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Importance: Corneal opacity is a leading cause of visual impairment worldwide; however, the specific features of corneal scars, which decrease visual acuity, have not been well characterized., Objective: To investigate which features of a postfungal keratitis corneal scar contribute to decreased visual acuity after an episode of infectious keratitis and evaluate whether any corneal features may be used as outcomes for clinical trials., Design, Setting, and Participants: In this ancillary, prospective cross-sectional study, a subset of study participants treated for fungal keratitis (n = 71) as part of the Mycotic Ulcer Treatment Trial I (MUTT I) underwent best spectacle-corrected visual acuity (BSCVA) and best contact lens-corrected visual acuity examination, Scheimpflug imaging, and anterior segment optical coherence tomography at a referral hospital in India approximately 2 years after enrollment. Data were collected from December 3, 2012, to December 19, 2012, and analyses were performed from December 2, 2013, to October 2, 2019., Main Outcomes and Measures: Linear regression models were used to evaluate the importance of various corneal features for BSCVA and to assess whether these features could be used to differentiate the 2 treatment arms of the MUTT I trial., Results: Seventy-one patients (42 men [59.1%]; median age, 48 [range, 39-60] years) were examined at a median (IQR) time of 1.8 (1.4-2.2) years after enrollment. The mean (SD) logMAR BSCVA was 0.17 (0.19) (Snellen equivalent, 20/32). In multivariable linear regression models, BSCVA was most associated with irregular astigmatism (1.0 line of worse BSCVA per 1-line difference between BSCVA and contact lens visual acuity; 95% CI, 0.6-1.4) and corneal scar density (1.5 lines of worse vision per 10-unit increase in the mean central corneal density; 95% CI, 0.8-2.3). The thinnest point of the cornea was the metric that best discriminated between the natamycin- and voriconazole-treated ulcers in MUTT I, with 29.3 μm (95% CI, 7.1-51.6 μm) less thinning in natamycin-treated eyes., Conclusions and Relevance: Both irregular astigmatism and corneal scar density may be important risk factors for BSCVA in a population with relatively mild, healed fungal corneal ulcers. The thinnest point of the corneal scar may be a cornea-specific outcome that could be used to evaluate treatments for corneal ulcers.

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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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.

Purpose: To describe clinical outcomes associated with the use of topical difluprednate in treating uveitic cystoid macular edema., Design: Retrospective, interventional case series., Methods: Setting: Medical record review in a tertiary care uveitis center., Patient Population: Fifty-eight patients (72 eyes) with uveitic cystoid macular edema (CME) treated with difluprednate 0.05% ophthalmic solution between June 2012 and May 2016., Main Outcome Measures: Macular central subfield thickness (CST) determined by optical coherence tomography, improvement of CME (≥20% reduction in CST or resolution), and resolution of CME (CST ≤ 320 μm with no cysts) at 30 days after starting treatment. Outcomes were assessed up to 90 days., Results: CST on average decreased by 17% (95% CI: -33%, -7%) for eyes using only difluprednate (n = 43) and by 6% (95% CI: -17%, -2%) for eyes in patients using concomitant systemic immunosuppressive therapy (n = 29) at 30 days, a 12% difference between groups (95% CI: 2%, 21%, P = .02). Of eyes on difluprednate alone, 76% had improvement and 48% had resolution of CME. In patients using systemic therapy, 37% of eyes had improvement and 17% had resolution. Eight eyes (11%) had an intraocular pressure (IOP) > 24 mm Hg within the first 30 days. By 90 days, CME had improved in 69% of all eyes and resolved in 43% of eyes, with only 9 patients starting or increasing systemic immunosuppressive medications and 2 patients receiving periocular corticosteroid injections., Conclusions: Difluprednate was associated with an improvement in uveitic CME and could be a reasonable first-line therapy. IOP should be closely monitored., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the changes in quality of life in noninfectious uveitis patients treated with 2 of the most commonly prescribed antimetabolite treatments., Design: Secondary analysis of a multicenter, block-randomized clinical trial., Methods: Eighty patients at Aravind Eye Hospitals in Madurai and Coimbatore, India, with noninfectious intermediate, posterior, or panuveitis were randomized to receive oral methotrexate, 25 mg weekly, or oral mycophenolate mofetil, 1 g twice daily, and were followed up monthly for 6 months. Best-corrected visual acuity, Indian Vision Function Questionnaire (IND-VFQ), and Medical Outcomes Study 36-item Short Form Survey (SF-36) were obtained at enrollment and at 6 months (or prior, in the event of early treatment failure)., Results: IND-VFQ scores, on average, increased by 9.2 points from trial enrollment to 6 months (95% confidence interval [CI]: 4.9, 13.5, P = .0001). Although the SF-36 physical component summary score did not significantly differ over the course of the trial, the mental component summary score decreased by 2.3 points (95% CI: -4.4, -0.1, P = .04) and the vitality subscale decreased by 3.5 points (95% CI: -5.6, -1.4, P = .001). Quality-of-life scores did not differ between treatment arms. Linear regression modeling showed a 3.2-point improvement in IND-VFQ score for every 5-letter improvement in visual acuity (95% CI: 1.9, 4.3; P < .001)., Conclusions: Although uveitis treatment was associated with increased vision and vision-related quality of life, patient-reported physical health did not change after 6 months of treatment, and mental health decreased. Despite improved visual outcomes, uveitis patients receiving systemic immunosuppressive therapy may experience a deterioration in mental health-related quality of life., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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 < .001) and a 0.83-mm decreased infiltrate and/or scar size at 3 months after correcting for baseline values (95% CI, -1.33 to -0.32 mm; 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.

