroid. Because nepafenac is a neutral molecule, it has been hypothesized to have greater corneal permeability than other NSAIDS which have acidic structures. In a vitro study of rabbit tissue, nepafenac had 6 fold greater corneal penetration than diclofenac as well as faster rate of penetration 13. Similarly in another study, nepafenac aqueous humor C max values were 3.6 fold higher than those of ketorolac despite having a starting concentration 4-fold (0.1 % versus 0.4 %) 14. Nepafenac C max values were more than 8 fold higher than those of bromfenac, despite having similar starting concentrations (0.1 % versus 0.09 %). Thus the results in various studies support the fact that the prodrug nepafenac has faster corneal penetration rate than other conventional NSAIDs.

51 September 2009 SR John et al. - Nepafenac 287 Intraocular drug concentrations are expected to correspond with the anti-inflammatory efficacy of a drug. The near maximum concentrations of amfenac is maintained longer than those of Ketorolac suggesting that Nevanac may have a prolonged duration of action relative to other drugs in this class. This may be due to nepafenac prodrug structure which allows it to rapidly traverse the cornea, reaching C max in the aqueous humor within 30 minutes. Nepafenac is a non steroidal anti-inflammatory pro-drug that potentially inhibits Cox-1 and Cox-2 activity ex vivo following topical ocular administration. Nepafenac demonstrates low intrinsic cyclo-oxygenase inhibitory activity in vitro, yet exhibits in vivo efficacy equal to that of diclofenac in models of anterior segment ocular inflammation. In addition to its anterior segment efficacy, nepafenac exceeds diclofenac in its ability to reduce posterior segment ocular inflammation. Nevanac has been tested in various concentrations (upto 15 times its commercial concentration ) and in short as well as long term settings and it was found to be safe and well tolerated 15,16. Nepafenac penetrates the target intraocular tissues faster than any other topical NSAID, thus providing greater efficacy on a clinical basis. Once inside, it has rapid conversion and therapeutic onset and a very high level of tissue concentration. Studies show that its rate of systemic absorption in approximately 1700 times less than that of an oral dose. Nevanac hold the promise of fast, pain-free visual recovery without the potential common side effects noted with conventional NSAID therapies. As mentioned previously, its unique prodrug formulation ensures optimal intraocular distribution 17 with superior inflammation suppression. The superior bioavailability of Nevanac to the retina / choroid also ensures an unsurpassed potential for preventing CME after cataract surgery. Nevanac suspension, which was filed with the FDA for the treatment of inflammation following cataract surgery, will provide a novel, target- specific structure that optimizes penetration throughout the relevant ocular tissues to deliver enhanced, longer lasting antiinflammatory efficacy all the way to the retina / choroid which is of particular relevance to ophthalmic surgeons. References 1. Flach AJ, Nonsteroidal anti-inflammatory drugs. In ; Tarman W, ed, Duances Foundation of Clinical Ophthalmology Philadelphia, PA, Lippincott 1994; Vol 3; Chapter O, Brien T.P. Emerging guidelines for use of NSAID therapy to optimize cataract surgery patient care. Curr Med Res Opin 2005;21: ; erratum, Flach AJ. Topical nonsteroidal anti-inflammatory drugs in Ophthalmology. Int Ophthalmol Clin 2002; 42 (1); Miyake K, Marnda K, Shirato S, et al. Comparison of diclofenac and fluorometholone in preventing cystoid macular edema after small incision cataract surgery; a multicentred prospective trial. Jpn J Ophthalmol 2000; 44: Price MO, Price FW. Efficacy of topical ketorolac tromethamine 0.4 % for control of pain or discomfort associated with cataract surgery. Cure Med Res Opin 2004; 20: Gamache DA, Draff G, Brady MT, et al. Nepafenac, a unique non steroidal prodrug with potential utility in the treatment of trauma-induced ocular inflammation. Assessment of anti-inflammatory efficacy. Inflammation 2000; 24: Kim DH, Stark WJ, O Brian TP, Dick JD. Aqueous penetration and biological activity of moxifloxacin 0.5 % ophthalmic solution and gatifloxacin 0.3 % solution in cataract surgery patients. Ophthalmology 2005;112: Ke T-L, Graffe G, Spellman JM, Yanne JM. Nepafenac, a unique nonsteroidal prodrug with potential utility in the treatment of trauma induced ocular inflammation. Inflammation 2000; 24: Tom Wallers, Michael Raizman, Paul Ernest. In vivo pharmacokinetics and in vitro pharmacodynamics of nepafenac, amfenac, ketorolac and bromfenac. J Cataract Refract Surg 2007;33: Heaton J, Hiddeman JW, Hackett RB, et al. Ocular effects of Nepafenac ophthalmic suspension following six months of topical ocular administration to pigmented rabbits. Paper presented at: The ARVO annual meeting ; May 03, 2005; Fort Lauderdale, FL. 11. Walker LM, Rice RL, Heaton JD, et al. Ocular effects of Nepafenac ophthalmic suspension following three months of topical ocular suspension to cynomolgus monkeys. Paper presented at: The ARVO annual meeting; May 03, 2005; Fort Lauderdale, FL. 12. Heier JS, Topping TM, Bauman W et al. Ketorolac versus predinisolone versus combination therapy in the treatment of acute pseudophakic cystoid macular edema. Ophthalmology.2000;107: Flach AJ. Discussion: ketorolac versus prednisolone versus combination therapy in the treatment of acute pseudophakic cystoid macular edema. Ophthalmology 2000;107:11:2039.

52 288 Kerala Journal of Ophthalmology Vol. XXI, No McColgin AZ, Raizman MB. Efficacy of topical Voltaren in reducing the incidence of postoperative cystoid macular edema. Invest Ophthalmol Vis Sci.1999; 409 (Suppl):S O Brien TP. Emerging guidelines for use of NSAID therapy to optimize cataract surgery patient care. Curr.Med REs Opin.2005;21:7: Kapin MA, Yanni JM, Brady MT, et al. Inflammation mediated retinal edema in the rabbits is inhibited by topical nepafenac. Inflammation.2003;27: Gamache DA, Graff G, Brady MT, et al. Nepafenac, a unique nonsteroidal prodrug with potential utility in the treatment of trauma induced ocular inflammation: Inflamamtion.2000; 24:4:

53 September 2009 SR John et al. - Nepafenac 289 OCULAR PHARMACOLOGY Recent Advances in The Back of The Eye Drug Delivery Dr. Meena Chakrabarti MS DO DNB Introduction Once the active treatment agent that is efficacious in the management of posterior segment diseases is determined, the next big obstacle is the back of the eye drug delivery. Topical eye drops are far superior to all other routes of administration with respect to safety, comfort, affordability and ease of use. However topical medications are least effective in delivering therapeutic concentrations of the drug to the retina 1. Hence the majority of developmental efforts in retina therapeutics is focussed on novel non-topical delivery systems. Intravitreal injections introduced in ,3 provides superior drug bioavailability in the posterior segment compared to topical and systematically delivered agents. However this method of drug administration has several drawbacks which includes frequent (monthly / bimonthly) outpatient visits, and carry the risk of serious complications such as vitreous hemorrhage, retinal detachment and endophthalmitis. Intraocular implants 4 are designed to provide drug release into the posterior segment for longer periods of time (months or even years) compared to particles or solutions. These implants are usually placed at the level of the parsplana during a surgical procedure. Compared to intravitreal injections, drugs released from implants deliver more consistent levels of the drug, avoids side effects associated with frequent intravitreal injections, minimize peak concentrations and result in smaller quantities of drug being required for Chakrabarti Eye Care Centre, Kochulloor, Trivandrum tvm_meenarup@sancharnet.in treatment 1,5. Like solutions and particles implants can also result in unequal drug distribution due to vitreous heterogenicity and placement of implant peripheral to retina to avoid disruption of the visual field. Implants however come close to the zero-order kinetics: ie the level of administered drug remains constant throughout the delivery period. Implants can be either biodegradable or non biodegradable. Biodegradable implants do not require surgical removal. Their disadvantages are a variability in release kinetics due to differing rates of vitreous turnover and a final burst in drug release profile. Non biodegradable implants provide a more controlled drug delivery but require a second surgical procedure for removal. Two ocular implants Vitrasert (Ganciclovir 4-5 mg Bausch and Lomb, Rochester, NY) and the recently approved Retisert (flucinolone acetonide 0.59 mg, Bausch and Lomb) are commercially available. Vitrasert releases ganciclovir for approximately 5-8 months while Retisert releases flucinolone for up to 30 months and is currently the only approved treatment for non-infectious uveitis of the posterior segment 6. Other implants that have been developed are 1. A novel doughnut shaped biodegradable implant 7 for delivery of ganciclovir and foscarnet. The central hole assures easier suturing and the implant does not need removal. 2. Biodegradable posudrex implant (Allergan, Irvine, CA) for delivery of dexamethasone in treatment

54 290 Kerala Journal of Ophthalmology Vol. XXI, No. 3 of macular edema associated with retinal vein occlusions. 3. Iluvien (Alimera, Alpharetta, GA) 8 a non biodegradable implant to deliver flucinolone acetonide in diabetic macular edema and designed to sustain therapy for months. In the past few years researchers have developed intraocular devices with fewer complications, and relatively safe, sustained and effective localized administration. These include 1. Particulate polymeric drug delivery systems (Microparticles / Nanoparticles) 2. Phospholipid bilayer encapsulated drug delivery system (liposomes) 3. Iontophoresis: where an electric current is used to drive ionized drugs into tissues. Microparticles, Nanoparticles and Liposomes The main problem that limits the effectiveness of intravitreal injections is the lack of homogenicity of the human vitreous caused by gradients. Injected drugs do not therefore spread throughout the vitreous resulting in a significant variability in the drug concentration at the target site. Nano particles or micro particles are new formations which can spread more uniformly throughout the vitreous, increase the duration of action, and decrease the peak concentration. Injectable nano particles 9 (1nm to 1000 nm in diameter) and microparticles (1 nm to 1000 nm in diameter ) made of polymer encapsulated drug are novel drug delivery systems that aim to increase the drug penetration and also increase the duration of action of small molecules. Particulate system can be in the form of 1. Nanospheres and microspheres: which are uniform polymer drug combinations in which the drug is dispersed homogenously throughout a polymer matrix. 2. Nanocapsules and Microcapsules: where the drug is surrounded by a spherical polymer capsule and released throughout its pores. 3. Polycion complex (PIC) micelles that can be laser activated are in development and have successfully inserted DNA into rat retinas through a process called photochemical internalization in which light induces the transfer of DNA directly into cells Liposomes: with encapsulated drug can bind to a cell membrane and facilitate drug transfer across the membrane. They are less stable than particles made of polymer. Both hydrophilic and hydrophobic drugs can be encapsulated into liposomes. Research have shown that they can effectively carry genes to the rat retina following injections. Almost any drug can be encapsulated. This method of drug delivery aids in (1) stabilizing the active form of the drug (2) increases its half life (3) increases drug absorption due to slower elimination rate (4) decreases peak concentrations reducing the risk of toxicity. One of the major disadvantages of this mode of delivery is that nanoparticles and microparticles are heavier than vitreous. So when they are injected they tend to sink to the bottom of the vitreous cavity. Particles size can also have a profound effect on the drug bioavailability after injection with larger particulate system tending to maintain superior sustained drug release. Nanotechnology may have an impact on the treatment of retinal diseases through gene delivery, drug delivery, cell delivery, retinal neural prosthetics and nano surgery. Gene delivery has been attempted with viral vectors but carry the risk of immunogenicity and mutagenesis. Non viral vectors such as polymers and lipids also have the ability to carry genes but with lower risk of immunogenecity, lower cost and greater ease of production than viral vectors. The electrostatic interaction of cationic polymers with RNA or DNA molecules carrying a negative charge results in condensation and formation of the material into particles in the nanoscale range. These polymer nanoparticles can protect genes from enzymes and mediate their entry into cells. Incani and colleagues 12 found that polyplexes complexes of cationic polymer with plasmid DNA can have transfection efficiencies comparable to adenoviral

55 September 2009 Meena Chakrabarti - Recent advances in the back of the eye drug delivery 291 vectors but with reduced safety risks. Colloidal nano particles carrier systems have been tried for sustained drug delivery for chronic diseases such as glaucoma and macular degeneration. Nano particles are also promising for targeted delivery of drugs to intra ocular tumors. Sustained submacular delivery may be enhanced by the use of biocompatible film that serves as a carrier for drug loaded nanoparticle Fig1. For an extra ocular approach arrays of hundreds of microneedles that penetrate the sclera to deliver drugs to the posterior segment have been designed using microfabrication technology Fig. 2. Polymer scaffold engineered on the nanoscale can increase the survival and differentiation of cells for retinal transplantation 13. Use of nanoparticles in engineering of retinal prosthetics is being investigated with the aim of rejenuvating, by passing, or taking advantage of the residual retinal function in patients with retinitis pigmentosa and other inherited degenerative retinal diseases 14. Iontophoresis and Suprachoroidal drug administration Iontophoresis is a method of drug delivery in which an electrical current drives charged drug molecule through either the cornea or sclera and into the retina and vitreous. It offers a non invasive alternative to intravitreal injections, particles or implants. The current leader in clinical ocular iotophoresis is Eye Gate pharma (Waltham, MA) which is currently investigating this technology for drug delivery. It uses a reusable battery powered generator and a disposable applicator. The Eyegate II uses an inert electrode that can accommodate both positive and negatively charged drugs. The mechanism of action of the inert electrode is electrorepulsion of the same charged molecule which creates high velocity to achieve flux to the targeted tissue.fig. 3 The surface area is important in this technology due to current density. By delivering the current to the sclera, the surface area is maximized and current density is lowered increasing the safety profiled of the device. The Eyegate II 16,17,18 has shown efficacy in delivering proteins, si RNA, corticosteroids and nanoparticles in rabbit studies. Safety of this device on human sclera 19 was shown using a buffer solution. Phase 2 study of EGP - 437, a corticosteroid delivered using this system for the treatment of dry eye syndrome has been completed. Phase II study in uveitis, glaucoma age related macular degeneration etc is underway. For patients with retinal tumors, iontophoresis is being researched as a potential alternative to the use of systemic chemotherapy. In a mouse model, investigators found that iontophoresis could successfully transport carboplatin, a cytotoxic compound for the treatment of retinoblastoma. The suprachoroidal drug delivery using a 300 mm microcatheter 21 (i track -400, i-science Interventional corporation, Menlo park, CA ), introduced through a small anterior incision at the parsplana has been shown to be able to access the suprachoroidal space. The safety, efficacy and pharmacokinetics with triamcinolone, a combination of triamcinolone A and Avastin is being investigated. (Fig. 5 & 6) Transporter Targeted Drug delivery to the retina: This method of drug delivery targets nutrient transporters on ocular barriers utilizing a prodrug approach. Nutrient transporters are transmembrane proteins involved in the transportation of essential nutrients and xenobiotics across biological membranes, thereby regulating the supply of essential ingredients into the cell. Several transporters for nutrients and endogenous compounds are expressed on both the apical and basolateral sides of the epithelial barriers of various tissues such as intestine, kidney, BBB, BRB and placenta. To take advantage of the nutrient transport system, the parent drug must be covalently conjugated to the nutrient moiety by an enzymatically cleavable bond generating a prodrug. Prodrugs significantly enhance absorption of poorly permeable parent drug. These prodrugs are recognized by the membrane transporters as substrates and are transported across the epithelial or endothelial barriers. Subsequently the prodrugs are enzymatically cleaved to release the parent drug and the ligand which in most cases is a nutrient, non toxic and easily eliminated. (Fig. 7) Super selective intra arterial chemotherapy in retinoblastoma aims to deliver a high concentration of

