The Correction of Myopia Evaluation Trial: lessons from the study design.

The Correction of Myopia Evaluation Trial (COMET), a multicentre clinical trial based in 4 schools of optometry in the United States, evaluated the effect of progressive addition lenses versus single vision lenses on myopia progression in an ethnically diverse group of 469 myopic children aged 6 to 11 years. Completion of the clinical trial phase of the study provides an opportunity to evaluate aspects of the study design that contribute to its success. This article describes aspects of the study design that were influential in ensuring the smooth conduct of COMET. These include a dedicated team of investigators, an organisational structure with strong leadership and an independent Co-ordinating Centre, regular communication among investigators, flexible and creative approaches to recruitment and retention, sensitivity to concerns for child safety and child participation, and methods for enhancing and monitoring data reliability. The experience with COMET has provided a number of valuable lessons for all aspects of the study design that should benefit the development and implementation of future clinical trials, particularly those done in similar populations of children. The use of a carefully designed protocol using standard methods by dedicated members of the study team is essential in ensuring achievement of the study aims.

The Correction of Myopia Evaluation Trial (COMET): design and general baseline characteristics.

The Correction of Myopia Evaluation Trial (COMET) is a multicenter, randomized, double-masked, controlled clinical trial evaluating whether there is a difference in the progression of myopia between children wearing progressive addition lenses (PALs) versus conventional single vision lenses (SVLs), as measured by cycloplegic autorefraction. Axial length, measured by A-scan ultrasonography, is an additional outcome measure. To meet the recruitment goal of 450 participants, eligible children ages 6-11 years (inclusive) with myopia in both eyes (spherical equivalent between -1.25 diopters (D) and -4.50 D, astigmatism < or = 1.50 D, and anisometropia < 1.00 D) were recruited at four clinical centers between September 1997 and September 1998. Children who participated were assigned to receive PALs (Varilux Comfort with a +2.00 D addition) or SVLs. Measures include standardized cycloplegic autorefraction (Nidek ARK700A autorefractor), axial length (Sonomed A2500 ultrasound), subjective refraction (Marco TRS system), visual acuity (modified Early Treatment Diabetic Retinopathy Study protocol), accommodation (Canon R-1), and phoria (cover test and Maddox rod). Outcome measures are collected annually; adherence is assessed and prescriptions updated semiannually. Participants are being followed for at least 3 years. COMET enrolled 469 children. Their mean age is 9.3 years (range 6-11 years); 52% are female. COMET children are ethnically diverse, according to a self-report with 46% White, 26% African American, 14% Hispanic, and 8% Asian. Best-corrected visual acuity is better than 20/32 in both eyes. Baseline mean (+/-SD) cycloplegic refractive correction is -2.38 D (+/-0.81) in the right eye and -2.40 D (+/-0.82) in the left eye; mean (+/-SD) axial length is 24.1 mm (+/-0.7) in both eyes. Follow-up of these children will provide a first step in answering the important question of whether there are effective means to slow myopia progression. Study results should be applicable to a large proportion of children with myopia. The study will also provide useful information on myopia progression in children wearing conventional single vision lenses.

Astigmatism and the development of myopia in children.

While it is now established that astigmatism is more prevalent in infants and young children than in the adult population, little is known about the functional significance of this astigmatism, especially its role, if any, in emmetropization and the development of myopia. Manifest refractions (mean of 16 per subject) were obtained from 245 subjects starting in the first year, with 6-23 years of regular follow-up. Results showed that infantile astigmatism is associated with increased astigmatism and myopia during the school years. Two possible mechanisms underlying this association are discussed: (1) infantile astigmatism disrupts focusing mechanisms; and (2) ocular growth induces astigmatism and myopia.

Effects of spectacle intervention on the progression of myopia in children.

