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Uvea Resolution of Serpiginous Choroiditis Monitored with Dynamic Play of Autofluorescence Imaging------1100 Dr. Annamalai O, Dr. S Bala Murugan, Dr. Aparajita Shinde Role of Endoscopic Ultrasound Guided Fnac in Confirming the Diagnosis of Ocular Tuberculosis------1103 Dr. Deepa Sharma, Dr. Manisha Agarwal Sakura Study Group: Key Outcomes for Intravitreal Sirolimus in Indian Subjects in Ni-PSU------1106 Dr. Rathinam Sivakumar R, Yusuf Ali, Yang Yang, Michelle Chernock Implications of Quantiferon Tb Gold Test in the Management of ------1110 Dr. Kalpana Babu Murthy, Dr. Sowmya S Ozurdex Implant in the Treatment of ------1111 Dr. Swetha Palla, Dr. Tarun Sharma, Dr. Biswas Jyotirmay Does Priming of Steroids Before Initiating Anti-Tubercular Therapy Affect the Final Visual Outcome?------1115 Dr. Rafi Ul Islam, Dr. S Bala Murugan, Dr. Annamalai O The Bothersome Bug in the ------1118 Dr. Manisha Agarwal, Dr. Sima Das, Dr. Kusum Sharma, Prof Amod Gupta 73rd AIOC 2015, New Delhi

Uvea Chairman: Dr. Gupta Amod Kumar l Co-Chairman: Dr. Shishir Narayan Convenor: Dr. Shahana Mazumdar l Moderator: Dr. Reema Bansal

Resolution of Serpiginous Choroiditis Monitored with Dynamic Play of Fundus Autofluorescence Imaging Dr. Annamalai O, Dr. S Bala Murugan, Dr. Aparajita Shinde erpiginous choroiditis is a bilateral, chronic and progressive disease of Sunknown etiology characterized by multiple recurrences at intervals of months to years. Fluorescein Angiography (FA) is an invasive investigation for the patient to be subjected to, whenever recurrences are suspected. Fundus Autofluorescence (FAF) is a non-invasive imaging method for in vivo mapping of naturally or pathologically occurring fluorophores of the ocular fundus. The dominant sources are lipofuscin (LF) granules accumulating in the retinal pigment epithelium (RPE). Here, we describe a case report of serpiginous choroiditis and the progression of FAF images over a period of time. 1100 Case History A 25 year old male presented with an insidious onset of painless decrease in vision in the left eye (LE) 2 years ago and sudden, painless decrease in vision in the right eye (RE) for the past 1 week. There was no history of redness, , flashes and . There was no history of trauma. There was no history of any systemic illness. His general examination suggested that he was a moderately built and nourished person. His BCVA was 6/18 in RE and 6/24p in LE. His anterior segment examination and IOP measurement were normal. Fundus examination showed a flat, yellowish retino-choroidal lesion with geographic borders involving papillo-macular area in the RE and a similar scarred lesion with hyperpigmentation in the LE. Fluorescein angiography (FA) in RE showed hypofluorescent lesion with hyperfluorescent borders during the early phase that became hyperfluorescent and intensified over time. FA in LE showed mottled hyperfluorescence with increased fluorescence in late phase Fundus autofluorescence (FAF) showed a hyperautofluorescent lesion surrounded by a small hypoautofluorescent halo in RE and a hypoauto- Uvea Free Papers

fluorescent lesion in the LE Baseline blood investigations were within normal limits. HIV was negative. Mantoux test was negative. Aqueous tap, Vitreous tap for PCR for tuberculosis and viruses were also negative. However, suspecting Figure 1: Colour fundus photograph of both tuberculosis, a trial of anti- tuberculosis therapy (ATT) in the intensive phase and titrated dose of oral steroids was initiated. 1 week later FAF showed a hyperautofluorescent lesion surrounded by a hypoauto- fluorescent halo in RE and a hypoautofluorescent lesion in the LE. Lesions showed improvement.

Two weeks later FAF showed hypo- Figure 2: Fluorescein angiography in RE autofluorescent lines surrounding all of the hyperautofluorescent lesions in RE. We continued ATT 1101 with slow taper of oral steroids. Periocular steroids were added. 6 weeks later, FAF showed large hypoautofluorescent areas Figure 3: Fundus autofluorescence of both surrounding all of the hyperauto- eyes fluorescent lesions in RE. We continued ATT with slow taper of oral steroids. Periocular steroids were given At 14 weeks, FAF showed predominantly hypoautofluorescent areas with minimal hyperautofluorescent spots in RE. We continued ATT in the continuation phase with slow taper of oral steroids.

At last visit at 9 months, lesions had Figure 4: Fluorescein angiography in LE resolved with large areas of chorio- retinal atrophy and vision improved to 6/9p in RE and 6/18 in LE. Choroidal neovascular membrane was absent at the borders of the scar. 73rd AIOC 2015, New Delhi

Figure 5: Colour fundus photograph and Figure 6: Colour fundus photograph and FAF at 1 week FAF at 2 weeks

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Figure 7: Colour fundus photograph and Figure 8: Colour fundus photograph and FAF at 6 weeks FAF at 14 weeks

Discussion Serpiginous choroiditis is a bilateral, chronic and progressive disease of unknown etiology. The lesions involve the outer , choriocapillaries and large choroidal vessels. It affects healthy males aged between 30 and 70 years. There is no family history. An association with HLA-B7 has been reported. Three types of SC has been described; Classic or peri-papillary geographic serpiginous choroiditis, macular serpiginous choroiditis, ampiginous choroiditis. Fundus Autofluorescence (FAF) is a non-invasive imaging method for in vivo mapping of naturally or pathologically occurring fluorophores of the ocular fundus. FAF in early stages of the active lesion of serpiginous choroiditis shows hypoautofluorescence due to the masking effect by the deep retinal edema Uvea Free Papers

on the normal RPE autofluorescence. After a few days (2-5 days) there is hyperautofluorescence which is due to hypertrophy and hyperplasia of RPE that causes accumulation of fluorophores. Healed lesions appear hypoautofluorescent due to RPE atrophy. In a healed lesion, if hyper- autofluorescent areas are seen in the margins of the hypoautofluorescent lesion it suggests reactivation.

