ExotropiaIXT2NCT01032330

Observation Versus Occlusion Therapy for Intermittent Exotropia

A study testing occlusion treatment in people with Exotropia, run by Jaeb Center for Health Research at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The present study is being conducted to assess the natural history of intermittent exotropia and to establish the effectiveness of occlusion in its treatment. Study Objectives: To determine the effectiveness of occlusion for the treatment of intermittent exotropia among patients aged 3 to < 11 years who have baseline… Read more about this study

Who is it for?: Ages 12 months to 10 years
Conditions the study is for: Exotropia
What is being tested?: occlusion treatment
Type of treatment: Medical device
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 611 participants
Where: 2 sitesUnited States
Study dates: Jan 2010to Dec 2015
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 12 months to 10 years
All sexes
No healthy volunteers
Child

Who may be able to join

Age 12 months to < 11 years
Intermittent exotropia (manifest deviation) meeting all of the following criteria:
Intermittent exotropia at distance OR constant exotropia at distance and either intermittent exotropia or exophoria at near
Exodeviation at least 15PD at distance OR near measured by prism and alternate cover test (PACT)
Exodeviation at least 10PD at distance measured by PACT
No previous surgical or non-surgical treatment for IXT (other than refractive correction)

Show all 13Show fewer

Visual acuity in the worse eye at least 0.3 logMAR (20/40 on ATS HOTV or 70 letters on E-ETDRS) for children ≥ 3 years of age
No interocular difference of visual acuity more than 0.2 logMAR (2 lines on ATS HOTV or 10 letters on E-ETDRS) for children ≥ 3 years of age
No hyperopia greater than +3.50 D spherical equivalent in either eye
No myopia greater than -6.00 D spherical equivalent in either eye
No prior strabismus, intraocular, or refractive surgery
No abnormality of the cornea, lens, or central retina
Investigator willing to observe the IXT untreated for 3 years unless specific criteria for deterioration are met

Who cannot join

Pure phoria at both distance and near
Prior non-surgical treatment for IXT other than refractive correction (e.g., vergence therapy, occlusion, vision therapy/orthoptics, or deliberate over-minus with spectacles more than 0.50D)
Previous amblyopia treatment other than refractive correction within 1 year
Vision therapy/orthoptics for any reason within the last year
Interocular visual acuity difference 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) (patients ≥ 3 years only) and/or investigator plans to initiate amblyopia treatment at this time.
Limitation of ocular rotations due to restrictive or paretic strabismus

Show all 13Show fewer

Craniofacial malformations affecting the orbits
Ocular disorders which would reduce visual acuity (except refractive error)
Prior strabismus surgery or botulinum injection, intraocular surgery, or refractive surgery
Strabismus surgery planned
Known skin reactions to patch or bandage adhesives
Significant neurological impairment such as cerebral palsy. Patients with mild speech delays or common reading and/or learning disabilities are not excluded.
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)

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Southern California College of Optometry
Fullerton, California, 92831-1699
Mayo Clinic Department of Ophthalmology
Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: A Randomized Clinical Trial of Observation Versus Occlusion Therapy for Intermittent Exotropia

The present study is being conducted to assess the natural history of intermittent exotropia and to establish the effectiveness of occlusion in its treatment.

Study Objectives:

To determine the effectiveness of occlusion for the treatment of intermittent exotropia among patients aged 3 to < 11 years who have baseline near stereoacuity of 400 arcsec or better by Preschool Randot stereotest
To determine the natural history of intermittent exotropia among patients aged 3 to < 11 years who have baseline near stereoacuity of 400 arcsec or better by Preschool Randot stereotest

Read the 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 in the distance but may also be present at near. Many cases of IXT are treated using non-surgical interventions, such as part-time occlusion, fusional vergence exercises, and over-minus lenses. The rationale for such interventions is that they may improve the ability to control the IXT and preserve stereoacuity, thereby potentially addressing both visual function and social concerns, and may delay or eliminate the need for surgical correction of IXT. Nevertheless, the natural history of IXT is unknown and in many cases it is not known whether withholding treatment may in fact allow for spontaneous resolution or improvement in IXT, making non-surgical or surgical intervention unnecessary. Moreover, although non-surgical treatments for IXT are commonly prescribed, such treatments have not been subjected to rigorous study and their efficacy in improving visual function or social concerns remains unclear.

