Author Affiliations: Aravind Eye Care System, Madurai (Drs N. V. Prajna, Mascarenhas, L. Prajna, and Srinivasan), Aravind Eye Care System, Pondicherry (Dr Krishnan), and Aravind Eye Care System, Coimbatore (Drs Rajaraman and Raghavan), India; Francis I. Proctor Foundation (Mss Oldenburg and Ray and Drs Porco, Acharya, and Lietman) and Departments of Ophthalmology (Drs McLeod, Acharya, and Lietman) and Epidemiology and Biostatistics (Drs Porco and Lietman), University of California, San Francisco; and Department of Surgery (Ophthalmology), Dartmouth Medical School, Lebanon, New Hampshire (Dr Zegans).
Group Information: The Mycotic Ulcer Treatment Trial Group members are listed at the end of this article.
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.
Trial Registration clinicaltrials.gov Identifier: NCT00996736
Prajna NV, Krishnan T, Mascarenhas J, Rajaraman R, Prajna L, Srinivasan M, Raghavan A, Oldenburg CE, Ray KJ, Zegans ME, McLeod SD, Porco TC, Acharya NR, Lietman TM, Mycotic Ulcer Treatment Trial Group FT. The Mycotic Ulcer Treatment TrialA Randomized Trial Comparing Natamycin vs Voriconazole. JAMA Ophthalmol. 2013;131(4):422-429. doi:10.1001/jamaophthalmol.2013.1497