Childhood Myopia Part I: Contemporary Treatment Options

Abstract

Childhood myopia is a growing global public health concern. Treatments to control myopia are a priority because myopia, particularly high myopia, poses significant lifelong risks of vision loss from myopia-associated ocular pathologies. Intensive research efforts over the past two decades have led to the development of several effective strategies for controlling myopia in children: increased time outdoors, atropine eye drops, dual-focus and multifocal contact lenses, orthokeratology lenses, and specialized spectacle lenses. While the efficacy of these strategies is variable, evidence is growing regarding the potential benefits of applying these interventions in children with myopia, although none completely halt myopia progression. Despite this evidence, dual-focus contact lenses remain the only myopia treatment in the United States approved by the US Food and Drug Administration. This critical review article provides an evidence-based overview of treatment options currently available to prevent the onset of myopia and slow its progression in children. It is the first part of the commissioned paper “Treatment of Childhood Myopia” submitted to the National Academies of Sciences, Engineering, and Medicine for the consensus study “Focus on Myopia—Pathogenesis and Rising Incidence.” Readers are referred to Part II for a review of treatment mechanisms, emerging and experimental treatments, and patient, treatment, and clinical trial considerations. Findings from this article demonstrate a growing body of strong evidence supporting the use of contemporary treatments in childhood myopia management. Regulatory approvals of these proven treatments worldwide would allow widespread, early intervention in at-risk children and potentially reduce the risk of vision loss from myopia-related complications later in life.

Myopia (also known as near-sightedness or short-sightedness) is a major public health problem rising in both frequency and severity worldwide.^1–6 The prevalence of myopia increased from 25% in 1971 to 41.6% in 2002 among US individuals aged 12 to 54 years⁷ and more than doubled among UK⁸ and Australian schoolchildren.⁹ In East Asia, myopia is already at epidemic levels, affecting 84% of 16- to 18-year-old schoolchildren in Taiwan,¹⁰ 96.5% of 19-year-old male military conscripts in South Korea,¹¹ and up to 80% to 95.5% of school and university students in other regions,^12–16 prompting the urgent development of prevention and control programs.^17,18 According to projected estimates, the global prevalence of myopia is 31%¹⁹ and may rise to 40% to 50% by 2050,^4,19 although some have questioned whether these predicted outcomes are realistic.²⁰ 

Public health concerns for myopia are increasing²¹ because myopia is a significant risk factor for several sight-threatening ocular pathologies,²² such as retinal detachment,²³ cataracts,²⁴ glaucoma,²⁵ and myopic macular degeneration (MMD).²⁶ Individuals with high levels of myopia carry substantial risks of developing these complications in later life, but even for those with low to moderate myopia, the risks are significant.^27,28 This has led to some calls from the scientific community to recognize myopia as a disease.^27,29–31 As myopia prevalence grows, the incidence of myopia-related complications is likely to surge, leading to a major public health crisis, as already evident in some parts of East Asia, where MMD is now a major cause of blindness among middle-aged and older adults.^26,32,33 If the current trend persists, it is estimated that MMD will increase the global burden of visual impairment and blindness fivefold by 2050.³⁴ Besides its growing threat to eye health, myopia is linked with profound economic impact,^35–38 massive loss of productivity,^39,40 and diminished quality of life.⁴¹ 

Most myopia starts in early childhood^42–44 and progresses rapidly into teenage years⁴⁵ and, in some cases, even up to adulthood,^46–48 primarily due to excessive and abnormal axial eye growth, which increases susceptibility to various ocular pathologies.²² Traditional methods of myopia management, such as corrective lenses and refractive surgery, restore clear distance vision but do not slow axial elongation and, hence, myopia-associated risks. Interests and efforts in developing myopia control treatments have intensified in recent years, many of which have met with success, leading to the discovery of treatment strategies to control myopia onset and progression in children.^49–52 These strategies include time outdoors^53,54; atropine eye drops^55–59; dual-focus,^58,60–62 bifocal,⁶³ multifocal,⁶⁴ and orthokeratology⁶⁵ contact lenses; and specialized spectacle lenses.^66–70 Several other treatments appear to be on the horizon.^69,71–74 

Randomized clinical trials of contemporary treatments have demonstrated a maximum efficacy of up to 1 diopter (D) refractive control or 0.45 mm axial control over 3 to 5 years.⁷⁵ While this treatment effect appears small over a short period, it has been predicted that delaying myopia onset by 1 year lowers final myopia by at least 0.75 D,⁷⁶ and slowing myopia progression by as little as 1 D reduces the risk of developing MMD by 37%, retinal detachment by 23%, posterior subcapsular cataract by 17%, open-angle glaucoma by 16%, and visual impairment by 20%.⁷⁷ In this regard, the implementation of contemporary myopia treatments seems justified: they are likely to reduce not only the prevalence of high myopia⁷⁸ but also the risks of vision loss from myopia-related pathologies,⁷⁹ potentially yielding significant public health benefits. However, the current myopia treatments have their limitations; none can completely halt axial elongation or myopia progression.^50,80 In the United States, dual-focus lenses remain the only treatment approved by the US Food and Drug Administration (FDA) for myopia control. Other treatments, such as atropine eye drops and multifocal and orthokeratology contact lenses, are used off-label, while myopia control spectacle lens options are unavailable. Developing safe and effective treatments that can optimally control eye growth and myopia remains an urgent priority to avoid the impending public health crisis due to myopia.^81,82 

This critical review article provides an evidence-based overview of current myopia treatments available in and outside the United States. Several recent review studies,^{51,75,83–86} including a living Cochrane review⁸⁰ and the International Myopia Institute article,⁵⁰ have discussed the efficacy of optical and pharmacologic interventions for childhood myopia. The objective of this article is to critically appraise the evidence base and summarize knowledge in this area with references to these reviews where applicable. This article is the first part of the commissioned paper “Treatment of Childhood Myopia,”⁸⁷ submitted to the National Academies of Sciences, Engineering, and Medicine for the consensus study “Focus on Myopia—Pathogenesis and Rising Incidence.”³¹ For a review of treatment mechanisms, emerging and experimental treatments, and patient, treatment, and clinical trial considerations, readers are referred to Part II: Treatment Mechanisms, Emerging Options, and Considerations. 

Treatments Available in the United States

Atropine

Atropine eye drops, a nonspecific muscarinic acetylcholine receptor antagonist, are used off-label for treating childhood myopia in the United States. Atropine use for myopia control has a long history that dates back more than 150 years,^88–93 when Donders, in 1864, first advocated its use to manage accommodative spasms in myopic patients.⁹⁴ However, atropine was not tested in randomized controlled trials until 1989, when Yen et al.⁹⁵ showed that myopic children progressed more slowly by 0.70 D after 1 year of treatment with 1% atropine compared with saline eye drops. In 1999, Shih et al.⁹⁶ compared the efficacy of different concentrations of atropine by randomly assigning 168 myopic children aged 6 to 13 years to atropine eye drops (0.5%, 0.25%, and 0.1%) or 0.5% tropicamide eye drops. After 2 years, the average rate of myopia progression (0.04 D/year with 0.5% atropine, 0.45 D/year with 0.25% atropine, and 0.47 D/year with 0.1% atropine) was significantly slower, and the proportion of participants with no myopia progression (<0.25 D/year) was significantly higher with atropine (61% in 0.5% atropine, 49% in 0.25% atropine, and 42% in 0.1% atropine) compared with 0.5% tropicamide (1.06 D/year, 8%). Refractive efficacy of 0.5% atropine was greater than 0.25% and 0.1% concentrations, but the latter two were not significantly different. In a follow-up study, the same authors randomized 227 myopic children into three groups: 0.5% atropine with multifocal spectacles, multifocal spectacles, and single-vision spectacles.⁹⁷ After 18 months, average myopia progression was −0.42 D in atropine with multifocal spectacles, −1.19 D with multifocal spectacles, and −1.40 D with single-vision spectacles, while average axial elongation was 0.22 mm, 0.49 mm, and 0.59 mm in the three groups, respectively. The differences were statistically significant between atropine with multifocal versus single-vision and multifocal versus single-vision groups. 

The efficacy of atropine eye drops was further investigated in several large and small-scale randomized controlled trials.^58,98,99 In the Atropine for the Treatment of Myopia (ATOM) study, 400 Singaporean children aged 6 to 12 years were randomized to monocular treatment with 1% atropine or vehicle (artificial tears) eye drops, while the fellow eye was left untreated.⁵⁸ After 2 years of treatment, myopia progression and axial elongation in the atropine-treated eyes (−0.28 D and −0.02 mm) were significantly slower than in the vehicle-treated eyes (−1.20 D and 0.38 mm). Treatment with 1% atropine eye drops completely blocked axial elongation in myopic eyes. Evidence from these trials showed that atropine in concentrations ranging from 0.1% to 1% slowed myopia progression and axial elongation in children. When participants in the ATOM study were followed up for 1 additional year following treatment cessation,¹⁰⁰ the atropine-treated eyes progressed by −1.14 D and 0.31 mm compared to the control eyes (−0.38 D and 0.14 mm), and the magnitude of progression in atropine-treated eyes was similar to that observed in the control eyes during the prior 2-year treatment period, suggesting a significant rebound effect (acceleration of progression after treatment cessation) with 1% atropine eye drops. 

