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.

Background and Objectives: Neuromyelitis optica spectrum disorder (NMOSD) and MOG antibody-associated disease (MOGAD) are distinct autoimmune demyelinating disorders of the central nervous system, characterized by different pathological and clinical features. Reliable biomarkers are essential for accurate diagnosis and monitoring of disease activity. Glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are promising candidates, reflecting astrocytic and axonal damage, respectively. Materials and Methods: To investigate the relationship between astroglial (GFAP) and neuronal (NfL) protein levels in the peripheral blood, 89 plasma samples were analyzed using Simoa immunoassays. The concentrations of pNfL and pGFAP were measured in three groups: AQP4-IgG-positive NMOSD patients (n = 18), MOGAD patients (n = 12), and healthy controls (HCs, n = 19). Statistical analyses assessed group differences, correlations, and the predictive value of biomarkers for disease activity. Results: Both NMOSD and MOGAD patients exhibited elevated pNfL compared with controls, indicating neuroaxonal injury. No significant differences in pNfL, pGFAP, or pGFAP/pNfL ratios were observed between patient groups. The pGFAP levels and the pGFAP/pNfL ratio were significantly higher in NMOSD patients, particularly during attacks, indicating prominent astrocyte damage. Correlations revealed associations between biomarker levels, disability, and disease duration. pNfL demonstrated high accuracy in predicting recent relapses (AUC = 0.906), whereas pGFAP showed moderate predictive capacity (AUC = 0.638). Elevated pNfL and pGFAP levels were associated with an increased likelihood of relapse within six months. Conclusions: Plasma NfL and GFAP are promising biomarkers for assessing tissue injury and disease activity in NMOSD and MOGAD. NfL predicts relapses, while GFAP primarily reflects astrocytic damage in NMOSD. Longitudinal studies are warranted to validate these biomarkers and establish clinical thresholds for disease management.