Clinical trial NCT06265454: Low Dose Atropine Eye Drops in Myopic Egyptian Children
Official title: Effect of Low Concentration Atropine Eye Drops on Choroidal Thickness, Central Corneal Thickness, Anterior Scleral Thickness and Axial Length in Myopic Children
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Myopia Progression
Axial Length, Eye
Sclera Thickness
Keywords: myopia
low dose
atropine eye drops
mypoic children
myopia progression
LAMP
Lead sponsor: Ain Shams University
Sponsor class: OTHER
First posted: 2024-02-20
Enrollment: 75
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Previous Studies reported that low concentration atropine eye drops may be effective in increasing the choroidal blood flow and thickness and this slows myopia progression.

purpose of the study is to compare changes in axial length, anterior chamber depth, choroidal thickness, central corneal thickness and anterior scleral thickness among myopic children receiving atropine 0.05% or 0.01% and placebo.

Detailed description: Myopia is the most common refractive error, and its prevalence rate is increasing worldwide, as per WHO, it is projected to increase from 22% in 2000 to 52% by 2050. It is more prevalent in developed, industrial areas and affects individuals of all ages (Singh et al., 2022). Myopia, especially the degenerative type, is associated with sight-threatening complications, including presenile cataract, glaucoma, retinal detachment, choroidal neovascularization, myopic macular degeneration, scleral and choroidal thinning (Sanchez-Cano et al., 2014 and Gupta et al., 2015) which makes myopia a major public health concern and finding an effective treatment to prevent myopia progression is critical (Wakazono et al., 2016).

Atropine is a nonselective muscarinic antagonist used for myopia control in previous studies. However, its actual mechanism of action is not well known (Yam et al., 2019).

But different mechanisms were described, first mechanism, that atropine may induce release of dopamine causing thickening of choroid (Nickla et al., 2010) Second mechanism,blockage of choroidal smooth muscle contraction through its anti-muscarinic action. Third one, increasing capillary permeability. Fourth, potentiating the synthesis and release of intraocular nitric oxide (Yam et al.,2022) also it stimulates retinal expression of the transcription factor ZENK which was considered an eye growth-inhibiting signal (Torii et al., 2017). All these mechanisms cause thickening of the choroid and increased choroidal blood flow which has been found to play a role in the regulation of eye growth and refractive error development through inhibition of the penetration of various retinal-derived growth factors that act as mechanical barriers and slow scleral growth (Nickla et al., 2015 \&amp; Guggenheim et al., 2011). Also, choroid can secrete growth factors that prevent scleral hypoxia (Wu et al., 2018).

According to the Low-concentration Atropine for Myopia Progression (LAMP) study, different atropine eye drops concentrations 0.05%, 0.025%, and 0.01% controlled myopia progression but the most effective concentration on spherical equivalent and axial length progression was 0.05% (Yam et al., 2019).

Zhang et al. reported in 2016 that administration of 1% atropine gel increased the choroidal thickness in young Chinese children with inhibition of eye growth.

Also, jiang et al. in 2021 mentioned that after one week of administration of 1% atropine significant changes in spherical equivalent, axial length and choroidal thickness and after cessation of the medication for 7 weeks those returned to baseline levels.

In 2022, Zhou et al. reported also increased sub foveal choroidal thickness and in all quadrants in myopes in contrast to increased thickness in nasal quadrant only in hyperopes and non-significant change in emmetropes.

A recent study in 2023 found a dose dependent ocular biometrics changes, including axial length and anterior chamber depth, during low-dose atropine treatment in children with myopia (Hvid-Hansen et al., 2023).

In Li et al. study in 2021 they mentioned that younger children required higher atropine concentrations to show better responses.

In 2023, Zhou et al. reported thinner anterior sclera in myopes compared to emmetropes and a negative correlation between anterior scleral thickness (AST)and axial length and recommended usage of AST as a tool for monitoring of myopia progression.

Optical Coherence Tomography (OCT) is a non-invasive imaging modality, it was first reported in 1991 as a diagnostic technology that provides a cross-sectional image of the retina and choroid. It creates a cross-sectional map of the retina based on low-coherence interferometry (Aumann et al., 2019).

There are two types of OCT, time domain OCT and spectral domain OCT but the most widely used now is spectral domain OCT as it has scan rate between 20,000 and 40,000 per second which improves resolution and reduces the likelihood of missing lesions (Xie et al., 2021).

Eligibility criteria: Inclusion Criteria:

* Age ranges from 6 to 12.
* Spherical equivalent ≥ -1.0 D.

Exclusion Criteria:

* Astigmatism ≥ 3.0 D.
* History of allergy to atropine or positive skin allergy test.
* Ocular pathology otherwise myopia.
* Recent ocular surgery.
* Chronic systemic disease.
* Use of rigid contact lenses or soft contact lenses for 1 week before participating in the study

Primary outcomes:
measure: change in the average Choroidal Thickness over follow up period.
timeFrame: from enrollment till end of eye drops trial over 3 months and after stopping the drops for 3 months
Secondary outcomes:
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Ain shams university
state: Abbasia
Study officials:
affiliation: Ain Shams University
name: Aya Mahmoud, Master's
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zhang Z, Zhou Y, Xie Z, Chen T, Gu Y, Lu S, Wu Z. The effect of topical atropine on the choroidal thickness of healthy children. Sci Rep. 2016 Oct 7;6:34936. doi: 10.1038/srep34936.
citation: Zhou J, He H, Yang Q, Wang JY, You ZP, Liu LL. Comparison of anterior sclera thickness in emmetropes and myopes. BMC Ophthalmol. 2023 Feb 14;23(1):67. doi: 10.1186/s12886-023-02775-x.
citation: Ye L, Shi Y, Yin Y, Li S, He J, Zhu J, Xu X. Effects of Atropine Treatment on Choroidal Thickness in Myopic Children. Invest Ophthalmol Vis Sci. 2020 Dec 1;61(14):15. doi: 10.1167/iovs.61.14.15.
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.
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citation: Wang Y, Zhu X, Xuan Y, Wang M, Zhou X, Qu X. Short-Term Effects of Atropine 0.01% on the Structure and Vasculature of the Choroid and Retina in Myopic Chinese Children. Ophthalmol Ther. 2022 Apr;11(2):833-856. doi: 10.1007/s40123-022-00476-0. Epub 2022 Feb 20.
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