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Multicenter Study
. 2016 Nov 1;13(1):282.
doi: 10.1186/s12974-016-0720-6.

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

Florence Pache  1   2 , Hanna Zimmermann  1   2 , Janine Mikolajczak  1 , Sophie Schumacher  1 , Anna Lacheta  1 , Frederike C Oertel  1 , Judith Bellmann-Strobl  1   3 , Sven Jarius  4 , Brigitte Wildemann  4 , Markus Reindl  5 , Amy Waldman  6 , Kerstin Soelberg  7   8 , Nasrin Asgari  7   8 , Marius Ringelstein  9 , Orhan Aktas  9 , Nikolai Gross  10 , Mathias Buttmann  11 , Thomas Ach  12 , Klemens Ruprecht  2 , Friedemann Paul  1   2   3 , Alexander U Brandt  13 ; in cooperation with the Neuromyelitis Optica Study Group (NEMOS)
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Multicenter Study

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

Florence Pache et al. J Neuroinflammation. .

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: 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.

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Figures

Fig. 1
Fig. 1
Sample images from patient 1. a Sample images from a peripapillary ring scan. On the left, a scanning laser ophthalmoscopy image shows scan positioning (in green). On the right, an OCT scan shows severe peripapillary retinal nerve fiber layer (pRNFL) loss (between the inner limiting membrane [ILM], shown in red, and the lower border, in turquoise). b Ring-scan data in comparison with normative device data from both eyes of this patient. Black numbers display the thickness measurements (in μm) of the subject, green numbers the average thickness in the age-matched reference group. Sectors are classified in comparison with the reference group: green, thickness values within the 5th and 95th percentile range; yellow, 1st to 5th percentile range; red, below the 1st percentile. Abbreviations: G global, NS nasal-superior, N nasal, NI nasal-inferior, TI temporal-inferior, T temporal, TS temporal-superior. c Macular scan of the same patient. On the left, the dark, sickle-shaped area on and around the macula represents tissue with microcysts in the inner nuclear layer (INL). The white circle indicates the 6-mm-diameter cylinder in which intraretinal layers are analyzed. The green line with arrow shows the scanning position of the OCT scan on the right. Here, the defined layers are the RNFL, the ganglion cell and inner plexiform layer (GCIP), then INL and the outer retinal layers (ORL). Macular microcysts can be seen as small black dots in the INL
Fig. 2
Fig. 2
Retinal layer measures of MOG-IgG-positive and AQP4-IgG-positive ON eyes. Boxplots for the comparison of retinal layer measures of the eyes in the healthy control group and the ON eyes of MOG-IgG-positive (MOG-IgG+) and AQP4-IgG-positive (AQP4-IgG+) NMOSD patients. (a) Peripapillary retinal nerve fiber layer thickness derived from a ring scan (pRNFL); (b-d) Intraretinal layer volumes quantified in a 6-mm-diameter cylinder around the fovea centralis: (b) ganglion cell and inner plexifom layer volume (GCIP); (c) inner nuclear layer volume (INL); (d) outer retinal layer volume comprising all layers from outer plexiform layer to Bruch’s membrane
Fig. 3
Fig. 3
Retinal nerve fiber layer loss as a function of optic neuritis in MOG-IgG-positive and AQP4-IgG-positive patients. Peripapillary retinal nerve fiber layer (pRNFL) loss caused by sequential episodes of optic neuritis (ON), estimated from cross-sectional data, in comparison with eyes without optic neuritis from the healthy control (HC) cohort. (a) ON eyes from MOG-IgG-seropositive patients (MOG-IgG+); (b) ON eyes from AQP4-IgG-seropositive patients (AQP4-IgG+). P-values were computed with linear regressions
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