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For peer review only

Low prevalence of amblyopia and strabismus in Hani school

children in rural southwest China

Journal: BMJ Open

Manuscript ID bmjopen-2018-025441

Article Type: Research

Date Submitted by the Author: 20-Jul-2018

Complete List of Authors: Zhu, Hui; The First Affiliated Hospital with Nanjing Medical University, Ophthalmology Pan, Chenwei; School of Public Health, Medical College of Soochow University, Sun, Qigang; The First Affiliated Hospital with Nanjing Medical University, Ophthalmology Huang, Dan; The First Affiliated Hospital with Nanjing Medical University, Ophthalmology

Fu, ZhuJun; Nanjing Children’s Hospital, Nanjing, Ophthalmology Wang, Jing; Jinling vision care center for children and adolescents Chen, XueJuan; The First Affiliated Hospital with Nanjing Medical University, Ophthalmology Wang, Zijing; The First Affiliated Hospital with Nanjing Medical University, Ophthalmology Liu, Hu; The First Affiliated Hospital with Nanjing Medical University, Ophthalmology

Keywords: Epidemiology < TROPICAL MEDICINE, Public health < INFECTIOUS DISEASES, Strabismus < OPHTHALMOLOGY, Paediatric ophthalmology < OPHTHALMOLOGY

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Title page

Low prevalence of amblyopia and strabismus in Hani school children in rural

southwest China

Hui Zhu,1 Chenwei Pan,

2 Qigang Sun,

1 Dan Huang,

1 Zhujun Fu,

3 Jing Wang,

4

Xuejuan Chen,1 Zijing Wang,

1 Hu Liu

1*

1The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

2School of Public Health, Medical College of Soochow University, Suzhou, China

3Nanjing Children’s Hospital, Nanjing, China

4Jinling vision care center for children and adolescents, Nanjing, China

*Correspondence to: Hu Liu, 300 Guangzhou Road, Department of Ophthalmology,

The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029,

China. Email: [email protected], Phone: +86 (25) 68136470, Fax: +86 (25)

83275171.

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ABSTRACT

Purpose: To determine the prevalence of amblyopia and strabismus in Chinese Hani

ethnic school-aged children.

Methods: All grade 1 and grade 7 students in Mojiang Hani Autonomous County,

located in southwest China, were invited for comprehensive eye examinations,

including visual acuity, ocular alignment and movements, cycloplegic refraction,

anterior segment and fundus examinations. Participants with amblyopia or strabismus

were identified.

Results: A total of 2432 (90.2% response rate) grade 1 students and 2346 (93.5%

response rate) grade 7 students participated in the study. Among them, 1656 grade 1

Hani students and 1394 grade 7 Hani students were analyzed. Amblyopia was present

in 25 Hani students (0.82%, 95% CI 0.50%-1.14%), with no significant differences in

grade (p=0.328) and gender (p=0.602). Among these, 17 had unilateral amblyopia and

8 had bilateral amblyopia, including 16 anisometropic, 8 binocular refractive, and 1

strabismic. Strabismus was found in 59 Hani students (1.93%, 95% CI 1.44%-2.42%),

including 47 with intermittent exotropia, 6 with constant exotropia, 5 with constant

esotropia, and 1 with unilateral superior oblique palsy. Grade 7 students had a

significantly higher strabismus prevalence than grade 1 (p=0.063), while no

significant difference in gender was observed (p=0.340).

Conclusion: The prevalence of amblyopia and strabismus in Chinese Hani school

children are both lower than that previously reported for Chinese Han children in

China and for many other racial/ethnic populations from non-China studies.

Refractive error is the main cause for amblyopia and intermittent exotropia is the

main strabismus type.

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Strengths and limitations of this study

� This is a school-based cohort study conducted in Mojiang Hani Autonomous

County, rural southwest China.

� Mojiang has 13.5% of the total Chinese Hani population, and an enrollment rate

of 99% for elementary and middle schools.

� A total of 1656 grade 1 Hani students and 1394 grade 7 Hani students were

analyzed.

� Standard definitions of amblyopia and strabismus were applied.

� The prevalence estimates might be distorted as children who dropped out of

schools or were incapable of studying in regular schools were not included.

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INTRODUCTION

Amblyopia and strabismus are primarily pediatric eye diseases and can lead to vision

loss, impaired binocular function and cosmetic consequences, which might persist

through adulthood if left untreated. To form a rational policy for early detection and

management of amblyopia and strabismus, it is necessary to do epidemiologic studies

to estimate the prevalence of both diseases in children. With standard study design

and diagnostic criteria, the Multi-ethnic Pediatric Eye Disease Study (MEPEDS)1,2

,

the Baltimore Pediatric Eye Disease Study (BPEDS)3, the Strabismus, Amblyopia,

and Refractive Error in Singaporean children Study (STARS)4, the Sydney Paediatric

Eye Disease Study (SPEDS)5, the Nanjing Pediatric Vision Project (NPVP)

6, and the

Anyang childhood eye study (ACES)7 reported rates ranging from 0.8% to 2.6% for

amblyopia and 0.8% to 5.7% for strabismus. This variation of reported prevalence

mostly comes from various characteristics of study populations, especially with

respect to ethnic origin of participants.

The Hani people, an ethnic minority group, form one of the 56 officially recognized

nationalities of China. Over 90% of Hani peoples live in Yunnan Province, rural

southwest China, which is located across mountains and less prosperous than the

eastern and southern regions in China. Previous Chinese amblyopia or strabismus

prevalence studies mainly focused on the Han nationality, which accounts for 91.5%

of the Chinese population, and none on the Hani nationality. However, data from Han

populations should not be extrapolated to Hani children because of potential ethnic

variations and health care disparities. Our study was designed to assess the prevalence

of amblyopia and strabismus among Chinese Hani school children based on standard

methodology and definitions. This analysis is part of the Mojiang Myopia Progression

Study (MMPS).

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METHODS

Survey design and population

MMPS is a school-based cohort study aiming to longitudinally observe the onset and

progression of myopia, amblyopia, strabismus and other childhood ocular diseases in

grade1 and grade 7 students in Mojiang Hani Autonomous County, Yunnan Province,

rural southwest China8–11

. The baseline survey was conducted in 2016 and all the

grade 1 students from elementary schools and grade 7 students from middle schools in

Mojiang were invited to participate in this study.

Mojiang Hani Autonomous County, an area of 5,312 km2, is one of the 6 main

residences of the Hani people in Yunnan Province, China. There were 222,174 Hani

people in Mojiang as of 2010, accounting for 61.7% of the total population in

Mojiang and 13.5% of the total Chinese Hani population. The compulsory schooling

system is well executed in Mojiang with an enrollment rate of 99% for elementary

and middle schools in 2014. Thus, school-based samples in Mojiang are highly

representative of the local population.

Ethics committee approval was obtained from the Institutional Review Board of

Kunming Medical University. We carried out the study according to the tenets of the

Declaration of Helsinki involving human participants and the approved guidelines.

Additionally, we obtained written informed consents from at least one parent or legal

guardian of each participant.

Questionnaire and eye examinations

A questionnaire was filled up by the parents or legal guardians of the children to

collect detailed information regarding ethnicity and medical history. Uncorrected

visual acuity (UCVA) was measured using the Early Treatment Diabetic Retinopathy

Study visual acuity (VA) chart at a distance of 4 m. For children with UCVA ≤20/40

or two-line interocular difference, subjective optometry was performed to obtain best

corrected VA (BCVA). Ocular alignment was assessed by using the Hirschberg light

reflex test, the cover-uncover test and the alternate cover test. Cover test was

performed by using fixation targets at both distance (6 m) and near (33 cm). Binocular

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and monocular ocular movements were examined at nine diagnostic positions of gaze

with the head in a stationary position. Strabismus magnitude was measured in prism

diopters (PD) using the simultaneous prism and cover test. Each participant's

refractive status was measured after cycloplegia using an autorefractor (RM-8000;

Topcon Corp., Tokyo, Japan) by optometrists. For cycloplegia, each participant was

first administered two drops of 1% cyclopentolate (Alcon) after a 5-minute interval.

Thirty minutes later, a third drop was administered if pupillary light reflex was still

present or the pupil size was less than 6.0 mm. Other ocular examinations including

slit lamp examination, digital retinal photographs, ocular biometry, and optical

coherence tomography, were conducted to exclude any abnormalities precluding

normal vision.

Definitions

Unilateral amblyopia was defined as a 2-line inter-ocular difference between eyes

with BCVA ≤20/32 (≥ logMAR 0.2) in the worse eye and at least one of the

following unilateral amblyopia risk of factors: (1) strabismus on examination; (2)

previous strabismus surgery; (3) anisometropia consistent with the worse eye (≥

1.00D spherical equivalent (SE) anisohyperopia, ≥3.00D SE anisomyopia, or ≥

1.50D anisoastigmatism); (4) past or present obstruction of visual axis2,12

. Bilateral

amblyopia was defined as BCVA in both eyes <20/40 (>logMAR 0.3) with bilateral

ametropia (≥4.00D SE hyperopia, ≥6.00D SE myopia, or ≥2.50D astigmatism) or

with past or present bilateral obstruction of visual axis2,12

.

Strabismus was defined if any tropia was present at distance or near, with or without

spectacles and then classified according to the primary direction (esotropia, exotropia,

and vertical) of the tropia. Strabismus is considered as constant tropia if constant at

both near and distance fixation, otherwise it is considered as intermittent tropia.

Statistical analysis

All data were analyzed using SPSS 13.0 (IBM, China) at the 0.05 significance level.

