Novel Genetic Variants and Pathophysiological Mechanisms. Traditional diabetic retinopathy genetic risk factors, including ZNF395, PLEKHG5, VCAM-1, HIF-1α, COL18A1, EPO, and VEGF, predominantly target single pathways related to angiogenesis and inflammatory responses with modest effect sizes (typically OR 1.2–1.8) [29]. This evidence concerns the gene PLEKHG5 and diabetic retinopathy.