Abstract:AIM: To characterize the composition and functional features of the aqueous humor microbiome in common ocular diseases, including myopia, cataract, primary open angle glaucoma (POAG), and Posner-Schlossman syndrome (PSS). METHODS: We performed metagenomic sequencing on 176 aqueous humor samples from patients with cataract (n=37), POAG (n=66), PSS (n=35), and myopia patients (n=38, as controls). Taxonomic profiling, functional annotation, and diversity analyses were conducted to characterize microbial communities, with adjustments for age and gender where appropriate. Associations between microbial features and clinical parameters were evaluated using correlation analyses. RESULTS: We identified 6635 bacterial, 141 archaeal, 96 eukaryotic, and 108 viral operational taxonomic units (OTUs) in the aqueous humor. The microbiome was dominated by Actinomycetota and Pseudomonadota at the phylum level. Compared to myopia controls, POAG and PSS patients showed significantly reduced alpha diversity after age adjustment (P<0.05), whereas cataract patients showed no significant difference. Additionally, we identified disease-specific microbial signatures including enrichment of Cytomegalovirus (CMV) in PSS. Functional analysis revealed enrichment of distinct metabolic pathways. Finally, correlations were observed between microbiota/pathway abundance and clinical phenotype, though none remained significant after multiple testing correction. CONCLUSION: This study provides a preliminary characterization of the aqueous humor microbiome in patients with POAG, PSS, cataract, and myopia controls. The identified microbial signatures and functional pathways offer new insights into potential microbiome-mediated mechanisms in ocular pathophysiology and may inform future diagnostic and therapeutic strategies.
