Efficacy and Safety of Low Dose Atropine and Caffeine Eye Drops for Myopia Control

Abstract

Aim: To determine the role of topical Caffeine, a Xanthine derivative in slowing myopia either as a single-drug or in combination with Atropine. Methods: A systematic review and meta-analysis for Atropine in myopia control was followed by a short-term dispensing trial to select a single Atropine concentration to use in combination with Caffeine. In a prospective, randomized, dispensing trial, children with myopia were assigned to daily use of either Caffeine-2%, Atropine-0.02% with Caffeine-2% or Atropine-0.02%. A parallel non-randomised group of spectacle lens wearers were controls. The six-month change in spherical equivalent, axial length, pupillary diameter, and accommodative amplitude were compared between groups. Finally, a validation trial monitored pupillary and accommodative amplitude changes over 24 hours with various concentrations of Atropine and Caffeine, either single or combined. Comparison between groups were performed using repeated measures Analysis of Variance with significance set at 5%. Post-hoc multiple comparisons conducted using Bonferroni correction. Results: Meta-analysis confirmed dose-dependent efficacy and side effects for all concentrations of Atropine excepting 0.01%. Similarly, short-term trial demonstrated no pupillary diameter/accommodative change with Atropine-0.01% in approximately 30% of eyes. Atropine-0.02% was selected to be used in combination with Caffeine and at six months, change in spherical equivalent/axial length was -0.20±0.34D/0.08±0.11mm, -0.20±0.30D/0.11±0.11mm, -0.39±0.38D/0.19±0.15mm and -0.33±0.29D/0.18±0.11mm with Atropine-0.02%, Atropine-0.02% with Caffeine-2%, Caffeine-2%, and single vision spectacles respectively. The pupillary diameter increase/reduction in accommodative amplitude was 1.20±0.85mm/-3.14±4.08D, 0.76±0.58mm/-2.84±4.35D, -0.07±0.47mm/-0.78±3.43D and -0.10±0.32mm/-0.22±3.81D respectively. Temporal observations of pupil diameter indicated, a) no significant variation with Caffeine, b) Post instillation to 60 minutes – Caffeine-2% combined with 0.05% and 0.1%-Atropine resulted in significantly fewer eyes reaching higher pupillary diameter compared to monotherapy with 0.05% and 0.1%-Atropine. There were no significant changes for accommodative amplitude. Conclusion: Caffeine-2% did not slow myopia when used either individually or in combination with Atropine. However, Caffeine in combination with Atropine significantly minimised the increase in pupillary diameter that occurs with use of Atropine.