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Cited by 6Multiple Sclerosis Research StudiesGlaucoma and retinal disordersOcular Diseases and Behçet’s Syndrome

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Retinal Changes in Double-Antibody Seronegative Neuromyelitis Optica Spectrum Disorders

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Oertel, Frederike C., Zimmermann, Hanna G., Motamedi, Seyedamirhosein, Bereuter, Charlotte, Manthey, Luca Magdalena, Ashtari, Fereshteh, Kafieh, Rahele, Dehghani, Alireza, Pourazizi, Mohsen, Pandit, Lekha, D'Cunha, Anitha, Aktas, Orhan, Albrecht, Philipp, Ringelstein, Marius, Martinez-Lapiscina, Elena H., Sanchez Dalmau, Bernardo F., Villoslada, Pablo, Asgari, Nasrin, Marignier, Romain, Cobo-Calvo, Alvaro, Leocani, Letizia, Pisa, Marco, Radaelli, Marta, Palace, Jacqueline, Roca-Fernandez, Adriana, Leite, Maria Isabel S., Sharma, Srilakshmi, De Seze, Jerome, Senger, Thomas, Yeaman, Michael R., Smith, Terry J., Cook, Lawrence J., Brandt, Alexander U., Paul, Friedemann, as the Guthy-Jackson Charitable Foundation·2024·Neurology Neuroimmunology & Neuroinflammation
DOI 10.1212/nxi.0000000000200273PMC PMC11214151
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Abstract

Background and Objectives To systematically describe the clinical picture of double-antibody seronegative neuromyelitis optica spectrum disorders (DN-NMOSD) with specific emphasis on retinal involvement. Methods Cross-sectional data of 25 people with DN-NMOSD (48 eyes) with and without a history of optic neuritis (ON) were included in this study along with data from 25 people with aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorder (AQP4-NMOSD, 46 eyes) and from 25 healthy controls (HCs, 49 eyes) for comparison. All groups were matched for age and sex and included from the collaborative retrospective study of retinal optical coherence tomography (OCT) in neuromyelitis optica (CROCTINO). Participants underwent OCT with central postprocessing and local neurologic examination and antibody testing. Retinal neurodegeneration was quantified as peripapillary retinal nerve fiber layer thickness (pRNFL) and combined ganglion cell and inner plexiform layer thickness (GCIPL). Results This DN-NMOSD cohort had a history of [median (inter–quartile range)] 6 (5; 9) attacks within their 5 ± 4 years since onset. Myelitis and ON were the most common attack types. In DN-NMOSD eyes after ON, pRNFL ( p < 0.001) and GCIPL ( p = 0.023) were thinner compared with eyes of HCs. Even after only one ON episode, DN-NMOSD eyes already had considerable neuroaxonal loss compared with HCs. In DN-NMOSD eyes without a history of ON, pRNFL ( p = 0.027) and GCIPL ( p = 0.022) were also reduced compared with eyes of HCs. However, there was no difference in pRNFL and GCIPL between DN-NMOSD and AQP4-NMOSD for the whole group and for subsets with a history of ON and without a history of ON—as well as between variances of retinal layer thicknesses. Discussion DN-NMOSD is characterized by severe retinal damage after ON and attack-independent retinal neurodegeneration. Most of the damage occurs during the first ON episode, which highlights the need for better diagnostic markers in DN-NMOSD to facilitate an earlier diagnosis as well as for effective and early treatments. In this study, people with DN-NMOSD presented with homogeneous clinical and imaging findings potentially suggesting a common retinal pathology in these patients.

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Metadata

Authors
Oertel, F. C., Zimmermann, H. G., Motamedi, S., Bereuter, C., Manthey, L. M., Ashtari, F., Kafieh, R., Dehghani, A., Pourazizi, M., Pandit, L., D'Cunha, A., Aktas, O., Albrecht, P., Ringelstein, M., Martinez-Lapiscina, E. H., Sanchez Dalmau, B. F., Villoslada, P., Asgari, N., Marignier, R., Cobo-Calvo, A., Leocani, L., Pisa, M., Radaelli, M., Palace, J., Roca-Fernandez, A., Leite, M. I. S., Sharma, S., De Seze, J., Senger, T., Yeaman, M. R., Smith, T. J., Cook, L. J., Brandt, A. U., Paul, F., & as the Guthy-Jackson Charitable Foundation
Affiliations
  • Max Delbrück Center (DE)
  • From the Experimental and Clinical Research Center (F.C.O., H.G.Z., S.M., C.B., L.M.M., A.U.B., F.P.), Max Delbrück Center for Molecular Medicine and Charité—Universitätsmedizin Berlin; Neuroscience Clinical Research Center (F.C.O., H.G.Z., S.M., C.B., L.M.M., A.U.B., F.P.); Department of Neurology (F.C.O., F.P.), Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin; Einstein Center Digital Future (H.G.Z.), Berlin, Germany; Kashani MS...
Corresponding author
Paul, Friedemann
ORCID
Venue
Neurology Neuroimmunology & Neuroinflammation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2024-09
Volume
11
Issue
5
Pages
e200273-e200273
ISSN
2332-7812 (ISSN-L)
DOI
10.1212/nxi.0000000000200273
PMC
PMC11214151
OpenAlex
W4400109812
Cited by
6
References
2
Citations by year
2026: 4 · 2025: 2
FWCI
1.82
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Neurology Neuroimmunology & Neuroinflammation (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • University of Southern Denmark Research Portal (University of Southern Denmark) (acceptedVersion, cc-by-nc-nd)
  • MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
  • Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
Funders
Medical Research Council (MR/T024682/1)
Topics
  • Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
  • Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
  • Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
Keywords
retinal neurodegeneration, optic neuritis, peripapillary retinal nerve fiber layer thickness, retinal optical coherence tomography, early diagnosis
MeSH terms
Adult, Autoantibodies, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Neuromyelitis Optica, Retina, Retrospective Studies, Tomography, Optical Coherence, Aquaporin 4

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