Amblyopia
Conditions
Keywords
Amblyopia
Brief summary
The purpose of the study is to compare the effectiveness of 1 hour/day of binocular game play 7 days per week with 2 hours/day patching 7 days per week in children 5 to \<17
Detailed description
The purpose of the study is to 1) compare the effectiveness of 1 hour/day of binocular game play 7 days per week (minimum of 4 days per week) with 2 hours/day patching 7 days per week, in children 5 to \<13 years of age (younger cohort), as a non-inferiority study; and 2) to compare the effectiveness of 1 hour/day of binocular game play 7 days per week (minimum of 4 days per week) with 2 hours/day patching 7 days per week, in children 13 to \<17 years of age (older cohort), as a superiority study.
Interventions
DEVICEiPad®
Binocular therapy on iPad®
OTHERPatching 2 hours per day, 7 days per week
Sponsors
Pediatric Eye Disease Investigator Group
National Eye Institute (NEI)
Jaeb Center for Health Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
5 Years to 16 Years
Healthy volunteers
No
Inclusion criteria
1. Age 5 to \<17 years 2. Amblyopia associated with strabismus, anisometropia, or both (previously treated or untreated) 1. Criteria for strabismus: At least one of the following must be met: * Presence of a heterotropia on examination at distance or near fixation (with or without spectacles) * Documented history of strabismus which is no longer present (which in the judgment of the investigator could have caused amblyopia) 2. Criteria for anisometropia: At least one of the following criteria must be met: * ≥0.50 diopter (D) difference between eyes in spherical equivalent * ≥1.50 D difference between eyes in astigmatism in any meridian 3. Criteria for combined-mechanism amblyopia: Both of the following criteria must be met: * Criteria for strabismus are met (see above) * ≥1.00 D difference between eyes in spherical equivalent OR ≥1.50 D difference between eyes in astigmatism in any meridian * Note: the spherical equivalent requirement differs from that in the definition for refractive/anisometropic amblyopia 3. No amblyopia treatment in the past 2 weeks (patching, atropine, Bangerter, vision therapy) 4. Refractive correction (spectacles or contact lenses, if applicable) must meet the following criteria at enrollment and be based on a cycloplegic refraction that is not more than 7 months old. 1. Requirements for Correction of Refractive Error: 1. For subjects meeting criteria for strabismic (only) amblyopia (see 2.2.1 #2 above): • Hypermetropia, if corrected, must not be under-corrected by more than +1.50 D spherical equivalent, and the reduction in plus sphere must be symmetric in the two eyes. 2. For subjects meeting criteria for anisometropic or combined-mechanism amblyopia (see 2.2.1 #2 above): * Spherical equivalent must be within 0.50 D of fully correcting the anisometropia * Hypermetropia must not be under-corrected by more than +1.50 D spherical equivalent, and reduction in plus must be symmetric in the two eyes * Cylinder power in both eyes must be within 0.50 D of fully correcting the astigmatism * Cylinder axis for both eyes must be within 6 degrees of the axis of the cycloplegic refraction when cylinder power is ≥1.00 D 2. Refractive corrections meeting the above criteria must be worn for either: * 16 weeks or more or * Until visual acuity in amblyopic eye is stable (defined as 2 consecutive visual acuity measurements by the same testing method at least 4 weeks apart with \<1 line change (\<5 letters if E-ETDRS)) 3. Monocular or binocular contact lens wear is allowed provided the contact lenses meet the above refractive requirements at the corneal plane. The same form of correction must be worn throughout the entire study during study procedures (i.e., no changing between contacts and spectacles while patching or while game-playing or study testing). Safety glasses are not required for subjects wearing contact lenses, but investigators are encouraged to suggest safety glasses be worn over contact lenses. 5. Visual acuity, measured in each eye without cycloplegia in current refractive correction (if applicable) within 7 days prior to randomization using the Amblyopia Treatment Study single-surround HOTV (ATS-HOTV) visual acuity protocol for children \< 7 years and the Electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) visual acuity protocol for children ≥ 7 years on a study-approved device displaying single surrounded optotypes, as follows: 1. Visual acuity in the amblyopic eye 20/40 to 20/200 inclusive (33 to 72 letters if E-ETDRS) 2. Visual acuity in the fellow eye 20/25 or better (≥ 78 letters if E-ETDRS) 3. Interocular difference ≥ 3 logMAR lines (≥ 15 letters if E-ETDRS) (i.e., amblyopic-eye acuity at least 3 logMAR lines worse than fellow-eye acuity) 6. Heterotropia or heterophoria with a total near deviation of ≤ 10∆ (measured by PACT). 7. Ability to align the nonius cross on the binocular game system (angles of ocular deviation \>10∆ would require the nonius cross to be adjusted to such an extent that playing of the game would be compromised). 8. Subject is able to play Hess Falling Blocks game on the study iPad® (on easy setting) under binocular conditions (with red-green glasses), as demonstrated by scoring at least 1 line in the office. 9. Investigator is willing to prescribe computer game play or patching per protocol. 10. Parent understands the protocol and is willing to accept randomization. 11. Parent has phone (or access to phone) and is willing to be contacted by Jaeb Center staff. 12. Relocation outside of area of an active Pediatric Eye Disease Investigator Group (PEDIG) site for this study within the next 16 weeks is not anticipated.
Exclusion criteria
A subject is excluded for any of the following reasons: 1. Prism in the refractive correction at time of enrollment (eligible only if prism is discontinued 2 weeks prior to enrollment). 2. Myopia greater than -6.00 D spherical equivalent in either eye. 3. Previous intraocular or refractive surgery. 4. Any treatment for amblyopia (patching, atropine, Bangerter filter, or vision therapy) during the past 2 weeks. Previous amblyopia therapy is allowed regardless of type, but must be discontinued at least 2 weeks immediately prior to enrollment. 5. Ocular co-morbidity that may reduce visual acuity determined by an ocular examination performed within the past 7 months (Note: nystagmus per se does not exclude the subject if the above visual acuity criteria are met). 6. No Down syndrome or cerebral palsy 7. No severe developmental delay that would interfere with treatment or evaluation (in the opinion of the investigator). Subjects with mild speech delay or reading and/or learning disabilities are not excluded. 8. Heterotropia or heterophoria with a total ocular deviation \>10∆ (phoria plus tropia \>10∆) at near (measured by PACT).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Distance Visual Acuity From Baseline in the Younger Cohort (5 to <13 Years) | Baseline and 16 weeks | Monocular distance visual acuity (VA) in current refractive correction (if required) in each eye by a certified examiner using the electronic Amblyopia Treatment Study single-surround HOTV (ATS-HOTV) visual acuity protocol for children \<7 years and the Electronic Early Treatment Diabetic Retinoscopy Study (E-ETDRS) visual acuity protocol for children ≥ 7 years on a study-certified acuity tester displaying single surrounded optotypes. For the younger cohort, the level of visual acuity is analyzed in the log of the Minimum Angle of Resolution (logMAR) scale (approximate range: -0.2 to 1.7) such that higher scores indicate poorer VA. Change in VA is computed as logMAR lines (positive values indicate improvement), defined as the difference between the enrollment and 16-week acuities (logMAR) multiplied by 10. |
| Distribution of Amblyopic-eye Visual Acuity | At 16 weeks | Monocular distance visual acuity (VA) in current refractive correction (if required) in each eye by a certified examiner using the electronic Amblyopia Treatment Study single-surround HOTV (ATS-HOTV) visual acuity protocol for children \<7 years and the Electronic Early Treatment Diabetic Retinoscopy Study (E-ETDRS) visual acuity protocol for children ≥ 7 years on a study-certified acuity tester displaying single surrounded optotypes. Younger cohort: The level of VA is analyzed in the log of the Minimum Angle of Resolution (logMAR) scale (previously defined) and change in VA from baseline as logMAR lines (previously defined). Older cohort: The level of VA is measured as letter scores (previously defined) and VA change from baseline is measured in letters (previously defined). |
| Distribution of Change in Amblyopic-eye Visual Acuity | Baseline and 16 weeks | Monocular distance visual acuity (VA) in current refractive correction (if required) in each eye by a certified examiner using the electronic Amblyopia Treatment Study single-surround HOTV (ATS-HOTV) visual acuity protocol for children \<7 years and the Electronic Early Treatment Diabetic Retinoscopy Study (E-ETDRS) visual acuity protocol for children ≥ 7 years on a study-certified acuity tester displaying single surrounded optotypes. Younger cohort: The level of VA is analyzed in the log of the Minimum Angle of Resolution (logMAR) scale (previously defined) and change in VA from baseline as logMAR lines (previously defined). Older cohort: The level of VA is measured as letter scores (previously defined) and VA change from baseline is measured in letters (previously defined). |
| Mean Amblyopic-eye Visual Acuity in the Older Cohort (13 to <17 Years) | 16 weeks | Monocular distance visual acuity (VA) in current refractive correction (if required) in each eye by a certified examiner using the Electronic Early Treatment Diabetic Retinoscopy Study (E-ETDRS) visual acuity protocol for children ≥ 7 years on a study-certified acuity tester displaying single surrounded optotypes. For the analyses in the older cohort, the level of VA is measured as letter scores (approximate range: 0 to 97 letters, lower scores indicate poorer VA) and change in VA from baseline is measured in letters (positive values indicate improvement), defined as the difference in letter scores between enrollment and follow-up. |
| Mean Change in Amblyopic-eye Visual Acuity in the Older Cohort (13 to <17 Years) | Baseline and 16 weeks | Monocular distance visual acuity (VA) in current refractive correction (if required) in each eye by a certified examiner using the Electronic Early Treatment Diabetic Retinoscopy Study (E-ETDRS) visual acuity protocol for children ≥ 7 years on a study-certified acuity tester displaying single surrounded optotypes. For the analyses in the older cohort, the level of VA is measured as letter scores (approximate range: 0 to 97 letters, lower scores indicate poorer VA) and change in VA from baseline is measured in letters (positive values indicate improvement), defined as the difference in letter scores between enrollment and follow-up. |
| Mean Amblyopic Eye Visual Acuity (Younger Cohort) | 16 Weeks from baseline | Monocular distance visual acuity (VA) in current refractive correction (if required) in each eye by a certified examiner using the electronic Amblyopia Treatment Study single-surround HOTV (ATS-HOTV) visual acuity protocol for children \<7 years and the Electronic Early Treatment Diabetic Retinoscopy Study (E-ETDRS) visual acuity protocol for children ≥ 7 years on a study-certified acuity tester displaying single surrounded optotypes. For the younger cohort, the level of visual acuity is analyzed in the log of the Minimum Angle of Resolution (logMAR) scale (approximate range: -0.2 to 1.7) such that higher scores indicate poorer VA. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Baseline and 16 weeks | Monocular distance visual acuity (VA) in current refractive correction (if required) in each eye by a certified examiner using the Electronic Early Treatment Diabetic Retinoscopy Study (E-ETDRS) visual acuity protocol for children ≥ 7 years on a study-certified acuity tester displaying single surrounded optotypes. For the analyses in the older cohort, the level of VA is measured as letter scores (previously defined) and change in VA from baseline is measured in letters (positive values indicate improvement), defined as the difference in letter scores between enrollment and follow-up. Subgroup factors of interest were pre-specified except for baseline stereoacuity (nil, better than nil). |
| Number of Participants With Resolution of Amblyopia | 16-week visit | Monocular distance visual acuity (VA) in current refractive correction (if required) in each eye by a certified examiner using the electronic Amblyopia Treatment Study single-surround HOTV (ATS-HOTV) visual acuity protocol for children \<7 years and the Electronic Early Treatment Diabetic Retinoscopy Study (E-ETDRS) visual acuity protocol for children ≥ 7 years on a study-certified acuity tester displaying single surrounded optotypes. The level of VA is analyzed in the log of the Minimum Angle of Resolution (logMAR) scale (previously defined) for the younger cohort and as letter scores (previously defined) for the older cohort. Resolution of amblyopia was defined as having an amblyopic-eye VA of 20/25 or better (≥ 78 letters if E-ETDRS) and within 1 logMAR line (5 letters if E-ETDRS) of the fellow eye VA. |
| Time Course of Visual Acuity Improvement | Baseline, 4 weeks, 8 weeks, 12 weeks and 16 weeks | Monocular distance visual acuity (VA) in current refractive correction (if required) in each eye by a certified examiner using the electronic Amblyopia Treatment Study single-surround HOTV (ATS-HOTV) visual acuity protocol for children \<7 years and the Electronic Early Treatment Diabetic Retinoscopy Study (E-ETDRS) visual acuity protocol for children ≥ 7 years on a study-certified acuity tester displaying single surrounded optotypes. For the younger cohort, the level of VA is analyzed in the log of the Minimum Angle of Resolution (logMAR) scale (approximate range: -0.2 to 1.7, higher values indicate poorer VA) and change in VA from baseline as logMAR lines (positive values indicate improvement), defined as the difference between the enrollment and follow-up acuities (logMAR) multiplied by 10. |
| Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Baseline and 16 weeks | Monocular distance visual acuity (VA) in current refractive correction (if required) in each eye by a certified examiner using the electronic Amblyopia Treatment Study single-surround HOTV (ATS-HOTV) visual acuity protocol for children \<7 years and the Electronic Early Treatment Diabetic Retinoscopy Study (E-ETDRS) visual acuity protocol for children ≥ 7 years on a study-certified acuity tester displaying single surrounded optotypes. For the younger cohort, the level of VA is analyzed in the log of the Minimum Angle of Resolution (logMAR) scale (previously defined) and change in VA from baseline as logMAR lines (previously defined, positive values indicate improvement), For both descriptive and formal subgroup analyses, all subgroup factors were pre-specified except for baseline stereoacuity (nil, better than nil). We performed post hoc descriptive analyses to explore treatment effect by baseline age (5 to \<7 yrs, 7 to \<13 yrs) and prior amblyopia treatment (yes/no). |
| Distribution of Stereoacuity Scores | 16 weeks | Stereoacuity was tested at near in current refractive correction. Stereoacuity scores (measure as seconds of arc) were calculated based on the Randot Butterfly (scores: 2000, Nil) and Randot Preschool stereoacuity (scores: 800, 400, 200, 100, 60 and 40) test methods. Lower scores indicate better stereoacuity. Results of the Randot Butterfly test were analyzed as 2000 seconds of arc (if correct response). Nil was assigned a score of 4000 seconds of arc and was defined as (1) an incorrect response on the butterfly in absence of a correct response on the 800 seconds of arc level of the Randot Preschool stereoacuity test or (2) an incorrect response on the 800 seconds of arc level if the butterfly was not attempted. |
| Median Stereoacuity Score (Seconds of Arc) | 16 weeks | Stereoacuity was tested at near in current refractive correction. Stereoacuity scores (measure as seconds of arc) were calculated based on the Randot Butterfly (scores: 2000, Nil) and Randot Preschool stereoacuity (scores: 800, 400, 200, 100, 60 and 40) test methods. Lower scores indicate better stereoacuity. Results of the Randot Butterfly test were analyzed as 2000 seconds of arc (if correct response). Nil was assigned a score of 4000 seconds of arc and was defined as (1) an incorrect response on the butterfly in absence of a correct response on the 800 seconds of arc level of the Randot Preschool stereoacuity test or (2) an incorrect response on the 800 seconds of arc level if the butterfly was not attempted. A logarithm base 10 transformation was used to convert stereoacuity scores (seconds of arc) to the log scale (conversion reference listed below), which was used to calculate descriptive statistics. Results of the descriptive analyses are reported as seconds of arc. |
| Distribution of Stereoacuity Scores (Participants With no History of Strabismus) | 16 weeks | Stereoacuity was tested at near in current refractive correction. Stereoacuity scores (measure as seconds of arc) were calculated based on the Randot Butterfly (scores: 2000, Nil) and Randot Preschool stereoacuity (scores: 800, 400, 200, 100, 60 and 40) test methods. Lower scores indicate better stereoacuity. Results of the Randot Butterfly test were analyzed as 2000 seconds of arc (if correct response). Nil was assigned a score of 4000 seconds of arc and was defined as (1) an incorrect response on the butterfly in absence of a correct response on the 800 seconds of arc level of the Randot Preschool stereoacuity test or (2) an incorrect response on the 800 seconds of arc level if the butterfly was not attempted. |