Conclusion FAF may be a useful tool for following up patients with SC. Autofluorescence can help to recognize activity or healing in SC. FAF can be repeated several times to monitor the response to treatment so that we can reserve other invasive techniques, such as FA, for cases with suspicious activity disclosed by FAF imaging (like CNVM). After initiation of ATT and steroids, when the size of the lesions increases due to paradoxical reaction, it merits use of hiked up steroids.

References 1. Carreño E, Portero A, Herreras JM, López MI. Assesment of fundus autofluorescence in serpiginous and serpiginous-like choroidopathy. Eye 2012;26:1232-6. 2. Piccolino FC, Grosso A, Savini E. Fundus autofluorescence in serpiginous 1103 choroiditis. Graefes Arch Clin Exp Ophthalmol 2009;247:179-85. 3. Mirza RG, Jampol LM. White Spot Syndromes and Related Diseases. In: Ryan SJ, editor. Retina, 5th ed. New york: Elsevier; 2013. p. 1346-50.

Role of Endoscopic Ultrasound Guided Fnac in Confirming the Diagnosis of Ocular Tuberculosis Dr. Deepa Sharma, Dr. Manisha Agarwal ntraocular tuberculosis presents with myriad of clinical presentations Iwith no definitive pathognomic features. A wide spectrum of clinical signs include anterior granulomatous uveitis, intermediate uveitis, vasculitis or choroiditis, choroidal granuloma and panuveitis. The differential diagnosis most commonly thought for granulomatous uveitis patients is tuberculosis or sarcoidosis. As the treatment differs between the two, it is important to confirm the diagnosis for appropriate management. 73rd AIOC 2015, New Delhi

However, confirming the diagnosis of tubercular uveitis has always been a clinical challenge especially in a TB-endemic country like ours. The intraocular specimen is seldom available for definitive diagnosis, also low bacterial counts from these samples amount to negative acid fast bacillus smear examination. A further delay in starting the treatment occurs because of awaited culture report. As a result we often rely on indirect evidences like mantoux and chest X-ray findings. Sarcoidosis which was initially more common in the west is now increasingly being seen in our country presenting with a similar clinical and radiological picture. Therefore we carried out this study wherein a confirmed diagnosis is possible by doing fnac of mediastinal or paratracheal lymph nodes. This was routinely done by bronchoscopy which can cause several complications. In our study endoscopic ultrasound (EUS) was used to study the configuration of lymph nodes and further fine needle aspiration (EUS guided FNAC) was done to attain the tissue for confirming the diagnosis.

Materials and methods It is a prospective clinical case series. 30 patients with diagnosis of uveitis, underwent clinical features suggestive of tubercular etiology were enrolled in the study and subjected to this extraocular imaging technique to confirm 1104 the diagnosis. The study was conducted at a tertiary care hospital where patients with suspected tubercular etiology were enrolled from November 2013 to October 2014. All the patients underwent routine investigations such as blood counts, mantoux test, ESR, CECT thorax followed by EUS FNA of mediastinal lymph nodes followed by cytopathological evaluation, based on cytological and microbiological findings, treatment started only after confirming the diagnosis.

Results Out of 30 patients, 14 patients showed mediastinal lymphadenopathy on CECT chest and were subjected to endoscopic ultrasound and fine needle aspiration. Epitheloid granulomas were seen on cytological evaluation in 9 cases. Acid fast bacilli (AFB) was positive on ZN staining in 2 cases and isolated after culture in 1 case. 13 patients responded well to the anti- tubercular treatment which was started after confirming the diagnosis. 1 patient with chronic uveitis had persistent vitritis and neovascularization at the disc (NVD) for which she underwent vitrectomy (PPV) and intravitral bevacizumab injection. Her EUSFNA report suggested reactive lymphadenopathy.Vitreous sample was sent for PCR testing and it came out to be positive for AFB which was Uvea Free Papers

sensitive for Rifampicin. Therefore her ATT was continued. There were no noted complications of this procedure.

