The Effectiveness and Safety of Low-intensity Single-wavelength Red Light in Controlling High Myopia in Children and Adolescents：A Randomized, Controlled, Multicenter Clinical Trial
Phase: NA
Conditions: Age 3 to 16 Years (Inclusive), Male or Female, Clinical Diagnosis Confirming That Myopia Has Occurred in at Least One Eye, The Guardian Voluntarily Signed the Subject's Informed Consent Form
Sponsor: Shanghai Eye Disease Prevention and Treatment Center

 
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Study Protocol  
 
 
 
A Randomized, Controlled, Multi-centre Clinical Study 
on the Effectiveness and Safety of repeated low-level 
red-light (RLRL) in Controlling High Myopia in 
Children and Adolescents 
  
 
 
 
 
Date: 10th January 2022 
Clinical Research Institution: Shanghai Ophthalmopathy Prevention & Treatment 
Centre 
Researchers: Haidong Zou & Yan Xu 
Sponsor: Zuoguan Medical Equipment Co., Ltd. at Suzhou Industrial Park 
Version number: 20200901.4  
 
 
 
 
 
 
 

 
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Confidentiality statement: The relevant information contained in this document 
involves the business secrets or business information of the registration applicant. 
These business secrets or business information are confidential or proprietary 
information. Unless required by laws and regulations, no one may disclose these 
confidential or proprietary information without authorization. Any individual who 
accesses to this document should understand the proprietary or confidentiality of the 
document, and shall not disclose this document without authorization. The above 
restrictions on document confidentiality will apply to any relevant documents and 
materials that indicate proprietary or confidentiality provided to you in future.  
 
 
 

 
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Abbreviation 
Abbreviation 
English 
Chinese 
AE 
Adverse Event 
不良事件 
CFDA 
China Food and Drug Administration 
国家食品药品监督管理总局
（旧称） 
CRF 
Case Report Form 
病例报告表  
CRO 
Contract Research Organization 
合同研究组织  
FAS 
Full Analysis Set 
全分析集  
GCP 
Good Clinical Practice  
临床试验质量管理规范  
ICH 
International 
Conference 
of 
Harmonization 
人用药品注册技术要求国际
技术协调会 
ITT 
Intention-to treat 
意向性分析 
LOCF 
Last observation carried forward 
最接近一次观察的结转 
Min 
Minute 
分钟 
NMPA 
National 
Medical 
Products 
Administration 
国家药品监督管理局 
PPS 
Per Protocol Set 
符合方案集 
SAE 
Serious Adverse Event 
严重不良事件 
SAP 
Statistical Analysis Plan 
统计分析计划 
SOP 
Standard Operating Procedure 
标准操作程序 
SS 
Safety Analysis Set 
安全性数据集 
 
 
 
 

 
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TABLE OF CONTENTS 
1. ABSTRACT 
2. INTRODUCTION 
2. 1 Sponsor Information 
2.2 Study Personnel and institution 
2.3 Study Purpose 
2.4 Research Background 
3. STUDY DESIGN 
3.1 Eligibility criteria 
3.2 Recruitment and informed consent  
3.3 Randomization and masking 
3.4 Intervention Study site 
3.5 Outcomes 
3.6 Study sample size 
4. FIELD WORK PROCEDURES 
4. 1 Summary flowchart 
4.2 Baseline and follow-up examinations 
4.3 Process of the practice 
5. DATA ENTRY AND ANALYSIS 
5. 1 Data collection 
5.2 Statistical analysis plan 
6. MONITORING 

 
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6. 1 Consent monitoring 
6.2 Implementation assessment 
6.3 Equipment assessment 
7. QUALITY ASSURANCE 
8. ETHICS 
8. 1 Ethical approval 
8.2 Plan modification 
8.3 Informed consent 
8.4 Confidentiality 
 
 

 
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1. ABSTRACT 
 
Basic information on clinical practice of medical devices: 
Device Classification: Class II medical devices 
Specification Model: RS-200-1A 
Date: September 20, 2020 
Sponsor: Zuoguan Medical Devices Co., Ltd. at Suzhou Industrial Park 
Practice Title 
A Randomized, Controlled, Multi-centre Clinical Study on the Effectiveness and Safety 
of repeated low-level red-light (RLRL) for myopia control in children and adolescents 
with high myopia 
Practice Purpose 
A Study on assessing the effectiveness and safety of RLRL for myopia control in 
children and adolescents with high myopia. 
Subject Population 
Subject: Children aged 6-16 with at least one eye with myopia of cycloplegic spherical 
equivalent refraction (SER)  at least –4.0 D 
Sample size: 192 subjects are planned to be enrolled and assigned to the intervention 
group or control group according to a ratio of 1:1 
Practice Design 
Overall design: 
This prospective, single-blind, parallel-group, multi-center randomized clinical trial 
was conducted at six tertiary hospitals. Participants between 6 and 16 years old with at 
least one eye with a spherical equivalent refraction (SER) of –4.0 D or greater were 
recruited. The enrolled participants were randomly placed at a 1:1 ratio into 

 
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intervention (RLRL treatment plus single-vision spectacles) or control (single-vision 
spectacles) groups. The participants attended follow-up appointments 1, 3, 6, 9, and 12 
months after the baseline evaluation.  
Outcomes: 
1. Primary Outcome: Change of Axial length (AL, mm) at 12-month follow-up 
2. Secondary Outcome: Change of cycloplegic spherical equivalent (SE, D) at 12-
month follow-up 
3. Optional Indicators： 
Changes of uncorrected visual acuity （UCVA），best-corrected visual acuity 
（BCVA），intraocular pressure, etc.; 
Changes of corneal thickness（CT）, anterior chamber depth（ACD） and lens 
thickness（LT）; 
Observe macula and the structure of fundus around the optic disc; 
Observe the choroid/retinal thickness of the fundus; 
Compliance index: frequency of equipment uses. 
Safety assessment  
①Sudden vision loss； 
②Afterimage time over 5 minutes; 
③Side effects such as glare, photophobia and flickering; 
④Structural damage to retina: tissue disruption or discontinuity, edema, or other 
abnormalities in the photosensory layer of the SS-OCT images; 
⑤Increased intraocular pressure etc. 
 
