Botox Instead of Strabismus Surgery (BISS)

Last updated: November 6, 2023
Sponsor: Insel Gruppe AG, University Hospital Bern
Overall Status: Completed

Phase

3

Condition

Eye Disease

Williams Syndrome

Vision Loss

Treatment

Botulinum toxin type A

Strabismus surgery

Clinical Study ID

NCT03459092
33IC30 173533
  • Ages 1-17
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Informed consent of trial participant and/or legal representative documented persignature
  2. Age > 1 year and <17 years
  3. Esotropia > 10Prisms
  4. Indication for an intervention (either Botox or surgery) has been made.
  5. Any of the following:
  • Presence of a secondary strabismus from binocular disruption the cause of thebinocular disruption is no longer present
  • Decompensated microstrabismus
  • Decompensated phoria
  • Acute acquired esotropia
  1. Positive test of binocular function at any time point in the past, including any ofthe following
  • Titmus test
  • Bagolini striated glasses test
  • Lang-stereo-test with correct naming of at least one panel
  • Good ocular alignment after 6 months of age on at least 2 photographs

Exclusion

Exclusion Criteria:

  1. Known hypersensitivity to botulinum toxin
  2. Known neuromuscular disorder
  3. Known present neurological disorder affecting the central nervous system Includingparesis on cranial nerves number 3, 4 and 6
  4. Any of the following:
  • nystagmus
  • dissociated vertical deviation
  1. Vertical deviation in any gaze direction greater than 5°
  2. Incomitance with more than 5° of difference between the left and right horizontal gazedirection
  3. Previous strabismus surgery
  4. Previous Botulinum toxin treatment on extraocular muscles
  5. Presence of ophthalmic pathologies significantly preventing binocular functions. A significant alteration of binocular function is assumed if vision is smaller than 0.1 or the visual field has a horizontal diameter of less than 20°.
  6. Pregnancy. A negative pregnancy test before randomization is required for all women ofchild-bearing potential.
  7. Preterm children born before 36 weeks of gestation.

Study Design

Total Participants: 63
Treatment Group(s): 2
Primary Treatment: Botulinum toxin type A
Phase: 3
Study Start date:
August 16, 2018
Estimated Completion Date:
July 31, 2023

Study 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.

Connect with a study center

  • Institut Ophtalmologique Sourdille Atlantique

    Saint-Herblain,
    France

    Site Not Available

  • Basel University Hopital

    Basel,
    Switzerland

    Site Not Available

  • Bern University Hospital

    Bern,
    Switzerland

    Site Not Available

  • Geneva University Hospital, HUG

    Geneva,
    Switzerland

    Site Not Available

  • Lausanne Univeristy Hospital, CHUV

    Lausanne,
    Switzerland

    Site Not Available

  • Luzerner Kantonsspital

    Lucerne,
    Switzerland

    Site Not Available

  • Kantonsspital St. Gallen

    Saint Gallen,
    Switzerland

    Site Not Available

  • University Hospital Zürich

    Zürich,
    Switzerland

    Site Not Available

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