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Future Relapse Remission in Multiple Sclerosis Impacted by Retinal Layer Thinning

The impact of retinal thinning was higher when using GCIPL rather than pRNFL thinning as it explained more of the variance in relapse remission.

Recently published data of patients with relapsing multiple sclerosis (MS) showed that incomplete remission of relapses following optic neuritis (ON) were associated with retinal layer thinning, more significantly from macular ganglion cell and inner plexiform layer (GCIPL).1

In multivariable analyses, incomplete remission of non-ON relapse was associated with ∆GCIPL thinning both from ON onset (OCTbaseline) to 3-6 months after ON (OCTfollow-up) and from within 1 week after ON onset (OCTacute) to OCTfollow-up (odds ratio [OR], 2.4 per 5 µm; P <.001, respectively), independently explaining 29% and 27% of variance, respectively. Thinning of peripapillary retinal nerve fiber layer (pRNFL) was also associated with incomplete relapse remission when measured from OCTbaseline to OCTfollow-up (OR, 1.9 per 10 µm; P <.001) independently accounting for 22% of the variance, but not when measured from OCTacute to OCTfollow-up.

"Retinal layer thinning after optic neuritis, ie MS-associated neuroaxonal damage, may be useful as a marker of future relapse remission in RMS, potentially informing treatment strategy," lead investigator Thomas Berger, MD, professor of neurology, Medical University of Vienna, and colleagues, concluded.

Berger et al analyzed 167 patients with MS from the Vienna MS database who had an episode of acute ON and at least 1 non-ON relapse after the ON episode. Patients with bilateral ON were excluded from the study. All non-ON relapses were extracted and classified based on change in Expanded Disability Status Scale (EDSS) assessed 6 months post relapse compared with the last documented EDSS before relapse. Incomplete remission was defined as EDSS post relapse of at least 0.5 points compared with EDSS scores before relapse.

Each patient underwent optical coherence tomography (OCT) imaging, which included a custom 3.4 mm ring scan centered on the optic nerve head for pRNFL measurement and a 20°×20° macular volume scan centered on the macula for GCIPL measurement. GCIPL thickness was defined as the mean layer thickness of the 4 inner and outer quadrants of the circular grid centered around the foveola corresponding to the 3 mm and 6 mm rings as defined by the Early Treatment Diabetic Retinopathy Study.

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Patients were analyzed during a mean observation period of 3.4 years (standard deviation [SD], 2.8) after the ON episode. Of the cohort, 36.5% (n = 61) of individuals had at least 1 relapse that showed incomplete remission. In all regression models, age at relapse (OR, 1.4 per 5 years increase), incomplete remission before ON (OR, 1.6 per 5 years increase) and severe relapse (OR, 1.7-1.8 per 5 years increase) remained significantly associated with incomplete remission, whereas highly effective disease-modifying therapy, defined as patients receiving either alemtuzumab, anti-CD20 monoclonal antibodies, cladribine, natalizumab, or sphingosine-1-phosphate receptor modulators,at relapse was associated with lower likelihood of incomplete recovery (OR, 0.6).

When factoring only those with complete recovery from ON (n = 87), incomplete remission of non-ON relapse was still associated with ∆GCIPL from OCTbaseline to OCTfollow-up (OR, 2.6 per 5 µm; 95% CI, 1.4-4.8; P <.001), and from OCTacute to OCTfollow-up (OR, 2.5 per 5 µm; 95% CI, 1.4-4.8; P <.001), independently explaining 38% and 30% of variance, respectively, after adjusting for age, relapse severity, and disease-modifying therapy status. In the model regarding ∆pRNFL, thinning from OCTbaseline to OCTfollow-up was also associated with incomplete relapse remission (OR, 2.1 per 10 µm, 95% CI 1.1-5.8, p = 0.032) independently accounting for 18% of variance, but again ∆RNFL from OCTacute to OCTfollow-up was not.

"In this context, the anterior visual pathway provides an ideal opportunity to study the degree of neuroaxonal damage: Acute ON represents the prototype of MS relapse as it is common comprising about 15% to 25% of relapses and displays both similar rates and predictors of recovery compared to other relapse types." Berger et al wrote. "Unlike in other MS relapses, the amount of neuroaxonal damage caused can be easily and reliably measured by means of OCT based measurement of retinal layer thicknesses. ON-associated reduction of both pRNFL and GCIPL thicknesses is completed and therefore measurable 3 to 6 months after the ON episode and its degree corresponds to the degree of structural neuroaxonal damage as well as functional visual recovery."

1. Bsteh G, Krajnc N, Riedl, et al. Retinal layer thinning after optic neuritis is associated with future relapse remission in relapsing multiple sclerosis. Neurology. Published August 2, 2022. doi:10.1212/WNL.0000000000200970