Neuronal responses in visual area V2 (V2) of macaque monkeys with strabismic amblyopia.

Amblyopia, a developmental disorder of spatial vision, is thought to result from a cascade of cortical deficits over several processing stages beginning at the primary visual cortex (V1). However, beyond V1, little is known about how cortical development limits the visual performance of amblyopic primates. We quantitatively analyzed the monocular and binocular responses of V1 and V2 neurons in a group of strabismic monkeys exhibiting varying depths of amblyopia. Unlike in V1, the relative effectiveness of the affected eye to drive V2 neurons was drastically reduced in the amblyopic monkeys. The spatial resolution and the orientation bias of V2, but not V1, neurons were subnormal for the affected eyes. Binocular suppression was robust in both cortical areas, and the magnitude of suppression in individual monkeys was correlated with the depth of their amblyopia. These results suggest that the reduced functional connections beyond V1 and the subnormal spatial filter properties of V2 neurons might have substantially limited the sensitivity of the amblyopic eyes and that interocular suppression was likely to have played a key role in the observed alterations of V2 responses and the emergence of amblyopia.

Linking structure and function in glaucoma.

The glaucomas are a group of relatively common optic neuropathies, in which the pathological loss of retinal ganglion cells causes a progressive loss of sight and associated alterations in the retinal nerve fiber layer and optic nerve head. The diagnosis and management of glaucoma are often dependent on methods of clinical testing that either, 1) identify and quantify patterns of functional visual abnormality, or 2) quantify structural abnormality in the retinal nerve fiber layer, both of which are caused by loss of retinal ganglion cells. Although it is evident that the abnormalities in structure and function should be correlated, propositions to link losses in structure and function in glaucoma have been formulated only recently. The present report describes an attempt to build a model of these linking propositions using data from investigations of the relationships between losses of visual sensitivity and thinning of retinal nerve fiber layer over progressive stages of glaucoma severity. A foundation for the model was laid through the pointwise relationships between visual sensitivities (behavioral perimetry in monkeys with experimental glaucoma) and histological analyses of retinal ganglion cell densities in corresponding retinal locations. The subsequent blocks of the model were constructed from clinical studies of aging in normal human subjects and of clinical glaucoma in patients to provide a direct comparison of the results from standard clinical perimetry and optical coherence tomography. The final formulation is a nonlinear structure-function model that was evaluated by the accuracy and precision of translating visual sensitivities in a region of the visual field to produce a predicted thickness of the retinal nerve fiber layer in the peripapillary sector that corresponded to the region of reduced visual sensitivity. The model was tested on two independent patient populations, with results that confirmed the predictive relationship between the retinal nerve fiber layer thickness and visual sensitivities from clinical perimetry. Thus, the proposed model for linking structure and function in glaucoma has provided information that is important in understanding the results of standard clinical testing and the neuronal losses caused by glaucoma, which may have clinical application for inter-test comparisons of the stage of disease.

Effects of perceptual learning on local stereopsis and neuronal responses of V1 and V2 in prism-reared monkeys.

Visual performance improves with practice (perceptual learning). In this study, we sought to determine whether or not adult monkeys reared with early abnormal visual experience improve their stereoacuity by extensive psychophysical training and testing, and if so, whether alterations of neuronal responses in the primary visual cortex (V1) and/or visual area 2 (V2) are involved in such improvement. Strabismus was optically simulated in five macaque monkeys using a prism-rearing procedure between 4 and 14 wk of age. Around 2 yr of age, three of the prism-reared monkeys ("trained" monkeys) were tested for their spatial contrast sensitivity and stereoacuity. Two other prism-reared monkeys received no training or testing ("untrained" monkeys). Microelectrode experiments were conducted around 4 yr of age. All three prism-reared trained monkeys showed improvement in stereoacuity by a factor of 7 or better. However, final stereothresholds were still approximately 10-20 times worse than those in normal monkeys. In V1, disparity sensitivity was drastically reduced in both the trained and untrained prism-reared monkeys and behavioral training had no obvious effect. In V2, the disparity sensitivity in the trained monkeys was better by a factor of approximately 2.0 compared with that in the untrained monkeys. These data suggest that the observed improvement in stereoacuity of the trained prism-reared monkeys may have resulted from better retention of disparity sensitivity in V2 and/or from "learning" by upstream neurons to more efficiently attend to residual local disparity information in V1 and V2.

