Link Identified Between PIRA and Retinal Atrophy in Multiple Sclerosis

Benjamin Knier, MD

Findings from a prospective cohort study of patients with relapsing-remitting multiple sclerosis (RRMS) showed that those with progression independent of relapse activity (PIRA) have more pronounced loss of ganglion cells. These data suggest that PIRA is associated with accelerated retinal atrophy, thus highlighting ganglion cell loss as a potential predictive marker.

Senior investigator Benjamin Knier, MD, department of neurology, Technical University of Munich, and colleagues presented these findings at MSMilan 2023, the joint ECTRIMS-ACTRIMS meeting, held October 11-13, in Milan, Italy. The trial included 155 patients with RRMS who had a longitudinal follow-up of at least 24 months with optical coherence tomography (OCT) and no relapse activity throughout that time.

Of the cohort, 30 patients had PIRA, defined as significant worsening of the Expanded Disability Status Scale (EDSS) for at least 3 months without relapses. In the study, both groups underwent retinal OCT with segmentation of the peripapillary retinal nerve fiber layer (pRNFL) and the combined ganglion cell and inner plexiform layer (GCIP). Those with eyes with a history of optic neuritis (ON) or assumed subclinical ON were excluded from the analysis.

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At the conclusion of the 24-month follow-up time, intraindividual GCIP loss was notably higher among those with PIRA (–0.31 µm/year) as compared with those without PIRA (–0.19 µm/year; P = .01). On multivariate Cox regression models, an increase of the annualized GCIP loss of 1 um/year was associated with a 6.7-fold (95% CI, 2.0-25.6; P = .002) elevated risk of developing PIRA in patients with RRMS. Between the PIRA and no PIRA groups, investigators observed no significant difference regarding pRNFL loss (–0.50 vs –0.49 µm/year; P = .41).

In terms of baseline characteristics between the groups, those with PIRA had a longer disease duration (44 vs 36 months; P = .97) with a similar amount of follow-up time (72 vs 72.2 months; P = .77). Category 1 disease-modifying therapies (DMTs), which included dimethyl fumarate, diroximel fumarate, glatiramer acetate, interferons, and teriflunomide, were the most used DMTs, accounting for 73.3% and 68.0% of patients in the PIRA and no PIRA groups, respectively. For the PIRA group, the median time to PIRA was 34 (25%-75% IQR, 16.3-49.0) months.

This was not the first example of the links between PIRA and retinal thinning. A 4-year, prospective observational study published in 2020 showed that each PIRA event was associated with a mean additional loss of GICPL (1.8 µm) and pRNFL (1.9 µm), similar to the impact of EDSS and Symbol Digit Modality Test worsening. The analysis, which featured 171 patients with relapsing MS, indicated that overall relapse and relapse without subsequent EDSS worsening did not influence retinal thinning, while a relapse with EDSS worsening was associated with an additional loss of GCIPL (1.3 µm) and pRNFL (1.4 µm).²

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REFERENCES
1. Straub EM, Aly L, Berthele A, Lambrecht S, Hemmer B, Knier B. Progression independent of relapse activity (PIRA) is associated with accelerated retinal atrophy in patients with relapsing remitting multiple sclerosis. Presented at: MSMilan; October 11-13, 2023; Milan, Italy. POSTER 389
2. Bsteh G, Hegen H, Altmann P, et al. Retinal layer thinning is reflecting disability progression independent of relapse activity in multiple sclerosis. Mult Scler J Transl Clin. 2020;6(4):205521730966344