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A-eyedrops on Ocular Alignment and Binocular Vision

Primary Purpose

Exotropia, Exophoria, Myopia

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
0.01% atropine eye drops
placebo eye drops (0.9% preservative free sodium chloride)
Sponsored by
Eye & ENT Hospital of Fudan University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Exotropia focused on measuring atropine, myopia, ocular alignment, binocular vision, exotropia, exophoria

Eligibility Criteria

5 Years - 14 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • The age ranged from 5 to 14 years;
  • Astigmatism < 2.5D, spherical power: - 1.00D ~ -6.00D; difference between eyes in spherical power < 1.5D, difference between eyes in astigmatism < 1.00D;
  • Intraocular pressure < 21mmHg;
  • Subgroups according to the ocular alignment: ortho group refers to exophoria with an exodeviation at near ≤ 6prism diopter(PD); exophoria group refers to exophoria with an exodeviation at near > 6PD[13]; intermittent exotropia group refers to exotropia with an exodeviation at distance 15 PD and a control ability score < 3[14]; after strabismus surgery group refers to the intermittent exotropia patients underwent strabismus surgery for the first time, without serious intraoperative and postoperative complications, 3 months after operation;
  • Subjects and their parents or legal guardians have signed informed consent and are willing to accept randomized grouping and regular follow-up.

Exclusion Criteria:

  • Amblyopia
  • Have heart disease or serious respiratory disease
  • Allergic to atropine, cyclopentantone, propoxybenzocaine and benzalkonium chloride;
  • Those who have used contact lenses, bifocal lenses, or other measures to control myopia (including atropine);
  • No binocular vision;
  • Combined with vertical strabismus, abnormal oblique muscle function, cyclodeviation, dissociated vertical deviation(DVD) or A-V pattern;
  • Previous history of strabismus surgery or other ocular surgery;
  • Severe complications during or after strabismus surgery, such as perforation of the sclera, tear and detachment of extraocular muscle; postoperative eye movement limitation; visual acuity decreased after operation;
  • Combined lateral incomitance;
  • Combined with other ocular diseases;
  • Craniofacial malformations affecting the orbits;
  • significant neurological disorders;
  • Birth less than 34 weeks or birth weight less than 1500 g;
  • Intraocular pressure > 21mmhg;
  • Unable to cooperate with the examination.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    low concentration atropine group

    placebo group

    Arm Description

    Subjects of the low concentration atropine group received 0.01% atropine eye drops both eyes once every night. Eye drops are prepackaged with identical eye drops bottle, pasted with number and shelf life, and stored in 4℃.

    Subjects of the control group received placebo eye drops (0.9% preservative free sodium chloride) both eyes once every night. Eye drops are prepackaged with identical eye drops bottle, pasted with number and shelf life, and stored in 4℃.

    Outcomes

    Primary Outcome Measures

    Ocular alignment
    Change from baseline in ocular alignment measured by a prism alternating cover test using an accommodative target at 6 m and 1/3 m.

    Secondary Outcome Measures

    Stereopsis
    Change from baseline in stereopsis measured with the Random dot stereogram.
    Fusion
    Change from baseline in fusion measured with the Worth Four-Dots.
    AC/A ratio
    Change from baseline in AC/A ratio measured using the Von Graefe method
    Negative and positive relative accommodation
    Change from baseline in negative and positive relative accommodation measured using a phoropter.
    Fusional convergence and divergence amplitudes
    Change from baseline in fusional convergence and divergence amplitudes measured using a phoropter.
    Accommodative facility
    Change from baseline in accommodative facility measured using flip lens technique.
    Accommodative amplitude
    Change from baseline in accommodative amplitude measured using the minus lens techniques.
    Near point of convergence
    Change from baseline in near point of convergence measured using standard push-up technique.

