The Mycotic Ulcer Treatment Trial A Randomized Trial Comparing Natamycin vs Voriconazole

Objective: To compare topical natamycin vs voriconazole in the treatment of filamentous fungal keratitis. Methods: This 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 Measures: The primary outcome was best spectacle-corrected visual acuity at 3 months; secondary outcomes included corneal perforation and/or therapeutic penetrating keratoplasty. Results: A 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%]). Natamycin-treated 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 < .001; odds ratio for perforation = 0.06; 95% CI, 0.01 to 0.28; P < .001), while non-Fusarium cases fared similarly (regression coefficient = -0.02 logMAR; 95% CI, -0.17 to 0.13; P = .81; odds ratio for perforation = 1.08; 95% CI, 0.48 to 2.43; P =. 86). Conclusions: Natamycin treatment was associated with significantly better clinical and microbiological outcomes than voriconazole treatment for smear-positive filamentous fungal keratitis, with much of the difference attributable to improved results in Fusarium cases. Application to Clinical Practice: Voriconazole should not be used as monotherapy in filamentous keratitis.