56 292 Kerala Journal of Ophthalmology Vol. XXI, No. 3 Fig. 1. Biocompatible film for drug delivery 20 nm thick biocompatible film with multiple drug loaded nanoparticles for sustained drug delivery. [Adapted from Retina Today May/ June 2009, Vol.4, No.4] Fig. 5. The Ophthalmic microcathete for suprachoroidal drug delivery. Fig. 2. Microneedle Array. The size of the experimental microneedle array is shown by its placement on the researcher s finger. There are 400 needles in the array. [Adapted from Retina Today May June 2009 Vol.4, No.4] Fig. 6. (a) & (b) View of the Microtheter beacon tip in supra choroidal space Fig. 3. The Eye Gate II delivery system. the drug to the trauma and achieve less exposure via a low dose systemically to the patient. The goal is to eliminate the need for enucleation and systemic chemotherapy in children with RB. Under general anaesthesia, the femoral artery is catheterized with a microcatheter (450 nm) which is passed up into the abdominal aorta, thoracic aorta, internal carotid arteries and into the ophthalmic artery which measures below 550 nm to 1000 nm in diameter in children. Fig. 4. The EyeGate II applicator is placed directly upon the sclera. References 1. Hughes PM, Olejnik O, Chang-Lin JE, Wilson CG. Topical and systemic drug delivery to the posterior segments. Adv Drug Deliv Rev.2005;57(14):

57 September 2009 Meena Chakrabarti - Recent advances in the back of the eye drug delivery Wu L, Martinez- Castellanos MA, Quiroz-Mercado- H et al. Twelve month safety of intravitreal injections of bevacizumab (Avastin): results of the Pan American Collaborative Retina Study Group (PACORES). Graefes Arch Clin Exp Ophthalmol.2008;246 (1) Von Sallmann L. Penicillin therapy of infections of the vitreous. Arch Ophthalmol 1945; 33: Bourges JL, Bloquel C, Thomas A et al. Intraocular implants for extended drug delivery: therapeutic applications. Adv Drug Deliv Rev. 2006; 58(11): Del Amo EM, Urtti A. Current and future ophthalmic drug delivery systems. A shift to the posterior segment. Drug Discov Today. 2008;13 (3-4): Hsu J. Drug delivery methods fro posterior segment disease. Curr Opin Ophthalmol.2007; 18(3): Choonara YE, Pillay V, Carmichael T, Danckwerts MP. Syudies on a novel doughnutshaped minitablet for intra ocular drug delivery. AAPS Pharm Sci Tech. 2007; 8(4):E Alimera. Iluvien: addressing the Ophthalmic Crisis of Diabetes.2008; v Csernus VJ, Szende B, Schally AV, Release of peptides from sustained delivery systems (microcapsules and microparticles) in vivo. A histological and immunohistochemical study. Int J Pept Protien Res.1990; 35(6): Tamaki Y. [Novel approach for management of agerelated macular degeneration-antiangiogenic therapy and retinal regenerative therapy]. Nippon Ganka Gakkai Zasshi. 2007;111(3):232-68; discussion Masuda I, Matsuo T, Yasuda T, Matsuo N. Gene transfer with liposomes to the intraocular tissues by different routes of administration. Invest Ophthalmol Vis Sci. 1996; 37(9): Incani V, Tunis E, Clements BA, Olson C, Kucharski C, Lavasanifar A, Uludag H. Palmitic acid substitution on cationic polymers for effective delivery of plasmid DNA to bone marrow stromal cells. J Biomed Mater Res A. 2007;81 (2): Tao SL, Desai TA. Aligned arrays to biodegradable poly (-carprolactone) nanowires and nanofibers by template sysnthesis. Nano lett.2007.;7 (6): doi: /nl Caspi A, Dorn JD, McClure KH, Humayun Ms, Greenberg RJ, McMahon MJ. Feasibility study of a retinal prosthesis: spatial vision with a 16-electrode implant. Arch Ophthalmol.2009; EyeGate. Pipeline [Internet]. Waltham, MA, Blalock T, Gee R, Manzo M, Ruiz- Perez B, Rao R. Single dose treatment with dexamehazone phosphate resolves concanavalin A induced dry eye in rabbits. Poster presented at the annual meeting of the Association for Research in vision and Ophthalmology meeting; April 27-May ; Fort Lauderadale, FL. 17. Ruiz Perez B, Blalock T, Dowie T, et al. Transscleral delivery of a 12.4k Da protein by ocular iontophoresis. Poster presented at the annual meeting of the Association for Research in Vision and Ophthalmology meeting; April 27-May : Fort Lauderdate, FL. 18. Patane M, Ji Guo, Schubert W, Landosca J. Iontophoretic delivery of PRINT (Particle Replication In nonwetting templates) Nanoparticles using the Eyegate II device. Poster presented at the annual meeting of the Controlled Release Society, July 12-16,2008; New York. 19. Reddy M, Thimmaiah R, Cohen A, et al. Clinical experience with the EyeGate II delivery system: safety and tolerability in healthy male and female adult volunteers. Poster presented at the annual meeting of the Association Research in Vision and Ophthalmology meeting; April 27- May ; Fort Lauderdale, FL. 20. Hayden B, Jockovich ME, Murray TG, et al. Iontophoretic delivery of carboplatin in a murine model of retinoblastoma. Invest Ophthalmol Vis Sci.2006; 47(9): Olsen TW, Feng X, Wabner K et al. Cannulation of the suprachoroidal space: a novel drug delivery methodology to the posterior segment. Am J. Ophthalmol.2006;142 (5): Kansara V, Hao Y, Mitra AK. Dipeptide monoester ganciclovir prodrugs for transscleral drug delivery: targeting the oligopeptide transporter on rabbit retina. J Ocul Pharmacol Ther.2007; 23:

58 294 Kerala Journal of Ophthalmology Vol. XXI, No. 3 CURRENT C0NCEPTS Care and Maintenance of Contact Lens An Overview Dr. Pravin Tellakula MS Care and maintenance is one of the most critical aspects of contact lens wear. It can influence the success of contact lens wear and patients satisfaction with their lenses. Choice of lens care regimen depends on factors such as lens type, lens material, replacement schedule of lens, lifestyle and specific patient needs. The biggest risk factor in Contact Lens wear is the person wearing them - Geoff Wilson Safe and effective wear depends on synergism of a good lens, a compliant patient and periodic professional monitoring. It is imperative that the purposes and importance of proper care and maintenance be impressed upon the prospective contact lens wearer as soon as contact lens wear is considered seriously. Role of Care and Maintenance The overall aims of care and maintenance are to prevent and minimise microbial contamination reduce deposits and attain and maintain ready-to-wear state of lenses The various products of care maintenance provide one or more of the following functions: - Cleaning Disinfection Protein Removal Wetting / re-wetting Adithya Eye Clinic, Chennai Regardless of the type of contact lens (except daily disposables), an appropriate care system must be used. A typical care system consists of the components listed Components of Care and Maintenance Daily cleaner Rinsing solution Disinfecting solution/unit Weekly/protein cleaner Lubricating/rewetting solution Lens storage case DAILY CLEANER - Function Daily cleaners usually contain surfactants and are used to remove most loosely bound foreign matter on the lens surface, such as, Cell debris, Mucus, Lipids, Proteins, Cosmetics, Micro-organisms, and inorganic deposits. The main functional component in a cleaner solution is the surface-active agent(s) also known as surfactant(s) (e.g. isopropyl alcohol, tyloxapol, polyvinyl alcohol, poloxamer-407, amphoteric 10, poloxamine, hexylene glycol, octylphenoxy ethanol, tween 21). Surfactant molecules emulsify, dissolve and/or disperse lipid globules, debris and other lens contaminants. This is accomplished by the surfactant forming a monomolecular layer over the contaminant using the polar ends of its molecules to bind the layer to the contaminant s surface. The coated contaminants repel one another mutually or exhibit a lowered surface tension 1.

59 September 2009 Pravin T. et al. - Contact Lens Care 295 The other main components are Non-ionic or ionic chemical compounds, to reduce interaction between the lens and the solution, and anti-microbial agents, primarily used as preservatives. The additional components in a cleaner include Osmolality adjusting agents, a buffer system to adjust the ph, Chelating agents for removing lens contaminants and viscosity enhancing agents. Viscosity-enhancing agents such as polyvinyl alcohol or methylcellulose also facilitate cleaning. Hypertonicity and abrasiveness are properties that have been added to enhance the efficacy of some lens cleaners. Hypertonicity results in extraction of water from soft lenses, which may help remove some soluble contaminants. Polymeric beads in some cleaners have a mildly abrasive effect on protein and other surface deposits. Apart from this Alcohol to remove lipids and Enzymes to digest proteins are also added. Fig: 1 Cleaning Procedure Rub and Rinse DAILY CLEANER Procedure 1. Wash hands and dry them (avoid moisturizing/ perfumed soaps) 2. Place lens in the palm of the hand 3. Place 2-3 drops of cleaner on each lens surface 4. Rub with forefinger for about 15 seconds per side using a to & fro and L-R action. Rolling the forefinger in both directions cleans the lens periphery 5. Rinse well Cleaning should be done with all types of lens including disposables. The mechanical action of rubbing and rinsing reduces significantly the amount of loose debris and the number of microorganisms on a lens. Rubbing also enhances the efficacy of the cleaning solution s surfactant properties. Caution to be observed when using abrasive cleaners. Excessive rubbing may cause scratches on the lens and can also sometimes induce minus power 2, 3. Rinsing Solution Value of Rinsing- regardless of the type of cleaner used it is important for the lens to be thoroughly rinsed to remove the excess Daily Cleaner, Loosened deposits and Micro-organisms. If the cleaner is allowed to remain on the lens and placed in the enzymatic cleaner, it may induce foaming resulting in the solution bubbling out and leaving the lens in a dehydrated state 4. It is also good to rinse lenses after overnight storage. Buffering agents are included in rinsing solution formulations so that their ph is approximate that of tears. The ph of normal tears is, on average 7.2, but is subject to individual variation. To enhance the compatibility of solution and tear phs at lens insertion, the solution is normally buffered lightly. Many different types of solutions can be used for rinsing, such as, Unpreserved Saline, Preserved Saline and Multi-purpose solutions. Use of buffered isotonic saline is preferred to un-buffered as absorption of atmospheric carbon dioxide lowers the ph. Disinfecting Systems Purpose of disinfection Contact lenses may compromise the eye s natural defence by: Inhibiting tear film washing action Introducing more micro-organisms Compromising epithelial barrier function Functions of the disinfecting solution are to kill or deactivate potentially pathogenic organisms including: Bacteria, fungi, viruses, amoebas and maintain lens hydration Antimicrobial activity can be divided into three levels of efficacy (Anger and Currie, 1995) 5. - Sterilization is the killing of all microbial life forms, a situation impossible to achieve with normal lens care products and procedures.

