Retinal Input to Macaque Superior Colliculus Derives from Branching Axons Projecting to the Lateral Geniculate Nucleus.

The superior colliculus receives a direct projection from retinal ganglion cells. In primates, it remains unknown if the same ganglion cells also supply the lateral geniculate nucleus. To address this issue, a double-label experiment was performed in 2 male macaques. The animals fixated a target while injection sites were scouted in the superior colliculus by recording and stimulating with a tetrode. Once suitable sites were identified, cholera toxin - subunit B Alexa Fluor 488 was injected via an adjacent micropipette. In a subsequent acute experiment, cholera toxin subunit B - Alexa Fluor 555 was injected into the lateral geniculate nucleus at matching retinotopic locations. After a brief survival period, ganglion cells were examined in retinal flatmounts. The percentage of double-labeled cells varied locally, depending on the relative efficiency of retrograde transport by each tracer and the precision of retinotopic overlap of injection sites in each target nucleus. In counting boxes with extensive overlap, 76-98% of ganglion cells projecting to the superior colliculus were double-labeled. Cells projecting to the superior colliculus constituted 4.0 - 6.7% of the labeled ganglion cell population. In one particularly large zone, there were 5,746 cells labeled only by CTB-AF555, 561cells double-labeled by CTB-AF555 and CTB-AF488, but no cell labeled only by CTB-AF488. These data indicate that retinal input to the macaque superior colliculus arises from a collateral axonal branch supplied by about 5% of the ganglion cells that project to the lateral geniculate nucleus. Surprisingly, there exist no ganglion cells that project exclusively to the SC.Significance statement The retina contains a multitude of ganglion cell classes, projecting in parallel to different brain targets. The superior colliculus receives retinal input, but its source remains controversial. In two macaques, a green tracer was injected into the superior colliculus and an orange tracer into the lateral geniculate nucleus. When retinotopic overlap was optimal, ganglion cells containing the green tracer were also labeled by the orange tracer. This finding indicates that retinal input to the superior colliculus arises from axon collaterals of ganglion cells that project to the lateral geniculate nucleus, even though these two retinal targets serve utterly different functions. The next challenge is to determine the purpose of this projection and why it is shared.

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.

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.

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.

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.

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.

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.

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.

Cortical Representation of a Myopic Peripapillary Crescent.

PURPOSE: To determine how formation of an acquired myopic crescent adjacent to the optic disc affects metabolic activity in the primary visual cortex. DESIGN: Laboratory animal study. PARTICIPANTS: Three macaque monkeys. METHODS: The blind spot region in the primary visual cortex was labeled by cytochrome oxidase (CO) histochemistry analysis or [(3)H]proline autoradiography. MAIN OUTCOME MEASURES: Visualization of the representation of the blind spot and myopic peripapillary crescent in the visual cortex. RESULTS: In high myopia, a region resembling the myopic peripapillary crescent was visible in cortical sections processed for CO. In this region, metabolic activity was reduced in ocular dominance columns that normally would be driven by input from retina corresponding to the myopic peripapillary crescent. CONCLUSIONS: The formation of a myopic crescent is accompanied by loss of metabolic activity in the cortex supplied by the affected retina. This observation confirms that retinal tissue is damaged by the development of a myopic crescent, rather than simply translocated in a temporal direction. The cortical defect matches the myopic peripapillary crescent in size and shape, indicating that fill-in of the retinotopic map by healthy, surrounding retina does not occur.

Vascular Supply of the Cerebral Cortex is Specialized for Cell Layers but Not Columns.