One aim of the present study is to better understand the natural history of IXT. Available reports on the natural history of IXT disagree on the progression of the disease. A 1966 study by von Noorden (cited in von Noorden and Campos) found that over an average of 3.5 years of follow-up, 75% of 51 patients showed signs of IXT progression, 9% showed no change, and 16% improved without therapy. A 1968 retrospective study by Hiles et al found that after a minimum of 6 years follow up with observation and nonsurgical treatment, 81% of 48 patients showed no change in angle of deviation. The results of more recent retrospective studies show some reporting that the majority of cases improve over time, others reporting that most cases remain stable, and still others reporting that most cases deteriorate. It is therefore unclear what proportion of patients, if left untreated, is likely to deteriorate, improve, or remain stable over time. Natural history data acquired during this study will help determine not only what proportion of patients change over time, but whether there are associated prognostic indicators of deterioration or improvement. Such data will not only enable better identification of those patients with IXT likely to benefit from treatment and those for whom treatment is likely to be unnecessary, but will also improve the quality of medical advice to parents regarding the likely progression of the disease, thus alleviating anxiety.

The aim of most forms of non-surgical treatments for IXT is to improve the strength and/or quality of binocular single vision by either eliminating suppression, increasing awareness of diplopia, and/or increasing positive fusional amplitudes. Commonly used non-surgical treatment methods include: occlusion, fusional vergence exercises (sometimes known as vision therapy or orthoptics), and over-minus lenses. When surveyed in 1990, members of the American Association for Pediatric Ophthalmology and Strabismus reported that occlusion was the most commonly used form of non-surgical treatment. More recently (2008), a poll of our investigator group revealed again that occlusion was the most widely prescribed non-surgical treatment for children affected by IXT.

Occlusion is thought to work by interrupting the development of or eliminating already present suppression, an adaptation to avoid diplopia in IXT. Persistent or entrenched suppression prevents normal binocular vision and may lead to permanent loss of stereoacuity. If successful, occlusion may then result in improved binocular sensory fusion.

As reported in recent reviews of treatment for IXT, previous studies of occlusion vary regarding the recommended occlusion dose (from 3 hours a day to full time), the optimum duration of occlusion treatment (from 6 weeks to 42 months), and which eye should be occluded (preferred/dominant eye or alternate eyes). For the majority of studies, part-time occlusion, rather than full-time occlusion was preferred. In the three occlusion studies conducted prospectively, the recommended dose was either 3 hours a day, 3 to 6 hours a day, or 4 to 6 hours a day, and the duration of occlusion ranged from 3 months to 6 months to up to 42 (mean 15) months. Nevertheless, these previous studies of occlusion for the treatment of IXT used a variety of outcome measures at a variety of non-standardized time points; therefore, no definite conclusions can be drawn from the existing literature.

Although occlusion treatment for IXT treatment is widely used, there have been no randomized clinical trials evaluating its effectiveness. Understanding the degree of effectiveness of occlusion treatment for IXT and the natural history of IXT has important public health implications. Successful restoration of binocular alignment and normal binocular function with occlusion therapy, or spontaneous improvement, will reduce the proportion of children undergoing surgery. Defining the rate of success with either occlusion or observation is therefore important in planning treatment for children with IXT. Alternatively, evidence of low treatment effectiveness with occlusion will help avoid unnecessary treatment.

The present study is being conducted to assess the natural history of IXT and to establish the effectiveness of occlusion in its treatment.

Conditions: Exotropia
Being tested: occlusion treatment
Keywords: intermittent exotropia, IXT, natural history, occlusion therapy, occlusion, patching, strabismus, strabismus treatment, stereoacuity, motor alignment
Medical subject headings: Exotropia, Bites and Stings, Strabismus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

occlusion treatmentDevice
Also called occlusion therapy, patching
Patients randomized to the occlusion treatment group will receive occlusion (patching) for 3 hours per day for at least 3 months. Choice of which eye to occlude, or whether to alternate daily, is at investigator's discretion.

Study groups in NCT01032330
Study group	Role	What they receive
Observation	No intervention	Patients randomized to the observation group will receive no treatment (other than refractive correction).
Occlusion Therapy	Active comparator	Patients randomized to the occlusion treatment group will receive occlusion (patching) for 3 hours per day for at least 3 months. Choice of which eye to occlude, or whether to alternate daily, is at investigator's discretion. Receives: Device: occlusion treatment

What is being measured

The primary outcome is the main question the study is designed to answer.