Prevalence was calculated as the ratio of the number of individuals with any type of

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amblyopia or strabismus to the total number of individuals evaluated. Age- and sex-

specific prevalence for amblyopia and strabismus was calculated; chi-square tests

were used to evaluate statistically significant differences in prevalence between

subgroups. 95% confidence intervals (CIs) of prevalence were also provided.

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RESULTS

Study population

A total of 2432 (90.2% response rate) grade 1 students aged 7-8 years and 2346 (93.5%

response rate) grade 7 students aged 13-14 years participated in the study, including

3050 Hani (63.8%), 774 Han (16.2%), 954 other ethnic minorities (20.0%). The 3050

Hani ethnic students were included in the analysis, including 1656 grade 1 (mean age,

7.7 ± 0.6 years; 54.6% male) and 1394 grade 7 students (mean age, 13.8 ± 0.7 years;

51.5% male). There was no statistically significant age difference between boys and

girls in the 3050 students (p=0.274).

Prevalence of amblyopia in Hani

According to the findings from comprehensive ocular examinations of the 3050 Hani

participants, amblyopia was present in 25 students (0.82%, 95% CI 0.50%-1.14%),

including 16 grade 1 students(0.97%, 95% CI 0.50%-1.44%) and 9 grade 7

students(0.65%, 95% CI 0.23%-1.07%). The prevalence of amblyopia did not differ

between grade 1 and grade 7 (p=0.328), or between boys and girls (p=0.602). Table 1

summarizes the prevalence of unilateral and bilateral amblyopia by different causes.

Unilateral amblyopia was diagnosed in 17 children (0.56%, 95% CI 0.30%-0.82%),

and bilateral amblyopia was diagnosed in 8 children (0.26%, 95% CI 0.07%-0.44%).

Anisometropia was the cause in 16 of the 17 children (94.1%) with unilateral

amblyopia and ametropic the cause in all bilateral amblyopia. Nearly half of the 33

amblyopic eyes (51%, 17/33) had severe amblyopia (BCVA ≤20/100) and one third

(27%, 9/33) had BCVA ≤20/160. According to the questionnaire information

reported by the parents or legal guardians, no children had been previously diagnosed

or treated as having amblyopia.

Table 1. Prevalence of unilateral and bilateral amblyopia by different causes in Hani

Amblyopia type With

amblyopia, n

Prevalence (95% CI)

(%)

Unilateral 17 0.6 (0.3-0.8)

Strabismic 1 0.0 (0.00-0.1)

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Anisometropic 16 0.5 (0.3-0.8)

≥1.00 D SE anisohyperopia 5 0.2 (0.0-0.3)

≥3.00 D SE anisomyopia 4 0.1 (0.0-0.3)

≥1.50 D anisoastigmatism 6 0.2 (0.0-0.4)

≥1.00 D SE anisohyperopia+≥1.50 D anisoastigmatism 1 0.0 (0.00-0.1)

Bilateral 8 0.3 (0.1-0.4)

Ametropic 8 0.3 (0.1-0.4)

≥4.00 D SE hyperopia 3 0.1 (0.0-0.2)

≥6.00 D SE myopia 1 0.0 (0.0-0.1)

≥2.50 D astigmatism 4 0.1 (0.0-0.3)

CI, confidence interval; SE, spherical equivalent.

Prevalence of strabismus in Hani

A total of 59 (1.93%, 95% CI 1.44%-2.42%) were found to have strabismus, including

25 grade 1 students (1.50%, 95% CI 0.91%-2.09%) and 34 grade 7 students (2.44%,

95% CI 1.63%-3.25%). Grade 7 students had a significantly higher strabismus

prevalence than grade 1 (p=0.063), while no significant difference between boys and

girls was observed (p=0.340). Of the 59 strabismic students, 47 (80%) had

intermittent exotropia, 6 (10%) had constant exotropia, 5 (8%) had constant esotropia,

1 (2%) had unilateral superior oblique palsy. 5 of the intermittent exotropia and 1 of

constant esotropia had bilateral inferior oblique muscle overaction. The distribution of

strabismus magnitude in 58 students with horizontal strabismus is shown in Table 2.

Nearly one third of the horizontal strabismic students had more than 30 PD strabismus

magnitude at near or at distance. Based on the questionnaire information reported by

the parents or legal guardians, no children had been previously diagnosed or treated as

having strabismus.

Table 2. Distribution of strabismus magnitude in 58 Hani

students with horizontal strabismus

Strabismus magnitude n (%)

At near

1-9 PD 5 (9%)

10-30 PD 31 (53%)

>30 PD 22 (38%)

At distance

1-9 PD 28 (48%)

10-30 PD 14 (24%)

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>30 PD 16 (28%)

PD, prism diopter.

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DISCUSSION

In this school-based sample of Hani school children in China, we reported a 0.82%

prevalence of amblyopia. Amblyopia definitions have significant influence on

amblyopia prevalence estimation. Compared with the MEPEDS, BPEDS, STARS,

SPEDS, NPVP, and ACES studies which applied the same definitions as our study, the

amblyopia prevalence in Hani children was at a low level (Table 3). The

multi-country Refractive Error Study in Children (RESC) study, although using

different definitions of amblyopia, found significant differences among ethnic groups,

with low prevalence rates reported for African and south Asian (Indian) ethnic groups,

and higher prevalence rates in Hispanic and east Asian (Chinese) ethnic groups13

. The

authors speculated that general loss of pigmentation in the European and east Asian

people might be associated with low amblyopia prevalence. Chinese Hani people live

near south Asia and have more pigmentation than Chinese Han and European, which

might be a possible reason for the low amblyopia prevalence in Hani group. In our

findings, amblyopia prevalence was not significantly related with age or gender, and

refractive error, especially anisometropia, was the main cause for amblyopia, which

were consistent with the results from MEPEDS, STARS, SPEDS, NPVP and ACES.

Globally, the prevalence of strabismus in the Hani sample was lower than rates in

school children from other countries, including England (2.3%)14

,

Australia

(2.7%-2.8%)15,16

, Mexico (2.3%)17

, and Sweden (2.7%)18

. In China, the strabismus

prevalence in our study was also lower than most Chinese school children, including

2.8% from Shunyi (representative of rural northern China)19

, 3.0% from Guangzhou

(representative of urban southern China)20

, 2.5% from Maqin (representative of rural

Tibetan area)21

, and 5.0% from Anyang (representative of rural central China)22

. In

addition, when compared with studies in preschool children, the strabismus

prevalence in our study was also at a low level (Table 3). Population differences in

genetic susceptibility, environment, and lifestyle factors may contribute to the low

strabismus prevalence in Chinese Hani students.

Table 3. Prevalence of amblyopia and strabismus in different studies

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Study Country Age, years (n) Ethnicity Prevalence of

amblyopia*

Prevalence of

strabismus

MEPEDS, 2008 United States 2.5-6 (3350) African American (1663)

Hispanic/Latino (1687)

1.5%

2.6%

2.5%

2.4%

MEPEDS, 2013 United States 2.5-6 (1883) Asian American (938)

Non-Hispanic White

(945)

1.8%

1.8%

3.6%

3.2%

BPEDS, 2009 United States 2.5-6 (1546) Non-Hispanic White

(673)

African American (873)

1.8%

0.8%

3.3%

2.1%

STARS, 2010 Singapore 2.5-6 (1682) Singaporean Chinese 1.2% 0.8%

SPEDS, 2012 Australia 2.5-6 (1422) predominantly white 1.9% N/A**

NPVP, 2015 China 3-6 (5667) Chinese Han 1.2% 5.7%

ACES, 2014 China 6-9 (2893) Chinese Han 1.0 % N/A**

MMPS, 2018 China 7-8 (2432),13-14

(2346)

Chinese Hani 0.8% 1.9%

*Same definitions of amblyopia were used.

** No strabismus data.

Regarding strabismus type, about 90% of the strabismus was exotropia in the present

study. Previous studies have found that east Asian populations had higher

exotropia:esotropia ratio than Caucasians, and presumed that less hyperopic in east

Asian populations and less myopic in Caucasians might be the cause of the

difference1–4,6,16,18,23,24

. Our previous research revealed that exotropia was associated

with astigmatism, myopia and low to moderate hyperopia, while esotropia had a

severity-dependent relationship with hyperopia25

. Thus, distribution characteristics of

refraction may be partly responsible for higher exotropia:esotropia ratio. The

MEPEDS and NPVP studies have found higher prevalence of strabismus in older

preschool children1,2,6

. In our study, grade 7 students did have higher strabismus

prevalence than grade 1. This finding suggests that strabismus might increase with

age. No significant statistical differences of strabismus were observed in gender from

our study, which was in line with previous studies2,5,6,14–16

.

Limitations of this study include the following. First, the study is a school-based study

rather than a population-based one. The prevalence estimates might be distorted as

children who dropped out of schools or were incapable of studying in regular schools

were not included. However, we expected that the non-responder bias is minimal

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because of the high school attendance rates of students in Mojiang. Second,

small-angle or intermittent strabismus may have been missed given the nature of both

conditions. Finally, information on the history of amblyopia or strabismus was

collected by questionnaires, which might be potentially inaccurate due to recall

biases.

CONCLUSIONS

Strabismus affects 1.93% of Chinese Hani school children and amblyopia affects

0.82%. The prevalence of amblyopia and strabismus in this population are both lower

than that previously reported for Chinese Han children and for many other

racial/ethnic populations from non-China studies. Further studies are needed to

explore why Chinese Hani children have low prevalence of amblyopia and

strabismus.

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Contributorship statement Conceived and designed the experiments: HL, HZ, and

CP. Performed the experiments: HZ, QS, DH, ZF, and JW. Analyzed the data: HL, HZ,

CP, XC, and ZW. Contributed reagents/materials/analysis tools: HL, HZ, CP, and DH.

