Myopia is a common ocular condition associated with decreased uncorrected distance vision. Poor distance vision in myopes is related to uncorrected refractive error as well as more serious ophthalmologic complications. High myopia is associated with an increased risk of cataracts, glaucoma, retinal detachment, and myopic macular degeneration [1–4]. Holden et al. reported an increasing prevalence of myopia and high myopia globally, estimating at more than 4.7 billion and almost 1 billion people, respectively, by 2050. Researchers continue to investigate methods to reduce myopic progression in children in an effort to reduce its vision-threatening complications. This article reviews the literature from the last 18 months on environmental, optical, and pharmaceutical interventions for pediatric myopia control.
TIME SPENT OUTDOORS
Research has shown that increasing time spent outdoors correlates with a decreased prevalence of myopia . A 22-year longitudinal study by Parssinen and Kauppinen [7▪] sought to investigate factors associated with the development of high myopia [spherical equivalent ≤ −6.0 diopters] from childhood into adulthood. They found an inverse correlation between time spent outdoors and myopic progression in children but not adults. A limitation in this study is the use of a questionnaire in reporting time spent outdoors, which can lead to recall bias. Additionally, this was a longitudinal study rather than a randomized clinical trial and assessed association rather than causality.
Nevertheless, other studies using randomization and more quantifiable means of assessing outdoor time have reported similar results. Specifically, Wu et al. performed a multicenter randomized clinical trial in Taiwan to evaluate whether a school-based program mandating increased time outdoors would be effective at controlling myopic progression. This study utilized light meter recorders to quantify outdoor time and light intensity supplemented by questionnaire use. Wu et al. found that at least 11 h of outdoor exposure per week is effective in preventing myopic shift in baseline nonmyopes and slowing down myopia progression in baseline myopes as measured by refractive error and axial length elongation. In nonmyopes, there was a difference of 0.11 diopters in refractive error (P = 0.02) and 0.03 millimeters (mm) in axial length elongation (P = 0.02) between the intervention and control groups, and a difference of 0.23 diopters (P = 0.007) and 0.15 mm (P = 0.02) between the two groups in myopes. Despite the statistical significance of the findings in this study, the degree of difference between the control and intervention groups was quantitatively so small that they may not be clinically relevant.
Xiong et al. performed a systematic review and meta-analysis of existing literature on myopia and outdoor time. They found a statistically significant protective effect of outdoor time on incident and prevalent myopia. There was a dose-dependent response, with an increase in outdoor exposure reducing the risk of myopia onset but not myopic progression in preexisting myopes. The results of this meta-analysis should be assessed with caution as the authors report a high heterogeneity among the studies analyzed.
Researchers continue to evaluate the relationship between outdoor time and myopia in studies, such as STORM and K-YAMS, which are currently in progress [10▪,11]. Overall, research trends suggest that increased time spent outdoors may be protective against myopia onset. It may also slow down myopic progression in myopes, but likely not in a clinically significant manner. Therefore, spending time outdoors should be encouraged as an adjunctive treatment rather than a stand-alone intervention for myopic control.
Single vision spectacles and contact lenses are the first line treatment for refractive error, including myopia. Single vision lenses are intended to correct the refractive error and are not prescribed for myopia control [12,13].
One theory for myopic progression suggests that axial elongation is driven by peripheral retinal hyperopic defocus [14,15]. Even if axial refractive error is corrected, any hyperopic blur in the peripheral retina of a myope has been shown in animal studies to promote eye growth and axial elongation, leading to progressive myopia. These findings have led researchers to consider that minimizing peripheral hyperopic defocus or inducing peripheral myopic defocus with bifocal or progressive addition lenses (PAL) via spectacle or contact lens wear may help prevent myopic progression.
Kang et al. performed a recent review of studies comparing spherical equivalent change from baseline after treatment with single vision spectacles, PAL, and bifocal and prismatic bifocal lenses . Most of the studies evaluated report a statistically significant reduction in spherical equivalent progression with PAL and bifocal spectacles. The numerical values reported, however, are so small as to be of questionable clinical significance with the exception of certain population subgroups, such as young children with parental myopia or esophoria, and one nonrandomized, unmasked trial that showed a 50% improvement in myopic control with bifocals [12,16].
