Trial Outcomes & Findings for Study of Binocular Computer Activities for Treatment of Amblyopia (NCT NCT02200211)

NCT ID: NCT02200211

Last Updated: 2019-02-27

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

485 participants

Primary outcome timeframe

Baseline and 16 weeks

Results posted on

2019-02-27

Participant Flow

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

Participant milestones

Participant milestones
Measure	Binocular Treatment Younger Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Patching Treatment Younger Patching 2 hours per day, 7 days per week	Binocular Treatment Older Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Patching Treatment Older Patching 2 hours per day, 7 days per week
Overall Study STARTED	190	195	40	60
Overall Study Included in 16-week Primary Analysis	177	186	39	56
Overall Study COMPLETED	182	188	39	58
Overall Study NOT COMPLETED	8	7	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Binocular Treatment Younger Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Patching Treatment Younger Patching 2 hours per day, 7 days per week	Binocular Treatment Older Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Patching Treatment Older Patching 2 hours per day, 7 days per week
Overall Study Lost to Follow-up	7	7	1	2
Overall Study Withdrawal by Subject	1	0	0	0

Baseline Characteristics

Descriptive statistics were computed for baseline stereoacuity by treatment group for all participants and a subset of participants with no history of strabismus. The younger (age 5 to \<7 years) and older (age 7 to \<13 years) were analyzed as separate study cohorts. Results of the descriptive analyses are reported as seconds of arc.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Binocular Treatment Younger Cohort (5 to <13 Years) n=190 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Patching Treatment Younger Cohort (5 to <13 Years) n=195 Participants Patching 2 hours per day, 7 days per week Patching 2 hours per day, 7 days per week	Binocular Treatment Older Cohort (13 to <17 Years) n=40 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Patching Treatment Older Cohort (13 to <17 Years) n=60 Participants Patching 2 hours per day, 7 days per week Patching 2 hours per day, 7 days per week	Total n=485 Participants Total of all reporting groups
Age, Categorical <=18 years	190 Participants n=190 Participants	195 Participants n=195 Participants	40 Participants n=40 Participants	60 Participants n=60 Participants	485 Participants n=485 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=190 Participants	0 Participants n=195 Participants	0 Participants n=40 Participants	0 Participants n=60 Participants	0 Participants n=485 Participants
Age, Categorical >=65 years	0 Participants n=190 Participants	0 Participants n=195 Participants	0 Participants n=40 Participants	0 Participants n=60 Participants	0 Participants n=485 Participants
Age, Continuous	8.4 years STANDARD_DEVIATION 1.8 • n=190 Participants	8.6 years STANDARD_DEVIATION 2.0 • n=195 Participants	14.3 years STANDARD_DEVIATION 1.1 • n=40 Participants	14.3 years STANDARD_DEVIATION 1.1 • n=60 Participants	9.7 years STANDARD_DEVIATION 2.9 • n=485 Participants
Age, Customized Age at enrollment, years : 5 to <7	43 Participants n=190 Participants	50 Participants n=195 Participants	0 Participants n=40 Participants	0 Participants n=60 Participants	93 Participants n=485 Participants
Age, Customized Age at enrollment, years : 7 to <9	78 Participants n=190 Participants	62 Participants n=195 Participants	0 Participants n=40 Participants	0 Participants n=60 Participants	140 Participants n=485 Participants
Age, Customized Age at enrollment, years : 9 to <13	69 Participants n=190 Participants	83 Participants n=195 Participants	0 Participants n=40 Participants	0 Participants n=60 Participants	152 Participants n=485 Participants
Age, Customized Age at enrollment, years : 13 to <17	0 Participants n=190 Participants	0 Participants n=195 Participants	40 Participants n=40 Participants	60 Participants n=60 Participants	100 Participants n=485 Participants
Sex: Female, Male Female	98 Participants n=190 Participants	89 Participants n=195 Participants	16 Participants n=40 Participants	26 Participants n=60 Participants	229 Participants n=485 Participants
Sex: Female, Male Male	92 Participants n=190 Participants	106 Participants n=195 Participants	24 Participants n=40 Participants	34 Participants n=60 Participants	256 Participants n=485 Participants
Race/Ethnicity, Customized White	134 Participants n=190 Participants	145 Participants n=195 Participants	30 Participants n=40 Participants	43 Participants n=60 Participants	352 Participants n=485 Participants
Race/Ethnicity, Customized Black/African American	11 Participants n=190 Participants	12 Participants n=195 Participants	2 Participants n=40 Participants	4 Participants n=60 Participants	29 Participants n=485 Participants
