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

Pullela, Mythri; Degler, Brittany A.; Coats, David K.; Das, Vallabh E.

doi:10.1167/iovs.16-20481

Cited by 16 publications

(15 citation statements)

References 43 publications

(52 reference statements)

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“…Additional details of the longitudinal change in alignment and dynamics of eye movements can be found in our previous publication. 34 Note that the data points on the plot shown here are chronologically arranged based on days when neural recording yielded cells. Frequently, more than one cell was recorded on a specific day.…”

Section: Resultsmentioning

confidence: 99%

“…In our previously published study describing the eye movement data from these same animals before and after surgical treatment, eye alignment changes were large and obvious but eye velocity changes (i.e., saccade peak velocity, and smooth-pursuit gains) were small, idiosyncratic, and inconsistent across the animals and directions of eye movement. 34 Correlating the dynamic changes in eye movements with the changes in the R coefficient was therefore challenging and not pursued in detail.…”

Section: Resultsmentioning

confidence: 99%

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Neural Plasticity Following Surgical Correction of Strabismus in Monkeys

Pullela

Aga-Oglu

Joshi

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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PurposeAlthough 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.MethodsSingle 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.ResultsSurgery 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.ConclusionsActive 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.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Neural Plasticity Following Surgical Correction of Strabismus in Monkeys

Pullela

Aga-Oglu

Joshi

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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“…In the treated (right) eye of M2, ‘R’ values of LTBT OMN cells showed no significant changes at P1 or P6 while ‘R’ values of abducens cells increased after surgical treatment at P1 and P6. In our previously published study describing the eye movement data from these same animals before and after surgical treatment, eye alignment changes were large and obvious but eye velocity changes (i.e., saccade peak velocity and smooth-pursuit gains) were small, idiosyncratic and inconsistent across the animals and directions of eye movement (Pullela et al 2016). Correlating the dynamic changes in eye movements with the changes in the ‘R’ coefficient was therefore challenging and not pursued in detail.…”

Section: Resultsmentioning

confidence: 97%

“…The data show that by the end of the P6 recording period, both monkeys showed large angle exotropia once again. Additional details of the longitudinal change in alignment and dynamics of eye movements can be found in our previous publication (Pullela et al 2016). Note that the data points on the plot are chronologically arranged based on days when neural recording yielded cells.…”

Section: Resultsmentioning

confidence: 99%

Neural plasticity following surgical correction of strabismus in monkeys

Pullela

Aga-Oglu

Joshi

et al. 2018

Preprint

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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.

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“…In a recent study in adult strabismic monkeys, in the short term after surgery on the strabismic muscles improved eye alignment was seen. However, the motor neurons altered their neuronal drive over the next 6 month period post-surgery, resulting in regression of eye alignment over this period [ 51 ]. This was hypothesized to be due to both motor neuron and muscle adaptation over time.…”

Section: Discussionmentioning

confidence: 99%

Changing muscle function with sustained glial derived neurotrophic factor treatment of rabbit extraocular muscle

Fitzpatrick¹,

Cucak²,

McLoon³

2018

PLoS ONE

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Recent microarray and RNAseq experiments provided evidence that glial derived neurotrophic factor (GDNF) levels were decreased in extraocular muscles from human strabismic subjects compared to age-matched controls. We assessed the effect of sustained GDNF treatment of the superior rectus muscles of rabbits on their physiological and morphological characteristics, and these were compared to naïve control muscles. Superior rectus muscles of rabbits were implanted with a sustained release pellet of GDNF to deliver 2μg/day, with the contralateral side receiving a placebo pellet. After one month, the muscles were assessed using in vitro physiological methods. The muscles were examined histologically for alteration in fiber size, myosin expression patterns, neuromuscular junction size, and stem cell numbers and compared to age-matched naïve control muscles. GDNF resulted in decreased force generation, which was also seen on the untreated contralateral superior rectus muscles. Muscle relaxation times were increased in the GDNF treated muscles. Myofiber mean cross-sectional areas were increased after the GDNF treatment, but there was a compensatory increase in expression of developmental, neonatal, and slow tonic myosin heavy chain isoforms. In addition, in the GDNF treated muscles there was a large increase in Pitx2-positive myogenic precursor cells. One month of GDNF resulted in significant extraocular muscle adaptation. These changes are interesting relative to the decreased levels of GDNF in the muscles from subjects with strabismus and preliminary data in infant non-human primates where sustained GDNF treatment produced a strabismus. These data support the view that GDNF has the potential for improving eye alignment in subjects with strabismus.

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

Cited by 16 publications

References 43 publications

Neural Plasticity Following Surgical Correction of Strabismus in Monkeys

Neural Plasticity Following Surgical Correction of Strabismus in Monkeys

Neural plasticity following surgical correction of strabismus in monkeys

Changing muscle function with sustained glial derived neurotrophic factor treatment of rabbit extraocular muscle

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