Cortical effects of brief daily periods of unrestricted vision during early monocular form deprivation.

Experiencing daily brief periods of unrestricted vision during early monocular form deprivation prevents or reduces the degree of resulting amblyopia. To gain insight into the neural basis for these "protective" effects, we analyzed the monocular and binocular response properties of individual neurons in the primary visual cortex (V1) of macaque monkeys that received intermittent unrestricted vision. Microelectrode-recording experiments revealed significant decreases in the proportion of units that were dominated by the treated eyes, and the magnitude of this ocular dominance imbalance was correlated with the degree of amblyopia. The sensitivity of V1 neurons to interocular spatial phase disparity was significantly reduced in all treated monkeys compared with normal adults. With unrestricted vision, however, there was a small but significant increase in overall disparity sensitivity. Binocular suppression was prevalent in monkeys with constant form deprivation but significantly reduced by the daily periods of unrestricted vision. If neurons exhibited consistent responses to stimulation of the treated eye, monocular response properties obtained by stimulation of the two eyes were similar. These results suggest that the observed protective effects of brief periods of unrestricted vision are closely associated with the ability of V1 neurons to maintain their functional connections from the deprived eye and that interocular suppression in V1 may play an important role in regulating synaptic plasticity of these monkeys.

The relative sensitivities of sensory and motor fusion to small binocular disparities.

Horizontal binocular disparity is the fundamental stimulus for both fusional vergence and stereopsis, but whether common disparity-sensitive mechanisms are involved in both responses is unknown. To determine whether the sensitivities of motor and sensory fusion are interdependent, we studied vergence eye movements and depth discrimination, using stimuli with haplopic binocular disparities, in subjects with normal stereopsis and in subjects with mild to severe stereoanomalies. Our results showed that the subjects' disparity discrimination functions varied from nearly perfect discrimination to chance performance for all of the experimental stimuli. Their sensory functions did not necessarily predict the shape of their motor fusion functions, but in most cases were correlated with the subject's fixation disparities. The results support the conclusion that the stereoanomalies and vergence anomalies that previously have been described for coarse binocular disparities also extend to the small, haplopic binocular disparities. The independence of the response properties of sensory and motor fusion suggests that neural pathways for sensory and motor fusion separate after the initial disparity-selective mechanisms in primary visual cortex.

Clinical suppression in monkeys reared with abnormal binocular visual experience.

To determine if monkeys exhibit clinical suppression in response to early abnormal binocular vision, we compared dichoptic to monocular luminance increment thresholds in monkeys reared with alternating monocular defocus or optically induced strabismus. In the absence of amblyopia, clinical suppression was associated with strabismus and with as little as 1.50 diopters of anisometropia. The severity of suppression was roughly correlated with the magnitude of anisometropia. The demonstration of clinical suppression in monkeys provides a model for future investigations of factors that may influence the development of suppression, but which are not possible to accurately document or manipulate in human subjects.

Experimental glaucoma in primates: changes in cytochrome oxidase blobs in V1 cortex.

PURPOSE: To evaluate the effects of ganglion cell depletion from experimental glaucoma on the relative metabolic activities of neurons in the cytochrome oxidase blobs of V1 cortex in the macaque visual system. METHODS: Monocular experimental glaucoma was induced in adult monkeys (Macaca mulatta and Macaca fascicularis) by laser application to the trabecular meshwork, increasing the intraocular pressure. After other experiments, the primary visual cortices were analyzed for functional excitation from surviving ganglion cells, as indicated by cytochrome oxidase histochemistry. RESULTS: Cytochrome oxidase reactivity was uniformly reduced in blobs with input from the glaucomatous eye in a manner consistent with loss of known afferent inputs. The average size of glaucomatous blobs in layers 2 and 3 of V1 cortex was reduced by half. CONCLUSIONS: Experimental glaucoma in monkeys reduces retinal input to the central nervous system, thereby reducing the metabolic drive to downstream targets, as indicated by the reduction in the size of cytochrome oxidase blobs in layers 2 and 3 of V1 cortex. The pattern of cytochrome oxidase loss within the blob was uniform, suggesting that all sources of afferent input to the blobs were affected by experimental glaucoma.