Wrote the paper: HL and HZ.

Competing interests None declared.

Funding This study is supported by Natural Science Foundation of Jiangsu Province

(Grant No. BK20161595); National Natural Science Foundation of China (Grant No.

81773449, No. 81560169 and No. 81673198).

Data sharing statement No additional data are available.

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CA: American Academy of Ophthalmology, www. aao. org/ppp.

13. Xiao O, Morgan IG, Ellwein LB, et al. Prevalence of Amblyopia in School-Aged

Children and Variations by Age, Gender, and Ethnicity in a Multi-Country

Refractive Error Study. Ophthalmology. 2015;122(9):1924-1931.

14. Williams C, Northstone K, Howard M, et al. Prevalence and risk factors for

common vision problems in children: data from the ALSPAC study. Br J

Ophthalmol. 2008;92(7):959-964.

15. Robaei D, Rose KA, Ojaimi E, et al. Causes and associations of amblyopia in a

population-based sample of 6-year-old Australian children. Arch Ophthalmol.

2006;124(6):878-884.

16. Robaei D, Kifley A, Rose KA, et al. Impact of amblyopia on vision at age 12

years: findings from a population-based study. Eye (Lond). 2008;22(4):496-502.

17. Ohlsson J, Villarreal G, Sjöström A, et al. Visual acuity, amblyopia, and ocular

pathology in 12- to 13-year-old children in Northern Mexico. J AAPOS.

2003;7(1):47-53.

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18. Ohlsson J, Villarreal G, Sjöström A, et al. Visual acuity, residual amblyopia and

ocular pathology in a screened population of 12-13-year-old children in Sweden.

Acta Ophthalmol Scand. 2001;79(6):589-595.

19. Zhao J, Pan X, Sui R, et al. Refractive Error Study in Children: results from

Shunyi District, China. Am J Ophthalmol. 2000;129(4):427-435.

20. He M, Zeng J, Liu Y, et al. Refractive error and visual impairment in urban

children in southern china. Invest Ophthalmol Vis Sci. 2004;45(3):793-799.

21. Lu P, Chen X, Zhang W, et al. Prevalence of ocular disease in Tibetan primary

school children. Can J Ophthalmol. 2008;43(1):95-99.

22. Fu J, Li SM, Liu LR, et al. Prevalence of amblyopia and strabismus in a

population of 7th-grade junior high school students in Central China: the Anyang

Childhood Eye Study (ACES). Ophthalmic Epidemiol. 2014;21(3):197-203.

23. Yu CB, Fan DS, Wong VW, et al. Changing patterns of strabismus: a decade of

experience in Hong Kong. Br J Ophthalmol. 2002;86(8):854-856.

24. Chia A, Roy L, Seenyen L. Comitant horizontal strabismus: an Asian perspective.

Br J Ophthalmol. 2007;91(10):1337-1340.

25. Zhu H, Yu JJ, Yu RB, et al. Association between childhood strabismus and

refractive error in Chinese preschool children. PloS One. 2015;10(3):e0120720.

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STROBE Statement—checklist of items that should be included in reports of observational studies

Item

No Recommendation

Page

No

Title and abstract 1 (a) Indicate the study’s design with a commonly used term in the title or the

abstract

1-2

(b) Provide in the abstract an informative and balanced summary of what

was done and what was found

1-2

Introduction

Background/rationale 2 Explain the scientific background and rationale for the investigation being

reported

4

Objectives 3 State specific objectives, including any prespecified hypotheses 4

Methods

Study design 4 Present key elements of study design early in the paper 5

Setting 5 Describe the setting, locations, and relevant dates, including periods of

recruitment, exposure, follow-up, and data collection

5-6

Participants 6 (a) Cohort study—Give the eligibility criteria, and the sources and methods

of selection of participants. Describe methods of follow-up

Case-control study—Give the eligibility criteria, and the sources and

methods of case ascertainment and control selection. Give the rationale for

the choice of cases and controls

Cross-sectional study—Give the eligibility criteria, and the sources and

methods of selection of participants

5

(b) Cohort study—For matched studies, give matching criteria and number

of exposed and unexposed

Case-control study—For matched studies, give matching criteria and the

number of controls per case

Variables 7 Clearly define all outcomes, exposures, predictors, potential confounders,

and effect modifiers. Give diagnostic criteria, if applicable

5-6

Data sources/

measurement

8* For each variable of interest, give sources of data and details of methods of

assessment (measurement). Describe comparability of assessment methods

if there is more than one group

5-6

Bias 9 Describe any efforts to address potential sources of bias 5-6

Study size 10 Explain how the study size was arrived at 5

Quantitative variables 11 Explain how quantitative variables were handled in the analyses. If

applicable, describe which groupings were chosen and why

6-7

Statistical methods 12 (a) Describe all statistical methods, including those used to control for

confounding

6-7

(b) Describe any methods used to examine subgroups and interactions 6-7

(c) Explain how missing data were addressed 6-7

(d) Cohort study—If applicable, explain how loss to follow-up was

addressed

Case-control study—If applicable, explain how matching of cases and

controls was addressed

Cross-sectional study—If applicable, describe analytical methods taking

account of sampling strategy

6-7

(e) Describe any sensitivity analyses 6-7

Continued on next page

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Results

Participants 13* (a) Report numbers of individuals at each stage of study—eg numbers potentially

eligible, examined for eligibility, confirmed eligible, included in the study, completing

follow-up, and analysed

8

(b) Give reasons for non-participation at each stage 8

(c) Consider use of a flow diagram

Descriptive

data

14* (a) Give characteristics of study participants (eg demographic, clinical, social) and

information on exposures and potential confounders

8

(b) Indicate number of participants with missing data for each variable of interest 8

(c) Cohort study—Summarise follow-up time (eg, average and total amount)

Outcome data 15* Cohort study—Report numbers of outcome events or summary measures over time

Case-control study—Report numbers in each exposure category, or summary

measures of exposure

Cross-sectional study—Report numbers of outcome events or summary measures 8-10

Main results 16 (a) Give unadjusted estimates and, if applicable, confounder-adjusted estimates and

their precision (eg, 95% confidence interval). Make clear which confounders were

adjusted for and why they were included

8-10

(b) Report category boundaries when continuous variables were categorized

(c) If relevant, consider translating estimates of relative risk into absolute risk for a

meaningful time period

Other analyses 17 Report other analyses done—eg analyses of subgroups and interactions, and

sensitivity analyses

8-10

Discussion

Key results 18 Summarise key results with reference to study objectives 11

Limitations 19 Discuss limitations of the study, taking into account sources of potential bias or

imprecision. Discuss both direction and magnitude of any potential bias

12-

13

Interpretation 20 Give a cautious overall interpretation of results considering objectives, limitations,

multiplicity of analyses, results from similar studies, and other relevant evidence

11-

13

Generalisability 21 Discuss the generalisability (external validity) of the study results 11-

23

Other information

Funding 22 Give the source of funding and the role of the funders for the present study and, if

applicable, for the original study on which the present article is based

14

*Give information separately for cases and controls in case-control studies and, if applicable, for exposed and

unexposed groups in cohort and cross-sectional studies.

Note: An Explanation and Elaboration article discusses each checklist item and gives methodological background and

published examples of transparent reporting. The STROBE checklist is best used in conjunction with this article (freely

available on the Web sites of PLoS Medicine at http://www.plosmedicine.org/, Annals of Internal Medicine at

http://www.annals.org/, and Epidemiology at http://www.epidem.com/). Information on the STROBE Initiative is

available at www.strobe-statement.org.

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For peer review onlyPrevalence of amblyopia and strabismus in Hani school

children in rural southwest China: a cross-sectional study

Journal: BMJ Open

Manuscript ID bmjopen-2018-025441.R1


Date Submitted by the Author: 17-Sep-2018

Complete List of Authors: Zhu, Hui; The First Affiliated Hospital with Nanjing Medical University, OphthalmologyPan, Chenwei; School of Public Health, Medical College of Soochow University, Sun, Qigang; The First Affiliated Hospital with Nanjing Medical University, OphthalmologyHuang, Dan; The First Affiliated Hospital with Nanjing Medical University, OphthalmologyFu, ZhuJun; Nanjing Children’s Hospital, Nanjing, OphthalmologyWang, Jing; Jinling vision care center for children and adolescentsChen, XueJuan; The First Affiliated Hospital with Nanjing Medical University, OphthalmologyWang, Zijing; The First Affiliated Hospital with Nanjing Medical University, OphthalmologyLiu, Hu; The First Affiliated Hospital with Nanjing Medical University, Ophthalmology

<b>Primary Subject Heading</b>: Ophthalmology

Secondary Subject Heading: Epidemiology, Paediatrics, Public health

Keywords: Strabismus < OPHTHALMOLOGY, Paediatric ophthalmology < OPHTHALMOLOGY, EPIDEMIOLOGY, PUBLIC HEALTH


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Title page

Prevalence of amblyopia and strabismus in Hani school children in rural

southwest China: a cross-sectional study

Hui Zhu,1 Chenwei Pan,

2 Qigang Sun,

1 Dan Huang,

1 Zhujun Fu,

3 Jing Wang,

4

Xuejuan Chen,1 Zijing Wang,

1 Hu Liu

1*








83275171.

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ABSTRACT

Purpose: To determine the prevalence rate of amblyopia and strabismus in Chinese

Hani ethnic school-aged children.


located in southwest China, were invited for comprehensive eye examinations

performed by experienced ophthalmologists and optometrists, including visual acuity,

ocular alignment and movements, cycloplegic refraction, anterior segment, and

fundus examinations. Standard definitions of amblyopia and strabismus were applied

to calculate their prevalence rate.

