Association between circadian rhythm sleep disorder and open-angle glaucoma: The modifying role of melatonin

Background: Circadian rhythm sleep disorders (CRSD) may disrupt neurovascular regulation and increase open-angle glaucoma (OAG) and ocular hypertension (OHT) risk. This study assessed associations with OAG, primary open-angle glaucoma (POAG), and OHT and examined melatonin’s modifying effect. Methods: A retrospective cohort study using TriNetX data included adults (≥ 18 years) with CRSD matched 1:1 to polysomnography-tested controls without sleep disorders. Melatonin subgroups were analyzed. Among 24,730 matched pairs, ICD-10–defined OAG, POAG, and OHT at 1, 3, and 5 years were assessed using adjusted hazard ratios (aHRs) and Kaplan–Meier analyses. Results: After matching, 24,730 patients were included in each group. The CRSD group had a significantly higher risk of OAG at 1 year (0.14% vs. 0.04%; P=.0005; aHR 2.67, 95% CI 1.42–5.02), 3 years (0.25% vs. 0.07%; P < .0001; aHR 3.02, 95% CI 1.81–5.05), and 5 years (0.27% vs. 0.08%; P < .0001; aHR 2.88, 95% CI 1.78–4.66). Similar trends were observed for POAG, while no significant differences were seen for OHT. Among CRSD patients not using melatonin (n = 24,150 pairs), OAG risk remained significantly elevated at all time points. In contrast, among melatonin users (n = 4,081 pairs), the risks of OAG, and OHT were not significantly different from controls (5-year OAG: 0.52% vs. 0.32%; P = .23; aHR 2.07, 95% CI 0.88–4.84). Conclusions: CRSD is associated with an increased risk of OAG and POAG, in patients not using melatonin. Melatonin use appears to decrease this risk, suggesting a potential protective effect.