Despite the impressive efficacy of 1% atropine, enthusiasm was limited mainly due to its undesirable side effects, such as mydriasis and loss of accommodation, and a rebound effect,^58,100 causing a shift in attention toward lower concentrations of atropine. In a subsequent ATOM2 trial,⁵⁷ 400 myopic children were randomized in a 2:2:1 ratio to binocular nightly treatments with 0.5%, 0.1%, and 0.01% atropine, the latter included as a control. After 2 years of treatment, average myopia progression was −0.30 D, −0.38 D, and −0.49 D, and axial elongation was 0.27 mm, 0.28 mm, and 0.41 mm in the 0.5%, 0.1%, and 0.01% groups, respectively. There was a dose-dependent effect of atropine concentrations on myopia progression and axial elongation. However, the lack of a control group made it impossible to establish the true treatment efficacy in this trial. When the vehicle-treated control group in ATOM1 was used as a historical control, all three concentrations appeared effective, and even 0.01% had significant treatment benefit, slowing myopia progression by 0.71 D. This led to increased popularity and widespread uptake of 0.01% atropine eye drops for the treatment of childhood myopia worldwide. However, there was a disconnect between refractive and axial length control efficacy with 0.01% atropine.^101,102 Relative to the control group in ATOM1 (progression of −1.20 D and 0.38 mm), 0.01% atropine slowed myopia progression by 0.79 D but demonstrated greater axial elongation (0.41 mm). The lack of axial length control efficacy of 0.01% atropine raises doubts about whether its use for myopia control is justified if the primary aim is to reduce the risks of myopia-related pathologies in later life.¹⁰² 

After 2 years of initial treatment, children in ATOM2 were followed for a 1-year washout period without treatment.¹⁰³ During the washout period, myopia progression and axial elongation were greater in the 0.5% atropine group (−0.87 D) compared with the 0.1% (−0.68 D) and 0.01% (−0.28 D) atropine groups, showing a stronger rebound effect with a higher concentration of atropine and resulting in a significantly higher myopia progression over the 3 years (2-year treatment and 1-year washout) in 0.5% atropine-treated eyes compared with 0.01% atropine-treated eyes (−1.15 D vs. −0.72 D). In the final 2 years of the 5-year ATOM2 trial, children showing a progression of −0.50 D or more in at least one eye during the washout period were restarted on 0.01% atropine.¹⁰⁴ At the end of 5 years, overall myopia progression and axial elongation were lowest in the 0.01% atropine group (−1.38 D and 0.75 mm) compared with 0.1% atropine (−1.83 D and 0.85 mm) and 0.5% (−1.98 D and 0.87 mm) atropine groups. The authors concluded, “Over 5 years, atropine 0.01% eyedrops were more effective in slowing myopia progression with fewer visual side effects compared with higher doses of atropine.”¹⁰⁴ It is noteworthy that refractive changes in this trial were calculated from the baseline taken after 2 weeks of treatments, resulting in different starting points for the three groups (0.5% vs. 0.01% atropine: 0.02 D and 0.1 mm; 0.1% vs. 0.01%: 0.02 D and 0.1 mm). Accounting for these baseline differences between the three groups, the relative effect of 0.01% atropine after 5 years appears rather modest. In addition, establishing an optimal concentration by allowing the use of more effective concentrations for only 2 years and stopping them for the remainder of the trial appears to be a less favorable approach. Recently, the Atropine Treatment Long-term Assessment Study reported no increased incidence of myopia-related complications in prior atropine and placebo groups among 71 ATOM1 and 158 ATOM2 study participants 10 to 20 years after treatment.¹⁰⁵ The atropine and placebo groups did not differ in the final amount of myopia and axial length, suggesting no long-term impact of treatment, although extrapolation of the initial benefit observed during a short initial treatment period to several years later is seldom expected to yield a positive result for a health outcome. 

The limitations of ATOM2 were somewhat addressed by the Low-concentration Atropine for Myopia Progression (LAMP) study, which included a concurrent control group and evaluated the efficacy of three low concentrations of atropine eye drops (0.05%, 0.025%, and 0.01%) in 438 four- to 12-year-old myopic children randomized to treatment or placebo groups.⁵⁶ After 1 year of treatment, the average myopia progression was −0.27 D in 0.05%, −0.46 D in 0.025%, −0.59 D in 0.01%, and −0.81 D in placebo groups, with the respective average axial elongation of 0.20 mm, 0.29 mm, 0.36 mm, and 0.41 mm. Low concentrations of atropine had dose-related treatment effects, with 0.05% atropine being the most effective treatment, slowing myopia progression by 0.54 D and axial elongation by 0.21 mm over 1 year. Notably, 0.01% atropine produced no greater slowing of axial elongation than placebo, with a modest (0.05 mm) and statistically insignificant axial length control efficacy. Unfortunately, in phase II (second year) of the LAMP trial, the placebo group was converted to 0.05% atropine for ethical reasons, limiting the efficacy assessment.¹⁰⁶ However, at the end of 2 years, the average myopia progression with 0.01% atropine (−1.12 D) was twice that with 0.05% atropine (0.55 D). In phase III, children were randomized 1:1 to continued treatment and washout groups and followed for 1 year.¹⁰⁷ Although 0.05% atropine showed a slightly stronger rebound effect (−0.68 D, 0.33 mm) compared with 0.025% (−0.57 D, 0.29 mm) and 0.01% (−0.56 D, 0.29 mm) atropine in the washout group, 0.05% atropine still had the highest treatment benefit over 3 years of the trial. The LAMP authors concluded that “0.05% atropine remained the optimal concentration over three years in Chinese children.” 

In another randomized controlled trial, the LAMP authors investigated the efficacy of low-concentration atropine eye drops in delaying the onset of myopia.¹⁰⁸ In this 2-year trial, 474 nonmyopic children aged 4 to 9 years with cycloplegic spherical equivalent refractive error between +1.00 D and 0.00 D received nightly instillation of 0.05% atropine, 0.01% atropine, or placebo in both eyes for 2 years. Among the 353 children who completed the trial, the 2-year cumulative incidence of myopia was lowest with 0.05% atropine (28.4%) in comparison with 0.01% atropine (45.9%) and placebo (53.0%) groups. The incidence of myopia was reduced by 28.9% with the application of 0.05% atropine but not affected by the application of 0.01% atropine. These results suggest that daily administration of 0.05% atropine eye drops reduced myopia onset, but 0.01% atropine eye drops had no effect. Whether the protective benefit achieved with 0.05% atropine simply delays typical myopia progression to later years and reduces the final degree of myopia remains unknown.¹⁰⁹ Furthermore, other concentrations greater than 0.01% may also offer benefits. In a retrospective cohort study, nightly bedtime administration of 0.025% atropine eye drops reduced myopia incidence by 25% and myopic shift by −0.34 D over 1 year.¹¹⁰ 

Owing to its greatly diminished side effects and minimal rebound,^107,111 the efficacy of 0.01% atropine eye drops for myopia control continues to be an active area of investigation, and several other trials have since been published with consistent findings.^112–115 These trials, like ATOM and LAMP, include children of primarily Asian descent. Although it has been argued that race has a minimal effect on myopia treatment efficacy,¹¹⁶ several recent trials, including two in the United States, have evaluated the efficacy of low-concentration atropine eye drops in predominantly non-Asian populations.^{55,59,117–119} 

The Childhood Atropine for Myopia Progression (CHAMP) study remains the only 3-year placebo-controlled trial of low-concentration atropine eye drops to date. In this US study, 483 children of European descent aged 6 to 10 years were randomized to binocular nightly treatment with preservative-free 0.01% or 0.02% atropine or placebo eye drops. At the end of 3 years, average myopia progression was −1.04 D, −1.18 D, and −1.28 D in 0.02% atropine, 0.01% atropine, and placebo groups, respectively, with the corresponding 3-year axial elongation of 0.73 mm, 0.68 mm, and 0.81 mm and the corresponding responder proportion (proportion of participants’ eyes with less than 0.50 D myopia progression) of 22.1%, 28.5%, and 17.5%. The trial failed to meet its primary efficacy endpoint, which was the proportion of responders to 0.02% atropine at 36 months. Analysis of secondary efficacy endpoints showed a disconnect between axial and refractive outcomes. Over 3 years, while 0.02% atropine slowed axial elongation by 0.08 mm but did not affect myopia progression (0.02% vs. placebo: 0.10 D), 0.01% atropine slowed myopia progression by 0.24 D and axial elongation by 0.13 mm. Based on the 11% (95% confidence interval [CI], 3%–18.5%) difference in responder proportion between 0.01% atropine and placebo, the authors concluded that the treatment effect observed with 0.01% atropine was clinically meaningful. However, as pointed out recently,¹²⁰ this conclusion must be interpreted in the context where the primary efficacy endpoint was not met, and the treatment effects of 0.01% atropine appear similar to that observed for progressive addition lenses (PALs) in a US trial, Correction for Myopia Evaluation Trial (COMET), in which the authors concluded, “The small magnitude of the effect does not warrant a change in clinical practice” and “This difference is not clinically significant, suggesting that PALs should not be routinely prescribed for children with myopia as is common in some practices.”¹²¹ In the 3-year COMET study,¹²¹ the treatment effect was observed primarily in the first year, during which the difference in the proportion of participants requiring a prescription change (at least −0.50 D change in at least one eye, also defined as responder proportion in CHAMP) between PAL and single-vision lens groups was 16% (PAL: 43%, single-vision lens: 59%), which is higher than the difference in responder proportion for 0.01% atropine versus placebo (11%) in the CHAMP study. The magnitude of a clinically meaningful myopia control effect is debated.¹²² However, the observed efficacy of 0.01% atropine eye drops in slowing myopia progression in CHAMP is less than the 40% slowing indicated by the International Myopia Institute consensus paper and 30% slowing indicated by the FDA workshop as clinically meaningful effects.^123,124 

The lack of myopia control efficacy of 0.01% atropine eye drops was demonstrated in another recent National Institute of Health–funded US trial by the Pediatric Eye Disease Investigator Group. In this double-masked randomized controlled clinical trial, 187 myopic children aged 5 to 12 years were randomly assigned in a 2:1 ratio to preservative-free 0.01% atropine or placebo groups. After treatment for 2 years, average myopia progression was −0.82 D in the atropine group and −0.80 D in the placebo group, and the corresponding average axial elongation was 0.44 mm and 0.45 mm in the atropine and placebo groups, respectively. The authors concluded, “These results do not support the use of atropine, 0.01%, eye drops to slow myopia progression or axial elongation in US children.” After the treatment period of 2 years, the authors also evaluated the potential rebound effect by stopping the treatment at 24 months. Comparison of data from baseline to 24 months with data from baseline to 30 months showed little rebound effect, but whether it was a true effect or due to a short period of treatment cessation is unclear.¹²⁵ Moreover, considering there was no treatment effect in the first place, the lack of rebound effect seems to be an expected outcome. 