Results: A total of 1656 (91.0% response rate) grade 1 Hani students and 1394 (92.8%

response rate) grade 7 Hani students participated in the study. Amblyopia was present

in 25 Hani students (0.82%, 95% CI 0.55%-1.20%), with no significant differences in

grade (p=0.42) and gender (p=0.69). Among these 25 amblyopic children, 17 had

unilateral amblyopia and 8 had bilateral amblyopia, including 16 anisometropic, 8

binocular refractive, and 1 strabismic. Strabismus was found in 59 Hani students

(1.93%, 95% CI 1.50%-2.48%), including 47 with intermittent exotropia, 6 with

constant exotropia, 5 with constant esotropia, and 1 with unilateral superior oblique

palsy. The prevalence rate of strabismus was higher in grade 7 students than grade 1

students with borderline significance (2.44% vs. 1.50%, p=0.07), but was similar by

gender (2.16% in boys vs. 1.68% in girls, p=0.36).




Refractive error is the major cause for amblyopia and intermittent exotropia is the

primary strabismus type.

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� This is a large school-based cohort study conducted in Mojiang Hani

Autonomous County, rural southwest China.

� Mojiang has 13.5% of the total Chinese Hani population, and an enrollment rate


� A total of 1656 grade 1 Hani students and 1394 grade 7 Hani students were

analyzed, with high study participation rate (>90%).

� Standard definitions of amblyopia and strabismus were applied.

� The prevalence estimates might be biased as small percent of students did not

participate, and children who dropped out of schools or were not enrolled into

regular schools were not included.

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INTRODUCTION



through adulthood if left untreated. To develop a rational policy for early detection

and management of amblyopia and strabismus, it is necessary to conduct

population-based epidemiologic studies to estimate their prevalence in children. With

standard study design and diagnosis criteria, the Multi-ethnic Pediatric Eye Disease

Study (MEPEDS)1,2

, the Baltimore Pediatric Eye Disease Study (BPEDS)3, the

Strabismus, Amblyopia, and Refractive Error in Singaporean children Study

(STARS)4, the Sydney Paediatric Eye Disease Study (SPEDS)

5, the Nanjing Pediatric

Vision Project (NPVP)6, the Anyang childhood eye study (ACES)

7 and the Yuhuatai

Pediatric Eye Disease Study (YPEDS)8 reported prevalence rates ranging from 0.8%

to 2.6% for amblyopia and 0.8% to 5.7% for strabismus. This large variation in

reported prevalence rate most likely is due to differences in the characteristics of

study populations, particularly the ethnicity of participants.

The Hani, an ethnic minority group, is one of the 56 officially recognized nationalities

in China. Over 90% of Hani people live in Yunnan Province, rural southwest China,

which is located across mountains and is less prosperous than the eastern and southern

regions in China. Previous Chinese amblyopia or strabismus prevalence studies

mainly focused on the Han nationality, which accounts for 91.5% of the Chinese

population, and these studies did not include the Hani nationality. However, data from

Han populations could not be extrapolated to Hani children because of potential

impact of ethnic variations and health care disparities on prevalences of eye diseases.

Our study was designed to assess the prevalence of amblyopia and strabismus among

Chinese Hani school children using standard methodology and definitions. This

analysis is part of the Mojiang Myopia Progression Study (MMPS).

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METHODS


MMPS is a school-based cohort study designed to longitudinally assess the onset and


grade 1 and grade 7 students in Mojiang Hani Autonomous County, Yunnan Province,

rural southwest China9–12

. The baseline eye examination was conducted in 2016 and

all grade 1 students from elementary schools and grade 7 students from middle

schools in Mojiang were invited to participate in this study. This paper used data from

this baseline eye examination in grade 1 and grade 7 Hani students.




Mojiang and 13.5% of the total Chinese Hani population. The compulsory 9-year

mandatory education system is well executed in Mojiang with an enrollment rate of

99% for elementary and middle schools in 2014. Thus, school-based samples in

Mojiang are highly representative of this school-aged population.







A questionnaire was completed by the parents or legal guardians of the children to

collect detailed information regarding ethnicity and medical history. Comprehensive

eye examinations were performed by experienced ophthalmologists and optometrists.

Uncorrected visual acuity (UCVA) was measured using the Early Treatment Diabetic

Retinopathy Study visual acuity (VA) chart at a distance of 4 m. For children with

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UCVA ≤20/40 or at-least two-line interocular difference, subjective optometry was

performed to obtain best corrected VA (BCVA). Ocular alignment was assessed by

using the Hirschberg light reflex test, the cover-uncover test and the alternate cover

test. Cover test was performed by using fixation targets at both distance (6 m) and

near (33 cm). Binocular and monocular ocular movements were examined at nine

diagnostic positions of gaze with the head in a stationary position. Strabismus

magnitude was measured in prism diopters (PD) using the simultaneous prism and

cover test. Each participant's refractive status was measured after cycloplegia using an

autorefractor (RM-8000; Topcon Corp., Tokyo, Japan) by optometrists. For

cycloplegia, each participant was first administered two drops of 1% cyclopentolate

(Alcon) after a 5-minute interval. Thirty minutes later, a third drop was administered

if pupillary light reflex was still present or the pupil size was less than 6.0 mm. Other

ocular examinations including slit lamp examination, digital retinal photographs,

ocular biometry, and optical coherence tomography, were conducted to exclude any

abnormalities precluding normal vision.

Definitions

Unilateral amblyopia was defined as at least 2-line inter-ocular difference between

eyes with BCVA ≤20/32 (≥0.2 logMAR) in the worse eye and presence of at least

one of the following unilateral amblyopia risk of factors: (1) strabismus on

examination; (2) previous strabismus surgery; (3) anisometropia consistent with the

worse eye (≥ 1.00D spherical equivalent (SE) anisohyperopia, ≥ 3.00D SE

anisomyopia, or ≥1.50D anisoastigmatism); (4) past or present obstruction of visual

axis (e.g., cataract, corneal opacity, ptosis, eyelid hemangioma) which could not

explain the vision loss directly2,13

. Bilateral amblyopia was defined as BCVA in both

eyes <20/40 (>0.3 logMAR) with bilateral ametropia (≥4.00D SE hyperopia, or ≥

6.00D SE myopia, or ≥2.50D astigmatism) or with past or present bilateral

obstruction of visual axis (see above) which could not directly explain the vision

loss2,13

.

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Strabismus was defined present if any tropia was present at distance or near, with or

without spectacles and was classified according to the primary direction (esotropia,

exotropia, and vertical) of the tropia. Strabismus is considered as constant tropia if

constant at both near and distance fixation, otherwise it is considered as intermittent

tropia.


All data were analyzed using SPSS 13.0 (IBM, China) and 2-sided p<0.05 was

considered statistical significant. Prevalence rate for amblyopia and strabismus was

calculated as the percent of children with amblyopia or strabismus among all the Hani

children evaluated. Age- and sex- specific prevalence rate for amblyopia and

strabismus was calculated; Fisher exact test was used to compare the prevalence rate

between grade 1 and grade 7 and between boys and girls. 95% confidence intervals

(CIs) for prevalence rates were calculated using Wilson method.

Patient and Public Involvement

Patients and public were not involved in any aspects of the study including the

development of study question, study design, conduct of the study and dissemination

of results.

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RESULTS

Study population

A total of 1656 (91.0% response rate) grade 1 Hani students aged 7-8 years and 1394

(92.8% response rate) grade 7 Hani students aged 13-14 years participated in the study.

The mean age was 7.7 ± 0.6 and 13.8 ± 0.7 years for grade 1 and 7 students

respectively. There was similar percentage of boys among grade 1 students and grade

7 students (54.6% vs. 51.5%).


Based on the findings from comprehensive ocular examinations of the 3050 Hani


including 16 grade 1 students (0.97%, 95% CI 0.59%-1.56%) and 9 grade 7 students

(0.65%, 95% CI 0.34%-1.22%). The prevalence of amblyopia did not differ between

grade 1 and grade 7 (p=0.42), or between boys and girls (p=0.69). Unilateral

amblyopia was diagnosed in 17 children (0.56%, 95% CI 0.35%-0.89%), and bilateral

amblyopia was diagnosed in 8 children (0.26%, 95% CI 0.13%-0.51%). Table 1

summarizes the prevalence of unilateral and bilateral amblyopia by different causes.

Anisometropia was the cause in 16 of the 17 children (94.1%) with unilateral

amblyopia and ametropic was the cause in all bilateral amblyopia. Nearly half of the

33 amblyopic eyes (51%, 17/33) had severe amblyopia (BCVA ≤20/100) and one

third (27%, 9/33) had BCVA ≤20/160. Based on the questionnaire responses from

their parents or legal guardians, no children had been previously diagnosed with

amblyopia or treated for amblyopia.