Discussion Tuberculosis presents with a variable clinical spectrum more commonly seen as granulomatous uveitis. It may also present as chronic uveitis, intermediate uveitis, vasculitis or choroiditis, choroidal granuloma and panuveitis. Sarcoidosis and Tuberculosis are the two major differentials in a case of granulomatous uveitis. It is imperative to differentiate between the two as the treatment lines are different for each. Making a definitive diagnosis is important as the therapy is prolonged and expensive, lined with significant side effects. Therefore in our study we tried to confirm our diagnosis of tubercular uveitis before imperically starting the ATT in the absence of any conclusive evidence. The gold standard for diagnosis of intraocular tuberculosis still remains the demonstration of AFB in the intraocular fluids. A number of previous reports have shown biopsy proven tubercular uveitis but for the major intervention like enucleation. Also the microbial yield from these specimens is usually inadequate and diagnosis awaits the prolonged culture reports. One of our patient had to 1105 undergo pars plana vitrectomy for recurrent vitritis. The vitreous sample on PCR testing came out to be positive for AFB which was sensitive to Rifampicin. Mantoux and chest X-ray are the commonly used tool by the physicians to suspect a tubercular etiology in patients presenting with granulomatous uveitis. All the cases were mantoux positive and chest X-ray was suggestive of some granulomatous infiltration. The cases which were diagnosed with tuberculosis on the basis of sputum examination or x-ray finding were started on ATT. Those in which diagnosis could not be confirmed were subjected to CT Chest and EUS/EUS guided FNAC so that a confirmed tissue diagnosis is made before starting the patient on ATT imperically. The EUS was used to study the size/morphology of the nodes. Heterogenous and conglomerating nodes are suggestive of tuberculosis, and homogenous nodes can be enlarged because of either tuberculosis or sarcoidosis, FNA was obtained for cytological and microbiologicals studies. Therefore it was only after confirming the diagnosis that the patients were started on antitubercular treatment. 73rd AIOC 2015, New Delhi

Sakura Study Group: Key Outcomes for Intravitreal Sirolimus in Indian Subjects in Ni-PSU Dr. Rathinam Sivakumar R, Yusuf Ali, Yang Yang, Michelle Chernock on-infectious uveitis (NIU) of the posterior segment is an autoimmune Ndisorder characterized by repeated bouts of inflammation in the uvea and other structures of the eye, including the retina and vitreous.1 The disease is a major cause of visual morbidity: It is estimated that uveitis is responsible for 25% of severe vision loss in the developing world.2 Treatments are available in the forms of systemic corticosteroids and other immunosuppressants (e.g., mycophenolate, cyclosporine, methotrexate). However, these agents are associated with significant adverse effects and are generally only partially effective, which limits their utility as chronic therapies.3,4 In the case of corticosteroids, these agents are often used at doses far in excess of established guidelines, raising serious safety concerns for long-term use.5,6 While locally administered corticosteroids are available, these agents can be associated with a high incidence of ocular complications, including , , and the need for interventions in order to lower intraocular pressure (IOP).7 Thus, there is a significant unmeet need for treatments that are both effective and safe for managing 1106 this chronic disorder over the long term. Intravitreal sirolimus is a proprietary formulation of sirolimus (rapamycin) that is being developed for the treatment of NIU of the posterior segment. Intravitreal sirolimus is an mTOR inhibitor that plays an immunoregulatory role in uveitis by interrupting T-cell proliferation and the release of interleukin (IL)-2 and other proinflammatory cytokines.8,10 Systemic exposure and drug accumulation are negligible when intravitreal sirolimus is administered at 2 months intervals, 8 supporting its potential use as a long-term monotherapy. The Study Assessing double-masKed Uveitis treatment (SAKURA) trial (Clinical Trials. Gov: NCT01358266) consists of 2 international, multicenter, randomized, double-masked, phase III studies examining the safety and efficacy of bimonthly injections of 3 doses of intravitreal sirolimus (44, 440, or 880 µg) as monotherapy for NIU of the posterior segment. The first study, SAKURA Study 1, enrolled 347 subjects (348 eyes) at 103 sites in 15 countries. At the 5 months primary endpoint, intravitreal sirolimus 440 µg as monotherapy significantly reduced uveitis-related inflammation on the vitreous haze (VH) scale: In the 440 µg group, 22.8% achieved a VH score of 0 at Month 5 (p=.025 vs. 44 µg), and 52.6% achieved a VH score of 0 or 0.5+ (p = .008 vs. 44 µg). Further, intravitreal sirolimus preserved the subjects’ best corrected visual acuity (BCVA), with improvements in vision seen in those Uvea Free Papers

with worse BCVA at baseline. Overall, 33.1% (N = 115) of SAKURA Study 1 subjects were enrolled at sites in India; here we report the primary results for these subjects.

MATERIALs AND METHODS The SAKURA trial was a phase III, randomized, multicenter, double- masked, international, 24 months study that evaluated the safety and efficacy of intravitreal sirolimus injections of 440 μg and 880 μg vs. 44 μg for the treatment of active NIU of the posterior segment (44 μg was used as an active treatment control). Subjects were randomized to 1 of these 3 doses, administered every 2 months (Months 0 [Baseline], 2, and 4). The primary endpoint assessments were conducted at Month 5 (double-masked treatment phase). At the Month 6 visit, subjects originally randomized to 44 μg and 440 μg were crossed over to 880 μg, and all subjects then received 880 μg injections of intravitreal sirolimus every 2 months (open-label treatment phase). At the Month 12 visit, all subjects are being assessed by their Study Investigator to determine if they have “achieved clinical benefit” during study participation. All subjects who have achieved clinical benefit during the first 12 months of the study are invited to continue participating in the study for an additional 12 months of PRN dosing. 1107 Included in the SAKURA trial were subjects ≥18 years with a diagnosis of active NIU of the posterior segment (investigator determined) and a VH score of >1+ in the study eye. BCVA was ≥19 letters (20/400 Snellen equivalent) in the study eye. Excluded were subjects with uncontrolled glaucoma (IOP >21 mm Hg while on medical therapy) and those with active infectious uveitis, ocular/periocular infection, vision-compromising ocular diseases (including, but not limited, to PDR, NPDR, wet AMD, and CVO), opacities, previous vitrectomy, or recent intraocular surgery. The primary endpoint was the percentage of subjects achieving a VH score of 0 at Month 5. A key secondary endpoint was the percentage of subjects achieving a VH score of 0 or 0.5+ at Month 5. Change in BCVA was a secondary endpoint. SAKURA was designed as a monotherapy study with a compulsory tapering schedule, with subjects tapered off of all topical corticosteroids and systemic non-corticosteroid immunosuppressants before receiving the first dose of intravitreal sirolimus. Systemic corticosteroids at baseline were only allowed for those already receiving systemic corticosteroids. These subjects (the intent-to-taper population) were rapidly tapered beginning on Day 1 with the goal of stopping corticosteroids. 73rd AIOC 2015, New Delhi

