Shanghai Child and Adolescent Large-scale Eye Study -High Myopia Registration
Conditions: High Myopia, Pathologic Myopia
Sponsor: Shanghai Eye Disease Prevention and Treatment Center

Shanghai Child and Adolescent Large-
scale Eye Study  
–High Myopia Registration
Implementation Plan 
(Internal Information) 
2018

1. introduction 
1.1 Overview of myopia and high myopia 
Myopia is the most common eye disease in the world 
[1].  Among them, 
the incidence and prevalence of myopia are highest in developed 
countries and regions in East and Southeast Asia 
[2-8].  It is predicted 
that by 2050, global myopia patients would reach 5 billion, 1 billion 
of which were high myopia 
[9].  In developed countries and regions in 
East and Southeast Asia, the prevalence of myopia in high school 
graduates is as high as 80% to 90% 
[2].  A study in Taiwan showed that 
more than 80% of adolescents suffered from myopia when they graduated 
from high school, 10% of whom were high myopia 
[10].  Another study which 
focused on university students in Shanghai showed that 95.5% of college 
students suffered from myopia, and 19.5% of them were high myopia 
[11].  
In stark contrast, the prevalence of myopia in the same age in western 
developed countries is between 20% and 40% 
[2, 12-14].  In less developed 
countries and regions of the world, the incidence of myopia in young 
people is about 5% to 10% 
[15-18] due to the low level of education. 
 
At present, the etiology and pathogenesis of myopia and high myopia 
are still unclear.  Environmental and genetic factors are involved in 
the development of myopia and high myopia.  Among them, the level of 
education and outdoor activity time are closely related to the 
development of myopia and high myopia.  At present, most studies 
believe that the higher the education level, the higher the incidence 
of myopia and the deeper the degree of myopia 
[19-21].  In addition, most 
studies suggest that outdoor activities was a protective factor for 
myopia, and increasing outdoor activity time could reduce the incidence 
of myopia 
[22-25].  Also, some studies have shown that the age of onset 
of myopia was closely related to high myopia 
[26-27].  Furthermore, genes 

may also be closely related to the occurrence of myopia and high myopia.  
At least 19 myopic loci 
[28] have been identified through family studies 
and twin studies till now.  With the completion of the Human Genome 
Project, genome-wide association analysis technology is becoming more 
and more mature, and more and more related genes and mutation sites 
have been elucidated 
[28], but the pathogenic genes of myopia are still 
not completely clear.  In addition, the genes related to pathological 
myopia and fundus lesions are currently unclear. In recent studies, 
high myopia and pathological myopia are not strictly differentiated 
(pathological myopia is defined by diopter or axial length alone).  
Therefore, genes related to pathological myopia need further research, 
in order to judge whether high myopia and pathological myopia are two 
different diseases at genetic level or different states controlled by 
the same genes. 
 
1.2 Relationship between high myopia and pathological myopia 
The fundus of patients with high myopia is often accompanied by a 
series of pathological changes, such as posterior scleral staphyloma, 
retinal choroidal atrophy, lacquer crack, choroidal neovascularization, 
macular hemorrhage, Fuchs plaque, retinal palpebral fissure, retinal 
tear, retinal detachment. These pathological changes are important 
causes of decreased vision and even blindness. Some studies have shown 
that macular degeneration caused by myopia has become a major cause of 
blindness and low vision 
[29-32].  In Jing'an District of Shanghai, high 
myopia with macular degeneration has leapt to the first place in adult 
blindness 
[29].  A study in Beijing showed that pathological myopia has 
become the leading cause of blindness and visual impairment in the 40-
49 age group 
[30]. 
 

Although high myopia is closely related to pathological myopia, 
and most patients with pathological myopia are highly myopic, high 
myopia is not equivalent to pathological myopia. The change of diopter 
and axial length do not fully reflect the characteristics of 
pathological myopia.  Some patients with high myopia have no definite 
fundus lesions, and some non-high myopia patients may also have 
posterior scleral staphyloma, retinochoroid atrophy and other 
complications.  At present, Ohno-Matsui K et al define pathological 
myopia as: myopic macular degeneration ≥ 2 (diffuse retinochoroid 
atrophy), or additional lesions (lacquer cracks, CNV, Fuchs plaque), 
or posterior scleral staphyloma 
[33].  In this definition of pathological 
myopia, we focus on fundus lesions caused by myopia, and do not 
emphasize diopter and axial length. 
 
