Systemic diseases to the mechanism of primary open angle glaucoma

Primary open angle glaucoma (POAG) is a complex neurodegenerative disorder involving genetic susceptibility, environmental factors, and systemic abnormalities, whose pathogenesis has not been fully elucidated. Based on baseline intraocular pressure (IOP), POAG is classified into two subtypes: high-tension glaucoma (HTG) and normal-tension glaucoma (NTG). This review summarizes and integrates recent research advances, focusing on the roles of systemic disorders including cardiovascular, endocrine, neurodegenerative, and autoimmune diseases, as well as obstructive sleep apnea-hypopnea syndrome (OSAHS), in the onset and progression of POAG from an integrated eye-brain-body axis perspective. Current evidence suggests that optic nerve damage in POAG involves multiple interconnected pathological pathways, such as IOP-related mechanical stress, hemodynamic disturbances, impaired neurovascular coupling, microvascular dysfunction, oxidative stress, and chronic inflammation. Among them, dysfunctions of the eye–brain axis, gut–eye axis, and ocular lymphatic–glymphatic system serve as key regulatory networks that mediate and integrate the aforementioned pathological processes. The two subtypes display distinct pathogenic features: HTG is primarily driven by elevated IOP, whereas NTG relies more on IOP-independent mechanisms and is more susceptible to systemic influences. This integrative perspective deepens our understanding of POAG pathogenesis and provides a novel theoretical foundation for early diagnosis, multidimensional intervention, and precision therapy.