Myopia is on the rise worldwide, and the hunt to find a way to slow it continues. With this in mind, a team of researchers from the UK suggests genetic information may be helpful in predicting children at high and very high risk for myopia development.
“Now that we can identify children who are genetically predisposed to high myopia, it will be important to discover if these at-risk children benefit from ‘myopia control’ interventions to a greater or lesser extent than other children,” says investigator Jeremy A. Guggenheim, director of research at the School of Optometry & Vision Sciences at Cardiff University.
Currently, the best predictor of myopia risk is a low hyperopic refractive error at an age before myopia typically manifests, which suggests a screening regimen of cycloplegic autorefraction would be an effective approach, the study noted. However, cycloplegia in young children can be time-consuming and expensive, and since the transition from moderate to low hyperopia may be part of the process of myopia development, cycloplegic autorefraction screening may be done too late.
In this meta-analysis of three genome-wide association studies, a polygenic risk score derived from 711,984 participants was evaluated in an independent validation sample of 1,516 participants. A measure of statistical validity called area under the receiver operating characteristics (AUROC) curve was 0.67 for predicting myopia and 0.73 for predicting high myopia. Additionally, researchers reported individuals with polygenic risk scores in the top 10% appeared to be at a five- to six-fold higher risk of high myopia.
The study categorized the sample of children into three groups: a group at low risk of myopia, which made up 75% of the sample; a high-risk group, comprising 25% of the sample, who were at a three to five times increased risk; and the very high risk subsample of the latter group. The high and very high risk groups may benefit most from interventions to reduce the incidence of myopia, such as time spent outdoors, the researchers said. Orthokeratolgy or atropine treatment interventions could also be implemented to reduce the rate of myopia progression, they added.
Still, the study pointed out genetic prediction for myopia in children remains far from perfect. Case in point: the study’s best AUROC was 0.75 for predicting moderate myopia, which was less accurate than the previously reported approach of screening for a low level of hyperopia by cycloplegic autorefraction. Sensitivity and specificity of genetic testing also fell short of the previously reported results from cycloplegic autorefraction (0.67 vs. 0.87).
However, there are still benefits to genetic prediction, including the advantage of not requiring eye drops or a specialist clinical assessment, and genetic prediction could also be used to detect children who would benefit from interventions to prevent incident myopia as well as to slow myopia progression, the researchers noted in their paper.
The study results suggest a personalized medicine approach to detecting children at risk of myopia is now feasible, although currently the accuracy of polygenic risk scores is not yet good enough to warrant their use in clinical practice, the investigators wrote.
The study was funded by a PhD studentship from the College of Optometrists.
|Mojarrad G, Plotnikov D, Williams C, et al. Association between polygenic risk score and risk of myopia. JAMA Ophthalmol. October 31, 2019. [Epub ahead of print].|