Incidence, clinical features, risk factors, and outcomes of Intraocular inflammation following Brolucizumab in Indian eyes – A multicentric study

Purpose: To report the incidence, clinical features, potential risk factors, and outcomes of intraocular inflammation (IOI) following brolucizumab in Indian eyes. Methods: All consecutive patients diagnosed with brolucizumab?induced IOI from 10 centers in eastern India between October 2020 and April 2022 were included. Results: Of 758 injections given during the study period across centers, 13 IOI events (1.7%) were recorded attributable to brolucizumab. The IOI occurred after the first dose in two eyes (15%) (median 45 days after brolucizumab), second dose in six eyes (46%) (median = 8.5 days), and third dose (39%) in the remaining five eyes (median 7 days). Reinjections of brolucizumab were administered at a median interval of 6 weeks (interquartile range = 4–10 weeks) in the 11 eyes, where IOI occurred after the second or third dose. Eyes that experienced IOI after the third dose had received a significantly greater number of previous antivascular endothelial growth factor injections (median = 8) compared to those who developed it after the first or second dose (median = 4) (P = 0.001). Anterior chamber cells were seen in almost all eyes (n = 11, 85%), while peripheral retinal hemorrhages were seen in two eyes, and one eye showed branch artery occlusion. Two?thirds of patients (n = 8, 62%) recovered with a combination of topical and oral steroids, while remaining recovered with topical steroids alone. Irreversible visual loss was not seen in any eye, and median vision recovered to pre?IOI levels by 3 months’ time point. Conclusion: Brolucizumab?induced IOI was relatively rare, occurring in 1.7% of eyes, was more common after the second or third injection, especially in those who required frequent reinjections every 6 weeks, and occurred earlier with increasing number of previous brolucizumab injections. Continued surveillance is necessary even after repeated doses of brolucizumab.

Efficacy of a biosimilar ranibizumab monotherapy for the treatment of retinopathy of prematurity

Purpose: To evaluate the efficacy of a biosimilar ranibizumab (Razumab) on outcomes of retinopathy of prematurity (ROP) for the first time. Methods: This retrospective study included infants presenting with stage 3+ ROP either in zone 1 or zone 2 posterior or aggressive posterior ROP (APROP). All eligible infants received intravitreal razumab (0.25 mg/0.025 ml) monotherapy. Follow?up was continued monthly till complete retinal vascularization was achieved while retreatment with razumab was given when recurrent neovascularization was noted. In case of no recurrence but incomplete vascularization, laser photocoagulation was done to the residual avascular retina. Results: We included 118 eyes of 59 infants with a median gestational age of 30 weeks and median birth weight of 1250 grams. At presentation, APROP was found in 28 eyes (24%) of 14 babies while stage 3 disease was seen in zone 1 in another 28 eyes (24%) and the remaining 62 eyes (52%) had stage 3 ROP in zone 2 posterior region. Complete resolution of ROP along with complete vascularization was seen in 22 eyes (19%) at a median of 55 days (IQR = 31–56 days) and 42 eyes (35%) showed a recurrent neovascularization at a median of 51 days post razumab (IQR = 42– 55 days). The cumulative incidence of recurrence of neovascularization (21%, 95% CI = 14%–29%) peaked at seven weeks and was significantly higher in eyes with APROP (43%, 95% CI = 27%–63%) compared to eyes without APROP (13.4%, 95%CI, 8%?22%) (P < 0.001). Conclusion: Razumab appears to be safe and effective in treating ROP, with about a third requiring reinjection at seven weeks after the first dose.

