Elementary school comprehensive intervention and myopia development: the Wenzhou Epidemiology of Refraction Error Study

INTRODUCTION

Myopia is a global health problem and nearly 50% of the global population has been estimated to be affected by 2050

. The increasing prevalence and severity of myopia in school-age children during the last decades has become a major health problem in East Asia

. This increase is too rapid to be explained by genetic changes, and implies the involvement of environmental factors

. Thus, by modifying environmental exposure it is potentially possible to prevent or mitigate myopia onset and/or progression in children. Myopia is one of the six categories of disease prevention for schools stipulated by the 1992 Students’ Common Disease Control Programme of China

. This program includes establishing recommendations for schoolchildren myopia control such as an eye exercise system, increased outdoor activities, the use of standardized classroom desks and chairs, and specific lighting requirements.

Many randomized controlled trials (RCTs) and epidemiological studies have reported that myopia is significantly associated with environmental factors, such as time outdoors, inadequate lighting when reading or writing, and time spent on hand-held devices and near work

. Results for reading posture, Chinese eye exercises, and time spent using computers have been inconsistent

. Only a few countries such as the Singapore have practiced health care education and screening of ocular diseases in children, with improved control of myopia progression

.

In the Wenzhou Epidemiology of Refraction Error (WERE)study, school-based comprehensive intervention was offered to children, teachers, and parents with a 2.5y follow-up. The study aimed to evaluate the effects of comprehensive intervention on the prevention of myopia in elementary school children.

用于预防家禽球虫病。用法与用量：混饮每升水，鸡0.17～0.34 g。规格：100 g∶1 g，休药期：肉鸡5日。批准文号：兽药字（2016）190466209，生产日期20180910，有效期至20200909。生产企业：佛山市正典生物技术有限公司。

SUBJECTS AND METHODS

Ethics Committee of the Eye Hospital of Wenzhou Medical University approved this study. The study obtained permission from the parents and teachers from school. The research clung to the tenets of the Declaration of Helsinki. The nature of the study and details regarding the eye examination and questionnaire were explained to the parents and children, and informed written consent was obtained from at least one parent.

The study was a prospective, interventional school-based research in which grades 1-3 children were selected from the WERE study and followed for 2.5y(September 2012 to March 2015; Figure 1).

There was a significant difference in the myopic shift in the two groups. The overall mean myopia progression during the 2.5y follow-up was-0.49±1.04 D in the intervention group and -0.65±1.08 D in the control group (

=0.004; Table 2).

IOL Master (Carl Zeiss Meditec AG, Jena, Germany) was used to measure AL. The measurements of AL were considered valid if individual measurements varied by no more than 0.02 mm. Because of difficulties in getting the IOL master on a regular basis and introducing it into the examination plan,measurement was only taken once per year. Children with bestcorrected visual acuity worse than 20/25 at baseline were excluded.

The number of students in the one campus was approximately equal to the sum of other two. The campus with the most students was served as intervention group, whereas the other two campuses served as control group. The interventions were provided every semester to the intervention group; none was provided to the control group.

Intervention methods included education intervention and behaviour intervention. First, students, their parents and teachers received ocular health-related knowledge education,which included a powerpoint presentation, 3-D model eyes,eyeglasses, and other displays. Different ways to prevent myopia, such as correct near work related behaviours, increase outdoor activities, use standardized classroom desks and chairs, and use specific lighting were taught or adopted. Theme class meetings about ocular health were provided to every class in the intervention school at the beginning of every semester(which was approximately every 6mo). The intervention started at the beginning of October 2012. Parents and teachers were also educated on ocular health at the first semester. In addition, a handbook of ocular health prepared by the research team was issued to the children and their parents. Second,children were cultivated to develop correct near-work related behaviours. Behavioural intervention was implemented during their classes. The researchers corrected their reading posture and near-work distance. Teachers also encouraged students to go outside during class breaks.

通过对直接粉碎、经减压干燥法、液氮冻干法、冻干法处理的枸杞子颗粒，粉碎后测定特性量值。实验结果表明，经3种预处理方法得到的枸杞子样品，其水分测定结果均低于直接粉碎的枸杞子样品；而其他检测项目，3种处理方法得到的样品与直接粉碎的枸杞子样品基本相同，理化性质均符合《中国药典》2015年版要求，可以作为对照药材标准品使用。但基于成本考虑，减压干燥法最经济实惠，采用冻干法或液氮加冻干法的运行成本基本相似，均较高。因此，在实际工作中，推荐使用减压干燥法最佳。

“秦晨蕊，你不要担心没有新鲜的瓜果蔬菜吃，你妈不能种了，我还能种给你们吃。”父亲花白的头发在阳光下格外显眼。

The participants underwent eye examinations given by 4 trained ophthalmic nurses, two experienced senior optometrists and two ophthalmic graduate students a week after theme class meetings about ocular health every semester.Visual acuity and noncycloplegic refraction were assessed each semester (6 times total), axial length (AL) was assessed annually for 2y (3 times). The autorefractor measurements were performed without cycloplegia by skilled optometrists.Each eye was measured at least three times by an autorefractor(Topcon RM8900, Topcon Co., Tokyo, Japan). Three reliable measurements were then be averaged.

