Comparative Evaluation of Topical versus Intrastromal Voriconazole as an Adjunct to Natamycin in Recalcitrant Fungal Keratitis

Objective: To compare the efficacy of topical voriconazole and topical natamycin with that of intrastromal voriconazole and topical natamycin in patients with recalcitrant fungal keratitis. Design: Randomized clinical trial. Participants: Forty eyes of 40 patients with fungal keratitis (positive smear or culture results or both) larger than 2 mm, involving up to two thirds of the stromal depth, and not responding to topical natamycin therapy for 2 weeks were recruited. Intervention: The patients were randomized to receive either topical 1% voriconazole therapy (n = 20) or intrastromal injections of voriconazole 50 μg/0.1 ml (n = 20). The patients in both groups continued topical natamycin 5% every 4 hours until the ulcer healed. Main Outcome Measures: Primary outcome measure was best spectacle-corrected visual acuity (BSCVA) 3 months after intervention, and secondary outcome measures were time to healing and the size of the scar. Results: The patients in both groups had comparable baseline parameters. The mean BSCVA after treatment was 1.295±0.5 logarithm of the minimum angle of resolution (logMAR) units in the topical group and 1.692±0.29 logMAR units in the intrastromal group. The visual acuity after treatment was significantly better in the topical voriconazole group (P = 0.008). Nineteen patients receiving topical voriconazole and 16 patients who were given intrastromal voriconazole healed with therapy. Conclusions: Topical voriconazole seems to be a useful adjunct to natamycin in fungal keratitis not responding to topical natamycin. Intrastromal injections did not offer any beneficial effect over topical therapy. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.