Cross-Compartment Proteomic Signatures in Human Diabetic Retinopathy: A Systematic Review and Meta-Analysis

PURPOSE: Diabetic retinopathy (DR) is a leading cause of preventable blindness, with complex molecular pathophysiology spanning multiple biological compartments. This systematic review and meta-analysis aimed to synthesize proteomic findings from human DR studies to identify consistent cross-compartment molecular signatures and evaluate their clinical translation potential. METHODS: fold-change (Log2FC) with reconstructed SEs where necessary. Random-effects multilevel models (REML) incorporated protein- and study-level variance. Prespecified subgroup analyses (aqueous, vitreous, plasma), meta-regression (compartment, protein family, interactions), and diagnostics (Egger's test, trim-and-fill, leave-one-out) probed robustness. Qualitative synthesis integrated 28 eligible studies across vitreous, aqueous, plasma/serum, tears, and urine. RESULTS: = 5) yielded a reduced but still significant effect (Log2FC = 1.10). Qualitative evidence highlighted vitronectin, RBP4, prothrombin, and afamin as additional stage-specific candidates, while tear- and urine-based markers showed potential for noninvasive screening. CONCLUSION: This first integrated systematic review and meta-analysis of multicompartment proteomic studies in diabetic retinopathy shows consistent upregulation of fibrinogen chains across ocular compartments, highlights vitronectin and stage-specific proteins as additional candidates, and establishes a rigorous evidence base to guide biomarker validation and clinical translation.