Acquired Esotropia Clinical Trial
— BISSOfficial title:
A Pragmatic, Randomized, Non-inferiority Trial Comparing the Effectiveness of Botulinum Toxin-based Treatment With Conventional Strabismus Surgery in Acquired Esotropia.
| Verified date | November 2023 |
| Source | Insel Gruppe AG, University Hospital Bern |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 63 |
| Est. completion date | July 31, 2023 |
| Est. primary completion date | July 31, 2023 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 1 Year to 17 Years |
| Eligibility | Inclusion Criteria: 1. Informed consent of trial participant and/or legal representative documented per signature 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 the binocular disruption is no longer present - Decompensated microstrabismus - Decompensated phoria - Acute acquired esotropia 6. Positive test of binocular function at any time point in the past, including any of the 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 Criteria: 1. Known hypersensitivity to botulinum toxin 2. Known neuromuscular disorder 3. Known present neurological disorder affecting the central nervous system Including paresis on cranial nerves number 3, 4 and 6 4. Any of the following: - nystagmus - dissociated vertical deviation 5. Vertical deviation in any gaze direction greater than 5° 6. Incomitance with more than 5° of difference between the left and right horizontal gaze direction 7. Previous strabismus surgery 8. Previous Botulinum toxin treatment on extraocular muscles 9. 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°. 10. Pregnancy. A negative pregnancy test before randomization is required for all women of child-bearing potential. 11. Preterm children born before 36 weeks of gestation. |
| Country | Name | City | State |
|---|---|---|---|
| France | Institut Ophtalmologique Sourdille Atlantique | Saint-Herblain | |
| Switzerland | Basel University Hopital | Basel | |
| Switzerland | Bern University Hospital | Bern | |
| Switzerland | Geneva University Hospital, HUG | Geneva | |
| Switzerland | Lausanne Univeristy Hospital, CHUV | Lausanne | |
| Switzerland | Luzerner Kantonsspital | Lucerne | |
| Switzerland | Kantonsspital St. Gallen | Saint Gallen | |
| Switzerland | University Hospital Zürich | Zürich |
| Lead Sponsor | Collaborator |
|---|---|
| Insel Gruppe AG, University Hospital Bern |
France, Switzerland,
Ares C, Superstein R. Retrobulbar hemorrhage following strabismus surgery. J AAPOS. 2006 Dec;10(6):594-5. doi: 10.1016/j.jaapos.2006.04.005. Epub 2006 Oct 2. — View Citation
Baggesen K, Arnljot HM. Treatment of congenital esotropia with botulinum toxin type A. Acta Ophthalmol. 2011 Aug;89(5):484-8. doi: 10.1111/j.1755-3768.2009.01737.x. Epub 2009 Oct 30. — View Citation
Biglan AW, Burnstine RA, Rogers GL, Saunders RA. Management of strabismus with botulinum A toxin. Ophthalmology. 1989 Jul;96(7):935-43. doi: 10.1016/s0161-6420(89)32776-x. — View Citation
Bradbury JA, Taylor RH. Severe complications of strabismus surgery. J AAPOS. 2013 Feb;17(1):59-63. doi: 10.1016/j.jaapos.2012.10.016. Epub 2013 Jan 23. — View Citation
BURIAN HM, MILLER JE. Comitant convergent strabismus with acute onset. Am J Ophthalmol. 1958 Apr;45(4 Pt 2):55-64. doi: 10.1016/0002-9394(58)90223-x. No abstract available. — View Citation
Campos EC, Schiavi C, Bellusci C. Critical age of botulinum toxin treatment in essential infantile esotropia. J Pediatr Ophthalmol Strabismus. 2000 Nov-Dec;37(6):328-32; quiz 354-5. doi: 10.3928/0191-3913-20001101-05. — View Citation
Carruthers JD, Kennedy RA, Bagaric D. Botulinum vs adjustable suture surgery in the treatment of horizontal misalignment in adult patients lacking fusion. Arch Ophthalmol. 1990 Oct;108(10):1432-5. doi: 10.1001/archopht.1990.01070120080033. — View Citation
de Alba Campomanes AG, Binenbaum G, Campomanes Eguiarte G. Comparison of botulinum toxin with surgery as primary treatment for infantile esotropia. J AAPOS. 2010 Apr;14(2):111-6. doi: 10.1016/j.jaapos.2009.12.162. — View Citation
