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中华眼科医学杂志(电子版)

中华眼科医学杂志(电子版) ›› 2019, Vol. 09 ›› Issue (04) : 212 -217. doi: 10.3877/cma.j.issn.2095-2007.2019.04.004

论著

低浓度阿托品控制近视眼进展适宜浓度与剂型的临床研究
孙芸芸1, 李仕明1, 康梦田1, 白大勇2, 彭晓霞3, 王宁利1,†()   
  1. 1. 100730　首都医科大学附属北京同仁医院　北京同仁眼科中心　北京市眼科研究所　北京市眼科学与视觉科学重点实验室
    2. 北京儿童医院眼科中心
    3. 北京儿童医院临床流行病与循证医学中心
  • 收稿日期:2019-06-20 出版日期:2019-08-28
  • 通信作者: 王宁利
  • 基金资助:
    国家973重点基础研究发展计划项目(2011CB504601); 国家自然科学基金重大国际合作项目(81120108007); 国家自然科学基金项目(81300797); 北京市科技新星项目(Z121107002512055); 首都卫生发展专项基金(京医研2016-5)

Appropriate atropine dose and formulation without clinical signs or symptoms

Yunyun Sun1, Shiming Li1, Mengtian Kang1, Dayong Bai2, Xiaoxia Peng3, Ningli Wang1,†()   

  1. 1. Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Institute of Ophthalmology, Beijing Ophthalmology & Visual Science Key Lab., Beijing 100730, China
    2. Eye Center, Beijing Children'sHospital, Beijing 100045, China
    3. Clinical Epidemiology and Evidence-based Medicine Center, Beijing Children's Hospital, Beijing 100045, China
  • Received:2019-06-20 Published:2019-08-28
  • Corresponding author: Ningli Wang
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引用本文：

孙芸芸, 李仕明, 康梦田, 白大勇, 彭晓霞, 王宁利. 低浓度阿托品控制近视眼进展适宜浓度与剂型的临床研究[J]. 中华眼科医学杂志(电子版), 2019, 09(04): 212-217.

Yunyun Sun, Shiming Li, Mengtian Kang, Dayong Bai, Xiaoxia Peng, Ningli Wang. Appropriate atropine dose and formulation without clinical signs or symptoms[J]. Chinese Journal of Ophthalmologic Medicine(Electronic Edition), 2019, 09(04): 212-217.

目的

探索阿托品用于控制近视眼进展的适宜浓度和剂型。

方法

本研究为随机对照试验。2017年2月在北京同仁医院招募了受试者10名(20只眼)，双眼的等效球镜度数在-0.5 D至-5.0 D间，虹膜均为棕色。其中，男性2名、女性8名，年龄24~26岁，平均年龄(24.8±0.79)岁。依次给予受试者0.005%、0.01%、0.025%及0.05%的低浓度阿托品滴眼，应用滴眼液与凝胶的眼别随机，双侧剂型不同。检查近视力、调节幅度及瞳孔大小，并通过问卷记录受试者的主观视觉症状。采用三因素重复测量方差分析检验实验结果。

结果

0.005%、0.01%、0.025%及0.05%浓度的阿托品用药(包括滴眼液和凝胶)，均引起了一定程度的瞳孔散大、调节幅度降低，且随着浓度升高程度增大。经三因素重复测量方差分析，0.005%、0.01%及0.025%的阿托品用药，对瞳孔大小、调节幅度及近视力影响的差异均无统计学意义(F＝1.70，4.38，0.92；P>0.05)、(F＝0.27，3.28，0.82；P>0.05)及(F＝0.14，0.29，0.57；P>0.05)。凝胶对瞳孔大小的影响大于滴眼液，差异有统计学意义(F＝7.51，P<0.05)。0.05%的阿托品用药后产生毒性反应，受试者的主观不适评分明显升高。0.005%、0.01%及0.025%的阿托品用药均无毒性反应，主观不适评分虽升高但可耐受。

结论

0.025%阿托品用药可能是控制近视眼发展的适宜浓度；滴眼液与凝胶两种剂型的副作用均可耐受。

关键词: 近视眼, 阿托品, 视力, 调节幅度, 瞳孔大小
Objective

The aim of this study was to explore the appropriate concentration and better formulation of atropinethat can be prescribed for controlling children myopia progression without significantly clinical visual symptoms, pupillary dilation and accommodative paralysis.

Methods

This was a randomized controlled trial with ten subjects (20 eyes) of spherical equivalent from -0.5 D to -5.0 D included. Subjects with brown iris were recruited from Beijing Tongren Hospital, in February 2017. Two of them are men and the average age is (24.8±0.79), ranging from 24 to 26 years. Atropine of 0.005%, 0.01%, 0.025% and 0.05% were administered to each subject successively. One eye was randomly given atropine eye drops with the contralateral eye gel. Ocular examinations included near visual acuity, accommodative amplitude and pupil size. Questionnaires were used to record subjects' visual symptoms. Multiple-factor repetitive measurement and analysis was used to compare the effects of different dosages and formulations on accommodative amplitude, pupil size and near visual acuity.

