Exotropia
Conditions
Keywords
intermittent exotropia, IXT, natural history, occlusion therapy, occlusion, patching, strabismus, strabismus treatment, stereoacuity, motor alignment
Brief 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 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
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.
Interventions
DEVICEocclusion treatment
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.
Sponsors
Pediatric Eye Disease Investigator Group
National Eye Institute (NEI)
Jaeb Center for Health Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Months to 10 Years
Healthy volunteers
No
Inclusion criteria
* 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) * 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
Exclusion criteria
* 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 * 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Deterioration by 6 Months - Older Cohort | 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 | 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 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Exotropia Control at Distance - 3 Years | 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. |
| Exotropia Control at Near - 6 Months | 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. |
| Exotropia Control at Near - 3 Years | 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. |
| Distance Stereoacuity - 3 Years | Between baseline and 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. |
| PACT at Distance - 3 Years | 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 |
| PACT at Near - 6 Months | 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 |
| PACT at Near - 3 Years | 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 |
| PACT Exodeviation at Distance - 6 Months | 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 |
| Near Stereoacuity - 6 Months | 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. |
| Near Stereoacuity - 3 Years | between baseline and 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. |
| Exotropia Control at Distance - 6 Months | 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. |
Countries
United States
Participant flow
Pre-assignment details
Aside from the two primary cohorts (older and younger), there were 52 patients in a separate exploratory cohort of patients who had little or no stereoacuity (800 or Nil); this cohort is not being reported based on the criteria listed in the protocol.
Participants by arm
| Arm | Count |
|---|---|
| Older Cohort Observation Group Patients randomized to the observation group will receive no treatment (other than refractive correction). | 183 |
| Older Cohort Occlusion Therapy Group Occlusion treatment: 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. | 175 |
| Younger Cohort Observation Group Patients randomized to the observation group will receive no treatment (other than refractive correction). | 97 |
| Younger Cohort Occlusion Therapy Group Occlusion treatment: 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. | 104 |
| Total | 559 |
Baseline characteristics
| Characteristic | Older Cohort Observation Group | Total | Older Cohort Occlusion Therapy Group | Younger Cohort Observation Group | Younger Cohort Occlusion Therapy Group |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 183 Participants | 559 Participants | 175 Participants | 97 Participants | 104 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 6.1 years STANDARD_DEVIATION 2 | 6.0 years STANDARD_DEVIATION 2 | 5.9 years STANDARD_DEVIATION 2 | 2.0 years STANDARD_DEVIATION 0.54 | 2.0 years STANDARD_DEVIATION 0.57 |
| Age, Customized 1.5 to <2 years | 0 Participants | 46 Participants | 0 Participants | 28 Participants | 18 Participants |
| Age, Customized 1 to <1.5 years | 0 Participants | 45 Participants | 0 Participants | 22 Participants | 23 Participants |
| Age, Customized 2.5 to <3 years | 0 Participants | 51 Participants | 0 Participants | 23 Participants | 28 Participants |
| Age, Customized 2 to <2.5 years | 0 Participants | 58 Participants | 0 Participants | 24 Participants | 34 Participants |
| Age, Customized 3 to <5 years | 61 Participants | 129 Participants | 68 Participants | 0 Participants | 0 Participants |
| Age, Customized 5 to <7 years | 67 Participants | 131 Participants | 64 Participants | 0 Participants | 0 Participants |
| Age, Customized 7 to <9 years | 33 Participants | 59 Participants | 26 Participants | 0 Participants | 0 Participants |
| Age, Customized 9 to <11 years | 22 Participants | 39 Participants | 17 Participants | 0 Participants | 0 Participants |
| Average Exodeviation (∆) by PACT Distance | 23.3 Prism Diopters STANDARD_DEVIATION 6.7 | 24.8 Prism Diopters STANDARD_DEVIATION 7.3 | 23.6 Prism Diopters STANDARD_DEVIATION 6.7 | 27.4 Prism Diopters STANDARD_DEVIATION 7.1 | 27.2 Prism Diopters STANDARD_DEVIATION 8.2 |