At present, there are still many unknowns about the relationship 
between high myopia and pathological myopia. The process of developing 
simple high myopia in children and adolescents as pathological myopia 
is still unclear.  Does high myopia eventually evolve into pathological 
myopia? Are pathological myopia and high myopia different stages of 
the same disease or two different diseases? Which fundus changes can 
predict the occurrence of pathological myopia? These problems need 
further exploration. 
 
1.3 Morphology and visual function changes in fundus of children with 
high myopia 
At present, there are few studies on the changes of fundus 
morphology and visual function in children with high myopia. And long-
term follow-up studies are also lacking. 
 

Morphological studies suggest that the common fundus changes in 
children with high myopia include β-PPA, optic disc tilt, etc., but 
the incidence of posterior scleral staphyloma and retinochoroid atrophy 
is low in childhood 
[34-35]. Furthermore, some studies have suggested that 
diffuse retinohoroid atrophy around the optic disc in childhood could 
easily develop into pathological myopia 
[36] in adulthood.  In addition, 
thinning of the retina, choroid, and sclera is also present in children 
with myopia and high myopia 
[37-40].  In addition to the fundus of the 
posterior pole, there are also multiple lesions 
[41-44] in the peripheral 
fundus.  Some studies considered that peripheral fundus lesions such 
as lattice-like degeneration, non-compressive whitening, and retinal 
tears are more common in children with high myopia 
[42]. 
 
Corresponding to structural changes, there are also changes in 
micro-field and electrophysiology of patients with high myopia 
[45-52].  
However, there is few studies focusing on children and adolescents with 
high myopia 
[49-50], and no long-term follow-up studies has been reported.  
There are still many unknowns in the early morphological changes, 
evolution process and visual function of high myopia, which deserve 
further exploration. 
 
1.4 The direction of this research 
A． Follow-up study of morphological changes in the fundus of children 
with high myopia; 
B． Follow-up study of visual function changes in children with high 
myopia; 
C． Etiological studies related to high myopia in children; 
D． Follow-up study of quality of life, psychology, behavior, and 
social interactions in children with high myopia. 
 

2. Goal and design 
2.1 Research objectives 
A．To observe the fundus changes in the posterior pole (morphology, 
thickness, asymmetry, blood flow density, etc) with the myopia 
progression. 
B．To observe morphological changes in choroid and peripheral region 
of retina with myopia progression. 
C. To observe changes of visual function (contrast sensitivity, 
Microperimetry, etc) with myopia progression. 
D. To detect the susceptibility genes related to high myopia and myopic 
fundus changes; to test the levels of Vitamin D, riboflavin, TGF, IGF, 
FGF, etc. 
E. To observe the changes of living quality, psychology, behavior and 
social activities of high myopic children. 
 
2.2 Research design 
Prospective cohort study.  After completing the baseline survey, 
the planned follow-up frequency is once a year. 
 
2.3 Research cycle 
2018.06~2038.06 (at least). 
 
2.4 Expected results 
A． Registration completed a study of high myopia research for children 
and adolescents covering around 3,000 people; 
B． Establish a database information management system and workflow 
SOP file for the study of high myopia registration in children and 
adolescents; 
C． Further clarify the changes in the retinal, choroidal and scleral 

tissue structures, blood flow density, etc. in the macular area 
and the optic disc; 
D． Revealing the changes of the retina, choroid and other tissues in 
the peripheral area with the progression of myopia; 
E． To clarify the relationship between changes in the fundus structure 
and changes in visual function in the posterior pole; 
F． Further clarify the etiology and pathogenesis of high myopia, 
pathological myopia and myopic fundus lesions, and identify the 
relationship between high myopia and pathological myopia; 
G． From the perspectives of society, behavior and psychology, the 
effects of high myopia and pathological myopia on children and 
adolescents will be fully demonstrated. 
 
3. Research object 
3.1 General characteristics of the research object 
Based on the refraction development archive system that has been 
constructed in Shanghai, the list of children and adolescents with high 
myopia was selected from the database of children's refractive 
development archives information in Shanghai.  Children of different 
ages with high myopia must meet the following conditions: 
(1) 4-5 years old, equivalent spherical error ≤ -4.0 D; 
(2) 6-8 years old, equivalent spherical error ≤ -6.0 D; 
(3) 9-18 years old, equivalent spherical error ≤ -8.0 D. 
 
