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Safety and Efficacy of Low-Dose Atropine Eyedrops for the Treatment of Myopia Progression in Chinese Children A Randomized Clinical Trial
低剂量阿托品眼药水治疗中国儿童近视进展的安全性和有效性 随机临床试验

Shifei Wei, MD, PHD; Shi-Ming Li, MD, PhD; Wenzai An, MD; Jialing Du, MD; Xintong Liang, MD; Yunyun Sun, MD, PhD; Duoxing Zhang, MD; Jiaxin Tian, MD; Ningli Wang, MD, PhD

Abstract 摘要

IMPORTANCE Because studies have suggested that atropine might slow the progression of myopia in children, randomized clinical trials are warranted to understand this potential causal relationship.
重要性 因为研究表明阿托品可能会减缓儿童近视的进展，因此有必要进行随机临床试验以了解这种潜在的因果关系。

OBJECTIVE To evaluate the efficacy and safety of atropine, 0.01%, eyedrops on slowing myopia progression and axial elongation in Chinese children.
目的 评估 0.01%阿托品眼药水在减缓中国儿童近视进展和轴向延长方面的疗效和安全性。

DESIGN, SETTING, AND PARTICIPANTS This was a randomized, placebo-controlled, double-masked study. A total of 220 children aged 6 to 12 years with myopia of -1.00 D to -6.00 D in both eyes were enrolled between April 2018 and July 2018 at Beijing Tongren Hospital, Beijing, China. Cycloplegic refraction and axial length were measured at baseline, 6 months, and 12 months. Adverse events were also recorded.
设计、设置和参与者 这是一项随机、安慰剂对照、双盲研究。共有 220 名年龄在 6 至 12 岁之间、双眼近视度数在-1.00 D 至-6.00 D 的儿童于 2018 年 4 月至 2018 年 7 月在中国北京同仁医院入组。基线、6 个月和 12 个月时测量了睫状麻痹屈光度和轴长。同时也记录了不良事件。

INTERVENTIONS Patients were randomly assigned in a 1:1 ratio to atropine, 0.01 % 0.01 % 0.01%0.01 \%, or placebo groups to be administered once nightly to both eyes for 1 year.
干预 患者以 1:1 的比例随机分配到阿托品、 0.01 % 0.01 % 0.01%0.01 \% 或安慰剂组，每晚在双眼中使用一次，持续 1 年。

MAIN OUTCOMES AND MEASURES Mean changes and percentage differences in myopia progression and axial elongation between atropine, 0.01%, or placebo groups.
主要结果和测量：阿托品 0.01%组或安慰剂组之间近视进展和轴向延长的平均变化和百分比差异。

RESULTS Of 220 participants, 103 were girls (46.8%), and the mean (SD) age was 9.64 (1.68) years. The mean (SD) baseline refractive error and axial length were -2.58 (1.39) D and 24.59 ( 0.87 ) mm. Follow-up at 1 year included 76 children ( 69 % 69 % 69%69 \% ) and 83 children ( 75 % 75 % 75%75 \% ) allocated into the atropine, 0.01 % 0.01 % 0.01%0.01 \%, and placebo groups, respectively, when mean myopia progression was - 0.49 (0.42) D and -0.76 (0.50) D in the atropine, 0.01%, and placebo groups (mean difference, 0.26 D ; 95 % Cl , 0.12 − 0.41 D ; P < .001 0.26 D ; 95 % Cl , 0.12 − 0.41 D ; P < .001 0.26D;95%Cl,0.12-0.41D;P < .0010.26 \mathrm{D} ; 95 \% \mathrm{Cl}, 0.12-0.41 \mathrm{D} ; \mathrm{P}<.001 ), with a relative reduction of 34.2 % 34.2 % 34.2%34.2 \% in myopia progression. The mean (SD) axial elongation in the atropine, 0.01 % 0.01 % 0.01%0.01 \%, group was 0.32 (0.19) mm compared with 0.41 (0.19) mm in the placebo group (mean difference, 0.09 mm ; 95 % Cl , 0.03 − 0.15 mm ; P = .004 ) 95 % Cl , 0.03 − 0.15 mm ; P = .004 ) 95%Cl,0.03-0.15mm;P=.004)95 \% \mathrm{Cl}, 0.03-0.15 \mathrm{~mm} ; P=.004), with relative reduction of 22.0 % 22.0 % 22.0%22.0 \% in axial elongation. Fifty-one percent and 13.2 % 13.2 % 13.2%13.2 \% of children progressed by at least 0.50 D and 1.00 D in the atropine, 0.01 % 0.01 % 0.01%0.01 \%, group, compared with 69.9 % 69.9 % 69.9%69.9 \% and 34.9 % 34.9 % 34.9%34.9 \% in the placebo group. No serious adverse events related to atropine were reported.
结果 在 220 名参与者中，103 名为女孩（46.8%），平均年龄（标准差）为 9.64（1.68）岁。基线屈光不正和轴长的平均值（标准差）分别为-2.58（1.39）D 和 24.59（0.87）mm。1 年的随访包括 76 名儿童（ 69 % 69 % 69%69 \% ）和 83 名儿童（ 75 % 75 % 75%75 \% ），分别分配到阿托品、 0.01 % 0.01 % 0.01%0.01 \% 和安慰剂组，当时阿托品、0.01%和安慰剂组的平均近视进展为-0.49（0.42）D 和-0.76（0.50）D（平均差异， 0.26 D ; 95 % Cl , 0.12 − 0.41 D ; P < .001 0.26 D ; 95 % Cl , 0.12 − 0.41 D ; P < .001 0.26D;95%Cl,0.12-0.41D;P < .0010.26 \mathrm{D} ; 95 \% \mathrm{Cl}, 0.12-0.41 \mathrm{D} ; \mathrm{P}<.001 ），近视进展的相对减少为 34.2 % 34.2 % 34.2%34.2 \% 。阿托品、 0.01 % 0.01 % 0.01%0.01 \% 组的平均（标准差）轴向延长为 0.32（0.19）mm，而安慰剂组为 0.41（0.19）mm（平均差异，0.09 mm； 95 % Cl , 0.03 − 0.15 mm ; P = .004 ) 95 % Cl , 0.03 − 0.15 mm ; P = .004 ) 95%Cl,0.03-0.15mm;P=.004)95 \% \mathrm{Cl}, 0.03-0.15 \mathrm{~mm} ; P=.004) ，轴向延长的相对减少为 22.0 % 22.0 % 22.0%22.0 \% 。51%和 13.2 % 13.2 % 13.2%13.2 \% 的儿童在阿托品、 0.01 % 0.01 % 0.01%0.01 \% 组中至少进展了 0.50 D 和 1.00 D，而安慰剂组中分别为 69.9 % 69.9 % 69.9%69.9 \% 和 34.9 % 34.9 % 34.9%34.9 \% 。没有报告与阿托品相关的严重不良事件。

CONCLUSIONS AND RELEVANCE While the clinical relevance of the results cannot be determined from this trial, these 1-year results, limited by approximately 70% follow-up, suggest that atropine, 0.01 % 0.01 % 0.01%0.01 \%, eyedrops can slow myopia progression and axial elongation in children and warrant future studies to determine longer-term results and potential effects on slowing sight-threatening pathologic changes later in life.
结论与相关性 虽然无法从本试验中确定结果的临床相关性，但这些为期 1 年的结果（约 70%的随访限制）表明，阿托品 0.01 % 0.01 % 0.01%0.01 \% 眼药水可以减缓儿童近视进展和轴向延长，值得未来研究以确定长期结果及其对减缓日后可能威胁视力的病理变化的潜在影响。

