Li-Fang Hung

Spectacle lenses alter eye growth and the refractive status of young monkeys

The influence of visual experience on ocular development in higher primates is not well understood. To investigate the possible role of defocus in regulating ocular growth, spectacle lenses were used to optically simulate refractive anomalies in young monkeys (for example, myopia or nearsightedness). Both positive and negative lenses produced compensating ocular growth that reduced the lens-induced refractive errors and, at least for low lens powers, minimized any refractive-error differences between the two eyes. These results indicate that the developing primate visual system can detect the presence of refractive anomalies and alter each eyes growth to eliminate these refractive errors. Moreover, these results support the hypothesis that spectacle lenses can alter eye development in young children.

The role of optical defocus in regulating refractive development in infant monkeys

Early in life, the two eyes of infant primates normally grow in a coordinated manner toward the ideal refractive state. We investigated the extent to which lens-induced changes in the effective focus of the eye affected refractive development in infant rhesus monkeys. The main finding was that spectacle lenses could predictably alter the growth of one or both eyes resulting in appropriate compensating refractive changes in both the hyperopic and myopic directions. Although the effective operating range of the emmetropization process in young monkeys is somewhat limited, the results demonstrate that emmetropization in this higher primate, as in a number of other species, is an active process that is regulated by optical defocus associated with the eyes effective refractive state.

Relative peripheral hyperopic defocus alters central refractive development in infant monkeys

Understanding the role of peripheral defocus on central refractive development is critical because refractive errors can vary significantly with eccentricity and peripheral refractions have been implicated in the genesis of central refractive errors in humans. Two rearing strategies were used to determine whether peripheral hyperopia alters central refractive development in rhesus monkeys. In intact eyes, lens-induced relative peripheral hyperopia produced central axial myopia. Moreover, eliminating the fovea by laser photoablation did not prevent compensating myopic changes in response to optically imposed hyperopia. These results show that peripheral refractive errors can have a substantial impact on central refractive development in primates.

Protective Effects of High Ambient Lighting on the Development of Form-Deprivation Myopia in Rhesus Monkeys

PURPOSE Time spent outdoors reduces the likelihood that children will develop myopia, possibly because light levels are much higher outdoors than indoors. To test this hypothesis, the effects of high ambient lighting on vision-induced myopia in monkeys were determined. METHODS Monocular form deprivation was imposed on eight infant rhesus monkeys. Throughout the rearing period (23 ± 2 to 132 ± 8 days), auxiliary lighting increased the cage-level illuminance from normal lighting levels (15-630 lux) to ∼25,000 lux for 6 hours during the middle of the daily 12-hour light cycle. Refractive development and axial dimensions were assessed by retinoscopy and ultrasonography, respectively. Comparison data were obtained in previous studies from 18 monocularly form-deprived and 32 normal monkeys reared under ordinary laboratory lighting. RESULTS Form deprivation produced axial myopia in 16 of 18 normal-light-reared monkeys. In contrast, only 2 of the 8 high-light-reared monkeys developed myopic anisometropias, and in 6 of these monkeys, the form-deprived eyes were more hyperopic than their fellow eyes. The treated eyes of the high-light-reared monkeys were more hyperopic than the form-deprived eyes of the normal-light-reared monkeys. In addition, both eyes of the high-light-reared monkeys were more hyperopic than those of normal monkeys. CONCLUSIONS High ambient lighting retards the development of form-deprivation myopia in monkeys. These results are in agreement with the hypothesis that the protective effects of outdoor activities against myopia in children are due to exposure to the higher light levels encountered outdoors. It is possible that therapeutic protection against myopia can be achieved by manipulating indoor lighting levels.

Form-deprivation myopia in monkeys is a graded phenomenon.

