Sleep regularity and age-related eye diseases: prospective analyses with retinal imaging and multimorbidity assessment in the UK Biobank

STUDY OBJECTIVES: Sleep regularity, a key circadian dimension of sleep health, has been linked to cardiometabolic and neurodegenerative outcomes, yet its relevance to ocular aging remains unclear. The retina is a metabolically active, circadian-regulated neural tissue, suggesting that irregular sleep may contribute to the development of age-related eye diseases. METHODS: We studied 78 839 adults in the UK Biobank. Sleep regularity was quantified using the sleep regularity index (SRI). Associations with age-related macular degeneration (AMD), cataract, glaucoma, retinal vein occlusion (RVO), and diabetic retinopathy (DR) were examined using Cox models, restricted cubic splines, subgroup analyses, and propensity-score matching. Retinal structural and vascular metrics were additionally evaluated. Nomogram models integrating the SRI with clinical risk factors were developed. RESULTS: A lower SRI was consistently associated with higher risks of AMD (hazard ratio [HR] = 0.87), cataract (HR = 0.95), and glaucoma (HR = 0.89), with clear dose-response patterns; no robust associations were found for RVO or DR. A higher SRI correlated with greater macular, retinal ganglion cell, and retinal nerve fiber layer thicknesses, and with more favorable retinal vascular geometry. Incorporating the SRI improved prediction performance for AMD, cataract, and glaucoma (area under the curve 0.72-0.74). The SRI also declined markedly with increasing ocular multimorbidity. CONCLUSIONS: Sleep regularity was consistently associated with major age-related eye diseases, ocular multimorbidity, and retinal structural and vascular characteristics. These findings highlight sleep regularity as a clinically relevant behavioral correlate of ocular aging and a potential adjunctive marker for prevention-oriented risk stratification. Statement of Significance In a large UK Biobank cohort with device-measured sleep data, lower sleep regularity was independently associated with higher risks of age-related macular degeneration, cataract, and glaucoma, but not retinal vein occlusion or diabetic retinopathy. Sleep irregularity correlated with adverse retinal neurovascular features, shared inflammatory and metabolic proteomic signatures, and greater ocular multimorbidity, supporting sleep regularity as a modifiable determinant of ocular aging.