The neurostructural consequences of glaucoma and their overlap with disorders exhibiting emotional dysregulations: A voxel-based meta-analysis and tripartite system model

Background Glaucoma, a progressive neurodegenerative disorder leading to irreversible blindness, is associated with heightened rates of generalized anxiety and depression. This study aims to comprehensively investigate brain morphological changes in glaucoma patients, extending beyond visual processing areas, and explores potential overlaps with alterations observed in anxiety and depression. Methods A comparative meta-analysis was conducted, using case-control studies of brain structural integrity in glaucoma patients. We aimed to identify regions with gray matter volume (GMV) changes, examine their role within distinct large-scale networks, and assess overlap with generalized anxiety disorder (GAD) and major depressive disorder (MDD). Results Glaucoma patients exhibited significant GMV reductions in visual processing regions (lingual gyrus, thalamus). Notably, volumetric reductions extended beyond visual systems, encompassing the left putamen and insula. Behavioral and functional network decoding revealed distinct large-scale networks, implicating visual, motivational, and affective domains. The insular region, linked to pain and affective processes, displayed reductions overlapping with alterations observed in GAD. Limitations While the study identified significant VBM changes, the inclusion of studies from both the glaucoma and GAD cohorts is limited due to the lack of independent studies meeting our inclusion criteria. Conclusion The study proposes a tripartite brain model for glaucoma, connecting visual processing changes to the lingual gyrus and suggesting additional alterations in the putamen and insular regions tied to emotional or motivational functions. These neuroanatomical changes extend beyond the visual system, implying broader implications for brain structure and potential pathological developments, providing insights into the overall neurological consequences of this visually focused disorder.