Study design
This cluster RCT will be carried out in 6 schools from 3 municipalities, each of which represents a distinctive level of socioeconomic development geographically clustered in Jiangsu Province, i.e., Peicounty a rapid-developing city located in the north, Yizheng a steady-developing city in the middle, Changshu an advanced-developing city in the south. Before the RCT study, sufficient observational (Surveillance) and analytical (Cohort) studies were carried out. We concluded that education pressure and time outdoors are still at play in the formation of myopia[6, 19, 20]. The intervention program mainly focuses on the improvement of the environment and behaviour of students. (Fig.1) Baseline data collection will start at the second year of the cohort study (ES-SCI study cohort section). All participating students will be assessed annually on visual indices (such as refractive error, axial length) and followed up for a total of 5 years. During the first year follow-up visit, additional assessments will occur at 3-, 6-, 9--months after the baseline.
Patient and Public Involvement
The project was developed Eastern Chinses Student common disease Surveillance Cohort and Intervention (ES-SCI) study. Patient and public (children and their parent) involvement representatives were supported by annually basic public health of child and adolescent health (myopia intervention) funding. Relevant schools, CDC and Community hospitals ensured public involvement at all stages. They collaborated on intervention design, recruitment and consent processes, accessibility of information leaflets, data collection, interpretation and dissemination. Parent and their child would receive physical examination feedback every year. In addition, children involved in myopia prevention and control are not patients.
Eligibility criteria
Inclusion criteria for students to receive targeted environmental or behaviour interventions: (1) No severe other eye diseases;(2) Chinese Han ethnicity;(3) Ability of parents/guardians to provide informed consent;(4) Aged between 7.5 to 9.5 years. Inclusion criteria for students to Low-Intensity Laser Therapy for Slowing the progression of Myopia added an additional rule is: myopia ranges from -1.50D to -5.00D.
Exclusion criteria: (1) There are serious eye diseases, including nystagmus, glaucoma, cataract, photosensitivity, retinal detachment, etc. (2) The age of students is not 7.5 ~ 9.5 years old. (3) Parents or guardians did not provide informed consent.
Sample size calculation
The specific parameters are as follows: α= 0.01, PC = 38.1%, PE (intervention group) =16.2%, Zα= 2.576,Zβ= 2.326, design effect = 1.2, drop-out rate =5%, the calculated intervention and control sample size were respectively, intervention(1-4) group = 120, control group = 120,total sample size=960.
The intervention group and control group
Targeted environmental or behaviour intervention methods of this cluster randomized controlled trial are as follows: the intervention population was divided into four groups. Each intervention group was matched with a control group.
Intervention method 1: This population in the intervention group and the control group simultaneously implemented recess activities, and the intervention increased an additional 40 minutes of outdoor activities. On holidays the intervention group is also to ensure 40 minutes of outdoor activities for the intervention group. The intervention is called locked the door to increase the time for outdoor activities.
Intervention method 2: The intervention group was arranged in the school where the government transformed lighting and desks and chairs, while the control group is set in another entire school. This research design is closer to the actual world study. The intervention is called Indoor lighting of light source equipment transformation, desks and chairs adjustment.
Intervention method 3: Study concerning low-Intensity laser therapy for slowing the progression of myopia has been ongoing [12]. There is no sufficient evidence to prove the long-term effect of the intervention, so we will combine the cohort design to observe the long-term effect of the intervention population for at least five years. The control group came from another school. The intervention is called Low-Intensity Laser Therapy for Slowing the progression of Myopia.
Intervention method 4: Students' near sight habits are considered to be essential factors affecting myopia [6, 21]. The intervention program is to use wearable environment monitoring equipment to warn of lousy eye habits to students. The control group come from another school.
Randomization, allocation and confidentially
A total of 6 primary schools have been randomly selected into the ES-SCI cohort study from the school directory in the provincial Department of Education to minimize contamination which may occur if two classes of the same school receive the intervention and the other does not. All Grade Two to three students from each primary school will be considered. To avoid spill-over effects within school classes, we will conduct a cluster-randomized controlled trial using school class as a randomization unit, with four classes as an intervention group and four classes as a control group for each intervention method. We will use block randomization with computer randomly generated to guarantee the equality of sample sizes between study groups. However, due to the nature of the intervention, study participants cannot be completely blinded to the intervention.
Junior scientists supervise the baseline assessment until students have been recruited and baseline data collection has been completed. Research assistants who perform the computer-assisted follow up assessments for primary and secondary outcomes will be blinded to the group allocation. The Senior Program Coordinator will be informed under circumstances when these assistants inadvertently are un-blinded.
Students allocated to the control group are from the cohort study database matching with the intervention group in gender, age and refractive parameters. They will also be tracked (attending clinical examination) at baseline and 3-,6-.9-.12-,24-,36-,48-,60-months. Considering the nature of the intervention method 2, control participants may not be immune to its effects. Therefore, during the same study period, control participants will be observed for the same exposure.
Study variables and methods of assessment
The effectiveness measures are physical, biological, and economical from baseline and after 3,6,9,12,24,36,48 and 60 months. (Table1)
Primary outcomes:
Refractive error: Pupils participated in an ophthalmic examination with an auto-refractor applied with cycloplegia. The cycloplegic refraction is measured using tropicamide phenylephrine eye drops every 5 min, three times. Then refractive error is measured 30 min after the first drop of tropicamide by auto-refractor with five repeated measurements.
Uncorrected visual acuity: is defined as visual acuity measured without correcting refractive errors. Best-corrected visual acuity (BCVA) is examined after correcting refractive errors.
Axial length: The Axis of the eye is described as an optical instrument. The distance from the surface layer of the eyeball receiving light, that is, from the cornea lens vitreous retina (the innermost layer of receiving light), is regarded as a central axis of the optical system in physics is called the "eye axis".
Secondary outcomes:
Biological samples: Collecting biological samples includes urine, saliva, and faeces.
Height, Weight, and Blood pressure: Anthropometric measurements were taken to obtain height, weight, and blood pressure according to standard techniques.
Overweight and obesity: was defined by the Screening for overweight and obesity among school-age children and adolescents (WST586-2018) and BMI is specified as weight in kilograms divided by height in meters squared [22].
Elevated blood pressure: was defined using the National Blood Pressure Reference for Chinese Han Children and Adolescents (CCBP) thresholds, i.e., ≥95th percentile as elevated BP [23].
Cost-effectiveness: All health system costs/ Health outcomes.
Adverse events and evaluations:
Intraocular pressure: Non-contact tonometer was used to check intraocular pressure.
Fundus examination: Direct ophthalmoscopy was used to examine the fundus. Attention should be paid to congenital fundus abnormalities, optic atrophy, retinopathy, macular disease, retinal detachment, vitreous opacity, and primary vitreous hyperplasia.
Statistical analysis plan
Descriptive statistics will present the sample characteristics, and the results will be written as mean, standard deviation and percentage. Pearson’s chi-square test and Student’s t-test will be used to compare categorical and continuous variables, respectively. Generalized linear mixed models analysis will be used for repeated measurements (baseline and 3-,6-.9-.12-,24-,36-,48-,60-months)[24, 25].
All data will be analyzed according to the intention-to-treat principle. The statistics will be carried out in office software, SAS 10.0 software and R software. A P<0.05 will be considered statistically significant.
Ethics approval and Study status (Trial status)
Ethics approval was obtained from the Institutional Review Board of Ethics committee of Jiangsu Province CDC. (Ethics Approval Number: JSJK2021-B008-02, JSJK2021-B010-01, JSJK2021-B011-01).
Student recruitment has begun in August 2021.