Deterioration by 6 Months - Older Cohort
The primary outcome measure for this study was whether the participant's condition had deteriorated within 6 months after randomization. Deterioration was defined as meeting one or both of the following criteria during a masked examination at either the 3-month or 6-month visit: 1) a constant exotropia (throughout the exam) of 10∆ or greater at distance and near by SPCT, confirmed by a retest, or 2) loss of near stereoacuity of 2 octaves (0.6 log arcsec) or more from the better of a test and retest of Preschool Randot stereoacuity at baseline, confirmed by a retest. In addition, participants were classified as deteriorated for the primary analysis if they started using non-randomized treatment (i.e., any treatment in the observation group; any treatment other than patching in the patching group) without first meeting one of the two protocol-specified deterioration criteria.
Measured: 6 months
Deterioration by 3 Years - Older Cohort
The primary outcome measure for this study was whether the participant's condition had deteriorated within 3 years after randomization. Deterioration was defined as meeting one or both of the following criteria during any masked examination between 3 months and 3 years after randomization: 1) a constant exotropia (throughout the exam) of 10∆ or greater at distance and near by SPCT, confirmed by a retest, or 2) loss of near stereoacuity of 2 octaves (0.6 log arcsec) or more from the better of a test and retest of Preschool Randot stereoacuity at baseline, confirmed by a retest. In addition, participants were classified as deteriorated for the primary analysis if they started using non-randomized treatment (i.e., any treatment in the observation group; any treatment other than patching in the patching group) without first meeting one of the two protocol-specified deterioration criteria.
Measured: 3 years
Deterioration by 6 Months - Younger Cohort
The primary outcome measure was deterioration of the intermittent exotropia (IXT) within 6 months after randomization. Motor deterioration was deﬁned as a constant exotropia of 10 D or more at distance and near by SPCT, conﬁrmed by a retest, at either the 3- or 6-month visit.
Measured: 6 months
Deterioration by 3 Years - Younger Cohort
The primary outcome measure was deterioration of the intermittent exotropia (IXT) within 6 months after randomization. Motor deterioration was deﬁned as a constant exotropia of 10 D or more at distance and near by SPCT, conﬁrmed by a retest, during any masked examination between 3 months and 3 years after randomization.
Measured: 3 years

Secondary outcomes (11)

