Optic neuritis in Asian type opticospinal multiple sclerosis (OSMS-ON) in a non-Asian population: A functional-structural paradox

Background: Biomarkers have improved the classification of autoimmune inflammatory disorders, including optic neuritis (ON) as a frequent presentation of multiple sclerosis, neuromyelitis spectrum disorders, MOG antibody-related disease (MOGAD), and opticospinal multiple sclerosis (OSMS). The phenotype of OSMS in nonAsian populations is less well known. Objective: We investigated the clinical features and prognosis of OSMS-ON in a Brazilian cohort. Methods: This was a single-center cohort study of patients from Rio de Janeiro (Brazil) with OSMS. All individuals were MOG- and AQP4-seronegative, clinically diagnosed with ON, and had magnetic resonance imaging-confirmed transverse myelitis (TM). Subjects and healthy controls (HCs) were assessed for visual acuity (logMAR VA), automated perimetry mean deviation (MD), intraocular pressure, and spectral-domain optical coherence tomography (OCT), followed by automated retinal layer segmentation of the peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell and inner plexiform layer (mGCIPL). Receiver operator characteristic curves were plotted and the area under the curve (AUC) was calculated for group comparisons of retinal asymmetry of the pRNFL and mGCIPL. Results: The 30 patients with OSMS were predominantly female and white. The mean age was 48 years (range 20-70 years). Unilateral ON was the index event in 83.3% of patients. Over the average 18-year follow-up period, there were 89 relapses of ON. In individuals with OSMS, the average VA was 0.07 +/- 0.14 in the right eye (RE) and 0.13 +/- 0.30 in the left eye (LE). The MD was -5.37 +/- 5.88 dB and -5.23 +/- 3.34 dB for the RE and LE, respectively. There was a significant cumulative loss of VA (p = 0.0003) and MD (p = 0.0001) with a higher number of recurrent episodes. Atrophy of the pRNFL thickness was significant in OSMS (RE, 78.62 +/- 16.01 mu m; LE, 79.86 +/- 13.79 mu m) relative to the HC group (RE, 98.87 +/- 10.68 mu m; LE, 97.87 +/- 10.85 mu m, p = 0.0001). Likewise, there was significant mGCIPL atrophy in patients with OSMS (RE, 74.96 +/- 14.46 mu m; LE, 73.88 +/- 13.79 mu m) relative to the HC group (RE, 90.50 +/- 6.74 mu m; LE, 90.41 +/- 6.89 mu m; p = 0.0001). Retinal asymmetry, inter-eye percentage, and absolute differences accurately separated patients with unilateral ON from HCs (AUC=0.89 and AUC=0.85, respectively). Conclusion: A structural-functional paradox was found in OSMS with a high diagnostic value for a novel metric based on retinal asymmetry. The functional visual outcome are excellent despite significant structural damage to the inner retinal layers in patients with a high ON relapse rate and long-term bilateral sequential involvement.

Automated summary

The study investigated the clinical features and prognosis of OSMS-ON in a Brazilian cohort and found a paradox in OSMS with significant structural damage yet excellent functional visual outcome. The novel metric based on retinal asymmetry showed high diagnostic value in distinguishing patients with unilateral ON from healthy controls.