Permanent transduction of retinal ganglion cells by rAAV2-retro.

Adeno-associated virus (AAV) is widely used as a vector for delivery of gene therapy. Long term therapeutic benefit depends on perpetual expression of the wild-type gene after transduction of host cells by AAV. To address this issue in a mass population of identified single cells, 4 rats received an injection of a 1:1 mixture of rAAV2-retro-hSyn-EGFP and rAAV2-retro-hSyn-mCherry into each superior colliculus. After the virus was transported retrogradely to both retinas, serial fundus imaging was performed at days 14, 45, 211, and 375 to visualize individual fluorescent ganglion cells. The location of each cell was plotted to compare labeling at each time point. In 12/16 comparisons, 97% or more of the cells identified in the initial baseline fundus image were still labeled at day 375. In 4 cases the percentage was lower, but in these cases the apparent reduction in the number of labeled cells at day 375 was attributable to the lower quality of follow-up fundus images, rather than true loss of transgene expression. These data indicate that retinal ganglion cells transduced by rAAV2-retro are transduced permanently.

Quotidian Profile of Vergence Angle in Ambulatory Subjects Monitored With Wearable Eye Tracking Glasses.

Purpose: Wearable eye trackers record gaze position as ambulatory subjects navigate their environment. Tobii Pro Glasses 3 were tested to assess their accuracy and precision in the measurement of vergence angle. Methods: Four subjects wore the eye tracking glasses, with their head stabilized, while fixating at a series of distances corresponding to vergence demands of: 0.25, 0.50, 1, 2, 4, 8, 16, and 32°. After these laboratory trials were completed, 10 subjects wore the glasses for a prolonged period while carrying out their customary daily pursuits. A vergence profile was compiled for each subject and compared with interpupillary distance. Results: In the laboratory, the eye tracking glasses were comparable in accuracy to remote video eye trackers, outputting a mean vergence value within 1° of demand at all angles except 32°. In ambulatory subjects, the glasses were less accurate, due to tracking interruptions and measurement errors, partly mitigated by the application of data filters. Nonetheless, a useful record of vergence behavior was obtained in every subject. Vergence profiles often had a bimodal distribution, reflecting a preponderance of activities at near (mobile phone and computer) or far (driving and walking). As expected, vergence angle correlated with interpupillary distance. Conclusions: Wearable eye tracking glasses make it possible to compile a nearly continuous record of vergence angle over hours, which can be correlated with the corresponding visual scene viewed by ambulatory subjects. Translational Relevance: This technology provides new insight into the diversity of human ocular motor behavior and may become useful for the diagnosis of disorders that affect vergence function such as: convergence insufficiency, Parkinson disease, and strabismus.

Ambulatory Monitoring With Eye Tracking Glasses to Assess the Severity of Intermittent Exotropia.

PURPOSE: To explore the utility of eye tracking glasses in patients with intermittent exotropia as a means for quantifying the occurrence of exotropia, defined as the percentage of time that the eyes are misaligned. DESIGN: Prospective observational study. METHODS: Eye tracking glasses were used to obtain 68 recordings in 44 ambulatory patients with a history of intermittent exotropia. Vergence angle was monitored for up to 12 hours to document the occurrence of exotropia. RESULTS: Intermittent exotropia was present in 31 of 44 patients. They had a mean exotropia of 19.3 ± 5.3° and a mean occurrence of 40% (range 3-99%). There was a moderate correlation between the magnitude of exotropia and its occurrence (r = 0.59). In 13 patients the occurrence of exotropia was <1%; they were deemed to have an exophoria only. In 35 of 44 cases, families reported an occurrence of intermittent exotropia greater than that measured by the eye tracking glasses. CONCLUSIONS: Eye tracking glasses may be a useful tool for quantifying the severity of intermittent exotropia and for defining more precisely its clinical features.

Decussating axons segregate within the anterior core of the primate optic chiasm.

