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Purpose: To model juvenile-onset myopia progression as a function of race/ethnicity, age, sex, parental history of myopia, and time spent reading or in outdoor/sports activity., Methods: Subjects were 594 children in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study with at least three study visits: one visit with a spherical equivalent (SPHEQ) less myopic/more hyperopic than -0.75 diopter (D), the first visit with a SPHEQ of -0.75 D or more myopia (onset visit), and another after myopia onset. Myopia progression from the time of onset was modeled using cubic models as a function of age, race/ethnicity, and other covariates., Results: Younger children had faster progression of myopia; for example, the model-estimated 3-year progression in an Asian American child was -1.93 D when onset was at age 7 years compared with -1.43 D when onset was at age 10 years. Annual progression for girls was 0.093 D faster than for boys. Asian American children experienced statistically significantly faster myopia progression compared with Hispanic (estimated 3-year difference of -0.46 D), Black children (-0.88 D), and Native American children (-0.48 D), but with similar progression compared with White children (-0.19 D). Parental history of myopia, time spent reading, and time spent in outdoor/sports activity were not statistically significant factors in multivariate models., Conclusions: Younger age, female sex, and racial/ethnic group were the factors associated with faster myopic progression. This multivariate model can facilitate the planning of clinical trials for myopia control interventions by informing the prediction of myopia progression rates.

Purpose: To investigate the ratio of accommodative convergence per diopter of accommodative response (AC/A ratio) before, during, and after myopia onset., Methods: Subjects were 698 children aged 6 to 14 years who became myopic and 430 emmetropic children participating in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error. Refractive error was measured using cycloplegic autorefraction, near work by parent survey, and the AC/A ratio by simultaneously monitoring convergence and accommodative response. The response AC/A ratios of children who became myopic were compared with age-, sex-, and ethnicity-matched model estimates for emmetropic children from 5 years before through 5 years after the onset of myopia., Results: The response AC/A ratio was not significantly different between the two groups 5 years before onset, then increased monotonically in children who became myopic until reaching a plateau at myopia onset of about 7 Δ/D compared to about 4 Δ/D for children who remained emmetropic (differences between groups significant at P < 0.01 from 4 years before onset through 5 years after onset). A higher AC/A ratio was associated with greater accommodative lag but not with the rate of myopia progression regardless of the level of near work., Conclusions: An increasing AC/A ratio is an early sign of becoming myopic, is related to greater accommodative lag, but does not affect the rate of myopia progression. The association with accommodative lag suggests that the AC/A ratio increase is from greater neural effort needed per diopter of accommodation rather than change in the accommodative convergence crosslink gain relationship.

Purpose: We determined the correlation between sibling refractive errors adjusted for shared and unique environmental factors using data from the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study., Methods: Refractive error from subjects' last study visits was used to estimate the intraclass correlation coefficient (ICC) between siblings. The correlation models used environmental factors (diopter-hours and outdoor/sports activity) assessed annually from parents by survey to adjust for shared and unique environmental exposures when estimating the heritability of refractive error (2*ICC)., Results: Data from 700 families contributed to the between-sibling correlation for spherical equivalent refractive error. The mean age of the children at the last visit was 13.3 ± 0.90 years. Siblings engaged in similar amounts of near and outdoor activities (correlations ranged from 0.40-0.76). The ICC for spherical equivalent, controlling for age, sex, ethnicity, and site was 0.367 (95% confidence interval [CI] = 0.304, 0.420), with an estimated heritability of no more than 0.733. After controlling for these variables, and near and outdoor/sports activities, the resulting ICC was 0.364 (95% CI = 0.304, 0.420; estimated heritability no more than 0.728, 95% CI = 0.608, 0.850). The ICCs did not differ significantly between male-female and single sex pairs., Conclusions: Adjusting for shared family and unique, child-specific environmental factors only reduced the estimate of refractive error correlation between siblings by 0.5%. Consistent with a lack of association between myopia progression and either near work or outdoor/sports activity, substantial common environmental exposures had little effect on this correlation. Genetic effects appear to have the major role in determining the similarity of refractive error between siblings., (Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.)

Purpose: To investigate the association between myopia progression and time spent outdoors and in various visual activities., Methods: Subjects were 835 myopes (both principal meridians -0.75 diopters [D] or more myopia by cycloplegic autorefraction) in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study with both progression data and at least one measure of activity associated with a progression interval. Activity data were collected by parental survey. Average activity level (mean of the activity at the beginning and the end of a 1-year progression interval) was the primary predictor in a repeated-measures mixed model. The model controlled for age, sex, ethnicity, refractive error at the beginning of the progression interval, clinic site, and type of autorefractor used. Effects were scaled based on performing an additional 10 hours per week of an activity., Results: In the multivariate model, the number of hours of reading for pleasure per week was not significantly associated with annual myopia progression at an a priori level of P ≤ 0.01, nor were the other near activities, the near-work composite variable diopter-hours, or outdoor/sports activity. The magnitude of effects was clinically small. For example, the largest multivariate effect was that each additional 10 hours of reading for pleasure per week at the end of a progression interval was associated with an increase in average annual progression by -0.08 D., Conclusions: Despite protective associations previously reported for time outdoors reducing the risk of myopia onset, outdoor/sports activity was not associated with less myopia progression following onset. Near work also had little meaningful effect on the rate of myopia progression.