The literature on myopigenesis suggests an active emmetropization mechanism regulated by optical defocus. The strongest evidence comes from compensatory ocular growth in response to lens-induced defocus in different species of animals. Based on these results, it has been suggested that, however useful, spectacle intervention for the optical correction of human myopia would lead to its exacerbation. The present study seeks to evaluate the progression of juvenile-onset myopia in children differentiated by their lens wear patterns. Data from 43 myopes from our longitudinal study of refraction were evaluated, with myopia defined as a spherical equivalent of at least -0.50 D. Refractions were obtained in the laboratory by noncycloplegic retinoscopy performed by one experienced optometrist at regular intervals. Information regarding the subjects' prescription lens-wearing history was obtained from the subjects and their eye care providers. Based on their wearing patterns, subjects were divided into four categories: (1) full-time wearers; (2) myopes who switched from distance to full-time wear; (3) distance wearers; and (4) nonwearers. Exponential functions were fit to the individual refraction data. The age of onset of myopia, the mean myopia at onset of spectacle wear, and the refractive shift over a period of at least 3 years were derived from these fits. Results show that the 3-year refractive shifts are not significantly different among the four groups. A comparison of the extreme conditions, i.e., full-time vs. nonwear categories, also revealed no significant difference when the data were corrected for age effects despite the fact that the nonwearers exhibited an age-adjusted 3-year progression approximately one-half that of the full-time wearers. In summary, the present study failed to demonstrate any overall effects of spectacle intervention on the progression of human myopia. Further investigation using a larger sample is warranted.

Role of genetic factors in the etiology of juvenile-onset myopia based on a longitudinal study of refractive error.

In an attempt to determine the role of genetic factors in the development of myopia, we examined the relationship of infantile refractive error and parental history to juvenile-onset myopia and analyzed 43 pedigrees affected by juvenile-onset myopia. Refraction data collected at regular intervals from a sample of juvenile subjects participating in a 24-year longitudinal study of refractive error were used. Results showed that children with two myopic parents were 6.42 times as likely to become myopic as children with one or no myopic parents. Furthermore, children who had refractions in the lower half of the distribution at 6 to 12 months of age were 4.33 times as likely to develop myopia as children who had refractions in the upper half of the distribution at 6 to 12 months of age. The pedigree analysis indicated that 63% of individuals considered at risk for developing juvenile-onset myopia actually became myopic, with an equal number of affected males and females. These results suggest that juvenile-onset myopia of moderate amounts may be inherited as a complex trait involving both genetic and environmental factors.

Development of refraction and strabismus.

In the past year, as in recent years, most of the research on the development of refraction has focused on the following: 1) mechanisms whereby the eye can maintain coordinated growth to achieve emmetropia and 2) disruptions of emmetropization resulting in myopia or hyperopia. Preterm children and those with Down syndrome have higher refractive errors than other children, suggesting a failure of emmetropization. One of the most intriguing studies of the past year and one certain to lead to follow-up studies reported that ambient room illumination at night in a child's first two years is associated with a higher prevalence of myopia than sleeping in darkness. Reports on the development of hyperopia showed that it is axial in nature, similar to myopia. The effects of spectacle interventions to correct refractive errors are still being debated, with recent evidence from children suggesting that lenses do not exacerbate myopia. Analyses of risk factors and numerous new screening procedures detect patients with strabismus for referral at a variety of sensitivity and specificity levels. Hyperopia and high AC/A ratios are most clearly associated as causal agents for esotropia and intermittent exotropia. However, the action of even these simple mechanisms is confounded by abnormal binocular fusion mechanisms and the inability of optical correction to align the eyes of many patients. Asymmetric optokinetic nystagmus, latent nystagmus, and dissociated vertical deviation appear to be linked to infantile esotropia from before its onset. But the way the mechanisms underlying these oculomotor anomalies are causally related to the onset of infantile esotropia remains a mystery.

Response AC/A ratios are elevated in myopic children.