The vascular supply to layers and columns was compared in macaque primary visual cortex (V1) by labeling red blood cells via their endogenous peroxidase activity. Alternate sections were processed for cytochrome oxidase to reveal "patches" or "blobs," which anchor the interdigitated column systems of striate cortex. More densely populated cell layers received the most profuse blood supply. In the superficial layers the blood supply was organized into microvascular lobules, consisting of a central venule surrounded by arterioles. Each vessel was identified as an arteriole or venule by matching it with the penetration site where it entered the cortex from a parent arteriole or venule in the pial circulation. Although microvascular lobules and cytochrome oxidase patches had a similar periodicity, they bore no mutual relationship. The size and density of penetrating arterioles and venules did not differ between patches and interpatches. The red blood cell labeling in patches and interpatches was equal. Moreover, patches and interpatches were supplied by an anastomotic pial arteriole system, with no segregation of blood supply to the two compartments. Often a focal constriction was present at the origin of pial arterial branches, indicating that local control of cortical perfusion may be accomplished by vascular sphincters.

Eye choice for acquisition of targets in alternating strabismus.

In strabismus, potentially either eye can inform the brain about the location of a target so that an accurate saccade can be made. Sixteen human subjects with alternating exotropia were tested dichoptically while viewing stimuli on a tangent screen. Each trial began with a fixation cross visible to only one eye. After the subject fixated the cross, a peripheral target visible to only one eye flashed briefly. The subject's task was to look at it. As a rule, the eye to which the target was presented was the eye that acquired the target. However, when stimuli were presented in the far nasal visual field, subjects occasionally performed a "crossover" saccade by placing the other eye on the target. This strategy avoided the need to make a large adducting saccade. In such cases, information about target location was obtained by one eye and used to program a saccade for the other eye, with a corresponding latency increase. In 10/16 subjects, targets were presented on some trials to both eyes. Binocular sensory maps were also compiled to delineate the portions of the visual scene perceived with each eye. These maps were compared with subjects' pattern of eye choice for target acquisition. There was a correspondence between suppression scotoma maps and the eye used to acquire peripheral targets. In other words, targets were fixated by the eye used to perceive them. These studies reveal how patients with alternating strabismus, despite eye misalignment, manage to localize and capture visual targets in their environment.

Contrasting effects of strabismic amblyopia on metabolic activity in superficial and deep layers of striate cortex.

To probe the mechanism of visual suppression, we have raised macaques with strabismus by disinserting the medial rectus muscle in each eye at 1 mo of age. Typically, this operation produces a comitant, alternating exotropia with normal acuity in each eye. Here we describe an unusual occurrence: the development of severe amblyopia in one eye of a monkey after induction of exotropia. Shortly after surgery, the animal demonstrated a strong fixation preference for the left eye, with apparent suppression of the right eye. Later, behavioral testing showed inability to track or to saccade to targets with the right eye. With the left eye occluded, the animal demonstrated no visually guided behavior. Optokinetic nystagmus was absent in the right eye. Metabolic activity in striate cortex was assessed by processing the tissue for cytochrome oxidase (CO). Amblyopia caused loss of CO in one eye's rows of patches, presumably those serving the blind eye. Layers 4A and 4B showed columns of reduced CO, in register with pale rows of patches in layer 2/3. Layers 4C, 5, and 6 also showed columns of CO activity, but remarkably, comparison with more superficial layers showed a reversal in contrast. In other words, pale CO staining in layers 2/3, 4A, and 4B was aligned with dark CO staining in layers 4C, 5, and 6. No experimental intervention or deprivation paradigm has been reported previously to produce opposite effects on metabolic activity in layers 2/3, 4A, and 4B vs. layers 4C, 5, and 6 within a given eye's columns.

Co-localization of glutamic acid decarboxylase and vesicular GABA transporter in cytochrome oxidase patches of macaque striate cortex.

The patches in primary visual cortex constitute hot spots of metabolic activity, manifested by enhanced levels of cytochrome oxidase (CO) activity. They are also labeled preferentially by immunostaining for glutamic acid decarboxylase (GAD), γ-aminobutyric acid (GABA), and parvalbumin. However, calbindin shows stronger immunoreactivity outside patches. In light of this discrepancy, the distribution of the vesicular GABA transporter (VGAT) was examined in striate cortex of two normal macaques. VGAT immunoreactivity was strongest in layers 4B, 4Cα, and 5. In tangential sections, the distribution of CO, GAD, and VGAT was compared in layer 2/3. There was a close match between all three labels. This finding indicates that GABA synthesis is enriched in patches, and that inhibitory synapses are more active in patches than interpatches.