Participants selection and exclusion criteria: 
Eligibility criteria: 
Inclusion criteria: 
①Age 6-16 years old, no gender limit; 
②Either eye meets the diagnosis of myopic refractive error and the myopia of 
cycloplegic spherical equivalent refraction (SER)  at least –4.0 D, astigmatism 2.0 D 

 
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or less, anisometropia 3.0 D or less, and best-corrected visual acuity (BCVA) of 
LogMAR 0.2 or better. 
③Have normal thinking and language communication skills, and be able to actively 
cooperate with the required treatment; 
④ No contraindications to the treatment of atropine such as acute ocular inflammation, 
dry eye, keratoconus, diabetes, etc.; 
⑤Written informed consent of the guardian and the child. 
Exclusion criteria: 
1. History of photosensitivity, glaucoma, glaucoma syndrome, ocular hypertension, and 
macular pathology or damage in the fundus; 
2. The average K value of the anterior surface of the cornea is ≥45 in corneal curvature 
examination; 
3. Patients with systemic diseases such as heart, liver, kidney, and congenital hereditary 
myopia; 
4. Patients with chronic eye diseases such as eye trauma and strabismus or surgical eye, 
atopic keratoconjunctivitis; 
5. People who have had other eye diseases such as inverted trichiasis, severe corneal 
and conjunctival infections in the past; 
6. People with neurological diseases and allergies or contraindications to atropine drugs 
or other therapeutic drugs; 
7. Patients with immune system and systemic diseases such as albinism, psoriasis, 
nephrotic syndrome, systemic lupus erythematosus, diabetes, etc.; 
8. People with epilepsy and mental disorders who cannot communicate normally; 
9. Individuals who have previously received other treatments to control the 
development of myopia, such as the use of anticholinergic drugs such as atropine within 
3 months, or participated in other related researches such as functional frame mirrors, 
multifocal soft mirrors, etc.; 
10. Other situations that the researcher judges are not suitable for participating in the 
study. 
Control type: 
     Comparison of the effect of routine single vision spectacle lenses 

 
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Statistical analysis plan： 
The intention-to-treat (ITT) population comprised participants randomly assigned to 
either group. Data from all participants who attended at least one subsequent follow-up 
visit were included in the analysis. Individuals who switched to other myopia treatment 
modalities or discontinued the RLRL treatment, were censored.  
Treatment efficacy was assessed using longitudinal mixed models for primary (changes 
in AL) and secondary (changes in SER and IOP) outcomes at multiple follow-up visits. 
Sensitivity analyses were conducted to assess the treatment effects of therapy in 
controlling myopia progression, specifically axial elongation and SER progression, 
across different baseline SER and age groups. 
A longitudinal mixed-model analysis was conducted to assess the relationship between 
treatment efficacy and compliance within the intervention group.  
Safety analyses were performed in the ITT population. All adverse events were reported 
individually.  
  
Ethics: 
The practice protocol (including the informed consent form) is submitted to the 
ethics committee for approval, and all subjects entering the trial screening must sign 
the informed consent form. Researchers should conduct experiments in strict 
accordance with the experimental protocol and GCP requirements to fully protect the 
legal rights and safety of the subjects. 
 
 
 
 
 

 
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2. INTRODUCTION 
2.1 Sponsor Information 
Sponsor name：Zuoguan Medical Equipment Co., Ltd. at Suzhou Industrial Park 
Sponsor adress：Tonghe Road, Weiting Technology Park, Suzhou Industrial Park, 
Suzhou, Jiangsu, China 
Sponsor Contact: Xianyong Wu, 13801252099 
2.2 Study Personnel and institution 
Site code 
Study Institution 
Researchers 
professional title 
Contact 
01 
Shanghai Ophthalmopathy Prevention 
& Treatment Centre 
Haidong 
Zou，Yan Xu 
Study Chair ，
Clinic site PI    
13311986528 
18621080996 
02 
Children’s Hospital of Soochow 
University 
Kehong Feng 
Clinic site PI   18994305527 
03 
Xinhua Hospital Affiliated to Shanghai 
Jiaotong University School of Medicine 
Huang Zhu 
Clinic site PI   13801946402 
04 
Shanghai East Hospital 
Hongping Cui 
Clinic site PI   13671900868 
05 
The Children’s Hospital Zhejiang 
University School of Medicine 
Caiping Shi 
Clinic site PI   13957125522 
06 
Shanxi Eye Hospital 
Xueliang 
Feng 
Clinic site PI   13934517456 
 
2.3 Study Purpose 
Study on effectiveness and safety of repeated low-level red-light in controlling high 
myopia in children and adolescents. 
2.4 Research Background 
Myopia, or nearsightedness, is a prevalent refractive error of the eye characterized by 
the ability to see close objects clearly while distant objects appear blurred. High myopia, 
defined as a refractive error of -6.00 diopters or more, poses a significant public health 
concern due to its increasing prevalence, particularly among children and adolescents 
worldwide[1-4] . High myopia not only impairs visual acuity but also substantially raises 
the risk of sight-threatening complications such as myopic macular degeneration, 

 
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glaucoma or even retinal detachment [5]. 
Despite the growing prevalence and potential vision-threatening consequences of high 
myopia, effective strategies for its control and management remain elusive. High 
myopia is often out of range as an indication for orthokeratology[6]. Low-concentration 
atropine[7-10] or defocus spectacles[11] have demonstrated reasonable efficacy on 
controlling low or moderate myopia in multiple randomized controlled trials (RCTs) 
but no evidence suggests their efficacy among highly myopic eyes. 
The Eyerising amblyopia treatment instrument has been widely used in mainland China 
to treat amblyopia. The instrument utilizes repeated low-level red-light (RLRL) for 
treatment. Some studies confirm that it can improve the vision of patients, and no local 
or systemic side effects have been found [12]. Low-intensity lasers can cause 
photochemical reactions in the retina, including increasing the activity of cytochrome 
C oxidase [13,14] changing gene expression to regulate the mitochondrial respiratory 
chain [15], and increasing the biological activity of nitric oxide [16]. Preliminary trial data 
shows that it has a significant effect on slowing down the progression of myopia. This 
study will explore the effect of RLRL therapy in the prevention and treatment of high 
myopia for the first time. If successful, it will provide new ideas for effectively 
controlling myopia. 
 