To shed light on the potential role of the phenomenon of form-deprivation myopia in normal refractive development, we investigated the degree of image degradation required to produce axial myopia in rhesus monkeys. Starting at about 3 weeks of age, diffuser spectacle lenses were employed to degrade the retinal image in one eye of 13 infant monkeys. The diffusers were worn continuously for periods ranging between 11 and 19 weeks. The effects of three different strengths of optical diffusers, which produced reductions in image contrast that ranged from about 0.5 to nearly 3 log units, were assessed by retinoscopy and A-scan ultrasonography. Control data were obtained from ten normal infants and three infants reared with clear, zero-powered lenses over both eyes. Eleven of the 13 treated infants developed form-deprivation myopia. Qualitatively similar results were obtained for the three diffuser groups, however, the degree of axial myopia varied directly with the degree of image degradation. Thus, form-deprivation myopia in monkeys is a graded phenomenon and can be triggered by a modest degree of chronic image degradation.

Normal Ocular Development in Young Rhesus Monkeys (Macaca mulatta)

PURPOSE The purpose of this study was to characterize normal ocular development in infant monkeys and to establish both qualitative and quantitative relationships between human and monkey refractive development. METHODS The subjects were 214 normal rhesus monkeys. Cross-sectional data were obtained from 204 monkeys at about 3 weeks of age and longitudinal data were obtained from 10 representative animals beginning at about 3 weeks of age for a period of up to 5 years. Ocular development was characterized via refractive status, corneal power, crystalline lens parameters, and the eyes axial dimensions, which were determined by retinoscopy, keratometry, phakometry and A-scan ultrasonography, respectively. RESULTS From birth to about 5 years of age, the growth curves for refractive error and most ocular components (excluding lens thickness and equivalent lens index) followed exponential trajectories and were highly coordinated between the two eyes. However, overall ocular growth was not a simple process of increasing the scale of each ocular component in a proportional manner. Instead the rates and relative amounts of change varied within and between ocular structures. CONCLUSION The configuration and contribution of the major ocular components in infant and adolescent monkey eyes are qualitatively and quantitatively very comparable to those in human eyes and their development proceeds in a similar manner in both species. As a consequence, in both species the adolescent eye is not simply a scaled version of the infant eye.

Developmental visual system anomalies and the limits of emmetropization

Optical defocus can within certain limits predictably alter ocular growth and refractive development in infant monkeys. However defocus, particularly unilateral defocus associated with anisometropia, can also promote abnormal sensory and motor development. We investigated the relationship between the effective operating range for emmetropization in infant monkeys and the refractive errors that produced amblyopia. Specifically, we examined the refractive-error histories of monkeys that did not demonstrate compensating ocular growth for imposed refractive errors and used operant psychophysical methods to measure contrast sensitivity functions for 17 infant monkeys that were reared with varying degrees of optically imposed anisometropia. Imposed anisometropias that were within the operating range of the monkeys emmetropization process were eliminated by differential interocular growth and did not produce amblyopia. On the other hand imposed anisometropias that failed to initiate compensating growth consistently produced amblyopia; the depth of the amblyopia varied directly with the magnitude of the imposed anisometropia. These results indicate that amblyopia and anisometropia are frequently associated because persistent anisometropia causes amblyopia. However, the failure of emmetropization in infants with refractive conditions that are known to promote sensory and motor anomalies indicates that factors other than optical defocus, presumably factors associated with the development of amblyopia and/or strabismus, can also influence early refractive development and in some cases cause anisometropia.

Negative lens-induced myopia in infant monkeys: effects of high ambient lighting.

