T. Smith
University of Michigan Medical School

Author Of 1 Presentation

 Program
Neuromyelitis Optica and Anti-MOG Disease Oral Presentation

PS15.03 - Optical coherence tomography in aquaporin-4-IgG positive neuromyelitis optica spectrum disorders: a collaborative multi-center study

Speakers
Authors
Presentation Number
PS15.03
Presentation Topic
Neuromyelitis Optica and Anti-MOG Disease
Lecture Time
13:15 - 13:27

Abstract

Background

Optic neuritis (ON) is a frequent manifestation in aquaporin-4 antibody (AQP4-IgG) seropositive neuromyelitis optica spectrum disorders (NMOSD). Due to limited samples, existing optical coherence tomography (OCT) studies are inconsistent regarding retinal changes in eyes with a history of ON (NMO-ON) and without a history of ON (NMO-NON), and their functional relevance.

Objectives

The CROCTINO (Collaborative Retrospective Study on retinal OCT in Neuromyelitis Optica) project aims to reveal correlates of retinal pathology and to generate hypotheses for prospective OCT studies in NMOSD. The objective of this study was to analyze retinal changes of AQP4-IgG seropositive NMO-ON and NMO-NON eyes in an international cross-sectional OCT dataset.

Methods

Of 656 subjects, we enrolled 283 AQP4-IgG seropositive NMOSD patients and 72 healthy controls (HC) from 22 international expert centers. OCT data was acquired with Spectralis SD-OCT, Cirrus HD-OCT and Topcon 3D OCT-1. Mean thickness for the combined ganglion cell and inner plexiform layer (GCIP) and inner nuclear layer (INL) were calculated from macular volume scans. Clinical, functional and laboratory testing were performed at discretion of each center.

Results

We compared NMO-ON eyes (N = 260), NMO-NON eyes (N = 241) and HC eyes (N = 136). GCIP was reduced in NMO-ON (57.4 ± 12.2 µm) compared with NMO-NON (75.9 ± 7.7 µm; p < 0.001) and HC (81.4 ± 5.7 µm; p < 0.001). NMO-NON had thinner GCIP (p < 0.001) compared with HC. INL was thicker in NMO-ON (40.3 ± 3.9 µm) compared with NMO-NON (38.6 ± 3.9µm; p < 0.001), but not HC (39.4 ± 2.6 µm). Microcystic macular edema were visible in 6.6 % of NMOSD eyes.

Conclusions

AQP4-IgG seropositive NMOSD is characterized by a functionally relevant loss of retinal neuroaxonal content and a - probably inflammatory - increase of INL after ON. Our study further supports the existence of attack-independent damage in the visual system of patients with AQP4-IgG seropositive NMOSD.

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Author Of 2 Presentations

 On-Demand Program
Imaging Late Breaking Abstracts

LB1177 - PAMRINO: International MRI and clinical data repository for neuromyelitis optica spectrum disorder (ID 469)

Speakers
Authors
Presentation Number
LB1177
Presentation Topic
Imaging

Abstract

Background

Neuromyelitis optica spectrum disorders (NMOSD) encompasses a group of rare inflammatory diseases which primarily target the optic nerves, spinal cord, and brain. Typically, magnetic resonance imaging (MRI) data from single-center studies comprise 20-50 patients, limiting statistical power for outcomes research. Using retrospective data from the PArallel MRI in NmOsd (PAMRINO) study, a novel prospective NMOSD image repository (NMOsDIR) representing multiple international sites was coordinated by Charité-Universitätsmedizin Berlin and the Medical Image Analysis Center (Basel).

Objectives

The PAMRINO study aimed to investigate and analyze retrospective MRIs collected from NMOSD-specialized centers, potentially for the evaluation of disease-related brain and spinal cord changes. NMOsDIR serves as an international imaging research resource (comprising standardized retinal optical coherence tomography and MRI scans) and clinical data hub for prospective studies in NMOSD. Linking imaging and clinical data, as well as enabling analysis pipelines for each modality, will facilitate multi-centered studies using sufficient data and statistical power to advance outcomes research in this rare disease.