Race/Ethnicity, Customized Hispanic or Latino	33 Participants n=190 Participants	24 Participants n=195 Participants	8 Participants n=40 Participants	11 Participants n=60 Participants	76 Participants n=485 Participants
Race/Ethnicity, Customized Asian, American Indian, Alaskan Native	9 Participants n=190 Participants	6 Participants n=195 Participants	0 Participants n=40 Participants	1 Participants n=60 Participants	16 Participants n=485 Participants
Race/Ethnicity, Customized >1 Race	2 Participants n=190 Participants	5 Participants n=195 Participants	0 Participants n=40 Participants	1 Participants n=60 Participants	8 Participants n=485 Participants
Race/Ethnicity, Customized Unknown/not reported	1 Participants n=190 Participants	3 Participants n=195 Participants	0 Participants n=40 Participants	0 Participants n=60 Participants	4 Participants n=485 Participants
Distance Amblyopic-Eye Visual Acuity 20/200 (33-37 Letters)	5 Participants n=190 Participants	4 Participants n=195 Participants	0 Participants n=40 Participants	2 Participants n=60 Participants	11 Participants n=485 Participants
Distance Amblyopic-Eye Visual Acuity 20/160 (38-42 Letters)	6 Participants n=190 Participants	7 Participants n=195 Participants	2 Participants n=40 Participants	5 Participants n=60 Participants	20 Participants n=485 Participants
Distance Amblyopic-Eye Visual Acuity 20/125 (43-47 Letters)	8 Participants n=190 Participants	4 Participants n=195 Participants	4 Participants n=40 Participants	8 Participants n=60 Participants	24 Participants n=485 Participants
Distance Amblyopic-Eye Visual Acuity 20/100 (48-52 Letters)	16 Participants n=190 Participants	12 Participants n=195 Participants	3 Participants n=40 Participants	4 Participants n=60 Participants	35 Participants n=485 Participants
Distance Amblyopic-Eye Visual Acuity 20/80 (53-57 Letters)	30 Participants n=190 Participants	24 Participants n=195 Participants	7 Participants n=40 Participants	12 Participants n=60 Participants	73 Participants n=485 Participants
Distance Amblyopic-Eye Visual Acuity 20/63 (58-62 Letters)	37 Participants n=190 Participants	46 Participants n=195 Participants	6 Participants n=40 Participants	10 Participants n=60 Participants	99 Participants n=485 Participants
Distance Amblyopic-Eye Visual Acuity 20/50 (63-67 Letters)	61 Participants n=190 Participants	52 Participants n=195 Participants	12 Participants n=40 Participants	14 Participants n=60 Participants	139 Participants n=485 Participants
Distance Amblyopic-Eye Visual Acuity 20/40 (68-72 Letters)	27 Participants n=190 Participants	46 Participants n=195 Participants	6 Participants n=40 Participants	5 Participants n=60 Participants	84 Participants n=485 Participants
Baseline Stereoacuity (Seconds of Arc) 4000	69 Participants n=190 Participants	57 Participants n=195 Participants	16 Participants n=40 Participants	29 Participants n=60 Participants	171 Participants n=485 Participants
Baseline Stereoacuity (Seconds of Arc) 2000	28 Participants n=190 Participants	37 Participants n=195 Participants	3 Participants n=40 Participants	7 Participants n=60 Participants	75 Participants n=485 Participants
Baseline Stereoacuity (Seconds of Arc) 800	18 Participants n=190 Participants	26 Participants n=195 Participants	5 Participants n=40 Participants	4 Participants n=60 Participants	53 Participants n=485 Participants
Baseline Stereoacuity (Seconds of Arc) 400	17 Participants n=190 Participants	19 Participants n=195 Participants	7 Participants n=40 Participants	7 Participants n=60 Participants	50 Participants n=485 Participants
Baseline Stereoacuity (Seconds of Arc) 200	23 Participants n=190 Participants	18 Participants n=195 Participants	2 Participants n=40 Participants	4 Participants n=60 Participants	47 Participants n=485 Participants
Baseline Stereoacuity (Seconds of Arc) 100	23 Participants n=190 Participants	23 Participants n=195 Participants	6 Participants n=40 Participants	6 Participants n=60 Participants	58 Participants n=485 Participants
Baseline Stereoacuity (Seconds of Arc) 60	10 Participants n=190 Participants	9 Participants n=195 Participants	1 Participants n=40 Participants	1 Participants n=60 Participants	21 Participants n=485 Participants
Baseline Stereoacuity (Seconds of Arc) 40	2 Participants n=190 Participants	6 Participants n=195 Participants	0 Participants n=40 Participants	2 Participants n=60 Participants	10 Participants n=485 Participants