3.2 Sample size 
A total of 1.25 million children and adolescents are currently 
registered, 4,006 (0.32%) of which  meet the entry requirements.  
Among the 4~5 year olds, there are 815 people with SE≤-4D; 842 people 
with SE≤-6 D among the 6~8 year olds; 2349 people with SE≤-8D among 
the people aged 9 and over .  Taking into account the 50% non-response 

and the proportion of the exclusion, the initial registration number 
is about 2,000. 
 
3.3 Source of study object 
Children and adolescents who meet the inclusion criteria in the 
Shanghai Children's Refractive Development Archives Information 
Database System. 
 
3.4 Inclusion criteria 
A. Children and adolescents between the ages of 4 and 18 years old, 
SE ≤ -4 D under 5 years old, SE ≤ -6 D at 6-8 years old, SE ≤ -
8 D over 9 years old;   
B. No eye disease, good general condition, can cooperate with the 
examiner; 
C. Obtaining the consent of the child and his/her guardian; 
D. Long-term residence in this city, there is no plan to move out of 
this city in the short term. 
 
3.5 Exclusion criteria 
A. Amblyopia (best corrected visual acuity (BCVA) less than 0.8 for 
children over 6 years old, BCVA less than 0.63 for children 6 years 
old and younger) and strabismus; 
B. Secondary myopia, genetic disease or connective tissue-related 
myopia; 
C. Moderate or severe ptosis; 
D. Congenital cataract, glaucoma; 
E. Other fundus diseases other than myopic related fundus lesions; 
F. Intraocular or refractive surgery history; 
G. The refractive medium is turbid, and it is impossible to take a 

clear fundus image; 
H. Unable to cooperate with fundus image shooting and other 
examination; 
I. Do not receive cycloplegia or have contraindications; 
J. Poor overall condition, unable to follow up for a long time; 
K. The child or the guardian refuses to participate in the research; 
L. Other cases in which the researcher judges that it is not suitable 
for participation in the study. 
 
4. Data collection 
4.1 Preparatory work 
A． Establish 
Shanghai 
Children 
and 
Adolescents 
High 
Myopia 
Registration Information System and Workflow: a set of information 
function modules including appointment, real-time collection of 
exam data, online feedback of exam results, daily consultation 
contact and data management analysis. And then establish the 
workflow SOP file; 
B． Train physicians, optometrists and other relevant staff responsible 
for the research; 
C． Print promotional materials, questionnaires, informed consent forms 
and examination flow charts; 
D． Contact the children and adolescents in the Shanghai Children's 
Refractive Development Archives Information Database System through 
their school and use science lectures, WeChat official accounts, 
Weibo(Chinese version of Twitter), paper leaflets to promote the 
harm of high and pathological myopia to children, adolescents and 
their parents, as well as introduction of the content of this study, 
the participants' benefits and potential risks; 
E． Sign an informed consent form to collect information on the 

participants; 
F． The appointment is registered through the information system. 
 
4.2 Examination process 
The brief process is as follows: Identity information registration > 
height, weight > naked eye vision & wearing vision > axial length > 
intraocular pressure > slit lamp anterior segment examination > 
Microperimetry (selected) > cycloplegia > Autorefraction and 
subjective refraction > Pentacam, SS-OCT(Topcon), wide-angle 
OCT/OCTA(Zeiss-9000), fundus color photography + 
autofluorescence(Topcon), Ultra wide Angle fundus photography 
 (Optos), mfERG (optional), wavefront aberrations > blood sample 
collection / saliva specimens > fill out the questionnaire. 
The specific flow chart is as follows. 
 
4.3 Ophthalmology inspection project operation rules 
4.3.1 Vision test 
The eyesight examination used the ETDRS visual acuity chart (LCD 
backlit lamp, WH0701, Guangzhou Xieyi Weishikang), the test distance 
was 4 meters, and the visual target at 20/20 was the same height as 
the eye of the examinee.  The recognition time of each visual target 
is 2~3s; the eye of the subject is required to be opened normally for 
examination, and the blinking, hoeing, neck stretching and peeking are 
strictly prevented.  Vision is converted to a decimal count record.  
Visual acuity examination includes two parts: uncorrected visual acuity 
(UCVA) and corrected visual acuity (CVA).  Children who are not wearing 
glasses are only examined by UCVA, and children who wear glasses are 
required to check CVA after completing the UCVA test. 
 

