Anisometropia and Its Related Traits: Ocular, Systemic, and Genetic Characteristics—Results From the Gutenberg Health Study

Purpose: To analyze potential associations of anisometropia with ocular, systemic, and genetic factors in the general population in Germany. Methods: The Gutenberg Health Study is a population-based cohort study from Mainz, Germany, including 15,010 participants aged 35 to 74 years. We included 13,307 phakic participants with objective refraction; 8512 participants had axial length (AL) measurements. Anisometropia was defined by difference of the spherical equivalent refraction. Further intereye differences in AL and corneal power were evaluated. A multivariable logistic and quantile regression analysis and a genome-wide association study (GWAS) on anisometropia, intereye difference in AL, and corneal power were conducted. Results: Prevalence of anisometropia of ≥1 diopters (D) was 14.64% (95% confidence interval [CI], 14.04%-15.25%) and of ≥2 D 4.94% (95% CI, 4.58%-5.32%). The median AL difference between both eyes was 0.12 mm (range, 0-8.11 mm). With increasing myopia and hyperopia, there was a V-shaped increase in anisometropia with minimal anisometropia at 0 D. Age (odds ratio [OR], 1.01; 95% CI, 1.01-1.02; P < 0.001) and years of education (OR, 1.06; 95% CI, 1.03-1.08; P < 0.001) were associated with anisometropia of ≥1 D. Female sex was inversely associated with hyperopic anisometropia of ≥1 D (OR, 0.77; 95% CI, 0.62-0.96; P = 0.02). Body height, diabetes, and body mass index did not show an association. GWAS on intereye difference in AL revealed a significant (P < 5 × 10-8) association of 10 single nucleotide polymorphisms at the intron of DNAH5. Conclusions: Higher refractive error is associated with an increased risk for anisometropia. Myopic anisometropia was associated with years of education. The intereye difference in AL was associated with years of education and body height. This study identified a single genomic locus at the intron of DNAH5 to be associated with intereye differences in AL.