60 296 Kerala Journal of Ophthalmology Vol. XXI, No. 3 - Disinfection is a dynamic process, usually preceded by a cleaning and rinsing step, intended to kill and/or remove microbial and viral contaminants from contact lenses. - Preservation is the killing or inhibition of growth of a select range of microorganisms to prevent product spoilage during consumer use. The choice of preservative is governed to a large extent by the resistance of the microbial targets and the sensitivities of the eye exposed to the preservative via contact lenses or eye drops. Disinfection Systems Types The two main types of disinfection systems available for soft contact lenses are heat and chemical. 1. Heat-based disinfection systems use heat in the range from 70 C to 125 C to kill or deactivate living lens contaminants (ideally degrees for 10 minutes). The advantage is that it is very effective and does not cause any allergy or discomfort. However, heat can cause problems for the patient due to alterations that occur within the lens following long-term use. Heat disinfection systems generally decrease lens life span and eventually cause lens discolouration. The Optical and physical properties of the lens can sometimes be altered due to excessive heating and can result in denaturation of protein in and on the lens RGP lenses will warp when heated and hence cannot be used. Recently, a system for thermal disinfection of contact lenses in a domestic microwave oven has been released. 2. Chemical disinfection systems vary greatly and a wide variety of types exist. Included in the chemical systems category are the current hydrogen peroxide and multi-purpose solutions. Chemical disinfection can be subdivided into oxidative (hydrogen peroxide and chlorine) and conventional cold chemical. Disinfectants such as thimerosal, chlorhexidine, benzalkonium chloride and sorbic acid should be used with caution because of their potential for disinfectantinduced sensitivity reactions. The various chemicals used as disinfectants are listed below. Thimerosal, a mercurial antibacterial, is effective as an antifungal agent. It has been used extensively in the past in solutions for both rigid and soft CLs. It is most effective neutral or slightly alkaline phs. It acts by bonding with cell enzymes, inhibiting their activity and killing the organism. Its concentration in the solution varies from % %. However, it is reported to have reduced activity in combination with ethylenediamine tetracetic acid (EDTA or sodium edetate) and is incompatible with BAK. Thiomerosal can be decomposed by light. Cytotoxic reactions of the corneal epithelium have been reported 6. Chlorbutanol is a chlorinated alcohol preservative with broad spectrum of action. It is however, slow acting against and bacteria and has a distinctive odour. Originally used on PMMA lenses, it is now not a common ingredient. It is effective in acidic ph and used along with other preservatives. This unstable and volatile preservative is used in a concentration of 0.5 %. Benzyl Alcohol is a disinfectant and preservative for RGP and PMMA lenses. It is unsuitable for use with soft contact lenses. It is non-cytogenic and relatively non-sensitizing. It is a bactericidal and viricidal but ineffective against Pseudomonas aeruginosa in low concentrations. Like other alcohols (isopropyl alcohol, isopropanol, ethanol), it behaves like a lipid solvent. Chlorhexidine gluconate (CHG - a biguanide antimicrobial) is used both in hard and soft contact Conventional Cold Chemical Disinfectant- Based Solutions The characteristics of the disinfectants should be such that they are compatible with other ingredients, non-toxic and non-irritating, stable over time and effective against a wide range of organisms. Fig. 2. Solution induced corneal toxicity

61 September 2009 Pravin T. et al. - Contact Lens Care 297 Fig. 3. Thiomerosal Toxicity of skin lens solutions. Chlorhexidine inhibits cation transport and membrane bound ATP in cell membranes. It can bind on protein deposits on lenses and can cause irritation. Not compatible with Thimerosal. It is known to adsorb until saturation and leach from the lens causing toxic reactions on the cornea. Benzalkonium chloride (BAK) is a quaternary ammonium compound and used mainly for PMMA lenses. It works by adsorbing to cell s membrane, thereby increasing its permeability and leading to rupture of the cell. For this reason corneal exposure to the solution should be avoided. The concentration of BAK in solution is % and is effective at an alkaline ph of 8. BAK decomposes in light. Long-term use of this preservative may cause the lens surface to become hydrophobic. EDTA, Edetate, Disodium edentate, Edetic acid are not strictly preservatives. They are variously described as preservative enhancers, preservative potentiators and chelating agents. EDTA is contained in most CL solutions. EDTA potentiates the action of quaternary ammonium compounds against gramnegative organisms but not gram-positive ones. EDTA s action removes, by chelation, divalent cations such as calcium and magnesium ions from solutions and/or cell walls of gram-negative organisms. Such cell wall disruptions slow or prevent cell growth. EDTA does not bind to lens materials significantly and is normally used in combination with other preservatives. It has a synergistic action with BAK, which enhances the effectiveness of the blended solution. Sorbic acid has antibacterial and limited antifungal activity. Its concentration in SCLs has not been shown to cause death of the corneal epithelial cells but adherence to contact lenses is facilitated by its organic reaction with the amino acid (lysine) in tear proteins, and causes a yellow or brown discolouration. DYMED : Poly aminopropyl biguanide (PAPB), Poly hexamethlene biguanide (PHMB) are new generation of preservatives developed to address the problems previous preservatives created, like ocular irritation and hypersensitivity. Dymed is the marketing name for PAPB. Initially used in anti-malarial water treatment and swimming pool chemical has now found a place as an adjuvant in the treatment of Acanthamoebakeratitis 7. PAPB selectively binds with negatively charged phospholipids of the cell walls causing membrane damage, cell content leakage and ultimately cell death. It is used in a low concentration of %. Polyquad is the marketing name for a high molecular weight (polymeric) quaternary ammonium compound: Poly(quaternium-1), polidromium chloride, onamer M This type of preservative is used in both rigid and soft lenses in concentrations of %. Its high molecular weight of 5000 restricts its entry into lens materials thus minimizing ocular reactions. Chlorine Systems : The use of chlorine-releasing tablets in SCL disinfection systems dates back to the 1970s. The recent systems are supplied as convenient blister packed anhydrous effervescent tablets of either stabilized halane or halazone benzoic acid. Both tablets slightly differ in the amount of available chlorine (4 8 ppm). The tablet is dissolved in 10ml of unpreserved saline to make a disinfecting solution of ph between 5.5 and hours exposure is recommended. The antimicrobial activity will depend on the concentration of undissociated hypochlorous acid. Lenses should be thoroughly rinsed before re-insertion. The dissociated hypochlorous acid produces hypochlorite and chlorine, which are also bleaching agents. Lenses tinted with reactive dyes can have their colour altered. Hydrogen Peroxide based chemical disinfectant solutions may be either preserved or preservative free and can be divided into two main types: One-step system Two-step systems Hydrogen peroxide systems are normally formulated

62 298 Kerala Journal of Ophthalmology Vol. XXI, No. 3 with a 3 % peroxide concentration whose ph is often acidic at For a lens to be wearable following disinfection, neutralization is required. For the purpose of neutralization substances like sodium pyruvate, sodium thiosulphite, catalase and sodium bicarbonate have been used. Most systems decompose hydrogen peroxide into saline and oxygen catalytically. Disinfection in hydrogen peroxide is reasonably effective in minutes. One-step systems are formulated so that the peroxide disinfection and neutralization are performed during the recommended time. With tablet-using systems a delay is applied to the neutralization phase. With disc-based systems, no delay is applied to the neutralization phase. Regardless of which of these systems is used special vented lens cases are required to allow the oxygen generated to escape. One-step systems use either a catalytic (platinum) disc (6 hours) or a time-delayed catalase tablet (2 hours). When neutralization is performed as a separate step, the system is called a two-step system. Very early systems neutralized peroxide using pre-measured quantities of sodium bicarbonate for a minimum of 10 minutes. In fact, the process was not true neutralization and usually took longer than 10 minutes. Rather, the bicarbonate altered the solution ph (upwards) to levels at which peroxide was inherently less stable. The peroxide solution then began to decompose slowly into water and oxygen. With two-step systems it is recommended that lenses are stored overnight in the peroxide and neutralized immediately before lens usage. Advantages of the hydrogen peroxidase system is that they are rapid killing large numbers of most organisms in a short time period, minute soaking time. High anti microbial efficacy and non-toxic decomposition products are its other advantages. Disadvantages being that once it is neutralized, a peroxide system has no antimicrobial power and can sometimes cause irritation in the eye if not neutralized properly. It is not perfectly compatible especially with high water content, ionic contact lenses in that it can reversibly alter lens parameters and water content. Multi-step peroxidase systems can be overly complex and confuse the patient. Multi- Purpose Solution Many modern lens care systems use one solution to perform the functions of a number of components, thereby reducing the actual number of solutions required. Fig. 4. Hydrogen peroxide System For ease of use and patient convenience, multi-purpose solutions (one-bottle systems) are formulated to allow Table: Summary of recommended Disinfecting Systems based on Lens Material 1 HEAT COLD CHEMICAL PEROXIDE MULTI-PURPOSE SCL Low Non-ionic Yes Yes Yes Yes X Yes X Yes Low Ionic Some Yes Yes Yes High Non-ionic X Yes X Yes High Ionic X Yes Yes Yes Uncommon PMMA RGP X Yes Special Yes Uncommon Formulation For coloured contact lenses heat or hydrogen peroxide should not be used as it cause bleaching/ fading of the colour.

63 September 2009 Pravin T. et al. - Contact Lens Care 299 cleaning, rinsing and disinfection functions to be combined. More recently even protein removers have been added to these solutions. Protein Remover Protein removers, also known erroneously as enzymatic cleaners, are included in the care systems for soft Cleaving Enzyme tablets act as protein removers by cleaving the peptide bonds in tear proteins deposited on contact lens surfaces 1. Since the action of the enzyme tablet only loosens the protein, it is important to instruct the patient to clean the lenses by rubbing and rinsing upon completion of the deproteinizing process. Rewetting Drops and Lubricants Fig:5 protein deposits source: IACLE Fig: 6 Calcium deposits contact lenses, and some RGP lenses, that are not replaced regularly (>1 month). Not all protein removers are enzyme-based. Those that are, are usually supplied in tablet form. Chemical-based systems are usually supplied as readyto-use liquids. These cleaners are effective in loosening tightly bound protein deposits. However, they cannot be expected to remove all proteins. Prior to protein removal, the lenses should be cleaned and rinsed before being placed in the recommended container with the tablet or solution for the recommended time. Enzyme cleaners are ineffective in the presence of lipid deposits or other debris. Protein treatment is usually done weekly or at a frequency dependent on the rate of patient protein deposition. Heavy protein depositors, especially ionic high water material lens wearers, may require an increased frequency. Frequent use of protein removers are required if heat is used as a disinfectant. Lenses should be soaked in the remover for 15 minutes to two hours, depending on the type of protein remover used and rate of protein build-up. Enzymes used include papain, pancreatin, subtilisin, pronase, amylase, lipase, and hydroxyalkylphosphonate. It is to be noted that Papain is not compatible with hydrogen peroxide 9. Lens Lubricants permit lubrication and rewetting of the lens while on the eye. Typically, they contain a low concentration of a non-ionic surfactant to promote cleaning, a polymer to lubricate the lens, buffering agents and preservatives 10. Lens lubricants are particularly helpful for wearers of extended wear lenses, but can also be used with daily wear lenses. The drying out of the lens on the eye from exposure to wind, low humidity, and high temperatures may be relieved by these products. Patients who experience difficulty removing hydrogel lenses because of dehydration or who frequently damage their lenses on removal may also benefit from the use of lubricants. Lubricating and re-wetting drops are formulated with viscosityenhancing agents (commonly polyvinyl alcohol, methylcellulose, etc.). Lens Storage and Cases A poorly maintained contact lens case can be a source of heavy contamination of contact lenses with microorganisms. Biofilm or glycocalyx formation on the surface of contact lens storage cases can harbour Pseudomonas aeruginosa and Serratia marcereens 11. The biofilm is produced by the bacteria themselves. It protects the host bacterial cells from chemical or preservative attack and traps nutrient particles and Fig: 7 Dirty lens case

64 300 Kerala Journal of Ophthalmology Vol. XXI, No. 3 organisms. To avoid contamination, the lens case should be rinsed after use and the lenses should be stored in fresh solution. CIBA vision has come out with a unique Pro Guard lens case, infused with an anti-microbial agent that helps prevent contamination. The contact lens case contains silver atoms that have been electrically charged (ions), and help reduce the possibility of contamination by up to 40%. Care of Lens Cases Discard all the used solution from the case. This prevents loss of disinfecting efficacy when fresh solution is mixed with used solutions. Scrub with a toothbrush and detergent weekly. Oil free soaps or detergents are recommended for this step. Rinse with hot water and rub thoroughly with a clean, dry tissue. Air dry. Keeping the lens case dry will prevent colonization by microorganisms such as protozoa that thrive in moist or wet environments. It is also recommended that the lens case be replaced at frequent intervals. Lens Replacement Schedule and Care Regimen Daily Disposables Because of its single use concept, this lens does not require use of surfactant cleaner, disinfecting solution or weekly enzyme. If needed, the patient can use in-eye re-wetting drops or sterile saline for rinsing prior to insertion. Regular Disposables These lenses are replaced weekly or bi-weekly. Suitable care includes multi-purpose solutions given as complete care system. If preferred, lenses can be rinsed with saline prior to insertion or a lubrication solution used to re-wet the lenses. No weekly protein removal is needed. If a multi-purpose solution causes irritation or discomfort, a surfactant cleaner can be used along with hydrogen peroxide as disinfectant. Frequently Replaced Lenses Clean lenses with a multi-purpose solution or a surfactant cleaner. Rinse with multi-purpose solution or a saline solution (unit-dose, aerosol or preserved). Disinfection may be done with heat, cold chemical, oxidative or multipurpose systems. The final choice depends on lens material and patient compliance. Protein removal is required for 3 and 6 monthlyreplaced lenses but with lower frequency compared to conventional lenses. It can be avoided in the case of monthly disposables. Lubricating/re-wetting drops may be used if required. Conventional Lenses Clean lenses with a multi-purpose solution or a surfactant cleaner. Rinse with multi-purpose solution or a saline solution (unit-dose, aerosol or preserved). Disinfection may be done with heat, cold chemical, Conventional Frequent Replacement Disposable > 6 months 1 month 3 months 1 month Surfactant Cleaner Yes Maybe No All Purpose Yes Yes Yes Peroxide One Step Yes Yes Yes Two Step Yes No No Enzyme Yes Maybe No Clean Lens Cases weekly Yes Yes Yes

65 September 2009 Pravin T. et al. - Contact Lens Care 301 oxidative or multipurpose systems. The final choice depends on lens material and patient compliance. Protein removal is done weekly. It is performed using a tablet or liquid form of protein remover which may be chemical or enzymatic in nature. Some wearers may benefit from wetting drops especially if they are working in air-conditioned environment. For regular wearers of conventional lenses heat or thimerosal/chlorhexidine-based disinfection is not recommended. In-office Maintenance Of Diagnostic (Trial Set) Lenses SCL: RGP: Use heat if possible, otherwise peroxide Use peroxide or store lenses dry Re-disinfect non-disposable inventory trial lenses at least once a month. Multi-purpose solutions should only be applied to trial lenses used very frequently and are not suitable for long term storage. Regardless of the storage method, all trial lenses should be cleaned and rinsed thoroughly before storage. In-office Procedures to Clean and Disinfect Lenses Various in-office procedures can be used to clean and disinfect lenses. Heater/stirrer units with/without: -special-purpose care products -oxidizing agents (hydrogen peroxide, sodium perborate, sodium percarbonate, sodium hypochlorite, etc.) -special saline (e.g. saline with a calcium chelating agent). Oxidizing agents (e.g. 6 or 9 % hydrogen peroxide with or without heat). Standing waves. A lens cleaning system involving low-frequency agitation of a lens vial containing contact lenses and a cleaning solution is said to create turbulence, which in turn dislodges surface contaminants. Ultrasound. Ultrasonic (using high frequency audible waves between 15 and 20 khz) agitation causes removal of particulate matter from contact lens surfaces by cavitation (intense agitation of small bubbles at the lens surface). Is effective on low water content soft lenses. If used for longer duration lens can become opaque. Ultraviolet. A lens disinfection system using either direct UV irradiation of microbes or the production of ozone by a UV-emitting (253.7nm) discharge tube 13. The ozone is the actual disinfectant. It kills microorganisms by breaking bonds and cross-links between nucleic acids. It effectively disinfects SCLs and RGPs. Microwaves. This is an alternative form of heat disinfection 12, albeit high heat. Microwave oven of 2.5GHz, 500 watts and turntable is used. While undoubtedly effective against microorganisms, the temperatures involved may also have deleterious effects on the lenses and decrease their life expectancy. Vented containers must be used and the lenses should be re-hydrated in saline after irradiation. Some systemic medications can cause lens damage and ocular signs and symptoms, which have to be differentiated from those of the care products. Some care products may also not be compatible with certain systemic medication. Table: Possible Systemic Medication Interaction with Soft contact lenses 14. Clinical Findings Medication Lens Discolouration (yellow to orange) NtrofurantoinPhenazopyridine Phenophthalein Rifampin Rifadin Sulfasalazine Tetracycline Corneal Staining Tetracycline when used with Thiomerosal Preserved products Contact lens-related epithelial irritation

