The mycotic ulcer treatment trial: A randomized trial comparing natamycin vs voriconazole

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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%]). 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




Venkatesh Prajna, N., Krishnan, T., Mascarenhas, J., Rajaraman, R., Prajna, L., Srinivasan, M., … Lietman, T. M. (2013). The mycotic ulcer treatment trial: A randomized trial comparing natamycin vs voriconazole. JAMA Ophthalmology, 131(4), 422–429.

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