王宁利教授团队：低浓度阿托品滴眼液控制儿童近视进展的一项随机临床试验
2024-08-15
引言：为明确0.01%硫酸阿托品滴眼液在大陆地区近视儿童中的近视防控效果和安全性，首都医科大学附属北京同仁医院王宁利教授团队发表了题为“Safety and Efficacy of Low-Dose Atropine Eyedrops for the Treatment of Myopia Progression in Chinese Children: A Randomized Clinical Trial”的研究论文，该论文已被在国际知名医学期刊JAMA Ophthalmology接收并在线发表。
背景
近视当前呈现出“发病年龄提前、患病率急剧上升、近视程度高和进展快”的趋势，已成为在全球范围内威胁儿童青少年眼健康的公共卫生问题。近视患者尤其是高度近视，甚至病理性近视导致的眼底并发症可能增加不可逆致盲的风险。当前阿托品滴眼液被认为是延缓近视进展的药物，然而目前多数研究通过非随机对照试验来评估低浓度阿托品滴眼液的有效性和安全性，尚缺乏高质量的研究证据。
此外，接受0.5%和0.1%阿托品治疗的近视儿童停止使用药物后，近视反弹程度更大（ATOM 2研究），而接受0.01%浓度阿托品的近视儿童在停止使用后效果持续，而且变化最小。因此，0.01%浓度的阿托品在亚洲越来越多地应用于延缓儿童近视。
既往除ATOM2和LAMP研究外，大多数研究都是通过非随机对照试验来评估低浓度0.01%硫酸阿托品滴眼液的有效性和安全性，很少有数据来自随机对照试验。因此，低浓度阿托品(0.01%)的效果尚未通过安慰剂对照试验被广泛评估。
研究方法
本研究团队自2018年4月到2020年7月展开随机、双盲、安慰剂对照试验。采用电脑自动验光仪(hrk7000a;Huvitz)连续3次测量睫状肌麻痹后的屈光度，同时测量其眼轴长度和眼压。对受试者及其父母进行调查问卷，主要收集受试者的近视发病年龄、父母近视情况、放学后近距离工作时间和户外活动时长等信息。所有受试儿童随机接受0.01%硫酸阿托品滴眼液或安慰剂滴眼液，每天一次，分配比例为1:1，为期1年。所有参与这项研究的儿童在试验开始时、6个月和12个月随访时都接受相同的标准化检查。
图1 随机个体流程图
研究结果
2018年4月至2018年7月，共有268名儿童在本研究中进行初步评估；其中21名儿童不符合纳入标准，12名儿童符合排除标准，其中15名儿童拒绝参与本研究，剩下220名儿童被纳入本研究，两组受试者随机化分配。
表1 参与者的人口统计学和基线特征
1.受试者基线检查结果提示两组在人口统计学、初始等效球镜度数、初始眼轴长度、眼压、近视发病年龄、父母近视情况、户外活动时间和近距离工作方面没有显著差异。
表2.随访时SE和AL的平均变化情况
2.在1年的随访中，0.01%阿托品组和安慰剂组的近视进展分别为 -0.49(0.42)D和-0.76(0.50)D(平均差，0.26 D;95%CI,0.12-0.41D; p<.001)，0.01%阿托品组近视进展相对减少34.2%。
图2 阿托品组、0.01%组和安慰剂组6个月和12个月轻度、中度和重度近视进展的分布
3.
1）6个月时，0.01%硫酸阿托品滴眼液组中81.6%儿童进展小于0.5D，而安慰剂组有61.5%儿童进展小于0.5D;
2）0.01%阿托品组中没有儿童近视进展超过1D，而安慰剂组有3.6%视进展超过1D。
3）12个月时，0.01%阿托品组有48.7%儿童的近视进展小于0.50D，而13.2%儿童近视进展至少1.0D，但在安慰剂组相应比例分别为30.1%和34.9%。
表3 包含0.01%阿托品制剂的病例对照研究的设计和主要结果总结
4. 2012年-2020年期间0.01%-0.05%低浓度阿托品对不同国家，不同年龄段孩子近视的影响情况汇总如表3，这些研究均表明阿托品在控制近视进展中具有一定的疗效。
本文小结
本研究首次采用随机双盲对照试验证实0.01%硫酸阿托品滴眼液在中国大陆地区近视儿童中的效果和安全性，相比于安慰剂，0.01%硫酸阿托品滴眼液可以减缓低中度近视儿童的近视进展和眼轴延长，每天一次的0.01%硫酸阿托品滴眼液耐受性良好，无严重不良事件发生。这为今后0.01%硫酸阿托品滴眼液用于我国儿童近视的防控提供重要依据。
相关信息
阿托品是一种抗胆碱药，为M-受体阻断剂，主要解除平滑肌痉挛，量大可解除小血管痉挛，改善微循环。通常人们将阿托品分为高浓度阿托品（0.5%~1%）、中等浓度阿托品（0.1%~0.49%）和低浓度阿托品（小于0.1%）。鉴于低浓度阿托品临床研究证据和市场使用尚不充分，副作用研究仍也相对匮乏，目前对于近视并没有太多治疗药物，低浓度阿托品配合OK镜及低强度红光重复照射仍然是当前预防和延缓近视的重要手段。
信源：Wei S, Li SM, An W, et al. Safety and Efficacy of Low-Dose Atropine Eyedrops for the Treatment of Myopia Progression in Chinese Children: A Randomized Clinical Trial. JAMA Ophthalmol. 2020;138(11):1178-1184.doi:10.1001/jamaophthalmol.2020.3820
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