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Biomedical subjects

R G Boothe

Publications and source records attributed to R G Boothe.

At least 37 records · Page 2Linked to original sources

Natural strabismus in monkeys. Convergence errors assessed by cover test and photographic methods.

A standard set of clinical prism and cover tests and a recently developed photographic method were used to assess binocular alignment in ten monkeys that previously were determined to have a naturally occurring infantile strabismus. Extensive measurements of the alignment state were made for fixation attempts throughout the field of gaze. Patterns of alignment errors were examined in an attempt to compared the strabismus found in individual monkeys with common syndromes of human infantile strabismus. Two monkeys showed patterns consistent with the syndrome of essential infantile esotropia. Five monkeys had patterns consistent with accommodative esotropia. One monkey that had bilateral anterior chamber hemorrhage at birth had a constant-angle esotropia. One monkey that previously had been shown to have a large-angle esotropia during development exhibited only exophoria, and in a final monkey in which large-angle esotropia was found during development, the strabismus had resolved. These results demonstrate that naturally occurring strabismus in monkeys might be related to syndromes seen in children. In addition, they provide extensive information about other characteristics of strabismus that have not been examined previously. These include a characterization of the magnitude of the misalignment in terms of error surface plots of bias and a detailed analysis of scatter in the measurements that show coupling relationships between the two eyes.

Animals↗

A photographic technique for measuring horizontal and vertical eye alignment throughout the field of gaze.

We present a photographic method based upon corneal light reflections for the measurement of binocular misalignment. Our procedures allow for the measurement of eye alignment errors to fixation targets presented at any distance throughout the subject's field of gaze, and allow for the measurement of errors in the horizontal and vertical directions. Furthermore, estimates of the alignment state can be made simultaneously from both eyes while fixation targets are presented monocularly or binocularly. This photographic method represents an enhancement of typical clinical prism and cover methods because: (1) it can provide extensive information efficiently about patterns of misalignment across a large number of fixation locations; (2) it also can provide information about the scatter in addition to the magnitude of convergence error; and (3) it can be easily applied to noncooperative subjects such as animals and young children. Furthermore, the procedure requires relatively inexpensive equipment and technical expertise that are readily available in most clinical or animal research laboratory settings. The method is validated by comparing the results obtained photographically to standard prism and cover assessments of macaque monkeys with strabismus. This comparison demonstrates that results obtained by the two methods are in good agreement and that the degree of accuracy is similar for the two methods. An estimate of the angle of deviation based on 10 photographs has a 95% confidence interval of about two degrees.

Animals↗

Effects of aphakia on the geniculostriate system of infant rhesus monkeys.

The effects on the visual system of rearing rhesus monkeys with monocular aphakia, corrected with extended-wear contact lenses, were assessed with anatomical, electrophysiological and behavioral methods. The major finding was that the effects of the various treatments on the aphakic eye varied in degree depending upon the amount of focused pattern input received by the aphakic eye compared to its fellow eye. The behavioral, electrophysiological and anatomical assessments of the treatment effects on the aphakic eyes correlated closely with each other. Because this experimental paradigm is similar to current clinical procedures for treating human infantile monocular cataracts, it provides a nonhuman primate model for studying aphakia.

Animals↗

Accessory lateral rectus orbital geometry in normal and naturally strabismic monkeys.

We conducted anatomic dissections of macaque monkey orbits and made a quantitative assessment of the orbital geometry of the accessory lateral rectus muscle. Our results show that the expected effect of this muscle on rotations of the globe is to produce elevation and abduction. The abducting component could counteract nasal drifts, and thus our findings provide support for the hypothesis that this muscle could render monkeys resistant to the development of esodeviations. Dissections of the orbits from two naturally esotropic monkeys also are consistent with this hypothesis. The accessory lateral rectus muscle was absent in one of them and abnormally small in the other. Humans do not have an accessory lateral rectus muscle, and we speculate that the high prevalence of esodeviations in humans may be related to an evolutionary loss of this muscle system.

Animals↗

Visual fields of monocularly deprived macaque monkeys.

