Neural plasticity following surgical correction of strabismus in monkeys

Abstract

The preferred treatment for correcting strabismus in humans involves the surgical manipulation of extraocular muscles (EOM). Although widely practiced, this treatment has varying levels of success and permanence, possibly due to adaptive responses within the brain or at the muscle. We investigated neural plasticity following strabismus surgery by recording responses from cells in the oculomotor and abducens nuclei before and after two monkeys 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 a period of 6-10 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 the viewing and deviated eyes. Surgery resulted in an ~70% reduction in strabismus angle in both animals that reverted towards pre-surgical misalignment by about 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. Although these neuronal drive changes resolved by 6 months, we also found evidence for an inappropriate peripheral muscle adaptation that limited the effectiveness of surgery over the long term. Outcome of strabismus correction surgery could be improved by identifying ways to enhance ‘positive’ adaptation and limit ‘negative’ adaptation.Significance statementThis is the first study of its kind to longitudinally follow behavioral and neural responses before and after a typical strabismus correction surgery in a monkey model for strabismus. We show the nature of muscle and neuronal plasticity that follows strabismus correction surgery.

Visualizing Neuronal Adaptation Over Time After Treatment of Strabismus

“… 15 – 20 The power of the study by Das and colleagues is based on their ability to record changes to motor neuron activity before and after a corrective surgery and correlate this activity with changes in eye alignment in adult non-human primates. 7 The results show that the neuronal drive to the “strengthened” medial rectus muscle is actually reduced, which would drive the eye alignment back into a more exotropic state, thus “undoing” the effects of muscle surgery. By 6 months, neuronal drive had returned to presurgical values, maintaining the original exotropia in these monkeys.…”

“…The other important discovery in this publication by Das and colleagues is the demonstration that the neuronal drive to the unoperated muscles on the contralateral side also changes. 7 These changes are coordinated and opposite to those seen in the neuronal drive to the treated muscles. Similar types of coordinated changes to untreated extraocular muscles on the contralateral side also have been demonstrated following growth factor treatment of extraocular muscles in adult strabismic monkeys.…”

“… 3 – 6 There are almost 9000 published studies on the effects of strabismus surgery, yet the fundamental cause(s) of its failure to produce and maintain long-term, normal eye alignment is still not understood. The publication by Pullela et al 7 provides us great insight into the process of neuronal changes that occurs longitudinally, both acutely and chronically, after resection/recession surgery using a well-established model for infantile strabismus. 8 …”

“… 10 , 12 The manifestation of bilateral changes in muscle size and myosin expression corresponds to the bilateral change in the postsurgical eye alignment within even this 1-week time period. 7 , 8 …”

Longitudinal Development of Ocular Misalignment in Nonhuman Primate Models for Strabismus

“…23,[29][30][31][32][33] This established model for inducing sensory strabismus in monkeys replicates the clinical signs and symptoms seen in humans with sensory strabismus, and many insights into neural mechanisms have been gained through the use of this model. 6,[9][10][11][12][13] This model is thought to most closely mimic human sensory strabismus because it involves decorrelation of visual information between the two eyes. Although it is evident that decorrelating binocular vision during development via prismrearing induces misalignment, the evolution and progression of ocular misalignment in the primate model is still unknown.…”