In children little is known about the relationship between the AC/A ratio and the development of myopia, although they have been linked in adults. The purpose of this study was to investigate the interaction between accommodation and convergence and its relationship to refractive errors in children. Accommodation was measured for the right eye using the Canon R-1 autorefractor, and concomitant changes in vergence were assessed using a Maddox rod and a Risley prism before the left eye. Thirty-three myopic and 68 emmetropic children were tested wearing best subjective correction while looking at a distant (4.0 m) letter array and a near (0.33 m) one through additional plus and minus lenses. Lens-induced and distance-induced response AC/A ratios were calculated from the data. Both types of AC/A ratios are elevated in myopic children, who show reduced accommodation and enhanced accommodative convergence. Myopic children with esophoria underaccommodate at near. This suggests that a child who is esophoric must relax accommodation to reduce accommodative convergence and maintain single binocular vision. The reduction in accommodation could produce blur during near work, which could induce myopia as in animal models.

Development of refraction and strabismus.

In the past year a number of studies have provided insights into the mechanisms whereby the eye can maintain coordinated growth to achieve emmetropia. Research into factors that may lead to a failure to emmetropize also has been promising. The effect of early spectacle intervention has been debated, with some evidence from animal studies suggesting that lenses may interfere with emmetropization. Human data on this topic are limited but do not appear to show the deleterious effects of lenses reported in the animal studies. The role of early astigmatism in the emmetropization process is not clear. Myopia research continues to hold promise for the eventual discovery of treatments to slow progression. With respect to the development of strabismus, there are many mechanisms for its induction. The problem is to identify the primary ones and their interactions. This article reviews some of the newer candidates, including pulleys that affect extraocular-muscle action and the role of nasally biased monocular optokinetic nystagmus. An understanding of the critical periods of the various visual dimensions involved in the development of strabismus is also crucial.

Development of spatial contrast sensitivity from infancy to adulthood: psychophysical data.

PURPOSE: This study examined changes in contrast sensitivity, the location of the peak of the contrast sensitivity function (CSF), and the shape of the function from infancy to adulthood. METHODS: Contrast thresholds were obtained using behavioral methods, preferential looking for infants, and operant techniques for older children and adults, with the same stimuli for all ages. RESULTS: Contrast sensitivity at the peak improved almost two log units from infancy to adulthood. Much of the shift in the peak to higher spatial frequencies occurred in infancy. Sensitivity was not yet at adult levels at 8 years of age. CONCLUSIONS: The reduction in contrast sensitivity at the lowest frequency between 2 and 4 months of age suggests an increase in lateral inhibition during early infancy. Contrast sensitivity at the peak increased by two log units from then until adulthood.

The oblique effect in Chinese infants and adults.

PURPOSE: Lessened acuity for oblique contours as compared with horizontal and vertical contours, the oblique effect, is characteristic of humans and animals. The magnitude of the oblique effect in humans varies with ethnic origin. Three experiments were performed to determine the source and extent of this variation in Chinese and Caucasian subjects. METHODS AND RESULTS: Experiment I. Acuity for vertical and oblique gratings was measured in Chinese infants with a preferential looking technique. The development of visual acuity for Chinese infants was found to be strikingly similar to that reported for Caucasian infants. For infants of both races at about 1 year of age, the magnitude of the oblique effect was about 1 octave. Experiment II. Acuity for main-axis (horizontal and vertical) and oblique gratings was measured in Chinese and Caucasian adults. The oblique effect in Chinese subjects was significantly smaller than in Caucasian subjects. The Chinese also had significantly better acuity for oblique gratings, but not for main-axis gratings. Experiment III. To determine whether differential sensitivity to main-axis and oblique-axis gratings extends to suprathreshold spatial frequencies, contrast sensitivity for four orientations at each of five spatial frequencies was assessed in Chinese and Caucasian adults. There were no significant differences in contrast sensitivity between Chinese and Caucasian subjects at any spatial frequency. The differential sensitivity increased with increasing spatial frequency for both ethnic groups. CONCLUSION: The difference in the magnitudes of the oblique effect in Chinese and Caucasian subjects appears in acuity thresholds in adults, and may result solely from the Chinese having better acuity for obliquely oriented gratings.

Development of refraction and strabismus.

