Oral Voriconazole for Fungal Keratitis in the MUTT II Trial
JAMA Ophthalmology, December 2016
Topical antifungals often are supplemented with oral medication for treatment of fungal keratitis, despite insufficient supporting evidence. Prajna et al. conducted a randomized controlled trial to determine whether the combination of topical antifungal eyedrops and oral voriconazole is more effective than topical antifungals alone. They found that oral voriconazole conferred no added benefit and increased the likelihood of adverse events.
This multicenter double-masked placebo-controlled randomized trial included 240 patients from India and Nepal with severe filamentous fungal keratitis and visual acuity of 20/400 or worse. All patients were treated with voriconazole (1%) and natamycin (5%) eyedrops and were randomized to receive oral voriconazole (119 patients) or placebo (121 patients). The main outcomes evaluated were rate of corneal perforation and need for therapeutic penetrating keratoplasty (PK) during 3 months of follow-up. Corneal lesions were examined with a slit-lamp biomicroscope to assess re-epithelialization and dimensions of the infiltrate and scar. Levels of liver enzymes also were determined. Intention-to-treat statistical analysis was used.
Supplementing topical antifungal treatment with oral voriconazole did not reduce the likelihood of corneal perforation (voriconazole vs. placebo, 35 vs. 30 perforations) or the need for PK (49 vs. 56 PKs). These findings remained robust on sensitivity analyses. After correcting for baseline parameters, no between-group differences were noted in visual acuity, infiltrate or scar size, or rate of re-epithelialization. However, the patients who received oral voriconazole were significantly more likely to experience adverse events (58 vs. 28 events in placebo group), which included visual hallucinations and elevated levels of aspartate aminotransferase and alanine aminotransferase. When patients were subgrouped by infecting fungal genera, no significant difference in culture positivity was observed between oral voriconazole and placebo in any subgroup.
The authors concluded that oral voriconazole, when prescribed to patients with fungal keratitis as an adjuvant to topical antifungal treatment, confers no additional benefit but poses significant risks.
The original article can be found here.