Distance Stereoacuity - 3 Years
Stereoacuity scores (seconds of arc) were calculated based on the Randot Preschool stereoacuity test (scores: 800, 400, 200, 100, 60 and 40). Seconds of arc refers to the visual angle that is being measured in order to determine depth perception. Lower scores indicate better stereoacuity.
A logarithm base 10 transformation was used to convert stereoacuity scores to the log scale to calculate descriptive statistics (reported as log of seconds of arc, or log arcsec). The stereoacuity at distance is reported at 3 years, as is the change in distance stereoacuity from baseline to 3 years. Both were reported as log of seconds of arc, or log arcsec. For change in stereo, positive change indicates improvement in stereo.
Measured: Between baseline and 3 years
Near Stereoacuity - 6 Months
Stereoacuity scores (seconds of arc) were calculated based on the Randot Preschool stereoacuity test (scores: 800, 400, 200, 100, 60 and 40). Seconds of arc refers to the visual angle that is being measured in order to determine depth perception. Lower scores indicate better stereoacuity.
A logarithm base 10 transformation was used to convert stereoacuity scores to the log scale to calculate descriptive statistics (reported as log of seconds of arc, or log arcsec). The stereoacuity at near is reported at 3 years, as is the change in near stereoacuity from baseline to 3 years. Both were reported as log of seconds of arc, or log arcsec.
Outcome based on initial testing regardless of whether a retest was completed for suspected deterioration. Change is calculated as baseline level minus 6-month level. For change in stereo, positive change indicates improvement in stereo.
Measured: 6 months
Near Stereoacuity - 3 Years
Stereoacuity scores (seconds of arc) were calculated based on the Randot Preschool stereoacuity test (scores: 800, 400, 200, 100, 60 and 40). Seconds of arc refers to the visual angle that is being measured in order to determine depth perception. Lower scores indicate better stereoacuity.
A logarithm base 10 transformation was used to convert stereoacuity scores to the log scale to calculate descriptive statistics (reported as log of seconds of arc, or log arcsec). The stereoacuity at near is reported at 3 years, as is the change in near stereoacuity from baseline to 3 years. Both were reported as log of seconds of arc, or log arcsec. For change in stereo, positive change indicates improvement in stereo.
Measured: between baseline and 3 years
Exotropia Control at Distance - 6 Months
Change in control is calculated as baseline level minus 3-year level, so positive change = improvement. Scale Range: 0 to 5. Improvement in control was defined as an improvement of 3 points based on the 3-point threshold for real change.
Numeric values for exotropia control were assigned so that the following categories were created:
Not applicable (no exodeviation) 0: No exotropia unless dissociated, recovers <1 secs (phoria)
1. No exotropia unless dissociated, recovers 1-5 secs
2. No exotropia unless dissociated, recovers >5 secs
3. Exotropia <50% of 30-second observation
4. Exotropia >50% of 30-second observation
5. Constant exotropia
Lower scores indicate better control.
Measured: 6 months
Exotropia Control at Distance - 3 Years
Change in control is calculated as baseline level minus 3-year level, so positive change = improvement. Scale Range: 0 to 5. Improvement in control was defined as an improvement of 3 points based on the 3-point threshold for real change.
Numeric values for exotropia control were assigned so that the following categories were created:
Not applicable (no exodeviation) 0: No exotropia unless dissociated, recovers <1 secs (phoria)
1. No exotropia unless dissociated, recovers 1-5 secs
2. No exotropia unless dissociated, recovers >5 secs
3. Exotropia <50% of 30-second observation
4. Exotropia >50% of 30-second observation
5. Constant exotropia
Lower scores indicate better control.
Measured: 3 years
Exotropia Control at Near - 6 Months
Change in control is calculated as baseline level minus 3-year level, so positive change = improvement. Scale Range: 0 to 5. Improvement in control was defined as an improvement of 3 points based on the 3-point threshold for real change.
Numeric values for exotropia control were assigned so that the following categories were created:
Not applicable (no exodeviation) 0: No exotropia unless dissociated, recovers <1 secs (phoria)
1. No exotropia unless dissociated, recovers 1-5 secs
2. No exotropia unless dissociated, recovers >5 secs
3. Exotropia <50% of 30-second observation
4. Exotropia >50% of 30-second observation
5. Constant exotropia
Lower scores indicate better control.
Measured: 6 months
Exotropia Control at Near - 3 Years
Change in control is calculated as baseline level minus 3-year level, so positive change = improvement. Scale Range: 0 to 5. Improvement in control was defined as an improvement of 3 points based on the 3-point threshold for real change.
Numeric values for exotropia control were assigned so that the following categories were created:
Not applicable (no exodeviation) 0: No exotropia unless dissociated, recovers <1 secs (phoria)
1. No exotropia unless dissociated, recovers 1-5 secs
2. No exotropia unless dissociated, recovers >5 secs
3. Exotropia <50% of 30-second observation
4. Exotropia >50% of 30-second observation
5. Constant exotropia
Lower scores indicate better control.
Measured: 3 years
PACT Exodeviation at Distance - 6 Months
The prism and alternate cover test (PACT) is used to measure the angle of strabismus, or deviation, in prism diopters. This is measured separately at distance and at near. Smaller numbers are better because they indicate a smaller angle of deviation. For change in PACT, positive change indicates improvement (i.e. decrease in angle over time).
log arcsec = logarithm of seconds of arc; Δ = prism diopter
Measured: 6 months
PACT at Distance - 3 Years
The prism and alternate cover test (PACT) is used to measure the angle of strabismus, or deviation, in prism diopters. This is measured separately at distance and at near. Smaller numbers are better because they indicate a smaller angle of deviation. For change in PACT, positive change indicates improvement (i.e. decrease in angle over time). Improvement in PACT at distance was defined as a decrease of ≥8∆ because this amount exceed the repeatability coefficient of 7.2∆ for PACT angles larger than 20∆ at distance.
log arcsec = logarithm of seconds of arc; Δ = prism diopter
Measured: 3 years
PACT at Near - 6 Months
The prism and alternate cover test (PACT) is used to measure the angle of strabismus, or deviation, in prism diopters. This is measured separately at distance and at near. Smaller numbers are better because they indicate a smaller angle of deviation. For change in PACT, positive change indicates improvement (i.e. decrease in angle over time).
log arcsec = logarithm of seconds of arc; Δ = prism diopter
Measured: 6 months
PACT at Near - 3 Years
The prism and alternate cover test (PACT) is used to measure the angle of strabismus, or deviation, in prism diopters. This is measured separately at distance and at near. Smaller numbers are better because they indicate a smaller angle of deviation. For change in PACT, positive change indicates improvement (i.e. decrease in angle over time).
Improvement in PACT at near was defined as a decrease of ≥13∆ because this amount exceed the repeatability coefficient of 12.8∆ for PACT angles larger than 20∆ at near.
log arcsec = logarithm of seconds of arc; Δ = prism diopter
Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2010Dec 2015

