Rachel C Nolan-Kenney1,2, Mengling Liu1, Omar Akhand2, Peter A Calabresi3, Friedemann Paul4,5, Axel Petzold6,7,8, Lisanne Balk6,7,8, Alexander U Brandt4,9, Elena H Martínez-Lapiscina10, Shiv Saidha3, Pablo Villoslada10, Abdullah Abu Al-Hassan11, Raed Behbehani11, Elliot M Frohman12, Teresa Frohman12, Joachim Havla13,14, Bernhard Hemmer15, Hong Jiang16, Benjamin Knier17, Thomas Korn15,17, Letizia Leocani18, Athina Papadopoulou4,19, Marco Pisa18, Hanna Zimmermann4, Steven L Galetta2,20, Laura J Balcer2,20,21. 1. Department of Population Health, Sackler Institute for Biomedical Sciences, New York University School of Medicine, New York, NY. 2. Department of Neurology, New York University School of Medicine, New York, NY. 3. Department of Neurology, Johns Hopkins University, Baltimore, MD. 4. NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, Free University Berlin, Humboldt University of Berlin, and Berlin Institute of Health, Berlin, Germany. 5. Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Berlin, Germany. 6. Moorfields Eye Hospital, London, United Kingdom. 7. The National Hospital for Neurology and Neurosurgery & UCL Institute of Neurology, Queen Square, London, United Kingdom. 8. Neuro-ophthalmology Expertise Center & Multiple Sclerosis Center, Amsterdam UMC, The Netherlands. 9. Department of Neurology, University of California, Irvine, Irvine, CA. 10. Center of Neuroimmunology and Department of Neurology, Hospital Clinic of Barcelona, August Pi i Sunyer Biomedical Research Institute, University of Barcelona, Barcelona, Spain. 11. Dasman Institute, Kuwait City, Kuwait. 12. Department of Neurology and Ophthalmology, University of Texas at Austin, Austin, TX. 13. Institute of Clinical Neuroimmunology, Ludwig Maximilian University, Munich, Germany. 14. Data Integration for Future Medicine Consortium, Ludwig Maximilian University, Munich, Germany. 15. Munich Cluster for Systems Neurology, Munich, Germany. 16. Bascom Palmer Eye Institute, Department of Neurology, University of Miami Miller School of Medicine, Miami, FL. 17. Technical University of Munich, Munich, Germany. 18. Vita-Salute San Raffaele University and San Raffaele Hospital, Milan, Italy. 19. Department of Neurology, University Hospital of Basel, Basel, Switzerland. 20. Department of Ophthalmology, New York University School of Medicine, New York, NY. 21. Department of Population Health, New York University School of Medicine, New York, NY.
Abstract
OBJECTIVE: To determine the optimal thresholds for intereye differences in retinal nerve fiber and ganglion cell + inner plexiform layer thicknesses for identifying unilateral optic nerve lesions in multiple sclerosis. Current international diagnostic criteria for multiple sclerosis do not include the optic nerve as a lesion site despite frequent involvement. Optical coherence tomography detects retinal thinning associated with optic nerve lesions. METHODS: In this multicenter international study at 11 sites, optical coherence tomography was measured for patients and healthy controls as part of the International Multiple Sclerosis Visual System Consortium. High- and low-contrast acuity were also collected in a subset of participants. Presence of an optic nerve lesion for this study was defined as history of acute unilateral optic neuritis. RESULTS: Among patients (n = 1,530), receiver operating characteristic curve analysis demonstrated an optimal peripapillary retinal nerve fiber layer intereye difference threshold of 5μm and ganglion cell + inner plexiform layer threshold of 4μm for identifying unilateral optic neuritis (n = 477). Greater intereye differences in acuities were associated with greater intereye retinal layer thickness differences (p ≤ 0.001). INTERPRETATION: Intereye differences of 5μm for retinal nerve fiber layer and 4μm for macular ganglion cell + inner plexiform layer are robust thresholds for identifying unilateral optic nerve lesions. These thresholds may be useful in establishing the presence of asymptomatic and symptomatic optic nerve lesions in multiple sclerosis and could be useful in a new version of the diagnostic criteria. Our findings lend further validation for utilizing the visual system in a multiple sclerosis clinical trial setting. Ann Neurol 2019;85:618-629.