Methods

For clinical data collection in PAMRINO, a Research Electronic Data Capture (REDCap) platform was used, where participating centers entered data relevant for NMOSD patient monitoring. An image database (XNAT) was established for image uploads. This large collection of MRI data is currently being analyzed in a joint international effort of NMOSD clinical neuroradiologists and scientists.

Results

Brain, spinal cord, and optic nerve MRI scans with associated clinical data were collected from 514 NMOSD patients and 56 healthy controls from 17 international centers. Roughly 20,000 individual MRI scans from patients and healthy controls were collected. Of these, 78% had T1-weighted cerebral MRIs (55% with 3D scans), 80% had T2-weighted cerebral MRIs (54% with 3D scans), 86% had T2-weighted spinal cord MRIs (55% with 3D scans), and 35% had optic nerve MRIs.

Conclusions

We successfully established PAMRINO, an international collaborative retrospective MRI and clinical data repository. The knowledge gained during this process provided important new insights, where the initial analysis of the dataset has underscored the large degree of heterogeneity in image and clinical data collection in NMOSD-specialized centers. Thus, calling for more standardized methods of data acquisition and imaging analysis, as not to limit research opportunities. The new longitudinal, prospective NMOsDIR will help us to answer many pressing - yet open - questions regarding patients seropositive for aquaporin-4-IgG+, myelin oligodendrocyte glycoprotein-IgG+ and other autoimmune-related diseases. In turn, such a strategy will strengthen future capabilities in research, diagnosis, monitoring and improving NMOSD patient care.

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Neuromyelitis Optica and Anti-MOG Disease Poster Presentation

P0695 - Burden of disease in patients with neuromyelitis optica spectrum disorder: insights from the CIRCLES study cohort (ID 802)

Speakers
Authors
Presentation Number
P0695
Presentation Topic
Neuromyelitis Optica and Anti-MOG Disease

Abstract

Background

In patients with neuromyelitis optica spectrum disorder (NMOSD), relapses may result in cumulative neurological damage and disability. Disease burden may include pain, sensory, cognitive and visual impairment, bowel/bladder dysfunction, weakness or paralysis, and necessitate caregiver support. Prior to 2019, no therapies had received regulatory approval for NMOSD. Thus, off-label immunosuppressive therapies (IST) were commonly used for maintenance therapy. CIRCLES is a prospective, longitudinal, cross-sectional study of disease epidemiology and treatment in North American patients with NMOSD.

Objectives

This study analyzed real-world disease burden in North American patients with NMOSD enrolled in the CIRCLES study from 2013 to 2019.

Methods

Of 629 CIRCLES participants, 523 (83.1%) with anti-aquaporin-4 immunoglobulin G-positive (AQP4-IgG+) NMOSD were assessed for disease burden, including vision loss, paralysis, annual relapse rate (ARR) relative to mobility level, and steroid side effects.

Results

Baseline assessment of disability indicated at least partial (136/523, 26.0%) or complete (55/523, 10.5%) dependence on caregiver support. Among patients on off-label maintenance IST and having ≥60 days of on-study follow-up (n = 469), 136 (29.0%) experienced a total of 209 on-study relapses. The unadjusted ARR (95% confidence interval [CI]) by mobility level was 0.17 (0.14–0.20), 0.21 (0.16–0.27), and 0.24 (0.16–0.34) for independent, partially dependent, and completely dependent patients, respectively. Side effects from steroids were assessed in 429 respondents, of whom, 35 (8.2%) had gastroesophageal reflux disease, 30 (6.9%) had depression/anxiety, and 28 (6.5%) had osteoporosis. Of 77 patients with on-study relapses and vision assessment, 24 (31.2%) had vision loss (unadjusted ARR, 0.18 [CI, 0.13–0.24]; P > 0.05 vs. no relapses). Furthermore, of 129 patients with on-study relapses and paralysis assessment, 68 (52.7%) had partial or complete paralysis (unadjusted ARR, 0.23 [CI, 0.19–0.27]; P = 0.03 vs. no relapses).

Conclusions

NMOSD imposes significant disease burden, including vision loss and paralysis resulting in dependence on caregiver support in over one-third of patients. Despite the use of off-label maintenance ISTs, a substantial proportion of patients with NMOSD continue to experience relapses, disability, and neurological damage. These findings underscore the need for safe, effective, and well-tolerated treatments for preventing relapses.

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