Altered fovea in AQP4-IgG-seropositive neuromyelitis optica spectrum disorders

Seyedamirhosein Motamedi; Frederike C Oertel; Sunil K Yadav; Ella M Kadas; Margit Weise; Joachim Havla; Marius Ringelstein; Orhan Aktas; Philipp Albrecht; Klemens Ruprecht; Judith Bellmann-Strobl; Hanna G Zimmermann; Friedemann Paul; Alexander U Brandt

doi:10.1212/NXI.0000000000000805

Altered fovea in AQP4-IgG-seropositive neuromyelitis optica spectrum disorders

Neurol Neuroimmunol Neuroinflamm. 2020 Jun 23;7(5):e805. doi: 10.1212/NXI.0000000000000805. Print 2020 Sep.

Affiliations

¹ From the Experimental and Clinical Research Center (S.M., F.C.O., J.B.-S., H.G.Z., F.P., A.U.B.), Max-Delbrück Center for Molecular Medicine and Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; NeuroCure Clinical Research Center (S.M., F.C.O., S.K.Y., E.M.K., J.B.-S., H.G.Z., F.P., A.U.B.), Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany; Division of Neuroinflammation and Glial Biology (F.C.O.), University of California, San Francisco; Nocturne GmbH (S.K.Y., E.M.K.), Berlin; Department of Neurology (M.W., M.R., O.A., P.A.), Medical Faculty, Heinrich Heine University, Düsseldorf; Institute of Clinical Neuroimmunology (J.H.), LMU Hospital, Ludwig-Maximilians University, Munich; Department of Neurology (M.R.), Center for Neurology and Neuropsychiatry, LVR-Klinikum Düsseldorf; Department of Neurology (K.R., F.P.), Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany; and Department of Neurology (A.U.B.), University of California, Irvine.
² From the Experimental and Clinical Research Center (S.M., F.C.O., J.B.-S., H.G.Z., F.P., A.U.B.), Max-Delbrück Center for Molecular Medicine and Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; NeuroCure Clinical Research Center (S.M., F.C.O., S.K.Y., E.M.K., J.B.-S., H.G.Z., F.P., A.U.B.), Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany; Division of Neuroinflammation and Glial Biology (F.C.O.), University of California, San Francisco; Nocturne GmbH (S.K.Y., E.M.K.), Berlin; Department of Neurology (M.W., M.R., O.A., P.A.), Medical Faculty, Heinrich Heine University, Düsseldorf; Institute of Clinical Neuroimmunology (J.H.), LMU Hospital, Ludwig-Maximilians University, Munich; Department of Neurology (M.R.), Center for Neurology and Neuropsychiatry, LVR-Klinikum Düsseldorf; Department of Neurology (K.R., F.P.), Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany; and Department of Neurology (A.U.B.), University of California, Irvine. alexander.brandt@charite.de.

Abstract

Objective: To investigate disease-specific foveal shape changes in patients with neuromyelitis optica spectrum disorders (NMOSDs) using foveal morphometry.

Methods: This cross-sectional study included macular spectral domain optical coherence tomography scans of 52 eyes from 28 patients with aquaporin-4 immunoglobulin G (AQP4-IgG)-seropositive NMOSD, 116 eyes from 60 patients with MS, and 123 eyes from 62 healthy controls (HCs), retrospectively, and an independent confirmatory cohort comprised 33/33 patients with NMOSD/MS. The fovea was characterized using 3D foveal morphometry. We included peripapillary retinal nerve fiber layer (pRNFL) thickness and combined macular ganglion cell and inner plexiform layer (GCIPL) volume to account for optic neuritis (ON)-related neuroaxonal damage.

Results: Group comparison showed significant differences compared with HC in the majority of foveal shape parameters in NMOSD, but not MS. Pit flat disk area, average pit flat disk diameter, inner rim volume, and major slope disk length, as selected parameters, showed differences between NMOSD and MS (p value = 0.017, 0.002, 0.005, and 0.033, respectively). This effect was independent of ON. Area under the curve was between 0.7 and 0.8 (receiver operating characteristic curve) for discriminating between NMOSD and MS. Pit flat disk area and average pit flat disk diameter changes independent of ON were confirmed in an independent cohort.

Conclusions: Foveal morphometry reveals a wider and flatter fovea in NMOSD in comparison to MS and HC. Comparison to MS and accounting for ON suggest this effect to be at least in part independent of ON. This supports a primary retinopathy in AQP4-IgG-seropositive NMOSD.

Publication types

Comparative Study
Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aquaporin 4 / immunology*
Cross-Sectional Studies
Female
Fovea Centralis / diagnostic imaging
Fovea Centralis / pathology*
Humans
Immunoglobulin G
Male
Middle Aged
Multiple Sclerosis / diagnostic imaging
Multiple Sclerosis / pathology*
Neuromyelitis Optica / diagnostic imaging
Neuromyelitis Optica / immunology*
Neuromyelitis Optica / pathology*
Retrospective Studies
Tomography, Optical Coherence

Substances

AQP4 protein, human
Aquaporin 4
Immunoglobulin G