Astrocytic outer retinal layer thinning is not a feature in AQP4-IgG seropositive neuromyelitis optica spectrum disorders

Angelo Lu; Hanna G. Zimmermann; Svenja Specovius; Seyedamirhosein Motamedi; Claudia Chien; Charlotte Bereuter; Marco A. Lana-Peixoto; Mariana Andrade Fontenelle; Fereshteh Ashtari; Rahele Kafieh; Alireza Dehghani; Mohsen Pourazizi; Lekha Pandit; Anitha D'Cunha; Ho Jin Kim; Jae-Won Hyun; Su-Kyung Jung; Letizia Leocani; Marco Pisa; Marta Radaelli; Sasitorn Siritho; Eugene F. May; Caryl Tongco; J. rôme de Sèze; Thomas Senger; Jacqueline Palace; Adriana Roca-Fernández; Maria Isabel Leite; Srilakshmi M. Sharma; Hadas Stiebel-Kalish; Nasrin Asgari; Kerstin Kathrine Soelberg; Elena H. Martinez-Lapiscina; Joachim Havla; Yang Mao-Draayer; Zoe Rimler; Allyson Reid; Romain Marignier; Alvaro Cobo-Calvo; Ayse Altintas; Uygur Tanriverdi; Rengin Yildirim; Orhan Aktas; Marius Ringelstein; Philipp Albrecht; Ivan Maynart Tavares; Denis Bernardi Bichuetti; Anu Jacob; Saif Huda; Ibis Soto de Castillo; Axel Petzold; Ari J. Green; Michael R. Yeaman; Terry J. Smith; Lawrence Cook; Friedemann Paul; GJCF International Clinical Consortium for NMOSD; Alexander U. Brandt; Frederike Cosima Oertel

doi:10.1136/jnnp-2021-327412

Astrocytic outer retinal layer thinning is not a feature in AQP4-IgG seropositive neuromyelitis optica spectrum disorders

Angelo Lu, Hanna G. Zimmermann, Svenja Specovius, Seyedamirhosein Motamedi, Claudia Chien, Charlotte Bereuter, Marco A. Lana-Peixoto, Mariana Andrade Fontenelle, Fereshteh Ashtari, Rahele Kafieh, Alireza Dehghani, Mohsen Pourazizi, Lekha Pandit, Anitha D'Cunha, Ho Jin Kim, Jae-Won Hyun, Su-Kyung Jung, Letizia Leocani, Marco Pisa, Marta RadaelliSasitorn Siritho, Eugene F. May, Caryl Tongco, J. rôme de Sèze, Thomas Senger, Jacqueline Palace, Adriana Roca-Fernández, Maria Isabel Leite, Srilakshmi M. Sharma, Hadas Stiebel-Kalish, Nasrin Asgari, Kerstin Kathrine Soelberg, Elena H. Martinez-Lapiscina, Joachim Havla, Yang Mao-Draayer, Zoe Rimler, Allyson Reid, Romain Marignier, Alvaro Cobo-Calvo, Ayse Altintas, Uygur Tanriverdi, Rengin Yildirim, Orhan Aktas, Marius Ringelstein, Philipp Albrecht, Ivan Maynart Tavares, Denis Bernardi Bichuetti, Anu Jacob, Saif Huda, Ibis Soto de Castillo, Axel Petzold, Ari J. Green, Michael R. Yeaman, Terry J. Smith, Lawrence Cook, Friedemann Paul, GJCF International Clinical Consortium for NMOSD, Alexander U. Brandt, Frederike Cosima Oertel