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 < 0.001) and epithelial defect size (P = 0.02). Multivariate regression analysis demonstrated that pretreatment was associated with significantly worse 3-month visual acuity (P = 0.006), larger 3-month scar size (P < 0.001) and increased odds of corneal perforation and/or transplant (P = 0.001)., Conclusions: Fungal keratitis that is smear-positive despite being pretreated with appropriate antifungal agents appears to be a risk factor for worse outcomes, likely a result of initial ulcer severity and treatment failure. These patients may benefit from more aggressive multimodal therapy at a tertiary centre., Competing Interests: None, (© 2016 Royal Australian and New Zealand College of Ophthalmologists.)

Background/aims: The 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., Methods: The 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., Results: 323 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<0.001). Those who required therapeutic penetrating keratoplasty had an average of 25.2 points decrease on VFQ after correcting for treatment arm (95% CI -31.8 to -18.5, p<0.001). Study participants who were unemployed had on average 28.5 points decrease on VFQ (95% CI -46.9 to -10.2, p=0.002) after correcting for treatment arm., Conclusions: Monocular vision loss from corneal opacity due to fungal keratitis reduced vision-related quality of life. Given the relatively high worldwide burden of corneal opacity, improving treatment outcomes of corneal infections should be a public health priority., Trial Registration Number: Clinicaltrials.gov Identifier: NCT00996736., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Purpose: To 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., Methods: The 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., Results: Indian 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)., Conclusion: Indian 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: To characterize the level of depression in patients with ocular inflammatory disease and to determine predictors of depression in this population., Design: Prospective cross-sectional survey and medical record review., Methods: Participants were consecutive patients with noninfectious ocular inflammatory disease in a university-based tertiary referral center. Subjects were given the self-administered Beck Depression Inventory-II (BDI-II), National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25), and additional supplemental questions. Medical records were reviewed for clinical characteristics. Univariate analyses were conducted to compare clinical characteristics between patients with and without a positive screen for depression, and a multivariate regression model was performed to determine the most significant predictors of depression., Results: Of the 104 participants, 26.9% screened positive for depression with the BDI-II. Of these subjects, only 39.3% had been previously diagnosed with depression. NEI VFQ-25 scores were significantly lower in depressed patients in all subscales except driving and color vision. Predictors of depression were inadequate emotional support, lower visual functioning (VFQ composite score), history of changing immunomodulatory treatment, and current oral corticosteroid use., Conclusions: Depression may be a significant but underrecognized comorbid condition in patients with ocular inflammatory disease. Worse visual function was associated with depression. The authors recommend heightened awareness of potential depression in patients with ocular inflammatory disease., (Copyright © 2012 Elsevier Inc. All rights reserved.)

PurposeTo investigate time trade-off (TTO) utility values in patients with noninfectious uveitis and determine whether patient demographics and clinical characteristics are associated with utility scores.DesignTime trade-off utility analysis.MethodsSetting: A tertiary care uveitis center in San Francisco, California, USA.Patient populationOne hundred and four consecutive adults with noninfectious uveitis, enrolled between November 2016 and February 2017.Main outcome measuresTTO utility values, as collected by an interviewer-guided survey. Information regarding general health, ocular symptoms, and religion was also collected and medical record review was conducted to record anatomic location of uveitis, disease activity, visual acuity, and treatments. Multivariable regression analysis with backward selection was used to identify variables associated with TTO values.ResultsMedian TTO score was 0.975 (interquartile range [IQR]: 0.8-1.0), corresponding to trading a median 1.28 years of remaining life for healthy eyes (IQR: 0-6.29). Regression analysis revealed that worse eye visual acuity, >6 months of oral corticosteroid use, and current antidepressant use were associated with lower TTO scores (P = .008, P = .006, P = .008, respectively), controlling for age and sex. In particular, patients who had been taking oral corticosteroids for more than 6 months, regardless of dose, were 10.5 times more likely to trade 20% or more years of remaining life (TTO ≤0.8) than patients not taking oral corticosteroids (95% confidence interval: 2.3, 48.1; P = .002).ConclusionsPatients with noninfectious uveitis had measurable, though modest, reductions in quality of life, as assessed by TTO, and these decreases were significantly associated with visual acuity in the worse eye and long-term oral corticosteroid use.

