Optic nerve imaging with OCT predicts disease progression and monitors brain and spinal atrophy in primary progressive multiple sclerosis

Background: Optical coherence tomography (OCT) enables in vivo assessment of retinal layers and is an emerging biomarker of neurodegeneration in multiple sclerosis (MS). In relapsing MS, peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness predict disease progression, but their role in primary progressive multiple sclerosis (PPMS) is unclear. Objective: To determine whether pRNFL and GCIPL predict disability progression and retinal, brain, and spinal cord atrophy (SCA) in PPMS. Methods: Retrospective longitudinal study of 69 PPMS patients with clinical, OCT, and magnetic resonance imaging (MRI) data. Patients stratified by pRNFL and GCIPL thickness tertiles (lower vs intermediate-upper). Annual thinning rates for pRNFL and GCIPL (aLpRNFL and aLGCIPL) estimated via linear regression. MRI assessed baseline and follow-up brain volumes, spinal cord area, and percentage of brain volume change (PBVC). Analyses included regression models, Kaplan–Meier, and Cox survival regression. Results: pRNFL ⩽ 87 μm was associated with higher follow-up Expanded Disability Status Scale (EDSS) (6.0 (interquartile range (IQR) = 4.5–6.5) vs 4.0 (IQR = 3.0–6.0), p = 0.013). Risk of confirmed disability progression (CDP) increased 3.4-fold (95% confidence interval (CI) = 1.03–11.30, p = 0.044) over 2 years (IQR = 1.0–3.0), with median time to CDP of 1.84 vs 3.67 years ( p = 0.027). Longitudinally, pRNFL ⩽87 μm showed faster retinal thinning (aLpRNFL = −1.66 vs −0.31 µm/year, p < 0.001), greater whole-brain atrophy (PBVC = −1.20%, p = 0.037), and greater SCA ( B = 0.333, p = 0.008). Conclusion: In PPMS, pRNFL predicts disability progression and greater retinal, brain, and SCA, supporting its role as a surrogate marker of neurodegeneration in clinical trials.