MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 4: Afferent visual system damage after optic neuritis in MOG-IgG-seropositive versus AQP4-IgG-seropositive patients.
Antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) have been reported in patients with aquaporin-4 antibody (AQP4-IgG)-negative neuromyelitis optica spectrum disorders (NMOSD). The objective of this study was to describe optic neuritis (ON)-induced neuro-axonal damage in the retina of MOG-IgG-positive patients in comparison with AQP4-IgG-positive NMOSD patients.



Afferent visual system damage following ON was bilaterally assessed in 16 MOG-IgG-positive patients with a history of ON and compared with that in 16 AQP4-IgG-positive NMOSD patients. In addition, 16 healthy controls matched for age, sex, and disease duration were analyzed. Study data included ON history, retinal optical coherence tomography, visual acuity, and visual evoked potentials.



Eight MOG-IgG-positive patients had a previous diagnosis of AQP4-IgG-negative NMOSD with ON and myelitis, and eight of (mainly recurrent) ON. Twenty-nine of the 32 eyes of the MOG-IgG-positive patients had been affected by at least one episode of ON. Peripapillary retinal nerve fiber layer thickness (pRNFL) and ganglion cell and inner plexiform layer volume (GCIP) were significantly reduced in ON eyes of MOG-IgG-positive patients (pRNFL = 59 ± 23 μm; GCIP = 1.50 ± 0.34 mm3) compared with healthy controls (pRNFL = 99 ± 6 μm, p < 0.001; GCIP = 1.97 ± 0.11 mm3, p < 0.001). Visual acuity was impaired in eyes after ON in MOG-IgG-positive patients (0.35 ± 0.88 logMAR). There were no significant differences in any structural or functional visual parameters between MOG-IgG-positive and AQP4-IgG-positive patients (pRNFL: 59 ± 21 μm; GCIP: 1.41 ± 0.27 mm3; Visual acuity = 0.72 ± 1.09 logMAR). Importantly, MOG-IgG-positive patients had a significantly higher annual ON relapse rate than AQP4-IgG-positive patients (median 0.69 vs. 0.29 attacks/year, p = 0.004), meaning that on average a single ON episode caused less damage in MOG-IgG-positive than in AQP4-IgG-positive patients. pRNFL and GCIP loss correlated with the number of ON episodes in MOG-IgG-positive patients (p < 0.001), but not in AQP4-IgG-positive patients.



Retinal neuro-axonal damage and visual impairment after ON in MOG-IgG-positive patients are as severe as in AQP4-IgG-positive NMOSD patients. In MOG-IgG-positive patients, damage accrual may be driven by higher relapse rates, whereas AQP4-IgG-positive patients showed fewer but more severe episodes of ON. Given the marked damage in some of our MOG-IgG-positive patients, early diagnosis and timely initiation and close monitoring of immunosuppressive therapy are important.
NeuroCure Clinical Research Center (NCRC), Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.|Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Florence
F
Pache
NeuroCure Clinical Research Center (NCRC), Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.|Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Hanna
H
Zimmermann
NeuroCure Clinical Research Center (NCRC), Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
Janine
J
Mikolajczak
NeuroCure Clinical Research Center (NCRC), Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
Sophie
S
Schumacher
NeuroCure Clinical Research Center (NCRC), Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
Anna
A
Lacheta
NeuroCure Clinical Research Center (NCRC), Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
Frederike C
FC
Oertel
NeuroCure Clinical Research Center (NCRC), Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.|Experimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine and Charité - Universitätsmedizin Berlin, Berlin, Germany.
Judith
J
Bellmann-Strobl
Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany.
Sven
S
Jarius
Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany.
Brigitte
B
Wildemann
Clinical Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
Markus
M
Reindl
Division of Neurology, Children's Hospital of Philadelphia, Pennsylvania, USA.
Amy
A
Waldman
Department of Neurology, Vejle Hospital, Vejle, Denmark.|Department of Neurobiology, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Kerstin
K
Soelberg
Department of Neurology, Vejle Hospital, Vejle, Denmark.|Department of Neurobiology, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Nasrin
N
Asgari
Department of Neurology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
Marius
M
Ringelstein
Department of Neurology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
Orhan
O
Aktas
Department of Ophthalmology, Medical Faculty, University of Freiburg, Freiburg, Germany.
Nikolai
N
Gross
Department of Neurology, University of Würzburg, Würzburg, Germany.
Mathias
M
Buttmann
Department of Ophthalmology, University of Würzburg, Würzburg, Germany.
Thomas
T
Ach
Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Klemens
K
Ruprecht
NeuroCure Clinical Research Center (NCRC), Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.|Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany.|Experimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine and Charité - Universitätsmedizin Berlin, Berlin, Germany.
Friedemann
F
Paul
NeuroCure Clinical Research Center (NCRC), Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany. Alexander.Brandt@charite.de.
Alexander U
AU
Brandt
D000328:Adult; D051401:Aquaporin 4 / Q000276:immunology*; D005074:Evoked Potentials, Visual / Q000502:physiology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D008297:Male; D008875:Middle Aged; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology*; D009902:Optic Neuritis / Q000097:blood / Q000150:complications / Q000276:immunology; D010775:Photic Stimulation; D011930:Reaction Time / Q000502:physiology; D012160:Retina / Q000473:pathology; D012164:Retinal Diseases / Q000209:etiology*; D018709:Statistics, Nonparametric; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000502:physiology; D014795:Visual Pathways / Q000473:pathology / Q000503:physiopathology
D051401:Aquaporin 4; D007074:Immunoglobulin G; D063308:Myelin-Oligodendrocyte Glycoprotein
Devic syndrome; Myelin oligodendrocyte glycoprotein antibodies (MOG-IgG); NMO-IgG; aquaporin-4 antibodies (AQP4-IgG); neuromyelitis optica; neuromyelitis optica spectrum disorders (NMOSD); optic neuritis; optical coherence tomography; retinal neuro-axonal damage; visual acuity; visual evoked potentials