The Aravind Pseudoexfoliation Study: Surgical and First-Year Postoperative Results in Eyes without Phacodonesis and Nonmiotic Pupils.

PURPOSE: To compare intraoperative complication rates, 1-year visual outcomes, and postoperative complication rates over the first postoperative year in eyes with and without pseudoexfoliation undergoing cataract surgery. DESIGN: Prospective, comparative, interventional study. PARTICIPANTS: Nine hundred thirty eyes with cataract and uncomplicated pseudoexfoliation (without phacodonesis, clinically shallow anterior chambers, or pupil size <4 mm) and 476 controls with cataract but without pseudoexfoliation recruited from 4 centers of the Aravind Eye Care System in Southern India. The 2 groups were randomized separately to receive either a single-piece acrylic intraocular lens (IOL; SA60AT; Alcon Laboratories, Fort Worth, TX) or a 3-piece acrylic IOL (MA60AS; Alcon Laboratories). The pseudoexfoliation group also was randomized to receive or not receive a capsular tension ring. METHODS: All eyes underwent phacoemulsification with IOL implantation and were followed up at 1 day, 1 month, 3 months, and 1 year after surgery. MAIN OUTCOME MEASURES: Association of pseudoexfoliation status with intraoperative complication rates, 1-year best-corrected visual acuity, and any other complications. RESULTS: Mean ages were 63.0±6.9 years and 57.9±7.3 years in the pseudoexfoliation and control groups, respectively (P < 0.001). Pseudoexfoliation patients were more likely to be men (P = 0.014), to have a nuclear opalescence grade of more than 4 (P = 0.001), and to have a pupil size of less than 6 mm (P < 0.001) when compared with controls. Intraoperative complication rates were 2.9% and 1.9% in the pseudoexfoliation and control groups, respectively (P = 0.29). One-year postoperative best-corrected visual acuity was comparable (P = 0.09). Complication rates at 1 year were 2.7% and 2.5% in the pseudoexfoliation and control groups, respectively (P = 0.82). Average endothelial cell loss was 14.7% in the pseudoexfoliation group and 12.7% in the control group at 1 year (P = 0.066) when adjusting for age and nuclear opacity. CONCLUSIONS: Pseudoexfoliation eyes without shallow anterior chamber, small pupils, or apparent zonulopathy may represent eyes with lower risks of complications. Despite smaller pupils and denser cataracts, pseudoexfoliation eyes without clinically apparent preoperative zonulopathy were not at a higher risk of intraoperative or postoperative complications or worse visual outcomes after cataract surgery.

Residents' Learning Curve for Manual Small-Incision Cataract Surgery at Aravind Eye Hospital, India.

PURPOSE: The goal of this study was to document the resident learning curve for manual small-incision cataract surgery (MSICS) and to identify implications for the design of ophthalmology residency programs aimed to train surgeons for developing countries. DESIGN: Hospital-based retrospective cohort study. PARTICIPANTS: All 38 residents entering 2 postgraduate residency programs at Aravind Eye Hospital, Madurai, in 2012 and 2013. METHODS: Surgical complications and reoperations for all MSICSs performed by residents during the residency training period were evaluated using a computerized patient database. Multivariate logistic regression models were used to estimate the effect of the cumulative number of surgeries performed on incidence of intraoperative complications, postoperative complications, and reoperations, controlling for covariates. MAIN OUTCOME MEASURES: Incidence of intraoperative and first-day postoperative complications of Oxford Cataract Treatment and Evaluation Team (OCTET) grades II and III and the incidence of reoperations. Analyses controlled for patient-, resident-, and residency program-level covariates. RESULTS: The study evaluated 13 159 surgeries performed by the 38 residents between October 15, 2012, and August 24, 2016. The mean number of surgeries performed by a resident was 346.3 (standard deviation, 269.4). Three hundred forty-two eyes (2.60%) with at least 1 intraoperative complication, 234 eyes (1.78%) with at least 1 first-day postoperative complication, and 154 reoperations (1.17%) were observed. After controlling for baseline covariates, increasing surgical experience was associated with reduced risk of intraoperative and postoperative complications, as well as reoperations. The odds decreased by 17% (intraoperative complications), 12% (postoperative complications measured 1 day after surgery), and 7% (reoperations) per 100 additional surgeries performed. Patient-level factors such as older age, left eye surgery, and lower preoperative uncorrected visual acuity were found to be associated with higher risk of intraoperative complications (P < 0.01 for all). CONCLUSIONS: The risk of surgical complications and reoperations in MSICS decreased steadily with surgical experience gained by resident surgeons. We recommend that ophthalmology residency programs in developing nations teaching MSICS provide opportunities to perform 300 surgeries or more by residents so as to achieve rates of intraoperative and postoperative complications of less than 2%.

