Increasing Patching for Amblyopia in Children 3 to < 8 Years Old

Study Overview
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Brief Summary
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This study is designed to evaluate the effectiveness of increasing prescribed patching treatment from 2 to 6 daily hours after visual acuity has stabilized with initial treatment and amblyopia is still present. Children ages 3 to <8 years with visual acuity of 20/50 to 20/400 in the amblyopic eye will be enrolled in a run-in phase with 2 hours daily patching until no improvement, followed by randomization of eligible patients to patching 2 hours daily versus an average of 6 hours daily (42 hours per week). The primary objective is to determine if increasing patching dosage will improve visual acuity in patients with amblyopia still present after visual acuity has stabilized with initial treatment.

Detailed Description
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Amblyopia is the most common cause of monocular visual impairment in both children and young and middle-aged adults. Both patching and atropine are accepted treatment modalities for the management of moderate amblyopia in children.1 Many practitioners prescribe 2 hours daily patching as initial therapy for amblyopia. However, many children fail to achieve normal visual acuity in the amblyopic eye with this regimen. In a randomized trial conducted by PEDIG comparing patching regimens, 71 of 92 patients with moderate amblyopia (77%) had amblyopic eye visual acuity of 20/32 or worse after 4 months of patching 2 hours daily.2 In another PEDIG randomized trial comparing patching to spectacles alone after a period of refractive adaptation, patients were treated with 2 hours daily patching and followed every 5 weeks until there was no improvement in amblyopic eye acuity. Fifty-five of 70 patients with moderate amblyopia (79%) and 14 of 14 patients with severe amblyopia (100%) had best-measured amblyopic eye visual acuity of 20/32 or worse after a median treatment period of 10 weeks.3 When improvement with initial therapy stops and amblyopia is still present, treatment options include increasing the dosage of current treatment, switching to another treatment, maintaining the same treatment and dosage for additional months, or combining treatments. Many clinicians will choose to increase the dosage of the current treatment, in part because families have become comfortable with that particular mode of treatment. However, it is unknown whether increasing occlusion dosage will improve amblyopic eye visual acuity in these patients. We are unaware of any reports of response to intensified treatment of amblyopia.

Official Title
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Increasing Patching for Amblyopia in Children 3 to < 8 Years Old

Conditions
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Amblyopia

Intervention / Treatment
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* Device: Eye Patch
* Device: Eye Patch


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Major Eligibility Criteria for Run-in Phase Age 3 to < 8 years Amblyopia associated with strabismus, anisometropia, or both Visual acuity in the amblyopic eye between 20/50 and 20/400 inclusive Visual acuity in the sound eye 20/32 or better and inter-eye acuity difference >3 logMAR lines Amblyopia treatment within the past 6 months subject to the following stipulations: No more than 6 weeks of any amblyopia treatment other than spectacles (except for patients being treated with 2 hours of patching per day who are entering the study on treatment) No simultaneous treatment with patching and atropine No use of atropine in combination with the sound eye spectacle lens reduced by more than 1.50 D Maximum level of treatment within the past 6 months: Patching: up to 2 hours daily Atropine: up to once daily Wearing spectacles with optimal correction (if applicable); if amblyopic eye acuity is 20/80 or better, then VA must be stable in glasses. If amblyopic eye acuity is 20/100 or worse, then spectacles and patching can be initiated simultaneously. Eligibility Criteria for Randomization: Amblyopic eye acuity of 20/40 to 20/160 with an inter-ocular difference of >2 lines, or amblyopic eye acuity of 20/32 with 3 lines of IOD. Reasonable compliance with prescribed treatment, defined as wearing the patch at least 10 hours per week. Exclusion Criteria: Currently using vision therapy or orthoptics Ocular cause for reduced visual acuity (nystagmus per se does not exclude the patient if the above visual acuity criteria are met) Prior intraocular or refractive surgery Known skin reaction to patch or bandage adhesives

