Optical Coherence Tomography Angiography Is Associated with Disease Activity Expressed by NEDA-3 Status in Patients with Relapsing Multiple Sclerosis

Background: Retinal microvascular changes may serve as biomarkers for disease activity in multiple sclerosis (MS). This study evaluated macular and peripapillary vascular plexus densities using optical coherence tomography angiography (OCTA) in patients with relapsing MS (RMS) and healthy controls (HCs), exploring their association with disease activity based on the NEDA-3 concept. Methods: In a cross-sectional study, 117 RMS patients and 37 HCs underwent OCTA imaging. Parameters analyzed included superficial vascular plexus (SVP), deep vascular plexus (DVP), foveal avascular zone (FAZ), and radial peripapillary capillary (RPC) density. Images with artifacts were excluded. Associations between OCTA metrics and demographic, clinical, and MRI volumetrics, as well as NEDA-3 status, were evaluated using multivariate generalized estimating equations. Receiver operating characteristic (ROC) curves assessed predictive capacity. Results: Compared to HCs, MS eyes with prior optic neuritis showed significantly lower SVP density (p < 0.05). DVP and FAZ parameters did not differ between groups. SVP and DVP densities correlated with age, disease duration, relapse history, and MRI volumetrics, including gray matter and whole brain volume. SVP density predicted NEDA-3 status (AUC = 0.82), while DVP also showed predictive value (AUC = 0.64). FAZ FD (Foveal density) was associated with gray matter and whole brain atrophy (AUC = 0.62–0.61). Conclusions: Retinal vascular alterations correlate with clinical and MRI measures in MS. Reduced SVP and DVP densities may serve as markers of recent disease activity, and FAZ metrics reflect neurodegeneration. OCTA may be a valuable non-invasive tool for monitoring MS progression.