BACKGROUND: The axons of ganglion cells in the nasal retina decussate at the optic chiasm. It is unclear why tumours cause more injury to crossing nasal fibres, thereby giving rise to temporal visual field loss in each eye. To address this issue, the course of fibres through the optic chiasm was examined following injection of a different fluorescent tracer into each eye of a monkey. METHODS: Under general anaesthesia, cholera toxin subunit B-Alexa Fluor 488 was injected into the right eye and cholera toxin subunit B-Alexa Fluor 594 was injected into the left eye of a single normal adult male rhesus monkey. After a week's survival for anterograde transport, serial coronal sections through the primary optic pathway were examined. RESULTS: A zone within the core of the anterior and mid portions of the optic chiasm was comprised entirely of crossing fibres. This zone of decussation was delineated by segregated, interwoven sheets of green (right eye) and red (left eye) fibres. It expanded steadily to fill more of the optic chiasm as fibres coursed posteriorly towards the optic tracts. Eventually, crossed fibres became completely intermingled with uncrossed fibres, so that ocular separation was lost. CONCLUSIONS: A distinct, central compartment located within the anterior two-thirds of the optic chiasm contains only crossing fibres. Sellar tumours focus their compressive force on this portion of the structure, explaining why they so often produce visual field loss in the temporal fields.

Retinal Input to the Primate Lateral Geniculate Nucleus Revealed by Injection of a Different Label Into Each Eye.

ABSTRACT: The primate lateral geniculate nucleus has long been a favorite structure among anatomists because of its striking lamination. It has been shown that each lamina receives input from a different eye using various single label techniques but never by double labeling. Here, we illustrate the organization of retinal inputs to the lateral geniculate nucleus by injection of cholera toxin-B conjugated to Alexa Fluor-488 into the right eye and cholera toxin-B conjugated to Alexa Fluor-594 into the left eye.

Fundus imaging of retinal ganglion cells transduced by retrograde transport of rAAV2-retro.

Access of adeno-associated virus (AAV) to ganglion cells following intravitreal injection for gene therapy is impeded by the internal limiting membrane of the retina. As an alternative, one could transduce ganglion cells via retrograde transport after virus injection into a retinal target nucleus. It is unknown if recombinant AAV2-retro (rAAV2-retro), a variant of AAV2 developed specifically for retrograde transport, is capable of transducing retinal ganglion cells. To address this issue, equal volumes of rAAV2-retro-hSyn-EGFP and rAAV2-retro-hSyn-mCherry were mixed in a micropipette and injected into the rat superior colliculus. The time-course of viral transduction was tracked by performing serial in vivo fundus imaging. Cells that were labeled by the fluorophores within the first week remained consistent in distribution and relative signal strength on follow-up imaging. Most transduced cells were double-labeled, but some were labeled by only EGFP or mCherry. Fundus images were later aligned with retinal wholemounts. Ganglion cells in the wholemounts matched precisely the cells imaged by fundus photography. As seen in the fundus images, ganglion cells in wholemounts were sometimes labeled by only EGFP or mCherry. Overall, there was detectable label in 32-41% of ganglion cells. Analysis of the number of cells labeled by 0, 1, or 2 fluorophores, based on Poisson statistics, yielded an average of 0.66 virions transducing each ganglion cell. Although this represents a low number relative to the quantity of virus injected into the superior colliculus, the ganglion cells showed sustained and robust fluorescent labeling. In the primate, injection of rAAV2-retro into the lateral geniculate nucleus might provide a viable approach for the transduction of ganglion cells, bypassing the obstacles that have prevented effective gene delivery via intravitreal injection.

Columnar and Laminar Segregation of Retinal Input to the Primate Superior Colliculus Revealed by Anterograde Tracer Injection Into Each Eye.

Purpose: After the lateral geniculate nucleus, the superior colliculus is the richest target of retinal projections in primates. Hubel et al. used tritium autoradiography to show that axon terminals emanating from one eye form irregular columns in the stratum griseum superficiale. Unlabeled gaps were thought to be filled by the other eye, but this assumption was never tested directly. Methods: Experiments were performed in two normal macaques. In monkey 1, [3H]proline was injected into the left eye and the pattern of radiolabeling was examined in serial cross-sections through the entire superior colliculus. In monkey 2, cholera toxin subunit B conjugated to Alexa 488 was injected into the right eye and cholera toxin subunit B - Alexa 594 was injected into the left eye. The two fluorescent labels were compared in a reconstruction of the superior colliculus prepared from serial sections. Results: In monkey 1, irregular columns of axon terminals were present in the superficial grey. The projection from the peripheral retina was stronger than the projection from the macula. In monkey 2, the two fluorescent Alexa tracers mainly interdigitated: a conspicuous gap in one label was usually filled by a clump of the other label. There was also partial laminar segregation of ocular inputs. In the far peripheral field representation, the contralateral eye's input generally terminated closer to the tectal surface. In the midperiphery the eyes switched, bringing the ipsilateral input nearer the surface. Conclusions: Direct retinal input to the macaque superior colliculus is segregated into alternating columns and strata, despite the fact that tectal cells respond robustly to stimulation of either eye.

