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Purpose To determine if smartphone photography could be a useful adjunct to blindness prevalence surveys by providing an accurate diagnosis of corneal opacity. Methods A total of 174 patients with infectious keratitis who had undergone corneal culturing over the past 5 years were enrolled in a diagnostic accuracy study at an eye hospital in South India. Both eyes had an ophthalmologist-performed slit lamp examination, followed by anterior segment photography with a handheld digital single lens reflex (SLR) camera and a smartphone camera coupled to an external attachment that provided magnification and illumination. The diagnostic accuracy of photography was assessed relative to slit lamp examination. Results In total, 90 of 174 enrolled participants had a corneal opacity in the cultured eye and no opacity in the contralateral eye, and did not have a penetrating keratoplasty or missing photographs. Relative to slit lamp examination, the sensitivity of corneal opacity diagnosis was 68% (95%CI 58-77%) using the smartphone's default settings and 59% (95%CI 49-69%) using the SLR, and the specificity was 97% (95%CI 93-100%) for the smartphone and 97% (95%CI 92-100%) for the SLR. The sensitivity of smartphone-based corneal opacity diagnosis was higher for larger scars (81% for opacities 2 mm in diameter or larger), more visually significant scars (100% for eyes with visual acuity worse than 20/400), and more recent scars (85% for eyes cultured in the past 12 months). Conclusion The diagnostic performance of a smartphone coupled to an external attachment, while somewhat variable, demonstrated high specificity and high sensitivity for all but the smallest opacities.

This study quantifies the performance of an international cohort of cornea specialists in image-based differentiation of bacterial and fungal keratitis, identifying significant regional variation and establishing a reference standard for comparison against machine learning models.

Purpose To develop and evaluate an automated, portable algorithm to differentiate active corneal ulcers from healed scars using only external photographs. Design A convolutional neural network was trained and tested using photographs of corneal ulcers and scars. Participants De-identified photographs of corneal ulcers were obtained from the Steroids for Corneal Ulcers Trial (SCUT), Mycotic Ulcer Treatment Trial (MUTT), and Byers Eye Institute at Stanford University. Methods Photographs of corneal ulcers (n = 1313) and scars (n = 1132) from the SCUT and MUTT were used to train a convolutional neural network (CNN). The CNN was tested on 2 different patient populations from eye clinics in India (n = 200) and the Byers Eye Institute at Stanford University (n = 101). Accuracy was evaluated against gold standard clinical classifications. Feature importances for the trained model were visualized using gradient-weighted class activation mapping. Main Outcome Measures Accuracy of the CNN was assessed via F1 score. The area under the receiver operating characteristic (ROC) curve (AUC) was used to measure the precision-recall trade-off. Results The CNN correctly classified 115 of 123 active ulcers and 65 of 77 scars in patients with corneal ulcer from India (F1 score, 92.0% [95% confidence interval (CI), 88.2%–95.8%]; sensitivity, 93.5% [95% CI, 89.1%–97.9%]; specificity, 84.42% [95% CI, 79.42%–89.42%]; ROC: AUC, 0.9731). The CNN correctly classified 43 of 55 active ulcers and 42 of 46 scars in patients with corneal ulcers from Northern California (F1 score, 84.3% [95% CI, 77.2%–91.4%]; sensitivity, 78.2% [95% CI, 67.3%–89.1%]; specificity, 91.3% [95% CI, 85.8%–96.8%]; ROC: AUC, 0.9474). The CNN visualizations correlated with clinically relevant features such as corneal infiltrate, hypopyon, and conjunctival injection. Conclusions The CNN classified corneal ulcers and scars with high accuracy and generalized to patient populations outside of its training data. The CNN focused on clinically relevant features when it made a diagnosis. The CNN demonstrated potential as an inexpensive diagnostic approach that may aid triage in communities with limited access to eye care.

Purpose To report a case of late spontaneous detachment of Descemet membrane (DM) in a donor penetrating keratoplasty (PKP) graft and its successful management using a supra-Descemetic venting incision combined with gas descemetopexy. Methods Case report with review of literature. Results A 56-year-old man who had undergone PKP after acute hydrops in pellucid marginal degeneration 27 years before presentation experienced sudden onset vision loss. Clinical features mimicked acute graft rejection but detailed evaluation and anterior segment optical coherence tomography showed a DM detachment (DMD) of the graft. Ten weeks after the onset of DMD, he underwent descemetopexy with a supra-Descemetic stromal venting incision and sulfur hexafluoride gas tamponade. DM reattached with complete resolution of graft edema. Conclusions Late spontaneous DMD of the graft after PKP is very uncommon and must be differentiated from acute graft rejection. Anterior segment optical coherence tomography may help to diagnose this entity that can be managed successfully despite late intervention. The addition of a venting incision that drains fluid from the supra-Descemetic space can increase the chance of success of descemetopexy when compared with descemetopexy with air or gas alone.

Purpose: To study the demographic profile, clinical features, treatment outcome, and ocular morbidity of microbiologically proven Pythium keratitis in South India. Methods: A retrospective analysis of clinical records of microbiologically proven Pythium keratitis at a tertiary eye care referral center in South India from January 2016 to November 2017 was performed. Demographic details, predisposing risk factors, microbiological investigations, clinical course, and visual outcome were analyzed. Results: Seventy-one patients with microbiologically proven Pythium keratitis were identified. The mean age was 44(±18.2) years with an increase in male preponderance and 50% were farmers. Duration of delay at time of presentation to the hospital was a mean of 14(±7.2) days. The visual acuity at baseline ranged from 6/6 to no light perception (median 2.1 logMAR). A combination of 5% natamycin and 1% voriconazole was given to 42% patients, and natamycin alone was given to 39.4% patients. 1% itraconazole eye drops alone was initiated in 7 (10%) patients and 3 among this group responded. Therapeutic keratoplasty (TPK) was performed in 48 (67.6%) patients. None of the primary grafts remained clear after a period of 1 month. Twenty-six eyes (54.2%) had graft reinfection and all these eyes either developed anterior staphyloma (4) or were eviscerated (3) and 13 eyes became phthisical. The remaining 22 patients who had TPK resulted in failed graft. Among these, re-grafts were performed in 6 patients, of which 5 were doing well at the last follow-up. Conclusion: We report a large series of patients with Pythium keratitis. Promoting early and differential diagnosis, awareness of clinicians and specific treatment options are needed for this devastating corneal disease.

Objective To compare oral voriconazole vs placebo in addition to topical antifungals in the treatment of filamentous fungal keratitis. Design Non-prespecified, secondary case-control analysis from a multicenter, double-masked, randomized placebo-controlled clinical trial. Methods Study Participants : Patients with smear-positive filamentous fungal ulcers and visual acuity of 20/400 or worse who eventuated to therapeutic penetrating keratoplasty (TPK). Intervention : Study participants were randomized to oral voriconazole vs oral placebo; all received topical antifungal drops. Main Outcome Measures : TPK button culture positivity. Results A total of 95 of 194 (49.5%) study participants enrolled at Madurai, Coimbatore, or Pondicherry, India eventuated to TPK in an average of 20.9 days (standard deviation 15.2 days, range 2-71 days). TPK button cultures were available for 67 of 95 (71%) of the TPKs performed and were positive for filamentous fungus in 45 of 67 (67%) cases. For each 1-day increase in the time to TPK there was 0.94-fold decreased odds of fungal culture positivity (95% confidence interval [CI] 0.90–0.98, P = .005). Those randomized to oral voriconazole had 1.26-fold increased odds of TPK button culture positivity after controlling for time to TPK and baseline organism, but this was not statistically significant (95% CI 0.32–4.87; P = .74). Those who underwent TPK for lack of response to medical therapy were 10.64-fold more likely to be culture positive than if the indication for surgery was perforation and this was statistically significant (95% CI 2.16–51.70; P = .003). Conclusions There appears to be no benefit to adding oral voriconazole to topical antifungal agents in the treatment of severe filamentous fungal ulcers. Infection rather than inflammation appears to be the reason for the worsening clinical picture in many of these patients.

