Preventing Nearsightedness in Children: What Science Says About Slowing Myopia Progression

Table of Contents

• Key Points
• Background: Why Myopia Is a Growing Global Problem
• How Common Is Myopia? The Numbers Behind the Epidemic
• Why High Myopia Matters: Risks to the Eye
• Study Methods: How This Review Was Conducted
• What Causes Myopia? Genetics and Biology
• The Role of the Environment: Outdoors and Near Work
• Treatment Options Tested in Clinical Trials
• Summary Table of Randomized Clinical Trials
• Eye Exercises and Biofeedback Visual Training
• Spectacles and Contact Lenses
• Orthokeratology (Ortho-K)
• Atropine and Other Medicated Eye Drops
• What This Means for Patients and Families
• Limitations: What This Review Could Not Prove
• Practical Recommendations
• Frequently Asked Questions
• Source Information

Key Points

• Projections estimate myopia will affect 4,758 million people, 49% of the world, by 2050, up from 1,406 million in 2000.
• Low-dose atropine 0.01% drops were identified as the most effective and safest long-term treatment, with the smallest rebound effect and negligible side effects.
• Orthokeratology should not be a first-line choice because of high risk of infectious keratitis and low patient compliance.
• Outdoor time is more powerful for preventing myopia from starting than for slowing it once it has begun.
• Every treatment in the randomized trial table produced only small to moderate benefit; no current treatment stops myopia completely.

Background: Why Myopia Is a Growing Global Problem

Myopia, commonly called nearsightedness, is one of the most common refractive diseases (focusing disorders) in the world. It happens mainly because the eyeball grows too long from front to back, a process called excessive axial elongation. This stretching of the eye means light focuses in front of the retina instead of on it, so distant objects look blurry. The problem usually develops during childhood and gets worse as the eye continues to grow.

The journal Nature recently described myopia as an epidemic in the developed countries of East and South-East Asia. In those regions, the prevalence (how many people are affected) reaches peaks of 80–90% in children attending secondary school at ages 17–18. That means roughly 8 or 9 out of every 10 teenagers in some of these populations are nearsighted.

The picture is not limited to Asia. The European Eye Epidemiology Consortium published a meta-analysis (a study that combines results from many studies) of population-based, cross-sectional data. Cross-sectional means the researchers took a snapshot of the population at one point in time. They found that myopia is growing dramatically in Western countries too, with large differences between age groups. Among 25-year-olds, 46% (about 1 in 2) were nearsighted. Among 75-year-olds, only 15% (about 1 in 7) were affected. That gap between generations strongly suggests something about modern life is driving the increase, not just genetics.

How Common Is Myopia? The Numbers Behind the Epidemic

Holden and colleagues estimated how myopia and high myopia will grow worldwide. They defined high myopia as a loss of 6.00 diopters (D) or more. A diopter is the unit used to measure the focusing power of a lens and the size of a refractive error—the more negative the number, the stronger the nearsightedness.

Their projections showed exponential growth:

• In 2000: 1,406 million people had myopia (22.9%, about 1 in 4), and 163 million had high myopia (2.7%, about 1 in 37).
• Projected for 2050: 4,758 million people will have myopia (49%, about 1 in 2), and 938 million will have high myopia (9.8%, about 1 in 10).

The authors of this review describe those figures as alarming. If the projections hold, half the world's population may be affected by myopia by 2050. That would represent a significant social and economic burden on global healthcare systems.

Not every country shows the same trend, however. A Danish cross-sectional study by Jacobsen and colleagues reported a significant decrease in high myopia from 1882 onward and a continuing downward tendency between 1964 and 2004. The study examined 4,681 male Danish military conscripts. In that sample, the prevalence of myopia (defined as a spherical equivalent of −0.5 D or worse) was 12.8% (about 1 in 8). High myopia (spherical equivalent worse than −6.5 D) was only 0.3% (about 3 in 1,000).

Similarly, French and colleagues compared refractive errors in European Caucasian children aged 6 to 7 years and 12 to 13 years living in Sydney, Australia and in Northern Ireland. They found a relatively low prevalence of myopia in both samples: 5% (about 1 in 20) and 15.0% (about 1 in 7), respectively.

Why High Myopia Matters: Risks to the Eye

High myopia is not just a matter of thick glasses. The stretched, elongated eye is vulnerable to serious structural damage in the macula (the central part of the retina responsible for sharp vision). The stretched, elongated eye is also vulnerable in the peripheral retina, the optic nerve, and the lens.