Table 1. Prevalence of unilateral and bilateral amblyopia by different causes in Hani students

(N=3050)

Amblyopia type With amblyopia, n Prevalence (95% CI) (%)

Unilateral 17 0.56 (0.35-0.89)

Strabismic 1 0.03 (0.00-0.18)

Anisometropic 16 0.52 (0.32-0.84)

≥≥≥≥1.00 D SE anisohyperopia 5 0.16 (0.07-0.37)

≥≥≥≥3.00 D SE anisomyopia 4 0.13 (0.05-0.33)

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≥≥≥≥1.50 D anisoastigmatism 6 0.20 (0.09-0.43)

≥≥≥≥ 1.00 D SE anisohyperopia+ ≥≥≥≥ 1.50 D

anisoastigmatism

1 0.03 (0.00-0.18)

Bilateral 8 0.26 (0.13-0.51)

Ametropic 8 0.26 (0.13-0.51)

≥≥≥≥4.00 D SE hyperopia 3 0.10 (0.03-0.29)

≥≥≥≥6.00 D SE myopia 1 0.03 (0.00-0.18)

≥≥≥≥2.50 D astigmatism 4 0.13 (0.05-0.33)



A total of 59 (1.93%, 95% CI 1.50%-2.48%) children were found to have strabismus,


(2.44%, 95% CI 1.75%-3.38%). The prevalence of strabismus was higher in grade 7

students than grade 1 students with borderline significance (2.44% vs. 1.50%, p=0.07),

but was similar in boys and girls (2.16% and 1.68% respectively, p=0.36). Of the 59

strabismic students, 47 (80%) had intermittent exotropia, 6 (10%) had constant

exotropia, 5 (8%) had constant esotropia, 1 (2%) had unilateral superior oblique palsy,

5 of the intermittent exotropia and 1 of constant esotropia had bilateral inferior

oblique muscle overaction. The distribution of strabismus magnitude in 58 students

with horizontal strabismus is shown in Table 2. Nearly one third of the horizontal

strabismic students had more than 30 PD strabismus magnitude at near or at distance.

Based on the questionnaire responses from the parents or legal guardians, no children

had been previously diagnosed with or treated for strabismus.

Table 2. Distribution of strabismus magnitude in 58 Hani

students with horizontal strabismus

Strabismus magnitude n (%)

At near

1-9 PD 5 (9%)

10-30 PD 31 (53%)

>30 PD 22 (38%)

At distance

1-9 PD 28 (48%)

10-30 PD 14 (24%)

>30 PD 16 (28%)

PD, prism diopter.

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DISCUSSION

In this school-based sample of Hani school children in China, we found a low (0.82%)

prevalence rate of amblyopia. Amblyopia definitions can have significant impact on

amblyopia prevalence estimate. Using the same standard amblyopia definition as

MEPEDS, BPEDS, STARS, SPEDS, NPVP, ACES and YPEDS studies, the

amblyopia prevalence in Hani children was lower than all these studies, including

these in Chinese Han children (Table 3). Compared with a study from Western China

in school children that used different amblyopia definition from this study14

, the

amblyopia prevalence rate in Hani school children was lower. The multi-country

Refractive Error Study in Children (RESC) study15

, also using different amblyopia

definition, reported higher amblyopia prevalence rates in Hispanic and Chinese

(predominantly Han) school children and lower amblyopia prevalence rates in African

and south Asian (Indian) school children than that in this study15

. General loss of

pigmentation in Hispanic and Chinese Han people might be associated with high

amblyopia prevalence. Chinese Hani people live near south Asia and have more

pigmentation than Chinese Han and Hispanic, which might be a possible reason for

the low amblyopia prevalence in Hani group. In a recent Israel study among young

adults, the prevalence of amblyopia was 0.8% in the population born between 1986

and 1994, which is similar to the rate in our study16

. Besides the difference in

amblyopia definition, the implementation of mandatory vision screening and the

universal healthcare provided to all Israel citizens by legislation might explain the low

prevalence rate of amblyopia in Israel. In this study, we found age and gender was not

significantly associated with amblyopia prevalence rate while refractive error,

particularly anisometropia, was the major cause for amblyopia. These findings are

consistent with the results from MEPEDS, STARS, SPEDS, NPVP, ACES and

YPEDS.

Globally, the prevalence rate of strabismus (1.90%) in the Hani sample was lower

than rates in school children from other countries, including England (2.3%)17

,

Australia (2.7%-2.8%)18,19

, Mexico (2.3%)20

, and Sweden (2.7%)21

. The strabismus

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prevalence rate in our study was also lower than most Chinese school children in

China, including 2.8% from Shunyi (representative of rural northern China)22

, 3.0%

from Guangzhou (representative of urban southern China)23

, 2.5% from Maqin

(representative of rural Tibetan area)24

, and 5.0% from Anyang (representative of rural

central China)25

. The strabismus prevalence rate in our study was also lower than

those from studies in preschool children (Table 3). Differences in genetic

susceptibility, environmental factors, and lifestyle may contribute to the lower rate of

strabismus in Chinese Hani students.

Table 3. Prevalence of amblyopia and strabismus in different studies

Study Country Age, years (n) Ethnicity Prevalence of

amblyopia*

Prevalence of

strabismus

MEPEDS, 2008 United States 2.5-6 (3350) African American (1663)

Hispanic/Latino (1687)

1.5%

2.6%

2.5%

2.4%

MEPEDS, 2013 United States 2.5-6 (1883) Asian American (938)

Non-Hispanic White

(945)

1.8%

1.8%

3.6%

3.2%

BPEDS, 2009 United States 2.5-6 (1546) Non-Hispanic White

(673)

African American (873)

1.8%

0.8%

3.3%

2.1%

STARS, 2010 Singapore 2.5-6 (1682) Singaporean Chinese 1.2% 0.8%

SPEDS, 2012 Australia 2.5-6 (1422) predominantly white 1.9% N/A**

NPVP, 2015 China 3-6 (5667) Chinese Han 1.2% 5.7%

ACES, 2014 China 6-9 (2893) Chinese Han 1.0 % N/A**

YPEDS, 2018 China 3-4 (1695) Chinese Han 1.47% N/A**

MMPS, 2018 China 7-8 (2432),13-14

(2346)


*Same definition of amblyopia was used.

** No strabismus data.

Our study found about 90% of the strabismus was exotropia. Previous studies have

found that east Asian populations had higher exotropia : esotropia ratio than

Caucasians, which might be due to less hyperopia in east Asian population than

Caucasians1–4,6,19,21,26,27

. Our previous research found that exotropia was associated

with astigmatism, myopia and low to moderate hyperopia, while esotropia was

associated with hyperopia in a dose-response manner28

. Thus, difference in refractive

error distribution may be responsible for higher exotropia : esotropia ratio in the study

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compared with other studies. Consistent with the MEPEDS and NPVP studies that

found higher prevalence of strabismus in older preschool children1,2,6

, our study found

that prevalence rate of strabismus was higher in grade 7 students than grade 1 students,

although the difference is only borderline significant (2.44% vs. 1.50%, p=0.07). This

finding suggests that strabismus might increase with age. Consistent with other

studies2,5,6,17–19

, our study did not find any significant difference in prevalence rate of

strabismus between boys and girls.

Our study has some limitations. First, the study is school-based rather than

population-based. The prevalence estimates might be biased as small percent of

school children did not participate in this study, and children who dropped out of

schools or did not attend regular schools were not included into the study. However,

we expect that this small percent of children not in our study will not substantially

bias our prevalence estimate. Second, small-angle or intermittent strabismus may have

been missed given the nature of both conditions. Third, the study used the cycloplegic

autorefraction instead of cycloplegic retinoscopy, and it could potentially bias the

refractive error measure. Finally, information on the history of amblyopia or

strabismus was collected by questionnaires, which might be potentially inaccurate due

to recall biases.

CONCLUSIONS

In this large school-based study of Chinese Hani school children, we found amblyopia

affects 0.82% children and strabismus affects 1.93% children. These prevalence rates

are both lower than those previously reported for Chinese Han children and for many

other racial/ethnic populations from non-China studies. Further studies are needed to

explore why Chinese Hani children have low prevalence of amblyopia and

strabismus.

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CP. Performed the experiments: HZ, QS, DH, ZF, and JW. Analyzed the data: HL, HZ,

CP, XC, and ZW. Contributed reagents/materials/analysis tools: HL, HZ, CP, and DH.

Wrote the paper: HL and HZ.




81773449, No. 81560169 and No. 81673198).


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REFERENCES

1. Multi-ethnic Pediatric Eye Disease Study Group. Prevalence of amblyopia and strabismus in

African American and Hispanic children ages 6 to 72 months the multi-ethnic pediatric eye

disease study. Ophthalmology 2008;115:1229-36.e1.

2. McKean-Cowdin R, Cotter SA, Tarczy-Hornoch K, et al. Prevalence of amblyopia or

strabismus in asian and non-Hispanic white preschool children: multi-ethnic pediatric eye

disease study. Ophthalmology 2013;120:2117-24.

3. Friedman DS, Repka MX, Katz J, et al. Prevalence of amblyopia and strabismus in white

and African American children aged 6 through 71 months the Baltimore Pediatric Eye

Disease Study. Ophthalmology 2009;116:2128-34.e1-2.

4. Chia A, Dirani M, Chan YH, et al. Prevalence of amblyopia and strabismus in young

singaporean chinese children. Invest Ophthalmol Vis Sci 2010;51:3411-7.

5. Pai AS, Rose KA, Leone JF, et al. Amblyopia prevalence and risk factors in Australian

preschool children. Ophthalmology 2012;119:138-44.

6. Chen X, Fu Z, Yu J, et al. Prevalence of amblyopia and strabismus in Eastern China: results

from screening of preschool children aged 36-72 months. Br J Ophthalmol 2016;100:515-9.

7. Fu J, Li SM, Li SY, et al. Prevalence, causes and associations of amblyopia in year 1

students in Central China : The Anyang childhood eye study (ACES). Graefes Arch Clin

Exp Ophthalmol 2014;252:137-43.

8. Huang D, Chen X, Zhu H, et al. Prevalence of amblyopia and its association with refraction

in Chinese preschool children aged 36-48 months. Br J Ophthalmol 2018;102:767-71.

9. Pan CW, Wu RK, Li J, et al. Low prevalence of myopia among school children in rural

China. BMC Ophthalmol 2018;18:140.