| Distribution of Change in Stereoacuity Scores From Baseline | Baseline and 16 weeks | Stereoacuity was tested at near in current refractive correction. Stereoacuity scores (seconds of arc) were calculated based on the Randot Butterfly (scores: 2000, Nil) and Randot Preschool stereoacuity (scores: 800, 400, 200, 100, 60 and 40) test methods. Lower scores indicate better stereoacuity. Results of the Randot Butterfly test were analyzed as 2000 (if correct response). Nil (4000 ) was defined as (1) an incorrect response on the butterfly in absence of a correct response on the 800 seconds of arc level of the Randot Preschool stereoacuity test or (2) an incorrect response on the 800 seconds of arc level if the butterfly was not attempted. For each visit, stereoacuity scores were ordered and assigned a rank score. Change in stereoacuity was calculated as the difference in ranked score between the enrollment and 16-week stereoacuity scores. |
| Distribution of Change in Stereoacuity Scores From Baseline (Participants With no History of Strabismus) | Baseline and 16 weeks | Stereoacuity was tested at near in current refractive correction. Stereoacuity scores (seconds of arc) were calculated based on the Randot Butterfly (scores: 2000, Nil) and Randot Preschool stereoacuity (scores: 800, 400, 200, 100, 60 and 40) test methods. Lower scores indicate better stereoacuity. Results of the Randot Butterfly test were analyzed as 2000 (if correct response). Nil (4000 ) was defined as (1) an incorrect response on the butterfly in absence of a correct response on the 800 seconds of arc level of the Randot Preschool stereoacuity test or (2) an incorrect response on the 800 seconds of arc level if the butterfly was not attempted. For each visit, stereoacuity scores were ordered and assigned a rank score. Change in stereoacuity was calculated as the difference in ranked score between the enrollment and 16-week stereoacuity scores. |
| Binocular Treatment Group: Adherence and Fellow-eye Contrast (iPad Log File Data) | Entire study period, up to 16 weeks | Participants assigned to binocular treatment were prescribed the binocular falling blocks game for 1 hour per day (allowing division into shorter sessions), 7 days per week for 16 weeks, with instructions to perform therapy a minimum of 4 days per week if unable to play for 7 days per week. The iPad device automatically recorded duration of game play, fellow-eye contrast, and performance. Adherence was calculated as the total hours of game play since baseline divided by the total prescribed hours (based on intended dose of 1 hour a day, 7 days per week) since baseline. The fellow-eye contrast was initially set to 20% (amblyopic eye always at 100%) and automatically increased or decreased by 10% increments (lowest level of 10%) or left unchanged from the last contrast level, based on the previous day's game play duration (at least 30 minutes required for contrast change) and performance (increased if scored 1000 points or more). Post hoc analysis: 4-week fellow-eye contrast. |
| Binocular Treatment Group: Median Adherence With Prescribed Game Play (iPad Log File Data) | Entire study period, up to 16 weeks | Participants assigned to binocular treatment were prescribed the binocular falling blocks game for 1 hour per day (allowing division into shorter sessions), 7 days per week for 16 weeks, with instructions to perform therapy a minimum of 4 days per week if unable to play for 7 days per week. The iPad device automatically recorded duration of game play, fellow-eye contrast, and performance. Adherence was calculated as the % of prescribed treatment actually completed: total hours of game play since baseline divided by the total prescribed hours (based on intended dose of 1 hour a day, 7 days per week) since baseline. |
| Number of Participants With Amblyopic-eye VA Improvement of 2 or More logMAR Lines (10 or More Letters if E-ETDRS) From Baseline | Baseline and 16-week visit | Monocular distance visual acuity (VA) in current refractive correction (if required) in each eye by a certified examiner using the electronic Amblyopia Treatment Study single-surround HOTV (ATS-HOTV) visual acuity protocol for children \<7 years and the Electronic Early Treatment Diabetic Retinoscopy Study (E-ETDRS) visual acuity protocol for children ≥ 7 years on a study-certified acuity tester displaying single surrounded optotypes. Younger cohort: The level of VA is analyzed in the log of the Minimum Angle of Resolution (logMAR) scale (previously defined) and change in VA from baseline as logMAR lines (previously defined). Older cohort: The level of VA is measured as letter scores (previously defined) and VA change from baseline is measured in letters (previously defined). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Participant-reported) | 16 weeks | A standardized questionnaire was administered to participants and their parents to assess the presence and frequency of any diplopia since the last study visit. |
| Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Follow-up (Parent-reported) | Across study follow-up visits, up to 16 weeks | A standardized questionnaire was administered to participants and their parents to assess the presence and frequency of any diplopia since the last study visit. |
| Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Study Follow-up (Participant-reported) | Across study follow-up visits, up to 16 weeks | A standardized questionnaire was administered to participants and their parents to assess the presence and frequency of any diplopia since the last study visit. |
| Safety Analysis: Development of a New Tropia and/or Worsening of a Pre-existing Deviation by 10 pd | 16 weeks | Ocular alignment will be assessed in current refractive correction by the cover/uncover test, simultaneous prism and cover test (SPCT), and prism and alternate cover test (PACT) in primary gaze at distance (3 meters) and at near (1/3 meter). Participants were classified according to whether they met the any of the following criteria at the 16-week visit: development of a new tropia (measured by SPCT) and/or worsening of a pre-existing deviation by 10 prism diopters (pd) measured by SPCT. |
| Safety Analysis: Change in Fellow-eye Visual Acuity From Baseline (Older Cohort) | 16-week visit | Monocular distance visual acuity (VA) in current refractive correction (if required) in each eye by a certified examiner using the Electronic Early Treatment Diabetic Retinoscopy Study (E-ETDRS) visual acuity protocol for children ≥ 7 years on a study-certified acuity tester displaying single surrounded optotypes. For the analyses in the older cohort, the level of VA is measured as letter scores (approximate range: 0 to 97 letters, lower scores indicate poorer VA) and change in VA from baseline is measured in letters (positive values indicate improvement), defined as the difference in letter scores between enrollment and follow-up. The change in fellow-eye visual acuity (letters) from baseline (positive values indicate improvement) was computed by treatment group, adjusting for baseline visual acuity. |
| Safety Analysis: Change in Fellow-eye Visual Acuity From Baseline (Younger Cohort) | 16-week visit | Monocular distance visual acuity (VA) in current refractive correction (if required) in each eye by a certified examiner using the electronic Amblyopia Treatment Study single-surround HOTV (ATS-HOTV) visual acuity protocol for children \<7 years and the Electronic Early Treatment Diabetic Retinoscopy Study (E-ETDRS) visual acuity protocol for children ≥ 7 years on a study-certified acuity tester displaying single surrounded optotypes. For the younger cohort, the level of visual acuity is analyzed in the log of the Minimum Angle of Resolution (logMAR) scale (approximate range: -0.2 to 1.7) such that higher scores indicate poorer VA. Change in VA is computed as logMAR lines (positive values indicate improvement), defined as the difference between the enrollment and 16-week acuities (logMAR) multiplied by 10. For this safety analysis, the change in fellow-eye visual acuity (logMAR lines) was computed by treatment group, adjusting for baseline visual acuity. |
| Safety Analysis: Distribution of the Change in Fellow-eye Visual Acuity From Baseline | 16-week visit | Monocular distance visual acuity (VA) in current refractive correction (if required) in each eye by a certified examiner using the electronic ATS-HOTV visual acuity protocol for children \<7 years and the E-ETDRS visual acuity protocol for children ≥ 7 years on a study-certified acuity tester displaying single surrounded optotypes. The change in visual acuity is analyzed as logMAR lines for the younger cohort and as letters for the older cohort. |
| Percentage of Participants Reporting >75% of Prescribed Treatment Completed (Subjective Measures of Adherence) | 16 Weeks from baseline | Participants who were randomly assigned to binocular treatment were prescribed 1 hour of game play per day, 7 days a week while those assigned to the patching group were prescribed 2 hours of daily patching, 7 days per week. Parents were asked to record the amount of time that the participant played the binocular game (binocular treatment group) or wore the patch (patching group) each day on a calendar. At each study visit, the investigator estimated the frequency and duration of treatment that the participant completed based on the parent-reported calendars and discussion with the participant and/or parent(s). For analysis, the percentage of prescribed treatment completed was calculated as the total number of reported hours of treatment completed since baseline divided by the total number of prescribed hours (refer to the intended treatment dose/frequency listed above) since baseline. |
| Participants Who Received Non-protocol, Alternative Treatment During the Study | Entire study period, up to 16 weeks | Participants who were randomly assigned to binocular treatment were prescribed 1 hour of game play per day, 7 days a week while those assigned to the patching group were prescribed 2 hours of daily patching, 7 days per week. The number of participants who received non-protocol, alternative treatment was tabulated by treatment group. |
| Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Parent-reported) | 16 weeks | A standardized questionnaire was administered to participants and their parents to assess the presence and frequency of any diplopia since the last study visit. |
Countries
United States
Participant flow
Recruitment details
Two separate sub-studies based on age at enrollment Younger Cohort defined as 5 to \<13 years of age Older Cohort defined as 13 to \<17 years of age
Participants by arm
| Arm | Count |
|---|---|
| Binocular Treatment Younger Cohort (5 to <13 Years) Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week)
iPad®: Binocular therapy on iPad® | 190 |
| Patching Treatment Younger Cohort (5 to <13 Years) Patching 2 hours per day, 7 days per week
Patching 2 hours per day, 7 days per week | 195 |
| Binocular Treatment Older Cohort (13 to <17 Years) Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week)
iPad®: Binocular therapy on iPad® | 40 |
| Patching Treatment Older Cohort (13 to <17 Years) Patching 2 hours per day, 7 days per week
Patching 2 hours per day, 7 days per week | 60 |
| Total | 485 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 7 | 7 | 1 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Patching Treatment Younger Cohort (5 to <13 Years) | Total | Binocular Treatment Younger Cohort (5 to <13 Years) | Patching Treatment Older Cohort (13 to <17 Years) | Binocular Treatment Older Cohort (13 to <17 Years) |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 195 Participants | 485 Participants | 190 Participants | 60 Participants | 40 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 8.6 years STANDARD_DEVIATION 2 | 9.7 years STANDARD_DEVIATION 2.9 | 8.4 years STANDARD_DEVIATION 1.8 | 14.3 years STANDARD_DEVIATION 1.1 | 14.3 years STANDARD_DEVIATION 1.1 |
| Age, Customized Age at enrollment, years : 13 to <17 | 0 Participants | 100 Participants | 0 Participants | 60 Participants | 40 Participants |
| Age, Customized Age at enrollment, years : 5 to <7 | 50 Participants | 93 Participants | 43 Participants | 0 Participants | 0 Participants |
| Age, Customized Age at enrollment, years : 7 to <9 | 62 Participants | 140 Participants | 78 Participants | 0 Participants | 0 Participants |
| Age, Customized Age at enrollment, years : 9 to <13 | 83 Participants | 152 Participants | 69 Participants | 0 Participants | 0 Participants |
| Amblyopia Cause Anisometropia | 92 Participants | 250 Participants | 107 Participants | 29 Participants | 22 Participants |
| Amblyopia Cause Strabismus | 44 Participants | 80 Participants | 22 Participants | 9 Participants | 5 Participants |
| Amblyopia Cause Strabismus/anisometropia combined | 59 Participants | 155 Participants | 61 Participants | 22 Participants | 13 Participants |
| Baseline Stereoacuity (Seconds of Arc) 100 | 23 Participants | 58 Participants | 23 Participants | 6 Participants | 6 Participants |
| Baseline Stereoacuity (Seconds of Arc) 200 | 18 Participants | 47 Participants | 23 Participants | 4 Participants | 2 Participants |
| Baseline Stereoacuity (Seconds of Arc) 2000 | 37 Participants | 75 Participants | 28 Participants | 7 Participants | 3 Participants |
| Baseline Stereoacuity (Seconds of Arc) 40 | 6 Participants | 10 Participants | 2 Participants | 2 Participants | 0 Participants |
| Baseline Stereoacuity (Seconds of Arc) 400 | 19 Participants | 50 Participants | 17 Participants | 7 Participants | 7 Participants |
| Baseline Stereoacuity (Seconds of Arc) 4000 | 57 Participants | 171 Participants | 69 Participants | 29 Participants | 16 Participants |
| Baseline Stereoacuity (Seconds of Arc) 60 | 9 Participants | 21 Participants | 10 Participants | 1 Participants | 1 Participants |
| Baseline Stereoacuity (Seconds of Arc) 800 | 26 Participants | 53 Participants | 18 Participants | 4 Participants | 5 Participants |
| Baseline Stereoacuity (Seconds of Arc) All participants | 800 Seconds of Arc | NA Seconds of Arc | 2000 Seconds of Arc | 2000 Seconds of Arc | 800 Seconds of Arc |
| Baseline Stereoacuity (Seconds of Arc) Participants with no history of strabismus | 400 Seconds of Arc | NA Seconds of Arc | 400 Seconds of Arc | 800 Seconds of Arc | 400 Seconds of Arc |
| Distance Amblyopic-Eye Visual Acuity 20/100 (48-52 Letters) | 12 Participants | 35 Participants | 16 Participants | 4 Participants | 3 Participants |
| Distance Amblyopic-Eye Visual Acuity 20/125 (43-47 Letters) | 4 Participants | 24 Participants | 8 Participants | 8 Participants | 4 Participants |
| Distance Amblyopic-Eye Visual Acuity 20/160 (38-42 Letters) | 7 Participants | 20 Participants | 6 Participants | 5 Participants | 2 Participants |
| Distance Amblyopic-Eye Visual Acuity 20/200 (33-37 Letters) | 4 Participants | 11 Participants | 5 Participants | 2 Participants | 0 Participants |
| Distance Amblyopic-Eye Visual Acuity 20/40 (68-72 Letters) | 46 Participants | 84 Participants | 27 Participants | 5 Participants | 6 Participants |
| Distance Amblyopic-Eye Visual Acuity 20/50 (63-67 Letters) | 52 Participants | 139 Participants | 61 Participants | 14 Participants | 12 Participants |
| Distance Amblyopic-Eye Visual Acuity 20/63 (58-62 Letters) | 46 Participants | 99 Participants | 37 Participants | 10 Participants | 6 Participants |
| Distance Amblyopic-Eye Visual Acuity 20/80 (53-57 Letters) | 24 Participants | 73 Participants | 30 Participants | 12 Participants | 7 Participants |
| Race/Ethnicity, Customized >1 Race | 5 Participants | 8 Participants | 2 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian, American Indian, Alaskan Native | 6 Participants | 16 Participants | 9 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Black/African American | 12 Participants | 29 Participants | 11 Participants | 4 Participants | 2 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 24 Participants | 76 Participants | 33 Participants | 11 Participants | 8 Participants |
| Race/Ethnicity, Customized Unknown/not reported | 3 Participants | 4 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 145 Participants | 352 Participants | 134 Participants | 43 Participants | 30 Participants |
| Sex: Female, Male Female | 89 Participants | 229 Participants | 98 Participants | 26 Participants | 16 Participants |
| Sex: Female, Male Male | 106 Participants | 256 Participants | 92 Participants | 34 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 190 | 0 / 195 | 0 / 40 | 0 / 60 |
| serious Total, serious adverse events | 0 / 190 | 0 / 195 | 0 / 40 | 0 / 60 |
Outcome results
Primary
Change in Distance Visual Acuity From Baseline in the Younger Cohort (5 to <13 Years)
Monocular distance visual acuity (VA) in current refractive correction (if required) in each eye by a certified examiner using the electronic Amblyopia Treatment Study single-surround HOTV (ATS-HOTV) visual acuity protocol for children \<7 years and the Electronic Early Treatment Diabetic Retinoscopy Study (E-ETDRS) visual acuity protocol for children ≥ 7 years on a study-certified acuity tester displaying single surrounded optotypes. For the younger cohort, the level of visual acuity is analyzed in the log of the Minimum Angle of Resolution (logMAR) scale (approximate range: -0.2 to 1.7) such that higher scores indicate poorer VA. Change in VA is computed as logMAR lines (positive values indicate improvement), defined as the difference between the enrollment and 16-week acuities (logMAR) multiplied by 10.