| Average Exodeviation (∆) by PACT Near | 18.0 Prism Diopters STANDARD_DEVIATION 8.9 | 17.8 Prism Diopters STANDARD_DEVIATION 10 | 16.7 Prism Diopters STANDARD_DEVIATION 9.3 | 18.1 Prism Diopters STANDARD_DEVIATION 10.8 | 19.4 Prism Diopters STANDARD_DEVIATION 12.1 |
| Average Exotropia (∆) by SPCT Distance | 16 Prism Diopters | 16 Prism Diopters | 16 Prism Diopters | 20 Prism Diopters | 14 Prism Diopters |
| Average Exotropia (∆) by SPCT Near | 0 Prism Diopters | 0 Prism Diopters | 0 Prism Diopters | 0 Prism Diopters | 0 Prism Diopters |
| Average Exotropia Control Score Distance | 2.4 scores on a scale STANDARD_DEVIATION 1.2 | 2.4 scores on a scale STANDARD_DEVIATION 1.2 | 2.3 scores on a scale STANDARD_DEVIATION 1.2 | 2.5 scores on a scale STANDARD_DEVIATION 1.2 | 2.3 scores on a scale STANDARD_DEVIATION 1.1 |
| Average Exotropia Control Score Near | 1.1 scores on a scale STANDARD_DEVIATION 1 | 1.1 scores on a scale STANDARD_DEVIATION 1.1 | 1.1 scores on a scale STANDARD_DEVIATION 1.1 | 1.2 scores on a scale STANDARD_DEVIATION 1.2 | 1.0 scores on a scale STANDARD_DEVIATION 1 |
| Average Visual Acuity 20/12 or 20/16 | 21 Participants | 43 Participants | 22 Participants | 0 Participants | 0 Participants |
| Average Visual Acuity 20/20 | 65 Participants | 135 Participants | 70 Participants | 0 Participants | 0 Participants |
| Average Visual Acuity 20/25 | 73 Participants | 118 Participants | 45 Participants | 0 Participants | 0 Participants |
| Average Visual Acuity 20/32 | 17 Participants | 45 Participants | 28 Participants | 0 Participants | 0 Participants |
| Average Visual Acuity 20/40 or worse | 7 Participants | 13 Participants | 6 Participants | 0 Participants | 0 Participants |
| Average Visual Acuity | 0.04 logMAR STANDARD_DEVIATION 0.09 | 0.04 logMAR STANDARD_DEVIATION 0.1 | 0.04 logMAR STANDARD_DEVIATION 0.1 | — | — |
| Deviation Type Distance Constant exotropia | 9 Participants | 29 Participants | 8 Participants | 9 Participants | 3 Participants |
| Deviation Type Distance Exophoria | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Deviation Type Distance Intermittent exotropia | 174 Participants | 530 Participants | 167 Participants | 88 Participants | 101 Participants |
| Deviation Type Distance No Exodeviation | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Deviation Type Near Constant exotropia | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants |
| Deviation Type Near Exophoria | 49 Participants | 135 Participants | 44 Participants | 21 Participants | 21 Participants |
| Deviation Type Near Intermittent exotropia | 129 Participants | 389 Participants | 119 Participants | 69 Participants | 72 Participants |
| Deviation Type Near No Exodeviation | 4 Participants | 33 Participants | 11 Participants | 7 Participants | 11 Participants |
| Distance Randot Stereoacuity (arcsec) 100 | 39 Participants | 77 Participants | 38 Participants | — | — |
| Distance Randot Stereoacuity (arcsec) 200 | 30 Participants | 53 Participants | 23 Participants | — | — |
| Distance Randot Stereoacuity (arcsec) 400 | 18 Participants | 38 Participants | 20 Participants | — | — |
| Distance Randot Stereoacuity (arcsec) 60 | 64 Participants | 141 Participants | 77 Participants | — | — |
| Distance Randot Stereoacuity (arcsec) Nil | 28 Participants | 44 Participants | 16 Participants | — | — |
| Distance Randot Stereoacuity (arcsec) | 2.22 log arcsec STANDARD_DEVIATION 0.5 | 2.17 log arcsec STANDARD_DEVIATION 0.47 | 2.12 log arcsec STANDARD_DEVIATION 0.44 | — | — |
| Exodeviation (∆) by Prism and Alternate Cover Test (PACT) Distance 10-14 | 7 Participants | 18 Participants | 11 Participants | 0 Participants | 0 Participants |
| Exodeviation (∆) by Prism and Alternate Cover Test (PACT) Distance 16-18 | 34 Participants | 90 Participants | 33 Participants | 9 Participants | 14 Participants |
| Exodeviation (∆) by Prism and Alternate Cover Test (PACT) Distance 1-9 | 0 Participants | 0 Participants | 0 Participants | 00 Participants | 0 Participants |
| Exodeviation (∆) by Prism and Alternate Cover Test (PACT) Distance 20-25 | 101 Participants | 276 Participants | 87 Participants | 44 Participants | 44 Participants |
| Exodeviation (∆) by Prism and Alternate Cover Test (PACT) Distance 30-35 | 35 Participants | 149 Participants | 39 Participants | 39 Participants | 36 Participants |
| Exodeviation (∆) by Prism and Alternate Cover Test (PACT) Distance 40-45 | 5 Participants | 21 Participants | 5 Participants | 3 Participants | 8 Participants |
| Exodeviation (∆) by Prism and Alternate Cover Test (PACT) Distance ≥50 | 1 Participants | 5 Participants | 0 Participants | 2 Participants | 2 Participants |
