This article was originally published in a sponsored newsletter.

Over the past few years, researchers have been investigating the potential additive benefits of combination therapy for myopia management. Studies have explored combining atropine (0.01%) and orthokeratology, atropine (0.01%) and soft multifocal contact lenses, as well as atropine (0.01%) and myopia control spectacles. Although practitioners are still unsure how combination therapy works to slow myopia greater than monotherapy, Tan and colleagues found that larger pupils correlated with increased efficacy.¹ However, this accounted for only 20% of the effect, so there must be other mechanisms at play. This article will explore the results thus far of combination therapies.

Atropine and Orthokeratology

Atropine and orthokeratology are believed to work through different mechanisms, atropine via antimuscarinic effects on atropine/sclera and orthokeratology through peripheral hyperopic defocus. Therefore, it was theorized that these two mechanisms could potentially work synergistically to slow myopia.

Kinoshita and co-workers were some of the first investigators of combined atropine and orthokeratology treatment.²They followed low-moderate myopes for two years who were randomly assigned to two groups, either atropine (0.01%) and orthokeratology versus orthokeratology alone. They did find a significant slowing in axial length of the combined group versus the orthokeratology-alone group; however, the effects were only apparent up to 12 months.²

Tan and colleagues performed a similar study and found orthokeratology and atropine combination was superior to monotherapy but only for the first six months.¹ They also found an association with larger pupil size and choroidal thickness with reduction in axial length, but this was not considered causation.

Similarly, Zhao and co-workers found that combination therapy was more effective in reducing change in refractive error as well as in slowing axial length than monotherapy in younger baseline age or shorter baseline over a two-year period.³Vincent and colleagues discovered that 0.01% atropine and orthokeratology reduced axial length progression, which was correlated with increased pupil size and higher-order aberrations.⁴

Chen and colleagues evaluated adding 0.01% atropine to patients not responding well to orthokeratology alone (≥ 0.30mm of axial length elongation after one year). They found no additional benefits to adding atropine after two years.⁵

The only study thus far to study a higher concentration atropine (0.025% and 0.125%) combined with orthokeratology was by Wan and colleagues.⁶ The study’s authors found that 0.025% was effective in slowing axial length but 0.125% was not effective.⁶

Combination Atropine and Soft Multifocal Contact Lenses

Two studies compared patients treated with atropine 0.01% plus distance-centered multifocal soft contact lens (+2.50 add) compared with single-vision contact lenses alone.^7,8 They did not find any benefits of adding atropine to multifocal contact lens therapy.

Combination Atropine and Spectacles

Two studies compared defocus incorporated multiple segments (DIMS) spectacle lenses plus atropine versus DIMS lenses alone. Nucci and co-workers found that the combination group demonstrated a significant reduction in refractive error, but not axial length, compared to monotherapy after one year.⁹ Huang and colleagues found a significant difference in both axial length and refractive error compared to monotherapy groups after one year.¹⁰ The discrepancy between these two studies may have been the patient population; Nucci and co-workers studied European patients whereas Huang and colleagues studied an Asian population.

Conclusion

Although some of these studies have demonstrated a significant benefit of combination therapy, some of these results are only based off a short time frame and subjects were low to moderate myopes. We need longer-term studies to determine the true benefit of combination therapy. That being said, there has been no major adverse events reported with combining therapies and may be an option worth trying if you are not achieving the desired results in your patients.

1. Tan Q, Ng AL, Cheng GP, Woo VC, Cho P. Combined 0.01% atropine with orthokeratology in childhood myopia control (AOK) study: A 2-year randomized clinical trial. Cont Lens Anterior Eye. 2023 Feb;46:101723.
2. Kinoshita N, Konno Y, Hamada N, et al. Efficacy of combined orthokeratology and 0.01% atropine solution for slowing axial elongation in children with myopia: a 2-year randomised trial. Sci Rep. 2020 Jul 29;10:12750.
3. Zhao Q, Hao Q. Clinical efficacy of 0.01% atropine in retarding the progression of myopia in children. Int Ophthalmol. 2021 Mar;41:1011-1017.
4. Vincent SJ, Tan Q, Ng ALK, Cheng GPM, Woo VCP, Cho P. Higher order aberrations and axial elongation in combined 0.01% atropine with orthokeratology for myopia control. Ophthalmic Physiol Opt. 2020 Nov;40:728-737.
5. Chen Z, Zhou J, Xue F, Qu X, Zhou X. Two-year add-on effect of using low concentration atropine in poor responders of orthokeratology in myopic children. Br J Ophthalmol. 2022 Aug;106:1069-1072.
6. Wan L, Wei CC, Chen CS, et al. The Synergistic Effects of Orthokeratology and Atropine in Slowing the Progression of Myopia. J Clin Med. 2018 Sep;7:259.
7. Jones JH, Mutti DO, Jones-Jordan LA, Walline JJ. Effect of Combining 0.01% Atropine with Soft Multifocal Contact Lenses on Myopia Progression in Children. Optom Vis Sci. 2022 May 1;99:434-442.
8. Erdinest N, London N, Lavy I, et al. Low-Concentration Atropine Monotherapy vs. Combined with MiSight 1 Day Contact Lenses for Myopia Management. Vision (Basel). 2022 Dec 12;6:73.
9. Nucci P, Lembo A, Schiavetti I, Shah R, Edgar DF, Evans BJW. A comparison of myopia control in European children and adolescents with defocus incorporated multiple segments (DIMS) spectacles, atropine, and combined DIMS/atropine. PLoS One. 2023 Feb 16;18:e0281816.
10. Huang Z, Chen XF, He T, Tang Y, Du CX. Synergistic effects of defocus-incorporated multiple segments and atropine in slowing the progression of myopia. Sci Rep. 2022 Dec 24;12:22311.