Time frame: Baseline and 16 weeks
Population: Visual acuity analyses included only data from participants who completed the 16-week visit within the predefined analysis window (14 to \<20 weeks after randomization), analysis is adjusted for baseline covariates of age and visual acuity.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Binocular Treatment Younger | Change in Distance Visual Acuity From Baseline in the Younger Cohort (5 to <13 Years) | Adjusted for baseline VA and age | 1.05 LogMAR lines |
| Binocular Treatment Younger | Change in Distance Visual Acuity From Baseline in the Younger Cohort (5 to <13 Years) | Unadjusted | 1.08 LogMAR lines |
| Patching Treatment Younger | Change in Distance Visual Acuity From Baseline in the Younger Cohort (5 to <13 Years) | Adjusted for baseline VA and age | 1.35 LogMAR lines |
| Patching Treatment Younger | Change in Distance Visual Acuity From Baseline in the Younger Cohort (5 to <13 Years) | Unadjusted | 1.32 LogMAR lines |
Comparison: The primary outcome measure was change in amblyopic-eye VA from baseline to 16 weeks (14 to \<20 week window). The upper limit of a 1-sided 95% confidence interval (CI) was computed on the treatment group difference, using an analysis of covariance (ANCOVA) model, adjusted for baseline age and VA, including only participants completing the 16-week outcome in a modified intent-to-treat analysis. There was no imputation for missing data.
Comparison: The primary analysis was repeated for the treatment group comparison of change in amblyopic-eye VA from baseline to 16 weeks, adjusting for baseline covariates of age and visual acuity. For this sensitivity analysis, the primary analysis repeated but excluded data from participants (n=35) who completed the 16-week visit outside of the pre-defined protocol window (16 +/- 1 week).
Comparison: The primary analysis was repeated for the treatment group comparison of change in amblyopic-eye from baseline to 16 weeks, adjusting for baseline covariates of age and visual acuity. For this sensitivity analysis, multiple imputation was used to impute 16-week visual acuity scores for participants who missed the exam (n=15) or completed the 16-week exam outside of the pre-specified analysis window (n=7).
Comparison: The primary analysis was repeated for the treatment group comparison of change in amblyopic-eye VA from baseline to 16 weeks, adjusting for baseline covariates for age and visual acuity. For this post hoc sensitivity analysis, all participants with 16-week exams were included in the analysis regardless of whether or not the exam was completed within the pre-specified analysis window (14 to \<20 weeks after randomization).
Comparison: The primary analysis was repeated for the treatment group comparison of change in amblyopic-eye VA from baseline to 16-weeks, adjusting for baseline covariates of age and visual acuity. For this sensitivity analysis, we excluded 16-week outcomes from enrolled participants who were subsequently found to be ineligible for the study (n=7).
Comparison: The primary analysis was repeated for the treatment group comparison of change in amblyopic-eye visual acuity from baseline to 16 week, adjusting for baseline covariates of age and visual acuity. For this sensitivity analysis, we excluded 16-week outcomes from participants who received alternative treatment for at least 1 week during study follow-up (n=4).
Comparison: Analysis of covariance included baseline age and visual acuity as adjustment covariates. The primary outcome measure was change in amblyopic-eye VA from baseline to 16 weeks (14 to \<20 week window). For this post hoc analysis, a 2-sided 95% confidence interval (CI) was computed on the treatment group difference, using an analysis of covariance (ANCOVA) model, adjusted for baseline age and VA, including only participants completing the 16-week outcome in a modified intent-to-treat analysis.95% CI: [0.04, 0.58]
Primary
Distribution of Amblyopic-eye Visual Acuity
Monocular distance visual acuity (VA) in current refractive correction (if required) in each eye by a certified examiner using the electronic Amblyopia Treatment Study single-surround HOTV (ATS-HOTV) visual acuity protocol for children \<7 years and the Electronic Early Treatment Diabetic Retinoscopy Study (E-ETDRS) visual acuity protocol for children ≥ 7 years on a study-certified acuity tester displaying single surrounded optotypes. Younger cohort: The level of VA is analyzed in the log of the Minimum Angle of Resolution (logMAR) scale (previously defined) and change in VA from baseline as logMAR lines (previously defined). Older cohort: The level of VA is measured as letter scores (previously defined) and VA change from baseline is measured in letters (previously defined).
Time frame: At 16 weeks
Population: Participants that completed 16-week visit within pre-specified analysis window (148 to 196 days after randomization)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Binocular Treatment Younger | Distribution of Amblyopic-eye Visual Acuity | 20/200 (33-37 letters) | 2 Participants |
| Binocular Treatment Younger | Distribution of Amblyopic-eye Visual Acuity | 20/160 (38-42 letters) | 2 Participants |
| Binocular Treatment Younger | Distribution of Amblyopic-eye Visual Acuity | 20/125 (43-47 letters) | 10 Participants |
| Binocular Treatment Younger | Distribution of Amblyopic-eye Visual Acuity | 20/100 (48-52 letters) | 12 Participants |
| Binocular Treatment Younger | Distribution of Amblyopic-eye Visual Acuity | 20/80 (53-57 letters) | 18 Participants |
| Binocular Treatment Younger | Distribution of Amblyopic-eye Visual Acuity | 20/63 (58-62 letters) | 25 Participants |
| Binocular Treatment Younger | Distribution of Amblyopic-eye Visual Acuity | 20/50 (63-67 letters) | 30 Participants |
| Binocular Treatment Younger | Distribution of Amblyopic-eye Visual Acuity | 20/40 (68-72 letters) | 32 Participants |
| Binocular Treatment Younger | Distribution of Amblyopic-eye Visual Acuity | 20/32 (73-77 letters) | 33 Participants |
| Binocular Treatment Younger | Distribution of Amblyopic-eye Visual Acuity | 20/25 (78-82 letters) | 8 Participants |
| Binocular Treatment Younger | Distribution of Amblyopic-eye Visual Acuity | 20/20 (83-87 letters) | 3 Participants |
| Binocular Treatment Younger | Distribution of Amblyopic-eye Visual Acuity | 20/16 (88-92 letters) | 2 Participants |
| Patching Treatment Younger | Distribution of Amblyopic-eye Visual Acuity | 20/63 (58-62 letters) | 22 Participants |
| Patching Treatment Younger | Distribution of Amblyopic-eye Visual Acuity | 20/50 (63-67 letters) | 38 Participants |
| Patching Treatment Younger | Distribution of Amblyopic-eye Visual Acuity | 20/25 (78-82 letters) | 22 Participants |
| Patching Treatment Younger | Distribution of Amblyopic-eye Visual Acuity | 20/100 (48-52 letters) | 7 Participants |
| Patching Treatment Younger | Distribution of Amblyopic-eye Visual Acuity | 20/125 (43-47 letters) | 2 Participants |
| Patching Treatment Younger | Distribution of Amblyopic-eye Visual Acuity | 20/40 (68-72 letters) | 37 Participants |
| Patching Treatment Younger | Distribution of Amblyopic-eye Visual Acuity | 20/160 (38-42 letters) | 3 Participants |
| Patching Treatment Younger | Distribution of Amblyopic-eye Visual Acuity | 20/20 (83-87 letters) | 10 Participants |
| Patching Treatment Younger | Distribution of Amblyopic-eye Visual Acuity | 20/80 (53-57 letters) | 17 Participants |
| Patching Treatment Younger | Distribution of Amblyopic-eye Visual Acuity | 20/32 (73-77 letters) | 27 Participants |
| Patching Treatment Younger | Distribution of Amblyopic-eye Visual Acuity | 20/200 (33-37 letters) | 1 Participants |
| Patching Treatment Younger | Distribution of Amblyopic-eye Visual Acuity | 20/16 (88-92 letters) | 0 Participants |
| Binocular Treatment Older Cohort | Distribution of Amblyopic-eye Visual Acuity | 20/80 (53-57 letters) | 5 Participants |
| Binocular Treatment Older Cohort | Distribution of Amblyopic-eye Visual Acuity | 20/200 (33-37 letters) | 1 Participants |
| Binocular Treatment Older Cohort | Distribution of Amblyopic-eye Visual Acuity | 20/160 (38-42 letters) | 0 Participants |
| Binocular Treatment Older Cohort | Distribution of Amblyopic-eye Visual Acuity | 20/63 (58-62 letters) | 5 Participants |
| Binocular Treatment Older Cohort | Distribution of Amblyopic-eye Visual Acuity | 20/25 (78-82 letters) | 0 Participants |
| Binocular Treatment Older Cohort | Distribution of Amblyopic-eye Visual Acuity | 20/125 (43-47 letters) | 2 Participants |
| Binocular Treatment Older Cohort | Distribution of Amblyopic-eye Visual Acuity | 20/100 (48-52 letters) | 4 Participants |
| Binocular Treatment Older Cohort | Distribution of Amblyopic-eye Visual Acuity | 20/20 (83-87 letters) | 1 Participants |
| Binocular Treatment Older Cohort | Distribution of Amblyopic-eye Visual Acuity | 20/50 (63-67 letters) | 11 Participants |
| Binocular Treatment Older Cohort | Distribution of Amblyopic-eye Visual Acuity | 20/16 (88-92 letters) | 0 Participants |
| Binocular Treatment Older Cohort | Distribution of Amblyopic-eye Visual Acuity | 20/40 (68-72 letters) | 6 Participants |
| Binocular Treatment Older Cohort | Distribution of Amblyopic-eye Visual Acuity | 20/32 (73-77 letters) | 4 Participants |
| Patching Treatment Older | Distribution of Amblyopic-eye Visual Acuity | 20/125 (43-47 letters) | 4 Participants |
| Patching Treatment Older | Distribution of Amblyopic-eye Visual Acuity | 20/80 (53-57 letters) | 8 Participants |
| Patching Treatment Older | Distribution of Amblyopic-eye Visual Acuity | 20/100 (48-52 letters) | 7 Participants |
| Patching Treatment Older | Distribution of Amblyopic-eye Visual Acuity | 20/63 (58-62 letters) | 4 Participants |
| Patching Treatment Older | Distribution of Amblyopic-eye Visual Acuity | 20/50 (63-67 letters) | 9 Participants |
| Patching Treatment Older | Distribution of Amblyopic-eye Visual Acuity | 20/20 (83-87 letters) | 1 Participants |
| Patching Treatment Older | Distribution of Amblyopic-eye Visual Acuity | 20/40 (68-72 letters) | 7 Participants |
| Patching Treatment Older | Distribution of Amblyopic-eye Visual Acuity | 20/16 (88-92 letters) | 0 Participants |
| Patching Treatment Older | Distribution of Amblyopic-eye Visual Acuity | 20/32 (73-77 letters) | 11 Participants |
| Patching Treatment Older | Distribution of Amblyopic-eye Visual Acuity | 20/200 (33-37 letters) | 1 Participants |
| Patching Treatment Older | Distribution of Amblyopic-eye Visual Acuity | 20/160 (38-42 letters) | 1 Participants |
| Patching Treatment Older | Distribution of Amblyopic-eye Visual Acuity | 20/25 (78-82 letters) | 3 Participants |
Primary
Distribution of Change in Amblyopic-eye Visual Acuity
Monocular distance visual acuity (VA) in current refractive correction (if required) in each eye by a certified examiner using the electronic Amblyopia Treatment Study single-surround HOTV (ATS-HOTV) visual acuity protocol for children \<7 years and the Electronic Early Treatment Diabetic Retinoscopy Study (E-ETDRS) visual acuity protocol for children ≥ 7 years on a study-certified acuity tester displaying single surrounded optotypes. Younger cohort: The level of VA is analyzed in the log of the Minimum Angle of Resolution (logMAR) scale (previously defined) and change in VA from baseline as logMAR lines (previously defined). Older cohort: The level of VA is measured as letter scores (previously defined) and VA change from baseline is measured in letters (previously defined).