First posted15 Dec 2009 (estimated)
Study startJan 2010
Primary completionDec 2015
Study completionDec 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (6)Papers the sponsor has linked to this study.
Other trials for ExotropiaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind
Who is masked: Outcomes assessor
Enrolment: 611 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01032330
Sponsor's protocol ID: NEI-146
Other IDs: 2U10EY011751
Acronym: IXT2
Status last verified: May 2020
First submitted: 11 Dec 2009
Last updated: 19 May 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Yes: In accordance with the NIH data sharing policy, a de-identified database is placed in the public domain on the PEDIG public website after the completion of each protocol and publication of the primary manuscript.

Publications

Pediatric Eye Disease Investigator Group; Cotter SA, Mohney BG, Chandler DL, Holmes JM, Repka MX, Melia M, Wallace DK, Beck RW, Birch EE, Kraker RT, Tamkins SM, Miller AM, Sala NA, Glaser SR. A randomized trial comparing part-time patching with observation for children 3 to 10 years of age with intermittent exotropia. Ophthalmology. 2014 Dec;121(12):2299-310. doi: 10.1016/j.ophtha.2014.07.021. Epub 2014 Sep 16.
PubMed 25234012
Pediatric Eye Disease Investigator Group; Mohney BG, Cotter SA, Chandler DL, Holmes JM, Chen AM, Melia M, Donahue SP, Wallace DK, Kraker RT, Christian ML, Suh DW. A Randomized Trial Comparing Part-time Patching with Observation for Intermittent Exotropia in Children 12 to 35 Months of Age. Ophthalmology. 2015 Aug;122(8):1718-25. doi: 10.1016/j.ophtha.2015.04.025. Epub 2015 Jun 11.
PubMed 26072346
Pediatric Eye Disease Investigator Group; Writing Committee; Mohney BG, Cotter SA, Chandler DL, Holmes JM, Wallace DK, Yamada T, Petersen DB, Kraker RT, Morse CL, Melia BM, Wu R. Three-Year Observation of Children 3 to 10 Years of Age with Untreated Intermittent Exotropia. Ophthalmology. 2019 Sep;126(9):1249-1260. doi: 10.1016/j.ophtha.2019.01.015. Epub 2019 Jan 26.
PubMed 30690128
Cotter SA, Mohney BG, Chandler DL, Holmes JM, Wallace DK, Melia BM, Wu R, Kraker RT, Superstein R, Crouch ER, Paysse EA; Pediatric Eye Disease Investigator Group. Three-year observation of children 12 to 35 months old with untreated intermittent exotropia. Ophthalmic Physiol Opt. 2020 Mar;40(2):202-215. doi: 10.1111/opo.12668.
PubMed 32202318
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.
PubMed 34516656
Holmes JM, Hercinovic A, Melia BM, Leske DA, Hatt SR, Chandler DL, Dean TW, Kraker RT, Enyedi LB, Wallace DK, Mohney BG, Cotter SA; Pediatric Eye Disease Investigator Group. Health-related quality of life in children with untreated intermittent exotropia and their parents. J AAPOS. 2021 Apr;25(2):80.e1-80.e4. doi: 10.1016/j.jaapos.2020.10.011. Epub 2021 Mar 8.
PubMed 33705917

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Recruiting
Near Vergence Training for Distance Control in Intermittent Exotropia
Intermittent Exotropia
Active, not recruiting
Improving Control of Alignment in Intermittent Exotropia
Intermittent Exotropia
Recruiting
True Muscle Transplantation Surgery Versus Augmented Semi Hang Back Recession in Large Angle Exotropia: Evaluation of Efficacy and Lateral Gaze Incomitance
Large Angle Exotropia
Not yet recruiting
A Comparative Study of the Efficacy of Myopia Control Lenses With Different Mechanisms on Controlling Myopia Progression in Patients With Intermittent Exotropia
Intermittent Exotropia, Myopia
Not yet recruiting
Visual Therapy for Intermittent Strabismus
Intermittent Strabismus, Exotropia Intermittent