Cortical metabolic activity matches the pattern of visual suppression in strabismus.

When an eye becomes deviated in early childhood, a person does not experience double vision, although the globes are aimed at different targets. The extra image is prevented from reaching perception in subjects with alternating exotropia by suppression of each eye's peripheral temporal retina. To test the impact of visual suppression on neuronal activity in primary (striate) visual cortex, the pattern of cytochrome oxidase (CO) staining was examined in four macaques raised with exotropia by disinserting the medial rectus muscles shortly following birth. No ocular dominance columns were visible in opercular cortex, where the central visual field is represented, indicating that signals coming from the central retina in each eye were perceived. However, the border strips at the edges of ocular dominance columns appeared pale, reflecting a loss of activity in binocular cells from disruption of fusion. In calcarine cortex, where the peripheral visual field is represented, there were alternating pale and dark bands resembling ocular dominance columns. To interpret the CO staining pattern, [(3)H]proline was injected into the right eye in two monkeys. In the right calcarine cortex, the pale CO columns matched the labeled proline columns of the right eye. In the left calcarine cortex, the pale CO columns overlapped the unlabeled columns of the left eye in the autoradiograph. Therefore, metabolic activity was reduced in the ipsilateral eye's ocular dominance columns which serve peripheral temporal retina, in a fashion consistent with the topographic organization of suppression scotomas in humans with exotropia.

Perception via the deviated eye in strabismus.

Misalignment of the eyes can lead to double vision and visual confusion. However, these sensations are rare when strabismus is acquired early in life, because the extra image is suppressed. To explore the mechanism of perceptual suppression in strabismus, the visual fields were mapped binocularly in 14 human subjects with exotropia. Subjects wore red/blue filter glasses to permit dichoptic stimulation while fixating a central target on a tangent screen. A purple stimulus was flashed at a peripheral location; its reported color ("red" or "blue") revealed which eye's image was perceived at that locus. The maps showed a vertical border between the center of gaze for each eye, splitting the visual field into two separate regions. In each region, perception was mediated by only one eye, with suppression of the other eye. Unexpectedly, stimuli falling on the fovea of the deviated eye were seen in all subjects. However, they were perceived in a location shifted by the angle of ocular deviation. This plasticity in the coding of visual direction allows accurate localization of objects everywhere in the visual scene, despite the presence of strabismus.

Multicenter evaluation of Neurelec Digisonic® SP cochlear implant reliability.

Over the past decade, the adoption of universal hearing screening in newborns has led to earlier detection of hearing problems and significant lowering of the age of first cochlear implantation. As a consequence, recipients are now expected to keep their cochlear implants (CIs) for a longer period of time. Comprehensive longitudinal information on CI reliability is essential for device choice. The aim of this study was to assess the reliability (in children and adults) of the latest generation of the Digisonic(®) SP CI launched in 2006 by Neurelec. Failure rate (FR) and cumulative survival rate (CSR) for a 5-year period were calculated. This survey is a multicenter retrospective study. A questionnaire was sent to nine CI centers requesting information about patients implanted with Neurelec Digisonic(®) SP CIs. FR and CSR over a 5-year period were calculated on this group. Collaborating centers collected data on 672 patients (362 children and 310 adults) implanted between March 2006 and March 2011. The overall rate of explantation was 2.23 % (15 cases): six devices were explanted due to device failure (0.89 %) and nine were explanted for medical reasons (1.34 %). Four patients were lost to follow-up. The CSR at 5 years was 98.51 % on all patients, 98.48 % for children and 98.57 % for adults. FR was 0.97 % for adults and 0.83 % for children. This first independent study that assesses FR and CSR on the current generation of Digisonic(®) SP CI represents an important resource that can help clinicians and patients during their device choice.

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.

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.