Diagnostic value of intereye difference metrics for optic neuritis in aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorders

Frederike Cosima Oertel; Hanna G Zimmermann; Seyedamirhosein Motamedi; Claudia Chien; Orhan Aktas; Philipp Albrecht; Marius Ringelstein; Anitha Dcunha; Lekha Pandit; Elena H Martinez-Lapiscina; Bernardo Sanchez-Dalmau; Pablo Villoslada; Jacqueline Palace; Adriana Roca-Fernández; Maria Isabel Leite; Srilakshmi M Sharma; Letizia Leocani; Marco Pisa; Marta Radaelli; Marco Aurélio Lana-Peixoto; Mariana Andrade Fontenelle; Joachim Havla; Fereshteh Ashtari; Rahele Kafieh; Alireza Dehghani; Mohsen Pourazizi; Romain Marignier; Alvaro Cobo-Calvo; Nasrin Asgari; Anu Jacob; Saif Huda; Yang Mao-Draayer; Ari J Green; Rachel Kenney; Michael R Yeaman; Terry J Smith; Lawrence Cook; Alexander U Brandt; Friedemann Paul; Axel Petzold

doi:10.1136/jnnp-2022-330608

Diagnostic value of intereye difference metrics for optic neuritis in aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorders

J Neurol Neurosurg Psychiatry. 2023 Jul;94(7):560-566. doi: 10.1136/jnnp-2022-330608. Epub 2023 Feb 21.

Authors

Frederike Cosima Oertel^{1

2

3}, Hanna G Zimmermann^{1

2

4}, Seyedamirhosein Motamedi^{1

2}, Claudia Chien^{1

2}, Orhan Aktas⁵, Philipp Albrecht⁵, Marius Ringelstein^{5

6}, Anitha Dcunha⁷, Lekha Pandit⁷, Elena H Martinez-Lapiscina⁸, Bernardo Sanchez-Dalmau⁸, Pablo Villoslada^{8

9}, Jacqueline Palace¹⁰, Adriana Roca-Fernández¹⁰, Maria Isabel Leite¹⁰, Srilakshmi M Sharma¹¹, Letizia Leocani¹², Marco Pisa¹², Marta Radaelli¹², Marco Aurélio Lana-Peixoto¹³, Mariana Andrade Fontenelle¹³, Joachim Havla¹⁴, Fereshteh Ashtari¹⁵, Rahele Kafieh¹⁶, Alireza Dehghani¹⁷, Mohsen Pourazizi¹⁷, Romain Marignier¹⁸, Alvaro Cobo-Calvo^{18

19}, Nasrin Asgari^{20

21}, Anu Jacob^{22

23}, Saif Huda²², Yang Mao-Draayer²⁴, Ari J Green³, Rachel Kenney²⁵, Michael R Yeaman^{26