Purpose: We compare results from regression discontinuity (RD) analysis to primary results of a randomized controlled trial (RCT) utilizing data from two contemporaneous RCTs for treatment of fungal corneal ulcers. Methods: Patients were enrolled in the Mycotic Ulcer Treatment Trials I and II (MUTT I & MUTT II) based on baseline visual acuity: patients with acuity ≤ 20/400 (logMAR 1.3) enrolled in MUTT I, and >20/400 in MUTT II. MUTT I investigated the effect of topical natamycin versus voriconazole on best spectacle-corrected visual acuity. MUTT II investigated the effect of topical voriconazole plus placebo versus topical voriconazole plus oral voriconazole. We compared the RD estimate (natamycin arm of MUTT I [N = 162] versus placebo arm of MUTT II [N = 54]) to the RCT estimate from MUTT I (topical natamycin [N = 162] versus topical voriconazole [N = 161]). Results: In the RD, patients receiving natamycin had mean improvement of 4-lines of visual acuity at 3 months (logMAR −0.39, 95% CI: −0.61, −0.17) compared to topical voriconazole plus placebo, and 2-lines in the RCT (logMAR −0.18, 95% CI: −0.30, −0.05) compared to topical voriconazole. Conclusions: The RD and RCT estimates were similar, although the RD design overestimated effects compared to the RCT.

Author(s): Ung, Lawson; Acharya, Nisha R; Agarwal, Tushar; Alfonso, Eduardo C; Bagga, Bhupesh; Bispo, Paulo Jm; Burton, Matthew J; Dart, John Kg; Doan, Thuy; Fleiszig, Suzanne Mj; Garg, Prashant; Gilmore, Michael S; Gritz, David C; Hazlett, Linda D; Iovieno, Alfonso; Jhanji, Vishal; Kempen, John H; Lee, Cecilia S; Lietman, Thomas M; Margolis, Todd P; McLeod, Stephen D; Mehta, Jod S; Miller, Darlene; Pearlman, Eric; Prajna, Lalitha; Prajna, N Venkatesh; Seitzman, Gerami D; Shanbhag, Swapna S; Sharma, Namrata; Sharma, Savitri; Srinivasan, Muthiah; Stapleton, Fiona; Tan, Donald Th; Tandon, Radhika; Taylor, Hugh R; Tu, Elmer Y; Tuli, Sonal S; Vajpayee, Rasik B; Van Gelder, Russell N; Watson, Stephanie L; Zegans, Michael E; Chodosh, James

Background/Purpose: To explore changes in the phenotypic features of Sjoogren's syndrome (SS), and in SS status among participants in the Sjoogren's International Collaborative Clinical Alliance (SICCA) registry over a 2 to 3-year interval. Methods: All participants in the SICCA registry who were found to have any objective measures of salivary hypofunction, dry eye, focal lymphocytic sialadenitis in minor salivary gland biopsy, or anti-SSA/B antibodies, were recalled over a window of 2 to 3 years after their baseline examinations to repeat all clinical examinations and specimen collections to determine whether there was any change in phenotypic features and in SS status. Results: As of September 15, 2013, 3,514 participants had enrolled in SICCA, and among 3,310 eligible, 771 presented for a follow-up visit. Among participants found to have SS using the 2012 ACR classification criteria, 93% again met the criteria after 2 to 3 years, and this proportion was 89% when using the 2016 ACR-EULAR criteria. Among those who did not meet ACR or ACR-EULAR criteria at baseline, 9% and 8%, respectively, had progressed and met them at follow-up. Those with hypergammaglobulinemia and hypocomplementemia at study entry were respectively 4 and 6 times more likely to progress to SS by ACR criteria than those without these characteristics (95%Confidence Interval: 1.5 – 10.1 and 1.8 – 20.4, respectively). Conclusion: While there was stability over a 2-3-year period of both individual phenotypic features of SS and of SS status, hypergammaglobulinemia and hypocomplementemia at study entry were predictive of progression to SS. This article is protected by copyright. All rights reserved.

To determine whether patients who had a positive repeated culture was predictive of worse clinical outcome than those who achieved microbiological cure at 6 days in the Mycotic Ulcer Treatment Trial I (MUTT-I).Secondary analysis from a multicenter, double-masked, randomized clinical trial.setting: Multiple hospital sites of the Aravind Eye Care System, India.Patients with culture-positive filamentous fungal ulcers and visual acuity of 20/40 to 20/400 reexamined 6 days after initiation of treatment.Corneal scraping and cultures were obtained from study participants at day 6 after enrollment.We assessed 3-month best spectacle-corrected visual acuity (BSCVA), 3-month infiltrate/scar size, corneal perforation, and re-epithelialization rates stratified by culture positivity at day 6.Of the 323 patients with smear-positive ulcers enrolled in MUTT-I, 299 (92.6%) were scraped and cultured 6 days after enrollment. Repeat culture positivity was 31% (92/299). Among patients who tested positive at enrollment, those with positive 6-day cultures had significantly worse 3-month BSCVA (0.39 logMAR; 95% confidence interval [CI]: 0.24-0.44; P.001), had larger 3-month scar size (0.39 mm; 95% CI: 0.06-0.73; P = .02), were more likely to perforate or require therapeutic penetrating keratoplasty (odds ratio: 6.27; 95% CI: 2.73-14.40; P.001), and were slower to re-epithelialize (hazard ratio: 0.33; 95% CI: 0.21-0.50; P.001) than those with a negative 6-day culture result.Early microbiological cure on culture is a predictor of clinical response to treatment.

Purpose To compare longitudinal outcomes of visual acuity after fungal corneal ulcers with those of bacterial ulcers. Design Prospective cohort study. Methods This study was conducted in a tertiary eye hospital in South India. The population consisted of 100 of 152 individuals whose fungal or bacterial keratitis had been diagnosed 4 years prior and had been enrolled in 1 of 2 concurrent randomized trials. Causative organisms of infectious keratitis were either bacterial or fungal. Presenting visual acuity consisted of best spectacle corrected visual acuity (BSCVA) and hard contact lens-corrected visual acuity (CLVA). Results Fifty study participants with prior fungal keratitis and 50 with prior bacterial keratitis were enrolled. Four years after treatment for keratitis, participants' presenting vision in the better eye was worse than 20/60 for 12 individuals (24.0%) in the fungal group and 10 individuals (20.0%) in the bacterial group. Median BSCVA in the affected eye at the 4-year visit in the fungal group was similar to that in the bacterial group (Snellen equivalent, 20/32 for each), although vision worse than 20/400 was more common in the fungal ulcer group after spectacle correction (odds ratio [OR] 4.19; 95% confidence interval [CI], 1.11-15.8) and contact lens correction (OR, 5.74; 95% CI, 1.37-24.1). Conclusions In this South Indian population with a previous episode of fungal or bacterial keratitis, correctable bilateral visual impairment was common. Although long-term visual outcomes were, on average, similar between fungal and bacterial ulcers, fungal ulcers were more likely to produce severe visual impairment.

To report the clinical features and outcomes of toxic keratitis after application of powdered custard apple seeds for hair washing for head lice infestation.Retrospective review of all patients with toxic keratitis after application of powdered custard apple seed for head lice infestation during the time period from January 2015 to December 2017. Demographic details, clinical features, and visual outcomes were documented.Thirty-one eyes of 19 patients with toxic keratitis after application of crushed custard apple seeds for head lice infestation were included in the study. Eighteen females and 1 male with a median age of 14 years [interquartile range (IQR) 12-34 years] presented with severe epiphora, congestion, photophobia, and defective vision (median logMar visual acuity 0.4, IQR 0.2-0.8) after application of custard apple seed powder for hair washing. Ten eyes (32.2%) had an epithelial defect (median size 9 mm, IQR 5-12 mm), and 21 (67.7%) eyes had punctate epithelial erosions. All the patients were treated with topical antibiotics, and at 3 days follow-up, all of them had resolution of symptoms and signs with a median logarithm of the minimum angle of resolution (logMAR) visual acuity of 0 (IQR 0-0.2).Health education about the harmful effect of this traditional practice for head lice infestation will prevent further similar events.