Baseline Stereoacuity (Seconds of Arc) All participants	2000 Seconds of Arc n=190 Participants • Descriptive statistics were computed for baseline stereoacuity by treatment group for all participants and a subset of participants with no history of strabismus. The younger (age 5 to \<7 years) and older (age 7 to \<13 years) were analyzed as separate study cohorts. Results of the descriptive analyses are reported as seconds of arc.	800 Seconds of Arc n=195 Participants • Descriptive statistics were computed for baseline stereoacuity by treatment group for all participants and a subset of participants with no history of strabismus. The younger (age 5 to \<7 years) and older (age 7 to \<13 years) were analyzed as separate study cohorts. Results of the descriptive analyses are reported as seconds of arc.	800 Seconds of Arc n=40 Participants • Descriptive statistics were computed for baseline stereoacuity by treatment group for all participants and a subset of participants with no history of strabismus. The younger (age 5 to \<7 years) and older (age 7 to \<13 years) were analyzed as separate study cohorts. Results of the descriptive analyses are reported as seconds of arc.	2000 Seconds of Arc n=60 Participants • Descriptive statistics were computed for baseline stereoacuity by treatment group for all participants and a subset of participants with no history of strabismus. The younger (age 5 to \<7 years) and older (age 7 to \<13 years) were analyzed as separate study cohorts. Results of the descriptive analyses are reported as seconds of arc.	NA Seconds of Arc n=485 Participants • Descriptive statistics were computed for baseline stereoacuity by treatment group for all participants and a subset of participants with no history of strabismus. The younger (age 5 to \<7 years) and older (age 7 to \<13 years) were analyzed as separate study cohorts. Results of the descriptive analyses are reported as seconds of arc.
Baseline Stereoacuity (Seconds of Arc) Participants with no history of strabismus	400 Seconds of Arc n=107 Participants • Descriptive statistics were computed for baseline stereoacuity by treatment group for all participants and a subset of participants with no history of strabismus. The younger (age 5 to \<7 years) and older (age 7 to \<13 years) were analyzed as separate study cohorts. Results of the descriptive analyses are reported as seconds of arc.	400 Seconds of Arc n=92 Participants • Descriptive statistics were computed for baseline stereoacuity by treatment group for all participants and a subset of participants with no history of strabismus. The younger (age 5 to \<7 years) and older (age 7 to \<13 years) were analyzed as separate study cohorts. Results of the descriptive analyses are reported as seconds of arc.	400 Seconds of Arc n=22 Participants • Descriptive statistics were computed for baseline stereoacuity by treatment group for all participants and a subset of participants with no history of strabismus. The younger (age 5 to \<7 years) and older (age 7 to \<13 years) were analyzed as separate study cohorts. Results of the descriptive analyses are reported as seconds of arc.	800 Seconds of Arc n=29 Participants • Descriptive statistics were computed for baseline stereoacuity by treatment group for all participants and a subset of participants with no history of strabismus. The younger (age 5 to \<7 years) and older (age 7 to \<13 years) were analyzed as separate study cohorts. Results of the descriptive analyses are reported as seconds of arc.	NA Seconds of Arc n=250 Participants • Descriptive statistics were computed for baseline stereoacuity by treatment group for all participants and a subset of participants with no history of strabismus. The younger (age 5 to \<7 years) and older (age 7 to \<13 years) were analyzed as separate study cohorts. Results of the descriptive analyses are reported as seconds of arc.
Amblyopia Cause Strabismus	22 Participants n=190 Participants	44 Participants n=195 Participants	5 Participants n=40 Participants	9 Participants n=60 Participants	80 Participants n=485 Participants
Amblyopia Cause Anisometropia	107 Participants n=190 Participants	92 Participants n=195 Participants	22 Participants n=40 Participants	29 Participants n=60 Participants	250 Participants n=485 Participants
Amblyopia Cause Strabismus/anisometropia combined	61 Participants n=190 Participants	59 Participants n=195 Participants	13 Participants n=40 Participants	22 Participants n=60 Participants	155 Participants n=485 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Binocular Treatment Older Cohort n=186 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Younger n=177 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Older Cohort Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Patching Treatment Older Cohort Patching 2 hours per day, 7 days per week
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 Interval 1.17 to 1.54	1.05 LogMAR lines Interval 0.85 to 1.24	—	—
Change in Distance Visual Acuity From Baseline in the Younger Cohort (5 to <13 Years) Unadjusted	1.32 LogMAR lines Interval 1.14 to 1.51	1.08 LogMAR lines Interval 0.86 to 1.29	—	—

PRIMARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Binocular Treatment Older Cohort n=186 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Younger n=177 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Older Cohort Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Patching Treatment Older Cohort Patching 2 hours per day, 7 days per week
Mean Amblyopic Eye Visual Acuity (Younger Cohort)	0.35 LogMAR Standard Deviation 0.20	0.41 LogMAR Standard Deviation 0.21	—	—

PRIMARY outcome

Timeframe: 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)

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.

Outcome measures

Outcome measures
Measure	Binocular Treatment Older Cohort n=56 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Younger n=39 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Older Cohort Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Patching Treatment Older Cohort Patching 2 hours per day, 7 days per week
Mean Change in Amblyopic-eye Visual Acuity in the Older Cohort (13 to <17 Years) Unadjusted	6.5 letters Interval 4.4 to 8.5	3.5 letters Interval 1.3 to 5.7	—	—
Mean Change in Amblyopic-eye Visual Acuity in the Older Cohort (13 to <17 Years) Adjusted for baseline visual acuity	6.3 letters Interval 4.4 to 8.3	3.7 letters Interval 1.3 to 6.0	—	—

PRIMARY outcome

Timeframe: 16 weeks

Population: Participants that completed 16-week visit within pre-specified analysis window (148 to 196 days after randomization)

Outcome measures

Outcome measures
Measure	Binocular Treatment Older Cohort n=56 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Younger n=39 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Older Cohort Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Patching Treatment Older Cohort Patching 2 hours per day, 7 days per week
Mean Amblyopic-eye Visual Acuity in the Older Cohort (13 to <17 Years)	62.5 letters Standard Deviation 11.6	62.0 letters Standard Deviation 9.7	—	—

PRIMARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Binocular Treatment Older Cohort n=186 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Younger n=177 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Older Cohort n=39 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Patching Treatment Older Cohort n=56 Participants Patching 2 hours per day, 7 days per week
Distribution of Change in Amblyopic-eye Visual Acuity 1 LogMAR line (5-9 letters) worse	6 Participants	12 Participants	1 Participants	1 Participants
Distribution of Change in Amblyopic-eye Visual Acuity 2 LogMAR lines (10-14 letters) worse	0 Participants	1 Participants	0 Participants	0 Participants
Distribution of Change in Amblyopic-eye Visual Acuity ≥ 3 LogMAR lines (≥ 15 letters) better	29 Participants	19 Participants	2 Participants	7 Participants
Distribution of Change in Amblyopic-eye Visual Acuity 2 LogMAR lines (10-14 letters) better	36 Participants	32 Participants	4 Participants	10 Participants
Distribution of Change in Amblyopic-eye Visual Acuity 1 LogMAR line (5-9 letters) better	46 Participants	47 Participants	9 Participants	19 Participants
Distribution of Change in Amblyopic-eye Visual Acuity 0 LogMAR line (within 4 letters)	69 Participants	64 Participants	22 Participants	18 Participants
Distribution of Change in Amblyopic-eye Visual Acuity ≥3 LogMAR lines (≥ 15 letters) worse	0 Participants	2 Participants	1 Participants	1 Participants

PRIMARY outcome

Timeframe: At 16 weeks

Population: Participants that completed 16-week visit within pre-specified analysis window (148 to 196 days after randomization)

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).

Outcome measures

Outcome measures
Measure	Binocular Treatment Older Cohort n=186 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Younger n=177 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Older Cohort n=39 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Patching Treatment Older Cohort n=56 Participants Patching 2 hours per day, 7 days per week
Distribution of Amblyopic-eye Visual Acuity 20/125 (43-47 letters)	2 Participants	10 Participants	2 Participants	4 Participants
Distribution of Amblyopic-eye Visual Acuity 20/200 (33-37 letters)	1 Participants	2 Participants	1 Participants	1 Participants
Distribution of Amblyopic-eye Visual Acuity 20/160 (38-42 letters)	3 Participants	2 Participants	0 Participants	1 Participants
Distribution of Amblyopic-eye Visual Acuity 20/100 (48-52 letters)	7 Participants	12 Participants	4 Participants	7 Participants
Distribution of Amblyopic-eye Visual Acuity 20/80 (53-57 letters)	17 Participants	18 Participants	5 Participants	8 Participants
Distribution of Amblyopic-eye Visual Acuity 20/63 (58-62 letters)	22 Participants	25 Participants	5 Participants	4 Participants
Distribution of Amblyopic-eye Visual Acuity 20/50 (63-67 letters)	38 Participants	30 Participants	11 Participants	9 Participants
Distribution of Amblyopic-eye Visual Acuity 20/40 (68-72 letters)	37 Participants	32 Participants	6 Participants	7 Participants
Distribution of Amblyopic-eye Visual Acuity 20/32 (73-77 letters)	27 Participants	33 Participants	4 Participants	11 Participants
Distribution of Amblyopic-eye Visual Acuity 20/25 (78-82 letters)	22 Participants	8 Participants	0 Participants	3 Participants
Distribution of Amblyopic-eye Visual Acuity 20/20 (83-87 letters)	10 Participants	3 Participants	1 Participants	1 Participants
Distribution of Amblyopic-eye Visual Acuity 20/16 (88-92 letters)	0 Participants	2 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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).

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).