27}, Terry J Smith^{28

29}, Lawrence Cook³⁰, Alexander U Brandt^{1

2

31}, Friedemann Paul^#^{32

2

33}, Axel Petzold^#^{34

35}

Affiliations

¹ NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
² Experimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine and Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
³ Department of Neurology, University of California San Francisco, San Francisco, California, USA.
⁴ Einstein Center Digital Future, Berlin, Germany.
⁵ Department of Neurology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
⁶ Centre for Neurology and Neuropsychiatry, Landschaftsverband Rheinland-Klinikum Düsseldorf, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
⁷ Department of Neurology, KS Hegde Medical Academy, Nitte University, Mangalore, Karnataka, India.
⁸ Hospital Clinic of Barcelona-Institut d'Investigacions, Biomèdiques August Pi Sunyer, (IDIBAPS), Barcelona, Spain.
⁹ Wu Tsai Neurosciences Institute, Stanford University, Palo Alto, California, USA.
¹⁰ Department of Neurology, Oxford University Hospitals, National Health Service Trust, Oxford, UK.
¹¹ Department of Ophthalmology, Oxford University Hospitals, National Health Service Trust, Oxford, UK.
¹² Experimental Neurophysiology Unit, Institute of Experimental Neurology (INSPE) Scientific Institute San Raffaele and University Vita-Salute San Raffaele, Milan, Italy.
¹³ CIEM MS Research Center, University of Minas Gerais, Medical School, Belo Horizonte, Brazil.
¹⁴ Institute of Clinical Neuroimmunology, LMU Hospital, Ludwig-Maximilians Universität München, Munich, Germany.
¹⁵ Kashani MS Center, Isfahan University of Medical Sciences, Isfahan, Iran.
¹⁶ School of advanced technologies in medicine and Medical Image and Signal processing Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
¹⁷ Department of Ophthalmology, Isfahan Eye Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
¹⁸ Neurology, Multiple Sclerosis, Myelin Disorders and Neuroinflammation, Pierre Wertheimer Neurological Hospital, Hospices Civils de Lyon, Lyon, France.
¹⁹ Centre d'Esclerosi Múltiple de Catalunya (Cemcat). Department of Neurology/Neuroimmunology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
²⁰ Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
²¹ Departments of Neurology, Slagelse Hospitals Denmark, Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark.
²² Department of Neurology, The Walton Centre NHS Foundation Trust, Liverpool, UK.
²³ Department of Neurology, Cleveland Clinic Abu Dhabi, Abu Dhabi, UAE.
²⁴ Department of Neurology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
²⁵ Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
²⁶ Department of Medicine, Divisions of Molecular Medicine & Infectious Diseases, Harbor-University of California at Los Angeles (UCLA) Medical Center, and Lundquist Institute for Biomedical Innovation, Torrance, California, USA.
²⁷ Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
²⁸ Departments of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan Medical School, Ann Arbor, Michigan, USA.
²⁹ Division of Metabolism, Endocrine and Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.
³⁰ Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA.
³¹ Department of Neurology, University of California, Irvine, Irvine, California, USA.
³² NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany friedemann.paul@charite.de.
³³ Department of Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
³⁴ Moorfield's Eye Hospital, The National Hospital for Neurology and Neurosurgery, Queen Square Institute of Neurology, University College London, London, UK.
³⁵ Neuro-ophthalmology Expert Center, Amsterdam UMC, Amsterdam, Netherlands.

^# Contributed equally.

Abstract

Background: The novel optic neuritis (ON) diagnostic criteria include intereye differences (IED) of optical coherence tomography (OCT) parameters. IED has proven valuable for ON diagnosis in multiple sclerosis but has not been evaluated in aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorders (AQP4+NMOSD). We evaluated the diagnostic accuracy of intereye absolute (IEAD) and percentage difference (IEPD) in AQP4+NMOSD after unilateral ON >6 months before OCT as compared with healthy controls (HC).

Methods: Twenty-eight AQP4+NMOSD after unilateral ON (NMOSD-ON), 62 HC and 45 AQP4+NMOSD without ON history (NMOSD-NON) were recruited by 13 centres as part of the international Collaborative Retrospective Study on retinal OCT in Neuromyelitis Optica study. Mean thickness of peripapillary retinal nerve fibre layer (pRNFL) and macular ganglion cell and inner plexiform layer (GCIPL) were quantified by Spectralis spectral domain OCT. Threshold values of the ON diagnostic criteria (pRNFL: IEAD 5 µm, IEPD 5%; GCIPL: IEAD: 4 µm, IEPD: 4%) were evaluated using receiver operating characteristics and area under the curve (AUC) metrics.

Results: The discriminative power was high for NMOSD-ON versus HC for IEAD (pRNFL: AUC 0.95, specificity 82%, sensitivity 86%; GCIPL: AUC 0.93, specificity 98%, sensitivity 75%) and IEPD (pRNFL: AUC 0.96, specificity 87%, sensitivity 89%; GCIPL: AUC 0.94, specificity 96%, sensitivity 82%). The discriminative power was high/moderate for NMOSD-ON versus NMOSD-NON for IEAD (pRNFL: AUC 0.92, specificity 77%, sensitivity 86%; GCIP: AUC 0.87, specificity 85%, sensitivity 75%) and for IEPD (pRNFL: AUC 0.94, specificity 82%, sensitivity 89%; GCIP: AUC 0.88, specificity 82%, sensitivity 82%).

Conclusions: Results support the validation of the IED metrics as OCT parameters of the novel diagnostic ON criteria in AQP4+NMOSD.

Keywords: neuroimmunology; neuroophthalmology; vision.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aquaporin 4
Aquaporins*
Autoantibodies
Benchmarking
Humans
Neuromyelitis Optica* / diagnosis
Optic Neuritis* / diagnosis
Retrospective Studies
Tomography, Optical Coherence / methods

Substances

Autoantibodies
Aquaporins
Aquaporin 4