The degree of image degradation and the depth of amblyopia.

PURPOSE: To determine whether the depth of monocular form-deprivation amblyopia is dependent on the degree of retinal image degradation. METHODS: Chronic monocular form deprivation was produced in nine infant rhesus monkeys by securing one of three different strengths of diffuser spectacle lenses in front of the treated eye and a clear zero-powered lens in front of the fellow eye. Three infant monkeys reared with plano lenses in front of both eyes provided control data. The treatment lenses were worn continuously from approximately 3 weeks of age for periods ranging between 11 and 19 weeks. When the monkeys were approximately 18 months of age, psychophysical procedures were used to measure the effects of the rearing procedures on the spatial contrast sensitivity function for each eye. RESULTS: The treated eyes of all nine diffuser-reared monkeys showed contrast sensitivity deficits that were indicative of amblyopia. On average, the interocular grating acuity difference increased systematically from 0.6 octaves for the weakest diffuser lens to 2.3 +/- 0.7 and 3.5 +/- 0.8 octaves for the intermediate and strongest diffuser lenses, respectively. There was a close correspondence between the magnitude of the amblyopic deficits and the reduction in retinal image contrast produced by the diffuser lenses. CONCLUSIONS: The results demonstrate that the depth of monocular, nonstrabismic amblyopia is strongly influenced by the degree of retinal image degradation experienced early in life.

Glaucoma in primates: cytochrome oxidase reactivity in parvo- and magnocellular pathways.

PURPOSE: To evaluate the differential effects of ganglion cell depletion from experimental glaucoma on the relative metabolic activities of neurons in the parvo (P)- and magno (M)-cellular visual pathways of the macaque visual system. METHODS: Monocular experimental glaucoma was induced in monkeys (Macaca mulatta and M. fascicularis) by applying a laser to the trabecular meshwork to increase intraocular pressure (IOP). After other behavioral and electrophysiological studies, the lateral geniculate nuclei (LGNs) and the primary visual cortices were analyzed for functional afference from surviving ganglion cells, indicated by cytochrome oxidase (CO) histochemistry. RESULTS: CO reactivity (COR) indicated a general reduction in neural metabolism with increasing severity of glaucoma. COR in the LGNs was reduced to the same degree in both the P- and M-cellular layers. In layer 4Cbeta of the V1 cortex, the reactivity was always reduced more than in the layer 4Calpha division. CONCLUSIONS: Experimental glaucoma in monkeys reduces visual afference to the central nervous system, thereby reducing the metabolic drive as indicated by COR. The detrimental effect of glaucoma did not appear to be any greater for the M-cell, rather than the P-cell pathway in the LGN or in the visual cortex. Both are affected by the duration and severity of the experimental glaucoma. Overall, the alterations in metabolism of neurons in the parallel visual pathways supplied by the Palpha and Pbeta ganglion cells do not suggest that tests based on the functional properties of one or the other would provide optimal assessment of glaucoma.

Effects of experimental glaucoma in macaques on the multifocal ERG. Multifocal ERG in laser-induced glaucoma.

