A retrospective study of ocular manifestations and aquaporin 4 antibody concentrations in 132 patients with neuromyelitis optica_Chinese Journal of Ocular Fundus Diseases

Authors：

Liu Wenting ¹ , Zhang Jiaying ¹ , Quan Chao ² , Ye Wen ¹ , Chen Xiangjun ² ,  Lu Zhaozeng ¹

1. Department of Ophthalmology, Huashan Hospital of Fudan University, Shanghai 200030, China;
2. Department of Neurology, Huashan Hospital of Fudan University, Shanghai 200030, ChinaLiu Wenting is working on the Department of Ophthalmology, Huadong Hospital of Fudan University, Shanghai 200030, China; Zhang Jiaying is working on the Department of Ophthalmology, West China Hospital, Sichun University, Chengdu 610041, China;

Corresponding author：

Lu Zhaozeng, Email: luzc@shmu.edu.cn

Keywords：

Neuromyelitis optica; Vision; Aquaporin 4

DOI：

10.3760/cma.j.issn.1005-1015.2019.03.007

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Objective To observe the ocular manifestations and the titer of aquaporin 4 antibody (AQP-4) in NMO patients, and to evaluate the BCVA prognosis in patients with different titers of AQP-4Ab.Methods A retrospective case study. From September 2009 to March 2014, 132 NMO patients diagnosed in Department of Neurology and Ophthalmology in Huashan Hospital of Fudan University were included in the study. Among the patients, 74 patients (56.06%) were involved in optic nerve for the first time, among which 63 patients (47.72%) were involved in optic nerve alone, and 11 patients (8.33%) were involved in optic nerve and spinal cord at the same time. The recurrence rate was 62.88% (twice or more). All patients underwent BCVA, slit lamp microscope, fundus examination, thyroid function, sex hormones, and serum AQP-4Ab detection. BCVA was recorded at admission and before discharge from hospital, and worse BCVA was recorded in binocular patients. The BCVA of patients with different titers of AQP-4Ab were analyzed comparatively.Results Among the 74 patients with optic nerve involved in the first onset, 50 patients with BCVA＜0.1 at the initial diagnosis (67.57%); AQP-4Ab positive was found in 56 patients, which including 13, 9 and 34 patients of AQP-4Ab titer 5 - 60, 61 - 100 and ＞100 RSRU/ml. After 2 weeks of treatment, BCVA improved in 40 patients (71.42%), including 11 (84.62%), 6 (66.67%) and 23 (67.64%) of AQP-4Ab titer 5 - 60, 61 - 100 and ＞ 100 RSRU/ml. Among 132 patients, 98 patients (74.24%) were AQP-4Ab positive. There were 73 patients (55.30%) with abnormal immune rheumatoid index.Conclusions The optic nerve is involved in 56.06% patients with NMO for the first time, and 67.57% of the patients had poor vision with BCVA＜0.1. BCVA prognosis is better in patients with serum AQP-4Ab titer of 5 - 60 RSRU/ml.

Citation： Liu Wenting, Zhang Jiaying, Quan Chao, Ye Wen, Chen Xiangjun, Lu Zhaozeng. A retrospective study of ocular manifestations and aquaporin 4 antibody concentrations in 132 patients with neuromyelitis optica. Chinese Journal of Ocular Fundus Diseases, 2019, 35(3): 246-250. doi: 10.3760/cma.j.issn.1005-1015.2019.03.007 Copy

