Optical coherence tomography in myelin-oligodendrocyte-glycoprotein antibody-seropositive patients: a longitudinal study

Frederike C Oertel; Olivier Outteryck; Benjamin Knier; Hanna Zimmermann; Nadja Borisow; Judith Bellmann-Strobl; Astrid Blaschek; Sven Jarius; Markus Reindl; Klemens Ruprecht; Edgar Meinl; Reinhard Hohlfeld; Friedemann Paul; Alexander U Brandt; Tania Kümpfel; Joachim Havla

doi:10.1186/s12974-019-1521-5

Optical coherence tomography in myelin-oligodendrocyte-glycoprotein antibody-seropositive patients: a longitudinal study

J Neuroinflammation. 2019 Jul 25;16(1):154. doi: 10.1186/s12974-019-1521-5.

Authors

Frederike C Oertel^{1

2}, Olivier Outteryck³, Benjamin Knier⁴, Hanna Zimmermann^{1

2}, Nadja Borisow^{1

2}, Judith Bellmann-Strobl^{1

2}, Astrid Blaschek⁵, Sven Jarius⁶, Markus Reindl⁷, Klemens Ruprecht⁸, Edgar Meinl⁹, Reinhard Hohlfeld^{10

9}, Friedemann Paul^{1

2

8}, Alexander U Brandt^{11

12

13}, Tania Kümpfel⁹, Joachim Havla^{9

14}

Affiliations

¹ Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Robert-Rössle-Straße 10, 13125, Berlin, Germany.
² NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.
³ Department of Neurology and Neuroradiology, Roger Salengro Hospital, University of Lille, INSERM 1171, Avenue du Professeur Emile Laine, 59037, Lille, France.
⁴ Department of Neurology, Klinikum Rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675, Munich, Germany.
⁵ Department of Pediatric Neurology and Developmental Medicine, Dr. von Hauner's Children's Hospital, University of Munich, Lindwurmstraße 4, 80337, Munich, Germany.
⁶ Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.
⁷ Clinical Department of Neurology, Medical University of Innsbruck, Anichstraße 35, 6020, Innsbruck, Austria.
⁸ Department of Neurology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin, Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.
⁹ Institute of Clinical Neuroimmunology, Ludwig-Maximilians University, Marchioninistr. 15, 81377, Munich, Germany.
¹⁰ Munich Cluster for Systems Neurology, Feodor-Lynen-Str 17, 81377, Munich, Germany.
¹¹ Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Robert-Rössle-Straße 10, 13125, Berlin, Germany. alexander.brandt@charite.de.
¹² NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany. alexander.brandt@charite.de.
¹³ Department of Neurology, University of California Irvine, 30, 101 The City Dr S, Orange, CA, 92868, USA. alexander.brandt@charite.de.
¹⁴ Data Integration for Future Medicine consortium (DIFUTURE), Ludwig-Maximilians University, Marchioninistr. 15, Munich, 81377, Germany.

Abstract

Background: Serum antibodies against myelin-oligodendrocyte-glycoprotein (MOG-IgG) are detectable in a proportion of patients with acute or relapsing neuroinflammation. It is unclear, if neuro-axonal damage occurs only in an attack-dependent manner or also progressively. Therefore, this study aimed to investigate longitudinally intra-retinal layer changes in eyes without new optic neuritis (ON) in MOG-IgG-seropositive patients.

Methods: We included 38 eyes of 24 patients without ON during follow-up (F/U) [median years (IQR)] 1.9 (1.0-2.2) and 56 eyes of 28 age- and sex-matched healthy controls (HC). The patient group's eyes included 18 eyes without (Eye^ON-) and 20 eyes with history of ON (Eye^ON+). Using spectral domain optical coherence tomography (OCT), we acquired peripapillary retinal nerve fiber layer thickness (pRNFL) and volumes of combined ganglion cell and inner plexiform layer (GCIP), inner nuclear layer (INL), and macular volume (MV). High-contrast visual acuity (VA) was assessed at baseline.

Results: At baseline in Eye^ON-, pRNFL (94.3 ± 15.9 μm, p = 0.36), INL (0.26 ± 0.03 mm³, p = 0.11), and MV (2.34 ± 0.11 mm³, p = 0.29) were not reduced compared to HC; GCIP showed thinning (0.57 ± 0.07 mm³; p = 0.008), and VA was reduced (logMAR 0.05 ± 0.15 vs. - 0.09 ± 0.14, p = 0.008) in comparison to HC. Longitudinally, we observed pRNFL thinning in models including all patient eyes (annual reduction - 2.20 ± 4.29 μm vs. - 0.35 ± 1.17 μm, p = 0.009) in comparison to HC. Twelve Eye^ON- with other than ipsilateral ON attacks ≤ 6 months before baseline showed thicker pRNFL at baseline and more severe pRNFL thinning in comparison to 6 Eye^ON- without other clinical relapses.

Conclusions: We observed pRNFL thinning in patients with MOG-IgG during F/U, which was not accompanied by progressive GCIP reduction. This effect could be caused by a small number of Eye^ON- with other than ipsilateral ON attacks within 6 months before baseline. One possible interpretation could be a reduction of the swelling, which could mean that MOG-IgG patients show immune-related swelling in the CNS also outside of an attack's target area.

Keywords: Myelin-oligodendrocyte-glycoprotein; Optic neuritis; Optical coherence tomography.

MeSH terms

Adolescent
Adult
Aged
Autoantibodies / blood*
Child
Humans
Longitudinal Studies
Middle Aged
Myelin-Oligodendrocyte Glycoprotein / immunology*
Optic Neuritis / blood
Optic Neuritis / diagnostic imaging*
Optic Neuritis / immunology
Retina / diagnostic imaging*
Tomography, Optical Coherence
Young Adult

Substances

Autoantibodies
Myelin-Oligodendrocyte Glycoprotein

Abstract

MeSH terms

Substances

Grants and funding