Time frame: Baseline and 16 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Binocular Treatment Younger | Distribution of Change in Amblyopic-eye Visual Acuity | ≥ 3 LogMAR lines (≥ 15 letters) better | 19 Participants |
| Binocular Treatment Younger | Distribution of Change in Amblyopic-eye Visual Acuity | 2 LogMAR lines (10-14 letters) worse | 1 Participants |
| Binocular Treatment Younger | Distribution of Change in Amblyopic-eye Visual Acuity | 1 LogMAR line (5-9 letters) worse | 12 Participants |
| Binocular Treatment Younger | Distribution of Change in Amblyopic-eye Visual Acuity | 2 LogMAR lines (10-14 letters) better | 32 Participants |
| Binocular Treatment Younger | Distribution of Change in Amblyopic-eye Visual Acuity | ≥3 LogMAR lines (≥ 15 letters) worse | 2 Participants |
| Binocular Treatment Younger | Distribution of Change in Amblyopic-eye Visual Acuity | 1 LogMAR line (5-9 letters) better | 47 Participants |
| Binocular Treatment Younger | Distribution of Change in Amblyopic-eye Visual Acuity | 0 LogMAR line (within 4 letters) | 64 Participants |
| Patching Treatment Younger | Distribution of Change in Amblyopic-eye Visual Acuity | 2 LogMAR lines (10-14 letters) worse | 0 Participants |
| Patching Treatment Younger | Distribution of Change in Amblyopic-eye Visual Acuity | 0 LogMAR line (within 4 letters) | 69 Participants |
| Patching Treatment Younger | Distribution of Change in Amblyopic-eye Visual Acuity | 1 LogMAR line (5-9 letters) better | 46 Participants |
| Patching Treatment Younger | Distribution of Change in Amblyopic-eye Visual Acuity | 1 LogMAR line (5-9 letters) worse | 6 Participants |
| Patching Treatment Younger | Distribution of Change in Amblyopic-eye Visual Acuity | ≥3 LogMAR lines (≥ 15 letters) worse | 0 Participants |
| Patching Treatment Younger | Distribution of Change in Amblyopic-eye Visual Acuity | 2 LogMAR lines (10-14 letters) better | 36 Participants |
| Patching Treatment Younger | Distribution of Change in Amblyopic-eye Visual Acuity | ≥ 3 LogMAR lines (≥ 15 letters) better | 29 Participants |
| Binocular Treatment Older Cohort | Distribution of Change in Amblyopic-eye Visual Acuity | 0 LogMAR line (within 4 letters) | 22 Participants |
| Binocular Treatment Older Cohort | Distribution of Change in Amblyopic-eye Visual Acuity | ≥ 3 LogMAR lines (≥ 15 letters) better | 2 Participants |
| Binocular Treatment Older Cohort | Distribution of Change in Amblyopic-eye Visual Acuity | 2 LogMAR lines (10-14 letters) better | 4 Participants |
| Binocular Treatment Older Cohort | Distribution of Change in Amblyopic-eye Visual Acuity | 1 LogMAR line (5-9 letters) better | 9 Participants |
| Binocular Treatment Older Cohort | Distribution of Change in Amblyopic-eye Visual Acuity | 1 LogMAR line (5-9 letters) worse | 1 Participants |
| Binocular Treatment Older Cohort | Distribution of Change in Amblyopic-eye Visual Acuity | 2 LogMAR lines (10-14 letters) worse | 0 Participants |
| Binocular Treatment Older Cohort | Distribution of Change in Amblyopic-eye Visual Acuity | ≥3 LogMAR lines (≥ 15 letters) worse | 1 Participants |
| Patching Treatment Older | Distribution of Change in Amblyopic-eye Visual Acuity | 1 LogMAR line (5-9 letters) better | 19 Participants |
| Patching Treatment Older | Distribution of Change in Amblyopic-eye Visual Acuity | ≥3 LogMAR lines (≥ 15 letters) worse | 1 Participants |
| Patching Treatment Older | Distribution of Change in Amblyopic-eye Visual Acuity | 2 LogMAR lines (10-14 letters) worse | 0 Participants |
| Patching Treatment Older | Distribution of Change in Amblyopic-eye Visual Acuity | 2 LogMAR lines (10-14 letters) better | 10 Participants |
| Patching Treatment Older | Distribution of Change in Amblyopic-eye Visual Acuity | ≥ 3 LogMAR lines (≥ 15 letters) better | 7 Participants |
| Patching Treatment Older | Distribution of Change in Amblyopic-eye Visual Acuity | 1 LogMAR line (5-9 letters) worse | 1 Participants |
| Patching Treatment Older | Distribution of Change in Amblyopic-eye Visual Acuity | 0 LogMAR line (within 4 letters) | 18 Participants |
Primary
Mean Amblyopic-eye Visual Acuity in the Older Cohort (13 to <17 Years)
Monocular distance visual acuity (VA) in current refractive correction (if required) in each eye by a certified examiner using the Electronic Early Treatment Diabetic Retinoscopy Study (E-ETDRS) visual acuity protocol for children ≥ 7 years on a study-certified acuity tester displaying single surrounded optotypes. For the analyses in the older cohort, the level of VA is measured as letter scores (approximate range: 0 to 97 letters, lower scores indicate poorer VA) and change in VA from baseline is measured in letters (positive values indicate improvement), defined as the difference in letter scores between enrollment and follow-up.
Time frame: 16 weeks
Population: Participants that completed 16-week visit within pre-specified analysis window (148 to 196 days after randomization)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Binocular Treatment Younger | Mean Amblyopic-eye Visual Acuity in the Older Cohort (13 to <17 Years) | 62.0 letters | Standard Deviation 9.7 |
| Patching Treatment Younger | Mean Amblyopic-eye Visual Acuity in the Older Cohort (13 to <17 Years) | 62.5 letters | Standard Deviation 11.6 |
Primary
Mean Amblyopic Eye Visual Acuity (Younger Cohort)
Monocular distance visual acuity (VA) in current refractive correction (if required) in each eye by a certified examiner using the electronic Amblyopia Treatment Study single-surround HOTV (ATS-HOTV) visual acuity protocol for children \<7 years and the Electronic Early Treatment Diabetic Retinoscopy Study (E-ETDRS) visual acuity protocol for children ≥ 7 years on a study-certified acuity tester displaying single surrounded optotypes. For the younger cohort, the level of visual acuity is analyzed in the log of the Minimum Angle of Resolution (logMAR) scale (approximate range: -0.2 to 1.7) such that higher scores indicate poorer VA.
Time frame: 16 Weeks from baseline
Population: Visual acuity analyses included only data from participants who completed the 16-week visit within the predefined analysis window (14 to \<20 weeks after randomization).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Binocular Treatment Younger | Mean Amblyopic Eye Visual Acuity (Younger Cohort) | 0.41 LogMAR | Standard Deviation 0.21 |
| Patching Treatment Younger | Mean Amblyopic Eye Visual Acuity (Younger Cohort) | 0.35 LogMAR | Standard Deviation 0.2 |
Primary
Mean Change in Amblyopic-eye Visual Acuity in the Older Cohort (13 to <17 Years)
Monocular distance visual acuity (VA) in current refractive correction (if required) in each eye by a certified examiner using the Electronic Early Treatment Diabetic Retinoscopy Study (E-ETDRS) visual acuity protocol for children ≥ 7 years on a study-certified acuity tester displaying single surrounded optotypes. For the analyses in the older cohort, the level of VA is measured as letter scores (approximate range: 0 to 97 letters, lower scores indicate poorer VA) and change in VA from baseline is measured in letters (positive values indicate improvement), defined as the difference in letter scores between enrollment and follow-up.
Time frame: Baseline and 16 weeks
Population: Mean change in amblyopic-eye visual acuity from baseline to 16 weeks from participants who completed 16-week visit within pre-specified analysis window (148 to 196 days after randomization)
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Binocular Treatment Younger | Mean Change in Amblyopic-eye Visual Acuity in the Older Cohort (13 to <17 Years) | Unadjusted | 3.5 letters |
| Binocular Treatment Younger | Mean Change in Amblyopic-eye Visual Acuity in the Older Cohort (13 to <17 Years) | Adjusted for baseline visual acuity | 3.7 letters |
| Patching Treatment Younger | Mean Change in Amblyopic-eye Visual Acuity in the Older Cohort (13 to <17 Years) | Adjusted for baseline visual acuity | 6.3 letters |
| Patching Treatment Younger | Mean Change in Amblyopic-eye Visual Acuity in the Older Cohort (13 to <17 Years) | Unadjusted | 6.5 letters |
Comparison: A modified intent-to-treat analysis was performed using an ANCOVA model to compare the effectiveness of two treatments (2-sided hypothesis test), adjusting for baseline visual acuity. The primary outcome measure was change in amblyopic-eye VA from baseline to 16 weeks (14 to \<20 week window). A 2-sided 95% confidence interval (CI) was computed on the adjusted treatment group difference at 16 weeks. There was no imputation for missing data.p-value: 0.08295% CI: [-5.7, 0.3]ANCOVA
Comparison: A modified intent-to-treat analysis was performed using an ANCOVA model to compare the change in amblyopic-eye visual acuity from baseline to 16 weeks for two treatments (2-sided hypothesis test), adjusting for baseline visual acuity. For this sensitivity analyses, the primary analysis was repeated but excluded data from participants who completed the 16-week visit outside of the pre-specified 16 +/- 1 week protocol window (n=10 participants).95% CI: [-5.9, 0.5]
Comparison: A modified intent-to-treat analysis was performed using an ANCOVA model to compare the change in amblyopic-eye visual acuity from baseline to 16 weeks (14 to \<20 week window) for two treatments (2-sided hypothesis test), adjusting for baseline visual acuity. For this sensitivity analyses, the primary analysis was repeated but excluded data from participants later found to be ineligible for the study (n=2).95% CI: [-5.9, 0.3]
Comparison: The primary analysis was repeated for the treatment group comparison of change in amblyopic-eye from baseline to 16 weeks, adjusting for baseline visual acuity. For this sensitivity analysis, multiple imputation was used to impute 16-week visual acuity scores for participants who missed the exam (n=3) or completed the 16-week exam outside of the pre-specified analysis window (n=2).95% CI: [-5, 1.2]
Comparison: An ANCOVA model was fit to compare the change in amblyopic-eye visual acuity from baseline to 16 weeks (14 to \<20 week window) for two treatments (2-sided hypothesis test), adjusting for baseline visual acuity. For this post hoc sensitivity analyses, the primary analysis was repeated but included data from participants who completed the 16-week visit outside the analysis window (n=2, range:14 to 28 weeks post randomization).95% CI: [-5.5, 0.5]
Comparison: An ANCOVA model was fit to compare the change in amblyopic-eye visual acuity from baseline to 16 weeks (14 to \<20 week window) for two treatments (2-sided hypothesis test), adjusting for baseline visual acuity. For this sensitivity analyses, the primary analysis was repeated but included prior amblyopia treatment as an adjustment covariate (in addition to baseline visual acuity) in the model.95% CI: [-5.7, 0.4]
Secondary
Binocular Treatment Group: Adherence and Fellow-eye Contrast (iPad Log File Data)
Participants assigned to binocular treatment were prescribed the binocular falling blocks game for 1 hour per day (allowing division into shorter sessions), 7 days per week for 16 weeks, with instructions to perform therapy a minimum of 4 days per week if unable to play for 7 days per week. The iPad device automatically recorded duration of game play, fellow-eye contrast, and performance. Adherence was calculated as the total hours of game play since baseline divided by the total prescribed hours (based on intended dose of 1 hour a day, 7 days per week) since baseline. The fellow-eye contrast was initially set to 20% (amblyopic eye always at 100%) and automatically increased or decreased by 10% increments (lowest level of 10%) or left unchanged from the last contrast level, based on the previous day's game play duration (at least 30 minutes required for contrast change) and performance (increased if scored 1000 points or more). Post hoc analysis: 4-week fellow-eye contrast.
Time frame: Entire study period, up to 16 weeks
Population: The descriptive analysis included data from participants in the binocular treatment group who had log file data available.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Binocular Treatment Younger | Binocular Treatment Group: Adherence and Fellow-eye Contrast (iPad Log File Data) | Fellow-eye contrast of 100% (4 weeks) | 35 Participants |
| Binocular Treatment Younger | Binocular Treatment Group: Adherence and Fellow-eye Contrast (iPad Log File Data) | Fellow-eye contrast of 100% (16 weeks) | 86 Participants |
| Binocular Treatment Younger | Binocular Treatment Group: Adherence and Fellow-eye Contrast (iPad Log File Data) | Fellow-eye contrast of 20% or worse (16 weeks) | 31 Participants |
| Binocular Treatment Younger | Binocular Treatment Group: Adherence and Fellow-eye Contrast (iPad Log File Data) | Completed >75% prescribed game play | 39 Participants |
| Patching Treatment Younger | Binocular Treatment Group: Adherence and Fellow-eye Contrast (iPad Log File Data) | Fellow-eye contrast of 100% (4 weeks) | 6 Participants |
| Patching Treatment Younger | Binocular Treatment Group: Adherence and Fellow-eye Contrast (iPad Log File Data) | Completed >75% prescribed game play | 5 Participants |
| Patching Treatment Younger | Binocular Treatment Group: Adherence and Fellow-eye Contrast (iPad Log File Data) | Fellow-eye contrast of 20% or worse (16 weeks) | 3 Participants |
| Patching Treatment Younger | Binocular Treatment Group: Adherence and Fellow-eye Contrast (iPad Log File Data) | Fellow-eye contrast of 100% (16 weeks) | 23 Participants |
Secondary
Binocular Treatment Group: Median Adherence With Prescribed Game Play (iPad Log File Data)
Participants assigned to binocular treatment were prescribed the binocular falling blocks game for 1 hour per day (allowing division into shorter sessions), 7 days per week for 16 weeks, with instructions to perform therapy a minimum of 4 days per week if unable to play for 7 days per week. The iPad device automatically recorded duration of game play, fellow-eye contrast, and performance. Adherence was calculated as the % of prescribed treatment actually completed: total hours of game play since baseline divided by the total prescribed hours (based on intended dose of 1 hour a day, 7 days per week) since baseline.
Time frame: Entire study period, up to 16 weeks
Population: The descriptive analysis included data from participants in the binocular treatment group who had log file data available.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Binocular Treatment Younger | Binocular Treatment Group: Median Adherence With Prescribed Game Play (iPad Log File Data) | 46 % of prescribed treatment completed |
| Patching Treatment Younger | Binocular Treatment Group: Median Adherence With Prescribed Game Play (iPad Log File Data) | 21 % of prescribed treatment completed |
Secondary
Distribution of Change in Stereoacuity Scores From Baseline
Stereoacuity was tested at near in current refractive correction. Stereoacuity scores (seconds of arc) were calculated based on the Randot Butterfly (scores: 2000, Nil) and Randot Preschool stereoacuity (scores: 800, 400, 200, 100, 60 and 40) test methods. Lower scores indicate better stereoacuity. Results of the Randot Butterfly test were analyzed as 2000 (if correct response). Nil (4000 ) was defined as (1) an incorrect response on the butterfly in absence of a correct response on the 800 seconds of arc level of the Randot Preschool stereoacuity test or (2) an incorrect response on the 800 seconds of arc level if the butterfly was not attempted. For each visit, stereoacuity scores were ordered and assigned a rank score. Change in stereoacuity was calculated as the difference in ranked score between the enrollment and 16-week stereoacuity scores.
Time frame: Baseline and 16 weeks
Population: The analysis included all participants who completed stereoacuity testing at both baseline and the 16-week visit (regardless of whether or not the exam was completed within the pre-specified analysis window).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Binocular Treatment Younger | Distribution of Change in Stereoacuity Scores From Baseline | 2 or more levels worse | 19 Participants |
| Binocular Treatment Younger | Distribution of Change in Stereoacuity Scores From Baseline | 2 or more levels better | 32 Participants |
| Binocular Treatment Younger | Distribution of Change in Stereoacuity Scores From Baseline | Within 1 level | 130 Participants |
| Patching Treatment Younger | Distribution of Change in Stereoacuity Scores From Baseline | 2 or more levels worse | 24 Participants |
| Patching Treatment Younger | Distribution of Change in Stereoacuity Scores From Baseline | 2 or more levels better | 42 Participants |
| Patching Treatment Younger | Distribution of Change in Stereoacuity Scores From Baseline | Within 1 level | 122 Participants |
| Binocular Treatment Older Cohort | Distribution of Change in Stereoacuity Scores From Baseline | Within 1 level | 29 Participants |
| Binocular Treatment Older Cohort | Distribution of Change in Stereoacuity Scores From Baseline | 2 or more levels worse | 4 Participants |
| Binocular Treatment Older Cohort | Distribution of Change in Stereoacuity Scores From Baseline | 2 or more levels better | 6 Participants |
| Patching Treatment Older | Distribution of Change in Stereoacuity Scores From Baseline | 2 or more levels worse | 8 Participants |
| Patching Treatment Older | Distribution of Change in Stereoacuity Scores From Baseline | 2 or more levels better | 12 Participants |
| Patching Treatment Older | Distribution of Change in Stereoacuity Scores From Baseline | Within 1 level | 38 Participants |
Comparison: The Wilcoxon rank-sum test was used to compare the distribution of change in stereoacuity levels from baseline to 16 weeks by treatment group.p-value: 0.66Wilcoxon (Mann-Whitney)
Comparison: The Wilcoxon rank-sum test was used to compare the distribution of change in stereoacuity levels from baseline to 16 weeks by treatment group.p-value: 0.83Wilcoxon (Mann-Whitney)
Secondary
Distribution of Change in Stereoacuity Scores From Baseline (Participants With no History of Strabismus)
Stereoacuity was tested at near in current refractive correction. Stereoacuity scores (seconds of arc) were calculated based on the Randot Butterfly (scores: 2000, Nil) and Randot Preschool stereoacuity (scores: 800, 400, 200, 100, 60 and 40) test methods. Lower scores indicate better stereoacuity. Results of the Randot Butterfly test were analyzed as 2000 (if correct response). Nil (4000 ) was defined as (1) an incorrect response on the butterfly in absence of a correct response on the 800 seconds of arc level of the Randot Preschool stereoacuity test or (2) an incorrect response on the 800 seconds of arc level if the butterfly was not attempted. For each visit, stereoacuity scores were ordered and assigned a rank score. Change in stereoacuity was calculated as the difference in ranked score between the enrollment and 16-week stereoacuity scores.