Dichoptic visual field mapping of suppression in exotropia with homonymous hemianopia.

BACKGROUND: The purpose of this study was to investigate which portions of the visual scene are perceived by each eye in an exotropic subject with acquired hemianopia. The pattern of suppression is predictable from knowledge of how suppression scotomas are organized in exotropic subjects with intact visual fields. METHODS: Dichoptic perimetry was performed by having a subject wear red/blue goggles while fixating a cross that was either red or blue. Red, blue, or purple spots were presented briefly at peripheral locations. The subject's identification of the spot color revealed which eye was perceptually engaged at any given location in the visual fields. RESULTS: A 17-year-old female with a history of exotropia was evaluated after rupture of a right parietal arteriovenous malformation. Dichoptic perimetry showed a left homonymous hemianopia. All stimuli to the right of the right fovea's projection point were perceived via the right eye. Stimuli between the foveal projection points, which were separated horizontally by the 20° exotropia, were perceived by the left eye. CONCLUSIONS: Perception of the visual scene is shared by the eyes in hemianopia and exotropia. Suppression occurs only in the peripheral temporal retina of the eye contralateral to the brain lesion, regardless of which eye is engaged in fixation. Although exotropia expands the binocular field of vision in hemianopia, it is probably not an adaptive response, even when it develops after hemianopia.

Interocular suppression in primary visual cortex in strabismus: impact of staggering the presentation of stimuli to the eyes.

Diplopia (double vision) in strabismus is prevented by suppression of the image emanating from one eye. In a recent study conducted in two macaques raised with exotropia (an outward ocular deviation) but having normal acuity in each eye, simultaneous display of stimuli to each eye did not induce suppression in V1 neurons. Puzzled by this negative result, we have modified our protocol to display stimuli in a staggered sequence, rather than simultaneously. Additional recordings were made in the same two macaques, following two paradigms. In trial type 1, the receptive field in one eye was stimulated with a sine-wave grating while the other eye was occluded. After 5 s, the occluder was removed and the neuron was stimulated for another 5 s. The effect of uncovering the eye, which potentially exposed the animal to diplopia, was quantified by the peripheral retinal interaction index (PRII). In trial type 2, the receptive field in the fixating eye was stimulated with a grating during binocular viewing. After 5 s, a second grating appeared in the receptive field of the nonfixating eye. The impact of the second grating, which had the potential to generate visual confusion, was quantified by the receptive field interaction index (RFII). For 82 units, the mean PRII was 0.48 ± 0.05 (0.50 = no suppression) and the mean RFII was 0.46 ± 0.08 (0.50 = no suppression). These values suggest mild suppression, but the modest decline in spike rate registered during the second epoch of visual stimulation might have been due to neuronal adaptation, rather than interocular suppression. In a few instances neurons showed unequivocal suppression, but overall, these recordings did not support the contention that staggered stimulus presentation is more effective than simultaneous stimulus presentation at evoking interocular suppression in V1 neurons.NEW & NOTEWORTHY In strabismus, double vision is prevented by interocular suppression. It has been reported that inhibition of neuronal firing in the primary visual cortex occurs only when stimuli are presented sequentially, rather than simultaneously. However, these recordings in alert macaques raised with exotropia showed, with rare exceptions, little evidence to support the concept that staggered stimulus presentation is more effective at inducing interocular suppression of V1 neurons.

The Mechanism of Macular Sparing.

Patients with homonymous hemianopia sometimes show preservation of the central visual fields, ranging up to 10°. This phenomenon, known as macular sparing, has sparked perpetual controversy. Two main theories have been offered to explain it. The first theory proposes a dual representation of the macula in each hemisphere. After loss of one occipital lobe, the back-up representation in the remaining occipital lobe is postulated to sustain ipsilateral central vision in the blind hemifield. This theory is supported by studies showing that some midline retinal ganglion cells project to the wrong hemisphere, presumably driving neurons in striate cortex that have ipsilateral receptive fields. However, more recent electrophysiological recordings and neuroimaging studies have cast doubt on this theory by showing only a minuscule ipsilateral field representation in early visual cortical areas. The second theory holds that macular sparing arises because the occipital pole, where the macula is represented, remains perfused after occlusion of the posterior cerebral artery because it receives collateral flow from the middle cerebral artery. An objection to this theory is that it cannot account for reports of macular sparing in patients after loss of an entire occipital lobe. On close scrutiny, such reports turn out to be erroneous, arising from inadequate control of fixation during visual field testing. Patients seem able to detect test stimuli on their blind side within the macula or along the vertical meridian because they make surveillance saccades. A purported treatment for hemianopia, called vision restoration therapy, is based on this error. The dual perfusion theory is supported by anatomical studies showing that the middle cerebral artery perfuses the occipital pole in many individuals.In patients with hemianopia from stroke, neuroimaging shows preservation of the occipital pole when macular sparing is present. The frontier dividing the infarcted territory of the posterior cerebral artery and the preserved territory of the middle cerebral artery is variable, but always falls within the representation of the macula, because the macula is so highly magnified. For physicians, macular sparing was an important neurological sign in acute hemianopia because it signified a posterior cerebral artery occlusion. Modern neuroimaging has supplanted the importance of that clinical sign but at the same time confirmed its validity. For patients, macular sparing remains important because it mitigates the impact of hemianopia and preserves the ability to read fluently.