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 7 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control<br>2 hours daily patching | Device: Eye Patch<br>* 2 hours patching daily<br>* Other names: Ortopad;|
| Active Comparator: Intensified treatment<br>42 hours per week of patching (averaging 6 hours daily) | Device: Eye Patch<br>* 42 hours patching per week (averaging 6 hours patching daily)<br>* Other names: Ortopad;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Distribution of 10-week Amblyopic Eye Visual Acuity | The masked 10-week amblyopic eye visual acuity scores were tabulated for both treatment groups, and included data from 10-week visual acuity exams completed between 8 to 15 weeks (inclusive) with no imputation for missing data. The primary outcome analysis followed the intent-to-treat principle. Therefore, data from randomized participants were included in the analysis regardless of whether the assigned treatment was actually received or whether they deviated from treatment against protocol. In addition, randomized participants who were found to be ineligible upon subsequent review of enrollment data were included in the primary outcome analysis. | 10 weeks after randomization | 
| Mean 10-week Amblyopic Eye Visual Acuity | The primary outcome analysis was a treatment group comparison of the masked 10-week amblyopic eye visual acuity using an analysis of covariance (ANCOVA) model, adjusting for visual acuity at randomization. The analysis included data from 10-week visual acuity exams completed between 8 to 15 weeks (inclusive) with no imputation for missing data. The primary outcome analysis followed the intent-to-treat principle. Therefore, data from randomized participants were included in the analysis regardless of whether the assigned treatment was actually received or whether they deviated from treatment against protocol. In addition, randomized participants who were found to be ineligible upon subsequent review of enrollment data were included in the primary outcome analysis. | 10 weeks after randomization | 
| Distribution of the Change in Amblyopic Eye Visual Acuity at 10 Weeks From Randomization | The change in 10-week amblyopic eye visual acuity scores since randomization was tabulated for both treatment groups, and included data from 10-week visual acuity exams completed between 8 to 15 weeks (inclusive) with no imputation for missing data. The primary outcome analysis followed the intent-to-treat principle. Therefore, data from randomized participants were included in the analysis regardless of whether the assigned treatment was actually received or whether they deviated from treatment against protocol. In addition, randomized participants who were found to be ineligible upon subsequent review of enrollment data were included in the primary outcome analysis. | Randomization to 10 weeks | 
| Mean Change in Amblyopic Eye Visual Acuity at 10 Weeks From Randomization | The change in 10-week amblyopic eye visual acuity was computed for both treatment groups and included data from 10-week visual acuity exams completed between 8 to 15 weeks (inclusive) with no imputation for missing data. The primary outcome analysis followed the intent-to-treat principle. Therefore, data from randomized participants were included in the analysis regardless of whether the assigned treatment was actually received or whether they deviated from treatment against protocol. In addition, randomized participants who were found to be ineligible upon subsequent review of enrollment data were included in the primary outcome analysis. | Randomization to 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compliance With Prescribed Patching by Treatment Group at 10 Weeks | The distribution of compliance with prescribed treatment was tabulated for the 10-week outcome and as averaged scores across all study follow-up visits. Compliance was evaluated as excellent (>75%), good (51%-75%), fair (26%-50%), or poor (<26%) based on discussions with the parent and by reviewing study calendars maintained by the parent, who recorded the number of hours the child patched each day. | 10 weeks after randomization | 
| Average Compliance With Prescribed Patching by Treatment Group | The distribution of compliance with prescribed treatment was tabulated for the 10-week outcome and as averaged scores across all study follow-up visits. Compliance was evaluated as excellent (>75%), good (51%-75%), fair (26%-50%), or poor (<26%) based on discussions with the parent and by reviewing study calendars maintained by the parent, who recorded the number of hours the child patched each day. | 10 weeks after randomization or later | 
| Treatment Group Comparison of the Proportion of Participants Who Have Improved by 2 or More logMAR Visual Acuity Lines at 10 Weeks Since Randomization | The proportion of participants who improved at least 2 logMAR lines since randomization was computed at the 10-week outcome. The secondary outcome analysis was a treatment group comparison of the proportion of participants whose 10-week masked amblyopic eye visual acuity improved at least 2 logMAR lines since randomization using logistic regression, adjusting for visual acuity at randomization. The analysis included data from 10-week visual acuity exams completed between 8 to 15 weeks (inclusive) according to the principles specified in the primary outcome analysis. | 10 weeks after randomization | 
| Treatment Group Comparison of 10-week Interocular Difference | The secondary outcome analysis was a treatment group comparison of the 10-week interocular difference (IOD), computed as the difference between the masked amblyopic and fellow eye visual acuities, using an analysis of covariance (ANCOVA) model, adjusting for IOD at randomization. The analysis included data from 10-week visual acuity exams completed between 8 to 15 weeks (inclusive) according to the principles specified in the primary outcome analysis. | 10 weeks after randomization | 
| Distribution of Baseline Characteristics at the 10-week Outcome | The number of participants was tabulated by treatment group within categorical levels of prespecified baseline subgroup factors for participants with 10-week visual acuity exams completed between 8 to 15 weeks (inclusive)according to principles specified in the primary outcome analysis. | 10 weeks after randomization | 
| Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Mean amblyopic eye visual acuity at randomization was computed by treatment group within categorical levels of prespecified baseline subgroup factors. The analysis included data from participants with 10-week exams completed between 8 to 15 weeks (inclusive) according to the principles specified in the primary outcome analysis. | 10 weeks after randomization | 
| Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | A treatment comparison of mean amblyopic eye visual acuity change since randomization was performed at the 10-week outcome according to categorical levels of prespecified baseline subgroup factors. The analysis included data from participants with 10-week exams completed between 8 to 15 weeks (inclusive) according to the principles specified in the primary outcome analysis. | 10 weeks after randomization | 
| Distribution of Amblyopic Eye Visual Acuity at Visit of Best Post-randomization Visual Acuity | Participants in both groups who have improved by one or more lines from randomization to the 10-week outcome exam will continue in the study and visits will occur every 10 weeks until no improvement of one or more lines from the previous visit. The distribution of best post-randomization (10 weeks or later) visual acuity scores in the amblyopic eye was tabulated for both treatment groups using the initial visual acuity score (if a retest was obtained.) | 10 weeks after randomization or later | 
| Mean Amblyopic Eye Visual Acuity at Visit of Best Post-randomization Visual Acuity | Participants in both groups who have improved by one or more lines from randomization to the 10-week outcome exam will continue in the study and visits will occur every 10 weeks until no improvement of one or more lines from the previous visit. A treatment comparison of mean amblyopic eye visual acuity at the visit of best post-randomization visual acuity (10 weeks or later) was performed using an analysis of covariance, adjusting for amblyopic eye visual acuity at randomization. | 10 weeks after randomization or later | 
| Distribution of the Change in Best Post-randomization Visual Acuity in the Amblyopic Eye | Participants in both groups who have improved by one or more lines from randomization to the 10-week outcome exam will continue in the study and visits will occur every 10 weeks until no improvement of one or more lines from the previous visit. The distribution of change in best post-randomization (10 weeks or later) visual acuity in the amblyopic eye since randomization was tabulated for both treatment groups using the initial visual acuity score (if a retest was obtained.) | Randomization to 10 weeks or later | 
| Mean Change in Amblyopic Eye Visual Acuity Since Randomization at Visit of Best Post-randomization Visual Acuity | Participants in both groups who have improved by one or more lines from randomization to the 10-week outcome exam will continue in the study and visits will occur every 10 weeks until no improvement of one or more lines from the previous visit. The mean change in amblyopic eye visual acuity since randomization was computed for both treatment groups based on the visit of best post-randomization visual acuity (10 weeks or later) using the initial visual acuity score (if a retest was obtained.) | 10 weeks after randomization or later | 
| Treatment Group Comparison of the Proportion of Participants Who Have Improved by 2 or More logMAR Visual Acuity Lines Based on Visual Acuity at Best Post-randomization Visit | Participants in both groups who have improved by one or more lines from randomization to the 10-week outcome exam will continue in the study and visits will occur every 10 weeks until no improvement of one or more lines from the previous visit. The proportion of participants who improved at least 2 logMAR lines since randomization was computed based on the best post-randomization visual acuity in the amblyopic eye. The initial visual acuity score was used if a retest was obtained. | 10 weeks after randomization or later | 
| Distribution of Best Fellow Eye Visual Acuity at 10-week Outcome |  | 10 weeks after randomization | 
| Mean Best Fellow Eye Visual Acuity at 10-week Outcome |  | 10 weeks after randomization | 
| Distribution of Best Fellow Eye Visual Acuity at Final Visit |  | 10 weeks after randomization or later | 
| Mean Best Fellow Eye Visual Acuity at Final Visit |  | 10 weeks after randomization or later | 
| Distribution of Change in Best Fellow Eye Visual Acuity Since Randomization at 10 Weeks |  | 10 weeks after randomization | 
| Mean Change in Best Fellow Eye Visual Acuity Since Randomization at 10 Weeks |  | 10 weeks after randomization | 
| Distribution of Change in Best Fellow Eye Visual Acuity Since Randomization at Final Visit |  | 10 weeks after randomization or later | 
| Mean Change in Best Fellow Eye Visual Acuity Since Randomization at Final Visit |  | 10 weeks after randomization or later | 
| Distribution of Randot Preschool Stereoacuity Scores at Randomization | The Preschool Randot test measures random dot stereoacuity from 800 to 40 arc seconds (800, 400, 200, 100, 60, 40). Lower scores indicate better stereoacuity and subjects who fail the first level (800 seconds of arc) are assigned a score of >800. We administer a pretest, and those with a failed or uninterpretable score do not proceed with the Randot testing. The Preschool Randot test consists of 3 booklets each with 2 sets of 4 random dot shapes (one is blank, 3 are actual figures), which can be matched to non-stereo shapes on the opposite side of the booklets. There are six levels (seconds of arc) in the test with two levels in each book. Each level has 4 rectangles that contain 3 shapes and one blank. | Randomization | 
| Distribution of Randot Preschool Stereoacuity Scores at 10 Weeks |  | 10 weeks after randomization | 
| Change in Randot Preschool Stereoacuity Level at 10-week Outcome Since Randomization |  | 10 weeks after randomization | 
| Distribution of Randot Preschool Stereoacuity Scores at Randomization for Participants With Anisometropic Amblyopia |  | Randomization | 
| Distribution of Randot Preschool Stereoacuity Scores at 10 Weeks for Participants With Anisometropic Amblyopia |  | 10 weeks after randomization | 
| Change in Randot Preschool Stereoacuity Level at 10-week Outcome Since Randomization for Participants With Anisometropic Amblyopia |  | 10 weeks after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Amblyopia, patching, occlusion