66 302 Kerala Journal of Ophthalmology Vol. XXI, No. 3 Acetylsalicylic acid (aspirin) Decreased lens wetting comfort Antihypertensives Tricyclic antidepressants Antihistamines Belladonnas Anticholinergics Current trends in solution and lens care The trend in contact lens care is toward simpler, less toxic systems that rely on patient compliance to function optimally. Simplified soft Lens Regimens The common approach to soft contact lens care is to use a one-bottle system. The leading, simplified soft lens care products, ReNu (Bausch and Lomb), SOLO-care (CIBA), Complete (Allergan), Opti-free and Opti-one (Alcon) are very similar in their low toxicity and reliance on digital cleaning and rinsing with clean hands, followed by soaking in a clean case. While these products have helped reduce toxic and allergic reactions by using low toxicity preservatives and avoiding thimerosal, chlorhexidine and exposure to hydrogen peroxide, there is little evidence that they have led to better compliance. Fortunately, frequent lens replacement and the eye s defence mechanisms have kept most patients safe most of the time. Sicca-like syndrome has been sometimes associated with one-bottle lens care systems that contain surfactants. These patients need a saline rinse (sorbic acid preserved or sterile non-preserved) prior to lens insertion. If stronger measures are needed, switching to a hydrogen peroxide system can sometimes dramatically improve comfort. Hydrogen Peroxide and other Regimens The more difficult to use and more expensive hydrogen peroxide systems are often used only as problem-solvers and have lost market share in the last decade. AOSEPT one step is quick and ideal product for in-office disinfection before re-inserting for a patient. Liquid protein remover Unizyme, a product from CIBA Vision for use with peroxide products, is said to work in 10 minutes. For in-office trial lens storage, however there is no substitute for heat disinfection. RGP Lens Care RGP solutions for the most part are not new, but if one switches from cleaning/disinfecting/wetting/ conditioning/cushioning solution to cleaning/ disinfecting/ conditioning/but not wetting/cushioning solution it should be made sure that wetting/cushioning solution is added to the regime. Most of the currently available products for RGP equally work well. Allergy Sufferers For allergic patients pre- and post lens wear use of topical anti-histaminics or mast cell stabilizers or nonsteroidal anti-inflammatory agents will maximize comfort. To summarise while selecting a care regimen the practitioner needs to consider the wearing schedule of the patient, the lens type, replacement schedule and convenience of the patient and ocular sensitivity issues as well. It is a good practice to repeat instructions and assess demonstration by patient. Patients should be instructed not to mix solution types and brands and to consult the practitioner before substituting solutions. The message for care and maintenance can be stressed with the acronym CRADLE Clean, Rinse And Disinfect Lenses Everytime References 1. Sylvie Sulaiman, IACLE Contact Lens Course, Module 5: Units 5.1, pg 9, Carell BA et al: The effect of rigid gas permeable lens cleaners on lens parameter stability. J Am Optom Assoc 63:193, Bennett ES, Henry VA: PGP lens power change with abrasive cleaner use. Int Contact Lens Clin 17:152, Mandell RB: Lens Handling, care and storage. In Contact Lens Practice 4 th ed, pp , Anger, C. B., and J. P. Curie Preservation and disinfection, p. II-187 II-213. In Contact lenses: the CLAO guide to basic science and clinical practice, vol.

67 September 2009 Pravin T. et al. - Contact Lens Care 303 II. Soft and rigid contact lenses. Kendall-Hunt, Dubuque, Iowa. 6. Tripathi BJ, Tripathi RC, Kolli SP: Cytotoxicity of ophthalmic preservatives on human corneal epithelium. Lens Eye Toxic Res. 9(3&4): , Larkin DFP et al: Treatment of Acanthamoeba Keratitis with Polyhexamethylene biguanide. Opthalmology. 99: , Rogan M: Systems for hydrogen peroxide disinfection of soft contact lenses. Transactions of the British Contact Lens Association, Annual Clinical Conference, May 1985, Blackpool, England pp Campbell R, Caroline P: A strong case for enzymatic lens care compliance. Contact Lens Spectrum 11:56, Lowther GE et al: The Pharmacist s Guide to Contact Lenses and Lens Care. Atlanta, CIBA Vision corporation, Feldman GL et al: Control of Bacterial Biofilms on Rigid Gas Permeable Lenses. CL Spectrum 7(10): 36-39, Harris MG et al: In-office microwave disinfection of soft Contact Lenses. Optometry Vision Sci. 67(2): , Harris MG et al: Ultra Violet disinfection of Contact Lenses. Optometry Vision Sci. 70(10): , Shovlin J: Systemic Medications and their interaction with soft contact lenses. Int Contact lens Clin 17: 250, Edward S. Bennett and Barry A. Weissman, Clinical Contact Lens Practice text book, Chapters 25, 34 and IACLE Contact Lens Course, Module 5: Michael A. Ward, The Microbiology of Contact lens Wear, Contact Lens Spectrum Journal, Sept. 1997:

68 304 Kerala Journal of Ophthalmology Vol. XXI, No. 3 CASE REPORT A case report of colobomatous RD Dr. Arya A.R MS, Dr. Biju John MS DNB FRCS A 33 yr old housewife with no history of any systemic illness presented with sudden onset of defective vision in left eye 2 weeks back.there is no history of any significant ocular illness in the past.no history of prior trauma/seeing flashes/floaters prior to this episode. Ocular examination revealed a visual acuity of 6/6 in right eye and perception of light with accurate projection in left eye.anterior segment examination of left eye revealed typical iris coloboma. (Fig. 1) and microcornea (10 x 9mm) Fundus (LE) (RE) Fig. 2. showing retinochoroidal coloboma with RD in left eye. Fig. 1. showing microcornea and iris coloboma in left eye and normal appearance in right eye. Fundus examination revealed colobomatous area in the inferior quadrant involving the disc along with retinal detachment. (Fig. 2). No breaks were detected in the peripheral retina even after careful indirect ophthalmoscopy and slit lamp biomicroscopy with 3 mirror. It was presumend that location of the break/breaks was within the colobomatous area. Blood investigations were with in normal limits A diagnosis of iris coloboma (typical) with retinochoroidal coloboma and rhegmatogenous retinal detachment in left eye was made. Regional institute of Ophthalmology,Trivandrum. Management - The patient underwent pars plana vitrectomy. During removal of vitreous adjacent to the colobomatous area schlieren phenomenon was observed and this confirmed that the break was within the coloboma. Internal drainage of subretinal fluid along with simultaneous fluid air exchange was done with the help of a silicone tipped cannula positioned adjacent to the site of the presumed break.retina flattened and following this air silicone oil exchange was done. Subsequently 3 rows of barrage laser burns were placed all around the coloboma using LIO. Fig: 3,4,5 Arrow showing laser mark.

69 September 2009 Arya AR et al. - Colobomatous RD 305 Post operatively the retina remained attached and vision was 1/60.She was discharged on the 4 th day. Vision improved to 3/60 by the 2 nd post operative month and the retina remained attached with barrage laser burns in place. Discussion The term coloboma was introduced by Waltherindicates a condition wherein a portion of a structure of the eye is lacking.it occurs as result of inadequate closure of embryonic fissure 5-7 wks postconceptional. Childhood colobomas are important cause of childhood blindness and visual impairment. The development of retina lags behind in the region of embryonic cleft. Initially the inner layer (presumptive retina) normally grows more quickly than outer pigmentary layer of optic cup. Normally the lips of embryonic cleft meet in central part first and then extends proximally and distally. Proximally the cleft never closes where hyaloid artery enters and in this region the eversion of inner layer is present for sometime so that fusion of 2 outer layers is delayed and a short nonpigmented strip remains at proximal end of fissure. It is an accentuation of this process which cause the formation of coloboma.then the process of atrophy and regression affects the retina throughout the colobomatous area so that the layers disappear and tend to be replaced by glial and fibrous elements. At the same time sclera the development of which is largely dependent on influence of optic cup remains thin & poorly developed in abnormal region and tend to suffer ectatic change. If the process involves whole length of the fissure it results in complete coloboma. If isolated areas of cleft succeed in fusing it results in bridge coloboma. Colobomas are usually inferonasal(typical). It can be unilateral/bilateral. Even large coloboma which donot involve the fovea may exhibit relatively preserved visual acuity. Severe coloboma may be associated with microphthalmos. Ocular complications can be -amblyopia -refractive error - choroidal neovascularisation -retinal detachment. CHARGE Syndrome-when coloboma is associated with- Heart defects and other abnormalities such as -Atresia(coanal) -Retardation of Growth -Ear abnormality D/D -Trauma -Chorioretinal scar Staphyloma-idiopathic -myopic associated with connective tissue disorder -North Carolina macular dystrophy. OCT can provide insight into the pathology at the margin of coloboma. Coupled with the knowledge from histopathological information can guide the management of RDs secondary to coloboma of choroid with a high degree of success. Retinal detachments associated with coloboma of the choroid present a surgical challenge. Within the colobomatous area the retinal tissue is thin and hypoplastic, the choroid and retinal pigment epithelium (RPE) are not developed and the underlying sclera is thin and ectatic, producing a staphyloma. The breaks which are invariably within this area will be difficult to locate due to the lack of contrast and are often located correctly during vitrectomy as in our case. Complete vitrectomy with method to create chorioretinal adhesion around the coloboma and silicone oil or gas tamponade provide effective treatment for colobomatous retinal detachments. References 1. Stephen J.Ryan-Retina 4 th edition 2. System of ophthalmology-normal andabnormal development Vol 3.Sir Stewart Duke Elder. 3. Retina &Vitreous ; AAO. 4. Parsons Diseases of the eye. 20 th edition. 5. Jalali S, Das T. Selection of surgical technique for retinal detachment with coloboma of the choroid. Indian J Ophthalmol 1994;42:27-30

70 306 Kerala Journal of Ophthalmology Vol. XXI, No. 3 CASE REPORT Vasoproliferative Tumour of The Retina- A Case Report Dr Tufela Shafi MS, Dr Natasha Radhakrishnan MS DNB MRCophth, Dr Gopal S Pillai MD DNB FRCS, Dr Roshan George MS Retinal tumors are a rarity with peripheral retinal tumors being still more rare. Here we report a case where a peripheral retinal tumor presented with a progressive decrease in vision over a long time due to cystoid macular edema. A 37 yr old male presented with history of gradual painless progressive loss of vision left eye since 2 years, with no improvement with treatment. On examination, he had a best corrected visual acuity of 6/6 in the right eye and 6/18 in left eye. Intraocular pressure in both eyes was normal. Examination of the right eye including anterior and posterior segments was within normal limits. Anterior segment examination of the left eye revealed 1+ cells and haze in the anterior chamber. Vitreous showed 3+ cells and 2+ haze with membranes and strands signifying partial PVD. Fundus examination revealed hyperemic disc and stereoscopic examination of the macula revealed the presence of cystoid macular edema. There was fibrous proliferation and epiretinal membrane along the arcades. A yellowish pink elevated mass about 7 to 8 DD in size, with irregular surface was seen superotemporally beyond the equator. Vessels traversing and supplying the mass appeared dilated and mildly tortuous and there were retinal pigment epithelial changes at the base of the mass all around. There were some telangiectatic vessels over the mass along with hemorrhage. The lesion was also associated with some intraretinal and subretinal exudation (Fig 1). AIMS, Edapally, Kochi Fluorescein angiography showed patchy hyperfluorescence of lesion with multiple areas of window defects corresponding to the RPE changes and staining and blocked fluorescence secondary to the exudation and mass lesion. The hyperfluorescence increased in the late phase due to leakage in some areas. There were areas of blocked fluorescence over the lesion corresponding to areas of hemorrhage and in the periphery of the lesion secondary to the RPE hyperplasia. There was late disc leakage and flower petal leakage at fovea signifying cystoid macular edema (Fig 2). OCT showed macular edema with a cystoid pattern with a central macular thickness of about 450 microns. B Scan showed an elevated, acoustically solid mass about 9.7 x 7.1 x 3.2 mm in size and multiple echoes in the vitreous suggestive of opacities (Fig 3). The following differential diagnosis were entertained 1 Vasoproliferative tumour 2 An inflammatory or infective mass 3 Angioma of Von Hippel Lindau disease 4 Coats disease A complete systemic evaluation was sought to rule out coexistent systemic infections. Mantoux test was found to be negative after 48 hours. Peripheral smear showed normocytic normochromic blood picture. USG abdomen, CT Thorax and MRI brain (plain and contrast) were

