Is There Power in Combining Treatment?

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March 3, 2025

By Associate Professor Pauline Kang, BOptom, PhD, School of Optometry and Vision Science at UNSW in Sydney, Australia

As our understanding of the outcomes and safety profiles of single treatments for childhood myopia, including optical, pharmacological, light-based, and environmental options, becomes more established, there is growing interest in exploring the effects of combining different therapies. This has stemmed from clinical trials that have shown variable outcomes across all myopia control treatments, with some children showing no response to treatment.^1-3

Additionally, there is no reliable method to determine the optimal first line of treatment for an individual child, as only a few studies to date have directly compared different treatment types.⁴ A growing number of clinicians are quantifying risk factors to assess a child’s risk profile for myopia progression to guide treatment selection. Children at higher risk are often prescribed more aggressive approaches, which generally involve combining different types of myopia control treatments. The premise of combination treatment is that different treatment types slow or control myopia progression via distinct mechanisms, and their combination will result in a synergistic effect that offers greater efficacy compared to individual treatments alone. 

Understanding the Latest Clinical Trial Data
Clinical trials investigating combination treatment for progressive myopia are summarized in Table 1. Most clinical trials have explored combining optical and pharmacological or, more recently, light-based treatments. Trials include orthokeratology combined with atropine,^5-11 soft contact lenses and atropine,^12-14 myopia control spectacle lenses and atropine,^10,11,15,16  or red light therapy with orthokeratology.¹⁷

To accurately evaluate whether combining two different treatments provides more significant benefits compared to monotherapy, clinical trials should include both the combined treatment and individual treatment arms. While many studies failed to include all individual treatment arms, a growing number of clinical trials have overcome this limitation, providing greater confidence when evaluating the benefits of combining treatments. Overall, most studies report less myopia progression with combination compared to monotherapy (Table 1), and two studies to date have included the combination and all individual treatment arms, which are described below.^9,15 Interestingly, the first study reported the benefits of combining atropine with orthokeratology, while the second study found no improvement in treatment outcomes when combining atropine with Defocus Incorporated Multi-Segment (DIMS) spectacles compared to individual treatments alone. 

Xu et al.⁹ investigated the effect of combining orthokeratology with 0.01% atropine in 8- to 12-year-old Chinese children. There were four treatment arms: single vision spectacles + placebo drops (control group), 0.01% atropine + single vision spectacles (individual treatment group), orthokeratology + placebo drops (individual treatment group), and combined orthokeratology + 0.01% atropine (combination treatment group). Compared to the control single vision group, all other treatment groups had significantly less axial elongation over two years of treatment. Combining atropine and orthokeratology resulted in less axial elongation or myopia progression compared to atropine or orthokeratology monotherapy, supporting outcomes of other studies.^5-8,10,11

Nucci et al.¹⁵ explored atropine and DIMS spectacles on myopia progression in 6- to 18-year-old European children. Four treatment groups were included in the study: single vision spectacles (control group), 0.01% atropine (individual treatment group), DIMS spectacles (individual treatment group), and DIMS combined + 0.01% atropine (combination treatment group). Compared to the control single vision group, all other treatment groups had significantly less axial elongation over one year of treatment. Atropine and DIMS monotherapy produced comparable outcomes, and combining 0.01% atropine with DIMS did not result in a greater treatment effect compared to atropine or DIMS alone.  

Although there is growing evidence supporting the benefits of combining different treatments for progressive myopia in children, until future studies include all appropriate treatment arms to ensure robustness of results, outcomes remain under debate.   

 

 

Pauline Kang, BOptom, PhD, is an Associate Professor at the School of Optometry and Vision Science at UNSW in Sydney, Australia. Her research focuses on various treatments for myopia control and aims to enhance the understanding of the mechanisms underlying the development and progression of myopia in children. Pauline also coordinates the Myopia Clinic at the UNSW Optometry Clinic, which not only provides a clinic dedicated to myopia management but also teaches Optometry and Vision Science students about current evidence-based practices for managing progressive myopia.

 

References

1. Yam JC, Zhang XJ, Zhang Y, et al. Three-year clinical trial of Low-concentration Atropine for Myopia Progression (LAMP) study: continued versus washout: Phase 3 Report. Ophthalmology 2022;129:308-321.
2. Cho P, Cheung SW. Retardation of Myopia in Orthokeratology (ROMIO) study: A 2-year randomized clinical trial. Invest Ophthalmol Vis Sci 2012;53:7077-7085.
3. Lam CSY, Tang WC, Tse DY, et al. Defocus Incorporated Multiple Segments (DIMS) spectacle lenses slow myopia progression: a 2-year randomised clinical trial. Br J Ophthalmol 2020;104:363-368.
4. Jonas JB, Ang M, Cho P, et al. IMI Prevention of Myopia and Its Progression. Invest Ophthalmol Vis Sci 2021;62:6.
5. 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;10:12750.
6. 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 2022;101723.
7. Zhou H, Zhao G, Li Y. Adjunctive effects of orthokeratology and atropine 0.01% eye drops on slowing the progression of myopia. Clin Exp Optom 2022;105:520-526.
8. Yu S, Du L, Ji N, et al. Combination of orthokeratology lens with 0.01% atropine in slowing axial elongation in children with myopia: a randomized double-blinded clinical trial. BMC Ophthalmol 2022;22:438.
9. Xu S, Li Z, Zhao W, et al. Effect of atropine, orthokeratology and combined treatments for myopia control: a 2-year stratified randomised clinical trial. Br J Ophthalmol 2023;107:1812-1817.
10. Cao X, Guo Z, Wei Z, et al. Effect of 0.01% atropine eye drops combined with different optical treatments to control low myopia in Chinese children. Cont Lens Anterior Eye 2025;48:102317.
11. Tang T, Lu Y, Li X, et al. Comparison of the long-term effects of atropine in combination with Orthokeratology and defocus incorporated multiple segment lenses for myopia control in Chinese children and adolescents. Eye (Lond) 2024;38:1660-1667.
12. 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;99:434-442.
13. Erdinest N, Atar-Vardi M, Lavy I, et al. Effective decrease in myopia progression with two mechanisms of management. J Pediatr Ophthalmol Strabismus 2024;61:204-210.
14. 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;6.
15. 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;18:e0281816.
16. 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;12:22311.
17. Xiong R, Wang W, Tang X, et al. Myopia control effect of repeated low-level red-light therapy combined with orthokeratology: A multicenter randomized controlled trial. Ophthalmology 2024;131:1304-1313.
18. Xie R, Zhou XT, Lu F, et al. Correlation between myopia and major biometric parameters of the eye: a retrospective clinical study. Optom Vis Sci 2009;86:E503-508