Outcome measures

Outcome measures
Measure	Binocular Treatment Older Cohort n=186 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Younger n=177 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Older Cohort n=39 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Patching Treatment Older Cohort n=56 Participants Patching 2 hours per day, 7 days per week
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	51 Participants	6 Participants	17 Participants

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Binocular Treatment Older Cohort n=186 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Younger n=177 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Older Cohort n=39 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Patching Treatment Older Cohort n=56 Participants Patching 2 hours per day, 7 days per week
Number of Participants With Resolution of Amblyopia	18 Participants	8 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Binocular Treatment Older Cohort n=193 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Younger n=186 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Older Cohort Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Patching Treatment Older Cohort Patching 2 hours per day, 7 days per week
Time Course of Visual Acuity Improvement 4-week visit	0.76 logMAR lines Standard Deviation 1.09	0.53 logMAR lines Standard Deviation 1.14	—	—
Time Course of Visual Acuity Improvement 8-week visit	1.03 logMAR lines Standard Deviation 1.23	0.76 logMAR lines Standard Deviation 1.18	—	—
Time Course of Visual Acuity Improvement 12-week visit	1.21 logMAR lines Standard Deviation 1.26	0.90 logMAR lines Standard Deviation 1.37	—	—
Time Course of Visual Acuity Improvement 16-week visit	1.32 logMAR lines Standard Deviation 1.26	1.08 logMAR lines Standard Deviation 1.45	—	—

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Binocular Treatment Older Cohort n=186 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Younger n=177 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Older Cohort Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Patching Treatment Older Cohort Patching 2 hours per day, 7 days per week
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	0.8 LogMAR lines Standard Deviation 1.2	—	—
Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups Female	1.4 LogMAR lines Standard Deviation 1.2	1.2 LogMAR lines Standard Deviation 1.5	—	—
Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups Male	1.3 LogMAR lines Standard Deviation 1.3	1.0 LogMAR lines Standard Deviation 1.4	—	—
Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups White/Non-Hispanic	1.3 LogMAR lines Standard Deviation 1.2	1.0 LogMAR lines Standard Deviation 1.5	—	—
Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups Non-White or Hispanic	1.3 LogMAR lines Standard Deviation 1.4	1.2 LogMAR lines Standard Deviation 1.5	—	—
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	1.9 LogMAR lines Standard Deviation 1.8	—	—
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	1.1 LogMAR lines Standard Deviation 1.6	—	—
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	1.3 LogMAR lines Standard Deviation 1.6	—	—
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	1.0 LogMAR lines Standard Deviation 1.3	—	—
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	0.8 LogMAR lines Standard Deviation 1.2	—	—
Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups Baseline stereoacuity: Nil	1.1 LogMAR lines Standard Deviation 1.1	0.7 LogMAR lines Standard Deviation 1.3	—	—
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	1.3 LogMAR lines Standard Deviation 1.5	—	—
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	1.1 LogMAR lines Standard Deviation 1.3	—	—
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	0.9 LogMAR lines Standard Deviation 1.7	—	—
Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups No prior amblyopia treatment	2.2 LogMAR lines Standard Deviation 1.3	1.9 LogMAR lines Standard Deviation 1.5	—	—
Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups Prior amblyopia treatment	1.1 LogMAR lines Standard Deviation 1.2	0.8 LogMAR lines Standard Deviation 1.4	—	—
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	2.5 LogMAR lines Standard Deviation 1.5	—	—
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	1.4 LogMAR lines Standard Deviation 1.9	—	—
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	1.3 LogMAR lines Standard Deviation 1.2	—	—
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	0.7 LogMAR lines Standard Deviation 1.2	—	—

SECONDARY outcome

Timeframe: 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).

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).