    Full Information

    First Posted
    April 24, 2022
    Last Updated
    May 17, 2022
    Sponsor
    Eye & ENT Hospital of Fudan University
    Collaborators
    Children's Hospital of Fudan University, Shandong Provincial Hospital, Shanxi Eye Hospital, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Tianjin Eye Hospital, Renmin Hospital of Wuhan University, Aier Eye Affiliated Hospital of Wuhan University, The Second Affiliated Hospital of Harbin Medical University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05379855
    Brief Title
    A-eyedrops on Ocular Alignment and Binocular Vision
    Official Title
    The Effects of Atropine Eyedrops on Ocular Alignment and Binocular Vision
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    May 2022
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    July 1, 2022 (Anticipated)
    Primary Completion Date
    June 30, 2024 (Anticipated)
    Study Completion Date
    June 30, 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Eye & ENT Hospital of Fudan University
    Collaborators
    Children's Hospital of Fudan University, Shandong Provincial Hospital, Shanxi Eye Hospital, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Tianjin Eye Hospital, Renmin Hospital of Wuhan University, Aier Eye Affiliated Hospital of Wuhan University, The Second Affiliated Hospital of Harbin Medical University

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No

    5. Study Description

    Brief Summary
    Atropine is a non-selective muscarinic acetylcholine (M) receptor antagonist that paralyzes the ciliary muscle, dilates the pupil, and reduces the power of accommodation. Current studies have confirmed the effect of low concentrations of atropine drops in slowing the progression of myopia. In the atropine treatment for myopia (ATOM2) study, there was a rapid and dose-dependent decrease in accommodation after atropine drops: after 2 weeks of use, accommodation decreased from baseline 16.2D to 11.3D (4.9D) in the 0.01% atropine drops group, from baseline 16.7D to 3.8D (12.9D) in the 0.1% atropine group, and from baseline 15.8 D to 2.2 D (13.6 D) in the 0.5% atropine group; one year after withdrawal, there was some recovery of the accommodation in all the three groups, but it was still lower than the baseline values for each group, with a mean decrease of 2.56 D.Similar results were found in the Low-concentration Atropine for Myopia Progression (LAMP) Study by Janson C. Yam, 0.05% atropine drops reduced the accommodation by approximately 2D on average after 1 year of treatment. In general, if accommodation decreases by 2D or more compared to normal values, accommodation insufficiency is considered. There is a linkage between accommodation and convergence called accommodative convergence-to-accommodation (AC/A) which is closely related to exotropia. It was reported that the amount of accommodation required to maintain binocular fusion in patients with intermittent exotropia was greater than that of normal controls. In addition, pupil size and visual acuity are also factors that affect accommodation. In summary, the reduced accommodation amplitude, pupil dilation, and blurred near vision caused by atropine drops would affect the progression of intermittent exotropia and the ocular alignment after the surgery. In most cases, the reduced accommodation and convergence might induce exotropia, but in some patients, they may use more accommodative stimuli to compensate the insufficiency of accommodation, and there may be an increase in convergence or even esotropia. Taken together, due to the effect of atropine drops on pupil size, near visual acuity, and accommodation amplitude, the investigators hypothesize that atropine drops are likely to affect binocular vision and ocular alignment in patients with exotropia and exophoria.
    Detailed Description
    The prevalence of myopia in the world has exceeded 25% and is increasing year by year. Asia, especially China, is an area with high incidence of myopia. It is reported that the prevalence of myopia in children and adolescents in China was 53.6% in 2018. Low concentration atropine eye drops is one of the effective means to slow the progression of myopia. At present, low concentration atropine eye drops have been widely used in China, but its long-term efficacy and possible side effects still need to be studied. Atropine is a non-selective muscarinic acetylcholine (M) receptor antagonist that paralyzes the ciliary muscle, dilates the pupil, and reduces the power of accommodation. Current studies have confirmed the effect of low concentrations of atropine drops in slowing the progression of myopia. In the ATOM2 study, there was a rapid and dose-dependent decrease in accommodation after atropine drops: after 2 weeks of use, accommodation decreased from baseline 16.2D to 11.3D (4.9D) in the 0.01% atropine drops group, from baseline 16.7D to 3.8D (12.9D) in the 0.1% atropine group, and from baseline 15.8 D to 2.2 D (13.6 D) in the 0.5% atropine group; after 1 year of discontinuation, there was some recovery of the accommodation in all the three groups, but it was still lower than the baseline values for each group, with a mean decrease of 2.56 D. Similar results were found in the LAMP study by Janson C. Yam, 0.05% atropine drops reduced the accommodation by approximately 2D on average after 1 year of treatment. In general, if accommodation decreases by 2D or more compared to normal values, accommodation insufficiency is considered. There is a linkage between accommodation and convergence, therefore the decrease of accommodation will also affect the binocular vision. Above all, the effect of atropine eye drops on pupil size, near visual acuity, amplitude of accommodation which is still impaired after 1 years' withdrawal, make us have many concerns and doubts about indications of atropine eye drops in children with strabismus or after the strabismus surgery. Strabismus is a common eye disease in children, with an incidence rate of about 3%. It is reported that about 72% of strabismus cases in Asia are exotropia, of which intermittent exotropia is the most common type, and most cases are accompanied with myopia. It is found that patients with intermittent exotropia are often associated with abnormal accommodation. Ha SG reported that the amount of accommodation required to maintain binocular fusion in patients with intermittent exotropia was greater than that of normal controls. In addition, pupil size and visual clarity are also factors affecting accommodation. In conclusion, atropine eye drops may affect the occurrence and development of intermittent exotropia by reducing the amplitude of accommodation, dilating pupils and blurred near vision. At the same time, the reduction of accommodation causes poor focusing and inappropriate afferent signals of the convergence system, which will lead to the fatigue of the convergence and divergence system, which may affect the ocular alignment of exotropia after surgery. In most cases, the reduced accommodation and convergence might induce exotropia, but in some patients, they may use more accommodative stimuli to compensate the insufficiency of accommodation, and there may be an increase in convergence or even esotropia. In general, in China, myopia with exotropia or exophoria is a high incidence of eye disease in children, and low concentration atropine eye drops have been widely used to control the progression of myopia. It is urgent to carry out a large sample randomized controlled clinical trial to evaluate the impact of low concentration atropine on the ocular alignment and binocular vision of patients with exotropia and exophoria, and guide much safer application of the low concentration atropine eye drops.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Exotropia, Exophoria, Myopia
    Keywords
    atropine, myopia, ocular alignment, binocular vision, exotropia, exophoria