Development of a rapid point-of-care patient reported outcome measure for cataract surgery in India.

BACKGROUND: For patient undergoing cataract surgery in India, existing patient-reported outcome (PRO) measures are either not culturally relevant, have not been adequately validated, or are too long to be used in a busy clinical setting. We sought to develop and validate a brief and culturally relevant point-of-care PRO measure to address this need. METHODS: Twelve items from the Indian Visual Functioning Questionnaire (IND-VFQ) were selected based on preliminary data. Patients 18 years and older were prospectively recruited at Aravind Eye Care System in Madurai, India. Clinical and sociodemographic data were collected and the 12-item short-form IND-VFQ (SF-IND-VFQ) was administered pre- and post-operatively to 225 patients; Factor analysis and Rasch modeling was performed to assess its psychometric properties. RESULTS: One item that did not fit a unidimensional scale and had poor fit with the Rasch model was eliminated from the questionnaire. The remaining 11 items represented a single construct (no residual correlations> 0.1) and were largely unaffected by differential item functioning. Five items had disordered thresholds resolved by collapsing the response scale from four to three categories. The survey had adequate reliability (0.80) and good construct (infit range, 0.77-1.29; outfit range, 0.56-1.30) and content (item separation index, 5.87 logits) validity. Measurement precision was fair (person separation index, 1.97). There was evidence that items were not optimally targeted to patients' visual ability (preoperatively, - 1.92 logits; overall, - 3.41 logits), though the survey measured a very large effect (Cohen's d 1.80). In a subset of patients, the average time to complete the questionnaire was 2 min 6.3 s. CONCLUSIONS: The SF-IND-VFQ is a valid, reliable, sensitive, and rapidly administered point-of-care PRO measure to assess changes in visual functioning in patients undergoing cataract surgery in India.

Intracameral antibiotics during cataract surgery: evidence and barriers.

PURPOSE OF REVIEW: There is continuing debate regarding the safety, efficacy, and necessity of intracameral antibiotics to prevent postoperative endophthalmitis. We summarize the most recent evidence-based publications that either support or caution against this practice. RECENT FINDINGS: Several additional large, international retrospective clinical studies found a significant reduction in endophthalmitis rates with intracameral antibiotic prophylaxis. Many surgeons are looking for alternatives to vancomycin for intracameral prophylaxis because of its association with the rare but sight-threatening complication of hemorrhagic occlusive retinal vasculitis. Although most efficacy data has been reported for intracameral cefuroxime, one of the largest clinical studies to date shows convincing efficacy with intracameral moxifloxacin prophylaxis. This same study reported a significant benefit with intracameral moxifloxacin following posterior capsular rupture, and surgeons should consider intracameral prophylaxis in these high risk cases. SUMMARY: Despite mounting evidence that routine prophylaxis with intracameral cefuroxime and moxifloxacin reduce the endophthalmitis rate following cataract surgery, many surgeons have not adopted this practice. Reasons include lack of level 1 evidence from randomized trials, and the potential risks from compounding or mixing antibiotic solutions when no approved formulations are commercially available. Countries with commercially approved intraocular antibiotic formulations have the highest adoption rates of routine intracameral prophylaxis.

MTHFR and MTHFD1 gene polymorphisms are not associated with pseudoexfoliation syndrome in South Indian population.