1.	Fazio R, Radaelli M, Furlan R. Neuromyelitis optica: Concepts in evolution[J]. J Neuroimmunol, 2011, 23(1-2): 100-104. DOI: 10.1016/j.jneuroim.2010.10.012.
2.	Hasegawa T, Sugawara Y, Suzuki M, et al. Spatial and temporal expression of the ventral pelvic skin aquaporins during metamorphosis of the tree frog, Hyla japonica[J]. J Membr Biol, 2004, 199(2): 119-126. DOI: 10.1007/s00232-004-0677-8.
3.	Lennon VA, Wingerchuk DM, Kryzer TJ, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis[J]. Lancet, 2004, 364(9451): 2106-2112. DOI: 10.1016/S0140-6736(04)17551-X.
4.	Merle H, Olindo S, Bonnan M, et al. Natural history of the visual impairment of relapsing neuromyelitis optica[J]. Ophthalmology, 2007, 114(4): 810-815. DOI: 10.1016/j.ophtha.2006.06.060.
5.	王家伟, 邓娟, 戚朝秀, 等. 多发性硬化与视神经脊髓炎的眼部特征及其治疗效果[J]. 中华眼底病杂志, 2014, 22(4): 328-330. DOI: 10.3760/cma.jissn.1005-1015.2010.04.07.Wang JW, Deng J, Qi CX, et al. Ocular manifestation of multiple sclerosis and neuromyelitis optica[J]. Chin J Ocul Fundus Dis, 2014, 22(4): 328-330. DOI: 10.3760/cma.jissn.1005-1015.2010.04.07.
6.	王颖云, 魏世辉. 水通道蛋白4抗体及抗核抗体在视神经炎中的分布及相关性分析[J]. 中国实用眼科杂志, 2012, 30(11): 1288-1291. DOI: 10.3760/ema.j.iss.1006-4443.2012.11.008.Wang YY, Wei SH. Distribution and relevance study of aquaporin-4 antibodies and antinuclear antibodies in patients with optic neuritis[J]. Chin J Pract Ophthalmol, 2012, 30(11): 1288-1291. DOI: 10.3760/ema.j.iss.1006-4443.2012.11.008.
7.	Wingerchuk DM, Lennon VA, Pittock SJ, et al. Revised diagnostic criteria for neuromyelitis optica[J]. Neurology, 2006, 66(10): 1485-1489. DOI: 10.1212/01.wnl.0000216139.44259.74.
8.	Smith CH. Optic neuritis[M]//Miller NR, Newman NJ, Biousse V, et al. Walsh and Hoyt Clinical neuro-ophthalmology.6th ed. Baltimore: Lippincott Williams&Wilkins, 2005: 293-326.
9.	Transverse Myelitis Consortium Working Group. Proposed diagnostic criteria and nosology of acute transverse myelitis[J]. Neurology, 2002, 59(4): 499-505. DOI: 10.1212/WNL.59.4.499.
10.	Jarius S, Franciotta D, Paul JE, et al. Testing for antibodies to human aquaporin-4 by ELISA: sensitivity, specificity, and direct comparison with immunehisto-chemistry[J]. J Neurol Sci, 2012, 320(1-2): 32-37. DOI: 10.1016/j.jns.2012.06.002.
11.	Zhang JY, Shen XZ, Sun L, et al. Clinical and pathological features of acute optic neuritis in Chinese patients[J]. Chin Med J(Engl), 2013, 126(9): 1689-1692. DOI: 10.3760/cma.j.issn.0366-6999.20123599.
12.	Wandinger KP, Stangel M, Witte T, et al. Autoantibodies against aquaporin-4 in patients with neuropsychiatric systemic lupus erythematosus and primary Sjögren's syndrome[J]. Arthritis Rheum, 2010, 62(4): 1198-1200. DOI: 10.1002/art.27337.
13.	Jarius S, Jacobi C, de Seze J, et al. Frequency and syndrome specificity of antibodies to aquaporin-4 in neurological patients with rheumatic disorders[J]. Mult Scler, 2011, 17(9): 1067-1073. DOI: 10.1177/1352458511403958.
14.	Pittock SJ, Lennon VA, de Seze J, et al. Neuromyelitis optica and non organ-specific autoimmunity[J]. Arch Neurol, 2008, 65(1): 78-83. DOI: 10.1001/archneurol.2007.17.
15.	张包静子, 全超, 卢家红, 等. 血清水通道蛋白4抗体阳性的中枢神经系统脱髓鞘病104例临床特点分析[J]. 中华临床神经科学, 2014, 22(4): 361-368.Zhang Bao JZ, Quan C, Lu JH, et al. The clinical characteristics of central nervous system demyelinating disorders with positive serum AQP-4 antibody: a retrospective study of 104 Chinese Cases[J]. Chin J Clin Neursci, 2014, 22(4): 361-368.
16.	Wingerchuk DM, Banwell B, Bennett JL, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders[J]. Neurology, 2015, 85(2): 177-189. DOI: 10.1212/WNL.0000000000001729.
17.	Waters P, Reindl M, Saiz A, et al. Multicentre comparison of a diagnostic assay: aquaporin-4 antibodies in neuromyelitis optica[J]. J Neurol Neurosurg Psychiatry, 2016, 87(9): 1005-1015. DOI: 10.1136/jnnp-2015-312601.
18.	Nakashima I, Fujihara K, Miyazawa I, et al. Clinical and MRI features of Japanese patients with multiple sclerosis positive for NMO-IgG[J]. J Neurol Neurosurg Psychiatry, 2006, 77(9): 1073-1075. DOI: 10.1136/jnnp.2005.080390.
19.	Takahashi T, Fujihara K, Nakashima I, et al. Anti-aquaporin-4 antibody is involved in the pathogenesis of NMO: a study on antibody titre[J]. Brain, 2007, 130(Pt5): 1235-1243. DOI: 10.1093/brain/awm062.
20.	Matsuoka T, Matsushita T, Kawano Y, et al. Heterogeneity of aquaporin-4 autoimmunity and spinal cord lesions in multiple sclerosis in Japanese[J]. Brain, 2007, 130(Pt5): 1206-1223. DOI: 10.1093/brain/awm027.

