Effect of voriconazole and ultraviolet - A combination therapy compared to voriconazole single treatment on fusarium solani fungal keratitis

Purpose: To demonstrate that ultraviolet-A (UV-A) and voriconazole combination therapy is more effective than voriconazole single treatment for fungal keratitis. Methods: The in vitro UV-A (375nm) fungicidal effect was evaluated on Fusarium solani solutions. Each fungal solution was irradiated with different UV-A irradiation doses. Also, a fungal solution containing voriconazole was also irradiated with UV-A. The in vivo therapeutic effect of UV-A and voriconazole treatment was studied in a rabbit keratitis model. Fungi were injected intrastromally into the cornea of 16 rabbits. Each treatment was initiated 3 days after fungal injection and continued up to 8 days for the following groups: Group 1, control; Group 2, treated with UV-A once a day; Group 3, treated with voriconazole 3 times a day; Group 4, treated with voriconazole 3 times a day and UV-A once a day. On the last day, the sclera-cornea buttons were extracted and microbiological and histological evaluations were performed. Results: The colony-forming units (CFUs) of fungal solutions in culture significantly decreased with UV-A irradiation. The CFUs of fungal solutions containing voriconazole also decreased with UV-A irradiation. In vivo, clinical scores of Group 3 (P=0.03) and Group 4 (P=0.02) 5 days after treatment were significantly lower compared to that of Group 1. The clinical score of Group 4 (P=0.03) 5 days after treatment was significantly lower compared to that of Group 3. The histopathological scores 5 days after treatment were significantly lower in Group 4 compared to those of Group 1 (P<0.01) and Group 3 (P=0.02). Based on our CFU analysis, only Group 4 showed significantly lower CFUs compared to Group 1 (P=0.04). Conclusions: UV-A and voriconazole combination treatment could be a safe and effective alternative to voriconazole single treatment for fungal keratitis.