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    334 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    low concentration atropine group
    Arm Type
    Experimental
    Arm Description
    Subjects of the low concentration atropine group received 0.01% atropine eye drops both eyes once every night. Eye drops are prepackaged with identical eye drops bottle, pasted with number and shelf life, and stored in 4℃.
    Arm Title
    placebo group
    Arm Type
    Placebo Comparator
    Arm Description
    Subjects of the control group received placebo eye drops (0.9% preservative free sodium chloride) both eyes once every night. Eye drops are prepackaged with identical eye drops bottle, pasted with number and shelf life, and stored in 4℃.
    Intervention Type
    Drug
    Intervention Name(s)
    0.01% atropine eye drops
    Other Intervention Name(s)
    placebo eye drops (0.9% preservative free sodium chloride)
    Intervention Description
    using 0.01% atropine eye drops for both eyes every night
    Intervention Type
    Drug
    Intervention Name(s)
    placebo eye drops (0.9% preservative free sodium chloride)
    Intervention Description
    placebo eye drops (0.9% preservative free sodium chloride)
    Primary Outcome Measure Information:
    Title
    Ocular alignment
    Description
    Change from baseline in ocular alignment measured by a prism alternating cover test using an accommodative target at 6 m and 1/3 m.
    Time Frame
    1 year
    Secondary Outcome Measure Information:
    Title
    Stereopsis
    Description
    Change from baseline in stereopsis measured with the Random dot stereogram.
    Time Frame
    1 year
    Title
    Fusion
    Description
    Change from baseline in fusion measured with the Worth Four-Dots.
    Time Frame
    1 year
    Title
    AC/A ratio
    Description
    Change from baseline in AC/A ratio measured using the Von Graefe method
    Time Frame
    1 year.
    Title
    Negative and positive relative accommodation
    Description
    Change from baseline in negative and positive relative accommodation measured using a phoropter.
    Time Frame
    1 year
    Title
    Fusional convergence and divergence amplitudes
    Description
    Change from baseline in fusional convergence and divergence amplitudes measured using a phoropter.
    Time Frame
    1 year
    Title
    Accommodative facility
    Description
    Change from baseline in accommodative facility measured using flip lens technique.
    Time Frame
    1 year
    Title
    Accommodative amplitude
    Description
    Change from baseline in accommodative amplitude measured using the minus lens techniques.
    Time Frame
    1 year
    Title
    Near point of convergence
    Description
    Change from baseline in near point of convergence measured using standard push-up technique.
    Time Frame
    1 year