Kanda et al. performed a multicenter prospective, randomized, double-blinded, placebo-controlled study to evaluate MyoVision, a novel spectacle lens with an asymmetrically designed central area with inferior extension for full refractive correction and positive additional peripheral power to reduce peripheral hyperopia. Myopic children ages 6–12 years who had at least one parent with myopia were randomized to MyoVision or single vision spectacle correction. After 2 years, there was no statistical difference in spherical equivalent and axial elongation between the two groups. The authors suggest that the lack of statistical significance in this study may be because of ‘misalignment between the line of sight and the optical axis of the lens is more susceptible to eye movements in spectacles than in contact lenses.’ In other words, the correction of peripheral hyperopia in spectacles can be more difficult to achieve than in contact lenses because of the increased vertex distance.
Although convincing evidence for peripheral myopic defocus spectacles for myopia control is lacking, special design contact lenses may show greater promise. A review of clinical trials shows a range of 20–72% reduction in spherical equivalent and 27–79% slowing of axial length elongation for contact lenses that are designed to reduce peripheral hyperopic focus [13,16].
A recently published randomized trial from Spain looked at MiSight contact lenses compared to single vision spectacles for myopia control in children ages 8–12 years over a 2 year trial period [18▪]. MiSight lenses are designed with a large central area for distance vision correction surrounded by concentric rings of alternating distance and near powers. This study found that MiSight contact lenses provided a 39.3% reduction in myopic progression and 36% slower axial length elongation compared to controls.
Although more research needs to be done on this topic, contact lenses, rather than spectacles, designed for peripheral hyperopic defocus may show some promise for the future of myopia control.
Orthokeratology refers to the application of a rigid contact lens worn overnight to induce temporary changes in corneal curvature allowing for clear, unaided daytime vision. Although these lenses were designed for the correction of refractive error, studies have shown a secondary advantage of slowing myopic progression . Of note, most orthokeratology studies use axial length elongation as a surrogate measure for myopia progression instead of changes in spherical equivalent. Axial elongation is an important endpoint, as most sight-threatening complications of myopia are associated with excessive eyeball growth. Numerous studies have shown a 30–71% reduction in axial elongation for orthokeratology compared with control [13,16,19▪].
A commonly proposed mechanism of action for the myopic control effect of orthokeratology is the creation of peripheral myopic defocus because of corneal reshaping [12,20]. Diminished peripheral hyperopic blur and increased myopic defocus lead to a decreased stimulus for eye growth as previously discussed with bifocal and PAL lenses.
A recent study by Na et al. investigated myopic progression in orthokeratology wearers by utilizing a contralateral eye design. This was a 1-year retrospective study of children ages 7–13 years with myopic anisometropia who underwent orthokeratology treatment in their myopic eye and no correction in their emmetropic or near-emmetropic eye. The contralateral eye design was thought to minimize confounding factors. The researchers found a statistically significant reduction in axial length elongation in the orthokeratology eye (0.07 ± 0.21 mm, P = 0.038) as compared with the contralateral control eye (0.36 ± 0.23 mm, P < 0.001).
Typical orthokeratology lenses are spherical in design. However, newer orthokeratology lenses are being created to correct for astigmatism. A retrospective study by Zhang et al. evaluated effects of toric versus spherical design orthokeratology lenses on myopic progression in myopic children with moderate to high with-the-rule astigmatism (cylinder >1.5 diopters). They found a 55.6% slower rate of axial elongation in toric orthokeratology wearers than in the spherical intervention group. Of note, the brand of contact lenses used was different between the toric and spherical lenses.
Although evidence supports orthokeratology as effective in myopia control, other considerations need to be taken into account when deciding whether or not to pursue this intervention. The biggest concern with overnight contact lens wear is the risk of microbial keratitis. Infectious keratitis has been reported in orthokeratology wearers as case reports and case series [23,24]. A recent systemic review of clinical profiles of infectious keratitis related to orthokeratology use found that the majority of cases occurred in patients less than 18 years of age after 19.4 months of wear. The most common pathogens were Pseudomonas aeruginosa (36.4%), Acanthamoeba (32.4%), and coagulase-negative Staphylococcus spp. (6.9%) . Most clinical trials report a good safety profile of orthokeratology lenses, and adverse events are generally limited to eye irritation and redness [21,22,25]. The discrepancy between case reports and clinical trials may be because of selection bias. Clinical trial participants may be more compliant at baseline, receive better lens care and hygiene education, and have more frequent follow-up than in standard clinical practice. Also, study duration may be less than the average time of onset of infectious keratitis, and perhaps the lack of long-term follow-up in the orthokeratology studies leads to cases being missed.