Background To determine if pretreatment with antifungal agents is predictive of worse clinical outcome in a fungal keratitis clinical trial. Design Non-pre-specified subgroup analysis of a randomized controlled trial in a tertiary hospital. Participants Three hundred twenty-three fungal ulcer cases with an enrolment visual acuity of 20/40 to 20/400. Methods The Mycotic Ulcer Treatment Trial I was a randomized, double-masked trial to determine the optimal treatment for filamentous fungal keratitis at the Aravind Eye Care System, India. Enrolled cases were randomized to receive topical natamycin or voriconazole. Prior antifungal medication use, dose and duration were collected at enrolment. A subgroup analysis was performed to determine if patients using natamycin or azoles at presentation have worse clinical outcomes compared with those who were not pretreated. Main Outcome Measures Three-month visual acuity (primary), 3-month infiltrate or scar size, corneal perforation and/or transplant and re-epithelialization time. Results Of the 323 patients enrolled, 44% presented on an antifungal agent. Pretreated patients had larger mean baseline infiltrate size (P

Background: The aim of this study was to compare the donor characteristics, quality of tissues, and utilization rate of corneas collected through Hospital cornea retrieval program (HCRP) and voluntary eye donation (VED). Methods: A prospective nonrandomized comparative study of all consecutive donor corneas collected through HCRP and VED during December 2015 to November 2016 was performed. Details of the donor such as age, sex, cause of death, need for medicolegal clearance, death to enucleation time, slit-lamp grading, specular microscopy, and tissue utilization were documented. Results: Nine hundred and eighty-five eyes of 493 donors were included in the study, of which 606 (61.5%) eyes belonged to HCRP and 379 (38.5%) eyes in VED. HCRP donors were significantly younger (HCRP: 43.87 ± 19 years; VED: 72.8 ± 13 years; P < 0.001). Males were more common in HCRP (HCRP: 236, 77.6%; VED: 99, 52.2%; P < 0.001). The most common cause of death was road traffic accident (132, 43.6%) in HCRP and cardiovascular disease (93, 49%) in VED. 73.3% (222) of HCRP donors needed medicolegal clearance. Phakic donor eyes were significantly higher in HCRP (HCRP: 561, 92.6%; VED: 184, 48.6%; P < 0.001). Specular microscopy was possible in 396 (65.3%) eyes of HCRP and 129 (34%) eyes of VED. The mean endothelial cell density was 2931 ± 431.1 in HCRP and 2668.6 ± 381.1 in VED. The tissue utilization rate was significantly higher in HCRP (HCRP: 481, 79.4%; VED: 201, 53%; P < 0.001). Eighty-two percent of endothelial keratoplasty, 78.5% of optical penetrating keratoplasty, and 58% of therapeutic keratoplasty were from HCRP donors. Conclusion: Donor corneas collected through HCRP have higher tissue utilization.

IntroductionCorneal opacity is a leading cause of blindness worldwide. In resource-limited settings, untreated traumatic corneal abrasions may result in infection and ultimately, opacity. Although antimicrobial treatment of corneal ulcers may successfully cure infections, the scarring that accompanies the resolution of infection can still result in visual impairment. Prevention may be the optimal approach for reducing corneal blindness. Studies have employed community health workers to provide prompt administration of antimicrobials after corneal abrasions to prevent infections, but these studies were not designed to determine the effectiveness of such a programme.Methods and analysisThe Village-Integrated Eye Worker trial (VIEW) is a cluster-randomised trial designed to assess the effectiveness of a community health worker intervention to prevent corneal ulcers. Twenty-four Village Development Committees (VDCs) in Nepal were randomised to receive a corneal ulcer prevention programme or to no intervention. Female Community Health Volunteers (FCHVs) in intervention VDCs are trained to diagnose corneal abrasions, provide antimicrobials and to refer participants when needed. An annual census is conducted over 3 years in all study VDCs to assess the incidence of corneal ulceration via corneal photography (primary outcome). Masked outcome assessors grade corneal photographs to determine the presence or absence of incident corneal opacities. The primary analysis is negative binomial regression to compare the incidence of corneal ulceration by study arm.Ethics and disseminationThe University of California San Francisco Committee on Human Research, Nepal Netra Jyoti Sangh and the Nepal Health Research Council have given ethical approval for the trial. The results of this trial will be presented at local and international meetings and submitted to peer-reviewed journals for publication.Trial registration numberNCT01969786; Pre-results.

Background/aimsThe Mycotic Ulcer Treatment Trial I (MUTT I) was a double-masked, multicentre, randomised controlled trial, which found that topical natamycin is superior to voriconazole for the treatment of filamentous fungal corneal ulcers. In this study, we determine risk factors for low vision-related quality of life in patients with fungal keratitis.MethodsThe Indian visual function questionnaire (IND-VFQ) was administered to MUTT I study participants at 3 months. Associations between patient and ulcer characteristics and IND-VFQ subscale score were assessed using generalised estimating equations.Results323 patients were enrolled in the trial, and 292 (90.4%) completed the IND-VFQ at 3 months. Out of a total possible score of 100, the average VFQ score for all participants was 81.3 (range 0-100, SD 23.6). After correcting for treatment arm, each logMAR line of worse baseline visual acuity in the affected eye resulted in an average 1.2 points decrease on VFQ at 3 months (95% CI -1.8 to 0.6, p

Objective To determine whether the Sjogren9s syndrome B (SSB)-positive/Sjogren9s syndrome A (SSA)-negative antibody profile is associated with key phenotypic features of SS. Methods Among registrants in the Sjogren9s International Collaborative Clinical Alliance (SICCA) with possible or established SS, we compared anti-SSA/anti-SSB reactivity profiles against concurrent phenotypic features. We fitted logistic regression models to explore the association between anti-SSA/anti-SSB reactivity profile and each key SS phenotypic feature, controlling for potential confounders. Results Among 3297 participants, 2061 (63%) had negative anti-SSA/anti-SSB, 1162 (35%) had anti-SSA with or without anti-SSB, and 74 (2%) anti-SSB alone. Key SS phenotypic features were more prevalent and had measures indicative of greater disease activity in those participants with anti-SSA, either alone or with anti-SSB, than in those with anti-SSB alone or negative SSA/SSB serology. These between-group differences were highly significant and not explained by confounding by age, race/ethnicity or gender. Participants with anti-SSB alone were comparable to those with negative SSA/SSB serology in their association with these key phenotypic features. Among SICCA participants classified with SS on the basis of the American-European Consensus Group or American College of Rheumatology criteria, only 2% required the anti-SSB-alone test result to meet these criteria. Conclusions The presence of anti-SSB, without anti-SSA antibodies, had no significant association with SS phenotypic features, relative to seronegative participants. The solitary presence of anti-SSB antibodies does not provide any more support than negative serology for the diagnosis of SS. This serological profile should thus be interpreted cautiously in clinical practice and potentially eliminated from future classification criteria.

A 51-year-old immunocompetent male with a history of Fuchs' endothelial dystrophy and immature cataract who underwent Descemet's stripping automated endothelial keratoplasty with intraocular lens implantation in both eyes presented with redness and defective vision of 1-day duration in his left eye. Slit lamp examination revealed coarse superficial punctate lesions with graft edema. He was diagnosed with acute graft rejection and treated with topical steroids. Two days later, symptoms worsened in his left eye with the involvement of his right eye showing a similar clinical picture. An infectious etiology was suspected and in vivo confocal microscopy ordered, which revealed hyperreflective dots, highly suggestive of microsporidial spores. The patient was prescribed topical fluconazole 0.3% in both eyes. This unique presentation of bilateral graft edema following microsporidial keratoconjunctivitis in postgraft patients requires a high index of suspicion as it can be easily be mistaken for and mismanaged as acute graft rejection.

