Randomized, controlled study leads to clear treatment recommendation for fungal corneal ulcers

Results of a large, randomized, double-masked clinical trial indicate that voriconazole should not be used as monotherapy for filamentous fungal keratitis, said Venkatesh Prajna, MD, at Cornea Day during the 26th Asia-Pacific Association of Cataract & Refractive Surgeons Annual Meeting.

Dr. Prajna discussed the recently published findings from the Mycotic Ulcer Treatment Trial (MUTT) that compared natamycin 5% and voriconazole 1% in patients with a smear-positive filamentous fungal ulcer and visual acuity of 20/40 to 20/400. The study was conducted in south India and undertaken after a pilot trial of 120 patients found no differences between the two agents in analyses of healing or perforation rates.

Planned enrollment for MUTT was 368 patients, but recruitment was stopped after entry of only 323 patients when an interim analysis showed clear differences favoring natamycin. In the primary efficacy analysis of best spectacle-corrected visual acuity at 3 months, the mean outcome was 1.4 lines better in patients treated with natamycin compared with the voriconazole group. In addition, the natamycin group had a significantly lower treatment failure rate and a lower rate of culture positivity when smears were repeated at 6 days. 

Fusarium was the most common causative organism, isolated at entry in half of culture-positive eyes, and the superiority of voriconazole was mainly attributable to its providing better results in the Fusarium cases. Outcomes for eyes with infection caused by non-Fusarium sp. were similar in the two treatment groups.

"We were very surprised by the findings of this study because they were not consistent with in vitro data indicating superior efficacy of voriconazole over natamycin or with the preference we found for voriconazole as topical treatment for filamentous keratitis in a survey of corneal specialists worldwide," said Dr. Prajna, principal investigator and chief, cornea clinic, Aravind Eye Hospital, Madurai, India.

He added there are some limitations of the study to consider that pertain mainly to the characteristics of the study population, which included patients from a single geographic location, no contact lens wearers, and predominantly Fusarium cases.