Seyedamirhosein Motamedi1, Frederike C Oertel1, Sunil K Yadav1, Ella M Kadas1, Margit Weise1, Joachim Havla1, Marius Ringelstein1, Orhan Aktas1, Philipp Albrecht1, Klemens Ruprecht1, Judith Bellmann-Strobl1, Hanna G Zimmermann1, Friedemann Paul1, Alexander U Brandt2. 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.
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.
Authors: Alexander U Brandt; Hanna G Zimmermann; Norman K Gigengack; Frederike C Oertel; Seyedamirhosein Motamedi; Charlotte Bereuter; Ankelien Duchow; Rebekka Rust; Judith Bellmann-Strobl; Klemens Ruprecht; Tanja Schmitz-Hübsch; Friedemann Paul Journal: Sci Rep Date: 2022-10-20 Impact factor: 4.996
Authors: Otto Jesus Hernandez Fustes; Cláudia S K Kay; Paulo José Lorenzoni; Renata D-P Ducci; Lineu C Werneck; Rosana Herminia Scola Journal: J Cent Nerv Syst Dis Date: 2021-12-21
Authors: Alexander U Brandt; Frederike Cosima Oertel; Angelo Lu; Hanna G Zimmermann; Svenja Specovius; Seyedamirhosein Motamedi; Claudia Chien; Charlotte Bereuter; Marco A Lana-Peixoto; Mariana Andrade Fontenelle; Fereshteh Ashtari; Rahele Kafieh; Alireza Dehghani; Mohsen Pourazizi; Lekha Pandit; Anitha D'Cunha; Ho Jin Kim; Jae-Won Hyun; Su-Kyung Jung; Letizia Leocani; Marco Pisa; Marta Radaelli; Sasitorn Siritho; Eugene F May; Caryl Tongco; Jérôme De Sèze; Thomas Senger; Jacqueline Palace; Adriana Roca-Fernández; Maria Isabel Leite; Srilakshmi M Sharma; Hadas Stiebel-Kalish; Nasrin Asgari; Kerstin Kathrine Soelberg; Elena H Martinez-Lapiscina; Joachim Havla; Yang Mao-Draayer; Zoe Rimler; Allyson Reid; Romain Marignier; Alvaro Cobo-Calvo; Ayse Altintas; Uygur Tanriverdi; Rengin Yildirim; Orhan Aktas; Marius Ringelstein; Philipp Albrecht; Ivan Maynart Tavares; Denis Bernardi Bichuetti; Anu Jacob; Saif Huda; Ibis Soto de Castillo; Axel Petzold; Ari J Green; Michael R Yeaman; Terry J Smith; Lawrence Cook; Friedemann Paul Journal: J Neurol Neurosurg Psychiatry Date: 2021-10-28 Impact factor: 13.654
Authors: Axel Petzold; Philipp Albrecht; Laura Balcer; Erik Bekkers; Alexander U Brandt; Peter A Calabresi; Orla Galvin Deborah; Jennifer S Graves; Ari Green; Pearse A Keane; Jenny A Nij Bijvank; Josemir W Sander; Friedemann Paul; Shiv Saidha; Pablo Villoslada; Siegfried K Wagner; E Ann Yeh Journal: Ann Clin Transl Neurol Date: 2021-05-19 Impact factor: 4.511
Authors: Alexander U Brandt; Friedemann Paul; Svenja Specovius; Hanna G Zimmermann; Frederike Cosima Oertel; Claudia Chien; Charlotte Bereuter; Lawrence J Cook; Marco Aurélio Lana Peixoto; Mariana Andrade Fontenelle; Ho Jin Kim; Jae-Won Hyun; Su-Kyung Jung; Jacqueline Palace; Adriana Roca-Fernandez; Alejandro Rubio Diaz; Maria Isabel Leite; Srilakshmi M Sharma; Fereshte Ashtari; Rahele Kafieh; Alireza Dehghani; Mohsen Pourazizi; Lekha Pandit; Anitha Dcunha; Orhan Aktas; Marius Ringelstein; Philipp Albrecht; Eugene May; Caryl Tongco; Letizia Leocani; Marco Pisa; Marta Radaelli; Elena H Martinez-Lapiscina; Hadas Stiebel-Kalish; Mark Hellmann; Itay Lotan; Sasitorn Siritho; Jérôme de Seze; Thomas Senger; Joachim Havla; Romain Marignier; Caroline Tilikete; Alvaro Cobo Calvo; Denis Bernardi Bichuetti; Ivan Maynart Tavares; Nasrin Asgari; Kerstin Soelberg; Ayse Altintas; Rengin Yildirim; Uygur Tanriverdi; Anu Jacob; Saif Huda; Zoe Rimler; Allyson Reid; Yang Mao-Draayer; Ibis Soto de Castillo; Michael R Yeaman; Terry J Smith Journal: BMJ Open Date: 2020-10-29 Impact factor: 2.692