Risk of new-onset glaucoma in people with carpal tunnel syndrome: a global-federated, multicenter retrospective cohort study.

Background: Carpal tunnel syndrome (CTS) is a common entrapment neuropathy involving chronic inflammation, while glaucoma is an optic neuropathy linked to neuroinflammation and vascular insufficiency. Shared pathogenic mechanisms have been hypothesized, but large-scale epidemiologic evidence is lacking. This study aims to evaluate whether CTS patients present an elevated risk of glaucoma compared to CTS-free individuals. Materials and Methods: We conducted a retrospective cohort study using the TriNetX global research network. Adults diagnosed with CTS were matched 1:1 with CTS-free controls based on demographics, comorbidities, and healthcare utilization. The primary outcome was new-onset glaucoma, with subtypes assessed separately. Cox proportional hazard models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Sensitivity analyses included alternative matching algorithms, washout periods, and comparisons with autoimmune musculoskeletal diseases. Results: After matching (n = 733,997 per group), CTS was associated with an increased risk of glaucoma (HR = 1.57, 95% CI: 1.52-1.62). Risks were elevated across glaucoma subtypes, including open-angle glaucoma (HR = 1.55, 95% CI: 1.44-1.66) and angle-closure glaucoma (HR = 1.67, 95% CI: 1.38-2.02). Sensitivity analyses confirmed the robustness of the association across multiple models. When compared to patients with autoimmune musculoskeletal diseases, CTS patients had a higher risk of glaucoma than those with rheumatoid arthritis (HR = 1.73, 95% CI: 1.60-1.87) or ankylosing spondylitis (HR = 1.36, 95% CI: 1.20-1.53). Conclusion: Carpal tunnel syndrome is associated with a significantly increased risk of glaucoma. These findings support the involvement of shared inflammatory or vascular mechanisms and highlight the growing concern about ocular comorbidities in patients with CTS.