The Rotterdam Eye Study, a population-based cohort study, documented bilateral visual impairment (vision loss in both eyes) in highly myopic eyes. Among these patients:

• 39% (about 2 in 5) had myopic maculopathy (damage to the central retina)
• 17% (about 1 in 6) had open-angle glaucoma (a disease that damages the optic nerve)
• 5% (about 1 in 20) had cataracts (clouding of the lens)

Another important finding is that an early onset of myopia is more dramatically related to a more severe degree of the disease during adulthood. In other words, a child who becomes nearsighted young is more likely to end up with high myopia—and its complications—as an adult. This is exactly why researchers focus on slowing progression in the pediatric population.

The aim of this review was to analyze all the possible behavioral, interventional, and pharmacological strategies that can be adopted in children to slow the progression of myopia. A recent network meta-analysis published by Huang and colleagues compared the effectiveness of several interventions. These interventions were atropine and other anti-muscarinic agents (drugs that block certain nerve signals). They also included orthokeratology (Ortho-K), soft bifocal contact lenses (SCLs), bifocal spectacles (PBSLs), progressive lens spectacles (PASLs), and more outdoor activities. This review goes further than just clinical efficacy. It also evaluates side effects, patient tolerability, and the real long-term advantages for children.

Study Methods: How This Review Was Conducted

The authors performed a systematic computerized search of the medical literature, covering all publications from the earliest available date ("inception") until December 2017. They restricted their search to English-language articles about myopia control therapies. The electronic databases searched were PubMed, MEDLINE, and the Cochrane Collaborations.

The keywords and MeSH terms (standardized medical subject headings used by databases) they used were:

• "Myopia" alone, or in combination with "control," "progression," "pediatrics," "prevention"
• "atropine," "orthokeratology," "contact lenses," "spectacles"
• "outdoor activities," "near work"
• "epidemiology," "genetics," "pathogenesis," "dopamine"

The authors thoroughly assessed every pertinent article. They also reviewed the reference lists of those articles to identify any additional studies that could be included. It is worth noting a methodological detail: the reviewers were not blinded to the names of the investigators or the sources of publication. This means they knew who had written each study. Such blinding is a way to reduce bias in a review.

Eligibility of studies was first assessed based on titles and abstracts. Full manuscripts were then obtained for all chosen studies, and the final decision for inclusion was made only after a thorough examination of each paper.

What Causes Myopia? Genetics and Biology

Myopia is a multifactorial disease. That means it is caused by a deep interaction between genetic factors—including parental myopia and ethnicity—and environmental factors. Neither genes nor environment alone explains who becomes nearsighted.

Genetic Background

Researchers have long recognized a positive association between parental myopia and a child's risk of developing myopia. Ip and colleagues showed a significant influence of both parental myopia and ethnicity on spherical equivalent refraction (the overall focusing error of the eye). Parental myopia and ethnicity also influenced axial length (the front-to-back length of the eyeball). This was in a sample of 12-year-old Australian children.

Common myopia is generally transmitted as a complex trait, meaning many genes each contribute a small amount. High myopia, by contrast, can be transmitted either as a complex trait or as a Mendelian trait (following simple inheritance patterns). Those Mendelian patterns include autosomal dominant, autosomal recessive, and X-linked recessive inheritance. Linkage analysis has allowed scientists to identify 18 loci (chromosomal locations) for myopia and high myopia, including MYP2, MYP3, and MYP5. These findings give researchers the opportunity to screen for possible candidate genes responsible for the disease.

Twin studies have been especially informative. The Twin Eye Study demonstrated that the heritability of myopia in monozygotic twins (identical twins, who share all their genes) was 90%, with a 95% confidence interval of 81–95%. A 95% confidence interval is the range in which the true value likely falls. A more recent cohort study, the Guangzhou Twin Eye Study, was the first to identify the important role played by peripheral refraction. Peripheral refraction is how light focuses in the outer parts of the visual field, and it plays a role in myopia progression. That study also suggested a significant genetic contribution to peripheral refraction, with heritability between 55% and 84%.

Experimental myopia studies in animals have helped characterize the specific genes involved. These genes share common features: they can regulate ocular growth. These genes can be modulated in models of induced myopia. These genes are expressed throughout the sclera (the white outer coat of the eye), choroid (the vascular layer beneath the retina), and retina. Among them, the TGF-beta/BMP pathway appears to play an important role. Animal models have shown that reduced expression of TGF-beta isoforms in the sclera was associated with decreased collagen synthesis, and therefore with a more consistent predisposition to pathological axial elongation.

