Myopia Control Current treatments that can be used to slow myopia progression include frames, corneal contact lenses, and medications. Many of the interventional studies used to evaluate these treatments have methodological limitations that require care in the interpretation and application of their results. To be evaluated objectively and evidence-based, clinical trials evaluating treatments should have these characteristics: contemporaneous control groups, randomized designs, blinded designs for investigators collecting outcomes, standardized measures, sufficiently large samples, and small dropout rates. There are many evidence-based results showing that most myopia treatments have little effect on the progression of myopia, have a short treatment maintenance time, or have significant side effects. The results of some recent clinical studies designed to meet these principles are described below. Feng Xue, Department of Optometry and Strabismus, Fudan University Eye, Ear, Nose and Throat Hospital Single Vision Lenses SVLs There are many experiments that demonstrate that optical defocus can actively modulate the process of orthokeratology. In animal models with strong evidence of lens-mimicking defocus from animal experiments, compensatory eye growth was produced: hyperopic defocus resulted in longer eye axis length and increased myopic refraction. Based on these results, it may be suggested that treating children with commonly applied monovision glasses (SVLs) for myopia may lead to accelerated myopic progression and longer eye axes. The myopic population wears glasses in different ways such as all-day wear and distance-only use, but cohort studies have shown that the progression of myopia is similar across wearing styles. Undercorrection is the correction method used by some clinicians. Only one randomized, blinded clinical trial of 106 children aged 9-14 years completed a 2-year trial of monovision for myopia correction. The group was divided into a foot-corrected group and an undercorrected 0.75D group. The 2-year progression was 0.77 D in the full correction group and 1.0 D in the undercorrection group, which was significantly less than the undercorrection group. Bifocal Lenses & Multifocal Progressive Lenses PALs The overall effect of bifocal or progressive multifocal glasses to stop myopia progression was weak. Overall the slowing is 0.15 to 0.5 D over a period of 1.5 to 3 years, but the effect is better within particular subgroups. The largest research project evaluating the effectiveness of this type of treatment is the U.S. Myopia Correction Evaluation Trial (COMET), a multicenter, randomized, double-blind clinical trial designed to assess whether PALs slow the progression of myopia more than traditional SVLs. 469 children aged 6-11 years of various races (46% white, 26% black American, 14% Hispanic and 8% Asian) with a baseline of myopia ranged between ?1.25 D and ?4.50. An indicator to evaluate the progression of myopia was the value of the auto-optometry after ciliary muscle paralysis (tropicamide). Follow-up was well accomplished, with 462/469 (98.5%) of children completing 3 years of follow-up. Adjusted mean myopic progression values from baseline levels were 1.28 ± 0.06 in the PALs group and 1.48 ± 0.06 D in the SVLs group. The overall 3-year treatment effect was 0.20 ± 0.08 D. Although the data were statistically significant, they were not clinically meaningful. All treatment effects occurred within the first year of lens wear. Further analysis of the data showed that myopia progression was 0.64 D ± 0.21 in children with large accommodation lags and internal hypotropia. in the COMET study, children with large accommodation lags had a more significant treatment effect than children with small accommodation lags (0.61 D vs. 0.15 D); the orthokeratology or internal hypotropia group had a more significant treatment effect than the external hypotropia group (0.55 D vs. 0.18 D). A study similar to COMET, which used a crossover design, is also underway in Japan. Children aged 6-12 years wore Pals or SVLs with a myopic baseline of ?1.25 to ?6.0 D. In the first phase of the trial, one lens was randomly selected and switched to the other correction at a subsequent time. At the end of the first 18-month treatment period, PALs showed 0.17 D less progression than SVLs. At the end of the second 18 months, the PALs-first group showed 0.29 D less myopic progression than the SVLs-first group. This suggests that early intervention with PALs may be better than SVLs. Corneal Contact Lenses The corneal contact lenses used for myopia treatment are soft corneal contact lenses (SCLs), high permeability corneal contact lenses (RGPs) and keratoplasty lenses (Ortho-K). Some of the earlier studies on the control of myopia progression with rigid, highly permeable corneal contact lenses (RGPs) suffered from an unrandomized experimental design and a high failure rate. The Corneal Contact Lens and Myopic Progression (CLAMP) study program better controlled the high failure rate by introducing an entry period to ensure good RGP wear. 116 children who successfully passed the entry period were randomized to the RGP group or to soft corneal contact lenses (SCLs). The three-year results showed significant differences, with myopic progression of ? 1.56 ± 0.95 D and ? 