 
 
 
Check flow chart 
 
 

 
4.3.2 Axis measurement 
The axial measurement was performed using an IOL Master (version 
5.02, Carl Zeiss Meditec, Germany).  Simulated eye calibration was 
needed before measurement.  Each eye was measured repeatedly for 3 
times, and the difference was less than 0.02 mm each time.  For those 
who still have large fluctuations in multiple measurements, the 
examiner needs to record it. 
 
4.3.3 Intraocular pressure measurement 
Intraocular pressure was measured using a non-contact tonometer 
(NT-4000, Nidek, USA).  Each eye was repeatedly measured 3 times and 
averaged, and the difference between each two was less than 5 mmHg.  
Those with an intraocular pressure higher than 24 mmHg should be 
recorded and added for visual field examination.   
 
4.3.4 Ophthalmologist examination 
Ophthalmologist examinations included anterior segment slit lamp 
examination 
(66 
Vision. 
Tech, 
Suzhou) 
and 
ophthalmoscopy 
examination(66 Vision. Tech, Suzhou).  The examination of the anterior 
segment slit lamp includes the eyelid, conjunctiva, cornea, anterior 
chamber, iris, pupil, lens and anterior vitreous body, which is 
completed by our senior ophthalmologist.  For patients with peripheral 
anterior chamber depth less than 1/2 corneal thickness, or acute 
inflammation of the anterior segment of the eye and other related 
diseases, it is not suitable for cycloplegia afterwards. It should be 
registered by the examining physician and suspended or excluded from 
the study.  In addition, the ophthalmologist should use corneal 
reflection, occlusion-de-covering, etc. to determine whether the 

subject has strabismus (hidden strabismus or strabismus). Those who 
were strabismus should be excluded from the study.  For those suspected 
of having fundus diseases, ophthalmoscopy (direct ophthalmoscope or 
90D) can be performed after cycloplegia, and the nature of fundus 
disease is judged by an ophthalmologist.  Participants with myopia-
related fundus lesions can be registered and included in the study, 
while participants with other fundus lesions need to be excluded after 
recorded.  Those who had other organic eye diseases were also excluded 
after recording. 
 
4.3.5 Microperimetry  
Microperimetry examinations were performed in the darkroom and 
needed to be performed prior to OCT and fundus photographic 
examinations to avoid influence by bright light. Microperimetry was 
performed using an MP1 micro-perimeter (MP-1, Nidek, Japan), and the 
Goldman III, 4-2-1 mode was selected to detect retinal light 
sensitivity within 10 degrees of the macula. There were a total of 40 
stimulation points (1°-8 stimulation points, 3°-16 stimulation points, 
5°-16 stimulation points), and the stimulation intensity of each point 
is from 20 decibels (dB) (equivalent to 20 asb) to 0 dB ( Equivalent 
to 400 asb) change. Initial stimulation intensity is 16 dB and 
stimulation duration is 100 ms.  The background light is white, 4asb.  
All participants will receive at least 5 light stimuli before the 
formal test, making them familiar with the examination process and 
minimizing the impact of learning effects.  The test procedure is as 
follows: the infrared fundus camera takes a fundus shot (45° field of 
view) and transmits it to the video monitor. The fixation target and 
the stimulation point are projected onto the retina by the liquid 
crystal display. The eyeball automatic tracking system tracks the 

position of the retina in real time to ensure each stimulation point 
in the predetermined retinal position.  Every 60 s system will project 
a super-threshold stimulus on the physiological blind spot to monitor 
the false positive reaction. If a false positive reaction occurs, it 
needs to be re-examined.  This item is optional for children under 10 
years old. 
 