| Exodeviation (∆) by Prism and Alternate Cover Test (PACT) Distance No exodeviation (orthophoria) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Exodeviation (∆) by Prism and Alternate Cover Test (PACT) Near 10-14 | 49 Participants | 133 Participants | 45 Participants | 24 Participants | 15 Participants |
| Exodeviation (∆) by Prism and Alternate Cover Test (PACT) Near 16-18 | 32 Participants | 78 Participants | 24 Participants | 9 Participants | 13 Participants |
| Exodeviation (∆) by Prism and Alternate Cover Test (PACT) Near 1-9 | 19 Participants | 65 Participants | 31 Participants | 7 Participants | 8 Participants |
| Exodeviation (∆) by Prism and Alternate Cover Test (PACT) Near 20-25 | 52 Participants | 160 Participants | 48 Participants | 30 Participants | 30 Participants |
| Exodeviation (∆) by Prism and Alternate Cover Test (PACT) Near 30-35 | 21 Participants | 68 Participants | 15 Participants | 14 Participants | 18 Participants |
| Exodeviation (∆) by Prism and Alternate Cover Test (PACT) Near 40-45 | 4 Participants | 17 Participants | 5 Participants | 3 Participants | 5 Participants |
| Exodeviation (∆) by Prism and Alternate Cover Test (PACT) Near ≥50 | 0 Participants | 3 Participants | 0 Participants | 1 Participants | 2 Participants |
| Exodeviation (∆) by Prism and Alternate Cover Test (PACT) Near No exodeviation (orthophoria) | 6 Participants | 35 Participants | 7 Participants | 9 Participants | 13 Participants |
| Exotropia (∆) by Simultaneous Prism Cover Test (SPCT) Distance 0 (no measureable tropia) | 48 Participants | 167 Participants | 50 Participants | 28 Participants | 41 Participants |
| Exotropia (∆) by Simultaneous Prism Cover Test (SPCT) Distance 10-14 | 18 Participants | 39 Participants | 12 Participants | 4 Participants | 5 Participants |
| Exotropia (∆) by Simultaneous Prism Cover Test (SPCT) Distance 16-18 | 30 Participants | 80 Participants | 29 Participants | 8 Participants | 13 Participants |
| Exotropia (∆) by Simultaneous Prism Cover Test (SPCT) Distance 1-9 | 15 Participants | 48 Participants | 18 Participants | 8 Participants | 7 Participants |
| Exotropia (∆) by Simultaneous Prism Cover Test (SPCT) Distance 20-25 | 57 Participants | 155 Participants | 47 Participants | 30 Participants | 21 Participants |
| Exotropia (∆) by Simultaneous Prism Cover Test (SPCT) Distance 30-35 | 13 Participants | 56 Participants | 15 Participants | 16 Participants | 12 Participants |
| Exotropia (∆) by Simultaneous Prism Cover Test (SPCT) Distance 40-50 | 2 Participants | 12 Participants | 4 Participants | 3 Participants | 3 Participants |
| Exotropia (∆) by Simultaneous Prism Cover Test (SPCT) Distance >50 | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Exotropia (∆) by Simultaneous Prism Cover Test (SPCT) Near 0 (no measureable tropia) | 108 Participants | 354 Participants | 108 Participants | 63 Participants | 75 Participants |
| Exotropia (∆) by Simultaneous Prism Cover Test (SPCT) Near 10-14 | 21 Participants | 39 Participants | 11 Participants | 4 Participants | 3 Participants |
| Exotropia (∆) by Simultaneous Prism Cover Test (SPCT) Near 16-18 | 13 Participants | 32 Participants | 12 Participants | 3 Participants | 4 Participants |
| Exotropia (∆) by Simultaneous Prism Cover Test (SPCT) Near 1-9 | 23 Participants | 69 Participants | 27 Participants | 11 Participants | 8 Participants |
| Exotropia (∆) by Simultaneous Prism Cover Test (SPCT) Near 20-25 | 14 Participants | 44 Participants | 9 Participants | 12 Participants | 9 Participants |
| Exotropia (∆) by Simultaneous Prism Cover Test (SPCT) Near 30-35 | 4 Participants | 15 Participants | 5 Participants | 3 Participants | 3 Participants |
| Exotropia (∆) by Simultaneous Prism Cover Test (SPCT) Near 40-50 | 0 Participants | 5 Participants | 3 Participants | 1 Participants | 1 Participants |
| Exotropia (∆) by Simultaneous Prism Cover Test (SPCT) Near >50 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Exotropia control score Distance Constant XT | 12 Participants | 36 Participants | 11 Participants | 9 Participants | 4 Participants |
| Exotropia control score Distance No exodeviation | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Exotropia control score Distance No XT unless dissociated, recovers 1-5 sec | 34 Participants | 126 Participants | 47 Participants | 18 Participants | 27 Participants |
| Exotropia control score Distance No XT unless dissociated, recovers <1 sec | 5 Participants | 14 Participants | 5 Participants | 2 Participants | 2 Participants |
| Exotropia control score Distance No XT unless dissociated, recovers >5 sec | 71 Participants | 198 Participants | 56 Participants | 38 Participants | 33 Participants |
