Purpose: To determine the efficacy of eugenol for the treatment of Candida keratitis in an experimental model. Methods: The in vitro antifungal activity of eugenol and fluconazole was tested against C. albicans strains via the microbroth dilution method. An experimental model of Candida albicans keratitis was used. Rabbits were classified into those that received no treatment (control; group 1) and those that started eugenol treatment immediately (group 2) or after 4 days (group 3) of keratitis induction (n = 12–16 rabbits/group). The 2 treatment groups were assigned to 50 μL of 4 mg/mL eugenol drops hourly for 15 days, while the control group received saline. Corneal penetration of eugenol was measured using HPLC, and corneal toxicity was evaluated clinically and histopathologically. Results: The in vitro minimum inhibitory concentrations of eugenol and fluconazole against C. albicans were 2 and > 0.4 mg/mL, respectively. A 4-mg/mL preparation of eugenol in propylene glycol was the maximum nontoxic dose on rabbit corneas as suggested by clinical and histopathologic findings. At least 75% of all eugenol-treated eyes recovered from keratitis, with improvement in the remaining 25% of the eyes compared to controls. Conclusions: Eugenol can act as a natural, safe, and effective treatment for fungal keratitis, regardless of whether treatment is started immediately or after 4 days of keratitis induction.

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