Glaucoma Linked to Increased Risk of Sleep-Wake Disorders

A recent AJO study reveals a significant association between glaucoma and an increased risk of sleep-wake disorders, including circadian rhythm disruptions. Researchers found that Medicare beneficiaries with glaucoma were 26% more likely to experience sleep-wake disorders than those without the diagnosis. This large-scale study suggests that glaucomatous damage may impact light-dependent melatonin pathways, which are crucial for regulating sleep cycles. Photo: Michael Chaglasian, OD. Click image to enlarge. In a world where sleep is a precious commodity, research into causes of sleep disturbances shows glaucoma may be a prime suspect. Associations have been found suggesting glaucomatous disease may disrupt circadian rhythms and sleep-wake functions as a result of its damage of melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) and axons in the optic nerve. Due to the role of ipRGCs in stimulating the pineal gland, which modulates physiological sleep-wake functions, this is further evidence of a mechanistic link between glaucoma and sleep disorders. In order to support these findings, a group of researchers from the University of California used a large and diverse population of the state’s Medicare beneficiaries. Their results, published recently in American Journal of Ophthalmology, found that individuals with glaucoma had a higher likelihood of experiencing any sleep-wake disorder, and specifically circadian rhythm sleep disorders (CRSD). Over 2.7 million California Medicare beneficiaries met the inclusion criteria. All were 65 years old or older, had both Parts A and B coverage and had one or more Part B claims in their records. The associations between glaucoma, CRSD and any sleep-wake disorders were estimated using multivariable logistic regression models, adjusting for age, sex, race and ethnicity, age-related macular degeneration (AMD), diabetic retinopathy, cataracts, pseudophakia and systemic disease burden defined by the Charlson Comorbidity Index (CCI) score. The effect estimate was expressed as an adjusted odds ratio (aOR).Of the 220,662 subjects included in the study, 8.1% had glaucoma, 0.1% had CRSD and 13.1% had any sleep-wake disorder. Of the beneficiaries with glaucoma, 15.7% had a concurrent sleep-wake disorder, and 0.2% had a concurrent CRSD diagnosis. Beneficiaries with glaucoma were 26% more likely than those without it to have any sleep-wake disorder (OR: 1.26) in unadjusted analyses. This association remained consistent after adjusting for covariates (aOR: 1.12). Additionally, beneficiaries with glaucoma had increased odds of CRSD in both unadjusted and adjusted models (unadjusted OR:1.29; aOR: 1.20). “The findings of the present study strengthen findings from previous studies, which were mainly conducted in small populations with questionnaires and self-reporting, by demonstrating consistency of associations between glaucoma and increased likelihood of sleep disorders in the large and diverse CA Medicare population,” wrote the study authors in AJO. “In addition to the association between glaucoma and increased prevalence of any sleep-wake disorders, we also found an association between glaucoma and increased likelihood specifically of CRSD.” They noted that previous studies have suggested changes in circadian rhythm body temperatures and reductions in mean sleep duration in primary open-angle glaucoma patients. “One potential explanation for these findings is that glaucomatous damage may potentially influence light-dependent melatonin pathways, a main driver for circadian rhythm cycles, which may influence the risk of CRSD.”The UCLA researchers expressed their confidence in the statistical power of this study due to the size and prevalence of glaucoma and sleep-wake disorders in the sample. However, they did note limitations, such as the inability to evaluate patient medications—which could contribute to sleep-wake disorders—and incomplete information regarding the severity and type of glaucoma. “Similarly, the current study did not evaluate for the prevalence or associations of other types of sleep-wake disorders in those with glaucoma subtypes,” wrote the authors in their paper discussion, where they advocated for future studies using a more granular approach to evaluate for all types of sleep-wake disorders among various glaucoma subtypes.Another shortcoming they acknowledged was the absence of illumination on the pathophysiology at work in the associations. “The current study provides a contextual framework on how glaucoma affects sleep-wake disorders and CRSD; however, it does not evaluate the cause-and-effect relationships nor any mechanistic relationships between glaucoma, sleep-wake disorders and CRSDs,” they wrote. “As such, this warrants further investigation into the mechanistic pathways and associations of ipRGCs, melatonin, the SCN pathway and glaucoma.”Although further research is warranted to understand the underlying mechanism for this association, the study authors are confident in their findings and say “investigations of screening strategies for sleep-wake disorders including CRSD in individuals with glaucoma may be beneficial to reduce morbidity and increase quality of life.”Click here for the journal source. Ramirez M, Kitayama K, Puran A, Tseng VL, Yu F, Coleman AL. The associations between glaucoma and circadian rhythm sleep disorders in California Medicare beneficiaries. Am J Ophthalmol. June 13, 2025. [Epub ahead of print.]