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

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.

• Botulinum toxin A (Drug), also known as Botox: BTX-A 4.0 units to each medial rectus
• bilateral medial rectus recession (Procedure), also known as BMRrec: Graded bilateral medial rectus recession

Primary outcomes

• Motor Alignment Success [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.

Sex: All, ages: 4 Months to 17 Years

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.

NIH grants: UG1EY011751