Disability accumulation in multiple sclerosis often occurs independent of relapses and inflammatory activity, yet reliable predictors for early progression remain limited. Our aim was to evaluate the utility of baseline fluid and optical coherence tomography (OCT) biomarkers for predicting early disability progression in newly diagnosed relapsing–remitting MS (RRMS). We performed a monocentric observational cohort study on 72 RRMS patients that were enrolled within 6 months of diagnosis and followed for 2 years. Baseline serum and cerebrospinal fluid (CSF) samples were analyzed for neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP) and chitinase-3-like protein 1 (CHI3L1). Confirmed disability progression at 1 year (1yCDP) was defined by either an increase in Expanded Disability Status Scale or a ≥20% worsening on Nine-Hole Peg Test or Timed 25-Foot Walk. Seventeen patients (23.6%) developed 1yCDP. Elevated baseline CSF GFAP (OR = 5.79, 95% CI 1.72–19.45; p = 0.005) and CSF CHI3L1 thickness (OR = 4.14, 95% CI 1.49–11.49; p = 0.006) and reduced ganglion cell-inner plexiform layer (GCIPL) thickness (OR = 0.90, 95% CI 0.84–0.97; p = 0.006) independently predicted 1yCDP. A multivariate model including age, CSF GFAP and GCIPL achieved AUC = 0.831, with a sensitivity of 87.5% and specificity of 61.5%. This study provides evidence that baseline patient profiling using CSF GFAP, CSF CHI3L1 and GCIPL thickness may help predict early disability progression in RRMS.

Background: The eye has shown potential as a reliable, readily accessible and clinically relevant site for investigating patients with multiple sclerosis (pwMS). Optical coherence tomography angiography (OCTA) shows promise in revealing new metabolic and vascular elements driving multiple sclerosis (MS) disease pathology. This study aimed to explore correlations between OCTA parameters and clinical characteristics in newly diagnosed relapsing–remitting MS (RRMS) patients. Methods: In this cross-sectional study, forty-one newly diagnosed RRMS patients underwent comprehensive evaluations, including neurological examinations, functional and cognitive tests (9-Hole Peg Test, Montreal Cognitive Assessment), and OCT/OCTA scans. Multiple regression analyses assessed correlations between OCT/OCTA parameters and baseline clinical characteristics. Results: Lower superficial capillary plexus (SCP) vessel density was associated with longer disease duration, higher EDSS scores (visual, pyramidal, cerebellar, ambulation), and impaired 9-Hole Peg Test performance, especially in the non-dominant hand. Higher values of choriocapillaris (CC) flow voids correlated with worse cognitive performance (MoCA). Structural OCT parameters showed limited clinical correlations. Conclusions: OCTA-derived parameters are associated with disability, fine motor function, and cognitive performance in newly diagnosed RRMS patients without prior ON. These findings suggest that retinal vascular alterations may reflect early neurodegenerative processes and provide complementary information beyond structural OCT metrics. OCTA may represent a sensitive, non-invasive imaging biomarker for patient assessment in early MS.