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Current evidence indicates that the pathogenesis begins with retinal hypoxia caused by hyperglycemia\u2010induced capillary occlusion, which stabilizes hypoxia\u2010inducible factor\u20101\u03b1 (HIF\u20101\u03b1) and upregulates vascular endothelial growth factor (VEGF). VEGF\u2010A and placental growth factor (PlGF) drive abnormal angiogenesis in the retina, iris, and anterior chamber angle. Downregulation of endogenous inhibitors such as pigment epithelium\u2010derived factor (PEDF) may exacerbate this process. Concomitant inflammation mediated by cytokines including interleukin\u20106 (IL\u20106) and tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1), followed by transforming growth factor\u2010\u03b2 (TGF\u2010\u03b2)\u2010induced fibrotic angle closure, collectively leads to refractory intraocular pressure elevation and optic nerve damage. Clinical outcomes are influenced by genetic polymorphisms, renal comorbidities, and the aqueous humor biomarker profile. 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