1. Fazio R, Radaelli M, Furlan R. Neuromyelitis optica: Concepts in evolution[J]. J Neuroimmunol, 2011, 23(1-2): 100-104. DOI: 10.1016/j.jneuroim.2010.10.012.
2. Hasegawa T, Sugawara Y, Suzuki M, et al. Spatial and temporal expression of the ventral pelvic skin aquaporins during metamorphosis of the tree frog, Hyla japonica[J]. J Membr Biol, 2004, 199(2): 119-126. DOI: 10.1007/s00232-004-0677-8.
3. Lennon VA, Wingerchuk DM, Kryzer TJ, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis[J]. Lancet, 2004, 364(9451): 2106-2112. DOI: 10.1016/S0140-6736(04)17551-X.
4. Merle H, Olindo S, Bonnan M, et al. Natural history of the visual impairment of relapsing neuromyelitis optica[J]. Ophthalmology, 2007, 114(4): 810-815. DOI: 10.1016/j.ophtha.2006.06.060.
5. 王家伟, 邓娟, 戚朝秀, 等. 多发性硬化与视神经脊髓炎的眼部特征及其治疗效果[J]. 中华眼底病杂志, 2014, 22(4): 328-330. DOI: 10.3760/cma.jissn.1005-1015.2010.04.07.Wang JW, Deng J, Qi CX, et al. Ocular manifestation of multiple sclerosis and neuromyelitis optica[J]. Chin J Ocul Fundus Dis, 2014, 22(4): 328-330. DOI: 10.3760/cma.jissn.1005-1015.2010.04.07.
6. 王颖云, 魏世辉. 水通道蛋白4抗体及抗核抗体在视神经炎中的分布及相关性分析[J]. 中国实用眼科杂志, 2012, 30(11): 1288-1291. DOI: 10.3760/ema.j.iss.1006-4443.2012.11.008.Wang YY, Wei SH. Distribution and relevance study of aquaporin-4 antibodies and antinuclear antibodies in patients with optic neuritis[J]. Chin J Pract Ophthalmol, 2012, 30(11): 1288-1291. DOI: 10.3760/ema.j.iss.1006-4443.2012.11.008.
7. Wingerchuk DM, Lennon VA, Pittock SJ, et al. Revised diagnostic criteria for neuromyelitis optica[J]. Neurology, 2006, 66(10): 1485-1489. DOI: 10.1212/01.wnl.0000216139.44259.74.
8. Smith CH. Optic neuritis[M]//Miller NR, Newman NJ, Biousse V, et al. Walsh and Hoyt Clinical neuro-ophthalmology.6th ed. Baltimore: Lippincott Williams&Wilkins, 2005: 293-326.
9. Transverse Myelitis Consortium Working Group. Proposed diagnostic criteria and nosology of acute transverse myelitis[J]. Neurology, 2002, 59(4): 499-505. DOI: 10.1212/WNL.59.4.499.
10. Jarius S, Franciotta D, Paul JE, et al. Testing for antibodies to human aquaporin-4 by ELISA: sensitivity, specificity, and direct comparison with immunehisto-chemistry[J]. J Neurol Sci, 2012, 320(1-2): 32-37. DOI: 10.1016/j.jns.2012.06.002.
11. Zhang JY, Shen XZ, Sun L, et al. Clinical and pathological features of acute optic neuritis in Chinese patients[J]. Chin Med J(Engl), 2013, 126(9): 1689-1692. DOI: 10.3760/cma.j.issn.0366-6999.20123599.