Purpose: The purpose of this study is to describe the presenting features, management strategies, and clinical outcome following bee sting injury to the cornea. Methods: Retrospective case series involving 11 eyes of 11 patients with corneal bee sting injuries who presented over a period of 2 years. Nine of these 11 eyes had the presence of intact bee stinger in the cornea, which was removed immediately under an operating microscope and sent for microbiological and histopathological evaluation. The patients were managed as per the individual treatment protocol of the respective treating physicians. Results: Six eyes (54.5%) had a good clinical outcome (best-corrected visual acuity [BCVA] >20/40) with medical therapy alone with no need for surgical intervention. Five eyes (45.5%) had a poor clinical outcome (BCVA

Importance Identifying patients with infectious keratitis who are at risk of experiencing a poor outcome may be useful to allocate resources toward high- risk patients, particularly in resource-poor settings. Objective To determine baseline patient and ulcer characteristics that predict a high risk of developing corneal perforation and/or the need to undergo therapeutic penetrating keratoplasty (TPK). Design, Setting, and Participants This is a secondary analysis of Mycotic Ulcer Treatment Trial II, a multicenter, double-masked, placebo-controlled randomized clinical trial that enrolled 240 patients with smear-positive filamentous fungal corneal ulcers who enrolled between May 2010 and August 2015. Participants had a baseline visual acuity of 20/400 or worse and were randomized to receive oral voriconazole or a placebo (all participants received topical voriconazole, 1%). After 39 participants (16.3%) were enrolled, topical natamycin, 5%, was also added. Main Outcomes and Measures The primary outcome of this secondary analysis was the rate of corneal perforation or the need to undergo TPK. Results The mean (SD) age at enrollment was 49 (13) years, 104 participants (43.3%) were women, and all were of Southeast Asian descent. The presence of hypopyon at baseline indicated 2.28 times the odds of the patient developing corneal perforation and/or needing TPK (95% CI, 1.18-4.40; P = .01). Study participants whose infiltrate involved the posterior one-third had a 71.4% risk of developing corneal perforation and/or needing TPK. For each 1-mm increase in the geometric mean of the infiltrate, there was 1.37 (95% CI, 1.12-1.67; P = .002) increased odds of developing perforation and/or needing TPK. Other clinical features such as visual acuity, baseline culture positivity, type of filamentous fungal organism and duration of symptoms, and demographic characteristics, such as sex and occupation, were not significant predictors in the multivariable regression analysis. Conclusions and Relevance These results suggest that risk stratification from baseline ulcer characteristics can identify those at highest risk for developing corneal perforation and/or needing TPK. Trial Registration clinicaltrials.gov Identifier:NCT00996736

PurposeTo validate computer software developed to assess digital corneal photographs of fungal keratitis in clinical research.MethodsA cornea specialist and five medical students (after training) graded on two occasions 100 corneal photographs of patients with fungal keratitis using Optscore software. Variables assessed were lesion area, location, degree of opacity, percentage of the ulcer lying within a central 4 mm circle of the cornea. Intraclass correlation coefficients (ICCs) were used to assess intragrader reliability, agreement of the students with the corneal specialist, and the reliability of the group mean of the student raters. The area determined using Optscore was compared to the area estimated from slit lamp and to visual acuity.ResultsAs a group, medical students achieved an ICC greater than 0.9 for five out of the seven assessed variables. Similar levels of consistency were found after analyzing the graders' individual results compared to the specialist. The area estimated using slit lamp examination was highly correlated with the mean area determined by Optscore, as was the logarithm of the minimum angle of resolution visual acuity at enrollment.ConclusionsNon-expert graders using Optscore to assess digital photographs of fungal keratitis are self-consistent, agree with an expert grader both as a group and individually, and measurements of ulcer area obtained from Optscore are highly correlated with measurements of the same patients obtained on clinical examination. These observations support the validity of Optscore for assessing corneal pathology associated with fungal keratitis and make it a promising clinical research tool.

Aim To study the demographic profile, clinical features, treatment outcome and ocular morbidity of smear-positive microsporidial keratoconjunctivitis. Methods Retrospective case series of all patients with clinical features of microsporidial keratoconjunctivitis and who were smear positive for the same on Gram stain from January 2013 to December 2015. Demographic data, predisposing factors, microbiological investigations, clinical course and visual outcome were analysed. Results Of the 10 655 patients with conjunctivitis, 550 (5.2%) patients were positive for microsporidia on Gram stain during this time period. The disease was prevalent throughout the year with an increased incidence from July to December. Bilateral involvement was seen in 27 (4.9%) patients. There was no predisposing risk factor in 428 (77.8%) patients. 384 (69.1%) patients had received prior treatment before presentation to us with the most common drug being antibiotic in 285 (49.4%) patients. All the patients underwent diagnostic corneal debridement and received topical 0.3% fluconazole eye drops four times a day. Of the 296 patients who followed-up, 187 (63.1%) patients had complete resolution without sequelae. 68 (22.9%) had persistent superficial punctate keratopathy, 30 (10.1%) developed subepithelial nummular keratitis. No significant change in visual acuity was seen in 255 (80.7%) eyes, two or more line improvement was seen in 48 (15.2%) eyes, while two or more line worsening was seen in 13 (4.1%) eyes. Conclusions Microsporidial keratoconjunctivitis is prevalent in South India throughout the year. The characteristic clinical signs and simple microbiological investigation help us to differentiate it from adenoviral keratoconjunctivitis. The visual prognosis is good.

The LasR transcription factor is an important regulator of quorum sensing in P. aeruginosa and positively controls multiple virulence-associated pathways. The emergence of strains with lasR loss-of-function alleles in chronic disease is well described and is thought to represent a specific adaptation to the host environment. However, the prevalence and virulence of these strains in acute infections remain unclear. This report describes observations revealing that lasR mutants were common among isolates from a large, multicenter clinical study of keratitis and were associated with worse clinical outcomes than LasR-intact strains despite reduced production of LasR-regulated factors. Additionally, these lasR mutants were closely related strains or clones, as determined by molecular analysis. Because bacterial keratitis is community acquired, these data indicate infection by endemic, LasR-deficient strains in the environment. These results suggest that the conventional paradigm regarding the role for LasR-mediated regulation of virulence is more complex than previously appreciated., The Steroids for Corneal Ulcers Trial (SCUT) was a multicenter, international study of bacterial keratitis in which 101 Pseudomonas aeruginosa infections were treated. Twenty-two of 101 P. aeruginosa isolates collected had a colony morphology characteristic of a loss-of-function mutation in lasR, the gene encoding a quorum-sensing master regulator. Ulcers caused by these 22 strains were associated with larger areas of corneal opacification, worse vision, and a lower rate of vision recovery in response to treatment than ulcers caused by the other isolates. The lasR sequences from these isolates each contained one of three nonsynonymous substitutions, and these strains were deficient in production of LasR-regulated protease and rhamnolipids. Replacement of lasR with either of the two most common lasR alleles from the SCUT isolates was sufficient to decrease protease and rhamnolipid production in PA14. Loss of LasR function is associated with increased production of CupA fimbriae, and the LasR-defective isolates exhibited higher production of CupA fimbriae than LasR-intact isolates. Strains with the same lasR mutation were of the same multilocus sequence type, suggesting that LasR-deficient, environmental P. aeruginosa strains were endemic to the area, and infections caused by these strains were associated with worse patient outcomes in the SCUT study. (This study has been registered at ClinicalTrials.gov under registration no. NCT00324168.) IMPORTANCE The LasR transcription factor is an important regulator of quorum sensing in P. aeruginosa and positively controls multiple virulence-associated pathways. The emergence of strains with lasR loss-of-function alleles in chronic disease is well described and is thought to represent a specific adaptation to the host environment. However, the prevalence and virulence of these strains in acute infections remain unclear. This report describes observations revealing that lasR mutants were common among isolates from a large, multicenter clinical study of keratitis and were associated with worse clinical outcomes than LasR-intact strains despite reduced production of LasR-regulated factors. Additionally, these lasR mutants were closely related strains or clones, as determined by molecular analysis. Because bacterial keratitis is community acquired, these data indicate infection by endemic, LasR-deficient strains in the environment. These results suggest that the conventional paradigm regarding the role for LasR-mediated regulation of virulence is more complex than previously appreciated.

