CoChat
Sign Up
Cited by 102Multiple Sclerosis Research StudiesGlaucoma and retinal disordersOcular Diseases and Behçet’s Syndrome

OCT retinal nerve fiber layer thickness differentiates acute optic neuritis from MOG antibody-associated disease and Multiple Sclerosis

Open access
Chen, John J., Sotirchos, Elias S., Henderson, Amanda D., Vasileiou, Eleni S., Flanagan, Eoin P., Bhatti, M. Tariq, Jamali, Sepideh, Eggenberger, Eric R. +17 more·2022·Multiple Sclerosis and Related Disorders
DOI 10.1016/j.msard.2022.103525PMC PMC8882134
Open this paper in CoChat — free account

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.msard.2022.103525

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

No references could be resolved yet.

Research works printed but not linked: 43

  1. [1]Jitprapaikulsan J, Chen JJ, Flanagan EP, Tobin WO, Fryer JP, Weinshenker BG, Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein Autoantibody Status Predict Outcome of Recurrent Optic Neuritis. Ophthalmology. 2018. 29716788
  2. [2]Jarius S, Ruprecht K, Stellmann JP, Huss A, Ayzenberg I, Willing A, MOG-IgG in primary and secondary chronic progressive multiple sclerosis: a multicenter study of 200 patients and review of the literature. J Neuroinflammation. 2018; 15(1): 88. 29554927 PMC5859439
  3. [3]Jurynczyk M, Messina S, Woodhall MR, Raza N, Everett R, Roca-Fernandez A, Clinical presentation and prognosis in MOG-antibody disease: a UK study. Brain. 2017; 140(12): 3128– 38. 29136091
  4. [4]Jarius S, Ruprecht K, Kleiter I, Borisow N, Asgari N, Pitarokoili K, MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 2: Epidemiology, clinical presentation, radiological and laboratory features, treatment responses, and long-term outcome. J Neuroinflammation. 2016; 13(1): 280. 27793206 PMC5086042
  5. [5]Cobo-Calvo A, Ruiz A, Maillart E, Audoin B, Zephir H, Bourre B, Clinical spectrum and prognostic value of CNS MOG autoimmunity in adults: The MOGADOR study. Neurology. 2018; 90(21): e1858– e69. 29695592
  6. [6]Jarius S, Ruprecht K, Kleiter I, Borisow N, Asgari N, Pitarokoili K, MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 1: Frequency, syndrome specificity, influence of disease activity, long-term course, association with AQP4-IgG, and origin. J Neuroinflammation. 2016; 13(1): 279. 27788675 PMC5084340
  7. [7]Weber MS, Derfuss T, Metz I, Bruck W. Defining distinct features of anti-MOG antibody associated central nervous system demyelination. Ther Adv Neurol Disord. 2018; 11: 1756286418762083. 29623106 PMC5881972
  8. [8]Jarius S, Paul F, Aktas O, Asgari N, Dale RC, de Seze J, MOG encephalomyelitis: international recommendations on diagnosis and antibody testing. J Neuroinflammation. 2018; 15(1): 134. 29724224 PMC5932838
  9. [9]Reindl M, Jarius S, Rostasy K, Berger T. Myelin oligodendrocyte glycoprotein antibodies: How clinically useful are they? Curr Opin Neurol. 2017; 30(3): 295– 301. 28248700
  10. [10]Chen JJ, Flanagan EP, Jitprapaikulsan J, Chiriboga A, Fryer JP, Leavitt JA, Myelin Oligodendrocyte Glycoprotein Antibody–Positive Optic Neuritis: Clinical Characteristics, Radiologic Clues, and Outcome. Am J Ophthalmol. 2018; 195: 8– 15. 30055153 PMC6371779
  11. [11]Tajfirouz DA, Bhatti MT, Chen JJ. Clinical Characteristics and Treatment of MOG-IgG-Associated Optic Neuritis. Curr Neurol Neurosci Rep. 2019; 19(12): 100. 31773369
  12. [12]Reindl M, Schanda K, Woodhall M, Tea F, Ramanathan S, Sagen J, International multicenter examination of MOG antibody assays. Neurol Neuroimmunol Neuroinflamm. 2020; 7(2). PMC7051197 32024795