Outcome measures

Outcome measures
Measure	Binocular Treatment Older Cohort n=56 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Younger n=39 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Older Cohort Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Patching Treatment Older Cohort Patching 2 hours per day, 7 days per week
Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups Female	6.0 Letters Standard Deviation 6.7	1.0 Letters Standard Deviation 6.8	—	—
Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups Male	6.8 Letters Standard Deviation 8.4	5.0 Letters Standard Deviation 6.4	—	—
Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups White/Non-Hispanic	6.4 Letters Standard Deviation 7.6	3.6 Letters Standard Deviation 7.1	—	—
Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups Non-White or Hispanic	6.7 Letters Standard Deviation 8.2	3.2 Letters Standard Deviation 6.1	—	—
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	5.2 Letters Standard Deviation 7.8	—	—
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	3.2 Letters Standard Deviation 2.8	—	—
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	2.9 Letters Standard Deviation 4.2	—	—
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	-0.4 Letters Standard Deviation 10.9	—	—
Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups No prior amblyopia treatment	10.3 Letters Standard Deviation 8.0	2.9 Letters Standard Deviation 6.4	—	—
Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups Prior amblyopia treatment	6.0 Letters Standard Deviation 7.6	3.6 Letters Standard Deviation 7.0	—	—
Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups Baseline stereoacuity: Nil	5.7 Letters Standard Deviation 7.6	4.1 Letters Standard Deviation 7.7	—	—
Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups Baseline stereoacuity: Better than Nil	7.2 Letters Standard Deviation 7.8	3.0 Letters Standard Deviation 6.2	—	—
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	2.0 Letters Standard Deviation 6.1	—	—
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	5.7 Letters Standard Deviation 7.4	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Binocular Treatment Older Cohort n=188 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Younger n=182 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Older Cohort n=39 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Patching Treatment Older Cohort n=58 Participants Patching 2 hours per day, 7 days per week
Distribution of Stereoacuity Scores 40 seconds of arc	4 Participants	12 Participants	1 Participants	5 Participants
Distribution of Stereoacuity Scores Missing/Not done	0 Participants	1 Participants	0 Participants	0 Participants
Distribution of Stereoacuity Scores 4000 seconds of arc	50 Participants	62 Participants	13 Participants	25 Participants
Distribution of Stereoacuity Scores 2000 seconds of arc	32 Participants	32 Participants	6 Participants	11 Participants
Distribution of Stereoacuity Scores 800 seconds of arc	28 Participants	19 Participants	6 Participants	7 Participants
Distribution of Stereoacuity Scores 400 seconds of arc	17 Participants	14 Participants	3 Participants	4 Participants
Distribution of Stereoacuity Scores 200 seconds of arc	27 Participants	15 Participants	2 Participants	2 Participants
Distribution of Stereoacuity Scores 100 seconds of arc	19 Participants	17 Participants	6 Participants	2 Participants
Distribution of Stereoacuity Scores 60 seconds of arc	11 Participants	10 Participants	2 Participants	2 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Binocular Treatment Older Cohort n=188 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Younger n=181 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Older Cohort n=39 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Patching Treatment Older Cohort n=58 Participants Patching 2 hours per day, 7 days per week
Median Stereoacuity Score (Seconds of Arc) All participants	800 Seconds of arc Interval 40.0 to 4000.0	2000 Seconds of arc Interval 40.0 to 4000.0	800 Seconds of arc Interval 40.0 to 4000.0	2000 Seconds of arc Interval 40.0 to 4000.0
Median Stereoacuity Score (Seconds of Arc) Participants with no history of strabismus	400 Seconds of arc Interval 40.0 to 4000.0	400 Seconds of arc Interval 40.0 to 4000.0	400 Seconds of arc Interval 40.0 to 4000.0	2000 Seconds of arc Interval 40.0 to 4000.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Binocular Treatment Older Cohort n=90 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Younger n=105 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Older Cohort n=21 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Patching Treatment Older Cohort n=27 Participants Patching 2 hours per day, 7 days per week
Distribution of Stereoacuity Scores (Participants With no History of Strabismus) 40 seconds of arc	3 Participants	10 Participants	1 Participants	5 Participants
Distribution of Stereoacuity Scores (Participants With no History of Strabismus) Missing/Not done	0 Participants	1 Participants	0 Participants	0 Participants
Distribution of Stereoacuity Scores (Participants With no History of Strabismus) 4000 seconds of arc	13 Participants	23 Participants	4 Participants	10 Participants
Distribution of Stereoacuity Scores (Participants With no History of Strabismus) 2000 seconds of arc	12 Participants	14 Participants	1 Participants	4 Participants
Distribution of Stereoacuity Scores (Participants With no History of Strabismus) 800 seconds of arc	14 Participants	12 Participants	4 Participants	3 Participants
Distribution of Stereoacuity Scores (Participants With no History of Strabismus) 400 seconds of arc	10 Participants	10 Participants	2 Participants	1 Participants
Distribution of Stereoacuity Scores (Participants With no History of Strabismus) 200 seconds of arc	17 Participants	12 Participants	2 Participants	1 Participants
Distribution of Stereoacuity Scores (Participants With no History of Strabismus) 100 seconds of arc	15 Participants	14 Participants	5 Participants	1 Participants
Distribution of Stereoacuity Scores (Participants With no History of Strabismus) 60 seconds of arc	6 Participants	9 Participants	2 Participants	2 Participants

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Binocular Treatment Older Cohort n=188 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Younger n=181 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Older Cohort n=39 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Patching Treatment Older Cohort n=58 Participants Patching 2 hours per day, 7 days per week
Distribution of Change in Stereoacuity Scores From Baseline 2 or more levels worse	24 Participants	19 Participants	4 Participants	8 Participants
Distribution of Change in Stereoacuity Scores From Baseline Within 1 level	122 Participants	130 Participants	29 Participants	38 Participants
Distribution of Change in Stereoacuity Scores From Baseline 2 or more levels better	42 Participants	32 Participants	6 Participants	12 Participants