PURPOSE: Pseudoexfoliation syndrome (PEX) is a late onset disorder of extracellular matrix turnover, associated systemically with cardiovascular and cerebrovascular disease. To evaluate the suggested association of polymorphisms of homocysteine metabolism genes MTHFR (rs1801131, rs1801133) and MTHFD1 (rs8006686) with PEX. METHODS: A case-control association study was undertaken, comprising a total of 1472 individuals including 860 unrelated PEX cases and 612 ethnic-matched cataract controls (CC). All the study subjects were genotyped for three SNPs using the TaqMan allelic discrimination assay. Association and statistical analysis were performed with PLINK 1.07 and STATA 11.1. RESULTS: Among the three SNPs genotyped, MTHFR polymorphisms did not exhibit significant association with PEX (rs1801131; p = 0.549, rs1801133; p = 0.408). The intronic SNP rs8006686 showed nearly significant association (p = 0.069), and however did not remain significant after Bonferroni correction. CONCLUSION: Our study suggests no significant genetic association of MTHFR (rs1801131, rs1801133) and MTHFD1 (rs8006686) polymorphisms in South Indian PEX patients.

Endophthalmitis Reduction with Intracameral Moxifloxacin Prophylaxis: Analysis of 600 000 Surgeries.

PURPOSE: To compare the postoperative endophthalmitis rate before and after initiation of intracameral (IC) moxifloxacin prophylaxis for both phacoemulsification and sutureless, manual small-incision cataract surgery (M-SICS), as well as in patients with posterior capsular rupture (PCR). DESIGN: Retrospective, clinical registry. PARTICIPANTS: All cataract surgeries (617 453) performed during the 29-month period from January 2014 to May 2016 at the 10 regional Aravind eye hospitals were included. METHODS: The electronic health record data for all study eyes were analyzed. Endophthalmitis rates before and after moxifloxaxin were statistically compared for all eyes and separately for both phacoemulsification and M-SICS, and for the eyes complicated by PCR. MAIN OUTCOME MEASURES: The postoperative endophthalmitis rates before and after initiation of IC moxifloxacin prophylaxis. RESULTS: Overall, 302 815 eyes did not receive IC moxifloxacin and 314 638 eyes did, and there was a significant decline in the endophthalmitis rate, from 0.07% (214/302 815) to 0.02% (64/314 638) (P < 0.001), with moxifloxacin. For the 194 252 phacoemulsification eyes, the endophthalmitis rate was 0.07% (75/104 894) without IC moxifloxacin prophylaxis, compared with 0.01% (11/89 358) with moxifloxacin (P < 0.001). For the 414 657 M-SICS eyes, the endophthalmitis rate was 0.07% (135/192 149) without IC moxifloxacin prophylaxis, compared with 0.02% (52/222 508) with moxifloxacin (P < 0.001). Approximately half of the 8479 eyes that had PCR received IC moxifloxacin, and half did not. Without IC moxifloxacin, PCR increased the endophthalmitis rate nearly 7-fold to 0.48% (20/4186); IC moxifloxacin reduced the endophthalmitis rate with PCR to 0.21% (9/4293) (P = 0.034). No adverse events were due to IC moxifloxacin. CONCLUSIONS: Routine IC moxifloxacin prophylaxis reduced the overall endophthalmitis rate by 3.5-fold (3-fold for M-SICS and nearly 6-fold for phacoemulsification). There was also a statistical benefit for eyes complicated by PCR, and IC antibiotic prophylaxis should be strongly considered for this high-risk population. These conclusions are strengthened by the high volume of cases analyzed at a single hospital network over a comparatively short time frame. Considering the association of hemorrhagic occlusive retinal vasculitis with vancomycin and the commercial unavailability of IC cefuroxime in many countries, moxifloxacin appears to be an effective option for surgeons electing IC antibiotic prophylaxis.

Long-term Posterior Capsule Opacification Reduction with Square-Edge Polymethylmethacrylate Intraocular Lens: Randomized Controlled Study.

