John J Chen1, Elias S Sotirchos2, Amanda D Henderson3, Eleni S Vasileiou2, Eoin P Flanagan4, M Tariq Bhatti5, Sepideh Jamali6, Eric R Eggenberger7, Marie Dinome8, Larry P Frohman9, Anthony C Arnold10, Laura Bonelli10, Nicolas Seleme10, Alvaro J Mejia-Vergara11, Heather E Moss12, Tanyatuth Padungkiatsagul13, Hadas Stiebel-Kalish14, Itay Lotan15, Mark A Hellmann15, Dave Hodge16, Frederike Cosima Oertel17, Friedemann Paul18, Shiv Saidha2, Peter A Calabresi3, Sean J Pittock4. 1. Departments of Ophthalmology; Departments of Neurology, Mayo Clinic, Rochester, MN. Electronic address: Chen.john@mayo.edu. 2. Departments of Neurology. 3. Departments of Neurology; Departments of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD. 4. Departments of Neurology, Mayo Clinic, Rochester, MN; Departments of Laboratory Medicine and Pathology; Center for MS and Autoimmune Neurology, Mayo Clinic, Rochester, MN. 5. Departments of Ophthalmology; Departments of Neurology, Mayo Clinic, Rochester, MN. 6. Departments of Ophthalmology. 7. Departments of Neurology, Neurosurgery, Neuro-Ophthalmology Mayo Clinic, Jacksonville, FL. 8. Departments of Ophthalmology, Neurology, Mayo Clinic, Scottsdale, AZ. 9. Departments of Ophthalmology & Visual Sciences and Neurology & Neurosciences, Rutgers-New Jersey Medical School, Newark, New Jersey. 10. Department of Ophthalmology, University of California Los Angeles, CA. 11. Department of Ophthalmology, University of California Los Angeles, CA; Hospital Universitario San Ignacio, Pontificia Universidad Javeriana, Colombia Department of Ophthalmology, Sanitas Eye Institute. Fundación Universitaria Sanita, Bogotá. Colombia. 12. Department of Neurology & Neurological Sciences, Stanford University, Palo Alto, CA; Department of Ophthalmology, Stanford University, Palo Alto, CA. 13. Department of Ophthalmology, Stanford University, Palo Alto, CA; Department of Ophthalmology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. 14. Felsenstein Research Center, Sackler School of Medicine, Tel Aviv University, Israel; Department of Ophthalmology and Neurology, Rabin Medical Center, Sackler School of Medicine, Tel Aviv University, Israel. 15. Department of Ophthalmology and Neurology, Rabin Medical Center, Sackler School of Medicine, Tel Aviv University, Israel. 16. Department of Quantitative Health Sciences (D.O.H.), Mayo Clinic, Jacksonville, Florida, USA. 17. Experimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Department of Neurology, University of California San Francisco, San Francisco, CA, USA. 18. Experimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Department of Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Abstract
BACKGROUND: Optic neuritis (ON) is the most common manifestation of myelin oligodendrocyte glycoprotein antibody associated disorder (MOGAD) and multiple sclerosis (MS). Acute ON in MOGAD is thought to be associated with more severe optic disk edema than in other demyelinating diseases, but this has not been quantitatively confirmed. The goal of this study was to determine whether optical coherence tomography (OCT) can distinguish acute ON in MOGAD from MS, and establish the sensitivity of OCT as a confirmatory biomarker of ON in these entities. METHODS: This was a multicenter cross-sectional study of MOGAD and MS patients with peripapillary retinal nerve fiber layer (pRNFL) thickness measured with OCT within two weeks of acute ON symptom. Cirrus HD-OCT (Carl Zeiss Meditec, Inc. Dublin, CA, USA) was used to measure the pRNFL during acute ON. Eyes with prior ON or disk pallor were excluded. A receiver operating characteristic (ROC) curve analysis was performed to assess the ability of pRNFL thickness to distinguish MOGAD from MS. RESULTS: Sixty-four MOGAD and 50 MS patients met study inclusion criteria. Median age was 46.5 years (interquartile range [IQR]: 34.3-57.0) for the MOGAD group and 30.4 