Results

Our results suggested that at all dosages of atropine eye drop and gel, there was certain degree of pupillary dilationand reduction in accommodative amplitudeand the effects became larger with higher dosages. Meanwhile, there was no significant difference between the dosages of 0.005%, 0.01% and 0.025% in accommodative amplitude (F=0.27, 3.28, 0.82; P>0.05), near visual acuity (F=0.14, 0.29, 0.57; P>0.05) and pupil size (F=1.70, 4.38, 0.92; P>0.05), with only the effect on pupil size larger for atropine eye gel than atropine eye drops (F=7.51, P<0.05). Subjects' complaints disappear with clinically acceptable findings for dosage of 0.005%, 0.01% and 0.025%, while 0.05% atropine presents the highest scores and toxic effects.

Conclusions

Atropine 0.025% might be the appropriate concentration to control myopia progression without significantly clinical symptoms both subjectively and objectively. What′s more, the side-effects of both formulationsare acceptable without significant differences between them.

Key words: Myopia, Atropine, Visual acuity, Accommodative amplitude, Pupil size
图1 0.005%、0.01%、0.025%和0.05%阿托品滴眼液或凝胶点眼后患者瞳孔、残余调节力、近视力及主观不适评分变化图　图A显示各时间点的瞳孔直径变化；图B显示各时间点的残余调节变化；图C显示各时间点的近视力变化；图D显示受试者各项主观不适评分的平均值(图中竖线表示标准差)
表1 不同浓度的阿托品用药(包括滴眼液和凝胶)对患者瞳孔直径影响的情况
剂型与浓度 眼数 时间
基线 30 min 60 min 90 min 120 min 24 h
阿托品滴眼液              
0.005% 10 5.25±0.79 5.55±0.84 6.41±0.83 6.67±0.86 6.77±0.76 6.05±0.77
0.01% 10 5.34±0.83 6.20±0.79 6.70±0.77 7.00±0.53 6.90±0.57 6.18±0.69
0.025% 10 5.49±0.78 6.81±0.78 7.22±0.70 7.36±0.65 7.35±0.62 6.79±0.80
0.05% 10 6.39±0.79 7.10±0.62 6.39±0.79 7.40±0.55 7.54±0.50 6.99±0.71
阿托品凝胶              
0.005% 10 5.44±0.96 6.03±0.64 6.89±0.66 7.07±0.63 7.16±0.61 6.47±0.62
0.01% 10 5.65±0.71 6.77±0.72 7.24±0.52 7.39±0.45 7.51±0.48 6.97±0.72
0.025% 10 5.97±0.87 7.07±0.63 7.34±0.47 7.47±0.49 7.42±0.45 7.26±0.65
0.05% 10 6.80±0.67 7.34±0.45 7.54±0.39 7.56±0.43 7.57±0.43 7.38±0.44
表2 不同浓度的阿托品用药(包括滴眼液和凝胶)对患者残余调节影响的情况
剂型与浓度 眼数 时间
基线 30 min 60 min 90 min 120 min 24 h
阿托品滴眼液              
0.005% 10 1.40±0.34 1.46±0.64 1.42±0.40 1.26±0.59 1.45±0.41 1.44±0.52
0.01% 10 1.44±0.58 1.44±0.44 1.60±0.35 1.51±0.33 1.52±0.60 1.39±0.45
0.025% 10 1.42±0.30 1.27±0.70 1.36±0.57 1.30±0.47 1.40±0.37 1.27±0.44
0.05% 10 1.34±0.44 1.11±0.43 1.01±0.53 0.90±0.66 0.94±0.58 1.00±0.72
阿托品凝胶              
0.005% 10 1.44±0.39 1.41±0.56 1.21±0.47 1.33±0.50 1.26±0.45 1.19±0.39
0.01% 10 1.26±0.40 1.21±0.44 1.14±0.43 1.02±0.64 1.19±0.42 1.04±0.42
0.025% 10 1.29±0.78 1.16±0.75 1.06±0.59 1.09±0.60 1.09±0.57 1.06±0.66
0.05% 10 1.09±0.62 0.71±0.69 0.60±0.62 0.54±0.54 0.75±0.44 0.80±0.62
表3 不同浓度的阿托品用药(包括滴眼液和凝胶)对患者近视力影响的情况
剂型与浓度 眼数 时间
基线 30 min 60 min 90 min 120 min 24 h
阿托品滴眼液              
0.005% 10 -0.01±0.05 -0.05±0.05 -0.04±0.05 -0.03±0.05 -0.03±0.04 -0.08±0.05
0.01% 10 -0.05±0.04 -0.04±0.04 -0.03±0.04 -0.04±0.04 -0.05±0.05 -0.03±0.01
0.025% 10 -0.04±0.05 -0.09±0.06 -0.08±0.05 -0.06±0.06 -0.07±0.05 -0.03±0.08
0.05% 10 -0.05±0.08 -0.01±0.14 0.04±0.16 0.03±0.14 0.01±0.17 -0.01±0.12
阿托品凝胶              
0.005% 10 -0.02±0.05 -0.04±0.05 -0.03±0.06 -0.04±0.05 -0.01±0.05 -0.07±0.07
0.01% 10 -0.06±0.04 -0.03±0.07 0.00±0.04 -0.03±0.06 -0.05±0.08 -0.02±0.05
0.025% 10 -0.06±0.05 -0.06±0.06 -0.07±0.06 -0.04±0.05 -0.05±0.05 -0.02±0.07
0.05% 10 -0.05±0.05 0.05±0.14 0.06±0.15 0.10±0.15 0.09±0.14 0.09±0.12
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