Initial experience in treating polypoidal choroidal vasculopathy with brolucizumab in Indian eyes � A multicenter retrospective study

Purpose: To report the initial experience of managing treatment?resistant and treatment?na飗e eyes with polypoidal choroidal vasculopathy (PCV) by using brolucizumab 6 mg. Methods: This was a retrospective multicentric series of all consecutive eyes with PCV treated with brolucizumab. Treatment resistance was defined as taking at least six prior anti?VEGF injections over the past 1 year and showing persistent disease activity in the form of intra (IRF) or subretinal fluid (SRF) or both. All patients were treated on a pro re nata (PRN) basis and followed up monthly. Retreatment was considered when either SRF or IRF were present at any time point during the study. Results: We included 21 eyes of 21 patients with PCV with a mean age of 65.1 � 9.9 years, of which 16 eyes (76%) were treatment?resistant. The mean follow?up period from receiving the first brolucizumab was 27.3 � 3.3 weeks. Of the 21 eyes, seven eyes (33%) received three injections during follow?up, 13 eyes (62%) received two injections, and one eye received one injection. The mean injection?free interval was 12 � 1.2 weeks. The median pretreatment vision was 0.6 logMAR (IQR = 0.47�logMAR) and improved to 0.3 logMAR (IQR = 0.25�6 logMAR), whereas the mean macular thickness improved from 443 � 60 ?m at baseline to 289 � 25 ?m (P < 0.001) at the last follow?up period. None of the eyes experienced any intraocular inflammation across 48 injection sessions. Conclusion: Brolucizumab is safe and effective in controlling PCV disease in both treatment?resistant and treatment?na飗e eyes

Utilization rate of corneal tissue obtained from donors over 75 years of age in Western India for keratoplasty

Purpose: To examine the utilization patterns of cornea procured from diseased individuals ?75 years of age at an eye bank in western India. Methods: In this retrospective study, data from 1,217 eyes of 653 donors with age ?75 years were reviewed from October 2008 to December 2019. Donor age, lens status, endothelial cell count (ECD), utilization of the tissue for transplantation or non?clinical purposes (e.g., research, training/discarded), and causes of non?utilization were noted. Results: The mean age of the donors was 80.9 ± 4.6 years and the tissue utilization rate was 36.5% (445 out of 1,217 eyes). The eyes used for keratoplasty procedures had a lower donor age (79.6 ± 5.7 vs. 81.5 ± 5.1; P < 0.001), a higher endothelial cell count (2493 ± 531 vs. 2034 ± 581; P < 0.001), and were more often phakic (61% vs. 36.6%) compared to the unused group. A multivariable logistic regression analysis showed that the likelihood of tissue utilization for keratoplasty was 13% higher with every 100?cell increment in donor ECD (odds ratio [OR] = 1.13, 95% CI = 1.10–1.16, P < 0.001) and 33% lower with having a pseudophakic status in the donor eye (OR = 0.67, 95% CI = 0.52–0.87, P = 0.03). Age was not a significant determinant of tissue utilization when used in the same multivariable model. Conclusion: More than one?third of the eyes (36.5%) can be utilized even when the donors are above 75 years of age. Eyes that were more likely to be utilized for keratoplasty were phakic and had a significantly higher ECD; age was not a determinant in tissue utilization

Publication rates from the All India Ophthalmic Conference 2010 compared to 2000: Are we improving.

Purpose: To determine the publication rates of free papers and posters presented at the All India Ophthalmic Conference (AIOC) 2010 in peer‑reviewed journals up to December 2015 and compare this with publication rates from AIOC2000 published previously. Methods: A thorough literature search was conducted using PubMed, Google Scholar, and the general Google search engine by two independent investigators. The title of the paper, keywords and author names were used to “match” the AIOC free‑paper with the published paper. In addition, the “purpose,” “methods,” and “outcome measures” between the two were studied to determine the “match.” Results: A total of 58 out of 394 free‑papers (14.7%) from AIOC2010 were published till December 2015 compared to 16.5% from AIOC2000. Out of these, 52 (90%) were published in PubMed indexed journals. Maximum publications were seen in pediatric ophthalmology (50%) followed by glaucoma (24.4%) and cornea (23.8%). Fifteen out of 272 posters (5.5%) were published; orbit/oculoplastics had the highest poster publications (13%). Excluding papers in nonindexed journals and those by authors with international affiliations, the publication rate was approximately 12%. Conclusion: The publication rate of free papers from AIOC2010 has marginally reduced compared to AIOC2000. Various causes for this such as lack of adequate training, motivation, and lack of incentives for research in the Indian scenario have been explored, and measures to improve this paradigm have been discussed. It will be prudent to repeat this exercise every decade to compare publication rates between periodic AIOC, stimulate young minds for quality research and educate policy makers toward the need for developing dedicated research departments across the country.