3. STUDY DESIGN 
This trial is a randomized, controlled, multi-centre clinical trial. The subjects selected 
192 children aged 6-16 who had developed high myopia, and divided them into 
intervention group and control group with 96 cases each. The intervention group was 
treated with the Eyerising RLRL and single vision spectacle lenses, and the control 
group was treated with single vision spectacle lenses. Then, we compare the changes 
of myopia during the observation period between the two groups, and evaluate the 
safety and effectiveness of the test device. 
Subjects will be screened after signing the informed consent form (as early as 7 days 
before the randomization day). The screening test can use the results of the 
ophthalmological examination in hospital within 1 week, and subjects enter the group 
after confirming that they meet the selection conditions. On the day of enrolment, the 
group is confirmed after consultation with the parents, and determine whether to receive 

 
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equipment for treatment based on the results of the grouping. Visits were conducted 
30±14 days, 90±14 days, 180±14 days, 270±14 days, and 365±14 days after enrolment. 
 
3.1 Eligibility criteria 
Inclusion criteria 
①Age 6-16 years old, no gender limit; 
②Either eye meets the diagnosis of myopic refractive error and the myopia of 
cycloplegic spherical equivalent refraction (SER)  at least –4.0 D, astigmatism 2.0 D 
or less, anisometropia 3.0 D or less, and best-corrected visual acuity (BCVA) of  
LogMAR 0.2 or better. 
③Have normal thinking and language communication skills, and be able to actively 
cooperate with the required treatment; 
④ No contraindications to the treatment of atropine such as acute ocular inflammation, 
dry eye, keratoconus, diabetes, etc.; 
⑤Written informed consent of the guardian and the child. 
 
 Exclusion criteria 
①A history of photosensitivity, glaucoma, glaucoma syndrome, ocular hypertension, 
and macular pathology or damage in the fundus; 
② Corneal curvature examination, the average K value of the anterior surface of the 
cornea is ≥45; 
③Patients with heart, liver, kidney and other systemic diseases and congenital 
hereditary myopia; 
④Patients with chronic eye diseases such as ocular trauma and oblique or surgical 
eyes, atopic keratoconjunctivitis; 
⑤Patients with previous eye diseases such as inverted trichiasis, severe corneal and 
conjunctival infections; 
⑥Patients with neurological diseases and allergies or contraindications to atropine 
drugs or other therapeutic drugs; 
⑦Patients with immune system and systemic diseases such as albinism, psoriasis, 
nephrotic syndrome, systemic lupus erythematosus, diabetes, etc.; 
⑧ People with epilepsy, mental disorders and unable to communicate normally; 

 
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⑨ Those who have previously received other treatments to control the development 
of myopia, such as the use of anticholinergic drugs such as atropine within 3 months, 
or participated in other functional frame mirrors, multifocal soft mirrors and other 
related researchers; 
⑩ Other situations that the researcher judges are not suitable for participating in the 
research. 
 
Participant withdrawal or termination 
A study investigator will terminate participation in the study for the following reasons: 
1) The patient receives other myopia control treatments; 
2) Patients continuously stop using Eyerising equipment for more than 14 days; 
3) Severe comorbidities or adverse events: patients cannot tolerate light, have obvious 
eye allergies such as tearing, skin rash, and the after-image time after low-energy 
laser treatment exceeds 5 minutes; 
4) Serious safety problems occurred repeatedly during the test (such as serious 
adverse events related to the test); 
5) China Food and Drug Administration ordered the suspension of the test for some 
reason; 
6) Sponsor requests suspension (such as funding reasons, management reasons, etc.). 
3.2 Recruitment and informed consent 
Children who met the Inclusion criteria and their parents or guardians will be invited to 
participate in the study at the refractive clinic and optometry center of the research 
hospital through poster advertisements and physician referrals. Prior to collecting 
baseline data, written informed consent will be obtained from the parents/guardians of 
all participants. 
3.3 Randomization and masking 
A statistician without contacts with the participants generated the randomization 
sequence using SAS software (version 9.4; Cary, NC, USA). All eligible participants 
were randomly assigned to the intervention (RLRL plus SVS) or control (SVS only) 
groups at a 1:1 ratio. The randomization process adopted central stratification block 
randomization with block sizes of four or six. Each eligible participant was assigned a 
number based on their study entry sequence. Random assignment outcomes were 

 
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recorded in sealed envelopes with the corresponding sequential numbers written on the 
covers. Then, an investigator at the main center took custody of the envelopes. Each 
time an eligible participant’s informed consent was acquired, the investigators 
responsible for group allocation at the six centers contacted the investigator holding the 
envelopes by telephone. The investigator immediately opened the envelopes and 
provided information on the group allocation of the newly enrolled participants. Owing 
to the nature of the intervention, the participants were aware of their assigned treatment 
groups. However, outcome assessors, including clinical examination technicians, 
optometrists, ophthalmologists, and statisticians, were blinded to the treatment 
allocation. 
3.4 Intervention 
1. Intervention group: Use the Eyerising RLRL device to treat with the treatment device 
twice a day, three minutes each time, with an interval of 4 hours. The method of use is 
as follows: 
A. Put the instrument on a stable desktop, confirm the interface before connecting 
accessories; 
B. Connect the power supply and turn on the power switch; 
C. Let the user sit in a suitable position, loosen the hand-wheel on the side of the 
treatment device, and adjust it up and down to the most suitable angle to make the eyes 
relatively comfortable when resting on the goggles, and fix the hand-wheel to a fixed 
angle; 
D. Enter the subject’s unique account and password, and click Confirm to log in; 
E. After logging in, the first interface enters the photo-kinetic energy treatment item by 
default, take off the glasses, click OK. Then, making sure that there is visible red light 
in the eye position corresponding to the instrument, and put the eyes close to the blue 
eye mask; 
F. For the first use, please place your hands on the top of the treatment device and adjust 
the interpupillary wheel on the top at the same time. It is better to regard the two light 
points as one light point. If not, the brightest light also can be used.  
G. After three minutes of use, the light kinetic energy will automatically stop, leave the 
blue eye mask, close your eyes and rest for 3-5 minutes, until the front and back image 
spots disappear; 