Dysli M, Abegg M. Gaze-dependent phoria and vergence adaptation. J Vis. 2016;16(3):2. doi: 10.1167/16.3.2. — View Citation
Dysli M, Keller F, Abegg M. Acute onset incomitant image disparity modifies saccadic and vergence eye movements. J Vis. 2015 Mar 18;15(3):12. doi: 10.1167/15.3.12. — View Citation
Gursoy H, Basmak H, Sahin A, Yildirim N, Aydin Y, Colak E. Long-term follow-up of bilateral botulinum toxin injections versus bilateral recessions of the medial rectus muscles for treatment of infantile esotropia. J AAPOS. 2012 Jun;16(3):269-73. doi: 10.1016/j.jaapos.2012.01.010. — View Citation
Hatt SR, Leske DA, Liebermann L, Holmes JM. Comparing outcome criteria performance in adult strabismus surgery. Ophthalmology. 2012 Sep;119(9):1930-6. doi: 10.1016/j.ophtha.2012.02.035. Epub 2012 Apr 26. — View Citation
Helveston EM, Ellis FD, Schott J, Mitchelson J, Weber JC, Taube S, Miller K. Surgical treatment of congenital esotropia. Am J Ophthalmol. 1983 Aug;96(2):218-28. doi: 10.1016/s0002-9394(14)77790-6. — View Citation
Kushner BJ, Morton GV. A randomized comparison of surgical procedures for infantile esotropia. Am J Ophthalmol. 1984 Jul 15;98(1):50-61. doi: 10.1016/0002-9394(84)90188-0. — View Citation
Lee J, Harris S, Cohen J, Cooper K, MacEwen C, Jones S. Results of a prospective randomized trial of botulinum toxin therapy in acute unilateral sixth nerve palsy. J Pediatr Ophthalmol Strabismus. 1994 Sep-Oct;31(5):283-6. doi: 10.3928/0191-3913-19940901-03. — View Citation
Liu M, Lee HC, Hertle RW, Ho AC. Retinal detachment from inadvertent intraocular injection of botulinum toxin A. Am J Ophthalmol. 2004 Jan;137(1):201-2. doi: 10.1016/s0002-9394(03)00837-7. — View Citation
Lueder GT, Galli M, Tychsen L, Yildirim C, Pegado V. Long-term results of botulinum toxin-augmented medial rectus recessions for large-angle infantile esotropia. Am J Ophthalmol. 2012 Mar;153(3):560-3. doi: 10.1016/j.ajo.2011.08.019. Epub 2011 Oct 13. — View Citation
Lyons CJ, Tiffin PA, Oystreck D. Acute acquired comitant esotropia: a prospective study. Eye (Lond). 1999 Oct;13 ( Pt 5):617-20. doi: 10.1038/eye.1999.169. — View Citation
Mahan M, Engel JM. The resurgence of botulinum toxin injection for strabismus in children. Curr Opin Ophthalmol. 2017 Sep;28(5):460-464. doi: 10.1097/ICU.0000000000000408. — View Citation
McNeer KW, Tucker MG, Spencer RF. Botulinum toxin management of essential infantile esotropia in children. Arch Ophthalmol. 1997 Nov;115(11):1411-8. doi: 10.1001/archopht.1997.01100160581010. — View Citation
Pediatric Eye Disease Investigator Group; Christiansen SP, Chandler DL, Lee KA, Superstein R, de Alba Campomanes A, Bothun ED, Morin J, Wallace DK, Kraker RT. Tonic pupil after botulinum toxin-A injection for treatment of esotropia in children. J AAPOS. 2016 Feb;20(1):78-81. doi: 10.1016/j.jaapos.2015.09.011. — View Citation
Pehere N, Jalali S, Mathai A, Naik M, Ramesh K. Inadvertent intraocular injection of botulinum toxin A. J Pediatr Ophthalmol Strabismus. 2011 Jan 25;48 Online:e1-3. doi: 10.3928/01913913-20110118-06. — View Citation
Rowe FJ, Noonan CP. Botulinum toxin for the treatment of strabismus. Cochrane Database Syst Rev. 2017 Mar 2;3(3):CD006499. doi: 10.1002/14651858.CD006499.pub4. — View Citation
Scheiman M, Ciner E, Gallaway M. Surgical success rates in infantile esotropia. J Am Optom Assoc. 1989 Jan;60(1):22-31. — View Citation
Scott AB. Botulinum toxin injection into extraocular muscles as an alternative to strabismus surgery. Ophthalmology. 1980 Oct;87(10):1044-9. doi: 10.1016/s0161-6420(80)35127-0. — View Citation
Tejedor J, Rodriguez JM. Early retreatment of infantile esotropia: comparison of reoperation and botulinum toxin. Br J Ophthalmol. 1999 Jul;83(7):783-7. doi: 10.1136/bjo.83.7.783. — View Citation
Tejedor J, Rodriguez JM. Retreatment of children after surgery for acquired esotropia: reoperation versus botulinum injection. Br J Ophthalmol. 1998 Feb;82(2):110-4. doi: 10.1136/bjo.82.2.110. — View Citation
Wan MJ, Mantagos IS, Shah AS, Kazlas M, Hunter DG. Comparison of Botulinum Toxin With Surgery for the Treatment of Acute-Onset Comitant Esotropia in Children. Am J Ophthalmol. 2017 Apr;176:33-39. doi: 10.1016/j.ajo.2016.12.024. Epub 2017 Jan 3. — View Citation