71 September 2009 T. Shafi et al. - Vasoproliferative retinal tumours 307 normal. Therefore infective or inflammatory mass was ruled out. However, cholesterol levels were found to be high (496.4mg/dl). During the differential diagnosis, Von Hippel-Lindau was excluded because of absence of grossly tortuous and engorged blood vessels, absence of family history for the disease and absence of other features of Von Hippel-Lindau disease. In VHL even small tumours are associated with grossly engorged and tortuous blood vessels. Also the angiographic characteristics of Von Hippel-Lindau like rapid filling of arteries and rapid AV transit were not seen. Coats disease was excluded because that is usually seen in boys at a younger age, and usually does not cause tumour like lesions even when exudation is severe. The exudations in Coats disease are often flat and not elevated. Besides tumour like lesions, if present in Coats are accompanied by advanced exudative retinal detachment. Our patient showed the typical clinical picture of vasoproliferative tumour. He had a solitary, unilateral, yellowish vascularized tumour associated with intraretinal exudation, RPE hyperplasia at the base, telengiectasias and hemorrhage over lesion. He had additional findings of anterior chamber cells, vitreous cells and cystoid macular edema all of which have been reported in various literature 1,2,3. We believe these changes to be a secondary reactionary process to the Fig. 1. Fundus picture showing the vasoproliferative tumor mass Fig 2. FFA showing CME Fig. 3. B-Scan ultrasound showing acoustically solid tumour. presence of tumour in the eye. FFA picture further helped to confirm the diagnosis. Presence of elevated levels of cholesterol in patients with vasoproliferative tumour has been reported in literature 4. With the diagnosis of vasoproliferative tumour, decision to treat with multiple sessions of cryotherapy was taken and patient given first session of cryotherapy. He is at present on follow up. Discussion The term vasoproliferative tumour was coined by Shields et al in Previously these tumours were called presumed acquired haemangiomas, angioma like lesions and peripheral retinal telengiectasia. Vasoproliferative tumours of the retina are benign vascular tumours of unknown origin. These tumours generally present as yellow pink, one or more retinal nodules seen usually in the pre-equatorial fundus, generally in the inferotemporal quadrant but may also be seen in the upper retinal quadrants 2,5 or even at posterior pole 6,7. Their feeding and draining vessels are slightly dilated but not enlarged or convoluted. These tumours can be associated with additional clinical changes like intraretinal and subretinal hemorrhages, intraretinal and subretinal exudation, exudative retinal detachments, hyperpigmentation of RPE, vitreous and anterior chamber cells, vitreous hemorrhage, preretinal macular fibrosis and macular edema 1,2,7. Exudation in vasoproliferative tumours tends to creep back towards the fovea and is hence seen in continuity with the lesion 4,7. However preretinal gliosis can occur remote from the lesion 7. The pathogenesis of these tumours has not been established. In a study of 103 patients, Shields et al found that these lesions were idiopathic or primary in 74 % and secondary to congenital, inflammatory, vascular, traumatic, dystrophic and degenerative ocular diseases in the rest 1. Primary vasoproliferative tumours are solitary, unilateral and generally located in the inferotemporal quadrant of the retina. Many of the patients with primary vasoproliferative tumours also have systemic hypertension. Secondary vasoproliferative tumours on the other hand are bilateral, multifocal and can be located in any quadrant of the retina. Secondary

72 308 Kerala Journal of Ophthalmology Vol. XXI, No. 3 tumours also tend to be more ill defined and diffuse 7. These tumours are believed to represent gliovascular proliferations with varying degrees of both gliosis and vascular proliferation. Histopathology of these tumours shows them to be composed predominantly of elongated, spindle shaped cells, corresponding to glial cell origin imposed over a fine capillary background. Mitotic figures, pleomorphism or cellular atypia has not been shown to be present.another important feature of these tumours is the presence of dilated blood vessels within the tumour mass 2,5. Various treatment options have been described for vasoproliferative tumours like periodic observation 1,2, cryotherapy 1,2,3,4, laser photocoagulation 1,4 and plaque radiotherapy 1,2,8. Some reports suggest that these tumours may be treated successfully with photodynamic therapy. Vitrectomy may also be needed for complications accompanying these tumours like vitreous haemorrhage and retinal detachment. Irvine F et al 9 have suggested that trans scleral resection be attempted if there is difficulty in diagnosis. This would give tissue for diagnosis and also avoid unnecessary enucleation in case of diagnostic dilemma. In conclusion, vasoproliferative tumours should be included in the differential diagnosis of any peripheral retinal tumour. They should be recognized by their distinctive clinical features and angiographic characteristics and being decidedly benign their recognition would avoid unnecessary morbidity for the patient. References 1 Shields CL, Shields JA, Barret j, et al. Vasoproliferative tumours of the ocular fundus. Classification and clinical manifestations in 103 patients.arch Ophthalmol 1995;113: Heimann H,Bornfeld N,Vij O,Coupland SE,Bechaakisne, Kellner U, Forster MM. Vasoproliferative tumours of the retina. Br J Ophthalmol 2000;84: Bianciotto C, Shields CL. Retinal vasoproliferative tumour with associated cystoid macular edema treated with cryotherapy and intravitreal triamcinolone.retina Today 2008; Shields JA. Ocular oncology essentials. Retinal physician Jain K, Berger A R,Yucil Y H, McGowan H D. Vasoproliferative tumours of the retina.eye 2003;17: Dunbar MT. Is only seeing eye now threatened?. Review of Optometry Vol. No: 141: 04 Issue 4/15/04. 7 Shields JA, Shields Cl.Intra ocular Tumours: An atlas and text book 2007; Cohen VM, Shields CL, Demirci H, Shields JA. Iodine I 125 Plaque radiotherapy for vasoproliferative tumours of the retina in 30 eyes.arch Ophthalmol 2008; 126(9): Irvine F, O Donnell N, Kemp E, Lee WR. Retinal vasoproliferative tumours:surgical management and histological findings.arch Ophthalmol 2000;118:

73 September 2009 Kerala Journal of Ophthalmology 309 COMMUNITY OPHTHALMOLOGY Go Green for a Healthier Life Dr. Meena Chakrabarti MS DO DNB The news is crystal clear: After decades and decades of polluting our surroundings, the planet is suffering. Scientists have been very vocal about the impact our driving, manufacturing, and consumption is having on the future environment, like melting icebergs, rising ocean levels, and a disappearing ozone layer. Indeed, global warming and greenhouse gases have become regular parts of our vernacular. The most comprehensive modeling yet carried out on the likelihood of how much hotter the Earth s climate will get in this century shows that without rapid and massive action, the problem will be about twice as severe as previously estimated six years ago - and could be even worse than that. American Meteorological Society s Journal of Climate, indicate a median probability of surface warming of 5.2 degrees Celsius by 2100, with a 90% probability range of 3.5 to 7.4 degrees. This can be compared to a median projected increase in the 2003 study of just 2.4 degrees. The difference is caused by several factors rather than any single big change. Among these are improved economic modeling and newer economic data showing less chance of low emissions than had been projected in the earlier scenarios. Other changes include accounting for the past masking of underlying warming by the cooling induced by 20th century volcanoes, and for emissions of soot, which can add to the warming effect. In addition, measurements of deep ocean temperature rises, which enable estimates of how fast heat and carbon dioxide are removed from the atmosphere and transferred to the ocean depths, imply Chakrabarti Eye Care Centre, Kochulloor, Trivandrum tvm_meenarup@sancharnet.in lower transfer rates than previously estimated. Now, the question being asked is can the damage be reversed? Experts are unsure of a definitive answer, but they all agree that if individuals assume a certain level of personal responsibility, the future will be cleaner. With more than 200 million cars on the roads, it is evident that we have a love affair with the automobile. Whether it is in a luxury sedan, massive sports utility vehicle, racy speedster, or cost-conscious compacts, we enjoy driving. That infatuation, however, has come with a heavy price tag of urban congestion and plenty of pollution. The problem develops when gasoline burns because it produces a byproduct of nearly 20 pounds of carbon dioxide (CO 2 ) for each gallon of fuel. CO 2 is one of the dominant chemicals in greenhouse gases and a major contributor to global warming. On a closer level, tailpipe emissions react with sunlight and oxygen to create ground level ozone. Not surprising, heavy loads of this toxic gas are prevalent in major cities and so we live in areas with poor air quality. First, check out hybrid automobiles. These cars operate off both gas engines and electric motors. The electric motor supplies added power during acceleration, thereby allowing designers to install smaller traditional engines. Ultimately, they consume less fuel, which saves you cash and cuts down on CO 2 emissions. If you drive a totally gas-powered vehicle, you can still minimize the negatives. One of the best ways to downgrade its polluting potential is to upgrade your

74 310 Kerala Journal of Ophthalmology Vol. XXI, No. 3 vehicle s performance. Schedule regular service appointments to change oil, belts, and filters. For example, a clogged air filter can decrease your mileage by 10%. Also, measure your tire pressure every few months or before each long-distance trip. Proper inflation saves you approximately 3% in fuel costs, and provides you with a safer drive. Under-inflated tires are more susceptible to damage, such as flats and blowouts two things you definitely want to avoid when heading to a new job. Remember to refer to your car s operating manual or contact a trusted mechanic before attempting any major maintenance. Other simple, but earthfriendly, motoring techniques include engaging cruise control on long stretches and avoiding rapid acceleration or braking If you drive a totally gaspowered vehicle, you can still minimize the negatives. For one thing, recycling pays. Items such as paper, newspapers, cardboard, glass, plastic, and aluminum, can be broken down and repurposed into other useful products. And, we use a lot of these substances. Instead of expending energy and natural resources to create new containers, recycling one glass bottle saves enough power to light a 100-watt bulb for up to 4 hours. One recycled aluminum can has the potential to save enough energy to run a television or computer for 3 hours. Fortunately, many municipalities and apartment complexes have turned recycling into a simple process by supplying bins dedicated to specific items. All you have to do is separate the various pieces from the regular trash. If your apartment organization does not yet recycle, volunteer to work with the management to help set up and promote a new system. You also can go green by turning off and unplugging. Sure, it is common sense to switch off a light or television when leaving a room, but it s even better to unplug major electronics and appliances when not in use. Does your coffee pot really need to be plugged in while you are on duty for 12 hours? Also, your computer, printer, and cell phone charger eat up energy when left plugged in and not turned on. That is a phenomenon known as vampire power, and is estimated to waste nearly millions in electric bills each year. Swapping incandescent light bulbs for the long-lasting, energy-efficient compact fluorescent type is another money saving and eco-friendly tip. These are designed to use 75% less energy, and boast of a 10 times longer life cycle. Energy is not the only commodity you can affect. Water is another resource in need of conservation case in point, several parts of the world suffered devastating droughts this past summer. While you have no control over Mother Nature, you can do your part by taking 4- minute showers, and turning off the faucet while brushing your teeth or sudsing your hands. Also, postpone running washers and dishwashers until you have full loads, and look for phosphate-, petroleum, and chlorine-free detergents to avoid feeding unnecessary chemicals into local water systems. Using either cold or warm water temperature settings can prevent an estimated 350 pounds of CO 2 production because you minimize the energy used to heat the water. These simple steps can be followed at home, in apartment laundry centers, or in coin-operated Laundromats. Taking control of your thermostat is yet another green habit. Researchers believe that for every two degrees you lower the thermostat, the atmosphere is saved from approximately 350 pounds of CO 2. The general advice is to set your house temperature for 68 degrees during winter days, and slightly lower at night and pile on the blankets. Also, if you have access, clean your heater s filters every few months or sooner. On hot days, the opposite theory applies. Cool off with an oscillating or ceiling fan, both of which use less power than an air conditioner (AC). If you must chill out, limit your AC usage. For a central air system, set the thermostat high, around 78 degrees, and run window units for fewer, shorter operating cycles. To help maintain a comfortable climate, rely on your curtains or blinds. In the winter, open them up to let the sunlight warm your rooms, and do the opposite in summer to keep the heat out. On your own, follow these simple policies. Start off by bringing in your own coffee mug or refillable water bottle instead of choosing disposable cups or plastic bottles. You can save money and act eco-friendly by bringing your lunch with you to work on most days. If

75 September 2009 Meena Chakrabarti - Go Green for a Healthier Life 311 you plan to brown bag it, literally, reuse that bag as much as possible. Even better, buy a soft insulated lunchbox. These tend to be easy to clean and keep food hot or cold. Store food in containers or wash out and reuse plastic storage bags whenever feasible. A healthy byproduct? You control what you eat. What better way to acquaint yourself with a region than through sampling the local cuisine? Buying locally grown produce, flowers, and other items helps cut down on transportation of goods over highways while also supporting the regional economy. Wherever you grocery shop, skip the plastic or paper debate and pack up your own canvas bags. This will reduce the number of plastic items ending up in landfills. On everyday items, look for green products. Some brands promote the fact that they are environmentally friendly. For others, there are a few simple rules to abide by, such as choosing pump sprays over aerosols and picking up brown coffee filters instead of the traditional bleached white ones. If you do buy something in a plastic bottle, such as body lotion, flip it over and look for a number. This is an indicator about which type of plastic was used to create it. No number means the item isn t recyclable. Finally, put your money where it counts. There are numerous organizations that work toward protecting the planet through research, lobbying, and raising public awareness. Making it work The planet s future is yet to be written, but for now, the message is fairly clear: Do what you can to minimize the negative impact. Going green may take some effort at first, but you will most likely find that it quickly becomes force of habit, no matter where you are. Being Green When shopping for a new car, consider a hybrid model. Schedule regular maintenance to change out filters and oil Check tire pressure Ease up on the pedals and drive at consistent speeds Recycle whenever possible Unplug unused electronics and appliances Adjust thermostat to seasons BYOL: Bring your own lunch (and coffee mug) Buy local products Use canvas bags when shopping Donate to environmental organizations

76 312 Kerala Journal of Ophthalmology Vol. XXI, No. 3 PHOTO ESSAY Masquerade Syndrome Dr. Meena Chakrabarti MS DO DNB Masquerade syndrome includes a group of malignant and non-malignant systemic or primary ocular disease that clinically present in the eye as an intraocular inflammation or uveitis Uveitis Masquerade accounts for 5 % of patients with uveitis in a tertiary care centre. An awareness of the presence of and early recognition of the masquerade is of utmost importance as Ocular Masquerade may be the first sign of a life threatening disease. The various conditions that can manifest in the eye as a masquerade includes MALIGNANCIES Adults: Primary Central Nervous System lymphomas / Primary Intra Ocular lymphomas Systemic NHL Metastatic To The Eye Metastatic Carcinoma : Breast / Lung / Renal Uveal Melanomas Children: Leukaemia Retinoblastoma Medulloepithelioma Juvenile Xanthogranuloma NON-MALIGNANT MASQUERADE Intraocular foreign body / Retinal Detachment / Retinitis pigmentosa / Pigment Dispersion Syndrome / P. Acnes Infection Chakrabarti Eye Care Centre, Kochulloor, Trivandrum tvm_meenarup@sancharnet.in Many entities present as chronic intraocular inflammation and a thorough workup to exclude a masquerade syndrome should be carried out in the following situations. 1. All undiagnosed inflammatory disease 2. Intraocular inflammations with atypical clinical features and course 3. Inflammations that do not respond to adequate medical therapy 4. Age <5 years />50 years Because of the nature of the underlying disease, which has detrimental consequences, early diagnosis and prompt treatment are critical. This photoessay is on primary intraocular lymphoma (PIL) Primary Intraocular Lymphoma is the commonest condition presenting as an ocular masquerade.piol is a large B cell Non Hodgkin Lymphoma, presenting in the 5 th to 7 th decade in immunocompetent persons. Presentation in an younger age group is seen in the immunocompromised.this entity is commonly associated with CNS lymphoma and rarely with visceral and nodal lymphoma. This condition is bilateral in 80 % of cases. The ocular presentation may be varied and may manifest as vitritis, sub retinal and sub RPE creamy white infiltrates, vasculitis, retinitis or as an uveal mass lesion. 90 % of patients with PIOL develop CNS Lymphoma while only 5 % of patients with CNS Lymphoma will develop intraocular manifestations. Hence a detailed systemic workup, neurological investigations,

77 September 2009 Meena Chakrabarti - Masquerade syndrome 313 like cranial MRI and lumbar puncture are essential. Vitreous biopsy, sub retinal or subrpe aspirates or a retinochoroidotomy may be necessary for histopathological confirmation. Table 1. Scheme of Investigating a patient with chronic Intraocular Inflammation Treatment recommendations depend on whether the lesions are confined to the eye alone both eye and CNS involvement or there is recurrence following primary therapy. Treatment recommendations: 1. Intraocular Lymphoma alone XRT to eyes only Systemic Chemotherapy 2. Intraocular and CNS Lymphoma XRT to eyes + / - BRAIN Systemic Chemotherapy 3. Recurrent Intraocular Lymphoma Intravitreal salvage chemotherapy with Methotrexate, Rituximab, Anti CD-20 Monoclonal antibody. Requires Fig. 1. a-c : (a) Fundus picture at presentation showing optic nerve infiltration in Primary Intraocular lymphoma. (b) Histopathological evidence of large B cells in vitreous biopsy specimen (c)fundus photograph comparing the lesion before and after radiotherapy.