TRIAL REGISTRATION http://www.chictr.org.cn Identifier: ChiCTR-IOR-17013898
试验注册 http://www.chictr.org.cn 标识符：ChiCTR-IOR-17013898
Supplemental content 补充内容
Author Affiliations: Beijing Tongren Eye Center, Beijing Tongren Hospital, Beijing Ophthalmology and Visual Science Key Lab, Beijing Institute of Ophthalmology, Capital Medical University, Beijing, China (Wei, Li, An, Du, Liang, Sun, Tian, Wang); Peking Union Medical College, Beijing, China (Zhang).
作者单位：北京同仁眼科中心，北京同仁医院，北京眼科与视觉科学重点实验室，北京眼科研究所，首都医科大学，中国北京（魏，李，安，杜，梁，孙，田，王）；北京协和医学院，中国北京（张）。
Corresponding Author: Ningli Wang, MD, PhD, Beijing Tongren Eye Center, Beijing Tongren Hospital, Beijing Ophthalmology and Visual Science Key Lab, Beijing Institute of Ophthalmology, Capital Medical University, No. 1 Dongjiaominxiang St, Dongcheng District, Beijing, China, 100730 (wningli@vip.163.com).
通讯作者：王宁丽，医学博士，北京同仁眼科中心，北京同仁医院，北京市眼科与视觉科学重点实验室，北京眼科研究所，首都医科大学，东城区东交民巷街 1 号，中国，北京，100730（wningli@vip.163.com）。
Myopia has become a critical public health problem among both children and adults, especially in some East and Southeast Asian countries such as China and Singapore. 1 , 2 1 , 2 ^(1,2){ }^{1,2} A 2016 review 3 3 ^(3){ }^{3} predicted that approximately half of the world’s population will have myopia by 2050, with 10 % 10 % 10%10 \% being high myopia. 3 3 ^(3){ }^{3} In China, the prevalence of myopia reaches 5.2 % 5.2 % 5.2%5.2 \% in children aged 6 years, nearly 70 % 70 % 70%70 \% in seventh-grade students, and exceeds 80 % 80 % 80%80 \% in university students. 4 − 6 4 − 6 ^(4-6){ }^{4-6} Myopia is not only the most common cause of avoidable visual impairment and blindness, but high or pathologic myopia is also associated with increased risk of irreversible blinding conditions, including myopic retinopathy, retinal detachment, choroidal neovascularization, and glaucoma, 7 − 10 7 − 10 ^(7-10){ }^{7-10} leading to a heavy cost burden on individuals and communities. 11 11 ^(11){ }^{11}
近视已成为儿童和成人中一个严重的公共卫生问题，尤其是在中国和新加坡等一些东亚和东南亚国家。2016 年的一项回顾预测，到 2050 年，全球约一半的人口将患有近视，其中高近视的比例较高。在中国，6 岁儿童的近视患病率达到近 70%，七年级学生接近 80%，大学生超过 90%。近视不仅是可避免的视觉障碍和失明的最常见原因，高度或病理性近视还与不可逆失明病症的风险增加相关，包括近视性视网膜病、视网膜脱落、脉络膜新生血管和青光眼，这给个人和社区带来了沉重的经济负担。
Several randomized clinical trials have been investigated to halt or slow myopic progression including undercorrection, progressive addition lenses, contact lenses, pirenzepine gel, and increased outdoor activity. 12 − 16 12 − 16 ^(12-16){ }^{12-16} However, the results of their effects are disappointing or positive results of marginal clinical significance. At present, topical atropine has been demonstrated to have the strongest clinical effect on slowing the progression of myopia. 17 − 19 17 − 19 ^(17-19){ }^{17-19} In 2006, the Atropine for the Treatment of Myopia 1 (ATOM 1) study found that the mean (SD) rate of myopia progression after 2 years was only -0.28 (0.92) D in the atropine, 1 % 1 % 1%1 \%, group compared with -1.20 (0.69) D in the placebo group. 18 18 ^(18){ }^{18} However, ocular adverse effects induced by atropine, 1 % 1 % 1%1 \%, such as blurred near vision, photophobia cycloplegia, and allergy, have limited its use. Furthermore, there was a greater myopic rebound in eyes that had received atropine, 0.5 % 0.5 % 0.5%0.5 \% and 0.1 % 0.1 % 0.1%0.1 \%, after treatment was discontinued (ATOM 2 study), whereas those receiving a low-dose 0.01 % 0.01 % 0.01%0.01 \% concentration proved sustained and minimal change after treatment cessation. 20 20 ^(20){ }^{20} Therefore, low concentration of atropine, 0.01 % 0.01 % 0.01%0.01 \%, is increasingly applied to clinical treatment for children with myopia in Asia.
已经进行了几项随机临床试验，以阻止或减缓近视进展，包括不足矫正、渐进多焦点镜片、隐形眼镜、吡仑帕尼凝胶和增加户外活动。 12 − 16 12 − 16 ^(12-16){ }^{12-16} 然而，它们的效果结果令人失望或仅有边际临床意义的积极结果。目前，局部阿托品已被证明对减缓近视进展具有最强的临床效果。 17 − 19 17 − 19 ^(17-19){ }^{17-19} 2006 年，阿托品治疗近视 1（ATOM 1）研究发现，阿托品组在 2 年后近视进展的平均（标准差）速度仅为-0.28（0.92）D，而安慰剂组为-1.20（0.69）D。 18 18 ^(18){ }^{18} 然而，阿托品引起的眼部不良反应，如近距离视力模糊、畏光、睫状肌麻痹和过敏，限制了其使用。此外，在停止治疗后，接受阿托品治疗的眼睛出现了更大的近视反弹 0.5 % 0.5 % 0.5%0.5 \% ，而接受低剂量 0.01 % 0.01 % 0.01%0.01 \% 浓度治疗的患者在停止治疗后表现出持续且变化最小的效果。 因此，低浓度的阿托品在亚洲越来越多地应用于儿童近视的临床治疗。
Most studies have been performed to evaluate the efficacy and safety of low concentration of atropine, 0.01 % 0.01 % 0.01%0.01 \%, through nonrandomized controlled trials, 21 − 23 21 − 23 ^(21-23){ }^{21-23} but few data are available from randomized clinical trials, with the exception of 2 in Singapore (ATOM 2 study) and Hong Kong, China (LowConcentration Atropine for Myopia Progression [LAMP] study). 19 , 24 19 , 24 ^(19,24){ }^{19,24} However, the lack of a placebo control group was an acknowledged weakness of the ATOM 2 study. The LAMP study from Hong Kong, China, first provided placebocompared data of low-concentration atropine eyedrops in slowing myopia progression. 24 24 ^(24){ }^{24} Thus, the effect of low concentration of atropine, 0.01 % 0.01 % 0.01%0.01 \%, has not been extensively evaluated through placebo-controlled trial. Therefore, we aimed to evaluate the efficacy and safety of low concentrations of atropine, 0.01 % 0.01 % 0.01%0.01 \%, in this randomized, double-masked, placebocontrolled trial in mainland China.
大多数研究都是为了评估低浓度阿托品的疗效和安全性，通过非随机对照试验，但来自随机临床试验的数据很少，除了新加坡的 2 项（ATOM 2 研究）和中国香港的（低浓度阿托品对近视进展的影响[LAMP]研究）。然而，ATOM 2 研究缺乏安慰剂对照组被认为是一个公认的弱点。来自中国香港的 LAMP 研究首次提供了低浓度阿托品眼药水在减缓近视进展方面的安慰剂对照数据。因此，低浓度阿托品的效果尚未通过安慰剂对照试验进行广泛评估。因此，我们旨在在中国大陆进行这项随机、双盲、安慰剂对照试验，以评估低浓度阿托品的疗效和安全性。

Methods 方法

Study Design 研究设计

This is a randomized, double-masked, placebo-controlled trial aimed to investigate the efficacy and safety of low concentra-
这是一个随机、双盲、安慰剂对照试验，旨在研究低浓度的疗效和安全性

Key Points 关键点

Question Do atropine, 0.01%, eyedrops slow the myopia progression and axial elongation when compared with a placebo group in Chinese children?
阿托品 0.01%眼药水在中国儿童中与安慰剂组相比，是否能减缓近视进展和轴向延长？
Findings In this randomized clinical trial, atropine, 0.01%, eyedrops reduced myopia progression and axial elongation compared with placebo treatment after 1 year.
在这项随机临床试验中，0.01%的阿托品眼药水在 1 年后与安慰剂治疗相比，减少了近视进展和轴向延长。
Meaning While the clinical relevance of the results cannot be determined from this trial, these results support the potential that atropine, 0.01 % 0.01 % 0.01%0.01 \%, eyedrops can slow myopia progression in Chinese children and warrant future studies to determine longer-term results and potential effects on slowing sight-threatening pathologic changes later in life.
虽然无法从这项试验中确定结果的临床相关性，但这些结果支持阿托品 0.01 % 0.01 % 0.01%0.01 \% 眼药水在中国儿童中减缓近视进展的潜力，并值得未来的研究以确定长期结果及其对减缓日后可能威胁视力的病理变化的潜在影响。
tions of atropine, 0.01 % 0.01 % 0.01%0.01 \%, in children with low and moderate myopia from April 2018 to July 2020. Two phases were included in this study. All children were recruited and randomized to receive either atropine, 0.01 % 0.01 % 0.01%0.01 \%, or placebo eyedrops in both eyes once daily at an allocation ratio of 1:1 for 1 year in phase 1. At the beginning of the second year, the atropine, 0.01 % 0.01 % 0.01%0.01 \%, group will be crossed over to the placebo group, and the placebo group will be crossed over to the atropine, 0.01 % 0.01 % 0.01%0.01 \%, group for 1 year in phase 2 . All eyedrops in monodose preparation were prepared by Shenyang Xingqi Pharmaceutical Co Ltd. Informed written consent was obtained from at least 1 parent as well as verbal assent from each child. No compensation or incentives were offered to the children and parents. This clinical trial adhered to the tenets of the Declaration of Helsinki and was approved by the institutional review board of Beijing Tongren Hospital, Capital Medical University. The trial protocol is available in Supplement 1.
在 2018 年 4 月至 2020 年 7 月期间，对低度和中度近视儿童使用阿托品的研究。该研究包括两个阶段。所有儿童均被招募并随机分配接受阿托品、 0.01 % 0.01 % 0.01%0.01 \% 或安慰剂眼药水，每天在双眼中使用一次，分配比例为 1:1，持续 1 年。在第二年的开始，阿托品 0.01 % 0.01 % 0.01%0.01 \% 组将交叉到安慰剂组，安慰剂组将交叉到阿托品 0.01 % 0.01 % 0.01%0.01 \% 组，持续 1 年，作为第二阶段。所有单剂量眼药水均由沈阳星奇药业有限公司制备。至少 1 名家长签署了知情书面同意书，并且每个儿童均口头同意。未向儿童和家长提供任何补偿或奖励。本临床试验遵循《赫尔辛基宣言》的原则，并获得了首都医科大学北京同仁医院伦理委员会的批准。试验方案可在补充材料 1 中获得。

Study Population 研究人群

We recruited the children with myopia who visited Beijing Tongren Hospital, Beijing, China, between April 2018 and July 2018. All participants met the following inclusion criteria: children aged 6 to 12 years with refractive error of spherical equivalent (SE) range of -1.00 D to -6.00 D in both eyes, astigmatism of -1.50 D or less in both eyes, best-corrected distance visual acuity 0.20 logMAR 0.20 logMAR 0.20 logMAR0.20 \operatorname{logMAR} or better in both eyes, and intraocular pressure (IOP) of less than 21 mm Hg . Exclusion criteria were as follows: children with other combined ocular diseases (eg, amblyopia, strabismus, corneal scar, cataract, glaucoma, or ocular tumor); previous or current treatment with atropine, pirenzepine, contact lenses, bifocals, or progressive addition lenses for myopia; and allergy to atropine, cyclopentolate, or excipients.
我们招募了在 2018 年 4 月至 2018 年 7 月期间访问中国北京同仁医院的近视儿童。所有参与者符合以下纳入标准：年龄在 6 至 12 岁之间，双眼球面等效屈光不正（SE）范围为-1.00 D 至-6.00 D，双眼散光不超过-1.50 D，双眼最佳矫正远视力 0.20 logMAR 0.20 logMAR 0.20 logMAR0.20 \operatorname{logMAR} 或更好，眼内压（IOP）低于 21 mm Hg。排除标准如下：有其他合并眼病的儿童（例如，弱视、斜视、角膜瘢痕、白内障、青光眼或眼肿瘤）；曾经或目前使用阿托品、吡仑帕尼、隐形眼镜、双光眼镜或渐进多焦点眼镜治疗近视；以及对阿托品、环戊酮或辅料过敏。