Results A total of 347 subjects (348 eyes) were enrolled at 103 sites in 15 countries. 115; 33.1%) of the subjects were enrolled at sites in India and comprised the intent-to-treat population. Of these, 40 subjects were randomized to intravitreal sirolimus 44µg, 35 to 440µg, and 40 to 880µg. A total of 4 subjects (3.5%) discontinued the study prior to Month 5. The mean age of the subjects was 40.4±11.9 years, 53% were female, and 60% had bilateral disease. The mean baseline VH score in the study eye was 1.94 ± 0.43. The etiology of uveitis was idiopathic in 85.2%, Vogt-Koyanagi-Harada syndrome in 6.1%, sarcoidosis in 7.0%, and other or not reported in 1.8%. The most common anatomic location was intermediate in 65.2%, followed by panuveitis (23.5%) and posterior (11.3%). The baseline characteristics were evenly distributed across the 3 treatment groups. The mean time since first diagnosis of uveitis was 40.2±46.9 months. The mean baseline BCVA was 63.7 ± 16.6 letters. The mean prednisone-equivalent dose in the intent-to-taper population (n = 35) was 24.2±15.2 mg/d. Intravitreal sirolimus as monotherapy significantly improved inflammation in the subjects from India: 31.4% of those receiving bimonthly doses of 440 µg achieved a VH score of 0 at Month 5—representing complete resolution of inflammation—vs. 10.0% of those receiving 44 µg (p=.04). Further, 62.9% of subjects receiving 440 µg 1108 intravitreal sirolimus achieved a VH score of 0 or 0.5+ at Month 5, vs. 40.0% of those receiving 44 µg. There was a trend toward statistical significance on this endpoint (p=.06). The most favorable risk:benefit profile was seen with the 440 µg dose. 75% of those in the intent-to-taper group who received 440 µg intravitreal sirolimus were able to reduce their prednisone-equivalent dose to ≤5 mg/d by Month 5. The incidence of serious ocular adverse events (AEs) was low. In the 440 µg dose group, there were single instances of cataract, fibrin, uveitis, iritis, and reduced visual acuity, while in the 880 µg group, there were single instances of eye inflammation, uveitis, cataract, and increased IOP (defined as pressure >35 mm Hg that persisted for ≥7 days despite pharmacologic therapy or per investigator decision). Discussion In SAKURA Study 1, intravitreal sirolimus 440 µg as monotherapy significantly reduced uveitis-related inflammation in the subgroup of subjects from India. The improvements were similar to those observed in the overall SAKURA Study 1 population. Given the chronic nature of NIU of the posterior segment, it is expected that many patients will require treatment over an extended period. Thus, good tolerability is a crucial consideration in the development of any new Uvea Free Papers

treatment option. In SAKURA Study 1, the incidence of serious AEs was low both in the subjects from India and in the overall study. Most notable was the low incidence of AEs, including IOP elevations and cataract, that pose significant challenges with the use of corticosteroids. In the overall SAKURA Study 1 population, intravitreal sirolimus preserved BCVA and improved BCVA in those subjects who presented with worse BCVA at baseline (<20/40). Reductions were also seen in the corticosteroid burden in those who were still taking corticosteroids at baseline: Approximately 2/3 were successfully tapered off corticosteroids over the course of the study. These outcomes are currently being analyzed for the subgroup of subjects from India. Overall, the results of this study support the efficacy and safety of intravitreal sirolimus for treatment of this chronic disease.

References 1. Jabs DA, Nussenblatt RB, Rosenbaum JT; Standardization of Uveitis Nomenclature (SUN) Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol 2005;140:509–16. 2. De Smet MD, Taylor SR, Bodaghi B, et. al. Understanding uveitis: the impact of research on visual outcomes. Prog Retina Eye Res 2011;30:452–70. 1109 3. Huscher D, Thiele K, Gromnica-Ihle E, et. al. Dose-related patterns of glucocorticoid-induced side effects. Ann Rheum Dis 2009;68:1119–24. 4. Cunningham ET Jr, Goldstein DA, Zierhut M. Uveitis treatment trials—a cross- study perspective. Ocul Immunol Inflamm 2012;20:63–7. 5. Jabs DA, Rosenbaum JT, Foster CS, et. al. Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: recommendations of an expert panel. Am J Ophthalmol 2000;130:492–513. 6. Nguyen QD, Hatef E, Kayen B. A cross-sectional study of the current treatment patterns in noninfectious uveitis among specialists in the United States. Ophthalmology 2011;118:184–90. 7. Multicenter Uveitis Steroid Treatment (MUST) Trial Research Group, Kempen JH, Altaweel MM, Holbrook JT, et. al. Randomized comparison of systemic anti- inflammatory therapy versus fluocinolone acetonide implant for intermediate, posterior, and panuveitis: the Multicenter Uveitis Steroid Treatment trial. Ophthalmology 2011;118:1916–26. 8. Mudumba S, Bezwada P, Takanaga H, et. al. Tolerability and pharmacokinetics of intravitreal sirolimus. J Ocular Pharmacol Ther 2012;28:507–14. 9. Powell JD, Pollizzi KN, Heikamp EB, Horton MR. Regulation of immune responses by mTOR. Annu Rev Immunol 2012;30:39-68. 10. Gonzalez J, Harris T, Childs G, Prystowsky MB. Rapamycin blocks IL-2-driven T cell cycle progression while preserving T cell survival. Blood Cells Mol Dis 2001;27:572–85. 73rd AIOC 2015, New Delhi