Purpose of reviewTopical corticosteroid use in the setting of infectious keratitis has been a controversial issue. The aim of this review is to provide an update on the evidence for use of topical corticosteroids in addition to antibiotics in bacterial keratitis.Recent findingsJudicious use of steroids is postulated to limit the inflammatory component of bacterial keratitis, but can theoretically retard healing. Three small randomized controlled trials and one large-scale trial, the Steroids for Corneal Ulcers Trial, have provided the most recent evidence to address this debate. Adjunctive topical corticosteroids initiated after at least 48 h of antibiotic usage in cases of culture-proven bacterial keratitis appear generally safe in the treatment of bacterial keratitis. They may be beneficial in cases of severe ulcers especially when initiated early in the course of the infection, in non-Nocardia ulcers, and in certain Pseudomonas ulcers.SummarySeveral randomized controlled trials have greatly contributed to our understanding of the controversy over steroid use in the management of bacterial keratitis. Future studies are needed to confirm subgroup analysis findings and define optimal timing, dosage, and the most appropriate treatment populations.

Importance The development of multiple triazole resistance in pathogenic filamentous fungi has become an increasing clinical concern and has been shown to increase the risk for treatment failure. Objective To determine whether antifungal resistance increased during the Mycotic Ulcer Treatment Trial I (MUTT I), as measured by minimum inhibitory concentrations (MICs) in baseline cultures. Design, Setting, and Participants This secondary analysis of a double-masked, multicenter, randomized clinical trial included patients with culture- or smear-positive filamentous fungal corneal ulcer and a baseline visual acuity of 20/40 to 20/400. Culture-positive samples with susceptibility testing were included in this analysis. The patients were treated at multiple locations of the Aravind Eye Care Hospital system in South India. Data were collected from April 3, 2010, to December 31, 2011, and analyzed from July 15 to September 1, 2015. Interventions Corneal smears and cultures were obtained from all study participants at baseline. Susceptibility testing was performed for each culture-positive specimen. Main Outcomes and Measures Minimum inhibitory concentration of voriconazole and natamycin in baseline cultures. Results Of 323 participants with smear-positive specimens (183 men [56.7%]; 140 women [43.3%]; median [interquartile range] age, 47 [38-56] years), fungal-positive cultures were obtained for 256 (79.3%). The MIC data were available for 221 of 323 participants (68.4%), because 35 samples had no growth during susceptibility testing. A 2.14-fold increase per year (95% CI, 1.13-4.56; P = .02) in voriconazole MICs after controlling for the infectious organism was found. This association was not found when looking at natamycin MICs of baseline cultures after controlling for the infectious organism (1.26; 95% CI, 0.13-12.55; P = .85). Conclusions and Relevance Susceptibility to voriconazole appeared to decrease during the relatively short enrollment period of the clinical trial. This decrease may be more related to increased resistance of environmental fungi rather than previous treatment with azoles, because presenting with azole treatment was not a risk factor for resistance. Trial Registration clinicaltrials.gov Identifier:NCT00996736

PurposeTo elicit expert opinion on the use of adjunctive corticosteroid therapy in bacterial corneal ulcers. To perform a Bayesian analysis of the Steroids for Corneal Ulcers Trial (SCUT), using expert opinion as a prior probability.MethodsThe SCUT was a placebo-controlled trial assessing visual outcomes in patients receiving topical corticosteroids or placebo as adjunctive therapy for bacterial keratitis. Questionnaires were conducted at scientific meetings in India and North America to gauge expert consensus on the perceived benefit of corticosteroids as adjunct treatment. Bayesian analysis, using the questionnaire data as a prior probability and the primary outcome of SCUT as a likelihood, was performed. For comparison, an additional Bayesian analysis was performed using the results of the SCUT pilot study as a prior distribution.ResultsIndian respondents believed there to be a 1.21 Snellen line improvement, and North American respondents believed there to be a 1.24 line improvement with corticosteroid therapy. The SCUT primary outcome found a non-significant 0.09 Snellen line benefit with corticosteroid treatment. The results of the Bayesian analysis estimated a slightly greater benefit than did the SCUT primary analysis (0.19 lines verses 0.09 lines).ConclusionIndian and North American experts had similar expectations on the effectiveness of corticosteroids in bacterial corneal ulcers; that corticosteroids would markedly improve visual outcomes. Bayesian analysis produced results very similar to those produced by the SCUT primary analysis. The similarity in result is likely due to the large sample size of SCUT and helps validate the results of SCUT.

PURPOSE Previous studies suggest that fungal keratitis is more common in hot humid climates and that bacterial keratitis is independent of seasonal variation. This study analyzes seasonal trends in the incidence of fungal and bacterial keratitis at the Aravind Eye Hospital in southeast India. METHODS Using microbiology records from August 2006 to July 2009, retrospective analyses of infectious keratitis were performed. Bacterial and fungal keratitis incidence data were analyzed for seasonal patterns. RESULTS Among the 6967 infectious keratitis cases, cultures were performed in 5221 (74.9%) cases; among them, 3028 (58%) were positive. Of the culture-positive cases, 1908 (63%) and 1081 (35.7%) were of fungal and bacterial etiology, respectively. The predominant fungal organism was Fusarium spp (42.3%) and the predominant bacterial organisms were Streptococcus pneumoniae (35.1%), Pseudomonas aeruginosa (24.3%), and Nocardia spp (8.1%). Analyses revealed an uneven distribution of fungal keratitis throughout the year (P < 0.001) with peaks in July and January. No significant seasonal trend was observed for the combined bacterial keratitis group. CONCLUSIONS A higher incidence of fungal keratitis occurs during the months corresponding to the windy and harvest seasons, during which time infection from vegetative corneal injury may be more likely. Robust screening efforts during these periods may mitigate visually debilitating sequelae from infectious keratitis.

PurposeTo analyse predictors of clinical outcome in fungal keratitis.MethodsData was collected during a prospective, randomized, controlled, double-masked clinical trial of treatment for fungal keratitis. Clinical features at presentation and demographics were collected at the enrollment visit for all patients. Pre-specified clinical outcomes included 3-month visual acuity and infiltrate/scar size, time to re-epithelialization, and corneal perforation. A separate multivariable model with each outcome as the dependent variable included all predictor variables.ResultsPredictors for worse 3-month visual acuity include older age (P=0.024), worse presentation visual acuity (P

Purpose: In light of the increased incidence of contact lens associated Acanthamoeba keratitis in recent years, this study analyzed longitudinal trends of its incidence among predominantly non-contact lens wearers in a high-volume referral center in South India.Methods: A retrospective analysis of microbiology laboratory records at the Aravind Eye Hospital from 1988–2009 was performed. The Maximum Excess Events Test (MEET) was used to identify epidemics of Acanthamoeba keratitis.Results: There were a total of 38,529 unique cases of infectious keratitis evaluated over this time period, of which 372 were culture-positive for Acanthamoeba. Only three cases (0.9%) of Acanthamoeba keratitis occurred among contact lens wearers. MEET identified unique Acanthamoeba keratitis epidemics in 1993 and 2002.Conclusion: Discrete epidemics of Acanthamoeba keratitis occurred among a rural, non-contact lens wearing, population in South India in 1993 and 2002.

Mooren’s ulcer (MU) is an inflammatory peripheral ulcerative keratopathy that occurs most commonly in the developing world. Recent evidence supports the notion that autoimmune mechanisms are involved in the pathogenesis of this disease. Patients with MU typically develop painful, progressive peripheral ulceration of the cornea that, if untreated, can lead to corneal perforation and blindness. Risk factors for the development of MU include HLA-DR17 haplotype expression, prior corneal surgery or trauma, and hookworm infestation. A thorough ocular and systemic history and clinical examination, together with directed laboratory testing, should be carried out to rule out other causes of corneal ulceration, including both infectious keratitis and peripheral ulcerative keratitis secondary to an underlying systemic autoimmune disease. Treatment of MU is often challenging, but typically includes local and/or systemic corticosteroids. Noncorticosteroid immunosuppressive agents, conjunctival resection or advancement...