The goal of current research on the development of refraction is not to establish whether refraction is either genetically programmed or environmentally influenced, but to assess how heredity and environment interact in the genesis of refractive error. The continuing problem in strabismus research is one of cause and effect. Do binocular deficiencies induce strabismus, or is it the other way around? The papers highlighted in this article address these critical issues. The new findings have the potential to influence the treatment and clinical care of patients with refractive errors and strabismus.

A dynamic relationship between myopia and blur-driven accommodation in school-aged children.

Previously we reported that recently myopic children accommodated insufficiently to blur induced by negative lenses. The purpose of the present study was to relate changes in blur-driven accommodation to myopia development in children. Refractive errors and the accommodation response function (ARF) were measured in 23 myopic and 40 emmetropic children on two occasions separated by periods ranging from 6 to 12 months. Repeated measures of accommodation were made with a Canon R-1 autorefractor while negative lenses of increasing power were placed in front of the child's right eye viewing 20/100 letters at 4 m. Concomitant changes in refractive error and in accommodative function over periods of 6-12 months were found to be highly correlated in myopes (r = 0.77) but not in emmetropes (r = 0.09).

Shifts in tonic accommodation after near work are related to refractive errors in children.

A link between changes in tonic accommodation (TA) produced by sustained near work and the development of adult-onset myopia has been suggested in studies of young adults. Measures of TA before and after near work have been lacking in children of school age, which is the most susceptible period for the development and progression of juvenile-onset myopia. In the present study accommodation was measured in 87 children, aged 7 to 16 years, before and after 15 minutes of video game playing. All children were refracted before testing and wore optical correction during measures of accommodation with a Canon R1 autorefractor. Most children showed initial values of TA (far focus minus dark focus) between 0.0 and 1.0 D, with a mean of 0.68 D. Grouped by refractive status, the myopic children initially showed 0.30 D of TA, while the emmetropic children showed 0.75 D and the hyperopic children showed 0.94 D. After playing the video game, TA of the myopes increased by 1.15 D, compared to smaller increases for the emmetropes (0.68 D) and hyperopes (0.24 D). Comparable values have been obtained from young adults. These results indicate that the smallest initial values of TA and the largest inward shifts in TA are found during the period of acquisition and progression of myopia, regardless of age.

The development of eye alignment, convergence, and sensory binocularity in young infants.

PURPOSE: To measure and compare the development of ocular alignment, sensory binocularity, and convergence in infants during the first 5 months of life. METHODS: Healthy infants were tested between 2 and 21 weeks of age. Ocular alignment was measured by the Hirschberg test; convergence was determined by visual examination as an illuminated toy approached an infant's face; and sensory binocularity was measured by preferential looking for fusible versus rivalrous gratings. In experiment 1 we compared the proportion of infants at different ages demonstrating orthotropic ocular alignment with those showing convergence. In experiment 2, we compared the age of onset of convergence to that of sensory binocularity. RESULTS: Experiment 1: Most infants were orthotropic during the first month, and almost all of the others showed small amounts of exotropia. None of the infants showed accurate convergence until 6 weeks of age. By 4 months of age virtually all were orthotropic and had good convergence. Experiment 2: The onset of sensory binocular fusion occurred at 12.8 +/- 3.3 weeks. Full convergence did not occur until 13.7 +/- 3.2 weeks, although the first signs of convergence occurred slightly earlier. For individual infants there was a high correlation between the age of onset of sensory binocularity and convergence, and both onsets occurred earlier in girls than in boys. CONCLUSIONS: Ocular alignment did not require the development of binocularity mechanisms, and the development of binocularity mechanisms did not await the onset of good ocular alignment. The relatively sudden onset of binocularity, both sensory (preference for fusion and stereopsis) and motor (convergence) at about 3 months of age and the high correlation between these measures indicate a common causal mechanism that probably involves refinements in striate cortex circuitry.

Myopic children show insufficient accommodative response to blur.