Another consideration is the rebound effect noted after orthokeratology cessation. Discontinuations of lens wear has been associated with an increase in axial length elongation that was faster compared with controls and continuous orthokeratology wearers . Additional studies are needed to further investigate this rebound effect and the ideal duration of orthokeratology to obtain maximal myopic control.
Cheung et al.[19▪] suggest that the ideal candidates for orthokeratology are likely young children (around 6–9 years of age) with rapid myopic progression (increase in axial length of ≥0.20 mm/7 months or spherical equivalent of ≥1 diopter/year). They recommend an observational trial period to assess a patient's rate of myopic progression prior to offering orthokeratology as an intervention [19▪].
Atropine is a nonselective, antimuscarinic agent that has been extensively studied for its effect on myopia control. Initially used as an agent for myopia control because of its cycloplegic effect, atropine's mechanism of action is no longer well understood. There is some thought that atropine may work through local retinal/scleral signaling [12,16,26,27▪]. Atropine has been the most effective intervention employed for slowing down myopic progression with reduction rates ranging from 56 to 96% . According to a publication by the American Academy of Ophthalmology, there is evidence to suggest up to 1 diopter per year reduction in myopic progression with atropine treatment [27▪].
The landmark trials ATOM 1 and ATOM 2 paved the way for research into atropine treatment for myopic control [28,29]. Given the significant side effect profile of 1% atropine, including photophobia, reduced near vision, and allergy, and the rebound effect seen after 1% atropine discontinuation, research has moved towards low-dose atropine as a more suitable intervention for myopia control [26,30].
The LAMP study is a four-phase, randomized, double- blinded, placebo-controlled trial that is evaluating the efficacy and safety of low-dose atropine (0.05, 0.025, and 0.01%) versus placebo [31▪▪]. The results of the first phase of this study show that low-dose atropine decreases myopic progression and axial length elongation compared with placebo. There was a concentration-dependent response seen with a 67, 43, and 27% reduction in spherical equivalent and a 51, 29, and 12% reduction in axial elongation in the 0.05, 0.025, and 0.01% atropine groups, respectively. The authors point out that the difference in axial length between the 0.01% atropine and placebo groups was not statistically significant, which is important to be aware of because axial growth is accompanied by the degenerative changes associated with pathologic myopia. Changes in accommodation amplitude and pupil size also followed a dose-dependent response. There was no significant effect on near or distance vision reported among any of the atropine groups. The next phases of the LAMP study are currently underway and will help determine the long-term, washout, and rebound effects of low-dose atropine treatment.
A study by Moon and Shin  demonstrates a similar concentration-dependent response on spherical equivalent and axial elongation when assessing the efficacy of 0.05, 0.025, and 0.01% atropine in children. However, study participant assignment was based on the pretreatment rate of myopic progression so that rapid progressors were assigned to the 0.05% atropine group, moderate progressors to the 0.025% atropine group, and slow progressors to the 0.01% atropine group. This study, therefore, suggests that the atropine dose for optimal myopia control may need to be tailored to the rate of myopic progression.
In addition to the dose-dependent response of atropine on myopic progression detailed above, a dose-dependent rebound effect has also been documented with discontinuation of atropine treatment [27▪]. This finding, as well as the dose-related side effect profile, should not be overlooked when considering treatment with atropine.
Wu et al. constructed a well informed clinical algorithm for atropine use in myopia control. Before initiating treatment, they recommend practitioners have an open discussion with the parents and patients about the treatment plan including goals and duration of therapy, potential side effects including risk of rebound progression, and the need for continued corrective lens use concomitantly with atropine therapy. Wu et al. recommend a minimum of 2 years of therapy starting with 0.01% atropine because of its low side effect profile. The patient should be reassessed every 6 months. If the patient experiences less than 0.5 diopter of myopic progression, therapy should be continued. If the progression rate is greater than 0.5 diopter over a 6 month period, then three options can be considered: increasing the atropine concentration, adding another treatment modality, such as orthokeratology, to the current atropine regimen, or continuing the current atropine dose and encouraging more time outdoors. After 2 years, atropine can be stopped entirely, tapered to a stop, or continued until adolescence depending on provider and patient preference. These guidelines by Wu et al. are reasonable and based on a review of the atropine literature. Ultimately, treatment should be individualized to each patient.
