• Written By:
    Comprehensive Ophthalmology, Neuro-Ophthalmology/Orbit

    Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are both autoimmune demyelinating conditions that cause optic neuritis. It is important to differentiate these 2 entities because the prognosis and treatment are different. This cross-sectional retrospective study assessed patterns of axonal loss and demyelination in the optic nerve of patients with MS and NMOSD.

    Study design

    Investigators compared OCT images and multifocal visual evoked potential (mfVEP) recordings from 136 patients with MS and 19 patients with NMOSD. Of these, 67 in the MS group and 15 in the NMOSD group had optic neuritis. Thirty-seven healthy participants served as controls.


    Eyes with optic neuritis within the NMOSD group had more severe ganglion cell-inner plexiform layer (GCIPL) loss and mfEVP amplitude reduction compared with eyes with optic neuritis from MS. By contrast, mfVEP latency delay was more evident in MS patients. The GCIPL loss occurred predominantly in the foveal and parafoveal region in NMOSD eyes with optic neuritis.

    In eyes with prior optic neuritis, OCT images revealed a stronger structure (OCT) to function (mfEVP) correlation in NMOSD than MS patients. In contrast, MS eyes without optic neuritis had a thinner GCIPL, reduced VEP amplitude and delayed VEP latency compared with controls, which was not seen in NMOSD eyes. In addition, MS patients had a larger lesional load involving the optic radiations on MRI than NMOSD.


    Limitations include the retrospective nature of the study and the relatively low number of NMOSD patients compared to MS. In addition, 4 of the NMOSD patients were not positive for AQP4 antibody, which adds to the heterogeneity of this cohort.

    Clinical significance

    This study highlights the structural and functional differences in NMOSD versus MS patients. It confirms that optic neuritis from NMOSD causes more severe damage and functional loss than MS. Of note, NMOSD eyes without a prior history of optic neuritis appear truly unaffected while MS eyes without optic neuritis show deficits in structure and function.

    These findings can be used to help differentiate MS from NMOSD patients, and suggest NMOSD predominantly causes axonal loss involving the anterior visual pathways while MS causes a higher degree of demyelination along the entire visual pathway.