Efficacy and Safety of 1% Atropine "5+3" Regimen in Children and Adolescents Controlling Myopia

Studies have shown that atropine eye drops are effective in controlling myopia in children and adolescents. 1% atropine ophthalmic drug has obvious curative effect for controlling myopia, but its side effects such as photophobia and blurred vision limit its popularization and use. In the early stage, our research group used 1% atropine "5+3" myopia control program and 1% atropine alternate eye myopia control program. Retrospective clinical research data showed that it could significantly reduce side effects and improve use compliance, but there is currently no evidence from prospective clinical studies.

Study Overview

• Status: Recruiting
• Conditions: Myopia
• Intervention / Treatment: Drug: 1% atropine 5+3

Detailed Description

Studies have shown that atropine eye drops are effective in controlling myopia in children and adolescents. Among them, low-concentration atropine has few side effects and is the primary recommendation, but many clinical practices and studies suggest that its effect in controlling myopia is limited. 1% atropine ophthalmic drug has obvious curative effect advantages in controlling myopia, but its side effects such as photophobia and blurred vision limit its popularization and use. In the early stage, our research group used 1% atropine "5+3" myopia control (eye instillation for 5 consecutive nights in the first week of each month, one night per week in the 2nd, 3rd, and 4th weeks; after 3 months of monocular application, change to the contralateral eye), data from retrospective clinical studies have shown that it can significantly reduce side effects and improve compliance, but there is currently a lack of evidence from prospective clinical studies. Therefore, this study intends to use a randomized controlled trial, with 1% atropine used in both eyes once a week as the control group, to evaluate the effect of the "5+3" regimen in controlling myopia (spherical equivalent and axial length), safety (accommodation amplitude, amount of phoria, binocular vision function, etc.), and the compliance and side effects (photophobia, blurred vision, etc.).

• Study Type: Interventional
• Enrollment (Anticipated): 192
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Yan Xu, M.D.; Phone Number: +86 18621080996; Email: drxuyan_2004@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200040
      • Recruiting
      • Shanghai Eye Diseases Prevention & Treatment Center
      • Contact: Haidong Zou, M.D.; Phone Number: +86 13311986528; Email: zouhaidong@sjtu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 6 to 12 years old;
• Both eyes are in line with the diagnosis of myopic refractive error and 0.25D < myopia spherical lens <4.00D after mydriasis, astigmatism <2.00D, binocular anisometropia <3.00D, and the best corrected distance vision is at least 0.8, myopia The force is at least 0.8;
• Visual function: Timus≤100 seconds, exophoria <5△, accommodation amplitude (AMP) ≥ age-related minimum accommodation amplitude value (minimum accommodation amplitude=15-0.25×age);
• No contraindications for atropine treatment such as acute eye inflammation, dry eye, keratoconus, diabetes, etc.;
• The written informed consent of the guardian and the child himself.

Exclusion Criteria:

