Use of PALs compared with SVLs slowed the progression of myopia in COMET children by a small, statistically significant amount only during the first year. The size of the treatment effect remained similar and significant for the next 2 years. The results provide some support for the COMET rationale-that is, a role for defocus in progression of myopia. The small magnitude of the effect does not warrant a change in clinical practice.

The results support the COMET rationale (i.e., a role for retinal defocus in myopia progression). In clinical practice in the United States children with large lags of accommodation and near esophoria often are prescribed PALs or bifocals to improve visual performance. Results of this study suggest that such children, if myopic, may have an additional benefit of slowed progression of myopia.

Experiments in several species have shown that the axial elongation rate of the developing eye can be increased or decreased by manipulating the visual environment, indicating that a visually guided emmetropization mechanism controls the enlargement of the vertebrate eye during postnatal development. Previous studies in tree shrews (Tupaia glis belangeri) suggest that regulation of the mechanical properties of the sclera may be an important part of the mechanism that controls the axial elongation rate in this mammal. To learn whether the mechanical properties of the sclera change when the axial elongation rate is increased or decreased under visual control, uniaxial mechanical tests were performed on 3-mm wide strips of tree shrew sclera. The creep rate was measured under 1, 3, and 5 g of tension, maintained for 30 min at each level. The modulus of elasticity was calculated from the elastic extension that occurred when the force was increased from 0 to 1 g, 1 to 3 g, and 3 to 5 g. Both were measured in the sclera of both eyes from animals exposed to four experimental conditions: (1) Normal development, at intervals from the day of natural eyelid opening (day 1 of visual experience [VE]) to greater than 5 years of age; (2) Monocular form deprivation (MD), for varying lengths of time; (3) Recovery from MD; (4) Monocular -5 D lens treatment. The creep rate was low in normal animals (1-2% elongation/h), did not change significantly between day 1 and day 75 of VE, and was not significantly different between the two eyes. Four days of MD produced a 200-300% increase in creep rate in the sclera from deprived eyes. Creep rate remained similarly elevated after 11 and 21 days of MD. After 2 days of recovery, which followed 11 days of MD, the creep rate of sclera from the recovering eyes was below normal levels. In animals that wore a monocular -5 D lens for up to 21 days, creep rate increased, and then decreased, in concert with the increase, and decrease, in axial elongation rate as the eyes compensated for the lens. The modulus of elasticity of the sclera was not significantly affected by any manipulation. The temporal correspondence between changes in axial elongation rate and changes in creep rate support the hypothesis that regulation of the time-dependent mechanical properties of fibrous mammalian sclera plays a role in controlling axial elongation rate during both normal emmetropization and the development of refractive errors.

The purpose of this study was to learn whether visual form deprivation, which produces myopia in the deprived eye, alters the scleral extracellular matrix in tree shrew, a mammal closely related to primates. Axial myopia was induced in 10 tree shrews by monocular deprivation imposed with a translucent diffuser. The other eye in each animal was an untreated control. After 21 days of deprivation the refractive state and axial component dimensions were measured and the eyes were assayed for levels of DNA, hydroxyproline, and sulfated glycosaminoglycans (GAGs) in samples of the sclera and the cornea. In comparison to the open control eye, the deprived eyes became myopic and elongated. In the sclera, DNA levels were not significantly changed from the control eye. Sulfated GAG levels were significantly lower in the deprived eyes, as compared to the control eyes, at the posterior pole (-15.6%), at the nasal equatorial region (-18.1%), and in the rest of the sclera (-11.6%). The hydroxyproline level was significantly lower only at the posterior pole (-11.8%). Levels of sulfated GAGs were significantly reduced relative to DNA and relative to hydroxyproline in the total sclera. No significant changes were found in the cornea. The lower level of sulfated GAGs throughout the sclera of the deprived eyes, as compared with the control eyes, suggests that the deprived sclera contained less proteoglycan, or that the proteoglycans were less glycosylated or less sulfated. In contrast, the regional reduction of hydroxyproline suggests that collagen accumulation was specifically reduced only at the posterior pole of deprived eyes. These results suggest that form deprivation slows or reverses the normal process of extracellular matrix accumulation in the sclera of this mammal. This may allow the sclera to be more distensible, permitting the vitreous chamber elongation and resultant myopia.

To identify the baseline factors independently related to 3-year myopia progression and axial elongation in COMET.Methods: A total of 469 children were enrolled, randomly assigned to progressive addition lenses with aϩ2.00 diopter (D) addition or to single vision lenses and observed for 3 years. Eligible children were 6 to 11 years old, with spherical equivalent myopia of − 1.25 to−4.50 D, bilaterally. The primary and secondary outcomes, myopia progression by cycloplegic autorefraction and axial elongation by A-scan ultrasonography, were measured annually. Multiple linear regression was used to adjust for covariates, including treatment.Results: Younger baseline age (6-7 vs 11 years, 8 vs 11 years, and 9 vs 11 years, PϽ.001; 10 vs 11 years, P=.04), female sex (P=.01), and each ethnic group compared with African Americans (Asian, P = .02; Hispanic, P = .002; mixed, P=.002; white, P = .001) were independently as-sociated with faster 3-year progression. Children aged 6 to 7 years had the fastest progression of all age groups, progressing by a mean (±SD) of 1.31 D±0.13 more than children aged 11 years. Females progressed 0.16 D more than the males. Children of mixed, Hispanic, Asian, and white ethnicity progressed more than African American children by 0.49 D±0.16, 0.33 D±0.11, 0.32 D±0.13, 0.27 D±0.08, respectively. Age and ethnicity, but not sex, were independently associated with axial elongation. Among these myopic children, a 0.5 mm increase in axial length was associated with 1 D of myopia progression.Conclusions: Younger baseline age was the strongest factor independently associated with faster myopic progression and greater axial elongation at 3 years. African American children had less myopic progression and axial elongation than the other ethnic groups.

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Recent epidemiological evidence in children indicates that time spent outdoors is protective against myopia. Studies in animal models (chick, macaque, tree shrew) have found that light levels (similar to being in the shade outdoors) that are mildly elevated compared to indoor levels, slow form-deprivation myopia and (in chick and tree shrew) lens-induced myopia. Normal chicks raised in low light levels (50 lux) with a circadian light on/off cycle often develop spontaneous myopia. We propose a model in which the ambient illuminance levels produce a continuum of effects on normal refractive development and the response to myopiagenic stimuli such that low light levels favor myopia development and elevated levels are protective. Among possible mechanisms, elevation of retinal dopamine activity seems the most likely. Inputs from intrinsically-photosensitive retinal ganglion cells (ipRGCs) at elevated light levels may be involved, providing additional activation of retinal dopaminergic pathways.

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