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

BACKGROUND: Patients with anti-aquaporin-4 antibody seropositive (AQP4-IgG+) neuromyelitis optica spectrum disorders (NMOSDs) frequently suffer from optic neuritis (ON) leading to severe retinal neuroaxonal damage. Further, the relationship of this retinal damage to a primary astrocytopathy in NMOSD is uncertain. Primary astrocytopathy has been suggested to cause ON-independent retinal damage and contribute to changes particularly in the outer plexiform layer (OPL) and outer nuclear layer (ONL), as reported in some earlier studies. However, these were limited in their sample size and contradictory as to the localisation. This study assesses outer retinal layer changes using optical coherence tomography (OCT) in a multicentre cross-sectional cohort. METHOD: 197 patients who were AQP4-IgG+ and 32 myelin-oligodendrocyte-glycoprotein antibody seropositive (MOG-IgG+) patients were enrolled in this study along with 75 healthy controls. Participants underwent neurological examination and OCT with central postprocessing conducted at a single site. RESULTS: No significant thinning of OPL (25.02±2.03 µm) or ONL (61.63±7.04 µm) were observed in patients who were AQP4-IgG+ compared with patients who were MOG-IgG+ with comparable neuroaxonal damage (OPL: 25.10±2.00 µm; ONL: 64.71±7.87 µm) or healthy controls (OPL: 24.58±1.64 µm; ONL: 63.59±5.78 µm). Eyes of patients who were AQP4-IgG+ (19.84±5.09 µm, p=0.027) and MOG-IgG+ (19.82±4.78 µm, p=0.004) with a history of ON showed parafoveal OPL thinning compared with healthy controls (20.99±5.14 µm); this was not observed elsewhere. CONCLUSION: The results suggest that outer retinal layer loss is not a consistent component of retinal astrocytic damage in AQP4-IgG+ NMOSD. Longitudinal studies are necessary to determine if OPL and ONL are damaged in late disease due to retrograde trans-synaptic axonal degeneration and whether outer retinal dysfunction occurs despite any measurable structural correlates.

Original language	English
Pages (from-to)	188-195
Number of pages	8
Journal	Journal of neurology, neurosurgery, and psychiatry
Volume	93
Issue number	2
DOIs	https://doi.org/10.1136/jnnp-2021-327412
Publication status	Published - 1 Feb 2022

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Lu, A., Zimmermann, H. G., Specovius, S., Motamedi, S., Chien, C., Bereuter, C., Lana-Peixoto, M. A., Fontenelle, M. A., Ashtari, F., Kafieh, R., Dehghani, A., Pourazizi, M., Pandit, L., D'Cunha, A., Kim, H. J., Hyun, J-W., Jung, S-K., Leocani, L., Pisa, M., ... Oertel, F. C. (2022). Astrocytic outer retinal layer thinning is not a feature in AQP4-IgG seropositive neuromyelitis optica spectrum disorders. Journal of neurology, neurosurgery, and psychiatry, 93(2), 188-195. https://doi.org/10.1136/jnnp-2021-327412

@article{72b82bbfea0144279b06708d706e58d6,

title = "Astrocytic outer retinal layer thinning is not a feature in AQP4-IgG seropositive neuromyelitis optica spectrum disorders",

abstract = "BACKGROUND: Patients with anti-aquaporin-4 antibody seropositive (AQP4-IgG+) neuromyelitis optica spectrum disorders (NMOSDs) frequently suffer from optic neuritis (ON) leading to severe retinal neuroaxonal damage. Further, the relationship of this retinal damage to a primary astrocytopathy in NMOSD is uncertain. Primary astrocytopathy has been suggested to cause ON-independent retinal damage and contribute to changes particularly in the outer plexiform layer (OPL) and outer nuclear layer (ONL), as reported in some earlier studies. However, these were limited in their sample size and contradictory as to the localisation. This study assesses outer retinal layer changes using optical coherence tomography (OCT) in a multicentre cross-sectional cohort. METHOD: 197 patients who were AQP4-IgG+ and 32 myelin-oligodendrocyte-glycoprotein antibody seropositive (MOG-IgG+) patients were enrolled in this study along with 75 healthy controls. Participants underwent neurological examination and OCT with central postprocessing conducted at a single site. RESULTS: No significant thinning of OPL (25.02±2.03 µm) or ONL (61.63±7.04 µm) were observed in patients who were AQP4-IgG+ compared with patients who were MOG-IgG+ with comparable neuroaxonal damage (OPL: 25.10±2.00 µm; ONL: 64.71±7.87 µm) or healthy controls (OPL: 24.58±1.64 µm; ONL: 63.59±5.78 µm). Eyes of patients who were AQP4-IgG+ (19.84±5.09 µm, p=0.027) and MOG-IgG+ (19.82±4.78 µm, p=0.004) with a history of ON showed parafoveal OPL thinning compared with healthy controls (20.99±5.14 µm); this was not observed elsewhere. CONCLUSION: The results suggest that outer retinal layer loss is not a consistent component of retinal astrocytic damage in AQP4-IgG+ NMOSD. Longitudinal studies are necessary to determine if OPL and ONL are damaged in late disease due to retrograde trans-synaptic axonal degeneration and whether outer retinal dysfunction occurs despite any measurable structural correlates.",