| Exotropia control score Distance XT <50% of 30-seconds | 40 Participants | 123 Participants | 37 Participants | 19 Participants | 27 Participants |
| Exotropia control score Distance XT >50% of 30-seconds | 21 Participants | 62 Participants | 19 Participants | 11 Participants | 11 Participants |
| Exotropia control score Near Constant XT | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Exotropia control score Near No exodeviation | 5 Participants | 25 Participants | 7 Participants | 3 Participants | 10 Participants |
| Exotropia control score Near No XT unless dissociated, recovers 1-5 sec | 71 Participants | 203 Participants | 63 Participants | 30 Participants | 39 Participants |
| Exotropia control score Near No XT unless dissociated, recovers <1 sec | 58 Participants | 175 Participants | 58 Participants | 31 Participants | 28 Participants |
| Exotropia control score Near No XT unless dissociated, recovers >5 sec | 28 Participants | 86 Participants | 26 Participants | 17 Participants | 15 Participants |
| Exotropia control score Near XT <50% of 30-seconds | 18 Participants | 55 Participants | 14 Participants | 12 Participants | 11 Participants |
| Exotropia control score Near XT >50% of 30-seconds | 2 Participants | 14 Participants | 7 Participants | 4 Participants | 1 Participants |
| Exotropia Type Basic | 127 Participants | 378 Participants | 119 Participants | 61 Participants | 71 Participants |
| Exotropia Type Convergence insufficiency | 5 Participants | 8 Participants | 0 Participants | 2 Participants | 1 Participants |
| Exotropia Type High AC/A | 4 Participants | 13 Participants | 7 Participants | 2 Participants | 0 Participants |
| Exotropia Type Missing exotropia classification | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants |
| Exotropia Type Pseudodivergence excess | 39 Participants | 128 Participants | 39 Participants | 26 Participants | 24 Participants |
| Exotropia Type True divergence excess | 7 Participants | 30 Participants | 10 Participants | 5 Participants | 8 Participants |
| Interocular difference in visual acuity (lines) 0 | 86 Participants | 171 Participants | 85 Participants | — | — |
| Interocular difference in visual acuity (lines) >0 to<1 | 45 Participants | 82 Participants | 37 Participants | — | — |
| Interocular difference in visual acuity (lines) 1 | 42 Participants | 85 Participants | 43 Participants | — | — |
| Interocular difference in visual acuity (lines) >1 to<2 | 4 Participants | 9 Participants | 5 Participants | — | — |
| Interocular difference in visual acuity (lines) 2 | 6 Participants | 7 Participants | 1 Participants | — | — |
| Interocular difference in visual acuity (lines) | 0.05 logMAR STANDARD_DEVIATION 0.06 | 0.04 logMAR STANDARD_DEVIATION 0.05 | 0.04 logMAR STANDARD_DEVIATION 0.05 | — | — |
| Preschool Randot Near Stereoacuity (arcsec) 100 | 43 Participants | 68 Participants | 25 Participants | — | — |
| Preschool Randot Near Stereoacuity (arcsec) 200 | 19 Participants | 35 Participants | 16 Participants | — | — |
| Preschool Randot Near Stereoacuity (arcsec) 40 | 75 Participants | 144 Participants | 69 Participants | — | — |
| Preschool Randot Near Stereoacuity (arcsec) 400 | 7 Participants | 29 Participants | 22 Participants | — | — |
| Preschool Randot Near Stereoacuity (arcsec) 60 | 39 Participants | 82 Participants | 43 Participants | — | — |
| Preschool Randot Near Stereoacuity (arcsec) | 1.84 log arcsec STANDARD_DEVIATION 0.27 | 1.87 log arcsec STANDARD_DEVIATION 0.31 | 1.89 log arcsec STANDARD_DEVIATION 0.34 | — | — |
| Race/Ethnicity, Customized Black/African American | 23 Participants | 75 Participants | 25 Participants | 13 Participants | 14 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 32 Participants | 88 Participants | 22 Participants | 13 Participants | 21 Participants |
| Race/Ethnicity, Customized Other | 14 Participants | 42 Participants | 13 Participants | 6 Participants | 9 Participants |
| Race/Ethnicity, Customized Unknown/not reported | 2 Participants | 8 Participants | 6 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 112 Participants | 346 Participants | 109 Participants | 65 Participants | 60 Participants |
| Sex: Female, Male Female | 115 Participants | 337 Participants | 98 Participants | 58 Participants | 66 Participants |
| Sex: Female, Male Male | 68 Participants | 222 Participants | 77 Participants | 39 Participants | 38 Participants |
| Spectacle Wear | 42 Participants | 94 Participants | 38 Participants | 5 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 183 | 0 / 175 | 0 / 97 | 0 / 104 |
| other Total, other adverse events | 0 / 183 | 0 / 175 | 0 / 97 | 0 / 104 |
| serious Total, serious adverse events | 0 / 183 | 0 / 175 | 0 / 97 | 0 / 104 |
Outcome results
Primary
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.
