Association of serum TIM-3 and Galectin-9 levels with glaucoma progression: implications for clinical monitoring.

BACKGROUND: Primary open-angle glaucoma (POAG) causes irreversible blindness via retinal ganglion cell loss. Neuroinflammation and immune dysfunction drive its progression, yet the role of the TIM-3/Galectin-9 axis remains unclear. OBJECTIVE: To investigate the association of serum soluble TIM-3 (sTIM-3) and Galectin-9 levels with the progression of primary open-angle glaucoma (POAG). METHODS: This retrospective analysis enrolled POAG patients from our ophthalmology department (January 2022-December 2024). After a minimum 12-month follow-up, participants were categorized as progression or stable based on visual field and optical coherence tomography (OCT) assessments. Healthy controls were age/sex-matched. Recorded clinical variables included IOP, CCT, visual fields, and OCT measures. Baseline concentrations of sTIM-3 and Galectin-9 in serum were determined by ELISA. Multivariate logistic regression assessed independent links between these markers and disease progression, supplemented by trend tests, E-value calculations, and subgroup analyses. RESULTS: The study included 120 POAG patients (52 progression, 68 stable) and 60 healthy controls. Baseline measures were balanced across groups. Both sTIM-3 and Galectin-9 were significantly elevated in progression relative to stable patients and controls (all P < 0.001). Multivariate logistic regression identified sTIM-3 (OR = 2.14, P = 0.004) and Galectin-9 (OR = 3.39, P < 0.001) as independent factors linked to disease progression. Trend analyses revealed dose-response patterns (P for trend = 0.015 and 0.004, respectively). These findings were further corroborated by E-value and subgroup analyses, supporting their robustness. CONCLUSIONS: Higher baseline sTIM-3 and Galectin-9 levels correlate independently with POAG progression risk, showing a dose-response pattern. These biomarkers may serve as adjunctive references for risk stratification, although their utility warrants prospective validation with longitudinal sampling.