Visual Outcomes Following Plasma Exchange for Optic Neuritis: An International Multicenter Retrospective Analysis of 395 Optic Neuritis Attacks

John J Chen¹, Eoin P Flanagan², Sean J Pittock², Nicole Caroline Stern³, Nanthaya Tisavipat⁴, M Tariq Bhatti⁵, Kevin D Chodnicki³, Deena A Tajfirouz⁶, Sepideh Jamali³, Amy Kunchok⁷, Eric R Eggenberger⁸, Marie A Di Nome⁹, Elias S Sotirchos¹⁰, Eleni S Vasileiou¹⁰, Amanda D Henderson¹¹, Anthony C Arnold¹², Laura Bonelli¹², Heather E Moss¹³, Sylvia Elizabeth Villarreal Navarro¹⁴, Tanyatuth Padungkiatsagul¹⁵, Hadas Stiebel-Kalish¹⁶, Itay Lotan¹⁷, Adi Wilf-Yarkoni¹⁷, Helen Danesh-Meyer¹⁸, Stefan Ivanov¹⁸, Saif Huda¹⁹, Mirasol Forcadela¹⁹, David Hodge²⁰, Pascale Poullin²¹, Julie Rode²¹, Caroline Papeix²², Samir Saheb²³, Marine Boudot de la Motte²⁴, Catherine Vignal²⁵, Yael Hacohen²⁶, Julie Pique²⁷, Elisabeth Maillart²³, Romain Deschamps²⁴, Bertrand Audoin²¹, Romain Marignier²⁷

