A disrupted circadian rhythm does more than leave you groggy — it may also threaten your sight. A large retrospective study published as a preprint on Research Square reports that people diagnosed with circadian rhythm sleep disorder (CRSD) develop open-angle glaucoma at roughly three times the rate of matched controls. Among those who took melatonin, the excess risk was no longer statistically significant.
The findings come from a team led by Taher Eleiwa and Abdelrahman Elhusseiny at the University of Texas Medical Branch and the University of Miami, who analyzed electronic health records from the TriNetX research network — one of the largest real-world clinical databases available. The study has not yet been peer reviewed.
What they found
The researchers identified 24,730 adults with a recorded diagnosis of circadian rhythm sleep disorder and matched them one-to-one with controls who had undergone polysomnography but had no sleep disorder diagnosis. The two groups were balanced for age, sex, race, and common glaucoma risk factors including diabetes, hypertension, and intraocular pressure-lowering medication use.
Over five years of follow-up, the CRSD group consistently showed higher rates of open-angle glaucoma (OAG):
- At 1 year: 0.14% versus 0.04% — an adjusted hazard ratio (aHR) of 2.67 (95% CI 1.42–5.02, P = .0005)
- At 3 years: 0.25% versus 0.07% — aHR 3.02 (95% CI 1.81–5.05, P < .0001)
- At 5 years: 0.27% versus 0.08% — aHR 2.88 (95% CI 1.78–4.66, P < .0001)
The pattern was similar for primary open-angle glaucoma (POAG) and was consistent across subgroup analyses stratified by age, sex, and comorbidities. Notably, there was no significant difference for ocular hypertension (OHT), suggesting the effect relates to glaucomatous optic nerve damage rather than simply elevated eye pressure.
The melatonin finding
Perhaps the most intriguing result involved melatonin. Among 4,081 matched pairs where the CRSD group had documented melatonin use, the glaucoma risk difference between CRSD patients and controls shrank substantially and lost statistical significance. At five years, OAG occurred in 0.52% of melatonin-taking CRSD patients versus 0.32% of controls — an aHR of 2.07 (95% CI 0.88–4.84, P = .23).
This finding held for POAG and OHT as well, and it was observed only among CRSD patients with documented melatonin use — not in the CRSD group overall.
The authors are careful not to overstate the result. “Melatonin use appears to decrease the risk of developing OAG among CRSD patients,” they write, noting that the observational design cannot prove causation. But the data raise a clear hypothesis: that melatonin’s known properties as a circadian rhythm regulator, antioxidant, and intraocular pressure modulator may collectively protect the optic nerve in patients whose circadian systems are compromised.
Why it matters
Glaucoma is the leading cause of irreversible blindness worldwide, affecting roughly 80 million people. Open-angle glaucoma — the most common form — is insidious: it destroys retinal ganglion cells and optic nerve fibers gradually, often without symptoms until vision loss is advanced. Elevated intraocular pressure is the only modifiable risk factor targeted by current treatments, yet many patients continue to lose vision despite well-controlled pressure.
The idea that circadian disruption itself could be an independent risk factor for glaucoma has been gaining ground. The eye has its own intrinsic circadian clock, and melatonin receptors are present throughout ocular tissues, including the ciliary body and retina. Disrupted sleep-wake cycles have been linked to elevated intraocular pressure in previous studies, but the TriNetX analysis is among the largest to examine the connection using real-world clinical outcomes.
If confirmed, the findings would open a new avenue for risk stratification and possibly prevention. Sleep disorders are common, treatable, and underdiagnosed — and melatonin is a widely available, low-cost supplement with a favorable safety profile. A simple intervention targeting circadian health could, in principle, reduce glaucoma risk in a subset of patients.
Limits
The study has significant limitations that warrant caution. As a retrospective analysis of electronic health records, it can identify associations but cannot prove that CRSD causes glaucoma. The absolute event rates were low — below 0.3% in both groups even at five years — meaning the absolute risk increase for an individual with CRSD remains modest, even if the relative increase is large.
The CRSD diagnosis relied on ICD billing codes rather than objective circadian phase measurements, which introduces classification uncertainty. Melatonin use was inferred from prescription records, so over-the-counter use was not captured. And because the study draws from the TriNetX database, results may not generalize to populations not represented in that network.
Crucially, this is a preprint: it has not undergone peer review and should be interpreted as preliminary evidence pending formal evaluation.
Bottom line
Circadian rhythm sleep disorder was associated with approximately a threefold higher risk of open-angle glaucoma in this large retrospective analysis. Melatonin use appeared to attenuate the excess risk, though the observational design precludes causal conclusions. For clinicians, the findings reinforce the importance of sleep health as part of overall medical care — and for researchers, they point toward a testable hypothesis about melatonin’s potential role in neuroprotection.
Source
Eleiwa, T., Chauhan, M., Kishor, K., Al Aref, S., Khodeiry, M., Abboud, I., Bhattacharya, S., Lee, R., & Elhusseiny, A. “Association between circadian rhythm sleep disorder and open-angle glaucoma: The modifying role of melatonin.” Research Square Preprint] (2026). DOI: [10.21203/rs.3.rs-9740601/v1. PMCID: PMC13321238.
This is a preprint — not yet peer reviewed.