Spectrum of infantile esotropia in primates: Behavior, brains, and orbits.

ABSTRACT

INTRODUCTION: Recent studies of human infants have described a spectrum of early-onset esotropia, from small angle to large heterotropias. We report here a similar spectrum of early-onset esotropia in infant monkeys, with emphasis on the relationship between visuomotor deficits, central nervous system circuitry, and orbital anatomy. METHODS: Eye movements were recorded in macaque monkeys with natural, infantile-onset esotropia (n = 7) and in control monkeys (n = 2) to assess alignment, latent nystagmus, dissociated vertical deviation (DVD), and pursuit/optokinetic nystagmus (OKN) asymmetries. Acuity was measured by preferential-looking technique or spatial sweep visual-evoked potentials. Geniculo-striate pathways were then analyzed with neuroanatomic tracers and ocular dominance column labels. Extraocular muscles were examined by high-resolution magnetic resonance imaging (MRI) and anatomic sectioning of whole orbits. RESULTS: Esotropia ranged from 4 to 13.5 degrees (7-24(Delta)) with fixation preference (if any) varying idiosyncratically (as in human). Severity of ocular motor dysfunction (ie, nystagmus velocity, DVD amplitude, pursuit-OKN nasal bias index) increased as the magnitude of esotropia angle. Animals with greater ocular motor deficits tended to have greater visual area V1 (striate cortex) neuroanatomic deficits, evident as fewer binocular horizontal connections in V1. Orbital MRI/anatomic analysis showed no difference in horizontal rectus cross-sectional areas, muscle paths, innervation densities, or cytoarchitecture compared with normal animals. CONCLUSIONS: The infantile esotropia spectrum in nonhuman primates is remarkably similar to that reported in human infants. Concomitant esotropia in these primates cannot be ascribed to abnormalities of the extraocular muscles or orbit. These findings, combined with epidemiologic studies of humans, suggest that perturbations of cerebral binocular pathways in early development are the primary cause of the infantile esotropia syndrome.