Time frame: Baseline and 16 weeks
Population: The analysis included a subset of participants with no history of strabismus who completed stereoacuity testing at both baseline and the 16-week visit (regardless of whether or not the exam was completed within the pre-specified analysis window).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Binocular Treatment Younger | Distribution of Change in Stereoacuity Scores From Baseline (Participants With no History of Strabismus) | 2 or more levels worse | 12 Participants |
| Binocular Treatment Younger | Distribution of Change in Stereoacuity Scores From Baseline (Participants With no History of Strabismus) | 2 or more levels better | 25 Participants |
| Binocular Treatment Younger | Distribution of Change in Stereoacuity Scores From Baseline (Participants With no History of Strabismus) | Within 1 level | 67 Participants |
| Patching Treatment Younger | Distribution of Change in Stereoacuity Scores From Baseline (Participants With no History of Strabismus) | 2 or more levels worse | 14 Participants |
| Patching Treatment Younger | Distribution of Change in Stereoacuity Scores From Baseline (Participants With no History of Strabismus) | 2 or more levels better | 18 Participants |
| Patching Treatment Younger | Distribution of Change in Stereoacuity Scores From Baseline (Participants With no History of Strabismus) | Within 1 level | 58 Participants |
| Binocular Treatment Older Cohort | Distribution of Change in Stereoacuity Scores From Baseline (Participants With no History of Strabismus) | Within 1 level | 15 Participants |
| Binocular Treatment Older Cohort | Distribution of Change in Stereoacuity Scores From Baseline (Participants With no History of Strabismus) | 2 or more levels worse | 2 Participants |
| Binocular Treatment Older Cohort | Distribution of Change in Stereoacuity Scores From Baseline (Participants With no History of Strabismus) | 2 or more levels better | 4 Participants |
| Patching Treatment Older | Distribution of Change in Stereoacuity Scores From Baseline (Participants With no History of Strabismus) | 2 or more levels worse | 4 Participants |
| Patching Treatment Older | Distribution of Change in Stereoacuity Scores From Baseline (Participants With no History of Strabismus) | 2 or more levels better | 7 Participants |
| Patching Treatment Older | Distribution of Change in Stereoacuity Scores From Baseline (Participants With no History of Strabismus) | Within 1 level | 16 Participants |
Comparison: The Wilcoxon rank-sum test was used to compare the distribution of change in stereoacuity levels from baseline to 16 weeks by treatment group.p-value: 0.19Wilcoxon (Mann-Whitney)
Comparison: The Wilcoxon rank-sum test was used to compare the distribution of change in stereoacuity levels from baseline to 16 weeks by treatment group.p-value: 0.69Wilcoxon (Mann-Whitney)
Secondary
Distribution of Stereoacuity Scores
Stereoacuity was tested at near in current refractive correction. Stereoacuity scores (measure as seconds of arc) were calculated based on the Randot Butterfly (scores: 2000, Nil) and Randot Preschool stereoacuity (scores: 800, 400, 200, 100, 60 and 40) test methods. Lower scores indicate better stereoacuity. Results of the Randot Butterfly test were analyzed as 2000 seconds of arc (if correct response). Nil was assigned a score of 4000 seconds of arc and was defined as (1) an incorrect response on the butterfly in absence of a correct response on the 800 seconds of arc level of the Randot Preschool stereoacuity test or (2) an incorrect response on the 800 seconds of arc level if the butterfly was not attempted.
Time frame: 16 weeks
Population: The analysis included all participants who completed a 16-week exam regardless of whether or not the exam was completed within the pre-specified analysis window.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Binocular Treatment Younger | Distribution of Stereoacuity Scores | 100 seconds of arc | 17 Participants |
| Binocular Treatment Younger | Distribution of Stereoacuity Scores | 200 seconds of arc | 15 Participants |
| Binocular Treatment Younger | Distribution of Stereoacuity Scores | 40 seconds of arc | 12 Participants |
| Binocular Treatment Younger | Distribution of Stereoacuity Scores | 800 seconds of arc | 19 Participants |
| Binocular Treatment Younger | Distribution of Stereoacuity Scores | 60 seconds of arc | 10 Participants |
| Binocular Treatment Younger | Distribution of Stereoacuity Scores | 4000 seconds of arc | 62 Participants |
| Binocular Treatment Younger | Distribution of Stereoacuity Scores | 2000 seconds of arc | 32 Participants |
| Binocular Treatment Younger | Distribution of Stereoacuity Scores | 400 seconds of arc | 14 Participants |
| Binocular Treatment Younger | Distribution of Stereoacuity Scores | Missing/Not done | 1 Participants |
| Patching Treatment Younger | Distribution of Stereoacuity Scores | 400 seconds of arc | 17 Participants |
| Patching Treatment Younger | Distribution of Stereoacuity Scores | 100 seconds of arc | 19 Participants |
| Patching Treatment Younger | Distribution of Stereoacuity Scores | 4000 seconds of arc | 50 Participants |
| Patching Treatment Younger | Distribution of Stereoacuity Scores | Missing/Not done | 0 Participants |
| Patching Treatment Younger | Distribution of Stereoacuity Scores | 40 seconds of arc | 4 Participants |
| Patching Treatment Younger | Distribution of Stereoacuity Scores | 2000 seconds of arc | 32 Participants |
| Patching Treatment Younger | Distribution of Stereoacuity Scores | 200 seconds of arc | 27 Participants |
| Patching Treatment Younger | Distribution of Stereoacuity Scores | 800 seconds of arc | 28 Participants |
| Patching Treatment Younger | Distribution of Stereoacuity Scores | 60 seconds of arc | 11 Participants |
| Binocular Treatment Older Cohort | Distribution of Stereoacuity Scores | 400 seconds of arc | 3 Participants |
| Binocular Treatment Older Cohort | Distribution of Stereoacuity Scores | Missing/Not done | 0 Participants |
| Binocular Treatment Older Cohort | Distribution of Stereoacuity Scores | 4000 seconds of arc | 13 Participants |
| Binocular Treatment Older Cohort | Distribution of Stereoacuity Scores | 2000 seconds of arc | 6 Participants |
| Binocular Treatment Older Cohort | Distribution of Stereoacuity Scores | 800 seconds of arc | 6 Participants |
| Binocular Treatment Older Cohort | Distribution of Stereoacuity Scores | 200 seconds of arc | 2 Participants |
| Binocular Treatment Older Cohort | Distribution of Stereoacuity Scores | 100 seconds of arc | 6 Participants |
| Binocular Treatment Older Cohort | Distribution of Stereoacuity Scores | 60 seconds of arc | 2 Participants |
| Binocular Treatment Older Cohort | Distribution of Stereoacuity Scores | 40 seconds of arc | 1 Participants |
| Patching Treatment Older | Distribution of Stereoacuity Scores | 200 seconds of arc | 2 Participants |
| Patching Treatment Older | Distribution of Stereoacuity Scores | 800 seconds of arc | 7 Participants |
| Patching Treatment Older | Distribution of Stereoacuity Scores | Missing/Not done | 0 Participants |
| Patching Treatment Older | Distribution of Stereoacuity Scores | 60 seconds of arc | 2 Participants |
| Patching Treatment Older | Distribution of Stereoacuity Scores | 2000 seconds of arc | 11 Participants |
| Patching Treatment Older | Distribution of Stereoacuity Scores | 4000 seconds of arc | 25 Participants |
| Patching Treatment Older | Distribution of Stereoacuity Scores | 400 seconds of arc | 4 Participants |
| Patching Treatment Older | Distribution of Stereoacuity Scores | 40 seconds of arc | 5 Participants |
| Patching Treatment Older | Distribution of Stereoacuity Scores | 100 seconds of arc | 2 Participants |
Secondary
Distribution of Stereoacuity Scores (Participants With no History of Strabismus)
Stereoacuity was tested at near in current refractive correction. Stereoacuity scores (measure as seconds of arc) were calculated based on the Randot Butterfly (scores: 2000, Nil) and Randot Preschool stereoacuity (scores: 800, 400, 200, 100, 60 and 40) test methods. Lower scores indicate better stereoacuity. Results of the Randot Butterfly test were analyzed as 2000 seconds of arc (if correct response). Nil was assigned a score of 4000 seconds of arc and was defined as (1) an incorrect response on the butterfly in absence of a correct response on the 800 seconds of arc level of the Randot Preschool stereoacuity test or (2) an incorrect response on the 800 seconds of arc level if the butterfly was not attempted.
Time frame: 16 weeks
Population: The analysis was limited to a subset of participants (no history of strabismus) who completed a 16-week exam regardless of whether or not the exam was completed within the pre-specified analysis window.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Binocular Treatment Younger | Distribution of Stereoacuity Scores (Participants With no History of Strabismus) | 60 seconds of arc | 9 Participants |
| Binocular Treatment Younger | Distribution of Stereoacuity Scores (Participants With no History of Strabismus) | 400 seconds of arc | 10 Participants |
| Binocular Treatment Younger | Distribution of Stereoacuity Scores (Participants With no History of Strabismus) | 40 seconds of arc | 10 Participants |
| Binocular Treatment Younger | Distribution of Stereoacuity Scores (Participants With no History of Strabismus) | 800 seconds of arc | 12 Participants |
| Binocular Treatment Younger | Distribution of Stereoacuity Scores (Participants With no History of Strabismus) | 100 seconds of arc | 14 Participants |
| Binocular Treatment Younger | Distribution of Stereoacuity Scores (Participants With no History of Strabismus) | 4000 seconds of arc | 23 Participants |
| Binocular Treatment Younger | Distribution of Stereoacuity Scores (Participants With no History of Strabismus) | 2000 seconds of arc | 14 Participants |
| Binocular Treatment Younger | Distribution of Stereoacuity Scores (Participants With no History of Strabismus) | 200 seconds of arc | 12 Participants |
| Binocular Treatment Younger | Distribution of Stereoacuity Scores (Participants With no History of Strabismus) | Missing/Not done | 1 Participants |
| Patching Treatment Younger | Distribution of Stereoacuity Scores (Participants With no History of Strabismus) | 800 seconds of arc | 14 Participants |
| Patching Treatment Younger | Distribution of Stereoacuity Scores (Participants With no History of Strabismus) | 200 seconds of arc | 17 Participants |
| Patching Treatment Younger | Distribution of Stereoacuity Scores (Participants With no History of Strabismus) | 100 seconds of arc | 15 Participants |
| Patching Treatment Younger | Distribution of Stereoacuity Scores (Participants With no History of Strabismus) | 2000 seconds of arc | 12 Participants |
| Patching Treatment Younger | Distribution of Stereoacuity Scores (Participants With no History of Strabismus) | Missing/Not done | 0 Participants |
| Patching Treatment Younger | Distribution of Stereoacuity Scores (Participants With no History of Strabismus) | 40 seconds of arc | 3 Participants |
| Patching Treatment Younger | Distribution of Stereoacuity Scores (Participants With no History of Strabismus) | 400 seconds of arc | 10 Participants |
| Patching Treatment Younger | Distribution of Stereoacuity Scores (Participants With no History of Strabismus) | 4000 seconds of arc | 13 Participants |
| Patching Treatment Younger | Distribution of Stereoacuity Scores (Participants With no History of Strabismus) | 60 seconds of arc | 6 Participants |
| Binocular Treatment Older Cohort | Distribution of Stereoacuity Scores (Participants With no History of Strabismus) | Missing/Not done | 0 Participants |
| Binocular Treatment Older Cohort | Distribution of Stereoacuity Scores (Participants With no History of Strabismus) | 100 seconds of arc | 5 Participants |
| Binocular Treatment Older Cohort | Distribution of Stereoacuity Scores (Participants With no History of Strabismus) | 200 seconds of arc | 2 Participants |
| Binocular Treatment Older Cohort | Distribution of Stereoacuity Scores (Participants With no History of Strabismus) | 4000 seconds of arc | 4 Participants |
| Binocular Treatment Older Cohort | Distribution of Stereoacuity Scores (Participants With no History of Strabismus) | 800 seconds of arc | 4 Participants |
| Binocular Treatment Older Cohort | Distribution of Stereoacuity Scores (Participants With no History of Strabismus) | 40 seconds of arc | 1 Participants |
| Binocular Treatment Older Cohort | Distribution of Stereoacuity Scores (Participants With no History of Strabismus) | 2000 seconds of arc | 1 Participants |
| Binocular Treatment Older Cohort | Distribution of Stereoacuity Scores (Participants With no History of Strabismus) | 60 seconds of arc | 2 Participants |
| Binocular Treatment Older Cohort | Distribution of Stereoacuity Scores (Participants With no History of Strabismus) | 400 seconds of arc | 2 Participants |
| Patching Treatment Older | Distribution of Stereoacuity Scores (Participants With no History of Strabismus) | 100 seconds of arc | 1 Participants |
| Patching Treatment Older | Distribution of Stereoacuity Scores (Participants With no History of Strabismus) | Missing/Not done | 0 Participants |
| Patching Treatment Older | Distribution of Stereoacuity Scores (Participants With no History of Strabismus) | 4000 seconds of arc | 10 Participants |
| Patching Treatment Older | Distribution of Stereoacuity Scores (Participants With no History of Strabismus) | 2000 seconds of arc | 4 Participants |
| Patching Treatment Older | Distribution of Stereoacuity Scores (Participants With no History of Strabismus) | 800 seconds of arc | 3 Participants |
| Patching Treatment Older | Distribution of Stereoacuity Scores (Participants With no History of Strabismus) | 400 seconds of arc | 1 Participants |
| Patching Treatment Older | Distribution of Stereoacuity Scores (Participants With no History of Strabismus) | 200 seconds of arc | 1 Participants |
| Patching Treatment Older | Distribution of Stereoacuity Scores (Participants With no History of Strabismus) | 60 seconds of arc | 2 Participants |
| Patching Treatment Older | Distribution of Stereoacuity Scores (Participants With no History of Strabismus) | 40 seconds of arc | 5 Participants |
Secondary
Median Stereoacuity Score (Seconds of Arc)
Stereoacuity was tested at near in current refractive correction. Stereoacuity scores (measure as seconds of arc) were calculated based on the Randot Butterfly (scores: 2000, Nil) and Randot Preschool stereoacuity (scores: 800, 400, 200, 100, 60 and 40) test methods. Lower scores indicate better stereoacuity. Results of the Randot Butterfly test were analyzed as 2000 seconds of arc (if correct response). Nil was assigned a score of 4000 seconds of arc and was defined as (1) an incorrect response on the butterfly in absence of a correct response on the 800 seconds of arc level of the Randot Preschool stereoacuity test or (2) an incorrect response on the 800 seconds of arc level if the butterfly was not attempted. A logarithm base 10 transformation was used to convert stereoacuity scores (seconds of arc) to the log scale (conversion reference listed below), which was used to calculate descriptive statistics. Results of the descriptive analyses are reported as seconds of arc.
