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To characterize the susceptibility of filamentous fungi isolated from keratitis to amphotericin B, natamycin, caspofungin acetate, itraconazole, voriconazole, and posaconazole. Methods: Ninety isolates from fungal keratitis cases at Aravind Eye Hospital in South India were tested using macrobroth dilution for susceptibility to amphotericin B, natamycin, caspofungin, itraconazole, voriconazole, and posaconazole. The minimum inhibitory concentration (MIC) median and 90th percentile were determined. Results: The 90 isolates included 41 Aspergillus species, 38 Fusarium species, and 11 others. The triazoles and caspofungin had the lowest MICs against Aspergillus species; voriconazole, amphotericin B, and posaconazole had the lowest MICs against Fusarium species, and none of the Fusarium species were inhibited by itracona

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Objective-To conduct a therapeutic exploratory clinical trial comparing clinical outcomes of treatment with topical natamycin vs topical voriconazole for fungal keratitis.Methods-The multicenter, double-masked, clinical trial included 120 patients with fungal keratitis at Aravind Eye Hospital in India who were randomized to receive either topical natamycin or topical voriconazole and either had repeated scraping of the epithelium or not.Main Outcome Measures-The primary outcome was best spectacle-corrected visual acuity (BSCVA) at 3 months. Other outcomes included scar size, perforations, and a sub-analysis of BSCVA at 3 months in patients with an enrollment visual acuity of 20/40 to 20/400.Results-Compared with those who received natamycin, voriconazole-treated patients had an approximately 1-line improvement in BSCVA at 3 months after adjusting for scraping in a multivariate regression model but the difference was not statistically significant (P=.29). Scar size at 3 months was slightly greater with voriconazole after adjusting for scraping (P=.48). Corneal perforations in the voriconazole group (10 of 60 patients) were not significantly different than in the natamycin-treated group (9 of 60 patients) (P>.99). Scraping was associated with worse BSCVA at 3 months after adjusting for drug (P=.06). Patients with baseline BSCVA of 20/40 to 20/400 showed a trend toward a 2-line improvement in visual acuity with voriconazole (P=.07).Conclusions-Overall, there were no significant differences in visual acuity, scar size, and perforations between voriconazole-and natamycin-treated patients. There was a trend toward scraping being associated with worse outcomes.

for the Mycotic Ulcer Treatment Trial II Group OBJECTIVE To compare oral voriconazole with placebo in addition to topical antifungals in the treatment of filamentous fungal keratitis. DESIGN, SETTING, AND PARTICIPANTSThe Mycotic Ulcer Treatment Trial II (MUTT II), a multicenter, double-masked, placebo-controlled, randomized clinical trial, was conducted in India and Nepal, with 2133 individuals screened for inclusion. Patients with smear-positive filamentous fungal ulcers and visual acuity of 20/400 (logMAR 1.3) or worse were randomized to receive oral voriconazole vs oral placebo; all participants received topical antifungal eyedrops. The study was conducted from May 24, 2010, to November 23, 2015. All trial end points were analyzed on an intent-to-treat basis.INTERVENTIONS Study participants were randomized to receive oral voriconazole vs oral placebo; a voriconazole loading dose of 400 mg was administered twice daily for 24 hours, followed by a maintenance dose of 200 mg twice daily for 20 days, with dosing altered to weight based during the trial. All participants received topical voriconazole, 1%, and natamycin, 5%. MAIN OUTCOMES AND MEASURESThe primary outcome of the trial was rate of corneal perforation or the need for therapeutic penetrating keratoplasty (TPK) within 3 months. Secondary outcomes included microbiologic cure at 6 days, rate of re-epithelialization, best-corrected visual acuity and infiltrate and/or scar size at 3 weeks and 3 months, and complication rates associated with voriconazole use.RESULTS A total of 2133 patients in India and Nepal with smear-positive ulcers were screened; of the 787 who were eligible, 240 (30.5%) were enrolled. Of the 119 patients (49.6%) in the oral voriconazole treatment group, 65 were male (54.6%), and the median age was 54 years (interquartile range, 42-62 years). Overall, no difference in the rate of corneal perforation or the need for TPK was determined for oral voriconazole vs placebo (hazard ratio, 0.82; 95% CI, 0.57-1.18; P = .29). In prespecified subgroup analyses comparing treatment effects among organism subgroups, there was some suggestion that Fusarium species might have a decreased rate of perforation or TPK in the oral voriconazole-treated arm; however, this was not a statistically significant finding after Holms-Šidák correction for multiple comparisons (effect coefficient, 0.49; 95% CI, 0.26-0.92; P = .03). Patients receiving oral voriconazole experienced a total of 58 adverse events (48.7%) compared with 28 adverse events (23.1%) in the placebo group (P < .001 after Holms-Šidák correction for multiple comparisons). CONCLUSIONS AND RELEVANCEThere appears to be no benefit to adding oral voriconazole to topical antifungal agents in the treatment of severe filamentous fungal ulcers. All patients in this study were enrolled in India and Nepal; therefore, it is possible that organisms in this region may exhibit characteristics different from those in other regions of the world. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00996736

AimsInternational criteria for the diagnosis of ocular sarcoidosis (OS) was established by the first International Workshop on Ocular Sarcoidosis (IWOS) and validations studies revealed certain limitations of the criteria. To overcome the limitations, revised IWOS criteria was established in an international meeting. This manuscript was aimed at reporting the revised IWOS criteria.MethodsA consensus workshop was carried out to discuss and revise the IWOS criteria. The workshop was held on 27 April 2017, in Nusa Dua, Bali, Indonesia. Prior to the workshop, a questionnaire proposing revised criteria and consisting of one item for differential diagnosis, seven items for ocular clinical signs, 10 items for systemic investigations and three categories of diagnostic criteria was circulated to 30 uveitis specialists. Questionnaire items with over 75% support were taken as consensus agreement; items with below 50% support were taken as consensus disagreement and items with 50%–75% support were discussed at the workshop. Of the latter items, those supported by two-thirds majority in the workshop were taken as consensus agreement.ResultsThe survey and subsequent workshop reached consensus agreements of the revised criteria for the diagnosis of OS as follows: (1) other causes of granulomatous uveitis must be ruled out; (2) seven intraocular clinical signs suggestive of OS; (3) eight results of systemic investigations in suspected OS and (4) three categories of diagnostic criteria depending on biopsy results and combination of intraocular signs and results of systemic investigations.ConclusionsRevised IWOS criteria were proposed by a consensus workshop.