The overall purpose of this research is to improve the therapy of fungal keratitis by an enhanced understanding of the efficacy and pharmacokinetics of antifungal agents as they relate to the eye. This will be accomplished by the development of the chitin assay as a specific measure of fungal growth within ocular tissues utilizing the highly sensitive technique of gas chromatography with mass spectrometry. The test will be compared to a standardized histologic measure of fungal growth and then applied to studies involving the administration of several antifungal agents by different routes. The value of combined treatment with antifungal agents and immunoadjuvant therapy alone and in combination with antifungal agents will be evaluated by this assay and by standard quantitative isolate recovery techniques. The pathophysiology of experimental fungal keratitis will be explored to examine events surrounding attachment to the corneal surface and stromal invasion using histological techniques. The fungal growth enhancing effect of corticosteroids will be investigated to determine the relative roles of inflammatory cell suppression and the depression of eiconasoids and cytokines in the establishment and progression of fungal keratitis.
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