氢溴酸樟柳碱治疗非动脉炎性前部缺血性视神经病变的有效性和安全性评价:中国多中心非随机对照临床研究

Effectiveness and security of anisodine hydrobromide tablets in treating nonarteritic anterior ischemic optic neuropathy:a Chinese multicenter nonrandomized controlled study

目的评估口服氢溴酸樟柳碱片治疗急性期非动脉炎性前部缺血性视神经病变(NAION)的有效性和安全性。方法采用多中心非随机对照临床研究,于2020年7月至2021年5月在中国共16所医院眼科纳入首次发病的急性期NAION患者282例282眼,按照治疗方法不同将患者分为2个组,其中对照组124例124眼,接受口服胞磷胆碱钠片、银杏叶提取物片/银杏叶提取物滴剂和甲钴胺片治疗;试验组158例158眼,在采用对照组治疗方法的基础上口服氢溴酸樟柳碱片1 mg/次,2次/日,连续用药2~3个月。分别于入组后1、2、3和6个月进行随访,采用标准小数视力表测定最佳矫正视力(BCVA),采用750i Humphery视野计(30-2程序)检查视野获得视野指数(VFI),采用HD 4000/HD 5000型光学相干断层扫描仪(OCT)测量视盘周围视网膜神经纤维层厚度(pRNFL),采用RTVue-XR OCT仪测定视盘放射状毛细血管网血管密度(RPC)。主要结局指标为随访末BCVA、VFI,次要结局指标为pRNFL、RPC,以及随访期间不良反应。结果共242例242眼完成主要结局指标BCVA随访,98例98眼完成主要结局指标VFI随访。在视功能变化方面,2个组患者随时间推移BCVA和VFI均有明显改善,其中试验组在各个随访时间点BCVA均显著优于对照组,VFI均显著高于对照组,差异均有统计学意义(均P<0.05)。在结构指标方面,2个组患者pRNFL均随治疗时间的延长而逐渐变薄,其中试验组在各个随访时间点pRNFL均显著薄于对照组,差异均有统计学意义(均P<0.05),但2个组间最终随访RPC差异无统计学意义(P>0.05)。试验组共有2例发生药物相关不良反应,其中1例因药物不良反应于治疗后25 d退出研究。结论口服氢溴酸樟柳碱片可以改善NAION患者的视力和视野,加速视盘水肿消退,具有良好的安全性。

Objective To evaluate the efficacy and safety of oral anisodine hydrobromide tablets in the treatment of nonarteritic anterior ischemic optic neuropathy(NAION).Methods A multicenter nonrandomized controlled trial was conducted.A total of 282 acute NAION patients(282 eyes)were recruited from 16 hospitals in China from July 2020 to May 2021.Patients were divided into two groups according to treatment methods,which were control group(124 cases,124 eyes)receiving regular treatment including citicoline sodium plus Ginkgo biloba leaf liquid extract or Ginkgo biloba leaf extract tablets plus mecobalamin,and experimental group(158 cases,158 eyes)receiving treatment in control group plus oral anisodine hydrobromide tablets 1 mg,twice daily for 2 to 3 months.Best corrected visual acuity(BCVA),visual field index(VFI),peripapillary retinal nerve fiber layer(pRNFL)and radial peripapillary capillary vessel density(RPC)were assessed at 1,2,3,and 6 months after enrollment using the standard decimal visual acuity chart,750i Humphery visual field analyzer,Cirrus HD-OCT 4000/Cirrus HD-OCT 5000,RTVue-XR optical coherence tomography respectively.The primary outcomes were BCVA and VFI,and the secondary outcomes were pRNFL,RPC,and the side effects during the follow-up.The study adhered to the Declaration of Helsinki.All patients were fully informed about the treatment and purpose of this study and voluntarily signed the informed consent form.The study protocol was approved by Chinese PLA General Hospital(No.S2020-021-01).Results In all,242 patients(242 eyes)completed the follow-up of BCVA,and 98 patients(98 eyes)completed the VFI follow-up.In terms of visual function,BCVA and VFI improved significantly over time in the two groups,and BCVA and VFI were better in experimental group than in control group at various follow-up time points(all at P<0􀆰05).In terms of structure,pRNFL gradually decreased in both groups with the extension of treatment,and pRNFL was significanthy thinner in experimental group than in control group at various follow-up time points(all at P<0􀆰05).There was no significant difference in RPC between the two groups at the last follow-up(P>0􀆰05).There were two cases with side effects and one case was discontinued due to side effects 25 days after enrollment.Conclusions Oral anisodine hydrobromide can improve visual acuity and visual field in NAION and accelerate the regression of optic disc edema,with good safety.