PurposeTo compare longitudinal outcomes of visual acuity after fungal corneal ulcers with those of bacterial ulcers.DesignProspective cohort study.MethodsThis 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).ResultsFifty 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).ConclusionsIn 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.

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 mm1; 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.

ImportanceIdentifying 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.ObjectiveTo 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 participantsThis 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 measuresThe primary outcome of this secondary analysis was the rate of corneal perforation or the need to undergo TPK.ResultsThe 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 relevanceThese results suggest that risk stratification from baseline ulcer characteristics can identify those at highest risk for developing corneal perforation and/or needing TPK.Trial registrationclinicaltrials.gov Identifier: NCT00996736.

PurposeTo evaluate the changes in quality of life in noninfectious uveitis patients treated with 2 of the most commonly prescribed antimetabolite treatments.DesignSecondary analysis of a multicenter, block-randomized clinical trial.MethodsEighty patients at Aravind Eye Hospitals in Madurai and Coimbatore, India, with noninfectious intermediate, posterior, or panuveitis were randomized to receive oral methotrexate, 25 mg weekly, or oral mycophenolate mofetil, 1 g twice daily, and were followed up monthly for 6 months. Best-corrected visual acuity, Indian Vision Function Questionnaire (IND-VFQ), and Medical Outcomes Study 36-item Short Form Survey (SF-36) were obtained at enrollment and at 6 months (or prior, in the event of early treatment failure).ResultsIND-VFQ scores, on average, increased by 9.2 points from trial enrollment to 6 months (95% confidence interval [CI]: 4.9, 13.5, P = .0001). Although the SF-36 physical component summary score did not significantly differ over the course of the trial, the mental component summary score decreased by 2.3 points (95% CI: -4.4, -0.1, P = .04) and the vitality subscale decreased by 3.5 points (95% CI: -5.6, -1.4, P = .001). Quality-of-life scores did not differ between treatment arms. Linear regression modeling showed a 3.2-point improvement in IND-VFQ score for every 5-letter improvement in visual acuity (95% CI: 1.9, 4.3; P < .001).ConclusionsAlthough uveitis treatment was associated with increased vision and vision-related quality of life, patient-reported physical health did not change after 6 months of treatment, and mental health decreased. Despite improved visual outcomes, uveitis patients receiving systemic immunosuppressive therapy may experience a deterioration in mental health-related quality of life.

PurposeTo report outcomes of Vogt-Koyanagi-Harada (VKH) disease from a clinical trial of antimetabolite therapies.DesignSubanalysis from an observer-masked randomized clinical trial for noninfectious intermediate, posterior, and panuveitis.Methodssetting: Clinical practice at Aravind Eye Hospitals, India.Patient populationForty-three of 80 patients enrolled (54%) diagnosed with VKH.InterventionPatients were randomized to either 25 mg oral methotrexate weekly or 1 g mycophenolate mofetil twice daily, with a corticosteroid taper.Main outcome measuresPrimary outcome was corticosteroid-sparing control of inflammation at 5 and 6 months. Secondary outcomes included visual acuity, central subfield thickness, and adverse events. Patients were categorized as acute (diagnosis ≤3 months prior to enrollment) or chronic (diagnosis >3 months prior to enrollment).ResultsTwenty-seven patients were randomized to methotrexate and 16 to mycophenolate mofetil; 30 had acute VKH. The odds of achieving corticosteroid-sparing control of inflammation with methotrexate were 2.5 times (95% CI: 0.6, 9.8; P = .20) the odds with mycophenolate mofetil, a difference that was not statistically significant. The average improvement in visual acuity was 12.5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters. On average, visual acuity for patients with acute VKH improved by 14 more ETDRS letters than those with chronic VKH (P < .001), but there was no difference in corticosteroid-sparing control of inflammation (P = .99). All 26 eyes with a serous retinal detachment at baseline resolved, and 88% achieved corticosteroid-sparing control of inflammation.ConclusionsThe majority of patients treated with antimetabolites and corticosteroids were able to achieve corticosteroid-sparing control of inflammation by 6 months. Although patients with acute VKH gained more visual improvement than those with chronic VKH, this did not correspond with a higher rate of controlled inflammation.

