Ying Qiao-Grider

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.

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.

Astigmatism in Monkeys with Experimentally Induced Myopia or Hyperopia

Purpose. Astigmatism is the most common ametropia found in humans and is often associated with large spherical ametropias. However, little is known about the etiology of astigmatism or the reason(s) for the association between spherical and astigmatic refractive errors. This study examines the frequency and characteristics of astigmatism in infant monkeys that developed axial ametropias as a result of altered early visual experience. Methods. Data were obtained from 112 rhesus monkeys that experienced a variety of lens-rearing regimens that were intended to alter the normal course of emmetropization. These visual manipulations included form deprivation (n = 13); optically imposed defocus (n = 48); and continuous ambient lighting with (n = 6) or without optically imposed defocus (n = 6). In addition, data from 19 control monkeys and 39 infants reared with an optically imposed astigmatism were used for comparison purposes. The lens-rearing period started at approximately 3 weeks of age and ended by 4 to 5 months of age. Refractive development for all monkeys was assessed periodically throughout the treatment and subsequent recovery periods by retinoscopy, keratometry, and A-scan ultrasonography. Results. In contrast to control monkeys, the monkeys that had experimentally induced axial ametropias frequently developed significant amounts of astigmatism (mean refractive astigmatism = 0.37 ± 0.33 D [control] vs. 1.24 ± 0.81 D [treated]; two-sample t-test, p < 0.0001), especially when their eyes exhibited relative hyperopic shifts in refractive error. The astigmatism was corneal in origin (Pearson’s r; p < 0.001 for total astigmatism and the JO and J45 components), and the axes of the astigmatism were typically oblique and bilaterally mirror symmetric. Interestingly, the astigmatism was not permanent; the majority of the monkeys exhibited substantial reductions in the amount of astigmatism at or near the end of the lens-rearing procedures. Conclusions. In infant monkeys, visual conditions that alter axial growth can also alter corneal shape. Similarities between the astigmatic errors in our monkeys and some astigmatic errors in humans suggest that vision-dependent changes in eye growth may contribute to astigmatism in humans.

Continuous ambient lighting and lens compensation in infant monkeys.

Purpose. Protracted daily lighting cycles do not promote abnormal ocular enlargement in infant monkeys as they do in a variety of avian species. However, observations in humans suggest that ambient lighting at night may reduce the efficiency of the emmetropization process in primates. To test this idea, we investigated the ability of infant monkeys reared with continuous light to compensate for optically imposed changes in refractive error. Methods. Beginning at about 3 weeks of age, a hyperopic or myopic anisometropia was imposed on 12 infant rhesus monkeys by securing either a −3 D or +3 D lenses in front of one eye and a zero-powered lens in front of the fellow eye. Six of these monkeys were reared with the normal vivarium lights on continuously, whereas the other six lens-reared monkeys were maintained on a 12-h-light/12-h-dark lighting cycle. The ocular effects of the lens-rearing procedures were assessed periodically during the treatment period by cycloplegic retinoscopy, keratometry, and A-scan ultrasonography. Results. Five of six animals in each of the lighting groups demonstrated clear evidence for compensating anisometropic growth. In both lighting groups, eyes that experienced optically imposed hyperopic defocus (−3 D lenses) exhibited faster axial growth rates and became more myopic than their fellow eyes. In contrast, eyes treated with +3 D lenses showed relatively slower axial growth rates and developed more hyperopic refractive errors. The average amount of compensating anisometropia (continuous light, 1.6 ± 0.5 D vs. control, 2.3 ± 0.5 D), the structural basis for the refractive errors, and the ability to recover from the induced refractive errors were also not altered by continuous light exposure. Conclusion. Ambient lighting at night does not appear to overtly compromise the functional integrity of the vision-dependent mechanisms that regulate emmetropization in higher primates.

Nature of the refractive errors in rhesus monkeys (Macaca mulatta) with experimentally induced ametropias

We analyzed the contribution of individual ocular components to vision-induced ametropias in 210 rhesus monkeys. The primary contribution to refractive-error development came from vitreous chamber depth; a minor contribution from corneal power was also detected. However, there was no systematic relationship between refractive error and anterior chamber depth or between refractive error and any crystalline lens parameter. Our results are in good agreement with previous studies in humans, suggesting that the refractive errors commonly observed in humans are created by vision-dependent mechanisms that are similar to those operating in monkeys. This concordance emphasizes the applicability of rhesus monkeys in refractive-error studies.

