Amblyopia
Conditions
Keywords
Amblyopia, atropine, Plano lens
Brief summary
This study is designed to evaluate the effectiveness of adding a plano lens to weekend atropine after visual acuity has stabilized with weekend atropine but 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 weekend atropine until no improvement, followed by randomization of eligible patients to weekend atropine treatment with a plano lens over the sound eye versus without a plano lens over the sound eye. The primary objective is to determine if adding a plano lens to weekend atropine will improve visual acuity in patients with amblyopia still present after visual acuity has stabilized with initial treatment.
Detailed description
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 weekend atropine as initial therapy for amblyopia. However, many children fail to achieve normal visual acuity in the amblyopic eye after treatment with this regimen. In a randomized trial conducted by PEDIG comparing atropine regimens, 58 of 83 patients with moderate amblyopia (70%) had amblyopic eye visual acuity of 20/32 or worse after 4 months of treatment with weekend atropine.2 In another PEDIG randomized trial comparing atropine with a plano lens versus without a plano lens for initial treatment of amblyopia, 60 of 84 patients with moderate amblyopia (71%) had amblyopic eye visual acuity of 20/32 or worse after 16 weeks of treatment with weekend atropine.3 When improvement stops after initial therapy and amblyopia is still present, treatment options include increasing the dosage of current treatment, switching to another treatment, maintaining the same treatment and dosage, or combining treatments. Many clinicians will add a plano lens over the sound eye to atropine treatment, in part because families using atropine have become comfortable with its use. This option is limited to children with hypermetropia in the sound eye. However, it is unknown whether adding a plano lens over the sound eye will improve amblyopic eye visual acuity more than continuing atropine alone in patients who have shown no improvement after initial treatment with atropine. In a PEDIG randomized trial comparing patching to atropine for initial treatment of amblyopia, a plano lens was prescribed for the sound eye for 55 patients who had not improved to 20/30 or at least 3 lines after 4 months of daily atropine use.1, 4 Their mean acuity improvement prior to using the plano lens was 1.0 line, compared with 1.6 lines after prescribing the plano lens. We are unaware of any reports of the response of treatment of amblyopia still present after initial treatment with weekend atropine.
Interventions
DRUGAtropine
Weekend atropine 1%
DEVICEPlano lens
plano lens over the sound eye
Sponsors
National Eye Institute (NEI)
Jaeb Center for Health Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 7 Years
Healthy volunteers
No
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 atropine 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 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 atropine can be initiated simultaneously). * Hypermetropia and spectacle correction in sound eye of +1.50 D or more 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. * Compliance with weekend atropine treatment based on investigator judgment.
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 allergy to atropine or other cycloplegic drugs * Down Syndrome present
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Distribution of 10-week Amblyopic-Eye Visual Acuity | 10 weeks after randomization | 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. |
| Mean 10-week Amblyopic-Eye Visual Acuity | 10 weeks after randomization | 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. |
| Distribution of the Change in Amblyopic-Eye Visual Acuity | Randomization to 10 weeks | 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. |
| Mean Change in Amblyopic-Eye Visual Acuity at 10 Weeks From Randomization | Randomization to 10 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Atropine Compliance at 10 Weeks by Treatment Group | 10 weeks after randomization | The distribution of compliance with prescribed treatment was tabulated for the 10-week outcome. 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 frequency of atropine administration. |
| Average Atropine Compliance by Treatment Group | 10 weeks after randomization or later (until no further VA improvement, up to maximum of 84 weeks for one subject) | 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 frequency of atropine administration. |
| Distribution of Interocular Difference at 12-week Exam | 12 weeks after randomization | Distribution of Interocular Difference Between Eyes at 12-week Exam |
| Mean Interocular Difference at 12-week Exam | 12 weeks after randomization | Mean Interocular Difference Between Eyes at 12-week Exam |
| Distribution of 12-week Fellow-Eye Visual Acuity | 12 weeks after randomization | Following the 10-week primary outcome exam, participants discontinued the randomized treatment and returned 2 weeks later for a 12-week visit to measure off-treatment fellow-eye visual acuity. |
| Mean Fellow-Eye Visual Acuity at 12-week Exam | 12 weeks after randomization | — |
| Distribution of Change in Fellow-Eye Visual Acuity at 12 Weeks From Randomization | 12 weeks after randomization | — |
| Mean Change in Fellow-Eye Visual Acuity at 12 Weeks From Randomization | 12 weeks after randomization | — |
| Distribution of Baseline Characteristics at the 10-week Outcome | 10 weeks after randomization | 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. |
| Treatment Group Comparison of the Proportion of Participants Who Achieved 20/25 or Better Visual Acuity at 10 Weeks Since Randomization | 10 weeks after randomization | The proportion of participants who achieved 20/25 or better visual acuity 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 was 20/25 or better since 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. |
| Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | 10 weeks after randomization | 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. |
| Distribution of Amblyopic-Eye Visual Acuity at Best Outcome Visit | 10 weeks after randomization or later (until no further VA improvement, up to maximum of 84 weeks for one subject) | 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.) |
| Mean Amblyopic-Eye Visual Acuity at Best Outcome Visit | 10 weeks after randomization or later (until no further VA improvement, up to maximum of 84 weeks for one subject) | 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. |
| Distribution of Change in Amblyopic-Eye Visual Acuity From Randomization to Best Outcome Visit | Randomization to 10 weeks or later (until no further VA improvement, up to maximum of 84 weeks for one subject) | 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.) |
| Mean Change in Amblyopic-Eye Visual Acuity at Best Outcome Visit | 10 weeks after randomization or later (until no further VA improvement, up to maximum of 84 weeks for one subject) | 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.) |
| 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 Outcome Visit | 10 weeks after randomization or later (until no further VA improvement, up to maximum of 84 weeks for one subject) | — |
| Distribution of Randot Preschool Stereoacuity Score at 12 Weeks | 12 weeks after randomization | Distribution of Randot Preschool Stereoacuity Score at 12 Weeks; Participants with a Randot Preschool test of \>800 seconds of arc were classified as having a stereoacuity of 3000 seconds of arc if the Titmus fly test was positive or as nil if the Titmus fly test was negative. |
| Distribution of Randot Preschool Stereoacuity Scores at 12 Weeks for Participants With Anisometropic Amblyopia | 12 weeks after randomization | — |
| Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | 10 weeks after randomization | 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. |
| Treatment Group Comparison of the Proportion of Participants Who Have Improved by 2 or More logMAR Visual Acuity Lines at 10 Weeks Since Randomization | 10 weeks after 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. |
| Spectacle Compliance at 10 Weeks by Treatment Group | 10 weeks after randomization | The distribution of compliance with prescribed treatment was tabulated for the 10-week outcome. 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 frequency of atropine administration. |
| Average Spectacle Compliance by Treatment Group | 10 weeks after randomization or later (until no further VA improvement, up to maximum of 84 weeks for one subject) | 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 frequency of atropine administration. |
Countries
United States
Participant flow
Recruitment details
Between November 2009 and August 2013, 73 participants from 20 sites were randomly assigned to either augmenting weekend atropine by changing the lens over the fellow eye to plano (n=33) or continuing with weekend atropine with best spectacle correction (n=40).
