Project Summary Approximately 2% of children in the United States have strabismus, a condition in which the eyes are not aligned properly. As a consequence, stereovision may be lost and the deviated eye is at risk for reduced vision from amblyopia. There are many other potential consequences, including reduced eye-hand coordination, diminished quality of life, employment discrimination, social prejudice, and psychological distress. The goal of this project is to investigate the most common form of strabismus, intermittent exotropia. A translational approach is used that combines a prospective, longitudinal observational study of patients with intermittent exotropia to define its natural history and clinical features along with analysis of data from a parallel set of laboratory studies in nonhuman primates. Aim 1 will focus on the problem of defining the severity of intermittent exotropia. Patients wear tracking glasses that record the fixation point of each eye within the visual scene while they go about their normal daily activities. This technology makes it possible to measure the “occurrence rate” of exotropia – defined as the percentage of time that an ocular deviation is present. This data will enable eye doctors to identify which patients have a stable versus a progressive form of intermittent exotropia. The latter group may need surgery to re-align their eyes, but there is currently no consensus regarding the criteria for recommending surgery, in part because it has not previously been possible to quantify the occurrence rate. The project will also stratify patients into the 3 recognized subtypes of intermittent exotropia (basic, convergence insufficiency, divergence excess) to probe the relationship between fusion loss and vergence demand. Insights from that correlation could also influence surgical planning. Successful introduction of ambulatory eye tracking into pediatric eye care would thus have a major impact on the management of intermittent exotropia. Aim 2 will explore the contingent of retinal ganglion cells that projects to the superior colliculus, a brainstem center controlling eye movements. Experiments have been performed in monkeys, injecting a retrograde tracer into the superior colliculus to label these cells. A different retrograde tracer has been injected in the lateral geniculate nucleus in the same monkeys. The data from these animals will be analyzed to determine the percentage of ganglion cells which is double-labeled, signifying that the cells send a branching axon to both targets.