From fields to eyes: the epidemiology and immune challenges of fungal keratitis

Objectives To investigate the regional epidemiological characteristics, immune mechanisms, and potential therapeutic strategies for fungal keratitis (FK) in order to provide evidence for improving patient outcomes. Methods Clinical data from 145 patients diagnosed with FK between 2018 and 2024 were collected to analyze epidemiological features and predisposing factors. Aqueous humor (AqH) and peripheral blood samples from a subset of patients underwent flow cytometric analysis and cytokine profiling, with glaucoma patients serving as controls. The composition, function, and cytokine profiles of immune cells in the AqH of FK patients were characterized to elucidate the ocular immune microenvironment. Results The majority of FK patients were middle-aged and elderly males (male-to-female ratio: 1.9:1), with agricultural injuries representing the predominant etiology (73.10%) and Fusarium species identified as the leading pathogen (44.12%). Peak incidence occurred in October and November, coinciding with local harvest activities. In the AqH, neutrophils were the predominant infiltrating cells (81.25%), accompanied by a significantly elevated proportion of B cells (30.70%) and marked reductions in both the proportion and function of T cells and NK cells. Concentrations of IL-6 and IL-8 in the AqH were approximately 20-fold and 200-fold higher, respectively, than in controls. Immunosuppressive cell populations, including regulatory B (Breg) cells, activated regulatory T (Treg) cells, and polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), were significantly expanded. Additionally, hyperglycemic patients exhibited heightened inflammatory responses, with significantly elevated concentrations of pro-inflammatory cytokines (IL-4, IL-6, IL-8, and TNF-α) in their AqH compared with normoglycemic patients. Conclusions FK in this region is strongly associated with agricultural activities. Patients demonstrated diminished adaptive immune function alongside expansion of immunosuppressive cell populations, resulting in an ocular microenvironment characterized by suppressed adaptive immunity coexisting with enhanced innate immune responses. IL-6 may play a central role in shaping this immunosuppressive microenvironment by amplifying pro-inflammatory responses and inhibiting T cell function. Hyperglycemia appears to further exacerbate immune dysregulation, potentially impacting prognosis. Early therapeutic targeting of IL-6 may represent a strategy to alleviate ocular inflammation and reduce complications in FK; however, this hypothesis requires validation in future studies.