keywords = "clinical neurology, ophthalmology, vision",

author = "Angelo Lu and Zimmermann, {Hanna G.} and Svenja Specovius and Seyedamirhosein Motamedi and Claudia Chien and Charlotte Bereuter and Lana-Peixoto, {Marco A.} and Fontenelle, {Mariana Andrade} and Fereshteh Ashtari and Rahele Kafieh and Alireza Dehghani and Mohsen Pourazizi and Lekha Pandit and Anitha D'Cunha and Kim, {Ho Jin} and Jae-Won Hyun and Su-Kyung Jung and Letizia Leocani and Marco Pisa and Marta Radaelli and Sasitorn Siritho and May, {Eugene F.} and Caryl Tongco and {de S{\`e}ze}, {J. r{\^o}me} and Thomas Senger and Jacqueline Palace and Adriana Roca-Fern{\'a}ndez and Leite, {Maria Isabel} and Sharma, {Srilakshmi M.} and Hadas Stiebel-Kalish and Nasrin Asgari and Soelberg, {Kerstin Kathrine} and Martinez-Lapiscina, {Elena H.} and Joachim Havla and Yang Mao-Draayer and Zoe Rimler and Allyson Reid and Romain Marignier and Alvaro Cobo-Calvo and Ayse Altintas and Uygur Tanriverdi and Rengin Yildirim and Orhan Aktas and Marius Ringelstein and Philipp Albrecht and Tavares, {Ivan Maynart} and Bichuetti, {Denis Bernardi} and Anu Jacob and Saif Huda and {Soto de Castillo}, Ibis and Axel Petzold and Green, {Ari J.} and Yeaman, {Michael R.} and Smith, {Terry J.} and Lawrence Cook and Friedemann Paul and {GJCF International Clinical Consortium for NMOSD} and Brandt, {Alexander U.} and Oertel, {Frederike Cosima}",

note = "Publisher Copyright: {\textcopyright} Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.",

year = "2022",

month = feb,

day = "1",

doi = "10.1136/jnnp-2021-327412",

language = "English",

volume = "93",

pages = "188--195",

journal = "Journal of Neurology, Neurosurgery and Psychiatry",

issn = "0022-3050",

publisher = "BMJ Publishing Group",

number = "2",

}

Lu, A, Zimmermann, HG, Specovius, S, Motamedi, S, Chien, C, Bereuter, C, Lana-Peixoto, MA, Fontenelle, MA, Ashtari, F, Kafieh, R, Dehghani, A, Pourazizi, M, Pandit, L, D'Cunha, A, Kim, HJ, Hyun, J-W, Jung, S-K, Leocani, L, Pisa, M, Radaelli, M, Siritho, S, May, EF, Tongco, C, de Sèze, JR, Senger, T, Palace, J, Roca-Fernández, A, Leite, MI, Sharma, SM, Stiebel-Kalish, H, Asgari, N, Soelberg, KK, Martinez-Lapiscina, EH, Havla, J, Mao-Draayer, Y, Rimler, Z, Reid, A, Marignier, R, Cobo-Calvo, A, Altintas, A, Tanriverdi, U, Yildirim, R, Aktas, O, Ringelstein, M, Albrecht, P, Tavares, IM, Bichuetti, DB, Jacob, A, Huda, S, Soto de Castillo, I, Petzold, A, Green, AJ, Yeaman, MR, Smith, TJ, Cook, L, Paul, F, GJCF International Clinical Consortium for NMOSD, Brandt, AU & Oertel, FC 2022, 'Astrocytic outer retinal layer thinning is not a feature in AQP4-IgG seropositive neuromyelitis optica spectrum disorders', Journal of neurology, neurosurgery, and psychiatry, vol. 93, no. 2, pp. 188-195. https://doi.org/10.1136/jnnp-2021-327412