Sample Size 样本大小

Sample size was calculated based on the results from the previous studies. 18 , 19 , 23 18 , 19 , 23 ^(18,19,23){ }^{18,19,23} We assume that atropine, 0.01 % 0.01 % 0.01%0.01 \%, reduces the myopia progression rate by at least -0.36 D with standard deviation of 0.70 D , assuming a power of 90 % 90 % 90%90 \% with a 2 -sided test of 5 % 5 % 5%5 \%. Thus, this study required 80 participants in each group. Considering a dropout rate of 25 % 25 % 25%25 \%, a total of 220 participants would be adequate.
样本量是根据之前研究的结果计算得出的。 18 , 19 , 23 18 , 19 , 23 ^(18,19,23){ }^{18,19,23} 我们假设阿托品， 0.01 % 0.01 % 0.01%0.01 \% ，将近视进展率降低至少 -0.36 D，标准差为 0.70 D，假设功效为 90 % 90 % 90%90 \% ，进行 5 % 5 % 5%5 \% 的双侧检验。因此，本研究需要每组 80 名参与者。考虑到 25 % 25 % 25%25 \% 的流失率，总共需要 220 名参与者。
Randomization and Masking
随机化和盲法
With the schedule generated by SAS program (SAS Institute Inc), a statistician operated the randomization independently. Every eligible 4 children were randomly allocated into the intervention group or control group according to the priority order the children visited the hospital for treatment. The atropine, 0.01 % 0.01 % 0.01%0.01 \%, and placebo eyedrops were packaged in identical bottles, and thus, investigators and participants were not able to identify the contents. The data analysts were also blinded to minimize observational bias.
根据 SAS 程序（SAS Institute Inc）生成的时间表，一名统计学家独立地进行了随机分配。每 4 名符合条件的儿童根据他们就医的优先顺序随机分配到干预组或对照组。阿托品、 0.01 % 0.01 % 0.01%0.01 \% 和安慰剂眼药水被包装在相同的瓶子中，因此研究人员和参与者无法识别内容。数据分析师也被盲化以最小化观察偏差。

Study Procedures 研究程序

All children who participated in this study underwent the same, standardized examination procedure at the baseline, 6-month, and 12 -month visits. Patients were given a calendar to mark out the days when the trial medications were used and, with more than 80 % 80 % 80%80 \% compliance rate, were considered to be included in the results analysis. Children were also provided photochromatic glasses (which darken on exposure to ultraviolet light or sunlight) if they experienced glare or their parents were worried of excessive light exposure or progressive glasses (reading add) if they experienced difficulty with near vision.
所有参与本研究的儿童在基线、6 个月和 12 个月的访视中都进行了相同的标准化检查程序。患者被提供一个日历，以标记试验药物使用的日期，且在合规率超过 80 % 80 % 80%80 \% 的情况下，才被视为纳入结果分析。儿童还被提供光变眼镜（在紫外线或阳光照射下变暗），如果他们感到眩光，或者如果他们的父母担心过度光照，或者提供渐进眼镜（阅读加）如果他们在近距离视力上遇到困难。
Cycloplegic refraction was measured by an autorefractor (HRK7000 A; Huvitz) 3 times consecutively, with average data used for analysis. All 3 readings should be at most 0.25 D apart in both the spherical and cylinder components. During the examination of each patient, 3 drops of cyclopentolate, 1 % 1 % 1%1 \% (Alcon), were administered at a 5-minute interval. Thirty min-
通过自动折射仪（HRK7000 A；Huvitz）连续测量了 3 次调节麻痹屈光度，使用平均数据进行分析。所有 3 个读数在球面和柱面分量上相差最多应为 0.25 D。在对每位患者的检查过程中，每 5 分钟滴入 3 滴环戊烯（Alcon）。三十分钟-
utes after the last drop, if pupillary light reflex was still present or the pupil size was less than 6.0 mm , a fourth drop of 1 % 1 % 1%1 \% cyclopentolate was administered and the examination was repeated 15 minutes later. Axial length (AL) was measured using the Lenstar LS900 (Haag-Streit), with 5 readings taken and averaged. A noncontact tonometer (HNT-7000; Huvitz) was used to measure the intraocular pressure with 3 repeated measurements.
在最后一滴药水后 5 分钟，如果瞳孔光反射仍然存在或瞳孔大小小于 6.0 毫米，则给予第四滴 1 % 1 % 1%1 \% 环戊烯酮，并在 15 分钟后重复检查。使用 Lenstar LS900（Haag-Streit）测量轴长（AL），进行了 5 次读数并取平均值。使用非接触式眼压计（HNT-7000；Huvitz）测量眼内压，进行了 3 次重复测量。
Additionally, a detailed interviewer-administered questionnaire answered by parents was used to collect the information of their children on the age at myopia onset, number of parents with myopia, and time near work and outdoors activities (hours per day) after school hours.,425,26
此外，使用了一份由访谈者管理的详细问卷，由父母填写，以收集他们孩子的近视发病年龄、近视父母的数量以及课后近距离工作和户外活动的时间（每天小时）。

Outcomes 结果

The SE was calculated as the dioptric powers of the sphere and half of the cylinder (sphere + 0.5 × + 0.5 × +0.5 xx+0.5 \times cylinder). Myopia progression defined as the mean change in cycloplegic SE over 1 year. Three levels of myopia progression were defined as less than 0.50 D (mild), between 0.50 D and less than 1.00 D (moderate), and 1.00 D or greater (severe). If the myopia progression was less than 0.50 D over 1 year, children were considered as nonprogressors and otherwise as progressors. The secondary outcomes included AL change over 1 year. Adverse events were recorded based on what patients and parents were asked and examined during the treatment.
SE 的计算为球镜的屈光度和圆柱镜的一半（球镜 + 0.5 × + 0.5 × +0.5 xx+0.5 \times 圆柱镜）。近视进展定义为 1 年内循环麻痹 SE 的平均变化。近视进展分为三个级别：小于 0.50 D（轻度）、介于 0.50 D 和小于 1.00 D 之间（中度）以及 1.00 D 或更大（重度）。如果 1 年内近视进展小于 0.50 D，则儿童被视为非进展者，否则视为进展者。次要结果包括 1 年内 AL 的变化。根据患者和家长在治疗期间被询问和检查的内容记录不良事件。

Statistical Analyses 统计分析

For all analyses, SPSS, version 20.0 (SPSS), was used. For continuous variables, the independent t t tt test and analysis of covariance were used to determine statistical significance between the atropine and control groups. The χ 2 χ 2 chi^(2)\chi^{2} tests were used to compare the categorized data. To explore potential risk factors, including age at baseline, sex, initial spherical equivalent, intraocular pressure, age at myopia onset, parental myopia, time outdoors, and near work, associated with progressors in atropine, 0.01 % 0.01 % 0.01%0.01 \%, group, the multiple log-binomial regression analysis was performed using those factors as the dependent variable. Analyses were only performed on the right eye. A 2 -sided P P PP-value less than .05 was considered statistically significant for the primary outcome.
对于所有分析，使用了 SPSS 20.0 版本（SPSS）。对于连续变量，使用独立 t t tt 检验和协方差分析来确定阿托品组和对照组之间的统计显著性。使用 χ 2 χ 2 chi^(2)\chi^{2} 检验来比较分类数据。为了探索与阿托品 0.01 % 0.01 % 0.01%0.01 \% 组进展者相关的潜在风险因素，包括基线年龄、性别、初始球面等效、眼内压、近视发病年龄、父母近视、户外时间和近距离工作，进行了多重对数二项回归分析，使用这些因素作为因变量。分析仅在右眼进行。对于主要结果，双侧 P P PP 值小于 0.05 被认为具有统计学显著性。