As the prevalence of myopia continues to increase worldwide, vision-threatening complications of high myopia will continue to increase as well. Myopic control has thus become a popular target for research. To date, studies have shown that environmental modification, such as spending more time outdoors, can decrease the risk of myopia onset. Optical interventions, such as contact lenses designed to diminish peripheral hyperopic defocus and orthokeratology show moderate reduction rates for myopia progression. However, pharmacologic treatment with atropine has proven to be the most well studied and most effective therapy for myopia control to date. Treatment plans need to be tailored to each individual patient. More research is warranted to help define long-term effects of intervention and the ideal patient and time for initiation of therapy.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
REFERENCES AND RECOMMENDED READING
Papers of particular interest, published within the annual period of review, have been highlighted as:
- ▪ of special interest
- ▪▪ of outstanding interest
1. Praveen MR, Vasavada AR, Jani UD, et al. Prevalence of cataract type in relation to axial length in subjects with high myopia and emmetropia in an Indian population. Am J Ophthalmol 2008; 145:176–181.
2. Marcus MW, de Vries MM, Junoy Montolio FG, Jansonius NM. Myopia as a risk factor for open-angle glaucoma: a systematic review and meta-analysis. Ophthalmology 2011; 118:1989.e2–1994.e2.
3. Foster PJ, Jiang Y. Epidemiology of myopia. Eye (Lond) 2014; 28:202–208.
4. Saw SM, Gazzard G, Shih-Yen EC, Chua WH. Myopia and associated pathological complications. Ophthalmic Physiol Opt 2005; 25:381–391.
5. Holden BA, Fricke TR, Wilson DA, et al. Global prevalence of myopia and high myopia and temporal trends from 2000 through 2050. Ophthalmology 2016; 123:1036–1042.
6. Sun JT, An M, Yan XB, et al. Prevalence and related factors for myopia in school-aged children in Qingdao. J Ophthalmol 2018; 2018:9781987.
7▪. Parssinen O, Kauppinen M. Risk factors for high myopia: a 22-year follow-up study from childhood to adulthood. Acta Ophthalmol 2018; doi: 10.1111/aos.13964. [Epub ahead of print].
This is a 22-year longitudinal study on risk factors for high myopia. This study is distinctive in its long-term follow-up period. Researchers found that parental myopia, age at baseline, early myopic progression, more time spent on reading/near work, and less time outdoors in childhood are associated with myopia in adulthood.
8. Wu PC, Chen CT, Lin KK, et al. Myopia prevention and outdoor light intensity in a school-based cluster randomized trial. Ophthalmology 2018; 125:1239–1250.
9. Xiong S, Sankaridurg P, Naduvilath T, et al. Time spent in outdoor activities in relation to myopia prevention and control: a meta-analysis and systematic review. Acta Ophthalmol 2017; 95:551–566.
10▪. He X, Sankaridurg P, Xiong S, et al. Shanghai time outside to reduce myopia trial: design and baseline data. Clin Exp Ophthalmol 2018; 47:171–178.
This is a randomized clinical trial that is currently in process looking at the effects of outdoor time on myopic progression in children. Time outdoors and light exposure will be measured by wearable light meter devices, improving the quantifiability and reliability of measurements. This study will hopefully provide more insight into the relationship of time outdoors and myopia. Results are still pending.
11. Lingham G, Milne E, Cross D, et al. Investigating the long-term impact of a childhood sun-exposure intervention, with a focus on eye health: protocol for the Kidskin-Young Adult Myopia Study. BMJ Open 2018; 8:e020868.
12. Kang P. Optical and pharmacological strategies of myopia control
. Clin Exp Optom 2018; 101:321–332.
13. Sankaridurg P. Contact lenses to slow progression of myopia. Clin Exp Optom 2017; 100:432–437.
14. Benavente-Perez A, Nour A, Troilo D. Axial eye growth and refractive error development can be modified by exposing the peripheral retina to relative myopic or hyperopic defocus. Invest Ophthalmol Vis Sci 2014; 55:6765–6773.
15. Sun YY, Li SM, Li SY, et al. Effect of uncorrection versus full correction on myopia progression
in 12-year-old children. Graefes Arch Clin Exp Ophthalmol 2017; 255:189–195.
16. Sankaridurg P, Conrad F, Tran H, Zhu J. Controlling progression of myopia: optical and pharmaceutical strategies. Asia Pac J Ophthalmol (Phila) 2018; 7:405–414.