  13. [13]Sechi E, Buciuc M, Pittock SJ, Chen JJ, Fryer JP, Jenkins SM, Positive Predictive Value of Myelin Oligodendrocyte Glycoprotein Autoantibody Testing. JAMA Neurol. 2021. PMC8077043 33900394
  14. [14]Hassan MB, Stern C, Flanagan EP, Pittock SJ, Kunchok A, Foster RC, Population-Based Incidence of Optic Neuritis in the Era of Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein Antibodies. Am J Ophthalmol. 2020; 220: 110– 4. 32707199 PMC8491771
  15. [15]Filippatou AG, Mukharesh L, Saidha S, Calabresi PA, Sotirchos ES. AQP4-IgG and MOG-IgG Related Optic Neuritis-Prevalence, Optical Coherence Tomography Findings, and Visual Outcomes: A Systematic Review and Meta-Analysis. Front Neurol. 2020; 11: 540156. 33132999 PMC7578376
  16. [16]Soelberg K, Jarius S, Skejoe H, Engberg H, Mehlsen JJ, Nilsson AC, A population-based prospective study of optic neuritis. Mult Scler. 2017; 23(14): 1893– 901. 28980518
  17. [17]Zhao Y, Tan S, Chan TCY, Xu Q, Zhao J, Teng D, Clinical features of demyelinating optic neuritis with seropositive myelin oligodendrocyte glycoprotein antibody in Chinese patients. Br J Ophthalmol. 2018; 102(10): 1372– 7. 29363529
  18. [18]Chen JJ, Bhatti MT. Clinical phenotype, radiological features, and treatment of myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG) optic neuritis. Curr Opin Neurol. 2020; 33(1): 47– 54. 31743235
  19. [19]Biotti D, Bonneville F, Tournaire E, Ayrignac X, Dalliere CC, Mahieu L, Optic neuritis in patients with anti-MOG antibodies spectrum disorder: MRI and clinical features from a large multicentric cohort in France. J Neurol. 2017; 264(10): 2173– 5. 28914353
  20. [20]Lopez-Chiriboga AS, Majed M, Fryer J, Dubey D, McKeon A, Flanagan EP, Association of MOG-IgG Serostatus With Relapse After Acute Disseminated Encephalomyelitis and Proposed Diagnostic Criteria for MOG-IgG-Associated Disorders. JAMA Neurol. 2018; 75(11): 1355– 63. 30014148 PMC6248120
  21. [21]Waters PJ, Komorowski L, Woodhall M, Lederer S, Majed M, Fryer J, A multicenter comparison of MOG-IgG cell-based assays. Neurology. 2019; 92(11): e1250– e5. 30728305 PMC6511109
  22. [22]Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, Comi G, Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018; 17(2): 162– 73. 29275977
  23. [23]Tewarie P, Balk L, Costello F, Green A, Martin R, Schippling S, The OSCAR-IB consensus criteria for retinal OCT quality assessment. PLoS One. 2012; 7(4): e34823. 22536333 PMC3334941
  24. [24]Cruz-Herranz A, Balk LJ, Oberwahrenbrock T, Saidha S, Martinez-Lapiscina EH, Lagreze WA, The APOSTEL recommendations for reporting quantitative optical coherence tomography studies. Neurology. 2016; 86(24): 2303– 9. 27225223 PMC4909557
  25. [25]Youden WJ. Index for rating diagnostic tests. Cancer. 1950; 3(1): 32– 5. 15405679
  26. [26]Sotirchos ES, Filippatou A, Fitzgerald KC, Salama S, Pardo S, Wang J, Aquaporin-4 IgG seropositivity is associated with worse visual outcomes after optic neuritis than MOG-IgG seropositivity and multiple sclerosis, independent of macular ganglion cell layer thinning. Mult Scler. 2020; 26(11): 1360– 71. 31364464 PMC6992495
  27. [27]Ramanathan S, Prelog K, Barnes EH, Tantsis EM, Reddel SW, Henderson AP, Radiological differentiation of optic neuritis with myelin oligodendrocyte glycoprotein antibodies, aquaporin-4 antibodies, and multiple sclerosis. Mult Scler. 2016; 22(4): 470– 82. 26163068