Purpose: To investigate visual activities before and after the onset of juvenile myopia., Methods: The subjects were 731 incident myopes (-0.75 D or more myopia on cycloplegic autorefraction in both meridians) and 587 emmetropes (between -0.25 and +1.00 D) in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study. Parents supplied visual activity data annually. Data from myopic children 5 years before through 5 years after myopia onset were compared to data from age-, sex-, and ethnicity-matched models of children who remained emmetropic., Results: Hours per week spent reading or using a computer/playing video games did not differ between the groups before myopia onset; however, hours per week for both activities were significantly greater in myopes than in emmetropes at onset and in 4 of the 5 years after onset by 0.7 to 1.6 hours per week. Hours per week spent in outdoor/sports activities were significantly fewer for children who became myopic 3 years before onset through 4 years after onset by 1.1 to 1.8 hours per week. Studying and TV watching were not significantly different before myopia onset., Conclusions: Before myopia onset, near work activities of future myopic children did not differ from those of emmetropes. Those who became myopic had fewer outdoor/sports activity hours than the emmetropes before, at, and after myopia onset. Myopia onset may influence children's near work behavior, but the lack of difference before onset argues against a major causative role for near work. Less outdoor/sports activity before myopia onset may exert a stronger influence on development than near work.

Purpose: To investigate whether relative peripheral hyperopia is a risk factor for either the onset of myopia in children or the rate of myopic progression., Methods: The risk of myopia onset was assessed in 2043 nonmyopic third-grade children (mean age ± SD = 8.8 ± 0.52 years) participating in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study between 1995 and 2007, 324 of whom became myopic by the eighth grade. Progression analyses used data from 774 myopic children in grades 1 to 8. Foveal and relative peripheral refractive error 30° in the nasal visual field was measured annually by using cycloplegic autorefraction. Axial length was measured by A-scan ultrasonography., Results: The association between more hyperopic relative peripheral refractive error in the third grade and the risk of the onset of myopia by the eighth grade varied by ethnic group (Asian children odds ratio [OR] = 1.56, 95% confidence interval [CI] = 1.06-2.30; African-American children OR = 0.75, 95% CI = 0.58-0.96; Hispanics, Native Americans, and whites showed no significant association). Myopia progression was greater per diopter of more hyperopic relative peripheral refractive error, but only by a small amount (-0.024 D per year; P = 0.02). Axial elongation was unrelated to the average relative peripheral refractive error (P = 0.77), regardless of ethnicity., Conclusions: Relative peripheral hyperopia appears to exert little consistent influence on the risk of the onset of myopic refractive error, on the rate of myopia progression, or on axial elongation.

Purpose: To determine the utility of a child's first grade refractive error and parental history of myopia as predictors of myopia onset between the second and eighth grades., Methods: Subjects were nonmyopic children in the first grade who were enrolled in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study. Myopia was defined as -0.75 D or more myopia in both meridians (by cycloplegic autorefraction). The children were classified as having a high (versus low) risk of myopia with a cycloplegic sphere cutoff of +0.75 D or less (versus more) of hyperopia. Parental myopia was determined by a parent-completed survey. Discrete-time survival models predicted the risk of myopia., Results: Of the 1854 nonmyopic first graders, 21.3% were at high risk of myopia. More high-risk subjects had two myopic parents, 25.4% compared with 16.5% in the low-risk group (P < 0.0001). The low-risk survival function was similar regardless of the number of myopic parents. Among high-risk eighth graders, the survival probability was lower than in the low-risk group, decreasing with an increase in the number of myopic parents. The sensitivity and specificity of first grade refractive error with the number of myopic parents as predictors for myopia onset were 62.5% and 81.9%, respectively., Conclusions: First grade refractive error and the number of myopic parents can predict a child's risk of myopia; however, because the sensitivity of these factors is low, these two predictors may not be sufficient at this young age when a more accurate prediction of myopia onset is needed.

Purpose: The C677T polymorphism of methylene tetrahydrofolate reductase (MTHFR) lowers the activity of this enzyme, producing moderate elevation of blood levels of homocysteine (Hcy) and lowering the levels of 5-methyl-tetrahydro-folic acid (5-MeTHFA), methionine (Meth), and S-adenosylmethionine (SAM). In this study we examined 100 apparently normal subjects of both sexes (average age 25.6 +/- 4.25) for the genotypic presence of the T allele and its association with accommodative amplitude (AA)., Methods: The amplitude of accommodation was measured by the subjective "push-up" technique. DNA from buccal cells was genotyped for the C677T polymorphism of MTHFR by a PCR-restriction fragment length polymorphism genotyping assay. Descriptive statistics were obtained by frequency distribution and univariate analysis. Comparisons between monocular and binocular AA were obtained by t-test statistics or ANOVA. Associations between genotype and phenotype were analyzed using regression models., Results: The C677T polymorphism was associated with decreased binocular AA (p = 0.0087). Monocular AA was not associated with the MTHFR genotype., Conclusions: Our results suggest a role for the C677T polymorphism in damaging the neural aspects of binocular vergence accommodation. The postulated neural damage could be due to the decreased formation of 5-MeTHFA and the defective synthesis of Meth, SAM and neurotransmitters or other methyl acceptors in nervous tissue of bearers of the C677T polymorphism. The differential effect upon monocular and binocular accommodation is hypothetically explained by a greater involvement of methylation reactions in vergence accommodation. A similar mechanism is proposed to explain the prevalent insufficient accommodation of Down's syndrome in which the blood levels of Meth and SAM are reduced.