All Exotropia trials

Study at a glance

From the registry record, last updated by the sponsor on 19 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized Clinical Trial of Observation Versus Occlusion Therapy for Intermittent Exotropia
ClinicalTrials.gov ID: NCT01032330
Acronym / sponsor ID: IXT2 / NEI-146
Conditions: Exotropia
Keywords: intermittent exotropia, IXT, natural history, occlusion therapy, occlusion, patching, strabismus, strabismus treatment
Study type: Interventional
Recruitment status: Completed
Enrolment: 611 participants (actual)
Lead sponsor: Jaeb Center for Health ResearchUniversity, hospital or other
Collaborators: Pediatric Eye Disease Investigator Group, National Eye Institute (NEI)
Study start: Jan 2010
Primary completion: Dec 2015 (actual)
Study completion: Dec 2015 (actual)
First posted: 15 Dec 2009 (estimated)
Results: Posted 8 May 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The present study is being conducted to assess the natural history of intermittent exotropia and to establish the effectiveness of occlusion in its treatment.

Study Objectives:

To determine the effectiveness of occlusion for the treatment of intermittent exotropia among patients aged 3 to < 11 years who have baseline near stereoacuity of 400 arcsec or better by Preschool Randot stereotest
To determine the natural history of intermittent exotropia among patients aged 3 to < 11 years who have baseline near stereoacuity of 400 arcsec or better by Preschool Randot stereotest

Detailed description

The present study is being conducted to assess the natural history of IXT and to establish the effectiveness of occlusion in its treatment.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Observation	No intervention	–Patients randomized to the observation group will receive no treatment (other than refractive correction).
Occlusion Therapy	Active comparator	Device: occlusion treatmentPatients randomized to the occlusion treatment group will receive occlusion (patching) for 3 hours per day for at least 3 months. Choice of which eye to occlude, or whether to alternate daily, is at investigator's discretion.

Who may qualify

Ages: 12 months to 10 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (13 listed)

Age 12 months to < 11 years
Intermittent exotropia (manifest deviation) meeting all of the following criteria:
No previous surgical or non-surgical treatment for IXT (other than refractive correction)
Visual acuity in the worse eye at least 0.3 logMAR (20/40 on ATS HOTV or 70 letters on E-ETDRS) for children ≥ 3 years of age
No interocular difference of visual acuity more than 0.2 logMAR (2 lines on ATS HOTV or 10 letters on E-ETDRS) for children ≥ 3 years of age

Key exclusion criteria (13 listed)

Pure phoria at both distance and near
Prior non-surgical treatment for IXT other than refractive correction (e.g., vergence therapy, occlusion, vision therapy/orthoptics, or deliberate over-minus with spectacles more than 0.50D)
Previous amblyopia treatment other than refractive correction within 1 year
Vision therapy/orthoptics for any reason within the last year
Interocular visual acuity difference 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) (patients ≥ 3 years only) and/or investigator plans to initiate amblyopia treatment at this time.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
occlusion treatmentAlso: occlusion therapy, patchingPatients randomized to the occlusion treatment group will receive occlusion (patching) for 3 hours per day for at least 3 months. Choice of which eye to occlude, or whether to alternate daily, is at investigator's discretion.	Device	Occlusion Therapy

