Written by: Allison Kirk Babiuch
Myopia, near-sightedness, is the most common ocular disorder worldwide with increasing prevalence over the past decades, especially in East Asia. The World Health Organization estimates that myopia affected 27% and high myopia affected 2.8% of the world population in 2010 and projects the prevalence of myopia to reach 50% by 2050, with as many as 10% being highly myopic. In addition to its hindering effects on vision and quality of life, high myopia is associated with an increased risk of serious sight-threatening retinal damage, cataracts, and glaucoma. Myopia is a major public health concern, posing a heavy health and economic burden to society. Numerous interventions are being studied to prevent the progression of myopia. These range from increasing sunlight exposure and limiting near work, to anti-muscarinic pharmacological agents, to special contact lenses.
Several studies in the U.S. and other countries have shown a recent dramatic increase in the prevalence of myopia in school children. Although genetic factors play a role in the development of myopia, the rapid increase is likely attributable to environmental and lifestyle factors. Environmental causes include lack of time spent outdoors and greater amount of time spent doing near-work, such as reading, computer time, and use of hand-held electronic devices. Studies have shown that children who spend more time outdoors have a lower chance of becoming nearsighted. Children from urban environments are more than twice as likely to be myopic as those from rural environments. While the exact mechanism for why time spent outdoors prevents progression of myopia, it is thought that natural sunlight or sufficient distance viewing time may provide important cues for eye development. Animal experiments suggest that near work may result in hyperopic defocus of the retina leading to excessive growth of the eye with resultant myopia.
Low dose atropine is an emerging therapy for myopia progression, but optimal concentration remains uncertain. The exact mechanism by which atropine, a nonselective muscarinic antagonist, works to slow myopia is unknown. Possible mechanisms include: elimination of accommodation; local retinal effects that slow progression; potential biochemical changes; and increased UVA exposure as a result of a dilated pupil potentially limiting axial lengthening. Since the prevalence of myopia is much higher in Asia than in other areas, it is not surprising that the majority of randomized trials in myopia control have been conducted in Asia, three of which are discussed below.
Atropine in the Treatment of Myopia (ATOM 1) found that atropine 1% drops reduced myopia progression and axial elongation. However, atropine 1% commonly results in unwanted side effects, including: blurred near vision, photophobia, and has a higher chance of myopic rebound effect after atropine discontinuation. Subsequently, lower-concentration atropine eye drops were found to slow myopia progression with less side effects. In the ATOM 2 trial, 0.5%, 0.1%, and 0.01% atropine slowed myopia progression to -0.3±0.60 D, -0.38±0.60 D, and -0.49±0.63 D, respectively, over 2 years. With fewer side effects and rebound after drop cession, 0.01% atropine was found to have a better treatment-to-side effect ratio. This study was limited by a lack of a placebo control group. In addition, axial length elongation in the 0.01% group remained significant (0.41±0.32 mm / 2 years), rendering an uncertain role of low concentration atropine in myopia control. A report by the American Academy of Ophthalmology in 2017 concluded that there is level 1 evidence that supports the use of atropine to prevent myopia progression, and that given the more sustained effect and fewer adverse effects of 0.01% atropine, it may be the most reasonable approach, though the optimal time to initiate and discontinue therapy is not known. A recent global survey among members of pediatric ophthalmology societies found that nearly two-thirds of members regularly prescribe 0.01% atropine to reduce myopia progression.
More recently, the Low-Concentration Atropine for Myopia (LAMP) Study found that 0.05% atropine (vs 0.01% and 0.025%) was superior at myopia control. After 2 years, the mean spherical equivalent progression was 0.55±0.86 D, 0.85±0.73 D, and 1.12±0.85 D in the 0.05%, 0.025%, and 0.01% atropine groups, respectively. Meanwhile, with mean axial length changes over 2 years of 0.39±0.35 mm, 0.50±0.33 mm, and 0.59±0.38 mm. The most common side effects (loss of accommodation and enlarged pupil size) were mild and well-tolerated in all groups. The LAMP study contributed to the understanding of low concentration atropine for myopia control in several aspects. First, it is the first double-blinded, randomized placebo-controlled trial on low concentration atropine drops, which provides the strongest evidence to support its role in myopia control. Second, it has resolved the previous controversy from the ATOM2 study, and delineated a concentration-dependent response in both the efficacy and side effect profile in the low-atropine concentration range from 0.05% to 0.01%. Third, the study has further suggested that a higher concentration of low-concentration atropine 0.05% is most efficacious among the three concentrations, and remained well tolerated.
Several cohort studies about myopia in non-Asian population have been published and globally, over 30 registered clinical trials involving low-dose atropine in various concentrations, ranging from 0.0005% to 0.05% are ongoing. The future results from these trials should better inform the choice of atropine concentration for myopia control and the issue of rebound with discontinuation of atropine.
Other treatments have looked at optical methods, including overnight corneal reshaping contact lenses (orthokeratology) and dual-focus daily soft contact lenses. The FDA recently approved MiSight, a single-use, disposable soft contact lens worn during the day for children ages 8 – 12 years old. MiSight has a central zone containing myopic refractive error with concentric peripheral rings of myopic defocus (additional positive power) and distance correction. A three-year randomized controlled trial found that MiSight resulted in a 59% reduction in myopic progression and a 52% reduction in axial length. Further studies are indicated to assess for safety of long-term contact lens wear in children as well as rebound myopic progression after discontinuation of contact lenses.
Numerous large-scale studies looking at treatments and causes for myopia progression are in progress world-wide. Understanding the role of factors influencing the onset and progression of pediatric myopia will facilitate the development of successful treatments and reduction of disease burden.
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