Time frame: 3 years
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Older Cohort Observation Group | Deterioration by 3 Years - Older Cohort | 25 Participants |
| Older Cohort Occlusion Therapy Group | Deterioration by 3 Years - Older Cohort | 0 Participants |
95% CI: [0.1, 0.22]
Primary
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.
Time frame: 3 years
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Older Cohort Observation Group | Deterioration by 3 Years - Younger Cohort | 24 Participants |
| Older Cohort Occlusion Therapy Group | Deterioration by 3 Years - Younger Cohort | 0 Participants |
Primary
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.
Time frame: 6 months
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Older Cohort Observation Group | Deterioration by 6 Months - Older Cohort | Both criteria | 0 Participants |
| Older Cohort Observation Group | Deterioration by 6 Months - Older Cohort | Constant exotropia >= 10 PD at distance and near | 7 Participants |
| Older Cohort Observation Group | Deterioration by 6 Months - Older Cohort | Stereoacuity worsening of >= 2 octaves | 1 Participants |
| Older Cohort Observation Group | Deterioration by 6 Months - Older Cohort | Started treatment w/o meeting criteria | 3 Participants |
| Older Cohort Observation Group | Deterioration by 6 Months - Older Cohort | Formal deterioration criteria met | 10 Participants |
| Older Cohort Occlusion Therapy Group | Deterioration by 6 Months - Older Cohort | Started treatment w/o meeting criteria | 0 Participants |
| Older Cohort Occlusion Therapy Group | Deterioration by 6 Months - Older Cohort | Constant exotropia >= 10 PD at distance and near | 1 Participants |
| Older Cohort Occlusion Therapy Group | Deterioration by 6 Months - Older Cohort | Both criteria | 0 Participants |
| Older Cohort Occlusion Therapy Group | Deterioration by 6 Months - Older Cohort | Formal deterioration criteria met | 1 Participants |
| Older Cohort Occlusion Therapy Group | Deterioration by 6 Months - Older Cohort | Stereoacuity worsening of >= 2 octaves | 0 Participants |
p-value: 0.004One-sided Barnard's Test
Primary
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.
Time frame: 6 months
Population: Previously untreated children aged 12 to 35 months. Motor deterioration was measured by simultaneous prism and cover test.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Older Cohort Observation Group | Deterioration by 6 Months - Younger Cohort | Constant exotropia >= 10 PD at distance and near | 2 Participants |
| Older Cohort Observation Group | Deterioration by 6 Months - Younger Cohort | Started nonprotocol tmt w/o motor deterioration | 2 Participants |
| Older Cohort Observation Group | Deterioration by 6 Months - Younger Cohort | Deterioration | 4 Participants |
| Older Cohort Occlusion Therapy Group | Deterioration by 6 Months - Younger Cohort | Constant exotropia >= 10 PD at distance and near | 2 Participants |
| Older Cohort Occlusion Therapy Group | Deterioration by 6 Months - Younger Cohort | Started nonprotocol tmt w/o motor deterioration | 0 Participants |
| Older Cohort Occlusion Therapy Group | Deterioration by 6 Months - Younger Cohort | Deterioration | 2 Participants |
p-value: 0.2795% CI: [-0.038, 0.094]One-sided Barnard's Test
Secondary
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.
Time frame: Between baseline and 3 years
Population: Since 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. For the observation group, the number reported is those who completed the 3-Year visit and had not been prescribed treatment anytime during the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Older Cohort Observation Group | Distance Stereoacuity - 3 Years | At 3 Years | 2.03 log arsec | Standard Deviation 0.36 |
| Older Cohort Observation Group | Distance Stereoacuity - 3 Years | Change between baseline and 3 years | 0.14 log arsec | Standard Deviation 0.4 |
Comparison: P-value for the change between baseline and 3 years. Two-sided p values for comparisons of continuous outcomes are from analysis of covariance models adjusting for the baseline level of the outcome.p-value: <0.001ANCOVA
Secondary
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.