10. Pan CW, Wu RK, Wang P, et al. Reduced vision, refractive errors and health-related quality

of life among adolescents in rural China. Clin Exp Optom 2018.

11. Pan CW, Wu RK, Liu H, et al. Types of Lamp for Homework and Myopia among Chinese

School-Aged Children. Ophthalmic Epidemiol 2018;25:250-6.

12. Pan CW, Qiu QX, Qian DJ, et al. Iris colour in relation to myopia among Chinese

school-aged children. Ophthalmic Physiol Opt 2018;38:48-55.

13. American academy of Ophthalmology Pediatric Ophthalmology/ Strabismus Panel (2012):

Preferred practice pattern guidelines. Amblyopia. San Francisco, CA: American Academy

of Ophthalmology, www. aao. org/ppp.

14. Pi LH, Chen L, Liu Q, et al. Prevalence of eye diseases and causes of visual impairment in

school-aged children in Western China. J Epidemiol 2012;22:37-44.

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15. Xiao O, Morgan IG, Ellwein LB, et al. Prevalence of Amblyopia in School-Aged Children

and Variations by Age, Gender, and Ethnicity in a Multi-Country Refractive Error Study.

Ophthalmology 2015;122:1924-31.

16. Shapira Y, Machluf Y, Mimouni M, et al. Amblyopia and strabismus: trends in prevalence

and risk factors among young adults in Israel. Br J Ophthalmol 2018;102:659-66.

17. Williams C, Northstone K, Howard M, et al. Prevalence and risk factors for common vision

problems in children: data from the ALSPAC study. Br J Ophthalmol 2008;92:959-64.

18. Robaei D, Rose KA, Ojaimi E, et al. Causes and associations of amblyopia in a

population-based sample of 6-year-old Australian children. Arch Ophthalmol

2006;124:878-84.

19. Robaei D, Kifley A, Rose KA, et al. Impact of amblyopia on vision at age 12 years: findings

from a population-based study. Eye (Lond) 2008;22:496-502.

20. Ohlsson J, Villarreal G, Sjöström A, et al. Visual acuity, amblyopia, and ocular pathology in

12- to 13-year-old children in Northern Mexico. J AAPOS 2003;7:47-53.

21. Ohlsson J, Villarreal G, Sjöström A, et al. Visual acuity, residual amblyopia and ocular

pathology in a screened population of 12-13-year-old children in Sweden. Acta Ophthalmol

Scand 2001;79:589-95.

22. Zhao J, Pan X, Sui R, et al. Refractive Error Study in Children: results from Shunyi District,

China. Am J Ophthalmol 2000;129:427-35.

23. He M, Zeng J, Liu Y, et al. Refractive error and visual impairment in urban children in

southern china. Invest Ophthalmol Vis Sci 2004;45:793-9.

24. Lu P, Chen X, Zhang W, et al. Prevalence of ocular disease in Tibetan primary school

children. Can J Ophthalmol 2008;43:95-9.

25. Fu J, Li SM, Liu LR, et al. Prevalence of amblyopia and strabismus in a population of

7th-grade junior high school students in Central China: the Anyang Childhood Eye Study

(ACES). Ophthalmic Epidemiol 2014;21:197-203.

26. Yu CB, Fan DS, Wong VW, et al. Changing patterns of strabismus: a decade of experience

in Hong Kong. Br J Ophthalmol 2002;86:854-6.

27. Chia A, Roy L, Seenyen L. Comitant horizontal strabismus: an Asian perspective. Br J

Ophthalmol 2007;91:1337-40.

28. Zhu H, Yu JJ, Yu RB, et al. Association between childhood strabismus and refractive error

in Chinese preschool children. PloS One 2015;10:e0120720.

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For peer review onlyPrevalence of amblyopia and strabismus in Hani school

children in rural southwest China: a cross-sectional study

Journal: BMJ Open

Manuscript ID bmjopen-2018-025441.R2


Date Submitted by the Author: 10-Nov-2018

Complete List of Authors: Zhu, Hui; The First Affiliated Hospital with Nanjing Medical University, OphthalmologyPan, Chenwei; School of Public Health, Medical College of Soochow University, Sun, Qigang; The First Affiliated Hospital with Nanjing Medical University, OphthalmologyHuang, Dan; The First Affiliated Hospital with Nanjing Medical University, OphthalmologyFu, ZhuJun; Nanjing Children’s Hospital, Nanjing, OphthalmologyWang, Jing; Jinling vision care center for children and adolescentsChen, XueJuan; The First Affiliated Hospital with Nanjing Medical University, OphthalmologyWang, Zijing; The First Affiliated Hospital with Nanjing Medical University, OphthalmologyLiu, Hu; The First Affiliated Hospital with Nanjing Medical University, Ophthalmology

<b>Primary Subject Heading</b>: Ophthalmology

Secondary Subject Heading: Epidemiology, Paediatrics, Public health

Keywords: Strabismus < OPHTHALMOLOGY, Paediatric ophthalmology < OPHTHALMOLOGY, EPIDEMIOLOGY, PUBLIC HEALTH


BMJ Open



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Title page

Prevalence of amblyopia and strabismus in Hani school children in rural

southwest China: a cross-sectional study

Hui Zhu,1 Chenwei Pan,2 Qigang Sun,1 Dan Huang,1 Zhujun Fu,3 Jing Wang,4

Xuejuan Chen,1 Zijing Wang,1 Hu Liu1*








83275171.

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ABSTRACT

Purpose: To determine the prevalence rate of amblyopia and strabismus in Chinese

Hani ethnic school-aged children.


located in southwest China, were invited for comprehensive eye examinations

performed by experienced ophthalmologists and optometrists, including visual acuity,

ocular alignment and movements, cycloplegic autorefraction, anterior segment, and

fundus examinations. Standard definitions of amblyopia and strabismus were applied

to calculate their prevalence rate.

Results: A total of 1656 (91.0% response rate) grade 1 Hani students and 1394

(92.8% response rate) grade 7 Hani students participated in the study. Amblyopia was

present in 25 Hani students (0.82%, 95% CI 0.55%-1.20%), with no significant

differences in grade (p=0.42) and gender (p=0.69). Among these 25 amblyopic

children, 17 had unilateral amblyopia and 8 had bilateral amblyopia, including 16

anisometropic, 8 binocular refractive, and 1 strabismic. Strabismus was found in 59

Hani students (1.93%, 95% CI 1.50%-2.48%), including 47 with intermittent

exotropia, 6 with constant exotropia, 5 with constant esotropia, and 1 with unilateral

superior oblique palsy. The prevalence rate of strabismus was higher in grade 7

students than grade 1 students with borderline significance (2.44% vs. 1.50%,

p=0.07), but was similar by gender (2.16% in boys vs. 1.68% in girls, p=0.36).




Refractive error is the major cause for amblyopia and intermittent exotropia is the

primary strabismus type.

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This is a large school-based cohort study conducted in Mojiang Hani

Autonomous County, rural southwest China.

Mojiang has 13.5% of the total Chinese Hani population, and an enrollment rate


A total of 1656 grade 1 Hani students and 1394 grade 7 Hani students were

analyzed, with high study participation rate (>90%).

Standard definitions of amblyopia and strabismus were applied.

The prevalence estimates might be biased as small percent of students did not

participate, and children who dropped out of schools or were not enrolled into

regular schools were not included.

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INTRODUCTION



through adulthood if left untreated. To develop a rational policy for early detection

and management of amblyopia and strabismus, it is necessary to conduct

population-based epidemiologic studies to estimate their prevalence in children. With

standard study design and diagnosis criteria, the Multi-ethnic Pediatric Eye Disease

Study (MEPEDS)1,2, the Baltimore Pediatric Eye Disease Study (BPEDS)3, the

Strabismus, Amblyopia, and Refractive Error in Singaporean children Study

(STARS)4, the Sydney Paediatric Eye Disease Study (SPEDS)5, the Nanjing Pediatric

Vision Project (NPVP)6, the Anyang childhood eye study (ACES)7 and the Yuhuatai

Pediatric Eye Disease Study (YPEDS)8 reported prevalence rates ranging from 0.8%

to 2.6% for amblyopia and 0.8% to 5.7% for strabismus. This large variation in

reported prevalence rate most likely is due to differences in the characteristics of

study populations, particularly the ethnicity of participants.

The Hani, an ethnic minority group, is one of the 56 officially recognized nationalities

in China. Over 90% of Hani people live in Yunnan Province, rural southwest China,

which is located across mountains and is less prosperous than the eastern and southern

regions in China. Previous Chinese amblyopia or strabismus prevalence studies

mainly focused on the Han nationality, which accounts for 91.5% of the Chinese

population, and these studies did not include the Hani nationality. However, data from

Han populations could not be extrapolated to Hani children because of potential

impact of ethnic variations and health care disparities on prevalences of eye diseases.

Our study was designed to assess the prevalence of amblyopia and strabismus among

Chinese Hani school children using standard methodology and definitions. This

analysis is part of the Mojiang Myopia Progression Study (MMPS).

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METHODS


MMPS is a school-based cohort study designed to longitudinally assess the onset and


grade 1 and grade 7 students in Mojiang Hani Autonomous County, Yunnan Province,

rural southwest China9–12. The baseline eye examination was conducted in 2016 and

all grade 1 students from elementary schools and grade 7 students from middle

schools in Mojiang were invited to participate in this study. This paper used data from

this baseline eye examination in grade 1 and grade 7 Hani students.




Mojiang and 13.5% of the total Chinese Hani population. The compulsory 9-year

mandatory education system is well executed in Mojiang with an enrollment rate of

99% for elementary and middle schools in 2014. Thus, school-based samples in

Mojiang are highly representative of this school-aged population.