 
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H. After using the instrument, turn it off. 
2. Control group:  single vision spectacle lenses 
 
3.5 Outcomes 
1. Primary Outcome: Change of Axial length (AL, mm) at 12-month follow-up 
2. Secondary Outcome: Change of cycloplegic spherical equivalent (SE, D) at 12-
month follow-up 
3. Optional Indicators： 
Changes of uncorrected visual acuity （UCVA），best-corrected visual acuity 
（BCVA），intraocular pressure, etc.; 
Changes of corneal thickness（CT）, anterior chamber depth（ACD） and lens 
thickness（LT）; 
Observe macula and the structure of fundus around the optic disc; 
Observe the choroid/retinal thickness of the fundus; 
Compliance index: frequency of equipment uses. 
3.6 Study sample size 
Sample size calculation 
The sample size estimation was conducted assuming an α level of 0.05, 90% power, an 
annual axial elongation of 0.40 mm with a standard deviation of 0.40 mm over 12 
months (based on previous results from our study group), and a 50% treatment effect 
(reducing axial elongation by 0.20 mm). The required sample size was 86 participants 
per group, totaling 172 participants. After adjusting for a 10% loss to follow-up, the 
total sample size was 192 participants. 
 
4. FIELD WORK PROCEDURES 
 
4.1 Summary flow chart 
 

 
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4.2 Baseline and Follow-up Examination 
1. Baseline examinations 
Standardized case report form (CRF) will be administered. The measurements outlined 
below will be performed at the baseline examination. 
1）Registration: Name, date of birth, gender, ethnicity, contact information, and history 
of ocular disease or surgery, outdoor activities, time and habits of using eyes at close 
range, history and treatment of myopia, history of general medical conditions, history 
of allergies, will be obtained from questionnaire interviews and input into the EDC 
system. 
2）Visual acuity: An ETDRS chart (Guangzhou Xieyi Weishikang, Guangzhou, China) 
with standard illumination will be used to measure distance visual acuity. Visual acuity 
measurement is performed at a distance of 4 meters. Uncorrected and best corrected 
visual acuity will be measured.  
3）Cover-uncover test: Children will be asked to focus on a near object. The cover-

 
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uncover test will be used to confirm strabismus and determine the type of ocular 
deviation  
4）Ocular biometric measurements via IOL Master: Before cycloplegia, IOL Master 
(version 5.02, Carl Zeiss, Jena, Germany) is used to measure axial length. Using model 
eye to calibrate before measurement. Taking the average of 3 consecutive 
measurements. The difference between any two measurements cannot exceed 0.05mm, 
otherwise the measurement shall be performed again. 
5）Cycloplegia: 1% cyclopentolate hydrochloride (Cyclogyl) is used as a mydriatic 
agent. Each time, the patient firstly puts 1 drop of Proparacaine Hydrochloride, 1 drop 
of Cyclogyl after 15 seconds, and 1 drop Cyclogyl 5 minutes later. 45 minutes after the 
last drop, checking the degree of pupil dilation and light reflection. Dilation and light 
reflex status will be recorded and full cycloplegia will be justified if the pupil dilates to 
6 mm or greater and the light reflex is absent. If the requirements for cycloplegia are 
not met, the third drop of Cyclogyl will be given. Then the cycloplegia will be 
reconfirmed after 15 minutes. 
6）Cycloplegic auto-refraction: Cycloplegic auto-refraction will be conducted using an 
auto-refractor (KR-8900, Topcon, Tokyo, Japan). The same auto-refractor will be used 
throughout the study. It will be calibrated before each examination session to ensure 
there is no equipment drift during the long follow-up process. 
7）Slit-lamp examination: Slit-lamp examination will be used to examine the anterior 
segment, lens, vitreous, and fundus, and any abnormalities will be recorded. 
8）Optical coherence tomography (optional): SS-OCT fundus image acquisition and 
data processing: using swept source OCT (DRI OCT-1 Atlantis, Topcon) 9 Line Radial 
follow-up mode to scan and collect images to obtain fundus pictures and fundus tissue 
tomographic images. Before the collection, the subjects should be asked to sit still for 
a while, avoid taking coffee and drinks; during collection, doctors should pay attention 
to correct the axial magnification; researchers should concentrate on collection time to 
avoid the influence of the time rhythm fluctuation of choroidal thickness. After the 
choroidal boundary is automatically segmented by the machine's built-in software, 