Purpose: To evaluate refractive error, axial length, and relative peripheral refractive error before, during the year of, and after the onset of myopia in children who became myopic compared with emmetropes., Methods: Subjects were 605 children 6 to 14 years of age who became myopic (at least -0.75 D in each meridian) and 374 emmetropic (between -0.25 D and +1.00 D in each meridian at all visits) children participating between 1995 and 2003 in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study. Axial length was measured annually by A-scan ultrasonography. Relative peripheral refractive error (the difference between the spherical equivalent cycloplegic autorefraction 30 degrees in the nasal visual field and in primary gaze) was measured using either of two autorefractors (R-1; Canon, Lake Success, NY [no longer manufactured] or WR 5100-K; Grand Seiko, Hiroshima, Japan). Refractive error was measured with the same autorefractor with the subjects under cycloplegia. Each variable in children who became myopic was compared to age-, gender-, and ethnicity-matched model estimates of emmetrope values for each annual visit from 5 years before through 5 years after the onset of myopia., Results: In the sample as a whole, children who became myopic had less hyperopia and longer axial lengths than did emmetropes before and after the onset of myopia (4 years before through 5 years after for refractive error and 3 years before through 5 years after for axial length; P < 0.0001 for each year). Children who became myopic had more hyperopic relative peripheral refractive errors than did emmetropes from 2 years before onset through 5 years after onset of myopia (P < 0.002 for each year). The fastest rate of change in refractive error, axial length, and relative peripheral refractive error occurred during the year before onset rather than in any year after onset. Relative peripheral refractive error remained at a consistent level of hyperopia each year after onset, whereas axial length and myopic refractive error continued to elongate and to progress, respectively, although at slower rates compared with the rate at onset., Conclusions: A more negative refractive error, longer axial length, and more hyperopic relative peripheral refractive error in addition to faster rates of change in these variables may be useful for predicting the onset of myopia, but only within a span of 2 to 4 years before onset. Becoming myopic does not appear to be characterized by a consistent rate of increase in refractive error and expansion of the globe. Acceleration in myopia progression, axial elongation, and peripheral hyperopia in the year prior to onset followed by relatively slower, more stable rates of change after onset suggests that more than one factor may influence ocular expansion during myopia onset and progression.

Purpose: To evaluate accommodative lag before, during the year of, and after the onset of myopia in children who became myopic, compared with emmetropes., Methods: The subjects were 568 children who became myopic (at least -0.75 D in each meridian) and 539 children who were emmetropic (between -0.25 D and +1.00 D in each meridian at all visits) participating between 1995 and 2003 in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study. Accommodative lag was measured annually with either a Canon R-1 (Canon USA., Lake Success, NY; no longer manufactured) or a Grand Seiko WR 5100-K (Grand Seiko Co., Hiroshima, Japan) autorefractor. Subjects wore their habitual refractive corrections while viewing a letter target accommodative stimulus of 4 D (either in a Badal system or at 25 cm from the subject, designated Badal and near, respectively) or of 2 D (Badal only). Refractive error was measured with the same autorefractor in subjects under cycloplegia. Accommodative lag in children who became myopic was compared to age-, gender-, and ethnicity-matched model estimates of emmetropic values for each annual visit from 5 years before, through 5 years after, the onset of myopia., Results: In the sample as a whole, accommodative lag was not significantly different in children who became myopic compared with model estimates in emmetropes in any year before onset of myopia for either the 4-D or 2-D Badal stimulus. For the 4-D near target, there was only a greater amount of accommodative lag in children who became myopic compared with emmetropes 4 years before onset (difference, 0.22 D; P = 0.0002). Accommodative lag was not significantly elevated during the year of onset of myopia in any of the three measurement conditions (P < 0.82 for all three). A consistently higher lag was seen in children after the onset of their myopia (range, 0.13-0.56 D; P < 0.004 for all comparisons). These patterns were generally followed by each ethnic group, with Asian children typically showing the most, African-American and white children showing the least, and Hispanic children having intermediate accommodative lag., Conclusions: Substantive and consistent elevations in accommodative lag relative to model estimates of lag in emmetropes did not occur in children who became myopic before the onset of myopia or during the year of onset. Increased accommodative lag occurred in children after the onset of myopia. Elevated accommodative lag is unlikely to be a useful predictive factor for the onset of myopia. Increased hyperopic defocus from accommodative lag may be a consequence rather than a cause of myopia.