Visual Cortex Activity and Retinal Changes in Primary Open-Angle Glaucoma: An fMRI and OCTA Study

Background and Objectives: Glaucoma is a neurodegenerative disease involving retinal ganglion cell loss, optic nerve damage and alterations within the central visual pathway. We evaluated visual cortex activity using functional magnetic resonance imaging (fMRI) in patients with primary open-angle glaucoma (POAG) and its associations with retinal structural and microvascular parameters assessed using optical coherence tomography (OCT) and OCT angiography (OCTA). Materials and Methods: This prospective clinical study included 19 patients with POAG and 18 healthy controls. All participants underwent ophthalmological examination, standard automated perimetry (Humphrey 24-2 SITA Standard), swept-source OCT, OCTA of the optic nerve head (ONH) (DRI-OCT Triton, Topcon, Tokyo, Japan), and visual stimulation fMRI (3T Siemens Magnetom Skyra, Siemens Healthineers, Erlangen, Germany). Retinal nerve fiber layer (RNFL) thickness, vessel density (VD), and visual cortex activity were compared between groups. Associations were assessed using Pearson's or Spearman's correlation according to data distribution, with Benjamini-Hochberg false discovery rate correction. Unadjusted p and adjusted q values are reported. Results: RNFL thickness was reduced in POAG patients in all four sectors. VD was lower in every sector of the superficial and deep plexus (all q < 0.05), as was outer retinal signal. Choriocapillaris findings were heterogeneous. RNFL thickness correlated with choriocapillaris VD in two of three corresponding nasal sectors, in POAG patients only. Visual cortex activation was lower in POAG patients (p = 0.046; Hedges' g = -0.68, 95% CI -1.34 to -0.01), but not after adjustment for age (p = 0.086). No association between VD and cortical activity survived FDR correction. Conclusions: In POAG, choriocapillaris VD tracked RNFL thickness in corresponding nasal sectors, an association not detected in controls. Reduced cortical activation did not persist after adjustment for age, and no retinal-cortical microvascular association was found. These exploratory findings suggest that distinct retinal vascular layers may carry different pathophysiological information and require confirmation in larger cohorts.