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.

ImportanceThe 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.ObjectiveTo 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 participantsThis 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.InterventionsCorneal smears and cultures were obtained from all study participants at baseline. Susceptibility testing was performed for each culture-positive specimen.Main outcomes and measuresMinimum inhibitory concentration of voriconazole and natamycin in baseline cultures.ResultsOf 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 relevanceSusceptibility 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 registrationclinicaltrials.gov Identifier: NCT00996736.

ImportanceGiven the limitations in health care resources, quality-of-life measures for interventions have gained importance.ObjectiveTo determine whether vision-related quality-of-life outcomes were different between the natamycin and voriconazole treatment arms in the Mycotic Ulcer Treatment Trial I, as measured by an Indian Vision Function Questionnaire.Design, setting, and participantsSecondary analysis (performed October 11-25, 2014) of a double-masked, multicenter, randomized, active comparator-controlled, clinical trial at multiple locations of the Aravind Eye Care System in South India that enrolled patients with culture- or smear-positive filamentous fungal corneal ulcers who had a baseline visual acuity of 20/40 to 20/400 (logMAR of 0.3-1.3).InterventionsStudy participants were randomly assigned to topical voriconazole, 1%, or topical natamycin, 5%.Main outcomes and measuresSubscale score on the Indian Vision Function Questionnaire from each of the 4 subscales (mobility, activity limitation, psychosocial impact, and visual function) at 3 months.ResultsA total of 323 patients were enrolled in the trial, and 292 (90.4%) completed the Indian Vision Function Questionnaire at 3 months. The majority of study participants had subscale scores consistent with excellent function. After adjusting for baseline visual acuity and organism, we found that study participants in the natamycin-treated group scored, on average, 4.3 points (95% CI, 0.1-8.5) higher than study participants in the voriconazole-treated group (P = .046). In subgroup analyses looking at ulcers caused by Fusarium species and adjusting for baseline best spectacle-corrected visual acuity, the natamycin-treated group scored 8.4 points (95% CI, 1.9-14.9) higher than the voriconazole-treated group (P = .01). Differences in quality of life were not detected for patients with Aspergillus or other non-Fusarium species as the causative organism (1.5 points [95% CI, -3.9 to 6.9]; P = .52).Conclusions and relevanceWe found evidence of improvement in vision-related quality of life among patients with fungal ulcers who were randomly assigned to natamycin compared with those randomly assigned to voriconazole, and especially among patients with Fusarium species as the causative organism. Incorporation of quality-of-life measures in clinical trials is important to fully evaluate the effect of the studied interventions.Trial registrationclinicaltrials.gov Identifier:NCT00996736.

BackgroundTo 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.MethodsConfirmed 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.ResultsA 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.ConclusionsFluoroquinolone 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.

ObjectiveTo compare the relative effectiveness of methotrexate and mycophenolate mofetil for noninfectious intermediate uveitis, posterior uveitis, or panuveitis.DesignMulticenter, block-randomized, observer-masked clinical trial.ParticipantsEighty patients with noninfectious intermediate, posterior, or panuveitis requiring corticosteroid-sparing therapy at Aravind Eye Hospitals in Madurai and Coimbatore, India.InterventionPatients were randomized to receive 25 mg weekly oral methotrexate or 1 g twice daily oral mycophenolate mofetil and were monitored monthly for 6 months. Oral prednisone and topical corticosteroids were tapered.Main outcome measuresMasked examiners assessed the primary outcome of treatment success, defined by achieving the following at 5 and 6 months: (1) ≤0.5+ anterior chamber cells, ≤0.5+ vitreous cells, ≤0.5+ vitreous haze and no active retinal/choroidal lesions in both eyes, (2) ≤10 mg of prednisone and ≤2 drops of prednisolone acetate 1% a day, and (3) no declaration of treatment failure because of intolerability or safety. Additional outcomes included time to sustained corticosteroid-sparing control of inflammation, change in best spectacle-corrected visual acuity, resolution of macular edema, adverse events, subgroup analysis by anatomic location, and medication adherence.ResultsForty-one patients were randomized to methotrexate and 39 to mycophenolate mofetil. A total of 67 patients (35 methotrexate, 32 mycophenolate mofetil) contributed to the primary outcome. Sixty-nine percent of patients achieved treatment success with methotrexate and 47% with mycophenolate mofetil (P = 0.09). Treatment failure from adverse events or tolerability was not different by treatment arm (P = 0.99). There were no differences between treatment groups in time to corticosteroid-sparing control of inflammation (P = 0.44), change in best spectacle-corrected visual acuity (P = 0.68), or resolution of macular edema (P = 0.31).ConclusionsThere was no statistically significant difference in corticosteroid-sparing control of inflammation between patients receiving methotrexate or mycophenolate mofetil. However, there was a 22% difference in treatment success favoring methotrexate.

