Botox Instead of Strabismus Surgery (BISS)
Condition: Acquired Esotropia
MeSH terms: Strabismus; Esotropia
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of the study is to evaluate if strabismus can be successfully treated requiring
      less surgical interventions with a Botox-based treatment regimen compared to a purely surgery
      based treatment regimen.

      Experimental arm: Botulinum toxin injection in the horizontal extraocular muscles.

      Control (active comparator) arm: Strabismus surgery on the horizontal extraocular muscles. No
      investigational product is used.

      In Switzerland the standard procedure for treating large angle esotropia is surgery, which is
      performed on the horizontal eye muscles that may be either recessed or shortened leading to
      reduced or increased muscle function respectively.

      As an alternative to strabismus surgery, botulinum toxin (Botox) can be applied in
      extraocular muscles. Botox prevents the release of acetylcholine in the synaptic cleft and
      thereby blocks the neuromuscular transmission thus inducing a palsy.

      Current evidence on the use of Botox in strabismus is incoherent, is poorly supported by
      basic research findings and leaves dedicated clinicians in the dark. The objective is to shed
      light into this field of clinical research, which may help to guide future pediatric
      ophthalmologists in their management of strabismic patients. In a best case scenario, the
      results from this trial will prevent strabismus operation for many children with acquired
      large angle esotropia.
    

Detailed description: 
      Patients with acquired large angle esotropia (an inward deviation of the ocular axis by more
      than 5°) that develops after one year of age have a potential to regain binocular vision if a
      retinal image appears on corresponding retinal areas of both eyes. The main goal of therapy
      in these patients is the restoration of binocular vision.

      In Switzerland the standard procedure for treating large angle esotropia is surgery, which is
      performed on the horizontal eye muscles that may be either recessed or shortened leading to
      reduced or increased muscle function respectively.

      As an alternative to strabismus surgery, botulinum toxin (Botox) can be applied in
      extraocular muscles. Botox prevents the release of acetylcholine in the synaptic cleft and
      thereby blocks the neuromuscular transmission thus inducing a palsy.

      Current evidence on the use of Botox in strabismus is incoherent, is poorly supported by
      basic research findings and leaves dedicated clinicians in the dark. The goal is to shed
      light into this field of clinical research, which may help to guide future pediatric
      ophthalmologists in their management of strabismic patients.

      The goal of the study is to test if, with a botulinum-toxin-based treatment regimen,
      strabismus can be successfully treated requiring less surgical interventions.

      The primary objective is to test if the Botox-based treatment regimen is not inferior to
      surgical treatment in terms of orthotropic success. If this is shown, the number of surgeries
      required will be compared between the two groups (main secondary objective).

      The hypothesis is that the Botox-based treatment regimen, which permits performance of rescue
      surgery, is successful in a similar proportion of patients as the purely surgical approach.
      The second hypothesis is that only about 20% of patients treated with Botox require surgery
      at all as compared to about 10% of patients in the surgical arm that need a second surgery.

      Analysis of the primary outcome The proportion of orthotropic success for both groups will be
      calculated with a corresponding 95% confidence interval. For the comparison between the two
      groups, the stratified risk difference for the stratification factors used in randomization
      will be calculated with a corresponding one-sided lower 95% confidence limit. If the lower
      limit lies above -12%, non-inferiority will be claimed.

      Analysis of the main secondary outcome The proportion of second interventions for both groups
      will be calculated with a corresponding 95% confidence interval. For the comparison between
      the two groups, a stratified risk difference for the stratification factors used in
      randomization will be calculated with a corresponding one-sided upper 95% confidence limit.
      If the upper limit lies below 40% and if non-inferiority for the primary outcome could be
      demonstrated, a clinical benefit of the new treatment will be claimed.
    

Intervention name(s): Botulinum toxin type A; Strabismus surgery
Intervention type(s): Drug; Procedure
Intervention description(s): Botulinum toxin injection in the horizontal extraocular muscles.; Strabismus surgery on the horizontal extraocular muscles
Intervention MeSH terms: Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Botulinum toxin, strabismus surgery, binocular vision