Adult onset retinoblastoma.

Retinoblastoma (RB) is the most common primary malignant intraocular tumor of childhood presenting usually before 5 years of age. RB in adults older than 20 years is extremely rare. A literature search using PubMed/PubMed Central, Scopus, Google Scholar, EMBASE, and Cochrane databases revealed only 45 cases till date. Over the past decade, there has been a significant increase in the number of such reports, indicating heightened level of suspicion among ophthalmologists. Compared to its pediatric counterpart, adult onset RB poses unique challenges in diagnosis and treatment. This article summarizes available literature on adult onset RB and its clinical and pathologic profile, genetics, association with retinocytoma, diagnostics, treatment, and outcomes.

Factors affecting treatment outcome in congenital nasolacrimal duct obstruction: A retrospective analysis from South India.

Purpose: To investigate outcomes for different treatment modalities in congenital nasolacrimal duct obstruction (CNLDO) in an Indian population. Design: Retrospective, interventional, case series. Materials and Methods: In an institutional setting, case records of patients with CNLDO from January 2008 to 2012, were reviewed, and data on patient demographics, clinical presentation, and treatment details (sac massage, probing, and/or dacryocystorhinostomy) were recorded. Success of treatment was defined as complete resolution of symptoms and negative regurgitation on pressure over lacrimal sac (ROPLAS) area. Results: Two hundred and ninety‑eight eyes of 240 patients with a mean age of 22.2 ± 26.14 months (median = 12 months, interquartile range = 17) were analyzed. Sac massage (n = 226) was successful in 67 eyes (30%). Multivariable logistic regression analyses showed that children with mucoid ROPLAS were almost 6 times more likely (odds ratio [OR] = 5.55 vs. clear ROPLAS, 95% confidence interval [CI] = 2.35–13.09, P < 0.001) to experience failure of sac massage. Overall probing (n = 193) was successful for 143 (74%) eyes. Multivariable logistic regression showed that older children were 25% more likely to experience probing failure (OR = 1.25 for every 6 months increment in age, 95%, CI = 1.09–1.42, P = 0.001). Conclusion: Sac massage is successful in only a third of our patients and those with mucoid ROPLAS are more likely to experience failure. Probing is successful in three‑quarter of our subjects, and its success declines with a progressive increase in age. Lower socioeconomic status, poor general health, and recurrent respiratory infections are unique to our population and may influence outcomes.

Goat’s eye integrated with a human cataractous lens: A training model for phacoemulsification.

A relatively simple and inexpensive technique to train surgeons in phacoemulsification using a goat’s eye integrated with a human cataractous nucleus is described. The goat’s eye is placed on a bed of cotton within the lumen of a cylindrical container. This is then mounted on a rectangular thermocol so that the limbus is presented at the surgical field. After making a clear corneal entry with a keratome, the trainer makes a 5–5.5 mm continuous curvilinear capsulorhexis in the anterior lens capsule, creates a crater of adequate depth in the cortex and inserts the human nucleus within this crater in the goat’s capsular bag. The surgical wound is sutured, and the goat’s eye is ready for training. Creating the capsulorhexis with precision and making the crater of adequate depth to snugly accommodate the human nucleus are the most important steps to prevent excessive wobbling of the nucleus while training.

Publish or perish: The art of scientific writing.

