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Yes / Importance: Myopia is a leading cause of untreatable visual impairment and is increasing in prevalence worldwide. Interventions for slowing childhood myopia progression have shown success in randomized clinical trials; hence, there is a need to identify which children would benefit most from treatment intervention. Objectives: To examine whether genetic information alone can identify children at risk of myopia development and whether including a child’s genetic predisposition to educational attainment is associated with improved genetic prediction of the risk of myopia. Design, Setting, and Participants: Meta-analysis of 3 genome-wide association studies (GWAS) including a total of 711 984 individuals. These were a published GWAS for educational attainment and 2 GWAS for refractive error in the UK Biobank, which is a multisite cohort study that recruited participants between January 2006 and October 2010. A polygenic risk score was applied in a population-based validation sample examined between September 1998 and September 2000 (Avon Longitudinal Study of Parents and Children [ALSPAC] mothers). Data analysis was performed from February 2018 to May 2019. Main Outcomes and Measures: The primary outcome was the area under the receiver operating characteristic curve (AUROC) in analyses for predicting myopia, using noncycloplegic autorefraction measurements for myopia severity levels of less than or equal to −0.75 diopter (D) (any), less than or equal to -3.00 D (moderate), or less than or equal to −5.00 D (high). The predictor variable was a polygenic risk score (PRS) derived from genome-wide association study data for refractive error (n = 95 619), age of onset of spectacle wear (n = 287 448), and educational attainment (n = 328 917). Results: A total of 383 067 adults aged 40 to 69 years from the UK Biobank were included in the new GWAS analyses. The PRS was evaluated in 1516 adults aged 24 to 51 years from the ALSPAC mothers cohort. The PRS had an AUROC of 0.67 (95% CI, 0.65-0.70) for myopia, 0.75 (95% CI, 0.70-0.79) for moderate myopia, and 0.73 (95% CI, 0.66-0.80) for high myopia. Inclusion in the PRS of information associated with genetic predisposition to educational attainment marginally improved the AUROC for myopia (AUROC, 0.674 vs 0.668; P = .02), but not those for moderate and high myopia. Individuals with a PRS in the top 10% were at 6.1-fold higher risk (95% CI, 3.4–10.9) of high myopia. Conclusions and Relevance: A personalized medicine approach may be feasible for detecting very young children at risk of myopia. However, accuracy must improve further to merit uptake in clinical practice; currently, cycloplegic autorefraction remains a better indicator of myopia risk (AUROC, 0.87). / PhD studentship grant from the College of Optometrists (Drs Guggenheim and Williams; supporting Mr Mojarrad) entitled Genetic prediction of individuals at-risk for myopia development) and National Institute for Health Research (NIHR) Senior Research Fellowship award SRF-2015-08-005 (Dr Williams). The UK Medical Research Council and Wellcome grant 102215/2/13/2 and the University of Bristol provide core support for the Avon Longitudinal Study of Parents and Children (ALSPAC). A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). This research was conducted using the UK Biobank Resource (application 17351). The UK Biobank was established by the Wellcome Trust, the UK Medical Research Council, the Department for Health (London, England), the Scottish government (Edinburgh, Scotland), and the Northwest Regional Development Agency (Warrington, England). It also received funding from the Welsh Assembly Government (Cardiff, Wales), the British Heart Foundation, and Diabetes UK.