Results 结果

Between April 2018 and July 2019, a total of 268 children were initially assessed in this study; 21 of them did not meet the inclusion criteria, 12 of them met the exclusion criteria, and 15 of them declined to participate in this study, leaving 220 children were enrolled in the study with equal randomization to the atropine, 0.01%, and the placebo-control groups (Figure 1). At baseline, there were no relevant differences identified in demographics, initial SE, initial AL, IOP, age at myopia onset, parental myopia, time outdoors, and near work between 2 groups (Table 1). Twenty-five participants ( 11.4 % 11.4 % 11.4%11.4 \% ) did not complete the first 6 months of the study ( 16 in the atropine, 0.01%, group and 9 in the placebo group; Figure 1). Finally, a total of 76 children (69%) and 83 children (75%) allocated into
在 2018 年 4 月至 2019 年 7 月期间，本研究最初评估了 268 名儿童；其中 21 名未满足纳入标准，12 名符合排除标准，15 名拒绝参与本研究，最终有 220 名儿童被纳入研究，并随机分配到阿托品 0.01%组和安慰剂对照组（图 1）。在基线时，两个组在人口统计学、初始屈光度、初始眼轴、眼内压、近视发病年龄、父母近视、户外活动时间和近距离工作方面没有发现相关差异（表 1）。25 名参与者（ 11.4 % 11.4 % 11.4%11.4 \% ）未能完成研究的前 6 个月（阿托品 0.01%组 16 名，安慰剂组 9 名；图 1）。最终，共有 76 名儿童（69%）和 83 名儿童（75%）被分配到
the atropine, 0.01%, and placebo groups, respectively, returned for the 1-year primary outcome assessment visit (Figure 1). There was no significant difference in initial SE and AL between completed and discontinued patients in the atropine, 0.01 % 0.01 % 0.01%0.01 \%, group as well as placebo group. Baseline characteristics for those children who completed the 1-year fol-low-up are shown in eTable 1 in Supplement 2.
阿托品、0.01%和安慰剂组分别返回进行 1 年主要结果评估访视（图 1）。在阿托品、 0.01 % 0.01 % 0.01%0.01 \% 组以及安慰剂组中，完成和中断患者的初始 SE 和 AL 之间没有显著差异。完成 1 年随访的儿童的基线特征见补充材料 2 中的 eTable 1。
At the 1-year follow-up, the mean (SD) myopia progression values for the atropine, 0.01 % 0.01 % 0.01%0.01 \%, group and the placebo group were -0.49 (0.42) D and -0.76 (0.50) D (mean difference, 0.26 D ; 95% CI, 0.12-0.41 D; P P PP < .001), with relative reduction of 34.2 % 34.2 % 34.2%34.2 \% in myopia progression (Table 2). Nonprogressors had a mean myopia progression of -0.14 (0.23) D compared with -0.83 ( 0.24 ) D for progressors ( P < .001 P < .001 P < .001P<.001 ). The mean 1-year change in spherical equivalent was -0.49 D ( 95 % 95 % 95%95 \% CI, -0.59 to -0.39 D ) for the atropine, 0.01 % 0.01 % 0.01%0.01 \%, group and -0.77 D ( 95 % CI , − 0.86 95 % CI , − 0.86 95%CI,-0.8695 \% \mathrm{CI},-0.86 to -0.67 D ) for the placebo group (analysis of covariance, mean difference, 0.28 D ; 95 % CI 95 % CI 95%CI95 \% \mathrm{CI}, 0.14-0.42 D; P P PP < .001) after adjusting for age at baseline. The mean (SD) axial elongation values for the atropine, 0.01 % 0.01 % 0.01%0.01 \%, group and placebo group were 0.32 (0.19) mm and 0.41 (0.19) mm (mean difference, 0.09 mm ; 95% CI, 0.03-0.15 mm ; P = .004 mm ; P = .004 mm;P=.004\mathrm{mm} ; P=.004 ), with a reduction of 22.0 % 22.0 % 22.0%22.0 \% in axial elongation (Table 2). Nonprogressors had a mean (SD) axial elongation of − 0.18 ( 0.14 ) mm − 0.18 ( 0.14 ) mm -0.18(0.14)mm-0.18(0.14) \mathrm{mm}, compared with -0.45 ( 0.14 ) mm for progressors ( P P PP < .001). The mean 1-year change in axial length was 0.31 mm ( 95 % 95 % 95%95 \% CI, 0.27 − 0.35 mm 0.27 − 0.35 mm 0.27-0.35mm0.27-0.35 \mathrm{~mm} ) for the atropine, 0.01 % 0.01 % 0.01%0.01 \%, group and 0.41 mm ( 95 % CI , 0.37 − 0.45 mm 95 % CI , 0.37 − 0.45 mm 95%CI,0.37-0.45mm95 \% \mathrm{CI}, 0.37-0.45 \mathrm{~mm} ) for the placebo group (analysis of covariance, mean difference, 0.10 mm ; 95% CI, 0.05-0.16 mm; P P PP < .001) after adjusting for age at baseline.
在 1 年随访中，阿托品组和安慰剂组的平均（标准差）近视进展值分别为-0.49（0.42）D 和-0.76（0.50）D（均值差，0.26 D；95%置信区间，0.12-0.41 D； P P PP < .001），近视进展相对减少了 34.2 % 34.2 % 34.2%34.2 \% （表 2）。非进展者的平均近视进展为-0.14（0.23）D，而进展者为-0.83（0.24）D（ P < .001 P < .001 P < .001P<.001 ）。阿托品组的球面等效 1 年平均变化为-0.49 D（ 95 % 95 % 95%95 \% 置信区间，-0.59 到-0.39 D），安慰剂组为-0.77 D（ 95 % CI , − 0.86 95 % CI , − 0.86 95%CI,-0.8695 \% \mathrm{CI},-0.86 到-0.67 D）（协方差分析，均值差，0.28 D； 95 % CI 95 % CI 95%CI95 \% \mathrm{CI} ，0.14-0.42 D； P P PP < .001），调整基线年龄后。阿托品组和安慰剂组的平均（标准差）轴向延长值分别为 0.32（0.19）mm 和 0.41（0.19）mm（均值差，0.09 mm；95%置信区间，0.03-0.15 mm ; P = .004 mm ; P = .004 mm;P=.004\mathrm{mm} ; P=.004 ），轴向延长减少了 22.0 % 22.0 % 22.0%22.0 \% （表 2）。非进展者的平均（标准差）轴向延长为 − 0.18 ( 0.14 ) mm − 0.18 ( 0.14 ) mm -0.18(0.14)mm-0.18(0.14) \mathrm{mm} ，而进展者为-0.45（0.14）mm（ P P PP < .001）。阿托品组的轴长 1 年平均变化为 0.31 mm（ 95 % 95 % 95%95 \% 置信区间， 0.27 − 0.35 mm 0.27 − 0.35 mm 0.27-0.35mm0.27-0.35 \mathrm{~mm} ），安慰剂组为 0。41 毫米 ( 95 % CI , 0.37 − 0.45 mm 95 % CI , 0.37 − 0.45 mm 95%CI,0.37-0.45mm95 \% \mathrm{CI}, 0.37-0.45 \mathrm{~mm} ) 对于安慰剂组（协方差分析，平均差异，0.10 毫米；95% CI，0.05-0.16 毫米； P P PP < .001）在基线年龄调整后。
At 6 months, 81.6 % 81.6 % 81.6%81.6 \% of children progressed by less than 0.5 D in the atropine, 0.01 % 0.01 % 0.01%0.01 \%, group compared with 61.5 % 61.5 % 61.5%61.5 \% in the placebo group, whereas no children progressed by 1.00 D or greater, compared with 3.6% in the placebo group (Figure 2). At 12 months, 48.7 % 48.7 % 48.7%48.7 \% of children progressed by less than 0.50 D and 13.2 % 13.2 % 13.2%13.2 \% at least 1.00 D in the atropine, 0.01 % 0.01 % 0.01%0.01 \%, group, compared with 30.1 % 30.1 % 30.1%30.1 \% and 34.9 % 34.9 % 34.9%34.9 \%, respectively, in the placebo group (Figure 2).
在 6 个月时， 81.6 % 81.6 % 81.6%81.6 \% 的儿童在阿托品组中进展少于 0.5 D，而在安慰剂组中为 61.5 % 61.5 % 61.5%61.5 \% ，而且没有儿童进展达到 1.00 D 或更高，而安慰剂组为 3.6%（图 2）。在 12 个月时， 48.7 % 48.7 % 48.7%48.7 \% 的儿童在阿托品组中进展少于 0.50 D， 13.2 % 13.2 % 13.2%13.2 \% 至少为 1.00 D，而在安慰剂组中分别为 30.1 % 30.1 % 30.1%30.1 \% 和 34.9 % 34.9 % 34.9%34.9 \% （图 2）。