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Binocular Treatment Older Cohort n=90 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Younger n=104 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Older Cohort n=21 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Patching Treatment Older Cohort n=27 Participants Patching 2 hours per day, 7 days per week
Distribution of Change in Stereoacuity Scores From Baseline (Participants With no History of Strabismus) 2 or more levels worse	14 Participants	12 Participants	2 Participants	4 Participants
Distribution of Change in Stereoacuity Scores From Baseline (Participants With no History of Strabismus) Within 1 level	58 Participants	67 Participants	15 Participants	16 Participants
Distribution of Change in Stereoacuity Scores From Baseline (Participants With no History of Strabismus) 2 or more levels better	18 Participants	25 Participants	4 Participants	7 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Binocular Treatment Older Cohort n=38 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Younger n=176 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Older Cohort Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Patching Treatment Older Cohort Patching 2 hours per day, 7 days per week
Binocular Treatment Group: Adherence and Fellow-eye Contrast (iPad Log File Data) Completed >75% prescribed game play	5 Participants	39 Participants	—	—
Binocular Treatment Group: Adherence and Fellow-eye Contrast (iPad Log File Data) Fellow-eye contrast of 100% (16 weeks)	23 Participants	86 Participants	—	—
Binocular Treatment Group: Adherence and Fellow-eye Contrast (iPad Log File Data) Fellow-eye contrast of 20% or worse (16 weeks)	3 Participants	31 Participants	—	—
Binocular Treatment Group: Adherence and Fellow-eye Contrast (iPad Log File Data) Fellow-eye contrast of 100% (4 weeks)	6 Participants	35 Participants	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Binocular Treatment Older Cohort n=38 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Younger n=176 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Older Cohort Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Patching Treatment Older Cohort Patching 2 hours per day, 7 days per week
Binocular Treatment Group: Median Adherence With Prescribed Game Play (iPad Log File Data)	21 % of prescribed treatment completed Interval 13.0 to 38.0	46 % of prescribed treatment completed Interval 20.0 to 72.0	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Binocular Treatment Older Cohort n=186 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Younger n=177 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Older Cohort n=39 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Patching Treatment Older Cohort n=56 Participants Patching 2 hours per day, 7 days per week
Percentage of Participants Reporting >75% of Prescribed Treatment Completed (Subjective Measures of Adherence)	172 Participants	118 Participants	24 Participants	42 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Entire study period, up to 16 weeks

Population: All randomized participants in 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.

Outcome measures

Outcome measures
Measure	Binocular Treatment Older Cohort n=195 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Younger n=190 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Older Cohort n=40 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Patching Treatment Older Cohort n=60 Participants Patching 2 hours per day, 7 days per week
Participants Who Received Non-protocol, Alternative Treatment During the Study	0 Participants	4 Participants	0 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Binocular Treatment Older Cohort n=188 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Younger n=182 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Older Cohort n=39 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Patching Treatment Older Cohort n=58 Participants Patching 2 hours per day, 7 days per week
Safety Analysis: Distribution of the Change in Fellow-eye Visual Acuity From Baseline 2 lines (10-14 letters) better	2 Participants	6 Participants	0 Participants	2 Participants
Safety Analysis: Distribution of the Change in Fellow-eye Visual Acuity From Baseline 1 line (5-9 letters) better	30 Participants	36 Participants	10 Participants	9 Participants
Safety Analysis: Distribution of the Change in Fellow-eye Visual Acuity From Baseline 0 line (within 4 letters)	133 Participants	128 Participants	29 Participants	46 Participants
Safety Analysis: Distribution of the Change in Fellow-eye Visual Acuity From Baseline 1 line (5-9 letters) worse	22 Participants	11 Participants	0 Participants	1 Participants
Safety Analysis: Distribution of the Change in Fellow-eye Visual Acuity From Baseline 2 lines (10-14 letters) worse	1 Participants	1 Participants	0 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Binocular Treatment Older Cohort n=188 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Younger n=182 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Older Cohort Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Patching Treatment Older Cohort Patching 2 hours per day, 7 days per week
Safety Analysis: Change in Fellow-eye Visual Acuity From Baseline (Younger Cohort)	0.14 logMAR lines Interval 0.04 to 0.24	0.30 logMAR lines Interval 0.2 to 0.4	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Binocular Treatment Older Cohort n=58 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Younger n=39 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Older Cohort Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Patching Treatment Older Cohort Patching 2 hours per day, 7 days per week
Safety Analysis: Change in Fellow-eye Visual Acuity From Baseline (Older Cohort)	2.0 Letters Interval 1.3 to 2.8	2.2 Letters Interval 1.2 to 3.1	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Binocular Treatment Older Cohort n=188 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Younger n=182 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Older Cohort n=39 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Patching Treatment Older Cohort n=58 Participants Patching 2 hours per day, 7 days per week
Safety Analysis: Development of a New Tropia and/or Worsening of a Pre-existing Deviation by 10 pd	11 Participants	16 Participants	3 Participants	3 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 16 weeks

Population: Participants whose parent completed a 16-week diplopia assessment.

A standardized questionnaire was administered to participants and their parents to assess the presence and frequency of any diplopia since the last study visit.

