Combination Therapy for Childhood Myopia

Emerging evidence suggests combining myopia therapies may enhance myopia control beyond monotherapy in select patients.^1-3 While most children can be successfully managed with a single evidence-based intervention, combination therapy may be appropriate for those who have rapid progression or continued axial elongation despite treatment.⁴ To date, the strongest evidence supports combining 0.01% atropine with orthokeratology, while evidence supporting other treatment combinations—including soft multifocal contact lenses and myopia control spectacles—continues to evolve.^1-4

This article reviews the current evidence supporting combination therapy (organized by combination), provides related clinical pearls, and discusses when to prescribe combination therapy.

ATROPINE AND ORTHOKERATOLOGY

Randomized clinical trials and a recent systematic review and meta-analysis consistently demonstrate greater slowing of axial elongation with combination therapy than with orthokeratology alone, particularly in children younger than 10 years of age, who typically experience faster rates of myopia progression.^1-3

As an example, in a 2-year randomized clinical trial, children receiving 0.01% atropine combined with orthokeratology exhibited 0.29 mm of axial elongation versus 0.40 mm in the orthokeratology-only group, representing an additional reduction of approximately 0.11 mm (28%).¹ Additionally, the greatest treatment effect occurred during the first 6 to 12 months, with a further reduction in axial elongation of approximately 0.10 mm to 0.15 mm over 2 years.¹

Also, a recent systematic review and meta-analysis of eight randomized controlled trials demonstrated significantly less axial elongation with combination therapy up to 24 months.³

Of note: Higher concentrations (0.025% and 0.05%) are increasingly used clinically for persistent progression; however, robust randomized evidence supporting these regimens in combination with orthokeratology remains limited.

• Clinical Pearl. Consider combination therapy for children younger than 10 years of age who have rapid progression or continued axial elongation despite orthokeratology monotherapy. Additionally, monitor axial length every 6 months to objectively assess treatment response.

ATROPINE AND SOFT MULTIFOCAL CONTACT LENSES

Evidence supporting combined atropine and soft multifocal contact lenses is limited and inconsistent.

To start, the Bifocal and Atropine in Myopia study shows no clinically meaningful additional benefit with the addition of 0.01% atropine to soft multifocal contact lenses versus multifocal contact lenses alone.⁵

More recently, researchers conducted a retrospective study of 142 children in which those whose myopia continued to progress rapidly despite 0.05% atropine monotherapy (≥ 0.75 D/year or ≥ 0.25 mm/year axial elongation) had dual-focus soft contact lenses added to their regimen. Following this addition, myopia progression and axial elongation slowed significantly within the combination group, with outcomes matching those of children who remained stable on atropine alone. This suggests dual-focus contact lenses can be effective in poor atropine responders. The additive benefit was most pronounced in children who had low-to-moderate myopia versus those with high myopia.⁶

Consequently, additional prospective randomized clinical trials are needed.

• Clinical Pearl. Consider combination therapy for children who have continued progression despite soft multifocal contact lens wear, generally defined as axial elongation ≥ 0.20 mm/year or myopia progression ≥ 0.50 D/year, despite good treatment adherence. Also, monitor axial length every 6 months to objectively assess treatment response.

ATROPINE AND MYOPIA CONTROL SPECTACLES

While Highly Aspherical Lenslet Target spectacle lenses were recently FDA approved to correct myopia in children, as this articles goes to press, no study findings are yet available on combining them with atropine.

Early clinical studies evaluating defocus-incorporated multiple segments (DIMS) spectacle lenses, however, show combination therapy is effective at slowing myopia progression versus DIMS lenses alone, although findings for axial elongation have been less consistent.^7,8

Most recently, the Atropine and Spectacle Lens Combination Treatment randomized clinical trial reveals that combining 0.025% atropine with DIMS lenses resulted in significantly less axial elongation than atropine used with standard spectacles alone over 12 months (0.07 mm vs. 0.18 mm), with nearly 40% of children in the combination group showing no axial elongation—rates comparable to emmetropic peers.⁹

A prospective comparative study reported that children treated with 0.01% atropine and DIMS spectacle lenses demonstrated significantly less refractive progression than those receiving either treatment alone, although differences in axial elongation among the combination and DIMS-only groups were not statistically significant.⁷

Conversely, other researchers found that combining 0.01% atropine with DIMS spectacle lenses resulted in greater slowing of both myopia progression and axial elongation than DIMS monotherapy.⁸

• Clinical Pearl. Early evidence suggests adding 0.01% atropine to DIMS spectacle lenses may provide additional benefit in select children who have progressive myopia. That said, more prospective randomized clinical trials are needed before this routine combination therapy can be broadly recommended. Additionally, we must keep in mind that DIMS spectacle lenses are not approved for use in the United States.

