PURPOSE: Primary open angle glaucoma (POAG, hereafter referred to as glaucoma) is a neuro-ophthalmic disease characterized by progressive degeneration of the retinal ganglion cells and nerve fibers. However, the exact pathogenesis of this disease remains unresolved, notably including its effect on the neural circuits of the visual pathway and cortex. METHODS: We used both resting state (RS) and stimulus-driven functional MRI and applied a novel analysis technique (Bayesian Connective Field Modelling) to investigate the intra-cortical functional connective organization of the early visual cortex of patients with POAG. Analogous to population receptive field modelling for stimulus-driven activity, our connective field approach models how the activity in one cortical area (e.g. V2) can be explained based on that of another (e.g. V1). RESULTS: We compared the CF parameters obtained for the early visual cortical areas in glaucoma to those of control participants. Our results show that in both RS and stimulus-driven conditions, CF sizes in early visual areas are smaller in glaucoma compared to control participants. To assess if these differences could be related to the ocular damage altering the visual input to the visual cortex, the control participants also observed the visual stimuli with a simulated scotoma (SS), designed to match the visual sensitivity of a participant affected by glaucoma as assessed using standard automated perimetry (SAP). In this condition, no differences in CF size were observed. Moreover, we found that CF size did not correlate with glaucoma severity, as assessed using both SAP and optical coherence tomography (OCT). CONCLUSION: The observed differences in CF metrics may be the result of local reorganization or neurodegeneration of the early visual cortex that must have developed already at an early disease stage.

The authors have declared no competing interest.

AI and JC were supported by the European Union s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No. 661883 (EGRET) and No. 641805 (NextGenVis). AI and JC received additional funding from the Graduate School of Medical Sciences (GSMS), University of Groningen, The Netherlands. The funding organizations had no role in the design, conduct, analysis, or publication of this research.

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The study procedures followed the Declaration of Helsinki and were approved by the ethics board of the University Medical Center Groningen (UMCG)

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