Glymphatic Function Abnormality and Its Association With Pathophysiology in Primary Open-Angle Glaucoma

Primary open-angle glaucoma (POAG) has been increasingly viewed as a neurodegenerative condition, yet whether there are changes in the brain glymphatic function in patients with POAG has remained unclear. This study aimed to investigate the changes of glymphatic function in POAG based on multi-modal magnetic resonance imaging (MRI).

Thirty-eight patients with POAG and 25 age- and sex-matched healthy controls underwent structural MRI and functional MRI scans to assess abnormalities in cerebrospinal fluid circulation by choroid plexus (CP) volume and cortical glymphatic system clearance function by blood-oxygen-level-dependent signals and cerebrospinal fluid signals (BOLD-CSF) coupling. Comparisons of CP volume and BOLD-CSF coupling were conducted between the control and POAG groups. Correlation analysis was performed to assess the association between the function of the glymphatic system and clinical scales of POAG.

The CP volume and the ratio of CP volume to intracranial volume was significantly higher in patients with POAG compared to healthy controls (pFDR < 0.001). Additionally, the strength of BOLD-CSF coupling in the middle and posterior cortical regions were significantly weaker in POAG patients compared to controls (pFDR < 0.05). Negative correlations of glymphatic functional indicators with the thickness of the retinal nerve fibre layer (RNFL) (r from -0.427 to -0.351, p from 0.033 to 0.045) were observed, and positive correlations between BOLD-CSF of the posterior region and intraocular pressure were found (r = 0.375, p = 0.033).

POAG patients experienced impaired glymphatic function, which may be related to the pathophysiology of the disease.