 
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manual verification and correction are carried out, and the choroidal thickness data of 
9 regions of the fovea and the inner, middle and outer rings (upper, lower, nasal, and 
temporal) are obtained. 
2. Follow-up Examinations: 
1) Questionnaire: A questionnaire on adverse events following the intervention will be 
administered at each follow-up visit and unexpected visits for children in the 
intervention group. Children and their parents/guardians will be asked about the side 
effects, including but not limited to short-term glare, flash blindness, and afterimages. 
2) Visual acuity: An ETDRS chart (Guangzhou Xieyi Weishikang, Guangzhou, China) 
with standard illumination will be used to measure distance visual acuity. Visual acuity 
measurement is performed at a distance of 4 meters. Uncorrected visual acuity will be 
measured for each follow-up visit, best corrected visual acuity will be measured for the 
baseline, 6-month and 12-month follow-up visit.  
3) Ocular biometric measurements via IOLMaster:  IOLMaster will be used to 
measure the axial length of both eyes. Five measurements will be taken for each eye. 
The axial length measurement will be based on the mean of these five values if the 
desired precision (<0.05 mm) is achieved. 
4) Cycloplegia: Cycloplegia will be induced with three drops of 1% cyclopentolate 
administered at the 0, 5th, and 20th minute to each eye. The light reflex and pupil 
dilation will be checked after an additional 15 minutes. Dilation and light reflex status 
will be recorded and full cycloplegia will be justified if the pupil dilates to 6 mm or 
greater and the light reflex is absent. 
5) Cycloplegic auto-refraction: Cycloplegic auto-refraction will be conducted using an 
auto-refractor (KR-8800, Topcon, Tokyo, Japan). The same auto-refractor will be used 
throughout the study. It will be calibrated before each examination session to ensure 
there is no equipment drift during the long follow-up process. 
6) Slit-lamp examination: Slit-lamp examination will be used to examine the anterior 
segment, lens, vitreous, and fundus, and any abnormalities will be recorded. 

 
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7) Optical coherence tomography (optional): Swept Source-OCT (DRI OCT-1 Atlantis, 
Topcon) will be used to capture the macular scan. Shooting mode: 12 mm radial scan 
mode (follow up mode). 
8）Safety assessment  
①The incidence of allergic reactions; 
②Afterimage duration exceeds 5 minutes; 
③Decreased near visual acuity； 
④ Levels of side effects such as photophobia and blurred vision; 
⑤Increased intraocular pressure, headache, nausea and vomiting, etc. 
 
Follow-up  Schedule 
(1) Visit 1: Screening period (-7～0 days) 
1) Sign the "Informed Consent"; 
2) Record the general information of the patient; 
3) Record the medical history; 
4) Perform visual inspection, axial inspection, intraocular pressure inspection, 
equivalent spherical lens measurement, slit lamp inspection, OCT inspection; 
5) Review the inclusion and exclusion criteria; 
6) Record the combined/concomitant medication; 
 
(2) Visit 2: Enrolment and randomization (day 0) 
1) Randomly group, and the intervention group will receive experimental devices; 
2) Record device defects; 
3) Record the combined/concomitant medication; 
 
(3) Visit 3: Day 30±14 
1) Perform visual inspection, axial inspection, and intraocular pressure inspection; 
2) Record the combined/concomitant medication; 
3) Record adverse events/device defects. 
 
(4) Visit 4: Day 90±14 
1) Perform visual inspection, axial inspection, and intraocular pressure inspection; 

 
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2) Record the combined/concomitant medication; 
3) Record adverse events/device defects. 
 
(5) Visit 5: Day 180±14 
1) Perform vision examination, axial examination, intraocular pressure examination, 
equivalent spherical lens, slit lamp examination, and OCT; 
2) Record the combined/concomitant medication; 
3) Record adverse events/device defects. 
 
(6) Visit 6: Day 270±14 
1) Perform visual inspection, axial inspection, and intraocular pressure inspection; 
2) Record the combined/concomitant medication; 
3) Record adverse events/device defects. 
 
(7) Visit 7: Day 365±14 
1) Perform vision examination, axial examination, intraocular pressure examination, 
equivalent spherical lens, slit lamp examination, and OCT; 
2) Record the combined/concomitant medication; 
3) Record adverse events/device defects. 
 
4.3 Process of the practice 
Schedule of events table 
Phase 
Perio
d of 
Filter 
Enrol
l and 
rando
m 
Period of Treatment 
Visit Time 
Visit 
1  
Visit 
2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Observed 
Time Point 
Day-
7~0  
Day 0 
Day 
30±14  
Day 
90±14 
Day 
180±14 
Day 270±14 Day 365±14
天 
Demographic 
data 
√ 
 
 
 
 
 
 
History-taking 
√ 
 
 
 
 
 
 
Examination of 
Distant Vision  
√ 
 
√ 
√ 
√ 
√ 
√ 
Examination of 
Axial 
√ 
 
√ 
√ 
√ 
√ 
√ 

 
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Intraocular 
Pressure (IOP) 
√ 
 
√ 
√ 
√ 
√ 
√ 
Spherical 
Equivalent 
(SE) 
√ 
 
 
 
√ 
 
√ 
Examination 
with Slit-lamp 
√ 
 
 
 
√ 
 
√ 
OCT 
√ 
 
 
 
√ 
 
√ 
Sign Informed 
Consent 
√ 
 
 
 
 
 
 
Determine 
Inclusion/Excl
usion Criteria 
√ 
 
 
 
 
 
 
Random 
Grouping 
√ 
 
 
 
 
 
 
Distribute 
Equipment 
 
√ 
 
 
 
 
 
Record Device 
Defects 
 
√ 
√ 
√ 
√ 
√ 
√ 
Record 
Concomitant 
Medications 
√ 
 
√ 
√ 
√ 
√ 
√ 
Record 
Adverse 
Events 
√ 
 
√ 
√ 
√ 
√ 
√ 
End of Practice 
 
 
 
 
 
 
√ 
  
5. Data entry and Analysis 
5.1 Data collection 
The case report forms (CRFs) will serve as the means to document and collect clinical 
data throughout the trial. These forms will be in physical paper format, ensuring that 
the original material remains intact. It is important to note that the CRFs should not be 
altered or modified arbitrarily. 
All pertinent information regarding the patients involved in the trial will be recorded 
accurately and promptly on the CRFs. This includes any relevant data related to their 
medical condition, treatment received, and any observed outcomes or adverse events. 
It is crucial that this information is recorded truthfully to maintain the integrity and 
validity of the trial results. 
Data collected on site will be entered on a real-time basis using the EDC system to 
ensure that all required items are entered. The EDC will automatically verify that there 
are no missing values during submission. After examinations are completed, the paper 
examination forms will be stored in a locker of the research center to protect the privacy 

 
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of participants and ensure access for data review and audit. 
 