PURPOSE: The study was performed to establish the relationship between the slope of the accommodative response function and refractive error in children. METHODS: Using an autorefractor, accommodative responses were measured in children under the following conditions. The subjects wore their best subjective refraction to view targets (a 3 x 3 array of 20/100 letters) displayed at seven distances (4.0 to 0.25 m). They viewed letters placed at 4.0 m through a series of negative lenses and letters placed at 0.25 m through a series of positive lenses. RESULTS: Myopic children accommodate significantly less than emmetropic children for real targets at near distances. Compared with emmetropic subjects, myopic children use blur poorly to increase accommodation, as shown by shallow slopes of the accommodative response functions for negative lenses. However, with positive lenses, requiring relaxation of accommodation, there is no significant difference in slope between myopic and emmetropic children. CONCLUSIONS: Blur is not an effective stimulus for accommodation in myopic children.

Detection of amblyopia and development of binocular vision in infants and children.

Studies of visual development indicate that rapid changes occur in the first months of life and that it is during this period that the visual system is prone to aberrant development. The call for visual screening of children younger than 3 years of age is sensible in light of recent research findings. For children with visual problems, some recovery of visual function can occur if treatment is begun early. New tests of stereoacuity and vernier acuity may aid in the diagnosis of amblyopia, which is underestimated by grating acuity measures. Electrophysiologic testing, using visual evoked potentials and electroretinograms, is helpful in diagnosing visual problems at an early age.

From visual acuity to hyperacuity: a 10-year update.

Visual acuity, the most basic measure of developing pattern vision in human infants, has been used extensively for detecting anomalies of vision and oculomotor coordination. In the past 10 years much has been learned about the development of two hyperacuities, namely, vernier acuity and stereoacuity. These two acuities become superior to grating acuity after the third month and remain so throughout life. Compared to females, males show slower development of stereopsis and vernier acuity, but not grating acuity, during the third through sixth months. We have suggested that this may result from the neurotrophic effects of the early pulse of testosterone found in males. Measures of vernier acuity have proven effective in detecting meridional amblyopia in older children who had significant astigmatism in the first year and subsequently lost it. The susceptible period for acquiring meridional amblyopia extends from the second half of the first year to at least the end of the second year. Deviations from the typical oblique effect (equal acuity for vertical and horizontal edges; equal, but lower, acuity for left oblique and right oblique) may result from uncorrected astigmatism early in life.

Binocular function in human infants: correlation of stereoptic and fusion-rivalry discriminations.

Studies of stereopsis in infants have shown that the average age of onset is 3.5 months. This is the same age at which infants first show evidence of another binocular function, namely, preference for binocularly fusible patterns over rivalrous ones. We tracked the development, using two-alternative forced-choice preferential looking, of the two forms of binocular function in 17 infants, 11 male and six female. They were tested at regular intervals until they showed preferences for 1) a fusible pattern (vertical stripes presented to each eye) over a rivalrous one (vertical stripes presented to one eye, horizontal stripes to the other), and 2) a line stereogram of 32 min crossed disparity over a comparable stereogram with zero disparity. The correlation between the age of onset of the fusion preference (mean 12.4 weeks) and the age of onset of stereopsis (mean 11.0 weeks) was r = 0.79. Female infants showed a preference for the fusible stimulus at a mean age of 9.9 weeks, significantly earlier than the males at a mean age of 13.8 weeks. Similarly, females also showed evidence of stereopsis at an earlier age (9.1 weeks compared with 12.1 weeks for males).

Congenital myopic esotropia: a case study.

A congenital myope developed a 20 delta left esotropia at 8 months of age. His eyes aligned immediately with a -4.00 D correction and would become esotropic when the glasses were removed. Before eyeglass wear best corrected acuity was reduced for both eyes with the left eye acuity significantly lower than the right. From age 8 to 12 months with part-time eyeglass wear, acuity improved and became equal for the two eyes. At 12 months of age the eyeglasses were lost and within 1 month the strabismus no longer responded to minus lenses and amblyopia reappeared in the left eye. This indicates that a myopic infant may stop bifixating blurred images beyond his far point and then cease to be able to relax convergence thereafter. It has the broader implication that tonic vergence posture and AC/A ratio may develop according to the visual experience of each infant.