Time frame: 16 weeks
Population: Participants who completed stereoacuity testing at the 16-week visit (regardless of whether or not the visit was completed within the pre-specified analysis window).~Descriptive analyses were repeated for a subset of participants with no history of strabismus.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Binocular Treatment Younger | Median Stereoacuity Score (Seconds of Arc) | All participants | 2000 Seconds of arc |
| Binocular Treatment Younger | Median Stereoacuity Score (Seconds of Arc) | Participants with no history of strabismus | 400 Seconds of arc |
| Patching Treatment Younger | Median Stereoacuity Score (Seconds of Arc) | Participants with no history of strabismus | 400 Seconds of arc |
| Patching Treatment Younger | Median Stereoacuity Score (Seconds of Arc) | All participants | 800 Seconds of arc |
| Binocular Treatment Older Cohort | Median Stereoacuity Score (Seconds of Arc) | Participants with no history of strabismus | 400 Seconds of arc |
| Binocular Treatment Older Cohort | Median Stereoacuity Score (Seconds of Arc) | All participants | 800 Seconds of arc |
| Patching Treatment Older | Median Stereoacuity Score (Seconds of Arc) | All participants | 2000 Seconds of arc |
| Patching Treatment Older | Median Stereoacuity Score (Seconds of Arc) | Participants with no history of strabismus | 2000 Seconds of arc |
Secondary
Number of Participants With Amblyopic-eye VA Improvement of 2 or More logMAR Lines (10 or More Letters if E-ETDRS) From Baseline
Monocular distance visual acuity (VA) in current refractive correction (if required) in each eye by a certified examiner using the electronic Amblyopia Treatment Study single-surround HOTV (ATS-HOTV) visual acuity protocol for children \<7 years and the Electronic Early Treatment Diabetic Retinoscopy Study (E-ETDRS) visual acuity protocol for children ≥ 7 years on a study-certified acuity tester displaying single surrounded optotypes. Younger cohort: The level of VA is analyzed in the log of the Minimum Angle of Resolution (logMAR) scale (previously defined) and change in VA from baseline as logMAR lines (previously defined). Older cohort: The level of VA is measured as letter scores (previously defined) and VA change from baseline is measured in letters (previously defined).
Time frame: Baseline and 16-week visit
Population: Analysis was limited to participants who completed the 16-week visit within the pre-specified analysis window (14 to \<20 weeks after randomization).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Binocular Treatment Younger | Number of Participants With Amblyopic-eye VA Improvement of 2 or More logMAR Lines (10 or More Letters if E-ETDRS) From Baseline | 51 Participants |
| Patching Treatment Younger | Number of Participants With Amblyopic-eye VA Improvement of 2 or More logMAR Lines (10 or More Letters if E-ETDRS) From Baseline | 65 Participants |
| Binocular Treatment Older Cohort | Number of Participants With Amblyopic-eye VA Improvement of 2 or More logMAR Lines (10 or More Letters if E-ETDRS) From Baseline | 6 Participants |
| Patching Treatment Older | Number of Participants With Amblyopic-eye VA Improvement of 2 or More logMAR Lines (10 or More Letters if E-ETDRS) From Baseline | 17 Participants |
Comparison: Binomial regression was used for the treatment group comparison of the proportion of participants classified as improving 2 or more logMAR lines (10 or more letters if E-ETDRS) from baseline at the 16-week visit, adjusting for baseline age group (5 to \<7, 7 to \<13 years) and baseline visual acuity (treated as a continuous covariate).95% CI: [-4, 13]
Comparison: Binomial regression was used for the treatment group comparison of the proportion of participants classified as improving 2 or more logMAR lines (10 or more letters if E-ETDRS) from baseline at the 16-week visit, adjusting for baseline visual acuity.95% CI: [-31, 2]
Secondary
Number of Participants With Resolution of Amblyopia
Monocular distance visual acuity (VA) in current refractive correction (if required) in each eye by a certified examiner using the electronic Amblyopia Treatment Study single-surround HOTV (ATS-HOTV) visual acuity protocol for children \<7 years and the Electronic Early Treatment Diabetic Retinoscopy Study (E-ETDRS) visual acuity protocol for children ≥ 7 years on a study-certified acuity tester displaying single surrounded optotypes. The level of VA is analyzed in the log of the Minimum Angle of Resolution (logMAR) scale (previously defined) for the younger cohort and as letter scores (previously defined) for the older cohort. Resolution of amblyopia was defined as having an amblyopic-eye VA of 20/25 or better (≥ 78 letters if E-ETDRS) and within 1 logMAR line (5 letters if E-ETDRS) of the fellow eye VA.
Time frame: 16-week visit
Population: Analysis was limited to participants who completed the 16-week visit within the pre-specified analysis window (14 to \<20 weeks after randomization).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Binocular Treatment Younger | Number of Participants With Resolution of Amblyopia | 8 Participants |
| Patching Treatment Younger | Number of Participants With Resolution of Amblyopia | 18 Participants |
| Binocular Treatment Older Cohort | Number of Participants With Resolution of Amblyopia | 0 Participants |
| Patching Treatment Older | Number of Participants With Resolution of Amblyopia | 0 Participants |
Comparison: Binomial regression was used for the treatment group comparison of the proportion of participants classified as improving 2 or more logMAR lines (10 or more letters if E-ETDRS) from baseline at the 16-week visit, adjusting for baseline age group (5 to \<7, 7 to \<13 years) and baseline visual acuity (20/40, 20/50 or worse).95% CI: [-1, 5]
Secondary
Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups
Monocular distance visual acuity (VA) in current refractive correction (if required) in each eye by a certified examiner using the Electronic Early Treatment Diabetic Retinoscopy Study (E-ETDRS) visual acuity protocol for children ≥ 7 years on a study-certified acuity tester displaying single surrounded optotypes. For the analyses in the older cohort, the level of VA is measured as letter scores (previously defined) and change in VA from baseline is measured in letters (positive values indicate improvement), defined as the difference in letter scores between enrollment and follow-up. Subgroup factors of interest were pre-specified except for baseline stereoacuity (nil, better than nil).
Time frame: Baseline and 16 weeks
Population: Visual acuity analyses included only data from participants who completed the 16-week visit within the predefined analysis window (14 to \<20 weeks after randomization).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Binocular Treatment Younger | Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Presence of a near heterotropia at baseline | 5.7 Letters | Standard Deviation 7.4 |
| Binocular Treatment Younger | Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Female | 1.0 Letters | Standard Deviation 6.8 |
| Binocular Treatment Younger | Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Male | 5.0 Letters | Standard Deviation 6.4 |
| Binocular Treatment Younger | Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | White/Non-Hispanic | 3.6 Letters | Standard Deviation 7.1 |
| Binocular Treatment Younger | Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Non-White or Hispanic | 3.2 Letters | Standard Deviation 6.1 |
| Binocular Treatment Younger | Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Baseline amblyopic-eye VA: 20/80 to 20/200 | 5.2 Letters | Standard Deviation 7.8 |
| Binocular Treatment Younger | Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Baseline amblyopic-eye VA: 20/63 | 3.2 Letters | Standard Deviation 2.8 |
| Binocular Treatment Younger | Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Baseline amblyopic-eye VA: 20/50 | 2.9 Letters | Standard Deviation 4.2 |
| Binocular Treatment Younger | Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Baseline amblyopic-eye VA: 20/40 | -0.4 Letters | Standard Deviation 10.9 |
| Binocular Treatment Younger | Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | No prior amblyopia treatment | 2.9 Letters | Standard Deviation 6.4 |
| Binocular Treatment Younger | Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Prior amblyopia treatment | 3.6 Letters | Standard Deviation 7 |
| Binocular Treatment Younger | Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Baseline stereoacuity: Nil | 4.1 Letters | Standard Deviation 7.7 |
| Binocular Treatment Younger | Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Baseline stereoacuity: Better than Nil | 3.0 Letters | Standard Deviation 6.2 |
| Binocular Treatment Younger | Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | No presence of a near heterotropia at baseline | 2.0 Letters | Standard Deviation 6.1 |
| Patching Treatment Younger | Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Prior amblyopia treatment | 6.0 Letters | Standard Deviation 7.6 |
| Patching Treatment Younger | Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Presence of a near heterotropia at baseline | 7.9 Letters | Standard Deviation 6.9 |
| Patching Treatment Younger | Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Baseline amblyopic-eye VA: 20/50 | 6.0 Letters | Standard Deviation 4.4 |
| Patching Treatment Younger | Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Female | 6.0 Letters | Standard Deviation 6.7 |
| Patching Treatment Younger | Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Baseline stereoacuity: Better than Nil | 7.2 Letters | Standard Deviation 7.8 |
| Patching Treatment Younger | Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Male | 6.8 Letters | Standard Deviation 8.4 |
| Patching Treatment Younger | Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Baseline amblyopic-eye VA: 20/40 | 6.8 Letters | Standard Deviation 6.4 |
| Patching Treatment Younger | Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | White/Non-Hispanic | 6.4 Letters | Standard Deviation 7.6 |
| Patching Treatment Younger | Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Baseline stereoacuity: Nil | 5.7 Letters | Standard Deviation 7.6 |
| Patching Treatment Younger | Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Non-White or Hispanic | 6.7 Letters | Standard Deviation 8.2 |
| Patching Treatment Younger | Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | No prior amblyopia treatment | 10.3 Letters | Standard Deviation 8 |
| Patching Treatment Younger | Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Baseline amblyopic-eye VA: 20/80 to 20/200 | 7.1 Letters | Standard Deviation 8.3 |
| Patching Treatment Younger | Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | No presence of a near heterotropia at baseline | 5.6 Letters | Standard Deviation 8.1 |
| Patching Treatment Younger | Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Baseline amblyopic-eye VA: 20/63 | 5.0 Letters | Standard Deviation 10.6 |
Secondary
Time Course of Visual Acuity Improvement
Monocular distance visual acuity (VA) in current refractive correction (if required) in each eye by a certified examiner using the electronic Amblyopia Treatment Study single-surround HOTV (ATS-HOTV) visual acuity protocol for children \<7 years and the Electronic Early Treatment Diabetic Retinoscopy Study (E-ETDRS) visual acuity protocol for children ≥ 7 years on a study-certified acuity tester displaying single surrounded optotypes. For the younger cohort, the level of VA is analyzed in the log of the Minimum Angle of Resolution (logMAR) scale (approximate range: -0.2 to 1.7, higher values indicate poorer VA) and change in VA from baseline as logMAR lines (positive values indicate improvement), defined as the difference between the enrollment and follow-up acuities (logMAR) multiplied by 10.
Time frame: Baseline, 4 weeks, 8 weeks, 12 weeks and 16 weeks
Population: Analysis included participants with at least one follow-up visit (completed within the analysis window). There were 6 participants (4 in the binocular group, 2 in the patching group) who were excluded from the time course analysis because they did not have any follow-up exams.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Binocular Treatment Younger | Time Course of Visual Acuity Improvement | 4-week visit | 0.53 logMAR lines | Standard Deviation 1.14 |
| Binocular Treatment Younger | Time Course of Visual Acuity Improvement | 8-week visit | 0.76 logMAR lines | Standard Deviation 1.18 |
| Binocular Treatment Younger | Time Course of Visual Acuity Improvement | 12-week visit | 0.90 logMAR lines | Standard Deviation 1.37 |
| Binocular Treatment Younger | Time Course of Visual Acuity Improvement | 16-week visit | 1.08 logMAR lines | Standard Deviation 1.45 |
| Patching Treatment Younger | Time Course of Visual Acuity Improvement | 16-week visit | 1.32 logMAR lines | Standard Deviation 1.26 |
| Patching Treatment Younger | Time Course of Visual Acuity Improvement | 4-week visit | 0.76 logMAR lines | Standard Deviation 1.09 |
| Patching Treatment Younger | Time Course of Visual Acuity Improvement | 12-week visit | 1.21 logMAR lines | Standard Deviation 1.26 |
| Patching Treatment Younger | Time Course of Visual Acuity Improvement | 8-week visit | 1.03 logMAR lines | Standard Deviation 1.23 |
Comparison: A linear mixed model was used to compare the rate of amblyopic-eye visual acuity improvement between the treatment groups. The ANCOVA model included an interaction term with treatment group and time to compare the change in visual acuity over follow-up by treatment group, adjusting for the main effects of the interaction term and baseline covariates of age and visual acuity. If the interaction term was not statistically significant (p\>0.05), no further comparisons would be performed.p-value: 0.83ANCOVA
Secondary
Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups
Monocular distance visual acuity (VA) in current refractive correction (if required) in each eye by a certified examiner using the electronic Amblyopia Treatment Study single-surround HOTV (ATS-HOTV) visual acuity protocol for children \<7 years and the Electronic Early Treatment Diabetic Retinoscopy Study (E-ETDRS) visual acuity protocol for children ≥ 7 years on a study-certified acuity tester displaying single surrounded optotypes. For the younger cohort, the level of VA is analyzed in the log of the Minimum Angle of Resolution (logMAR) scale (previously defined) and change in VA from baseline as logMAR lines (previously defined, positive values indicate improvement), For both descriptive and formal subgroup analyses, all subgroup factors were pre-specified except for baseline stereoacuity (nil, better than nil). We performed post hoc descriptive analyses to explore treatment effect by baseline age (5 to \<7 yrs, 7 to \<13 yrs) and prior amblyopia treatment (yes/no).
