title: Microstructural visual system changes in AQP4-antibody-seropositive NMOSD.
abstract: OBJECTIVE
  To trace microstructural changes in patients with aquaporin-4 antibody (AQP4-ab)-seropositive neuromyelitis optica spectrum disorders (NMOSDs) by investigating the afferent visual system in patients without clinically overt visual symptoms or visual pathway lesions.
  
  
  METHODS
  Of 51 screened patients with NMOSD from a longitudinal observational cohort study, we compared 6 AQP4-ab-seropositive NMOSD patients with longitudinally extensive transverse myelitis (LETM) but no history of optic neuritis (ON) or other bout (NMOSD-LETM) to 19 AQP4-ab-seropositive NMOSD patients with previous ON (NMOSD-ON) and 26 healthy controls (HCs). Foveal thickness (FT), peripapillary retinal nerve fiber layer (pRNFL) thickness, and ganglion cell and inner plexiform layer (GCIPL) thickness were measured with optical coherence tomography (OCT). Microstructural changes in the optic radiation (OR) were investigated using diffusion tensor imaging (DTI). Visual function was determined by high-contrast visual acuity (VA). OCT results were confirmed in a second independent cohort.
  
  
  RESULTS
  FT was reduced in both patients with NMOSD-LETM (p= 3.52e-14) and NMOSD-ON (p= 1.24e-16) in comparison with HC. Probabilistic tractography showed fractional anisotropy reduction in the OR in patients with NMOSD-LETM (p= 0.046) and NMOSD-ON (p= 1.50e-5) compared with HC. Only patients with NMOSD-ON but not NMOSD-LETM showed neuroaxonal damage in the form of pRNFL and GCIPL thinning. VA was normal in patients with NMOSD-LETM and was not associated with OCT or DTI parameters.
  