78 314 Kerala Journal of Ophthalmology Vol. XXI, No. 3 Fig. 2. a-c. (a) Fundus picture at presentation showing the creamy subretinal infiltrates temporal to the macula in a patient with PIOL. (b)hitopathological confirmation of large B cell infiltrates in the chorioretinal biopsy speciemen (c)comparative fundus pictures before and after systemic chemotherapy showing good resolution and residual RPE scarring multiple intravitreal injection and carry a very high recurrence rate on cessation of therapy. The first case shows regression after radiotherapy in a biopsy proven case of primary intraocular lymphoma which presented as disc inflitration, disc edema and vitritis. Vitreous biopsy specimen showed large B cells suggestive of PIOL. Note that regression of the lesion is unfortunately associated with optic atrophy as evidenced by the disc pallor and functional loss in this patient. (Fig. 1 a-c) The second case presented as creamy subretinal infiltrates temporal to the macula in a 55 year old male patient who attended our clinic with complaints of defective vision and floaters. Vitreous biopsy and chorioretinal biopsy specimen showed large B cells suggestive of PIOL. This patient was managed by systemic chemotherapy and showed good resolution of the lesion with residual rpe scarring (Fig 2 a-c).

79 September 2009 Meena Chakrabarti - Masquerade syndrome 315 CONSULTATION SECTION Management of A Case of Post-traumatic Cyclodialysis With Cataract Dr. Mohan Rajan MS 1, Dr. Andrew Braganza MS 2, Dr. Arup Chakrabarti MS 3, Dr. V. Sahasranamam MS 4, Dr. Simon George MS 4 A 48 year old diabetic lady was seen in our OPD with complaints of defective vision right eye following a closed globe injury (blunt trauma) 3 years back. She was having moderate visual loss at that time and was being treated by ophthalmologists at two local hospitals. Available records show that she was on systemic steroids for some time. Presently examination of her right eye revealed a clear cornea, dilated non reacting pupil, mature (white) cataract with phacodonesis. IOP recorded was 4mm of Hg in the right eye and vision was perception of light with accurate light projection. Gonioscopy revealed cyclodialysis from 9 O clock to 2 O clock. The cyclodialysis was confirmed by UBM. B Scan did not show any retinal detachment. Left eye was normal, BCVA of 6/6. How would you approach this case? Dr. Mohan Rajan Cyclodialysis clefts are due to disinsertion of the longitudinal fibres of the ciliary body from the scleral spur. They can occur following blunt trauma or due to surgery for cataract or glaucoma.the result is a communication between the anterior chamber and the suprachoroidal space which results in internal filtration and therefore hypotony. Hypotony causes choroidal effusions, macular / optic disc edema and decreased visual acuity. Later generalised detachment of the ciliary 1 Chennai 2 CMC, VELLORE, 3 Chakrabarti Eye Care Centre, Kochulloor, Trivandrum 4 RIO, Trivandrum body occurs which results in decreased aqueous humour production which further aggravates hypotony. The goal of treatment is to reverse hypotony and restore visual function. The indications for treatment of cyclodialysis include hypotonous maculopathy, macular folds, choroidal detachment, corneal edema & worsening vision. A cyclodialysis cleft with hypotony but without structural or functional abnormalities does not require treatment. The management algorithm includes treatment by medical, laser or surgical methods. Medical management consists of apposition of ciliary body against the scleral spur and promotion of adherence by scar formation. This is enhanced by strong mydriasis ( 1% atropine eye drops) and minimising / stopping of steroid medication for up to 6 weeks. Noninvasive laser methods include treatment by argon laser to the ciliary body and sclera through a goniolens. If visualisation of the cleft is difficult due to shallow anterior chamber, the chamber can be deepened with viscoelastics prior to the procedure.joondeph who did the first argon laser treatment used powers of mw, 200 micron spot and sec exposure time. Other noninvasive methods include use of transcleral yag / diode laser,transcleral cryotherapy. If medical /noninvasive laser methods do not work then sugical methods become the next option. Methods adopted depend on the size of the cleft. Small clefts <2 clock hours can be approached by direct /indirect cyclopexy or ciliochoroidal diathermy. Medium clefts

80 316 Kerala Journal of Ophthalmology Vol. XXI, No. 3 of 2-4 clock hours need to be approached by direct cyclopexy or diathermy. Large clefts >4 clock hours can be approached by direct cyclopexy or by anterior scleral buckling. Large chronic clefts are reported to benefit from parsplana vitrectomy, cryotherapy and gas tamponade.delay of treatment for> 8 weeks increases the risk of loosing 1-3 snellen lines of visual acuity. With respect to our patient, medical management with Atropine eye drops and transcleral diode laser in two rows of contiguous burns 2 to 3mm behind the limbus or argon laser photocoagulation. Following this since the patient has mature cataract, phacoemulsification and implantation of nonfoldable intraocular lens in the ciliary sulcus will enhance closure of the Cyclodialysis cleft. If the above treatment fails then direct repair of the cleft is recomended. In cases of traumatic cyclodialysis there could be alterations in the iridocorneal angle which persists after cyclodialysis repair and therefore regular monitoring of intraocular pressure is recommended. Dr. Andrew Braganza This is a very interesting clinical scenario. One more piece of information I would like is to know whether there is a relative afferent pupillary defect in the affected (right) eye. Even though the pupil is dilated and non reactive, presumably secondary to traumatic mydriasis, this information is easily obtained by the swinging flashlight test and observation of its effects on the left eye. I assume there is no RAPD and that therefore there is no significant disc damage in the right eye.the problems that need addressing are the following: 1.Cataract 2.Cyclodialysis and hypotony The traumatic mydriasis may be a problem, but can be addressed subsequently. Diabetes related ocular problems is unlikely to be an issue here in view of the normal fellow eye. Cataract: The cataract needs to be removed and an IOL implanted. It is likely that there is extensive zonular damage, and capsular support for the IOL may be lacking. I would plan a superior scleral tunnel incision with the intention of doing a manual small incision surgery, converting to a sclerally fixated lens if needed. It is easy enough to pass the sutures needed through the posterior lip of the tunnel and under a scleral flap 180 degrees away, so that they remain buried under partial thickness sclera after being tied. Alternatively, there are techniques available to handle this cataract by phaco even to the extent of sclerally fixating or iris fixating a foldable lens. Details of this are outside the scope of this discussion. Please note that scleral fixation of the IOL must be done only after repair of the cyclodialysis Cyclodialysis: Applying laser treatment or cryo is a conservative option for a cyclodialysis cleft. With a small cleft the results are quite good, the advantage of this approach being that it is non invasive and can be repeated if it fails, still leaving a surgical option open. With a large cleft, this treatment is unlikely to succeed; in this patient, therefore, I would recommend commitment to a surgical repair, especially as the cataract surgery has to be done anyway. The technique involved is similar to scleral fixation of an IOL. A double armed suture needs to be passed through or just behind the root of the iris, through the scleral spur and out under a partial thickness scleral flap and tied, to appose the dialysed ciliary body to its normal attachment prolene is a suitable material, though over tightening must be avoided as the delicate ciliary and iris tissue cheese-wires quite easily. For a superior cleft like this, an open-sky approach through a scleral tunnel using 10-0 monofilament nylon on a curved needle is also possible. The procedure is to some extent blind, as one cannot directly visualize the exact entry point of the suture from the inside. But, as with sclerally fixating an IOL, using external surface anatomy and a 26 or 30G hypodermic needle introduced from outside the eyeball as a guide, precise placement can be achieved by railroading the prolene suture through the hypodermic needle. Many variations of technique have been described; the reader can study these in detail and decide for him- or herself which makes the most sense. With 5 clock hours of dialysis in this patient it is likely that two separate sutures will be needed for the repair. If a scleral tunnel incision is being used for the cataract, it should be possible to pass both these sutures through the bed of the tunnel without the need for separate scleral flaps or dissections.

81 September 2009 R. Sahasranamam et al. - Post-traumatic cyclodialysis 317 Apart from the technical difficulty of the repair, the challenging part of treating a cyclodialysis is handling the IOP once the repair is achieved. A steep rise to 40 or 50 mmhg can be expected in the postoperative period associated with pain and acute danger to the optic nerve head. Prophylactic administration of Diamox is obviously not an option in a hypotonic eye. Early removal of the bandage and checking of IOP postoperatively, probably within 12 hours of the procedure is a logical precaution. The initial reversal and upswing of IOP does eventually stabilize in most cases, but requires monitoring and treatment; it may take days to weeks to stabilize and the patient needs to be closely followed up during this period. Permanent secondary glaucoma may ensue, and require lifelong treatment. To my mind this is preferable to macular damage from hypotony. If surgical control of IOP is needed later, this would usually take the form of a glaucoma drainage device, not a trabeculectomy.in this patient, even assuming that surgery is successful, the visual prognosis remains guarded. This is because we don t know the condition of the macula preoperatively. Prolonged hypotony may result in permanent damage and irreversible visual loss.the dilated pupil may cause the patient problems. If so, an iris implant can be considered at a later stage. Dr. Arup Chakrabarti The given patient presents with a couple of intriguing problems. The condition of the patient is to be tackled at two levels. 1. Visual rehabilitation 2. Management of hypotony Visual rehabilitation Careful preoperative counseling is mandatory. Patient is to be informed that non improvement of vision postoperatively may be related to subtle changes in the posterior segment which may not be evident preoperatively in view of the media opacity. Late postoperative complications may arise because of the prior trauma unrelated to the cataract surgery. The extend of subluxation should be evaluated with the patient in supine position. A scan biometry may be difficult in view of the hypotonicity. Injection of viscoelastic through a paracentesis site on the slit lamp has been recommended prior to gonioscopy. Another option would be to perform A scan biometry on the surgical table with sterile precautions. It is preferred to use peribulbar anesthesia since the surgery is likely to be complicated and a prolonged one. A temporal scleral tunnel incision would be appropriate since it will render conversion to a non phaco technique easier, should the need arise, due to intraoperative complications. Anterior capsule must be stained with trypan blue dye. The capsulorhexis should be performed with a closed chamber technique preferably with micro rhexis forceps. Fibrotic anterior capsular plaque may be seen in similar situations. In difficult situations, placement of iris hooks may be called for, to support the capsular bag, during capsulorhexis. Hydrodissection may perhaps be avoided since this is a traumatic mature cataract and a preexisting posterior capsular dehiscence may not be completely ruled out. A good quality viscoelastic agent should be employed to protect the endothelium and maintain the anterior chamber depth. Excessive chamber depth fluctuation should be avoided. Direct phaco chop would be an ideal technique to remove the nucleus since it is less traumatic to the zonules. Vitreous if present should be managed by automated anterior vitrectomy. A foldable hydrophobic or hydrophilic acrylic intraocular lens should be implanted in the capsular bag. After nucleus removal, it may be a good idea to implant a capsular tension ring within the capsular bag. A double eyelet Cionni ring sutured to the sclera may have to be considered if there is extensive zonular loss. If the capsular bag stability is inadequate for safe phacoemulsification, one should think of converting to a non phaco technique. In that case, the PCIOL may have to be sutured to the ciliary sulcus (scleral fixation). There are several techniques available for scleral fixation and the surgeon can choose a technique he is comfortable with. Postoperative evaluation should be intensive since more than usual post operative inflammation is to be expected. A thorough evaluation of the posterior segment should be performed. The postoperative course may be complicated by retinal detachment as a result of the prior trauma and the patient should be informed about it.

