Visual Function, Social Position, and Health and Life Chances: The UK Biobank Study

Importance: The adverse impact of visual impairment and blindness and correlations with socioeconomic position are known. Understanding of the effect of the substantially more common near-normal vision (mild impairment) and associations with social position as well as health and life chances is limited. Objective: To investigate the association of visual health (across the full acuity spectrum) with social determinants of general health and the association between visual health and health and social outcomes. Design, Setting, and Participants: A cross-sectional epidemiologic study was conducted using UK Biobank data from 6 regional centers in England and Wales. A total of 112 314 volunteers (aged 40-73 years) were assessed in June 2009 and July 2010. Data analysis was performed from May 20, 2013, to November 19, 2014. Main Outcomes and Measures: Habitual (correction if prescribed) distance visual acuity was used to assign participants to 1 of 8 categories from bilateral normal visual acuity (logMAR, 0.2 or better; Snellen equivalent, 6/9.5 or better) to visual impairment or blindness (logMAR, 0.5 or worse; Snellen equivalent, 6/19 or worse) using World Health Organization and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision taxonomy. Relationships between vision, key social determinants and health and social outcomes (including the main factors that define an individual's life-the social, economic, educational, and employment opportunities and outcomes experienced by individuals during their life course) were examined using multivariable regression. Results: Of the of 112 314 participants, 61 169 were female (54.5%); mean (SD) age was 56.8 (8.1) years. A total of 759 (0.7%) of the participants had visual impairment or blindness, and an additional 25 678 (22.9%) had reduced vision in 1 or both eyes. Key markers of social position were independently associated with vision in a gradient across acuity categories; in a gradient of increasing severity, all-cause impaired visual function was associated with adverse social outcomes and impaired general and mental health. These factors, including having no educational qualifications (risk ratio [RR], 1.86 [95% CI, 1.69-2.04]), having a higher deprivation score (RR, 1.08 [95% CI, 1.07-1.09]), and being in a minority ethnic group (eg, Asian) (RR, 2.05 [95% CI, 1.83-2.30]), were independently associated with being in the midrange vision category (at legal threshold for driving). This level of vision was associated with an increased risk of being unemployed (RR, 1.55 [95% CI, 1.31-1.84]), having a lower-status job (RR, 1.24 [95% CI, 1.09-1.41]), living alone (RR, 1.24 [95% CI, 1.10-1.39]), and having mental health problems (RR, 1.12 [95% CI, 1.04-1.20]). Conclusions and Relevance: Impaired vision in adults is common, and even near-normal vision, potentially unrecognized without assessment, has a tangible influence on quality of life. Because inequalities in visual health by social position mirror other health domains, inclusion of vision in generic initiatives addressing health inequalities could address the existing significant burden of underrecognized and/or latent visual disability. Longitudinal investigations are needed to elucidate pathophysiologic pathways and target modifiable mechanisms

Cohort profile: design and methods in the eye and vision consortium of UK Biobank

PURPOSE: To describe the rationale, methods and research potential of eye and vision measures available in UK Biobank. PARTICIPANTS: UK Biobank is a large, multisite, prospective cohort study. Extensive lifestyle and health questionnaires, a range of physical measures and collection of biological specimens are collected. The scope of UK Biobank was extended midway through data collection to include assessments of other measures of health, including eyes and vision. The eye assessment at baseline included questionnaires detailing past ophthalmic and family history, measurement of visual acuity, refractive error and keratometry, intraocular pressure (IOP), corneal biomechanics, spectral domain optical coherence tomography (OCT) of the macula and a disc-macula fundus photograph. Since recruitment, UK Biobank has collected accelerometer data and begun multimodal imaging data (including brain, heart and abdominal MRI) in 100 000 participants. Dense genotypic data and a panel of 20 biochemistry measures are available, and linkage to medical health records for the full cohort has begun. FINDINGS TO DATE: A total of 502 665 people aged between 40 and 69 were recruited to participate in UK Biobank. Of these, 117 175 took part in baseline assessment of vision, IOP, refraction and keratometry. A subgroup of 67 321 underwent OCT and retinal photography. The introduction of eye and vision measures in UK Biobank was accompanied by intensive training, support and a data monitoring quality control process. FUTURE PLANS: UK Biobank is one of the largest prospective cohorts worldwide with extensive data on ophthalmic diseases and conditions. Data collection is an ongoing process and a repeat of the baseline assessment including the questionnaires, measurements and sample collection will be performed in subsets of 25 000 participants every 2-3 years. The depth and breadth of this dataset, coupled with its open-access policy, will create a powerful resource for all researchers to investigate the eye diseases in later life

Genome-wide association studies for corneal and refractive astigmatism in UK Biobank demonstrate a shared role for myopia susceptibility loci.