• History of photosensitivity, glaucoma, blue eye syndrome, ocular hypertension, fundus macular lesions or damage;
• Corneal curvature examination, the average K value of the anterior surface of the cornea is ≥45;
• Patients with ocular trauma, oblique or surgical eyes, atopic keratoconjunctivitis and other chronic eye diseases;
• Those with previous ophthalmia, severe angular, conjunctival infection and other eye diseases;
• Patients with neurological diseases and allergic or contraindications to atropine or other therapeutic drugs;
• Received other treatments to control the development of myopia in the past, such as the use of anticholinergic drugs such as atropine within 3 months, or participated in other relevant researchers such as functional frame mirrors and multifocal flexible mirrors;
• Other circumstances judged by the investigator to be unsuitable to participate in the research.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1% atropine 5+3; Put the 1% atropine eye drops into the conjunctival sac, then close the eyes and press the nasolacrimal duct used for 5 consecutive nights in the first week of each month, one night per week in the 2nd, 3rd, and 4th weeks; after 3 months of monocular application, change to the contralateral eye Total treatment time 1 year	Drug: 1% atropine 5+3; A method for myopia control using high-concentration atropine
Placebo Comparator: 1% atropine weekly; Put the 1% atropine eye drops into the conjunctival sac, then close the eyes and press the nasolacrimal duct once a week in both eyes Total treatment time 1 year	Drug: 1% atropine 5+3; A method for myopia control using high-concentration atropine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
spherical equivalent	spherical equivalent(SE)，Diopter(D), measured by subjective optometry	Before atropine treatment
spherical equivalent	spherical equivalent(SE)，Diopter(D), measured by subjective optometry	1months after treatment
spherical equivalent	spherical equivalent(SE)，Diopter(D), measured by subjective optometry	3months after treatment
spherical equivalent	spherical equivalent(SE)，Diopter(D), measured by subjective optometry	6months after treatment
spherical equivalent	spherical equivalent(SE)，Diopter(D), measured by subjective optometry	9months after treatment
spherical equivalent	spherical equivalent(SE)，Diopter(D), measured by subjective optometry	12months after treatment
axial length	axial length(AL), millimeter(mm), measured by IOL master	Before atropine treatment
axial length	axial length(AL), millimeter(mm), measured by IOL master	1months after treatment
axial length	axial length(AL), millimeter(mm), measured by IOL master	3months after treatment
axial length	axial length(AL), millimeter(mm), measured by IOL master	6months after treatment
axial length	axial length(AL), millimeter(mm), measured by IOL master	9months after treatment
axial length	axial length(AL), millimeter(mm), measured by IOL master	12months after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
accommodation amplitude	Accommodation amplitude is measured by the amount of diopter change as the target is moved closer, diopter(D)	Before atropine treatment
accommodation amplitude	Accommodation amplitude is measured by the amount of diopter change as the target is moved closer, diopter(D)	1months after treatment
accommodation amplitude	Accommodation amplitude is measured by the amount of diopter change as the target is moved closer, diopter(D)	3months after treatment
accommodation amplitude	Accommodation amplitude is measured by the amount of diopter change as the target is moved closer, diopter(D)	6months after treatment
accommodation amplitude	Accommodation amplitude is measured by the amount of diopter change as the target is moved closer, diopter(D)	9months after treatment
accommodation amplitude	Accommodation amplitude is measured by the amount of diopter change as the target is moved closer, diopter(D)	12months after treatment
amount of phoria	measured by Von-Graefe method, degree(°)	Before atropine treatment
amount of phoria	measured by Von-Graefe method, degree(°)	1months after treatment
amount of phoria	measured by Von-Graefe method, degree(°)	3months after treatment
amount of phoria	measured by Von-Graefe method, degree(°)	6months after treatment
amount of phoria	measured by Von-Graefe method, degree(°)	9months after treatment
amount of phoria	measured by Von-Graefe method, degree(°)	12months after treatment
binocular vision function	measured by Titmus method, second	Before atropine treatment
binocular vision function	measured by Titmus method, second	1months after treatment
binocular vision function	measured by Titmus method, second	3months after treatment
binocular vision function	measured by Titmus method, second	6months after treatment
binocular vision function	measured by Titmus method, second	9months after treatment
binocular vision function	measured by Titmus method, second	12months after treatment
photophobia	the prevalence of photophobia known from Atropine Use and Adverse Reactions Questionnaire	1months after treatment
photophobia	the prevalence of photophobia known from Atropine Use and Adverse Reactions Questionnaire	3months after treatment
photophobia	the prevalence of photophobia known from Atropine Use and Adverse Reactions Questionnaire	6months after treatment
photophobia	the prevalence of photophobia known from Atropine Use and Adverse Reactions Questionnaire	9months after treatment
photophobia	the prevalence of photophobia known from Atropine Use and Adverse Reactions Questionnaire	12months after treatment
blurred vision	the prevalence of blurred vision known from Atropine Use and Adverse Reactions Questionnaire	1months after treatment
blurred vision	the prevalence of blurred vision known from Atropine Use and Adverse Reactions Questionnaire	3months after treatment
blurred vision	the prevalence of blurred vision known from Atropine Use and Adverse Reactions Questionnaire	6months after treatment
blurred vision	the prevalence of blurred vision known from Atropine Use and Adverse Reactions Questionnaire	9months after treatment
blurred vision	the prevalence of blurred vision known from Atropine Use and Adverse Reactions Questionnaire	12months after treatment
Other discomfort	Other discomfort reported by the patient but not included in the Atropine Use and Adverse Reactions Questionnaire	1months after treatment
Other discomfort	Other discomfort reported by the patient but not included in the Atropine Use and Adverse Reactions Questionnaire	3months after treatment
Other discomfort	Other discomfort reported by the patient but not included in the Atropine Use and Adverse Reactions Questionnaire	6months after treatment
Other discomfort	Other discomfort reported by the patient but not included in the Atropine Use and Adverse Reactions Questionnaire	9months after treatment
Other discomfort	Other discomfort reported by the patient but not included in the Atropine Use and Adverse Reactions Questionnaire	12months after treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
