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.

Is there a link between passive smoke exposure and early-onset myopia in preschool Asian children?

PURPOSE: To investigate the association of passive tobacco smoke exposure with early-onset myopia among three-year-old children in Singapore. METHODS: Pregnant mothers who attended their first trimester clinic at two major maternity units were recruited into the GUSTO birth cohort. The current analysis comprised 572 three-year-old children, who underwent cycloplegic autorefraction and axial length (AL) measurements. Myopia was defined as spherical equivalent (SE) of ≤-0.50 dioptres (D). Either parent completed questionnaires describing their child's exposure to passive smoke at six months, one and two years of age. RESULTS: There were 197 children (36.2%) who were exposed to passive smoke from birth to before six months. Compared to non-exposed children, children exposed to any passive smoke from birth to before six months experienced greater myopia prevalence (adjusted OR = 2.79; 95% CI: 1.24-6.29; p = 0.01). The odds of myopia in a child was greater if a smoker smokes at home, in the family car, or in the presence of the child (adjusted OR = 3.95; 95% CI: 1.41-11.09; p < 0.01) compared to non-exposed child. In contrast to myopia, childhood exposure to passive smoke did not systematically shift mean values for SE or AL. CONCLUSIONS: In this prospective birth cohort study, we found that childhood exposure to passive smoke from birth to before six months slightly increased the risk of early-onset myopia. This may indicate a delayed response to passive smoke exposure before six months and the development of myopia at three years of age. Our study is limited by the small number of myopic children at this young age. Thus, larger prospective studies using more objective cotinine level measures are required to fully establish and understand the influence of tobacco smoke on refractive development in older children.

Axial Length/Corneal Radius of Curvature Ratio and Myopia in 3-Year-Old Children.

PURPOSE: This study investigated the association of axial length (AL) to corneal radius of curvature (CRC) ratio with spherical equivalent (SE) in a 3-year old Asian cohort. METHODS: Three-hundred forty-nine 3-year old Asian children from The Growing Up in Singapore towards Healthy Outcomes (GUSTO) birth cohort study underwent AL and CRC measurements with a noncontact ocular biometer and cycloplegic refraction using an autorefractor. The ratio of AL to CRC (AL/CRC) was calculated for all the participants, and subsequently AL, CRC, and AL/CRC were analyzed in relationship to SE. RESULTS: The SE showed better correlation with AL/CRC (Spearman's correlation coefficient, ρ = -0.53; 95% confidence interval [CI]: -0.66; -0.49; P < 0.001) compared to either AL or CRC alone ([ρ = -0.36; 95% CI: -0.51 to 0.51; P = 0.01] and [ρ = 0.05; 95% CI: -0.04 to 0.17; P = 0.34], respectively). Mean AL/CRC was 2.91 ± 0.06 among myopes and decreased to 2.79 ± 0.06 among hyperopes. Axial length to corneal radius of curvature was strongly correlated with SE in myopes (ρ = -0.78; 95% CI: -3.76; -0.79; P = < 0.001), but not in emmetropes and hyperopes ([ρ = -0.39; 95% CI: -10.73; -0.57; P = 0.01] and [ρ = -0.18; 95% CI: -17.28; 12.42; P = 0.38], respectively). Linear regression adjusted for gender and ethnicity showed a 0.74-diopter shift in SE towards myopia with every 0.1 increase in AL/CRC ratio (P < 0.001, r2 = 0.33). CONCLUSION: The correlation between SE and AL/CRC is stronger than that between AL or CRC alone. This suggests that in a research setting, when cycloplegic refraction is difficult to perform on 3-year-old children, AL/CRC may be the next best reference for refractive error. TRANSLATIONAL RELEVANCE: In the research setting, AL/CRC may be the next best reference for refractive error over AL alone when cycloplegic refraction is unavailable in 3-year old children.

Relative Contribution of Risk Factors for Early-Onset Myopia in Young Asian Children.

PURPOSE: To investigate the associations of near work, outdoor activity, and anthropometric risk factors with early-onset myopia in Singaporean preschool children. METHODS: Pregnant women who attended their first-trimester clinic at two major maternity units were recruited for the GUSTO birth cohort (n = 1236). Cycloplegic autorefraction and axial length (AL) were obtained in 3-year-old children (n = 572). Parents completed detailed questionnaires on parental myopia, near work, and outdoor activities when the child was 2 years of age. Height and weight were measured in the children at various time points from birth to 3 years of age. RESULTS: Among the cohort of 572 children, 35 children (6.1%) had early-onset myopia. In multivariable regression models, compared to children whose parents were not myopic, those with two myopic parents were more likely to have a more myopic spherical equivalent (SE) (regression coefficient: -0.36; 95% confidence interval [CI]: -0.61 to -0.11) and longer AL (regression coefficient: 0.24; 95% CI: 0.10-0.39) and more likely to have myopia (odds ratio [OR] = 4.8; 95% CI: 1.4-16.6). Neither near work nor outdoor activity was associated with SE, AL, and myopia. Taller children were found to have longer AL at birth and at 12, 24, and 36 months, but there were no associations with SE. CONCLUSIONS: Genetic factors may have a greater contribution to early development of refractive error compared to environmental factors.