A new cross-sectional study published in Medicine has uncovered compelling evidence linking glaucoma to structural and genetic changes in the brain, offering fresh insight into the so-called “eye–brain axis.”
To explore the causal relationship between glaucoma and brain cortical structure, the researchers – based at the Eye Center of Xiangya Hospital in Hunan, China – conducted a large-scale Mendelian randomization (MR) analysis. Data were sourced from major genomic and imaging consortia, including the UK Biobank, FinnGen, ENIGMA, and the Gene Expression Omnibus. Six glaucoma-related traits – including intraocular pressure (IOP), cup-to-disc ratio (CDR), visual field defects, and retinal nerve fiber layer (RNFL) thickness – were analyzed against measures of cortical surface area and thickness across 34 brain regions (categorized according to the Desikan–Killiany atlas).
The MR analysis demonstrated that glaucoma-related genetic variants are associated with structural changes in specific cortical regions, particularly the superior and middle temporal gyri, cuneus, entorhinal cortex, and insula. These regions are known to play central roles in visual processing, memory, and higher cognition. Importantly, no global cortical effects were observed, indicating that glaucoma exerts localized rather than widespread structural influence.
Transcriptomic analysis revealed 18 overlapping genes between primary open-angle glaucoma (POAG) and Alzheimer’s disease (AD), including MYH14, EFNA1, and FZD1, which are implicated in neuronal development, axon guidance, and Wnt signaling. Further WGCNA identified 11 hub genes common to both diseases, highlighting shared pathways such as lipid metabolism, endocytosis, and the mTOR signaling cascade. These mechanisms align with observed phenomena in glaucoma, including retinal ganglion cell loss and transneuronal degeneration extending into central visual and cognitive pathways.
The findings strengthen the hypothesis that glaucoma is not merely an ocular disease but part of a broader neurodegenerative spectrum. These structural brain changes observed in regions tied to vision, memory, and emotion may explain why glaucoma patients are at increased risk of cognitive decline and dementia.
From a clinical perspective, the findings reinforce the importance of early detection and comprehensive patient management. MRI-based assessment of cortical regions could one day complement ophthalmic screening, helping identify patients at risk of neurodegenerative comorbidities. Furthermore, shared molecular mechanisms point to potential therapeutic targets that extend beyond lowering IOP – such as modulating lipid metabolism or the mTOR pathway.
To explore the causal relationship between glaucoma and brain cortical structure, the researchers – based at the Eye Center of Xiangya Hospital in Hunan, China – conducted a large-scale Mendelian randomization (MR) analysis. Data were sourced from major genomic and imaging consortia, including the UK Biobank, FinnGen, ENIGMA, and the Gene Expression Omnibus. Six glaucoma-related traits – including intraocular pressure (IOP), cup-to-disc ratio (CDR), visual field defects, and retinal nerve fiber layer (RNFL) thickness – were analyzed against measures of cortical surface area and thickness across 34 brain regions (categorized according to the Desikan–Killiany atlas).
The MR analysis demonstrated that glaucoma-related genetic variants are associated with structural changes in specific cortical regions, particularly the superior and middle temporal gyri, cuneus, entorhinal cortex, and insula. These regions are known to play central roles in visual processing, memory, and higher cognition. Importantly, no global cortical effects were observed, indicating that glaucoma exerts localized rather than widespread structural influence.
Transcriptomic analysis revealed 18 overlapping genes between primary open-angle glaucoma (POAG) and Alzheimer’s disease (AD), including MYH14, EFNA1, and FZD1, which are implicated in neuronal development, axon guidance, and Wnt signaling. Further WGCNA identified 11 hub genes common to both diseases, highlighting shared pathways such as lipid metabolism, endocytosis, and the mTOR signaling cascade. These mechanisms align with observed phenomena in glaucoma, including retinal ganglion cell loss and transneuronal degeneration extending into central visual and cognitive pathways.
The findings strengthen the hypothesis that glaucoma is not merely an ocular disease but part of a broader neurodegenerative spectrum. These structural brain changes observed in regions tied to vision, memory, and emotion may explain why glaucoma patients are at increased risk of cognitive decline and dementia.
From a clinical perspective, the findings reinforce the importance of early detection and comprehensive patient management. MRI-based assessment of cortical regions could one day complement ophthalmic screening, helping identify patients at risk of neurodegenerative comorbidities. Furthermore, shared molecular mechanisms point to potential therapeutic targets that extend beyond lowering IOP – such as modulating lipid metabolism or the mTOR pathway.
