Atropine for Children and Adolescent Myopia Progression Study (ACAMP)
Phase: PHASE4
Conditions: Myopia
Sponsor: Shanghai Eye Disease Prevention and Treatment Center

 
 
 
 
 
 
 
Atropine for Myopia Progression Control Study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Shanghai Eye Disease Prevention and Control 
Center/Shanghai Eye Hospital, Shanghai General 
Hospital 
May 2019 
 
 
 
 
 
 
 
 

1. Introduction:  
1.1 Myopia is a major public health problem around the world 
At present, myopia has become a major public health problem. World Health Organization 
(WHO) statistics show that there are about 75 million visual impairment patients in China, 
2010, and uncorrected myopia is the first cause (42%). Over the past 50-60 years, the 
prevalence of myopia in East Asia such as China has risen rapidly, and the incidence of 
myopia shows a progressive trend after the onset of early age. In cities, the prevalence of 
myopia among middle school students is over 70%, and among high school graduates, 80-
90% are myopia, of which 10-20% are high myopia. According to the degree of myopia, 
myopia above - 6D is defined as high myopia. The harm of high myopia mainly lies in its 
complications, some blinding eye diseases, such as macular degeneration and retinal 
detachment, are caused by corresponding changes of other tissues in the eye, and the 
quality of life of patients with high myopia is seriously affected. Morgan et al. pointed out in 
the comments of myopia experts published in Lancet in 2012 that the risk of complications 
such as posterior scleral staphyloma, choroidal neovascularization, retinal splitting and 
choroidal atrophy, which may cause blindness, has increased dramatically in a large 
number of new-onset high myopic people in Asia in the past 100 years. WHO has 
considered the prevention and treatment of myopia as part of the global blindness 
prevention plan, especially in East Asia. Recent epidemiological studies on 
ophthalmopathy show that with the improvement of the national ophthalmological service 
level, the rate of cataract surgery has increased rapidly, and the proportion of cataract-
curable blindness in the population has continued to decline, while high myopia-Related 
retinopathy has gradually become the first irreversible blinding eye disease in China. 
1.2 The overview of high myopia 
From the occurrence of high myopia to pathological myopia and the final occurrence of 
blindness and visual impairment is a long-term process. First, myopia occurs in early 
childhood (the age of initial myopia is often before school age). The growth rate of myopia 
is significantly higher than that of most people. It often exceeds - 6D at the age of 15 
(graduation from junior middle school). Secondly, unlike myopia in general children, myopia 
degree and axis length continue to progress in adulthood. With the extension of eye axis, 
posterior choroid and sclera continue to develop and become thinner. When pathological 
changes such as chorioretinal atrophy and choroidal neovascularization occur, they are 
generally over 50 years old. In order to avoid blindness and visual impairment caused by 
complications of high myopia, it is necessary to start myopia screening and intervention 
from childhood and adolescence. 
1.3 Studies about atropine for controlling myopia progression  
In order to reduce the incidence of high myopia, many myopia control interventions have 
been carried out in children and adolescents at home and abroad. Among them, atropine, 
an M-receptor antagonist, has been shown to be effective in myopia control in many 
experimental and clinical trials in recent years. In ATOM2 study in Singapore, a randomized 
controlled clinical trial was conducted. Two years after the use of 1% atropine eye drops, 
children's myopia decreased by 0.92D and eye axis increased by 0.4mm compared with 
the control group. After 2 years of treatment with 0.5%, 0.1% and 0.01% respectively, the 
myopia of children increased by 0.30D, 0.38D and 0.49D, respectively, which were 