Publishing manuscripts is the only way by which scientists communicate with each other. In recent times, there is an increasing desire to publish manuscripts from the developing world for a variety of reasons. Though, performing a research study is challenging in itself, writing it for publication is the final frontier that can be daunting, especially for the novice. Work that remains unpublished in one form or the other is essentially incomplete or undone. Hence, it is critically important for one to publish one’s findings in a reputed journal. The purpose of this paper is to alleviate the mystique involved in manuscript writing and provide a blueprint where the subheadings given under each of the sections of introduction, methods, results and discussion can be expanded as per the particular study and the manuscript can be constructed in a stepwise manner. We hope that by following this approach, potential researchers and practicing ophthalmologists will develop the skill and aptitude for medical writing, and that the developing world shall do justice to its tremendous intellectual capital by making meaningful contributions to global scientific literature.

Relationship between systemic hypertension, perfusion pressure and glaucoma: A comparative study in an adult Indian population.

Aims: To study the relationship between blood pressure (BP), intraocular pressure (IOP), mean ocular perfusion pressure (MOPP) and primary open angle glaucoma (POAG) in patients with hypertension and compare it to a control group of normotensives. Design: Cross‑sectional observational study. Materials and Methods: A total of 108 subjects with primary hypertension and 100 age‑matched controls without hypertension were enrolled for the study. IOP measurement using Noncontact Tonometer and dilated fundus evaluation using + 90 D lens were done for all cases. Single recording of BP was taken. Gonioscopy, Humphrey’s central visual fields, optical coherence tomography and pachymetry were done for all subjects with IOP > 21 mm Hg or C: D ratio ≥ 0.5 or asymmetry of > 0.2. Statistical Analysis: Univariate and multivariate multinomial regression models were used to determine the association between covariates and risk of glaucoma or glaucoma suspect. Results: There was no difference in the glaucoma status between subjects with and without hypertension. Subjects on antihypertensive medications were 1½ times more likely to have suspicious glaucoma (odds ratio [OR] =1.56] and nearly twice as likely to have POAG (OR = 1.85). In addition, we found a 31% and 12% reduction in risk of having POAG (95% confidence interval [CI] =13–45%, P = 0.001) and glaucoma suspect (95% CI = 2–21%, P = 0.03) respectively with every 1 mm Hg increment in MOPP. Conclusion: Subjects on antihypertensive medications are more likely to have either glaucoma or glaucoma suspect, and higher ocular perfusion pressure offers relative protection from glaucomatous damage.

Submacular hemorrhage: A study amongst Indian eyes.

Aim: To evaluate the management outcomes amongst various treatment modalities for submacular hemorrhage (SMH) in Indian subjects. Settings and Design: Retrospective, single-center study. Materials and Methods: Patients presenting with SMH between 1999 and 2006 were included. Treatment modalities included: vitrectomy with subretinal recombinant tissue plasminogen activator (r-tPA) assisted SMH evacuation (group 1, n = 14); pneumatic displacement with intravitreal r-tPA and gas (group 2, n = 25); and pneumatic displacement with intraocular gas (group 3, n = 7). Favorable anatomical outcome was defined as complete displacement of SMH from fovea and favorable functional outcome was defined as a gain of >2 Snellen lines from the baseline. Kruskal–Wallis, analysis of variance (ANOVA), and Chi-square tests were used to compare the three groups, while Mann–Whitney and independent t-test were used to evaluate the influence of duration and size of SMH on outcomes. Results: There was no difference amongst groups in terms of favorable anatomical (P = 0.121) or functional outcomes (P = 0.611). Eyes with median duration of SMH less than 7.5 days had a significantly higher probability of achieving favorable anatomical outcome compared to eyes with SMH >14.5 days (P = 0.042). However, duration of SMH did not influence functional outcome (P = 0.595). Similarly, size of SMH did not affect anatomical (P = 0.578) or functional (P = 0.381) outcome. Median follow-up was 31.5, 6.5, and 2.5 months in the three groups, respectively. Conclusions: Co- existing posterior segment conditions and duration of SMH may influence the choice of treatment modality and treatment outcomes. Pneumatic displacement with r-tPA and r-tPA assisted vitrectomy appear to be favorable options for the management of SMH.

Fifteen-year trends in indications for enucleation from a tertiary care center in South India.

