Frequency and Distribution of Refractive Error in Adult Life: Methodology and Findings of the UK Biobank Study

PURPOSE: To report the methodology and findings of a large scale investigation of burden and distribution of refractive error, from a contemporary and ethnically diverse study of health and disease in adults, in the UK. METHODS: U K Biobank, a unique contemporary resource for the study of health and disease, recruited more than half a million people aged 40-69 years. A subsample of 107,452 subjects undertook an enhanced ophthalmic examination which provided autorefraction data (a measure of refractive error). Refractive error status was categorised using the mean spherical equivalent refraction measure. Information on socio-demographic factors (age, gender, ethnicity, educational qualifications and accommodation tenure) was reported at the time of recruitment by questionnaire and face-to-face interview. RESULTS: Fifty four percent of participants aged 40-69 years had refractive error. Specifically 27% had myopia (4% high myopia), which was more common amongst younger people, those of higher socio-economic status, higher educational attainment, or of White or Chinese ethnicity. The frequency of hypermetropia increased with age (7% at 40-44 years increasing to 46% at 65-69 years), was higher in women and its severity was associated with ethnicity (moderate or high hypermetropia at least 30% less likely in non-White ethnic groups compared to White). CONCLUSIONS: Refractive error is a significant public health issue for the UK and this study provides contemporary data on adults for planning services, health economic modelling and monitoring of secular trends. Further investigation of risk factors is necessary to inform strategies for prevention. There is scope to do this through the planned longitudinal extension of the UK Biobank study

Frequency and Distribution of Refractive Error in Adult Life: Methodology and Findings of the UK Biobank Study

PURPOSE: To report the methodology and findings of a large scale investigation of burden and distribution of refractive error, from a contemporary and ethnically diverse study of health and disease in adults, in the UK.METHODS:U K Biobank, a unique contemporary resource for the study of health and disease, recruited more than half a million people aged 40-69 years. A subsample of 107,452 subjects undertook an enhanced ophthalmic examination which provided autorefraction data (a measure of refractive error). Refractive error status was categorised using the mean spherical equivalent refraction measure. Information on socio-demographic factors (age, gender, ethnicity, educational qualifications and accommodation tenure) was reported at the time of recruitment by questionnaire and face-to-face interview.RESULTS: Fifty four percent of participants aged 40-69 years had refractive error. Specifically 27% had myopia (4% high myopia), which was more common amongst younger people, those of higher socio-economic status, higher educational attainment, or of White or Chinese ethnicity. The frequency of hypermetropia increased with age (7% at 40-44 years increasing to 46% at 65-69 years), was higher in women and its severity was associated with ethnicity (moderate or high hypermetropia at least 30% less likely in non-White ethnic groups compared to White).CONCLUSIONS: Refractive error is a significant public health issue for the UK and this study provides contemporary data on adults for planning services, health economic modelling and monitoring of secular trends. Further investigation of risk factors is necessary to inform strategies for prevention. There is scope to do this through the planned longitudinal extension of the UK Biobank study

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

Laser refractive surgery in the UK Biobank study: Frequency, distribution by sociodemographic factors, and general health, happiness, and social participation outcomes

PURPOSE: To evaluate the frequency and distribution of laser refractive surgery in the United Kingdom by sociodemographic factors and outcomes of social participation and well-being. SETTING: Six regional recruitment centers in England and Wales. DESIGN: Cross-sectional epidemiological study. METHODS: Data were collected on sociodemographic factors and medical history; self-report on eyes/vision included reason for wearing optical correction, eye diseases, and treatment received (including refractive laser surgery). Mean spherical equivalent was used to categorize individuals as myopic (+1.0 diopter). RESULTS: Between 2009 and 2010, 117 281 subjects recruited by UK Biobank undertook an ophthalmic assessment, including autorefraction. Of those with refractive error within a range eligible for laser refractive surgery (n = 60 352), 1892 (3.1%) reported having bilateral refractive surgery and 549 (0.9%) unilateral surgery. Frequency of bilateral surgery decreased with increasing age and was higher in women. Frequency did not vary with educational attainment or accommodation status but increased with income among working age adults. Social participation, for example, regular visits to a pub or social club, was more common among those who underwent surgery. Other eye conditions were reported by 28% of those reporting refractive surgery compared with 11% of those eligible for treatment but not reporting surgery. CONCLUSION: This study provides information not available routinely on the frequency and distribution of laser refractive surgery in an adult UK population. A high frequency of ocular conditions conventionally considered contraindications to laser refractive surgery raises the possibility that extant guidance on patient selection may not be followed

Findings from retinal optical coherence tomography in a large cohort, UK Biobank

Background: UK Biobank is a large prospective multi-center community-based study, which included macular optical coherence tomography (OCT) of 67,321 people. OCT is a mainstay of ophthalmic imaging and is a potential screening test for dementia. Aim of research: Cross-sectional analysis examined retinal layers, to determine the range of findings in normal individuals, as well as describe associations with demographic and physiologic variation. Longitudinal analysis assessed associations with not only current cognitive function, but future cognitive decline. Results: All layers showed progressive thinning with older age. As compared to white people, black ethnicity was associated with significantly thicker retinal pigment epithelium (RPE) (+3.35 μm; p<0.001), but thinner photoreceptor inner segment-outer segment (IS-OS), ganglion cell layer-inner plexiform layer complex (GCL-IPL), and macular retinal nerve fibre layer (mRNFL) (-3.76 μm, -4.29 μm, and -3.97 μm, respectively; p<0.001). Higher intraocular pressure was associated with thinner RPE (- 0.04 μm per mmHg, p<0.001), but was not significant at GCL-IPL or mRNFL. Higher body mass index was associated with thinner photoreceptor IS-OS (-0.12 μm per kg/m2, p<0.001). Asian and Chinese ethnicity, refractive error, height, sex, smoking, and blood pressure showed mixed results. Socioeconomic deprivation, educational levels, and cognitive function were examined for GCL-IPL and mRNFL. Socioeconomic deprivation was associated with significantly thinner GCL-IPL, but was not significant at mRNFL. In contrast, lower education was significantly associated with thinner mRNFL but was not significant at GCL-IPL. Thinner mRNFL was associated with worse baseline cognitive performance. Follow-up cognitive tests were performed for 1251 participants. Participants with mRNFL thickness in the two thinnest quintiles were almost twice as likely to have at least one test score worse at follow-up cognitive testing (quintile 1: odds ratio (OR) 1.92, 95% CI: 1.29, 2.85, p<0.001, quintile 2: OR: 2.08, 95% CI: 1.40, 3.08, P< 0.001). While there were some associations between GCL-IPL and baseline cognitive function, no association was detected for risk of future cognitive decline. Significance: Retinal thickness is variable and dynamic. This work will inform interpretation of both past and future research, as physiologic and demographic variation is associated with thickness of each layer. Of note, I show an association between IOP and RPE but not mRNFL. Further, thinner mRNFL is associated with greater likelihood of cognitive decline in the future. These observations have implications for future research, as well as prevention and treatment of dementia

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