82 318 Kerala Journal of Ophthalmology Vol. XXI, No. 3 Management of hypotony Patient has to be watched carefully in the postoperative period. Hypotony is known to have deleterious effects in the posterior segment including hypotonous maculopathy. In such a case, the condition may have to be managed surgically. There are various procedures described in literature for the treatment of cyclodialysis clefts which implies that the condition is difficult to treat. Direct Argon laser photocoagulation through a gonioprism ( in cases with good visualization) has been found to be successful by several investigators. Confluent applications of 100 mm spots at 0.1 to 0.2 sec and mw are delivered to the base of the cleft followed by postoperative cycloplegics. Repeat treatment may be required in some cases to progressively close the cleft. In cases with poor visibility, the cleft can be treated indirectly from outside by cryotherapy or photocoagulate it with either a diode or transcleral Yag laser. All these indirect approaches require a peribulbar anesthesia for comfort, as well as post operative cycloplegics. More aggressive surgical therapy has been described and involves external diathermy to the bed of the scleral flap that is created over the cleft. This can be combined with suturing the cleft with 9-0 or 10-0 nylon through the scleral bed, either with or without direct visualization. Recalcitrant clefts may require pars plana vitrectomy, cryotherapy and tamponade with SF 6 gas. The patient can experience a period of extremely high pressure and acute pain once the cleft is closed. The patient should always be warned of this possibility and prophylactic aqueous suppressants may have to be prescribed. In summary, management of this complicated case is quite complex. Difficulties are expected during cataract surgery in view of the mature state of cataract, subluxation and very soft eye. Inspite of a well done cataract surgery, visual success may not be satisfactory in view of the posterior segment complications induced by the blunt trauma. In the event of a persistently low post operative intraocular pressure affecting structure and function, cyclodialysis cleft will have to be dealt with surgically using one of the techniques described. Compilation As opined by our expert panel, this is a difficult, intriguing problem. Our approach to the problem was, two pronged 1. Tackle the hypotony 2. Visual rehabilitation In a primary sitting, we planned to take care of the hypotony. Being a large cyclodialysis cleft, of long standing, we planned a surgical cyclopexy. Under a partial thickness sclera flap we did a continuous 10-0 nylon(curved needle) suturing of the ciliary body to its scleral bed. As indicated by our panelists this procedure, is to a good extent a blind procedure. The appositioning of the CB to its scleral bed should be full, to get a desired effect but you can easily cheese wire through delicate ciliary / uveal tissue. Even a small cyclodialysis cleft remaining open shall keep the IOP low and in the other hand you can have raised IOP post operatively. The balance is delicate. In our case, the post op IOP was around 8mm of Hg (1 week and 3 weeks post op).post-op evaluation revealed cyclodialysis persisting in one clock hour. Though our intention was to close the cleft fully,it has not worked out in one sitting. Regarding the cataract we planned to deal with it 3 weeks post cyclopexy, but the patient disclosed chicken pox during this period, which delayed the second surgery by more than 6 weeks. SICS through a scleral tunnel made close to the limbus ( to avoid the cyclopexy site) was done. Through the patient developed a phacodonesis, intraoperatively, capsulorhexis, lens nucleus delivery and IOL implantation were uneventful. The dilated non reacting pupil (traumatic mydriasis) is persisting. Seen 10 days post op the patient had a UCVA of 6/36. Fundus examination revealed, normal disc and vessels with a dull fovea. Post cataract surgery also, the IOP is in the range of 8mm of Hg. On 16/9/09 (last follow up, when the patient is reviewed by her local ophthalmologist at Cochin), the visual acuity in the operated eye is 6/12 improving to 6/6p with glasses and the IOP is 8.5mm Hg Compiled by: Dr. V. Sahasranamam and Dr. Simon George, RIO Trivandrum

83 September 2009 Meena Chakrabarti - Masquerade syndrome 319 OPTHALMIC HISTORY A Tribute to Charles L. Schepens, MD Dr. Meena Chakrabarti MS DO DNB The current practice of ophthalmology owes a great debt to Charles Schepens passion for science, which revolutionized ophthalmic practice by combining clinical practice and eye research. He is considered by many to be the father of modern retinal surgery, not to mention the grandfather of the corneal subspecialty. He was the brilliant inventor of the indirect binocular ophthalmoscope, and his devices, as well as surgical techniques such as scleral buckling, have been credited with raising the success rate of retinal reattachment surgery to 90 percent.the Belgian-born Dr. Schepens began his training in mathematics, which led to his interest in ophthalmic instrumentation. He received his medical degree from the University of Gand in 1935 and went on to train at Moorfields Eye Hospital, London, from 1935 to He then returned to Belgium to practice medicine, and in 1939 joined the medical corps of the Belgian Air Force. After the German invasion of Belgium in 1940, he became a courageous leader in the French Resistance who masterminded the escape through the Pyrenees of more than 100 people. He was later decorated for bravery by both the French and the Belgian governments.in 1947, Dr. Schepens emigrated to the United States and took a fellowship post at the Howe Laboratory of Ophthalmology at Harvard Medical School. Two years later, he established and became the first director of the retina service at Chakrabarti Eye Care Centre, Kochulloor, Trivandrum tvm_meenarup@sancharnet.in Fig. 1. The old prototype model of the binocular indirect ophthalmoscope invented by Dr. Charles Schepens Fig.2 The technique of placing staggered rows of diathermy burns on the bed of the dissected seleral flap was a very efficient form of retinopexy during detachment repair surgery popularised by Dr. Schepens. Fig. 3. The MIRA SERIES of silicon buckles and sponges have withstood the test of time and are used for both implant and explant procedures.

84 320 Kerala Journal of Ophthalmology Vol. XXI, No. 3 Fig. 4. The meridonal buckles (No. 135 & 137) were extensively used during inplant procedures for preventing fish mouthing of a large posterior horse shoe tear. the Massachusetts Eye and Ear Infirmary, the first of its kind. In 1950, he established the Retina Foundation, a center for the intensive investigation of retinal detachment and allied conditions. This illustrious organization is now known as the Schepens Eye Research Institute and is the largest independent eye research organization in the United States, a living legacy to the basic biomedical and clinical eye research Dr. Schepens thought so important.(fig.1-4) He was the author of more than 340 medical papers and four books, trained more than 170 vitreoretinal surgeons, gave countless lectures and courses, and received innumerable honors during his distinguished career. In 1999, he was selected as one of the 10 Most Influential Ophthalmologists of the 20th Century by his peers 33,000 ophthalmologists in the United States and abroad for his innovations and inventions that have so greatly improved ophthalmology. In 2003, he was honored as an inaugural recipient of the American Academy of Ophthalmology s highest honor, the Laureate Recognition Award.He had an unlimited amount of kinetic energy and seemed always focused, engaged, passionate and driven. He was quite engaging, and never forgot anything about anyone he ever met. In his presence, you could feel the energy he radiated the fire of so many things to do and questions to be answered. This energy was contagious, and gave him the ability to inspire others with his passion and enthusiasm. He created in every one a sense of the importance of the projects in which we were involved. His logical thought processes, attention to detail and formidable intellect are legendary.of course, Dr. Schepens will be missed, but we are fortunate that so much of his energy and passion persist in the many physicians and researchers he inspired.

85 September 2009 Journal Review 321 JOURNAL REVIEW Photodynamic Therapy for Age-Related Macular Degeneration : Epidemiological and Clinical Analysis of a Long Term Study Jorge Mataix, M Carmen Desco, Elna Palacios. Ophthalmic Surg Lasers Imaging 2009; 40: Age related macular degeneration (AMD) is a degenerative dystrophic disease that goes through several phases in its natural evolution. Its consequences range from minor forms of dry AMD to severe forms of exudative AMD with choroidal neovascularization, in which more serious loss of vision occurs. CNV is a self limiting lesion that grows progressively, producing a serious injury to the retina, until a disciform scar appears. There are different and multiple treatments to stop this disease, but photodynamic therapy is the only one with long term follow up. The clinical results of PDT can be of great interest and potential concern to clinicians as a basis of comparative efficacy of new treatments. The principal aim of this prospective non randomized clinical trial from Valencia, Spain was to analyze the long term results of patients with exudative age related macular degeneration treated with photodynamic therapy. 262 patients were included with exudative age related macular degeneration who were treated with PDT in accordance with a protocol of the Treatment of Age Related Macular Degeneration with Photodynamic Therapy Study. The follow up lasted 48 months. There was significant loss of visual acuity 3 months after the first PDT treatment, a slow progressive decrease of vision until month 12, and then visual acuity remained stable from months 24 to 48.The choroidal neovascularization size increased noticeably during the first 12 months, particularly the first 3 months after PDT. The higher the classic component of choroidal neovascularization, the better it responded to PDT. The evolution of juxtafoveal choroidal neovascularization was worse than that of subfoveal choroidal neovascularization after PDT because it grew quickly towards the fovea and visual acuity loss was greater. The authors conclude that PDT is a safe, long term treatment for exudative age related macular degeneration, but it is not definitive because this treatment cannot stop the initial growth of the choroidal neovascularization lesion. Future studies on long term visual acuity changes for exudative AMD treated with antiangiogenic drugs will show us the difference with PDT treatment for this disease.

86 322 Kerala Journal of Ophthalmology Vol. XXI, No. 3 Corneal Collagen Cross Linking Using Riboflavin and Ultraviolet-A Light For Keratoconus : One-year Analysis Using Scheimpflug Imaging Dilraj S Grewal, Gagandeep S Brar, Rajeev Jain, Vardaan Sood. J Cataract Refract Surg 2009; 35: There is a mounting evidence of the efficacy of corneal collagen cross linking treatment using photo sensitizer riboflavin and ultraviolet-a(uva) light with wavelength of 370 nm in halting the progression of keratoconus and post refractive surgery corneal ectasia with minimal toxicity. This study from Grewal Eye Institute, Chandigarh aim to evaluate changes in corneal curvature, corneal elevation, corneal thickness, lens density and foveal thickness after corneal collagen cross linking with riboflavin and ultraviolet-a light in eyes with progressive keratoconus. This study recruited 102 patients older than 18 years with a corneal thickness of atleast 400 μm diagnosed with progressive keratoconus. All patients had subjective refraction, best corrected visual acuity(bcva) measurement, Pentacam rotating Scheimpflug imaging and OCT imaging before cross linking and 1 week,1,3 and 6 months and 1 year after cross linking.the mean preoperative BCVA remained stable from preoperative levels in all postoperative visits. The mean spherical equivalent decreased steadily postoperatively to a low of -4.90±3.52D at 1 year. The mean cylinder vector was º±3.8D before cross linking and º±3.5D, 1 year after cross linking. There was no significant difference in mean measurements between preoperatively and 1 year postoperatively, respectively for Central Corneal Thickness (CCT) (458.9±40μm and 455.2± 48.6μm), anterior corneal curvature (50.6±7.4D and 51.5±3.6D), posterior corneal curvature (-7, 7±1.2D and -7.4 ±1.1D) apex anterior (p=.9),posterior corneal elevation (p=.7), lens density( p=.33) foveal thickness (175.7±35.6μm and 146.4±8.5 μm; p=.1). Stable BCVA, spherical equivalent, anterior and posterior corneal curvatures and corneal elevation one year after cross linking indicate that keratoconus did not progress. Unchanged lens density and foveal thickness suggest that lens and macula were not affected after UVA exposure during cross linking. Authors admit that this study included limited number of patients with limited follow up. Long term stability, indications and contraindications of riboflavin- UVA collagen cross linking must be evaluated. Refractive Errors and Strabismus in Children with Down Syndrome: A Controlled Study Arsen Akinci, Ozgur Oner, Ozlem Hekim Bozkurt. J Pediatr Ophthalmol Strabismus 2009;46: Ocular manifestations of Down syndrome have been well described in numerous studies and include eyelid anomalies such as prominent epicanthal folds, upward slanting of palpebral fissures, epiblepharon,

87 September 2009 Journal Review 323 nasolacrimal duct obstruction, blepharitis, keratoconus, retinal abnormalities, glaucoma and amblyopia due to strabismus, refractive errors, and media opacities. However in all these studies an appropriate control group was lacking and the authors compared their findings with previous normative studies. In this study authors from Boston aim to evaluate the prevalence of refractive errors, strabismus, nystagmus and congenital cataract in children with Down syndrome and control subjects of similar age and socioeconomic group. Seventy seven children with Down syndrome and 151 control subjects were evaluated for the prevalence of ocular findings. The diagnosis of Down syndrome was made through clinical and genetic findings. All children underwent cycloplegic auto refraction, retinoscopy, or both, slit lamp biomicroscopy and detailed fundus examination. Ocular movements were checked and ocular alignment was assessed by Hirschberg corneal reflex test, Krimsky prism test or prism cover test. Ocular findings were discovered in 97.4% of children with Down syndrome and 42.4% of control subjects (p<.0001). The point prevalence of nystagmus, strabismus, hypermetropia, astigmatism and congenital cataract was significantly higher in children with Down syndrome (p<.0001 for first four categories, and p<.01 for congenital cataract). The authors conclude that evaluation, treatment and regular review of ocular and refractive findings in children with Down syndrome is essential and likely to significantly enhance the quality of life of individuals with Down syndrome. Compiled by Dr. Reesha, Little Flower Hospital, Angamaly

88 324 Kerala Journal of Ophthalmology Vol. XXI, No. 3 BOOK REVIEW Manual of SQUINT Author Leela Ahuja, Ex- Professor of Strabismology, Ex- Director, Institute of Ophthalmology Aligarh Muslim University, Aligarh, UP Published by Jaypee Brothers, New Delhi First Edition, 2008 Price - Rs; 350/- A lot of literary works have been done on squint but still there is a dearth of standard books on strabismus for post graduate students. No doubt, surgery of squint is done by many ophthalmologists, but mostly, it is on cosmetic grounds and that too without the help of proper orthoptic department. It is also a fact that general public is reluctant to have treatment, particularly surgical treatment of squint, as this malady is considered to be due to displeasure of some goddess. The importance is not to cure deviation, but to improve binocular function. The prevalence of squint in Indian population is estimated to be 3-4 % and prevalence of amblyopia 1%. Squint topics are very much comprehensive so the author has tried to simplify them by providing their description in simple and easily understood language. Most controversial aspects of certain condition have been deliberately left out for the sake of easy understanding. This book includes materials from Duke Elder, Kyeth Lyle, von Noordan, Kanski, Muller and Peymann. This book gives a reasonable background for understanding the ocular muscles and their functional anomalies. The surgeon s update knowledge of the subject, efficiency and dedication alltogether can find solution to the squint problem. Appropriate diagrams, figures and photographs have been provided in this book. I do hope the postgraduates are benefited by going through this work, not only during the course of their formal study but also, subsequently in their practices. Ophthalmology Secrets In Color Authors James F. Vander MD, Janice A. Gault, MD, FACS Published by, MOSBY ELSEVIER, New Delhi Third Edition 2009 Price Rs: 850/- Much of the information in this book can be found in a number of other ophthalmology text books. The table of contents is similar to that of many other books already in print. So why bother to write a new ophthalmology text? The value of the book is in the unique manner in which the material is presented, continuing the tradition the Secrets Series has established in numerous other specialties. The question and answer Socratic Method format reflects the process by which a large portion of clinical medical education actually takes place. This completely updated top seller in ophthalmology continues the tradition of the highly popular Secrets