Interocular Suppression in Primary Visual Cortex in Strabismus.

People with strabismus acquired during childhood do not experience diplopia (double vision). To investigate how perception of the duplicate image is suppressed, we raised two male monkeys with alternating exotropia by disinserting the medial rectus muscle in each eye at age four weeks. Once the animals were mature, they were brought to the laboratory and trained to fixate a small spot while recordings were made in primary visual cortex (V1). Drifting gratings were presented to the receptive fields of 500 single neurons for eight interleaved conditions: (1) right eye monocular; (2) left eye monocular; (3) right eye's field, right eye fixating; (4) right eye's field, left eye fixating; (5) left eye's field, right eye fixating; (6) left eye's field, left eye fixating; (7) both eyes' fields, right eye fixating; (8) both eyes' fields, left eye fixating. As expected, ocular dominance histograms showed a monocular bias compared with normal animals, but many cells could still be driven via both eyes. Overall, neuronal responses were not affected by switches in ocular fixation. Individual neurons exhibited binocular interactions, but mean population indices indicated no net interocular suppression or facilitation. Even neurons located in cortex with reduced cytochrome oxidase (CO) activity, representing portions of the nasal visual field where perception is suppressed during binocular viewing, showed no net inhibition. These data indicate that V1 neurons do not appear to reflect strabismic suppression and therefore the elimination of diplopia is likely to be mediated at a higher cortical level.SIGNIFICANCE STATEMENT In patients with strabismus, images fall on non-corresponding points in the two retinas. Only one image is perceived, because signals emanating from the other eye that convey the duplicate image are suppressed. The benefit is that diplopia is prevented, but the penalty is that the visual feedback required to adjust eye muscle tone to realign the globes is eliminated. Here, we report the first electrophysiological recordings from the primary visual cortex (V1) in awake monkeys raised with strabismus. The experiments were designed to reveal how perception of double images is avoided.

Bilateral Occlusion Reduces the Ocular Deviation in Intermittent Exotropia.

Purpose: The most common form of strabismus, intermittent exotropia, is thought to become manifest when the drive to fuse is overcome by excessive divergent muscle tone. This principle is tested by examining the alignment of the eyes in the absence of vision. We compare the ocular deviation in patients with intermittent exotropia under conditions of monocular versus binocular occlusion. Methods: This prospective study of a patient cohort referred to our laboratory enrolled 18 patients with typical findings of well-controlled intermittent exotropia. Eye positions were recorded with video eye trackers while patients looked at a fixation spot at a distance of 57 cm. One eye was occluded, and the resulting ocular deviation was measured. Both eyes were then occluded, and the ocular deviation was re-measured. Results: The majority of patients (11/18) had a smaller deviation when both eyes were covered. Occlusion of one eye resulted in a mean exotropia of 13.5° ± 4.7°. Occlusion of both eyes reduced the mean exotropia to 6.0° ± 6.5° (paired t-test, P < 0.001), corresponding to a 56% reduction in the ocular deviation. This reduction persisted during prolonged bilateral occlusion but reversed as soon as vision was restored. Conclusions: Bilateral occlusion reveals a fixation-free state of alignment that is different from orthotropia and usually less than the exotropia that occurs spontaneously during binocular viewing. This finding demonstrates that the deviation angle in patients with intermittent exotropia is actively mediated by visual feedback, which the fixating eye is capable of providing alone.

Vertical Optokinetic Stimulation Induces Diagonal Eye Movements in Patients with Idiopathic Infantile Nystagmus.