PURPOSE To determine whether high light levels, which have a protective effect against form-deprivation myopia, also retard the development of lens-induced myopia in primates. METHODS Hyperopic defocus was imposed on 27 monkeys by securing -3 diopter (D) lenses in front of one eye. The lens-rearing procedures were initiated at 24 days of age and continued for periods ranging from 50 to 123 days. Fifteen of the treated monkeys were exposed to normal laboratory light levels (∼350 lux). For the other 12 lens-reared monkeys, auxiliary lighting increased the illuminance to 25,000 lux for 6 hours during the middle of the daily 12 hour light cycle. Refractive development, corneal power, and axial dimensions were assessed by retinoscopy, keratometry, and ultrasonography, respectively. Data were also obtained from 37 control monkeys, four of which were exposed to high ambient lighting. RESULTS in normal- and high-light-reared monkeys, hyperopic defocus accelerated vitreous chamber elongation and produced myopic shifts in refractive error. the high light regimen did not alter the degree of myopia (high light: -1.69 ± 0.84 D versus normal light: -2.08 ± 1.12 D; P = 0.40) or the rate at which the treated eyes compensated for the imposed defocus. Following lens removal, the high light monkeys recovered from the induced myopia. The recovery process was not affected by the high lighting regimen. CONCLUSIONS In contrast to the protective effects that high ambient lighting has against form-deprivation myopia, high artificial lighting did not alter the course of compensation to imposed defocus. These results indicate that the mechanisms responsible for form-deprivation myopia and lens-induced myopia are not identical.

Peripheral refraction in normal infant rhesus monkeys.

PURPOSE To characterize peripheral refractions in infant monkeys. METHODS Cross-sectional data for horizontal refractions were obtained from 58 normal rhesus monkeys at 3 weeks of age. Longitudinal data were obtained for both the vertical and horizontal meridians from 17 monkeys. Refractive errors were measured by retinoscopy along the pupillary axis and at eccentricities of 15 degrees , 30 degrees , and 45 degrees . Axial dimensions and corneal power were measured by ultrasonography and keratometry, respectively. RESULTS In infant monkeys, the degree of radial astigmatism increased symmetrically with eccentricity in all meridians. There were, however, initial nasal-temporal and superior-inferior asymmetries in the spherical equivalent refractive errors. Specifically, the refractions in the temporal and superior fields were similar to the central ametropia, but the refractions in the nasal and inferior fields were more myopic than the central ametropia, and the relative nasal field myopia increased with the degree of central hyperopia. With age, the degree of radial astigmatism decreased in all meridians, and the refractions became more symmetrical along both the horizontal and vertical meridians. Small degrees of relative myopia were evident in all fields. CONCLUSIONS As in adult humans, refractive error varied as a function of eccentricity in infant monkeys and the pattern of peripheral refraction varied with the central refractive error. With age, emmetropization occurred for both central and peripheral refractive errors, resulting in similar refractions across the central 45 degrees of the visual field, which may reflect the actions of vision-dependent, growth-control mechanisms operating over a wide area of the posterior globe.

Prevalence of astigmatism in infant monkeys

PURPOSE Human infants exhibit a high prevalence of astigmatism. Although macaque monkeys are commonly used as animal models in experiments on early ocular growth and emmetropization, the prevalence of astigmatism in infant monkeys is unexplored. In this study we examine the prevalence and nature of astigmatism in infant monkeys. METHODS Refractive and corneal astigmatism were measured in 132, 2-5-week-old rhesus monkeys (Macaca mulatta) using cycloplegic retinoscopy and keratometry, respectively. Longitudinal measures of refractive development were obtained from 16 normal infants over the first 6 months of life. RESULTS Infant monkeys exhibited a low prevalence of astigmatism. Approximately 90% of the 2-5-week-old infants had <1.00 D of either refractive or corneal astigmatism. When refractive astigmatism was observed, it was well correlated with the direction and magnitude of corneal astigmatism. When corneal astigmatism was >1.00 D (n=20), it was predominantly against-the-rule in nature (70.0%). The infant monkeys that were followed longitudinally rarely showed significant astigmatic errors at any time during the observation period. When these infant monkeys exhibited significant astigmatism, it was usually transient and not present on subsequent measurements. CONCLUSIONS Unlike human infants, infant monkeys exhibit relatively little astigmatism. The low prevalence of astigmatism during early development suggests that astigmatism does not provide an essential cue for vision-dependent eye growth in infant primates.