Tel Aviv University
Sackler School of Medicine

Author Of 1 Presentation

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

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 3 Presentations

Imaging Late Breaking Abstracts

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

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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COVID-19 Late Breaking Abstracts

LB1275 - Enriching neuroimmunology telemedicine encounters with objective measures of vision during the SARS-CoV-2 pandemic (ID 2174)

Speakers
Presentation Number
LB1275
Presentation Topic
COVID-19

Abstract

Background


Patients with multiple sclerosis (MS) and antibody-mediated optic neuritis attend periodic outpatient clinic visits to quantify visual acuity, color vision and visual fields. Many of these tests involve prolonged proximity and contact, which patients who are immunocompromised may wish to avoid during the SARS-CoV-2 pandemic. Telemedicine is increasingly used to lessen the need for clinic visits but lacks objective means for vision monitoring.

Objectives

With the goal of enriching pandemic telemedicine encounters, we conducted a pilot study testing the feasibility of telemedicine-guided computer tests for monitoring vision.

Methods

For this pilot study, 22 patients with optic neuropathies from the Neuro-Ophthalmology outpatient clinic were recruited. Participants were asked to repeat their clinic eye exams with a home-based adaptation of the Freiburg Acuity Test (FRACT ), a robust and validated computer-based method for measuring visual acuity, the EYESAGE visual field test (http://www.eyesage.org/?lang=us), and a computer-based Ishihara color perception application. Blinded reviewers interpreted the results of both home-based and outpatient tests, and the correlation of the results was analyzed alongside patient cooperation and reliability indices.

Results

18/22 patients completed the visual monitoring tests during the telemedicine-guided encounters. Patients’ mean age was 44yrs. (SD 13.42), of whom four were male. Patients with low vision (n=2, one patient with hand motion, second patient 6/30) on clinic visit had a similar low visual acuity with the telemedicine guided FRACT method. No patient with good FRACT vision had low visual acuity documented during their clinic visit. Significant visual field defects (n=6, homonymous hemianopsia and quadrantanopia (n=3), inferior altitudinal (n=1) and central scotomas (n=2)) were all picked up by the EYESAGE home method. Smaller nasal steps and peripheral concentric field scotomas were unreliably detected by the EYESAGE method.

Conclusions

This pilot study of enriching telemedicine visits with a method for monitoring vision reveals that FRACT and EYESAGE potentially identify low visual acuities and severe visual field defects. Further improvement of home vision monitoring methods can enrich telemedicine encounters with objective means of monitoring vision. A large-scale multicenter international study is currently underway to examine the sensitivity of these visual monitoring methods in patients with demyelinating disease.

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Neuromyelitis Optica and Anti-MOG Disease Poster Presentation

P0730 - More rapid recovery and improved outcome with early steroid therapy in MOG-IgG associated  optic neuritis (ID 1109)

Speakers
Presentation Number
P0730
Presentation Topic
Neuromyelitis Optica and Anti-MOG Disease

Abstract

Background

Antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) are a biomarker of MOG-IgG associated disorder (MOGAD), a CNS demyelinating disease that disproportionately affects the optic nerves as optic neuritis (ON). MOG-IgG ON is usually associated with pain and is often steroid responsive, but details of this in a large cohort are lacking.

Objectives

To investigate whether timing of steroid treatment affects the rate and extent of visual recovery in a large cohort of MOGAD patients and examine the temporal relation of eye pain to visual loss.

Methods

We included consecutive patients evaluated by the neuro-ophthalmology departments at 5 centers from January 2017 to April 2020. Patients fulfilling the following criteria were included: (1) clinically documented history of ON; (2) serum positivity for MOG-IgG by live cell-based-assay. The details of each ON attack was recorded, including presence of eye pain, days of eye pain prior to the onset of vision loss, nadir of visual acuity loss, type of acute treatment, time to treatment, time to recovery, and final visual acuity after each attack.

Results

A total of 221 ON attacks in 115 patients with one or more episodes of MOG-IgG ON were included. The average age at the initial ON onset was 36.8 (SD 19.3); 71 (62%) were female. Eye pain was present in 171/193 (89%) of attacks with data collected on eye pain. Among 98 attacks with available temporal data, the pain began a mean of 4.2 (SD 4.2) days prior to the vision loss. Early steroid therapy administered to 9 patients (6 with MRI optic nerve enhancement; 3 had clinical ON but no MRI) with eye pain but lacking vision loss had resolution of eye pain and never developed vision loss.

Among 37 ON attacks treated with intravenous methylprednisolone (IVMP) within 2 days of onset of vision loss, the average time to recovery was 1.9 days (SD 3.1) compared to 12.1 days (SD 12.1) in 84 ON attacks treated later than 2 days (p<0.001). Those treated within 2 days had less severe visual acuity (VA) loss at time of treatment (mean LogMAR VA 0.62, SD .77) compared to those treated later than 2 days (mean LogMAR VA 1.6, SD 0.9), p<0.001, and also had a better final VA after IVMP (mean LogMAR VA 0.05, SD 0.11) compared to those treated later than 2 days (LogMAR VA 0.26, SD 0.57), p=0.034.

Conclusions

The observational findings that early IVMP leads to faster recovery and better outcomes and that pain precedes vision loss in the majority of MOG-IgG ON attacks suggests there may be a therapeutic window for steroid treatment that reduces the risk of permanent deficits.

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