significantly lower than that of the control group (1.20D). Although 1% atropine eye drops 
had myopic rebound effect after discontinuation, the rebound effect disappeared when the 
concentration of atropine was reduced to 0.1% and 0.01%. 
In the LAMP study in Hong Kong, after one year of treatment with 0.05%, 0.025% and 0.01% 
respectively, the myopia of children increased by 0.27D, 0.46D and 0.59D, which were 
significantly lower than that of the control group (0.81D), and the ocular axis increased by 
0.20mm, 0.29mm and 0.36mm, respectively, which were lower than that of the control 
group (0.41mm). Similar studies at home and abroad have also confirmed that the use of 
low-concentration atropine has a good effect on myopia control. At present, in Taiwan, 
Hong Kong, Singapore and other Chinese areas, children with high myopia risk and rapid 
growth of myopia have been more commonly treated with low-concentration atropine eye 
drops for intervention. 
The mechanism of atropine controlling myopia has not been fully elucidated. Early studies 
suggested that atropine could control myopia by regulating mechanism. However, McBrien 
found that atropine could still control the development of myopia after cutting off the 
regulating pathway through animal experiments. Therefore, the mainstream view is that 
atropine controls myopia by non-regulating mechanism. It may be through the antagonism 
of M receptor signaling pathway on the retina or scleral surface to slow down the 
development of myopia, but the specific mechanism has not yet been fully elucidated. 
Atropine eye drops belong to mydriasis and ciliary paralysis drugs. Long-term use of 
atropine eye drops can lead to symptoms such as dilatation of pupils, photophobia and 
blurring of close-range objects. These symptoms are closely related to drug concentration 
and frequency of use. 
1.4 The objectives of our study 
From previous studies, investigators can find that 1% atropine has good effect in early 
myopia control, but its side effects are great, long-term use compliance is poor, and there 
is a rebound effect; 0.01% atropine has poor effect in early myopia control, and the effect 
of follow-up for one year is not as good as 0.05%, but the effect of follow-up for two years 
is equal to 1%, that is, long-term use effect is good, and there are few side effects. 
Considering that only 1% or 0.01% atropine eyedrops (gels) are available in atropine 
eyedrops approved by the drug administration, investigators consider whether 1% atropine 
can be used for six months, and 0.01% atropine for one and a half years to achieve better 
early myopia control, late consolidation efficacy and side effects. In addition, the current 
clinical studies mainly focus on diopter and ocular axis. This project will explore the 
changes of lens and fundus after atropine treatment, whether there are indicators that 
reflect the effect of atropine control earlier and more accurately than diopter and ocular 
axis, and explore the target of atropine for myopia control. 
 
2. Research Objectives 
To explore a better way to control myopia progression and eliminate adverse effects at the 
same time;  
To provide reliably evidence for clinical guideline of atropine use in children;  
To investigate the mechanism of atropine on eyes. 
 

3.Trail Design 
a randomized controlled, prospective cohort study, no mask.  
3.1 Eligibility  
3.1.1 Case Selection Criteria 
⚫ 
7-12 years old (grade 1 to grade 6 of primary school); 
⚫ 
Spherical Equivalent ranged from - 0.5D to - 6.0D, astigmatism < 0.75D, binocular 
diopter gap < 1.0D; 
⚫ 
No ophthalmopathy except ametropia was found. 
3.1.2 Exclusion criteria for cases 
⚫ 
has amblyopia, strabismus and other eye diseases. 
⚫ 
Serious allergy to atropine eye drops; 
⚫ 
Atropine eye drops have been used to control myopia. 
⚫ 
Other therapeutic eye drops are being used or have not been discontinued for more 
than a month. 
⚫ 
There is a contraindication of mydriasis. 
⚫ 
Patients with severe heart, lung, liver, gallbladder and kidney diseases; 
⚫ 
Patients who had to take other drugs because of other diseases affected the results 
of this test; 
⚫ 
Those who have participated in other clinical trials in the past three months; 
⚫ 
Researchers believe that there are other unsuitable participants. 
3.2 Groups and Sample size 
Myopic children aged from 7-12 years old are randomly allocated into two groups: 
combined use of atropine sulfate 1% ophthalmic ointment and atropine sulfate 0.01% eye 
drop (experimental group) and atropine sulfate 0.01% eye drop (control group). Each 
group includes 111 participants.   
3.3 Medications and usage: 
3.3.1 control group: atropine sulfate 0.01% eye drop, once a day, once a drop, for two 
years;  
3.3.2 Combined application group: atropine sulfate 1% ophthalmic ointment, once a day 
for the first week, once a drop for both eyes; and then once a week, once a drop for both 
eyes for half a year. Half a year later, atropine sulfate 0.01% eye drop is used once a 
day, one drop each time, with both eyes for one and a half years. Usage: Drop it into 
conjunctival sac, about the size of a rice grain, press the nasal root with thumb and index 
finger for 2 minutes after dripping, and use it before going to bed. Patients once a week 
are advised to use it before going to bed on Friday night. 
3.4 Examination 
3.4.1. Examination process: The brief process is as follows: Identity information 
registration > height, weight > naked eye vision & wearing vision > intraocular pressure > 
accommodation, near vison acuity > mesopic pupil size > slit lamp anterior segment 