PurposeTo assess the association between minimum inhibitory concentration (MIC) and clinical outcomes in a fungal keratitis clinical trial.DesignExperimental study using data from a randomized comparative trial.ParticipantsOf the 323 patients enrolled in the trial, we were able to obtain MIC values from 221 patients with monocular fungal keratitis.MethodsThe Mycotic Ulcer Treatment Trial I was a randomized, double-masked clinical trial comparing clinical outcomes of monotherapy with topical natamycin versus voriconazole for the treatment of fungal keratitis. Speciation and determination of MIC to natamycin and voriconazole were performed according to Clinical and Laboratory Standards Institute guidelines. The relationship between MIC and clinical outcome was assessed.Main outcome measuresThe primary outcome was 3-month best spectacle-corrected visual acuity. Secondary outcomes included 3-month infiltrate or scar size; corneal perforation and/or therapeutic penetrating keratoplasty; and time to re-epithelialization.ResultsA 2-fold increase in MIC was associated with a larger 3-month infiltrate or scar size (0.21 mm; 95% confidence interval [CI], 0.10-0.31; P < 0.001) and increased odds of perforation (odds ratio, 1.32; 95% CI, 1.04-1.69; P = 0.02). No correlation was found between MIC and 3-month visual acuity. For natamycin-treated cases, an association was found between higher natamycin MIC with larger 3-month infiltrate or scar size (0.29 mm; 95% CI, 0.15-0.43; P < 0.001) and increased perforations (odds ratio, 2.41; 95% CI, 1.46-3.97; P < 0.001). Among voriconazole-treated cases, the voriconazole MIC did not correlate with any of the measured outcomes in the study.ConclusionsDecreased susceptibility to natamycin was associated with increased infiltrate or scar size and increased odds of perforation. There was no association between susceptibility to voriconazole and outcome.

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.).

BackgroundTo 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.MethodsConfirmed 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.ResultsA 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.ConclusionsFluoroquinolone 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.

PurposeTo determine whether topical corticosteroids as adjunctive therapy for bacterial keratitis improves long-term clinical outcomes.DesignRandomized, placebo-controlled, double-masked clinical trial.MethodsThis 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.ResultsNo 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).ConclusionsAdjunctive topical corticosteroid therapy may be associated with improved long-term clinical outcomes in bacterial corneal ulcers not caused by Nocardia species.

To evaluate how changes in visual acuity are associated with changes in quality of life (QoL) among patients with non-infectious uveitis taking antimetabolites. This secondary analysis of the multicenter First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial involves 216 participants randomized to methotrexate or mycophenolate mofetil. Vision-related (NEI-VFQ and IND-VFQ) and health-related (PCS and MCS SF-36v2) QoL and visual acuity were measured at baseline and 6-month primary endpoint. Visual acuity was significantly associated and correlated with all QoL measures (Spearman correlation coefficients = 0.5, 0.5, 0.3, and 0.4 for NEI-VFQ, IND-VFQ, SF-36v2 MCS and PCS, respectively). All observed changes in QoL met or exceeded the minimal clinically important difference definition on each scale. Treatment group was not significantly associated with any QoL measure. By adding insight beyond visual acuity, QoL provides a more comprehensive picture of the patient experience during uveitis treatment. Abbreviations and Acronyms: QoL = quality of life; VR-QoL = vision-related quality of life; HR-QoL = health-related quality of life; FAST = First-line Antimetabolites as Corticosteroid Sparing Treatment; NEI-VFQ = National Eye Institute Visual Functioning Questionnaire; IND-VFQ = Indian Visual Functioning Questionnaire; SF-36v2 = Medical Outcomes Study 36-Item Short Form Survey; PCS = physical component score; MCS = mental component score; 95% CI = 95% confidence interval; MCID = minimal clinically important difference [ABSTRACT FROM AUTHOR]

