Toxicity of Topical Antifungal Agents on Corneal Epithelium of Rabbits

ABSTRACT

Though topical administration of antifungal agents for fungal keratitis is effective, it results various toxic effect on cornea depending on the kinds of agents. So, the authors applied several kinds of antifungal agents on the cornea of rabbit and made a comparative study for corneal epithelial damage of which is related to each agents and instillation time using scanning electron microscope. Forty eyes from twenty rabbits were instilled with 0.15% amphotericin B, 5% natamycin, 1% clotrimazole, 0.2% fluconazole and BSS(as a control) in single drop in each eight eyes and then each two corneas resected and examined after 30 minutes, 1 hours, 3 hours and 6 hours. All antifungals showed toxic effects on the corneal epithelium. Significant loss, elongation or swelling in microvilli, especially at the cell periphery, were noted. The top layer of epithelial cells showed moth-eaten appearance or punched-out lesions, and localized destruction. The surface cells were shrunken with wrinkling of plasma membrane and bulging of nucleous. Part of surface cells lost intercellular attachment leaving retraction fibrils. Rarely first and second layer cells of the epithelium were destructed, exposing third layer cells. Dark cells and premature desquamating cells increased significantly with the lapse of time. In general, 5% natamycin and 1% clotrimazole showed relatively severe epithelial toxicity, on the other hand, 0.15% amphotericin B and 0.2% fluconazole shoed mild epithelial toxicity. Localized damages in the epithelial cells were developed in the early stage, and an extent and the depth of the damage in the cells increased in the course of time after instillation.