examination > cycloplegia > Autorefraction and subjective refraction > IOL-Master, 
Pentacam, Swept-source optical coherence tomography（SS-OCT，Topcon), wide-
angle optical coherence tomography angiography(OCTA,Zeiss-9000)> fill out the 
questionnaire. 
3.4.2 Ophthalmology inspection project operation rules  
3.4.2.1 Vision test:The eyesight examination used the ETDRS visual acuity chart (LCD 
backlit lamp, WH0701), 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. 
3.4.2.2 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. 
3.4.2.3 Accommodation, near visual acuity: Accommodation is measured using a Royal 
Air Force (RAF) near point rule (Harlow, Essex, UK) with best-corrected distance 
spectacle correction. Near visual acuity is assessed using best-corrected distance 
spectacle correction with a reduced logMAR reading chart placed at 40 cm under well-lit 
conditions  
3.4.2.4 Mesopic pupil size: measured by automated computer refractometer (KR-8900, 
Topcon, Japan) after staying in a dark room for 5 minutes at least. At least 5 pupil size 
readings were recorded and averaged. 
3.4.2.5 Ophthalmologist examination Ophthalmologist examinations included anterior 
segment slit lamp examination (66 Vision. Tech, Suzhou, China) and ophthalmoscopy 
examination(66 Vision. Tech, Suzhou, China). To exclude those children with cycloplegia 
contradictions. 
3.4.2.6 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 1 drop of 1% 
cyclopentolate is added to each eye after 15 seconds. (Cyclogyl, Alcon), 5 minutes apart. 
After each drip, ask the participant to press the inner canthus for a few seconds gently 
and try to take the head back posture. The last drop of cyclopentolate 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 cyclopentolate, 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. 
3.4.2.7 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. 
3.4.2.8 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. 
3.4.2.9 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. 
3.4.2.10 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. 
3.4.2.11 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, participants need to re-shoot. If 

participants still can't meet the requirements, participants 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. 
3.4.2.12 Wide angle OCT/OCTA (Zeiss-9000) 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, participants need to re-
shoot. This item is optional for children under 6 years old. 
3.4.3 Questionnaire: The questionnaire is about the time children spend on outdoor 
activities and near work. 
4. Follow up  
4.1Frequency: Combined use of 1% atropine and 0.01% atropine group is followed up 
after first week, then every three months. 0.01% atropine group is followed up every 
three months. 
4.2 Examinations:  
4.2.1 First week follow up for combined use group: accommodation, near vison acuity > 
mesopic pupil size > Autorefraction and subjective refraction > IOL-Master, Pentacam, 
Swept-source optical coherence tomography（SS-OCT，Topcon), wide-angle optical 
coherence tomography angiography(OCTA,Zeiss-9000  
4.2.2 Every three months: accommodation, near vison acuity > mesopic pupil size > slit 
lamp anterior segment examination > cycloplegia > Autorefraction and subjective 
refraction > IOL-Master, Pentacam, Swept-source optical coherence tomography（SS-
OCT，Topcon), wide-angle optical coherence tomography angiography(OCTA,Zeiss-
9000 
5. Statistical Analysis 
5.1 Descriptive statistics A．Continuity variables: sample size, mean, standard deviation, 
minimum, maximum, quartile B．Classification variable or grade variable: frequency 
distribution  
5.2 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. 
5.3 Statistical significance All differences were statistically defined as P < 0.05 (bilateral)  
5.4 Subgroup analysis Subjects will be assigned to different subgroups for subgroup 
analysis based on age, gender, diopter, axial length, fundus structure, and functional 
changes. 
5.5 Interim analysis Baseline data (2019) and follow-up data are used for analysis and 
reporting. 
6. Ethical issues 
6.1 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. 
6.2 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. 
6.3 Informed consent The informed consent form will be distributed to the children and 
adolescents participating in the study and their parents or guardians after approval by the 
ethics committee. For children and adolescents and their parents or guardians who 
voluntarily agree to participate in the study, parents or guardians are required to sign an 
informed consent form prior to the baseline study. Before signing the informed consent 
form, the researcher should fully introduce the content of the study, the benefit of the 
subject and the potential risks, and confirm that the children and adolescents and their 
parents or guardians fully understand and voluntarily sign the informed consent form. 
When signing the informed consent form, the parent or guardian has sufficient time to 
consider and has the right to ask questions. For questions from parents or guardians, the 
researcher needs to provide adequate answers. For parents or guardians who agree to 
sign an informed consent form, the investigator signs the informed consent form after the 
informed consent is fully explained and states the relationship with the child and 
adolescent. Informed consent is in duplicate, one of which is kept by the parent or 
guardian and the other is kept by the researcher. During the research process, if there is 
a major change in the research content, the revised informed consent form should be 
sent to the ethics committee for approval. After the approval, the researcher must fully 
communicate with the children and adolescents and their parents or guardians, and 
confirm that they agree to continue to participate in the study and re-sign the informed 
consent form. 
7. Funds and insurance funds  

Before the start of the study, funds were raised by the Shanghai Eye Disease Prevention 
and Treatment Center. 
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