Time frame: 3 years
Population: Since 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. For the observation groups, the number reported is those who completed the 3-Year visit and had not been prescribed treatment anytime during the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Older Cohort Observation Group | Exotropia Control at Distance - 3 Years | At 3 Years | 1.8 score on a scale | Standard Deviation 1.4 |
| Older Cohort Observation Group | Exotropia Control at Distance - 3 Years | Change between Baseline and 3 Years | 0.6 score on a scale | Standard Deviation 1.5 |
| Younger Cohort Observation Group | Exotropia Control at Distance - 3 Years | Change between Baseline and 3 Years | 0.2 score on a scale | Standard Deviation 1.4 |
| Younger Cohort Observation Group | Exotropia Control at Distance - 3 Years | At 3 Years | 2.2 score on a scale | Standard Deviation 1.5 |
Comparison: P-value for the change between baseline and 3 Years in the Older cohort. Two-sided p values for comparisons of continuous outcomes are from analysis of covariance models adjusting for the baseline level of the outcome.p-value: <0.001ANCOVA
Comparison: P-value for the change between baseline and 3 Years in the Younger cohort. Two-sided p values for comparisons of continuous outcomes are from analysis of covariance models adjusting for the baseline level of the outcome.p-value: 0.33ANCOVA
Secondary
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.
Time frame: 6 months
Population: For the Older Cohort, 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Older Cohort Observation Group | Exotropia Control at Distance - 6 Months | Change between Baseline and 6 months | 0.1 score on a scale | Standard Deviation 1.4 |
| Older Cohort Observation Group | Exotropia Control at Distance - 6 Months | At 6 months | 2.3 score on a scale | Standard Deviation 1.4 |
| Older Cohort Occlusion Therapy Group | Exotropia Control at Distance - 6 Months | At 6 months | 2.0 score on a scale | Standard Deviation 1.2 |
| Older Cohort Occlusion Therapy Group | Exotropia Control at Distance - 6 Months | Change between Baseline and 6 months | 0.3 score on a scale | Standard Deviation 1.4 |
| Younger Cohort Observation Group | Exotropia Control at Distance - 6 Months | At 6 months | 2.8 score on a scale | Standard Deviation 1.3 |
| Younger Cohort Observation Group | Exotropia Control at Distance - 6 Months | Change between Baseline and 6 months | -0.3 score on a scale | Standard Deviation 1.3 |
| Younger Cohort Occlusion Therapy Group | Exotropia Control at Distance - 6 Months | Change between Baseline and 6 months | 0.1 score on a scale | Standard Deviation 1.5 |
| Younger Cohort Occlusion Therapy Group | Exotropia Control at Distance - 6 Months | At 6 months | 2.3 score on a scale | Standard Deviation 1.5 |
Comparison: P-value for the change between baseline and 6 months in the Older cohort. Two-sided p values for comparisons of continuous outcomes are from analysis of covariance models adjusting for the baseline level of the outcome.p-value: 0.09ANCOVA
Comparison: P-value for the change between baseline and 6 months in the Younger cohort. Two-sided p values for comparisons of continuous outcomes are from analysis of covariance models adjusting for the baseline level of the outcome.p-value: 0.02ANCOVA
Secondary
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.
Time frame: 3 years
Population: Since 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. For the observation groups, the number reported is those who completed the 3-Year visit and had not been prescribed treatment anytime during the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Older Cohort Observation Group | Exotropia Control at Near - 3 Years | At 3 Years | 0.9 score on a scale | Standard Deviation 1.1 |
| Older Cohort Observation Group | Exotropia Control at Near - 3 Years | Change between Baseline and 3 Years | 0.1 score on a scale | Standard Deviation 1.2 |
| Younger Cohort Observation Group | Exotropia Control at Near - 3 Years | At 3 Years | 1.0 score on a scale | Standard Deviation 1.4 |
| Younger Cohort Observation Group | Exotropia Control at Near - 3 Years | Change between Baseline and 3 Years | 0.1 score on a scale | Standard Deviation 1.4 |
Comparison: P-value for the change between baseline and 3 Years in the Older cohort. Two-sided p values for comparisons of continuous outcomes are from analysis of covariance models adjusting for the baseline level of the outcome.p-value: 0.42ANCOVA
Comparison: P-value for the change between baseline and 3 Years in the Younger cohort. Two-sided p values for comparisons of continuous outcomes are from analysis of covariance models adjusting for the baseline level of the outcome.p-value: 0.61ANCOVA
Secondary
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.
