Botulinum Toxin Augmented Surgery vs Conventional Surgery in the Management of Large Angle Horizontal Deviations

Study Overview
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Brief Summary
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Horizontal strabismus includes esotropia and exotropia where there is inward or outward deviation of visual axes of the eyes respectively. The most common initial treatment of horizontal strabismus is either bilateral rectus muscle recessions or unilateral recession resection surgery. For large angle deviations (>50 prism diopters [PD]), surgery on 2 muscles alone may not be adequate with high reoperation rates. Approaches to these patients included large bilateral muscle recessions, supramaximal unilateral recession resection procedure, three or four horizontal muscle surgery, or botulinum toxin augmented surgery. Botulinum toxin augmentated strabismus surgery was reported in several studies. Owens et al.reported successful botulinum toxin augmentation of monocular recession-resection surgeries in 3 large-angle exotropia patients with successful results in two of the 3 patients. Khan reported 8 patients with > 60 PD esotropia treated with botulinum-augmented surgery. Six of 8 had deviations of 10 PD or less following surgery. Özkan et al used botulinum augmentation in a group of older patients with large angle esotropia of different etiologies, with a success rate of 57%. Lueder et al evaluated the long-term outcomes in patients with infantile esotropia. The results were good, with a 74% success rate. Based on historical comparisons, this technique appears equally as effective as 3- or 4-muscle surgery and more effective than large bilateral medial rectus recessions alone. Ideally, a prospective randomized study should be performed to more definitively determine the effectiveness of intraoperative botulinum toxin augmentation compared to surgery alone.

Detailed Description
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Strabismus is defined as inability of the two eyes to align their visual axes to a common object of regard. Horizontal strabismus may be in the form of esotropia or exotropia depending on whether the visual axes and the eyes are converging or diverging respectively. There are multiple surgical techniques used to treat horizontal strabismus with the main goal being to align the visual axes so that binocular vision may develop. The most common initial treatment is either bilateral rectus muscle recessions or unilateral recession resection surgery. For large angle deviations (>50 prism diopters [PD]), surgery on 2 muscles alone may not be adequate to correct the strabismus with high reoperation rates. Approaches to these patients have included large bilateral muscle recessions, supramaximal unilateral recession resection procedure, three or four horizontal muscle surgery, or botulinum toxin augmented surgery. Botulinum toxin exerts its effect by interfering with release of acetylcholine at the neuromuscular junction, thus inhibiting muscle contraction. Although the pharmacologic effect of botulinum toxin is temporary, permanent results in patients with strabismus may occur. These effects include a change in the length-tension curves of the muscles and permanent changes in sarcomere density and myosin heavy chain composition. Botulinum toxin alone has been advocated by McNeer and associates as a primary treatment for infantile esotropia in children with smaller angles of deviation. The advantage of this approach is that incisional surgery is not required. However, it was found that botulinum alone was less effective in establishing binocularity when compared to standard surgery. This is likely because multiple injections are often needed, which prolongs the duration of misalignment. On the other hand, the concomitant use of botulinum toxin and surgery allowed for rapid establishment of alignment. Other advantages of botulinum augmentation are that only 2 muscles are operated upon, thus decreasing anesthesia duration and the risk of surgical complications, and the lateral rectus muscles are preserved for additional surgery, if needed. Botulinum toxin augmentation of strabismus surgery was reported in several previous studies. Owens et al. reported the successful intraoperative use of botulinum toxin to augment monocular recession-resection surgeries in three large-angle exotropia patients. Two of these patients had orthotropia ±10 PD at their final examinations, while the third patient demonstrated a stable 18 PD exotropia which was cosmetically satisfactory. Khan reported 8 patients with > 60 PD esotropia treated with botulinum-augmented horizontal muscle surgery. Six of 8 had deviations of 10 PD or less following surgery, with an average follow-up of 9 months. Özkan et al. used botulinum augmentation in a group of older patients (age range 5-50 years) with large-angle esotropia of different etiologies, with a success rate of 57% and an average follow-up of 14 months. Minguini et al. compared the results of surgery alone versus surgery plus treatment with botulinum toxin for treatment of 23 patient with large angle strabismus. Lueder et al. evaluated the long-term outcomes in patients with infantile esotropia who had been followed for more than 2 years after treatment. The results were good, with a 74% success rate. This study demonstrated that this procedure is an effective treatment for infants with large-angle infantile esotropia, with stable results over time2. Based on historical comparisons, it appears equally as effective as 3- or 4-muscle surgery and more effective than large bilateral medial rectus recessions alone. Ideally, a prospective randomized study should be performed to more definitively determine the effectiveness of the addition of intraoperative botulinum toxin compared to surgery alone.

Official Title
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Botulinum Toxin Augmented Surgery Versus Conventional Surgery in the Management of Large Angle Concomitant Horizontal Deviations

Conditions
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Large Angle Horizontal Strabismus

Intervention / Treatment
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* Procedure: botulinum toxin augmented surgery
* Procedure: conventional surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Large angle concomitant horizontal strabismus (>50 prism diopters) Exclusion Criteria: Other neurologic, or developmental disorders Vertical deviation Significant A or V patterns Paralytic or restrictive forms of strabismus History of eye surgery (strabismus or otherwise)

Ages Eligible for Study
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Minimum Age: 6 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Botulinum toxin augmented surgery group<br>unilateral recess-resect procedure, or bilateral rectus muscle recession plus intraoperative injection of 2.5 to 5 units of botulinum toxin A into the recessed muscle. | Procedure: botulinum toxin augmented surgery<br>* unilateral recess-resect procedure, or bilateral rectus muscle recession plus intraoperative injection of 2.5 to 5 units of botulinum toxin A into the recessed muscle.<br>|
| Active Comparator: conventional surgery group<br>unilateral recess-resect procedure, bilateral rectus muscle recession, or 3 horizontal rectus muscle surgery according to the type of strabismus and the presence or absence of deep amblyopia.The standard correction tables will be used as a guide for the amount of muscle recession and, or resection | Procedure: conventional surgery<br>* unilateral recess-resect procedure, bilateral rectus muscle recession, or 3 horizontal rectus muscle surgery according to the type of strabismus and the presence or absence of deep amblyopia. The standard correction tables will be used as a guide for the amount of muscle recession and, or resection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| success rate | Outcomes will be considered successful if the patients had orthotropia ±10 PD | Patients will be examined at 1 week after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| incidence of complications | ptosis vertical deviation under-correction (residual esotropia) overcorrection (consecutive exotropia) | Patients will be examined at 1 week after surgery | 
| Ocular alignment | Orthotropia or angle of deviation if present | 12 months postoperative | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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botulinum toxin, horizontal strabismus