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

Abstract

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.

The Role of Optical Coherence Tomography in Differential Diagnosis of Multiple Sclerosis and Autoimmune Connective Tissue Diseases with CNS Involvement

“…Recently, RNFL thinning observed in patients with neuromyelitis optica spectrum disorders (NMOSD) was associated with spreading of inflammatory activity. The same longitudinal study revealed macular ganglion cell-inner plexiform layer (GCIPL) reduction over time in all NMOSD patients, as well as in all progressive MS (PMS) and active relapsing-remitting MS (RRMS) patients, but not in stable RRMS patients [10]. Another study showed GCIPL thinning in AQP4-IgG-seropositive NMOSD patients over time [11], in contrast to a group of MOG-IgG-seropositive NMOSD patients in which progression of GCIPL reduction was not observed [12].…”

A window into the future? MRI for evaluation of neuromyelitis optica spectrum disorder throughout the disease course

“…It is not yet clear how subclinical activity correlates with future relapses and disease course, and future studies addressing this gap are necessary. 13 , 15 , 16 , 123 – 125 …”

“…However, with the emergence of highly effective immunotherapies for NMOSD and growing evidence of subclinical disease activity, it is imperative to highlight the potential utility of MRI at various disease stages in NMOSD ( Figure 1 ). 8 – 17 In fact, MRI may prove to be a key tool for diagnostic accuracy and personalized therapy at the earliest possible juncture of the disease course. First, MRI facilitates diagnosis, with differentiation of NMOSD from MS, MOGAD, and other mimics in combination with serologic testing for AQP4 and MOG antibodies, preferably by employing cell-based assays.…”

Effects of Vitamin D Supplementation on Inflammatory Markers in Multiple Sclerosis Patients: A Systematic Review and Meta-analysis

“…Multiple sclerosis (MS) is described as an immune system hemostasis disorder (1), in which widespread demyelination occurs in the central nervous system (2). The main mechanism of MS includes an autoimmune inflammatory reaction of the immune system to neurons of the central nervous system (3).…”

“…Studies with the following characteristics were entered into the study: (1) RCTs that assessed the effects of vitamin D supplementation on inflammatory markers (i.e., IL-10, IL-17, and IFN-γ) of multiple sclerosis disease; (2) studies that reported mean ± SDs for inflammatory markers, or any other effect sizes according to which the calculation of mean ± SDs was possible; and (3) studies that included placebo and intervention groups, where the only difference between the two groups was vitamin D intake.…”