Exploring the Shared Pathophysiological Mechanisms Between Diabetic Retinopathy and High Myopia: Insights from OCTA and Bioinformatics Analysis

Objective: To investigate the common pathophysiological mechanisms between diabetic retinopathy (DR) and high myopia (HM) using optical coherence tomography angiography (OCTA) and integrated bioinformatics approaches. Methods: A total of 72 patients with type 2 diabetes were enrolled and stratified based on axial length and DR severity. OCTA was performed to evaluate macular vascular density (VD), central macular thickness (CMT), and foveal avascular zone (FAZ). Gene expression profiles were retrieved from the GEO database (GSE160310 for DR; GSE138247 for HM). Differentially expressed genes (DEGs) were identified using the Limma package. Functional enrichment, Weighted Gene Co-expression Network Analysis (WGCNA), and transcription factor prediction were conducted to reveal shared molecular pathways and key regulatory genes. Results: Axial length (AL) was inversely associated with DR severity and positively correlated with FAZ area ( r = 0.576) and negatively with CMT ( r =–0.292). OCTA revealed reduced vascular density in eyes with longer AL. Bioinformatics analysis identified 757 DEGs in DR and 191 in HM. Functional enrichment suggested involvement of immune response, oxidative stress, and ECM remodeling. WGCNA revealed common gene modules, with three hub genes ( SBNO1 , GLTP , NUCKS1 ) potentially mediating ferroptosis, autophagy, and immune pathways. Conclusions: High myopia may exert a protective effect against DR via structural and hemodynamic remodeling. Shared molecular signatures between DR and HM suggest overlapping pathogenic pathways, providing potential therapeutic targets for both diseases.