Myopia Mix and Match: Combination Treatments for Management

When eye care practitioners are asked which approach they consider most effective for slowing myopia progression, combination therapy comes out on top. This was a repeated finding of the International Myopia Institute’s (IMI’s) 2021 and 2024 Global Trends in Myopia Management clinical surveys with combinations – typically low-dose atropine paired with an optical treatment – rated as the most efficacious approach.¹

The picture has expanded considerably in the past year or two. Combinations of atropine with all classes of optical treatment have been investigated through new randomised controlled trials (RCTs) and clinical cohort studies. At the same time, light therapies – repeated low-level red-light (RLRL) and a blue-light head-mounted device known as MyopiaX – are defining an entirely new combination frontier. This article walks through this new evidence, and what it means for tailoring myopia management to the individual child.

If 0.01% atropine is now widely seen as a relatively modest monotherapy, where is its place? Increasingly, it appears to be as the additive partner to an optical treatment

Setting The Scene: Atropine Concentration as a Monotherapy

Before discussing atropine in combination, it is worth revisiting how the concentrations stack up as monotherapies. The Low Concentration Atropine for Myopia Progression (LAMP) study established the dose-response relationship across 0.05%, 0.025%, and 0.01% atropine in Hong Kong Chinese children, with 0.05% emerging as the most effective concentration over one,² two,³ and now seven years of follow-up.⁴ The MOSAIC2 study, published in 2025, extended this evidence into a primarily White cohort of European descent. In Irish children, one year of 0.05% atropine treatment produced similar efficacy as two years of 0.01%.⁵

So, if 0.05% is better than 0.01%, would going higher again deliver more? The evidence suggests no. The original ATOM-1 RCT on 1% atropine demonstrated strong myopia control but with significant near vision blur and photophobia limiting clinical translation.⁶ More recently, a three-year Danish placebo-controlled RCT tested whether a six-month 0.1% atropine ‘loading dose’ followed by 0.01% would outperform 0.01% alone – it did not, with a clear rebound effect observed when the dose was reduced.⁷ While the literature is scant, it appears that atropine concentrations above 0.05% offer no consistent additional efficacy in slowing myopia progression, but do drive up the rate of side effects. Where it is well tolerated, 0.05% emerges as the best balance for most children.

This sets up an important clinical question. If 0.01% atropine is now widely seen as a relatively modest monotherapy, where is its place? Increasingly, it appears to be as the additive partner to an optical treatment – although as we are learning, the combination concentration question is far from settled.

Atropine Plus OK: The Most Established Combination

OK paired with 0.01% atropine has the longest history and strongest evidence base of any combination treatment. The two-year AOK randomised controlled trial showed mean axial elongation of 0.17 mm in children using OK plus 0.01% atropine, compared to 0.34 mm with OK alone, with the additive effect strongest in the first six months.8 Multiple retrospective studies and a 2022 network meta-analysis confirmed this short-term boost effect.⁹

More recently, attention has turned to higher concentrations. A 2025 retrospective study of Chinese children who continued to progress despite OK showed that adding 0.05% atropine reduced annual axial elongation from 0.27 mm to 0.14 mm, with the strongest effect again in the first six months.¹⁰ The fast-progressor profile – children whose axial elongation exceeds 0.20 to 0.25 mm per year on monotherapy – is emerging as an indication for escalating to combination treatment.

Atropine Plus Soft Contact Lenses: A Story of Concentration

Here, the data is sparser. A three-year RCT of CooperVision Biofinity centre-distance multifocal soft contact lenses (+2.50D Add), with or without 0.01% atropine, found no statistically significant additive effect for either refractive or axial outcomes.¹¹ An earlier retrospective study, of 0.01% atropine combined with CooperVision MiSight 1 day, similarly did not show a clear additive benefit, although that study did not measure axial length.¹²

The story changed with a recent retrospective study of 142 Korean children with rapid progression (-0.75D or 0.25 mm/yr) on 0.05% atropine monotherapy. This study showed 0.28D less refractive progression and 0.13 mm less axial elongation over 12 months when switched from single vision spectacles to MiSight 1 day.¹³ Does this mean that 0.01% atropine is too weak to potentiate the soft lens effect, and that 0.05% may be required for measurable synergy, or are these differential findings more about the study designs? This is a question ripe for further investigation.