Results from overseas trials of predominantly non-Asian participants also appear consistent with these findings. In the Western Australia (WA)–ATOM trial where 153 myopic children aged 6 to 16 years were randomly assigned in a 2:1 ratio to 0.01% atropine and placebo groups, the 2-year difference in primary efficacy endpoints between atropine and placebo groups (−0.14 D for myopia progression and 0.04 mm for axial elongation) was not statistically significant, although the higher dropout rate in the placebo group may have affected the efficacy results.⁵⁹ This trial also evaluated the rebound effect of atropine treatment as children were followed for an additional year without treatment.¹²⁶ During this washout period, the atropine group showed a −0.13-D faster progression and a 0.07-mm greater axial elongation than the placebo group, resulting in no difference in 3-year myopia progression between the two groups. These results suggested a significant rebound effect after the withdrawal of 0.01% atropine, which contrasts with minimal rebound effects with 0.01% atropine observed in ATOM2,¹⁰³ LAMP,¹⁰⁷ and ATOM-J¹¹¹ trials, although the former two trials lacked a concurrent control to assess the rebound adequately, and the latter trial suffered from a high attrition rate during the washout period (∼68%). 

Another European trial with a similar design to WA-ATOM randomly assigned 250 myopic children in a 2:1 ratio into 0.01% atropine and placebo groups and found no change in myopia progression between the atropine and placebo groups (0.10 D) but a modest yet statistically significant difference in axial elongation (0.07 mm) between the two groups after 2 years of treatment.⁵⁹ Surprisingly, in this trial, treatment effects did not occur for nonwhite children and high COVID-19 impact groups (participants enrolled before the first COVID-19 lockdown) but were significant for low COVID-19 impact groups. This was stipulated as a potential factor affecting the efficacy results, although there appeared to be no lockdown effect on the placebo group, and average myopia progression and axial elongation were similar between the low and high COVID-19 impact placebo groups. Figure 1 shows the treatment effects of 0.01% atropine on myopia progression at 12, 24, and 36 months in randomized controlled trials. Figure 2 shows the corresponding treatment effects of 0.01% on axial elongation. The overall effect size for both myopia progression control (0.17 D at 12 months, 0.17 D at 24 months, and 0.24 D at 36 months) and axial length control (0.06 mm, 0.09 mm, and 0.13 mm, respectively) appears modest and clinically insignificant with remarkable consistency in effect size across the studies. Although the overall effect size at 36 months is marginally better, it is limited by data from only one study to date.⁵⁵ By statistical convention, when the effect size of an investigational treatment is small, it may manifest in some studies but not in others; however, this should not be regarded as inconsistency but rather a part of a continuum. 

Figure 1.

 

Forest plot showing absolute treatment effect size (treatment minus control) of 0.01% atropine eye drops for slowing myopia progression. Mean difference values to the right of the green line favor treatment, and those to the left of the green line favor control.

Figure 2.

 

Forest plot showing absolute treatment effect size (treatment minus control) of 0.01% atropine eye drops for slowing axial elongation. Mean difference values left of the green line favor treatment, and those to the right of the green line favor control.

Soft Dual-Focus or Multifocal Contact Lenses

Soft contact lenses with peripheral plus power have been shown to slow myopia progression and axial elongation in children. These lenses consist of a central zone that corrects myopia surrounded by regions of increased positive power in the periphery that induce simultaneous myopic retinal defocus. Several designs are available, although the dual-focus contact lens design (commercialized as MiSight lenses by CooperVision, Pleasanton, CA, USA) remains the only treatment approved for childhood myopia control by the FDA. The dual-focus lenses consist of multiple concentric treatment zones of +2.00 D relative power alternating with distance correction power surrounding a 3.36-mm central distance correction zone.⁶¹ Other effective designs for myopia treatments include increased positive power in multiple alternating concentric treatment⁶² or spherical zones^64,127 or by deliberate induction of positive spherical aberration.¹²⁸ These designs are used off-label for myopia treatment in children in the United States. 

The initial direct evidence that childhood myopia progression can be slowed by imposing blur at the retina was provided by a pioneering study by John Phillips.¹²⁹ In this small clinical study of 13 myopic children, deliberately undercorrecting the nondominant eye for 18 months while fully correcting the dominant eye reduced myopia progression by −0.36 D/year and axial elongation by 0.13 mm/year in the undercorrected eye. The resultant anisometropia returned to baseline levels when the undercorrected eyes were refitted in fully correcting single-vision spectacles. These results demonstrated for the first time that sustained myopic defocus slows myopia progression and axial elongation in human children, although the lack of a control group left the question of whether the treatment effect was due to slower progression in the undercorrected eye or faster progression in the fully corrected eye unanswered.¹³⁰ 

In 2011, Anstice and Phillips⁶⁰ tested the myopia control efficacy of dual-focus soft contact lenses in a randomized, paired-eye control, investigator-masked clinical trial. In this crossover trial, 40 myopic children aged 11 to 14 years wore a dual-focus lens on one randomly assigned eye and a single-vision distance lens as a control on the other eye for 10 months, after which lenses were switched between the eyes. Children were followed for another 10 months. Single-vision soft contact lenses are suitable as a control because they do not affect myopia progression.¹³¹ In the first treatment period, average myopia progression and axial elongation in the dual-focus lens (−0.44 D, 0.11 mm) were slower than those in the single-vision lens (−0.69 D, 0.22 mm), producing a treatment effect of 0.25 D and 0.11 mm. In the second treatment period (i.e., after lens switching), the treated eyes had a slowing of myopia progression and axial elongation of similar amounts to the first period (0.20 D, 0.12 mm), showing little influence of prior treatment and age on the treatment effect of dual-focus lenses. At the end of the study, the crossover study design eliminated anisometropia induced by monocular treatment at the end of the first treatment period. 

In 2014, another dual-focus lens design, the Defocus Incorporated Soft Contact (DISC) lens, was tested by Lam et al.⁶² on 221 Hong Kong Chinese children aged 8 to 13 years. The DISC lens was similar in design to the dual-focus lenses tested by Anstice and Phillips,⁶⁰ except that the peripheral concentric treatment zones incorporated an increased plus power of 2.50 D. In a 2-year randomized clinical trial, participants were randomly assigned to wear either a DISC lens or a single-vision soft contact lens for 2 years. On average, children wearing the DISC lens showed slower myopia progression by 0.10 D/year and axial elongation by 0.06 mm/year, and the treatment effect was greater with increased lens wearing time. Although these results demonstrated the myopia control efficacy of the DISC lens, only 58% of the enrolled children completed the trial. 

In a 3-year, double-masked, multisite randomized clinical trial (also known as MiSight trial), Chamberlain et al.¹³² tested the efficacy of a dual-focus soft contact lens of the same design as used by Anstice and Phillips⁶⁰ in their study. In total, 144 myopic children aged 8 to 12 years wore dual-focus or single-vision soft contact lenses full-time daily for 3 years. Among the 53 test and 56 control participants who completed phase I of the study, mean 3-year myopia progression and axial elongation in the dual-focus lens group (−0.65 D, 0.34 mm) were slower than those in the single-vision lens group (−1.31 D, 0.62 mm), showing a treatment effect of 0.67 D and 0.28 mm over 3 years. These progression rates in control and treated eyes appeared similar to those predicted using virtual cohorts built with data from two large cohort studies, namely, the Orinda Longitudinal Study of Myopia (OLSM) and the Singapore Cohort Study of the Risk Factors for Myopia (SCORM), suggesting that eye growth in myopic eyes treated with MiSight lenses were closer to the physiological levels of eye growth in emmetropic children. Based on these impressive efficacy results, the FDA approved the MiSight lens for the treatment of myopia in children ages 8 to 12 years. The efficacy of MiSight lenses was tested separately in the MiSight Assessment Study Spain (MASS) trial of 41 children who wore the MiSight lenses and 33 who wore single-vision spectacle lenses.¹³³ This study found a similar treatment effect over 2 years (0.29 D), although the axial length control efficacy (0.16 mm) was lower than that observed during 2 years of treatment (0.22 mm) in Chamberlain et al.¹³² The MiSight lens trial was extended to 6 years, and all participants were treated with MiSight lenses for 3 additional years (second phase). Results showed a continued long-term myopia control benefit of the MiSight lenses with similar treatment effects in the MiSight lens-treated children between phase I and phase II and no influence of prior treatment on efficacy with similar treatment effects between previously treated and untreated children during phase II.¹³⁴ In the seventh year of the MiSight trial, children wore single-vision soft contact lenses for a year. The average 1-year axial elongation in children with 3 and 6 years of prior treatment was 0.09 and 0.10 mm, respectively.¹³⁵ Based on myopic eye growth models, these rates are comparable to the age-appropriate normative values for children ages 14 to 18 years,¹³⁶ suggesting retainment of treatment benefits and no evidence of rebound effect. The MiSight trial remains the longest continuously running myopia control study. 

In a 2-year, five-arm randomized clinical trial, Sankaridurg et al.¹²⁷ tested the efficacy of four soft contact lenses, two designed to reduce central and peripheral defocus and the other two designed to incorporate higher-order aberrations to modulate retinal image quality and provide extended depth of focus. In the control group of children wearing single-vision soft contact lenses, mean 2-year myopia progression was −1.12 D, and axial elongation was 0.58 mm. By contrast, treatment groups showed myopia progression ranging from −0.78 D to −0.87 D and axial elongation from 0.41 to 0.46 mm on average, providing evidence for myopia control effects with all tested lenses. One of the two extended depth of focus contact lenses is now European Conformity (CE) marked and available on the market as the Mark'envoy MYLO lens (Madrid, Spain). 

Two US studies have evaluated the myopia control efficacy of distance-centered bifocal and multifocal soft contact lenses designed for presbyopia correction. The Control Of Nearsightedness–TRial Of Lenses (CONTROL) study randomized myopic children to multiring bifocal and single-vision soft contact lens groups.⁶³ After 1 year of treatment, children wearing bifocal lenses progressed significantly slower (−0.22 D and 0.05 mm) than those wearing single-vision lenses (−0.79 D and 0.24 mm), resulting in −0.57 D and 0.19 mm slowing of myopia progression and axial elongation, respectively. It is unclear whether these impressive treatment effects were due to the inclusion of participants with only eso fixation disparity and a history of rapid myopia progression (at least −0.50 D from last examination) and/or adjustment of bifocal adds on an individual basis to neutralize the associated phoria. 