Affiliations

¹ Departments of Ophthalmology (J.J.C., N.C.S., K.D.C., D.A.T., S.J.); Neurology (J.J.C., E.P.F., S.J.P., N.T., D.A.T., A.K.). Electronic address: Chen.john@mayo.edu.
² Neurology (J.J.C., E.P.F., S.J.P., N.T., D.A.T., A.K.); Laboratory Medicine and Pathology (E.P.F., S.J.P.); Center for MS and Autoimmune Neurology (E.P.F., S.J.P., A.K.), Mayo Clinic, Rochester, Minnesota, USA.
³ Departments of Ophthalmology (J.J.C., N.C.S., K.D.C., D.A.T., S.J.).
⁴ Neurology (J.J.C., E.P.F., S.J.P., N.T., D.A.T., A.K.).
⁵ The Permanente Medical Group (M.T.B.), Kaiser Permanente-Northern California, Roseville, California, USA.
⁶ Departments of Ophthalmology (J.J.C., N.C.S., K.D.C., D.A.T., S.J.); Neurology (J.J.C., E.P.F., S.J.P., N.T., D.A.T., A.K.).
⁷ Neurology (J.J.C., E.P.F., S.J.P., N.T., D.A.T., A.K.); Center for MS and Autoimmune Neurology (E.P.F., S.J.P., A.K.), Mayo Clinic, Rochester, Minnesota, USA; Department of Neurology, Cleveland Clinic (A.K.), Cleveland, Ohio, USA.
⁸ Departments of Neurology, Neurosurgery, and Neuro-Ophthalmology, Mayo Clinic (E.R.E.), Jacksonville, Florida, USA.
⁹ Departments of Ophthalmology (M.A.D.N.); Neurosurgery, Mayo Clinic (M.A.D.N.), Scottsdale, AZ.
¹⁰ Department of Neurology, Johns Hopkins University (E.S.S., E.S.V., A.D.H.), Baltimore, Maryland, USA.
¹¹ Department of Neurology, Johns Hopkins University (E.S.S., E.S.V., A.D.H.), Baltimore, Maryland, USA; Department of Ophthalmology, Johns Hopkins University School of Medicine (A.D.H.), Baltimore, Maryland, USA.
¹² Department of Ophthalmology, University of California Los Angeles (A.C.A., L.B.), Los Angeles, California, USA.
¹³ Department of Neurology & Neurological Sciences, Stanford University (H.E.M.), Palo Alto, California, USA; Department of Ophthalmology, Stanford University (H.E.M., S.E.V.N., T.P.), Palo Alto, California, USA.
¹⁴ Department of Ophthalmology, Stanford University (H.E.M., S.E.V.N., T.P.), Palo Alto, California, USA.
¹⁵ Department of Ophthalmology, Stanford University (H.E.M., S.E.V.N., T.P.), Palo Alto, California, USA; Department of Ophthalmology, Faculty of Medicine, Ramathibodi Hospital (T.P.), Mahidol University, Bangkok, Thailand.
¹⁶ Department of Ophthalmology (H.S.-K.), Neuro-Ophthalmology Division, Rabin Medical Center and Sackler School of Medicine, Tel Aviv University, Israel; Felsenstein Medical Research Center (H.S.-K.), Tel Aviv University, Israel.
¹⁷ Department of Neurology, Rabin Medical Center, Sackler School of Medicine (I.L., A.W.-Y.), Tel Aviv University, Israel.
¹⁸ Department of Ophthalmology, University of Auckland, New Zealand, and Vision Research Foundation (H.D.-M., S.I.), Auckland, New Zealand.
¹⁹ Department of Neurology, The Walton Centre NHS Foundation Trust (S.H., M.F.), Liverpool, United Kingdom.
²⁰ Department of Quantitative Health Sciences, Mayo Clinic (D.H.), Jacksonville, Florida.
²¹ Department of Neurology, University Hospital of Marseille (P.P., J.R., B.A.), Marseille, France; Aix-Marseille University, CRMBM UMR 7339, CNRS (P.P., J.R., B.A.), Marseille, France.
²² Department of Neurology, Pitie-Salpetriere Hospital, APHP (C.P., S.S., E.M.), Paris, France; Centre de référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle (MIRCEM) (C.P., S.S., E.M.); Department of Neurology, Adolphe de Rothschild Foundation Hospital (C.P., M.B.d.l.M., R.D.), Paris, France.
²³ Department of Neurology, Pitie-Salpetriere Hospital, APHP (C.P., S.S., E.M.), Paris, France; Centre de référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle (MIRCEM) (C.P., S.S., E.M.).
²⁴ Department of Neurology, Adolphe de Rothschild Foundation Hospital (C.P., M.B.d.l.M., R.D.), Paris, France.
²⁵ Department of Neuro-Ophthalmology, Adolphe de Rothschild Foundation Hospital (C.V.), Paris, France.
²⁶ Department of Neurology, Great Ormond Street Hospital for Children (Y.H.), London, United Kingdom; Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, Faculty of Brain Sciences, University College London (Y.H.), London, United Kingdom.
²⁷ Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle (MIRCEM), Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-inflammation, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon (J.P., R.M.), Lyon, France.

PMID: 36822570
PMCID: PMC10363193
DOI: 10.1016/j.ajo.2023.02.013

Multicenter Study

Visual Outcomes Following Plasma Exchange for Optic Neuritis: An International Multicenter Retrospective Analysis of 395 Optic Neuritis Attacks

John J Chen et al. Am J Ophthalmol. 2023 Aug.

. 2023 Aug:252:213-224.

doi: 10.1016/j.ajo.2023.02.013. Epub 2023 Feb 21.

