Associations Among Sleep Duration, Sleep Quality, and Age-Related Ocular Diseases: Insights From Longitudinal and Mediation Analyses

Abstract

Purpose: To investigate the associations among sleep duration, sleep quality, and age-related ocular diseases, accounting for interactions with systemic inflammation.

Methods: A total of 380,182 participants in the UK Biobank were included in this prospective population-based cohort study. The investigated exposures were sleep duration, sleep quality (quantified through an established algorithm comprised of five sleep traits), and traits including insomnia, daytime dozing, chronotype, and snoring. Outcomes were incidences of cataract, primary open-angle glaucoma (POAG), diabetic retinopathy (DR), and age-related macular degeneration (AMD). Cox proportional hazards models were used to estimate the hazard ratios (HRs), with mediation analysis of systematic inflammatory indicators further performed to explore potential mechanisms.

Results: During a median follow-up of 12.6 years, 42,971 cataract cases, 5793 POAG cases, 4267 DR cases, and 7775 AMD cases were documented. Sleep duration displayed U-shaped relationships with cataract, POAG, and DR (all P nonlinear < 0.001), identifying 7 hours per day as optimal. Poor sleep quality also elevated the risks of cataract (HR = 1.17; P < 0.001) and POAG (HR = 1.21; P = 0.019), whereas for DR this effect was not significant but suggestive (HR = 1.15; P = 0.082). Sleep behavior traits including insomnia and daytime dozing were found to predict higher risks of these diseases. Mediation analysis indicated significant contributions of inflammatory indicators to the associations of poor sleep quality with cataract and DR.

Conclusions: Our findings suggest that sleep patterns might be modifiable risk factors for age-related ocular diseases and highlight the potential value of anti-inflammatory therapies to delay the manifestations of ocular aging.

Figure 1.

(A–D) Associations between sleep duration and incident cataract (A), POAG (B), DR (C), or AMD (D). HRs and 95% CIs were calculated by Cox proportional hazards regression models. Model 1 was adjusted for age and sex; model 2 included model 1 plus ethnicity, Townsend deprivation index, alcohol intake frequency, smoking status, and physical activity; and model 3 included model 2 plus BMI, history of hypertension, and history of diabetes.

Figure 2.

(A–C) U-shaped associations between sleep duration and incident cataract (A), POAG (B), or DR (C). HRs and 95% CIs were calculated by restricted cubic splines fitted in Cox proportional hazards regression models, with a dashed vertical line indicating the nadir. The analysis was adjusted for age, sex, ethnicity, Townsend deprivation index, alcohol intake frequency, smoking status, physical activity, BMI, history of hypertension, and history of diabetes.

Figure 3.

(A–D) Associations between sleep quality type and incident cataract (A), POAG (B), DR (C), or AMD (D). HRs and 95% CIs were calculated by Cox proportional hazards regression models. Model 1 was adjusted for age and sex; model 2 included model 1 plus ethnicity, Townsend deprivation index, alcohol intake frequency, smoking status, and physical activity; and model 3 included model 2 plus BMI, history of hypertension, and history of diabetes.

Figure 4.

(A–C) Mediation analyses of inflammatory indicators in the associations between sleep quality and cataract (A), POAG (B), or DR (C). The mediating effects of a combination of significant original indicators or the INFLA-score are presented as P values and proportions of mediation (95% CIs). Data were fully adjusted for model 3. WBC, white blood cell. ***P < 0.001, **P < 0.01, *P < 0.05.