4.3.6 Cycloplegia 
The cycloplegia procedure is as follows: 1 drop of 0.5% 
proparacaine (Alcaine, Alcon) is added to the conjunctival sac of each 
eye, and 2 drops of 1% cyclopentolate are added to each eye after 15 
seconds. (Cyclogyl, Alcon), 5 minutes apart.  After each drip, ask the 
participant to presse the inner canthus for a few seconds gently and 
try to take the head back posture.  The last drop of cyclopentalate 
was instilled into the conjunctival sac for 30 minutes to check for 
light reflection. If the light reflection disappeared and the pupil 
diameter was greater than 6 mm, cycloplegia was considered complete.  
If the light reflection still exists, add a third drop of cyclopentate, 
and re-examine the light reflection and pupil diameter after 20 minutes.  
If there was still light reflection, the inspector needs to record 
this.  During cycloplegia, if the participant has symptoms of ocular 
discomfort, the ophthalmologist should carefully examine it and give 
an appropriate treatment. 
 
4.3.7 Measurement of refractive state and corneal radius of curvature 
(CR) 
The refractive status and CR measurements were performed using an 
automated computer refractometer (KR-8900, Topcon, Japan), which was 
performed after ciliary muscle paralysis.  Simulated eye calibration 

needed before measurement.  Each eye was repeatedly measured three 
times to average, and if any two results differ by more than 0.5 D, 
the measurement needed to be repeated.  If there were still significant 
differences in the results of multiple measurements, the examiner 
needed to record it. 
 
4.3.8 Subjective optometry 
Children who do not wear glasses have a UCVA of less than 0.8 (less 
than 0.63 for children 6 years of age and younger) or children with 
glasses have a CVA of less than 0.8 (children under 6 years of age and 
below 0.63) need to finish a subjective optometry after cycloplegia in 
order to measure the best corrected visual acuity (BCVA).  If the BCVA 
is less than 0.8 (less than 0.63 for children aged 6 and under), or 
the degree of compliance during the examination is poor, the examiner 
should record it.  If the BCVA is less than 0.8 (children under 6 years 
of age and below is less than 0.63), further examination by an 
ophthalmologist is required to determine whether the inclusion 
conditions are still met. 
 
4.3.9 Pentacam 
Pentacam (OCULUS Optikgeratic Gmbh, Germany) was examined after 
cycloplegia.  Measurements include corneal diameter and curvature, 
anterior chamber depth and volume, anterior chamber angle, pupil 
diameter, crystal thickness, etc.  Shooting requirements: Image 
quality display "OK", crystal thickness value is available.  This item 
is optional for children under 6 years old. 
 
4.3.10 SS-OCT （Topcon） 
SS-OCT (DRI OCT Triton, Topcon, Tokyo, Japan) was examined after 

cycloplegia.  OCT location: Macular + optic disc area. Shooting mode: 
12*9 mm 3D scan mode (4 overlap) / Line scan (64 overlap) + 9 mm radial 
scan mode (16 overlap, follow up mode) + optic disc area 9 Mm radial 
scan mode (16 overlap, follow up mode) + macular area 7*7 mm 3D scan 
mode (4 overlap) + optic disc area 6*6 mm 3D scan mode (4 overlap).  
Shooting requirements: input spherical error, cylinder, axis length, 
corneal curvature radius correction magnification before shooting; 
image signal of strength 3D scan mode is not less than 50, radial scan 
mode is not lower than 60, peripheral image avoids mirror flip as much 
as possible. When shooting the disc area, we need to manually adjust 
the shooting center to the center of the disc. If the image quality is 
affected by blinking or eye movement during shooting, you need to re-
shoot. If you still can't meet the requirements, you need to record 
it.  SS-OCT comes with a fundus color photograph. The shooting position 
is required to be consistent with the SS-OCT scanning position and to 
avoid eyelids, eyelashes and hair occlusion. Dark areas are avoided in 
the image, and the image quality is not less than 90. This item is 
optional for children under 6 years old. 
 
 
4.3.11 Wide angle OCT/OCTA (Zeiss) 
Wide-angle OCT/OCTA examinations were performed after cycloplegia. 
OCT/OCTA location：macular + optic disc area. Shooting mode: 12*12mm, 
15*9mm angio mode; 16mm loop sweep mode (horizontal and vertical 
directions) a total of 8 scans. Shooting requirements: communicate more 
with the subject; the forehead and chin must be close to the instrument. 
If the image quality is affected by blinking or eye movement during 
shooting, you need to re-shoot. This item is optional for children 
under 6 years old. 

