Hypertension-Associated Anisometropia: Interocular Choroidal and Macular Asymmetry as Potential Mediators

Purpose: This study aimed to investigate the association between hypertension and anisometropia and determine whether interocular structural asymmetry mediates this relationship. Methods: In this cross-sectional study, nationally representative samples from the US (N = 12,749; NHANES 1999-2008) and Korea (N = 35,484; KNHANES 2008-2024) were analyzed. Associations between hypertension, blood pressure components (BPC), and anisometropia were examined using weighted multivariable logistic regression and restricted cubic splines. Mediation analysis assessed whether asymmetry in optical coherence tomography (OCT) structural parameters mediated the association between BPC and anisometropia. Results: Hypertensive individuals had higher odds of anisometropia in both cohorts (NHANES: OR = 1.32, 95% CI: 1.12-1.56, P = 0.001; KNHANES: OR = 1.12, 95% CI: 1.05-1.20, P < 0.001). Each 10 mmHg increase in systolic blood pressure (SBP) and pulse pressure (PP) was associated with 5% and 10% greater risk, respectively. Interocular differences in central macular and choroidal thickness partially mediated the association between BPCs and anisometropia. Time-course bulk RNA-seq identified Rock1 as a candidate gene downregulated under hypertensive conditions. Conclusions: Hypertension was associated with anisometropia across two national cohorts. Interocular differences in central macular and choroidal thickness partially mediated this association, suggesting a link between systemic hemodynamic alterations and ocular structural asymmetry. Translational Relevance: These findings suggest that interocular OCT structural asymmetry may serve as a clinically accessible imaging biomarker to identify individuals at increased risk of hypertension-associated anisometropia.