Glymphatic system impairment in primary angle-closure glaucoma: A cross-sectional study of disease severity

The glymphatic system plays a critical role in brain waste clearance and has been implicated in neurodegenerative diseases. Primary angle-closure glaucoma (PACG) is increasingly recognized as a neurodegenerative disorder extending beyond the eye. This study aimed to investigate glymphatic system function in patients with PACG using diffusion tensor imaging analysis along the perivascular space (DTI-ALPS). This cross-sectional study included patients with PACG and age- and sex-matched healthy controls. All participants underwent magnetic resonance imaging, including diffusion tensor imaging. The DTI-ALPS index was calculated to assess glymphatic function. Group differences and correlations with disease severity were analyzed. Patients with PACG showed a significantly lower whole-brain DTI-ALPS index compared with healthy controls (1.50 ± 0.14 vs 1.60 ± 0.15, P = .030; Cohen d = 0.63). Lower DTI-ALPS values were significantly correlated with worse visual field mean deviation and thinner retinal nerve fiber layer thickness (P < .05). Glymphatic system function appears to be impaired in PACG and is associated with disease severity. These findings provide further evidence supporting the concept of glaucoma as a neurodegenerative disease involving the central nervous system.