Multifocal ERGs (MERGs) of 5 adult monkeys (Macaca mulatta) with inner retinal defects caused by laser-induced glaucoma were compared to MERGs from 3 monkeys with inner retinal activity suppressed pharmacologically. MERGs were recorded with DTL fiber electrodes from anesthetized monkeys. Stimuli consisted of 103 equal size hexagons within 17 degrees of the fovea. Stimuli at each location passed through a typical VERIS m-sequence of white (200 cd/m2) and black (12 cd/m2) presentations. In animals with laser-induced glaucoma, visual field sensitivity was assessed by static perimetry using the Humphrey C24-2 full-threshold program modified for animal behavior. Inner retinal (amacrine and ganglion cell) activity was suppressed by intravitreal injection of TTX (4.7-7.6 microM) and NMDA (1.6-5 mM). In normal eyes the first order response (1st order kernel) was larger and more complex, with more distinct oscillations (>60 Hz) in central than in peripheral locations. The 2nd order kernel also was dominated by oscillatory activity. There were naso-temporal variations in both kernels. Pharmacological suppression of inner retinal activity reduced or eliminated the oscillatory behavior, and naso-temporal variations. The 1st order kernel amplitude was increased most and was largest at the fovea. Removed inner retinal responses also were largest at the fovea. The 2nd order kernel was greatly reduced at all locations. In eyes with advanced glaucoma, the effects were similar to those produced by suppressing inner retinal activity, but the later portion of the 1st order kernel waveform was different, lacking a dip after the large positive wave. Visual sensitivity losses and MERG changes both increased over the timecourse of glaucoma, with changes in the MERG being more diffusely distributed across the visual field. We conclude that 1st and 2nd order responses of the primate MERG can be identified that originate from inner retina and are sensitive indicators of glaucomatous neuropathy.

Progressive visual field defects from experimental glaucoma: measurements with white and colored stimuli.

PURPOSE: Our purpose was to study the effects of using monochromatic test stimuli to measure the relative rate of progression of visual field defects caused by experimental glaucoma. METHODS: Visual field measurements were obtained by static perimetry from trained macaque monkeys with laser-induced, unilateral glaucoma. The visual field defects were assessed by perimetric (global) indices derived from comparisons of experimental visual fields to the expected normal fields of monkeys. Three types of perimetry stimuli were used, the conventional white Goldmann III and two monochromatic (460 and 620 nm) Goldmann V test stimuli. The relationships between field defects with white and monochromatic stimuli were investigated by linear regression of the Z-scores for the perimetric indices. RESULTS: The correlations between the mean deviation global indices for chromatic vs. white stimuli were high (r > 0.9) and linear throughout the period of progression of field defects. The slopes of the regression lines typically were greater than unity, indicating that statistical significance was higher for visual field defects measured with chromatic stimuli than with white light stimuli. The higher significance level for defects measured with chromatic stimuli was not explained by a difference in visual thresholds, because the thresholds with chromatic and white light were highly correlated across the full range of visual field defects, from initial-onset to end-state. This result also suggests that the early detection of glaucomatous visual defects with monochromatic stimuli does not reflect a selective loss of retinal ganglion cells. CONCLUSIONS: Although these experiments do not suggest an alternative neural mechanism for the clinical utility of perimetry with chromatic light for the early detection of glaucoma, it is very likely that the combinations of neural and/or analytical factors that explain the utility of perimetry with chromatic stimuli will also provide an explanation for the higher sensitivities in identifying early glaucoma reported for other prototype stimuli.

Ganglion cell losses underlying visual field defects from experimental glaucoma.

PURPOSE: To investigate the relationship between ganglion cell losses and visual field defects caused by glaucoma. METHODS: Behavioral perimetry and histology data were obtained from 10 rhesus monkeys with unilateral experimental glaucoma that was induced by argon laser treatments to their trabecular meshwork. After significant visual field defects had developed, the retinas were collected for histologic analysis. The ganglion cells were counted by light microscopy in cresyl violet-stained retina sections, and the percentage of ganglion cell loss (treated to control eye counts) was compared with the depth of visual field defect (treated to control eye thresholds) at corresponding retinal and perimetry test locations. Sensitivity losses as a function of ganglion cell losses were analyzed for Goldmann III, white and Goldmann V, and short- and long-wavelength perimetry test stimuli. RESULTS: The relationship between the proportional losses of ganglion cells and visual sensitivity, measured with either white or colored stimuli, was nonlinear. With white stimuli, the visual sensitivity losses were relatively constant (approximately 6 dB) for ganglion cell losses of less than 30% to 50%, and then with greater amounts of cell loss the visual defects were more systematically related to ganglion cell loss (approximately 0.42 dB/percent cell loss). The forms of the neural-sensitivity relationships for visual defects measured with short- or long-wavelength perimetry stimuli were similar when the visual thresholds were normalized to compensate for differences in expected normal thresholds for white and colored perimetry stimuli. CONCLUSIONS: Current perimetry regimens with either white or monochromatic stimuli do not provide a useful estimate of ganglion cell loss until a substantial proportion have died. The variance in ganglion cell loss is large for mild defects that would be diagnostic of early glaucoma and for visual field locations near the fovea where sensitivity losses occur relatively late in the disease process. The neural-sensitivity relationships were essentially identical for both white and monochromatic test stimuli, and it therefore seems unlikely that the higher sensitivity for detecting glaucoma with monochromatic stimuli is based on the size-dependent susceptibility of ganglion cells to injury from glaucoma.