Pre-assignment details
Prior to being considered for the randomized trial, participants who had not completed at least 12 weeks of atropine were enrolled into a run-in phase and treated with weekend atropine 1% ophthalmic solution and spectacles based upon a recent cycloplegic refraction, with follow up every 6 weeks until no improvement
Participants by arm
| Arm | Count |
|---|---|
| Control Weekend atropine 1%
Atropine: Weekend atropine 1% | 40 |
| Intensified Treatment Weekend atropine 1% with plano lens over the sound eye
Atropine: Weekend atropine 1%
Plano lens: plano lens over the sound eye | 33 |
| Total | 73 |
Baseline characteristics
| Characteristic | Intensified Treatment | Total | Control |
|---|---|---|---|
| Age, Categorical <=18 years | 33 Participants | 73 Participants | 40 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 5.8 years STANDARD_DEVIATION 1.4 | 5.8 years STANDARD_DEVIATION 1.4 | 5.8 years STANDARD_DEVIATION 1.5 |
| Age, Customized 3 to <4 years | 4 participants | 9 participants | 5 participants |
| Age, Customized 4 to <5 years | 6 participants | 14 participants | 8 participants |
| Age, Customized 5 to <6 years | 9 participants | 18 participants | 9 participants |
| Age, Customized 6 to <7 years | 5 participants | 12 participants | 7 participants |
| Age, Customized >=7 years | 9 participants | 20 participants | 11 participants |
| Cause of Amblyopia Anisometropia | 6 participants | 16 participants | 10 participants |
| Cause of Amblyopia Strabismus | 13 participants | 22 participants | 9 participants |
| Cause of Amblyopia Strabismus and Anisometropia | 14 participants | 35 participants | 21 participants |
| Distance Visual Acuity in the Amblyopic Eye at Randomization 20/100 | 1 participants | 6 participants | 5 participants |
| Distance Visual Acuity in the Amblyopic Eye at Randomization 20/125 | 2 participants | 4 participants | 2 participants |
| Distance Visual Acuity in the Amblyopic Eye at Randomization 20/160 | 1 participants | 3 participants | 2 participants |
| Distance Visual Acuity in the Amblyopic Eye at Randomization 20/32 | 1 participants | 3 participants | 2 participants |
| Distance Visual Acuity in the Amblyopic Eye at Randomization 20/40 | 6 participants | 17 participants | 11 participants |
| Distance Visual Acuity in the Amblyopic Eye at Randomization 20/50 | 8 participants | 15 participants | 7 participants |
| Distance Visual Acuity in the Amblyopic Eye at Randomization 20/63 | 8 participants | 17 participants | 9 participants |
| Distance Visual Acuity in the Amblyopic Eye at Randomization 20/80 | 6 participants | 8 participants | 2 participants |
| Distance Visual Acuity in the Amblyopic Eye at Randomization | 0.48 logMAR STANDARD_DEVIATION 0.16 | 0.48 logMAR STANDARD_DEVIATION 0.18 | 0.48 logMAR STANDARD_DEVIATION 0.19 |
| Distance Visual Acuity in the Fellow Eye at Randomization 20/16 | 5 participants | 11 participants | 6 participants |
| Distance Visual Acuity in the Fellow Eye at Randomization 20/20 | 13 participants | 29 participants | 16 participants |
| Distance Visual Acuity in the Fellow Eye at Randomization 20/25 | 9 participants | 22 participants | 13 participants |
| Distance Visual Acuity in the Fellow Eye at Randomization 20/32 | 6 participants | 11 participants | 5 participants |
| Distance Visual Acuity in the Fellow Eye at Randomization | 0.05 logMAR STANDARD_DEVIATION 0.1 | 0.05 logMAR STANDARD_DEVIATION 0.09 | 0.04 logMAR STANDARD_DEVIATION 0.09 |
| Duration of Atropine Treatment Prior to Randomization 12 to <15 weeks | 5 participants | 16 participants | 11 participants |
| Duration of Atropine Treatment Prior to Randomization 15 to <21 weeks | 9 participants | 15 participants | 6 participants |
| Duration of Atropine Treatment Prior to Randomization 21 to <27 weeks | 9 participants | 22 participants | 13 participants |
| Duration of Atropine Treatment Prior to Randomization 27 to 84 weeks | 10 participants | 20 participants | 10 participants |
| Duration of Atropine Treatment Prior to Randomization | 26.4 weeks STANDARD_DEVIATION 14.6 | 25.0 weeks STANDARD_DEVIATION 12.8 | 24.0 weeks STANDARD_DEVIATION 11.2 |
| Interocular Eye Visual Acuity Difference at Randomization | 4.4 logMAR lines STANDARD_DEVIATION 1.7 | 4.4 logMAR lines STANDARD_DEVIATION 1.7 | 4.4 logMAR lines STANDARD_DEVIATION 1.8 |
| Race/Ethnicity, Customized African American | 1 participants | 4 participants | 3 participants |
| Race/Ethnicity, Customized Hispanic | 3 participants | 7 participants | 4 participants |
| Race/Ethnicity, Customized White | 29 participants | 62 participants | 33 participants |
| Region of Enrollment United States | 33 participants | 73 participants | 40 participants |
| Sex: Female, Male Female | 19 Participants | 41 Participants | 22 Participants |
| Sex: Female, Male Male | 14 Participants | 32 Participants | 18 Participants |
| Spherical Equivalent Refractive Error in Amblyopic Eye at Enrollment 0 to <+1.00 D | 0 participants | 0 participants | 0 participants |
| Spherical Equivalent Refractive Error in Amblyopic Eye at Enrollment +1.00 to <+2.00 D | 1 participants | 1 participants | 0 participants |
| Spherical Equivalent Refractive Error in Amblyopic Eye at Enrollment +2.00 to <+3.00 D | 1 participants | 2 participants | 1 participants |
| Spherical Equivalent Refractive Error in Amblyopic Eye at Enrollment +3.00 to <+4.00 D | 5 participants | 11 participants | 6 participants |
| Spherical Equivalent Refractive Error in Amblyopic Eye at Enrollment +4.00 D or more | 26 participants | 59 participants | 33 participants |
| Spherical Equivalent Refractive Error in Amblyopic Eye at Enrollment | 5.84 diopters STANDARD_DEVIATION 1.89 | 5.78 diopters STANDARD_DEVIATION 1.74 | 5.73 diopters STANDARD_DEVIATION 1.62 |
| Spherical Equivalent Refractive Error in Fellow Eye at Enrollment +1.50 to <+2.00 D | 5 participants | 10 participants | 5 participants |
| Spherical Equivalent Refractive Error in Fellow Eye at Enrollment +2.00 to <+3.00 D | 2 participants | 8 participants | 6 participants |
| Spherical Equivalent Refractive Error in Fellow Eye at Enrollment +3.00 to <+4.00 D | 9 participants | 16 participants | 7 participants |
| Spherical Equivalent Refractive Error in Fellow Eye at Enrollment +4.00 D or more | 17 participants | 39 participants | 22 participants |
| Spherical Equivalent Refractive Error in Fellow Eye at Enrollment | 4.55 diopters STANDARD_DEVIATION 2.28 | 4.22 diopters STANDARD_DEVIATION 1.95 | 3.95 diopters STANDARD_DEVIATION 1.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 40 | 9 / 33 |
| serious Total, serious adverse events | 0 / 40 | 0 / 33 |
Outcome results
Primary
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.
Time frame: 10 weeks after randomization
Population: The primary outcome analysis followed the intent-to-treat principle and included data from 10-week visual acuity exams completed between 8 and 15 weeks (inclusive) with no imputation for missing data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control | Distribution of 10-week Amblyopic-Eye Visual Acuity | 20/200 | 0 participants |
| Control | Distribution of 10-week Amblyopic-Eye Visual Acuity | 20/160 | 2 participants |
| Control | Distribution of 10-week Amblyopic-Eye Visual Acuity | 20/125 | 1 participants |
| Control | Distribution of 10-week Amblyopic-Eye Visual Acuity | 20/100 | 4 participants |
| Control | Distribution of 10-week Amblyopic-Eye Visual Acuity | 20/80 | 5 participants |
| Control | Distribution of 10-week Amblyopic-Eye Visual Acuity | 20/63 | 3 participants |
| Control | Distribution of 10-week Amblyopic-Eye Visual Acuity | 20/50 | 6 participants |
| Control | Distribution of 10-week Amblyopic-Eye Visual Acuity | 20/40 | 11 participants |
| Control | Distribution of 10-week Amblyopic-Eye Visual Acuity | 20/32 | 3 participants |
| Control | Distribution of 10-week Amblyopic-Eye Visual Acuity | 20/25 | 3 participants |
| Control | Distribution of 10-week Amblyopic-Eye Visual Acuity | 20/20 | 1 participants |
| Control | Distribution of 10-week Amblyopic-Eye Visual Acuity | 20/16 | 0 participants |
| Intensified Treatment | Distribution of 10-week Amblyopic-Eye Visual Acuity | 20/20 | 1 participants |
| Intensified Treatment | Distribution of 10-week Amblyopic-Eye Visual Acuity | 20/200 | 1 participants |
| Intensified Treatment | Distribution of 10-week Amblyopic-Eye Visual Acuity | 20/50 | 6 participants |
| Intensified Treatment | Distribution of 10-week Amblyopic-Eye Visual Acuity | 20/160 | 0 participants |
| Intensified Treatment | Distribution of 10-week Amblyopic-Eye Visual Acuity | 20/25 | 5 participants |
| Intensified Treatment | Distribution of 10-week Amblyopic-Eye Visual Acuity | 20/125 | 2 participants |
| Intensified Treatment | Distribution of 10-week Amblyopic-Eye Visual Acuity | 20/40 | 4 participants |
| Intensified Treatment | Distribution of 10-week Amblyopic-Eye Visual Acuity | 20/100 | 0 participants |
| Intensified Treatment | Distribution of 10-week Amblyopic-Eye Visual Acuity | 20/16 | 0 participants |
| Intensified Treatment | Distribution of 10-week Amblyopic-Eye Visual Acuity | 20/80 | 4 participants |
| Intensified Treatment | Distribution of 10-week Amblyopic-Eye Visual Acuity | 20/32 | 6 participants |
| Intensified Treatment | Distribution of 10-week Amblyopic-Eye Visual Acuity | 20/63 | 4 participants |
Primary
Distribution of the Change in Amblyopic-Eye Visual Acuity
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.