years (IQR: 25.7-38.4) for the MS group (p<0.001). Thirty-nine (61%) of MOGAD patients were female compared to 42 (84%) for MS (p = 0.007). The median pRNFL thickness was 164 µm (IQR: 116-212) in 96 acute MOGAD ON eyes compared to 103 µm (IQR: 93-113) in 51 acute MS ON eyes (p<0.001). The ROC area under the curve for pRNFL thickness was 0.81 (95% confidence interval 0.74-0.88) to discriminate MOGAD from MS. The pRNFL cutoff that maximized Youden's index was 118 µm, which provided a sensitivity of 74% and specificity of 82% for MOGAD. Among 31 MOGAD and 48 MS eyes with an unaffected contralateral eye or a prior baseline, the symptomatic eye had a median estimated pRNFL thickening of 45 µm (IQR: 17-105) and 7.5 µm (IQR: 1-18), respectively (p<0.001). All MOGAD affected eyes had a ≥ 5 µm pRNFL thickening, whereas 26 (54%) MS affected eyes had a ≥ 5 µm thickening. CONCLUSION: OCT-derived pRNFL thickness in acute ON can help differentiate MOGAD from MS. This can aid with early diagnosis and guide disease-specific therapy in the acute setting before antibody testing returns, and help differentiate borderline cases. In addition, pRNFL thickening is a sensitive biomarker for confirming acute ON in MOGAD, which is clinically helpful and could be used for adjudication of attacks in future MOGAD clinical trials.
BACKGROUND: Optic neuritis (ON) is the most common manifestation of myelin oligodendrocyte glycoprotein antibody associated disorder (MOGAD) and multiple sclerosis (MS). Acute ON in MOGAD is thought to be associated with more severe optic disk edema than in other demyelinating diseases, but this has not been quantitatively confirmed. The goal of this study was to determine whether optical coherence tomography (OCT) can distinguish acute ON in MOGAD from MS, and establish the sensitivity of OCT as a confirmatory biomarker of ON in these entities. METHODS: This was a multicenter cross-sectional study of MOGAD and MS patients with peripapillary retinal nerve fiber layer (pRNFL) thickness measured with OCT within two weeks of acute ON symptom. Cirrus HD-OCT (Carl Zeiss Meditec, Inc. Dublin, CA, USA) was used to measure the pRNFL during acute ON. Eyes with prior ON or disk pallor were excluded. A receiver operating characteristic (ROC) curve analysis was performed to assess the ability of pRNFL thickness to distinguish MOGAD from MS. RESULTS: Sixty-four MOGAD and 50 MS patients met study inclusion criteria. Median age was 46.5 years (interquartile range [IQR]: 34.3-57.0) for the MOGAD group and 30.4 years (IQR: 25.7-38.4) for the MS group (p<0.001). Thirty-nine (61%) of MOGAD patients were female compared to 42 (84%) for MS (p = 0.007). The median pRNFL thickness was 164 µm (IQR: 116-212) in 96 acute MOGAD ON eyes compared to 103 µm (IQR: 93-113) in 51 acute MS ON eyes (p<0.001). The ROC area under the curve for pRNFL thickness was 0.81 (95% confidence interval 0.74-0.88) to discriminate MOGAD from MS. The pRNFL cutoff that maximized Youden's index was 118 µm, which provided a sensitivity of 74% and specificity of 82% for MOGAD. Among 31 MOGAD and 48 MS eyes with an unaffected contralateral eye or a prior baseline, the symptomatic eye had a median estimated pRNFL thickening of 45 µm (IQR: 17-105) and 7.5 µm (IQR: 1-18), respectively (p<0.001). All MOGAD affected eyes had a ≥ 5 µm pRNFL thickening, whereas 26 (54%) MS affected eyes had a ≥ 5 µm thickening. CONCLUSION: OCT-derived pRNFL thickness in acute ON can help differentiate MOGAD from MS. This can aid with early diagnosis and guide disease-specific therapy in the acute setting before antibody testing returns, and help differentiate borderline cases. In addition, pRNFL thickening is a sensitive biomarker for confirming acute ON in MOGAD, which is clinically helpful and could be used for adjudication of attacks in future MOGAD clinical trials.
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