Purpose: Currently there are attempts to slow myopia progression by manipulating peripheral refractive error. This study proposed to establish the distribution of peripheral refractive errors in hyperopic, emmetropic and myopic children and to test the hypothesis that relative peripheral hyperopia is a risk factor in the onset and progression of myopia. Methods: Refraction was measured under non-cycloplegic conditions, at 0°, 10° (superior, inferior, temporal and nasal retina) and 30° (temporal and nasal retina), at distance and near. Central spherical equivalent refractive error (SER) was used to classify the eyes as myopic (≤ −0.75 D), emmetropic (−0.75 < SER < +0.75 D) or hyperopic (≥ +0.75 D). Relative peripheral refraction was calculated as the difference between the central (i.e. foveal) and peripheral refractive measurements. At baseline, measurements were taken from 554 children and in a subset of 300 of these same children at the follow-up visit. The time interval between initial and follow-up measurement was 9.71 ± 0.87 months. Results: Results were analysed on 528 participants (10.21 ±0.94 years old) at baseline and 286 longitudinally. At baseline, myopic children (n=61) had relative peripheral hyperopia at all eccentricities at distance and near, except at 10°-superior retina where relative peripheral myopia was observed at near. Hyperopic eyes displayed relative peripheral myopia at all eccentricities, at distance and near. The emmetropes showed a shift from relative peripheral myopia at distance to relative peripheral hyperopia at near at all eccentricities, except at 10°-superior retina, where the relative peripheral myopia was maintained at near. In the longitudinal data analysis, myopes who became more myopic did not show greater relative peripheral hyperopia at baseline compared with myopic sub-groups whose central refraction remained stable. Conclusions: The peripheral refractive profile differences between different refractive groups that are reported in other studies have been confirmed in this study. Relative peripheral hyperopia is not found to be a significant risk factor in the onset or progression of myopia in children.

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People who work in occupations that involve intensive near work are thought to have a higher chance of developing myopia than other people. For example, microscopists in the United Kingdom have a higher prevalence of myopia than that of the general community. The prevalence of myopia in Hong Kong is extremely high (71 %) and Hong Kong Chinese people are particularly susceptible to myopia development and progression due to environmental factors. It is possible that this environmental susceptibility may lead to Hong Kong Chinese microscopists developing even greater levels of myopia. We found that the prevalence of myopia in Hong Kong microscopists (n=47, mean age=31 years) was higher than that of United Kingdom microscopists (87 % c.f. 71 %) and similar aged people within the general Hong Kong population (87 % c.f. 71 %; −4.45 D c.f. -3.00 D). However, while in most microscopists (83 % of 36 microscopists followed for a two-year period) the amount of myopia and vitreous chamber depth increased over a two year monitoring period (−0.11 D, 0.06 mm), the increase was not clinically significant. We hypothesised that the slower myopia progression rate in Hong Kong microscopists may be the result of their older average age (Hong Kong microscopists: 31.7 years c.f. United Kingdom microscopists: 29.7 years). When a person looks into a microscope, excessive accommodation occurs even though the microscope is designed to render the magnified image at optical infinity (zero accommodation and vergence demand). This over accommodation is called instrument myopia. It is possible that this over accommodation is linked to the myopia development and progression that occurs in users of these instruments. We found that instrument myopia remained consistent with different viewing conditions and microscope settings (inexperienced microscopists, n=20, mean age: 24.1 years, mean spherical refractive error: −2.83 D). The magnitude of instrument myopia was not correlated with either the age or refractive error of the microscope user, while it was lower in those users with greater experience (inexperienced microscopists: 1.03 D c.f. experienced microscopists: 0.43 D). As the Hong Kong microscopists (n=10, mean age: 31.2 years, mean spherical refractive error: −3.39 D) who partook in this study were experienced (6.3 years spent working in this field), this may have contributed to the lower myopia progression that was observed. Studies to determine the main contribution to the phenomena of instrument myopia were also conducted. Instrument myopia was not correlated with convergence when looking into microscope (r= −0.224, p=0.342), near phoria (r=0.351, p=0.129), AC/A ratio (r= −0.135, p=0.571), the convergence induced by the excessive accommodative response (r= −0.028, p=0.906), lag of accommodation (r=0.065, p=0.785) and tonic accommodation (r=0.142, p=0.551). We suggest that the main contribution to instrument myopia during microscopy is proximal accommodation due to the awareness of the closeness, caused by the height of the microscope (i.e. the distance between the viewer and the table where the microscope is placed), during microscopy. For example, we found that the magnitude of instrument myopia increased significantly (from 0.64 D to 1.16 D) when the height of the microscope decreased from 50 cm to 35 cm. In conclusion we have added, through direct observation, to the understanding of the characteristics of instrument myopia. Guidelines for new microscopists aimed at minimising the amount of instrument myopia that is experienced have been developed. This information might help to reduce the amount of myopia progression in commencing microscopists.