Comparison of Oral Voriconazole Versus Oral Ketoconazole as an Adjunct to Topical Natamycin in Severe Fungal Keratitis: A Randomized Controlled Trial

PURPOSE: To compare the efficacy of oral voriconazole (VCZ) with oral ketoconazole (KCZ) as an adjunct to topical natamycin in severe fungal keratitis. METHODS: Fifty eyes of 50 patients with proven severe fungal keratitis, (>5 mm size, involving >4 mm central cornea and >50% stromal depth), smear, and/or culture positive were randomized to receive either oral VCZ (n = 25) or oral KCZ (n = 25) 200 mg twice a day. Both groups received topical natamycin along with oral medication. The primary outcome measure was best spectacle-corrected visual acuity (BSCVA) at 3 months of follow-up. Secondary outcomes were the percentage of healed cases and scar size. RESULTS: The mean BSCVA after treatment was 1.3 ± 0.35 logarithm of minimum angle of resolution units in the VCZ group and 1.6 ± 0.39 logarithm of minimum angle of resolution units in the KCZ group [P = 0.004, 95% confidence interval (CI), -0.10 to 0.54]. The final mean scar size was smaller for oral VCZ than for oral KCZ (P = 0.04, 95% CI, -0.01 to 0.93 mm). The percentage of cases healed were 80% and 72% in VCZ and KCZ groups, respectively (P = 0.51, 95% CI, -0.15 to 0.31). The ratio of tear film to serum concentration of oral VCZ was better than oral KCZ at days 14 (P = 0.002) and 21 (P = 0.006). CONCLUSIONS: Although the duration and percentage of healing was similar in both groups, oral VCZ attained a significantly better tear film concentration with a smaller scar size and better BSCVA compared with oral KCZ. Thus, oral VCZ may be preferred over oral KCZ in severe fungal keratitis.