Time frame: 6 months
Population: For the Older Cohort, 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Older Cohort Observation Group | Exotropia Control at Near - 6 Months | A 6 months | 1.2 score on a scale | Standard Deviation 1.1 |
| Older Cohort Observation Group | Exotropia Control at Near - 6 Months | Change between Baseline and 6 months | -0.2 score on a scale | Standard Deviation 1.1 |
| Older Cohort Occlusion Therapy Group | Exotropia Control at Near - 6 Months | A 6 months | 0.9 score on a scale | Standard Deviation 1.1 |
| Older Cohort Occlusion Therapy Group | Exotropia Control at Near - 6 Months | Change between Baseline and 6 months | 0.1 score on a scale | Standard Deviation 1.1 |
| Younger Cohort Observation Group | Exotropia Control at Near - 6 Months | Change between Baseline and 6 months | -0.3 score on a scale | Standard Deviation 1.1 |
| Younger Cohort Observation Group | Exotropia Control at Near - 6 Months | A 6 months | 1.4 score on a scale | Standard Deviation 1.4 |
| Younger Cohort Occlusion Therapy Group | Exotropia Control at Near - 6 Months | A 6 months | 1.1 score on a scale | Standard Deviation 1.4 |
| Younger Cohort Occlusion Therapy Group | Exotropia Control at Near - 6 Months | Change between Baseline and 6 months | -0.1 score on a scale | Standard Deviation 1.3 |
Comparison: P-value for the change between baseline and 6 months in the Older cohort. Two-sided p values for comparisons of continuous outcomes are from analysis of covariance models adjusting for the baseline level of the outcome.p-value: 0.013ANCOVA
Comparison: P-value for the change between baseline and 6 months in the Younger cohort. Two-sided p values for comparisons of continuous outcomes are from analysis of covariance models adjusting for the baseline level of the outcome.p-value: 0.26ANCOVA
Secondary
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.
Time frame: between baseline and 3 years
Population: The older 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Older Cohort Observation Group | Near Stereoacuity - 3 Years | At 3 Years | 1.7 log arcsec | Standard Deviation 0.21 |
| Older Cohort Observation Group | Near Stereoacuity - 3 Years | Change between Baseline and 3 Years | 0.14 log arcsec | Standard Deviation 0.29 |
Comparison: P-value for the change between baseline and 3 years. Two-sided p values for comparisons of continuous outcomes are from analysis of covariance models adjusting for the baseline level of the outcome.p-value: <0.001ANCOVA
Secondary
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.
Time frame: 6 months
Population: Stereoacuity data is missing for 2 observation group participants because it was not tested at the visit at which treatment was started in the absence of meeting deterioration criteria. 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Older Cohort Observation Group | Near Stereoacuity - 6 Months | At 6 months | 1.84 log arsec | Standard Deviation 0.33 |
| Older Cohort Observation Group | Near Stereoacuity - 6 Months | Change between Baseline and 6 months | 0.00 log arsec | Standard Deviation 0.32 |
| Older Cohort Occlusion Therapy Group | Near Stereoacuity - 6 Months | Change between Baseline and 6 months | 0.06 log arsec | Standard Deviation 0.3 |
| Older Cohort Occlusion Therapy Group | Near Stereoacuity - 6 Months | At 6 months | 1.84 log arsec | Standard Deviation 0.31 |
Comparison: Two-sided p values for comparisons of continuous outcomes are from analysis of covariance models adjusting for the baseline level of the outcome; P values for comparisons of binary outcomes are from logistic regression models adjusting for the baseline level of the outcome.p-value: 0.38ANCOVA
Secondary
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
Time frame: 3 years
Population: Since 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. For the observation groups, the number reported is those who completed the 3-Year visit and had not been prescribed treatment anytime during the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Older Cohort Observation Group | PACT at Distance - 3 Years | At 3 Years | 21.0 prism diopters | Standard Deviation 8.7 |
| Older Cohort Observation Group | PACT at Distance - 3 Years | Change between Baseline and 3 Years | 2.2 prism diopters | Standard Deviation 8.3 |
| Younger Cohort Observation Group | PACT at Distance - 3 Years | At 3 Years | 23.4 prism diopters | Standard Deviation 9.5 |
| Younger Cohort Observation Group | PACT at Distance - 3 Years | Change between Baseline and 3 Years | 3.6 prism diopters | Standard Deviation 10.4 |
Comparison: P-value for the change between baseline and 3 Years in the Older cohort. Two-sided p values for comparisons of continuous outcomes are from analysis of covariance models adjusting for the baseline level of the outcome.p-value: 0.002ANCOVA
Comparison: P-value for the change between baseline and 3 Years in the Younger cohort. Two-sided p values for comparisons of continuous outcomes are from analysis of covariance models adjusting for the baseline level of the outcome.p-value: 0.01ANCOVA