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| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | Total duration of binocular vision (exploratory outcome) | The duration is calculated as the sum of time periods between consecutive assessments with presence of binocular vision. | At 12 months, at 18 months | |
| Other | Incidence of short-term adverse events (safety outcome) | Adverse event groups that will be evaluated separately are:
Ptosis Double vision Subjective post-treatment discomfort/pain New vertical strabismus >1° Limitations of ocular motility |
Within two weeks of intervention | |
| Other | Incidence of ocular adverse events | Within 18 months | ||
| Other | Incidence of serious adverse events related to the treatment | Within 18 months | ||
| Primary | Number of patients with presence of binocular vision | Presence of binocular vision is a binary variable set to yes when either of the following criteria is fulfilled:
No eye movement can be observed in the simultaneous prism covertest, performed according to the study specific SOP for full orthoptic workup, for both eyes measured at distance. This proves orthotropia and thus binocular vision can be assumed. An esotropia of less than 5° is observed in the covertest at distance AND at near. In addition at least one binocular test demonstrates binocular vision. This proves compensated microstrabismus with anomalous retinal correspondence. Binocular tests: Lang-Stereotest Butterfly- Stereotest Titmus test Bagolini striated glasses test TNO-Test Pencil-Test |
At 18 months | |
| Secondary | Number of patients with second intervention | Rescue surgery in Botox-based treatment arm and second surgery in surgery arm | At 12 months, at 18 months | |
| Secondary | Number of patients with binocular vision | Presence of binocular vision is a binary variable set to yes when either of the following criteria is fulfilled:
No eye movement can be observed in the simultaneous prism covertest, performed according to the study specific SOP for full orthoptic workup, for both eyes measured at distance. This proves orthotropia and thus binocular vision can be assumed. An esotropia of less than 5° is observed in the covertest at distance AND at near. In addition at least one binocular test demonstrates binocular vision. This proves compensated microstrabismus with anomalous retinal correspondence. Binocular tests: Lang-Stereotest Butterfly- Stereotest Titmus test Bagolini striated glasses test TNO-Test Pencil-Test |
At 12 months | |
| Secondary | Number of patients with incomitance | Incomitance is here defined as the absolute difference of strabismus angle measured with the alternate prism cover test at 25° left gaze and the angle measured at 25° right gaze | At 12 months, at 18 months | |
| Secondary | Number of patients with treatment-specific presence of binocular vision | For this outcome patients with a second intervention are defined as failures (no). | At 12 months, at 18 months | |
| Secondary | Number of surgeries per participant | At 12 months, at 18 months | ||
| Secondary | Number of surgeries needed per successful outcome | Successful outcome = binocular vision | At 12 months, at 18 months | |
| Secondary | Change in strabismus angle, measured in percent | Measured as percentage of preoperative deviation from baseline. The strabismus angle measured with the alternate prism cover test, performed in primary position at distance is used. Change of deviation in percent of preoperative deviation is calculated as follows:
100*(preoperative deviation - postoperative deviation) / preoperative deviation |
At 12 months, at 18 months | |
| Secondary | Binocular function, measured in arc seconds | When binocular vision is present, the binocular function is the best stereoscopic acuity, measured in arc seconds, achieved for any of the below mentioned tests.
Lang-Stereotest Butterfly- Stereotest Titmus test Bagolini striated glasses test TNO-Test Pencil-Test |
At 12 months, at 18 months |