Aim: To analyze the trends in clinicopathologic indications for enucleations over a 15-year period. Materials and Methods: Clinicopathologic details of all eyes that underwent enucleation from January 1996 to December 2010 were drawn up from a computerized database. The study was divided into three periods of 5 years each and comparison tables for each cause of enucleation during these periods were generated. Chi-square test was used to compare proportions. Results: Out of a total 1467 enucleations performed during the study period, 693 (46%) were attributable to retinoblastoma, 189 (12.5%) to uveal melanoma, 228 (15%) to trauma, and 149 (10%) to phthisis bulbi. Intraocular tumors accounted for more than 63% of all enucleations performed. Over the three time periods, proportion of enucleations secondary to retinoblastoma increased from 38% in the 1st period to 58% in the 3rd period (P < 0.001). Enucleations for trauma showed statistically significant reduction in trends over the three periods (24% in the 1st period vs. 4.4% in the 3rd period, P < 0.001). Similar trends were also seen in the proportion of enucleations due to intractable glaucoma and chronic uveitis. The absolute number of enucleations secondary to retinoblastoma out of the total cases seen during the study period did not change over the three periods (range 51–60%). Conclusion: Intraocular tumors were the commonest indications for enucleation in our patient population despite the availability of globe-conserving treatments such as chemotherapy and radioactive plaques. We observed increasing trends in the proportion of enucleations due to retinoblastoma and reduction of enucleations secondary to trauma, chronic uveitis, and glaucoma.

Comparative study on the incidence and outcomes of pigmented versus non pigmented keratomycosis.

Purpose: To determine the incidence, outcomes and establish factors determining visual prognosis of keratomycosis due to pigmented fungi in comparison with nonpigmented fungi. Materials and Methods: All culture-proven cases of fungal keratitis from January 2006 to August 2008 were drawn from a computerized database and cases with adequate documentation were analyzed for predisposing factors, clinical characteristics, microbiology and treatment methods. Outcomes of keratitis due to pigmented and nonpigmented fungi were compared using t-test and χ2 test. Results: Of 373 cases of keratomycosis during the study period, pigmented fungi were etiological agents in 117 eyes (31.3%) and nonpigmented fungi in 256 eyes (68.7%). Eyes with nonpigmented keratitis had significantly larger ulcers (14.96 mm2 ) and poorer vision (1.42 logMAR) at presentation compared to those with keratomycosis due to pigmented fungi (P=0.01). The characteristic macroscopic pigmentation was seen in only 14.5% in the pigmented keratitis group. Both groups responded favorably to medical therapy (78.1% vs. 69.1%) with scar formation (P=0.32) and showed a significant improvement in mean visual acuity compared with that at presentation (P<0.01). Visual improvement in terms of line gainers and losers in the subgroup of eyes that experienced healing was also similar. Location of the ulcer was the only factor that had significant predictive value for visual outcome (P=0.021). Conclusion: Incidence of keratomycosis due to pigmented fungi may be increasing as compared to previous data. These eyes have similar response to medical therapy and similar visual outcome compared to nonpigmented keratitis. Central ulcers have a poor visual outcome.

Risk factors for intraocular penetration of caterpillar hair in Ophthalmia Nodosa: A retrospective analysis.

We report risk factors associated with intraocular penetration of caterpillar hair seen at our institute from January 2005 to December 2007. Records of all patients with caterpillar hair induced ophthalmitis (CHIO) were retrospectively reviewed for clinical characteristics, anatomic location of lodgment of the caterpillar hair, treatment methods, and outcomes. Out of a total of 544 cases of CHIO, 19 eyes (seven in the anterior chamber and 12 in the posterior segment) experienced intraocular penetration (3.5%). The presence of deep intracorneal hair (80 cases, 14.7%) was found to be the only risk factor for intraocular penetration (P < 0.001). The removal of intracorneal hair was possible in only 29 out of 80 eyes (36%) and this was associated with a significantly reduced risk of intraocular penetration (P = 0.022). Patients with retained intracorneal hairs should be counseled regarding risk of intraocular penetration and closely followed up for at least six months.