Despite these genetic findings, genome-wide association studies (GWAS) have assessed that the susceptible loci causing refractive error play only a marginal role in the risk of developing myopia—between 0.5% and 2.9%. This suggests that other non-genomic factors are more important, such as epigenetic changes (chemical modifications that affect how genes are switched on or off) and the environment.

A prospective cohort study by Verhoeven and colleagues, which included 5,257 participants, makes this point clearly. When the researchers compared subjects with the same degree of genetic risk, they found that environmental factors were more significantly associated with the onset of myopia. Higher levels of education were more significantly associated with the onset of myopia than lower levels of education. The authors therefore conclude that we should consider myopia a complex mosaic, in which gene–environment interaction is crucial.

Physiology and Biological Mechanisms of Myopia

The story of how the eye controls its own growth began in 1977. Wiesel and Raviola accidentally discovered in animal models that visual form deprivation (blocking clear images from reaching the retina) was involved in the development of myopic axial elongation. From this, scientists proposed that the retina exercises local control over eye growth.

Several animal models have since shown that axial eye growth responds in order to compensate for an imposed defocus (a deliberately blurry focus). In non-human primate models, manipulating the peripheral retinal defocus with bifocal contact lenses can modify eye growth and the refractive status. More specifically, axial myopia can be produced by imposing a peripheral hyperopic defocus—that is, by making the outer parts of the visual field focus behind the retina. In another study on marmosets, Benavente-Perez and colleagues suggested that imposing a positive defocus on the retina could be an effective strategy to slow myopia progression. Researchers also found that this response could be triggered locally within the eye if visual deprivation was directed specifically to certain retinal areas.

The retina is therefore involved in modulating the eye's axial length when it detects a sign of defocus. More surprisingly, the underlying choroid can modify its own thickness to move the retina closer to the focal plane.

In humans, however, an imposed defocus causes smaller changes in axial length than it does in animal experiments. The COMET and STAMP clinical trials observed that children treated with progressive addition lenses showed a smaller change in refraction in proportion to the degree of refractive error imposed. The researchers hypothesized that a more gradual accommodation (the eye's focusing effort), induced by progressive addition lenses, would reduce the retinal peripheral defocus. This would therefore reduce the stimulus for eye growth. Further clinical studies are needed to better establish the role of accommodation in dampening the retinal error signal and inhibiting eye growth in children.

Many biochemical pathways have been investigated in myopia. Researchers have studied the cholinergic, nitric oxide (NO), and, more recently, insulin pathways. But the importance of dopamine (DA), a signaling chemical in the brain and retina, remains crucial in the development of experimental myopia. Stone and colleagues first demonstrated, in 1990, that chicks with visual deprivation had reduced levels of dopamine.

Several other studies confirmed that chicks treated with negative lenses had decreased values of DOPAC in the vitreous body, the gel inside the eye. DOPAC is 3,4-dihydroxyphenylacetic acid, the primary metabolite—breakdown product—of dopamine. These findings suggest an inverse relationship between dopamine levels and myopic eye growth: when dopamine goes down, eye growth goes up.

Based on this assumption, researchers tested dopaminergic drugs as anti-myopic agents in animal models. Dopamine exerts its effects through two families of receptors. D1-like receptors (D1 and D5) are located on bipolar, amacrine, and ganglion cells in the retina. D2-like receptors (D2, D3, D4) sit on retinal pigment epithelium (RPE) cells and neuroepithelial cells. Recent findings have extended the traditional view that D2-like receptors played the main role in myopia development. The newer evidence supports a combined action between D1-like and D2-like receptors.

Researchers have also focused attention on the role of the RPE (retinal pigment epithelium, a pigmented cell layer beneath the retina) in modulating eye growth. The RPE releases growth factors that regulate scleral remodeling in response to two experimental conditions: form deprivation myopia (FDM) and flickering light induced myopia (FLM). A recent study published by Luo and colleagues revealed paradoxically increased levels of dopamine in the RPE of guinea pigs with FLM. This would suggest the presence of different retinal pathways causing FDM and FLM, but with the RPE serving as the final common modulator in myopic scleral remodeling.