Atropine Plus Myopia Control Spectacles: A Flurry of New Data

Until recently, evidence for spectacle-and-atropine combinations was limited largely to retrospective studies showing modest additive effects of 0.01% atropine with defocus incorporated multiple segments (DIMS) lenses,¹⁴ commercially known as HOYA MiyoSmart. The past 18 months have brought more clarity.

The ASPECT randomised controlled trial – the first RCT to investigate DIMS in combination with atropine 0.025% – reported its 12-month interim results in 2025. In Spanish children aged 4–16 years, axial elongation was 0.18 mm in the atropine monotherapy group (who wore single vision spectacles) and just 0.07 mm in the DIMS plus atropine combination group, with nearly 40% of combination wearers showing no axial growth at all over the year.¹⁵ These findings strongly support an additive effect, although refraction differences were modest and not statistically significant.

A retrospective Taiwanese study, also published in 2025, asked whether the atropine concentration matters in combination with DIMS. Across three groups – DIMS alone, DIMS plus 0.01%, and DIMS plus 0.125% atropine – both atropine groups slowed progression beyond DIMS alone (refractive progression of 0.30D versus 0.17D and 0.16D, with axial elongation of 0.13 mm versus 0.06 mm and 0.06 mm respectively), but the 0.01% and 0.125% groups did not differ from each other.¹⁶ This is one of the few direct comparisons of atropine concentrations in combination, and it suggests that once an effective optical treatment is on board, adding more atropine doesn’t necessarily add more control.

For highly aspherical lenslet target (HALT) technology spectacles (Essilor Stellest), a 2025 Singapore study by Sim and colleagues took a clinically realistic approach. They added HALT lenses to children who were continuing to progress on low-dose atropine (≥0.50D over six months). After 12 months of combination treatment, mean progression slowed from -0.60D and 0.24 mm in the prior six months on atropine alone, to -0.07D and 0.13 mm with the HALT addition.¹⁷ The additive effect was similar regardless of whether children were using 0.01% atropine once daily, 0.01% twice daily, or 0.025% once daily – and given the latter two regimens deliver effectively similar overall exposure, this is not necessarily a true comparison of concentrations.

A real-world Chinese study, published in 2025, compared DIMS plus 0.01% atropine head-to-head with OK monotherapy. Treatment choice was by parental preference, but the groups were matched at baseline. Axial elongation was 0.14 mm in the DIMS-plus-atropine group versus 0.20 mm in the OK group over 12 months, suggesting that the combination can be a credible alternative for children unsuitable for, or unwilling to wear, contact lenses.¹⁸

This is by no means an exhaustive review – the evidence continues to grow, as independent investigators trial various combinations for diverse patient profiles in their practices, and share their findings.

Which Atropine Concentration for Combinations?

Weaving these threads together indicates that while 0.05% atropine is clearly more efficacious than 0.01% as a monotherapy, the picture is less clear-cut in combination. We have remarkably few direct comparisons of different atropine concentrations when paired with the same optical treatment. The Lee study on DIMS plus 0.01% versus 0.125% is one of the only ones, and the comparison there was at the extremes of dosing.¹⁶ The Sim study on HALT effectively compared 0.01% once daily to a slightly higher dose (0.01% twice daily or 0.025% nightly, which deliver similar overall exposure), and again found no difference.¹⁷ The spectrum between 0.01% and 0.05% in combination remains under-investigated for any optical treatment.

What we can reasonably take from this is that any low concentration of atropine is likely to provide a meaningful additive benefit to a myopia control optical treatment. The data on MiSight 1 day plus 0.05% in fast progressors suggests higher concentrations may extract additional benefit in children who are less treatment-responsive,¹³ but this remains an open question for spectacles, and needs further well-designed trials.

… light therapies are reshaping the combination conversation – specifically, RLRL and MyopiaX

The New Combination Frontier: Light Therapies

While ‘atropine plus an optical treatment’ has long been the default mental model, light therapies are reshaping the combination conversation – specifically, RLRL and MyopiaX.