Purpose: In patients with early ocular misalignment and nystagmus, vertical optokinetic stimulation reportedly increases the horizontal component of the nystagmus present during fixation, resulting in diagonal eye movements. We tested patients with infantile nystagmus syndrome but normal ocular alignment to determine if this crosstalk depends on strabismus. Methods: Eye movements were recorded in seven patients with infantile nystagmus. All but one patient had normal ocular alignment with high-grade stereopsis. Nystagmus during interleaved trials of right, left, up, and down optokinetic stimulation was compared with waveforms recorded during fixation. Six patients with strabismus but no nystagmus were also tested. Results: In infantile nystagmus syndrome, horizontal motion evoked a mostly jerk nystagmus with virtually no vertical component. A vertical optokinetic pattern produced nystagmus with a diagonal trajectory. It was not simply a combination of a vertical component from optokinetic stimulation and a horizontal component from the subject's congenital nystagmus, rather in six of seven patients, the slow-phase velocity of the horizontal component during vertical optokinetic stimulation differed from that recorded during fixation. In the six strabismus patients without nystagmus, responses to vertical optokinetic stimulation were normal. Conclusions: In patients with congenital motor nystagmus, a vertical noise pattern drives a diagonal nystagmus. This appears to arise because of crosstalk between the vertical and horizontal components of the optokinetic system. This abnormal response to vertical stimulation is not caused by strabismus because it occurs in patients with infantile nystagmus without strabismus. Moreover, it is absent in patients with strabismus and no spontaneous nystagmus.

Saccade Strategy in Alternating Exotropia.

Patient with exotropia frequently alternate fixation, looking at something with one eye and then switching their attention to acquire a new target with the other eye. Which eye informs the brain about the location of the new target? To address this issue, we presented targets dichoptically to 16 exotropes that were visible to the fixating eye, the deviated eye, or to both eyes. We then compared the subjects' choice of eye for target acquisition with the organization of their suppression scotomas. There was a correspondence between suppression scotoma maps and the eye used to acquire peripheral targets. In other words, a target perceived via an eye was also fixated by it. These studies reveal how patients with alternating strabismus, despite eye misalignment, manage to localize and fixate efficiently visual targets in their environment.

Spontaneous Reattachment of the Medial Rectus After Free Tenotomy.

PURPOSE: To assess the outcome of free tenotomy of the medial rectus muscle in post-natal monkeys. METHODS: The medial rectus muscle was disinserted in both eyes of 6 macaques at age 4 weeks to induce an alternating exotropia. After the impact on the visual cortex and superior colliculus was investigated, the animals were examined post-mortem to assess the anatomy of the medial rectus muscles. RESULTS: After tenotomy, the monkeys eventually recovered partial adduction. Necropsy revealed that all 12 medial rectus muscles had reattached to the globe. They were firmly connected via an abnormally long tendon, but at the native insertion site. CONCLUSIONS: Medial rectus muscles are able to reattach spontaneously to the eye following free tenotomy in post-natal macaques. The early timing of surgery and the large size of the globe relative to the orbit may explain why reinsertion occurs more readily in monkeys than in children with a lost muscle after strabismus surgery. [J Pediatr Ophthalmol Strabismus. 2018;55(5):335-338.].

Normal Topography and Binocularity of the Superior Colliculus in Strabismus.

In subjects with alternating strabismus, either eye can be used to saccade to visual targets. The brain must calculate the correct vector for each saccade, which will depend on the eye chosen to make it. The superior colliculus, a major midbrain center for saccade generation, was examined to determine whether the maps serving each eye were shifted to compensate for strabismus. Alternating exotropia was induced in two male macaques at age 1 month by sectioning the tendons of the medial recti. Once the animals grew to maturity, they were trained to fixate targets with either eye. Receptive fields were mapped in the superior colliculus using a sparse noise stimulus while the monkeys alternated fixation. For some neurons, sparse noise was presented dichoptically to probe for anomalous retinal correspondence. After recordings, microstimulation was applied to compare sensory and motor maps. The data showed that receptive fields were offset in position by the ocular deviation, but otherwise remained aligned. In one animal, the left eye's coordinates were rotated ∼20° clockwise with respect to those of the right eye. This was explained by a corresponding cyclorotation of the ocular fundi, which produced an A-pattern deviation. Microstimulation drove the eyes accurately to the site of receptive fields, as in normal animals. Single-cell recordings uncovered no evidence for anomalous retinal correspondence. Despite strabismus, neurons remained responsive to stimulation of either eye. Misalignment of the eyes early in life does not alter the organization of topographic maps or disrupt binocular convergence in the superior colliculus.SIGNIFICANCE STATEMENT Patients with strabismus are able to make rapid eye movements, known as saccades, toward visual targets almost as gracefully as subjects with normal binocular alignment. They can even exercise the option of using the right eye or the left eye. It is unknown how the brain measures the degree of ocular misalignment and uses it to compute the appropriate saccade for either eye. The obvious place to investigate is the superior colliculus, a midbrain oculomotor center responsible for the generation of saccades. Here, we report the first experiments in the superior colliculus of awake primates with strabismus using a combination of single-cell recordings and microstimulation to explore the organization of its topographic maps.