Authors

Affiliations

¹ Departments of Ophthalmology (J.J.C., N.C.S., K.D.C., D.A.T., S.J.); Neurology (J.J.C., E.P.F., S.J.P., N.T., D.A.T., A.K.). Electronic address: Chen.john@mayo.edu.
² Neurology (J.J.C., E.P.F., S.J.P., N.T., D.A.T., A.K.); Laboratory Medicine and Pathology (E.P.F., S.J.P.); Center for MS and Autoimmune Neurology (E.P.F., S.J.P., A.K.), Mayo Clinic, Rochester, Minnesota, USA.
³ Departments of Ophthalmology (J.J.C., N.C.S., K.D.C., D.A.T., S.J.).
⁴ Neurology (J.J.C., E.P.F., S.J.P., N.T., D.A.T., A.K.).
⁵ The Permanente Medical Group (M.T.B.), Kaiser Permanente-Northern California, Roseville, California, USA.
⁶ Departments of Ophthalmology (J.J.C., N.C.S., K.D.C., D.A.T., S.J.); Neurology (J.J.C., E.P.F., S.J.P., N.T., D.A.T., A.K.).
⁷ Neurology (J.J.C., E.P.F., S.J.P., N.T., D.A.T., A.K.); Center for MS and Autoimmune Neurology (E.P.F., S.J.P., A.K.), Mayo Clinic, Rochester, Minnesota, USA; Department of Neurology, Cleveland Clinic (A.K.), Cleveland, Ohio, USA.
⁸ Departments of Neurology, Neurosurgery, and Neuro-Ophthalmology, Mayo Clinic (E.R.E.), Jacksonville, Florida, USA.
⁹ Departments of Ophthalmology (M.A.D.N.); Neurosurgery, Mayo Clinic (M.A.D.N.), Scottsdale, AZ.
¹⁰ Department of Neurology, Johns Hopkins University (E.S.S., E.S.V., A.D.H.), Baltimore, Maryland, USA.
¹¹ Department of Neurology, Johns Hopkins University (E.S.S., E.S.V., A.D.H.), Baltimore, Maryland, USA; Department of Ophthalmology, Johns Hopkins University School of Medicine (A.D.H.), Baltimore, Maryland, USA.
¹² Department of Ophthalmology, University of California Los Angeles (A.C.A., L.B.), Los Angeles, California, USA.
¹³ Department of Neurology & Neurological Sciences, Stanford University (H.E.M.), Palo Alto, California, USA; Department of Ophthalmology, Stanford University (H.E.M., S.E.V.N., T.P.), Palo Alto, California, USA.
¹⁴ Department of Ophthalmology, Stanford University (H.E.M., S.E.V.N., T.P.), Palo Alto, California, USA.
¹⁵ Department of Ophthalmology, Stanford University (H.E.M., S.E.V.N., T.P.), Palo Alto, California, USA; Department of Ophthalmology, Faculty of Medicine, Ramathibodi Hospital (T.P.), Mahidol University, Bangkok, Thailand.
¹⁶ Department of Ophthalmology (H.S.-K.), Neuro-Ophthalmology Division, Rabin Medical Center and Sackler School of Medicine, Tel Aviv University, Israel; Felsenstein Medical Research Center (H.S.-K.), Tel Aviv University, Israel.
¹⁷ Department of Neurology, Rabin Medical Center, Sackler School of Medicine (I.L., A.W.-Y.), Tel Aviv University, Israel.
¹⁸ Department of Ophthalmology, University of Auckland, New Zealand, and Vision Research Foundation (H.D.-M., S.I.), Auckland, New Zealand.
¹⁹ Department of Neurology, The Walton Centre NHS Foundation Trust (S.H., M.F.), Liverpool, United Kingdom.
²⁰ Department of Quantitative Health Sciences, Mayo Clinic (D.H.), Jacksonville, Florida.
²¹ Department of Neurology, University Hospital of Marseille (P.P., J.R., B.A.), Marseille, France; Aix-Marseille University, CRMBM UMR 7339, CNRS (P.P., J.R., B.A.), Marseille, France.
²² Department of Neurology, Pitie-Salpetriere Hospital, APHP (C.P., S.S., E.M.), Paris, France; Centre de référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle (MIRCEM) (C.P., S.S., E.M.); Department of Neurology, Adolphe de Rothschild Foundation Hospital (C.P., M.B.d.l.M., R.D.), Paris, France.
²³ Department of Neurology, Pitie-Salpetriere Hospital, APHP (C.P., S.S., E.M.), Paris, France; Centre de référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle (MIRCEM) (C.P., S.S., E.M.).
²⁴ Department of Neurology, Adolphe de Rothschild Foundation Hospital (C.P., M.B.d.l.M., R.D.), Paris, France.
²⁵ Department of Neuro-Ophthalmology, Adolphe de Rothschild Foundation Hospital (C.V.), Paris, France.
²⁶ Department of Neurology, Great Ormond Street Hospital for Children (Y.H.), London, United Kingdom; Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, Faculty of Brain Sciences, University College London (Y.H.), London, United Kingdom.
²⁷ Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle (MIRCEM), Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-inflammation, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon (J.P., R.M.), Lyon, France.

