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Astrocytic Outer Retinal Layer Thinning Is Not a Feature in Aqp4-Igg Seropositive Neuromyelitis Optica Spectrum Disorders Publisher Pubmed



Lu A1, 2 ; Zimmermann HG1, 2 ; Specovius S1, 2 ; Motamedi S1, 2 ; Chien C1, 2 ; Bereuter C1, 2 ; Lanapeixoto MA3 ; Fontenelle MA3 ; Ashtari F4 ; Kafieh R5 ; Dehghani A6 ; Pourazizi M6 ; Pandit L7 ; Dcunha A7 Show All Authors
Authors
  1. Lu A1, 2
  2. Zimmermann HG1, 2
  3. Specovius S1, 2
  4. Motamedi S1, 2
  5. Chien C1, 2
  6. Bereuter C1, 2
  7. Lanapeixoto MA3
  8. Fontenelle MA3
  9. Ashtari F4
  10. Kafieh R5
  11. Dehghani A6
  12. Pourazizi M6
  13. Pandit L7
  14. Dcunha A7
  15. Kim HJ8
  16. Hyun JW8
  17. Jung SK9
  18. Leocani L10
  19. Pisa M10
  20. Radaelli M10
  21. Siritho S11
  22. May EF12
  23. Tongco C12
  24. De Seze J13
  25. Senger T13
  26. Palace J14
  27. Rocafernandez A14
  28. Leite MI14
  29. Sharma SM15
  30. Stiebelkalish H16, 17
  31. Asgari N18
  32. Soelberg KK19
  33. Martinezlapiscina EH20
  34. Havla J21
  35. Maodraayer Y22
  36. Rimler Z23
  37. Reid A23
  38. Marignier R24
  39. Cobocalvo A24, 25
  40. Altintas A26
  41. Tanriverdi U27
  42. Yildirim R28
  43. Aktas O29
  44. Ringelstein M29, 30
  45. Albrecht P29
  46. Tavares IM31
  47. Bichuetti DB32
  48. Jacob A33
  49. Huda S33
  50. De Castillo IS34
  51. Petzold A35
  52. Green AJ36
  53. Yeaman MR37, 38
  54. Smith TJ39, 40
  55. Cook L41
  56. Paul F1, 2, 42
  57. Brandt AU1, 2, 43
  58. Oertel FC1, 2, 36
Show Affiliations
Authors Affiliations
  1. 1. Experimental and Clinical Research Center, Max Delbruck Center for Molecular Medicine and Charite – Universitatsmedizin Berlin, corporate member of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Berlin, Germany
  2. 2. NeuroCure Clinical Research Center, Charite – Universitatsmedizin Berlin, corporate member of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Berlin, Germany
  3. 3. CIEM MS Research Center, University of Minas Gerais State, Medical School, Belo Horizonte, Brazil
  4. 4. Kashani MS Center, Isfahan University of Medical Sciences, Isfahan, Iran
  5. 5. School of Advanced Technologies in Medicine, Medical Image and Signal Processing Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
  6. 6. Isfahan Eye Research Center, Department of Ophthalmology, Isfahan University of Medical Sciences, Isfahan, Iran
  7. 7. Center for Advanced Neurological Research, Nitte University, Karnataka, Mangalore, India
  8. 8. Department of Neurology, National Cancer Center Korea, Goyang-si, South Korea
  9. 9. Department of Opthalmology, Research Institute, Hospital of National Cancer Center, Goyang, South Korea
  10. 10. Experimental Neurophysiology Unit, Institute of Experimental Neurology (INSPE) Scientific Institute, Hospital San Raffaele and University Vita-Salute San Raffaele, Milano, Italy
  11. 11. Division of Neurology, Department of Medicine, Siriraj Hospital, Bumrungrad International Hospital, Bangkok, Thailand
  12. 12. Swedish Neuroscience Institute Neuro-Ophthalmology, Seattle, WA, United States
  13. 13. Department of Neurology, Neurology Service, University Hospital of Strasbourg, Strasbourg, France
  14. 14. Department of Neurology, Oxford University Hospitals NHS Trust, Oxford, United Kingdom
  15. 15. Department of Ophthalmology, Oxford University Hospitals NHS Trust, Oxford, United Kingdom
  16. 16. Neuro-Opthalmology Division, Department of Opthalmology, Rabin Medical Center, Petah Tikva, Israel
  17. 17. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
  18. 18. Department of Neurology Slagelse, Institutes of Regional Health Research andMolecular Medicine, University of Southern Denmark, Syddanmark, Odense, Denmark
  19. 19. Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark
  20. 20. Hospital Clinic of Barcelona-Institut d’Investigacions, Biomediques August Pi Sunyer, University of Barcelona, Barcelona, Spain
  21. 21. Institute of Clinical Neuroimmunology, LMU Hospital, Ludwig-Maximilians-Universitat Munchen, Munich, Germany
  22. 22. Department of Neurology, University of Michigan Medical School, Ann Arbor, MI, United States
  23. 23. NYU Multiple Sclerosis Comprehensive Care Center, Department of Neurology, NYU, New York, NY, United States
  24. 24. Neurology, Multiple Sclerosis, Myelin Disorders and Neuroinflammation, Hospital for Neurology Pierre Wertheimer, Lyon, France
  25. 25. Centre d’Esclerosi Multiple de Catalunya (Cemcat), Department of Neurology/ Neuroimmunology, Universitat Autonoma de Barcelona, Barcelona, Spain
  26. 26. Department of Neurology, Koc University Research Center for Translational Medicine (KUTTAM), Koc University School of Medicine, Istanbul, Turkiye
  27. 27. Cerrahpasa Faculty of Medicine, Department of Neurology, Istanbul University-Cerrahpasa, Istanbul, Turkiye
  28. 28. Department of Ophthalmology, Cerrahpasa Medical Faculty, Istanbul Universitesi, Fatih, Turkiye
  29. 29. Department of Neurology, Medical Faculty, Heinrich-Heine-Universitat Dusseldorf, Nordrhein-Westfalen, Dusseldorf, Germany
  30. 30. Department of Neurology, Center for Neurology and Neuropsychiatry, LVRKlinikum, Heinrich-Heine-Universitat Dusseldorf, Dusseldorf, Germany
  31. 31. Department of Ophthalmology and Visual Sciences, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
  32. 32. Department of Neurology and Neurosurgery, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
  33. 33. The Walton Centre NHS Foundation Trust, Liverpool, United Kingdom
  34. 34. Department of Neurology, Hospital Clinico de Maracaibo, Maracaibo, Venezuela
  35. 35. Moorfield’s Eye Hospital, The National Hospital for Neurology and Neurosurgery, Queen Square Institute of Neurology, University College London, London, United Kingdom
  36. 36. Department of Neurology, University of California San Francisco, San Francisco, CA, United States
  37. 37. Department of Medicine, Harbor-University of California at Los Angeles (UCLA) Medical Center, Lundquist Institute for Biomedical Innovation, Torrance, CA, United States
  38. 38. Department of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA, United States
  39. 39. Departments of Ophthalmology and Visual Sciences, Kellogg Eye Center, Ann Arbor, MI, United States
  40. 40. Department of Metabolism, Endocrine and Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, United States
  41. 41. Department of Pediatrics, University of Utah Health, Salt Lake City, UT, United States
  42. 42. Department of Neurology, Charite – Universitatsmedizin Berlin, corporate member of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Berlin, Germany
  43. 43. Department of Neurology, University of California Irvine, Irvine, CA, United States

Source: Journal of Neurology, Neurosurgery and Psychiatry Published:2022


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. © Author(s) (or their employer(s)) 2022.
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