Other molecules have been investigated too. In young rabbits, administration of 7-methylxanthine reinforced the posterior sclera by increasing its collagen fibril content. In guinea pigs, 7-methylxanthine was proven to slow the amount of eye elongation induced by form deprivation, preventing thinning of the posterior sclera. Given these results in animal models, methylxanthines have been investigated as possible treatment options for preventing myopia.

Melatonin also appears to play a role. Systemic administration of melatonin in chicks has been proven to be associated with choroidal thinning. A recent human study showed that myopic subjects have higher serum levels of melatonin combined with lower serum dopamine compared with non-myopic subjects. These findings reinforce the important role played by light exposure and circadian rhythm (the body's internal daily clock) in the development of myopia. This is because both are strongly connected to melatonin metabolism.

The protective effect of light exposure is well documented. Animal models such as chicks and monkeys have revealed that the onset of experimental myopia can be limited by daily exposure to bright light at levels of 15,000–30,000 lux. For comparison, ordinary indoor lighting is typically a few hundred lux. Bright outdoor daylight can exceed 10,000 lux even on an overcast day. A proportional effect of light intensity in diminishing refractive error has also been demonstrated in chicks. Light exposure therefore plays an important role in preventing myopia because of its modulating effect on dopamine and other biomolecules. Still, further studies are needed to define the complex role played by dopamine and other possible neurohormones in the onset of myopia.

The Role of the Environment: Outdoors and Near Work

Outdoor Activities

The protective effect of time spent outdoors has been investigated in many epidemiological studies, and the evidence is strong—especially for preventing myopia from starting at all.

The Guangzhou randomized trial evaluated the efficacy of an additional daily outdoor activity over 3 years in 952 children aged 6–7 years. It compared that group with a control group of 951 children of the same age who followed their usual pattern of outdoor activities. The interventional group showed a smaller myopic shift in spherical equivalent refraction than the control group:

• Intervention group mean: −1.42 D
• Control group mean: −1.59 D
• Difference: 0.17 D (95% CI, 0.01 D to 0.33 D; p = 0.04)

In this study, the increase in outdoor activities produced a relative reduction of 23% in the incidence (new cases) of myopia in the intervention group. A p-value of 0.04 means there is a 4% probability that this result occurred by chance—statistically significant, though modest.

These findings agreed with a prospective, interventional study published by Wu and colleagues. They ran a recess outside the classroom program (ROC) in a sample of 571 children in Taiwan. More outdoor activities led to a reduction of 8.4 percentage points in the onset of myopia in the ROC group compared with the control group after 1 year: 8.41% versus 17.65% (p < 0.001). In other words, about 8 in 100 children in the outdoor-recess group developed myopia, compared with about 18 in 100 in the control group.

The "Anyang Childhood Eye Study" looked at 2,276 Chinese children aged 10–15. It revealed a significant association between outdoor activities and a slower axial elongation rate. This was only in children who were not myopic at the start of the study (highest versus lowest group: −0.036 mm/year; p = 0.009). Children who were already myopic at baseline did not show a significant effect of time spent outdoors on reducing axial elongation (highest versus lowest group: −0.005 mm/year; p = 0.595).

The recent "Handan offspring myopia study" reported a significant inverse relationship between outdoor activities and the incidence of myopia in rural children in China. However, the size of the effect was small (odds ratio 0.82; 95% CI 0.70–0.96).

All these studies demonstrate that outdoor activities have a more important impact on reducing the onset of myopia than on slowing down the progression of the disease. A recently published meta-analysis by Xiong and colleagues confirmed this pattern:

• Clinical trials: more time outdoors reduced myopia incidence (risk ratio = 0.536; 95% CI 0.338 to 0.850)
• Longitudinal cohort studies: risk ratio = 0.574 (95% CI 0.395 to 0.834)
• Cross-sectional studies: reduced prevalence of the disease (odds ratio = 0.964; 95% CI 0.945 to 0.982)
• Dose-response analysis: no significant association between more outdoor activities and myopia progression (R² = 0.00064)

Another important element could be the residential area where children live. A cross-sectional study of schoolchildren in Indonesia revealed that the prevalence of uncorrected refractive error was 10.1%, 12.3%, 3.8%, and 1% among urban, suburban, exurban, and rural areas, respectively. The higher prevalence in urban and suburban areas could be explained by a lack of outdoor activities combined with more intensive near work. This is driven by higher levels of education compared with rural areas.