Outcome measures

Outcome measures
Measure	Binocular Treatment Older Cohort n=187 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Younger n=182 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Older Cohort n=38 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Patching Treatment Older Cohort n=57 Participants Patching 2 hours per day, 7 days per week
Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Parent-reported) No diplopia	185 Participants	176 Participants	37 Participants	56 Participants
Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Parent-reported) Diplopia: Less than once a week	0 Participants	5 Participants	1 Participants	1 Participants
Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Parent-reported) Diplopia: Once a week	2 Participants	1 Participants	0 Participants	0 Participants
Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Parent-reported) Diplopia: Once a day	0 Participants	0 Participants	0 Participants	0 Participants
Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Parent-reported) Diplopia: Up to 10 times a day	0 Participants	0 Participants	0 Participants	0 Participants
Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Parent-reported) Diplopia: >10 times a day	0 Participants	0 Participants	0 Participants	0 Participants
Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Parent-reported) All the time	0 Participants	0 Participants	0 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 16 weeks

Population: Participants who completed a 16-week diplopia assessment.

A standardized questionnaire was administered to participants and their parents to assess the presence and frequency of any diplopia since the last study visit.

Outcome measures

Outcome measures
Measure	Binocular Treatment Older Cohort n=188 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Younger n=182 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Older Cohort n=39 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Patching Treatment Older Cohort n=58 Participants Patching 2 hours per day, 7 days per week
Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Participant-reported) No diplopia	181 Participants	166 Participants	37 Participants	56 Participants
Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Participant-reported) Diplopia: Less than once a week	3 Participants	5 Participants	0 Participants	0 Participants
Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Participant-reported) Diplopia: Once a week	3 Participants	5 Participants	2 Participants	1 Participants
Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Participant-reported) Diplopia: Once a day	1 Participants	2 Participants	0 Participants	0 Participants
Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Participant-reported) Diplopia: Up to 10 times a day	0 Participants	3 Participants	0 Participants	1 Participants
Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Participant-reported) Diplopia: >10 times a day	0 Participants	0 Participants	0 Participants	0 Participants
Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Participant-reported) All the time	0 Participants	1 Participants	0 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 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)

A standardized questionnaire was administered to participants and their parents to assess the presence and frequency of any diplopia since the last study visit.

Outcome measures

Outcome measures
Measure	Binocular Treatment Older Cohort n=188 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Younger n=182 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Older Cohort n=39 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Patching Treatment Older Cohort n=58 Participants Patching 2 hours per day, 7 days per week
Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Follow-up (Parent-reported) All the time	0 Participants	0 Participants	0 Participants	0 Participants
Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Follow-up (Parent-reported) No diplopia	182 Participants	172 Participants	38 Participants	54 Participants
Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Follow-up (Parent-reported) Diplopia: Less than once a week	4 Participants	6 Participants	0 Participants	2 Participants
Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Follow-up (Parent-reported) Diplopia: Once a week	1 Participants	2 Participants	1 Participants	1 Participants
Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Follow-up (Parent-reported) Diplopia: Once a day	0 Participants	2 Participants	0 Participants	1 Participants
Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Follow-up (Parent-reported) Diplopia: Up to 10 times a day	1 Participants	0 Participants	0 Participants	0 Participants
Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Follow-up (Parent-reported) Diplopia: >10 times a day	0 Participants	0 Participants	0 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

A standardized questionnaire was administered to participants and their parents to assess the presence and frequency of any diplopia since the last study visit.

Outcome measures

Outcome measures
Measure	Binocular Treatment Older Cohort n=188 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Younger n=182 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Binocular Treatment Older Cohort n=39 Participants Binocular computer game play 1 hour per day, 7 days per week (minimum of 4 days per week) iPad®: Binocular therapy on iPad®	Patching Treatment Older Cohort n=58 Participants Patching 2 hours per day, 7 days per week
Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Study Follow-up (Participant-reported) No diplopia	167 Participants	153 Participants	36 Participants	50 Participants
Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Study Follow-up (Participant-reported) Diplopia: Less than once a week	10 Participants	6 Participants	1 Participants	1 Participants
Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Study Follow-up (Participant-reported) Diplopia: Once a week	4 Participants	10 Participants	0 Participants	3 Participants
Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Study Follow-up (Participant-reported) Diplopia: Once a day	5 Participants	8 Participants	2 Participants	3 Participants
Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Study Follow-up (Participant-reported) Diplopia: Up to 10 times a day	2 Participants	3 Participants	0 Participants	1 Participants
Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Study Follow-up (Participant-reported) Diplopia: >10 times a day	0 Participants	1 Participants	0 Participants	0 Participants
Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Study Follow-up (Participant-reported) All the time	0 Participants	1 Participants	0 Participants	0 Participants

Adverse Events

Binocular Treatment Younger

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Patching Treatment Younger

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Binocular Treatment Older

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Patching Treatment Older

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Raymond Kraker, M.S.P.H., Director of PEDIG Coordinating Center

Jaeb Center for Health Research

Phone: 813-975-8690

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place