Clinical trial NCT01032603: Bilateral Lateral Rectus Recession Versus Unilateral Recess-Resect for Intermittent Exotropia
Official title: A Randomized Trial of Bilateral Lateral Rectus Recession Versus Unilateral Lateral Rectus Recession With Medial Rectus Resection for Intermittent Exotropia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Exotropia
Keywords: IXT
Exotropia
Strabismus
Intermittent exotropia
Lead sponsor: Jaeb Center for Health Research
Sponsor class: OTHER
Collaborators: name: Pediatric Eye Disease Investigator Group
name: National Eye Institute (NEI)
First posted: 2009-12-15
Enrollment: 197
Sex: ALL
Minimum age (years): 3
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the effectiveness of bilateral lateral rectus muscle recession versus unilateral lateral rectus recession with medial rectus resection procedures for the treatment of basic type and pseudo divergence excess type intermittent exotropia.

Detailed description: Intermittent exotropia (IXT) is the most common form of childhood onset exotropia with an incidence of 32.1 per 100,000 in children under 19 years of age. Intermittent exotropia is characterized by an exotropia that is not constant and is mainly present when viewing at distance, but may also be present at near. Normal binocular single vision (BSV) is typically present at near when the exotropia is controlled, with evidence of normal (occasionally sub-normal) stereoacuity. Although the natural history of the condition is largely unknown, many children with IXT are treated using either surgical or non-surgical interventions. The rationale for intervention in childhood IXT is that extended periods of misalignment may lead to entrenched suppression, resulting in loss of BSV. Intervention may also aim to address the social effects caused by the appearance of misaligned eyes. Many children treated for IXT are currently treated surgically.

There is poor agreement as to which type of surgery is most effective for the correction of IXT and the debate has long been related to differentiation between IXT sub-types. Based on distance-near angle disparity, IXT sub-types are classified as: 1) basic (similar magnitude of misalignment at distance and near); 2) true divergence excess (larger at distance); 3) pseudo divergence excess (initially larger at distance, but near angle increases following occlusion or with addition of plus lenses at near); 4) convergence insufficiency (larger at near). Basic and pseudo divergence excess appear to be the most common of the sub-types, and are also the types for which there is most disagreement regarding the optimum surgical approach. The two most common procedures are bilateral lateral rectus recession (BLRrec) and unilateral lateral rectus recession combined with a medial rectus resection in the same eye (R\&R). Traditionally, BLRrec has been advocated where there is a larger distance angle, and R\&R where there is a similar angle at distance and near. A survey of American strabismus surgeons published in 1990 found that the majority performed BLRrec for both basic and divergence excess types. Similarly, we found by polling our investigator group that the majority still perform a BLRrec for basic type IXT. Nevertheless, controversy still exists as to which of these surgical approaches is superior. Advocates of the BLRrec procedure tend to hold that surgery should be based purely on the distance angle of deviation. Proponents of R\&R surgery suggest resection of the medial rectus best addresses the exodeviation at near.

The proposed advantage of the R\&R procedure is that resecting the medial rectus, with a possible longer term initial overcorrection, is necessary for a stable and superior long-term outcome. Nevertheless, those who favor the BLRrec procedure suggest that the more profound and prolonged initial overcorrection occurring with R\&R is not only unnecessary, but may in fact be harmful. A persistent overcorrection may be associated with the development of diplopia, amblyopia, and loss of stereoacuity. On the other hand, critics of the BLRrec procedure suggest that long-term recurrence rates are higher. Poor motor outcomes are likely to require reoperation and therefore the long-term success rates of these surgeries have public health importance in terms of cost to society.

Evaluating initial and long-term surgical outcomes in the proposed randomized clinical trial (RCT) will answer questions regarding the failure rates of these surgeries and also provide needed data on the potential harm of each procedure.

