From the Experimental and Clinical Research Center (F.C.O., Svenja Specovius, H.G.Z., C.C., S.M., C.B., A.U.B., F.P.), Max Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany: NeuroCure Clinical Research Center (F.C.O., Svenja Specovius, H.G.Z., C.C., S.M., C.B., A.U.B., F.P.), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Germany; Department of Neurology (F.C.O., A.J.G.), University of California San Francisco, CA; Department of Pediatrics (L.C.), University of Utah, Salt Lake City; CIEM MS Research Center (M.A.L.P., M.A.F.), University of Minas Gerais, Medical School, Belo Horizonte, Brazil; Department of Neurology (H.J.K., J.-W.H.), National Cancer Center, Goyang, Republic of Korea; Department of Neurology (J.P., A.R.-F., M.I.L.), and Department of Ophthalmology (Srilakshmi Sharma), and Department of Ophthalmology (Srilakshmi Sharma), Oxford University Hospitals, National Health Service Trust, UK; Kashani MS Center (F.A.), School of Advanced Technologies in Medicine and Medical Image and Signal Processing Research Center (R.K.), Department of Ophthalmology, Isfahan Eye Research Center (A.D., Mohsen Pourazizi), Isfahan University of Medical Sciences, Iran; Department of Neurology (L.P., A.D'C.), KS Hegde Medical Academy, Nitte University, Mangalore, India; Department of Neurology (O.A., Marius Ringelstein, P.A.), Medical Faculty, Heinrich Heine University Düsseldorf, Germany; Swedish Neuroscience Institute Neuro-Ophthalmology (E.M., C.T.), Seattle, WA; Experimental Neurophysiology Unit (L.L., Marco Pisa, Marta Radaelli), Institute of Experimental Neurology (INSPE) Scientific Institute Hospital San Raffaele and University Vita-Salute San Raffaele, Milan, Italy; Hospital Clinic of Barcelona-Institut d'Investigacions (E.H.M.-L.), Biomèdiques August Pi Sunyer, (IDIBAPS), Spain; Sackler School of Medicine (H.S.-K.), Tel Aviv University, Israel; Neuro-Ophthalmology Division (H.S.-K.), Department of Ophthalmology, Rabin Medical Center, Petah Tikva, Israel; Division of Neurology (Sasitorn Siritho), Department of Medicine, Siriraj Hospital and Bumrungrad International Hospital, Bangkok, Thailand; Neurology Service (J.d.S., Thomas Senger), University Hospital of Strasbourg, France; Institute of Clinical Neuroimmunology (J.H.), Biomedical Center and University Hospital, Ludwig-Maximilians Universitaet Muenchen, Munich, Germany; Neurology (R.M., A.C.C.), Multiple Sclerosis, Myelin Disorders and Neuroinflammation, Pierre Wertheimer Neurological Hospital, Hospices Civils de Lyon, France; Centre d'Esclerosi Múltiple de Catalunya (Cemcat) (A.C.C.), Department of Neurology/Neuroimmunology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; Department of Neurology and Neurosurgery (D.B., I.M.T.), Escola Paulista de Medicina, Universidade Federal de São Paulo, Brazil; Departments of Neurology (N.A.), Slagelse Hospitals, Institute of Regional Health Research, University of Southern Denmark, Odense; Institute of Regional Health Research (N.A., K.S.), University of Southern Denmark, Odense; Department of Neurology (A.A., U.T.), and Department of Ophthalmology (R.Y.), Cerrahpasa Medical Faculty, Istanbul University, Turkey; The Walton Centre for Neurology and Neurosurgery (A.J., S.H.), Liverpool, UK; The Cleveland Clinic Abu Dhabi (A.J.), United Arab Emirates; NYU Multiple Sclerosis Comprehensive Care Center (Z.R., A.R.), Department of Neurology, NYU School of Medicine, New York; Department of Neurology (Y.M.-D.), University of Michigan Medical School, Ann Arbor; Department of Neurology (I.S.C.), Hospital Clínico de Maracaibo, Venezuela; Moorfield's Eye Hospital (A.P.), University College London, UK; Department of Medicine (M.R.Y.), Los Angeles Biomedical Research Institute at Harbor-University of California at Los Angeles (UCLA) Medical Center, Torrance, CA, United States of America; Department of Medicine (M.R.Y.), David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America; Departments of Ophthalmology and Visual Sciences (Terry Smith), Kellogg Eye Center, University of Michigan Medical School, Ann Arbor, United States of America; Division of Metabolism (Terry Smith), Endocrine and Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor; Department of Neurology (A.U.B.), University of California, Irvine; and Department of Neurology (F.P.), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany.