Previous studies have suggested that naturally occurring genetic variation contributes to the risk of astigmatism. The purpose of this investigation was to identify genetic markers associated with corneal and refractive astigmatism in a large-scale European ancestry cohort (UK Biobank) who underwent keratometry and autorefraction at an assessment centre. Genome-wide association studies for corneal and refractive astigmatism were performed in individuals of European ancestry (N = 86,335 and 88,005 respectively), with the mean corneal astigmatism or refractive astigmatism in fellow eyes analysed as a quantitative trait (dependent variable). Genetic correlation between the two traits was calculated using LD Score regression. Gene-based and gene-set tests were carried out using MAGMA. Single marker-based association tests for corneal astigmatism identified four genome-wide significant loci (P < 5 × 10-8) near the genes ZC3H11B (1q41), LINC00340 (6p22.3), HERC2/OCA2 (15q13.1) and NPLOC4/TSPAN10 (17q25.3). Three of these loci also demonstrated genome-wide significant association with refractive astigmatism: LINC00340, HERC2/OCA2 and NPLOC4/TSPAN10. The genetic correlation between corneal and refractive astigmatism was 0.85 (standard error = 0.068, P = 1.37 × 10-35). Here, we have undertaken the largest genome-wide association studies for corneal and refractive astigmatism to date and identified four novel loci for corneal astigmatism, two of which were also novel loci for refractive astigmatism. These loci have previously demonstrated association with axial length (ZC3H11B), myopia (NPLOC4), spherical equivalent refractive error (LINC00340) and eye colour (HERC2). The shared role of these novel candidate genes for astigmatism lends further support to the shared genetic susceptibility of myopia and astigmatism

Cohort profile:rationale and methods of UK Biobank repeat imaging study eye measures to study dementia

Purpose: the retina provides biomarkers of neuronal and vascular health that offer promising insights into cognitive ageing, mild cognitive impairment and dementia. This article described the rationale and methodology of eye and vision assessments with the aim of supporting the study of dementia in the UK Biobank Repeat Imaging study.Participants: UK Biobank is a large-scale, multicentre, prospective cohort containing in-depth genetic, lifestyle, environmental and health information from half a million participants aged 40-69 enrolled in 2006-2010 across the UK. A subset (up to 60 000 participants) of the cohort will be invited to the UK Biobank Repeat Imaging Study to collect repeated brain, cardiac and abdominal MRI scans, whole-body dual-energy X-ray absorptiometry, carotid ultrasound, as well as retinal optical coherence tomography (OCT) and colour fundus photographs.Findings to date: UK Biobank has helped make significant advances in understanding risk factors for many common diseases, including for dementia and cognitive decline. Ophthalmic genetic and epidemiology studies have also benefited from the unparalleled combination of very large numbers of participants, deep phenotyping and longitudinal follow-up of the cohort, with comprehensive health data linkage to disease outcomes. In addition, we have used UK Biobank data to describe the relationship between retinal structures, cognitive function and brain MRI-derived phenotypes.Future plans: the collection of eye-related data (eg, OCT), as part of the UK Biobank Repeat Imaging study, will take place in 2022-2028. The depth and breadth and longitudinal nature of this dataset, coupled with its open-access policy, will create a major new resource for dementia diagnostic discovery and to better understand its association with comorbid diseases. In addition, the broad and diverse data available in this study will support research into ophthalmic diseases and various other health outcomes beyond dementia

Cohort profile: rationale and methods of UK Biobank repeat imaging study eye measures to study dementia