More recently, the Bifocal Lens in Nearsighted Kids (BLINK) trial investigated whether distance-centered multifocal lenses slow myopia progression in children. In this double-masked, multicenter, randomized clinical trial, 294 children aged 7 to 11 years were randomized to wear high-add (+2.50) multifocal, medium-add (+1.50) multifocal, or single-vision contact lenses. After treatment for 3 years, adjusted mean myopia progression was −0.60 D for high-add multifocal lenses, −0.89 D for medium-add multifocal lenses, and −1.05 D for single-vision lenses. The corresponding 3-year mean axial elongation in high-add, medium-add, and single-vision lenses was 0.42 mm, 0.58 mm, and 0.66 mm, respectively. Children wearing high-add power multifocal lenses demonstrated a treatment effect of 0.46 D and 0.23 mm after 3 years of treatment. However, the difference in myopia progression between medium-add multifocal lenses and single-vision lenses was not significant, consistent with the observation from a previous study of low-add power contact lenses.¹³⁷ The observed efficacy may have been affected by slower progression of the control group (−1.05 D over 3 years) compared with the control cohorts of other US myopia control studies (range, −1.10 to −2.19 D).^{121,131,138,139} Nevertheless, the BLINK trial results suggest that wearing distance-centered multifocal soft contact lenses can slow myopia progression in children, although an add power greater than 1.50 D seems necessary to achieve treatment benefits. 

Several other randomized or nonrandomized studies have shown consistent efficacy of soft contact lenses with increased peripheral plus power in reducing axial elongation and myopia progression.^140–143 However, inconsistencies exist, as some soft contact lens designs have been shown to offer little control over myopia progression.¹⁴⁴ 

Orthokeratology Lenses

Orthokeratology lenses are rigid gas-permeable lenses with significantly flatter base curves than the corneal curvature. Overnight wear of these lenses with a flatter central optic zone than the adjacent reverse curve, also known as reverse geometry design, temporarily corrects myopia, giving optimal uncorrected vision for most of the day.¹⁴⁵ Because these lenses are designed to correct refractive error, axial length is the preferred metric to evaluate myopia control efficacy. In the United States, these lenses are used as an off-label treatment for slowing myopia progression in children. However, some designs (e.g., Menicon Bloom [Menicon, Nagoya, Japan]; Paragon [CooperVision]) are available in European markets as CE-marked treatments for myopia control. 

At the turn of the 21st century, the potential of using orthokeratology as a method of myopia control generated some interest.^146,147 In 2005, Cho et al.¹⁴⁸ published the first prospective study on the myopia control efficacy of these lenses in Hong Kong Chinese children, showing a significant difference in axial elongation between 35 participants fitted with orthokeratology lenses and a historical control group of 35 single-vision spectacle lens wearers (0.29 vs. 0.54 mm over 2 years). These results were confirmed later in a US study, Corneal Reshaping and Yearly Observation of Nearsightedness (CRAYON). This nonrandomized study found a 0.16-mm slowing of axial elongation in 28 children aged 8 to 11 years who were treated with orthokeratology lenses for 2 years compared with a historical control group of 28 children wearing soft contact lenses.¹⁴⁹ 

The first randomized clinical trial of orthokeratology lenses for myopia control was published in 2012.⁶⁵ In their 2-year study, Retardation of Myopia In Orthokeratology (ROMIO), Cho et al.⁶⁵ randomized 102 Hong Kong Chinese children to orthokeratology lenses or single-vision spectacle lenses and found a 0.27-mm difference in axial elongation between the groups after 2 years of treatment among 78 children who completed the study. To evaluate the myopia control efficacy of these lenses in children with high myopia (−5.00 D or more), the same authors assigned 52 high myopic children to partial treatment with orthokeratology (4 D) along with spectacle lens treatment of residual myopia (n = 26) or spectacle lens treatment alone (n = 26). Although the trial suffered from a high dropout rate (>50% in the treated group), comparisons of 2-year changes from baseline measures at 1 month among the 12 treated and 16 control participants completing the study found a significantly slower axial elongation (0.19 vs. 0.51 mm) and progression of residual myopia (0.13 vs. 1.00 D). In another 2-year single-masked (investigator-masked) trial, Orthokeratology Lenses with Increased Compression factor (OKIC),¹⁵⁰ treatment with an orthokeratology lens with 1.00 D flatter base curve (increased compression factor) produced a 0.20-mm greater slowing of axial elongation than the conventional orthokeratology lens, although again, the attrition rate in the control group was significantly high (68%) due to concerns over potential myopia progression. These efficacy results of orthokeratology lenses were confirmed in a 2-year randomized clinical trial by a different group that found a 0.23-mm reduction of axial elongation in 43 Hong Kong Chinese children treated with orthokeratology lenses compared with 28 untreated children wearing single-vision spectacle lenses. 

The foregoing trials were conducted primarily in children of Asian descent, leaving uncertainty about the effectiveness of orthokeratology lenses in other populations. However, there is some evidence of the efficacy of orthokeratology lenses in controlling myopia in children of European descent. In a 2-year trial of Danish children, the Clinical study Of Near-sightedness, TReatment with Orthokeratology Lenses (CONTROL) study found a 0.24-mm greater slowing of axial elongation between 19 children assigned to the orthokeratology lens group and 28 children in the single-vision spectacle lens group over 18 months.¹⁵¹ 

Several other reports have provided compelling evidence on the efficacy of orthokeratology lenses in slowing axial elongation in myopic children.^152–155 There are also long-term reports of continued efficacy greater than a 0.40-mm reduction in axial elongation over 5 to 10 years.^156–158 Meta-analyses show a remarkably consistent treatment effect of orthokeratology lenses across studies with an overall effect size of 0.26 to 0.27 mm (95% CI, 0.20–0.35 mm) over 2 years.^159–161 

There is limited evidence regarding the rebound effect following orthokeratology lens treatment. The Discontinuation of Orthokeratology on Eyeball Elongation (DOEE) study found a significant increase in axial elongation over 7 months when children who discontinued orthokeratology lens wear after treatment for 2 years were compared with children who wore spectacle lenses or continued to wear orthokeratology lenses during the same period.¹⁶² Surprisingly, this rebound effect was eliminated upon resuming treatment, and despite the cessation of treatment for 7 months, both the continued and discontinued lens wear groups appeared to have similar efficacy in the end. However, the lack of randomization of participants into different groups in this study meant that most children discontinuing the treatment were likely fast progressors and merely regressing to the mean after stopping the treatment. 

Another contralateral-eye crossover study fitted participants with an orthokeratology lens on one eye and a rigid gas-permeable lens on the other eye for 6 months before switching treatment between the eyes for another 6 months.¹⁶³ Axial elongation in the gas-permeable lens-wearing eye in the second 6-month period was approximately double the elongation found in the first 6 months when these eyes wore orthokeratology lenses, indicative of a strong rebound effect upon discontinuation of orthokeratology lens wear. Surprisingly, rigid gas-permeable lens-wearing eyes showed little myopia progression in this study despite its proven lack of efficacy in slowing myopia progression.¹³⁸ Collectively, data suggest a possible rebound effect upon cessation of treatment with orthokeratology lenses, but further studies seem necessary to assess this possibility. 

Combination Treatments

The availability of multiple treatment options for childhood myopia has opened the possibility of combining these approaches to enhance treatment efficacy. In the United States, switching between treatments and using combination therapy off-label is common in practice, particularly for children not responding to a single treatment and those of younger ages who are at risk of faster progression. However, some have cautioned against switching treatments for fast progressors or nonresponders, considering the lack of evidence on the effectiveness of switching treatments and the challenges in adequately identifying true nonresponders to any myopia treatment.^164,165 

Several studies using noninferiority designs have tested the efficacy of combining atropine eye drops with orthokeratology lenses and shown superior myopia control efficacy with combination therapy. In a randomized clinical trial, Kinoshita et al.¹⁶⁶ assigned 80 Japanese children aged 8 to 12 years to receive a combination therapy with 0.01% atropine and orthokeratology or monotherapy with orthokeratology for 2 years. Among the 73 participants who completed the study, axial elongation was slower in children receiving the combination therapy (0.29 mm) compared with children receiving the monotherapy (0.40 mm). The addition of 0.01% atropine to orthokeratology increased the axial length control efficacy of orthokeratology lenses by 0.11 mm over 2 years, although the enhancement in efficacy with combination therapy occurred entirely during the first 6 months of treatment with no accrual of benefit thereafter.¹⁶⁷ 

A similar additive effect of 0.01% atropine and orthokeratology lenses was reported by Tan et al.,¹⁶⁸ who found that Chinese children aged 6 to 11 years treated with the combination therapy progressed more slowly by 0.09 mm than those treated with monotherapy. Consistent with the aforementioned trial,¹⁶⁶ the additive benefit only occurred in the first 6 months. When the trial was extended to 2 years, some accrual of treatment benefit occurred as the average 2-year axial elongation in the combination therapy group was slower by 0.18 mm than in the monotherapy group.¹⁶⁹ The additive effect was observed for children with both low or moderate initial myopia, unlike the study in Japanese children.¹⁶⁶ The observed axial elongation for the orthokeratology group in this trial was similar to previous reports of orthokeratology treatment efficacy,^65,154,155 suggesting that the control group characteristics did not affect the efficacy results. 

