A-eyedrops on Ocular Alignment and Binocular Vision

Sponsor

Eye & ENT Hospital of Fudan University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05379855

Collaborator

Children's Hospital of Fudan University (Other), Shandong Provincial Hospital (Other), Shanxi Eye Hospital (Other), Xinhua Hospital, Shanghai Jiao Tong University School of Medicine (Other), Tianjin Eye Hospital (Other), Renmin Hospital of Wuhan University (Other), Aier Eye Affiliated Hospital of Wuhan University (Other), The Second Affiliated Hospital of Harbin Medical University (Other)

334

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Exotropia Exophoria Myopia	Drug: 0.01% atropine eye drops Drug: placebo eye drops (0.9% preservative free sodium chloride)	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

334 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

The Effects of Atropine Eyedrops on Ocular Alignment and Binocular Vision

Anticipated Study Start Date :

Jul 1, 2022

Anticipated Primary Completion Date :

Jun 30, 2024

Anticipated Study Completion Date :

Jun 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: low concentration atropine group 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℃.	Drug: 0.01% atropine eye drops using 0.01% atropine eye drops for both eyes every night Other Names: placebo eye drops (0.9% preservative free sodium chloride)
Placebo Comparator: placebo group 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℃.	Drug: placebo eye drops (0.9% preservative free sodium chloride) placebo eye drops (0.9% preservative free sodium chloride)

Arm

Intervention/Treatment

Experimental: low concentration atropine group

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℃.

Drug: 0.01% atropine eye drops

using 0.01% atropine eye drops for both eyes every night

Other Names:

placebo eye drops (0.9% preservative free sodium chloride)

Placebo Comparator: placebo group

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℃.

Drug: placebo eye drops (0.9% preservative free sodium chloride)

placebo eye drops (0.9% preservative free sodium chloride)

Outcome Measures

Primary Outcome Measures

Ocular alignment [1 year]
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 [1 year]
Change from baseline in stereopsis measured with the Random dot stereogram.
Fusion [1 year]
Change from baseline in fusion measured with the Worth Four-Dots.
AC/A ratio [1 year.]
Change from baseline in AC/A ratio measured using the Von Graefe method
Negative and positive relative accommodation [1 year]
Change from baseline in negative and positive relative accommodation measured using a phoropter.
Fusional convergence and divergence amplitudes [1 year]
Change from baseline in fusional convergence and divergence amplitudes measured using a phoropter.
Accommodative facility [1 year]
Change from baseline in accommodative facility measured using flip lens technique.
Accommodative amplitude [1 year]
Change from baseline in accommodative amplitude measured using the minus lens techniques.
Near point of convergence [1 year]
Change from baseline in near point of convergence measured using standard push-up technique.

Eligibility Criteria

Criteria

Ages Eligible for Study:

5 Years to 14 Years

Sexes Eligible for Study:

All

Accepts 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.