The effects of postnatal monocular deprivation have been studied in macaque monkeys using behavioral perimetry field testing. The types of deprivation were: (1) early eyelid suture at 22-26 days after birth and then reverse suture at 10-13 months postnatally, (2) late eyelid suture beginning at 3 or 5 months postnatally and continued for 18 months, and (3) long-term occlusion by contact lenses. Response levels were normal for group 1 monkeys with some reduction in visual field extent. A reduced response level but no change in visual field extent was observed for the deprived eyes of group 2 monkeys. One monkey from group 3 that wore an occluder lens from birth to 19 months postnatally had no responses in any part of the visual field. Two other monkeys of group 3, whose occlusion started at 9 or 12 days of age and lasted for 2 years, had no responses to stimuli presented to the previously occluded eyes in their nasal visual fields and had reduced levels of response to stimuli presented in their temporal fields. The results indicate that the effects of monocular deprivation on macaque monkeys are affected by the start, length and type of deprivation. Some of these results are also consistent with a model of binocular competition in which the magnitude of the competition declines along a nasal-to-temporal gradient of visual field eccentricity. However, a mechanism that is independent of binocular competition is needed to account for the loss of responses to stimuli presented in the monocular visual segment.

Animals↗

Early abnormal visual experience induces strabismus in infant monkeys.

We measured ocular alignment in the horizontal direction for 17 monkeys reared under deprivation paradigms that involved monocular defocus, monocular occlusion and optically corrected aphakia coupled with continuous or partial occlusion of the fellow eye. Alignment was measured at 3 and 7 months with a photographic corneal light reflex method. Results showed that a majority of the monkeys in each paradigm developed strabismus following deprivation rearing, the common factor being early abnormal visual experience. Results also indicated a trend in which many of the deviations seen at 3 months of age were exotropic while all of the animals with deviations at 7 months of age were esotropic. These results on deprivation-induced strabismus, which are the first reported in monkeys, are consistent with previous findings in cats and humans, providing further evidence that deprivation affects not only sensory, but motor systems as well. These findings provide evidence that infant monkeys are a good model for studies of the possible relationships between amblyopia and strabismus that are often noted in children with early visual deprivation. Furthermore, it raises the prospect that some of the findings in previous animal studies that have been attributed to the direct effects of deprivation may actually be secondary to the induced misalignment.

Animals↗

Measurement of binocular alignment in normal monkeys and in monkeys with strabismus.

Accurate assessment of ocular alignment in monkeys is difficult because typical clinical methods require extensive cooperation by the subject or provide only a rough estimate of the misalignment. Recently, Brodie derived a geometrical model for determining the Hirschberg ratio in humans, and validated it photographically. In this study, we have applied these procedures in order to determine corresponding values for monkeys. We have found the average Hirschberg ratio for macaques to be approximately 14 degrees of rotation per millimeter corneal light reflex displacement. We extended the model to binocular viewing conditions, which allows for a description of the visual axes in Cartesian coordinates in relation to the head. Fixation errors, computed in terms of lateral and axial error vectors from intended fixation targets, were then determined for one normal monkey and for three monkeys that have a naturally occurring strabismus. Assessment of the fixation errors was made at several different distances and angles in the horizontal plane. The standard deviation for our measurements averaged 2.1 degrees. Our data indicate that measurements must be made at multiple locations throughout the visual field in order to accurately specify the pattern of misalignment. Finally, a procedure is demonstrated which specifies the misalignment in terms of a cyclopian eye, which is independent of the interocular separation.

Animals↗

Development of acuity in a primate model of human infantile unilateral aphakia.

We are studying infant rhesus monkeys that have been reared under various conditions of deprivation to model infantile unilateral aphakia. Grating acuity was assessed in these monkeys from birth to approximately 1 year of age using the quick acuity card procedure. We found that an uncorrected aphakic eye develops little or no pattern vision. Undercorrection or near point optical correction of an aphakic eye with an extended-wear contact lens coupled with continuous occlusion of the opposite eye sometimes results in normal development of acuity in the aphakic eye but does so only at the cost of loss of vision in the occluded eye. Fifty percent partial occlusion coupled with near-point correction of the aphakic eye results in similar development of acuity for both eyes during the time tested. Monkeys wearing near-point correction in the aphakic eye and without any occlusion of the other eye show surprisingly good residual acuities in their aphakic eyes. Based on these results we conclude that aphakic eyes should be treated by providing them with an optical correction, and that occlusion of the opposite eye should be used cautiously.

Animals↗

Operant measurements of contrast sensitivity in infant macaque monkeys during normal development.

