Genetic association found between myopic refractive error, POAG
Shared genetic etiology was observed between myopic refractive error and the risk for primary open-angle glaucoma, according to a study in JAMA Ophthalmology.
“Our genetic correlation analyses provide evidence for shared genetic influences between refractive error, myopia, or high myopia and primary open-angle glaucoma, with the strongest genetic correlation detected with mean spherical equivalent refractive error,” Hélène Choquet, PhD, a research scientist in the division of research at Kaiser Permanente Northern California, and colleagues wrote.
In an observational analysis, Choquet and colleagues assessed 54,755 non-Hispanic white individuals (58% women) between July 2020 and October 2021 to understand the association between risk for primary open-angle glaucoma (POAG) and the continuous trait of mean spherical equivalent (MSE) refractive error (RE) or the binary trait of myopia.
A total of 4,047 participants had POAG (mean age, 73.64 years), and the remaining 50,708 were controls (mean age, 65.38 years).
Researchers used genome-wide association studies of MSE RE or myopia and POAG from the Genetic Epidemiology Research on Adult Health and Aging cohort to conduct genetic correlation analysis and quantify genetic overlap. They also performed two-sample Mendelian randomization to evaluate possible causal effects between variables.
According to results, individuals in the POAG group had a lower refractive MSE compared with the control group (0.71 vs. 0.38; P = 7.16 × 1014) and greater chances of having myopia and high myopia (myopia: 40.2% vs. 34.1%, P = 1.31 × 1011; high myopia: 8.5% vs 6.8%, P = .004). Both findings confirmed outcomes of previous reports, researchers wrote.
Choquet and colleagues also found that POAG was genetically linked with MSE RE (genetic correlations, 0.24; SE, 0.06; P = 3.90 × 105), myopia (genetic correlations, 0.21; SE, 0.07; P = .004) and high myopia (genetic correlations, 0.23; SE, 0.09; P = .01).
Further, an inverse-variance weighted model revealed a negative MSE RE was related to a higher POAG risk (OR per diopter more hyperopic MSE = 0.94; P = .01).
“Our results support the use of RE as a metric to help stratify risk of POAG in the general population,” Choquet and colleagues wrote. “Currently, general population screening for glaucoma is not recommended, in part due to the relatively low prevalence of undetected cases."
“Understanding which factors increase risk of POAG can help inform strategies for identifying glaucoma-enriched populations for targeted screening,” they continued, “which would lead to earlier diagnosis and preventive strategies for high-risk individuals.”
Perspective
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Glaucoma is the leading cause of permanent vision loss worldwide, yet estimates suggest that as many as one in two individuals with the disease remain undiagnosed. Among the myriad of risk factors for open-angle glaucoma, myopia has emerged as one that is relatively easy to identify and may be well-suited to inform targeted screening programs.
Myopia increases the incidence of OAG in a dose-response fashion, with highly nearsighted individuals having up to sevenfold the risk of emmetropes. In identifying a genetic influence shared by myopia and OAG, Choquet and colleagues have added to our understanding of this causal relationship. Previous investigations have suggested that the myopic posterior pole, by virtue of its thin peripapillary sclera/lamina and increased trans-laminar pressure gradient, is biomechanically susceptible to glaucomatous optic neuropathy. More recent OCT angiography studies have demonstrated that myopic eyes have lower vessel density that may contribute to retinal ganglion cell ischemic injury. Moreover, the atypical structure and function that accompanies myopia also makes it a confounding comorbidity in the diagnosis of glaucomatous optic neuropathy.
While the authors rightly identify population screening as critical, their work also reminds us that each and every time we examine a myopic individual, ruling out glaucoma must be front of mind.
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Choquet H, et al. JAMA Ophthalmol. 2022;doi:10.1001/jamaophthalmol.2022.2762.
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