Fungal endophthalmitis remains a significant cause of vision impairment and blindness. Moreover, the prognosis is poor, in part, due to delay in diagnosis and limited availability of effective antifungal agents with good ocular penetration. Thus, it is imperative to evaluate the therapeutic efficacy of newer antifungal agents in fungal endophthalmitis. In this study, we assessed the efficacy of isavuconazole in treating Aspergillus fumigatus (AF) endophthalmitis in an exogenous mouse model of the disease. Briefly, endophthalmitis was induced by intravitreal (IVT) injection of AF spores in immunocompetent C57BL/6 (B6) mouse eyes. Mice were randomized into five groups receiving isavuconazole via (1) oral gavage, (2) IVT injections, (3) intravenous, (4) IVT injection followed by oral gavage, and (5) IVT injection followed by intravenous. Our data showed that isavuconazole treatment via all routes reduced fungal burden in AF-infected eyes. This coincided with the preservation of retinal structural integrity (histology analysis) and retinal function (electroretinogram, ERG analysis), resulting in significantly improved disease outcome. Furthermore, isavuconazole treatment reduced the levels of inflammatory cytokines (TNF-α, IL-1β, IL-6) and cellular infiltration in the eyes. Notably, oral administration of isavuconazole was as effective in ameliorating endophthalmitis as intravitreal injection of the drug. Collectively, our study demonstrates that isavuconazole is effective in treating AF endophthalmitis in mice, indicating its potential use in human ocular infections.
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