Stereopsis, cyclovergence and the backwards tilt of the vertical horopter.

It is generally recognized that the vertical horopter has a backwards tilt such that it passes through the fixation point and a point near the feet of the observer. The basis of the tilt has been attributed to either a shear in binocular retinal correspondence along the vertical meridian or the presence of cyclovergence eye movements. In an attempt to determine empirically the mechanisms underlying the tilt of the vertical horopter, retinal correspondence along the vertical meridian was investigated as a function of viewing distance. In addition, binocular measurements of torsional eye position were made in the same observers under similar viewing conditions. The vertical horopter was determined using two criteria. In the first instance, increment depth discrimination thresholds for both crossed and uncrossed disparities were measured as a function of retinal eccentricity along the vertical meridian, up to 5 degrees superiorly and inferiorly, and the horopter was defined by the region in space which had the lowest stereo-threshold. Secondly, subjective alignment of dichoptically presented nonius lines defined the horopter by identical visual directions. Both criteria were used to determine the horopter at 2 m while only the criterion of identical visual direction was used at the nearer distance of 50 cm. The vertical horopter showed a backwards tilt that decreased from an average of about 12 degrees at 2 m to 3 degrees at 50 cm, with some variability between observers. Torsional eye position did not change significantly between fixation distances. These results confirmed the geometric relation between the backwards tilt in the vertical horopter and fixation distance and support Helmholtz's original contention that the tilt is a consequence of a shear in retinal correspondence in the vertical meridian.

The photopic negative response of the macaque electroretinogram: reduction by experimental glaucoma.

PURPOSE: To investigate the photopic flash electroretinograms (ERGs) of macaque monkeys in which visual field defects developed as a consequence of experimental glaucoma. METHODS: Unilateral experimental glaucoma was induced in 10 monkeys by argon laser treatment of the trabecular meshwork. Visual field sensitivity was assessed behaviorally by static perimetry. Photopic ERGs were recorded to brief- (< or = 5 msec) and long-duration (200 msec) red ganzfeld flashes on a rod-suppressing blue-adapting background. Electroretinograms were recorded in four other monkeys, after intravitreal injection of tetrodotoxin (TTX; 3.8-8 p.M) to suppress action potentials of retinal ganglion and amacrine cells, and in six normal adult human subjects. RESULTS: Experimental glaucoma removed a cornea-negative response, the photopic-negative response (PhNR), from the ERG. The PhNR in control eyes was maximal approximately 60 msec after a brief flash, 100 msec after onset, and 115 msec after offset of the long-duration stimulus. The PhNR in experimental eyes was greatly reduced when the mean deviation of the visual field sensitivity was as little as -6 dB. As visual sensitivity declined further, the PhNR was reduced only slightly more. The a- and b-waves were unchanged, even when sensitivity decreased by more than 16 dB. Tetrodotoxin also selectively reduced the PhNR. The PhNR was observed in normal human ERGs. CONCLUSIONS: The cornea-negative PhNR of the photopic ERG depends on spiking activity and is reduced in experimental glaucoma when visual sensitivity losses are still mild. The PhNR most likely arises from retinal ganglion cells and their axons, but its slow timing raises the possibility that it could be mediated by glia. Regardless of the mechanism of its generation, the PhNR holds promise as an indicator of retinal function in early glaucomatous optic neuropathy.

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 monkey's 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.

Effects of cue context on the perception of depth from combined disparity and perspective cues.