ObjectiveTo compare topical natamycin vs voriconazole in the treatment of filamentous fungal keratitis.MethodsThis phase 3, double-masked, multicenter trial was designed to randomize 368 patients to voriconazole (1%) or natamycin (5%), applied topically every hour while awake until reepithelialization, then 4 times daily for at least 3 weeks. Eligibility included smear-positive filamentous fungal ulcer and visual acuity of 20/40 to 20/400.Main outcome measuresThe primary outcome was best spectacle-corrected visual acuity at 3 months; secondary outcomes included corneal perforation and/or therapeutic penetrating keratoplasty.ResultsA total of 940 patients were screened and 323 were enrolled. Causative organisms included Fusarium (128 patients [40%]), Aspergillus (54 patients [17%]), and other filamentous fungi (141 patients [43%]). Natamycintreated cases had significantly better 3-month best spectacle-corrected visual acuity than voriconazole-treated cases (regression coefficient=0.18 logMAR; 95% CI, 0.30 to 0.05; P=.006). Natamycin-treated cases were less likely to have perforation or require therapeutic penetrating keratoplasty (odds ratio=0.42; 95% CI, 0.22 to 0.80; P=.009). Fusarium cases fared better with natamycin than with voriconazole (regression coefficient=0.41 logMAR; 95% CI,0.61 to 0.20; P

PurposeBacterial keratitis is a sight-threatening infection of the cornea that is one of the leading causes of blindness globally. In this report, we analyze the role of moxifloxacin susceptibility in the relationship between causative organisms and clinical outcome in bacteria keratitis.MethodsA mediation analysis is used to assess the role of moxifloxacin susceptibility in the relationship between causative organisms and clinical outcome in bacterial keratitis using data collected in a randomized, controlled trial.ResultsIn the Steroids for Corneal Ulcers Trial (SCUT), 500 corneal infections were treated with topical moxifloxacin. The outcome of 3-week best spectacle-corrected visual acuity was significantly associated with an organism (Streptococcus pneumoniae, Pseudomonas aeruginosa, etc., P = 0.008). An indirect effects mediation model suggests that MIC accounted for approximately 13% (95% confidence interval, 3%-24%, P = 0.015) of the effect of the organism on 3-week visual acuity.ConclusionsMoxifloxacin mediates the relationship between causative organisms and clinical outcome in bacterial keratitis, and is likely on the causal pathway between the organism and outcome. (ClinicalTrials.gov number, NCT00324168.).

ObjectivesTo determine whether cytotoxic and invasive Pseudomonas aeruginosa strains differentially influence clinical presentation, outcomes, or therapeutic response in bacterial keratitis.MethodsPseudomonas aeruginosa isolates from the National Eye Institute-funded Steroids for Corneal Ulcers Trial were subtyped as cytotoxic or invasive strains. The main outcome measure compared between the 2 subtypes was change in visual acuity at 3 months using Huber robust regression, adjusting for topical corticosteroid treatment.ResultsOf 101 confirmed P aeruginosa isolates from the Steroids for Corneal Ulcers Trial, 74 had a classically cytotoxic or invasive genotype. While corneal ulcers caused by genotypically invasive P aeruginosa strains were associated at presentation with significantly better visual acuity than corneal ulcers caused by genotypically cytotoxic P aeruginosa strains when adjusting for the effect of ulcer location (P= .008), invasive ulcers had improved significantly less than cytotoxic ulcers at 3 months (0.35; 95% CI, 0.04-0.66 logMAR; P= .03 [3.5-line difference]). Compared with topical moxifloxacin alone, adjunctive treatment with topical corticosteroids was associated with significantly more improvement in visual acuity in the invasive subgroup (P= .04) but was associated with less improvement in visual acuity in the cytotoxic subgroup (P= .07).ConclusionsRational profiling of differentially expressed virulence determinants (eg, cytotoxicity and invasiveness for P aeruginosa) could be used as a tool for decision making in the management of infections to optimize outcomes.

PurposeTo compare the clinical course of Nocardia species keratitis with keratitis resulting from other bacterial organisms and to assess the effect of corticosteroids as adjunctive therapy using data collected from the Steroids for Corneal Ulcers Trial.DesignSubgroup analysis of a randomized controlled trial.Methodssetting: Multicenter randomized controlled trial. study population: Five hundred patients with bacterial keratitis randomized 1:1 to topical corticosteroid or placebo who had received at least 48 hours of topical moxifloxacin. intervention/observation procedure: Topical prednisolone phosphate 1% or placebo and clinical course of Nocardia keratitis. main outcome measures: Best spectacle-corrected visual acuity and infiltrate or scar size at 3 months from enrollment.ResultsOf 500 patients enrolled in the trial, 55 (11%) had a Nocardia corneal ulcer. Patients with Nocardia ulcers had better presentation visual acuity compared with non-Nocardia ulcers (median Snellen visual acuity, 20/45, compared with 20/145; P < .001) and comparable 3-month visual acuity (median, 20/25, vs 20/40; P = .25). Nocardia ulcers had approximately 2 lines less of improvement in visual acuity compared with non-Nocardia ulcers (0.21 logarithm of the minimal angle of resolution; 95% confidence interval, 0.09 to 0.33 logarithm of the minimal angle of resolution; P = .001). This difference may reflect the better starting visual acuity in patients with Nocardia ulcers. In Nocardia ulcers, corticosteroids were associated with an average 0.4-mm increase in 3-month infiltrate or scar size (95% confidence interval, 0.03 to 0.77 mm; P = .03).ConclusionsNocardia ulcers responded well to treatment. They showed less overall improvement in visual acuity than non-Nocardia ulcers, but had better presentation acuity. Corticosteroids may be associated with worse outcomes.

