Associations of sleep apnoea with glaucoma and age-related macular degeneration: an analysis in the United Kingdom Biobank and the Canadian Longitudinal Study on Aging

Abstract

Background: Sleep apnoea, a common sleep-disordered breathing condition, is characterised by upper airway collapse during sleep resulting in transient hypoxia, hypoperfusion of the optic nerve, and spike in intracranial pressure. Previous studies have reported conflicting findings on the association of sleep apnoea with glaucoma, and there are limited reports on the link between sleep apnoea and age-related macular degeneration (AMD).

Methods: Middle-aged and older participants from the longitudinal United Kingdom (UK) Biobank (n = 502,505) and the Canadian Longitudinal Study on Aging (CLSA; n = 24,073) were included in this analysis. Participants in the UK Biobank and the CLSA were followed for 8 and 3 years, respectively. Participants with diagnosed glaucoma or AMD at baseline were excluded from the analysis. In the UK Biobank, sleep apnoea and incident cases of glaucoma and AMD were identified through hospital inpatient admission, primary care records, and self-reported data. Multivariable Cox proportional hazards models were used to explore associations of sleep apnoea with incidence of glaucoma or AMD.

Results: During the 8-year follow-up in the UK Biobank, glaucoma incidence rates per 1000 person-years were 2.46 and 1.59 for participants with and without sleep apnoea, and the AMD incidence rates per 1000 person-years were 2.27 and 1.42 for participants with and without sleep apnoea, respectively. Multivariable adjusted hazard ratios of glaucoma and AMD risk for sleep apnoea were 1.33 (95% confidence interval [CI] 1.10-1.60, P = 0.003) and 1.39 (95% CI 1.15-1.68, P < 0.001) relative to participants without sleep apnoea. In the CLSA cohort, disease information was collected through in-person interview questionnaires. During the 3-year follow-up, glaucoma incidence rates per 1000 person-years for those with and without sleep apnoea were 9.31 and 6.97, and the AMD incidence rates per 1000 person-years were 8.44 and 6.67, respectively. In the CLSA, similar associations were identified, with glaucoma and AMD odds ratios of 1.43 (95% CI 1.13-1.79) and 1.39 (95% CI 1.08-1.77), respectively, in participants with sleep apnoea compared to those without sleep apnoea (both P < 0.001).

Conclusions: In two large-scale prospective cohort studies, sleep apnoea is associated with a higher risk of both glaucoma and AMD. These findings indicate that patients with sleep apnoea might benefit from regular ophthalmologic examinations.

Keywords: Age-related macular degeneration; CLSA; Cohort study; Glaucoma; Sleep apnoea; UK Biobank.

Fig. 1

Flowchart of United Kingdom (UK) Biobank participants. A total of 502,505 participants aged between 40 and 69 at baseline were recruited between 2006 and 2010. a The Venn diagram of the UK Biobank participants who have any hospital inpatient records (82.3%), primary care clinical records (45.8%), giving consent to touchscreen questionnaires for self-reported eye problems/disorders (34.7%), or any records of self-reported non-cancer illness (99.8%). b The flowchart of the UK Biobank participants. In the analysis, glaucoma or age-related macular degeneration (AMD) cases were removed if age at diagnosis information was unavailable. Glaucoma and AMD cases were also removed if cases were prevalent before the baseline recruitment or before the age of sleep apnoea diagnosis (if sleep apnoea developed after baseline visit). The follow-up time was calculated from the time of recruitment (or age of sleep apnoea diagnosed if sleep apnoea developed after recruitment). Cox regression models were used to evaluate the associations between sleep apnoea and incidence risk of glaucoma and AMD. Sensitivity analysis was also performed to remove participants who developed sleep apnoea after the baseline visit

Fig. 2

Associations of sleep apnoea with the incidence of glaucoma and AMD by different subgroups in UK Biobank. Three different models were used to adjust for covariates. Sex was not included as a covariate for sex subgroup analysis, and disease status was not included as a covariate for its specific subgroup analysis. Model 1: cox regression models adjusted for age and sex; model 2: adjusted for age, sex, Townsend deprivation index, ethnic group, smoking status, diabetes, cardiovascular disease, systolic blood pressure, waist-to-hip ratio, total cholesterol, and high-density lipoprotein cholesterol. Model 3: included model 2 variables plus indicator variables for wearing glasses, having any hospital inpatient records, having any primary care clinical records, and giving consent to touchscreen questionnaires. AMD, age-related macular degeneration; CI, confidence interval; HR, hazard ratio; DM, diabetes; CVD, cardiovascular disease

Fig. 3

Associations of sleep apnoea with the incidence of glaucoma and AMD in the Canadian Longitudinal Study on Aging (CLSA). Three different models were used to adjust for covariates. Sex was not included as a covariate for sex subgroup analysis, and disease status was not included as a covariate for its specific subgroup analysis. Model 1: logistic regression models adjusted for age and sex; model 2: adjusted for age, sex, self-rated social standing, ethnic group, smoking status, diabetes, heart disease, systolic blood pressure, waist-to-hip ratio, total cholesterol, and high-density lipoprotein cholesterol. AMD, age-related macular degeneration; CI, confidence interval; OR, odds ratio; DM, diabetes; HD, heart disease