Retinal Layer Thinning After Optic Neuritis Is Associated With Future Relapse Remission in Relapsing Multiple Sclerosis

Abstract

Introduction:Remission of relapses is an important contributor to both short- and long-term prognosis in relapsing multiple sclerosis (RMS). In MS-associated acute optic neuritis (MS-ON), retinal layer thinning measured by optical coherence tomography (OCT) is a reliable biomarker of both functional recovery and the degree of neuroaxonal damage. However, prediction of non-ON relapse remission is challenging. We aimed to investigate whether retinal thinning after ON is associated with relapse remission after subsequent non-ON relapses.Methods:For this longitudinal observational study from the Vienna MS database (VMSD), we included MS patients with 1) an episode of acute ON, 2) available spectral-domain OCT scans within 12 months before ON onset (OCTbaseline), within 1 week after ON onset (OCTacute) and 3-6 months after ON (OCTfollow-up), and 3) at least one non-ON relapse after the ON episode. Subsequent non-ON relapses were classified as displaying either complete or incomplete remission based on change in expanded disability status scale (EDSS) assessed 6 months post-relapse. Association of retinal thinning in peripapillary retinal nerve fiber layer (ΔpRNFL) and macular ganglion-cell-and-inner-plexiform-layer (ΔGCIPL) with incomplete remission was tested by multivariate logistic regression models adjusting for age, sex, disease duration, relapse severity, time to steroid treatment, and DMT status.Results:We analyzed 167 MS patients (mean age 36.5 years [SD 12.3], 71.3% female, mean disease duration 3.1 years [SD 4.5]) during a mean observation period of 3.4 years (SD 2.8) after the ON episode. In 61 patients (36.5%) at least one relapse showed incomplete remission. In the multivariable analyses, incomplete remission of non-ON relapse was associated with ΔGCIPL thinning both from OCTbaseline to OCTfollow-up and from OCTacute to OCTfollow-up (odds ratio [OR] 2.4 per 5µm, p<0.001, respectively), independently explaining 29% and 27% of variance respectively. ΔpRNFL was also associated with incomplete relapse remission when measured from OCTbaseline to OCTfollow-up (OR 1.9 per 10µm, p<0.001) independently accounting for 22% of variance, but not when measured from OCTacute to OCTfollow-up.Conclusions:Retinal layer thinning after optic neuritis may be useful as a marker of future relapse remission in RMS.

Retinal layer thickness predicts disability accumulation in early relapsing multiple sclerosis

“…Going forward, we should strive to obtain a baseline OCT scan in every MS patient at the earliest possible time, ideally at initial diagnosis or first consultation, to improve risk stratification [4,5,22,37].…”

Novel and Emerging Treatments to Target Pathophysiological Mechanisms in Various Phenotypes of Multiple Sclerosis

“…The peripapillary retinal nerve fiber layer (pRNFL) and the combined macular ganglion cell and inner plexiform layer (GCIPL) are of particular interest in MS as markers of neuroaxonal degeneration (Petzold et al, 2017). The degree of pRNFL and GCIPL thinning is associated with clinical correlates of neuroaxonal damage such as disability worsening and PIRA (Bsteh et al, 2017(Bsteh et al, , 2020(Bsteh et al, , 2022Knier et al, 2017;Petzold et al, 2017). Rates of retinal atrophy have also been shown to vary according to treatment effect with high-efficacy DMTs reducing retinal atrophy (Button et al, 2017;Bsteh et al, 2021;You et al, 2021).…”

“…However, using retinal layer atrophy as a surrogate for treatment effects of on neuroaxonal damage in MS requires longer observation periods of at least 12-24 months with a baseline set at least 6 months after start of the intervention to differentiate therapeutic biological effects as it is primarily driven by retrograde axonal degeneration (Yong and Yong, 2022;Cagol et al, 2023;Ehrhardt et al, 2023). In acute optic neuritis, retinal layer thinning can also be used as an outcome marker to investigate treatment strategies aimed to achieve neuroprotection with observation periods of 3 to 6 months required (Raftopoulos et al, 2016;Bsteh et al, 2022).…”

Comparison of macular changes according to the etiology of optic neuritis: a cross-sectional study

“…Since the first report on the role of OCT in the study and treatment of ON was published in 1999 [3] , many studies have evaluated post-ON structural change using OCT, which has shown pathological changes in the visual system more clearly than ever before. Most of those studies focused on changes in RNFL and ganglion cell-inner plexiform layer (GCIPL) thicknesses [4][5][6][7][8] . In fact, RNFL and GCIPL analyses performed using OCT have helped to characterize ON according to the etiology, such as aquaporin-4 (AQP4) immunoglobulin G (IgG)-related ON (AQP4-ON), myelin oligodendrocyte glycoprotein (MOG) IgG-related ON (MOG-ON), and multiple sclerosis (MS)-related ON (MS-ON) [9][10][11][12][13][14][15][16][17] .…”