Primary outcome

Deterioration by 6 Months - Older Cohort
Time frame: 6 months
The primary outcome measure for this study was whether the participant's condition had deteriorated within 6 months after randomization. Deterioration was defined as meeting one or both of the following criteria during a masked examination at either the 3-month or 6-month visit: 1) a constant exotropia (throughout the exam) of 10∆ or greater at distance and near by SPCT, confirmed by a retest, or 2) loss of near stereoacuity of 2 octaves (0.6 log arcsec) or more from the better of a test and retest of Preschool Randot stereoacuity at baseline, confirmed by a retest. In addition, participants were classified as deteriorated for the primary analysis if they started using non-randomized treatment (i.e., any treatment in the observation group; any treatment other than patching in the patching group) without first meeting one of the two protocol-specified deterioration criteria.
Deterioration by 3 Years - Older Cohort
Time frame: 3 years
The primary outcome measure for this study was whether the participant's condition had deteriorated within 3 years after randomization. Deterioration was defined as meeting one or both of the following criteria during any masked examination between 3 months and 3 years after randomization: 1) a constant exotropia (throughout the exam) of 10∆ or greater at distance and near by SPCT, confirmed by a retest, or 2) loss of near stereoacuity of 2 octaves (0.6 log arcsec) or more from the better of a test and retest of Preschool Randot stereoacuity at baseline, confirmed by a retest. In addition, participants were classified as deteriorated for the primary analysis if they started using non-randomized treatment (i.e., any treatment in the observation group; any treatment other than patching in the patching group) without first meeting one of the two protocol-specified deterioration criteria.
Deterioration by 6 Months - Younger Cohort
Time frame: 6 months
The primary outcome measure was deterioration of the intermittent exotropia (IXT) within 6 months after randomization. Motor deterioration was deﬁned as a constant exotropia of 10 D or more at distance and near by SPCT, conﬁrmed by a retest, at either the 3- or 6-month visit.
Deterioration by 3 Years - Younger Cohort
Time frame: 3 years
The primary outcome measure was deterioration of the intermittent exotropia (IXT) within 6 months after randomization. Motor deterioration was deﬁned as a constant exotropia of 10 D or more at distance and near by SPCT, conﬁrmed by a retest, during any masked examination between 3 months and 3 years after randomization.

11 secondary outcomes

Distance Stereoacuity - 3 Years
Time frame: Between baseline and 3 years
Near Stereoacuity - 6 Months
Time frame: 6 months
Near Stereoacuity - 3 Years
Time frame: between baseline and 3 years
Exotropia Control at Distance - 6 Months
Time frame: 6 months
Exotropia Control at Distance - 3 Years
Time frame: 3 years
Exotropia Control at Near - 6 Months
Time frame: 6 months
Exotropia Control at Near - 3 Years
Time frame: 3 years
PACT Exodeviation at Distance - 6 Months
Time frame: 6 months
PACT at Distance - 3 Years
Time frame: 3 years
PACT at Near - 6 Months
Time frame: 6 months
PACT at Near - 3 Years
Time frame: 3 years

Results and safety

Results posted to the registry on 8 May 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Older Cohort Observation Group	183	165
Older Cohort Occlusion Therapy Group	175	151
Younger Cohort Observation Group	97	87
Younger Cohort Occlusion Therapy Group	104	90

Primary outcome: Deterioration by 6 Months - Older Cohort

Time frame: 6 months. Count of participants. Unit: Participants

Measure	Older Cohort Observation Group n = 165	Older Cohort Occlusion Therapy Group n = 159
Formal deterioration criteria met	10	1
Constant exotropia >= 10 PD at distance and near	7	1
Stereoacuity worsening of >= 2 octaves	1	0
Both criteria	0	0
Started treatment w/o meeting criteria	3	0

Older Cohort Observation Group vs Older Cohort Occlusion Therapy Group: Risk Difference (RD): 0.054, p = 0.004, One-sided Barnard's Test

Population analysed: Previously untreated children aged 3 to \<11 years. The 6-month primary outcome visit was completed by 165 participants (90%) in the observation group, and by 159 participants (91%) in the patching group.

Primary outcome: Deterioration by 3 Years - Older Cohort

Time frame: 3 years. Count of participants. Unit: Participants

Measure	Older Cohort Observation Group n = 183	Older Cohort Occlusion Therapy Group n = 0
Value	25	0

Older Cohort Observation Group: cumulative probability: .15 (95% CI .10 to .22)

Population analysed: The clinical trial ended after 6 months, after which the purpose of the study was to observe the natural history of patients in the Observation arm. Because only half the occlusion group underwent further occlusion between 6 months and 3 years, the long-term occlusion group data was not felt to be of value, and there are no plans for its analysis.

Primary outcome: Deterioration by 6 Months - Younger Cohort

Time frame: 6 months. Count of participants. Unit: Participants

Measure	Younger Cohort Observation Group n = 87	Younger Cohort Occlusion Therapy Group n = 90
Deterioration	4	2
Constant exotropia >= 10 PD at distance and near	2	2
Started nonprotocol tmt w/o motor deterioration	2	0

Younger Cohort Observation Group vs Younger Cohort Occlusion Therapy Group: Risk Difference (RD): 0.024 (95% CI -0.038 to 0.094), p = 0.27, One-sided Barnard's Test

Population analysed: Previously untreated children aged 12 to 35 months. Motor deterioration was measured by simultaneous prism and cover test.

