OCTA-derived retinal microvascular biomarkers in neuromyelitis optica spectrum disorder: clinical potential, methodological challenges, and possible links to astrocytopathy

Abstract

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune demyelinating condition of the central nervous system that chiefly affects the optic nerves and spinal cord. Optical coherence tomography angiography (OCTA), a non-invasive imaging method for viewing the retinal microvasculature, offers potential biomarkers for early detection, monitoring disease activity, and distinguishing NMOSD from multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). To determine the potential of OCTA-derived retinal biomarkers in NMOSD and determine their clinical impact in diagnosis, disease monitoring, and therapeutic assessment. A narrative review of PubMed-indexed studies was conducted, including NMOSD patient’s diagnosed according to the 2015 international consensus criteria. Κey OCTA parameters—radial peripapillary capillary density, macular vessel density, perfusion density, and foveal avascular zone (FAΖ)—were analyzed across NMOSD subgroups with and without optic neuritis and compared to healthy controls. NMOSD patients were found to have reduced vessel density in the superficial macular and radial peripapillary capillary plexuses regardless of their history of optic neuritis. These findings suggest possible subclinical retinal involvement. FAZ findings were inconsistent across studies, with reports of enlargement, reduction, or no significant difference. Reduced vessel density was also demonstrated to be correlated with poorer visual acuity, higher expanded disability status scale (EDSS) scores, and altered visual cortex connectivity. OCTA provides complementary information on retinal microvascular integrity in NMOSD and may help identify subclinical retinal involvement, particularly in the eyes without previous optic neuritis. Vessel density parameters, especially in the superficial macular and radial peripapillary capillary networks, appear more consistent than FAZ measurements, which remain heterogeneous and exploratory. OCTA may also contribute to multimodal differentiation among NMOSD, MS, and MOGAD, but it should not be considered a stand-alone diagnostic or monitoring tool. Standardized longitudinal studies with antibody stratification and rigorous confounder control are needed before OCTA-derived biomarkers can be incorporated into routine NMOSD decision-making.