Submitted:
14 July 2026
Posted:
15 July 2026
You are already at the latest version
Abstract
Keywords:
1. Introduction
2. Method of Literature Search
3. Combination Treatments
3.1. Atropine Drops and OK
3.2. Atropine Drops and Peripheral Designed Myopia Control Spectacles
3.2.1. Atropine Drops and DIMS
3.2.2. Atropine Drops and HAL
3.3. Atropine Drops and Dual Focus Contact Lenses
3.4. OK and RLRL
3.5. Peripheral Designed Myopia Control Spectacles and RLRL
3.6. Peripheral Designed Myopia Control Spectacles and Dual Focus Contact Lenses
4. Evidence Gaps and Future Combinations
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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| Study | Study design | Age (Years) | Ethicity |
Intervention | Follow-up | Effect |
|---|---|---|---|---|---|---|
| Kinoshita et al. 2020 | Randomised clinical trial | 8-12 | Japanese | OK + 0.01% atropine vs OK alone | 2 years | AL change 0.29 vs 0.40 mm /2 years with OK alone, especially in the first 6 months |
| Tsai et al. 2022 | Systematic review + network meta-analysis | Review | Review | Atropine vs OK vs OK+0.01% atropine | Review | Ranked efficacy: OK + 0.01% atropine highest among listed interventions |
| Tan et al. 2023 | Randomised clinical trial | 6-11 | Chinese | OK + 0.01% atropine vs OK alone | 2 years | Combination ~50% more effective than OK alone |
| Du et al. 2023 | Retrospective, age-matched comparative study | 7*14 | OK vs OK + 0.01% atropine | 2-year | AL 0.16 mm lower in the combination group, especially in younger cohort | |
| Wang et al. 2023 | Meta-analysis | Review | Review | 0.01% atropine alone vs 0.01% atropine + OK | Review | Combination increased efficacy vs either treatment alone. |
| Xu, S. et al. 2023 | Stratified randomised clinical trial | 8-12 | Chinese | Atropine vs OK vs combined treatment | 2 years | Combination treatment is effective for myopia control |
| Li, B. et al. 2024 | Randomised, double-masked, placebo-controlled, cross-over trial | 8-12 | Chinese | OK + 0.01% atropine (vs OK only and swapped after 1 year) | 2 years | Reduced axial elongation with combination (0.1mm on average less per year) |
| Tu et al. 2025 | meta-analysis of randomised controlled trials | Review | Review | OK + 0.01% atropine add-on | Review | Combination treatment is effective for myopia control |
| Yang, Xiao, et al. 2025 | Retrospective analysis | 8-14 | Chinese | OK + 0.01% atropine added if fast progression | 6 months in each group | Synergistic efficacy reported (reduced AL progression from 0.3 to 0.08 mm when atropine was added |
| Matsumura et al. 2025 | Inclusion if treated with atropine or combination | Mean age 8 | 0.01% atropine vs OK + atropine combination | 1 year | Additive effect suggested using choroidal thickness/blood flow markers | |
| Xu, H. et al. 2025 | Randomised clinical trial | 8-15 | Chinese | OK vs OK+0.01% atropine vs OK+0.04% atropine | 2 years | 0.04% combo showed greater efficacy than 0.01% combo, with more side effects |
| Wen et al. 2025 | Preliminary retrospective study | Mean 10 years | Chinese | OK + 0.05% atropine in fast progressors | 1 year | Add-on 0.05% atropine beneficial in fast progressors |
| Guo et al. 2025 | Fast progressors Stepwise regimen | 8-13 | Chinese | OK + escalating atropine (0.01–0.025% then 0.05%) | 1 year | Increased efficiency but more side effects (blur, photophobia) |
| Yuan et al. 2026 | Randomised clinical trial | 8-12 | Chinese | OK + 0.01% atropine vs OK alone vs 0.01% atropine alone | 2 years | Significantly less axial length change in combination-group |
| Study | Study design | Age | ethnicity | Intervention | Follow-up | Effect |
|---|---|---|---|---|---|---|
| Huang et al. 2022 | Retrospective comparative study | 7-12 | Chinese | DIMS + atropine 0.01% vs DIMS alone vs SVL alone | 1 year | Combination showed a greater effect than DIMS or SVL alone |
| Nucci et al. 2023 | Non-randomised, single-arm, masked cohort study | 6-18 | European | SVL vs atropine 0.01% vs DIMS vs DIMS + atropine 0.01% | 1 year | AL progression: 0.17 mm (control/SVL); 0.09 mm (atropine 0.01%); 0.066 mm (DIMS); 0.049 mm (DIMS+atropine 0.01%) |
| Jethani 2024 | Small study in atropine non-responders | Mean age 8.4 | Indian | Added DIMS lenses to children not responding to atropine 0.01% | 1 year | Additive effect of adding DIMS in atropine 0.01% “non-responders” |
| Tang, T. et al. 2024 | Retrospective comparative study with age stratification | 6-14 | Chinese | Orthokeratology vs OK+atropine 0.01% vs DIMS vs DIMS+atropine 0.01% | 1 year | OK and DIMS monotherapies had similar axial elongation; adding atropine slowed progression further; effect more pronounced in 10–14 yrs group |