TY - JOUR

T1 - Astrocytic outer retinal layer thinning is not a feature in AQP4-IgG seropositive neuromyelitis optica spectrum disorders

AU - Lu, Angelo

AU - Zimmermann, Hanna G.

AU - Specovius, Svenja

AU - Motamedi, Seyedamirhosein

AU - Chien, Claudia

AU - Bereuter, Charlotte

AU - Lana-Peixoto, Marco A.

AU - Fontenelle, Mariana Andrade

AU - Ashtari, Fereshteh

AU - Kafieh, Rahele

AU - Dehghani, Alireza

AU - Pourazizi, Mohsen

AU - Pandit, Lekha

AU - D'Cunha, Anitha

AU - Kim, Ho Jin

AU - Hyun, Jae-Won

AU - Jung, Su-Kyung

AU - Leocani, Letizia

AU - Pisa, Marco

AU - Radaelli, Marta

AU - Siritho, Sasitorn

AU - May, Eugene F.

AU - Tongco, Caryl

AU - de Sèze, J. rôme

AU - Senger, Thomas

AU - Palace, Jacqueline

AU - Roca-Fernández, Adriana

AU - Leite, Maria Isabel

AU - Sharma, Srilakshmi M.

AU - Stiebel-Kalish, Hadas

AU - Asgari, Nasrin

AU - Soelberg, Kerstin Kathrine

AU - Martinez-Lapiscina, Elena H.

AU - Havla, Joachim

AU - Mao-Draayer, Yang

AU - Rimler, Zoe

AU - Reid, Allyson

AU - Marignier, Romain

AU - Cobo-Calvo, Alvaro

AU - Altintas, Ayse

AU - Tanriverdi, Uygur

AU - Yildirim, Rengin

AU - Aktas, Orhan

AU - Ringelstein, Marius

AU - Albrecht, Philipp

AU - Tavares, Ivan Maynart

AU - Bichuetti, Denis Bernardi

AU - Jacob, Anu

AU - Huda, Saif

AU - Soto de Castillo, Ibis

AU - Petzold, Axel

AU - Green, Ari J.

AU - Yeaman, Michael R.

AU - Smith, Terry J.

AU - Cook, Lawrence

AU - Paul, Friedemann

AU - GJCF International Clinical Consortium for NMOSD

AU - Brandt, Alexander U.

