Adriana Roca-Fernández1,2, Frederike Cosima Oertel3,4, Tianrong Yeo5,6, Seyedamirhosein Motamedi3,4, Fay Probert5, Matthew J Craner1, Jaume Sastre-Garriga2, Hanna G Zimmermann3,4, Susanna Asseyer3,4, Joseph Kuchling3,4,7,8, Judith Bellmann-Strobl3,4, Klemens Ruprecht7, Maria Isabel Leite1, Friedemann Paul3,4,7, Alexander Ulrich Brandt3,4,9, Jacqueline Palace1. 1. Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK. 2. Department of Neurology/Neuroimmunology, Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain. 3. Experimental and Clinical Research Center, 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, Berlin, Germany. 4. NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany. 5. Department of Pharmacology, University of Oxford, Oxford, UK. 6. Department of Neurology, National Neuroscience Institute, Singapore, Singapore. 7. Department of Neurology, Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany. 8. Berlin Institute of Health (BIH, Berlin, Germany. 9. Department of Neurology, University of California Irvine, Irvine, CA, USA.
Abstract
BACKGROUND AND PURPOSE: Foveal changes were reported in aquaporin-4 antibody (AQP4-Ab) seropositive neuromyelitis optica spectrum disorder (NMOSD) patients; however, it is unclear whether they are independent of optic neuritis (ON), stem from subclinical ON or crossover from ON in fellow eyes. Fovea morphometry and a statistical classification approach were used to investigate if foveal changes in NMOSD are independent of ON and progressive. METHODS: This was a retrospective longitudinal study of 27 AQP4-IgG + NMOSD patients (49 eyes; 15 ON eyes and 34 eyes without a history of ON [NON eyes]), follow-up median (first and third quartile) 2.32 (1.33-3.28), and 38 healthy controls (HCs) (76 eyes), follow-up median (first and third quartile) 1.95 (1.83-2.54). The peripapillary retinal nerve fibre layer thickness and the volume of combined ganglion cell and inner plexiform layer as measures of neuroaxonal damage from ON were determined by optical coherence tomography. Nineteen foveal morphometry parameters were extracted from macular optical coherence tomography volume scans. Data were analysed using orthogonal partial least squares discriminant analysis and linear mixed effects models. RESULTS: At baseline, foveal shape was significantly altered in ON eyes and NON eyes compared to HCs. Discriminatory analysis showed 81% accuracy distinguishing ON vs. HCs and 68% accuracy in NON vs. HCs. NON eyes were distinguished from HCs by foveal shape parameters indicating widening. Orthogonal partial least squares discriminant analysis discriminated ON vs. NON with 76% accuracy. In a follow-up of 2.4 (20.85) years, no significant time-dependent foveal changes were found. CONCLUSION: The parafoveal area is altered in AQP4-Ab seropositive NMOSD patients suggesting independent neuroaxonal damage from subclinical ON. Longer follow-ups are needed to confirm the stability of the parafoveal structure over time.
BACKGROUND AND PURPOSE: Foveal changes were reported in aquaporin-4 antibody (AQP4-Ab) seropositive neuromyelitis optica spectrum disorder (NMOSD) patients; however, it is unclear whether they are independent of optic neuritis (ON), stem from subclinical ON or crossover from ON in fellow eyes. Fovea morphometry and a statistical classification approach were used to investigate if foveal changes in NMOSD are independent of ON and progressive. METHODS: This was a retrospective longitudinal study of 27 AQP4-IgG + NMOSD patients (49 eyes; 15 ON eyes and 34 eyes without a history of ON [NON eyes]), follow-up median (first and third quartile) 2.32 (1.33-3.28), and 38 healthy controls (HCs) (76 eyes), follow-up median (first and third quartile) 1.95 (1.83-2.54). The peripapillary retinal nerve fibre layer thickness and the volume of combined ganglion cell and inner plexiform layer as measures of neuroaxonal damage from ON were determined by optical coherence tomography. Nineteen foveal morphometry parameters were extracted from macular optical coherence tomography volume scans. Data were analysed using orthogonal partial least squares discriminant analysis and linear mixed effects models. RESULTS: At baseline, foveal shape was significantly altered in ON eyes and NON eyes compared to HCs. Discriminatory analysis showed 81% accuracy distinguishing ON vs. HCs and 68% accuracy in NON vs. HCs. NON eyes were distinguished from HCs by foveal shape parameters indicating widening. Orthogonal partial least squares discriminant analysis discriminated ON vs. NON with 76% accuracy. In a follow-up of 2.4 (20.85) years, no significant time-dependent foveal changes were found. CONCLUSION: The parafoveal area is altered in AQP4-Ab seropositive NMOSD patients suggesting independent neuroaxonal damage from subclinical ON. Longer follow-ups are needed to confirm the stability of the parafoveal structure over time.
Authors: Frederike Cosima Oertel; Svenja Specovius; Hanna G Zimmermann; Claudia Chien; Seyedamirhosein Motamedi; Charlotte Bereuter; Lawrence Cook; Marco Aurélio Lana Peixoto; Mariana Andrade Fontanelle; Ho Jin Kim; Jae-Won Hyun; Jacqueline Palace; Adriana Roca-Fernandez; Maria Isabel Leite; Srilakshmi Sharma; Fereshteh Ashtari; Rahele Kafieh; Alireza Dehghani; Mohsen Pourazizi; Lekha Pandit; Anitha D'Cunha; Orhan Aktas; Marius Ringelstein; Philipp Albrecht; Eugene May; Caryl Tongco; Letizia Leocani; Marco Pisa; Marta Radaelli; Elena H Martinez-Lapiscina; Hadas Stiebel-Kalish; Sasitorn Siritho; Jérome de Seze; Thomas Senger; Joachim Havla; Romain Marignier; Alvaro Cobo-Calvo; Denis 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; Axel Petzold; Ari J Green; Michael R Yeaman; Terry Smith; Alexander U Brandt; Friedemann Paul Journal: Neurol Neuroimmunol Neuroinflamm Date: 2021-09-15