Understanding options for combination myopia management

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Myopia management options and knowledge have proliferated over the past decade. This pursuit of knowledge has been fueled by the understanding that the worldwide prevalence of myopia is increasing and that this spike in myopia cases may increase the population’s ocular pathology burden.^1,2

With this dynamic landscape and urgent need to curb the onset and progression of myopia, it is imperative that clinicians explore every avenue for improving myopic progression treatment outcomes. Although most studies have focused on evaluating monotherapy options, there is growing evidence suggesting that dual therapy may further slow myopic progression. Thus, the purpose of this literature review is to explore the current state of knowledge related to using a low-dose atropine as an adjunct therapy in patients who are also being treated with optical-based myopia management strategies.

Atropine and Orthokeratology

Low-concentration atropine (0.1%-0.05%) has been demonstrated to be effective while having minimal adverse effects.³ Although atropine was once thought to exert its antimyopigenic effects as an antimuscarinic, its full mechanism is unknown.4 Orthokeratology and other optical-based clinically proven myopia management strategies are thought to reduce myopic progression by decreasing retinal peripheral hyperopic defocus.⁵ Thus, if a myopic patient were prescribed both atropine and orthokeratology, which appear to operate under different mechanisms, the atropine and orthokeratology might produce an additive treatment effect.

Kinoshita et al were some of the first investigators to report on this topic with their 2-year, parallel-group, randomized trial, which compared participants receiving combination orthokeratology with atropine (n = 43) with participants who were being treated with only orthokeratology (n = 37).^6,7 The authors found that the combination group had a significant slowing of axial length elongation compared with atropine alone over the duration of the study. Kinoshita et al interestingly found that most of the added benefit detected with the combination occurred during the first 6 months of treatment.6 This result has since been corroborated by Yu et al and Tan et al.^8,9

Xu et al completed a 2-year, randomized trial comparing the efficacy of standard spectacles (n = 40), standard spectacles plus atropine (n = 42), orthokeratology (n = 40), and combined atropine and orthokeratology (n = 42) treatments.10 The authors found a significant treatment difference among groups with their pairwise comparison determining that the combined treatment was superior to atropine or orthokeratology treatment alone. Tan et al later conducted a 2-year, randomized trial comparing the combination of orthokeratology plus atropine (n = 45) to orthokeratology alone (n = 44) with the authors determining a similar conclusion.⁹

Chen et al conducted a 3-year trial evaluating the effect of adding atropine for patients who were poorly responding to orthokeratology (≥ 0.30 mm of axial elongation after 1 year of treatment).11 The patients in this study were given the option to use atropine (n = 37) or not (n = 36) while continuing to use orthokeratology after 1 year of monotherapy. Chen et al determined after 2 years of combination treatment there were no additional benefits to adding atropine.

Combination atropine and soft contact lenses

Multifocal, soft contact lenses (CLs) have demonstrated the ability to slow myopic progression,12-14 and there are emerging data regarding their usefulness in combination with atropine. Jones et al were among the first to evaluate atropine in combination with soft CLs with the authors performing an ancillary study to the Bifocal Lenses in Nearsighted Kids study (BLINK; NCT02255474).13,15 The BLINK study compared monthly, center-distance soft CLs with +2.50 D or +1.50 D adds to single vision CLs of the same brand. The authors found that the +2.50 add CLs but not the +1.50 D add CLs were able to significantly slow myopic progression compared with single vision CLs.

Jones et al compared a group of 46 patients being treated with atropine and +2.50 add soft CLs with age-matched +2.50 D add and single vision CL wearers from the BLINK study. The authors found that combination atropine and +2.50 D add CLs did not provide an additional treatment benefit. Erdinest et al has since implemented a 3-year, retrospective review, which compared patients who were treated with a daily disposable CL plus atropine (n = 26), atropine (n = 29), or with single vision spectacles (n = 30). Patients taking atropine were treated for 2 years with the drop. They then were tapered off the drop for 6 months and followed for an additional 6 months. Erdinest et al determined that there was no significant benefit to combination treatment over atropine treatment alone.