Time frame: Randomization to 10 weeks
Population: The primary outcome analysis followed the intent-to-treat principle and included data from 10-week visual acuity exams completed between 8 and 15 weeks (inclusive) with no imputation for missing data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control | Distribution of the Change in Amblyopic-Eye Visual Acuity | 1 line worse | 4 participants |
| Control | Distribution of the Change in Amblyopic-Eye Visual Acuity | 1 line improved | 12 participants |
| Control | Distribution of the Change in Amblyopic-Eye Visual Acuity | 2 lines worse | 1 participants |
| Control | Distribution of the Change in Amblyopic-Eye Visual Acuity | 2 lines improved | 7 participants |
| Control | Distribution of the Change in Amblyopic-Eye Visual Acuity | No change | 14 participants |
| Control | Distribution of the Change in Amblyopic-Eye Visual Acuity | 3 or more lines improved | 1 participants |
| Control | Distribution of the Change in Amblyopic-Eye Visual Acuity | 3 or more lines worse | 0 participants |
| Intensified Treatment | Distribution of the Change in Amblyopic-Eye Visual Acuity | 3 or more lines improved | 7 participants |
| Intensified Treatment | Distribution of the Change in Amblyopic-Eye Visual Acuity | 3 or more lines worse | 0 participants |
| Intensified Treatment | Distribution of the Change in Amblyopic-Eye Visual Acuity | 2 lines worse | 2 participants |
| Intensified Treatment | Distribution of the Change in Amblyopic-Eye Visual Acuity | 1 line worse | 3 participants |
| Intensified Treatment | Distribution of the Change in Amblyopic-Eye Visual Acuity | No change | 6 participants |
| Intensified Treatment | Distribution of the Change in Amblyopic-Eye Visual Acuity | 1 line improved | 13 participants |
| Intensified Treatment | Distribution of the Change in Amblyopic-Eye Visual Acuity | 2 lines improved | 2 participants |
Primary
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.
Time frame: 10 weeks after randomization
Population: The primary outcome analysis followed the intent-to-treat principle and included data from 10-week visual acuity exams completed between 8 and 15 weeks (inclusive) with no imputation for missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Mean 10-week Amblyopic-Eye Visual Acuity | 0.42 logMAR | Standard Deviation 0.22 |
| Intensified Treatment | Mean 10-week Amblyopic-Eye Visual Acuity | 0.37 logMAR | Standard Deviation 0.23 |
Comparison: The primary 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 was a 2-sided test for efficacy to test the null hypothesis of no treatment difference, assuming 90% power and a type I error rate of 5%.p-value: 0.1295% CI: [-0.01, 0.12]ANCOVA
Primary
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.
Time frame: Randomization to 10 weeks
Population: The primary outcome analysis followed the intent-to-treat principle and included data from 10-week visual acuity exams completed between 8 and 15 weeks (inclusive) with no imputation for missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Mean Change in Amblyopic-Eye Visual Acuity at 10 Weeks From Randomization | 0.6 logMAR lines | Standard Deviation 1.1 |
| Intensified Treatment | Mean Change in Amblyopic-Eye Visual Acuity at 10 Weeks From Randomization | 1.1 logMAR lines | Standard Deviation 1.8 |
Secondary
Atropine Compliance at 10 Weeks by Treatment Group
The distribution of compliance with prescribed treatment was tabulated for the 10-week outcome. 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 frequency of atropine administration.
Time frame: 10 weeks after randomization
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control | Atropine Compliance at 10 Weeks by Treatment Group | Fair | 0 participants |
| Control | Atropine Compliance at 10 Weeks by Treatment Group | Excellent | 38 participants |
| Control | Atropine Compliance at 10 Weeks by Treatment Group | Good | 2 participants |
| Control | Atropine Compliance at 10 Weeks by Treatment Group | Poor | 0 participants |
| Intensified Treatment | Atropine Compliance at 10 Weeks by Treatment Group | Poor | 0 participants |
| Intensified Treatment | Atropine Compliance at 10 Weeks by Treatment Group | Fair | 0 participants |
| Intensified Treatment | Atropine Compliance at 10 Weeks by Treatment Group | Good | 2 participants |
| Intensified Treatment | Atropine Compliance at 10 Weeks by Treatment Group | Excellent | 31 participants |
Secondary
Average Atropine Compliance 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 frequency of atropine administration.
Time frame: 10 weeks after randomization or later (until no further VA improvement, up to maximum of 84 weeks for one subject)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control | Average Atropine Compliance by Treatment Group | Excellent | 39 participants |
| Control | Average Atropine Compliance by Treatment Group | Good | 1 participants |
| Control | Average Atropine Compliance by Treatment Group | Fair | 0 participants |
| Control | Average Atropine Compliance by Treatment Group | Poor | 0 participants |
| Intensified Treatment | Average Atropine Compliance by Treatment Group | Poor | 0 participants |
| Intensified Treatment | Average Atropine Compliance by Treatment Group | Excellent | 29 participants |
| Intensified Treatment | Average Atropine Compliance by Treatment Group | Fair | 0 participants |
| Intensified Treatment | Average Atropine Compliance by Treatment Group | Good | 4 participants |
Secondary
Average Spectacle Compliance 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 frequency of atropine administration.
Time frame: 10 weeks after randomization or later (until no further VA improvement, up to maximum of 84 weeks for one subject)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control | Average Spectacle Compliance by Treatment Group | Excellent | 39 participants |
| Control | Average Spectacle Compliance by Treatment Group | Good | 1 participants |
| Control | Average Spectacle Compliance by Treatment Group | Fair | 0 participants |
| Control | Average Spectacle Compliance by Treatment Group | Poor | 0 participants |
| Intensified Treatment | Average Spectacle Compliance by Treatment Group | Poor | 1 participants |
| Intensified Treatment | Average Spectacle Compliance by Treatment Group | Excellent | 30 participants |
| Intensified Treatment | Average Spectacle Compliance by Treatment Group | Fair | 0 participants |
| Intensified Treatment | Average Spectacle Compliance by Treatment Group | Good | 2 participants |
Secondary
Distribution of 12-week Fellow-Eye Visual Acuity
Following the 10-week primary outcome exam, participants discontinued the randomized treatment and returned 2 weeks later for a 12-week visit to measure off-treatment fellow-eye visual acuity.
Time frame: 12 weeks after randomization
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control | Distribution of 12-week Fellow-Eye Visual Acuity | 20/32 | 0 participants |
| Control | Distribution of 12-week Fellow-Eye Visual Acuity | 20/20 | 19 participants |
| Control | Distribution of 12-week Fellow-Eye Visual Acuity | 20/25 | 10 participants |
| Control | Distribution of 12-week Fellow-Eye Visual Acuity | 20/16 | 10 participants |
| Control | Distribution of 12-week Fellow-Eye Visual Acuity | 20/40 | 1 participants |
| Intensified Treatment | Distribution of 12-week Fellow-Eye Visual Acuity | 20/16 | 8 participants |
| Intensified Treatment | Distribution of 12-week Fellow-Eye Visual Acuity | 20/40 | 0 participants |
| Intensified Treatment | Distribution of 12-week Fellow-Eye Visual Acuity | 20/32 | 4 participants |
| Intensified Treatment | Distribution of 12-week Fellow-Eye Visual Acuity | 20/25 | 7 participants |
| Intensified Treatment | Distribution of 12-week Fellow-Eye Visual Acuity | 20/20 | 14 participants |
Secondary
Distribution of Amblyopic-Eye Visual Acuity at Best Outcome 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 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.)