Purpose The purpose of this study was to evaluate the subset of limbal epithelial cells with greater nucleus-to-cytoplasm (N/C) ratio expressing high levels of p63 for their slow-cycling property, a characteristic feature of stem cells (SCs). Methods Limbal and peripheral corneal explant cultures were pulse labeled with 5-5-bromo-2'-deoxyuridine (BrdU) for 5 days, followed by a period of 3-week chase. Cultured explants were cryosectioned and stained for BrdU. The epithelial cells in the outgrowth and those remaining on the explant were isolated and subjected to cytospin and double immunostaining for BrdU and p63, followed by identification of label-retaining cells (LRCs) and quantification of p63 expression using confocal microscopy. Results A distinct population of small cells with large N/C ratio expressing high levels of p63 retained the BrdU label after 21-day chase. Further, this population of LRCs, negative for the differentiation marker K3, was observed in the epithelial outgrowth of limbal but not in that of peripheral cornea. LRCs were seen to migrate along the cut edge of limbal explants in culture and were also observed as clusters of small cells in the outgrowth, which contained cells with the ability to form holoclone colonies. Conclusions These results demonstrate that the small cells with large N/C ratio and high levels of p63 have BrdU label retaining slow-cycling property, thus confirming that these 2 parameters in combination may serve as a precise marker for identification and quantification of ex vivo-expanded limbal SCs. This method would be useful to standardize the optimal culture conditions that can maintain and expand SCs for therapeutic applications.

PURPOSE. Prior cataract surgery is a recognized risk factor for the development of Mooren’s ulcer, but the demographic and clinical features of a large cohort of such patients have not been described. METHODS. The authors performed a retrospective review of demographic and clinical data from 14 eyes in 13 patients who developed Mooren’s ulcer following extracapsular cataract extraction at Aravind Eye Hospital in Madurai, South India. RESULTS. Eight (62%) of the 13 patients were men and 5 (39%) were women. The median age in our population was 65 years, with a range of 45 to 85 years. The median number of months from surgery to the onset of Mooren’s ulcer was 19, with a range of 4 to 156 months. Of the 14 eyes with prior cataract surgery, the location of the ulcer was at or contiguous with the wound in 10 eyes (71%), which was 2.5 times more likely than other circumlimbal locations, and only one patient (8%) had bilateral disease. C ONCLUSIONS. Mooren’s ulcer may occur following extracapsular cataract extraction and when it does it is most likely to be unilateral and contiguous with the wound. These findings support the notion that exposure of normally concealed corneal antigens may contribute to the pathogenesis of Mooren’s ulcer in some patients. (Eur J Ophthalmol 2008; 18: 351-5)

AIMS: To report trends in antibiotic resistance in cases of bacterial keratitis from a large eye hospital in South India. METHODS: In this retrospective cross-sectional study, the microbiology laboratory records of patients with infectious keratitis diagnosed at an eye hospital in South India from 2002–2013 were reviewed to determine the proportion with antibiotic non-susceptibility. RESULTS: 3685 bacterial isolates had susceptibility testing performed over the 12-year period. The two most common organisms with resistance results were Streptococcus pneumoniae (N=1204) and Pseudomonas aeruginosa (N=894). Antibiotic non-susceptibility was generally uncommon for these two organisms, and no significant trends were detected over the course of the study. In contrast, Staphylococcus aureus (N=211) isolates demonstrated a significant increase in fluoroquinolone non-susceptibility over the 12-year study period. This coincided with a significant increase in methicillin-resistant S. aureus (MRSA) during the study period, though the increase in fluoroquinolone resistance was likewise seen in methicillin-sensitive S. aureus (MSSA). For example, ofloxacin resistance in MSSA increased from 11.1% in 2002 to 66.7% in 2013 (P=0.002). No trends were apparent for the aminoglycocides, cefazolin, or vancomycin, for which in vitro non-susceptibility generally appeared to be low. CONCLUSIONS: Resistance to antibiotics was generally stable for infectious keratitis isolates from a large eye hospital in South India, except for S. aureus, which experienced a significant increase in fluoroquinolone resistance from 2002 to 2013. Fluoroquinolone antibiotics currently have poor in vitro activity against both methicillin-resistant and methicillin-sensitive S. aureus in South India and are therefore not the ideal therapy for Staphylococcal corneal ulcers.

Purpose To determine the intra-observer and inter-observer reliability of a novel ocular staining score among trained ophthalmologists. Design Reliability analysis within a prospective, observational, multicenter cohort study. Methods Those enrolled in the National Institutes of Health–funded Sjogren's International Collaborative Clinical Alliance (SICCA) who presented for follow-up at the University of California San Francisco, Aravind Eye Hospital, Johns Hopkins University, and the University of Pennsylvania were included. Study participants were graded using the ocular staining score by at least 2 masked SICCA-trained ophthalmologists. The primary outcome for this study was the intraclass correlation coefficient (ICC) for the total ocular staining score. ICCs were also calculated for tear break-up time (TBUT) and conjunctival and corneal staining. Results Total ocular staining score had an ICC of 0.91 for the right eye (95% confidence interval [CI] 0.85–0.96) and 0.90 for the left eye (95% CI 0.83–0.97). Corneal staining (right eye 0.86, 95% CI 0.76–0.93, left eye 0.90, 95% CI 0.81–0.95) and conjunctival staining (right eye 0.87, 95% CI 0.80–0.93, left eye 0.85, 95% CI 0.75–0.93) demonstrated excellent agreement. The ICC for TBUT was slightly lower (right eye 0.77, 95% CI 0.64–0.89; left eye 0.81, 95% CI 0.68–0.90). Conclusions Previous studies have shown that the ocular staining score is correlated with other diagnostic components of Sjogren syndrome. In this study, we demonstrate high reliability in grading among trained ophthalmologists, completing the validation of this test.

To determine the sensitivity, specificity and predictive values of potassium hydroxide (KOH) wet mount, Gram stain, Giemsa stain and Kinyoun's acid-fast stain in the diagnosis of infective keratitis.A retrospective analysis of all patients with clinically diagnosed infective keratitis presenting between September 1999 and September 2002 was carried out. Corneal scrapes were taken and subjected to direct microscopy and culture.3298 eyes of 3295 consecutive patients with infective keratitis were evaluated, of which 1138 (34.51%) eyes had fungal growth alone, 1069 (32.41%) had bacterial growth alone, 33 (1%) had Acanthamoeba growth alone, 83 (2.5%) had mixed microbial growth and the remaining 975 (29.56%) had no growth. The sensitivity of KOH wet mount was higher (99.3%; 95% confidence interval (CI) 98.6 to 99.6) in the detection of fungi, 100% (95% CI 90.4 to 100) in the detection of Nocardia and 91.4% (95% CI 75.8 to 97) in the detection of Acanthamoeba) than that of Gram-stained smears (89.2% (95% CI 87.3 to 90.8) in fungi, 87% (95% CI 73.0 to 94.6) in Nocardia and 60% (95% CI 42.2 to 75.6) in the detection of Acanthamoeba) in the detection of fungi, Nocardia and Acanthamoeba. 1764 of 3295 (53.54%) patients presented more than 7 days after onset of illness and 84.69% of the eyes had corneal ulcers with size2 mm in diameter. Positivities of KOH (44.46%; p0.001) and Gram-stained smears (77.37%; p0.001) were found to be higher among eyes with larger ulcers (2 mm) than among eyes with smaller ulcers (2 mm).KOH smear is of greater diagnostic value in the management of infective keratitis, and it is recommended in all clinics without exception for establishing timely treatment.

Purpose : To assess the changing trends in the antibiotic susceptibility of Pseudomonas spp . isolated from bacterial keratitis over a nine year period with special emphasis on fluoroquinolone susceptibilities. Methods : All corneal scraping cultures positive for Pseudomonas spp. (n=585) isolated from patients with bacterial keratitis at the Aravind Eye Hospital, Madurai from1995-2003 were evaluated. Cultures were performed in liquid and solid media and susceptibility testing was done against amikacin, gentamicin, tobramycin, ciprofloxacin and ofloxacin by Kirby-Bauer disc diffusion method. Results: The susceptibility of Pseudomonas spp. was over 90% from 1995-1998 to ciprofloxacin which decreased to 83% from 1999-2003. The total number of isolates resistant to ciprofloxacin was 51(9.4%). No statistically significant increase in the number of isolates resistant to ciprofloxacin was noted. Ofloxacin showed 54% susceptibility from 1995-1998 but increased to 64% from 1999-2003. Analysis of in vitro activity of amikacin reveals that there was 43% sensitivity from 1995-1998 but later it increased to 76% from 1999-2003. In case of gentamicin, the sensitivity decreased marginally from 80% to 70% through the years. Tobramycin showed 45% sensitivity from 1995-1998 but increased to 75% from 1999-2003. Conclusions : The fluoroquinolones remain a good choice in the treatment of ocular infections, with high susceptibility of Pseudomonas spp. Among the aminoglycosides, gentamicin was found to be highly effective against Pseudomonas corneal ulcers when compared to amikacin and tobramycin. The results show a need for continuous monitoring of bacterial resistance trends.