PURPOSE: In normal vision, stereoscopic cues are combined with perspective cues to provide veridical depth perception. The relative strengths of these depth cues, however, may be dependent upon context effects. We investigated the role of stimulus context on the interactions of binocular disparity, contrast, and size. METHODS: The subjects, four observers with normal stereoacuity and one stereo-amblyope, discriminated far vs. near perceived depth of Gabor patches; feedback was based on the sign of binocular disparity. Depth discrimination functions were measured under conditions in which depth cues were consonant or in conflict. Three stimulus contexts were used: (1) variable disparity with fixed spatial frequency and contrast; (2) variable contrast with fixed spatial frequency and disparity; and (3) variable spatial frequency with fixed contrast and disparity. The effects of stimulus context were derived from comparisons of discrimination rates for identical stimuli across the three sets of conditions. RESULTS: In subjects with normal stereopsis, for disparities less than 2 arcmin, depth perception was dominated by contrast in contrast-varying sessions, or by size in spatial frequency-varying sessions. With larger disparities, depth perception became dependent on disparity, regardless of the contrast or spatial frequency of the test stimulus. The results for the stereo-amblyope showed much greater dependence on perspective cues and, in most cases, the transition from perspective- to disparity-based depth perception did not occur. CONCLUSIONS: These investigations demonstrate strong stimulus context effects and have important implications for the combination rules of stereoscopic and perspective cues in depth perception of normal and stereo-deficient subjects.

Glutamine immunoreactivity in Müller cells of monkey eyes with experimental glaucoma.

The action of glutamate in retina is largely terminated through rapid uptake by Müller cells and subsequent conversion primarily to glutamine. Glutamine, transferred from Müller cells to neurons, serves as a precursor for the formation of glutamate in neurons completing the glutamate-glutamine cycle. In a monkey model of high-tension glaucoma, we have examined glutamine immunoreactivity in the Müller cell as well as the number of Müller cells to determine whether the activity of these cells in the glutamate-glutamine cycle is affected, particularly since high vitreal glutamate has been reported in glaucoma. Unilateral glaucoma was induced in three monkeys by argon laser application to the trabecular meshwork. LR White sections of retina from the temporal mid-periphery (about 23 degrees) and the parafovea (central 3 degrees) were immunolabeled for glutamine using immunogold and silver intensification. The percentage difference in labeling intensity (darkness) in the glaucomatous retina was determined relative to the labeling found in the control retina by image analysis. Ganglion cell density was estimated from radial sections in the parafovea and from retinal whole mounts in the mid-periphery. The number of Müller cells was estimated from vibratome sections immunolabeled by vimentin antibodies in the temporal mid-periphery (about 30 degrees). Glutamine immunoreactivity was localized predominately in ganglion cells and Müller cells. However, the intensity of glutamine immunolabeling was greater in Müller cells of glaucomatous eyes than in control eyes. This increase in glutamine immunolabeling was 25-32% in the temporal mid-periphery and 27-48% in the parafovea. Müller cell number in the glaucomatous eye was similar to that of the control in the temporal mid-periphery. The data in this study indicate that the increase in glutamine in Müller cells is not a consequence of their loss and that Müller cell function in the glutamate-glutamine cycle continues in glaucomatous eyes. These findings are consistent with a previous report that extracellular/vitreal glutamate concentration is elevated in high-tension glaucoma.

Residual binocular interactions in the striate cortex of monkeys reared with abnormal binocular vision.