eTable 2 in Supplement 2 presents a comparison of demographics and other characteristics between nonprogressors and progressors in the atropine, 0.01 % 0.01 % 0.01%0.01 \%, group. In multiple logbinomial regression analyses, among the atropine, 0.01 % 0.01 % 0.01%0.01 \%, group, a higher risk of being a progressor was associated with initial SE (relative risk [RR], 1.324; 95% CI, 1.048-1.620; P = .004 P = .004 P=.004P=.004; eTable 3 in Supplement 2). The adjusted analysis showed that the risk of progressive myopia increased by 32.4 % 32.4 % 32.4%32.4 \% for every 1.0 D less initial SE. However, among the placebo group, no association was found for risk factors with progressors in multiple log-binomial regression analyses (eTable 4 in Supplement 2).
补充材料 2 中的表 2 展示了在阿托品 0.01 % 0.01 % 0.01%0.01 \% 组中，非进展者与进展者之间的人口统计学和其他特征的比较。在多重对数二项回归分析中，在阿托品 0.01 % 0.01 % 0.01%0.01 \% 组中，初始 SE 与成为进展者的较高风险相关（相对风险[RR]，1.324；95% CI，1.048-1.620； P = .004 P = .004 P=.004P=.004 ；补充材料 2 中的表 3）。调整后的分析显示，随着初始 SE 每减少 1.0 D，进展性近视的风险增加了 32.4 % 32.4 % 32.4%32.4 \% 。然而，在安慰剂组中，在多重对数二项回归分析中未发现与进展者的风险因素相关的关联（补充材料 2 中的表 4）。
No serious adverse events associated with atropine were reported. Five children ( 4.5 % 4.5 % 4.5%4.5 \% ) reported photophobia in the atropine, 0.01 % 0.01 % 0.01%0.01 \%, group compared with 1 child ( 0.9 % 0.9 % 0.9%0.9 \% ) in the control group. Allergic reactions were uncommon, with 4 children experiencing allergic conjunctivitis; 1 of them was in control group. None of the children in either group reported near-blurred vision.
与阿托品相关的严重不良事件没有报告。五名儿童（ 4.5 % 4.5 % 4.5%4.5 \% ）在阿托品组（ 0.01 % 0.01 % 0.01%0.01 \% ）中报告了畏光，而对照组中有 1 名儿童（ 0.9 % 0.9 % 0.9%0.9 \% ）报告了畏光。过敏反应不常见，有 4 名儿童出现过敏性结膜炎；其中 1 名在对照组。两个组中的儿童都没有报告近距离模糊视力。
Table 1. Demographics and Baseline Characteristics of Participants
表 1. 参与者的人口统计学和基线特征
Variables 变量 Group, mean (SD) 组，均值（标准差）
Atropine  阿托品 ( n = 110 ) ( n = 110 ) (n=110)(n=110)
Placebo
( n = 110 n = 110 n=110\mathrm{n}=110 )
Placebo ( n=110 )| Placebo | | :--- | | ( $\mathrm{n}=110$ ) |
Age, y, No. (%)
年龄，岁，数量（%）
6 to <7 6 到 <7 9 (8.2) 4 (3.6)
7 to <8 7 到 <8 11 (10.0) 7 (6.4)
8 to <9 8 到<9 28 (25.5) 20 (18.2)
9 to <10 9 到 <10 22 (20.0) 27 (24.5)
10 to <11 10 到<11 20 (18.2) 23 (20.9)
11 to <12 11 到<12 20 (18.2) 29 (26.4)
Mean (SD) 均值 (标准差) 9.44 (1.80) 9.84 (1.53)
Male/female, No. 男/女，编号。 56/54 61/49
Initial SE, D 初始 SE, D
6 to < y -2.14 (1.25) -2.95 (2.43)
7 to < 8 y < 8 y < 8y<8 y 7 到 < 8 y < 8 y < 8y<8 y -1.89 (0.98) -2.30 (1.69)
8 to <9 y
8 到<9 y		 -2.20(1.03) -2.70 (1.22)
9 to <10y 9 到<10 岁 -2.53 (1.44) -2.23 (1.29)
10 to <11 y
10 到<11 岁		 -2.36 (1.09) -2.77 (1.44)
11 to <12 y
11 到<12 岁		 -3.04 (1.25) -2.91 (1.60)
Mean (SD) 均值 (标准差) -2.52 (1.33) -2.64(1.46)
Initial AL, mm 初始 AL，毫米
6 to <7y 6 到<7 岁 24.03 (0.82) 24.70 (0.50)
7 to < 8 y 8 y 8y8 y 24.00 (0.57) 24.37 (1.24)
8 to <9 y
8 到<9 y		 24.29 (0.57) 24.51 (0.73)
9 to <10y 9 到<10 岁 24.45 (0.59) 24.58 (0.94)
10 to < 11 y
10 到<11 岁		 24.69 (0.53) 24.86 (0.98)
11 to <12 y
11 到<12 岁		 24.99 (0.82) 24.86 (1.11)
Mean (SD) 均值 (标准差) 24.50 (0.76) 24.69 (0.97)
IOP, mm Hg 15.84 (2.89) 15.84 (2.76)
Age at myopia onset, D
近视发病年龄，D		 7.76 (1.70) 8.07 (1.68)
Parental myopia, No. (%)
父母近视，数量（%）
None 无 5 (4.5) 7 (6.4)
1 42 (38.2) 34 (30.9)
Both 两者 63 (57.3) 69 (62.7)
Time outdoors, h/d 户外时间，h/d 1.40 (0.59) 1.55 (0.57)
Near work, h/d 近距离工作，h/d 3.21 (1.42) 3.37 (1.44)
Table 1. Demographics and Baseline Characteristics of Participants Variables Group, mean (SD) Atropine (n=110) "Placebo ( n=110 )" Age, y, No. (%) 6 to <7 9 (8.2) 4 (3.6) 7 to <8 11 (10.0) 7 (6.4) 8 to <9 28 (25.5) 20 (18.2) 9 to <10 22 (20.0) 27 (24.5) 10 to <11 20 (18.2) 23 (20.9) 11 to <12 20 (18.2) 29 (26.4) Mean (SD) 9.44 (1.80) 9.84 (1.53) Male/female, No. 56/54 61/49 Initial SE, D 6 to < y -2.14 (1.25) -2.95 (2.43) 7 to < 8y -1.89 (0.98) -2.30 (1.69) 8 to <9 y -2.20(1.03) -2.70 (1.22) 9 to <10y -2.53 (1.44) -2.23 (1.29) 10 to <11 y -2.36 (1.09) -2.77 (1.44) 11 to <12 y -3.04 (1.25) -2.91 (1.60) Mean (SD) -2.52 (1.33) -2.64(1.46) Initial AL, mm 6 to <7y 24.03 (0.82) 24.70 (0.50) 7 to < 8y 24.00 (0.57) 24.37 (1.24) 8 to <9 y 24.29 (0.57) 24.51 (0.73) 9 to <10y 24.45 (0.59) 24.58 (0.94) 10 to < 11 y 24.69 (0.53) 24.86 (0.98) 11 to <12 y 24.99 (0.82) 24.86 (1.11) Mean (SD) 24.50 (0.76) 24.69 (0.97) IOP, mm Hg 15.84 (2.89) 15.84 (2.76) Age at myopia onset, D 7.76 (1.70) 8.07 (1.68) Parental myopia, No. (%) None 5 (4.5) 7 (6.4) 1 42 (38.2) 34 (30.9) Both 63 (57.3) 69 (62.7) Time outdoors, h/d 1.40 (0.59) 1.55 (0.57) Near work, h/d 3.21 (1.42) 3.37 (1.44)| Table 1. Demographics and Baseline Characteristics of Participants | | | | :---: | :---: | :---: | | Variables | Group, mean (SD) | | | | Atropine $(n=110)$ | Placebo <br> ( $\mathrm{n}=110$ ) | | Age, y, No. (%) | | | | 6 to <7 | 9 (8.2) | 4 (3.6) | | 7 to <8 | 11 (10.0) | 7 (6.4) | | 8 to <9 | 28 (25.5) | 20 (18.2) | | 9 to <10 | 22 (20.0) | 27 (24.5) | | 10 to <11 | 20 (18.2) | 23 (20.9) | | 11 to <12 | 20 (18.2) | 29 (26.4) | | Mean (SD) | 9.44 (1.80) | 9.84 (1.53) | | Male/female, No. | 56/54 | 61/49 | | Initial SE, D | | | | 6 to < y | -2.14 (1.25) | -2.95 (2.43) | | 7 to $<8 y$ | -1.89 (0.98) | -2.30 (1.69) | | 8 to <9 y | -2.20(1.03) | -2.70 (1.22) | | 9 to <10y | -2.53 (1.44) | -2.23 (1.29) | | 10 to <11 y | -2.36 (1.09) | -2.77 (1.44) | | 11 to <12 y | -3.04 (1.25) | -2.91 (1.60) | | Mean (SD) | -2.52 (1.33) | -2.64(1.46) | | Initial AL, mm | | | | 6 to <7y | 24.03 (0.82) | 24.70 (0.50) | | 7 to < $8 y$ | 24.00 (0.57) | 24.37 (1.24) | | 8 to <9 y | 24.29 (0.57) | 24.51 (0.73) | | 9 to <10y | 24.45 (0.59) | 24.58 (0.94) | | 10 to < 11 y | 24.69 (0.53) | 24.86 (0.98) | | 11 to <12 y | 24.99 (0.82) | 24.86 (1.11) | | Mean (SD) | 24.50 (0.76) | 24.69 (0.97) | | IOP, mm Hg | 15.84 (2.89) | 15.84 (2.76) | | Age at myopia onset, D | 7.76 (1.70) | 8.07 (1.68) | | Parental myopia, No. (%) | | | | None | 5 (4.5) | 7 (6.4) | | 1 | 42 (38.2) | 34 (30.9) | | Both | 63 (57.3) | 69 (62.7) | | Time outdoors, h/d | 1.40 (0.59) | 1.55 (0.57) | | Near work, h/d | 3.21 (1.42) | 3.37 (1.44) |
Abbreviations: AL, axial length; IOP, intraocular pressure; SE, spherical equivalent.
缩写：AL，轴长；IOP，眼内压；SE，球面等效。

