The purpose of this study was to report findings in a series of primates who had onset of natural esotropia in the first months of life. The first question we posed was whether infantile esotropia in monkeys was an all-or-none disorder – do the animals exhibit equally severe deficits (e.g. all large-angle strabismus and high-velocity nystagmus) or do they show a range of abnormality, from subtle to marked? The answer to this question is that they – like their human counterparts – display a range of quantitative severities. The esotropia in this group of animals spanned small to large, was constant, concomitant, and not related directly to refractive error. The majority of the animals freely alternated fixation; a minority displayed a consistent fixation preference. These features remarkably mimic features of early-onset esotropia in human infants.16
Our findings also reveal systematic relationships among the classical ocular motor signs of infantile strabismus. Each of the esotropic animals displayed the constellation of signs that typify the infantile esotropia syndrome in humans: constant heterotropia, latent nystagmus, pursuit/OKN asymmetry, and – in 5 of 6 measured – DVD. The magnitude of each sign, with small individual variation, increased in concordance with the other signs. Similar concordance between these signs has been reported in normal infant primates exposed to binocular decorrelation in the first weeks of life.2, 3
In those monkeys, each sign increased in severity with increasing duration of the decorrelation. In a small group of adult humans who had infantile esotropia, a crude correlation was found between magnitude of esotropia, severity of pursuit asymmetry, velocity of latent nystagmus, and DVD.17
We are unaware of other studies that have examined these inter-relations. The relationship is deserving of more study because it has important implications for the mechanisms linking vergence and gaze dysfunction.
The second question we posed was whether the severity of the ocular motor signs was related to the severity of reduced binocular connections in area V1. Area V1 is the first locus in the primate CNS for binocularity, and binocularity provides the absolute disparity signals necessary to guide vergence alignment.18, 19
Binocular output from area V1 to regions of extrastriate cortex is also important for development of stable gaze holding (absence of eye drift) and symmetric tracking.20
Disruptions of normal binocular development in the first months of life lead to permanent deficits of these functions, manifested as nasalward drift (latent nystagmus) and nasalward biases of pursuit/OKN. Our finding that reduced anatomic connections for binocularity in the esotropic monkeys related systematically to the their vergence and gaze deficits, reinforces the validity of this functional-structural linkage.
The third question we addressed was whether early-onset esotropia in primates could be explained by primary abnormalities of the horizontal rectus muscles. The answer is no; we found no evidence of a structural or innervational extraocular muscle anomaly. It may be useful in future experiments to also examine muscle composition using electron microscopy and immunohistochemistry. Our findings add to a large body of work in primate models, and to clinical observations, arguing against a primary EOM, motor neuron, or brainstem abnormality as the cause of infantile strabismus. We performed this analysis using a tedious method requiring serial sectioning of paraffin-embedded whole orbits, which has proven to be highly enlightening for revealing subtle abnormalities of orbital anatomy.8-10
Human infants at greatest risk of esotropia are those who suffer often subtle, direct or indirect perturbations to the geniculostriate pathways of the cerebral hemispheres during an early critical stage of visuomotor development.21-23
Experiments in normal infant monkeys have revealed that sensorial, binocular decorrelation alone is sufficient to produce all of the ocular motor and sensory signs of this syndrome, without any manipulation of the EOMs or motor pathways.2, 3
Taken together, the current results and those of previous animal and human studies, lead us to conclude that infantile esotropia is a natural default. The default is brought about when immature, unstable, nasally biased vergence and gaze circuits are impeded in their normal maturation, by intrinsic or extrinsic factors, during the first critical weeks and months of life.