We investigated the nature of residual binocular interactions in the striate cortex (V1) of monkey models for the two most common causes of visual dysfunction in young children, specifically anisometropia and strabismus. Infant rhesus monkeys were raised wearing either anisometropic spectacle lenses that optically defocused one eye or ophthalmic prisms that optically produced diplopia and binocular confusion. Earlier psychophysical investigations had demonstrated that all subjects exhibited permanent binocular vision deficits and, in some cases, amblyopia. When the monkeys were adults, the responses of individual V1 neurons were studied with the use of microelectrode recording techniques while the animals were anesthetized and paralyzed. The manner in which the signals from the two eyes were combined in individual cells was investigated by dichoptically stimulating both eyes simultaneously with drifting sine wave gratings. In both lens- and prism-reared monkeys, fewer neurons had balanced ocular dominances and greater numbers of neurons were excited by only one eye. However, many neurons that appeared to be monocular exhibited clear binocular interactions during dichoptic stimulation. For the surviving binocular neurons, the maximum binocular response amplitudes were lower than normal; fewer neurons, particularly complex cells, were sensitive to relative interocular spatial phase disparities; and the remaining disparity-sensitive neurons exhibited lower degrees of binocular interaction. In prism-reared monkeys, an unusually high proportion of complex cells exhibited binocular suppression during dichoptic stimulation. Binocular contrast summation experiments showed that for both cooperative and antagonistic binocular interactions, contrast signals from the two eyes were combined by individual neurons in a normal linear fashion in both lens- and prism-reared monkeys. The observed binocular deficits appear to reflect a reduction in functional inputs from one eye and/or spatial imprecision in the monocular receptive fields rather than an aberrant form of binocular interaction. In the prism-reared monkeys, the predominance of suppression suggests that inhibitory connections were, however, less susceptible to diplopia and confusion than excitatory connections. Overall, there were many parallels between V1 physiology in our monkey models and the residual vision of humans with anisometropia or strabismus.

Stereopsis and disparity vergence in monkeys with subnormal binocular vision.

The surgical treatment for strabismus in infants generally results in microtropia or subnormal binocular vision. Although the clinical characteristics of these conditions are well established, there are important questions about the mechanisms of binocular vision in these patients that can best be investigated in an appropriate animal model. In the present psychophysical investigations, spatial frequency response functions for disparity-induced fusional vergence and for local stereopsis were studied in macaque monkeys, who demonstrated many of the major visual characteristics of patients whose eyes were surgically aligned during infancy. In six rhesus monkeys, unilateral esotropia was surgically induced at various ages (30-184 days of age). However, over the next 12 months, all of the monkeys recovered normal eye alignment. Behavioral measurements at 4-6 years of age showed that the monkeys' prism-induced fusional vergence responses were indistinguishable from those of control monkeys or humans with normal binocular vision. Investigations of stereo-depth discrimination demonstrated that each of the experimental monkeys also had stereoscopic vision, but their stereoacuities varied from being essentially normal to severely stereo-deficient. The degree of stereo-deficiency was not related to the age at which surgical esotropia was induced, or to the presence or absence of amblyopia, and was not dependent on the spatial frequency of the test stimulus. Altogether, these experiments demonstrate that a temporary, early esotropia can affect the binocular disparity responses of motor and sensory components of binocular vision differently, probably because of different sensitive periods of development for the two components.

Experimental glaucoma: perimetric field defects and intraocular pressure.

PURPOSE: To investigate the relationship between intraocular pressure (IOP) and the progression of visual field defects caused by experimental glaucoma in Macaca mulatta monkeys. METHODS: Perimetric fields were measured by behavioral methods in 18 rhesus monkeys during the course of unilateral glaucoma produced by argon laser treatment of the trabecular meshwork. The monkeys' IOPs were measured by applanation tonometry. Visual field defects were quantified by the mean deviation perimetric index from Humphrey Field Analyzer C24-2, model 630 (Humphrey Allergan, San Leandro, CA, U.S.A.), full-threshold data. RESULTS: The monkeys' eyes demonstrated considerable variability in their susceptibility to pressure-induced neural damage. For 10 of the monkeys, significant field defects were correlated with the increases in their IOPs and the defects progressed monotonically to end-state glaucoma. For the other monkeys, the mean deviation index was not well correlated with IOP; some eyes withstood pressures in excess of 35 mm Hg for several months before significant reduction in visual sensitivity. However, once they began, the rate of progression of field defects was similar across subjects. CONCLUSIONS: Laser ablation of the trabecular meshwork in monkeys provides a model for investigations of the effects of IOP that are not confounded by other ocular or visual disorders. Behavioral perimetry showed the same intersubject variability in the effects of elevated IOP on visual field sensitivities of monkeys that are common with high-tension glaucoma or ocular hypertension in patients. Thus, these investigations provide additional support for the use of the model for a wide variety of clinical investigations on glaucoma.