  
  CONCLUSIONS
  Patients with AQP4-ab-seropositive NMOSD without a history of ON have microstructural changes in the afferent visual system. The localization of retinal changes around the Müller-cell rich fovea supports a retinal astrocytopathy.
authors.affiliation: NeuroCure Clinical Research Center (F.C.O., J.K., H.Z., C.C., F.S., J.B.-S., M.S., F.P., A.U.B.), and Department of Neurology (J.K., F.S., J.B.-S., K.R., F.P.), Charité-Universitätsmedizin Berlin; Department of Neurology (B.K., T.K.), Klinikum rechts der Isar, and Department of Experimental Neuroimmunology (T.K.), Technische Universität München; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Germany; Clinical Ophthalmology and Eye Health (A.K.), Central Clinical School, Save Sight Institute, Sydney, Australia; and Experimental and Clinical Research Center (F.P.), Max Delbrueck Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Frederike C
authors.initials: FC
authors.lastname: Oertel
authors.affiliation: NeuroCure Clinical Research Center (F.C.O., J.K., H.Z., C.C., F.S., J.B.-S., M.S., F.P., A.U.B.), and Department of Neurology (J.K., F.S., J.B.-S., K.R., F.P.), Charité-Universitätsmedizin Berlin; Department of Neurology (B.K., T.K.), Klinikum rechts der Isar, and Department of Experimental Neuroimmunology (T.K.), Technische Universität München; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Germany; Clinical Ophthalmology and Eye Health (A.K.), Central Clinical School, Save Sight Institute, Sydney, Australia; and Experimental and Clinical Research Center (F.P.), Max Delbrueck Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Joseph
authors.initials: J
authors.lastname: Kuchling
authors.affiliation: NeuroCure Clinical Research Center (F.C.O., J.K., H.Z., C.C., F.S., J.B.-S., M.S., F.P., A.U.B.), and Department of Neurology (J.K., F.S., J.B.-S., K.R., F.P.), Charité-Universitätsmedizin Berlin; Department of Neurology (B.K., T.K.), Klinikum rechts der Isar, and Department of Experimental Neuroimmunology (T.K.), Technische Universität München; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Germany; Clinical Ophthalmology and Eye Health (A.K.), Central Clinical School, Save Sight Institute, Sydney, Australia; and Experimental and Clinical Research Center (F.P.), Max Delbrueck Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Hanna
authors.initials: H
authors.lastname: Zimmermann
authors.affiliation: NeuroCure Clinical Research Center (F.C.O., J.K., H.Z., C.C., F.S., J.B.-S., M.S., F.P., A.U.B.), and Department of Neurology (J.K., F.S., J.B.-S., K.R., F.P.), Charité-Universitätsmedizin Berlin; Department of Neurology (B.K., T.K.), Klinikum rechts der Isar, and Department of Experimental Neuroimmunology (T.K.), Technische Universität München; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Germany; Clinical Ophthalmology and Eye Health (A.K.), Central Clinical School, Save Sight Institute, Sydney, Australia; and Experimental and Clinical Research Center (F.P.), Max Delbrueck Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Chien
authors.affiliation: NeuroCure Clinical Research Center (F.C.O., J.K., H.Z., C.C., F.S., J.B.-S., M.S., F.P., A.U.B.), and Department of Neurology (J.K., F.S., J.B.-S., K.R., F.P.), Charité-Universitätsmedizin Berlin; Department of Neurology (B.K., T.K.), Klinikum rechts der Isar, and Department of Experimental Neuroimmunology (T.K.), Technische Universität München; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Germany; Clinical Ophthalmology and Eye Health (A.K.), Central Clinical School, Save Sight Institute, Sydney, Australia; and Experimental and Clinical Research Center (F.P.), Max Delbrueck Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Schmidt
authors.affiliation: NeuroCure Clinical Research Center (F.C.O., J.K., H.Z., C.C., F.S., J.B.-S., M.S., F.P., A.U.B.), and Department of Neurology (J.K., F.S., J.B.-S., K.R., F.P.), Charité-Universitätsmedizin Berlin; Department of Neurology (B.K., T.K.), Klinikum rechts der Isar, and Department of Experimental Neuroimmunology (T.K.), Technische Universität München; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Germany; Clinical Ophthalmology and Eye Health (A.K.), Central Clinical School, Save Sight Institute, Sydney, Australia; and Experimental and Clinical Research Center (F.P.), Max Delbrueck Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Knier
authors.affiliation: NeuroCure Clinical Research Center (F.C.O., J.K., H.Z., C.C., F.S., J.B.-S., M.S., F.P., A.U.B.), and Department of Neurology (J.K., F.S., J.B.-S., K.R., F.P.), Charité-Universitätsmedizin Berlin; Department of Neurology (B.K., T.K.), Klinikum rechts der Isar, and Department of Experimental Neuroimmunology (T.K.), Technische Universität München; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Germany; Clinical Ophthalmology and Eye Health (A.K.), Central Clinical School, Save Sight Institute, Sydney, Australia; and Experimental and Clinical Research Center (F.P.), Max Delbrueck Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Bellmann-Strobl
authors.affiliation: NeuroCure Clinical Research Center (F.C.O., J.K., H.Z., C.C., F.S., J.B.-S., M.S., F.P., A.U.B.), and Department of Neurology (J.K., F.S., J.B.-S., K.R., F.P.), Charité-Universitätsmedizin Berlin; Department of Neurology (B.K., T.K.), Klinikum rechts der Isar, and Department of Experimental Neuroimmunology (T.K.), Technische Universität München; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Germany; Clinical Ophthalmology and Eye Health (A.K.), Central Clinical School, Save Sight Institute, Sydney, Australia; and Experimental and Clinical Research Center (F.P.), Max Delbrueck Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Korn
authors.affiliation: NeuroCure Clinical Research Center (F.C.O., J.K., H.Z., C.C., F.S., J.B.-S., M.S., F.P., A.U.B.), and Department of Neurology (J.K., F.S., J.B.-S., K.R., F.P.), Charité-Universitätsmedizin Berlin; Department of Neurology (B.K., T.K.), Klinikum rechts der Isar, and Department of Experimental Neuroimmunology (T.K.), Technische Universität München; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Germany; Clinical Ophthalmology and Eye Health (A.K.), Central Clinical School, Save Sight Institute, Sydney, Australia; and Experimental and Clinical Research Center (F.P.), Max Delbrueck Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Scheel
authors.affiliation: NeuroCure Clinical Research Center (F.C.O., J.K., H.Z., C.C., F.S., J.B.-S., M.S., F.P., A.U.B.), and Department of Neurology (J.K., F.S., J.B.-S., K.R., F.P.), Charité-Universitätsmedizin Berlin; Department of Neurology (B.K., T.K.), Klinikum rechts der Isar, and Department of Experimental Neuroimmunology (T.K.), Technische Universität München; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Germany; Clinical Ophthalmology and Eye Health (A.K.), Central Clinical School, Save Sight Institute, Sydney, Australia; and Experimental and Clinical Research Center (F.P.), Max Delbrueck Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Klistorner
authors.affiliation: NeuroCure Clinical Research Center (F.C.O., J.K., H.Z., C.C., F.S., J.B.-S., M.S., F.P., A.U.B.), and Department of Neurology (J.K., F.S., J.B.-S., K.R., F.P.), Charité-Universitätsmedizin Berlin; Department of Neurology (B.K., T.K.), Klinikum rechts der Isar, and Department of Experimental Neuroimmunology (T.K.), Technische Universität München; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Germany; Clinical Ophthalmology and Eye Health (A.K.), Central Clinical School, Save Sight Institute, Sydney, Australia; and Experimental and Clinical Research Center (F.P.), Max Delbrueck Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Klemens
authors.initials: K
authors.lastname: Ruprecht
authors.affiliation: NeuroCure Clinical Research Center (F.C.O., J.K., H.Z., C.C., F.S., J.B.-S., M.S., F.P., A.U.B.), and Department of Neurology (J.K., F.S., J.B.-S., K.R., F.P.), Charité-Universitätsmedizin Berlin; Department of Neurology (B.K., T.K.), Klinikum rechts der Isar, and Department of Experimental Neuroimmunology (T.K.), Technische Universität München; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Germany; Clinical Ophthalmology and Eye Health (A.K.), Central Clinical School, Save Sight Institute, Sydney, Australia; and Experimental and Clinical Research Center (F.P.), Max Delbrueck Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Friedemann
authors.initials: F
authors.lastname: Paul
authors.affiliation: NeuroCure Clinical Research Center (F.C.O., J.K., H.Z., C.C., F.S., J.B.-S., M.S., F.P., A.U.B.), and Department of Neurology (J.K., F.S., J.B.-S., K.R., F.P.), Charité-Universitätsmedizin Berlin; Department of Neurology (B.K., T.K.), Klinikum rechts der Isar, and Department of Experimental Neuroimmunology (T.K.), Technische Universität München; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Germany; Clinical Ophthalmology and Eye Health (A.K.), Central Clinical School, Save Sight Institute, Sydney, Australia; and Experimental and Clinical Research Center (F.P.), Max Delbrueck Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Alexander U
authors.initials: AU
authors.lastname: Brandt