12. Wandinger KP, Stangel M, Witte T, et al. Autoantibodies against aquaporin-4 in patients with neuropsychiatric systemic lupus erythematosus and primary Sjögren's syndrome[J]. Arthritis Rheum, 2010, 62(4): 1198-1200. DOI: 10.1002/art.27337.
13. Jarius S, Jacobi C, de Seze J, et al. Frequency and syndrome specificity of antibodies to aquaporin-4 in neurological patients with rheumatic disorders[J]. Mult Scler, 2011, 17(9): 1067-1073. DOI: 10.1177/1352458511403958.
14. Pittock SJ, Lennon VA, de Seze J, et al. Neuromyelitis optica and non organ-specific autoimmunity[J]. Arch Neurol, 2008, 65(1): 78-83. DOI: 10.1001/archneurol.2007.17.
15. 张包静子, 全超, 卢家红, 等. 血清水通道蛋白4抗体阳性的中枢神经系统脱髓鞘病104例临床特点分析[J]. 中华临床神经科学, 2014, 22(4): 361-368.Zhang Bao JZ, Quan C, Lu JH, et al. The clinical characteristics of central nervous system demyelinating disorders with positive serum AQP-4 antibody: a retrospective study of 104 Chinese Cases[J]. Chin J Clin Neursci, 2014, 22(4): 361-368.
16. Wingerchuk DM, Banwell B, Bennett JL, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders[J]. Neurology, 2015, 85(2): 177-189. DOI: 10.1212/WNL.0000000000001729.
17. Waters P, Reindl M, Saiz A, et al. Multicentre comparison of a diagnostic assay: aquaporin-4 antibodies in neuromyelitis optica[J]. J Neurol Neurosurg Psychiatry, 2016, 87(9): 1005-1015. DOI: 10.1136/jnnp-2015-312601.
18. Nakashima I, Fujihara K, Miyazawa I, et al. Clinical and MRI features of Japanese patients with multiple sclerosis positive for NMO-IgG[J]. J Neurol Neurosurg Psychiatry, 2006, 77(9): 1073-1075. DOI: 10.1136/jnnp.2005.080390.
19. Takahashi T, Fujihara K, Nakashima I, et al. Anti-aquaporin-4 antibody is involved in the pathogenesis of NMO: a study on antibody titre[J]. Brain, 2007, 130(Pt5): 1235-1243. DOI: 10.1093/brain/awm062.
20. Matsuoka T, Matsushita T, Kawano Y, et al. Heterogeneity of aquaporin-4 autoimmunity and spinal cord lesions in multiple sclerosis in Japanese[J]. Brain, 2007, 130(Pt5): 1206-1223. DOI: 10.1093/brain/awm027.

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A retrospective study of ocular manifestations and aquaporin 4 antibody concentrations in 132 patients with neuromyelitis optica

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