Incomitance and Eye Dominance in Intermittent Exotropia.

Purpose: To determine if the deviation angle changes in subjects with intermittent exotropia as they alternate fixation between the right and left eye in primary gaze. Methods: In this prospective observational cohort study, 37 subjects with intermittent exotropia were tested for evidence of incomitance. The position of each eye was recorded with a video tracker during fixation on a small central target. A cover-uncover test was performed by occluding one eye with a shutter that passed infrared light, allowing continuous tracking of both eyes. The deviation angle was measured during periods of right eye and left eye fixation. Incomitance was assessed as a function of eye preference, fixation stability, and exotropia variability. Results: The mean exotropia was 18.2° ± 8.1°. A difference between right exotropia and left exotropia was detectable in 16/37 subjects. Allowing for potential tracking error, the incomitance had a mean amplitude of 1.7°. It was not related to a difference in accommodative effort, eye preference, fixation stability, or variability in deviation. Conclusions: Comitance is regarded as a feature that distinguishes strabismus from paralytic or restrictive processes. Unexpectedly, eye tracking during the cover-uncover test showed that incomitance is present in approximately 40% of subjects with intermittent exotropia. It averages 10% of the exotropia, and can equal up to 5°. When substantial, it may be worth considering when planning surgical correction.

Capturing the Moment of Fusion Loss in Intermittent Exotropia.

PURPOSE: To characterize eye movements made by patients with intermittent exotropia when fusion loss occurs spontaneously and to compare them with those induced by covering 1 eye and with strategies used to recover fusion. DESIGN: Prospective study of a patient cohort referred to our laboratory. PARTICIPANTS: Thirteen patients with typical findings of intermittent exotropia who experienced frequent spontaneous loss of fusion. METHODS: The position of each eye was recorded with a video eye tracker under infrared illumination while fixating on a small central near target. MAIN OUTCOME MEASURES: Eye position and peak velocity measured during spontaneous loss of fusion, shutter-induced loss of fusion, and recovery of fusion. RESULTS: In 10 of 13 subjects, the eye movement made after spontaneous loss of fusion was indistinguishable from that induced by covering 1 eye. It reached 90% of full amplitude in a mean of 1.75 seconds. Peak velocity of the deviating eye's movement was highly correlated for spontaneous and shutter-induced events. Peak velocity was also proportional to exotropia amplitude. Recovery of fusion was more rapid than loss of fusion, and often was accompanied by interjection of a disconjugate saccade. CONCLUSIONS: Loss of fusion in intermittent exotropia is not influenced by visual feedback. Excessive divergence tone may be responsible, but breakdown of alignment occurs via a unique, pathological type of eye movement that differs from a normal, physiological divergence eye movement.

Normal correspondence of tectal maps for saccadic eye movements in strabismus.

The superior colliculus is a major brain stem structure for the production of saccadic eye movements. Electrical stimulation at any given point in the motor map generates saccades of defined amplitude and direction. It is unknown how this saccade map is affected by strabismus. Three macaques were raised with exotropia, an outwards ocular deviation, by detaching the medial rectus tendon in each eye at age 1 mo. The animals were able to make saccades to targets with either eye and appeared to alternate fixation freely. To probe the organization of the superior colliculus, microstimulation was applied at multiple sites, with the animals either free-viewing or fixating a target. On average, microstimulation drove nearly conjugate saccades, similar in both amplitude and direction but separated by the ocular deviation. Two monkeys showed a pattern deviation, characterized by a systematic change in the relative position of the two eyes with certain changes in gaze angle. These animals' saccades were slightly different for the right eye and left eye in their amplitude or direction. The differences were consistent with the animals' underlying pattern deviation, measured during static fixation and smooth pursuit. The tectal map for saccade generation appears to be normal in strabismus, but saccades may be affected by changes in the strabismic deviation that occur with different gaze angles.