Time frame: 10 weeks after randomization or later (until no further VA improvement, up to maximum of 84 weeks for one subject)
Population: The analysis includes data from participants who completed the 10-week exam and/or a later visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control | Distribution of Amblyopic-Eye Visual Acuity at Best Outcome Visit | 20/200 | 0 participants |
| Control | Distribution of Amblyopic-Eye Visual Acuity at Best Outcome Visit | 20/160 | 2 participants |
| Control | Distribution of Amblyopic-Eye Visual Acuity at Best Outcome Visit | 20/125 | 1 participants |
| Control | Distribution of Amblyopic-Eye Visual Acuity at Best Outcome Visit | 20/100 | 3 participants |
| Control | Distribution of Amblyopic-Eye Visual Acuity at Best Outcome Visit | 20/80 | 6 participants |
| Control | Distribution of Amblyopic-Eye Visual Acuity at Best Outcome Visit | 20/63 | 1 participants |
| Control | Distribution of Amblyopic-Eye Visual Acuity at Best Outcome Visit | 20/50 | 8 participants |
| Control | Distribution of Amblyopic-Eye Visual Acuity at Best Outcome Visit | 20/40 | 10 participants |
| Control | Distribution of Amblyopic-Eye Visual Acuity at Best Outcome Visit | 20/32 | 3 participants |
| Control | Distribution of Amblyopic-Eye Visual Acuity at Best Outcome Visit | 20/25 | 5 participants |
| Control | Distribution of Amblyopic-Eye Visual Acuity at Best Outcome Visit | 20/20 | 1 participants |
| Control | Distribution of Amblyopic-Eye Visual Acuity at Best Outcome Visit | 20/16 | 0 participants |
| Intensified Treatment | Distribution of Amblyopic-Eye Visual Acuity at Best Outcome Visit | 20/20 | 3 participants |
| Intensified Treatment | Distribution of Amblyopic-Eye Visual Acuity at Best Outcome Visit | 20/200 | 1 participants |
| Intensified Treatment | Distribution of Amblyopic-Eye Visual Acuity at Best Outcome Visit | 20/50 | 5 participants |
| Intensified Treatment | Distribution of Amblyopic-Eye Visual Acuity at Best Outcome Visit | 20/160 | 0 participants |
| Intensified Treatment | Distribution of Amblyopic-Eye Visual Acuity at Best Outcome Visit | 20/25 | 5 participants |
| Intensified Treatment | Distribution of Amblyopic-Eye Visual Acuity at Best Outcome Visit | 20/125 | 0 participants |
| Intensified Treatment | Distribution of Amblyopic-Eye Visual Acuity at Best Outcome Visit | 20/40 | 3 participants |
| Intensified Treatment | Distribution of Amblyopic-Eye Visual Acuity at Best Outcome Visit | 20/100 | 1 participants |
| Intensified Treatment | Distribution of Amblyopic-Eye Visual Acuity at Best Outcome Visit | 20/16 | 0 participants |
| Intensified Treatment | Distribution of Amblyopic-Eye Visual Acuity at Best Outcome Visit | 20/80 | 1 participants |
| Intensified Treatment | Distribution of Amblyopic-Eye Visual Acuity at Best Outcome Visit | 20/32 | 10 participants |
| Intensified Treatment | Distribution of Amblyopic-Eye Visual Acuity at Best Outcome Visit | 20/63 | 4 participants |
Secondary
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.
Time frame: 10 weeks after randomization
Population: The analysis included participants who completed 10-week exams between 8 and 15 weeks (inclusive) according to the principles specified in the primary outcome analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control | Distribution of Baseline Characteristics at the 10-week Outcome | Amblyopic-eye VA at randomization: 20/50 | 7 participants |
| Control | Distribution of Baseline Characteristics at the 10-week Outcome | Amblyopic-eye VA at randomization: 20/40 or better | 12 participants |
| Control | Distribution of Baseline Characteristics at the 10-week Outcome | Gender: Male | 18 participants |
| Control | Distribution of Baseline Characteristics at the 10-week Outcome | Cause of amblyopia: Strabismus | 8 participants |
| Control | Distribution of Baseline Characteristics at the 10-week Outcome | Age at randomization: 5 to <6 years | 9 participants |
| Control | Distribution of Baseline Characteristics at the 10-week Outcome | Cause of amblyopia: Anisometropia | 10 participants |
| Control | Distribution of Baseline Characteristics at the 10-week Outcome | Race/Ethnicity: Non-White/Hispanic | 7 participants |
| Control | Distribution of Baseline Characteristics at the 10-week Outcome | Cause of amblyopia: Combined mechanism | 21 participants |
| Control | Distribution of Baseline Characteristics at the 10-week Outcome | Age at randomization: 6 to <7 years | 7 participants |
| Control | Distribution of Baseline Characteristics at the 10-week Outcome | Atropine duration prior to randomization:12-<15wks | 11 participants |
| Control | Distribution of Baseline Characteristics at the 10-week Outcome | Gender: Female | 21 participants |
| Control | Distribution of Baseline Characteristics at the 10-week Outcome | Atropine duration prior to randomization:15-<21wks | 6 participants |
| Control | Distribution of Baseline Characteristics at the 10-week Outcome | Age at randomization: 7 years or older | 11 participants |
| Control | Distribution of Baseline Characteristics at the 10-week Outcome | Atropine duration prior to randomization:21-<27wks | 12 participants |
| Control | Distribution of Baseline Characteristics at the 10-week Outcome | Atropine duration prior to randomization:27-84 wks | 10 participants |
| Control | Distribution of Baseline Characteristics at the 10-week Outcome | Age at randomization: 3 to <4 years | 5 participants |
| Control | Distribution of Baseline Characteristics at the 10-week Outcome | Fellow-eye SE RE at enrollment: <+3.00 Diopters(D) | 10 participants |
| Control | Distribution of Baseline Characteristics at the 10-week Outcome | Amblyopic-eye VA at randomization: 20/63 | 9 participants |
| Control | Distribution of Baseline Characteristics at the 10-week Outcome | Fellow-eye SE RE at enrollment: +3.00 to <+4.50 D | 12 participants |
| Control | Distribution of Baseline Characteristics at the 10-week Outcome | Race/Ethnicity: White (non-Hispanic) | 32 participants |
| Control | Distribution of Baseline Characteristics at the 10-week Outcome | Fellow-eye SE RE at enrollment: +4.50 to +6.00 D | 12 participants |
| Control | Distribution of Baseline Characteristics at the 10-week Outcome | Age at randomization: 4 to <5 years | 7 participants |
| Control | Distribution of Baseline Characteristics at the 10-week Outcome | Fellow-eye SE RE at enrollment: >+6.00 D | 5 participants |
| Control | Distribution of Baseline Characteristics at the 10-week Outcome | Amblyopic-eye VA at randomization: 20/80 or worse | 11 participants |
| Intensified Treatment | Distribution of Baseline Characteristics at the 10-week Outcome | Fellow-eye SE RE at enrollment: >+6.00 D | 9 participants |
| Intensified Treatment | Distribution of Baseline Characteristics at the 10-week Outcome | Amblyopic-eye VA at randomization: 20/80 or worse | 10 participants |
| Intensified Treatment | Distribution of Baseline Characteristics at the 10-week Outcome | Amblyopic-eye VA at randomization: 20/50 | 8 participants |
| Intensified Treatment | Distribution of Baseline Characteristics at the 10-week Outcome | Gender: Female | 19 participants |
| Intensified Treatment | Distribution of Baseline Characteristics at the 10-week Outcome | Gender: Male | 14 participants |
| Intensified Treatment | Distribution of Baseline Characteristics at the 10-week Outcome | Race/Ethnicity: White (non-Hispanic) | 29 participants |
| Intensified Treatment | Distribution of Baseline Characteristics at the 10-week Outcome | Race/Ethnicity: Non-White/Hispanic | 4 participants |
| Intensified Treatment | Distribution of Baseline Characteristics at the 10-week Outcome | Age at randomization: 3 to <4 years | 4 participants |
| Intensified Treatment | Distribution of Baseline Characteristics at the 10-week Outcome | Age at randomization: 4 to <5 years | 6 participants |
| Intensified Treatment | Distribution of Baseline Characteristics at the 10-week Outcome | Age at randomization: 5 to <6 years | 9 participants |
| Intensified Treatment | Distribution of Baseline Characteristics at the 10-week Outcome | Age at randomization: 6 to <7 years | 5 participants |
| Intensified Treatment | Distribution of Baseline Characteristics at the 10-week Outcome | Age at randomization: 7 years or older | 9 participants |
| Intensified Treatment | Distribution of Baseline Characteristics at the 10-week Outcome | Atropine duration prior to randomization:21-<27wks | 9 participants |