According to a study published by Read and colleagues, daily light exposure plays a more important role in the development of myopia in Australian children. Daily light exposure plays a more important role than the amount of physical activity does. This suggests that it is the light itself, not the exercise, that matters most.

The biological mechanism explaining how time spent outdoors reduces the onset of myopia still needs to be clarified. Studies in animal models reinforce the role of dopamine in association with light exposure, as hypothesized by Rose and colleagues. Ashby and colleagues found that chicks exposed to high luminance levels failed to retard myopia development when injected with spiperone at 500 µM. Spiperone is a D2-dopaminergic antagonist (a drug that blocks dopamine D2 receptors). Further studies must be performed to clarify the complex relationship between dopamine levels, sunlight exposure, and outdoor activities.

Near Work Activity

Near work activity—reading, writing, and other close-up tasks—has been investigated in many studies as an independent risk factor for myopia. Unlike outdoor activities, however, consistent evidence is still needed.

A Singapore myopia study reported that teenagers spending more than 20.5 hours a week reading and writing were significantly more likely to develop myopia (odds ratio 1.12; 95% CI 1.04–1.20; p = 0.003). An odds ratio of 1.12 means a 12% higher relative chance.

The Sydney myopia study analyzed a population of 12-year-old Australian children. It looked at the impact of close reading distance (less than 30 cm) and continuous reading (more than 30 minutes) on spherical equivalent refraction. Children who read very close up had 2.5 times the probability of developing myopia compared with the control group (p = 0.02). Children who read continuously for more than 30 minutes had 1.5 times the probability (p = 0.0003). Despite the relevance of these individual variables, the overall time spent on near work activities was not significant in multivariate analyses for myopia. Myopia was defined as spherical equivalent of −0.50 D or worse.

Another 3-year follow-up cohort study, the Beijing Myopia Progression Study, revealed a positive association between myopia and near work. This association appeared only in the group of students who had a greater near work load at baseline (hazard ratio 5.19; 95% CI 1.49–18.13).

By contrast, other studies reported no significant correlation between near work activities and the onset of refractive error. Rose and colleagues, for example, did not find any relevant changes in myopia prevalence in 6-year-old children. This was despite low (0–2 hours), moderate (1.6–3.1 hours), and high (more than 3.0 hours) daily amounts of near work activity.

The recent systematic review and meta-analysis published by Huang and colleagues included 12 cohort studies and 15 cross-sectional studies on the association between myopia and near work in children. The results reported that:

• More near work activities were related to higher odds of myopia (odds ratio 1.14; 95% CI 1.08–1.20)
• The odds of myopia increased by 2% (odds ratio 1.02; 95% CI 1.01–1.03) for every one diopter-hour more of weekly near work. A diopter-hour combines how close the task is with how long it is performed.

More generally, several studies have demonstrated a strong positive association between higher tiers of education and the prevalence of myopia. These results could be explained by different factors: both the increase in near work activity and a simultaneous reduction in outdoor activities among more educated subjects. This evidence confirms the multifactorial pathogenesis of myopia, in which near work activity constitutes an important independent risk factor.

Treatment Options Tested in Clinical Trials

Clinical studies investigating the efficacy of treatments for myopia progression are summarized in the table below. Note the abbreviations used: AL = axial elongation (growth of the eye's length); Atr = atropine; BSLs = bifocal spectacle lenses; D = diopters; Ortho-K = orthokeratology. PASL = progressive addition spectacle lenses; PBO = placebo; PBSLs = prismatic bifocal spectacle lenses; Pir = pirenzepine; SCLs = soft contact lenses; SER = spherical equivalent refraction.

Summary Table of Randomized Clinical Trials

Eye Exercises and Biofeedback Visual Training

Biofeedback visual training is a technique that teaches patients to consciously influence their own focusing. Its roots go back to Bates' theory in the 1920s, which hypothesized that overwork of the extra-ocular muscles (the muscles that move the eye) could cause changes in accommodation. In particular, biofeedback visual training was thought to modify the action of the autonomic nervous system (the involuntary nervous system) on the accommodative process.

Rupolo and colleagues evaluated the efficacy of visual training using an acoustic biofeedback technique in a non-randomized prospective study including 33 female students. After 12 months, no significant differences were shown between the treated and control groups. Analogously, previous non-randomized clinical studies reported no efficacy for this treatment modality.

