What do we know about the neurobiology of infantile-onset strabismus (IOS)? What has clinical and basic science work in humans and nonhuman primates (NHPs) revealed during the last 25 years?
Infantile-onset strabismus in humans and NHPs is a constellation (or syndrome) of ocular motor behaviors: eye misalignment; subnormal binocular fusion; latent fixation nystagmus (LN); dissociated vertical deviation; and in some, dissociated horizontal deviation. Children at greatest risk are those who suffer cerebral lesions around the time of birth. The common lesion is damage to the posterior-most fibers of the optic radiations, the binocular inputs to striate cortex.1-3 These infants have a 30- to 60-fold greater chance of getting IOS compared with healthy infants. Similarly, in infant NHPs, the full IOS constellation is produced reliably (100%) by perturbation of inputs to visual cortex.4 No manipulation of eye muscles or brainstem pathways is needed. The severity of IOS in the NHP increases monotonically with neuroanatomic loss of cortical binocular connections.5 The binocular defect is passed forward from striate to extrastriate cortex, regions that mediate balanced gaze (middle temporal/medial superior temporal visual areas) and vergence.6,7 Infantile-onset strabismus behaviors, including LN, correlate with physiologic loss of binocular responses in these regions. These cortical regions drive brainstem gaze nuclei, most notably the midbrain nucleus of the optic tract and contiguous nuclei of the accessory optic system (AOS).8 The major visual drive in NHPs to brainstem gaze neurons is descending and cortical, not direct from the retina or subcortical. Taken together, the hunt for the perpetrator of IOS points upstairs to the cortex not downstairs to the brainstem.