| Intensified Treatment | Distribution of Baseline Characteristics at the 10-week Outcome | Amblyopic-eye VA at randomization: 20/63 | 8 participants |
| Intensified Treatment | Distribution of Baseline Characteristics at the 10-week Outcome | Amblyopic-eye VA at randomization: 20/40 or better | 7 participants |
| Intensified Treatment | Distribution of Baseline Characteristics at the 10-week Outcome | Cause of amblyopia: Strabismus | 13 participants |
| Intensified Treatment | Distribution of Baseline Characteristics at the 10-week Outcome | Cause of amblyopia: Anisometropia | 6 participants |
| Intensified Treatment | Distribution of Baseline Characteristics at the 10-week Outcome | Cause of amblyopia: Combined mechanism | 14 participants |
| Intensified Treatment | Distribution of Baseline Characteristics at the 10-week Outcome | Atropine duration prior to randomization:12-<15wks | 5 participants |
| Intensified Treatment | Distribution of Baseline Characteristics at the 10-week Outcome | Atropine duration prior to randomization:15-<21wks | 9 participants |
| Intensified Treatment | Distribution of Baseline Characteristics at the 10-week Outcome | Atropine duration prior to randomization:27-84 wks | 10 participants |
| Intensified Treatment | Distribution of Baseline Characteristics at the 10-week Outcome | Fellow-eye SE RE at enrollment: <+3.00 Diopters(D) | 7 participants |
| Intensified Treatment | Distribution of Baseline Characteristics at the 10-week Outcome | Fellow-eye SE RE at enrollment: +3.00 to <+4.50 D | 13 participants |
| Intensified Treatment | Distribution of Baseline Characteristics at the 10-week Outcome | Fellow-eye SE RE at enrollment: +4.50 to +6.00 D | 4 participants |
Secondary
Distribution of Change in Amblyopic-Eye Visual Acuity From Randomization to Best Outcome 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 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.)
Time frame: Randomization to 10 weeks or later (until no further VA improvement, up to maximum of 84 weeks for one subject)
Population: The analysis includes data from participants who completed the 10-week exam and/or a later visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control | Distribution of Change in Amblyopic-Eye Visual Acuity From Randomization to Best Outcome Visit | 1 line worse | 4 participants |
| Control | Distribution of Change in Amblyopic-Eye Visual Acuity From Randomization to Best Outcome Visit | 1 line improved | 12 participants |
| Control | Distribution of Change in Amblyopic-Eye Visual Acuity From Randomization to Best Outcome Visit | 2 lines worse | 1 participants |
| Control | Distribution of Change in Amblyopic-Eye Visual Acuity From Randomization to Best Outcome Visit | 2 lines improved | 9 participants |
| Control | Distribution of Change in Amblyopic-Eye Visual Acuity From Randomization to Best Outcome Visit | No change | 12 participants |
| Control | Distribution of Change in Amblyopic-Eye Visual Acuity From Randomization to Best Outcome Visit | 3 or more lines improved | 2 participants |
| Control | Distribution of Change in Amblyopic-Eye Visual Acuity From Randomization to Best Outcome Visit | 3 or more lines worse | 0 participants |
| Intensified Treatment | Distribution of Change in Amblyopic-Eye Visual Acuity From Randomization to Best Outcome Visit | 3 or more lines improved | 14 participants |
| Intensified Treatment | Distribution of Change in Amblyopic-Eye Visual Acuity From Randomization to Best Outcome Visit | 3 or more lines worse | 0 participants |
| Intensified Treatment | Distribution of Change in Amblyopic-Eye Visual Acuity From Randomization to Best Outcome Visit | 2 lines worse | 1 participants |
| Intensified Treatment | Distribution of Change in Amblyopic-Eye Visual Acuity From Randomization to Best Outcome Visit | 1 line worse | 3 participants |
| Intensified Treatment | Distribution of Change in Amblyopic-Eye Visual Acuity From Randomization to Best Outcome Visit | No change | 3 participants |
| Intensified Treatment | Distribution of Change in Amblyopic-Eye Visual Acuity From Randomization to Best Outcome Visit | 1 line improved | 6 participants |
| Intensified Treatment | Distribution of Change in Amblyopic-Eye Visual Acuity From Randomization to Best Outcome Visit | 2 lines improved | 6 participants |
Secondary
Distribution of Change in Fellow-Eye Visual Acuity at 12 Weeks From Randomization
Time frame: 12 weeks after randomization
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control | Distribution of Change in Fellow-Eye Visual Acuity at 12 Weeks From Randomization | 1 line worse | 1 participants |
| Control | Distribution of Change in Fellow-Eye Visual Acuity at 12 Weeks From Randomization | 1 line improved | 12 participants |
| Control | Distribution of Change in Fellow-Eye Visual Acuity at 12 Weeks From Randomization | 2 lines worse | 0 participants |
| Control | Distribution of Change in Fellow-Eye Visual Acuity at 12 Weeks From Randomization | 2 lines improved | 3 participants |
| Control | Distribution of Change in Fellow-Eye Visual Acuity at 12 Weeks From Randomization | No change | 23 participants |
| Control | Distribution of Change in Fellow-Eye Visual Acuity at 12 Weeks From Randomization | 3 or more lines improved | 0 participants |
| Control | Distribution of Change in Fellow-Eye Visual Acuity at 12 Weeks From Randomization | 3 or more lines worse | 1 participants |
| Intensified Treatment | Distribution of Change in Fellow-Eye Visual Acuity at 12 Weeks From Randomization | 3 or more lines improved | 0 participants |
| Intensified Treatment | Distribution of Change in Fellow-Eye Visual Acuity at 12 Weeks From Randomization | 3 or more lines worse | 0 participants |
| Intensified Treatment | Distribution of Change in Fellow-Eye Visual Acuity at 12 Weeks From Randomization | 2 lines worse | 0 participants |
| Intensified Treatment | Distribution of Change in Fellow-Eye Visual Acuity at 12 Weeks From Randomization | 1 line worse | 2 participants |
| Intensified Treatment | Distribution of Change in Fellow-Eye Visual Acuity at 12 Weeks From Randomization | No change | 22 participants |
| Intensified Treatment | Distribution of Change in Fellow-Eye Visual Acuity at 12 Weeks From Randomization | 1 line improved | 7 participants |
| Intensified Treatment | Distribution of Change in Fellow-Eye Visual Acuity at 12 Weeks From Randomization | 2 lines improved | 2 participants |
Secondary
Distribution of Interocular Difference at 12-week Exam
Distribution of Interocular Difference Between Eyes at 12-week Exam
Time frame: 12 weeks after randomization
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control | Distribution of Interocular Difference at 12-week Exam | 0 or less lines | 3 participants |
| Control | Distribution of Interocular Difference at 12-week Exam | 2 lines | 6 participants |
| Control | Distribution of Interocular Difference at 12-week Exam | 6 or more lines | 12 participants |
| Control | Distribution of Interocular Difference at 12-week Exam | 3 lines | 6 participants |
| Control | Distribution of Interocular Difference at 12-week Exam | 1 line | 2 participants |
| Control | Distribution of Interocular Difference at 12-week Exam | 4 lines | 5 participants |
| Control | Distribution of Interocular Difference at 12-week Exam | 5 lines | 5 participants |
| Intensified Treatment | Distribution of Interocular Difference at 12-week Exam | 4 lines | 4 participants |
| Intensified Treatment | Distribution of Interocular Difference at 12-week Exam | 5 lines | 5 participants |
| Intensified Treatment | Distribution of Interocular Difference at 12-week Exam | 6 or more lines | 4 participants |
| Intensified Treatment | Distribution of Interocular Difference at 12-week Exam | 0 or less lines | 2 participants |
| Intensified Treatment | Distribution of Interocular Difference at 12-week Exam | 1 line | 2 participants |
| Intensified Treatment | Distribution of Interocular Difference at 12-week Exam | 2 lines | 8 participants |
| Intensified Treatment | Distribution of Interocular Difference at 12-week Exam | 3 lines | 8 participants |
Secondary
Distribution of Randot Preschool Stereoacuity Score at 12 Weeks
Distribution of Randot Preschool Stereoacuity Score at 12 Weeks; Participants with a Randot Preschool test of \>800 seconds of arc were classified as having a stereoacuity of 3000 seconds of arc if the Titmus fly test was positive or as nil if the Titmus fly test was negative.