  28. [28]Beck RW, Cleary PA, Anderson MM Jr., Keltner JL, Shults WT, Kaufman DI, A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. The Optic Neuritis Study Group. N Engl J Med. 1992; 326(9): 581– 8. 1734247
  29. [29]Chen JJ, Tobin WO, Majed M, Jitprapaikulsan J, Fryer JP, Leavitt JA, Prevalence of Myelin Oligodendrocyte Glycoprotein and Aquaporin-4-IgG in Patients in the Optic Neuritis Treatment Trial. JAMA Ophthalmol. 2018; 136(4): 419– 22. 29470571 PMC5876803
  30. [30]Ramanathan S, Mohammad S, Tantsis E, Nguyen TK, Merheb V, Fung VSC, Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination. J Neurol Neurosurg Psychiatry. 2018; 89(2): 127– 37. 29142145 PMC5800335
  31. [31]Etemadifar M, Abbasi M, Salari M, Etemadifar F, Tavakoli H. Comparing myelin oligodendrocyte glycoprotein antibody (MOG-Ab) and non MOG-Ab associated optic neuritis: Clinical course and treatment outcome. Mult Scler Relat Disord. 2019; 27: 127– 30. 30368225
  32. [32]Stiebel-Kalish H, Hellmann MA, Mimouni M, Paul F, Bialer O, Bach M, Does time equal vision in the acute treatment of a cohort of AQP4 and MOG optic neuritis? Neurol Neuroimmunol Neuroinflamm. 2019; 6(4): e572. 31355308 PMC6624092
  33. [33]Kezuka T, Ishikawa H. Diagnosis and treatment of anti-myelin oligodendrocyte glycoprotein antibody positive optic neuritis. Jpn J Ophthalmol. 2018; 62(2): 101– 8. 29445944
  34. [34]Chen JJ, Flanagan EP, Bhatti MT, Jitprapaikulsan J, Dubey D, Lopez Chiriboga ASS, Steroid-sparing maintenance immunotherapy for MOG-IgG associated disorder. Neurology. 2020; 95(2): e111– e20. 32554760 PMC7455322
  35. [35]Whittam DH, Cobo-Calvo A, Lopez-Chiriboga AS, Pardo S, Gornall M, Cicconi S, Treatment of MOG-IgG-associated disorder with rituximab: An international study of 121 patients. Mult Scler Relat Disord. 2020; 44: 102251. 32629363 PMC7895306
  36. [36]Leung CK, Yu M, Weinreb RN, Ye C, Liu S, Lai G, Retinal nerve fiber layer imaging with spectral-domain optical coherence tomography: a prospective analysis of age-related loss. Ophthalmology. 2012; 119(4): 731– 7. 22264886
  37. [37]Alasil T, Wang K, Keane PA, Lee H, Baniasadi N, de Boer JF, Analysis of normal retinal nerve fiber layer thickness by age, sex, and race using spectral domain optical coherence tomography. J Glaucoma. 2013; 22(7): 532– 41. 22549477
  38. [38]Sotirchos ES, Gonzalez Caldito N, Filippatou A, Fitzgerald KC, Murphy OC, Lambe J, Progressive Multiple Sclerosis Is Associated with Faster and Specific Retinal Layer Atrophy. Ann Neurol. 2020; 87(6): 885– 96. 32285484 PMC8682917
  39. [39]Caldito NG, Saidha S, Sotirchos ES, Dewey BE, Cowley NJ, Glaister J, Brain and retinal atrophy in African-Americans versus Caucasian-Americans with multiple sclerosis: a longitudinal study. Brain. 2018; 141(11): 3115– 29. 30312381 PMC6202573
  40. [40]Mwanza JC, Chang RT, Budenz DL, Durbin MK, Gendy MG, Shi W, Reproducibility of peripapillary retinal nerve fiber layer thickness and optic nerve head parameters measured with cirrus HD-OCT in glaucomatous eyes. Invest Ophthalmol Vis Sci. 2010; 51(11): 5724– 30. 20574014 PMC3061508
  41. [42]Prasad S, Chen J. What You Need to Know About AQP4, MOG, and NMOSD. Semin Neurol. 2019; 39(6): 718– 31. 31847043
  42. [43]Hacohen Y, Palace J. Time to separate MOG-Ab-associated disease from AQP4-Ab-positive neuromyelitis optica spectrum disorder. Neurology. 2018; 90(21): 947– 8. 29695599
  43. [44]Chen JJ, Pittock SJ, Flanagan EP, Lennon VA, Bhatti MT. Optic neuritis in the era of biomarkers. Surv Ophthalmol. 2020; 65(1): 12– 7. 31425702

