Clinical trial NCT05379855: A-eyedrops on Ocular Alignment and Binocular Vision
Official title: The Effects of Atropine Eyedrops on Ocular Alignment and Binocular Vision
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Exotropia
Exophoria
Myopia
Keywords: atropine
myopia
ocular alignment
binocular vision
exotropia
exophoria
Lead sponsor: Eye & ENT Hospital of Fudan University
Sponsor class: OTHER
First posted: 2022-05-18
Enrollment: 339
Sex: ALL
Minimum age (years): 5
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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;
* Ocular alignment fulfilling the following criteria：Exophoria with an exodeviation at near \> 6PD12; Intermittent exotropia with an exodeviation ≤25 PD both at distance and at near, Titmus \<=400 arc seconds; Intermittent exotropia patients underwent strabismus surgery, 6 months after operation, fulling the criteria of exophoria and intermittent exotropia mentioned before.
* 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≥5PD, abnormal oblique muscle function≥ 2+, cyclodeviation, DVD or A-V pattern, paralytic and restrictive strabismus, comitant esotropia；
* Previous history of 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 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.

Primary outcomes:
measure: Refraction
timeFrame: 1 year and 2 years
measure: Axial length
timeFrame: 1 year and 2 years
Secondary outcomes:
measure: Stereopsis
timeFrame: 1 year and 2 years
measure: Fusion
timeFrame: 1 year and 2 years
measure: AC/A ratio
timeFrame: 1 year and 2 years
measure: Negative and positive relative accommodation
timeFrame: 1 year and 2 years
measure: Fusional convergence and divergence amplitudes
timeFrame: 1 year and 2 years
measure: Accommodative facility
timeFrame: 1 year and 2 years
measure: Accommodative amplitude
timeFrame: 1 year and 2 years
measure: Near point of convergence
timeFrame: 1 year and 2 years
measure: Ocular alignment
timeFrame: 1 year and 2 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Eye and ENT Hospital, Fudan University
Study officials:
References:
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