Neurol Neuroimmunol Neuroinflamm. 2021 Sep 15;8(6). doi: 10.1212/NXI.0000000000001068. Print 2021 Nov.
To determine optic nerve and retinal damage in aquaporin-4 antibody (AQP4-IgG)-seropositive neuromyelitis optica spectrum disorders (NMOSD) in a large international cohort after previous studies have been limited by small and heterogeneous cohorts.
The cross-sectional Collaborative Retrospective Study on retinal optical coherence tomography (OCT) in neuromyelitis optica collected retrospective data from 22 centers. Of 653 screened participants, we included 283 AQP4-IgG-seropositive patients with NMOSD and 72 healthy controls (HCs). Participants underwent OCT with central reading including quality control and intraretinal segmentation. The primary outcome was thickness of combined ganglion cell and inner plexiform (GCIP) layer; secondary outcomes were thickness of peripapillary retinal nerve fiber layer (pRNFL) and visual acuity (VA).
Eyes with ON (NMOSD-ON, N = 260) or without ON (NMOSD-NON, N = 241) were assessed compared with HCs (N = 136). In NMOSD-ON, GCIP layer (57.4 ± 12.2 μm) was reduced compared with HC (GCIP layer: 81.4 ± 5.7 μm, < 0.001). GCIP layer loss (-22.7 μm) after the first ON was higher than after the next (-3.5 μm) and subsequent episodes. pRNFL observations were similar. NMOSD-NON exhibited reduced GCIP layer but not pRNFL compared with HC. VA was greatly reduced in NMOSD-ON compared with HC eyes, but did not differ between NMOSD-NON and HC.
Our results emphasize that attack prevention is key to avoid severe neuroaxonal damage and vision loss caused by ON in NMOSD. Therapies ameliorating attack-related damage, especially during a first attack, are an unmet clinical need. Mild signs of neuroaxonal changes without apparent vision loss in ON-unaffected eyes might be solely due to contralateral ON attacks and do not suggest clinically relevant progression but need further investigation.
既往研究因队列规模小且异质性大，现有的研究均受到限制。本研究旨在通过大型国际队列来确定先前研究中视神经和视网膜损伤在水通道蛋白-4 抗体（AQP4-IgG）阳性视神经脊髓炎谱系疾病（NMOSD）中的作用。
本回顾性、合作性研究纳入了 22 个中心的 NMOSD 患者的回顾性数据，这些患者均接受了视神经 OCT 检查。在筛选出的 653 名参与者中，我们纳入了 283 名 AQP4-IgG 阳性 NMOSD 患者和 72 名健康对照者（HCs）。参与者接受了中心阅读的 OCT 检查，包括质量控制和视网膜内部分层。主要结局为节细胞和内丛状层（GCIP）厚度；次要结局为视盘周围视网膜神经纤维层（pRNFL）和视力（VA）。
与 HCs 相比，我们评估了伴有视神经炎（NMOSD-ON，N = 260）或不伴有视神经炎（NMOSD-NON，N = 241）的患者。NMOSD-ON 的 GCIP 层（57.4 ± 12.2 μm）比 HC 的 GCIP 层（81.4 ± 5.7 μm）更薄（<0.001）。首次视神经炎后 GCIP 层的损失（-22.7 μm）高于后续（-3.5 μm）和随后的发作。pRNFL 观察结果相似。与 HC 相比，NMOSD-NON 患者的 GCIP 层降低，但 pRNFL 层无差异。与 HC 相比，NMOSD-ON 患者的 VA 明显降低，但 NMOSD-NON 与 HC 之间的 VA 无差异。
我们的研究结果强调，预防发作是避免 NMOSD 中视神经炎引起严重神经轴突损伤和视力丧失的关键。改善与发作相关的损伤的治疗方法，特别是在首次发作时，是一种未满足的临床需求。在未受视神经炎影响的眼中，即使没有明显的视力丧失，也存在轻微的神经轴突改变迹象，这可能仅归因于对侧视神经炎发作，并不提示临床相关进展，但需要进一步研究。
