Neural mechanisms of oculomotor abnormalities in the infantile strabismus syndrome

Abstract

Infantile strabismus is characterized by numerous visual and oculomotor abnormalities. Recently nonhuman primate models of infantile strabismus have been established, with characteristics that closely match those observed in human patients. This has made it possible to study the neural basis for visual and oculomotor symptoms in infantile strabismus. In this review, we consider the available evidence for neural abnormalities in structures related to oculomotor pathways ranging from visual cortex to oculomotor nuclei. These studies provide compelling evidence that a disturbance of binocular vision during a sensitive period early in life, whatever the cause, results in a cascade of abnormalities through numerous brain areas involved in visual functions and eye movements.

Response Properties of Cells Within the Rostral Superior Colliculus of Strabismic Monkeys

“…3 Recent data from animal models of strabismus acquired using neurophysiological methods such as electrical stimulation, muscimol inactivation, and single cell recording within numerous brain areas including the motor nuclei, supraoculomotor area (SOA), fastigial and posterior interposed nuclei of the cerebellum, paramedian pontine reticular formation (PPRF), and the superior colliculus (SC), have shown that various structures within a vergence neural circuit contributes toward maintenance of the state of strabismus. [4][5][6][7][8][9][10][11] The SC has been extensively studied for its involvement in saccadic eye movements, [12][13][14] and this structure also appears to have a role in vergence. Van Horn et al, 15 in a study in normal monkeys, have shown that the rostral SC (rSC) contains vergence related neurons (convergence and divergence), which modulate with eye movements made to sinusoidal target motion in depth.…”

Neural plasticity following surgical correction of strabismus in monkeys

“…Prism-viewing starting from the first day of birth till they were ~ 4 months of age after which they were allowed unrestricted vision. Disruption of binocular vision (due to binocular decorrelation as a consequence of prism viewing) during the critical period is successful in inducing misalignment and other eye movement abnormalities associated with strabismus (Crawford et al 1996, Crawford et al 1996, Tusa et al 2002, Das 2016, Walton et al 2017).…”

“…Strabismus is a developmental disorder that affects ~ 4% of children worldwide (Von Noorden and Campos 2002, Govindan et al 2005, Greenberg et al 2007). In addition to ocular misalignment and sometimes visual acuity deficits (strabismic amblyopia), problems with binocular vision and oculomotor control such as deficits in processing disparity, poor stereo-acuity, disconjugate and cross-axis eye movements and nystagmus are also observed with strabismus and replicated in the monkey model (Lorenz 2002, Das 2008, Das 2009, Das 2016, Walton et al 2017). The most common treatment strategy for strabismus is the surgical manipulation of specific extraocular muscles to re-align the eyes.…”

Longitudinal Development of Ocular Misalignment in Nonhuman Primate Models for Strabismus

“…Additionally, there are other adaptive muscular or neurologic factors that play a role in the long-term maintenance of ocular alignment. 6,28 In a study by Smith et al, 46 the magnitude of ametropia and anisometropia was evaluated in monkeys with surgical and optical strabismus. The authors observed that in comparison to normal monkeys, monkeys with optical prism-reared strabismus (prism rearing started at 4 weeks of age) had a higher prevalence of hyperopic and myopic ametropia, as well as a significantly greater degree of anisometropia.…”

“…27 Each of these strabismus induction methods come with advantages and disadvantages that are reviewed elsewhere. 6,28 An optical prism-rearing paradigm that disrupts sensory fusion during the critical period of development is a popular method to induce strabismus and is the preferred method in our laboratory. 23,[29][30][31][32][33] This established model for inducing sensory strabismus in monkeys replicates the clinical signs and symptoms seen in humans with sensory strabismus, and many insights into neural mechanisms have been gained through the use of this model.…”