PurposeTo analyze the minimum inhibitory concentration (MIC) of isolates from fungal keratitis to natamycin and voriconazole and to assess the relationship between organism, MIC, and clinical outcome.MethodsData were collected as part of a randomized, controlled, double-masked clinical trial. Main outcome measures included best spectacle-corrected visual acuity, infiltrate/scar size, time to reepithelialization, and perforation. Speciation and analysis of MIC to natamycin and voriconazole were done according to Clinical and Laboratory Standards Institute standards. The relationship between MIC and organism, organism and outcome measure, and each outcome measure and MIC were assessed.ResultsOf the 120 samples obtained in the trial, 84 isolates had an identifiable organism and were available for further analyses. Fusarium spp and Aspergillus spp were the most commonly isolated organisms. MIC was significantly different across the groups of organisms (P = 0.0001). A higher MIC was significantly associated with an increased likelihood of perforation [odds ratio (OR), 2.03; 95% confidence interval (CI), 1.02-4.04; P = 0.04]. There was no significant association between MIC and 3-week visual acuity (OR, 0.058; 95% CI, -0.01 to 0.13; P = 0.11), 3-month visual acuity (OR, 0.01; 95% CI,-0.08 to 1.04; P = 0.79), 3-week infiltrate/scar size (OR, 0.12, 95% CI, -0.02 to 0.27; P = 0.10), 3-month infiltrate/scar size (OR, 0.12; 95% CI, -0.02 to 0.25; P = 0.09), or time to reepithelialization (hazards ratio, 1.19; 95% CI, 0.98-1.45; P = 0.08).ConclusionA higher MIC was associated with an increased odds of perforation. The results of this study suggest that resistance to antifungal medication may be associated with worse outcomes in fungal keratitis.

The role of antibiotic susceptibility testing on clinical outcome is unclear. In a randomized, controlled trial of bacterial keratitis, a higher minimum inhibitory concentration to moxifloxacin was significantly associated with worse visual acuity.Background. For bacterial infections, the susceptibility to antibiotics in vitro has been associated with clinical outcomes in vivo, although the importance of minimum inhibitory concentration (MIC) has been debated. In this study, we analyzed the association of MIC on clinical outcomes in bacterial corneal ulcers, while controlling for organism and severity of disease at presentation.Methods. Data were collected as part of a National Eye Institute–funded, randomized, controlled trial (the Steroids for Corneal Ulcers Trial [SCUT]). All cases enrolled in SCUT had a culture-positive bacterial corneal ulcer and received moxifloxacin. The MIC to moxifloxacin was measured by E test. Outcomes included best spectacle-corrected visual acuity, infiltrate/scar size, time to re-epithelialization, and corneal perforation.Results. Five hundred patients with corneal ulcers were enrolled in the trial, and 480 were included in this analysis. The most commonly isolated organisms were Streptococcus pneumoniae and Pseudomonas aeruginosa. A 2-fold increase in MIC was associated with an approximately 0.02 logMAR decrease in visual acuity at 3 weeks, approximately 1 letter of vision loss on a Snellen chart (0.019 logMAR; 95% confidence interval [CI], .0040–.033; P = .01). A 2-fold increase in MIC was associated with an approximately 0.04-mm larger infiltrate/scar size at 3 weeks (0.036 mm; 95% CI, .010–.061; P = .006). After controlling for organism, a higher MIC was associated with slower time to re-epithelialization (hazards ratio, 0.92; 95% CI, .86–.97; P = .005).Conclusions. In bacterial keratitis, a higher MIC to the treating antibiotic is significantly associated with worse clinical outcomes, with approximately 1 line of vision loss per 32-fold increase in MIC.Clinical Trials Registration: NCT00324168. [ABSTRACT FROM PUBLISHER]

