Continuous administration of voriconazole enhances therapeutic effect for recalcitrant fungal keratitis

Purpose: To evaluate the therapeutic effect of incorporating continuous administration of voriconazole in the treatment of recalcitrant fungal keratitis. Methods: In this prospective case study, 5 consecutive patients (5 eyes) with fungal keratitis were treated with a standard protocol after the failing maximal conventional medical treatment. The protocol involved continuous lavage of the ulcer with 1% voriconazole through an irrigator for 2 h, twice a day, combined with local and systemic antifungals. Visual acuity, slit lamp findings of the ulcer, and fungal hyphae density by confocal microscope were documented, respectively. Results: In 4 patients, the clinical symptoms and slit lamp examination were significantly improved after only 3 days of treatment. The hyphae were shown to decrease in number and morphologically fragmented in corneal stroma by confocal microscopy. After the infection was controlled, 2 cases required further keratoplasty. In one case, the treatment was deemed ineffective and a conjunctival flap had to be created to help control the infection. In all 5 patients, the best spectacle-corrected visual acuity had improved after treatment. With more than 3 months of follow-up, no recurrence of infection was seen in any cases. Conclusion: Our treatment protocol demonstrated improvement in the treatment of clinically resistant fungal keratitis. Continuous lavage of voriconazole is easy to be implemented and well-tolerated by patients. Modification of the current protocol should be further explored to optimize the therapeutic effectiveness in future.