The development of contrast sensitivity was measured longitudinally in seven Macaca nemestrina monkeys. Operant conditioning methods were used to train and then test infant monkeys from the ages of 1 to 12 months. Several changes were observed in the contrast sensitivity function, including an overall increase in sensitivity to contrast, a shift in the peak of the function toward higher spatial frequencies, and an increase in the cutoff spatial frequency. The time-courses for the changes in the contrast sensitivity function were characterized by rapid development during the first 10-20 weeks, followed by a gradual asymptotic development to adult levels over the remainder of the year. Sensitivity to contrast was found to develop with different time-courses for different spatial frequencies; sensitivity to low spatial frequencies reached adult levels much earlier than sensitivity to high spatial frequencies.

Aging↗

Effects of early unilateral blur on the macaque's visual system. II. Anatomical observations.

We studied the effects of early unilateral blur on the anatomical organization of the visual pathways in 8 macaque monkeys. Blur was induced in one eye, beginning 2-14 d after birth, by 0.5% atropine twice a day. Atropinization was stopped at 6-8 months of age, and the animals were studied for anatomy 3-24 months later. The retina and all other eye tissues showed normal histology. In the dorsal lateral geniculate nucleus (LGN), cells in parvocellular layers receiving input from the atropine-treated eye were 9-32% smaller and were more lightly stained than those in layers innervated by the untreated eye. These changes were generally larger in the LGN ipsilateral to the treated eye. LGN cell size changes were absent or much smaller in the magnocellular layers. In the striate cortex, the distribution of the oxidative enzyme cytochrome oxidase (CO) was markedly altered in layer 4C beta. Layer 4C beta is uniformly stained in normal animals, but showed a distinct pattern of alternating high and low CO bands in the atropine-treated animals; the bands of higher CO activity were narrower than the bands of lower activity and had a 857-1050 micron repeat. Fainter banding was seen in layers 4A, 4C alpha, and 6, but the density of the rows of dark CO-stained dots in layer 3 was unaffected. Double-labeling revealed that the narrow dark CO bands were associated with the centers of the ocular dominance columns devoted to the atropine-treated eye. The distribution of 14C-2-deoxyglucose uptake in visual cortex produced by 4.5-9 c/deg spatial frequency stimulation was strongly biased toward the untreated eye. The treated eye could, however, elicit reasonably strong uptake when stimulated with patterns containing lower spatial frequencies. These results suggest that unilateral neonatal blur preferentially affects the parvocellular layers of the LGN and layer 4C beta of striate cortex, which are the portions of the central visual system associated with the processing of information concerning fine spatial detail. These anatomical changes are consistent with the high spatial frequency loss of vision demonstrated behaviorally and electrophysiologically in the atropine eye-driven visual system of these same animals.

Animals↗

Effects of early unilateral blur on the macaque's visual system. I. Behavioral observations.

We raised 8 macaque monkeys with chronic atropinization of one eye throughout the first 6-10 months after birth. This rearing procedure produces retinal image blur, with the most pronounced contrast attenuation occurring at high spatial frequencies. Measurements of contrast sensitivity were made using behavioral methods in 6 monkeys and evoked potential methods in 2 monkeys. The results showed that this rearing procedure produced long-term deficits in the contrast sensitivity and spatial resolution of the atropinized eye, which were not due to residual losses in accommodative capacity. There was considerable interanimal variation in the magnitude of the effects on visual performance. Similar losses in visual performance are seen in some forms of human amblyopia. Rearing monkeys with chronic instillation of atropine therefore provides a nonhuman primate model for studying the underlying neural mechanisms of anisometropic amblyopia.

Amblyopia↗

Effects of early unilateral blur on the macaque's visual system. III. Physiological observations.

We studied the properties of visual cortical and lateral geniculate neurons in 5 macaque monkeys raised with the vision of one eye blurred by daily instillation of atropine. This rearing reduced the degree of binocular interaction in striate cortical neurons and caused a modest shift in eye dominance away from the atropine-treated eye. It also led to a difference in the spatial properties of neurons driven by the 2 eyes: neurons driven by the treated eye tended to have lower optimal spatial frequencies, poorer spatial resolution, and lower contrast sensitivity than neurons driven by the untreated eye. Some of the few binocularly driven neurons had receptive fields with sharply different spatial properties in the 2 eyes, with the treated eye's receptive field always having poorer spatial resolution. In striate cortex, the effects on neuronal spatial properties were less marked in layer 4 than in more superficial or deeper layers; there was no difference in the spatial properties of lateral geniculate neurons driven by the 2 eyes. A small sample of extrastriate cortical neurons from a single animal showed effects similar to those seen in striate cortex. The striate cortical changes varied consistently from animal to animal: The less affected animals had no discernible eye dominance shift and relatively small differences in spatial properties between the eyes; the more affected animals had substantial eye dominance shifts and larger interocular spatial differences. These variations were also reflected in, and consistent with, behavioral and anatomical measurements performed in the same monkeys.