Implications of Quantiferon Tb Gold Test in the Management of Uveitis Dr. Kalpana Babu Murthy, Dr. Sowmya S cular involvement due to mycobacterium tuberculosis can occur as a result Oof an active disease in the eye or an immunological reaction due to the disease elsewhere in the body. Majority of patients however do not manifest the active disease but have latent tuberculosis. The uveitis in these cases is probably due to an immunological reaction to the low number of bacilli. Interferon gamma release assays are used to detect latent tuberculosis. Not much data is available on the role of these tests in presumed ocular tuberculosis from TB endemic areas. In this article, we review the role of quantiferon tb gold test in presumed ocular tuberculosis in a south Indian patient population.

Materials and Methods Charts of 82 patients of Presumed ocular tuberculosis who have responded to a complete course of Antitubercular therapy and a minimum of 6 months follow up after completion of antitubercular therapy (ATT) were retrieved. Details included demographics, clinical and laboratory data. Clinical 1110 data included the type of uveitis. Laboratory data included the results of investigations including Erythrocyte sedimentation rate, mantoux test, serum angiotensin converting enzyme, CT thorax and QuantiFERON TB gold test were reviewed. Appropriate statistical software was used to analyse any significant associations. In those patients in whom results of QuantiFERON TB gold test were available post antitubercular therapy, the result was compared to the value prior to starting treatment. The study was conducted in accordance with declaration of Helsinki and approval of the institutional review board.

Results Among the 82 patients, the mean age was 42.6±13.47 years(Range: 17-71 years). Females were slightly more common (Male:Female=40:42). Active tuberculosis was seen in 3 cases. 2 cases developed cervical lymphadenitis during the course of ATT. Thirty eight cases received oral steroids during the last 6 months prior to starting ATT. Panuveitis was the most common ocular manifestation in 29 patients (35.4%) followed by Intermediate uveitis in 18 patients (22%), posterior uveitis in 16 patients(19.5%) and granulomatous anterior uveitis in 14 patients (17.1%). Retinal vasculitis was seen in 22 patients (26.8%). Choroiditis was seen in 18 patients(22%), out of which 12 patients had serpiginous like choroiditis. Uvea Free Papers

Laboratory investigations included positive findings on CT thorax seen in 62 cases (75.6%). Mantoux test was negative in 7 cases(8.5%) and high ESR in 55 cases (67.1%). QFT prior to ATT was positive in 63 cases (76.8%), negative in 18 cases (22%)and indeterminate in 1 case (1.2%). Values of QFT was obtained in 58 cases. QFT result of < 2 IU was seen in 32 cases, while 26 cases had a result of >2 IU. There was no significant difference in the result of the QFT in different age groups, gender or in those patients who had received oral steroids (in the last 6 months before starting ATT). There was a significant association of QFT with choroiditis. There was no association between QFT result and results of CT scan and mantoux test. There was also no association between QFT result and normal or elevated ESR and normal or elevated serum angiotensin converting enzyme. QFT results were available in 44 patients tested post ATT. 35 cases had a positive QFT even after a course of ATT. However there was a drop in the mean value of QFT values post ATT in comparison to the value pre ATT.

Conclusion Unlike in the developed world, we have limited data on the results of this test in our patient population. Our study indicates significant association of positive QFT in patients with choroiditis. From this data, we also know that most of the patients remained QFT positiveeven after a year of completion 1111 of ATT (with resolution of ocular manifestations) although there was a mean drop in the titre post ATT. To use the result of QFT test to monitor the progress of treatment may not be advisable in our patient population.

Ozurdex Implant in the Treatment of Intermediate Uveitis Dr. Swetha Palla, Dr. Tarun Sharma, Dr. Biswas Jyotirmay zurdex is a biodegradable intravitreal dexamethasone implant Oapproved by United States Food and Drug Administration for treatment of associated with Central retinal vein occlusion (CRVO) and for treatment of noninfectious posterior uveitis.1,4 Previous studies demonstrated that dexamethasone biodegradable implant (OZURDEX ;Allergan Inc, Irvine, CA,USA ) can improve the visual acuity and macular thickness in a variety of causes including uveitis.5. In this study we describe our experience with dexamethasone implant in the treatment of noninfectious intermediate uveitis. 73rd AIOC 2015, New Delhi