Only one prospective randomized clinical trial addresses success rates of BLRrec versus R\&R for IXT. After between 12-15 months of follow up, 82% of 17 patients undergoing an R\&R had a satisfactory outcome compared to 52% of 19 patients undergoing a BLRrec. Nevertheless, there are some important limitations of this previous study. The sample size was very small. The study population was a sub-group of patients with basic type IXT, excluding patients with basic IXT whose angle of deviation increased at far distance or following occlusion, thus limiting the generalizability of the results. In addition, outcomes were assessed unmasked, potentially biasing the results. One observational study of 103 patients (90% of whom had basic type IXT) found 1-year success rates of 56% for BLRrec and 60% for R\&R. A retrospective study of 115 patients with basic type IXT reported success rates of 69% for BLRrec and 77% for R\&R after an average of 15 months of follow up. Other studies comparing surgery types are limited not only by retrospective study design but also by inclusion of other types of exotropia, making it difficult to interpret results. In addition, many different criteria for success are used, precluding meaningful comparison of success rates between studies. This lack of evidence makes it very difficult to counsel parents of children with IXT regarding the likely success and complication rate of either procedure, limiting our ability to make informed management decisions. Establishing the respective failure rates through the proposed study will allow physicians to offer patients the type of surgery with the highest chance of long-term success, minimizing suboptimal results and repeat surgeries.

The present study is being conducted to compare the effectiveness of BLRrec with R\&R for the surgical treatment of basic type and pseudo divergence excess type IXT.

Eligibility criteria: Inclusion Criteria:

* Age 3 to \< 11 years
* Intermittent exotropia (manifest deviation) meeting all of the following:

  * Intermittent exotropia at distance OR constant exotropia at distance and either intermittent exotropia or exophoria at near
  * Largest exodeviation at either distance, near OR remote distance between 15 and 50 prism diopters (PD) (inclusive) by prism and alternate cover test (PACT)
  * Exodeviation at least 15 PD at distance and near by PACT
  * Basic type or pseudo divergence excess type
* Stereoacuity of 400 arcsec or better at near by Preschool Randot stereotest (better of 2 measures)
* Visual acuity in the worse eye at least 0.3 logMAR (20/40 on ATS HOTV or 70 letters on E-ETDRS)
* No interocular difference of visual acuity more than 0.2 logMAR (2 lines on ATS HOTV or 10 letters on E-ETDRS testing)
* Absence of high AC/A ratio (exclude \> 6:1)
* No previous intraocular surgery, strabismus surgery, or botulinum toxin treatment
* Investigator planning to perform surgery for correction of IXT
* No hyperopia greater than +3.50 D spherical equivalent (SE) in either eye

Exclusion Criteria:

* Coexisting vertical deviation, oblique muscle dysfunction, dissociated vertical deviation (DVD), or A or V pattern, any of which the investigator plans to address with vertical transposition of horizontal rectus muscles, oblique surgery, or vertical rectus muscle surgery, i.e., only small vertical deviations, oblique muscle dysfunction, DVD, and A or V patterns not requiring surgery are allowed
* Limitation of ocular rotations due to restrictive or paretic strabismus
* Craniofacial malformations affecting the orbits
* Interocular visual acuity difference of more than 0.2 logMAR (2 lines on ATS HOTV for patients 3 to \< 7 years old or 10 letters on E-ETDRS for patients ≥ 7 years old) and/or investigator plans to initiate amblyopia treatment at this time.
* High AC/A ratio (exclude \> 6:1 by gradient method)
* Prior strabismus surgery or botulinum toxin injection
* Ocular disorders that would reduce visual acuity (except refractive error)
* Prior intraocular or refractive surgery
* Significant neurological impairment such as cerebral palsy. Patients with mild speech and/or learning disabilities are eligible.
* Investigator planning to change refractive correction at this time (if the patient is otherwise eligible, the investigator should consider prescribing refractive correction and bringing the patient back at a later time for enrollment).