Time frame: 12 weeks after randomization
Population: The analysis includes all participants who completed the 12-week exam.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control | Distribution of Randot Preschool Stereoacuity Score at 12 Weeks | 60 arcsec | 2 participants |
| Control | Distribution of Randot Preschool Stereoacuity Score at 12 Weeks | Failed pretest | 4 participants |
| Control | Distribution of Randot Preschool Stereoacuity Score at 12 Weeks | >800 arcsec: Nil | 7 participants |
| Control | Distribution of Randot Preschool Stereoacuity Score at 12 Weeks | >800 arcsec: 3000 arcsec | 14 participants |
| Control | Distribution of Randot Preschool Stereoacuity Score at 12 Weeks | 800 arcsec | 7 participants |
| Control | Distribution of Randot Preschool Stereoacuity Score at 12 Weeks | 400 arcsec | 4 participants |
| Control | Distribution of Randot Preschool Stereoacuity Score at 12 Weeks | 200 arcsec | 0 participants |
| Control | Distribution of Randot Preschool Stereoacuity Score at 12 Weeks | 100 arcsec | 1 participants |
| Control | Distribution of Randot Preschool Stereoacuity Score at 12 Weeks | 40 arcsec | 1 participants |
| Intensified Treatment | Distribution of Randot Preschool Stereoacuity Score at 12 Weeks | 100 arcsec | 1 participants |
| Intensified Treatment | Distribution of Randot Preschool Stereoacuity Score at 12 Weeks | 400 arcsec | 3 participants |
| Intensified Treatment | Distribution of Randot Preschool Stereoacuity Score at 12 Weeks | Failed pretest | 2 participants |
| Intensified Treatment | Distribution of Randot Preschool Stereoacuity Score at 12 Weeks | 60 arcsec | 1 participants |
| Intensified Treatment | Distribution of Randot Preschool Stereoacuity Score at 12 Weeks | >800 arcsec: Nil | 10 participants |
| Intensified Treatment | Distribution of Randot Preschool Stereoacuity Score at 12 Weeks | 200 arcsec | 1 participants |
| Intensified Treatment | Distribution of Randot Preschool Stereoacuity Score at 12 Weeks | >800 arcsec: 3000 arcsec | 12 participants |
| Intensified Treatment | Distribution of Randot Preschool Stereoacuity Score at 12 Weeks | 40 arcsec | 0 participants |
| Intensified Treatment | Distribution of Randot Preschool Stereoacuity Score at 12 Weeks | 800 arcsec | 3 participants |
Comparison: The distribution of 12-week Randot Preschool Stereoacuity scores was compared between treatment groups using a Wilcoxon rank sum test.p-value: 0.23Wilcoxon (Mann-Whitney)
Secondary
Distribution of Randot Preschool Stereoacuity Scores at 12 Weeks for Participants With Anisometropic Amblyopia
Time frame: 12 weeks after randomization
Population: The analysis includes participants with anisometropic amblyopia (no strabismus) who completed the 12-week exam.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control | Distribution of Randot Preschool Stereoacuity Scores at 12 Weeks for Participants With Anisometropic Amblyopia | >800 arcsec: Nil | 1 participants |
| Control | Distribution of Randot Preschool Stereoacuity Scores at 12 Weeks for Participants With Anisometropic Amblyopia | 200 arcsec | 0 participants |
| Control | Distribution of Randot Preschool Stereoacuity Scores at 12 Weeks for Participants With Anisometropic Amblyopia | 800 arcsec | 3 participants |
| Control | Distribution of Randot Preschool Stereoacuity Scores at 12 Weeks for Participants With Anisometropic Amblyopia | 100 arcsec | 0 participants |
| Control | Distribution of Randot Preschool Stereoacuity Scores at 12 Weeks for Participants With Anisometropic Amblyopia | >800 arcsec: 3000 arcsec | 2 participants |
| Control | Distribution of Randot Preschool Stereoacuity Scores at 12 Weeks for Participants With Anisometropic Amblyopia | 60 arcsec | 1 participants |
| Control | Distribution of Randot Preschool Stereoacuity Scores at 12 Weeks for Participants With Anisometropic Amblyopia | 400 arcsec | 2 participants |
| Control | Distribution of Randot Preschool Stereoacuity Scores at 12 Weeks for Participants With Anisometropic Amblyopia | 40 arcsec | 1 participants |
| Control | Distribution of Randot Preschool Stereoacuity Scores at 12 Weeks for Participants With Anisometropic Amblyopia | Failed pretest | 0 participants |
| Intensified Treatment | Distribution of Randot Preschool Stereoacuity Scores at 12 Weeks for Participants With Anisometropic Amblyopia | 40 arcsec | 0 participants |
| Intensified Treatment | Distribution of Randot Preschool Stereoacuity Scores at 12 Weeks for Participants With Anisometropic Amblyopia | Failed pretest | 0 participants |
| Intensified Treatment | Distribution of Randot Preschool Stereoacuity Scores at 12 Weeks for Participants With Anisometropic Amblyopia | >800 arcsec: Nil | 1 participants |
| Intensified Treatment | Distribution of Randot Preschool Stereoacuity Scores at 12 Weeks for Participants With Anisometropic Amblyopia | >800 arcsec: 3000 arcsec | 2 participants |
| Intensified Treatment | Distribution of Randot Preschool Stereoacuity Scores at 12 Weeks for Participants With Anisometropic Amblyopia | 800 arcsec | 1 participants |
| Intensified Treatment | Distribution of Randot Preschool Stereoacuity Scores at 12 Weeks for Participants With Anisometropic Amblyopia | 400 arcsec | 0 participants |
| Intensified Treatment | Distribution of Randot Preschool Stereoacuity Scores at 12 Weeks for Participants With Anisometropic Amblyopia | 200 arcsec | 0 participants |
| Intensified Treatment | Distribution of Randot Preschool Stereoacuity Scores at 12 Weeks for Participants With Anisometropic Amblyopia | 100 arcsec | 1 participants |
| Intensified Treatment | Distribution of Randot Preschool Stereoacuity Scores at 12 Weeks for Participants With Anisometropic Amblyopia | 60 arcsec | 1 participants |
Comparison: The distribution of 12-week Randot Preschool Stereoacuity scores was compared between treatment groups using a Wilcoxon rank sum test.p-value: 0.66Wilcoxon (Mann-Whitney)
Secondary
Mean Amblyopic-Eye Visual Acuity at Best Outcome 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. 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.
Time frame: 10 weeks after randomization or later (until no further VA improvement, up to maximum of 84 weeks for one subject)
Population: The analysis includes data from participants who completed the 10-week exam and/or a later visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Mean Amblyopic-Eye Visual Acuity at Best Outcome Visit | 0.40 logMAR | Standard Deviation 0.23 |
| Intensified Treatment | Mean Amblyopic-Eye Visual Acuity at Best Outcome Visit | 0.29 logMAR | Standard Deviation 0.22 |
Secondary
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.
