Potential Choroidal Mechanisms Underlying Atropine's Antimyopic and Rebound Effects: A Mediation Analysis in a
Hannan Xu1,2, Luyao Ye1,2, Yajun Peng2
1Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China.
Insights
High-dose atropine thickens the choroid, with total choroidal area mediating its myopia control and rebound effects. Stromal area may predict treatment success.
Area of Science:
- Ophthalmology
- Pharmacology
- Medical Research
Background:
- Myopia is a growing public health concern.
- High-dose atropine is used to control myopia progression.
- The mechanisms underlying atropine's effects, including rebound, require further investigation.
Purpose of the Study:
- To determine if choroidal vascularity is involved in high-dose atropine's antimyopia and rebound mechanisms.
- To assess the role of total choroidal area (TCA), luminal area (LA), stromal area (SA), and choroidal vascularity index (CVI) as mediators.
Main Methods:
- A randomized controlled trial with mediation analysis.
- 207 myopic children were randomized into two groups.
- Group A received 1% atropine weekly then 0.01% atropine daily; Group B received 0.01% atropine daily.
Main Results:
- 1% atropine significantly increased LA, SA, and TCA, effects that diminished with 0.01% atropine.
- TCA mediated approximately one-third of the effect of 1% atropine on myopia progression.
- LA and SA mediated TCA's effect in phase 1, with only LA remaining significant in phase 2; CVI showed no mediation.
Conclusions:
- High-dose atropine (1%) induces choroidal thickening via increased LA and SA.
- TCA, not CVI, partially explains atropine's antimyopia and rebound effects.
- SA may be a biomarker for predicting post-rebound treatment efficacy.
Purpose:
To investigate whether choroidal vascularity participates in high-dose atropine's antimyopia and rebound mechanisms.
Methods:
A mediation analysis was embedded within a randomized controlled trial. In total, 207 myopic children were assigned randomly to group A/B. Participants in group A received 1% atropine weekly (phase 1) and 0.01% atropine daily (phase 2) for 6 months each. Those in group B received 0.01% atropine daily for 1 year. Four plausible intervention mediators were assessed: total choroidal area (TCA), luminal area (LA), stromal area (SA), and choroidal vascularity index (CVI).
Results:
In group A, LA, SA, and TCA increased significantly after receiving 1% atropine for 6 months. The increment diminished after tapering to 0.01% atropine. In group B, those parameters remained stable. TCA mediated approximately one-third of 1% atropine's effect on spherical equivalent progression in both phases. In phase 1, the mediation effect of TCA was shared by LA and SA, while only that of LA remained significant in phase 2. No mediation effect of CVI was found.
Conclusions:
One percent atropine induced choroidal thickening by increasing both LA and SA, while 0.01% atropine had little choroidal response. The choroidal changes following 1% atropine treatment diminished after switching to 0.01% atropine. TCA, but not CVI, partially explains atropine's antimyopic and myopic-rebound mechanisms. SA may serve as a potential biomarker to predict the postrebound treatment efficacy of high-dose atropine. (ClinicalTrials.gov number, NCT03949101.).
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