Discussion 讨论

In this study, we found that a once-nightly dose of atropine, 0.01 % 0.01 % 0.01%0.01 \%, eyedrops resulted in reduction of myopia progression by a mean (SD) of 0.26 (0.07) D (34.2% reduction) and axial elongation by 0.09 (0.03) mm (22.0% reduction) compared with placebo treatment. To our knowledge, this study is the first randomized, double-masked, placebo-controlled trial to show the efficacy of atropine, 0.01 % 0.01 % 0.01%0.01 \%, eyedrops in mainland China. However, the clinical relevance of these results cannot be determined from this trial because there was a loss to follow-up of approximately 30 % 30 % 30%30 \%, the follow-up is limited to 1 year, and it is not known whether these findings translate to a slowing of pathologic myopia.
在这项研究中，我们发现一次性夜间使用阿托品 0.01 % 0.01 % 0.01%0.01 \% 眼药水可以使近视进展平均减少 0.26（0.07）D（减少 34.2%），轴向延长减少 0.09（0.03）mm（减少 22.0%），与安慰剂治疗相比。据我们所知，这项研究是中国大陆首个随机、双盲、安慰剂对照试验，显示了阿托品 0.01 % 0.01 % 0.01%0.01 \% 眼药水的疗效。然而，由于大约 30 % 30 % 30%30 \% 的随访丢失、随访时间仅限于 1 年，并且尚不清楚这些发现是否能转化为病理性近视的减缓，因此无法从这项试验中确定这些结果的临床相关性。
Variables 变量 Group 组 Difference 差异 95% CI P P PP value
Atropine  阿托品 ( n = 76 ) ( n = 76 ) (n=76)(\mathrm{n}=76) Placebo  安慰剂 ( n = 83 ) ( n = 83 ) (n=83)(n=83)
SE, mean (SD), D
SE，均值（标准差），D
Change at 6 mo
6 个月时更改		 -0.21 (0.32) -0.36 (0.38) 0.16 (0.06) 0.05-0.27 . 005
Change at 12 mo
12 个月时更改		 -0.49(0.42) − 0.76 ( 0.50 ) − 0.76 ( 0.50 ) -0.76(0.50)-0.76(0.50) 0.26 (0.07) 0.12-0.41 <. 001
AL, mean (SD), mm
AL，均值（标准差），毫米
Change at 6 mo
6 个月时更改		 0.16 (0.12) 0.21 (0.11) 0.05 (0.02) 0.02-0.09 . 005
Change at 12 mo
12 个月时更改		 0.32 (0.19) 0.41 (0.19) 0.09 (0.03) 0.03-0.15 . 004
Variables Group Difference 95% CI P value Atropine (n=76) Placebo (n=83) SE, mean (SD), D Change at 6 mo -0.21 (0.32) -0.36 (0.38) 0.16 (0.06) 0.05-0.27 . 005 Change at 12 mo -0.49(0.42) -0.76(0.50) 0.26 (0.07) 0.12-0.41 <. 001 AL, mean (SD), mm Change at 6 mo 0.16 (0.12) 0.21 (0.11) 0.05 (0.02) 0.02-0.09 . 005 Change at 12 mo 0.32 (0.19) 0.41 (0.19) 0.09 (0.03) 0.03-0.15 . 004| Variables | Group | | Difference | 95% CI | $P$ value | | :---: | :---: | :---: | :---: | :---: | :---: | | | Atropine $(\mathrm{n}=76)$ | Placebo $(n=83)$ | | | | | SE, mean (SD), D | | | | | | | Change at 6 mo | -0.21 (0.32) | -0.36 (0.38) | 0.16 (0.06) | 0.05-0.27 | . 005 | | Change at 12 mo | -0.49(0.42) | $-0.76(0.50)$ | 0.26 (0.07) | 0.12-0.41 | <. 001 | | AL, mean (SD), mm | | | | | | | Change at 6 mo | 0.16 (0.12) | 0.21 (0.11) | 0.05 (0.02) | 0.02-0.09 | . 005 | | Change at 12 mo | 0.32 (0.19) | 0.41 (0.19) | 0.09 (0.03) | 0.03-0.15 | . 004 |
Abbreviations: AL, axial length; SE , spherical equivalent.
缩写：AL，轴长；SE，球面等效。
Figure 2. Distribution of Mild, Moderate, and Severe Myopia Progression in atropine, 0.01%, and Placebo Groups at 6 and 12 Months
图 2. 阿托品 0.01%组和安慰剂组在 6 个月和 12 个月时轻度、中度和重度近视进展的分布
Myopia progression from baseline if less than 0.50 D (mild), between 0.50 D and less than 1.00 D (moderate), and greater than 1.00 D (severe).
如果基线近视进展小于 0.50 D（轻度），在 0.50 D 和小于 1.00 D 之间（中度），以及大于 1.00 D（重度）。
A summary of the randomized clinical trials and casecontrol studies for atropine, 0.01%, is presented in Table 3. In a retrospective case-control study 21 21 ^(21){ }^{21} of 52 treated and 50 control European children, the atropine, 0.01 % 0.01 % 0.01%0.01 \%, group had a slower myopia progression of a mean (SD) of 0.54 ( 0.26 ) D / y 0.54 ( 0.26 ) D / y 0.54(0.26)D//y0.54(0.26) \mathrm{D} / \mathrm{y} than that of the control group at -1.09 (0.64) D/y. In 2019, the LAMP study 24 24 ^(24){ }^{24} first provided placebo-compared evidence of lowconcentration atropine eyedrops in myopia control. After 1 year, the mean (SD) myopic progression was -0.27 (0.61) D, -0.46 (0.45) D, -0.59 (0.61) D, and -0.81 (0.53) D, in the atropine, 0.05 % , 0.025 % 0.05 % , 0.025 % 0.05%,0.025%0.05 \%, 0.025 \%, and 0.01 % 0.01 % 0.01%0.01 \%, groups and placebo groups, respectively. In our study, the mean (SD) difference between the atropine, 0.01 % 0.01 % 0.01%0.01 \%, and placebo groups in myopia progression was 0.26 (0.07) D (34.2% reduction) at 1 year. It should be noted that the relative reduction of 34.2 % 34.2 % 34.2%34.2 \% in myopia progression in our study was smaller than the study conducted in the Europe. 21 21 ^(21){ }^{21} We hypothesize that this may owing to the fact that less pigmented eyes, on average, are more sensitive to cycloplegic agents for those of populations of European origin. In addition, the educational systems between Eastern and Western cultures, on average, may be different. 27 , 28 27 , 28 ^(27,28){ }^{27,28} Eastern students, on average, may be more likely to spend more time on their studies, potentially making them more susceptible to myopia progression. 26 , 29 , 30 26 , 29 , 30 ^(26,29,30){ }^{26,29,30} Therefore, it may be more difficult to slow the rate of myopia progression for Eastern students.
表 3 中展示了阿托品 0.01%的随机临床试验和病例对照研究的总结。在一项回顾性病例对照研究 21 21 ^(21){ }^{21} 中，52 名接受治疗的欧洲儿童和 50 名对照组儿童，阿托品 0.01 % 0.01 % 0.01%0.01 \% 组的近视进展速度较对照组的平均（标准差）为 0.54 ( 0.26 ) D / y 0.54 ( 0.26 ) D / y 0.54(0.26)D//y0.54(0.26) \mathrm{D} / \mathrm{y} ，对照组为-1.09（0.64）D/y。2019 年，LAMP 研究 24 24 ^(24){ }^{24} 首次提供了低浓度阿托品眼药水在近视控制中的安慰剂对照证据。经过 1 年，阿托品 0.05 % , 0.025 % 0.05 % , 0.025 % 0.05%,0.025%0.05 \%, 0.025 \% 组、 0.01 % 0.01 % 0.01%0.01 \% 组和安慰剂组的平均（标准差）近视进展分别为-0.27（0.61）D，-0.46（0.45）D，-0.59（0.61）D 和-0.81（0.53）D。在我们的研究中，阿托品 0.01 % 0.01 % 0.01%0.01 \% 组与安慰剂组在近视进展中的平均（标准差）差异为 0.26（0.07）D（减少 34.2%）在 1 年时。需要注意的是，我们研究中近视进展的相对减少 34.2 % 34.2 % 34.2%34.2 \% 小于在欧洲进行的研究。 21 21 ^(21){ }^{21} 我们假设这可能是因为平均而言，色素较少的眼睛对来自欧洲血统人群的调节麻痹剂更为敏感。 此外，东部和西部文化之间的教育系统平均可能存在差异。东部学生平均可能更倾向于花更多时间在学习上，这可能使他们更容易出现近视加深。因此，对于东部学生来说，减缓近视加深的速度可能更为困难。
The LAMP study 24 24 ^(24){ }^{24} found 43.8 % 43.8 % 43.8%43.8 \% of patients had myopic progression by less than 0.50 D in the atropine, 0.01 % 0.01 % 0.01%0.01 \%, group over 1 year, which is in agreement with the LAMP study, found 48.7% in our study. Thus, it should be noted that more than 50 % 50 % 50%50 \% of children progressed by at least 0.5 D after 1 year of atropine, 0.01 % 0.01 % 0.01%0.01 \%, treatment. Previous studies have demonstrated a dose-dependent effect of atropine on reducing myopia progression. 19 , 24 19 , 24 ^(19,24){ }^{19,24} It would may be a reasonable strategy for those children with myopia to be treated initially with atropine, 0.01 % 0.01 % 0.01%0.01 \%; if myopia progression was still faster, then change to a higher concentration. 31 31 ^(31){ }^{31} In a retrospective, casecontrol study, Lee et al 32 32 ^(32){ }^{32} found that only 16.7 % 16.7 % 16.7%16.7 \% of patients treated with atropine, 0.05 % 0.05 % 0.05%0.05 \%, eyedrops progressed greater than 0.50 D in 1 year.
LAMP 研究 24 24 ^(24){ }^{24} 发现 43.8 % 43.8 % 43.8%43.8 \% 的患者在阿托品 0.01 % 0.01 % 0.01%0.01 \% 组中，1 年内近视进展小于 0.50 D，这与 LAMP 研究一致，我们的研究发现 48.7%。因此，应注意超过 50 % 50 % 50%50 \% 的儿童在 1 年阿托品 0.01 % 0.01 % 0.01%0.01 \% 治疗后至少进展了 0.5 D。先前的研究表明，阿托品对减少近视进展具有剂量依赖性效果。 19 , 24 19 , 24 ^(19,24){ }^{19,24} 对于那些近视的儿童，最初用阿托品治疗可能是一个合理的策略 0.01 % 0.01 % 0.01%0.01 \% ；如果近视进展仍然较快，则更换为更高浓度。 31 31 ^(31){ }^{31} 在一项回顾性病例对照研究中，Lee 等人 32 32 ^(32){ }^{32} 发现仅有 16.7 % 16.7 % 16.7%16.7 \% 的患者在 1 年内使用阿托品 0.05 % 0.05 % 0.05%0.05 \% 眼药水治疗后进展超过 0.50 D。
A previous study 33 33 ^(33){ }^{33} has shown that the risk of progressive myopia was associated with younger age at baseline and higher initial SE among the 182 children treated with atropine, 1 % 1 % 1%1 \%, for 1 year. As found in this study, our study observed that the risk of progressive myopia was associated with younger age at baseline in the unadjusted regression analysis. This may be predominantly explained by the fact that younger children experience more myopia progression, 34 34 ^(34){ }^{34} leading to more progressors in younger age. Thus, it should be noted that younger children with myopia who received atropine, 0.01 % 0.01 % 0.01%0.01 \%, for treatment should be more aware of whether they need to switch to higher-concentration atropine treatment.
一项先前的研究 33 33 ^(33){ }^{33} 表明，182 名接受阿托品治疗的儿童中，进行性近视的风险与基线年龄较小和初始球镜度数（SE）较高相关， 1 % 1 % 1%1 \% ，为期 1 年。正如本研究所发现的，我们的研究观察到，在未调整的回归分析中，进行性近视的风险与基线年龄较小相关。这可能主要是因为年轻儿童经历更多的近视进展， 34 34 ^(34){ }^{34} ，导致年轻年龄段的进展者更多。因此，应注意接受阿托品治疗的年轻近视儿童， 0.01 % 0.01 % 0.01%0.01 \% ，应该更加关注他们是否需要更换为高浓度阿托品治疗。
Fewer studies have reported the efficacy of the atropine eyedrops in slowing axial elongation, although it is important to reflect the treatment effect. To date, the LAMP study 24 24 ^(24){ }^{24} has provided the only direct comparison of changes in AL between the atropine, 0.01 % 0.01 % 0.01%0.01 \%, and placebo. This study found that a mean (SD) axial length change was 0.36 ( 0.29 ) mm 0.36 ( 0.29 ) mm 0.36(0.29)mm0.36(0.29) \mathrm{mm} and 0.41 (0.22) mm in the atropine, 0.01 % 0.01 % 0.01%0.01 \%, and placebo groups over 1 year, with reduction of only 12 % 12 % 12%12 \% in axial elongation. Our study showed that mean (SD) axial elongation values for the atropine, 0.01 % 0.01 % 0.01%0.01 \%, group and placebo group were 0.32 (0.19) mm and 0.41 (0.19) mm at 1 year, with reduction of 22.0 % 22.0 % 22.0%22.0 \% in axial elongation. Although the mean progression of axial length was lower in the atropine, 0.01 % 0.01 % 0.01%0.01 \%, group compared with the control group in our study, the reduction of axial elongation by 0.09 mm at 1 year is not of great clinical significance.
尽管重要的是反映治疗效果，但关于阿托品眼药水在减缓轴向延长方面的有效性，报道的研究较少。迄今为止，LAMP 研究 24 24 ^(24){ }^{24} 提供了阿托品、 0.01 % 0.01 % 0.01%0.01 \% 和安慰剂之间轴长变化的唯一直接比较。该研究发现，阿托品、 0.01 % 0.01 % 0.01%0.01 \% 和安慰剂组在 1 年内的平均（标准差）轴长变化分别为 0.36 ( 0.29 ) mm 0.36 ( 0.29 ) mm 0.36(0.29)mm0.36(0.29) \mathrm{mm} 和 0.41（0.22）毫米，仅减少了 12 % 12 % 12%12 \% 的轴向延长。我们的研究显示，阿托品、 0.01 % 0.01 % 0.01%0.01 \% 组和安慰剂组在 1 年时的平均（标准差）轴向延长值分别为 0.32（0.19）毫米和 0.41（0.19）毫米，轴向延长减少了 22.0 % 22.0 % 22.0%22.0 \% 。尽管在我们的研究中，阿托品、 0.01 % 0.01 % 0.01%0.01 \% 组的轴长平均进展低于对照组，但在 1 年内减少 0.09 毫米的轴向延长在临床上并没有很大的意义。
Overall, atropine, 0.01 % 0.01 % 0.01%0.01 \%, was generally well tolerated and no serious adverse effects were observed. 19 , 24 , 35 19 , 24 , 35 ^(19,24,35){ }^{19,24,35} Similar to our experience, Yam et al 24 24 ^(24){ }^{24} observed 2 participants (2.1%) had photophobia and 7 participants (6.4%) had allergic conjunctivitis in the atropine, 0.01%, group. The LAMP study reported a small
总体而言，阿托品， 0.01 % 0.01 % 0.01%0.01 \% ，通常耐受良好，未观察到严重不良反应。 19 , 24 , 35 19 , 24 , 35 ^(19,24,35){ }^{19,24,35} 与我们的经验类似，Yam 等人 24 24 ^(24){ }^{24} 观察到在阿托品 0.01%组中，有 2 名参与者（2.1%）出现了畏光，7 名参与者（6.4%）出现了过敏性结膜炎。LAMP 研究报告了一个小
Source 源 Design 设计 Duration 持续时间 Myopia range, D 近视范围，D Treatments 治疗方法 Mean (SD) 均值 (标准差)
 年龄范围，岁
Age
range, y
Age range, y| Age | | :--- | | range, y |
 Size 大小 Duration 持续时间 Baseline age, y 基线年龄，岁 Average myopia, D 中度近视，D
 近视进展，D
Myopia
progression, D
Myopia progression, D| Myopia | | :--- | | progression, D |
 Axial elongation, mm 轴向延伸，毫米