Combination atropine and spectacles

Although different spectacles designs have been evaluated as a means for slowing the progression of myopia for many years, these early investigations have failed to find a clinically meaningful effect.16 Nevertheless, more recent designs that promote the reduction of peripheral retinal hyperopic defocus across the full peripheral retina have been shown to significantly reduce myopic progression.17 Nucci et al were among the first investigators to tackle this topic. The authors completed a 1-year, unmasked study that compared patients treated with defocus incorporated multiple segments (DIMS) spectacles (n = 30), atropine (n = 53), DIMS plus atropine (n = 31), and single-vision spectacles (control; n = 32). The authors determined that all 3 treatments provided a significant reduction in myopic progression; the combination group also obtained a significantly better treatment effect than monotherapy for refractive error, but not for axial length.18

Huang et al have completed a retrospective study, which compared the treatment effect between patients treated with DIMS plus atropine (n = 40), DIMS (n = 49), or single-vision spectacles (control; n = 47). The authors found a difference between the treatment groups and the control group and a greater treatment effect with the combination group.19 Between-study differences could be attributed to Huang et al enrolling Asian patients and Nucci et al enrolling European patients.

Conclusion

Although the literature is still emerging, most studies suggest that 0.01% atropine in combination with optical interventions provides an additional treatment benefit, though this additional reduction in ocular growth may be limited to the first 6 months of treatment. More work is needed to understand whether slightly higher concentrations of low-dose atropine (0.05%/0.025 vs 0.01%) will provide a better treatment effect when combined with optical interventions and to understand whether subsets of patients may have better results.

References

1. Holden BA, Fricke TR, Wilson DA, et al. Global prevalence of myopia and high myopia and temporal trends from 2000 through 2050. Ophthalmology. 2016;123(5):1036-1042.

2. Flitcroft DI. The complex interactions of retinal, optical and environmental factors in myopia aetiology. Prog Retin Eye Res. 2012;31(6):622-660.

3. Yam JC, Li FF, Zhang X, et al. Two-year clinical trial of the low-concentration atropine for myopia progression (LAMP) study: phase report. Ophthalmology. 2020;127(7):910-919.

4. Zhao Q, Hao Q. Clinical efficacy of 0.01% atropine in retarding the progression of myopia in children. Int Ophthalmol. 2021;41(3):1011-1017.

5. Smith EL 3rd, Hung LF, Huang J. Relative peripheral hyperopic defocus alters central refractive development in infant monkeys. Vision Res. 2009;49(19):2386-2392.

6.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(1):12750.

7. Kinoshita N, Konno Y, Hamada N, Kanda Y, Shimmura-Tomita M, Kakehashi A. Additive effects of orthokeratology and atropine 0.01% ophthalmic solution in slowing axial elongation in children with myopia: first year results. Jpn J Ophthalmol. 2018;62(5):544-553.

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(1):438.

9.T an 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;46(1):101723.

10. 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. Published online October 13, 2022. doi:10.1136/bjo-2022-321272

11. 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;106(8):1069-1072.

12. Walline JJ, Greiner KL, McVey ME, Jones-Jordan LA. Multifocal contact lens myopia control. Optom Vis Sci. 2013;90(11):1207-1214.

13. Walline JJ, Walker MK, Mutti DO, et al; BLINK Study Group. Effect of high add power, medium add power, or single-vision contact lenses on myopia progression in children: the BLINK randomized clinical trial. JAMA. 2020;324(6):571-580.

14. Chamberlain P, Peixoto-de-Matos SC, Logan NS, Ngo C, Jones D, Young G. A 3-year randomized clinical trial of misight lenses for myopia control. Optom Vis Sci. 2019;96(8):556-567.

15. 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(5):434-442.

16. Gwiazda J, Hyman L, Hussein M, et al. A randomized clinical trial of progressive addition lenses versus single vision lenses on the progression of myopia in children. Investig Ophthalmol Vis Sci. 2003;44(4):1492-1500.

17. Lam CS, Tang WC, Lee PH, et al. Myopia control effect of defocus incorporated multiple segments (DIMS) spectacle lens in Chinese children: results of a 3-year follow-up study. Br J Ophthalmol. 2022;106(8):1110-1114.

18. 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(2):e0281816.

19. 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(1):22311.

20. Hao Q, Zhao Q. Changes in subfoveal choroidal thickness in myopic children with 0.01% atropine, orthokeratology, or their combination. Int Ophthalmol 2021;41(9):2963-2971.

21. 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(4):73.

Andrew D. Pucker, OD, PhD, FAAO, FSLS, FBCLA

E: andrew.pucker@lexitas.com

Dr Pucker is senior director of clinical and medical sciences at Lexitas Pharma Services in Durham, North Carolina. He has received research or consulting support from Alcon Research, Art Optical, and Haymarket Media, Inc.