世界范围内资本账户开放的浪潮大致经历了80年代各国争相放开，90年代发展中国家陆续发生货币危机从而产生质疑，再到目前注重时序性和渐进性政策三个阶段。历史经验表明，资本项目开放的收益多体现在发达国家，而较少见诸发展中国家，而一些经济、金融欠发达的中小发展中国家，往往因为缺少资本管制的屏障保护而成为国际投机资本攻击的牺牲品。因此，如何充分享受资本项目开放的收益成为政策面临的重大挑战。前国际货币基金组织总裁Camdessus提出，亚洲金融危机的根源在于既定的宏观经济环境和制度背景下，资本项目开放措施与经济金融等改革的衔接出现了问题[1]。

The questionnaire was distributed to each class unit. Before children answered the questionnaire, researchers explained each question and instructed them how to answer it.

In total, 1579 students in grades 1-3 from these 3 campuses were eligible. Students with ocular inflammation, trauma,dysgnosia, and uncooperation (unable or unwilling to participate) behavior were excluded. At baseline, 1524 of the 1579 sampled and registered students were examined, and 1388 (87.9%) completed all the eye examinations during the 2.5y follow-up.

As expected, the percent of close reading distance (<30 cm) in the intervention group was less than in the control group (73.4%

76.2%,

<0.001) after comprehensive intervention (Table 4). Time spent in near work during the 2.5y follow-up decreased during the first 1.5y in the intervention group by -0.25 h/d and -0.14 h/d in the control group (

=0.020). But by 2.5y the difference was no longer significant. The intervention group spent slightly more time outdoors than the control group at baseline (1.81 h/d

1.67 h/d;

=0.014). But the two groups showed a similar small increase over 2.5y (difference in increase,

=0.196).

RESULTS

During the study period, 1388(87.9%) students were followed for 2.5y. There were 651 students in the intervention group (46.9%) and 737 (53.1%) in the control group; 45.2% in the intervention and 46.9% in the control groups were girls. The mean age was 7.3±0.9y in the intervention group and 7.2±0.9y in the control group. There were no significant differences between the intervention group and the control group in the prevalence of myopia, mean SE,and AL at baseline (Table 1).

1.2.2 AFC测定 选择经阴道超声检测AFC，使用西门子公司的SSD3500型超声诊断仪，配有3～5 MHz阴道探头。使探头的扫描面向前，在阴道穹窿部获得卵泡最大切面的信息，使用探头全方位整体性的扫描卵巢，取同一平面上的两条互相垂直的最大径线，对卵泡边缘进行测量，计算在左右卵巢中直径介于2和10 mm之间的总卵泡数，数据纳入AFC计数。测量误差低于5%。

根据受力求得颗粒位置，由各颗粒的新位置决定相邻颗粒是否接触或脱离，再由接触模型公式分别求出相互接触颗粒的接触力Fi和力矩Mi，返归上式迭代，直至最后达到稳定流动为止。

At baseline, there were no significant differences in two groups in near work-related behaviors, the time spent on near work in the two groups was similar (

=0.210), whereas outdoor activity was slightly different (intervention group: 1.81±1.04 h/d, control group:1.68±1.04 h/d (

=0.014).

The subjects of our study were from three branch campuses of one school from Lucheng district in Wenzhou.These three branch campuses of one school had similar campus cultures, quality of education and socioeconomic status. They were in the same urban area and located in three adjacent districts less than two kilometers apart.

In the nonmyopic children at baseline, the mean increase in myopia over the 2.5y was also smaller in the intervention group(-0.37±0.89 D) than in the control group [-0.51±0.93 D; difference of 0.14 D (27.5%),

=0.009]. The 0.14 D difference indicates a 27.5% lower myopic progression rate in the intervention group(Table 3). About 70% of the relative progression reduction occurred in the last 6mo (Table 2).

Among the myopes at baseline, the overall mean myopia progression during the 2.5y follow-up was -1.13±1.49 D in the intervention group and -1.55±1.46 D in the control group [a difference of 0.42 D (27.1%),

=0.048; Table 3].