PURPOSE: To objectively assess the long-term posterior capsule opacification (PCO) and neodymium-doped yttrium aluminium garnet (Nd:YAG) capsulotomy rate of a square-edge (SE) polymethylmethacrylate (PMMA) intraocular lens (IOL) modification in comparison with a round-edge (RE) PMMA IOL or an SE hydrophobic acrylic IOL (SE-Acrylic). DESIGN: Prospective, randomized, controlled fellow eye clinical study. PARTICIPANTS: Ninety-four patients scheduled for bilateral phacoemulsification had an SE-PMMA IOL implanted in 1 eye. An RE-PMMA IOL was implanted in the fellow eye in 46 patients (group A), and an SE-Acrylic IOL was implanted in the fellow eye in 48 patients (group B). Randomization was used to determine group assignment and which IOL was implanted in the first eye to undergo surgery. METHODS: Evaluation of Posterior Capsule Opacification (EPCO) image analysis software was used to objectively grade PCO density from standardized, high-resolution retroillumination photographs obtained annually for the first 5 postoperative years and at year 9. MAIN OUTCOME MEASURES: The PCO scores and Nd:YAG capsulotomy rate. RESULTS: Nine-year follow-up was achieved by 72% from group A and 63% from group B. In group A, the mean PCO score was significantly lower in the SE-PMMA IOL eyes compared with the contralateral RE-PMMA eyes at all follow-up visits (P < 0.05). In group B, the mean PCO score was statistically lower in the SE-PMMA IOL eyes compared with the contralateral SE-Acrylic IOL eyes at all but the 1- and 3-year follow-up visits. Nine-year Nd:YAG capsulotomy rates were 2% for SE-PMMA IOLs versus 37% for RE-PMMA IOLs in group A (P < 0.001), and 4% for SE-PMMA IOLs versus 10% for SE-Acrylic IOLs in group B (P = 0.435). The RE-PMMA PCO rate did not plateau and continued to increase throughout the 9-year study period. CONCLUSIONS: This prospective, 9-year fellow eye comparison study suggests that an inexpensive PMMA IOL design modification-a squared optic edge-could significantly reduce the burden of vision-impairing secondary membrane in developing countries.

Mapping standard ophthalmic outcome sets to metrics currently reported in eight eye hospitals.

BACKGROUND: To determine alignment of proposed international standard outcomes sets for ophthalmic conditions to metrics currently reported by eye hospitals. METHODS: Mixed methods comparative benchmark study, including eight eye hospitals in Australia, India, Singapore, Sweden, U.K., and U.S. All are major international tertiary care and training centers in ophthalmology. Main outcome measure is consistency of ophthalmic outcomes measures reported. RESULTS: International agreed standard outcomes (ICHOM) sets are available for cataract surgery (10 metrics) and macular degeneration (7 metrics). The eight hospitals reported 22 different metrics for cataract surgery and 2 for macular degeneration, which showed only limited overlap with the proposed ICHOM metrics. None of the hospitals reported patient reported visual functioning or vision-related quality of life outcomes measures (PROMs). Three hospitals (38%) reported rates for uncomplicated cataract surgeries only. There was marked variation in how and at what point postoperatively visual outcomes following cataract, cornea, glaucoma, strabismus and oculoplastics procedures were reported. Seven (87.5%) measured post-operative infections and four (50%) measured 30 day unplanned reoperation rates. CONCLUSIONS: Outcomes reporting for ophthalmic conditions currently widely varies across hospitals internationally and does not include patient-reported outcomes. Reaching consensus on measures and consistency in data collection will allow meaningful comparisons and provide an evidence base enabling improved sharing of "best practices" to improve eye care globally. Implementation of international standards is still a major challenge and practice-based knowledge on measures should be one of the inputs of the international standardization process.

Efficacy of Intracameral Moxifloxacin Endophthalmitis Prophylaxis at Aravind Eye Hospital.