89 September 2009 Book Review 325 Series. From basic science to visual fields and refraction, from the basic eye exam to discussions of all ophthalmologic disorders, from contact lenses to corneal transplantation, problems of the aging eye and pediatric disorders this book presents all the key elements of ophthalmology for clinical use, rounds, and board preparation. Presents figures in full color for enhanced visual guidance Expedites reference and review with a question and answer format, bulleted lists, mnemonics, and tips from the authors. Features a two color page layout, Key Points boxes, and lists of useful web sites to enhance your referencing power. Includes a chapter containing the Top 100 Secrets in ophthalmology, enabling you to quickly review essential material. Comes in a pocket size for easy access to key information. No matter what questions arise, whether preparing for examinations or in practice, Ophthalmology secrets, 3 rd Edition, has the answers you need Dr. Hoyos s Step by Step Lamellar Corneal Graft Edited by Eduardo Arenas, Jairo E Hoyos Published by Jaypee brothers New Delhi First Edition-2008 Price Rs: 595/- The time for lamellar keratoplasty has finally arrived; an old surgical procedure has always been outshined by the more glamorous technique of penetrating keratoplasty. Lamellar keratoplasty (LK) has fallen in and out of favor, being regarded as a tectonic procedure or as graft for superficial corneal scars. The editors of this book, Arenas and Hoyos, are experienced corneal surgeons, well known writers and editors of scientific articles. They have seen the need for this publications and have undertaken the formidable task of putting together actual information about a variety of techniques and indications for partial lamellar keratoplasty, some so revolutionary that they are still unknown in some medical centers. To this effect, they have obtained collaboration of a group of internationally known corneal surgeons to write specialized chapters. The numerous papers included in this book illustrate the multiple techniques and indications for this type of surgery at the present time. Some procedures were not even dreamed of a few years back, expect in the minds of a few that were ahead of their time. The table of contents shows what pathologists call sequence of events ; in this case, how a procedure has been gradually changed and perfected through the years with the help of new ideas and technical innovation. This review of the most recent lamellar keratoplasty techniques will be informative for the anterior segment surgeon.

90 326 Kerala Journal of Ophthalmology Vol. XXI, No. 3 Manual Small Incision Cataract Surgery (MSICS) Edited by Ashok Garg, Francisco J Gutierrez-Carmona, Luther L Fry, Amulya Sahu, M S Ravindra Published by Jaypee Brothers New Delhi First edition 2008 Price Rs 395/- Manual Small Incision Cataract Surgery (MSICS) has improved significantly with the passage of time. Similar visual results can be obtained as with phaco with much lesser costs. Being proficient in MSICS not only makes the ophthalmologists independent of machine technology but also it has many other advantages as it is very useful in difficult situations like hard cataracts. Proficiency in MSICS makes the transition to phaco emulsification much easy. This Mini Atlas of MSICS contains 15 chapters covering various techniques of MSICS beautifully by International Masters of this field. All MSICS techniques are described with more figures step by step for better understanding. Video DVD ROM provided with this book shows various important MSICS techniques by experts in this field. This book is mainly dedicated to describe several manual techniques including nuclear manipulation or fragmentation, fragment extraction, strategies in the use of several viscoelastic devices, the use of an anterior chamber maintainer, etc. A whole chapter on complications and their avoidance is also included. In other words, the reader will find many ideas to either learn or enrich from this manual small incision cataract surgery mini atlas. This Mini Atlas on MSICS shall be invaluable companion to ophthalmologists as ready reckoner in operation theatre and clinical OPD for quick review. Basic Ophthalmology Author - Renu Jogi Published by Jaypee Brothers Fourth Edition 2009 Price Rs: 895/- The need for a textbook for undergraduate medical students in ophthalmology dealing with the basic concepts and recent advances has been felt for a longtime. Keeping in mind the changed curriculum, this book is intended primarily as a first step in commencing and continuing the study for the fundamentals of ophthalmology. In essence, Basic Ophthalmology is both a text book and a note book that might as well have been written in the student s own hand. The idea is for the student to relate to the material; and not merely to memorize it mechanically for reproducing it during an examination. The past few years have witnessed not only an alarming multiplication of information in the field of ophthalmology, but more significantly, a definite paradigmatic shift in the focus and direction of ophthalmic research and study. The student will thus find a new section devoted to a discussion on Visual Display Terminal Syndrome (VDTS) that is an outcome of excessive exposure of the eyes to the computer monitor as well as the use of contact lenses. Two additional sections deal with the Early Treatment for Diabetic Retinopathy Study (ETDRS) classification and Scheie s classification for hypertensive retinopathy that replaces the pre-existent taxonomy prevalent for little less than seven decades.

91 September 2009 Book Review 327 Salient features of this book are: Fully revised and updated. Written as per syllabi of Indian Universities. Presents the basic aspects as well as recent advances in ophthalmology comprehensively. Highlights Visual Display Terminal Syndrome and ETDRS and Scheie s classifications of hypertensive retinopathy as new additions. Covers more than 500 MCQs with answers for easy recall of the concepts. Useful for graduate and postgraduate students and teachers as well as practicing ophthalmologists. Compiled by Dr. C.V. Andrews Kakkanatt, JMMC, Thrissur ERRATUM In the June 2009 issue an error in the names of the authors for the article in Community Ophthalmology was inadvertently published. We sincerely apologise for this error The corrected names of authors are 1. Dr. [Mrs.] R. Jose MD 2. Dr. Sandeep Sachdeva MD, DNB

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93 UPCOMING CME CME Programmes STATE CONFERENCES DRISHTI th Annual Conference of Kerala Society of Ophthalmic Surgeons th November 2009 Dinesh Auditorium, Thana, Kannur Dr.Sreeni Edakhlon NATIONAL CONFERENCES FOCUS 2009 XXIX th Annual Conference of the Maharashtra Ophthalmological Society & XVII th Annual Conference of the Bombay Ophthalmologists Association th September 2009 ITC Grand Maratha Sheraton, Hyatt Regency and Le Royal Meridien, Sahar, Mumbai Dr.Ragini Parekh: Kalpavriksha 2009 National PG CME Programme October 1-4, 2009 Organizer: Dr.Agarwal s Eye Hospital, Chennai VISTA 2009 XIX Annual Conference of the Glaucoma Society of India November 6 8, 2009 Nimhans Convention Centre Bangalore Dr.Gowri J Murthy: KSOC th Karnataka State Ophthalmic Conference November 27-29, 2009 J.J.M Medical College, Davangere Dr.Rajesh.P: AIX th Annual conference of All India Ophthalmological Society & 15th Afro Asian Congress of Ophthamology 21-24th January 2010 Science city Kolkata Dr. Ashish K. Bhattacharya INTERNATIONAL CONFERENCES XXVII Congress of the Europian Society of Cataract and Refractive Surgeons th September 2009 Barcelona, Spain AAO-PAAO th October, 2009 Sanfrancisco ASCRS.ASOA Boston th April /

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95 PG TEAR SHEET Glaucoma Drugs and Dry - Eyes Complications Potential ocular and/or systemic adverse effects: Prostaglandin Analogues: stinging, blurred vision, eye redness, itching, burning, possible changes in eye color and eyelid skin,. Beta Blockers: foreign body sensation, photophobia, itching, ocular irritation, low blood pressure, reduced pulse rate, fatigue, shortness of breath; rarely: reduced libido, depression, Alpha Agonists: burning or stinging, fatigue, headache, drowsiness, dry mouth and nose, relatively higher likelihood of allergic reaction. Carbonic Anhydrase Inhibitors: in eye drop form: stinging, burning, eye discomfort; in pill form: tingling hands and feet, stomach upset, memory problems, depression, frequent urination. Prevalence of Dry Eye in Glaucoma Patients Patients with open-angle glaucoma also have symptoms of concurrent ocular surface disease. Dr Leung studied 101 patients with either open-angle glaucoma or ocular hypertension. 60 patients (59 %) reported dry eye symptoms in at least one eye, and 27 patients (27 %) reported severe dry eye symptoms. Schirmer testing - 62 patients (61 %) experienced reduced tear production in at least one eye; 35 patients (35 %) had severe tear deficiency. Twenty-two patients (22 %) showed positive corneal and conjunctival lissamine green staining results Break-up time testing - 79 patients (78 %) showed abnormal tear quality, and 66 patients (65 %) had a severe decrease in tear quality in at least one eye. Glaucoma Drugs and dry eye condition Dry-eye condition also could be caused by Glaucoma medication. Side effects increase with the frequency of instillations. Risk of failure of filtration surgery. Subtle signs of ocular toxicity (break up time, superficial punctuate keratitis) have long term consequences. Long term use - conjunctival scarring known as drug induced pemphigoid. Dry eye symptoms with Preservatives Decrease the stability of the precorneal tear film through a detergent effect Decrease the density of goblet cells in the conjunctival epithelium. BAK causes toxic or immuno-inflammatory effect on the ocular surface. Topical preservatives cause inflammation, squamous metaplasia, and subconjunctival fibrosis in the conjunctiva and Tenon s capsule. These changes could probably also concern the trabeculum structures. Except for beta-blockers, all commercially currently available antiglaucoma eyedrops contain BAK. Preservatives decrease the stability of the precorneal tear film. They have a detergent effect on the lipid layer, resulting in increased evaporation. Preservatives also destabilise the tear film Worsens pre-existing dry eye. Surgical treatment failure in patients treated over the long term with glaucoma eye drops. A prospective epidemiological survey was carried out in All symptoms were more prevalent with P (Preservative) than with PF (Preservative Free) eye drops : discomfort upon instillation (43 % versus 17 %) symptoms between instillations such as burning-stinging (40 % versus 22 %) foreign body sensation (31 % versus 14 %) dry eye sensation (23 % versus 14 %) tearing (21 % versus 14 %) eyelid itching (18 % versus 10 %) An increased incidence (>2 times) of ocular signs was seen with P eye drops.

96 332 Kerala Journal of Ophthalmology Vol. XXI, No. 3 Other signs of ocular surface damage reported more frequently in patients treated with Containing Preservaties eye drops: Presence of conjunctival signs 49% 26 %* Conjunctival redness 41% 20 %* Conjunctival follicles 22% 11 %* Fluorescein staining in the nasal bulbar conjunctiva 13% 5 %* Presence of an SPK 19% 9 %* Superficial punctate keratitis Mild 17% 8.9 %* Severe 2% 0.6 %* Presence of at least one palpebral sign 22% 9 %* Anterior blepharitis 16% 7 %* Posterior blepharitis (meibomiitis) 7% 3 %* Eczema 6% 1 %* Dry eye symptoms with beta blockers The most common ocular complaints - transient stinging and burning. Other commonly reported symptoms Transient blurred vision Reversible myopia Foreign body sensation Photophobia, itching Ocular irritation Cystoid macular edema Objective ocular signs: superficial punctate keratatis keratitis sicca corneal hypoesthesia lid ptosis and allergic blepharoconjunctivitis Dry eye symptoms with beta blockers Timolol, timolol maleate, and benzalkonium chloride (BAK %) are used worldwide for lowering intraocular pressure. The mean tear turnover using timolol + BAK was significantly lower (32 %) than the value of healthy controls in the study by Kuppens et al. 50 % of Patients complained of burning or dry eye sensation when using Timolol + BAK. Basal tear turnover, intraocular pressure, and tear- film break up time Tear IOP Mean Number of subjects turnover (SD) with tearfilm Mean (SD) (mmhg) break up time (%/min) < 10 > 10 seconds seconds Patients* when using timolol + (3-0) (2-0) BAK Patients* when using (5-1) (3 0) timolol-bak Healthy controls (5 3) (2 9) Ocular complications with prostaglandin analogs Hypotensive lipids, named as eicosanoids, include latanoprost, travoprost and bimatoprost. Ocular side effects: hyperemia foreign body sensation hypertrichosis increased lower eyelid pigmentation with darkening of the periocular skin and cernes and superficial punctate keratopathy Allergic reactions occur in 1% of adult patients. It can also cause increased eyelash thickness, length and number. Can also cause permanent hyperchromia of the iris. Dry eye symptoms with Prostaglandin analogues Prostaglandin Analogues may affect corneal sensitivity. Kozobolis VP et al examined that central corneal mechanical sensitivity (CCMS) significantly reduced at the 5 minute interval for all analogs. The overall reduction in CCMS score at the 5-minute interval significantly correlated with Schirmer and BUT tests scores. Latanoprost caused highest reduction in CCMS, followed by Travoprost Bimatoprost caused least reduction in CCMS Administration of artificial tears in combination with prostaglandin analogs may therefore be considered Dry eye symptoms with alpha adrenergic agonists Apraclonidine and Brimonidine. Allergy has been reported in 4 to 26 % of patients. Eyedrop allergy and reduction of the tear film production is more common with brimonidine. Ocular Side effects: Rebound hyperemia Lid elevation Pupil dilatation (for apraclonidine) Allergy (up to 26 % for brimonidine, up to 36 % for apraclonidine) Uveitis ± allergic conjunctivitis ± IOP increase (brimonidine) Conjunctive hyperemia (for apraclonidine, 12.6 %) Itching and foreign body sensation (apraclonidine, 6.8 %) Tearing (apraclonidine, 4.5 %) Dry eye symptoms with Carbonic anhydrase inhibitors Dorzolamide and brinzolamide. Dorzolamide is known to induce stinging and burning upon instillation in more than one-third of patients. For both drugs, allergic reactions may be seen. Corneal decompensation may occur in patients with already compromised endothelium and pre-existing corneal edema. Compiled by Dr. Sonia Rani John

97 September 2009 Kerala Journal of Ophthalmology 333 GENERAL INSTRUCTIONS TO AUTHORS The 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 I 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 author s name, correct address (including 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: Give 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. 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.

98 334 Kerala Journal of Ophthalmology Vol. XXI, No 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 communication, 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: Authors(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 author s name and the top side (marked with an arrow) must be specified. Except for arrows, no text is to be on the photos. It is the duty of the author(s) to get the patient s 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 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. The manuscripts are to be sent to The Editor by Courier Mail or by Registered post. The corresponding author will receive communication from the Editor within two weeks of receiving the manuscript. 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 word summary that highlights the significance of the articles.

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