PURPOSE: The retina provides biomarkers of neuronal and vascular health that offer promising insights into cognitive ageing, mild cognitive impairment and dementia. This article described the rationale and methodology of eye and vision assessments with the aim of supporting the study of dementia in the UK Biobank Repeat Imaging study. PARTICIPANTS: UK Biobank is a large-scale, multicentre, prospective cohort containing in-depth genetic, lifestyle, environmental and health information from half a million participants aged 40-69 enrolled in 2006-2010 across the UK. A subset (up to 60 000 participants) of the cohort will be invited to the UK Biobank Repeat Imaging Study to collect repeated brain, cardiac and abdominal MRI scans, whole-body dual-energy X-ray absorptiometry, carotid ultrasound, as well as retinal optical coherence tomography (OCT) and colour fundus photographs. FINDINGS TO DATE: UK Biobank has helped make significant advances in understanding risk factors for many common diseases, including for dementia and cognitive decline. Ophthalmic genetic and epidemiology studies have also benefited from the unparalleled combination of very large numbers of participants, deep phenotyping and longitudinal follow-up of the cohort, with comprehensive health data linkage to disease outcomes. In addition, we have used UK Biobank data to describe the relationship between retinal structures, cognitive function and brain MRI-derived phenotypes. FUTURE PLANS: The collection of eye-related data (eg, OCT), as part of the UK Biobank Repeat Imaging study, will take place in 2022-2028. The depth and breadth and longitudinal nature of this dataset, coupled with its open-access policy, will create a major new resource for dementia diagnostic discovery and to better understand its association with comorbid diseases. In addition, the broad and diverse data available in this study will support research into ophthalmic diseases and various other health outcomes beyond dementia

Role of Educational Exposure in the Association Between Myopia and Birth Order.

IMPORTANCE: Visual impairment due to myopia is an important public health issue. A prior analysis of population-based cohorts aged 15 to 22 years recruited from the United Kingdom and Israel suggested myopia and high myopia were approximately 10% more common in first-born compared with later-born children. OBJECTIVE: To examine whether myopia was associated with birth order in an earlier generation than studied previously and, if so, whether the association was attenuated after adjusting for education exposure, as predicted by the hypothesis that the education of children with later birth orders is less intense. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study of UK Biobank participants recruited from 2006 to 2010. Analysis was restricted to participants aged 40 to 69 years who had a vision assessment, self-reported white ethnicity, and no history of eye disorders (N = 89,120). Myopia and high myopia were defined as autorefraction of -0.75 diopters (D) or less and -6.00 D or less, respectively. EXPOSURES: Birth order and information on potential confounders including highest educational qualification ascertained using a structured questionnaire. MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) for myopia and high myopia by birth order, using logistic regression and adjusting for age and sex (model 1) or age, sex, and highest educational qualification (model 2). RESULTS: In model 1 (no adjustment for education), birth order was associated with both myopia and high myopia (eg, comparing first- vs second-born individuals; OR, 1.12; 95% CI, 1.08-1.16; P = 1.40E-11 and OR, 1.21; 95% CI, 1.11-1.30; P = 3.60E-06 for myopia and high myopia, respectively). The risk for myopia became progressively lower for later birth orders, suggesting a dose response. In model 2 (after adjusting for education), the effect sizes were attenuated by approximately 25% (OR, 1.09; 95% CI, 1.05-1.12; P = 1.30E-06 and OR, 1.15; 95% CI, 1.06-1.25; P = 4.60E-04 for myopia and high myopia, respectively) and the apparent dose response was abolished. CONCLUSIONS AND RELEVANCE: These data suggest that the association between birth order and myopia is not due to a new environmental pressure in the last 30 to 40 years. The attenuated effect size after adjusting for educational exposure supports a role for reduced parental investment in education of children with later birth orders in their relative protection from myopia

Monocular and binocular visual impairment in the UK Biobank study: prevalence, associations and diagnoses