PURPOSE: To compare the rate of postoperative endophthalmitis before and after initiation of intracameral (IC) moxifloxacin for endophthalmitis prophylaxis in patients undergoing cataract surgery. DESIGN: Retrospective, clinical registry. PARTICIPANTS: All charity and private patients (116 714 eyes) who underwent cataract surgery between February 15, 2014, and April 15, 2015, at the Madurai Aravind Eye Hospital were included. Group 1 consisted of 37 777 eyes of charity patients who did not receive IC moxifloxacin, group 2 consisted of 38 160 eyes of charity patients who received IC moxifloxacin prophylaxis, and group 3 consisted of 40 777 eyes of private patients who did not receive IC moxifloxacin. METHODS: The electronic health record data for each of the 3 groups were analyzed, and the postoperative endophthalmitis rates were statistically compared. The cost of endophthalmitis treatment (groups 1 and 2) and the cost of IC moxifloxacin prophylaxis (group 2) were calculated. MAIN OUTCOME MEASURES: Postoperative endophthalmitis rate before and after initiation of IC moxifloxacin endophthalmitis treatment cost. RESULTS: Manual, sutureless, small incision cataract surgery (M-SICS) accounted for approximately all of the 75 937 cataract surgeries in the charity population (97%), but only a minority of the 40 777 private surgeries (21% M-SICS; 79% phacoemulsification). Thirty eyes in group 1 (0.08%) and 6 eyes in group 2 (0.02%) were diagnosed with postoperative endophthalmitis (P < 0.0001). The group 3 endophthalmitis rate was 0.07% (29 eyes), which was also higher than the second group's rate (P < 0.0001). There were no adverse events attributed to IC moxifloxacin in group 2. The total cost of treating the 30 patients with endophthalmitis in group 1 was virtually identical to the total combined cost in group 2 of routine IC moxifloxacin prophylaxis and treatment of the 6 endophthalmitis cases. CONCLUSIONS: Routine IC moxifloxacin prophylaxis achieved a highly significant, 4-fold reduction in postoperative endophthalmitis in patients undergoing M-SICS. Compared with previous studies, having such a high volume of patients undergoing surgery during a relatively short 14-month time period strengthens the conclusion. This study provides further evidence that moxifloxacin is an effective IC prophylactic antibiotic and suggests that IC antibiotics should be considered for M-SICS and phacoemulsification.

Carbon footprint and cost-effectiveness of cataract surgery.

PURPOSE OF REVIEW: This article raises awareness about the cost-effectiveness and carbon footprint of various cataract surgery techniques, comparing their relative carbon emissions and expenses: manual small-incision cataract surgery (MSICS), phacoemulsification, and femtosecond laser-assisted cataract surgery. RECENT FINDINGS: As the most commonly performed surgical procedure worldwide, cataract surgery contributes significantly to global climate change. The carbon footprint of a single phacoemulsification cataract surgery is estimated to be comparable to that of a typical person's life for 1 week. Phacoemulsification has been estimated to be between 1.4 and 4.7 times more expensive than MSICS; however, given the lower degree of postoperative astigmatism and other potential complications, phacoemulsification may still be preferable to MSICS in relatively resource-rich settings requiring high levels of visual function. Limited data are currently available regarding the environmental and financial impact of femtosecond laser-assisted cataract surgery; however, in its current form, it appears to be the least cost-effective option. SUMMARY: Cataract surgery has a high value to patients. The relative environmental impact and cost of different types of cataract surgery should be considered as this treatment becomes even more broadly available globally and as new technologies are developed and implemented.

Towards the Identification and Characterization of Putative Adult Human Lens Epithelial Stem Cells.

The anterior lens epithelium has the ability to differentiate into lens fibres throughout its life. The present study aims to identify and functionally characterize the adult stem cells in the human lens epithelium. Whole mounts of lens epithelium from donor eyes (normal/cataract) were immunostained for SOX2, gap junction protein alpha 1 (GJA1), PAX6, α, ß and γ-crystallins, followed by a confocal analysis. The functional property of adult stem cells was analysed by their sphere forming ability using cultured lens epithelial cells from different zones. Based on marker expression, the lens epithelium was divided into four zones: the central zone, characterized by a small population of PAX6+, GJA1-, ß-crystallin- and γ-crystallin- cells; the germinative zone, characterized by PAX6+, GJA1+, ß-crystallin- and γ-crystallin-; the transitional zone, characterized by PAX6+, GJA1+, ß-crystallin+ and γ-crystallin-; and the equatorial zone, characterized by PAX6+/-, GJA1+, ß-crystallin+, and γ-crystallin+ cells. The putative lens epithelial stem cells identified as SOX2+ and GJA1 membrane expression negative cells were located only in the central zone (1.89 ± 0.84%). Compared to the other zones, a significant percentage of spheres were identified in the central zone (1.68 ± 1.04%), consistent with the location of the putative adult lens epithelial stem cells. In the cataractous lens, an absence of SOX2 expression and a significant reduction in sphere forming ability (0.33 ± 0.11%) were observed in the central zone. The above findings confirmed the presence of putative stem cells in the central zone of the adult human lens epithelium and indicated their probable association with cataract development.

Changing operating room practices: the effect on postoperative endophthalmitis rates following cataract surgery.