Primary outcome: Deterioration by 3 Years - Younger Cohort

Time frame: 3 years. Count of participants. Unit: Participants

Measure	Younger Cohort Observation Group n = 97	Younger Cohort Occlusion Therapy Group n = 0
Value	24	0

Population analysed: The younger cohort occlusion therapy group was not reported on. The clinical trial ended after 6 months, after which the purpose of the study was to observe the natural history of patients in the Observation arm. No data were collected from participants from 6 months to 3 years, and there are no plans for analysis.

11 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Older Cohort Observation Group	0 of 183 (0%)	0 of 183 (0%)	0 of 183
Older Cohort Occlusion Therapy Group	0 of 175 (0%)	0 of 175 (0%)	0 of 175
Younger Cohort Observation Group	0 of 97 (0%)	0 of 97 (0%)	0 of 97
Younger Cohort Occlusion Therapy Group	0 of 104 (0%)	0 of 104 (0%)	0 of 104

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 25234012Pediatric Eye Disease Investigator Group; Cotter SA, Mohney BG, Chandler DL, Holmes JM, Repka MX, Melia M, Wallace DK, Beck RW, Birch EE, Kraker RT, Tamkins SM, Miller AM, Sala NA, Glaser SR. A randomized trial comparing part-time patching with observation for children 3 to 10 years of age with intermittent exotropia. Ophthalmology. 2014 Dec;121(12):2299-310. doi: 10.1016/j.ophtha.2014.07.021. Epub 2014 Sep 16.
Results publication: PubMed 26072346Pediatric Eye Disease Investigator Group; Mohney BG, Cotter SA, Chandler DL, Holmes JM, Chen AM, Melia M, Donahue SP, Wallace DK, Kraker RT, Christian ML, Suh DW. A Randomized Trial Comparing Part-time Patching with Observation for Intermittent Exotropia in Children 12 to 35 Months of Age. Ophthalmology. 2015 Aug;122(8):1718-25. doi: 10.1016/j.ophtha.2015.04.025. Epub 2015 Jun 11.
Results publication: PubMed 30690128Pediatric Eye Disease Investigator Group; Writing Committee; Mohney BG, Cotter SA, Chandler DL, Holmes JM, Wallace DK, Yamada T, Petersen DB, Kraker RT, Morse CL, Melia BM, Wu R. Three-Year Observation of Children 3 to 10 Years of Age with Untreated Intermittent Exotropia. Ophthalmology. 2019 Sep;126(9):1249-1260. doi: 10.1016/j.ophtha.2019.01.015. Epub 2019 Jan 26.
Results publication: PubMed 32202318Cotter SA, Mohney BG, Chandler DL, Holmes JM, Wallace DK, Melia BM, Wu R, Kraker RT, Superstein R, Crouch ER, Paysse EA; Pediatric Eye Disease Investigator Group. Three-year observation of children 12 to 35 months old with untreated intermittent exotropia. Ophthalmic Physiol Opt. 2020 Mar;40(2):202-215. doi: 10.1111/opo.12668.
Derived from this study: PubMed 34516656Pang 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.
Derived from this study: PubMed 33705917Holmes JM, Hercinovic A, Melia BM, Leske DA, Hatt SR, Chandler DL, Dean TW, Kraker RT, Enyedi LB, Wallace DK, Mohney BG, Cotter SA; Pediatric Eye Disease Investigator Group. Health-related quality of life in children with untreated intermittent exotropia and their parents. J AAPOS. 2021 Apr;25(2):80.e1-80.e4. doi: 10.1016/j.jaapos.2020.10.011. Epub 2021 Mar 8.
PubMed Abstract - Older CohortLink provided by the sponsor.
PubMed Central HHS Public Access - Full Text - Older CohortLink provided by the sponsor.
PubMed Abstract - Younger CohortLink provided by the sponsor.
Individual participant dataSharing planned: Yes. In accordance with the NIH data sharing policy, a de-identified database is placed in the public domain on the PEDIG public website after the completion of each protocol and publication of the primary manuscript.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Susan A Cotter, O.D., M.S. study chair

Southern California College of Optometry, Fullerton, CA

Brian G Mohney, M.D. study chair

Department of Ophthalmology, Mayo Clinic, Rochester, MN

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing occlusion treatment in people with Exotropia, run by Jaeb Center for Health Research at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 May 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Deterioration by 6 Months - Older Cohort (time frame: 6 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01032330, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2020.