Pseudo-time Series Structural MRI Revealing Progressive Gray Matter Changes with Elevated Intraocular Pressure in Primary Open-Angle Glaucoma: A Preliminary Study

Rationale and Objectives Primary open-angle glaucoma (POAG) is accompanied with gray matter (GM) changes across the brain. However, causal relationships of the GM changes have not been fully understood. Our aim was to investigate the causality of GM progressive changes in POAG using Granger causality (GC) analysis and structural MRI. Materials and Methods Structural MRI from 20 healthy controls and 30 POAG patients with elevated intraocular pressure (IOP) were collected. We performed voxel-wise GM volume comparisons between control and POAG groups, and between control and four POAG subgroups (categorized by IOP). Then, we sequenced the structural MRI data of all POAG patients and conducted both voxel-wise and region of interest (ROI)-wise GC analysis to investigate the causality of GM volume changes in POAG brain. Results Compared to healthy controls, reduced GM volumes across the brain were found, GM volume enlargements in the thalamus, caudate nucleus and cuneus were also observed in POAG brain (false discovery rate (FDR) corrected at q< 0.05). As IOP elevated, the reductions of GM volume were more severe in the cerebellum and frontal lobe. GC analysis revealed that the bilateral cerebellum, visual cortices, and the frontal regions served independently as primary hubs of the directional causal network, and projected causal effects to the parietal and temporal regions of the brain (FDR corrected at q<0.05). Conclusion POAG exhibits progressive GM alterations across the brain, with oculomotor regions and visual cortices as independent primary hubs. The current results may deepen our understanding of neuropathology of POAG.