Retinal Microvascular Biomarkers Measured by Optical Coherence Tomography Angiography in Neurodegenerative and Neurovascular Disorders: A Systematic Review and Meta-Analysis.

PURPOSE: Neurodegenerative and neurovascular disorders are increasingly recognized as major causes of disability worldwide and require accessible biomarkers for early detection and monitoring. Given the close anatomical and microvascular relationship between the retina and the central nervous system, optical coherence tomography angiography (OCTA) has emerged as a promising non-invasive technique for assessing retinal microvascular alterations associated with neurological disease. This systematic review and meta-analysis evaluated OCTA-derived retinal microvascular parameters as potential biomarkers of neurovascular dysfunction. METHODS: This systematic review and meta-analysis was conducted in accordance with PRISMA guidelines and registered in PROSPERO (CRD420261305354). PubMed, Embase, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from January 2015 to December 2025. Studies comparing OCTA-derived retinal vascular parameters between patients with neurodegenerative or neurovascular disorders and healthy controls were included. Primary outcomes were superficial capillary plexus vessel density (SCP-VD), deep capillary plexus vessel density (DCP-VD), and foveal avascular zone (FAZ) area. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were pooled using random-effects models. RESULTS: Thirteen studies were included in the quantitative synthesis. Compared with healthy controls, patients with neurodegenerative or neurovascular disorders demonstrated significantly reduced SCP vessel density (SMD -0.60, 95% CI -0.78 to -0.43; I2 = 43%) and DCP vessel density (SMD -0.84, 95% CI -1.15 to -0.53; I2 = 78%). FAZ area was significantly enlarged in disease groups (SMD 0.62, 95% CI 0.29 to 0.94; I2 = 83%). Disease-specific subgroup analyses demonstrated generally consistent trends across the included disorders. CONCLUSION: OCTA-derived retinal microvascular alterations were consistently associated with neurodegenerative and neurovascular disorders. Reduced retinal vessel density, particularly within the deep capillary plexus, and enlargement of the FAZ may reflect underlying neurovascular dysfunction. While these findings support the potential role of OCTA as a non-invasive biomarker of neurological disease, the available evidence remains limited by methodological heterogeneity and predominantly observational study designs. Further longitudinal studies using standardized OCTA protocols are needed to establish the diagnostic and prognostic utility of these biomarkers.