17. Kanda H, Oshika T, Hiraoka T, et al. Effect of spectacle lenses designed to reduce relative peripheral hyperopia on myopia progression
in Japanese children: a 2-year multicenter randomized controlled trial. Jpn J Ophthalmol 2018; 62:537–543.
18▪. Ruiz-Pomeda A, Perez-Sanchez B, Valls I, et al. MiSight Assessment Study Spain (MASS). A 2-year randomized clinical trial. Graefes Arch Clin Exp Ophthalmol 2018; 256:1011–1021.
This is a randomized trial evaluating the efficacy of a novel design contact lens called MiSight designed for daytime wear compared with single vision spectacles on myopic control. The authors found a 39% slower myopic progression rate and a 36% reduced axial elongation rate in the MiSight group compared with controls.
19▪. Cheung SW, Boost MV, Cho P. Pretreatment observation of axial elongation
for evidence-based selection of children in Hong Kong for myopia control
. Cont Lens Anterior Eye 2018; doi: 10.1016/j.clae.2018.10.006. [Epub ahead of print].
This prospective crossover study evaluated the rate of myopic progression in children with myopia prior to orthokeratology treatment. They found that patients who were identified as rapid myopic progressors has the most effective reduction in axial elongation with orthokeratology treatment. This study suggests a possible target population for orthokeratology.
20. Lipson MJ, Brooks MM, Koffler BH. The role of orthokeratology
in myopia control
: a review. Eye Contact Lens 2018; 44:224–230.
21. Na M, Yoo A. The effect of orthokeratology
on axial length elongation in children with myopia: contralateral comparison study. Jpn J Ophthalmol 2018; 62:327–334.
22. Zhang Y, Chen YG. Comparison of myopia control
between toric and spherical periphery design orthokeratology
in myopic children with moderate-to-high corneal astigmatism. Int J Ophthalmol 2018; 11:650–655.
23. Zada M, Cabrera-Aguas M, Branley M, et al. Microbial keratitis associated with long-term orthokeratology
. Clin Exp Ophthalmol 2018; 47:292–294.
24. Kam KW, Yung W, Li GKH, et al. Infectious keratitis and orthokeratology
lens use: a systematic review. Infection 2017; 45:727–735.
25. Zhao F, Zhao G, Zhao Z. Investigation of the effect of orthokeratology
lenses on quality of life and behaviors of children. Eye Contact Lens 2018; 44:335–338.
26. Wu PC, Chuang MN, Choi J, et al. Update in myopia and treatment strategy of atropine
use in myopia control
. Eye (Lond) 2018; 33:3–13.
27▪. Pineles SL, Kraker RT, VanderVeen DK, et al. Atropine
for the prevention of myopia progression
in children: a report by the American Academy of Ophthalmology. Ophthalmology 2017; 124:1857–1866.
This is a review of the published literature on atropine for myopia control published by the American Academy of Ophthalmology. The authors conclude that level 1 evidence supports atropine use for prevention of myopia progression.
28. Chua WH, Balakrishnan V, Chan YH, et al. Atropine
for the treatment of childhood myopia. Ophthalmology 2006; 113:2285–2291.
29. Chia A, Chua WH, Cheung YB, et al. Atropine
for the treatment of childhood myopia: safety and efficacy of 0.5%, 0.1%, and 0.01% doses (atropine
for the treatment of myopia 2). Ophthalmology 2012; 119:347–354.
30. Gong Q, Janowski M, Luo M, et al. Efficacy and adverse effects of atropine
in childhood myopia: a meta-analysis. JAMA Ophthalmol 2017; 135:624–630.
31▪▪. Yam JC, Jiang Y, Tang SM, et al. Low-Concentration Atropine
for Myopia Progression
(LAMP) Study: a randomized, double-blinded, placebo-controlled trial of 0.05%, 0.025%, and 0. 01% atropine
eye drops in myopia control
. Ophthalmology 2019; 126:113–124.
The LAMP study is a randomized, double-blinded, placebo-controlled trial evaluating low-dose atropine intervention for myopia control. This article discusses the published findings of the first phase of this in a four-phase study. Phase 1 results show a concentration-dependent reduction rate in myopic progression and side effect profile with atropine after 1 year of treatment. The next phases of the trial will evaluate the rebound effect after treatment washout and long-term effect of atropine treatment.
32. Moon JS, Shin SY. The diluted atropine
for inhibition of myopia progression
in Korean children. Int J Ophthalmol 2018; 11:1657–1662.