Potential Choroidal Mechanisms Underlying Atropine's Antimyopic and Rebound Effects: A Mediation Analysis in a Randomized Clinical Trial

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.)