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    5 Years
    Maximum Age & Unit of Time
    14 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: The age ranged from 5 to 14 years; Astigmatism < 2.5D, spherical power: - 1.00D ~ -6.00D; difference between eyes in spherical power < 1.5D, difference between eyes in astigmatism < 1.00D; Intraocular pressure < 21mmHg; Subgroups according to the ocular alignment: ortho group refers to exophoria with an exodeviation at near ≤ 6prism diopter(PD); exophoria group refers to exophoria with an exodeviation at near > 6PD[13]; intermittent exotropia group refers to exotropia with an exodeviation at distance 15 PD and a control ability score < 3[14]; after strabismus surgery group refers to the intermittent exotropia patients underwent strabismus surgery for the first time, without serious intraoperative and postoperative complications, 3 months after operation; Subjects and their parents or legal guardians have signed informed consent and are willing to accept randomized grouping and regular follow-up. Exclusion Criteria: Amblyopia Have heart disease or serious respiratory disease Allergic to atropine, cyclopentantone, propoxybenzocaine and benzalkonium chloride; Those who have used contact lenses, bifocal lenses, or other measures to control myopia (including atropine); No binocular vision; Combined with vertical strabismus, abnormal oblique muscle function, cyclodeviation, dissociated vertical deviation(DVD) or A-V pattern; Previous history of strabismus surgery or other ocular surgery; Severe complications during or after strabismus surgery, such as perforation of the sclera, tear and detachment of extraocular muscle; postoperative eye movement limitation; visual acuity decreased after operation; Combined lateral incomitance; Combined with other ocular diseases; Craniofacial malformations affecting the orbits; significant neurological disorders; Birth less than 34 weeks or birth weight less than 1500 g; Intraocular pressure > 21mmhg; Unable to cooperate with the examination.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Lianqun Wu, Doctor
    Phone
    +8613022110637
    Email
    wulianqun19@aliyun.com

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    IPD Sharing Plan Description
    The investigators concerns about patient privacy issues and it's better to protect the publication potential.
    Citations:
    PubMed Identifier
    21963266
    Citation
    Chia A, Chua WH, Cheung YB, Wong WL, Lingham A, Fong A, Tan D. 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 Feb;119(2):347-54. doi: 10.1016/j.ophtha.2011.07.031. Epub 2011 Oct 2.
    Results Reference
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    PubMed Identifier
    24315293
    Citation
    Chia A, Chua WH, Wen L, Fong A, Goon YY, Tan D. Atropine for the treatment of childhood myopia: changes after stopping atropine 0.01%, 0.1% and 0.5%. Am J Ophthalmol. 2014 Feb;157(2):451-457.e1. doi: 10.1016/j.ajo.2013.09.020. Epub 2013 Dec 4.
    Results Reference
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    PubMed Identifier
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    Citation
    Yam JC, Jiang Y, Tang SM, Law AKP, Chan JJ, Wong E, Ko ST, Young AL, Tham CC, Chen LJ, Pang CP. 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 Jan;126(1):113-124. doi: 10.1016/j.ophtha.2018.05.029. Epub 2018 Jul 6.
    Results Reference
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    PubMed Identifier
    27266700
    Citation
    Ha SG, Jang SM, Cho YA, Kim SH, Song JS, Suh YW. Clinical exhibition of increased accommodative loads for binocular fusion in patients with basic intermittent exotropia. BMC Ophthalmol. 2016 Jun 7;16:77. doi: 10.1186/s12886-016-0260-y.
    Results Reference
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    Citation
    Jampolsky A. Ocular divergence mechanisms. Trans Am Ophthalmol Soc. 1970;68:730-822. No abstract available.
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    3668152
    Citation
    Rutstein RP, Daum KM. Exotropia associated with defective accommodation. J Am Optom Assoc. 1987 Jul;58(7):548-54.
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    PubMed Identifier
    2622666
    Citation
    Schor C, Horner D. Adaptive disorders of accommodation and vergence in binocular dysfunction. Ophthalmic Physiol Opt. 1989 Jul;9(3):264-8. doi: 10.1111/j.1475-1313.1989.tb00904.x.
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    Citation
    Chia A, Lu QS, Tan D. Five-Year Clinical Trial on Atropine for the Treatment of Myopia 2: Myopia Control with Atropine 0.01% Eyedrops. Ophthalmology. 2016 Feb;123(2):391-399. doi: 10.1016/j.ophtha.2015.07.004. Epub 2015 Aug 11.
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    A-eyedrops on Ocular Alignment and Binocular Vision

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