A questionnaire was completed by the parents or legal guardians of the children to

collect detailed information regarding ethnicity and medical history. Comprehensive

eye examinations were performed by experienced ophthalmologists and optometrists.

Uncorrected visual acuity (UCVA) was measured using the Early Treatment Diabetic

Retinopathy Study visual acuity (VA) chart at a distance of 4 m. For children with

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UCVA 20/40 or at-least two-line interocular difference, subjective optometry was ≤

performed to obtain best corrected VA (BCVA). Ocular alignment was assessed by

using the Hirschberg light reflex test, the cover-uncover test and the alternate cover

test. Cover test was performed by using fixation targets at both distance (6 m) and

near (33 cm). Binocular and monocular ocular movements were examined at nine

diagnostic positions of gaze with the head in a stationary position. Strabismus

magnitude was measured in prism diopters (PD) using the simultaneous prism and

cover test. Each participant's refractive status was measured after cycloplegia using an

autorefractor (RM-8000; Topcon Corp., Tokyo, Japan) by optometrists. For

cycloplegia, each participant was first administered two drops of 1% cyclopentolate

(Alcon) after a 5-minute interval. Thirty minutes later, a third drop was administered

if pupillary light reflex was still present or the pupil size was less than 6.0 mm. Other

ocular examinations including slit lamp examination, digital retinal photographs,

ocular biometry, and optical coherence tomography, were conducted to exclude any

abnormalities precluding normal vision.

Definitions

Unilateral amblyopia was defined as at least 2-line inter-ocular difference between

eyes with BCVA ≤20/32 (≥0.2 logMAR) in the worse eye and presence of at least

one of the following unilateral amblyopia risk of factors: (1) strabismus on

examination; (2) previous strabismus surgery; (3) anisometropia consistent with the

worse eye ( ≥ 1.00D spherical equivalent (SE) anisohyperopia, ≥ 3.00D SE

anisomyopia, or ≥1.50D anisoastigmatism); (4) past or present obstruction of visual

axis (e.g., cataract, corneal opacity, ptosis, eyelid hemangioma) which could not

explain the vision loss directly2,13. Bilateral amblyopia was defined as BCVA in both

eyes <20/40 (>0.3 logMAR) with bilateral ametropia (≥4.00D SE hyperopia, or ≥

6.00D SE myopia, or ≥ 2.50D astigmatism) or with past or present bilateral

obstruction of visual axis (see above) which could not directly explain the vision

loss2,13.

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Strabismus was defined present if any tropia was present at distance or near, with or

without spectacles and was classified according to the primary direction (esotropia,

exotropia, and vertical) of the tropia. Strabismus is considered as constant tropia if

constant at both near and distance fixation, otherwise it is considered as intermittent

tropia.


All data were analyzed using SPSS 13.0 (IBM, China) and 2-sided p<0.05 was

considered statistical significant. Prevalence rate for amblyopia and strabismus was

calculated as the percent of children with amblyopia or strabismus among all the Hani

children evaluated. Age- and sex- specific prevalence rate for amblyopia and

strabismus was calculated; Fisher exact test was used to compare the prevalence rate

between grade 1 and grade 7 and between boys and girls. 95% confidence intervals

(CIs) for prevalence rates were calculated using Wilson method.

Patient and Public Involvement

Patients and public were not involved in any aspects of the study including the

development of study question, study design, conduct of the study and dissemination

of results.

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RESULTS

Study population

A total of 1656 (91.0% response rate) grade 1 Hani students aged 7-8 years and 1394

(92.8% response rate) grade 7 Hani students aged 13-14 years participated in the

study. The mean age was 7.7 ± 0.6 and 13.8 ± 0.7 years for grade 1 and 7 students

respectively. There was similar percentage of boys among grade 1 students and grade

7 students (54.6% vs. 51.5%).


Based on the findings from comprehensive ocular examinations of the 3050 Hani



(0.65%, 95% CI 0.34%-1.22%). The prevalence of amblyopia did not differ between

grade 1 and grade 7 (p=0.42), or between boys (0.74%, 95% CI 0.42%-1.28%) and

girls (0.91%, 95% CI 0.53%-1.54%; p=0.69). Unilateral amblyopia was diagnosed in

17 children (0.56%, 95% CI 0.35%-0.89%), and bilateral amblyopia was diagnosed in

8 children (0.26%, 95% CI 0.13%-0.51%). Table 1 summarizes the prevalence of

unilateral and bilateral amblyopia by different causes. Anisometropia was the cause in

16 of the 17 children (94.1%) with unilateral amblyopia and ametropia was the cause

in all bilateral amblyopia. Nearly half of the 33 amblyopic eyes (51%, 17/33) had

severe amblyopia (BCVA ≤20/100) and one third (27%, 9/33) had BCVA ≤20/160.

Based on the questionnaire responses from their parents or legal guardians, no

children had been previously diagnosed with amblyopia or treated for amblyopia.

Table 1. Prevalence of unilateral and bilateral amblyopia by different causes in Hani students (N=3050)Amblyopia type With amblyopia, n Prevalence (95% CI) (%)Unilateral 17 0.56 (0.35-0.89)Strabismic 1 0.03 (0.00-0.18)Anisometropic 16 0.52 (0.32-0.84)≥1.00 D SE anisohyperopia 5 0.16 (0.07-0.37)≥3.00 D SE anisomyopia 4 0.13 (0.05-0.33)

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≥1.50 D anisoastigmatism 6 0.20 (0.09-0.43)≥ 1.00 D SE anisohyperopia+ ≥ 1.50 D

anisoastigmatism1 0.03 (0.00-0.18)

Bilateral 8 0.26 (0.13-0.51)Ametropic 8 0.26 (0.13-0.51)≥4.00 D SE hyperopia 3 0.10 (0.03-0.29)≥6.00 D SE myopia 1 0.03 (0.00-0.18)≥2.50 D astigmatism 4 0.13 (0.05-0.33)



A total of 59 (1.93%, 95% CI 1.50%-2.48%) children were found to have strabismus,


(2.44%, 95% CI 1.75%-3.38%). The prevalence of strabismus was higher in grade 7

students than grade 1 students with borderline significance (2.44% vs. 1.50%,

p=0.07), but was similar in boys and girls (2.16% and 1.68% respectively, p=0.36).

Of the 59 strabismic students, 47 (80%) had intermittent exotropia, 6 (10%) had

constant exotropia, 5 (8%) had constant esotropia, 1 (2%) had unilateral superior

oblique palsy, 5 of the intermittent exotropia and 1 of constant esotropia had bilateral

inferior oblique muscle overaction. The distribution of strabismus magnitude in 58

students with horizontal strabismus is shown in Table 2. Nearly one third of the

horizontal strabismic students had more than 30 PD strabismus magnitude at near or

at distance. Based on the questionnaire responses from the parents or legal guardians,

no children had been previously diagnosed with or treated for strabismus.

Table 2. Distribution of strabismus magnitude in 58 Hani students with horizontal strabismusStrabismus magnitude n (%)At near

1-9 PD 5 (9%)10-30 PD 31 (53%)>30 PD 22 (38%)

At distance1-9 PD 28 (48%)10-30 PD 14 (24%)>30 PD 16 (28%)

PD, prism diopter.

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DISCUSSION

In this school-based sample of Hani school children in China, we found a low (0.82%)

prevalence rate of amblyopia. Amblyopia definitions can have significant impact on

amblyopia prevalence estimate. Using the same standard amblyopia definition as

MEPEDS, BPEDS, STARS, SPEDS, NPVP, ACES and YPEDS studies, the

amblyopia prevalence in Hani children was lower than all these studies, including

these in Chinese Han children (Table 3). Compared with a study from Western China

in school children that used different amblyopia definition from this study14, the

amblyopia prevalence rate in Hani school children was lower.

The multi-country Refractive Error Study in Children (RESC) study15, also using

different amblyopia definition, reported higher amblyopia prevalence rates in

Hispanic and Chinese (predominantly Han) school children and lower amblyopia

prevalence rates in African and south Asian (Indian) school children than that in this

study15. General loss of pigmentation in Hispanic and Chinese Han people might be

associated with high amblyopia prevalence, because that many studies have reported

the associations between low pigmentation and refractive errors, especially

astigmatism16–18. Chinese Hani people live near south Asia and have more

pigmentation than Chinese Han and Hispanic, which might be a possible reason for

the low amblyopia prevalence in Hani group. In a recent Israel study among young

adults, the prevalence of amblyopia was 0.8% in the population born between 1986

and 1994, which is similar to the rate in our study19. Besides the difference in

amblyopia definition, the implementation of mandatory vision screening and the

universal healthcare provided to all Israel citizens by legislation might explain the low

prevalence rate of amblyopia in Israel.

In this study, we found that age and gender was not significantly associated with

amblyopia prevalence rate while refractive error, particularly anisometropia, was the

major cause for amblyopia. These findings are consistent with the results from

MEPEDS, STARS, SPEDS, NPVP, ACES and YPEDS.

Globally, the prevalence rate of strabismus (1.90%) in the Hani sample was lower

than rates in school children from other countries, including England (2.3%)20,

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Australia (2.7%-2.8%)21,22, Mexico (2.3%)23, and Sweden (2.7%)24. The strabismus

prevalence rate in our study was also lower than most Chinese school children in

China, including 2.8% from Shunyi (representative of rural northern China)25, 3.0%

from Guangzhou (representative of urban southern China)26, 2.5% from Maqin

(representative of rural Tibetan area)27, and 5.0% from Anyang (representative of

rural central China)28. The strabismus prevalence rate in our study was also lower than

those from studies in preschool children (Table 3). Differences in genetic

susceptibility, environmental factors, and lifestyle may contribute to the lower rate of

strabismus in Chinese Hani students.

