A Randomized Trial of Botulinum Toxin A vs Strabismus Surgery for Esotropia >10 to ≤30PD (ETS4)

March 31, 2026 updated by: Jaeb Center for Health Research

Childhood esotropia (ET) is a common cause of visual disability, and its early management is critical for optimal visual and developmental outcomes.

The proposed study addresses a need to evaluate botulinum toxin A (BTX-A) as a less invasive, cost-effective alternative to incisional strabismus surgery. If BTX-A is demonstrated to be non-inferior to incisional strabismus surgery in treating ET >10 to ≤30PD, this could reduce surgical and anesthesia-related risks in infants, lower the economic burden on families and healthcare systems, and reduce disparities in access to care, particularly in underserved settings where surgical resources are limited.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

After receiving informed consent, participants with ET >10 to ≤30PD who are otherwise eligible will be randomly assigned to treatment with BTX-A or incisional strabismus surgery; and seen 6 weeks, 6- and 12- months after surgery.

The primary outcome is the cumulative probability of motor alignment success by 12 months. Success is defined as the absence of failure by 12 months.

Study Type

Interventional

Enrollment (Estimated)

244

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Raymond T Kraker, MSPH
  • Phone Number: 813-975-8690
  • Email: rkraker@jaeb.org

Study Contact Backup

  • Name: PEDIG Protocol Monitor
  • Phone Number: 813-975-8690
  • Email: pedig@jaeb.org

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Description

  1. A constant or intermittent ET needing intervention with BTX-A or surgery in the judgement of the investigator meeting one of the criteria below:

    Infantile Esotropia (IET)

    • Onset prior to six months of age by parental history.
    • Angle measuring >10 to ≤ 30 PD by PACT in the primary position at distance fixation on an accommodative target.

    Acquired Non-accommodative Esotropia (ANAET)

    • Onset after six months of age by parental history
    • Angle decreases less than 10 PD by PACT in the primary position at distance fixation with hyperopic correction.
    • Residual angle measuring >10 to ≤ 30 PD by SPCT in the primary position at distance fixation on an accommodative target.

    Acquired Partially Accommodative Esotropia (APAET)

    • Onset after six months of age by parental history
    • Angle decreases 10 PD or more by PACT in the primary position at distance fixation with correction.
    • Residual angle measuring >10 to ≤ 30 PD by SPCT in the primary position at distance fixation on an accommodative target.

  2. Age at enrollment:

    • For IET: > 4 months to <17 years old
    • For ANAET or APAET: >6 months to <17 years old
  3. No myopia ≥ 6.00D SE

  4. Current Spectacle Correction at Time of Enrollment

    • For IET: No spectacle wear prior to enrollment.
    • For ANAET or APAET: Must be wearing spectacles if significant refractive error as defined below based upon a cycloplegic refraction within 6 months of enrollment. If no significant refractive error, spectacles are at investigator discretion. In either case full hyperopic correction by cycloplegia worn for at least 2 weeks.

  5. Requirements for Spectacle Correction (if worn)

    • If myopia is < 6.00D SE, then full CR must be worn for at least 2 weeks.
    • For children < 5 years of age who have significant hyperopic refractive error (CR ≥ +2.50D SE), full hyperopic correction, determined by CR must have been worn for at least 2 weeks.
    • For children ≥ age 5 years, with significant hyperopic refractive error who are unable to tolerate correction of full CR due to blur, then maximally-tolerated hyperopic correction determined both with and without cycloplegia is prescribed and must be worn for at least 2 weeks.
    • For patients who do not have significant hyperopic refractive error (CR < +2.50D SE), whether to prescribe spectacles is at investigator discretion. However, if the investigator elects to prescribe spectacles, the full tolerated hyperopic correction determined with and without cycloplegia must have been worn for at least 2 weeks.
  6. Parent or legal guardian available for follow-up, has home phone (or access to phone), and willing to be contacted by Jaeb Center staff
  7. Gestational age > 34 weeks
  8. Birth weight > 1500 grams
  9. No use of atropine within the last two weeks.
  10. No history of CNS disease (e.g., IVH, PVL, meningitis, developmental abnormalities of the brain, hydrocephalus, cerebral palsy, hypoxic ischemic encephalopathy)
  11. No significant developmental delay in the investigator's judgment (isolated speech delay excepted)
  12. No limitation of abduction consistent with paralytic or restrictive myopathy (minor limitation of abduction due to cross fixation is acceptable)
  13. No craniofacial malformation affecting the orbits
  14. No prior BTX-A injection for strabismus
  15. No prior extraocular muscle surgery or intraocular surgery
  16. No structural ocular abnormalities (e.g., media opacity, optic atrophy, optic nerve hypoplasia, retinal detachment)
  17. No immediate family member (spouse, biological or legal guardian, child, sibling, parent) who is investigative site personnel directly affiliated with this study or who is an employee of the Jaeb Center for Health Research.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Botox
Group assigned to receive BTX-A injection
Drug: Botulinum toxin A
BTX-A 4.0 units to each medial rectus
Other Names:
  • Botox
Active Comparator: Surgery
Group assigned to receive Graded bilateral medial rectus recession
Procedure: bilateral medial rectus recession
Graded bilateral medial rectus recession
Other Names:
  • BMRrec

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Motor Alignment Success
Time Frame: 1 Year

The primary efficacy outcome will be motor alignment success defined as follows:

  1. Success is defined as the absence of failure by 1 year.

  2. Failure is defined as any of the following post-randomized treatment (BOTOX or SURGERY) up to 1 year:

    • ET at distance (determined by a cover/uncover test) with a magnitude of >10 PD by SPCT at or after the 6-month masked exam.
    • XT at distance at any time during the exam (determined by a cover/uncover test) with a magnitude of > 10 PD by SPCT at or after the 6-month masked exam.
    • Second surgery or injection at any time after the initial surgery/injection through 12 months post-procedure.
1 Year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jaeb Center for Health Research

Collaborators

National Eye Institute (NEI)
Pediatric Eye Disease Investigator Group

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 1, 2027

Primary Completion (Estimated)

January 1, 2030

Study Completion (Estimated)

January 1, 2030

Study Registration Dates

First Submitted

March 10, 2026

First Submitted That Met QC Criteria

March 10, 2026

First Posted (Actual)

March 13, 2026

Study Record Updates

Last Update Posted (Actual)

April 6, 2026

Last Update Submitted That Met QC Criteria

March 31, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ETS4
  • UG1EY011751 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

In accordance with the NIH data sharing policy, a de-identified database is placed in the public domain on the Pediatric Eye Disease Investigator Group (PEDIG) public website after the completion of each protocol and publication of the primary manuscript.

IPD Sharing Time Frame

Data will be made available after publication of each primary manuscript.

IPD Sharing Access Criteria

Users accessing the data must enter an email address.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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