PURPOSE To determine the feasibility and diagnostic precision of Frequency Doubling Technology (FDT) perimetry as a method to detect glaucoma in rural villages of a developing country. DESIGN Cross-sectional study. METHODS Testing included FDT perimetry (C-20-5 screening protocol), tonometry, anterior segment biomicroscopy, and dilated ophthalmoscopy in 296 rural, non-English speaking residents of Southern India over 35 years old. Participants repeated the FDT if they had a location with reduced sensitivity or an unreliable result. We defined an abnormal FDT as one location of reduced sensitivity present on both the initial and repeat examination. We determined the diagnostic precision of FDT separately for a glaucomatous optic disc, a cup to disc ratio (C/D) > or = 0.7, and a C/D > or = 0.8. RESULTS Ninety-three percent of subjects were able to complete the test satisfactorily. With repeat FDT testing, 37% of eyes with abnormal FDT results subsequently converted to normal and 67% of eyes with unreliable results subsequently became reliable. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for a glaucomatous optic disc were 7%, 87%, 13%, 76%, and 69%, respectively; for a C/D > or = 0.7, they were 0%, 87%, 0%, 91%, and 81%, respectively; and for a C/D > or = 0.8, they were 0%, 87%, 0%, 99%, and 87%, respectively. CONCLUSION Clinicians can use FDT perimetry to rapidly screen for glaucoma in rural villages of a developing country. FDT testing had high specificity and negative predictive value, but low sensitivity and positive predictive value. The low sensitivity suggests that FDT has limited applicability as the sole test for glaucoma screening in this population. Repeat testing of FDT results that are unreliable or suspected of being abnormal is beneficial for this screening procedure.

Purpose To determine if concurrent use of 5% natamycin and 2% econazole offers greater benefits than monotherapy with 5% natamycin for the management of fungal keratitis. Methods Subjects presenting to the cornea service were treated with 5% natamycin and 2% econazole used concurrently. We compared the results with a historical control of patients treated with 5% natamycin in the same calendar year. The same clinical and examination protocol including inclusion and exclusion criteria was used for both groups. Results We compared results of 47 subjects on concurrent use of 5% natamycin and 2% econazole with all 53 subjects who had received 5% natamycin in a previous study (historical controls). Baseline characteristics were similar between the 2 groups. There were no significant differences (P=0.9) between the 2 arms for success (defined as a healed or healing ulcer). Conclusions Concurrent use of 5% natamycin and 2% econazole does not appear to offer additional benefits over monotherapy with 5% natamycin for the management of fungal keratitis.

The use of topical corticosteroids as adjunctive therapy for corneal ulcers remains controversial and has been debated for more than six decades. Many ophthalmologists are not in favor of recommend...

ObjectiveTo assess the trends in microbiological organisms identified from corneal scrapings from patients with infectious keratitis at a tertiary care medical centre in South India.MethodsWe reviewed the records of the microbiology laboratory at Aravind Eye Hospital in Madurai, India, from 2002 until 2012. We identified the microbiological causes of all corneal ulcers from the culture and smear results, and assessed for trends in bacterial and fungal keratitis over time.ResultsOf 23 897 corneal patients with ulcer with a corneal smear from 2002 to 2012 a fungal organism was identified in 34.3%, a bacterial organism in 24.7% and no organism in 38.3%. During this period, the annual number of keratitis cases due to bacteria decreased from 677 to 412, and the annual number due to fungus increased from 609 to 863. In analyses accounting for the total number of outpatients seen each year, the decline in number of smears positive for bacteria was statistically significant (p

Importance Fusarium keratitis is common and often results in poor outcomes. No new treatments since natamycin have become available. Objective To explore the role of adjuvant oral voriconazole on clinical outcomes in Fusarium keratitis. Design, Setting, and Participants In this prespecified subgroup analysis of a multicenter, double-masked, placebo-controlled randomized clinical trial, 240 patients from the Aravind Eye Care System in India, the Lumbini Eye Hospital and Bharatpur Eye Hospital in Nepal, and the University of California, San Francisco, who had culture-positive fungal ulcer and baseline visual acuity of 20/400 or worse were randomized to receive oral voriconazole vs placebo. Enrollment started May 24, 2010, and the last patient study visit was November 23, 2015. All patients received topical voriconazole, 1%, and after the results of the Mycotic Ulcer Treatment Trial (MUTT) II became available, topical natamycin, 5%, was added for all patients. Data analysis was performed from September 2 to October 28, 2016. Main Outcomes and Measures The primary outcome of the trial was the rate of corneal perforation or the need for therapeutic penetrating keratoplasty. Secondary outcomes included rate of reepithelialization, best spectacle-corrected visual acuity, and infiltrate or scar size at 3 months. Results Of the 240 study participants, 72 (30.4%) were culture positive for Fusarium species (41 [56.9%] male and 31 [43.1%] female; median [interquartile range] age, 50 [45-57] years). Of these, 33 (45.8%) were randomized to oral voriconazole and 39 (54.2%) to placebo. Fusarium ulcers randomized to oral voriconazole had a 0.43-fold decreased hazard of perforation or therapeutic penetrating keratoplasty compared with placebo after controlling for baseline infiltrate depth (95% CI, 0.22-fold to 0.84-fold; P = .01). Multiple linear regression revealed a 1.89-mm decreased infiltrate and/or scar size at 3 weeks (95% CI, −2.69 to −1.09 mm; P P = .001) in eyes randomized to oral voriconazole vs placebo. Eyes treated with oral voriconazole also had a mean 0.29 decreased logMAR (improved) (Snellen equivalent 20/40) visual acuity at 3 months after controlling for baseline visual acuity, although this finding was not statistically significant (95% CI, −0.57 to 0.002; P = .052). Conclusions and Relevance Although MUTT II could not find a benefit for all corneal ulcers, Fusarium keratitis may benefit from the addition of oral voriconazole to topical natamycin, and physicians should consider prescribing oral voriconazole in these cases. Trial Registration clinicaltrials.gov Identifier:NCT00996736

PurposeWe described the change in visual acuity experienced by eyes successfully treated for bacterial keratitis.MethodsThis was a prospective cohort study of a subset of study participants who had previously enrolled in the Steroids for Corneal Ulcers Trial (SCUT). All study participants had been diagnosed with culture-proven bacterial keratitis before enrollment in SCUT and subsequently were randomized to adjunctive topical corticosteroids or placebo. During SCUT, we monitored study participants at enrollment, 3 weeks, 3 months, and 12 months. We invited a subset to complete a comprehensive eye examination approximately 4 years after enrollment in SCUT. Certified refractionists assessed best spectacle-corrected visual acuity (BSCVA) using the same protocol at each study visit.ResultsWe examined 50 SCUT participants at 4 years after enrollment. Among those in this cohort, mean logMAR BSCVA at enrollment was 0.85 (Snellen equivalent, 20/160; 95% confidence interval [CI], 0.71-0.99). On average, visual acuity improved by 2.9 logMAR lines from enrollment to 3 weeks (P < 0.001), 1.2 lines from 3 weeks to 3 months (P = 0.002), and 0.8 lines from 3 to 12 months (P = 0.01). The BSCVA did not change significantly between 12 months and 4 years (0.04-line improvement, P = 0.88). After controlling for visual acuity at enrollment, BSCVA was not significantly different between the corticosteroid and placebo groups at 4 years (P = 0.53).ConclusionsCases of bacterial keratitis may continue to demonstrate improvements in visual acuity up to 12 months following diagnosis, but further improvements are unlikely. These findings may guide the appropriate timing of surgical intervention in these patients. (ClinicalTrials.gov number, NCT00324168.).