More recently, a case-control study evaluated the efficacy of Chinese eye exercises in controlling myopia in a sample of 261 children (mean age 12.7 ± 0.5 years). Overall, the researchers found no significant association between eye exercises and the risk of developing myopia (odds ratio 0.73; 95% CI 0.24–2.21). The researchers also found no significant association between eye exercises and myopia progression (odds ratio 0.79; 95% CI 0.41–1.53) over a 2-year follow-up period.

In conclusion, no consistent evidence has been shown that biofeedback visual training is effective in slowing down myopia progression.

Spectacles and Contact Lenses

In daily clinical practice, single-vision spectacle lenses (SVSLs) and contact lenses are commonly prescribed to children for the correction of myopia. Progressive addition lenses (PALs) and bifocal spectacle lenses are occasionally prescribed for the specific purpose of slowing down the refractive disease. The underlying mechanism behind PALs treatment needs to be better understood, but several studies suggest an effect on reducing retinal hyperopic blur by reducing accommodative lag during near work. Accommodative lag is the gap between where the eye should focus and where it actually focuses when looking at something close.

Not all studies support this approach. A 3-year Finnish randomized controlled trial enrolling 240 schoolchildren aged 9 to 11 reported that myopia progression was more associated with the amount of near work performed. In that trial, diminishing the accommodative effort by using bifocal or reading spectacles was ineffective.

The randomized Correction of Myopia Evaluation Trial (COMET) enrolled 469 children aged 9. It randomly assigned them to the PALs group, with a +2.00 addition, or to the SVSLs group, with the prescription of the common spectacles used for myopia. Progression of myopia was measured by autorefraction (an automatic measurement of focusing error) after cycloplegia (paralysis of the focusing muscle using drops) over a 3-year follow-up period. The trial found a statistically positive gain of only 0.2 D and 0.11 mm in the PALs group. Therefore, despite achieving statistical significance, the clinical effect was small.

Relying on these data, Gwiazda and colleagues highlighted, in subgroup analyses, a greater effect in children who had larger accommodative lags. Larger accommodative lags meant more than 0.43 D for a 33 cm target, combined with near esophoria (a tendency for the eyes to turn inward when focusing close). In that subgroup, the PAL-versus-single-vision difference in progression was −1.08 D minus −1.72 D, which equals 0.64 ± 0.21 D.

The following COMET2 Study was another double-masked multicenter randomized trial. It selected for PALs treatment only myopic children with near esophoria and at least 1.00 D of accommodative lag. Accommodative lag was defined as an accommodative response of less than 2.50 D for a 3.00-D demand. Over a 3-year follow-up, the researchers found a gain in spherical equivalent refraction of only 0.28 D in that carefully selected group.

Orthokeratology (Ortho-K)

Orthokeratology uses specially designed rigid contact lenses worn overnight. The lenses temporarily reshape the cornea (the clear front surface of the eye) so that vision is clear during the day without glasses. Two studies in the review's trial table examined Ortho-K in children:

• Cho P, 2005 (pilot study): 35 children in Hong Kong, aged 7–12, followed for 2 years. The treated group showed a gain of 2.09 ± 1.34 D.
• Cho P, 2012 (randomized, single-masked): 102 children in Hong Kong, aged 6–10, with baseline refractive error from 0.50 to 4.00 D, followed for 2 years. The control group showed 0.63 ± 0.26 mm of axial elongation, while the treated group showed 0.36 ± 0.24 mm.

Those axial elongation numbers suggest Ortho-K may slow the growth of the eye. However, the review's authors caution that orthokeratology should not be considered a first-line strategy. They cite two reasons. First, there is a high risk of infectious keratitis, an infection of the cornea that can threaten vision. Second, there is relatively low compliance among patients, meaning children and families often struggle to follow the demanding nightly lens routine correctly.

Atropine and Other Medicated Eye Drops

To date, atropine ophthalmic drops appear to be the most effective treatment for slowing the progression of myopia. Atropine is an anti-muscarinic drug, meaning it blocks certain nerve signals. However, the exact mechanism of the treatment's effect is still uncertain.

In particular, low-dose atropine at 0.01% was proven to be an effective and safe treatment in the long term. The authors attribute this to two advantages: it produces the lowest rebound effect (the catch-up worsening of myopia that can occur when treatment is stopped). It also has negligible side effects.