The superior efficacy of 0.01% atropine combined with orthokeratology was also reported in a study by Yu et al.,¹⁷⁰ who included 60 Chinese children aged 8 to 12 years and found a 0.10-mm slower axial elongation with the combination therapy relative to the monotherapy group. Consistent with other trials, the additive treatment effect was only observed in the initial 4 months.¹⁷⁰ Other recent studies have further demonstrated an improvement in myopia control efficacy when 0.01% atropine was combined with orthokeratology lenses,^171–173 although adding 0.01% atropine to orthokeratology did not seem to provide any better efficacy in participants responding poorly to orthokeratology treatment in one study.¹⁷⁴ 

Contrary to the improved myopia control efficacy with the combination treatment of 0.01% atropine and orthokeratology, adding 0.01% atropine to distance-centered soft multifocal contact lenses appears to produce no enhancement in myopia control efficacy. In the Bifocal & Atropine in Myopia (BAM) study, Jones et al.¹⁷⁵ compared outcomes between 46 children who wore +2.50 add soft multifocal contact lenses and received nightly instillation of 0.01% atropine and 46 age-matched children from the BLINK study who wore +2.50 add multifocal lenses alone. The differences in average 3-year myopia progression (0.03 D) and axial elongation (0.08 mm) between the two groups were small and not statistically significant, suggesting no effect of combination therapy over monotherapy. Similar results were reported by Erdinest et al.,¹⁷⁶ who found no benefit in adding 0.01% atropine to dual-focus contact lenses. It remains unclear why 0.01% atropine improves the efficacy of orthokeratology lenses but not the efficacy of dual-focus or multifocal lenses, although differences in the mechanism by which these optical interventions, including the role of pupil size, could be a contributing factor.^169,173 The possibility of enhancing the efficacy of optical myopia control treatments by adding atropine eye drops in concentrations greater than 0.01% requires further investigation. 

Time Outdoors

Interest in time outdoors as a potential intervention for myopia emerged following evidence of a reciprocal relationship between time spent outdoors as a modifiable risk factor for myopia development in population-based observational studies.^52,177–183 For example, findings from the cross-sectional Sydney Myopia Study (SMS)¹⁷⁸ and its longitudinal extension, the Sydney Adolescent and Vascular Eye Study (SAVES),¹⁸⁴ revealed that children who spent more time outdoors had significantly reduced odds of becoming myopic, regardless of their near-work levels.^178,184 While these observational studies were fundamental in establishing the association between time outdoors and myopia, they were susceptible to bias (e.g., confounding), inherently limited to attribute causation, and provided weak evidence for making public health recommendations. 

More recently, school-based cluster-randomized trials of time outdoors as a potential intervention have provided direct, robust evidence for the protective effects of increased time outdoors against myopia development in children. In a school-based interventional study of children aged 7 to 11 years, 333 students from one school participated in a Recess Outside Classroom (ROC) program that encouraged students to spend 80 minutes per day outdoors.¹⁸⁵ A comparative group of 238 students from another school was included as the control group, and time spent outdoors was quantified using parent questionnaires. After 1 year, the intervention group showed a 9.24% decrease in myopic incidence (8.4% vs. 17.7%) and a 0.13-D reduction in myopic shift (−0.25 vs. −0.38 D) compared to the control group. Surprisingly, increased time outdoors had a protective effect only in children who were not yet myopic. In the follow-up multiarea, cluster-randomized trial, ROCT711, of 930 schoolchildren from 24 schools, students in the intervention group were encouraged to spend up to 11 hours of additional recess time weekly.¹⁸⁶ Myopia incidence in the intervention group decreased by 14.5% compared to the control group. Additionally, the intervention group showed a 0.12 D reduction in myopic shift (−0.35 vs. −0.47 D) and a 0.05-mm slower axial elongation (0.28 vs. 0.33 mm) over 1 year. Unlike the previous ROC study,¹⁸⁵ this trial included younger participants (6–7 years), employed light meters to measure time outdoors, and demonstrated that increased time outdoors also offers protective benefits for children with myopia by slowing myopia progression and axial elongation. 

In another cluster-randomized trial, He et al.¹⁸⁷ evaluated the efficacy of 40 minutes of additional daily outdoor activity in preventing myopia onset in children aged 6 to 9 years. Time spent outdoors was measured using questionnaires on children's daily activity. Over 3 years, the intervention group exhibited a 9.1% absolute reduction in myopia incidence (30.4% vs. 39.5%) and a 0.17-D smaller myopic shift (−1.42 vs. −1.59 D) compared to the control group. However, the difference in axial elongation between the two groups (0.95 vs. 0.98 mm) was not statistically significant. Likely, the trial was not adequately powered to detect these effects, as the sample size was estimated using a priori of a 50% reduction in myopia incidence over 3 years. Another randomized controlled trial, the Sujiatun Eye Care Study, tested the effect of incorporating two additional 20-minute outdoor recess periods every school day.¹⁸⁸ After 1 year, myopia incidence was lower by 4.8% (3.7% vs. 8.5%), and myopic shift was reduced by 0.17 D (−0.10 vs. −0.27 D). Despite using questionnaires to measure time outdoors as in the previous study,¹⁸⁷ this study found contrasting effects on eye growth, as axial elongation was slower by 0.05 mm (0.16 vs. 0.21 mm) in the intervention group relative to the control group. 

Consistent results were found in another cluster-randomized trial, Shanghai Time Outside to Reduce Myopia (STORM),¹⁸⁹ which employed a wrist-worn device to measure outdoor time objectively. Compared to the control group of children who spent habitual time outdoors, the 2-year adjusted incidence of myopia was 16% lower in children who spent 40 minutes of additional time outdoors and 11% lower in those who spent 80 minutes. Additionally, myopic shift was reduced by 0.20 D in the 40-minute group and by 0.13 D in the 80-minute group over 2 years. The corresponding 2-year reduction in axial elongation was 0.10 mm and 0.08 mm, respectively. The observed effect size in this study was lower than the estimated effect size of a 33% reduction in incident myopia used for sample size calculations. 

There is preliminary evidence that similar protective effects of time outdoors could also be achieved by modest increases in light intensity in an indoor environment. In a prospective, school-based intervention study of 317 children aged 6 to 14 years, Hua et al.¹⁹⁰ increased ambient classroom light levels to an average desk illuminance of 558 lux in the intervention schools compared to 98 lux in the control schools. After 1 year of intervention, nonmyopic children in the intervention group exhibited a significantly smaller myopic shift (−0.25 vs. −0.47 D) and slower axial elongation (0.13 vs. 0.18 mm) compared to the control group. Among myopic children, axial elongation was significantly slower in the intervention group (0.20 vs. 0.27 mm), although refractive error changes were not different (−0.25 vs. −0.31 D). Additionally, the incidence of new-onset myopia was lower in the intervention group (4% vs. 10%). 

In summary, school-based interventional trials of time outdoors provide compelling evidence that spending more time outdoors is protective against myopia development in children. Whether the protective effect of increased time outdoors in children also extends to those who are already myopic is equivocal. Meta-analyses of studies have shown little or no effect of increased time outdoors on slowing myopia progression in children with myopia.^53,54,191 Findings from interventional trials have also been mixed, with some finding a beneficial effect of increased time outdoors in slowing myopia progression,^186,190 yet others showing no effect.¹⁸⁵ The limited efficacy of increased time outdoors in slowing myopia progression could be related to behavioral factors, such as myopic children spending less time outdoors^180,192 or the emmetropization mechanism's inefficiency in responding to environmental visual cues in myopic eyes.^193,194 Further clinical trials with objective measurement of time outdoors seem necessary to resolve the inconsistency regarding the protective effects of time outdoors on myopia onset and progression. 

Spectacle Lenses

Traditional spectacle lens management strategies such as undercorrection,^195–197 overcorrection,¹⁹⁸ and part-time wear¹⁹⁹ are ineffective in slowing myopia progression in children. In a paired-eye study, monovision induced by fully correcting the dominant eye and undercorrecting the fellow nondominant eye, maintaining a constant anisometropia of ≤2.00 D, slowed the rate of myopia progression in the undercorrected eye by 0.36 D/year.¹²⁹ However, this benefit required sustained monocular myopic defocus in the undercorrected nondominant eye at all accommodation levels, as children accommodated to read with the dominant eye. Other randomized controlled trials with binocular lens wear have found that undercorrection does not slow myopia progression^195,196; instead, it may even accelerate the progression.¹⁹⁷ Overcorrection does not seem to offer any myopia control benefit either. In a randomized controlled trial of 3- to 10-year-old children with intermittent exotropia, children wearing over-minused spectacle lenses progressed faster by 0.37 D than those wearing full-correction spectacle lenses (−0.42 vs. −0.04 D).¹⁹⁸ 

Spectacle lens options for the treatment of childhood myopia in the United States are limited to PALs and executive bifocals. However, evidence regarding their myopia control efficacy is far from convincing.⁸⁰ In a small-scale study, Leung and Brown²⁰⁰ randomly allocated Chinese schoolchildren aged 9 to 12 years to wear PALs with +1.50 D add (n = 22), PALs with +2.00 D add (n = 14), or single-vision lenses (n = 32). After 2 years, average myopic progression was −1.23 D in the single-vision group, −0.76 D in the +1.50 D group, and −0.66 D in the +2.00 D group. Although these results suggested that wearing PALs, particularly with a +2.00 D addition, reduced myopia progression, the lack of randomization and small sample size limited the generalizability of the findings and strength of evidence. Other randomized controlled trials of PALs have demonstrated limited or no efficacy in slowing myopia progression. For instance, one study involving 86 children aged 6 to 12 years reported a small treatment effect of a 0.17-D slower progression over 18 months,²⁰¹ while another found no significant difference in myopia progression and axial elongation between groups of children wearing PALs and single-vision lenses,²⁰² although the latter trial suffered from a high dropout rate (12%–17%). 