| Lee, C. Y. et al. 2025 (Sci Rep) | Retrospective | 6-15 | Taiwan | DIMS alone vs DIMS + atropine 0.01% vs DIMS + atropine 0.125% | 1 year | Adding atropine significantly reduced elongation and refractive progression vs DIMS alone; higher atropine concentration little additional effect |
| Lee, C. Y. et al. 2025 (Cureus) | Retrospective cohort study (fast progressors) | 6-15 | Taiwan | DIMS + atropine 0.01% | 1 year | Reported benefit of DIMS plus atropine 0.01% in fast-progressing myopia |
| Lee, C. Y. et al. 2025 (In Vivo) | Study in high myopia population (>-6.0D) | 6-15 | Taiwan | DIMS spectacle lens + atropine 0.125% | 1 year | Reported myopia control effect in high myopia (AL elongation less than half) |
| Cao et al. 2025 | Retrospective study | 6-11 | Chinese | Atropine 0.01% + SVL vs atropine 0.01% + orthokeratology vs atropine 0.01% + DIMS | 6 months | DIMS + atropine 0.01% outperformed atropine 0.01%+SVL |
| Guemes-Villahoz et al. 2025 | Randomised study | 4-16 | European | Atropine 0.025% + SVL vs atropine 0025% + DIMS | 1 year | AL progression: 0.18 mm (atropine+SVL) vs 0.07 mm (atropine 0.025% + DIMS) |
| Hassan et al. 2026 | Systematic review | Review | Review | Defocus lenses vs atropine vs combined defocus lenses + atropine | Review | Concluded each intervention effective; combination produced greater effect than either alone |
| Zhao et al. 2024 | Retrospective | 6-15 | Chinese | SVL vs HAL alone vs HAL + atropine 0.01% | 1 year | HAL reduced axial elongation 0.34 mm → 0.19 mm vs control; adding atropine reduced further to 0.09 mm |
| Hu et al. 2025 | Retrospective study | 8-15 | Chinese | HAL + atropine 0.01% vs atropine 0.01% | 1 year | Combination yielded the best outcome |
| Sim et al. 2025 | Prospective study progressing on atropine (0.01% daily, 0.01% twice daily, or 0.025% daily) | 8-15 | Singaporean | Added HAL lenses and continued their atropine dose | 1 year | Benefit of combining HAL + atropine; no additional effect from higher atropine doses reported |
| Chen et al. 2025 | Retrospective study | 8-13 | Chinese | Groups: OK, HAL, SVL; and each optical treatment combined with atropine 0.01% | 1 year | All monotherapies better than SVL; HAL best monotherapy. Adding atropine 0.01% further reduced progression; HAL+atropine slower progression in older/low myopia) |
| Tang, Y. et al. 2025 | Retrospective study At least 4 D in 1 eye | 8-12 | Asian | HAL + atropine 0.01% | 1 year | Minimal additive effect of atropine 0.01% when combined with HAL in moderate–high myopia |
| Erdinest et al. 2024 | Prospective study | 8-15 | Mixed causaian | Atropine 0.01% + dual-focus contact lenses vs atropine 0.01% + SVL vs dual-focus contact lenses alone vs SVL alone | 3 years | No additional effect of adding atropine 0.01% to dual-focus contact lenses over 3 years (atropine 0.01% + SVL showed a statistically significant monotherapy effect) |
| Yum et al. 2025 | Retrospective study | 7-13 | Korean | Dual-focus contact lenses + atropine 0.05% vs dual-focus contact lenses alone | 1 year | Combination significantly reduced progression vs contact lenses alone |
| Study | Study design | Age | Ethnicity | Intervention | Follow-up | Effect |
|---|---|---|---|---|---|---|
| Xiong et al. 2024 | Multicentre randomised controlled trial | 8-13 | Chinese | RLRL + OK vs OK alone (rapid progressors previously on OK) | 1 year | No progression with add-on RLRL (0.00 mm) vs 0.27 mm axial elongation with OK alone |
| Yu et al. 2024 | Retrospective study Fast progressors |
7-15 | Chinese | RLRL + OK in poor responders to OK | 1 year | Additive effect with no progression in combination group |
| Wu et al. 2024 | Retrospective study | 5-15 | Chinese | RLRL combined with SVL or OK | 2 years | Statistically significant benefit of RLRL; additive effect of OK |
| Fernandez Fidalgo et al. 2025 | Randomised controlled study | 10-13 | European | RLRL + OK vs OK alone | 1 year | Combination showed axial length shortening; orthokeratology alone showed mild elongation |
| Elham and Meng 2026 | Retrospective study in fast progressors (>0.4 mm/year) | 8-14 | Chinese | RLRL + OK vs OK alone | 1 year | Combination had significantly greater effect than OK alone |
| Zhang et al. 2026 | Meta-analysis | Review | Review | Adjunctive RLRL with optical myopia control (including as adjunct to OK) | Review | Significant additive effect of adjunctive RLRL |
| Yang, Liu, et al. 2025 | Real-world observational study | 5-16 | Chinese | DIMS alone vs RLRL alone vs DIMS + RLRL | 1 year | Axial length change: +0.16 mm (DIMS); −0.04 mm (RLRL); −0.13 mm (DIMS+RLRL) |
| Luo et al. 2025 | Comparative study | 6-14 | Chinese | SVL vs DIMS vs RLRL vs RLRL + DIMS | 1 year | Axial length change: 0.26 mm (SVL); 0.16 mm (DIMS); −0.21 mm (RLRL); −0.14 mm (RLRL+DIMS); adding DIMS to RLRL not statistically significant |
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