REPEATED LOW-LEVEL RED LIGHT (RLRL) AND COMBINATION THERAPIES

RLRL therapy delivers 650 nm light for 3 minutes two times daily and promotes choroidal thickening through photobiomodulation.

In a multicenter randomized controlled trial, adding RLRL to orthokeratology in rapid progressors (axial elongation ≥ 0.50 mm/year despite orthokeratology) reduced mean 12-month axial elongation to -0.02 mm versus +0.27 mm with orthokeratology alone (-0.29 mm adjusted difference).¹⁰

Additionally, RLRL combined with DIMS spectacle lenses showed synergistic benefit (-0.13 mm/year versus +0.16 mm/year for DIMS alone).¹¹

• Clinical Pearl. Because RLRL acts through choroidal thickening, it may provide an additive benefit when combined with optical interventions. That said, RLRL devices are not currently FDA-approved.

WHEN TO PRESCRIBE COMBINATION THERAPY AND FOLLOW UP

Most children should begin with a single evidence-based therapy, as monotherapy effectively slows progression in many patients, while allowing clinicians to assess treatment response before escalating care (Figure).¹²

Combination therapy may be considered for children who were diagnosed < 10 years of age, have a strong family history of high myopia, have other risk factors for developing high myopia, and have an axial elongation of ≥ 0.20 mm/year and myopia progression ≥ 0.50 D.

Combination therapy is generally well tolerated. Side effects are primarily attributable to atropine and may include mild photophobia, glare, large pupil size, and reduced accommodation, although these effects are uncommon with 0.01% atropine. Orthokeratology carries the standard risks associated with overnight contact lens wear, including corneal staining, inflammatory events, and the rare risk of microbial keratitis. Relative contraindications include poor contact lens hygiene or poor compliance, significant ocular surface disease, corneal abnormalities that preclude orthokeratology, atropine intolerance, or inability to adhere to the treatment and follow-up regimen.

Patients initiating combination therapy may benefit from an earlier follow-up visit (typically within 1 month to 3 months, depending on the treatment modality) to assess treatment adherence, tolerability, and contact lens fit when applicable. Once treatment is established, following up approximately every 6 months is consistent with the International Myopia Institute Clinical Management Guidelines and the follow-up intervals used in most major myopia clinical trials.¹²

When available, axial length should be measured at each visit, as it provides a more sensitive assessment of treatment response than refractive error alone. As myopia progression stabilizes, treatment may be gradually de-escalated, typically by tapering atropine rather than abruptly discontinuing therapy to minimize rebound.

A randomized extension of the Low-Concentration Atropine for Myopia Progression trial shows that children who tapered atropine concentration stepwise before discontinuation experienced significantly less myopia progression and axial elongation over 3 years after treatment versus those who stopped abruptly (-0.54 D vs. -0.78 D, 0.33 mm vs. 0.44 mm axial elongation).^13,14 If rebound occurs, consider resuming the previous effective atropine concentration or combination regimen while continuing to closely monitor the patient (every 3 months to 6 months).

Environmental interventions remain an essential component of myopia management regardless of treatment strategy. Encouraging at least 2 hours of outdoor time daily and reinforcing healthy visual habits should be discussed with every child and their family.¹⁵

PUTTING COMBINATION THERAPY INTO PRACTICE

Combination therapy represents a reasonable escalation strategy for children who have progressive myopia and continue to demonstrate axial elongation despite monotherapy or who are at high risk for rapid progression.

Current evidence suggests combining therapies with complementary mechanisms of action may provide additional benefit in select patients, although the magnitude of benefit varies by treatment combination, and the strongest evidence currently supports 0.01% atropine combined with orthokeratology.^1-3

A stepwise, individualized approach that begins with a single evidence-based intervention and escalates treatment based on documented progression remains the best evidence-supported strategy. Treatment decisions should also consider efficacy, patient adherence, cost, and potential side effects. Ongoing monitoring, ideally with serial axial length measurements, is essential to evaluate treatment response and guide clinical decision making.¹