Materials AND METHODS This is a retrospective study of the medical records of the consecutive patients who were treated in our hospital for non-infectious intermediate uveitis with Ozurdex implant from 2011 to 2013. All the patients were treated by a single uveitis specialist. The outcomes analyzed were Best corrected visual acuity which was measured with Snellens visual acuity charts converted to logmar units for statistical purpose, Vitreous haze score graded according to Sun Working Group grading and Central retinal thickness (CRT) was assessed by Optical Coherence Tomography. Exclusion criteria includes all the patients who had infectious uveitis or had any intraocular procedure within 6 months of the implant or had macular edema due to any other cause other than uveitis (e.g. diabetes ,CRVO etc.). The outcomes were analyzed at baseline, 6 weeks, 6 months and the last visit within the one year period after the implant respectively. Ozurdex (700 micrograms, Allergan, Inc., Irvine, CA)) was administered in accordance with the manufacturer’s guidelines using the 22 gauge applicator device under aseptic conditions in the operation theatre. Data analysis was done with the help of computer using SPSS version 14.0, Chicago. Paired T was used to test the significance of difference between quantitative variables. A ‘p’ value less than 0.05 is taken to denote significant relationship. 1112 RESULTS A total of 20 eyes of 15 patients were included in the study. The baseline patient characteristics in this study were shown in Table 1. The percentage of males and females in our study are 53.34% and 46.66% respectively . The mean age group of patients who received Ozurdex implant during the study period was 39.8 years (range 7-59 years). The standard treatment which was given include oral steroids and immunosuppressants. Most common immunosuppressants used were methotrexate and mycophenolate mofetil. The mean baseline visual acuity improved from 0.666 logmar units to 0.479 logmar units at 6 weeks after the implant, which was statistically significant. The mean best corrected visual acuity at each follow up is represented in Graph 1. The mean central retinal thickness improved from 536.1 microns to 361.4 microns at 6 weeks post implant which is statistically significant. The mean CRT at each follow up is represented in Graph 2. The percentage of eyes attaining a Vitreous haze score of zero post implant was 60%, 45%, 30% at each follow up respectively. It was found that 25% (5 eyes) required cataract surgery within 1 year period (within an average period of 6-8 months) post implant. 15% (3 eyes) developed IOP greater than 21 mm hg at 6 weeks follow up post implant. 2 eyes had IOP greater than equal to 25 mm hg, out of which 1 eye Uvea Free Papers

Table 1: Patient Demographics and Baseline Characteristics No. Percentage Sex Male 8 53.3% female 7 46.6% Age Mean 39.8 years range 7-59 years Mean best corrected visual acuity 0.666 logmar units Mean central retinal thickness 536.1 microns No: of eyes having cataract at presentation 6 30% No: of eyes having at presentation 2 No: of eyes having CNVM at presentation 1

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Figure 1: Showing trend of mean best Figure 2: Showing trend of mean central corrected visual acuity at each follow up. retinal thickness at each follow up. was steroid responder. All eyes were medically managed for the . 1 eye diagnosed as pars planitis required vitrectomy to clear the severe vitreous opacities in the study period at 8 months post implant. No other complications like , etc. were noted. 1 eye required a second implant at 6 months follow-up.

Discussion Corticosteroids have remained the mainstay of treatment in non-infectious intermediate uveitis since many decades. Cystoid macular edema(CME) secondary to uveitis is difficult to treat and may persist despite multiple interventions.6 The mean central retinal thickness (CRT) in our study has shown statistically significant improvement at each follow up compared to the baseline reading and the improvement has been maintained up to our last 73rd AIOC 2015, New Delhi

follow up though maximum improvement has occurred within the 6 weeks of the implant. The study by Zhang L et. al.7 and Adan A et. al.8 has shown similar response with ozurdex implant in regards to CME at their follow ups respectively. The mean best corrected visual acuity(BCVA) in our study had significantly improved at 6 weeks and final follow up compared to the baseline but though there is improvement during the second follow up ,the difference is not statistically significant .This could be explained by the development of cataract to certain extent. Study by Sallam et .al. has shown similar improvement of BCVA at their 1 month follow up.9 Out of the 6 eyes which had preexisting cataract at the time of implant, 5 eyes (25%) had significant progression of cataract requiring cataract surgery . This number is more compared to other studies.7,10 This can be probably explained by a longer follow up period in our study comparatively. 15% of the eyes developed raised IOP in our study comparable to the other studies.7 1 eye had CNVM at presentation which required anti -vascular endothelial growth factor during the follow up period .It was found that the two eyes which had epiretinal membrane (ERM) at presentation had minimal improvement in CRT. A recent study demonstrated that the presence of an ERM may limit the response to medical therapy in uveitic cystoid macular edema.11 The maximum efficacy of the drug is found to be at 1-2 months post implantation. 1114 The main limitations of this study are that it has a retrospective study design , the study cohort was small . Development of cataract due to local therapies and the presence of ERM has affected our outcome measure BC VA.

Conclusion The Dexamethasone implant (Ozurdex) resulted in a statistically significant improvement in mean CRT and best corrected visual acuity and had favourable outcome in controlling the inflammation without any serious adverse events. This study was consistent with the safety profiles and the efficacy and in noninfectious uveitis as in previously published studies.