In the US-based multicenter COMET study, 469 participants aged 6 to 11 years with −1.25 to −4.50 D of myopia were randomized to wearing PALs with a +2.00-D add or single-vision lenses.¹²¹ The 3-year retention rate was excellent at 98.5%. After 3 years of treatment, children wearing PALs showed myopia progression of −1.28 D and axial elongation of 0.64 mm. The corresponding values in children wearing single-vision lenses were −1.48 D and 0.75 mm, respectively. Although the between-group differences were statistically significant, the treatment effect was modest (0.20 D in myopia progression and 0.11 mm in axial elongation over 3 years), leading the authors to conclude that “the small magnitude of the effect did not warrant a change in clinical practice” and that “PALs should not be routinely prescribed for children with myopia.” The modest myopia control benefit of PALs occurred in the first year, and by the end of 5 years, the effect was reduced to 0.13 D.²⁰³ In a subgroup analysis of the original COMET study, children with reduced accommodative response (<2.56 D at 33 cm) and near-point esophoria were found to have a more substantial treatment benefit of 0.49 ± 0.24 D over 5 years.²⁰³ Based on these findings, the authors conducted COMET2, limiting enrollment to children with esophoria and accommodative lag.¹³⁹ However, the treatment effect of PALs in COMET2 (0.28 D slowing of myopia progression over 3 years) was again modest, comparable to the original COMET study, and deemed clinically insignificant. Similar modest effects were observed in another randomized controlled trial of children with near-point esophoria.²⁰⁴ Over 18 months, children wearing +1.50-D flat-top segment bifocal lenses showed a 0.25-D slower myopia progression than those wearing single-vision lenses. 

The myopia control efficacy of executive bifocal spectacle lenses remains controversial due to mixed results across clinical trials. A 3-year randomized controlled trial by Grosvenor et al.²⁰⁵ randomized 207 children aged 6 to 15 years to single-vision lenses, executive bifocals with +1.00 D add, or executive bifocals with +2.00 D add. The average myopia progression was −0.34 D/year in the single-vision lens group, −0.36 D/year in the +1.00 add bifocal group, and −0.34 D/year in the +2.00 D/year group, suggesting no effect of these lenses on myopia progression. Consistent results were found in another randomized controlled trial in which 237 myopic children aged 9 to 11 years were randomized to full correction for continuous use, full correction for distant vision use, or +1.75 D bifocal lenses.²⁰⁶ Over 3 years, average myopia progression in the bifocal lens group (−1.22 D) was not significantly different from continuous use (−1.06 D) or distant use (−1.29 D) groups. Contrary to these findings, the 3-year trial by Cheng et al.²⁰⁷ showed myopia control benefits of executive bifocals. In this study, 135 Chinese Canadian children aged 8 to 13 years were randomized to single-vision lenses, +1.50 D with executive bifocals, or +1.50 D with 3∆ base-in prisms. After 3 years, average myopia progression in the bifocal (−1.25 D) and prism bifocal (−1.01 D) groups was slower than that in the single-vision lens group (−2.06 D) with consistent effects on axial elongation (single vision: 0.82 mm, bifocal: 0.57 mm, prismatic bifocal: 0.54 mm). It is unclear why trials of executive bifocals with similar designs produced contrasting outcomes, although Cheng et al. included participants with at least −0.50 D myopia progression in the year before recruitment. 

Additional Treatments Available Outside the United States

Spectacle Lenses

Recent advancements in spectacle lens technologies have led to the development of several new lens designs for myopia control. While these designs have yet to be approved for treating childhood myopia in the United States, their use is becoming increasingly common globally, including in parts of Europe, Asia, and Oceania. This section discusses the evidence for the myopia control efficacy of these newer spectacle lens technologies, along with their designs and limitations (see Supplementary Table S1 for a summary of outcomes). The treatment effects of different spectacle lens options across various studies are compared in Figure 3 for myopia progression and Figure 4 for axial elongation. 

Figure 3.

 

Absolute treatment efficacy of spectacle lens designs in slowing myopia progression. Mean difference values left of the green line favor control, and those to the right of the green line favor treatment.

Figure 4.

 

Absolute treatment efficacy of spectacle lens designs in slowing axial elongation. Mean difference values left of the green line favor treatment, and those to the right of the green line favor control.

Defocus Incorporated Multiple Segments

Defocus Incorporated Multiple Segments (DIMS) lenses, marketed by Hoya Corporation (Tokyo, Japan) as MiYOSMART, are classified as Class 1 medical devices under the European Medical Device Regulation 2017/745 and CE marked for myopia control. These lenses feature a central optical zone of 9.00 mm diameter for distance correction, surrounded by a honeycomb-shaped array of ∼1 mm diameter lenslets that create +3.50 D of relative myopic defocus.⁶⁷ Spaces between the lenslets allow for single-vision correction. DIMS lenses are thought to be based on the simultaneous defocus theory,²⁰⁸ which posits that the concurrent presence of focused and defocused images on the retina modulates eye growth and myopia progression.⁶⁷ 

In a randomized controlled trial, Lam et al.⁶⁷ tested the efficacy of DIMS lenses in slowing myopia progression by randomly allocating 183 Chinese children aged 8 to 13 years to either DIMS lenses or single-vision lenses. Over 2 years, children wearing DIMS lenses exhibited a 0.44-D slower myopia progression (−0.41 vs. −0.85 D) and a 0.34-mm slower axial elongation (0.21 vs. 0.55 mm) than those wearing single-vision lenses. Importantly, 21.5% of DIMS lens wearers experienced no myopia progression (defined as the change in spherical equivalent refraction ≤0.5 D) compared to 7.4% in the single-vision lens group. The trial was extended to a third year, during which children wearing single-vision lenses were switched to DIMS lenses due to ethical reasons, which resulted in the loss of randomization and increased risks of confounding.²⁰⁹ Average myopia progression and axial elongation during the third year were not different between children who switched to DIMS lenses and those who continued to wear DIMS lenses. Additionally, the continuous DIMS lens wear group showed significantly less myopia progression (by 0.18 D) and axial elongation (by 0.08 mm) during the third year compared to a historical control group matched in age, sex, refractive error, and axial length, possibly indicating a sustained myopia control effect of the DIMS lenses over 3 years. The trial was extended to 6 years by nonrandomly dividing participants into four groups: those who wore DIMS lenses continuously (group 1, n = 36), those who switched from DIMS to single-vision lenses after 3.5 years (group 2, n = 14), those who switched from single-vision to DIMS lenses after 2 years (group 3, n = 22), and those who switched from single-vision to DIMS lenses after 2 years, wore DIMS lenses for 1.5 years, and then returned to single-vision lenses (group 4, n = 18).²¹⁰ During the last 2.5 years, myopia progression and axial elongation in the DIMS lens groups (groups 1 and 3) were significantly less than the single-vision lens groups (groups 2 and 4). This finding suggested a possible sustained myopia control effect of DIMS lenses, albeit with weakened evidence due to the loss of randomization, self-selection of treatments by the participants, and small sample size of the subgroups. 

Highly Aspheric Lenslet Targets

The highly aspheric lenslet targets (HALTs) are marketed by Essilor (Charenton-le-Pont, France) as the STELLEST lenses. These lenses feature a central optical zone of 9 mm for distance refractive correction surrounded by a concentric array of 11 rings, each containing 1021 contiguous aspherical lenslets of approximately 1 mm in diameter.²¹¹ In each ring, the lenslets share the same power, but the power varies across the rings. These powers are based on the modified Atchison eye model²¹² and adjusted for peripheral refraction data from Chinese participants.^213–215 Similar to DIMS lenses, HALT lenses have single-vision zones between the lenslets, but their varying power across the rings creates a three-dimensional volume of myopic defocus, which is thought to be a stop signal for eye growth. The HALT lenses are available for sale within the European Union (EU) single market and are compliant with EU regulations on medical devices (2017/745). Although these lenses are not yet approved by the FDA, they have been recognized as a breakthrough device, a designation provided to select medical devices to speed up development, review, and approval and provide timely access to patients and health care providers in the United States. 

The efficacy of HALT lenses in slowing myopia progression was first demonstrated in a double-masked, randomized controlled trial of 170 Chinese children aged 8 to 13 years who were randomized in a 1:1:1 ratio to one of the two HALT designs (highly aspheric lenses [HALs] or slightly aspheric lenslets [SALs]) or single-vision lenses.²¹¹ After 1 year, the HAL group showed significantly reduced myopia progression (−0.27 D) and axial elongation (0.13 mm) compared to the SAL group (−0.48 D and 0.25 mm, respectively) and the single-vision lens group (−0.81 D and 0.36 mm, respectively). The 1-year treatment effect of HAL lenses was 0.54 D on myopia progression and 0.23 mm on axial elongation. In the second year of the trial,⁶⁶ the treatment effects continued to accrue, with the HAL group demonstrating a 0.80-D slower myopia progression and a 0.35-mm slower axial elongation over 2 years. Children wearing HAL lenses full-time (≥12 hours/day) experienced significantly greater myopia control compared to part-time wearers, indicating a possible dose–response relationship. The trial was extended to the third year in which children wearing SAL and single-vision lenses were switched to HAL lenses for ethical reasons, giving rise to three HAL subgroups (continuous HAL lens wear, SAL to HAL lens wear, and single-vision to HAL lens wear). Comparisons were made to a new control group of children wearing single-vision lenses.²¹⁶ During the third year, all three HAL subgroups exhibited significantly slower myopia progression and axial elongation compared to the new control group, with no difference in outcomes between the HAL subgroups. These results indicated a potential sustained effect of HAL lenses and no effect of prior lens wear on its myopia control efficacy, although the loss of randomization in the extension study increased the risk of selection bias and confounding. 

A separate double-masked crossover randomized controlled trial further tested the myopia control efficacy of HAL lenses.²¹⁷ In this trial, 119 Vietnamese children aged 7 to 13 years were randomized to wear HAL lenses or single-vision lenses for 6 months, after which the groups switched treatments. During the first 6 months, axial elongation in the HAL lens group was 0.07 mm slower than in the single-vision lens group (0.06 vs. 0.13 mm), although the between-group difference in myopia progression (−0.20 vs. −0.27 D) was not significant. When treatments were switched, the HAL lens group again exhibited significantly reduced myopia progression (−0.05 vs. −0.33 D) and axial elongation (0.05 vs. 0.17 mm) compared to the single-vision lens group. Although this trial provided further evidence for the myopia control benefits of wearing HAL lenses, the shorter duration and the inherent limitation of a crossover trial (e.g., the effect of prior treatment during the crossover period) may have affected the observed treatment effects. 