Wave aberrations in rhesus monkeys with vision-induced ametropias.

The purpose of this study was to investigate the relationship between refractive errors and high-order aberrations in infant rhesus monkeys. Specifically, we compared the monochromatic wave aberrations measured with a Shack-Hartman wavefront sensor between normal monkeys and monkeys with vision-induced refractive errors. Shortly after birth, both normal monkeys and treated monkeys reared with optically induced defocus or form deprivation showed a decrease in the magnitude of high-order aberrations with age. However, the decrease in aberrations was typically smaller in the treated animals. Thus, at the end of the lens-rearing period, higher than normal amounts of aberrations were observed in treated eyes, both hyperopic and myopic eyes and treated eyes that developed astigmatism, but not spherical ametropias. The total RMS wavefront error increased with the degree of spherical refractive error, but was not correlated with the degree of astigmatism. Both myopic and hyperopic treated eyes showed elevated amounts of coma and trefoil and the degree of trefoil increased with the degree of spherical ametropia. Myopic eyes also exhibited a much higher prevalence of positive spherical aberration than normal or treated hyperopic eyes. Following the onset of unrestricted vision, the amount of high-order aberrations decreased in the treated monkeys that also recovered from the experimentally induced refractive errors. Our results demonstrate that high-order aberrations are influenced by visual experience in young primates and that the increase in high-order aberrations in our treated monkeys appears to be an optical byproduct of the vision-induced alterations in ocular growth that underlie changes in refractive error. The results from our study suggest that the higher amounts of wave aberrations observed in ametropic humans are likely to be a consequence, rather than a cause, of abnormal refractive development.

A comparison of refractive development between two subspecies of infant rhesus monkeys (Macaca mulatta)

PURPOSE Different subspecies of rhesus monkeys (Macaca mulatta) that are derived from different geographical locations, primarily Indian and China, are commonly employed in vision research. Substantial morphological and behavioral differences have been reported between Chinese- and Indian-derived subspecies. The purpose of this study was to compare refractive development in Chinese- and Indian-derived rhesus monkeys. METHODS The subjects were 216 Indian-derived and 78 Chinese-derived normal infant rhesus monkeys. Cross-sectional data were obtained at 3 weeks of age for all subjects. In addition, longitudinal data were obtained from 10 Indian-derived (male=5, female=5) and 5 Chinese-derived monkeys (male=3, female=2) that were reared with unrestricted vision. Ocular and refractive development was assessed by retinoscopy, keratometry, video-based ophthalmophakometry, and A-scan ultrasonography. RESULTS Although the course of emmetropization was very similar in these two groups of rhesus monkeys, there were consistent and significant inter-group differences in ocular dimensions and refractive error. Throughout the observation period, the Chinese-derived monkeys were on average about 0.4D less hyperopic than the Indian-derived monkeys and the Chinese-derived monkeys had longer overall axial lengths, deeper anterior and vitreous chamber depths, thicker crystalline lenses, flatter corneas and lower powered crystalline lenses. CONCLUSIONS The ocular differences observed in this study presumably reflect genetic differences between subspecies but could reflect the differences in the genetic pool between isolated colonies rather than true subspecies differences. Nonetheless, the substantial ocular differences that we observed emphasize that caution must be exercised when comparing and/or pooling data from rhesus monkeys obtained from different colonies. These inter-subspecies differences might be analogous to the ethnic differences in ocular parameters that have been observed in humans.

Monochromatic ocular wave aberrations in young monkeys

High-order monochromatic aberrations could potentially influence vision-dependent refractive development in a variety of ways. As a first step in understanding the effects of wave aberration on refractive development, we characterized the maturational changes that take place in the high-order aberrations of infant rhesus monkey eyes. Specifically, we compared the monochromatic wave aberrations of infant and adolescent animals and measured the longitudinal changes in the high-order aberrations of infant monkeys during the early period when emmetropization takes place. Our main findings were that (1) adolescent monkey eyes have excellent optical quality, exhibiting total RMS errors that were slightly better than those for adult human eyes that have the same numerical aperture and (2) shortly after birth, infant rhesus monkeys exhibited relatively larger magnitudes of high-order aberrations predominately spherical aberration, coma, and trefoil, which decreased rapidly to assume adolescent values by about 200 days of age. The results demonstrate that rhesus monkey eyes are a good model for studying the contribution of individual ocular components to the eyes overall aberration structure, the mechanisms responsible for the improvements in optical quality that occur during early ocular development, and the effects of high-order aberrations on ocular growth and emmetropization.