References 1. Robinson MR, Whitcup SM. Pharmacologic and clinical profile of dexamethasone intravitreal implant. Publication: Expert Rev Clin Pharmacol 2012;5:629-47. 2. Haller J, Bandello F, Belfort R Jr, et. al. Randomised, sham-controlled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion. Ophthalmology 2010;117:1134-46. 3. Haller J, Bandello F, Belfort R Jr, et. al. Dexamethasone intravitreal implant in patients with macular edema related to branch or central retinal vein occlusion twelve month study results. Ophthalmology 2011;118:2453-60. Uvea Free Papers

4. Lowder C, Belfort R Jr, Lightman S ,et al. Dexamethasone intravitreal implant for noninfectious intermediate or posterior uveitis. Arch Ophthalmol 2011;129:545-53. 5. Kupperman BD, Blumenkranz MS, Haller JA et. al. .Randomised controlled study of an intravitreous dexamethasone drug delivery system in patients with persistent macular edema. Arch Ophthalmol 20 07;125:309-17. 6. Karim R, Sykakis E, Lightman S, Fraser-Bell S. Interventions for the treatment of uveitic macular edema: a systemic review and meta- analysis. Clin Ophthalmol 2013;7:1109-44. 7. Cao J, Mulvalhill , Zhang , Joondeph , Dacey .Dexamethasone Intravitreal Implant in the Treatment of Persistent Uveitic Macular Edema in the Absence of Active Inflammation. Ophthalmology 2014 Jun 3. pii: S0161-6420(14)00359-5. 8. Adán A, Pelegrín L, Rey A, Llorenç V, Mesquida M, Molins B, Ríos J, Keller J. Dexamethasone intravitreal implant for treatment of uveitic persistent cystoid macular edema in vitrectomized patients. Retina 2013;33:1435-40. 9. Zarranz-Ventura , Carreño , Johnston , Mohammed , Ross , Barker , Fonollosa , Artaraz , Pelegrin , Adan , Lee , Dick , Sallam . Multicenter study of intravitreal dexamethasone implant in non-infectious Uveitis: Indications, outcomes and reinjection frequency. Am J Ophthalmol 2014 Sep 8. pii: S0002-9394(14)00547-9. 10. Lowder C1, Belfort R Jr, Lightman S, Foster CS, Robinson MR, Schiffman RM, Li XY, Cui H, Whitcup SM; Dexamethasone intravitreal implant for noninfectious intermediate or posterior uveitis.O zurdex HURON Study Group. 11. Lehpamer B, Moshier E, Pahk P, et. al. Epiretinal membranes in uveitic macular 1115 edema: Effect on vision and response to therapy. Am J Ophthalmol 2014;157:1048- 55. Retina 2013;33:1435-40.

Does Priming of Steroids Before Initiating Anti- Tubercular Therapy Affect the Final Visual Outcome? Dr. Rafi Ul Islam, Dr. S Bala Murugan, Dr. Annamalai O ne-third of the world’s population is infected with Mycobacterium Otuberculosis and can potentially manifest features of ocular tuberculosis (TB). Not surprisingly, TB accounts for large proportion of infectious uveitis cases in endemic countries. The benefits of anti-tubercular therapy (ATT) in treatment of TB-associated uveitis are well documented. Several clinical indicators of ocular TB have also been identified based on the response to ATT. However, in most cases, the diagnosis of ocular TB remains presumptive because of lack of definitive (microscopy, culture) evidence. Giving steroids before starting ATT helps in better outcome. 73rd AIOC 2015, New Delhi

Immunological reaction to tubercular antigens is usually managed by escalating corticosteroid therapy. Full course of ATT+ corticosteroid prevents up to 80-85% chance of recurrence. Case History • 41 years gentleman working as operation theatre assistant presented to Aravind eye hospital with the complaints of loss of central area of vision in his right eye for 9 days and blurring of vision in right eye for 1 month. He had history of hypertension since 4 years. • On examinations in right eye had relative afferent defect. Left eye was within normal limit. best corrected visual acuity in right eye was 4/60 and in left eye 6/6. He had defective colour vision and centrocaecal in right eye. Fundus examination in right eye showed blurred disc margin with obliterated cup, flame shape haemorrhages and cotton wool spots. Macula had oedema with internal limiting membrane folds . Fundus evaluation of left eye was normal. With working diagnosis of we started parenteral methyl prednisolone 1 gram per day. Flourescein angiogram revealed disc-Hyperfluorescence with leakage in 1116 the late phase. Multiple well demarcated choroidal lesions with progressive hyperfluorescence with leakage were observed. B scan of the right eye revealed elevated optic nerve head and retino– choroidal-scleral thickness of 2 millimeters. Patient undergone haemoglobin, total leucocyte count, erythrocyte sedimentation rate, montoux test, blood sugar level, blood urea, serum creatinine, chest x ray, serum angiotensinogen converting enzyme level, Quantiferon tuberculosis gold test, Computed tomography chest. We found that only serum erythrocyte sedimentation rate is increased it 12 mm/hr after half hour and 24 mm/hr after 1 hour all other investigations were under normal limit. Patient started on oral steroid (prednisolone) 60 mg/day and weekly tapered and posterior subtenon injection prednisolone of 1cc given, topically napalact eye drops were given. On fifth day of starting treatment his vision was 3/60 not improving with glasses. Fundus picture shows resolving disc oedema Uvea Free Papers

