Cerebrovascular Function in Glaucoma: A Systematic Review and Meta-analysis

PRCIS: Glaucoma patients appear to exhibit variable cerebrovascular differences, including reduced MCA blood velocity and heterogeneous cerebral blood flow and neurovascular coupling responses. PURPOSE: Glaucoma is associated with neurodegenerative and cerebrovascular diseases, such as dementia, migraine, and stroke, indicating a possible shared underlying pathophysiology of cerebrovascular dysfunction. However, no previous systematic review or meta-analysis has investigated whether people with glaucoma have poorer cerebrovascular function than those without. This study aimed to compare cerebrovascular function in glaucoma patients to healthy controls. METHODS: Five electronic databases (Embase, Medline, PubMed, Scopus and Web of Science) were systematically searched until 28 October 2025 for full-text studies comparing measures of cerebrovascular function in people with glaucoma to controls. Meta-analyses were performed, where applicable, using mean differences (MD) and confidence intervals (CI) between glaucoma and control groups. RESULTS: Qualitative analysis of sixteen observational studies revealed that glaucoma patients exhibited varying neurovascular coupling responses (both higher and lower than controls) across frontal, occipital, and parietal regions along with varying cerebral blood flow differences. Cerebral blood flow tended to be lower within the occipital and parietal lobes, and higher within the frontal lobe. Data from six observational studies were included in meta-analyses, which revealed glaucoma patients had lower systolic (MD = -16.38, 95% CI -27.96 to -4.80, P=0.006) and mean (MD = -6.50, 95% CI -11.99 to -1.02, P=0.02) blood velocities in the middle cerebral artery than controls. Sensitivity analyses indicated findings were sensitive to the inclusion of individual studies. CONCLUSION: Glaucoma patients show heterogeneous cerebrovascular differences compared to controls, without a consistent directional or global pattern of dysfunction. Future longitudinal studies are needed to further characterise cerebrovascular measures in glaucoma.