Bidirectional pathogenesis involves three pathways: (1) Anxiety accelerates glaucoma via hypothalamic-pituitary-adrenal axis overactivation (43% lower retinal ganglion cell [RGC] survival), sympathetic catecholamine release, and microglial IL-1β/TNF-α secretion (P<0.001); (2) Glaucoma induces anxiety through RGC apoptosis-driven HMGB1/TLR4/NF-κB activation and abnormal amygdalar connectivity; (3) Anxiety correlates with 40% reduced treatment adherence, faster visual field progression (-1.5 dB/year), and 30% higher postoperative complications. Here, HMGB1 is linked to glaucoma.