Background To determine the relationship between type three secretion genotype and fluoroquinolone resistance for P. aeruginosa strains isolated from microbial keratitis during the Steroids for Corneal Ulcers Trial (SCUT) and for two laboratory strains, PA103 and PAO1. Methods Confirmed P. aeruginosa isolates from the SCUT were divided into exoU(+) or exoU(−). The exoU(+) strains contained the gene encoding ExoU, a powerful phospholipase toxin delivered into host cells by the type three secretion system. Isolates were then assessed for susceptibility to fluoroquinolone, cephalosporin, and aminoglycoside antibiotics using disk diffusion assays. Etest was used to determine the MIC of moxifloxacin and other fluoroquinolones. Laboratory isolates in which the exoU gene was added or deleted were also tested. Results A significantly higher proportion of exoU(+) strains were resistant to ciprofloxacin (p = 0.001), gatifloxacin (p = 0.003), and ofloxacin (p = 0.002) compared to exoU(−) isolates. There was no significant difference between exoU(+) or exoU(−) negative isolates with respect to susceptibility to other antibiotics except gentamicin. Infections involving resistant exoU(+) strains trended towards worse clinical outcome. Deletion or acquisition of exoU in laboratory isolates did not affect fluoroquinolone susceptibility. Conclusions Fluoroquinolone susceptibility of P. aeruginosa isolated from the SCUT is consistent with previous studies showing elevated resistance involving exoU encoding (cytotoxic) strains, and suggest worse clinical outcome from infections involving resistant isolates. Determination of exoU expression in clinical isolates of P. aeruginosa may be helpful in directing clinical management of patients with microbial keratitis.

To investigate the rate of undiagnosed rheumatologic diseases and hepatitis C infection among patients with the clinical diagnosis of Mooren ulcer seen at Aravind Eye Hospital, Madurai, South India.Twenty-one patients with the clinical diagnosis of Mooren ulcer and 44 control patients underwent a complete ophthalmic history and examination, as well as serologic testing for antinuclear antibodies, rheumatoid factor, antineutrophil cytoplasmic antibodies, herpes simplex virus 1 antibodies, and hepatitis C virus antibodies.There were no statistically significant differences in the rates of seropositivity for antinuclear antibodies, rheumatoid factor, antineutrophil cytoplasmic antibodies, herpes simplex virus 1 antibodies, and hepatitis C virus antibodies between patients with Mooren ulcer and control patients. Two patients with Mooren ulcer and four control patients were found to have a rheumatoid factor titer of greater than 1:20. One of the control patients, but none of the patients with Mooren ulcer, was found to have serologic evidence of hepatitis C infection. A history of corneal trauma, surgery, or infection was reported by 68% of patients with Mooren ulcer, compared with 20% of control patients (P.001). Among patients with Mooren ulcer, bilateral disease occurred in 37% of patients, visual acuity was reduced to light perception in 15% of eyes, and perforation occurred in 19% of eyes.Nineteen (90%) of 21 patients with the clinical diagnosis of Mooren ulcer were found to have no evidence of an underlying rheumatologic disease by history, examination, or serologic testing, and none was seropositive for hepatitis C. However, patients with Mooren ulcer were more likely than control patients to report a history of corneal trauma, surgery, or infection.

PURPOSE To describe the clinical features, disease course, management, and visual outcome of stromal microsporidial keratitis involving the corneal graft in an immunocompetent patient. METHODS Case report. RESULTS We report the case of a 21-year-old immunocompetent woman, who underwent penetrating keratoplasty for advanced keratoconus in her right eye and presented with features of acute graft rejection after 15 months. Standard treatment using topical and systemic steroids failed to reverse the graft rejection. A regraft was performed in that eye. Histopathology of the donor corneal button revealed microsporidiosis involving the deep stroma. CONCLUSIONS Microsporidiosis is rarely encountered in a corneal graft and masquerades as acute graft rejection. Histopathology could help in making a final diagnosis.

Aims/background—To determine the epidemiological characteristics and risk factors predisposing to corneal ulceration in Madurai, south India, and to identify the specific pathogenic organisms responsible for infection. Methods—All patients with suspected infectious central corneal ulceration presenting to the ocular microbiology and cornea service at Aravind Eye Hospital, Madurai, from 1 January to 31 March 1994 were evaluated. Sociodemographic data and information pertaining to risk factors were recorded, all patients were examined, and corneal cultures and scrapings were performed. Results—In the 3 month period 434 patients with central corneal ulceration were evaluated. A history of previous corneal injury was present in 284 patients (65.4%). Cornea cultures were positive in 297 patients (68.4%).Of those individuals with positive cultures 140 (47.1%) had pure bacterial infections, 139 (46.8%) had pure fungal infections, 15 (5.1%) had mixed bacteria and fungi, and three (1.0%) grew pure cultures of Acanthamoeba. The most common bacterial pathogen isolated was Streptococcus pneumoniae, representing 44.3% of all positive bacterial cultures, followed by Pseudomonas spp (14.4%). The most common fungal pathogen isolated was Fusarium spp, representing 47.1% of all positive fungal cultures, followed by Aspergillus spp (16.1%). Conclusions—Central corneal ulceration is a common problem in south India and most often occurs after a superficial corneal injury with organic material. Bacterial and fungal infections occur in equal numbers with Streptococcus pneumoniae accounting for the majority of bacterial ulcers and Fusarium spp responsible for most of the fungal infections. These findings have important public health implications for the treatment and prevention of corneal ulceration in the developing world. (Br J Ophthalmol 1997;81:965‐971)

AIMS The study was undertaken to test the feasibility of using the LOCS III cataract grading scale in the field and to determine the rate of cataract progression over a 1 year period of time. METHODS For 150 subjects between the ages of 33 and 55 who attended the refraction clinic at Aravind Eye Hospital in Madurai, India, lens abnormalities were graded at the slit lamp using the LOCS III scale. One year later, 99 of the subjects were re-evaluated by the same methodology to assess the amount of lens change. RESULTS Interrater reliability was high. A change of 0.5 or more in lens colour, cortical, nuclear, or posterior subcapsular cataract was observed in at least one eye of 54% of the subjects. CONCLUSION The LOCS III grading scale is a feasible method for measuring lens changes in the field with the slit lamp. Cataract progression in India is rapid enough to permit intervention studies to be performed with relatively small numbers of subjects over a short period of time (that is, 600 subjects for 2 years).

Purpose To determine whether topical corticosteroids as adjunctive therapy for bacterial keratitis improves long-term clinical outcomes. Design Randomized, placebo-controlled, double-masked clinical trial. Methods This multicenter trial compared 1.0% prednisolone sodium phosphate to placebo in the treatment of bacterial keratitis among 500 patients with culture-positive ulcers receiving 48 hours of moxifloxacin before randomization. The primary endpoint was 3 months from enrollment, and 399 patients were evaluated at 12 months. The outcomes examined were best spectacle-corrected visual acuity (BSCVA) and scar size at 12 months. Based on previous results, regression models with adjustments for baseline status and/or causative organism were used for analysis. Results No significant differences in clinical outcomes by treatment group were seen with the prespecified regression models (BSCVA: −0.04 logMAR, 95% CI, −0.12 to 0.05, P = .39; scar size: 0.03 mm, 95% CI, −0.12 to 0.18, P = .69). A regression model including a Nocardia -treatment arm interaction found corticosteroid use associated with a mean 1-line improvement in BSCVA at 12 months among patients with non- Nocardia ulcers (−0.10 logMAR, 95% CI, −0.19 to −0.02, P = .02). No significant difference was observed in 12-month BSCVA for Nocardia ulcers (0.18 logMAR, 95% CI, −0.04 to 0.41, P = .16). Corticosteroids were associated with larger mean scar size at 12 months among Nocardia ulcers (0.47 mm, 95% CI, 0.06-0.88, P = .02) and no significant difference was identified by treatment for scar size for non- Nocardia ulcers (−0.06 mm, 95% CI, −0.21 to 0.10, P = .46). Conclusions Adjunctive topical corticosteroid therapy may be associated with improved long-term clinical outcomes in bacterial corneal ulcers not caused by Nocardia species.