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Editors Selection IGR 16-2

Glaucoma and Systemic Diseases: Glaucoma linked to circadian rhythm sleep disorders in millions

Comment by Tina Wong & Nicholas Tan on:

127125 The Associations Between Glaucoma and Circadian Rhythm Sleep Disorders in California Medicare Beneficiaries, Ramirez M; Kitayama K; Kitayama K; Puran A et al., American Journal of Ophthalmology, 2025; 278: 250-256

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In a cross-sectional analysis of 2.7 million 2019 California Medicare beneficiaries, Ramirez and colleagues report that people coded as having glaucoma had higher adjusted odds of circadian rhythm sleep disorder (CRSD; aOR ~1.20) and of any sleep-wake disorder (aOR ~1.12), after adjustment for demographic factors, ocular diseases, and systemic comorbidity burden. A major strength of this study is its scale. With >2.7 million beneficiaries and >220,000 glaucoma cases, this is one of the largest “real-world” datasets investigating the glaucoma–sleep question. Amongst literature often dominated by smaller clinic cohorts and self-reported questionnaires, this breadth and use of objective clinical data is valuable. That said, the study’s key limitations are also inseparable from its main advantage: utilisation of ICD-coded claims data. First, glaucoma patients (particularly those with normal-tension glaucoma or progressive disease despite “controlled” IOP) may be more likely to get questioned about sleep and referred for evaluation. If so, the glaucoma–sleep disorder “association” may be partly due to differential surveillance rather than true excess disease. Second, the reported CRSD prevalence is so low (~0.1% overall; ~0.2% in glaucoma) that the presence of a CRSD code may reflect coding behaviour more so than true prevalence. This also raises a pragmatic question: why not disaggregate more common sleep-wake disorder subtypes within G47 (e.g., sleep apnoea) to identify what is driving the overall signal? Nevertheless, this study’s headline result is directionally consistent with a growing narrative that sleep disorders are implicated in glaucoma. However, as with any cross-sectional analysis, direction of causality cannot be inferred. The authors appropriately discuss the hypothesis that glaucoma damages ipRGCs, reducing photic input to the suprachiasmatic nucleus and disrupting circadian regulation. That pathway is biologically credible and supported by experimental and clinical data.1–3 However, the converse pathway is arguably the more clinically provocative one. Sleep is a fundamental biological process, and when dysregulated, it is increasingly linked to elevated risk across diverse diseases (and glaucoma may be among them). However, modern life increasingly drives circadian misalignment (e.g., light at night and screen use, irregular schedules, shift work) amidst a backdrop of increased multimorbidity in an ageing population—conditions already associated with poorer sleep quantity and quality. In this context, the most interesting question raised by this study is not simply whether glaucoma and sleep disorders co-occur, but whether worsening sleep health represents a modifiable risk exposure for glaucoma.

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