Subclinical neurodegeneration in multiple sclerosis and neuromyelitis optica spectrum disorder revealed by optical coherence tomography

Background: Neuroretinal atrophy is associated with whole-brain atrophy and disease activity in multiple sclerosis (MS). Recent findings support that subclinical visual pathway involvement might also occur in neuromyelitis optica spectrum disorders (NMOSDs).

Objective: The objective of this study is to assess retinal thinning in MS and NMOSD and its association with disease activity.

Methods: In total, 27 NMOSD and 54 propensity-score-matched MS patients underwent optical coherence tomography, visual acuity, and visual-evoked potentials at 2.4 years apart, in addition to routine clinical and magnetic resonance imaging (MRI) assessment. We excluded eyes with acute optic neuritis.

Results: In NMOSD, we detected peripapillary retinal nerve fiber layer (pRNFL) thinning in patients with disease activity during follow-up (-0.494 µm/year), but not in stable patients (-0.012 µm/year). Macular ganglion cell-inner plexiform layer (GCIPL) thinning occurred instead in all patients (-0.279 µm/year). Relapsing-remitting multiple sclerosis (RRMS) meeting NEDA-3 criteria had no pRNFL or GCIPL thinning during follow-up. Active-disease RRMS and progressive MS, both active and stable, displayed pRNFL (-0.724, -0.586, -0.556 µm/year, respectively) and GCIPL loss.

Conclusion: In MS, neuroretinal atrophy was associated with disease activity but occurred in progressive MS even when achieving NEDA-3 criteria. In NMOSD, pRNFL thinning was associated with non-ocular relapses due to a spreading of inflammatory activity. GCIPL thinning was found in all patients, supporting a primary retinal pathology targeting AQP4-rich structures.