HormonesMelatonin

Circadian rhythm sleep disorder increases risk of open-angle glaucoma, but melatonin use may reduce this risk

In a retrospective cohort study of 24,730 matched pairs, patients with circadian rhythm sleep disorder (CRSD) had a significantly higher risk of open-angle glaucoma (OAG) at 1 year (0.14% vs. 0.04%; aHR 2.67), 3 years (0.25% vs. 0.07%; aHR 3.02), and 5 years (0.27% vs. 0.08%; aHR 2.88). Among CRSD patients using melatonin, the risk of OAG was not significantly different from controls, suggesting a potential protective effect of melatonin.

Last updated: Jul 7, 2026•0 RCTs•📖 Read as article →

Evidence Score

Evidence Score34/100
Human RCT☆☆☆☆☆
Meta-analysis☆☆☆☆☆
Mechanism★★★★★
Safety★★★★☆
Confidencelow

Study Evidence

Study 1. Association between circadian rhythm sleep disorder and open-angle glaucoma: The modifying role of melatonin.

observational

Eleiwa T, Chauhan M, Kishor K, Al Aref S, Khodeiry M, Abboud I, Bhattacharya S, Lee R, Elhusseiny A · Research square (2026)

Participants: N/A
Duration: 5 years
Intervention: Circadian rhythm sleep disorder (CRSD) diagnosis vs. polysomnography-tested controls without sleep disorders; subgroup analysis of melatonin use
Outcome: Incidence of open-angle glaucoma (OAG), primary open-angle glaucoma (POAG), and ocular hypertension (OHT) at 1, 3, and 5 years
Effect Size: 5-year OAG aHR 2.88 (95% CI 1.78-4.66) for CRSD vs. controls; 5-year OAG aHR 2.07 (95% CI 0.88-4.84) for melatonin users
Population: Adults (≥18 years) with CRSD matched 1:1 to controls from TriNetX database

Result:

PubMed: 42396504DOI: 10.21203/rs.3.rs-9740601/v1

Mechanism Graph

CRSD disrupts neurovascular regulation
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Disrupted neurovascular regulation increases intraocular pressure or optic nerve vulnerability
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Melatonin may restore circadian rhythms or provide direct neuroprotective effects
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Result: Reduced risk of OAG in melatonin users

Limitations

  • ⚠Retrospective cohort design limits causal inference
  • ⚠Reliance on ICD-10 codes may introduce misclassification bias
  • ⚠Melatonin use was based on prescription records, not actual adherence or dosage

Frequently Asked Questions

What is the main finding of this study?▼

Circadian rhythm sleep disorder is associated with a nearly threefold increased risk of open-angle glaucoma over 5 years, but this risk appears to be mitigated in patients using melatonin.

How large was the study population?▼

The study included 24,730 matched pairs (49,460 total patients) from the TriNetX database.

Did melatonin completely eliminate the risk of glaucoma?▼

No, but the risk was no longer statistically significant in melatonin users (5-year OAG: 0.52% vs. 0.32%; aHR 2.07, 95% CI 0.88-4.84, P=.23).

What type of study was this?▼

This was a retrospective cohort study using electronic health record data from TriNetX.

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References

  1. 1.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, 2026. PMID: 42396504 DOI: 10.21203/rs.3.rs-9740601/v1
Disclaimer: This content is for educational purposes only and is not medical advice. Evidence scores reflect the quality and quantity of available research, not clinical recommendations. Always consult a healthcare professional before starting any supplement or intervention.