and perivascular retinal pigment epithelium alteration. After 12 day of starting treatment patients visual acuity drops down to 1/60 not improving with glasses. Suspecting of possible infectious aetiology anti tubercular treatment were started and vitreous tap was done to investigate for polymerase chain reaction to rule out tuberculosis. After three days of anti tuberculosis treatment patient’s visual acuity improves to 6/36 best corrected. After two month of anti tuberculosis treatment patient visual acuity improves to 6/24 further improving to 6/12 with-0.5DS/0.5X1800, fundus picture in right eye shows pallor glial tissue over disc,cup was obliterated and healing choroiditic features were present. 1117 Discussion Tuberculosis is known to cause a myriad of ophthalmic pathology. Approximately, 2 billion people are affected worldwide with tuberculosis, while only 10% of these people have clinical manifestations. The absence of pulmonary tuberculosis does not rule out ocular tuberculosis. Secondary ocular infection results from hematogenous spread of the organism or from a hypersensitivity reaction to extraocular infection. The clinical ocular manifestation of secondary infection is highly variable and depends on several factors, including the virulence of the organism, the degree of tissue hypersensitivity to the infection, and the extent of acquired host resistance. Choroidal tubercles are the most common manifestation of intraocular tuberculosis.,It may also present as multifocal progressive or diffuse choroiditis resembling serpiginous choroiditis. Immunological reaction to tubercular antigens is usually managed by priming corticosteroid before starting ATT, it helps in better outcome and reduces chances of recurrence. 73rd AIOC 2015, New Delhi

Conclusion • TB or not a TB is a never ending puzzle ! Spectrum of presentation is wide • Give therapeutic trial in suspicious cases • Priming with steroids before ATT has a better outcome • High degree of suspicion is warranted to diagnose ocular tuberculosis when all systemic investigation are negative

References 1. Sheu SJ Shyu JS, Chen LM, Chirn SC, Wang J S. Ocular manifestation of tuberculosis Oph 108;1580-5. 2. Rao NA, Saraswathy S,Smith RE. Distribution of myco TB in Retinal Pigment Epithelium. Arch oph. 2006:124:1777-8. 3. Donhue HC. Expenses in tuberculosis Sanatorium. AMJ oph 1967:64;742-8. 4. Islam SM, Tabbara KF. Causes of Uveitis at the Eye Centre in Saudi Arabia; A retrospective review. Ophthalmic Epidemiol 2002:9;239-49.

1118 The Bothersome Bug in the Eye Dr. Manisha Agarwal, Dr. Sima Das, Dr. Kusum Sharma, Prof Amod Gupta cular tuberculosis is on the rise in India. We are everyday seeing cases Oin our clinic which turn out to be tuberculosis. Tuberculosis can affect any part of the eye and have varied manifestations including vasculitis, granulomatos inflammation, endophthalmitis etc. This paper presents a whole gamut of ocular tuberculosis involving anterior to posterior segment. It also highlights the role of the newer investigations available today which enhance and support our clinical judgement and prove tuberculosis beyond doubt. Study design: Interventional case series

Materials and methods Case 1 and Case 2 Two cases of conjunctival tuberculosis presented with multiple small conjnctival nodules on the palpebral . The second case was immunocompromised due to co-existant HIV infection. Both were diagnosed by conjunctival biopsy which showed the acid fast bacilli on culture. Uvea Free Papers

Results Both the cases were treated with anti-tubercular treatment for 9 months and the second case was given HART therapy as well. The conjunctival lesions cleared completely. • Conclusions: Unilateral may masquerade as primary conjunctival tuberculosis • In an endemic country like India - laterality, chronicity and non- resolution of symptoms with steroids are indications for an early biopsy • In our patients the HPE which clinched the diagnosis resulted in a faster and complete resolution of the disease condition Case 3 Presented with recurrent attacks of CRVO treated with oral corticosteroids in the past with the worsening of vision in the left eye to counting fingers close to face. Slit lamp showed fine keratic precipitates. FFA and OCT was done which showed vasculitis with disc leakage. Vitreous sample on PCR was positive for mycobacterium tubercloisis. Treated with ATT and oral steroids No recurrence of CRVO in a follow up of 5 years and maintains a vision of 6/9, N6 in the left eye. 1119 • Conclusions: A first presentation of CRVO attributed to tuberculosis is rare • Young patients with CRVO caused by retinal vasculitis not responding to steroids may require an invasive procedure to reach a definitive diagnosis • May not be appropriate to stop further tests to confirm the presence of a tuberculosis infection when routine tests are normal Case 4 A 70 years old female patient with a history of tuberculosis 15 years back presented with endophthalmitis in the right eye with a BCVA of hand movements close to face. She under vitrectomy and intraocular antibiotics and the vitreous sample was sent for microbiology examination. Systemic evaluation with CT-Scan of the chest showed a reactivation of the lesions. She was treated with ATT and oral steroids. She recovered a vision of 6/24, N12.

Conclusion Intraocular tuberculosis can present as endophthalmitis and one needs to be aware of it. 73rd AIOC 2015, New Delhi

Case 5 and case 6 Two young girls who presented with choroiditis and granuloma formation in the left eye. Case-5 was diagnosed as a case of rifampicin resistant tuberculosis and the left eye became a painful blind eye and had to be enucleated. Histopathological examination showed necrotic caseating granulomas. She was treated with second line anti tubercular treatment and oral steroids. Case-6 underwent a pars plana vitrectomy and silicone oil injection. Microbiological examination of the vitreous sample showed acid fast bacilli which was sensitive to rifampicin on gene expert analysis. At 6 months follow up she had a vision of inaccurate projection of rays with a well attached retina. Intraocular tuberculosis can present with varied manifestations. Variuos diagnostic test help in confirming the diagnosis. EWraly intervention and proper management with anti-tubercular treatment can help in regaining the vision and salvaging the eye.

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