Dear Editor, Xiong et al.1 tackle a practical question: Does the timing of 0.01% atropine instillation influence myopia-control efficacy when combined with overnight orthokeratology (OK)? Their 12-month cohort of 163 right eyes reports less axial elongation with morning dosing than with evening dosing (0.13 vs 0.21 mm; ≈38% relative reduction) and a larger pupil diameter in the morning group. Multivariable analysis associates morning instillation, larger pupil, older age, and upright reading posture with slower growth. The finding is clinically relevant because OK optics depend on how much of the mid-peripheral plus-power ring and higher-order aberrations fall within the pupil. A larger daytime pupil could therefore allow more effective peripheral myopic defocus,2 and the combination of OK with low-dose atropine already outperforms either therapy alone.3 Their axial elongation data showed a consistent divergence across all follow-up visits, with the morning group exhibiting 0.13 mm growth versus 0.21 mm in the evening group. Even after adjustment for behavioral and biometric variables, morning instillation remained an independent predictor of reduced elongation. The morning group demonstrated a statistically larger photopic pupil diameter. Behavioral variables also correlated with slower growth, emphasizing the broader interaction between optical, pharmacological, and lifestyle factors. Mechanistically, administering atropine after OK lens removal may synchronize peak mydriasis with daytime peripheral-defocus signaling, whereas evening use may shift the pharmacological effect into a low-light or closed-eye period where its impact on retinal defocus may be diminished. These mechanistic links add biological plausibility to the findings and justify considering dosing-time as a modifiable factor in combined therapy. However, this was not a randomized study, and the timing of pupil measurement likely differed between groups. Morning instillation may also avoid the drug being trapped under the lens and align mydriasis with waking hours, but lens design and back optic zone diameter were not standardized.4 Therefore, clinicians should view this as hypothesis-generating. When prescribing OK with 0.01% atropine, it seems reasonable to instil the drop after lens removal in the morning and counsel families about glare protection and ergonomic reading habits. Stand-alone 0.01% atropine monotherapy remains less effective.5 Randomized or crossover trials that control lens design, pupil measurement, and adherence are needed to confirm whether morning dosing truly enhances combination therapy. Financial support and sponsorship: Nil. Conflicts of interest: There are no conflicts of interest.
Labishetty et al. (Thu,) studied this question.