Time frame: 10 weeks after randomization
Population: The analysis included participants who completed 10-week exams between 8 and 15 weeks (inclusive) according to the principles of the primary outcome analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Gender: Female | 0.51 logMAR | Standard Deviation 0.19 |
| Control | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Gender: Male | 0.45 logMAR | Standard Deviation 0.19 |
| Control | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Race/Ethnicity: White (non-Hispanic) | 0.50 logMAR | Standard Deviation 0.19 |
| Control | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Race/Ethnicity: Non-White/Hispanic | 0.41 logMAR | Standard Deviation 0.18 |
| Control | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Age at randomization: 3 to <4 years | 0.58 logMAR | Standard Deviation 0.22 |
| Control | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Age at randomization: 4 to <5 years | 0.50 logMAR | Standard Deviation 0.13 |
| Control | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Age at randomization: 5 to <6 years | 0.46 logMAR | Standard Deviation 0.21 |
| Control | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Age at randomization: 6 to <7 years | 0.43 logMAR | Standard Deviation 0.18 |
| Control | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Age at randomization: 7 years or older | 0.48 logMAR | Standard Deviation 0.21 |
| Control | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Cause of amblyopia: Strabismus | 0.48 logMAR | Standard Deviation 0.23 |
| Control | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Cause of amblyopia: Anisometropia | 0.42 logMAR | Standard Deviation 0.13 |
| Control | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Cause of amblyopia: Combined mechanism | 0.51 logMAR | Standard Deviation 0.2 |
| Control | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Atropine duration prior to randomization:12-<15wks | 0.54 logMAR | Standard Deviation 0.23 |
| Control | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Atropine duration prior to randomization:15-<21wks | 0.53 logMAR | Standard Deviation 0.23 |
| Control | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Atropine duration prior to randomization:21-<27wks | 0.43 logMAR | Standard Deviation 0.12 |
| Control | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Atropine duration prior to randomization:27-84 wks | 0.46 logMAR | Standard Deviation 0.18 |
| Control | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Fellow-eye SE RE at enrollment: <+3.00 Diopters(D) | 0.41 logMAR | Standard Deviation 0.2 |
| Control | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Fellow-eye SE RE at enrollment: +3.00 to <+4.50 D | 0.50 logMAR | Standard Deviation 0.18 |
| Control | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Fellow-eye SE RE at enrollment: +4.50 to +6.00 D | 0.53 logMAR | Standard Deviation 0.17 |
| Control | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Fellow-eye SE RE at enrollment: >+6.00 D | 0.48 logMAR | Standard Deviation 0.25 |
| Intensified Treatment | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Fellow-eye SE RE at enrollment: +3.00 to <+4.50 D | 0.51 logMAR | Standard Deviation 0.16 |
| Intensified Treatment | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Gender: Female | 0.46 logMAR | Standard Deviation 0.14 |
| Intensified Treatment | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Cause of amblyopia: Anisometropia | 0.35 logMAR | Standard Deviation 0.11 |
| Intensified Treatment | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Gender: Male | 0.51 logMAR | Standard Deviation 0.19 |
| Intensified Treatment | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Atropine duration prior to randomization:27-84 wks | 0.47 logMAR | Standard Deviation 0.19 |
| Intensified Treatment | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Race/Ethnicity: White (non-Hispanic) | 0.49 logMAR | Standard Deviation 0.17 |
| Intensified Treatment | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Cause of amblyopia: Combined mechanism | 0.56 logMAR | Standard Deviation 0.15 |
| Intensified Treatment | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Race/Ethnicity: Non-White/Hispanic | 0.43 logMAR | Standard Deviation 0.05 |
| Intensified Treatment | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Fellow-eye SE RE at enrollment: >+6.00 D | 0.47 logMAR | Standard Deviation 0.11 |
| Intensified Treatment | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Age at randomization: 3 to <4 years | 0.48 logMAR | Standard Deviation 0.17 |
| Intensified Treatment | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Atropine duration prior to randomization:12-<15wks | 0.38 logMAR | Standard Deviation 0.11 |
| Intensified Treatment | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Age at randomization: 4 to <5 years | 0.58 logMAR | Standard Deviation 0.23 |
| Intensified Treatment | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Fellow-eye SE RE at enrollment: <+3.00 Diopters(D) | 0.49 logMAR | Standard Deviation 0.2 |
| Intensified Treatment | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Age at randomization: 5 to <6 years | 0.42 logMAR | Standard Deviation 0.1 |
| Intensified Treatment | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Atropine duration prior to randomization:15-<21wks | 0.51 logMAR | Standard Deviation 0.18 |
| Intensified Treatment | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Age at randomization: 6 to <7 years | 0.50 logMAR | Standard Deviation 0.12 |
| Intensified Treatment | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Fellow-eye SE RE at enrollment: +4.50 to +6.00 D | 0.45 logMAR | Standard Deviation 0.24 |
| Intensified Treatment | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Age at randomization: 7 years or older | 0.48 logMAR | Standard Deviation 0.18 |
| Intensified Treatment | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Atropine duration prior to randomization:21-<27wks | 0.53 logMAR | Standard Deviation 0.12 |
| Intensified Treatment | Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome | Cause of amblyopia: Strabismus | 0.46 logMAR | Standard Deviation 0.16 |
Secondary
Mean Change in Amblyopic-Eye Visual Acuity at Best Outcome 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 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.)
Time frame: 10 weeks after randomization or later (until no further VA improvement, up to maximum of 84 weeks for one subject)
Population: The analysis includes data from participants who completed the 10-week exam and/or a later visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Mean Change in Amblyopic-Eye Visual Acuity at Best Outcome Visit | 0.8 logMAR lines | Standard Deviation 1.2 |
| Intensified Treatment | Mean Change in Amblyopic-Eye Visual Acuity at Best Outcome Visit | 1.9 logMAR lines | Standard Deviation 1.8 |
Secondary
Mean Change in Fellow-Eye Visual Acuity at 12 Weeks From Randomization
Time frame: 12 weeks after randomization
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Mean Change in Fellow-Eye Visual Acuity at 12 Weeks From Randomization | 0.4 change in lines | Standard Deviation 0.9 |
| Intensified Treatment | Mean Change in Fellow-Eye Visual Acuity at 12 Weeks From Randomization | 0.3 change in lines | Standard Deviation 0.7 |
Comparison: A treatment group difference in fellow-eye visual acuity change at the 12-week exam was evaluated using an ANCOVA model, adjusting for the fellow-eye visual acuity at randomization.p-value: 0.5595% CI: [-0.23, 0.43]ANCOVA
Secondary
Mean Fellow-Eye Visual Acuity at 12-week Exam
Time frame: 12 weeks after randomization
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Mean Fellow-Eye Visual Acuity at 12-week Exam | 0.01 logMAR | Standard Deviation 0.09 |
| Intensified Treatment | Mean Fellow-Eye Visual Acuity at 12-week Exam | 0.02 logMAR | Standard Deviation 0.1 |
Secondary
Mean Interocular Difference at 12-week Exam
Mean Interocular Difference Between Eyes at 12-week Exam
Time frame: 12 weeks after randomization
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Mean Interocular Difference at 12-week Exam | 4.3 logMAR lines | Standard Deviation 2.6 |
| Intensified Treatment | Mean Interocular Difference at 12-week Exam | 3.3 logMAR lines | Standard Deviation 2 |
Secondary
Spectacle Compliance at 10 Weeks by Treatment Group
The distribution of compliance with prescribed treatment was tabulated for the 10-week outcome. 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 frequency of atropine administration.
Time frame: 10 weeks after randomization
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control | Spectacle Compliance at 10 Weeks by Treatment Group | Excellent | 39 participants |
| Control | Spectacle Compliance at 10 Weeks by Treatment Group | Good | 1 participants |
| Control | Spectacle Compliance at 10 Weeks by Treatment Group | Fair | 0 participants |
| Control | Spectacle Compliance at 10 Weeks by Treatment Group | Poor | 0 participants |
| Intensified Treatment | Spectacle Compliance at 10 Weeks by Treatment Group | Poor | 1 participants |
| Intensified Treatment | Spectacle Compliance at 10 Weeks by Treatment Group | Excellent | 30 participants |
| Intensified Treatment | Spectacle Compliance at 10 Weeks by Treatment Group | Fair | 1 participants |
| Intensified Treatment | Spectacle Compliance at 10 Weeks by Treatment Group | Good | 1 participants |
Secondary
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.
