Longitudinal Investigation of Behavioral and Neuronal Responses before and after Strabismus Correction Surgery in Non-Human Primates
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Purpose: Strabismus is a developmental disorder observed in 2-4% of children. A preferred treatment of strabismus is the surgical manipulation of extraocular muscles (EOM) to alter muscle force-tension relationships to reduce ocular misalignment. Although widely practiced, treatment effects vary in success and permanence. The aims of this dissertation were to longitudinally follow the behavioral and neuronal changes that occur following surgical correction of strabismus in non-human primates with a goal of understanding neuronal plasticity following treatment. Fixation stability is an important aspect of gaining information about the visual scene, which is often compromised in strabismic patients. Another line of research in this dissertation was to examine the relationship between fixational saccades (Fsac) and fixation stability in normal and strabismic animals. Methods: Strabismus treatment studies: Single cell recordings from 530 cells in the oculomotor (OMN) and abducens (Abd) nuclei were obtained from two monkeys (M1 and M2) with divergent strabismus before and after they underwent a strabismus correction surgery. Neuronal drive (ND) to the deviated eye was calculated using the motoneuron responses as the monkeys performed a horizontal smooth pursuit task. Behavioral data such as eye alignment, saccade and smooth pursuit metrics were recorded before and after treatment using scleral search coils in the same animals to help interpret neuronal changes. Fixational saccade study: Eye movement data were recorded using scleral search coils as 5 strabismic and 3 normal monkeys fixated targets that varied in shape (between an optotype ‘%’ and a disk), size (0.5° and 2°) and viewing conditions (Left eye viewing, right eye viewing, binocular). Goal of the analysis was to examine relationship of Fsac direction to target shape and relationship of Fsac amplitude to fixation stability. Results: Strabismus treatment studies: Strabismus correction surgery resulted in a ~70% reduction in strabismus angle in both animals that reverted towards pre-surgical misalignment by about 6 months after treatment. Significant changes in saccade and smooth-pursuit eye movement gains were observed immediately after treatment, but these resolved within 1 month after surgery. Analysis of the population neural responses within the oculomotor and abducens nuclei showed that 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 observed. An analytical method used to determine muscle contractility showed that significant peripheral muscle remodeling after surgery also contributed to reversal of strabismus correction. Fixation saccade study: Target parameters had a significant effect on the amplitude of Fsac with the larger targets resulting in larger Fsac. A strong interaction of target size and shape was seen in the direction of Fsac in the normal monkey cohort. This effect was absent in the strabismic monkey group as the direction of Fsac were influenced largely by the direction of nystagmus present in these monkeys. Conclusion: Active neuronal and muscle plasticity following surgical correction of strabismus was identified in both the ND to the treated eye and untreated eye that lead to the failure of treatment in these two monkeys. We suggest that outcome of strabismus correction surgery could be improved by identifying ways to enhance ‘positive’ adaptation and limit ‘negative’ adaptation. Target parameters have an effect on Fsac metrics and suggest that they can be used in scanning salient features of the target. Fixation stability is hindered in strabismic monkeys due to the presence of nystagmus and large drifts.