AU - Oertel, Frederike Cosima

PY - 2022/2/1

Y1 - 2022/2/1

N2 - BACKGROUND: Patients with anti-aquaporin-4 antibody seropositive (AQP4-IgG+) neuromyelitis optica spectrum disorders (NMOSDs) frequently suffer from optic neuritis (ON) leading to severe retinal neuroaxonal damage. Further, the relationship of this retinal damage to a primary astrocytopathy in NMOSD is uncertain. Primary astrocytopathy has been suggested to cause ON-independent retinal damage and contribute to changes particularly in the outer plexiform layer (OPL) and outer nuclear layer (ONL), as reported in some earlier studies. However, these were limited in their sample size and contradictory as to the localisation. This study assesses outer retinal layer changes using optical coherence tomography (OCT) in a multicentre cross-sectional cohort. METHOD: 197 patients who were AQP4-IgG+ and 32 myelin-oligodendrocyte-glycoprotein antibody seropositive (MOG-IgG+) patients were enrolled in this study along with 75 healthy controls. Participants underwent neurological examination and OCT with central postprocessing conducted at a single site. RESULTS: No significant thinning of OPL (25.02±2.03 µm) or ONL (61.63±7.04 µm) were observed in patients who were AQP4-IgG+ compared with patients who were MOG-IgG+ with comparable neuroaxonal damage (OPL: 25.10±2.00 µm; ONL: 64.71±7.87 µm) or healthy controls (OPL: 24.58±1.64 µm; ONL: 63.59±5.78 µm). Eyes of patients who were AQP4-IgG+ (19.84±5.09 µm, p=0.027) and MOG-IgG+ (19.82±4.78 µm, p=0.004) with a history of ON showed parafoveal OPL thinning compared with healthy controls (20.99±5.14 µm); this was not observed elsewhere. CONCLUSION: The results suggest that outer retinal layer loss is not a consistent component of retinal astrocytic damage in AQP4-IgG+ NMOSD. Longitudinal studies are necessary to determine if OPL and ONL are damaged in late disease due to retrograde trans-synaptic axonal degeneration and whether outer retinal dysfunction occurs despite any measurable structural correlates.

AB - BACKGROUND: Patients with anti-aquaporin-4 antibody seropositive (AQP4-IgG+) neuromyelitis optica spectrum disorders (NMOSDs) frequently suffer from optic neuritis (ON) leading to severe retinal neuroaxonal damage. Further, the relationship of this retinal damage to a primary astrocytopathy in NMOSD is uncertain. Primary astrocytopathy has been suggested to cause ON-independent retinal damage and contribute to changes particularly in the outer plexiform layer (OPL) and outer nuclear layer (ONL), as reported in some earlier studies. However, these were limited in their sample size and contradictory as to the localisation. This study assesses outer retinal layer changes using optical coherence tomography (OCT) in a multicentre cross-sectional cohort. METHOD: 197 patients who were AQP4-IgG+ and 32 myelin-oligodendrocyte-glycoprotein antibody seropositive (MOG-IgG+) patients were enrolled in this study along with 75 healthy controls. Participants underwent neurological examination and OCT with central postprocessing conducted at a single site. RESULTS: No significant thinning of OPL (25.02±2.03 µm) or ONL (61.63±7.04 µm) were observed in patients who were AQP4-IgG+ compared with patients who were MOG-IgG+ with comparable neuroaxonal damage (OPL: 25.10±2.00 µm; ONL: 64.71±7.87 µm) or healthy controls (OPL: 24.58±1.64 µm; ONL: 63.59±5.78 µm). Eyes of patients who were AQP4-IgG+ (19.84±5.09 µm, p=0.027) and MOG-IgG+ (19.82±4.78 µm, p=0.004) with a history of ON showed parafoveal OPL thinning compared with healthy controls (20.99±5.14 µm); this was not observed elsewhere. CONCLUSION: The results suggest that outer retinal layer loss is not a consistent component of retinal astrocytic damage in AQP4-IgG+ NMOSD. Longitudinal studies are necessary to determine if OPL and ONL are damaged in late disease due to retrograde trans-synaptic axonal degeneration and whether outer retinal dysfunction occurs despite any measurable structural correlates.

KW - clinical neurology

KW - ophthalmology

KW - vision

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85123648130&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/34711650

U2 - 10.1136/jnnp-2021-327412

DO - 10.1136/jnnp-2021-327412

M3 - Article

C2 - 34711650

SN - 0022-3050

VL - 93

SP - 188

EP - 195

JO - Journal of Neurology, Neurosurgery and Psychiatry

JF - Journal of Neurology, Neurosurgery and Psychiatry

IS - 2

ER -

Astrocytic outer retinal layer thinning is not a feature in AQP4-IgG seropositive neuromyelitis optica spectrum disorders

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