本研究，2020 年，中国大陆
This study,
2020,
Mainland
China
This study, 2020, Mainland China| This study, | | :--- | | 2020, | | Mainland | | China |
 RCT 6-12 220 1 -0.5 to -6 -0.5 到 -6 A, 0.01% 9.44 (1.80) − 2.52 ( 1.33 ) − 2.52 ( 1.33 ) [-2.52],[(1.33)]\begin{aligned} & \hline-2.52 \\ & (1.33) \end{aligned} -0.49 (0.42) 0.32 (0.19)
Placebo 安慰剂 9.84 (1.53) − 2.64 ( 1.46 ) − 2.64 ( 1.46 ) {:[-2.64],[(1.46)]:}\begin{aligned} & -2.64 \\ & (1.46) \end{aligned} -0.76 (0.50) 0.41 (0.19)
Chia et al, 19 2012 , Singapore  Chia et al,  19 2012 ,  Singapore  {:[" Chia et al, "^(19)],[2012","],[" Singapore "]:}\begin{aligned} & \text { Chia et al, }{ }^{19} \\ & 2012, \\ & \text { Singapore } \end{aligned} RCT 6-12 400 2 -2 to -6 -2 到-6 A, 0.5% 9.7 (1.5) -4.3 (1.8) -0.30(0.60) 0.27 (0.25)
A, 0.1% 9.7 (1.6) -4.5 (1.4) -0.38 (0.60) 0.28 (0.28)
A, 0.01% 9.5 (1.5) -4.5 (1.5) -0.49 (0.63) 0.41 (0.32)
Clark et al, 23 2015, United States  Clark et al,  23  2015,   United   States  {:[" Clark et al, "^(23)],[" 2015, "],[" United "],[" States "]:}\begin{aligned} & \text { Clark et al, }{ }^{23} \\ & \text { 2015, } \\ & \text { United } \\ & \text { States } \end{aligned} Retrospective 回顾展 6-15 60 1 − 0.25 to − 8.00 − 0.25  to  − 8.00 {:[-0.25" to "],[-8.00]:}\begin{aligned} & -0.25 \text { to } \\ & -8.00 \end{aligned} A, 0.01% 10.2 (2.2) -2.0(1.6) -0.1 (0.6) NA
Placebo 安慰剂 10.2 (2.2) -2.0(1.5) -0.6(0.4) NA
Yam et al, 24 2018 , Hong Kong, China  Yam et al,  24 2018 ,  Hong Kong,   China  {:[" Yam et al, "^(24)],[2018","],[" Hong Kong, "],[" China "]:}\begin{aligned} & \text { Yam et al, }{ }^{24} \\ & 2018, \\ & \text { Hong Kong, } \\ & \text { China } \end{aligned} RCT 4-12 438 1
 至少 -1.0
At least
-1.0
At least -1.0| At least | | :--- | | -1.0 |
 A, 0.05% 8.45 (1.81) − 3.98 ( 1.69 ) − 3.98 ( 1.69 ) {:[-3.98],[(1.69)]:}\begin{gathered} -3.98 \\ (1.69) \end{gathered} -0.27 (0.61) 0.20 (0.25)
A, 0.025% 8.54 (1.71) − 3.71 ( 1.85 ) − 3.71 ( 1.85 ) {:[-3.71],[(1.85)]:}\begin{gathered} -3.71 \\ (1.85) \end{gathered} -0.46(0.45) 0.29 (0.20)
A, 0.01% 8.23 (1.83) − 3.77 ( 1.85 ) − 3.77 ( 1.85 ) {:[-3.77],[(1.85)]:}\begin{aligned} & -3.77 \\ & (1.85) \end{aligned} -0.59 (0.61) 0.36 (0.29)
Placebo 安慰剂 8.42 (1.72) − 3.85 ( 1.95 ) − 3.85 ( 1.95 ) {:[-3.85],[(1.95)]:}\begin{aligned} & -3.85 \\ & (1.95) \end{aligned} -0.81 (0.53) 0.41 (0.22)

萨基等， 21 21 ^(21){ }^{21} 2019，意大利
Sacchi
et al, 21 21 ^(21){ }^{21}
2019,
Italy
Sacchi et al, ^(21) 2019, Italy| Sacchi | | :--- | | et al, ${ }^{21}$ | | 2019, | | Italy |
 Retrospective 回顾展 5-16 102 1 NA A, 0.01% 9.7 (2.3) − 3.00 ( 2.23 ) − 3.00 ( 2.23 ) {:[-3.00],[(2.23)]:}\begin{aligned} & -3.00 \\ & (2.23) \end{aligned} -0.54 (0.61) NA
Placebo 安慰剂 12.1 (2.9) − 2.63 ( 2.68 ) − 2.63 ( 2.68 ) {:[-2.63],[(2.68)]:}\begin{aligned} & -2.63 \\ & (2.68) \end{aligned} -1.09 (0.64) NA
Larkin et al, 22 22 ^(22){ }^{22} 2019, United States
Larkin et al, 22 22 ^(22){ }^{22} 2019, 美国		 Retrospective 回顾展 6-15 198 2 − 0.25 to − 8.00 − 0.25  to  − 8.00 {:[-0.25" to "],[-8.00]:}\begin{aligned} & -0.25 \text { to } \\ & -8.00 \end{aligned} A, 0.01% 9.3 (2.1) -3.1 (1.9) -0.2(0.8) NA
Placebo 安慰剂 9.2 (2.1) -2.8 (1.6) -0.6(0.4) NA
Source Design Duration Myopia range, D Treatments Mean (SD) "Age range, y" Size Duration Baseline age, y Average myopia, D "Myopia progression, D" Axial elongation, mm "This study, 2020, Mainland China" RCT 6-12 220 1 -0.5 to -6 A, 0.01% 9.44 (1.80) "-2.52 (1.33)" -0.49 (0.42) 0.32 (0.19) Placebo 9.84 (1.53) "-2.64 (1.46)" -0.76 (0.50) 0.41 (0.19) " Chia et al, ^(19) 2012, Singapore " RCT 6-12 400 2 -2 to -6 A, 0.5% 9.7 (1.5) -4.3 (1.8) -0.30(0.60) 0.27 (0.25) A, 0.1% 9.7 (1.6) -4.5 (1.4) -0.38 (0.60) 0.28 (0.28) A, 0.01% 9.5 (1.5) -4.5 (1.5) -0.49 (0.63) 0.41 (0.32) " Clark et al, ^(23) 2015, United States " Retrospective 6-15 60 1 "-0.25 to -8.00" A, 0.01% 10.2 (2.2) -2.0(1.6) -0.1 (0.6) NA Placebo 10.2 (2.2) -2.0(1.5) -0.6(0.4) NA " Yam et al, ^(24) 2018, Hong Kong, China " RCT 4-12 438 1 "At least -1.0" A, 0.05% 8.45 (1.81) "-3.98 (1.69)" -0.27 (0.61) 0.20 (0.25) A, 0.025% 8.54 (1.71) "-3.71 (1.85)" -0.46(0.45) 0.29 (0.20) A, 0.01% 8.23 (1.83) "-3.77 (1.85)" -0.59 (0.61) 0.36 (0.29) Placebo 8.42 (1.72) "-3.85 (1.95)" -0.81 (0.53) 0.41 (0.22) "Sacchi et al, ^(21) 2019, Italy" Retrospective 5-16 102 1 NA A, 0.01% 9.7 (2.3) "-3.00 (2.23)" -0.54 (0.61) NA Placebo 12.1 (2.9) "-2.63 (2.68)" -1.09 (0.64) NA Larkin et al, ^(22) 2019, United States Retrospective 6-15 198 2 "-0.25 to -8.00" A, 0.01% 9.3 (2.1) -3.1 (1.9) -0.2(0.8) NA Placebo 9.2 (2.1) -2.8 (1.6) -0.6(0.4) NA| Source | Design | Duration | | | Myopia range, D | Treatments | Mean (SD) | | | | | :---: | :---: | :---: | :---: | :---: | :---: | :---: | :---: | :---: | :---: | :---: | | | | Age <br> range, y | Size | Duration | | | Baseline age, y | Average myopia, D | Myopia <br> progression, D | Axial elongation, mm | | This study, <br> 2020, <br> Mainland <br> China | RCT | 6-12 | 220 | 1 | -0.5 to -6 | A, 0.01% | 9.44 (1.80) | $\begin{aligned} & \hline-2.52 \\ & (1.33) \end{aligned}$ | -0.49 (0.42) | 0.32 (0.19) | | | | | | | | Placebo | 9.84 (1.53) | $\begin{aligned} & -2.64 \\ & (1.46) \end{aligned}$ | -0.76 (0.50) | 0.41 (0.19) | | $\begin{aligned} & \text { Chia et al, }{ }^{19} \\ & 2012, \\ & \text { Singapore } \end{aligned}$ | RCT | 6-12 | 400 | 2 | -2 to -6 | A, 0.5% | 9.7 (1.5) | -4.3 (1.8) | -0.30(0.60) | 0.27 (0.25) | | | | | | | | A, 0.1% | 9.7 (1.6) | -4.5 (1.4) | -0.38 (0.60) | 0.28 (0.28) | | | | | | | | A, 0.01% | 9.5 (1.5) | -4.5 (1.5) | -0.49 (0.63) | 0.41 (0.32) | | $\begin{aligned} & \text { Clark et al, }{ }^{23} \\ & \text { 2015, } \\ & \text { United } \\ & \text { States } \end{aligned}$ | Retrospective | 6-15 | 60 | 1 | $\begin{aligned} & -0.25 \text { to } \\ & -8.00 \end{aligned}$ | A, 0.01% | 10.2 (2.2) | -2.0(1.6) | -0.1 (0.6) | NA | | | | | | | | Placebo | 10.2 (2.2) | -2.0(1.5) | -0.6(0.4) | NA | | $\begin{aligned} & \text { Yam et al, }{ }^{24} \\ & 2018, \\ & \text { Hong Kong, } \\ & \text { China } \end{aligned}$ | RCT | 4-12 | 438 | 1 | At least <br> -1.0 | A, 0.05% | 8.45 (1.81) | $\begin{gathered} -3.98 \\ (1.69) \end{gathered}$ | -0.27 (0.61) | 0.20 (0.25) | | | | | | | | A, 0.025% | 8.54 (1.71) | $\begin{gathered} -3.71 \\ (1.85) \end{gathered}$ | -0.46(0.45) | 0.29 (0.20) | | | | | | | | A, 0.01% | 8.23 (1.83) | $\begin{aligned} & -3.77 \\ & (1.85) \end{aligned}$ | -0.59 (0.61) | 0.36 (0.29) | | | | | | | | Placebo | 8.42 (1.72) | $\begin{aligned} & -3.85 \\ & (1.95) \end{aligned}$ | -0.81 (0.53) | 0.41 (0.22) | | Sacchi <br> et al, ${ }^{21}$ <br> 2019, <br> Italy | Retrospective | 5-16 | 102 | 1 | NA | A, 0.01% | 9.7 (2.3) | $\begin{aligned} & -3.00 \\ & (2.23) \end{aligned}$ | -0.54 (0.61) | NA | | | | | | | | Placebo | 12.1 (2.9) | $\begin{aligned} & -2.63 \\ & (2.68) \end{aligned}$ | -1.09 (0.64) | NA | | Larkin et al, ${ }^{22}$ 2019, United States | Retrospective | 6-15 | 198 | 2 | $\begin{aligned} & -0.25 \text { to } \\ & -8.00 \end{aligned}$ | A, 0.01% | 9.3 (2.1) | -3.1 (1.9) | -0.2(0.8) | NA | | | | | | | | Placebo | 9.2 (2.1) | -2.8 (1.6) | -0.6(0.4) | NA |
Abbreviations: A, atropine; NA, not applicable; RCT, randomized clinical trial.
缩写：A，阿托品；NA，不适用；RCT，随机临床试验。
reduction in accommodation by 0.26 D , a dilation of pupils by 0.5 mm in atropine, 0.01 % 0.01 % 0.01%0.01 \%, group, which is not a major clinical issue. 24 24 ^(24){ }^{24} Cooper et al 36 36 ^(36){ }^{36} reported atropine, 0.02 % 0.02 % 0.02%0.02 \%, as the threshold dose without producing significant clinical symptoms from accommodation paresis or pupillary dilation by comparing different doses of topical atropine in adolescents.
在阿托品作用下，调节能力减少 0.26 D，瞳孔扩张 0.5 mm， 0.01 % 0.01 % 0.01%0.01 \% ，组，这不是一个主要的临床问题。 24 24 ^(24){ }^{24} Cooper 等人 36 36 ^(36){ }^{36} 报告了阿托品， 0.02 % 0.02 % 0.02%0.02 \% ，作为不引起调节麻痹或瞳孔扩张的显著临床症状的阈值剂量，通过比较青少年不同剂量的局部阿托品。