Time frame: 10 weeks after randomization
Population: The analysis included participants who completed 10-week exams between 8 and 15 weeks (inclusive) according to the principles of the primary outcome analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Age at randomization: 3 to <4 years | 0.2 logMAR lines | Standard Deviation 0.8 |
| Control | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Amblyopic-eye VA at randomization: 20/50 | 1.0 logMAR lines | Standard Deviation 1.3 |
| Control | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Gender: Male | 1.0 logMAR lines | Standard Deviation 1 |
| Control | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Amblyopic-eye VA at randomization: 20/40 or better | 0.5 logMAR lines | Standard Deviation 1.1 |
| Control | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Age at randomization: 4 to <5 years | 04 logMAR lines | Standard Deviation 1.5 |
| Control | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Cause of amblyopia: Strabismus | 0.1 logMAR lines | Standard Deviation 1.1 |
| Control | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Fellow-eye SE RE at enrollment: <+3.00 Diopters(D) | 0.7 logMAR lines | Standard Deviation 1.3 |
| Control | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Cause of amblyopia: Combined mechanism | 0.7 logMAR lines | Standard Deviation 1.1 |
| Control | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Age at randomization: 5 to <6 years | 0.8 logMAR lines | Standard Deviation 1.3 |
| Control | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Atropine duration prior to randomization:12-<15wks | 1.1 logMAR lines | Standard Deviation 0.7 |
| Control | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Race/Ethnicity: White (non-Hispanic) | 0.5 logMAR lines | Standard Deviation 1.1 |
| Control | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Atropine duration prior to randomization:15-<21wks | -0.3 logMAR lines | Standard Deviation 1 |
| Control | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Age at randomization: 6 to <7 years | 0.3 logMAR lines | Standard Deviation 0.5 |
| Control | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Atropine duration prior to randomization:21-<27wks | 0.6 logMAR lines | Standard Deviation 1.3 |
| Control | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Gender: Female | 0.2 logMAR lines | Standard Deviation 1 |
| Control | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Atropine duration prior to randomization:27-84 wks | 0.6 logMAR lines | Standard Deviation 0.8 |
| Control | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Age at randomization: 7 years or older | 0.9 logMAR lines | Standard Deviation 0.9 |
| Control | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Race/Ethnicity: Non-White/Hispanic | 0.9 logMAR lines | Standard Deviation 1.2 |
| Control | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Fellow-eye SE RE at enrollment: +3.00 to <+4.50 D | 0.7 logMAR lines | Standard Deviation 1.2 |
| Control | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Amblyopic-eye VA at randomization: 20/80 or worse | 0.5 logMAR lines | Standard Deviation 0.7 |
| Control | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Fellow-eye SE RE at enrollment: +4.50 to +6.00 D | 0.4 logMAR lines | Standard Deviation 0.9 |
| Control | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Cause of amblyopia: Anisometropia | 0.8 logMAR lines | Standard Deviation 0.9 |
| Control | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Fellow-eye SE RE at enrollment: >+6.00 D | 0.6 logMAR lines | Standard Deviation 1.1 |
| Control | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Amblyopic-eye VA at randomization: 20/63 | 0.4 logMAR lines | Standard Deviation 1.3 |
| Intensified Treatment | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Fellow-eye SE RE at enrollment: >+6.00 D | 1.3 logMAR lines | Standard Deviation 1.4 |
| Intensified Treatment | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Gender: Female | 1.2 logMAR lines | Standard Deviation 1.6 |
| Intensified Treatment | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Gender: Male | 1.1 logMAR lines | Standard Deviation 2 |
| Intensified Treatment | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Race/Ethnicity: White (non-Hispanic) | 1.1 logMAR lines | Standard Deviation 1.8 |
| Intensified Treatment | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Race/Ethnicity: Non-White/Hispanic | 1.0 logMAR lines | Standard Deviation 2.2 |
| Intensified Treatment | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Age at randomization: 3 to <4 years | 1.3 logMAR lines | Standard Deviation 1.3 |
| Intensified Treatment | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Age at randomization: 4 to <5 years | 0.7 logMAR lines | Standard Deviation 2.4 |
| Intensified Treatment | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Age at randomization: 5 to <6 years | 1.2 logMAR lines | Standard Deviation 1.4 |
| Intensified Treatment | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Age at randomization: 6 to <7 years | 2.4 logMAR lines | Standard Deviation 2 |
| Intensified Treatment | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Age at randomization: 7 years or older | 0.6 logMAR lines | Standard Deviation 1.7 |
| Intensified Treatment | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Amblyopic-eye VA at randomization: 20/80 or worse | 1.0 logMAR lines | Standard Deviation 2.4 |
| Intensified Treatment | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Amblyopic-eye VA at randomization: 20/63 | 1.5 logMAR lines | Standard Deviation 1.7 |
| Intensified Treatment | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Amblyopic-eye VA at randomization: 20/50 | 1.3 logMAR lines | Standard Deviation 1.7 |
| Intensified Treatment | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Amblyopic-eye VA at randomization: 20/40 or better | 0.7 logMAR lines | Standard Deviation 1 |
| Intensified Treatment | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Cause of amblyopia: Anisometropia | 1.0 logMAR lines | Standard Deviation 1.9 |
| Intensified Treatment | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Cause of amblyopia: Combined mechanism | 0.6 logMAR lines | Standard Deviation 1.6 |
| Intensified Treatment | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Atropine duration prior to randomization:12-<15wks | 1.2 logMAR lines | Standard Deviation 1.8 |
| Intensified Treatment | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Atropine duration prior to randomization:15-<21wks | 1.7 logMAR lines | Standard Deviation 2.2 |
| Intensified Treatment | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Atropine duration prior to randomization:21-<27wks | 1.2 logMAR lines | Standard Deviation 1.5 |
| Intensified Treatment | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Atropine duration prior to randomization:27-84 wks | 0.5 logMAR lines | Standard Deviation 1.6 |
| Intensified Treatment | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Fellow-eye SE RE at enrollment: <+3.00 Diopters(D) | 1.0 logMAR lines | Standard Deviation 2.7 |
| Intensified Treatment | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Fellow-eye SE RE at enrollment: +3.00 to <+4.50 D | 1.0 logMAR lines | Standard Deviation 1.2 |
| Intensified Treatment | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Fellow-eye SE RE at enrollment: +4.50 to +6.00 D | 1.3 logMAR lines | Standard Deviation 2.6 |
| Intensified Treatment | Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics | Cause of amblyopia: Strabismus | 1.7 logMAR lines | Standard Deviation 1.8 |
Secondary
Treatment Group Comparison of the Proportion of Participants Who Achieved 20/25 or Better Visual Acuity at 10 Weeks Since Randomization
The proportion of participants who achieved 20/25 or better visual acuity 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 was 20/25 or better since 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.
Time frame: 10 weeks after randomization
Population: The analysis includes data from participants who completed a 10-week exam.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control | Treatment Group Comparison of the Proportion of Participants Who Achieved 20/25 or Better Visual Acuity at 10 Weeks Since Randomization | 4 participants |
| Intensified Treatment | Treatment Group Comparison of the Proportion of Participants Who Achieved 20/25 or Better Visual Acuity at 10 Weeks Since Randomization | 6 participants |
Secondary
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.
Time frame: 10 weeks after randomization
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control | Treatment Group Comparison of the Proportion of Participants Who Have Improved by 2 or More logMAR Visual Acuity Lines at 10 Weeks Since Randomization | 8 participants |
| Intensified Treatment | Treatment Group Comparison of the Proportion of Participants Who Have Improved by 2 or More logMAR Visual Acuity Lines at 10 Weeks Since Randomization | 9 participants |
p-value: 0.3395% CI: [-10, 30]Binomial regression
Secondary
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 Outcome Visit
Time frame: 10 weeks after randomization or later (until no further VA improvement, up to maximum of 84 weeks for one subject)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control | 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 Outcome Visit | 11 participants |
| Intensified Treatment | 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 Outcome Visit | 20 participants |