2.19 ± 0.89 D in the RGP and SCLs groups, respectively. Most of the slowing of myopic progression in the RGP group occurred within the first year, and the steepening of corneal curvature was significantly less in the RGP group compared with the SCLs group, 0.62 ± 0.60 D compared with 0.88 ± 0.57 D. Again, this change was mainly in the first year. The change in eye axis length was not significant in the two groups over three years. Taken together, these findings suggest that the effect of RGP in slowing myopia progression is mainly due to corneal flattening, and that this change is reversible after discontinuation of wear. Based on the insignificant changes in axial length and the fact that the major changes occurred in the first year, the authors of the CLAMP study concluded that RGP may not be suitable as a prescription lens primarily for myopia control. The Longitudinal Study of Ortho-Keratomileusis in Children (LORIC) in Hong Kong was a cohort study to see if keratomileusis slowed the growth of the myopic axis. 35 children wore keratomileusis for 2 years and were compared to a historical control group wearing SVLs. The primary metric was to compare the length of the eye axis, as the curvature of the cornea changes with keratoplasty lenses. The results of the study showed that during the 2-year period, axial growth in the keratoplasty group was 0.29 mm compared to 0.54 mm in the SVLs group, a significant difference. Previous cohort studies have suggested that the use of SCLs accelerates the progression of myopia. However, a recent randomized trial examining the effect of SCLs on myopia progression in children reported no significant difference in results when compared to frame wearers. Medications (Medical) 1. Atropine Atropine is a non-selective M receptor blocker. A recent well-designed study showed a clinically significant effect of atropine ophthalmic solution on myopic progression.Shih et al. studied myopic children aged 6-13 years, randomized to 0.5% atropine + multifocal glasses and PALs or SVLs alone, with myopic progression of 0.41 D, 1.19 D, and 1.40 D over 18 months, respectively.Singapore Chua et al. In the study by Chua et al. in Singapore, 400 myopic children aged 6-12 years were randomly assigned to the atropine and placebo groups, with one eye treated once a night, and myopic progression was ?0.28 D and ?1.20 D after 2 years in the two groups, respectively. myopic progression in the untreated eye was similar to that in the control eye in both treatment groups. This result also implies that many children with atropine became refractively parsimonious at the end of the trial. There was no follow-up in this study to show whether there was a rebound effect (accelerated progression of myopia after stopping atropine treatment). The current study in Singapore is evaluating the effect of different concentrations of atropine applied to both eyes, and will also measure data after discontinuation of the drug. It is still used in a number of countries in Asia, but the use of atropine for myopia control purposes is rare in the United States. Because of the adverse effects that occur with atropine, such as photophobia and ciliary muscle paralysis (usually accompanied by the use of progressive multifocal lenses with photochromic effects) make long-term use of the drug unacceptable. 2, pirenzepine (Pirenzepine) Pirenzepine, similar to atropine, but produces pupillary dilation and ciliary muscle paralysis is weak. A study was conducted in Singapore, Hong Kong, and Thailand, and another study was done in the United States. In the Singapore study, myopia progression was 0.47 D in one year in the pirenzepine twice a day group, 0.70 D in the pirenzepine once a day group, and 0.84 D in the control group. In the U.S. study, myopia progression was 0.26 D in one year in the pirenzepine (once a day) group and 0.53 D in the control group. recently, the second year results of this study showed an increase in treatment effect from 0.3 in the first year to Some considerations for the evaluation of myopia progression control treatment Many of the studies of myopia progression control treatment described above showed statistically significant differences between the trial and control groups, but not clinically significant differences. This is partly because many treatments are effective initially, but after the initial months, the treatment effect increases minimally or not at all, and this effect has been seen in both medication and lens therapy. A possible solution is to switch to another treatment when the initially used method of myopia progression control is no longer effective, or to set a gap period (during which there is no treatment). Another reason for the limited effect of treatment is that the criteria for patient entry in clinical trials are very broad, but the treatment, especially the lenses, may not be effective for all myopia. It may also be necessary to include factors such as the degree of myopia, oculomotor parameters (e.g., accommodation, occlusion), and parental refractive status in the treatment regimen for a particular patient. For example, PALs were shown in the COMET study to be more effective than SVLs in slowing myopic progression in patients with low-grade myopia, large accommodation lag, and both parents’ myopia. Finally, if a treatment is found to slow myopic progression for more than a year with few side effects, it may be considered for children at risk for myopic progression. However, at this time, we cannot confirm with certainty which children are at high risk for myopic progression. Refractive errors of less than +0.75 D at the age of first school entry are considered to be at high risk for myopia progression in the teens and tweens. Possible future treatments for myopia progression control Correction of peripheral refractive error/aperture and extensive outdoor activities are possible promising treatment options. Recent animal studies suggest that visual signals from the macula may not be important for normal eye growth, as the peripheral retina is shown to modulate orthokeratology and produce myopia due to abnormal visual input from the peripheral retina. Correction of peripheral refractive error/aperture can be achieved with specially designed daytime wear keratocontact lenses or keratoplasty lenses. Research on this information is ongoing. Providing children with enough time outdoors each week may be the easiest way to delay myopia, but it still has to be confirmed by rigorous research, and the mechanisms have to be studied. A number of large studies around the world have reported that children who spend more time outdoors have a lower incidence of myopia than children who spend less time outdoors. Research suggests that being outdoors may be more important than the activity itself, as indoor activity has little to do with myopia. It may have something to do with the outdoor light environment, etc.