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Importance: Antifungal resistance has been shown to impact treatment success, but research analyzing antifungal resistance is scarce., Objective: To evaluate changes in antifungal resistance over time., Design, Setting, and Participants: Ad hoc analysis of 3 randomized clinical trials including consecutive patients 18 years and older presenting with smear-positive fungal ulcers to Aravind Eye Hospitals in Madurai, Coimbatore, Pondicherry, and Tirunelveli in South India who participated in 1 of 3 clinical trials: the Mycotic Ulcer Treatment Trials (MUTT) I (2010 to 2011) or II (2010 to 2015) or the Cross-Linking Assisted Infection Reduction (CLAIR) trial (2016 to 2018). This post hoc analysis was designed in March 2021 and data were analyzed in May and November 2021., Interventions: Minimum inhibitory concentration (MIC) of natamycin and voriconazole was determined from corneal cultures obtained using standardized methods outlined in the Clinical and Laboratory Standards Institute., Main Outcomes and Measures: The primary outcome of this post hoc analysis was MIC of natamycin and voriconazole., Results: A total of 890 fungal isolates were obtained from 651 patients (mean [SD] age, 49.6 [13.0]; 191 [43.3%] female) from 2010 to 2018. MICs were available for 522 samples in 446 patients. Fungal isolates overall demonstrated a 1.02-fold increase per year in voriconazole resistance as measured by MICs (95% CI, 1.00-1.04; P = .06). In subgroup analyses, Fusarium species demonstrated a 1.04-fold increase in voriconazole resistance per year (95% CI, 1.00-1.06; P = .01). Fungal isolates showed a 1.06-fold increase in natamycin resistance per year overall (95% CI, 1.03-1.09; P < .001). Fusarium species had a 1.06-fold increase in natamycin resistance (95% CI, 1.05-1.08; P < .001), Aspergillus had a 1.09-fold increase in resistance (95% CI, 1.05-1.15; P < .001), and other filamentous fungi had a 1.07-fold increase in resistance to natamycin per year (95% CI, 1.04-1.10; P < .001)., Conclusions and Relevance: This post hoc analysis suggests that susceptibility to both natamycin and voriconazole may be decreasing over the last decade in South India. While a trend of increasing resistance could impact treatment of mycoses in general and infectious fungal keratitis in particular, further study is needed to confirm these findings and determine their generalizability to other regions of the world., Trial Registration: ClinicalTrials.gov Identifiers: NCT00996736 and NCT02570321.

Purpose: To identify fungal keratitis patients who are at risk of a poor outcome and may benefit from closer follow-up or more aggressive treatment., Design: Secondary analysis of randomized clinical trial data., Methods: We compared the clinical outcomes of patients who had positive 6-day fungal cultures with those who did not, using backward stepwise regression with covariates for all baseline clinical characteristics., Subjects: Patients presenting with a smear-positive filamentous fungal ulcer and visual acuity of 20/400 or worse, and who subsequently had a 6-day fungal culture performed at the Aravind Eye Care system (India), Lumbini Eye Hospital (Nepal), or Bharatpur Eye Hospital (Nepal)., Main Outcome Measures: The primary outcome is rate of corneal perforation and/or the need for therapeutic penetrating keratoplasty. Secondary outcomes include 3-month best spectacle-corrected visual acuity (BSCVA), 3-month infiltrate and/or scar size, and rate of re-epithelialization., Results: Patients who tested positive at their 6-day culture had twice the hazard of experiencing a corneal perforation or the need for therapeutic penetrating keratoplasty (P = .002) than those who tested negative, even after controlling for baseline ulcer characteristics. These patients also had on average 0.26 logMAR lines worse BSCVA at 3 months (P = .001). Culture positivity at day 6 was not a statistically significant predictor of 3-month infiltrate/scar-size (-0.24 mm 1 ; P = .45) or time to re-epithelialization (hazard ratio = .81; P = .31)., Conclusions: Here we identify a uniquely valuable clinical tool, day 6 culture results, for the treatment of severe fungal keratitis. Risk stratification based on repeat culture positivity is an objective way to assess response to medical therapy and identify patients who are at high risk of a poor clinical outcome. This establishes a new standard of care for severe fungal keratitis management., (Published by Elsevier Inc.)

Purpose: To describe temporal trends in Pseudomonas aeruginosa resistance to moxifloxacin in keratitis isolates from South India., Methods: The Steroids for Corneal Ulcers Trial (SCUT) was a randomized, double-masked, placebo-controlled trial assessing outcomes in patients with culture positive bacterial corneal ulcers randomized to receive prednisolone phosphate or placebo. All patients received moxifloxacin, and susceptibility to moxifloxacin was measured at baseline using Etest. We investigated trends in moxifloxacin susceptibility of P. aeruginosa during 2007, 2008, and 2009 isolated in SCUT in South India., Results: There were 89 P. aeruginosa isolates during 2007, 2008, and 2009 in SCUT that were eligible for this study. There was an increase in the proportion of resistant isolates from 19% in 2007 to 52% in 2009 (p = 0.02, χ(2) test for trend). Logistic regression showed that there was a 2-fold increase in odds of resistance per 1 year increase during the study period (odds ratio 2.16, 95% confidence interval 1.09-4.26, p = 0.027)., Conclusions: We found a sharp increase in the proportion of isolates that were resistant to moxifloxacin from 2007 to 2009. Further work needs to be done to characterize the nature of this increase.

Aim: To describe the clinical characteristics at presentation of a large cohort of patients with Mooren's ulcer in South India., Methods: The medical records of patients with Mooren's ulcer examined in the cornea clinic at Aravind Eye Hospital Madurai, Tamil Nadu, India, over a 10-year period were reviewed in this retrospective observational case series., Results: The cohort contained 242 eyes of 166 patients. All patients were from South India, and men outnumbered women by a ratio of 4.7:1. The median and mean ages at presentation were 65 and 61 years, respectively, with a range of 13-95 years. One eye was affected in 90 of 166 (54%) patients. Visual acuity in the affected eye at presentation ranged from 6/6 to light perception, and was 6/12 or better in 34 of 242 (14%) eyes, between 6/12 and 3/60 in 168 (69%) eyes, and worse than 3/60 in 40 (17%) eyes. Partial peripheral corneal ulceration was observed in 222 (92%) eyes, complete peripheral corneal ulceration was observed in 15 (6%) eyes and total corneal ulceration was observed in 5 (2%) eyes. For those 222 eyes with partial peripheral ulceration, 152 (68%) showed temporal involvement, 129 (58%) showed nasal involvement, 116 (52%) showed inferior involvement and 30 (14%) showed superior involvement. Perforation was observed in 26 (11%) eyes, and was more common in eyes with peripheral as compared with total ulceration (p<0.001). Identified risk factors in the cohort included evidence of prior corneal surgery (22%), corneal trauma (17%) and corneal infection (2%)., Conclusions: Mooren's ulcer is a rare and potentially blinding eye condition observed not infrequently in the cornea clinic at Aravind Eye Hospital. Men are affected more often than women and may present with either unilateral or bilateral disease. Perforation is observed in approximately 1 in 10 affected eyes at presentation and occurs most often in the setting of peripheral ulceration. The occurrence of prior corneal surgery, trauma or infection in nearly one third of patients supports theories of exposure to corneal antigen in the pathogenesis of this disorder.