Comparison of topical antifungal agents in the treatment of fungal keratitis: an experimental study

BACKGROUND: Among infectious diseases of the cornea, fungal keratitis is characterized by a particularly severe and treatment-resistant course. Since the 1950s, and especially in recent decades, an increase in the number of cases has been observed. In contrast to bacterial and viral keratitis, for which specific topical agents are available, the management of fungal keratitis is complicated by the limited availability of approved topical antifungal agents in most countries, including Russia. Consequently, ophthalmologists are frequently required to use antifungal medications off-label, which is associated with limitations and is often accompanied by insufficient therapeutic efficacy. Furthermore, in this context, timely identification of fungal keratitis and rational selection of topical antifungal therapy are critically important. AIM: To compare the efficacy of different topical antifungal agents in the treatment of fungal keratitis under experimental conditions. METHODS: An experimental study was conducted in Chinchilla rabbits using a stromal fungal keratitis model induced by Fusarium solani. Treatment efficacy was assessed based on a combination of clinical (biomicroscopy), instrumental (optical coherence tomography), and morphological (histological) criteria. Animals were divided into four treatment groups: 1% voriconazole; 0.2% chlorhexidine bigluconate solution; 0.15% amphotericin B; and combination therapy with 1% voriconazole and 0.02% chlorhexidine bigluconate solution. RESULTS: The most pronounced restoration of physiological stromal architecture, as assessed by optical coherence tomography and histological examination, was observed in group 4. Combination therapy with 1% voriconazole and 0.02% chlorhexidine bigluconate solution was accompanied by an optical coherence tomography pattern closest to physiological, as well as more pronounced restoration of the corneal epithelial layers and reduced stromal infiltration. Monotherapy with amphotericin B or chlorhexidine bigluconate at higher concentrations demonstrated significantly lower efficacy. CONCLUSION: Combination therapy with 1% voriconazole and 0.02% chlorhexidine bigluconate in an experimental model of fungal keratitis demonstrated the greatest efficacy in restoring corneal structure and reducing signs of infectious inflammation, which suggests that this regimen is promising for use in clinical practice.