OBJECTIVE: To determine the optimal thresholds for intereye differences in retinal nerve fiber and ganglion cell + inner plexiform layer thicknesses for identifying unilateral optic nerve lesions in multiple sclerosis. Current international diagnostic criteria for multiple sclerosis do not include the optic nerve as a lesion site despite frequent involvement. Optical coherence tomography detects retinal thinning associated with optic nerve lesions. METHODS: In this multicenter international study at 11 sites, optical coherence tomography was measured for patients and healthy controls as part of the International Multiple Sclerosis Visual System Consortium. High- and low-contrast acuity were also collected in a subset of participants. Presence of an optic nerve lesion for this study was defined as history of acute unilateral optic neuritis. RESULTS: Among patients (n = 1,530), receiver operating characteristic curve analysis demonstrated an optimal peripapillary retinal nerve fiber layer intereye difference threshold of 5μm and ganglion cell + inner plexiform layer threshold of 4μm for identifying unilateral optic neuritis (n = 477). Greater intereye differences in acuities were associated with greater intereye retinal layer thickness differences (p ≤ 0.001). INTERPRETATION: Intereye differences of 5μm for retinal nerve fiber layer and 4μm for macular ganglion cell + inner plexiform layer are robust thresholds for identifying unilateral optic nerve lesions. These thresholds may be useful in establishing the presence of asymptomatic and symptomatic optic nerve lesions in multiple sclerosis and could be useful in a new version of the diagnostic criteria. Our findings lend further validation for utilizing the visual system in a multiple sclerosis clinical trial setting. Ann Neurol 2019;85:618-629.
Authors: Ruth Ann Marrie; Mark Allegretta; Lisa F Barcellos; Bruce Bebo; Peter A Calabresi; Jorge Correale; Benjamin Davis; Philip L De Jager; Christiane Gasperi; Carla Greenbaum; Anne Helme; Bernhard Hemmer; Pamela Kanellis; Walter Kostich; Douglas Landsman; Christine Lebrun-Frenay; Naila Makhani; Kassandra L Munger; Darin T Okuda; Daniel Ontaneda; Ronald B Postuma; Jacqueline A Quandt; Sharon Roman; Shiv Saidha; Maria Pia Sormani; Jon Strum; Pamela Valentine; Clare Walton; Kathleen M Zackowski; Yinshan Zhao; Helen Tremlett Journal: Nat Rev Neurol Date: 2022-07-15 Impact factor: 44.711
Authors: Rachel C Kenney; Mengling Liu; Lisena Hasanaj; Binu Joseph; Abdullah Abu Al-Hassan; Lisanne J Balk; Raed Behbehani; Alexander Brandt; Peter A Calabresi; Elliot Frohman; Teresa C Frohman; Joachim Havla; Bernhard Hemmer; Hong Jiang; Benjamin Knier; Thomas Korn; Letizia Leocani; Elena Hernandez Martinez-Lapiscina; Athina Papadopoulou; Friedemann Paul; Axel Petzold; Marco Pisa; Pablo Villoslada; Hanna Zimmermann; Lorna E Thorpe; Hiroshi Ishikawa; Joel S Schuman; Gadi Wollstein; Yu Chen; Shiv Saidha; Steven Galetta; Laura J Balcer Journal: Neurology Date: 2022-06-28 Impact factor: 11.800
Authors: Amy T Waldman; Leslie Benson; John R Sollee; Amy M Lavery; Geraldine W Liu; Ari J Green; Emmanuelle Waubant; Gena Heidary; Darrel Conger; Jennifer Graves; Benjamin Greenberg Journal: J Neuroophthalmol Date: 2021-12-01 Impact factor: 3.042
Authors: Shirley Z Wu; Rachel Nolan-Kenney; Nicholas J Moehringer; Lisena F Hasanaj; Binu M Joseph; Ashley M Clayton; Janet C Rucker; Steven L Galetta; Thomas M Wisniewski; Arjun V Masurkar; Laura J Balcer Journal: J Neuroophthalmol Date: 2021-05-17 Impact factor: 4.415
Authors: Amir H Kashani; Samuel Asanad; Jane W Chan; Maxwell B Singer; Jiong Zhang; Mona Sharifi; Maziyar M Khansari; Farzan Abdolahi; Yonggang Shi; Alessandro Biffi; Helena Chui; John M Ringman Journal: Prog Retin Eye Res Date: 2021-01-15 Impact factor: 19.704
Authors: Gabriel Bsteh; Harald Hegen; Patrick Altmann; Michael Auer; Klaus Berek; Franziska Di Pauli; Fritz Leutmezer; Paulus Rommer; Sebastian Wurth; Anne Zinganell; Tobias Zrzavy; Florian Deisenhammer; Thomas Berger Journal: Eur J Neurol Date: 2021-04-02 Impact factor: 6.089
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