该模型的复相关系数R为0.9842，判定系数R2为0.9687，经调整后的判定系数R2为0.9683，F=2221.46，F0.05(5,364)=2.23878，F﹥F0.05，显著水平为0.05，预测精度可达97.25%。

The mean overall elongation of AL during the 2y follow-up in the intervention group (0.56±0.32 mm)was significantly less than in the control group (0.61±0.38 mm,

=0.009; Table 2). The difference in AL elongation was 0.06 mm in nonmyopic and in myopic at baseline children,but this difference was statistically significant only among the children who were nonmyopic at baseline. It did not reach significance in those who were myopic at baseline because the myopic at baseline group was smaller sample and had a slightly larger variance (Table 3).

Myopia was defined as spherical equivalent(SE=spherical error+0.5×cylinder error) ≤-1.0 diopters (D).

-tests and Chi-square tests were used to compare the covariate distributions of the intervention and control groups in the descriptive analysis of baseline characteristics. Comparisons of refractive error and AL at the 2.5y follow-up in the two groups were tested by

-test. The near work activity and outdoor activity data were from the questionnaire survey conducted on the 1388 students. All

-values were based on 2-sided tests(

<0.05).

③后续检查。后续检查一般由水库管理人员或专业技术人员进行。根据详细检查提出的意见以及震损水库险情特点及其发展情况，定期进行巡视检查与监测，包括临时增设的监测设施，观测与记录大坝损伤的特征、位置和程度以及情况变化的速率。相关内容也应同时观测，如库水、尾水水位，天气状况，涌泉或渗漏等，以了解险情发展，判别是否产生新的险情，检查评估应急处置效果等。每次余震后应加强检查，以评估余震对大坝的影响。

DISCUSSION

In the present longitudinal study of Wenzhou school children, the prevalence of myopia was 6.7%, 14.7%, and 21.6% in 1

, 2

and 3

grade students at baseline. It is difficult to compare these refractive prevalences to those in other locations, because of criteria and procedural differences. For example, the prevalence of myopia was 0.2%, 13.3%, and 38.8% in 1

, 2

, and 3

grade students in Guangzhou

. The slightly lower prevalence of myopia in the 1

and 2

grade student in Guangzhou may be due to their use of cycloplegia. But then the sudden increase in myopia from grade 3 to grade 5 with little increase in higher grades is unusual and difficult to explain. Lyu

reported that the prevalence of myopia was 7.4%, 18.0%, and 28.5%in 6, 7, and 8 year old children in Chaoyang District, Beijing.Despite the use of cycloplegia, their children had a slightly higher prevalence and a slightly higher progression rate of myopia than in the Wenzhou sample. In contrast, much lower prevalences of myopia in elementary school children have been shown in many settings where educational pressures are not as great as in China

.

The present study showed a statistically significant slower progression of myopia for the intervention group in the overall sample and for the nonmyopic baseline sample. The myopic baseline group showed the same reduced progression (27%) but the smaller sample was barely significance. The 30-month myopia progression rate for the overall control sample was only-0.65 D which leaves little room for reduction (only 0.16 D)of intervention sample. Our control myopes progressed to-1.55 D and the 27% progression reduction was based on a-0.42 D reduction, which is clinically meaningful. In fact,this reduction is equal to that shown by several more invasive optical and pharmacological therapies. These other procedures induced about a 25% reduction in the first year but had almost no effect after that. Our health educational intervention started more slowly and had its strongest effect in the last half year of the program.

There is a coarse quantitative consistency between the SE refraction and AL measurements. The differences in AL progression between the intervention and control groups were small but statistically significant during the 2y. The mean 2.0-year myopia shift and elongation of AL were both smaller in the intervention group than in the control group. This is important because some studies have been questioned when they do not show a change in AL progression even though myopia progression slows

.

李大头拍拍他屁股旁的石块让我坐下，好像那长方形石块是一只凳子。我便在他身边坐下。当一个年近六十，满脸褶痕的老人被大头拦下来，要带他到他的工地时，我才知道，我与李大头说是巧遇，却也有着必然：他原来是特地在这里揽人。像我这样的接近流浪汉又不是流浪汉的人，都在他的视界里。

We suggest that long-term comprehensive intervention is useful. The intervention significantly slowed the rate of myopia progression and identified some effect on reading habits and little effect on outdoor activity and reading time.

Both the intervention and control groups were asked to complete a self-administered questionnaire after theme class meetings about ocular health every semester.The questionnaire included the students’ demographic characteristics, near work related behaviors (such as reading/writing distance, continuous near work time, frequency of perform eye exercises and so on), near work time and outdoor activities time. Near work time included time spent doing homework, extra-curriculum reading, video games, and computer use. Questions about time spent in outdoor activities concerned both leisure and sports. The average daily time spent on near work and outdoor activities was calculated using the formula: [(hours spent during a weekday) ×5+ (hours spent on a weekend day) ×2]/7.