Strengths and Limitations
优势与局限性

The strengths of this study included its randomized, doublemasked, and placebo-controlled trial design, the standardized measurement of refractive errors using cycloplegia, and the inclusion of outcome by performing axial length. However, there are several shortcomings in our study. First, we could not avoid the potential for unmasking of the participants attributable to the atropine-induced photophobia and cycloplegia as well as other atropine eyedrops studies. In addition, this study only evaluated the efficacy of lowconcentration atropine eyedrops at the level of 0.01%. Thus, further studies should be carried out to compare the efficacy of other lower doses of atropine in mainland China. Other limitations include the potential bias introduced by loss to fol-
本研究的优点包括其随机、双盲和安慰剂对照的试验设计，使用睫状麻痹标准化测量屈光不正，以及通过测量轴长来评估结果。然而，我们的研究也存在几个缺点。首先，我们无法避免由于阿托品引起的光敏感和睫状麻痹以及其他阿托品眼药水研究而导致的参与者揭盲的潜在可能。此外，本研究仅评估了 0.01%低浓度阿托品眼药水的疗效。因此，应进一步开展研究，以比较中国大陆其他低剂量阿托品的疗效。其他限制包括因失访引入的潜在偏倚。
low-up of approximately 70 % 70 % 70%70 \% in each group, follow-up only through 1 year, limited information on the clinical relevance of the magnitude of the greater slowing of myopia in the atropine group, and inability to determine whether the atropine effect has relevance for reducing the development or progression of pathologic myopia.
每组大约 70 % 70 % 70%70 \% 的低增量，随访仅持续 1 年，关于阿托品组近视减缓幅度的临床相关性信息有限，无法确定阿托品的效果是否与减少病理性近视的发展或进展相关。

Conclusions 结论

Our study discovered that atropine, 0.01 % 0.01 % 0.01%0.01 \%, can slow the progression of myopia and axial length in children with low and moderate myopia, compared with placebo treatment. A oncenightly dose of atropine, 0.01 % 0.01 % 0.01%0.01 \%, eyedrops was well tolerated without serious adverse events. While the clinical relevance of the results cannot be determined from this trial, these 1-year results, limited by approximately 70% follow-up, suggest that atropine, 0.01 % 0.01 % 0.01%0.01 \%, eyedrops can slow myopia progression and axial elongation in children and warrant future studies to determine longer-term results and potential effects on slowing sight-threatening pathologic changes later in life.
我们的研究发现，与安慰剂治疗相比，阿托品（ 0.01 % 0.01 % 0.01%0.01 \% ）可以减缓低度和中度近视儿童的近视进展和轴长。每晚一次的阿托品（ 0.01 % 0.01 % 0.01%0.01 \% ）眼药水耐受良好，没有严重的不良事件。虽然无法从这项试验中确定结果的临床相关性，但这些为期一年的结果（约 70%的随访限制）表明，阿托品（ 0.01 % 0.01 % 0.01%0.01 \% ）眼药水可以减缓儿童的近视进展和轴向延长，并值得未来的研究以确定长期结果及其对减缓未来可能威胁视力的病理变化的潜在影响。

ARTICLE INFORMATION 文章信息

Accepted for Publication: August 14, 2020.
接受出版：2020 年 8 月 14 日。
Published Online: October 1, 2020. doi:10.1001/jamaophthalmol.2020.3820
在线发表：2020 年 10 月 1 日。doi:10.1001/jamaophthalmol.2020.3820
Author Contributions: Drs Wei and Wang had full access to all the data in the study and take responsibility for the integrity of the data and the
作者贡献：魏博士和王博士对研究中的所有数据拥有完全访问权，并对数据的完整性负责
accuracy of the data analysis. Drs Wei and Li are co-first authors.
数据分析的准确性。魏博士和李博士是共同第一作者。
Concept and design: Wei, Li, Liang, Wang.
概念和设计：魏，李，梁，王。
Acquisition, analysis, or interpretation of data All authors.
数据的获取、分析或解释 所有作者。
Drafting of the manuscript: Wei, Li, Zhang
手稿的起草：魏，李，张
Critical revision of the manuscript for important intellectual content: Wei, Li, An, Du, Liang, Sun,
对手稿进行重要知识内容的关键修订：魏，李，安，杜，梁，孙，
Tian, Wang.
Statistical analysis: Wei, Du.
统计分析：魏，杜。
Obtained funding: Wang. 获得资金：王。
Administrative, technical, or material support: Wei, Li, Liang, Sun
行政、技术或物质支持：魏、李、梁、孙
Supervision: Li, Liang, Wang.
监督：李，梁，王。
Conflict of Interest Disclosures: None reported
利益冲突披露：无报告
Funding/Support: Supported by grants from the Integration, Translation and Development on Ophthalmic Technology (Jingyiyan 2016-5), the Capital Health Research and Development of Special (2016-4-2056), the Ministry of Science and Technology, Beijing Nova Program (Z121107002512055), the National Natural Science Foundation of China (81300797), Sanming Project of Medicine in Shenzhen (SZSM2O1512045) and the Beijing University-CMU, Advanced Innovation Centre for Big Data-Based Precision Medicine, Ophthalmic Subcenter (BHME2O18-2019)
资金/支持：由眼科技术的整合、转化和发展（京医研 2016-5）、首都卫生研究与发展专项（2016-4-2056）、科技部、北京新星计划（Z121107002512055）、国家自然科学基金（81300797）、深圳市医学三明项目（SZSM2O1512045）以及北京大学-卡内基梅隆大学大数据精准医学先进创新中心眼科分中心（BHME2O18-2019）资助
Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
资助者/赞助者的角色：资金来源在研究的设计和实施、数据的收集、管理、分析和解释、手稿的准备、审阅或批准以及提交手稿以供出版的决定中没有任何角色。
Data Sharing Statement: See Supplement 3.
数据共享声明：见补充材料 3。
Additional Contributions: We thank Kai Cao, MD, Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, for his assistance in data analysis.
额外贡献：我们感谢北京同仁医院、首都医科大学北京眼科研究所的曹凯医生在数据分析方面的帮助。

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  1. JAMA Ophthalmol. 2020;138(11):1178-1184. doi:10.1001/jamaophthalmol.2020.3820 Published online October 1, 2020.
    JAMA 眼科学. 2020;138(11):1178-1184. doi:10.1001/jamaophthalmol.2020.3820 线上发表日期：2020 年 10 月 1 日。