Time frame: Baseline and 16 weeks
Population: Visual acuity analyses included only data from participants who completed the 16-week visit within the predefined analysis window (14 to \<20 weeks after randomization). Formal subgroup analyses are adjusted for baseline covariates of visual acuity and age.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Binocular Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Female | 1.2 LogMAR lines | Standard Deviation 1.5 |
| Binocular Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Male | 1.0 LogMAR lines | Standard Deviation 1.4 |
| Binocular Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | White/Non-Hispanic | 1.0 LogMAR lines | Standard Deviation 1.5 |
| Binocular Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Non-White or Hispanic | 1.2 LogMAR lines | Standard Deviation 1.5 |
| Binocular Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Age at baseline: 5 to <7 years | 1.9 LogMAR lines | Standard Deviation 1.8 |
| Binocular Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Age at baseline: 7 to <13 years | 0.8 LogMAR lines | Standard Deviation 1.2 |
| Binocular Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Baseline amblyopic-eye VA: 20/80 to 20/200 | 1.1 LogMAR lines | Standard Deviation 1.6 |
| Binocular Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Baseline amblyopic-eye VA: 20/63 | 1.3 LogMAR lines | Standard Deviation 1.6 |
| Binocular Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Baseline amblyopic-eye VA: 20/50 | 1.0 LogMAR lines | Standard Deviation 1.3 |
| Binocular Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Baseline amblyopic-eye VA: 20/40 | 0.8 LogMAR lines | Standard Deviation 1.2 |
| Binocular Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Baseline stereoacuity: Nil | 0.7 LogMAR lines | Standard Deviation 1.3 |
| Binocular Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Baseline stereoacuity: Better than Nil | 1.3 LogMAR lines | Standard Deviation 1.5 |
| Binocular Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | No presence of a near heterotropia at baseline | 1.1 LogMAR lines | Standard Deviation 1.3 |
| Binocular Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Presence of a near heterotropia at baseline | 0.9 LogMAR lines | Standard Deviation 1.7 |
| Binocular Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | No prior amblyopia treatment | 1.9 LogMAR lines | Standard Deviation 1.5 |
| Binocular Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Prior amblyopia treatment | 0.8 LogMAR lines | Standard Deviation 1.4 |
| Binocular Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Baseline: Age 5 to <7 yrs, no prior treatment | 2.5 LogMAR lines | Standard Deviation 1.5 |
| Binocular Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Baseline: Age 5 to <7 yrs, prior treatment | 1.4 LogMAR lines | Standard Deviation 1.9 |
| Binocular Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Baseline: Age 7 to <13 yrs, no prior treatment | 1.3 LogMAR lines | Standard Deviation 1.2 |
| Binocular Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Baseline: Age 7 to <13 yrs, prior treatment | 0.7 LogMAR lines | Standard Deviation 1.2 |
| Patching Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Baseline: Age 5 to <7 yrs, prior treatment | 1.4 LogMAR lines | Standard Deviation 1.4 |
| Patching Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Female | 1.4 LogMAR lines | Standard Deviation 1.2 |
| Patching Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Baseline stereoacuity: Nil | 1.1 LogMAR lines | Standard Deviation 1.1 |
| Patching Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Male | 1.3 LogMAR lines | Standard Deviation 1.3 |
| Patching Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Prior amblyopia treatment | 1.1 LogMAR lines | Standard Deviation 1.2 |
| Patching Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | White/Non-Hispanic | 1.3 LogMAR lines | Standard Deviation 1.2 |
| Patching Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Baseline stereoacuity: Better than Nil | 1.4 LogMAR lines | Standard Deviation 1.3 |
| Patching Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Non-White or Hispanic | 1.3 LogMAR lines | Standard Deviation 1.4 |
| Patching Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Baseline: Age 7 to <13 yrs, prior treatment | 1.0 LogMAR lines | Standard Deviation 1.1 |
| Patching Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Age at baseline: 5 to <7 years | 2.0 LogMAR lines | Standard Deviation 1.4 |
| Patching Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | No presence of a near heterotropia at baseline | 1.3 LogMAR lines | Standard Deviation 1.2 |
| Patching Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Age at baseline: 7 to <13 years | 1.1 LogMAR lines | Standard Deviation 1.1 |
| Patching Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Baseline: Age 5 to <7 yrs, no prior treatment | 2.8 LogMAR lines | Standard Deviation 0.8 |
| Patching Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Baseline amblyopic-eye VA: 20/80 to 20/200 | 1.3 LogMAR lines | Standard Deviation 1.3 |
| Patching Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Presence of a near heterotropia at baseline | 1.4 LogMAR lines | Standard Deviation 1.3 |
| Patching Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Baseline amblyopic-eye VA: 20/63 | 1.4 LogMAR lines | Standard Deviation 1.3 |
| Patching Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Baseline: Age 7 to <13 yrs, no prior treatment | 1.5 LogMAR lines | Standard Deviation 1.3 |
| Patching Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Baseline amblyopic-eye VA: 20/50 | 1.3 LogMAR lines | Standard Deviation 1.3 |
| Patching Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | No prior amblyopia treatment | 2.2 LogMAR lines | Standard Deviation 1.3 |
| Patching Treatment Younger | Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups | Baseline amblyopic-eye VA: 20/40 | 1.2 LogMAR lines | Standard Deviation 1.2 |
Comparison: Exploratory subgroup analyses were conducted to assess the treatment effect according to subgroups of baseline factors. An analysis of covariance was used to test the interaction between treatment group and gender, adjusting for the main effects of the interaction term and baseline covariates of age and visual acuity.p-value: 0.83ANCOVA
Comparison: Exploratory subgroup analyses were conducted to assess the treatment effect according to subgroups of baseline factors. An analysis of covariance was used to test the interaction between treatment group and race/ethnicity status (White/non-Hispanic, Non-White or Hispanic), adjusting for the main effects of the interaction term and baseline covariates of age and visual acuity.p-value: 0.54ANCOVA
Comparison: Exploratory subgroup analyses were conducted to assess the treatment effect according to subgroups of baseline factors. An analysis of covariance was used to test the interaction between treatment group and age at baseline (treated as a continuous factor in the model), adjusting for the main effects of the interaction term and baseline visual acuity.p-value: 0.8ANCOVA
Comparison: Exploratory subgroup analyses were conducted to assess the treatment effect according to subgroups of baseline factors. An analysis of covariance was used to test the interaction between treatment group and baseline amblyopic-eye visual acuity (treated as a continuous factor in the model), adjusting for the main effects of the interaction term and baseline age.p-value: 0.99ANCOVA
Comparison: Exploratory subgroup analyses were conducted to assess the treatment effect according to subgroups of baseline factors. An analysis of covariance was used to test the interaction between treatment group and prior amblyopia treatment (Yes/No), adjusting for the main effects of the interaction term and baseline covariates of age and visual acuity.p-value: 0.87ANCOVA
Comparison: Exploratory subgroup analyses were conducted to assess the treatment effect according to subgroups of baseline factors. An analysis of covariance was used to test the interaction between treatment group and baseline stereoacuity (nil, better than nil), adjusting for the main effects of the interaction term and baseline covariates of age and visual acuity.p-value: 0.33ANCOVA
Comparison: Exploratory subgroup analyses were conducted to assess the treatment effect according to subgroups of baseline factors. An analysis of covariance was used to test the interaction between treatment group and presence of a near heterotropia (measured by SPCT) at baseline (Yes/No), adjusting for the main effects of the interaction term and baseline covariates of age and visual acuity.p-value: 0.23ANCOVA
Other Pre-specified
Participants Who Received Non-protocol, Alternative Treatment During the Study
Participants who were randomly assigned to binocular treatment were prescribed 1 hour of game play per day, 7 days a week while those assigned to the patching group were prescribed 2 hours of daily patching, 7 days per week. The number of participants who received non-protocol, alternative treatment was tabulated by treatment group.
Time frame: Entire study period, up to 16 weeks
Population: All randomized participants in the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Binocular Treatment Younger | Participants Who Received Non-protocol, Alternative Treatment During the Study | 4 Participants |
| Patching Treatment Younger | Participants Who Received Non-protocol, Alternative Treatment During the Study | 0 Participants |
| Binocular Treatment Older Cohort | Participants Who Received Non-protocol, Alternative Treatment During the Study | 0 Participants |
| Patching Treatment Older | Participants Who Received Non-protocol, Alternative Treatment During the Study | 0 Participants |
Other Pre-specified
Percentage of Participants Reporting >75% of Prescribed Treatment Completed (Subjective Measures of Adherence)
Participants who were randomly assigned to binocular treatment were prescribed 1 hour of game play per day, 7 days a week while those assigned to the patching group were prescribed 2 hours of daily patching, 7 days per week. Parents were asked to record the amount of time that the participant played the binocular game (binocular treatment group) or wore the patch (patching group) each day on a calendar. At each study visit, the investigator estimated the frequency and duration of treatment that the participant completed based on the parent-reported calendars and discussion with the participant and/or parent(s). For analysis, the percentage of prescribed treatment completed was calculated as the total number of reported hours of treatment completed since baseline divided by the total number of prescribed hours (refer to the intended treatment dose/frequency listed above) since baseline.
Time frame: 16 Weeks from baseline
Population: The descriptive analysis included data from participants who completed the 16-week visit within the predefined analysis window (14 to \<20 weeks after randomization).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Binocular Treatment Younger | Percentage of Participants Reporting >75% of Prescribed Treatment Completed (Subjective Measures of Adherence) | 118 Participants |
| Patching Treatment Younger | Percentage of Participants Reporting >75% of Prescribed Treatment Completed (Subjective Measures of Adherence) | 172 Participants |
| Binocular Treatment Older Cohort | Percentage of Participants Reporting >75% of Prescribed Treatment Completed (Subjective Measures of Adherence) | 24 Participants |
| Patching Treatment Older | Percentage of Participants Reporting >75% of Prescribed Treatment Completed (Subjective Measures of Adherence) | 42 Participants |
Other Pre-specified
Safety Analysis: Change in Fellow-eye Visual Acuity From Baseline (Older Cohort)
Monocular distance visual acuity (VA) in current refractive correction (if required) in each eye by a certified examiner using the Electronic Early Treatment Diabetic Retinoscopy Study (E-ETDRS) visual acuity protocol for children ≥ 7 years on a study-certified acuity tester displaying single surrounded optotypes. For the analyses in the older cohort, the level of VA is measured as letter scores (approximate range: 0 to 97 letters, lower scores indicate poorer VA) and change in VA from baseline is measured in letters (positive values indicate improvement), defined as the difference in letter scores between enrollment and follow-up. The change in fellow-eye visual acuity (letters) from baseline (positive values indicate improvement) was computed by treatment group, adjusting for baseline visual acuity.
Time frame: 16-week visit
Population: Participants who completed the 16-week visit (regardless of whether or not the visit was completed within the pre-specified analysis window).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Binocular Treatment Younger | Safety Analysis: Change in Fellow-eye Visual Acuity From Baseline (Older Cohort) | 2.2 Letters |
| Patching Treatment Younger | Safety Analysis: Change in Fellow-eye Visual Acuity From Baseline (Older Cohort) | 2.0 Letters |
Comparison: An analysis of covariance (ANCOVA) model was used to compute the treatment group difference in the mean change in fellow-eye visual acuity (letters) from baseline to 16 weeks, adjusting for baseline visual acuity. A 2-sided 95% confidence interval was computed on the adjusted treatment group difference.95% CI: [-1.1, 1.3]
Other Pre-specified
Safety Analysis: Change in Fellow-eye Visual Acuity From Baseline (Younger Cohort)
Monocular distance visual acuity (VA) in current refractive correction (if required) in each eye by a certified examiner using the electronic Amblyopia Treatment Study single-surround HOTV (ATS-HOTV) visual acuity protocol for children \<7 years and the Electronic Early Treatment Diabetic Retinoscopy Study (E-ETDRS) visual acuity protocol for children ≥ 7 years on a study-certified acuity tester displaying single surrounded optotypes. For the younger cohort, the level of visual acuity is analyzed in the log of the Minimum Angle of Resolution (logMAR) scale (approximate range: -0.2 to 1.7) such that higher scores indicate poorer VA. Change in VA is computed as logMAR lines (positive values indicate improvement), defined as the difference between the enrollment and 16-week acuities (logMAR) multiplied by 10. For this safety analysis, the change in fellow-eye visual acuity (logMAR lines) was computed by treatment group, adjusting for baseline visual acuity.
Time frame: 16-week visit
Population: Participants who completed the 16-week visit (regardless of whether or not the visit was completed within the pre-specified analysis window).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Binocular Treatment Younger | Safety Analysis: Change in Fellow-eye Visual Acuity From Baseline (Younger Cohort) | 0.30 logMAR lines |
| Patching Treatment Younger | Safety Analysis: Change in Fellow-eye Visual Acuity From Baseline (Younger Cohort) | 0.14 logMAR lines |
Comparison: The treatment group difference in the change in fellow-eye visual acuity from baseline to 16 weeks (logMAR lines) was evaluated in an analysis of covariance model, adjusted for baseline fellow-eye visual acuity.95% CI: [0.02, 0.3]
Other Pre-specified
Safety Analysis: Development of a New Tropia and/or Worsening of a Pre-existing Deviation by 10 pd
Ocular alignment will be assessed in current refractive correction by the cover/uncover test, simultaneous prism and cover test (SPCT), and prism and alternate cover test (PACT) in primary gaze at distance (3 meters) and at near (1/3 meter). Participants were classified according to whether they met the any of the following criteria at the 16-week visit: development of a new tropia (measured by SPCT) and/or worsening of a pre-existing deviation by 10 prism diopters (pd) measured by SPCT.
Time frame: 16 weeks
Population: Participants who completed the 16-week visit (regardless of whether or not the visit was completed within the pre-specified analysis window).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Binocular Treatment Younger | Safety Analysis: Development of a New Tropia and/or Worsening of a Pre-existing Deviation by 10 pd | 16 Participants |
| Patching Treatment Younger | Safety Analysis: Development of a New Tropia and/or Worsening of a Pre-existing Deviation by 10 pd | 11 Participants |
| Binocular Treatment Older Cohort | Safety Analysis: Development of a New Tropia and/or Worsening of a Pre-existing Deviation by 10 pd | 3 Participants |
| Patching Treatment Older | Safety Analysis: Development of a New Tropia and/or Worsening of a Pre-existing Deviation by 10 pd | 3 Participants |
Comparison: Fisher's exact test was used to perform the treatment group comparison of the proportion of participants who developed a new ocular deviation and/or worsening of a pre-existing ocular deviation by 10 prism diopters at the 16-week visit.p-value: 0.32Fisher Exact
Comparison: Fisher's exact test was used to perform the treatment group comparison of the proportion of participants who developed a new ocular deviation and/or worsening of a pre-existing ocular deviation by 10 prism diopters at the 16-week visit.p-value: 0.68Fisher Exact
Other Pre-specified
Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Parent-reported)
A standardized questionnaire was administered to participants and their parents to assess the presence and frequency of any diplopia since the last study visit.
Time frame: 16 weeks
Population: Participants whose parent completed a 16-week diplopia assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Binocular Treatment Younger | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Parent-reported) | No diplopia | 176 Participants |
| Binocular Treatment Younger | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Parent-reported) | Diplopia: Once a week | 1 Participants |
| Binocular Treatment Younger | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Parent-reported) | Diplopia: Less than once a week | 5 Participants |
| Binocular Treatment Younger | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Parent-reported) | All the time | 0 Participants |
| Binocular Treatment Younger | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Parent-reported) | Diplopia: Up to 10 times a day | 0 Participants |
| Binocular Treatment Younger | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Parent-reported) | Diplopia: Once a day | 0 Participants |
| Binocular Treatment Younger | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Parent-reported) | Diplopia: >10 times a day | 0 Participants |
| Patching Treatment Younger | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Parent-reported) | Diplopia: Once a week | 2 Participants |
| Patching Treatment Younger | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Parent-reported) | All the time | 0 Participants |
| Patching Treatment Younger | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Parent-reported) | No diplopia | 185 Participants |
| Patching Treatment Younger | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Parent-reported) | Diplopia: >10 times a day | 0 Participants |
| Patching Treatment Younger | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Parent-reported) | Diplopia: Less than once a week | 0 Participants |
| Patching Treatment Younger | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Parent-reported) | Diplopia: Up to 10 times a day | 0 Participants |
| Patching Treatment Younger | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Parent-reported) | Diplopia: Once a day | 0 Participants |
| Binocular Treatment Older Cohort | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Parent-reported) | Diplopia: Once a week | 0 Participants |
| Binocular Treatment Older Cohort | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Parent-reported) | Diplopia: Up to 10 times a day | 0 Participants |
| Binocular Treatment Older Cohort | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Parent-reported) | All the time | 0 Participants |
| Binocular Treatment Older Cohort | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Parent-reported) | Diplopia: >10 times a day | 0 Participants |
| Binocular Treatment Older Cohort | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Parent-reported) | No diplopia | 37 Participants |
| Binocular Treatment Older Cohort | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Parent-reported) | Diplopia: Once a day | 0 Participants |
| Binocular Treatment Older Cohort | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Parent-reported) | Diplopia: Less than once a week | 1 Participants |
| Patching Treatment Older | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Parent-reported) | All the time | 0 Participants |
| Patching Treatment Older | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Parent-reported) | Diplopia: Up to 10 times a day | 0 Participants |
| Patching Treatment Older | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Parent-reported) | No diplopia | 56 Participants |
| Patching Treatment Older | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Parent-reported) | Diplopia: Once a week | 0 Participants |
| Patching Treatment Older | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Parent-reported) | Diplopia: Once a day | 0 Participants |
| Patching Treatment Older | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Parent-reported) | Diplopia: >10 times a day | 0 Participants |
| Patching Treatment Older | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Parent-reported) | Diplopia: Less than once a week | 1 Participants |
Comparison: The Fisher exact test was used to compare the percentage of parents who reported that their child had experienced diplopia (yes/no) at the 16-week visit by treatment group.p-value: 0.17Fisher Exact
Comparison: The frequency of diplopia, across categories of diplopia, was compared between the treatment groups using the Cochran-Armitage trend test.p-value: 0.48Cochran-Armitage trend test
Comparison: The Fisher exact test was used to compare the percentage of parents who reported that their child had experienced diplopia (yes/no) at the 16-week visit by treatment group.p-value: >0.99Fisher Exact
Comparison: The frequency of diplopia, across categories of diplopia, was compared between the treatment groups using the Cochran-Armitage trend test.p-value: >0.99Cochran-Armitage trend test
Other Pre-specified
Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Participant-reported)
A standardized questionnaire was administered to participants and their parents to assess the presence and frequency of any diplopia since the last study visit.