4.3.12 Fundus photography + autofluorescence 
Fundus photography + autofluorescence was performed after 
cycloplegia. Shooting content: pseudo color eye fundus + spontaneous 
fluorescent fundus. Shooting requirements: The exposure intensity is 
30ws and 300ws respectively and it needs to focus on the split line 
and rotate the upper refractive compensation button. If you find the 
participant not completely cycloplegic, please take another drop of 
cyclopentolate, otherwise there will be a dark area. This item is 
recommended for final inspection as the exposure is too bright. 
 
4.3.13 Ultra wide-angle fundus photography (Optos) 
Optos ultra-wide-angle fundus photography was performed after 
cycloplegia.  Shooting content: pseudo color eye fundus + spontaneous 
fluorescent fundus.  Shooting requirements: the same as color fundus 
photography. 
 
4.3.14 mfERG 
mfERG (RETIscan, 3.15 version, Roland, Germany) was examined after 
cycloplegia.  After 0.5% topical anesthesia with procarbaine 
hydrochloride, the contact lens was placed on the cornea, the ground 
electrode was placed in the middle of the forehead, and the reference 
electrode was placed on the lateral iliac crest to correct refractive 
error.  The stimulator has an average brightness of 102 cd/m 
2 (4~200 
cd/m 
2), a contrast ratio of 99%, and stimulates the retina with a 
center of about 30° around the macula. There are 61 hexagons, each of 
which is six. The edge is flipped in black and white under the control 
of the binary m sequence.  Each stimulation cycle time is 47 s, 
stimulating 6 cycles.  This item is optional for children under 10 
years old. 
 

4.3.15 Wavefront aberration 
When the corneal topography and wavefront aberrations are measured, 
the subject's eyes are enlarged, and the operator or assistant pulls 
the upper eyelid if necessary. 
 
4.4 Collection of blood/saliva specimens 
5 ml of Blood/saliva specimens were collected.  Blood/saliva 
specimens are temporarily stored in a portable refrigerator on site 
and transferred to a -80 °C deep-temperature refrigerator as soon as 
possible.  The detection of serum riboflavin and related cytokine 
levels will be carried out in the Ophthalmology Laboratory of the 
Shanghai General Hospital affiliated to Shanghai Jiao Tong University. 
 
4.5 Questionnaire 
The questionnaire is divided into 5 parts: 
A． General information, including birth status (maternal pregnancy 
status, premature birth history, feeding status, etc.), family 
status (family history of myopia, family economic status, 
parental education level, parental physical condition, etc.), 
growth and development status, living and learning status 
(living environment , dietary status, sleep status, academic 
burden, academic performance, etc.), past medical history 
(including systemic and eye diseases); 
B． Quality of life for children with high myopia (NEI-VFQ-25 scale); 
C． High myopia children's psychology (NEI-VFQ-25 scale, depression 
self-assessment SDS, anxiety self-assessment table SAS, self-
esteem scale SES); 
D． High myopia child behavior (NEI-VFQ-25 scale); 
E． Social interaction for children with high myopia (NEI-VFQ-25 

scale). 
The questionnaire is completed by the parent or guardian.  Children 
and adolescents aged 10 or older are required to complete additional 
questionnaires to conduct self-evaluation on quality of life, 
psychology, behavior and social interaction.  The questionnaires are 
mainly filled in online. For parents or children who are not convenient 
to fill out the questionnaire online, a paper-based questionnaire can 
be issued and collected after completion. 
 
5. Organization and quality control of research 
5.1 Drafting, revision and finalization of the plan 
A. The program was drafted by the Shanghai Eye Disease Prevention and 
Control Center.  The draft is reviewed by the expert group, and 
the draft is discussed, revised, and finalized in the form of a 
seminar.  The research plan was implemented after approval by the 
ethics committee. 
B. In the process of research implementation, if major revisions to 
the research plan are required, they must be submitted to the ethics 
committee for approval before further implementation. 
 
5.2 Research institute 
A. The Shanghai Municipal Health Bureau and the Shanghai Municipal 
Education Bureau are responsible for the coordination of major 
issues. 
B. Shanghai third-level eye disease prevention and control system 
(city-district 
(county)-community) 
jointly 
guarantees 
the 
implementation of research 
C. The Shanghai Eye Disease Prevention and Control Center is the only 
municipal-level eye disease prevention and control institution in 

Shanghai. It leads the city's 16 districts and counties and more 
than 240 community-level eye care institutions to jointly develop 
eye care services. 
D. The Shanghai Eye Disease Prevention and Control Center can provide 
sufficient human resources for the research.  Most of the inspection 
teams are staff members of the hospital and have extensive clinical 
experience.  In addition, the Shanghai Eye Disease Prevention and 
Control Center has extensive experience in recruiting temporary 
volunteers. 
 
