Update on the Epidemiology and Genetics of Myopic Refractive Error

Justin C Sherwin; David A Mackey


Expert Rev Ophthalmol. 2013;8(1):63-87. 

In This Article

Expert Commentary

Myopia is a common, complex ocular disorder that is prevalent across all ethnicities in varying proportions. In parts of east Asia, the number of children and young adults with myopia far exceeds the number without. This was not the case in previous generations. We now have populations in which myopia is essentially universal in young adults[4] and this represents a major public health concern. All of these rapid changes have occurred in the context of increased urbanization and strong pressures to attain high levels of education. A concomitant increase has been seen for high myopia, which carries an elevated risk of sight-threatening sequalae. Understanding the factors leading to high myopia and axial elongation are pivotal in this regard. Correction rates for individuals with high myopia is high,[6] but those with high myopia should have regular long-term follow-up for surveillance of associated pathology. Genetic discoveries for less severe but more prevalent myopia have been less successful, but steady progress has been made in recent years.

Experimental, epidemiological and clinical studies indicate that refraction is influenced by both environmental and genetic factors and, possibly, their interaction.[209] The majority of the intra-population variance of refractive error within populations (heritability) is attributed to hereditary factors, and evidence supporting a genetic etiology for high myopia is compelling. Several syndromes, both ocular and systemic, are associated with high myopia and are commonly attributed to mutations in genes coding for ECM proteins or connective tissue components that are expressed in the eye (commonly the sclera). Many high myopia susceptibility loci have now been mapped and display different forms of inheritance. Some causative gene mutations have now been identified,[161,168] allowing a closer insight into the pathogenesis.

The advent of GWAS has been instrumental in unraveling the genetic complexity of myopia, and numerous unique susceptibility variants have been identified. Without a doubt, several additional variants will be identified in the ensuing years. Fortuitously, GWAS permit the identification of potential novel pathways involved in refraction such as mitochondrial-induced apoptosis[210] and photoreceptor-mediated signal transduction.[195] On the downside, few GWAS findings have been replicated and it appears that variants in several genes interact with each other, and possibly with environmental and lifestyle factors, to influence refractive error. Elucidating the genetic causes of chronic diseases such as myopia affords the opportunity of analyzing DNA samples from patients as an adjunct to clinical diagnosis, prognosis and counseling,[211] and enrolling patients in clinical trials of therapeutic agents.