Time frame: 16 weeks
Population: Participants who completed a 16-week diplopia assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Binocular Treatment Younger | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Participant-reported) | Diplopia: Less than once a week | 5 Participants |
| Binocular Treatment Younger | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Participant-reported) | Diplopia: >10 times a day | 0 Participants |
| Binocular Treatment Younger | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Participant-reported) | No diplopia | 166 Participants |
| Binocular Treatment Younger | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Participant-reported) | Diplopia: Once a week | 5 Participants |
| Binocular Treatment Younger | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Participant-reported) | All the time | 1 Participants |
| Binocular Treatment Younger | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Participant-reported) | Diplopia: Once a day | 2 Participants |
| Binocular Treatment Younger | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Participant-reported) | Diplopia: Up to 10 times a day | 3 Participants |
| Patching Treatment Younger | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Participant-reported) | Diplopia: >10 times a day | 0 Participants |
| Patching Treatment Younger | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Participant-reported) | No diplopia | 181 Participants |
| Patching Treatment Younger | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Participant-reported) | Diplopia: Up to 10 times a day | 0 Participants |
| Patching Treatment Younger | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Participant-reported) | Diplopia: Once a day | 1 Participants |
| Patching Treatment Younger | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Participant-reported) | All the time | 0 Participants |
| Patching Treatment Younger | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Participant-reported) | Diplopia: Once a week | 3 Participants |
| Patching Treatment Younger | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Participant-reported) | Diplopia: Less than once a week | 3 Participants |
| Binocular Treatment Older Cohort | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Participant-reported) | Diplopia: Up to 10 times a day | 0 Participants |
| Binocular Treatment Older Cohort | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Participant-reported) | Diplopia: Less than once a week | 0 Participants |
| Binocular Treatment Older Cohort | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Participant-reported) | Diplopia: Once a week | 2 Participants |
| Binocular Treatment Older Cohort | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Participant-reported) | Diplopia: Once a day | 0 Participants |
| Binocular Treatment Older Cohort | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Participant-reported) | No diplopia | 37 Participants |
| Binocular Treatment Older Cohort | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Participant-reported) | Diplopia: >10 times a day | 0 Participants |
| Binocular Treatment Older Cohort | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Participant-reported) | All the time | 0 Participants |
| Patching Treatment Older | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Participant-reported) | Diplopia: Once a day | 0 Participants |
| Patching Treatment Older | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Participant-reported) | All the time | 0 Participants |
| Patching Treatment Older | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Participant-reported) | Diplopia: >10 times a day | 0 Participants |
| Patching Treatment Older | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Participant-reported) | Diplopia: Once a week | 1 Participants |
| Patching Treatment Older | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Participant-reported) | Diplopia: Up to 10 times a day | 1 Participants |
| Patching Treatment Older | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Participant-reported) | Diplopia: Less than once a week | 0 Participants |
| Patching Treatment Older | Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Participant-reported) | No diplopia | 56 Participants |
Comparison: The Fisher exact test was used to compare the percentage of participants who reported diplopia (yes/no) at the 16-week visit by treatment group.p-value: 0.05Fisher Exact
Comparison: The frequency of diplopia, across categories of diplopia, was compared between the treatment groups using the Cochran-Armitage trend test.p-value: 0.02Cochran-Armitage trend test
Comparison: The Fisher exact test was used to compare the percentage of participants who reported diplopia (yes/no) at the 16-week visit by treatment group.p-value: >0.99Fisher Exact
Comparison: The frequency of diplopia, across categories of diplopia, was compared between the treatment groups using the Cochran-Armitage trend test.p-value: >0.99Cochran-Armitage trend test
Other Pre-specified
Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Follow-up (Parent-reported)
A standardized questionnaire was administered to participants and their parents to assess the presence and frequency of any diplopia since the last study visit.
Time frame: Across study follow-up visits, up to 16 weeks
Population: Participants whose parent completed a diplopia assessment at any follow-up visit (4-week, 8-week, 12-week, 16-week)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Binocular Treatment Younger | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Follow-up (Parent-reported) | Diplopia: >10 times a day | 0 Participants |
| Binocular Treatment Younger | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Follow-up (Parent-reported) | No diplopia | 172 Participants |
| Binocular Treatment Younger | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Follow-up (Parent-reported) | Diplopia: Up to 10 times a day | 0 Participants |
| Binocular Treatment Younger | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Follow-up (Parent-reported) | Diplopia: Once a week | 2 Participants |
| Binocular Treatment Younger | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Follow-up (Parent-reported) | All the time | 0 Participants |
| Binocular Treatment Younger | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Follow-up (Parent-reported) | Diplopia: Once a day | 2 Participants |
| Binocular Treatment Younger | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Follow-up (Parent-reported) | Diplopia: Less than once a week | 6 Participants |
| Patching Treatment Younger | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Follow-up (Parent-reported) | Diplopia: Once a day | 0 Participants |
| Patching Treatment Younger | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Follow-up (Parent-reported) | Diplopia: Up to 10 times a day | 1 Participants |
| Patching Treatment Younger | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Follow-up (Parent-reported) | All the time | 0 Participants |
| Patching Treatment Younger | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Follow-up (Parent-reported) | Diplopia: Less than once a week | 4 Participants |
| Patching Treatment Younger | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Follow-up (Parent-reported) | Diplopia: >10 times a day | 0 Participants |
| Patching Treatment Younger | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Follow-up (Parent-reported) | Diplopia: Once a week | 1 Participants |
| Patching Treatment Younger | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Follow-up (Parent-reported) | No diplopia | 182 Participants |
| Binocular Treatment Older Cohort | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Follow-up (Parent-reported) | Diplopia: Once a week | 1 Participants |
| Binocular Treatment Older Cohort | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Follow-up (Parent-reported) | No diplopia | 38 Participants |
| Binocular Treatment Older Cohort | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Follow-up (Parent-reported) | Diplopia: Less than once a week | 0 Participants |
| Binocular Treatment Older Cohort | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Follow-up (Parent-reported) | Diplopia: Once a day | 0 Participants |
| Binocular Treatment Older Cohort | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Follow-up (Parent-reported) | Diplopia: Up to 10 times a day | 0 Participants |
| Binocular Treatment Older Cohort | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Follow-up (Parent-reported) | Diplopia: >10 times a day | 0 Participants |
| Binocular Treatment Older Cohort | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Follow-up (Parent-reported) | All the time | 0 Participants |
| Patching Treatment Older | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Follow-up (Parent-reported) | Diplopia: Less than once a week | 2 Participants |
| Patching Treatment Older | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Follow-up (Parent-reported) | All the time | 0 Participants |
| Patching Treatment Older | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Follow-up (Parent-reported) | Diplopia: >10 times a day | 0 Participants |
| Patching Treatment Older | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Follow-up (Parent-reported) | No diplopia | 54 Participants |
| Patching Treatment Older | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Follow-up (Parent-reported) | Diplopia: Once a week | 1 Participants |
| Patching Treatment Older | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Follow-up (Parent-reported) | Diplopia: Up to 10 times a day | 0 Participants |
| Patching Treatment Older | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Follow-up (Parent-reported) | Diplopia: Once a day | 1 Participants |
Other Pre-specified
Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Study Follow-up (Participant-reported)
A standardized questionnaire was administered to participants and their parents to assess the presence and frequency of any diplopia since the last study visit.
Time frame: Across study follow-up visits, up to 16 weeks
Population: Participants who completed a diplopia assessment at any follow-up visit (4-week, 8-week, 12-week, 16-week) during the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Binocular Treatment Younger | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Study Follow-up (Participant-reported) | Diplopia: Once a week | 10 Participants |
| Binocular Treatment Younger | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Study Follow-up (Participant-reported) | All the time | 1 Participants |
| Binocular Treatment Younger | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Study Follow-up (Participant-reported) | Diplopia: Once a day | 8 Participants |
| Binocular Treatment Younger | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Study Follow-up (Participant-reported) | Diplopia: Less than once a week | 6 Participants |
| Binocular Treatment Younger | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Study Follow-up (Participant-reported) | No diplopia | 153 Participants |
| Binocular Treatment Younger | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Study Follow-up (Participant-reported) | Diplopia: >10 times a day | 1 Participants |
| Binocular Treatment Younger | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Study Follow-up (Participant-reported) | Diplopia: Up to 10 times a day | 3 Participants |
| Patching Treatment Younger | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Study Follow-up (Participant-reported) | No diplopia | 167 Participants |
| Patching Treatment Younger | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Study Follow-up (Participant-reported) | Diplopia: Less than once a week | 10 Participants |
| Patching Treatment Younger | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Study Follow-up (Participant-reported) | Diplopia: Once a week | 4 Participants |
| Patching Treatment Younger | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Study Follow-up (Participant-reported) | Diplopia: Once a day | 5 Participants |
| Patching Treatment Younger | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Study Follow-up (Participant-reported) | Diplopia: Up to 10 times a day | 2 Participants |
| Patching Treatment Younger | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Study Follow-up (Participant-reported) | Diplopia: >10 times a day | 0 Participants |
| Patching Treatment Younger | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Study Follow-up (Participant-reported) | All the time | 0 Participants |
| Binocular Treatment Older Cohort | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Study Follow-up (Participant-reported) | Diplopia: Once a day | 2 Participants |
| Binocular Treatment Older Cohort | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Study Follow-up (Participant-reported) | All the time | 0 Participants |
| Binocular Treatment Older Cohort | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Study Follow-up (Participant-reported) | Diplopia: Up to 10 times a day | 0 Participants |
| Binocular Treatment Older Cohort | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Study Follow-up (Participant-reported) | Diplopia: Less than once a week | 1 Participants |
| Binocular Treatment Older Cohort | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Study Follow-up (Participant-reported) | Diplopia: >10 times a day | 0 Participants |
| Binocular Treatment Older Cohort | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Study Follow-up (Participant-reported) | Diplopia: Once a week | 0 Participants |
| Binocular Treatment Older Cohort | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Study Follow-up (Participant-reported) | No diplopia | 36 Participants |
| Patching Treatment Older | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Study Follow-up (Participant-reported) | Diplopia: Once a day | 3 Participants |
| Patching Treatment Older | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Study Follow-up (Participant-reported) | Diplopia: Less than once a week | 1 Participants |
| Patching Treatment Older | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Study Follow-up (Participant-reported) | Diplopia: >10 times a day | 0 Participants |
| Patching Treatment Older | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Study Follow-up (Participant-reported) | No diplopia | 50 Participants |
| Patching Treatment Older | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Study Follow-up (Participant-reported) | Diplopia: Up to 10 times a day | 1 Participants |
| Patching Treatment Older | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Study Follow-up (Participant-reported) | Diplopia: Once a week | 3 Participants |
| Patching Treatment Older | Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Study Follow-up (Participant-reported) | All the time | 0 Participants |
Other Pre-specified
Safety Analysis: Distribution of the Change in Fellow-eye Visual Acuity From Baseline
Monocular distance visual acuity (VA) in current refractive correction (if required) in each eye by a certified examiner using the electronic ATS-HOTV visual acuity protocol for children \<7 years and the E-ETDRS visual acuity protocol for children ≥ 7 years on a study-certified acuity tester displaying single surrounded optotypes. The change in visual acuity is analyzed as logMAR lines for the younger cohort and as letters for the older cohort.
Time frame: 16-week visit
Population: Participants who completed the 16-week visit (regardless of whether or not the visit was completed within the pre-specified analysis window).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Binocular Treatment Younger | Safety Analysis: Distribution of the Change in Fellow-eye Visual Acuity From Baseline | 1 line (5-9 letters) worse | 11 Participants |
| Binocular Treatment Younger | Safety Analysis: Distribution of the Change in Fellow-eye Visual Acuity From Baseline | 1 line (5-9 letters) better | 36 Participants |
| Binocular Treatment Younger | Safety Analysis: Distribution of the Change in Fellow-eye Visual Acuity From Baseline | 2 lines (10-14 letters) worse | 1 Participants |
| Binocular Treatment Younger | Safety Analysis: Distribution of the Change in Fellow-eye Visual Acuity From Baseline | 0 line (within 4 letters) | 128 Participants |
| Binocular Treatment Younger | Safety Analysis: Distribution of the Change in Fellow-eye Visual Acuity From Baseline | 2 lines (10-14 letters) better | 6 Participants |
| Patching Treatment Younger | Safety Analysis: Distribution of the Change in Fellow-eye Visual Acuity From Baseline | 0 line (within 4 letters) | 133 Participants |
| Patching Treatment Younger | Safety Analysis: Distribution of the Change in Fellow-eye Visual Acuity From Baseline | 1 line (5-9 letters) worse | 22 Participants |
| Patching Treatment Younger | Safety Analysis: Distribution of the Change in Fellow-eye Visual Acuity From Baseline | 2 lines (10-14 letters) worse | 1 Participants |
| Patching Treatment Younger | Safety Analysis: Distribution of the Change in Fellow-eye Visual Acuity From Baseline | 1 line (5-9 letters) better | 30 Participants |
| Patching Treatment Younger | Safety Analysis: Distribution of the Change in Fellow-eye Visual Acuity From Baseline | 2 lines (10-14 letters) better | 2 Participants |
| Binocular Treatment Older Cohort | Safety Analysis: Distribution of the Change in Fellow-eye Visual Acuity From Baseline | 0 line (within 4 letters) | 29 Participants |
| Binocular Treatment Older Cohort | Safety Analysis: Distribution of the Change in Fellow-eye Visual Acuity From Baseline | 2 lines (10-14 letters) better | 0 Participants |
| Binocular Treatment Older Cohort | Safety Analysis: Distribution of the Change in Fellow-eye Visual Acuity From Baseline | 1 line (5-9 letters) better | 10 Participants |
| Binocular Treatment Older Cohort | Safety Analysis: Distribution of the Change in Fellow-eye Visual Acuity From Baseline | 1 line (5-9 letters) worse | 0 Participants |
| Binocular Treatment Older Cohort | Safety Analysis: Distribution of the Change in Fellow-eye Visual Acuity From Baseline | 2 lines (10-14 letters) worse | 0 Participants |
| Patching Treatment Older | Safety Analysis: Distribution of the Change in Fellow-eye Visual Acuity From Baseline | 1 line (5-9 letters) worse | 1 Participants |
| Patching Treatment Older | Safety Analysis: Distribution of the Change in Fellow-eye Visual Acuity From Baseline | 1 line (5-9 letters) better | 9 Participants |
| Patching Treatment Older | Safety Analysis: Distribution of the Change in Fellow-eye Visual Acuity From Baseline | 2 lines (10-14 letters) better | 2 Participants |
| Patching Treatment Older | Safety Analysis: Distribution of the Change in Fellow-eye Visual Acuity From Baseline | 0 line (within 4 letters) | 46 Participants |
| Patching Treatment Older | Safety Analysis: Distribution of the Change in Fellow-eye Visual Acuity From Baseline | 2 lines (10-14 letters) worse | 0 Participants |