Table 3. Prevalence of amblyopia and strabismus in different studiesStudy Country Age, years (n) Ethnicity Prevalence of

amblyopia*Prevalence of strabismus

MEPEDS, 2008 United States 2.5-6 (3350) African American (1663)Hispanic/Latino (1687)

1.5%2.6%

2.5%2.4%

MEPEDS, 2013 United States 2.5-6 (1883) Asian American (938)Non-Hispanic White (945)

1.8%1.8%

3.6%3.2%

BPEDS, 2009 United States 2.5-6 (1546) Non-Hispanic White (673)African American (873)

1.8%0.8%

3.3%2.1%

STARS, 2010 Singapore 2.5-6 (1682) Singaporean Chinese 1.2% 0.8%SPEDS, 2012 Australia 2.5-6 (1422) predominantly white 1.9% N/A**

NPVP, 2015 China 3-6 (5667) Chinese Han 1.2% 5.7%ACES, 2014 China 6-9 (2893) Chinese Han 1.0 % N/A**

YPEDS, 2018 China 3-4 (1695) Chinese Han 1.47% N/A**

MMPS, 2018 China 7-8 (2432),13-14 (2346)


*Same definition of amblyopia was used. ** No strabismus data.

Our study found that about 90% of the strabismus was exotropia. Previous studies

have found that east Asian populations had higher exotropia : esotropia ratio than

Caucasians, which might be due to less hyperopia in east Asian population than

Caucasians1–4,6,22,24,29,30. Our previous research found that exotropia was associated

with astigmatism, myopia and low to moderate hyperopia, while esotropia was

associated with hyperopia in a dose-response manner31. Thus, difference in refractive

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error distribution may be responsible for higher exotropia : esotropia ratio in the study

compared with other studies. Consistent with the MEPEDS and NPVP studies that

found higher prevalence of strabismus in older preschool children1,2,6, our study found

that prevalence rate of strabismus was higher in grade 7 students than grade 1

students, although the difference is only borderline significant (2.44% vs. 1.50%,

p=0.07). This finding suggests that strabismus might increase with age. Consistent

with other studies2,5,6,20–22, our study did not find any significant difference in

prevalence rate of strabismus between boys and girls.

Our study has some limitations. First, the study is school-based rather than

population-based. The prevalence estimates might be biased as small percent of

school children did not participate in this study, and children who dropped out of

schools or did not attend regular schools were not included into the study. However,

we expect that this small percent of children not in our study will not substantially

bias our prevalence estimate. Second, small-angle or intermittent strabismus may have

been missed given the nature of both conditions. Third, the study used the cycloplegic

autorefraction instead of cycloplegic retinoscopy, and it could potentially bias the

refractive error measure. However, a recent study among school children found that

the two methods had a strong correlation and agreement, and the differences between

their measures were clinically insignificant32. Finally, information on the history of

amblyopia or strabismus was collected by questionnaires, which might be potentially

inaccurate due to recall biases.

CONCLUSIONS

In this large school-based study of Chinese Hani school children, we found that

amblyopia affects 0.82% children and strabismus affects 1.93% children. These

prevalence rates are both lower than those previously reported for Chinese Han

children and for many other racial/ethnic populations from non-China studies. Further

studies are needed to explore why Chinese Hani children have low prevalence of

amblyopia and strabismus.

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CP. Performed the experiments: HZ, QS, DH, ZF, and JW. Analyzed the data: HL,

HZ, CP, XC, and ZW. Contributed reagents/materials/analysis tools: HL, HZ, CP, and

DH. Wrote the paper: HL and HZ.




81773449, No. 81560169, No. 81673198 and No. 81803258).


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REFERENCES1. Multi-ethnic Pediatric Eye Disease Study Group. Prevalence of amblyopia and

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2. McKean-Cowdin R, Cotter SA, Tarczy-Hornoch K, et al. Prevalence of amblyopia or strabismus in asian and non-Hispanic white preschool children: multi-ethnic pediatric eye disease study. Ophthalmology 2013;120:2117-24.

3. Friedman DS, Repka MX, Katz J, et al. Prevalence of amblyopia and strabismus in white and African American children aged 6 through 71 months the Baltimore Pediatric Eye Disease Study. Ophthalmology 2009;116:2128-34.e1-2.

4. Chia A, Dirani M, Chan YH, et al. Prevalence of amblyopia and strabismus in young singaporean chinese children. Invest Ophthalmol Vis Sci 2010;51:3411-7.

5. Pai AS, Rose KA, Leone JF, et al. Amblyopia prevalence and risk factors in Australian preschool children. Ophthalmology 2012;119:138-44.

6. Chen X, Fu Z, Yu J, et al. Prevalence of amblyopia and strabismus in Eastern China: results from screening of preschool children aged 36-72 months. Br J Ophthalmol 2016;100:515-9.

7. Fu J, Li SM, Li SY, et al. Prevalence, causes and associations of amblyopia in year 1 students in Central China : The Anyang childhood eye study (ACES). Graefes Arch Clin Exp Ophthalmol 2014;252:137-43.

8. Huang D, Chen X, Zhu H, et al. Prevalence of amblyopia and its association with refraction in Chinese preschool children aged 36-48 months. Br J Ophthalmol 2018;102:767-71.

9. Pan CW, Wu RK, Li J, et al. Low prevalence of myopia among school children in rural China. BMC Ophthalmol 2018;18:140.

10. Pan CW, Wu RK, Wang P, et al. Reduced vision, refractive errors and health-related quality of life among adolescents in rural China. Clin Exp Optom 2018;101:758-63.

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12. Pan CW, Qiu QX, Qian DJ, et al. Iris colour in relation to myopia among Chinese school-aged children. Ophthalmic Physiol Opt 2018;38:48-55.

13. American academy of Ophthalmology Pediatric Ophthalmology/ Strabismus Panel (2012): Preferred practice pattern guidelines. Amblyopia. San Francisco, CA: American Academy of Ophthalmology, www. aao. org/ppp.

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14. Pi LH, Chen L, Liu Q, et al. Prevalence of eye diseases and causes of visual impairment in school-aged children in Western China. J Epidemiol 2012;22:37-44.

15. Xiao O, Morgan IG, Ellwein LB, et al. Prevalence of Amblyopia in School-Aged Children and Variations by Age, Gender, and Ethnicity in a Multi-Country Refractive Error Study. Ophthalmology 2015;122:1924-31.

16. Schweigert A, Lunos S, Connett J, et al. Changes in refractive errors in albinism: a longitudinal study over the first decade of life. J AAPOS 2018.

17. Yahalom C, Tzur V, Blumenfeld A, et al. Refractive profile in oculocutaneous albinism and its correlation with final visual outcome. Br J Ophthalmol 2012;96:537-9.

18. Wildsoet CF, Oswald PJ, Clark S. Albinism: its implications for refractive development. Invest Ophthalmol Vis Sci 2000;41:1-7.

19. Shapira Y, Machluf Y, Mimouni M, et al. Amblyopia and strabismus: trends in prevalence and risk factors among young adults in Israel. Br J Ophthalmol 2018;102:659-66.

20. Williams C, Northstone K, Howard M, et al. Prevalence and risk factors for common vision problems in children: data from the ALSPAC study. Br J Ophthalmol 2008;92:959-64.

21. Robaei D, Rose KA, Ojaimi E, et al. Causes and associations of amblyopia in a population-based sample of 6-year-old Australian children. Arch Ophthalmol 2006;124:878-84.

22. Robaei D, Kifley A, Rose KA, et al. Impact of amblyopia on vision at age 12 years: findings from a population-based study. Eye (Lond) 2008;22:496-502.

23. Ohlsson J, Villarreal G, Sjöström A, et al. Visual acuity, amblyopia, and ocular pathology in 12- to 13-year-old children in Northern Mexico. J AAPOS 2003;7:47-53.

24. Ohlsson J, Villarreal G, Sjöström A, et al. Visual acuity, residual amblyopia and ocular pathology in a screened population of 12-13-year-old children in Sweden. Acta Ophthalmol Scand. 2001;79:589-95.

25. Zhao J, Pan X, Sui R, et al. Refractive Error Study in Children: results from Shunyi District, China. Am J Ophthalmol 2000;129:427-35.

26. He M, Zeng J, Liu Y, et al. Refractive error and visual impairment in urban children in southern china. Invest Ophthalmol Vis Sci 2004;45:793-9.

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27. Lu P, Chen X, Zhang W, et al. Prevalence of ocular disease in Tibetan primary school children. Can J Ophthalmol 2008;43:95-9.

28. Fu J, Li SM, Liu LR, et al. Prevalence of amblyopia and strabismus in a population of 7th-grade junior high school students in Central China: the Anyang Childhood Eye Study (ACES). Ophthalmic Epidemiol 2014;21:197-203.

29. Yu CBO, Fan DSP, Wong VWY, et al. Changing patterns of strabismus: a decade of experience in Hong Kong. Br J Ophthalmol 2002;86:854-6.

30. Chia A, Roy L, Seenyen L. Comitant horizontal strabismus: an Asian perspective. Br J Ophthalmol 2007;91:1337-40.

31. Zhu H, Yu JJ, Yu RB, et al. Association between childhood strabismus and refractive error in Chinese preschool children. PloS One 2015;10:e0120720.

32. Hashemi H, Khabazkhoob M, Asharlous A, et al. Overestimation of hyperopia with autorefraction compared with retinoscopy under cycloplegia in school-age children. Br J Ophthalmol 2018.

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