5.2 Statistical analysis plan 
The intention-to-treat (ITT) population comprised participants randomly assigned to 
either group. Data from all participants who attended at least one subsequent follow-up 
visit were included in the analysis, regardless of treatment or follow-up visit 
compliance. No imputation was used for the missing data. Individuals who switched to 
other myopia treatment modalities, such as orthokeratology or atropine eye drops, or 
discontinued the RLRL treatment, were censored. If a participant had only one eye with 
a SER exceeding –4.0 D, that eye was selected for the statistical analysis. In cases where 
both eyes were exceeding –4.0 D, the right eye was chosen for the analysis. 
Treatment efficacy was assessed using longitudinal mixed models for primary (changes 
in AL) and secondary (changes in SER and IOP) outcomes at multiple follow-up visits. 
The mixed effects model was fitted with a random intercept and random slope for the 
participant, where the group, visit, group-by-visit interaction, baseline age, sex, and 
baseline AL were fixed effects. Estimated mean treatment differences and 
corresponding 95% confidence intervals (CIs) were derived from mixed models. UCVA 
alterations were classified into three categories: decline by two or more lines, stable 
(within a line), or improvement by two or more lines. The BCVA at the 12-month and 
baseline was evaluated against the 20/25 standard. 
Sensitivity analyses were conducted to assess the treatment effects of therapy in 
controlling myopia progression, specifically axial elongation and SER progression, 
across different baseline SER and age groups. 
A longitudinal mixed-model analysis was conducted to assess the relationship between 
treatment efficacy and compliance within the intervention group. Treatment compliance 
in the intervention group was measured as a percentage of the total number of assigned 
treatment sessions. 
Safety analyses were performed in the ITT population. All adverse events were reported 
individually. Six ophthalmologists, one from each center, independently scrutinized the 
OCT scans for potential structural anomalies. 
 

 
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6.MONITORING 
Monitoring begins immediately after initiation. The first case from each participating 
center is enrolled, followed by monitoring at 30% and 50% of enrollment, and finally 
after completion of enrollment. The duration of surveillance is determined by the 
occurrence of serious adverse events. If there are abnormal enrollment situations or a 
high frequency of program violations, the frequency of monitoring will be increased 
accordingly. The monitoring focuses on subjects, investigators, and equipment used, 
primarily assessing the following aspects: 
 
1. Informed consent status: Ensuring that the number of signed informed consent forms 
matches the number of cases in the clinical trial report (including cases of screening 
failure), verifying that the version of the signed informed consent form aligns with the 
version approved by the ethics review, confirming that the ethics review was conducted 
prior to the signing of the informed consent form, assessing the completeness and 
standardization of the informed consent form (including inclusion of the clinical trial 
personnel’s contact information, signing date, etc.), and verifying that the subject’s 
signed informed consent form was signed by the subject or their legal representative (if 
necessary, confirming the actual participation of subjects in the trial). 
 
2. Implementation assessment: Whether the clinical trial procedures adhere to the 
clinical trial protocol, including the subject selection and exclusion criteria, sample size, 
selection of control devices, trial duration, observation endpoints, and the management 
and documentation of adverse events; verifying that the original data collection and 
case report forms are signed by the clinical trial personnel. 
 
3. Equipment assessment: Whether the delivered equipment product has a valid product 
inspection report issued by a qualified testing agency, and whether the management 
record of the tested product (including transportation, reception, processing, storage, 
distribution, recycling, and disposal) is complete; verifying if the quantity is consistent; 
assessing if the transportation conditions, storage temperature, storage conditions, 
storage duration, and safety validity period of the tested product meet the requirements; 
confirming if the tested product matches the product name, specification, and model 

 
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stated in the test report and clinical practice report. After each inspection, the inspector 
will generate an inspection report based on the findings. 
 
7. QUALITY ASSURANCE 
To ensure that this trial can be carried out in strict accordance with the clinical research 
protocol, clinical investigators, sponsors, and supervisors should strictly adhere to the 
requirements of the “Good Clinical Practice” (GCP) throughout the entire process 
of the clinical trial. This will help achieve standardized test procedures, accurate data, 
and reliable research conclusions. 
  
1.  Investigator's Responsibility 
1) Ensure that the “Informed Consent” is obtained and signed by each subject or 
their authorized representative. 
2) Carefully complete the case report form (CRF) as per the specified requirements. 
3) Collaborate with the regular visits of clinical monitors assigned by the sponsor. 
4) Maintain comprehensive records of laboratory inspections, clinical records, and 
original medical records of the subjects. 
 
2. Clinical Practice records  
The investigator is responsible for accurately and diligently documenting all cases 
according to the design requirements of the "case report form". The case report form 
serves as the original record and should not be altered. If any corrections are necessary, 
the original record should not be obscured. Instead, a horizontal line should be drawn 
at the location of the correction, accompanied by an explanation of the reason for the 
correction. This should be signed and dated by the physician who was involved in the 
clinical practice. 
 
3. Training  
The personnel involved in the clinical research should have a consistent and stable team. 
Prior to the commencement of the clinical trial, all personnel involved should undergo 
standardized training to ensure that they have a consistent understanding and 
knowledge of the clinical trial protocol. They should also be familiar with the recording 
method and judgment criteria of the case report form (CRF) in a uniform manner. 