Cylindrical Annular Refractive Elements

The cylindrical annular refractive element (CARE) lenses are marketed by Carl Zeiss (Oberkochen, Germany) as MyoCare. The initial prototype contained a 9.4-mm clear aperture that provided distance vision correction, surrounded by an annular array of microcylinders arranged in concentric circles.⁶⁸ These micro-cylinders, spaced 1.2 mm apart, add +8.00 D power to create higher-order aberrations, inducing phase retardation (shift in phase of different parts of the wavefront relative to one another) to impair peripheral retinal image quality and produce peripheral retinal defocus, which is thought to be a signal for slower eye growth.⁶⁸ 

Evidence for the myopia control efficacy of CARE lenses comes from a randomized clinical trial of 118 Chinese children aged 8 to 12 years who were randomly assigned to wear either CARE lenses or single-vision lenses.⁶⁸ After 1 year of treatment, average myopia progression was −0.56 D in children wearing CARE lenses and −0.71 D in those wearing single-vision lenses. The corresponding values for axial elongation were 0.27 mm and 0.35 mm, respectively. Although treatment with CARE lenses led to a modest reduction of 0.09 mm in axial elongation over 1 year, the difference in myopia progression between the groups (0.14 D) was not statistically significant, indicating that CARE lenses were ineffective in slowing myopia progression. Contrary to the HALT⁶⁶ and DIMS lenses,⁶⁷ the treatment effects of CARE lenses seemed to be greater in the second 6 months compared to the first 6 months of the trial, leading the authors to speculate that longer use of these lenses may yield stronger myopia control effects. It remains to be seen whether the 2-year results from this trial will support this speculation. Furthermore, a multiarm trial comparing different spectacle lens technologies is needed to determine which of these options provides the greatest treatment benefits. 

Diffusion Optics Technology

The diffusion optics technology (DOT) lenses, marketed by SightGlass Vision (Essilor and CooperVision), contain thousands of minuscule elements that are intended to scatter light and reduce retinal contrast.²¹⁸ These lenses have achieved CE marking for myopia control use in Europe and breakthrough device designation from the FDA. The DOT lenses feature a 5-mm central zone for distance vision correction surrounded by a treatment area with light-scattering microscopic diffusers, which are 0.14 mm in diameter and 0.2 mm in height, with a sharper radial curvature and a flat top. The base lens material has a refractive index of 1.53, while the translucent diffusers have a nominal index of 1.50. The DOT lenses were developed based on the link between high myopia and genetic mutations in the long- or middle-wavelength sensitive cones.^219,220 It was presumed that increased contract across neighboring cones produced by these mutations leads to myopia development, so deliberately reducing retinal contrast was thought to provide a signal to slow eye growth. However, this retinal contrast theory appears to contradict decades of research that have led to the traditionally accepted hyperopic defocus theory of myopia development.²²¹ 

The efficacy of DOT lenses in slowing myopia progression was tested in the Control of Myopia Using Peripheral Diffusion Lenses Efficacy and Safety Study (CYPRESS) randomized clinical trial conducted across 14 sites in North America. In this multicenter, double-masked trial, 256 children aged 6 to 10 years were randomized to wear either Test 1 lenses (known as DOT 0.2 commercially) with diffusers 0.365 mm apart, Test 2 lenses with denser diffusers spaced 0.240 mm apart, or single-vision control lenses. After 1 year of treatment, average myopia progression was −0.14 D with Test 1 lenses, −0.22 D with Test 2 lenses, and −0.54 D with single-vision lenses. The corresponding 1-year axial elongation was 0.15 mm, 0.20 mm, and 0.30 mm, respectively. The 1-year treatment effects for Test 1 lenses were 0.40 D for myopia progression and 0.15 mm for axial elongation. Despite the promising results in the first year, the myopia control effect did not seem to accrue thereafter, as the treatment effect of Test 1 lenses after 3 years (−0.33 D and 0.13 mm) was no greater than that observed after 1 year. The 1-year attrition rate (Test 1: 5.7%, control: 2.2%) in this trial was comparable to or better than other spectacle lens studies of similar duration (HAL, test: 3.6%, control: 5.5%; DIMS: test: 12.9%, control: 7.8%); however, the 3-year attrition rate (Test 1: 19%, control: 13%) was substantially higher (COMET: 2%¹²¹). 

The CYPRESS trial was extended to an additional year, where children in Test 2 lenses were switched to Test 1 lenses, while children in Test 1 and single-vision lens groups continued with their original assignments. During this extension period, the Test 1 lens group exhibited a 0.13-D slower myopia progression and a 0.05-mm slower axial elongation than the control group. Although these results suggested that treatment with DOT lenses was effective in slowing myopia progression, the treatment effects were modest and substantially smaller than those observed in the first year, likely due to slower physiological eye growth in older children who participated in the extension study.²²² The lack of treatment accrual during the second and third years of the trial was attributed to COVID-19–related lifestyle changes,²²³ although this would be expected to affect all arms of the trial and minimally influence the observed absolute effects. 

Myopic Peripheral Defocus Lenses

Myopic peripheral defocus lenses (MPDLs) are based on the principle of altering peripheral retinal signaling through an asymmetric peripheral myopic defocus.²²⁴ These lenses incorporate an ovoidal blur-free central distance vision area with a horizontal diameter of 7 mm surrounded by a peripheral treatment area with an asymmetric myopic defocus: +1.50 D at 25 mm nasally, +1.80 D at 25 mm temporally, and a +2.00 D myopic defocus inferiorly. This unique configuration is thought to slow eye growth by imposing controlled peripheral defocus patterns tailored to the eye’s anatomic and optical characteristics.²²⁴ 

The efficacy of MPDL lenses was evaluated in a double-blind randomized controlled trial of 83 Spanish children aged 5 to 12 years.²²⁴ After 1 year of treatment, average axial elongation was 0.16 mm in children wearing MPDL lenses and 0.24 mm in those wearing single-vision lenses. The 1-year axial length control treatment effect of MDPL lenses was 0.08 mm. Since refractive outcomes were not reported in this trial, it remains unclear whether treatment with MPDL lenses is effective in slowing myopia progression in children. Hence, the authors suggest that the asymmetric myopic peripheral defocus created by MPDL lenses effectively slowed axial eye growth in myopic children. 

Peripheral Plus Spectacle Lenses

In 2010, Sankaridurg et al.²²⁵ investigated the myopia control efficacy of peripheral plus spectacle lenses (PPSLs) in Chinese children aged 6 to 12 years. Three lens designs were tested: (1) Type I lenses featured a 20-mm clear central aperture with a rotationally symmetrical design, a positive power ramp around the center, and a maximum relative peripheral power of +1.00 D at 25 cm from the axis; (2) Type II lenses had a smaller 14-mm clear aperture and a steeper positive power ramp than Type I, with a maximum relative peripheral power of +2.00 D at 25 cm from the axis; and (3) Type III lenses were asymmetrical, with the clear central aperture extending 10 mm horizontally and inferiorly to aid convergence in down-gaze. These lenses eliminated horizontal meridian astigmatism and increased peripheral power by 1.90 D at 25 mm from the axis. 

The trial found no difference in myopia progression between the test groups compared to the single-vision lens group, although some benefit was observed in 6- to 7-year-old participants with a family history of myopia (one or both parents) who were treated with Type III lenses. This lens was commercialized as MyoVision (Carl Zeiss). Subsequently, another randomized controlled trial tested the myopia control efficacy of MyoVision in 207 children aged 6 to 12 years with at least one myopic parent and found no difference in the rate of myopia progression between MyoVision (−1.43 D) or single-vision lens wearers (−1.39 D) over 2 years. 

Positively Aspherized Progressive Addition Lenses

Hasebe et al.²²⁶ investigated the efficacy of positively aspherized progressive addition lenses (PA-PALs) in slowing early-onset myopia progression. These lenses were designed to reduce two potential myopiagenic stimuli: accommodative lag during near work and hyperopic defocus in the peripheral retina when viewing through the distance portion of the lens. In a multicenter, multinational trial involving sites in China, Japan, and South Korea, 197 children aged 6 to 12 years were randomly allocated to wear single-vision lenses, PA-PALs with +1.00 D add, and PA-PALs with +1.5 D add. After 3 years, average myopia progression was −0.87 D in the +1.50 D add group and −1.15 D in the single-vision lens group, whereas the rate of myopia progression was not different between the +1.00 D and single-vision lens groups. Treatment with +1.50 D add PA-PALs produced a rather modest 3-year treatment effect of 0.28 D slower myopia progression, nearly all of which was observed in the first year (0.24 D). Moreover, no corresponding treatment effect on axial elongation was observed. 

Defocus Distributed Multipoint Lenses

The Defocus Distributed Multipoint (DDM) lenses (Shanghai Weixing Optical Co., Shanghai, China) contain a hexagonal optical central zone with a 5.77-mm side length surrounded by multiple focal zones with aspheric microlenses that are strategically arranged to produce a gradient increase in defocus, ranging from +3.00 D to +4.50 D across the visual field.²²⁷ The efficacy of DDM lenses in slowing myopia progression was tested in a multicenter, randomized controlled trial,²²⁷ which randomly assigned 168 Chinese children aged 6 to 13 years to wear either a DDM lens or a single-vision lens. After 1 year, average myopia progression in the DDM group (−0.47 D) was significantly slower than that in the single-vision lens group (−0.71). Consistent effects were observed for axial elongation (0.21 vs. 0.32 mm, respectively). Results showed that the treatment effect of the DDM lens was stronger for full-time wear (over 12 hours/day), boys, and younger children (6–9 years). The myopia control benefits of DDM lenses beyond 1 year and in ethnically diverse populations remain to be investigated. 