5.3 Quality control and supervision 
A． All participants in the study are required to be trained before the 
study is officially launched.  The training content is printed as 
a work manual and distributed to researchers.  The clinician, 
optometrist or technician who participates in the examination needs 
to learn the corresponding part of the work requirements, 
procedures, instrument use and operation specifications before 
going to work. After the passing examination, the official 
examination can be carried out.  For items that are responsible by 
multiple people, it is necessary to complete the consistency test 
before the study is officially carried out to ensure that the 
results between different examiners are comparable. 
B． All inspectors are only able to know the relevant parameters 
necessary for the inspection items they are responsible for, and 
remain blind for other irrelevant parameters. 
C． The instrument should be calibrated before the start of the work 
on each inspection day. 
D． Researchers responsible for quality control should regularly check 
the inspection data of each inspection post. The quality control 

standards refer to the operating rules on the work manual.  For 
those who have higher failure rate, they need to re-train and pass 
the examination before they can re-employ. 
E． Follow-up content and criteria were consistent with baseline.  The 
equipment for follow-up examination is as close as possible to the 
baseline, and the examiner is as consistent as possible.  If 
inspection instrument must be replaced due to the upgrad, the 
comparability of the old and new instruments should be evaluated. 
F． The follow-up interval was as consistent as possible. 
G． The reliability and validity of the questionnaire needs to be 
assessed before use. 
 
5.4 Data entry, analysis and deletion 
A． The online data system is researched and developed by professional 
information technology companies, used to check real-time data 
entry, questionnaire filling, etc.  The accuracy and completeness 
of the data is automatically determined by the data system. 
B． The entry of non-electronic data is done independently by two people. 
C． Data deletion and analysis were performed independently by two 
statisticians. 
 
6. Statistical Analysis 
6.1 Descriptive statistics 
A． Continuity variables: sample size, mean, standard deviation, 
minimum, maximum, quartile 
B． Classification variable or grade variable: frequency distribution 
 
6.2 statistical methods 
A. Continuous variables: The normality test uses the Kolmogorov-

Smirnov test.  If the normal distribution is satisfied, the t test 
or one-way ANOVA is used; if the normal distribution is not 
satisfied, the Mann-Whitney U test or the Kruskal Wallis test is 
used.  The two-two comparison between groups was performed using 
the Bonferroni method. 
B. Categorical variable: chi-square test. 
C. Correlation analysis: simple linear regression and stepwise 
multiple linear regression, using nonlinear regression if necessary. 
 
6.3 Statistical significance 
All differences were statistically defined as P < 0.05 (bilateral) 
 
6.4 Subgroup analysis 
Subjects will be assigned to different subgroups for subgroup 
analysis based on age, gender, diopter, axial length, fundus structure, 
and functional changes. 
 
6.5 Interim analysis 
Baseline data (2018) and follow-up data for every 3 years are used 
for analysis and reporting. 
 
7. Ethical issues 
7.1 Ethics committee 
The study will be carried out after the approval of the Shanghai 
General Hospital Ethics Committee and strictly abide by the Helsinki 
Declaration. 
 
7.2 Protect the privacy of participants 
In order to protect the privacy of the children and adolescents in 

the test, when the research materials are provided to other 
organizations, the subject code or initials should be used instead of 
their ID number or real name.  In addition, the researcher and the 
relevant staff involved in the research must keep the privacy 
information of the children and adolescents in the test confidential. 
 
8. Funds and insurance 
8.1 funds 
Before the start of the study, funds were raised by the Shanghai 
Eye Disease Prevention and Control Center. 
 
8.2 Compensation and insurance 
If the subject is compromised by participating in the study and 
the damage is directly related to the research content, the research 
sponsor will provide the victim with the necessary treatment and 
compensation. 
Research sponsors need to purchase commercial insurance for 
children and adolescents involved in the study and temporary workers 
involved in the study. 
 
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