The table above also reports data on pirenzepine, another anti-muscarinic drug given as a 2% ophthalmic gel:

• Tan DT, 2005: 353 children in Singapore, aged 6–12, followed for 1 year. Myopia progression was 0.84 D in the control group. Myopia progression was 0.70 D in the group that switched from pirenzepine to placebo (Pir/PBO), and 0.47 D in the group that stayed on pirenzepine throughout (Pir/Pir).
• Siatkowski RM, 2008: 174 American children, aged 8–12, with baseline refractive error between −0.75 and −4.00 D and astigmatism of 1.00 D or less, followed for 2 years. The treated group gained 0.41 D.

The classic ATOM1 trial (Chua WH, 2006) used a much stronger concentration: atropine 1%. It enrolled 400 Asian children aged 6–12 with baseline refractive error between −1.00 and −6.00 D. Over 2 years, the control group progressed by −1.20 ± 0.69 D and elongated by 0.38 ± 0.38 mm. The treated group progressed by only 0.28 ± 0.92 D and actually showed a slight shortening of −0.02 ± 0.35 mm. That is a dramatic difference—but the 1% concentration is also associated with more side effects than the 0.01% formulation the review recommends for long-term use.

What This Means for Patients and Families

Three practical messages emerge from this review. The first is about prevention. If you want to reduce the chance that a child becomes nearsighted at all, the strongest evidence supports more time outdoors in bright light. The Guangzhou trial found a 23% relative reduction in new myopia cases, and the Taiwan recess program cut new cases roughly in half (8.41% versus 17.65%).

The second message is about slowing progression once myopia has started. Outdoor time does not appear to help much here. The Anyang study found a significant effect in children who were not yet myopic at baseline (−0.036 mm/year; p = 0.009). The Anyang study found no effect in children who were already myopic (−0.005 mm/year; p = 0.595). For children who are already nearsighted, the evidence points toward low-dose atropine 0.01% drops as the most effective and best-tolerated option.

The third message is about expectations. Every treatment in the randomized trial table produced only a small to moderate benefit. COMET's spectacles gained just 0.2 D over 3 years. COMET2's more targeted approach gained 0.28 D. This is real but modest progress. Families should understand that no current treatment stops myopia completely.

It is also worth remembering how the eye's own biology complicates treatment. The choroid can change its thickness to shift the retina toward the focal plane, and dopamine levels in the retina rise and fall with light exposure. This is why light-based and dopamine-related strategies attract so much research attention. It also explains why the timing of intervention matters so much: early onset predicts more severe disease in adulthood.

Limitations: What This Review Could Not Prove

Several limitations deserve attention. First, the review's authors note plainly that the exact mechanism by which atropine works remains uncertain, even though it is the most effective treatment available. Understanding the mechanism would help doctors refine dosing and predict who responds best.

Second, the treatments were studied in different populations, using different designs, over different follow-up periods. Comparing a 1-year trial in 186 American children with a 2-year trial in 400 Asian children is not straightforward. The review's authors acknowledge that its reviewers were not blinded to investigator names or publication sources, a design feature that can introduce bias.

Third, many of the reported benefits are statistically significant but clinically small. The difference of 0.17 D in the Guangzhou outdoor trial is a good example: it was statistically significant (p = 0.04), but small in absolute terms.

Fourth, some mechanisms remain unexplained. Researchers do not yet know why the RPE shows paradoxically increased dopamine levels in flickering-light myopia but decreased levels in form-deprivation myopia. They also do not fully understand the relationship between dopamine, sunlight, and outdoor activity.

Finally, the full text available for this summary was truncated partway through the discussion of the COMET2 Study. Detailed recommendations from later sections of the original review were not available in the excerpt used to prepare this article. These recommendations included full dosing guidance for atropine and the authors' complete discussion of combination therapies.

Practical Recommendations

Based on the evidence in this review, families and clinicians can consider the following steps:

1. Prioritize outdoor time for children who are not yet nearsighted. The evidence for preventing new myopia is strong. Aim for daily bright-light exposure, since light intensity—not physical activity level—appears to be the key factor in Australian children.
2. Ask about low-dose atropine 0.01% if a child is already progressing. The review identifies this as the most effective and safest long-term option, with the lowest rebound effect and negligible side effects.
3. Do not rely on eye exercises. Biofeedback training and Chinese eye exercises showed no significant benefit in controlled studies.
4. Be cautious about orthokeratology as a first choice. It may slow axial elongation (0.36 mm versus 0.63 mm over 2 years in one trial), but the risk of infectious keratitis and low compliance make it a secondary option.
5. Consider spectacles mainly for correction, not prevention. Progressive addition lenses produced only a 0.2 D gain over 3 years in COMET, though a subgroup of children with large accommodative lag and near esophoria gained 0.64 ± 0.21 D.
6. Watch reading distance and duration. Reading closer than 30 cm raised myopia odds 2.5 times, and continuous reading beyond 30 minutes raised them 1.5 times.
7. Act early. Early onset of myopia is linked to more severe disease in adulthood, so timely evaluation and treatment matter.