Near work related behaviors were changed after the comprehensive Intervention. Our intervention group reported better habits included longer reading distance (≥30 cm) and perform eye exercises everyday than the control group at the end of study, even they were worse than at baseline. Near work related behaviors have been found to be associated with refractive errors in children. Another large school-based sample study among Chinese children (6-10y) reported that various near work related behaviors, included maintaining an inappropriate near work distance, selecting inadequate lighting environments and continuing to perform near work without a rest period, were risk factors for myopic progression

.French

reported a similar result, that the development of myopia during early childhood was affected by lifestyle and reading habits. A longer-term intervention process may be needed to help children cultivate and keep measurable healthy behavior changes that can substantially slow myopic refractive error progression.

Both the nonmyopic and myopic children at baseline showed less myopia progression by 0.14 D (0.06 D/y) for the nonmyopic children and 0.42 D (0.17 D/y) for the myopic children, than their control group over 2.5y, a 27.5% and a 27.1% reduction. So ocular comprehensive intervention was shown to be as effective as many optical or drug based procedures in other studies when children were in their lower grades and not myopic

. AL elongation in those who were not myopic at baseline was slower in intervention group than control group but not in those who were myopic at baseline.

Low dose atropine and OrthoK appear to be most effective in reducing myopia

. But one method requires parents to instill eye drops each morning and the other requires wearing contact lenses each night. These requirements may be onerous to many families. The comprehensive intervention is not as effective but is far less invasive and unpleasant than these procedures, and authors do not yet even show the best way to present this procedure. Some less onerous optical methods have been shown to be promising, and in combination with the comprehensive intervention might have a stronger effect in reducing myopia.

The comprehensive intervention appeared to have no effect on time spent performing near work including homework,reading, playing videogames, and using a computer for study.In addition, they did not increase outdoor time significantly.But as we know, these students had heavier academic loads with grade increase. Students must perform more near work due to their increased homework and extra-curricular activities in the higher grades. Previous studies have demonstrated that children of East Asian ethnicity reported spending more time in near work than children of European ethnicity

.Comprehensive intervention could not have an impact on time spent on near work, when the children were compelled to perform a very heavy academic load.

Interestingly, the intervention group reported slightly more time spent on outdoor activities than the control group at baseline and at the end of study. However, the amount of time spent outdoors for either group is less than usually needed to reduce myopia, and no one has ever shown that a mean difference of only 6 to 9min could produce a measurable change in myopia progression. Many studies have suggested that outdoor activity reduces myopia onset and progression

. A cluster randomized trial of children in grade 1 reported an additional 40-minute class of outdoor activities during the school day reduced myopia progression (0.17 D)

.

Nonetheless, the study had some potential limitations. First,this study used noncycloplegic refraction data. Gwiazda

have shown in the COMET study that noncycloplegic refractions are only 0.23 D more myopic than cycloplegic refractions. Accordingly, noncycloplegic refractometry may result in an accurate slightly higher prevalence of myopia. So the authors intend to emphasize the association between the intervention program and the myopic shift in daily life, rather than the prevalence of myopia. Secondly, the authors used a simple questionnaire, in which the data were self-reported so they would be subject to recall errors. Recall bias may have been minimized by only requesting information about the previous week.

In summary, this prospective interventional school-based study suggests that comprehensive intervention can delay the onset age of myopia in emmetropes and reduce myopia progression in myopes with a significant impact over a 2.5-year period.The procedure is not an optical or pharmacological therapy,so it can be used as the basic intervention the government can institute. In time it may be possible to recommend one or more promising optical or drug therapies for general use. The authors will attempt to identify the exact relationships between comprehensive intervention, near work habits, and refractive error in a future study.

Childhood myopia is now an increasingly important problem in China as long as ophthalmic clinicians and teachers cannot offer systematic effective health therapies and education to the children. Thus, comprehensive intervention is a potentially important measure to improve ocular health. Knowledge about a health problem and strong health consciousness are the prerequisites to incentivize healthy behavior. The present study confirms that to a modest extent a well-organized comprehensive intervention program can reduce the incidence and progression of myopia in young schoolage children.

弗雷格的判断杠“|”出现的语境是：“|—▲”，其中的“▲”可以是任何一个单独词项（即命名或指称对象的表达式），而“—▲”则是更特殊的单独词项，即指称真值的表达式。“|—▲”是具有判断功能的表达式，人们可以使用它来断言—▲等于真。

ACKNOWLEDGEMENTS

Supported by National Natural Science Foundation of China (No.81873683).

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