PMID: 36822570
PMCID: PMC10363193
DOI: 10.1016/j.ajo.2023.02.013

Abstract

Purpose: To evaluate the effectiveness of plasma exchange (PLEX) for optic neuritis (ON).

Methods: We conducted an international multicenter retrospective study evaluating the outcomes of ON following PLEX. Outcomes were compared to raw data from the Optic Neuritis Treatment Trial (ONTT) using a matched subset.

Results: A total of 395 ON attack treated with PLEX from 317 patients were evaluated. The median age was 37 years (range 9-75), and 71% were female. Causes of ON included multiple sclerosis (108), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) (92), aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4+NMOSD) (75), seronegative-NMOSD (34), idiopathic (83), and other (3). Median time from onset of vision loss to PLEX was 2.6 weeks (interquartile range [IQR], 1.4-4.0). Median visual acuity (VA) at the time of PLEX was count fingers (IQR, 20/200-hand motion), and median final VA was 20/25 (IQR, 20/20-20/60) with no differences among etiologies except MOGAD-ON, which had better outcomes. In 81 (20.5%) ON attacks, the final VA was 20/200 or worse. Patients with poor outcomes were older (P = .002), had worse VA at the time of PLEX (P < .001), and longer delay to PLEX (P < .001). In comparison with the ONTT subset with severe corticosteroid-unresponsive ON, a final VA of worse than 20/40 occurred in 6 of 50 (12%) PLEX-treated ON vs 7 of 19 (37%) from the ONTT treated with intravenous methylprednisolone without PLEX (P = .04).

Conclusion: Most ON attacks improved with PLEX, and outcomes were better than attacks with similar severity in the ONTT. The presence of severe vision loss at nadir, older age, and longer delay to PLEX predicted a worse outcome whereas MOGAD-ON had a more favorable prognosis. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

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Figures

**Figure 1:. Flow chart of optic neuritis attacks treated with plasma exchange.**
Abbreviations: plasma exchange (PLEX), optic neuritis (ON), neuromyelitis optica spectrum disorder (NMOSD), AQP4 (aquaporin-4), multiple sclerosis (MS). *Among the 2 patients that were excluded because of PLEX intolerance, one had numbness and vomiting and the other had mild dizziness and paresthesias who elected to not continue with treatment.

**Figure 2:. Visual acuity at time of plasma exchange and final visual outcome.**
Box and whisker plots showing the median visual acuity at the time of plasma exchange and the final visual acuity after plasma exchange. The box represents the 25–75% interquartile intervals and the whiskers cover the minimum and maximum range.

**Figure 3:. Visual recovery is dependent on time to initiation of plasma exchange.**
The probability of having complete recovery to 20/20 VA (green), good recovery (20/40 or better, yellow), medium recovery (between 20/40 and 20/200, orange), and poor recovery (20/200 or worse, red) is stratified based on time from optic neuritis onset to the initiation of plasma exchange (among the 395 optic neuritis attacks treated with plasma exchange without a prior optic neuritis attack).

**Figure 4:. Comparison of Optic Neuritis Treatment Trial vs Plasma exchange.**
The chance of final outcome of 20/40 or better is compared across different matched time points between the Optic Neuritis Treatment Trial (ONTT) (blue solid line) and the Plasma exchange (PLEX) (red dashed line) cohorts among eyes that were 20/200 or worse with minimal response to intravenous methylprednisolone (IVMP). * indicates a statistically significant difference.

See this image and copyright information in PMC

References

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1. Bennett JL, Costello F, Chen JJ, et al. Optic neuritis and autoimmune optic neuropathies: advances in diagnosis and treatment. Lancet Neurol 2022. - PubMed
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Visual Outcomes Following Plasma Exchange for Optic Neuritis: An International Multicenter Retrospective Analysis of 395 Optic Neuritis Attacks

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Visual Outcomes Following Plasma Exchange for Optic Neuritis: An International Multicenter Retrospective Analysis of 395 Optic Neuritis Attacks

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