Frequently Asked Questions

Do eye exercises or biofeedback training slow myopia in children?

No consistent evidence supports them. A case-control study of 261 children found no significant link between Chinese eye exercises and either new myopia or progression over 2 years. A non-randomized study of 33 female students found no difference after 12 months of acoustic biofeedback visual training. These approaches are not supported for controlling myopia.

What are the risks of orthokeratology for my child?

Orthokeratology uses rigid lenses worn overnight to reshape the cornea. A review concluded it should not be a first-line choice because of a high risk of infectious keratitis, a potentially serious corneal infection. A review also concluded it should not be a first-line choice because of relatively low compliance, meaning families often struggle to follow the demanding nightly lens routine correctly. It may slow axial elongation, but these risks make it secondary.

Which treatment is most effective for slowing myopia once it has started?

Low-dose atropine 0.01% eye drops were identified as the most effective and safest long-term treatment for slowing myopia progression. This is mainly because they cause the smallest rebound effect when stopped and have negligible side effects. The exact mechanism by which atropine works remains uncertain. Families should discuss this option with an eye care professional.

Does spending more time outdoors help if my child is already nearsighted?

Outdoor time appears more powerful for preventing myopia from starting than for slowing it once it has begun. In the Anyang Childhood Eye Study of 2,276 Chinese children, outdoor activity was linked to slower axial elongation only in children not myopic at the start. Outdoor activity had no significant effect in those already nearsighted.

How much do spectacles actually slow myopia progression?

Benefits are small. In the COMET trial of 469 children, progressive addition lenses produced only a 0.2 D gain over 3 years. A subgroup with larger accommodative lag and near esophoria gained 0.64 D. The COMET2 trial, selecting children with near esophoria and at least 1.00 D accommodative lag, found only a 0.28 D gain over 3 years.

Does reading distance or time affect my child's risk of myopia?

In the Sydney myopia study of 12-year-old Australian children, reading closer than 30 cm raised the probability of developing myopia 2.5 times, and continuous reading beyond 30 minutes raised it 1.5 times. A meta-analysis found myopia odds rose 2% for every one diopter-hour more of weekly near work. Evidence overall remains mixed.

My child was just diagnosed with myopia and the eye doctor recommends low-dose atropine 0.01% drops — when should I seek a second opinion?

A second opinion is reasonable when a child is already nearsighted and a treatment is proposed, since options differ in benefit and risk. Low-dose atropine 0.01% is the most effective and safest long-term treatment, with the lowest rebound effect and negligible side effects. Spectacles and contact lenses produce only slight benefits, orthokeratology carries a high risk of infectious keratitis and poor compliance, and eye exercises show no significant benefit. Because early onset predicts more severe disease in adulthood, confirming the plan matters. Diagnostic Detectives Network provides independent expert second opinions.

Source Information

Original article title: Prevention of Progression in Myopia- A Systematic Review

Authors: Aldo Vagge, Lorenzo Ferro Desideri, Paolo Nucci, Massimiliano Serafino, Giuseppe Giannaccare, and Carlo E. Traverso

Author affiliations: Eye Clinic of Genoa, Policlinico San Martino, Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genova, Genova, Italy; School of Medicine and Pharmacy, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Genova, Italy; University Eye Clinic San Giuseppe Hospital, University of Milan, Milano, Italy; Ophthalmology Unit, Department of Experimental Diagnostic and Specialty Medicine (DIMES), University of Bologna, S. Orsola-Malpighi Teaching Hospital, Bologna, Italy; IRCCS Ospedale Policlinico San Martino, Genova, Italy.

Publication details: Published in Diseases 2018, volume 6, article 92; doi:10.3390/diseases6040092. Received 30 August 2018; accepted 13 September 2018; published 30 September 2018.

Keywords: myopia; myopia prevention; atropine; ATOM; orthokeratology; spectacles

Note: This patient-friendly article is based on peer-reviewed research. It is intended for educational purposes and does not replace personalized medical advice. Parents considering myopia control treatments for a child should consult a qualified eye care professional.