Myopia, Hyperopia Pose Minimal Risk for AMD


After a Mendelian analysis, investigators found that the genetic variants examined explained 4.4% of the variance in refractive error in their patient sample.

Ashley Wood, PhD

Ashley Wood, PhD

According to a new analysis, myopia and hyperopia only modestly effect the causal risk for the development of age-related macular degeneration (AMD).

Investigators performed a genome-wide association study on more than 33,000 participants and found that the 126 genetic variants used in the analysis explained 4.4% of the variance in refractive error in their patient sample.

Investigators from Cardiff University in Wales used a Mendelian randomization analysis including more than 95,000 patients in order to determine if refractive errors like myopia and hyperopia are cause for an increased risk of AMD. Additionally, investigators wanted to quantify the degree of risk for AMD, stating that the recognition of causal risk factors is key to developing new treatments and therapies.

Using a Mendelian randomization analysis allowed the investigators to draw what they called valid causal inferences using existing cross-sectional datasets, they explained. These analyses are especially useful when randomized controlled trials are not practical or before one may take place. Authors added they chose this type of analysis because it allows researchers to quantify the effect of the exposure of instrumental variables on the outcome.

In this analysis, the investigators identified 126 genetic variants associated with refractive error were selected as the instrumental variables. These variables were identified through the CREAM consortium and 23andMe Inc. Investigators then used a genome-wide association study of more than 33,000 participants to determine association with AMD with the 126 genetic variants.

Overall, the investigators found that these 126 genetic variants explained 4.4% of the variance in refractive error in their patient sample, which they felt suggested a weak instrument bias. Investigators added that many different Mendelian models produced causal effect estimates that were essentially null. However, the most statistical analysis estimated between 8 and 10% increased risk of AMD per 1 diopter (D) more hyperopic refractive error.

“It was pleasing that our observations confirmed existing evidence from observational studies of a link between increasing long-sightedness and AMD risk,” the study’s lead author Ashley Wood, PhD, told MD Magazine®. “Perhaps the most surprising finding was that the risk we determined was so similar to that from previous research, given that observational studies are more likely to be affected by confounder bias than the Mendelian randomization methodology we applied.”

A previous study showed that 1 D increase in hyperopia is linked to 6-9% increased risk for AMD, while another found an increased risk between 6-10% per 1 D increased hyperopia. Neither of those studies limited their patient populations to those of European ancestry, like Dr. Wood did, based on his use of the UK Biobank.

“Understanding risk factors aids clinicians in the detection of disease through informing monitoring intervals and advice provided to high risk patients,” Wood explained. “This is particularly important in the neovascular sub-type of AMD where timely detection can have significant impact on the visual prognosis. These findings add further evidence for the risk of AMD posed by increasing long-sightedness.”

The authors added that there is an increasing prevalence of myopia and a decreasing prevalence of hyperopia in the world, which could counter the higher incidence of AMD due to increased life expectancy. They concluded that their research research appears to show that refractive error does not pose as great a causal risk for AMD than other variables such as smoking status.

The paper, titled “Refractive error has minimal influence on the risk of age-related macular degeneration: A Mendelian randomization study,” was published in the American Journal of Ophthalmology.

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