AbstractPurposeMethodsResultsConclusionsThe choroidal thickening and serous retinal detachments that characterize Vogt-Koyanagi-Harada (VKH) disease can be imaged in detail using spectral domain optical coherence tomography (SD-OCT). Whether specific qualitative and quantitative SD-OCT features at presentation were associated with visual outcomes in a randomized controlled trial comparing methotrexate to mycophenolate for steroid-sparing control of uveitis were evaluated.An exploratory subanalysis of data from the FAST trial in which SD-OCT images from VKH participants were analyzed for presence/absence of bacillary detachments, retinal pigment epithelium (RPE) folds, and internal limiting membrane (ILM) fluctuations was performed. A modified RPE undulation index was calculated to provide a quantifiable surrogate marker for choroidal folds.SD-OCT images were available from 158 eyes with VKH. At baseline, bacillary detachments were present in 23.5% of eyes, RPE folds in 22.8% of eyes, and ILM fluctuations in 35.2% of eyes. For each 0.1 unit increase in modified RPE undulation index, there was an associated 0.13 increase in mean logMAR BSCVA at baseline. None of the SD-OCT features were associated with BSCVA at the 6-month primary endpoint. Indeed, mean final BSCVA was similar in those with and without the SD-OCT features of interest at baseline, and was between 0.1 and 0.2 logMAR (Snellen visual acuity 20/25 to 20/30).While eyes with VKH may present with a variety of SD-OCT imaging pathology prior to starting immunosuppression with methotrexate or mycophenolate mofetil, final visual outcome in our study was excellent. With appropriate immunosuppression, good visual outcomes are possible in VKH.ClinicalTrials.gov Identifier NCT01829295Date of Registration: April 11, 2013 [ABSTRACT FROM AUTHOR]

The article presents a study on the treatment of Fusarium cases within Aspergillus cases to evaluate the efficiency of natamycin and voriconazole. The study used various methods such as Wilcoxon rank sum, Fisher's exact tests, and linear regression analysis. Results show no difference in the best spectacle-corrected visual acuity (BSCVA) within three months of the patients' entrolment. It concludes that in a three-month period no difference between the drugs were observed.

Purpose: To determine whether clinical outcomes in bacterial keratitis are associated with antibiotic susceptibility.Design: Retrospective, ancillary study using data and samples from a completed randomized clinical trial.Methods: Forty-two patients were enrolled with culture-confirmed bacterial keratitis at Aravind Eye Hospital in South India. All patients received topical moxifloxacin and were randomized to receive either topical prednisolone phosphate or placebo. Outcomes included time to epithelialization, best spectacle-corrected visual acuity (BSCVA), and infiltrate/scar size at three months. Bacterial isolates were cultured, and minimum inhibitory concentration (MIC) to moxifloxacin was measured using Etests. Multiple linear regression was used to assess the effect of MIC on outcome, adjusting for enrollment characteristics.Results: MIC was associated with three-month infiltrate/scar size: each two-fold increase in MIC was associated with a 0.33-mm average diameter increase in scar size (P=.01). MIC was not associated with three-month BSCVA (P=.71) or time to epithelialization (P=.35).Conclusions: MIC was associated with infiltrate/scar size in bacterial keratitis. An ongoing larger, multicenter trial should provide further information on whether this association is maintained across subgroups of organisms. [ABSTRACT FROM AUTHOR]

Purpose: Subgroup data from a pivotal phase 3 study comparing ranibizumab (LUCENTIS) with verteporfin (VISUDYNE) photodynamic therapy (PDT) in patients with predominantly classic choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) were retrospectively analyzed to identify patient and disease characteristics that may predict visual acuity (VA) treatment outcomes.Design: Retrospective subgroup analysis of 12-month data from the ANCHOR study.Methods: Univariate analyses were performed to assess VA outcomes across subgroups based on patients' gender and baseline age, VA score, CNV lesion size, CNV lesion type, and duration of neovascular AMD, followed by multivariate analyses to identify predictors of the VA score change from baseline at 12 months. main outcome measures: Proportion of patients losing <15 letters and proportion gaining > or =15 letters from baseline VA; mean change from baseline VA.Results: On average, all subgroups of ranibizumab-treated patients did better than PDT patients for all three VA outcome measures. In the multivariate analysis, lower baseline VA score, smaller baseline CNV lesion size, and younger baseline age were associated with greater gain of letters with ranibizumab treatment and less loss of letters with PDT.Conclusions: Subgroup analysis of 12-month data from the ANCHOR study showed ranibizumab to be superior to PDT in all subgroups evaluated, and was consistent with the subgroup analysis of 24-month data from the other pivotal phase 3 study of ranibizumab (MARINA) in showing that the most important predictors of VA outcomes were, in decreasing order of impact, the patient's baseline VA score, CNV lesion size, and age. [ABSTRACT FROM AUTHOR]