Secondary
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
Time frame: 3 years
Population: Since 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. For the observation groups, the number reported is those who completed the 3-Year visit and had not been prescribed treatment anytime during the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Older Cohort Observation Group | PACT at Near - 3 Years | Change between Baseline and 3 Years | 0.4 prism diopters | Standard Deviation 9.3 |
| Older Cohort Observation Group | PACT at Near - 3 Years | At 3 Years | 17.0 prism diopters | Standard Deviation 10.1 |
| Younger Cohort Observation Group | PACT at Near - 3 Years | At 3 Years | 14.9 prism diopters | Standard Deviation 10.3 |
| Younger Cohort Observation Group | PACT at Near - 3 Years | Change between Baseline and 3 Years | 2.8 prism diopters | Standard Deviation 12 |
Comparison: P-value for the change between baseline and 3 Years in the Older cohort. Two-sided p values for comparisons of continuous outcomes are from analysis of covariance models adjusting for the baseline level of the outcome.p-value: 0.6ANCOVA
Comparison: P-value for the change between baseline and 3 Years in the Younger cohort. Two-sided p values for comparisons of continuous outcomes are from analysis of covariance models adjusting for the baseline level of the outcome.p-value: 0.09ANCOVA
Secondary
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
Time frame: 6 months
Population: For the Older Cohort, 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Older Cohort Observation Group | PACT at Near - 6 Months | At 6 months | 17.6 prism diopters | Standard Deviation 9.6 |
| Older Cohort Observation Group | PACT at Near - 6 Months | Change between Baseline and 6 months | 0.5 prism diopters | Standard Deviation 7.8 |
| Older Cohort Occlusion Therapy Group | PACT at Near - 6 Months | Change between Baseline and 6 months | 1.5 prism diopters | Standard Deviation 8 |
| Older Cohort Occlusion Therapy Group | PACT at Near - 6 Months | At 6 months | 15.4 prism diopters | Standard Deviation 10.1 |
| Younger Cohort Observation Group | PACT at Near - 6 Months | At 6 months | 19.3 prism diopters | Standard Deviation 9.6 |
| Younger Cohort Observation Group | PACT at Near - 6 Months | Change between Baseline and 6 months | -1.8 prism diopters | Standard Deviation 11.4 |
| Younger Cohort Occlusion Therapy Group | PACT at Near - 6 Months | Change between Baseline and 6 months | 0.9 prism diopters | Standard Deviation 12.8 |
| Younger Cohort Occlusion Therapy Group | PACT at Near - 6 Months | At 6 months | 17.0 prism diopters | Standard Deviation 12.2 |
Comparison: P-value for the change between baseline and 6 months in the Older cohort. Two-sided p values for comparisons of continuous outcomes are from analysis of covariance models adjusting for the baseline level of the outcome.p-value: 0.11ANCOVA
Comparison: P-value for the change between baseline and 6 months in the Younger cohort. Two-sided p values for comparisons of continuous outcomes are from analysis of covariance models adjusting for the baseline level of the outcome.p-value: 0.1ANCOVA
Secondary
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
Time frame: 6 months
Population: For the Older Cohort, 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Older Cohort Observation Group | PACT Exodeviation at Distance - 6 Months | At 6 months | 23.8 prism diopters | Standard Deviation 7.8 |
| Older Cohort Observation Group | PACT Exodeviation at Distance - 6 Months | Change between Baseline and 6 months | -0.3 prism diopters | Standard Deviation 6.8 |
| Older Cohort Occlusion Therapy Group | PACT Exodeviation at Distance - 6 Months | At 6 months | 22.2 prism diopters | Standard Deviation 7.4 |
| Older Cohort Occlusion Therapy Group | PACT Exodeviation at Distance - 6 Months | Change between Baseline and 6 months | 1.4 prism diopters | Standard Deviation 5.8 |
| Younger Cohort Observation Group | PACT Exodeviation at Distance - 6 Months | Change between Baseline and 6 months | -0.6 prism diopters | Standard Deviation 8.1 |
| Younger Cohort Observation Group | PACT Exodeviation at Distance - 6 Months | At 6 months | 27.9 prism diopters | Standard Deviation 8.2 |
| Younger Cohort Occlusion Therapy Group | PACT Exodeviation at Distance - 6 Months | Change between Baseline and 6 months | 2.0 prism diopters | Standard Deviation 8.6 |
| Younger Cohort Occlusion Therapy Group | PACT Exodeviation at Distance - 6 Months | At 6 months | 24.9 prism diopters | Standard Deviation 9.4 |
Comparison: P-value for the change between baseline and 6 months in the Older cohort. Two-sided p values for comparisons of continuous outcomes are from analysis of covariance models adjusting for the baseline level of the outcome.p-value: 0.012ANCOVA
Comparison: P-value for the change between baseline and 6 months in the Younger cohort. Two-sided p values for comparisons of continuous outcomes are from analysis of covariance models adjusting for the baseline level of the outcome.p-value: 0.02ANCOVA