Shamir Myopia Control Lenses

The Shamir myopia control (SMC) lens is a novel spectacle lens design with a unique peripheral defocus profile.⁷⁴ Unlike traditional concentric defocus designs, the SMC lens uses a U-shaped defocus pattern applied to the back surface, manufactured with Shamir Free Form technology (Shamir Optical Industry Ltd., Upper Galilee, Israel). This design features a central vertical canal, 10 mm wide, that provides clear vision for distance correction. Surrounding this central zone is the peripheral power zone with gradual increases in power from +0.5 D to +3.00 D horizontally and from +1.00 D to +1.50 D inferiorly. This configuration is intended to minimize visual disruption and maintain ergonomic advantages, such as supporting natural posture and head movement.⁷⁴ 

The efficacy of SMC lenses in slowing myopia progression was tested in a double-masked randomized controlled trial of 126 Israeli children aged 6 to 13 years who were randomized to SMC or single-vision spectacle lens groups. The average 1-year axial elongation was 0.21 mm in the SMC lens group and 0.32 mm in the single-vision lens group, yielding a 0.11-mm treatment effect. No difference was found in the rate of myopia progression between SMC and single-vision lens groups. Post hoc analyses showed potential benefits of SMC lenses in children with two myopic parents who showed a treatment effect of a 0.36-D slower myopia progression. An independent trial of children with two myopic parents is necessary to confirm the myopia control benefits of SMC lenses in this specific population. Additionally, whether SMC lenses can slow myopia progression in the long term and in the non-Israeli population requires further investigation. 

Soft Contact Lenses—Extended Depth of Focus

Extended depth of focus (EDOF) soft contact lens provides an additional contact lens option for the treatment of childhood myopia outside the United States. Variants of these lenses are available in markets as MYLO monthly-replacement lenses (Mark'ennovy), SEED 1-day pure lenses (SEED, Tokyo, Japan), NaturalVue multifocal 1-day lenses (Visioneering Technologies, Alpharetta, GA, USA), and Bloom Day lenses (Menicon). Although none of these options are approved by the FDA for myopia control, MYLO lenses are CE-marked for myopia management. 

Evidence for the myopia control efficacy of EDOF lenses primarily comes from randomized clinical trials conducted outside the United States. In a five-arm, double-blind randomized controlled trial, Sankaridurg et al.¹²⁷ randomized 508 Chinese children aged 8 to 13 years to single-vision soft contact lens, two soft contact lens designs that imposed +1.00 D myopic defocus centrally and either +2.50 D or +1.50 D at a 3-mm semi-chord peripherally, and two EDOF soft contact lens designs that incorporated higher-order aberrations to modulate retinal image quality and offered EDOF up to +1.75 D and +2.50 D. The average 2-year myopia progression was −1.12 D in the single-vision lens group and −0.78 to −0.87 D in the four test lens groups. The corresponding values for axial elongation were 0.58 mm for the single-vision group and 0.41 to 0.46 mm for the test lens groups. Despite the positive results, the trial suffered from a high attrition rate (129/508, 25.4%), which precluded the intent-to-treat analysis and likely affected the outcomes. Nevertheless, the myopia control efficacy of EDOF lenses was further demonstrated in a randomized controlled trial from India. In this study, 104 children aged 7 to 15 years were randomly assigned in a 1:1 ratio to wear SEED EDOF Mid (+1.50 D) soft contact lenses or single-vision spectacle lenses. After 1 year of treatment, EDOF lenses slowed myopia progression by 0.28 D and axial elongation by 0.11 mm compared to the single-vision lenses. This study was limited in its design by the lack of investigator and participant masking and the inclusion of single-vision spectacle lenses as a control, raising the possibility of a high risk of bias, although the latter is less of a concern, as myopia progression is unlikely to be different between single-vision spectacle lens wear and single-vision soft contact lens wear.¹³¹ Findings from the ongoing multinational randomized controlled trial of NaturalVue lenses could offer additional insights into the effectiveness of EDOF lenses in slowing myopia progression in children.²²⁸ 

Repeated Low-Level Red Light Therapy

Repeated “laser” red light (also known as repeated low-level red light [RLRL]) is currently used as a treatment for childhood myopia in several countries, including China, the United Kingdom, Australia, and New Zealand. The RLRL device houses a semiconductor laser diode that emits a collimated beam of 650 ± 10 nm red light and provides continuous exposure while participants fixate on the light foveally without wearing any correction. The recommended treatment regimen is 3 minutes twice a day for 5 days a week, and the reported illumination level is approximately 1600 lux with a power of 0.29 mW for a 4-mm pupil,²²⁹ although other variants of the RLRL device exist with different parameters. Adopting this treatment regimen, several randomized clinical trials of Chinese children, including double-blind, multicenter studies, have demonstrated an impressive efficacy of RLRL therapy in controlling childhood myopia over 12 months.^229–238 A detailed discussion of the treatment efficacy across these studies is available elsewhere.²³⁹ 

In the largest randomized clinical trial of RLRL therapy to date, Jiang et al.²²⁹ randomized 264 children of Chinese descent aged 8 to 13 years to receive RLRL treatment with single-vision lens wear or single-vision lens wear only. The retention rate after 1 year was 93.2%. Among the 246 children who completed the study, adjusted 1-year myopia progression was −0.20 D in the RLRL group and −0.79 D in the single-vision lens group. The corresponding values for axial elongation were 0.13 mm and 0.38 mm for the RLRL and single-vision lens groups, respectively. The study found a −0.59-D reduction in myopia progression and a 0.26-mm slowing of axial elongation after 1 year of treatment and reported no severe adverse events (sudden vision loss ≥2 lines or scotoma), decreases of best corrected visual acuity, or retinal structural damage. 

Meta-analyses on RLRL studies over 6 to 12 months report an overall treatment effect size of 0.22 to 0.25 mm for axial length and −0.32 to −0.46 D for spherical equivalent refraction, with no serious adverse events related to the treatment other than photosensitivity during treatment and temporary posttreatment after images.^73,240,241 In addition to slowing the progression of myopia, RLRL therapy appears to be effective in preventing the onset of myopia in children. In a randomized clinical trial of premyopic children with risk factors for myopia development, there was a 54% reduction in myopia incidence after treatment with RLRL therapy for 12 months.²⁴² Collectively, the aforementioned studies suggest that RLRL therapy is a safe and effective treatment for childhood myopia. However, clinical trials to date are limited to 1 year, so long-term treatment safety and efficacy remain unknown. Moreover, there appears to be a strong rebound effect upon treatment discontinuation, with studies reporting axial elongation of 0.20 mm over 3 months²³² and 0.42 mm over 1 year²³⁵ after cessation of treatment. 

A case report of retinal damage in a 12-year-old patient after 5 months of RLRL therapy has raised significant concerns about the safety of RLRL treatment.²⁴³ The clinical trials of RLRL therapy generally lack a detailed description of the optical characteristics of the red-light device, including the energy levels on the retina. Although the light is reportedly “low level” based on a 1600 lux value, it has been noted that looking directly at a coherent laser light of a particular lux level is seemingly different from looking at a natural scene of the same ambient illumination.²³⁹ Published studies have generally classified the RLRL devices as either Class 1^229,244 or Class 2²⁴⁵ laser instruments, indicating no to minimal potential light health hazards according to ANSI classification, although Class 2 lasers are labeled safe only for unintentional exposure less than a one-fourth second and not meant for direct fixation.²⁴⁶ While no serious adverse effects have been reported in RLRL clinical trials, the safety evaluation has been generally limited to subjective feedback from users and objective assessment of visual acuity and choroidal thickness. Moreover, several studies have reported posttreatment axial length shortening, which exceeds what can be explained by changes in choroidal thickness alone,^244,245 possibly pointing to underlying nonphysiological factors (such as inflammation) contributing to the RLRL effects. A recent evaluation of two RLRL treatment devices (Sky-n1201a [Beijing Akihito Vision, Vision Technology Co. Ltd., Beijing, China] and Future Vision [Hunan Medical Technology Co. Ltd., Hunan, China])²⁴⁷ found that these devices reached or exceeded the maximum permissible exposure after 3 minutes of continuous viewing, increasing the potential risks of photochemical and thermal damage to the retina. Several groups have since urged caution regarding the use of RLRL treatment for myopia control in children until safety standards are confirmed.^239,248,249 

In summary, despite the myopia control effectiveness of RLRL treatment demonstrated in several randomized controlled trials, concerns remain over the safety, long-term efficacy, potential benefits in children of non-Chinese descent, and likelihood of rebound effects upon discontinuation of the treatment. Further investigations of RLRL therapy seem critical to determine whether the risks outweigh the potential benefits of RLRL therapy. An ongoing US trial of RLRL therapy may provide some answers.²⁵⁰ 

Overall Summary

Intensive research over the past two decades has led to the development of several treatment options for controlling myopia in children. These options include time outdoors; low-concentration atropine eye drops; dual-focus, multifocal, and orthokeratology contact lenses; specialized spectacle lenses; and RLRL therapy. The safety and efficacy of these treatment options have been established in rigorous randomized clinical trials. Some treatments, such as increased time outdoors, low-concentration atropine eye drops, and RLRL therapy, are also effective in preventing the onset of myopia in children. However, only one treatment has received approval from the FDA to date, and most others are used off-label. Current treatments are only partially effective and still allow significant progression. There is also uncertainty over the effectiveness of these treatments in preventing high myopia and myopia-related complications. Additionally, treatments aimed at managing “dry” myopic macular degeneration are severely lacking. Consideration by the FDA for approval of evidence-based myopia treatments according to the previous precedent and their rapid and widespread adoption is an urgent need in the United States. Efforts and resources targeted at developing more effective preventative and curative treatments for childhood myopia remain a priority. Identification of a myopic child early in life and prompt treatment with monotherapy or combination therapy may provide maximal benefits in terms of reducing the risk of sight-threatening ocular pathologies in later life and lessening the global public health burden of visual impairment and blindness due to myopia and myopia-related blinding complications. 

Acknowledgments

Supported by a grant from the NIH/NEI (R21EY036536 to SK). 

This article is a part of the commissioned paper, “Treatment of Childhood Myopia,” submitted by the authors to the study committee for the National Academies of Sciences, Engineering, and Medicine (NASEM) consensus study, “Focus on Myopia: Pathogenesis and Rising Incidence.” This consensus study was supported by the American Academy of Optometry; the American Optometric Association; the Health Care Alliance for Patient Safety; the Herbert Wertheim School of Optometry & Vision Science, University of California, Berkeley; Johnson & Johnson Vision; the National Eye Institute; Reality Labs Research; Research to Prevent Blindness; and the Warby Parker Impact Foundation. 

Disclosure: S. Khanal, Meta (F, R); E.S. Tomiyama, CooperVision (R); S.C. Harrington, Thea Pharmaceuticals (R), CooperVision (R)