Fusion Maldevelopment (Latent) Nystagmus: How Insights from Nonhuman Primate Experiments Have Benefitted Clinical Practice

Binocular fusion is blending of corresponding images from each eye to form a single percept. Maldevelopment of fusion (binocular non-correspondence) in infancy causes a specific type of lifelong ocular instability: fusion maldevelopment nystagmus (FMN). Because fusion maldevelopment – in the form of strabismus and amblyopia – is common, FMN is the most prevalent pathologic nystagmus encountered in clinical practice. Experiments on nonhuman primates (NHP) with strabismus and amblyopia have revealed that loss of binocular connections within area V1 (striate cortex) in the first months of life is the necessary and sufficient cause of FMN. The severity of FMN increases with greater losses of V1 connections. No manipulation of brainstem motor pathways is required. The binocular maldevelopment originating in area V1 is passed on to downstream, extrastriate regions of cerebral cortex that drive conjugate gaze (notably MSTd). Conjugate gaze is stable when MSTd neurons of the right vs. left cerebral hemisphere have balanced, binocular activity. Fusion maldevelopment causes unbalanced, monocular activity. If input from one eye dominates and the other is suppressed, MSTd in one hemisphere becomes more active. Downstream projections to the ipsilateral nucleus of the optic tract (NOT) drive the eyes conjugately to that side. The unbalanced MSTd drive is evident as nasalward slow-phase nystagmus when viewing with either eye. Experiments on NHPs have provided the functional-structural correlations needed to explain the pathophysiology of LN. The translational value of NHP studies cannot be overstated. The NHP studies provide pivotal facts necessary to explain one of the most common ocular motor disorders encountered by eye care providers worldwide. The NHP studies have motivated pediatric ophthalmologists to repair fusion earlier in infancy (Tychsen, J AAPOS 9:510–21, 2005), thereby preventing FMN or reducing its severity.