 
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4. Supervision 
1) The sponsor appoints qualified monitors to regularly visit each study site during 
the trial period. Their role is to ensure that the investigator accurately completes 
the case report form, adheres to the research plan, conducts clinical trials, and 
collects completed case report forms. 
2) Monitors should be granted direct access to source documents, including original 
documents, data, and records. This access allows them to inspect, analyze, and 
verify any important records and reports related to the evaluation of clinical trials. 
3) The investigator should be able to contact the monitor at any time for discussions. 
The original data that the monitor should verify include (but are not limited to): 
ü Subjects’ information (subject's phone number, date of birth); 
ü The confirmation of participation in the clinical trial should include the subject’
s identity, the test device number, and the date of signing the informed consent 
form； 
ü Whether it meets the criteria for participating in clinical trials; 
ü Date of visit. 
5. Data validation 
1) The investigator should verify the data that significantly deviates from or is outside 
the acceptable range, and provide necessary explanations. 
2) Each test item must indicate the unit of measurement used. 
3) All observations and findings in clinical practice should be verified to ensure the 
reliability of the data and to ensure that all conclusions are derived from the original 
data. 
 
8. ETHICS 
Ethical approval 
This study will undergo review and approval from the Ethics Committee of Shanghai 
General Hospital. The study protocol must be granted approval by the ethics committee 
prior to its implementation. The implementation process must adhere to the regulations 
and requirements set by relevant institutions and study sites, and may require additional 
approval from the clinical site if necessary. Any modifications to the study protocol 
after ethical approval has been obtained will need to be submitted to the ethics 

 
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committee for re-approval before implementation. 
 
Plan modification 
Modifications to the study plan must be submitted to the sponsor and the ethics 
committee for review and approval before implementation, except for necessary 
modifications that intend to handle immediate hazards to subjects, or for modifications 
that are relevant for administrative management and/or related (such as changing the 
contact number). 
 
Informed consent 
The procedures and documentation for obtaining informed consent in the research study 
will be reviewed and approved by the ethics committee prior to implementation. The 
informed consent process will ensure that participants are provided with comprehensive 
information to make an informed decision about their participation, including the 
potential benefits and risks involved. The researcher will engage in discussions with 
the participants and their parents/guardians, allowing them to ask questions before, 
during, and after the study. Participants and their parents/guardians will have the right 
to be informed throughout the study and can withdraw their participation at any time 
without providing a reason. 
 
The informed consent process will provide an overview of the study, including the 
purpose of the study, procedures and scheduled plans, potential risks and benefits, and 
other treatment options.  The informed consent should include an explanation of the 
subjects’ rights once they participate in the study. Subjects should be given enough time 
to consider whether to participate in the study. If they agree to become volunteers, they 
need to sign off on the subjects’ informed consent. 
 
Confidentiality 
According to the relevant agreement, all parties involved must keep study data 
confidential throughout the study process. All data related to the test cannot be accessed 
without authorization. The private information of research subjects will be protected in 
the report and the publication of any clinical research data. 
 

 
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References 
 
1. Dong L, Kang YK, Li Y, Wei WB, Jonas JB. PREVALENCE AND TIME TRENDS OF MYOPIA 
IN CHILDREN AND ADOLESCENTS IN CHINA: A Systemic Review and Meta-Analysis. Retina 
2020;40:399-411. doi: 10.1097/iae.0000000000002590. 
2. Wang SK, Guo Y, Liao C, Chen Y, Su G, Zhang G, et al. Incidence of and Factors Associated 
With Myopia and High Myopia in Chinese Children, Based on Refraction Without Cycloplegia. 
JAMA Ophthalmol 2018;136:1017-1024. doi: 10.1001/jamaophthalmol.2018.2658. 
3. Wu LJ, You QS, Duan JL, Luo YX, Liu LJ, Li X, et al. Prevalence and associated factors of 
myopia 
in 
high-school 
students 
in 
Beijing. 
PLoS 
One 
2015;10:e0120764. 
doi: 
10.1371/journal.pone.0120764. 
4. Holden BA, Fricke TR, Wilson DA, Jong M, Naidoo KS, Sankaridurg P, et al. Global Prevalence 
of Myopia and High Myopia and Temporal Trends from 2000 through 2050. Ophthalmology 
2016;123:1036-1042. doi: 10.1016/j.ophtha.2016.01.006. 
5. Baird PN, Saw SM, Lanca C, Guggenheim JA, Smith Iii EL, Zhou X, et al. Myopia. Nat Rev Dis 
Primers 2020;6:99. doi: 10.1038/s41572-020-00231-4. 
6. Cho P, Tan Q. Myopia and orthokeratology for myopia control. Clin Exp Optom 2019;102:364-
377. doi: 10.1111/cxo.12839. 
7. Chia A, Chua WH, Cheung YB, Wong WL, Lingham A, Fong A, et al. Atropine for the treatment 
of childhood myopia: safety and efficacy of 0.5%, 0.1%, and 0.01% doses (Atropine for the 
Treatment of Myopia 2). Ophthalmology 2012;119:347-354. doi: 10.1016/j.ophtha.2011.07.031. 
8. Li FF, Yam JC. Low-Concentration Atropine Eye Drops for Myopia Progression. Asia Pac J 
Ophthalmol (Phila) 2019;8:360-365. doi: 10.1097/apo.0000000000000256. 
9. Yam JC, Jiang Y, Tang SM, Law AKP, Chan JJ, Wong E, et al. Low-Concentration Atropine for 
Myopia Progression (LAMP) Study: A Randomized, Double-Blinded, Placebo-Controlled Trial of 
0.05%, 0.025%, and 0.01% Atropine Eye Drops in Myopia Control. Ophthalmology 2019;126:113-
124. doi: 10.1016/j.ophtha.2018.05.029. 
10. Wu PC, Chuang MN, Choi J, Chen H, Wu G, Ohno-Matsui K, et al. Update in myopia and 
treatment strategy of atropine use in myopia control. Eye (Lond) 2019;33:3-13. doi: 
10.1038/s41433-018-0139-7. 
11. Lam CSY, Tang WC, Tse DY, Lee RPK, Chun RKM, Hasegawa K, et al. Defocus Incorporated 
Multiple Segments (DIMS) spectacle lenses slow myopia progression: a 2-year randomised clinical 
trial. Br J Ophthalmol 2020;104:363-368. doi: 10.1136/bjophthalmol-2018-313739. 