lens thickness	lens thickness(LT), millimeter(mm), measured by IOL master	Before atropine treatment
lens thickness	lens thickness(LT), millimeter(mm), measured by IOL master	1months after treatment
lens thickness	lens thickness(LT), millimeter(mm), measured by IOL master	3months after treatment
lens thickness	lens thickness(LT), millimeter(mm), measured by IOL master	6months after treatment
lens thickness	lens thickness(LT), millimeter(mm), measured by IOL master	9months after treatment
lens thickness	lens thickness(LT), millimeter(mm), measured by IOL master	12months after treatment
lens power	lens power(LP), diopter(D), calculated by Bennett formula	Before atropine treatment
lens power	lens power(LP), diopter(D), calculated by Bennett formula	1months after treatment
lens power	lens power(LP), diopter(D), calculated by Bennett formula	3months after treatment
lens power	lens power(LP), diopter(D), calculated by Bennett formula	6months after treatment
lens power	lens power(LP), diopter(D), calculated by Bennett formula	9months after treatment
lens power	lens power(LP), diopter(D), calculated by Bennett formula	12months after treatment
anterior chamber depth	anterior chamber depth(ACD), millimeter(mm), measured by IOL master	Before atropine treatment
anterior chamber depth	anterior chamber depth(ACD), millimeter(mm), measured by IOL master	1months after treatment
anterior chamber depth	anterior chamber depth(ACD), millimeter(mm), measured by IOL master	3months after treatment
anterior chamber depth	anterior chamber depth(ACD), millimeter(mm), measured by IOL master	6months after treatment
anterior chamber depth	anterior chamber depth(ACD), millimeter(mm), measured by IOL master	9months after treatment
anterior chamber depth	anterior chamber depth(ACD), millimeter(mm), measured by IOL master	12months after treatment
corneal power	corneal power, diopter(D), measured by IOL master	Before atropine treatment
corneal power	corneal power, diopter(D), measured by IOL master	1months after treatment
corneal power	corneal power, diopter(D), measured by IOL master	3months after treatment
corneal power	corneal power, diopter(D), measured by IOL master	6months after treatment
corneal power	corneal power, diopter(D), measured by IOL master	9months after treatment
corneal power	corneal power, diopter(D), measured by IOL master	12months after treatment
central corneal thickness	central corneal thickness(CTC), micron(um), measured by IOL master	Before atropine treatment
central corneal thickness	central corneal thickness(CTC), micron(um), measured by IOL master	1months after treatment
central corneal thickness	central corneal thickness(CTC), micron(um), measured by IOL master	3months after treatment
central corneal thickness	central corneal thickness(CTC), micron(um), measured by IOL master	6months after treatment
central corneal thickness	central corneal thickness(CTC), micron(um), measured by IOL master	9months after treatment
central corneal thickness	central corneal thickness(CTC), micron(um), measured by IOL master	12months after treatment
retinal thickness	retina thickness, microns(um), measured by SSOCT	Before atropine treatment
retinal thickness	retina thickness, microns(um), measured by SSOCT	1months after treatment
retinal thickness	retina thickness, microns(um), measured by SSOCT	3months after treatment
retinal thickness	retina thickness, microns(um), measured by SSOCT	6months after treatment
retinal thickness	retina thickness, microns(um), measured by SSOCT	9months after treatment
retinal thickness	retina thickness, microns(um), measured by SSOCT	12months after treatment
choroidal thickness	choroidal thickness, microns(um), measured by SSOCT	Before atropine treatment
choroidal thickness	choroidal thickness, microns(um), measured by SSOCT	1months after treatment
choroidal thickness	choroidal thickness, microns(um), measured by SSOCT	3months after treatment
choroidal thickness	choroidal thickness, microns(um), measured by SSOCT	6months after treatment
choroidal thickness	choroidal thickness, microns(um), measured by SSOCT	9months after treatment
choroidal thickness	choroidal thickness, microns(um), measured by SSOCT	12months after treatment
ciliary muscle thickness	ciliary muscle thickness, microns(um), photographed by ASOCT and measured by semiautomatic software	Before atropine treatment
ciliary muscle thickness	ciliary muscle thickness, microns(um), photographed by ASOCT and measured by semiautomatic software	1months after treatment
ciliary muscle thickness	ciliary muscle thickness, microns(um), photographed by ASOCT and measured by semiautomatic software	3months after treatment
ciliary muscle thickness	ciliary muscle thickness, microns(um), photographed by ASOCT and measured by semiautomatic software	6months after treatment
ciliary muscle thickness	ciliary muscle thickness, microns(um), photographed by ASOCT and measured by semiautomatic software	9months after treatment
ciliary muscle thickness	ciliary muscle thickness, microns(um), photographed by ASOCT and measured by semiautomatic software	12months after treatment
the distance between ciliary muscle apex and scleral spur	ciliary muscle thickness, microns(um), photographed by ASOCT and measured by semiautomatic software	Before atropine treatment
the distance between ciliary muscle apex and scleral spur	ciliary muscle thickness, microns(um), photographed by ASOCT and measured by semiautomatic software	1months after treatment
the distance between ciliary muscle apex and scleral spur	ciliary muscle thickness, microns(um), photographed by ASOCT and measured by semiautomatic software	3months after treatment
the distance between ciliary muscle apex and scleral spur	ciliary muscle thickness, microns(um), photographed by ASOCT and measured by semiautomatic software	6months after treatment
the distance between ciliary muscle apex and scleral spur	ciliary muscle thickness, microns(um), photographed by ASOCT and measured by semiautomatic software	9months after treatment
the distance between ciliary muscle apex and scleral spur	ciliary muscle thickness, microns(um), photographed by ASOCT and measured by semiautomatic software	12months after treatment

Collaborators and Investigators

• Sponsor: Shanghai Eye Disease Prevention and Treatment Center
• Investigators: Study Director: Yan Xu, M.D., Shanghai Eye Diseases Prevention Treatment Center

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: June 28, 2022
• First Submitted That Met QC Criteria: July 2, 2022
• First Posted (Actual): July 8, 2022

Study Record Updates

• Last Update Posted (Actual): July 12, 2022
• Last Update Submitted That Met QC Criteria: July 11, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Refractive Errors; Myopia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Adjuvants, Anesthesia; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Mydriatics; Atropine
• Other Study ID Numbers: 2021SQ001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No