视神经脊髓炎谱系疾病相关视神经炎是一种累及视神经的脱髓鞘性炎症疾病，视力损伤严重，预后差，复发率高。及时控制急性发作和有效预防复发是治疗的关键。目前治疗主要包括糖皮质激素、血浆置换、免疫吸附、免疫抑制剂、靶向单抗类药物。特别是近年来依库丽单抗、萨特利珠单抗、及依那利珠单抗取得重大进展。该文综述视神经脊髓炎谱系疾病相关视神经炎近年治疗研究进展，期望为临床决策提供有益参考。
Neuromyelitis optica spectrum disorders (NMOSD) is a central nervous system inflammatory demyelinating disease with involvement of the optic nerve and spinal cord, with poor prognosis and high recurrence rate. Timely control of acute attacks and effective prevention of recurrence are the keys to treatment. This article reviews the recent research progress in the treatment of optic neuritis associated with NMOSD , hoping to provide useful references for clinical decision-making.
目的：探讨小剂量利妥昔单抗(rituximab, RTX)预防视神经脊髓炎谱系疾病(neuromyelitis optica spectrum disorder, NMOSD)复发的有效性和安全性。方法：采用前瞻性自身对照试验，选取2020年7月至2021年4月临床确诊为NMOSD的38例患者进行研究，给予小剂量RTX治疗。所有患者均进行病史采集、眼科检查和血清学指标检测，记录NMOSD年复发率(ARR)、最佳矫正视力(BCVA)、合并自身抗体情况和追加治疗的情况。视力检查采用Snellen视力表进行，并将结果转换为最小分辨角对数(logMAR)视力记录。随访至少12个月（17.29±2.2）个月，以末次随访为疗效判定时间点，比较治疗前后ARR、BCVA；分析复发与发病年龄、是否合并自身免疫抗体阳性和患自身免疫性疾病的关系。记录不良反应的发生率和追加治疗的时间。结果：共38例患者61眼纳入研究。其中男性4例，女性34例。发病年龄12~60岁，中位发病年龄23 (18~29.3)岁。病程10.0~265个月，中位病程65 (48.3~101.0)个月。治疗前logMAR矫正视力(1.15±0.13)，治疗后logMAR矫正视力(1.54±0.39)，比较差异无统计学意义(t=1.120，P=0.267)。治疗前ARR(1.50±0.86)次/年，治疗后ARR降低为(0.12±0.07)次/年，比较差异有统计学意义(t=8.304，P<0.001)。追加治疗时间为(6.4±2.3)月。随访期间3例患者复发，复发次数为 5次。 复发者与未复发者的发病年龄、合并免疫抗体阳性比例、合并自身免疫性疾病比例比较，差异均无统计学意义(均P>0.05)。38例患者中，出现输注不良反应7例，给予减慢RTX滴速及加用地塞米松5 mg治疗后均缓解，随访期间未见其他明显不良反应。结论：小剂量RTX可以有效清除B淋巴细胞，预防NMOSD复发，且安全性较好。
Objective: To evaluate the efficacy and safety of long-term treatment with low-dose rituximab for neuromyelitis optica spectrum disorders (NMOSD). Methods: A prospective self-control study. A total of 38 patients who were diagnosed with NMOSD from July 2020 to April 2021 were recruited for rituximab treatment. All patients collected medical history, ophthalmic examination and serological test. Recorded the annual recurrence rate (ARR), best corrected visual acuity (BCVA), combined autoantibodies and therapy times after the first treatment. The BCVA was examined using Snellen chart, and converted to logMAR. The patients were followed up at least 12(17.29±2.2) months, and the last follow-up was taken as the time point of efficacy evaluation. ARR and BCVA before and after treatment were compared. To analyze the relationship between relapse and age of onset, combination of autoimmune antibodies and autoimmune diseases. The incidence of side effects and duration of additional therapy were recorded. Results: A total of 38 NMOSD patients (4 male/34 female, 61 involved eyes) were included in this study. The ages of onset age were 12-60 years, the median onset age was 23 (18~29.3) years. Duration of disease was 10.0~265 months, the median duration was 65 (48.3~101.0) months. Before treatment, the mean BCVA was 1.15 ± 0.13 , the mean BCVA at last follow-up was 1.54 ± 0.39, which was no significant difference (t=1.120, P=0.267). The mean ARR before and after treatment were 1.50±0.86 and 0.12 ± 0.07, respectively, with significant difference (t=8.304, P<0.001). The mean reinfusion period was 6. 4±2.3 months. Five relapses in 3 patients were observed. There were no significant difference between relapsed patients and non-relapsed patients on onset age, with/without auto-immune antibody ratio, with/without auto-immune diseases ratio (all P>0.05). Of 38 patients, 7 patients had side effects, all patients who had side effects, slowing down the infusion speed of RTX or infusing 5 mg of dexamethasone could relieve the discomfort. Conclusions: Low-dose RTX can effectively clear B lymphocytes, prevent NMOSD recurrence and with good safety.
视神经脊髓炎谱系疾病(neuromyelitis optica spectrum disorders，NMOSD)是一种中枢神经系统炎性脱髓鞘性疾病，以视神经、脊髓和大脑受累为主要特征，该疾病易复发且致盲、致残率高，严重威胁人类视力和健康。目前NMOSD病因尚不明确，现有治疗方案也无法彻底治愈NMOSD，而动物模型是探索其发病机制与病理生理特点的重要工具。NMOSD动物模型主要建立在抗水通道蛋白4抗体(anti-aquaporin 4 immunoglobulin G，AQP4-IgG)致病基础上，主要包括破坏或绕过血脑屏障(blood brain barrier，BBB)被动转移AQP4-IgG或AQP4特异性T细胞等，目前还没有一种动物模型可以完整模拟人类NMOSD的临床和病理特征，因此在研究中选择合适的动物模型对相关研究至关重要。
Neuromyelitis optica spectrum disorders (NMOSD) is an inflammatory demyelinating disease of the central nervous system. It is mainly characterized by the involvement of the optic nerve, spinal cord and brain. The disease is prone to relapse and has a high rate of blindness and disability, which seriously threatens human vision and health. At present, the etiology of NMSOD is not clear, and the existing treatment schemes can’t completely cure NMOSD. Animal models are important tools to explore its pathogenesis and pathophysiological characteristics. NMOSD animals were mainly established on the basis of anti-aquaporin 4 immunoglobulin G (AQP4-IgG), including destroying or bypassing the blood-brain barrier and passively transferring AQP4-IgG or AQP4 specific T cells. At present, no animal model can completely simulate the clinical and pathological characteristics of human NMOSD. Therefore, it is important to select appropriate animal models for the study. This article reviews various animal models of NMOSD in recent years, and discusses the advantages and disadvantages of various models, in order to provide references for the study of the progress and treatment of NMOSD.
