Refractive error is the most common eye disorder worldwide, and a prominent cause of blindness. Myopia affects over 30% of Western populations, and up to 80% of Asians. The CREAM consortium conducted genome-wide meta-analyses including 37,382 individuals from 27 studies of European ancestry, and 8,376 from 5 Asian cohorts. We identified 16 new loci for refractive error in subjects of European ancestry, of which 8 were shared with Asians. Combined analysis revealed 8 additional loci. The new loci include genes with functions in neurotransmission (GRIA4), ion channels (KCNQ5), retinoic acid metabolism (RDH5), extracellular matrix remodeling (LAMA2, BMP2), and eye development (SIX6, PRSS56). We also confirmed previously reported associations with GJD2 and RASGRF1. Risk score analysis using associated SNPs showed a tenfold increased risk of myopia for subjects with the highest genetic load. Our results, accumulated across independent multi-ethnic studies, considerably advance understanding of mechanisms involved in refractive error and myopia.

Time spent outdoors was predictive of incident myopia independently of physical activity level. The greater association observed for time outdoors suggests that the previously reported link between "sports/outdoor activity" and incident myopia is due mainly to its capture of information relating to time outdoors rather than physical activity.

Refractive errors, in particular myopia, are a leading cause of morbidity and disability worldwide and their prevalence is rising, largely due to cultural and environmental changes. Genetic investigation is a valuable tool to better understand the molecular mechanisms underlying abnormal eye development and impaired vision. We conducted a meta-analysis of genome-wide association studies involving 542,934 European participants and identified 336 novel genetic loci associated with refractive error that explain an additional 4.6% of spherical equivalent heritability, or an improvement by a third over the previous estimates. Collectively, all associated genetic variants explain 18.4% of heritability and improve the accuracy of myopia prediction (AUC=0.75). Our results suggest that refractive error is genetically heterogeneous, driven by genes participating in the development of every anatomical component of the eye. In addition, our analyses suggest that genetic factors controlling circadian rhythm and pigmentation are also involved in the development of myopia and refractive error. These results may make possible predicting refractive error and the development of personalized myopia prevention strategies in the future.

Myopia has been predicted to affect approximately 50% of the world's population based on trending myopia prevalence figures. Critical to minimizing the associated adverse visual consequences of complicating ocular pathologies are interventions to prevent or delay the onset of myopia, slow its progression, and to address the problem of mechanical instability of highly myopic eyes. Although treatment approaches are growing in number, evidence of treatment efficacy is variable. This article reviews research behind such interventions under four categories: optical, pharmacological, environmental (behavioral), and surgical. In summarizing the evidence of efficacy, results from randomized controlled trials have been given most weight, although such data are very limited for some treatments. The overall conclusion of this review is that there are multiple avenues for intervention worthy of exploration in all categories, although in the case of optical, pharmacological, and behavioral interventions for preventing or slowing progression of myopia, treatment efficacy at an individual level appears quite variable, with no one treatment being 100% effective in all patients. Further research is critical to understanding the factors underlying such variability and underlying mechanisms, to guide recommendations for combined treatments. There is also room for research into novel treatment options.

ObjectivesTo determine whether more years spent in education is a causal risk factor for myopia, or whether myopia is a causal risk factor for more years in education.DesignBidirectional, two sample mendelian randomisation study.SettingPublically available genetic data from two consortiums applied to a large, independent population cohort. Genetic variants used as proxies for myopia and years of education were derived from two large genome wide association studies: 23andMe and Social Science Genetic Association Consortium (SSGAC), respectively.Participants67 798 men and women from England, Scotland, and Wales in the UK Biobank cohort with available information for years of completed education and refractive error.Main outcome measuresMendelian randomisation analyses were performed in two directions: the first exposure was the genetic predisposition to myopia, measured with 44 genetic variants strongly associated with myopia in 23andMe, and the outcome was years in education; and the second exposure was the genetic predisposition to higher levels of education, measured with 69 genetic variants from SSGAC, and the outcome was refractive error.ResultsConventional regression analyses of the observational data suggested that every additional year of education was associated with a more myopic refractive error of −0.18 dioptres/y (95% confidence interval −0.19 to −0.17; P<2e-16). Mendelian randomisation analyses suggested the true causal effect was even stronger: −0.27 dioptres/y (−0.37 to −0.17; P=4e-8). By contrast, there was little evidence to suggest myopia affected education (years in education per dioptre of refractive error −0.008 y/dioptre, 95% confidence interval −0.041 to 0.025, P=0.6). Thus, the cumulative effect of more years in education on refractive error means that a university graduate from the United Kingdom with 17 years of education would, on average, be at least −1 dioptre more myopic than someone who left school at age 16 (with 12 years of education). Myopia of this magnitude would be sufficient to necessitate the use of glasses for driving. Sensitivity analyses showed minimal evidence for genetic confounding that could have biased the causal effect estimates.ConclusionsThis study shows that exposure to more years in education contributes to the rising prevalence of myopia. Increasing the length of time spent in education may inadvertently increase the prevalence of myopia and potential future visual disability.

PurposeTo generate percentile curves of axial length (AL) for European children, which can be used to estimate the risk of myopia in adulthood.MethodsA total of 12 386 participants from the population‐based studies Generation R (Dutch children measured at both 6 and 9 years of age; N = 6934), the Avon Longitudinal Study of Parents and Children (ALSPAC) (British children 15 years of age; N = 2495) and the Rotterdam Study III (RS‐III) (Dutch adults 57 years of age; N = 2957) contributed to this study. Axial length (AL) and corneal curvature data were available for all participants; objective cycloplegic refractive error was available only for the Dutch participants. We calculated a percentile score for each Dutch child at 6 and 9 years of age.ResultsMean (SD) AL was 22.36 (0.75) mm at 6 years, 23.10 (0.84) mm at 9 years, 23.41 (0.86) mm at 15 years and 23.67 (1.26) at adulthood. Axial length (AL) differences after the age of 15 occurred only in the upper 50%, with the highest difference within the 95th percentile and above. A total of 354 children showed accelerated axial growth and increased by more than 10 percentiles from age 6 to 9 years; 162 of these children (45.8%) were myopic at 9 years of age, compared to 4.8% (85/1781) for the children whose AL did not increase by more than 10 percentiles.ConclusionThis study provides normative values for AL that can be used to monitor eye growth in European children. These results can help clinicians detect excessive eye growth at an early age, thereby facilitating decision‐making with respect to interventions for preventing and/or controlling myopia.

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Refractive errors are common eye disorders of public health importance worldwide. Ocular axial length (AL) is the major determinant of refraction and thus of myopia and hyperopia. We conducted a meta-analysis of genome-wide association studies for AL, combining 12,531 Europeans and 8,216 Asians. We identified eight genome-wide significant loci for AL (RSPO1, C3orf26, LAMA2, GJD2, ZNRF3, CD55, MIP, and ALPPL2) and confirmed one previously reported AL locus (ZC3H11B). Of the nine loci, five (LAMA2, GJD2, CD55, ALPPL2, and ZC3H11B) were associated with refraction in 18 independent cohorts (n = 23,591). Differential gene expression was observed for these loci in minus-lens-induced myopia mouse experiments and human ocular tissues. Two of the AL genes, RSPO1 and ZNRF3, are involved in Wnt signaling, a pathway playing a major role in the regulation of eyeball size. This study provides evidence of shared genes between AL and refraction, but importantly also suggests that these traits may have unique pathways.