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Purpose To investigate the longitudinal change in horizontal and vertical ocular alignment in normal and prism-reared infant monkeys during the critical developmental period. Methods Ocular alignment was measured using Hirschberg photographic methods in 6 infant monkeys reared under prism-viewing from day 1 after birth to 4 months, and 2 monkeys reared with normal visual experience. Photographs were acquired twice a week for the first 6 months of life and analyzed to identify pupil center and the first Purkinje image from which eye positions and strabismus angle were calculated. Results At 3 weeks after birth, prism monkeys presented with significant horizontal ocular misalignment. A gradual change in alignment was seen in all prism-reared monkeys stabilizing at approximately 11 weeks, at which time 5 monkeys were exotropic (mean, 16° XT; range, 13°-24°) and 1 monkey was esotropic (5° ET). A reduction in ocular misalignment was observed after exposure to normal visual environment at 16 weeks, but at 34 weeks of age, that is, 18 weeks after removal of prisms, prism-reared monkeys displayed a mean horizontal strabismus of 7° XT (range, 2° ET to 20° XT), which was still significantly different from normal monkeys. Conclusions Prism-rearing disrupts binocular fusion mechanisms, and horizontal and vertical strabismus is seen to develop as early as 3 weeks of age in monkey models, equivalent to approximately 3 months in humans. The time course of change in alignment overlaps with disruption in various visual sensory functions, suggesting a causal temporal link between sensory and motor mechanisms for alignment.