Objective; To determine the prevalence of, associations with and diagnoses leading to mild visual impairment or worse (logMAR >0.3) in middle-aged adults in the UK Biobank study. Methods and analysis; Prevalence estimates for monocular and binocular visual impairment were determined for the UK Biobank participants with fundus photographs and spectral domain optical coherence tomography images. Associations with socioeconomic, biometric, lifestyle and medical variables were investigated for cases with visual impairment and matched controls, using multinomial logistic regression models. Self-reported eye history and image grading results were used to identify the primary diagnoses leading to visual impairment for a sample of 25% of cases. Results; For the 65 033 UK Biobank participants, aged 40–69 years and with fundus images, 6682 (10.3%) and 1677 (2.6%) had mild visual impairment or worse in one or both eyes, respectively. Increasing deprivation, age and ethnicity were independently associated with both monocular and binocular visual impairment. No primary diagnosis for the recorded level of visual impairment could be identified for 49.8% of eyes. The most common identifiable diagnoses leading to visual impairment were cataract, amblyopia, uncorrected refractive error and vitreoretinal interface abnormalities. Conclusions; The prevalence of visual impairment in the UK Biobank study cohort is lower than for population-based studies from other industrialised countries. Monocular and binocular visual impairment are associated with increasing deprivation, age and ethnicity. The UK Biobank dataset does not allow confident identification of the causes of visual impairment, and the results may not be applicable to the wider UK population

Measures of socioeconomic status and self-reported glaucoma in the UK Biobank cohort

Purpose: To determine ocular, demographic, and socioeconomic associations with self-reported glaucoma in the UK Biobank.Methods: Biobank is a study of UK residents aged 40–69 years registered with the National Health Service. Data were collected on visual acuity, intraocular pressure (IOP), corneal biomechanics, and questionnaire from 112?690 participants. Relationships between ocular, demographic, and socioeconomic variables with reported diagnosis of glaucoma were examined.Results: In all, 1916 (1.7%) people in UK Biobank reported glaucoma diagnosis. Participants reporting glaucoma were more likely to be older (mean 61.4 vs 56.7 years, P&lt;0.001) and male (2.1% vs 1.4%, P=0.001). The rate of reported glaucoma was significantly higher in Black (3.28%, P&lt;0.001) and Asian (2.14%, P=0.009) participants compared with White participants (1.62%, reference). Cases of reported glaucoma had a higher mean IOP (18?mm?Hg both eyes, P&lt;0.001), lower corneal hysteresis (9.96 right eye, 9.89 left eye, P&lt;0.001), and lower visual acuity (0.09 logMAR right eye, 0.08 logMAR left eye, P&lt;0.001) compared with those without (16?mm?Hg both eyes, hysteresis 10.67 right eye, 10.63 left eye, 0.03 logMAR right eye, 0.02 logMAR left eye). The mean Townsend deprivation index was ?0.72 for those reporting glaucoma and ?0.95 for those without (P&lt;0.001), indicating greater relative deprivation in those reporting glaucoma. Multivariable logistic regression showed that people in the lowest income group (&lt;£18?000/year) were significantly more likely to report a diagnosis of glaucoma compared with any other income level (P&lt;0.01). We observed increasing glaucoma risk across the full range of income categories, with highest risk among those of lowest income, and no evidence of a threshold effect.Conclusions: In a large UK cohort, individuals reporting glaucoma had more adverse socioeconomic characteristics. Study of the mechanisms explaining these effects may aid our understanding of health inequality and will help inform public health interventions

Associations with photoreceptor thickness measures in the UK Biobank.

Spectral-domain OCT (SD-OCT) provides high resolution images enabling identification of individual retinal layers. We included 32,923 participants aged 40-69 years old from UK Biobank. Questionnaires, physical examination, and eye examination including SD-OCT imaging were performed. SD OCT measured photoreceptor layer thickness includes photoreceptor layer thickness: inner nuclear layer-retinal pigment epithelium (INL-RPE) and the specific sublayers of the photoreceptor: inner nuclear layer-external limiting membrane (INL-ELM); external limiting membrane-inner segment outer segment (ELM-ISOS); and inner segment outer segment-retinal pigment epithelium (ISOS-RPE). In multivariate regression models, the total average INL-RPE was observed to be thinner in older aged, females, Black ethnicity, smokers, participants with higher systolic blood pressure, more negative refractive error, lower IOPcc and lower corneal hysteresis. The overall INL-ELM, ELM-ISOS and ISOS-RPE thickness was significantly associated with sex and race. Total average of INL-ELM thickness was additionally associated with age and refractive error, while ELM-ISOS was additionally associated with age, smoking status, SBP and refractive error; and ISOS-RPE was additionally associated with smoking status, IOPcc and corneal hysteresis. Hence, we found novel associations of ethnicity, smoking, systolic blood pressure, refraction, IOPcc and corneal hysteresis with photoreceptor thickness