Action Potentials↗

Abnormal development of the axial length of aphakic monkey eyes.

Neonatal cataract surgery is becoming more common because irreversible amblyopia occurs if an eye receives inadequate inputs during an early sensitive period of visual development. To model conditions for treating congenital monocular cataracts in humans, we have reared rhesus monkeys which underwent unilateral lensectomy as neonates. Post-surgical A-scan ultrasonography at 8-26 months revealed that the axial length of the aphakic eye in these monkeys was shorter when compared to that of the unoperated eye. This finding has important implications for the long-term clinical management of lensectomized infants in order to achieve good vision in the aphakic eye.

Animals↗

Extended-wear soft contact lenses for vision studies in monkeys.

The authors have designed and produced extended-wear contact lenses for rhesus monkeys. High-plus lenses to correct neonatal aphakia as well as lenses dyed black for use as occluders to treat amblyopia have been evaluated. Four infant monkeys fitted with soft lenses have successfully worn these extended-wear lenses almost continuously throughout their first year of life. These experiments demonstrate that rhesus monkeys tolerate extended-wear contact lenses well when these lenses are correctly designed, comfortably fitted, and their wear carefully monitored. Furthermore, the results demonstrate that usable levels of vision can be maintained in monocularly aphakic infant monkeys. Since similar methods are now used to treat children with monocular cataracts, our animal model using extended-wear contact lenses on young monkeys should facilitate new and clinically relevant amblyopia experiments.

Amblyopia↗

Accommodative range in amblyopic monkeys (Macaca nemestrina).

Three naturally strabismic and two chronic bilaterally atropinized monkeys were tested for spatial contrast sensitivity and range of accommodation. All eyes that showed deficits in contrast sensitivity also showed deficits in accommodation. The strabismic monkeys all showed interocular differences in their CSFs and in their accommodative ranges. The atropine monkeys had no interocular differences on either measure. However, one had depressed contrast sensitivity relative to normal and also showed a reduced accommodative range. A statistically significant correlation was found between the high frequency cutoffs of the CSFs and accommodative ranges. These deficits in accommodative range that accompany contrast sensitivity losses in the monkey are similar to the deficits in accommodative range that accompany amblyopia in humans.

Accommodation, Ocular↗

Effects of defocus on monkey (Macaca nemestrina) contrast sensitivity: behavioral measurements and predictions.

An observer's contrast sensitivity function (CSF) can be affected by degradation of either the optical or neural components of the visual system. In a continuing effort in this laboratory to separate these two components in infant and mature monkeys, we have measured behavioral CSF's with the retinal image defocused by as much as 6 D. With increased defocus, sensitivity decreases much more rapidly at high spatial frequencies than at low frequencies. Furthermore, we find that calculations of retinal image contrast, based upon available optical parameters of the monkey eye, underestimate the amount of optical defocus which still allows pattern detection by our monkeys at high spatial frequencies. Several possible explanations for this apparent conflict are discussed, including optical aberrations present in the primate eye, and the "spurious resolution" of defocused sinusoidal gratings.

Animals↗

Accomodative defocus does not limit development of acuity in infant Macaca nemestrina monkeys.

In an experiment with ten macaque monkeys (Macaca nemestrina), a combination of photorefraction and corneal reflex photography was used to measure simultaneously the plane of focus and direction of gaze while they were presented with fixation targets. The monkeys ranged in age from 2 days to 10 weeks. Some of the infants that were less than 1 month old failed to change accommodation to targets at any distance, whereas others showed limited accommodative abilities. The magnitude of the accommodative response of infants older than 4 weeks appeared to be adultlike. Infant monkey's visual acuity improves dramatically after 4 weeks. These results, which show that the improvement in spatial resolution cannot be accounted for by increased accommodative accuracy, parallel those obtained from human infants where accommodative competence is attained by about 4 months of age.

Age Factors↗