Cited by

Sorted by citations

Authors
Chen, J. J., Sotirchos, E. S., Henderson, A. D., Vasileiou, E. S., Flanagan, E. P., Bhatti, M. T., Jamali, S., Eggenberger, E. R., Dinome, M., Frohman, L. P., Arnold, A. C., Bonelli, L., Seleme, N., Mejia-Vergara, A. J., Moss, H. E., Padungkiatsagul, T., Stiebel-Kalish, H., Lotan, I., Hellmann, M. A., Hodge, D., Oertel, F. C., Paul, F., Saidha, S., Calabresi, P. A., & Pittock, S. J.
Affiliations
  • Mayo Clinic (US)
  • Johns Hopkins University (US)
  • Mayo Clinic in Florida (US)
  • Rutgers New Jersey Medical School (US)
  • University of California, Los Angeles (US)
  • Stanford University (US)
  • Mahidol University (TH)
  • Tel Aviv University (IL)
  • University of California, San Francisco (US)
  • Max Delbrück Center (DE)
Corresponding author
Chen, John J.
ORCID
Venue
Multiple Sclerosis and Related Disorders
Publisher
Elsevier BV
Published
2022-02
Volume
58
Pages
103525
ISSN
2211-0348 (ISSN-L)
DOI
10.1016/j.msard.2022.103525
PMC
PMC8882134
OpenAlex
W4205221810
Cited by
102
References
0
Citations by year
2026: 28 · 2025: 19 · 2024: 25 · 2023: 19 · 2022: 11
FWCI
12.32
Type
journal article
Language
en
Open access
Licence
Locations
  • Multiple Sclerosis and Related Disorders (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • National Multiple Sclerosis Society (RG-1606\u201308768, 08768, RG-1606)
  • National Institutes of Health (K23 EY 024345, P30 EY 026877)
  • Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine
  • National Institute of Neurological Disorders and Stroke (R01NS082347, R01NS113828, K23NS117883)
  • Mayo Clinic
  • Research to Prevent Blindness
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
  • Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
Keywords
acute optic neuritis, MOG antibody-associated disease, multiple sclerosis, peripapillary retinal nerve fiber layer thickness, optical coherence tomography, optic disc edema, differential diagnosis, diagnostic biomarkers, demyelinating disease, visual acuity, visual field defects, visual evoked potentials, brain MRI lesions, cerebrospinal fluid biomarkers, disease-modifying therapy
MeSH terms
Adult, Cross-Sectional Studies, Female, Humans, Middle Aged, Multiple Sclerosis, Nerve Fibers, Optic Neuritis, Tomography, Optical Coherence

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review