Longitudinal Development of Ocular Misalignment in Nonhuman Primate Models for Strabismus.

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.

Neural Plasticity Following Surgical Correction of Strabismus in Monkeys.

Purpose: Although widely practiced, surgical treatment of strabismus has varying levels of success and permanence. In this study we investigated adaptive responses within the brain and the extraocular muscles (EOM) that occur following surgery and therefore determine long-term success of the treatment. Methods: Single cell responses were collected from cells in the oculomotor and abducens nuclei before and after two monkeys (M1, M2) with exotropia (divergent strabismus) underwent a strabismus correction surgery that involved weakening of the lateral rectus (LR) and strengthening of the medial rectus (MR) muscle of one eye. Eye movement and neuronal data were collected for up to 10 months after surgery during a monocular viewing smooth-pursuit task. These data were fit with a first-order equation and resulting coefficients were used to estimate the population neuronal drive (ND) to each EOM of both eyes. Results: Surgery resulted in a ∼70% reduction in strabismus angle in both animals that reverted toward presurgical misalignment by approximately 6 months after treatment. In the first month after surgery, the ND to the treated MR reduced in one animal and ND to the LR increased in the other animal, both indicating active neural plasticity that reduced the effectiveness of the treatment. Adaptive changes in ND to the untreated eye were also identified. Conclusions: Active neural and muscle plasticity corresponding to both the treated and the untreated eye determines longitudinal success following surgical correction of strabismus. Outcome of surgical treatment could be improved by identifying ways to enhance "positive" adaptation and limit "negative" adaptation.

Fixational Saccades and Their Relation to Fixation Instability in Strabismic Monkeys.

Purpose: To evaluate the contribution of fixational saccades toward fixation instability in strabismic monkeys. Methods: Binocular eye movements were measured as six experimental monkeys (five strabismic monkeys and one monkey with downbeat nystagmus) and one normal monkey fixated targets of two shapes (Optotype, Disk) and two sizes (0.5°, 2°) during monocular and binocular viewing. Fixational saccades were detected using an unsupervised clustering algorithm. Results: When compared with the normal monkey, amplitude and frequency of fixational saccades in both the viewing and nonviewing eye were greater in 3 of 5 strabismic monkeys (1-way ANOVA on ranks P < 0.001; median amplitude in the normal monkey viewing eye: 0.33°; experimental animals: median amplitude range 0.20-0.82°; median frequency in the normal monkey: 1.35/s; experimental animals: median frequency range 1.3-3.7/s). Increase in frequency of fixational saccades was largely due to quick phases of ongoing nystagmus. Fixational saccade amplitude was increased significantly (3-way ANOVA; P < 0.001) but by small magnitude depending on target shape and size (mean difference between disk and optotype targets = 0.02°; mean difference between 2° and 0.5° targets = 0.1°). Relationship between saccade amplitude and the Bivariate Contour Ellipse Area (BCEA) was nonlinear, showing saturation of saccade amplitude. Fixation instability in depth was significantly greater in strabismic monkeys (vergence BCEA: 0.63 deg2-2.15 deg2) compared with the normal animal (vergence BCEA: 0.15 deg2; P < 0.001). Conclusions: Increased fixational instability in strabismic monkeys is only partially due to increased amplitude and more frequent fixational saccades. Target parameter effects on fixational saccades are similar to previous findings of target effects on BCEA.

Longitudinal Evaluation of Eye Misalignment and Eye Movements Following Surgical Correction of Strabismus in Monkeys.

PURPOSE: Strabismus correction surgery is well documented in both the literature and practice with varying levels of success and permanence. Our goal was to characterize longitudinal changes in eye alignment and eye movements following strabismus correction surgery in a monkey model for developmental strabismus. METHODS: We studied two juvenile rhesus monkeys with exotropia previously induced via an optical prism-rearing paradigm in infancy. Eye misalignment was corrected via a resection-recession surgery of the horizontal rectus muscles of one eye. Binocular search coils were used to collect eye movement data during smooth-pursuit, saccades, and fixation tasks before surgical treatment, immediately after surgery, and through 6 months after treatment. RESULTS: Both animals showed an immediate ∼70% reduction in misalignment as a consequence of surgery that regressed to a 20%-40% improvement by 6 months after treatment. Significant changes were observed in saccade and smooth-pursuit gain of the nonviewing eye after surgery, which also reverted to presurgical values by 6 months. A temporary improvement in fixation stability of the nonviewing eye was observed after surgery; naso-temporal (N/T) asymmetry of monocular smooth-pursuit remained unchanged. CONCLUSIONS: Surgical realignment is followed by plastic changes that often lead to reversal of surgery effects. Immediate improvement in misalignment and changes in eye movement gains are likely a result of contractility changes at the level of the extraocular muscle, whereas longer-term effects are likely a combination of neural and muscle adaptation.