RLRL therapy (650 nm, delivered twice daily for three minutes, five days per week) has rapidly accumulated efficacy evidence as a monotherapy.19,20 Its potential as a combination partner came to the fore with a 2024 multicentre RCT in Chinese children who were progressing rapidly on OK (≥0.50 mm/year). Adding RLRL produced a striking outcome, with mean axial length stability (difference -0.02 mm) in the combination group, versus 0.27 mm growth in the OK-monotherapy group, over 12 months.²¹ The first European data was published in late 2025: an RCT in Spanish children aged 10–13 years where RLRL was added to OK from baseline (not after monotherapy failure). Mean axial length change was -0.124 mm (shortening) in the combination group versus +0.102 mm elongation in the OK-only group, with 80% of combination wearers showing axial shortening greater than the repeatability measure of 0.05 mm.²² This evidence in both Asian and European populations indicates a strong synergistic effect.

A critical clinical caveat is that atropine use is currently cited as a contraindication for RLRL therapy, owing to atropine-induced pupil dilation potentially altering the eye’s response to the light and increasing the risk of retinal exposure.²³ For now, RLRL combinations are with optical treatments only – a ‘triple therapy’ is not on the horizon.

MyopiaX is a different proposition – a smartphone app delivering targeted blue light through a virtual reality-style headset, designed to selectively stimulate intrinsically photosensitive retinal ganglion cells at the optic nerve head and, via dopamine pathways, modulate ocular growth. The 12-month MyopiaX-1 multicentre RCT, published in 2025, randomised 101 European children aged 6–12 years to either MyopiaX for six months followed by MyopiaX plus DIMS for the next six months, or DIMS alone for 12 months as the active control.²⁴ In the first six months, MyopiaX as monotherapy produced slightly more axial elongation than DIMS (0.14 mm versus 0.08 mm); in the second six months, the MyopiaX-plus-DIMS combination performed similarly to DIMS alone. While MyopiaX did not show an additive ‘boost’ to DIMS over the second six months, it appears safe and well-tolerated, and the combination story for this device is still being written. Compliance with the daily app-based sessions emerged as a major variable affecting outcomes – a familiar challenge for any new myopia treatment requiring daily child and family engagement.

The question of ‘one treatment or two?’ is increasingly resolving into ‘which two, for whom, and when?’

Clinical Takeaways

So how does this all come together? As the evidence continues to expand, combination therapy looks less like a second-line approach for children failing monotherapy – where most of the initial data has sprung from – and more like a first-line option for those at higher risk, who are younger, have fast baseline progression, a strong family history of high myopia, or axial length well above age-normal centiles. By contrast, the ASPECT study,¹⁵ DIMS-plus-atropine real-world Chinese data,¹⁸ and the RLRL-plus-OK Spanish RCT²² all enrolled children in combination treatment from the outset, rather than those who had failed monotherapy or were identified as ‘high risk’, and all delivered impressive levels of axial control. Overall, clinical judgement on risk and level of parental concern is likely to be the best guide for justifying the additional impact of prescribing combination treatment.

For atropine combinations, low concentrations of 0.01% to 0.05% perhaps provide a similar additive boost to optical treatments, with no evidence that going higher in dose delivers more efficacy. Where tolerated, 0.05% may provide additional benefit in children inadequately controlled on lower-dose combinations. The light therapy combinations represent the most rapidly moving frontier, with RLRL plus OK now backed by trials in both Asian and European populations, and MyopiaX still in earlier proof-of-concept territory.

Interestingly, the IMI 2024 survey shows that the perceived efficacy gap between combination therapy and monotherapies is narrowing. While combination remains the most highly rated intervention for efficacy, its perceived efficacy has dropped by nearly 10% since 2022, and the perceived efficacy of myopia control soft contact lenses has more than doubled since 2015 (from 24% to 52%).¹ As monotherapies have matured – longer-term data, new lens designs, and proven efficacy across ethnic groups – combination care becomes less an exception driven by treatment failure, and more a deliberate, proactive choice for the children who most need it. The question of ‘one treatment or two?’ is increasingly resolving into ‘which two, for whom, and when?’

Dr Kate Gifford PhD BAppSc (Optom) Hons GCOT FCCLSA FBCLA FIACLE FAAO is a Director of Myopia Profile and Visiting Research Fellow, Queensland University of Technology.

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