Primary outcomes:
measure: Number of Participants With Suboptimal Surgical Outcome as Assessed by Motor Alignment and Stereoacuity at Near by 3 Years
timeFrame: 3 years
Secondary outcomes:
measure: Patients With Exotropia by 3 Years
timeFrame: Enrollment to 3 years
measure: Patients With Constant Esotropia by 3 Years
timeFrame: Enrollment to 3 years
measure: Number of Participants With Stereo Loss by 3 Years
timeFrame: Enrollment to 3 years
measure: Number of Participants With Exotropia Control at Distance at 3 Years
timeFrame: 3 years after enrollment
measure: Mean Distance Control at 3 Years
timeFrame: 3 years after enrollment
measure: Change in Distance Exotropia Control at 3 Years
timeFrame: Enrollment to 3 years
measure: Number of Participants With Exotropia Control at Near at 3 Years
timeFrame: 3 years after enrollment
measure: Mean Near Control at 3 Years
timeFrame: 3 years after enrollment
measure: Change in Near Exotropia Control at 3 Years
timeFrame: Enrollment to 3 Years
measure: Number of Participants With Distance PACT at 3 Years
timeFrame: 3 years after enrollment
measure: Mean Distance PACT at 3 Years
timeFrame: 3 years after enrollment
measure: Change in Distance PACT From Baseline to 3 Years
timeFrame: Enrollment to 3 years
measure: Number of Participants With Near PACT at 3 Years
timeFrame: 3 years after enrollment
measure: Mean Near PACT at 3 Years
timeFrame: 3 years after enrollment
measure: Change in Near PACT From Baseline to 3 Years
timeFrame: Enrollment to 3 years
measure: Participants With Near Stereoacuity Measures at 3 Years
timeFrame: 3 years after enrollment
measure: Mean Near Stereoacuity at 3 Years
timeFrame: 3 years after enrollment
measure: Change in Near Stereoacuity From Baseline to 3 Years
timeFrame: Enrollment to 3 years
measure: Participants Distance Stereoacuity at 3 Years
timeFrame: 3 years after enrollment
measure: Mean Distance Stereoacuity at 3 Years
timeFrame: 3 years after enrollment
measure: Change in Distance Stereoacuity From Baseline to 3 Years
timeFrame: Enrollment to 3 years
measure: Health Related Quality of Life
timeFrame: 3 years after enrollment
measure: Cumulative Number of Patients With Reoperation by 3 Years
timeFrame: 3 years after enrollment
measure: Number of Participants With Complete or Near-Complete Resolution at 3 Years
timeFrame: 3 years after enrollment
measure: Participants Suboptimal Surgical Outcome at 3 Years
timeFrame: 3 years after enrollment
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt Children's Hospital
state: Tennessee
Study officials:
affiliation: Pediatric Ophthalmology Service, Vanderbilt Children's Hospital, Nashville, TN
name: Sean P Donahue, M.D., Ph.D.
role: STUDY_CHAIR
References:
citation: Repka MX, Chandler DL, Holmes JM, Donahue SP, Hoover DL, Mohney BG, Phillips PH, Stout AU, Ticho BH, Wallace DK; Pediatric Eye Disease Investigator Group. The Relationship of Age and Other Baseline Factors to Outcome of Initial Surgery for Intermittent Exotropia. Am J Ophthalmol. 2020 Apr;212:153-161. doi: 10.1016/j.ajo.2019.12.008. Epub 2019 Dec 17.
citation: Pediatric Eye Disease Investigator Group; Writing Committee; Donahue SP, Chandler DL, Holmes JM, Arthur BW, Paysse EA, Wallace DK, Petersen DB, Melia BM, Kraker RT, Miller AM. A Randomized Trial Comparing Bilateral Lateral Rectus Recession versus Unilateral Recess and Resect for Basic-Type Intermittent Exotropia. Ophthalmology. 2019 Feb;126(2):305-317. doi: 10.1016/j.ophtha.2018.08.034. Epub 2018 Sep 3.
citation: Holmes JM, Hercinovic A, Melia BM, Leske DA, Hatt SR, Chandler DL, Dean TW, Kraker RT, Enyedi LB, Wallace DK, Donahue SP, Cotter SA; Pediatric Eye Disease Investigator Group. Improvement in health-related quality of life following strabismus surgery for children with intermittent exotropia. J AAPOS. 2021 Apr;25(2):82.e1-82.e7. doi: 10.1016/j.jaapos.2020.11.021. Epub 2021 Apr 24.
citation: Donahue SP, Chandler DL, Wu R, Marsh JD, Law C, Areaux RG Jr, Ghasia FF, Li Z, Kraker RT, Cotter SA, Holmes JM; Pediatric Eye Disease Investigator Group. Eight-Year Outcomes of Bilateral Lateral Rectus Recessions versus Unilateral Recession-Resection in Childhood Basic-Type Intermittent Exotropia. Ophthalmology. 2024 Jan;131(1):98-106. doi: 10.1016/j.ophtha.2023.09.004. Epub 2023 Sep 9.
citation: Pang Y, Gnanaraj L, Gayleard J, Han G, Hatt SR. Interventions for intermittent exotropia. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD003737. doi: 10.1002/14651858.CD003737.pub4.