 
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12. Ivandic BT, Ivandic T. Low-level laser therapy improves visual acuity in adolescent and adult 
patients with amblyopia. Photomedicine and laser surgery. 2012;30(3):167-171. 
13. Nickla DL, Wallman J. The multifunctional choroid. Prog Retin Eye Res 2010;29(2):144-68. 
14. Summers JA. The choroid as a sclera growth regulator. Exp Eye Res 2013;114:120-7. 
15. Nickla DL, Zhu X, Wallman J. Effects of muscarinic agents on chick choroids in intact eyes and 
eyecups: evidence for a muscarinic mechanism in choroidal thinning. Ophthalmic Physiol Opt 
2013;33(3):245-56. 
16. Nickla DL, Totonelly K, Dhillon B. Dopaminergic agonists that result in ocular growth 
inhibition also elicit transient increases in choroidal thickness in chicks. Exp Eye Res 
2010;91(5):715-20. 
 
 
 

 
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Introduction to Treatment Device and Data Managements System 
  
Specifications for the use of machinery  
After the start of the research, the sponsor will send special personnel to directly deliver 
the test materials to each research centre. The research centre and the sponsor will 
establish a complete test equipment handover procedure. Each research institution shall 
set up a test material administrator and establish a special "Clinical Practice Medical 
Device Use Record Form", register the device number, the name of the subject, and be 
signed by the device administrator. 
The management, issuance, and recycling of clinical devices in this practice are 
managed by special personnel. Researchers must ensure that all experimental devices 
are used only for subjects participating in the clinical practice. Their usage should 
follow the practice protocol and instructions. The sponsor shall contract with the 
hospital for disposal, and shall not transfer the clinical trial equipment to any non-
clinical practice participant. The supervisor is responsible for supervising the supply, 
use, storage of clinical trial equipment and the processing of the trial equipment. 
1. Features, structure, working principle, mechanism of action, and test scope of 
Eyerising products 
Eyerising amblyopia comprehensive treatment instrument is mainly composed of 
treatment module, housing, eye mask, interpupillary distance adjustment knob, locking 
hand wheel, touch screen, control circuit, and electrical interface (as shown in Figure 
1). The functions of each component structure are as follows: 
1) Treatment module: an electronic module that realizes four treatment functions; 
2) Shell: fix and install each component module, which is convenient for users to use 
the instrument; 
3) Eye mask: The user's eyes are close to the eye mask during treatment, and the eye 
mask has a good wrapping property to prevent the interference of external light; 
4) Interpupillary distance knob: The treatment device is a binocular product, and the 
user can adjust the distance of the emission window of the treatment device to be 
consistent with their own interpupillary distance, to achieve the best treatment 
effect; 
5) Hand wheel lock: The user adjusts the pitch angle of the treatment head to the best 
position according to his height and posture, and then locks it with the hand wheel 

 
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lock to prevent loosening. 
6) Touch screen: the user operates the machine through the touch screen; 
7) Circuit control: control each electronic module; 
8) Electrical interface: including power switch, power interface, USB interface and 
LAN interface. 
9) Power switch: use for starting and closing the machine; 
10) Power interface: connect the adapter for power supply; 
11) USB interface: used for manufacturers to detect and debug internal circuits; 
12) LAN interface: help machine connect to the external Internet. 
 
Figure 1: 
治疗眼罩：Treatment Eye Mask 
激光辐射窗⼝：Laser Radiation Window 
锁紧⼿轮：Hand Wheel Lock 
触摸屏：Touch Screen 
外壳：Shell 
 
 
2. Specifications and models 
RS-200-1A 
 
3. Working principle and mechanism 
The potential of low-intensity photochemical conversion can cause photochemical 
reactions in the retina, including increasing the activity of cytochrome C oxidase, 
changing gene expression to regulate the mitochondrial respiratory chain , and 
increasing the biological activity of nitric oxide . Also, it can increase Choroidal 
metabolism rate and circulation to improve scleral hypoxia, prevent or slow down the 
progression of myopia. 
 
4. product indications and contraindications, precautions, 
Indications: 
1) It is suitable for patients with ametropia, anisometropia and strabismus amblyopia. 
2) It is suitable for the treatment of juvenile myopia. 

 
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3) Applicable age for this product: 3-16 years old. 
 
Contraindications: 
1) Patients with a history of photosensitivity. 
2) Patients with fundus retinopathy, cataracts or other intraocular diseases. 
3) Patients with optic nerve damage or congenital optic nerve dysfunction. 
 
Precautions: 
1) Laser safety matters 
This product is classified as a Class 3R laser product according to GB7247.1-2012. For 
non-patients, direct vision may cause dazzling, flash blindness, and after-eye imaging 
and other adverse reactions. Non-patient users are requested not to look directly into 
the laser window (as shown in Figure 1). If you need to look directly into the laser for 
special reasons, please wear laser protective glasses and laser protective glasses with 
optical density OD≥3 in the visible light range. 
The laser parameters emitted by the treatment device are as follows: 
a) Wavelength: 650nm 
b) Divergence angle: 2.5° 
c) Pulse width and repetition frequency: continuous emission 
d) Power: 2.0mW±0.5mW 
2) Pay attention to eye hygiene during treatment, and stop using this product if you have 
eye diseases such as eye inflammation and swelling. 
3) To use this product, please follow the doctor's instructions and select appropriate 
functions for treatment. 
4) If discomfort occurs while using this product, stop using it or follow the doctor's 
advice. 
5) After each use, please turn off the power switch, and then unplug the power plug. 
6) If the external network voltage suddenly increases or the operator deliberately 
frequently starts and stops the equipment, the laser radiation of the equipment may 
exceed the maximum radiant power specified by this product. 
7) If the treatment device is expected to be used by more than one person in a hospital 
or clinic, a non-woven eye mask should be put on the eye mask of the treatment device 
to ensure that one person has a new eye mask. 

 
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8) Please strictly follow the operation method in this manual for operation and treatment. 
If this operation method is not followed, it may cause harmful laser irradiation.