PURPOSE: To determine whether four new operating room (OR) protocols instituted because of COVID-19 reduced the cataract surgical postoperative endophthalmitis rate (POE). DESIGN: Retrospective, sequential, clinical registry study. METHODS: 85 552 sequential patients undergoing cataract surgery at the Aravind Eye Hospitals between 1 January 2020 and 25 March 2020 (56 551 in group 1) and 3 May 2020 and 31 August 2020 (29 011 in group 2). In group 1, patients were not gowned, surgical gloves were disinfected but not changed between cases, OR floors were not cleaned between every case, and multiple patients underwent preparation and surgery in the same OR. In group 2, each patient was gowned, surgical gloves were changed between each case, OR floors and counters were cleaned between patients, and only one patient at a time underwent preparation and surgery in the OR. RESULTS: Group 1 was older, had slightly more females, and better preoperative vision. More eyes in group 2 underwent phacoemulsification (p=0.18). Three eyes (0.005%) in group 1 and 2 eyes (0.006%) in group 2 developed POE (p=0.77). Only one eye that underwent phacoemulsification developed POE; this was in group 1. There was no difference in posterior capsule rupture rate between the two groups. CONCLUSIONS: Adopting a set of four temporary OR protocols that are often mandatory in the Western world did not reduce the POE rate. Along with previously published studies, these results challenge the necessity of these common practices which may be needlessly costly and wasteful, arguing for the reevaluation of empiric and potentially unnecessary guidelines that govern ophthalmic surgeries.

Cytoskeletal drugs prevent posterior capsular opacification in human lens capsule in vitro.

BACKGROUND: To determine whether the cytoskeletal drugs H-7 and Latrunculin B (LAT-B) inhibit posterior capsular opacification (PCO) in the cultured human lens capsular bag. METHODS: Following extracapsular cataract (lens) extraction in human donor eyes, the capsular bag was prepared and cultured by standard techniques. Forty-eight capsular bags were studied, of which 13 were treated with H-7 (50, 100 or 300 µM), 12 with 1% BSS (vehicle of H-7), 11 with LAT-B (2, 5 or 10 µM), and 12 with 0.25% DMSO (vehicle of LAT-B). Forty out of the 48 capsular bags were from paired eyes of 20 donors, with one bag being treated with H-7/LAT-B and the other with BSS/DMSO for each pair, including 20 for the H-7-BSS protocol and 20 for the LAT-B-DMSO protocol. The medium with the cytoskeletal drug/vehicle was replaced every 3-4 days for 4 weeks. PCO was assessed daily using inverted phase-contrast microscopy, and scored on a 4-point scale. RESULTS: In all cultures with BSS or DMSO, residual lens epithelial cells (LECs) on the anterior capsule migrated to and proliferated on the posterior capsule by 3-7 days, and apparent LEC growth on the posterior capsule with severe capsular wrinkling (PCO Grade 3) was seen by 2-3 weeks. When treated continuously with H-7 or LAT-B, the migration and proliferation of LECs and the capsular wrinkling were inhibited in a dose-dependent manner, with the inhibition being complete (PCO Grade 0) in the 300 µM H-7 (n = 8, p < 0.001) or 10 µM LAT-B culture (n = 3, p = 0.002). CONCLUSION: H-7 and LAT-B dose-dependently inhibited PCO formation in the cultured human lens capsular bags, suggesting that cytoskeletal drugs might prevent PCO formation after surgery in the human eye.

A systematic approach to the management of microspherophakia.

Microspherophakia is a rare developmental abnormality of the crystalline lens with a myriad of ocular and systemic associations. Glaucoma is a serious complication associated with this disorder. Early identification of the disease, timely visual rehabilitation, and appropriate management of the lens and glaucoma can help us prevent blindness from this condition. Multidisciplinary care with lifelong follow-up is recommended, as this typically affects the younger population. Current treatment protocols for this condition are mainly based on case reports and retrospective studies with shorter follow-up. Due to the rarity of this disease, designing a large randomized controlled trial to identify the merits and demerits of each management strategy is challenging. With cataract, glaucoma, and vitreoretinal specialists, each having their preferred way of managing microspherophakic lenses, we decided to do a comprehensive review of the existing literature to devise an integrated approach toward effective management of these patients. This review will collate all evidence and provide a very practical decision-making tree for its management.