ATS20: Binocular Dig Rush Game Treatment for Amblyopia

• Sponsor: Jaeb Center for Health Research (Other)
• Overall Status: Completed
• CT.gov ID: NCT02983552
• Collaborator: Pediatric Eye Disease Investigator Group (Other), National Eye Institute (NEI) (NIH)
• Enrollment: 320
• Locations: 62
• Arms: 2
• Actual Duration (Months): 40.3
• Patients Per Site: 5.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

To compare the efficacy of 1 hour/day of binocular game play 5 days per week plus spectacle correction with spectacle correction only, for treatment of amblyopia in children 4 to <13 years of age.

Condition or Disease	Intervention/Treatment	Phase
Amblyopia	Other: iPad®; Other: Spectacle correction	N/A

Detailed Description

The purpose of the study is to compare the efficacy of 1 hour/day of binocular game play 5 days per week plus spectacle correction with spectacle correction only, for treatment of amblyopia in children 4 to <13 years of age.

Study Design

• Study Type: Interventional
• Actual Enrollment: 320 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Binocular Dig Rush Game Treatment for Amblyopia
• Actual Study Start Date: Mar 2, 2017
• Actual Primary Completion Date: Apr 20, 2020
• Actual Study Completion Date: Jul 10, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Binocular Computer Game Treatment Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required)	Other: iPad®; Binocular therapy using a Dig Rush application on an iPad®
Active Comparator: Continued Spectacle Correction Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks.	Other: Spectacle correction; Spectacle correction for all waking hours, 7 days per week

Outcome Measures

Primary Outcome Measures

1. Mean Change in Amblyopic-eye Visual Acuity (VA) Older Cohort [Baseline and 4 weeks]

   The primary objective is to compare the efficacy of 4 weeks of treatment with 1 hour/day of binocular game play 5 days per week plus spectacle correction to treatment with spectacle correction alone (control). 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. Adjusted values have been adjusted for amblyopic-eye visual acuity at randomization.

2. Mean Visual Acuity (VA) in Amblyopic-eye (Older Cohort) [4 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.

3. Mean Change in Amblyopic-eye Visual Acuity (VA) in Older Cohort [Baseline and 8 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.

4. Mean Visual Acuity (VA) in Amblyopic-eye (Older Cohort) [8 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.

5. Mean Change in Amblyopic-eye Visual Acuity (VA) Younger Cohort [baseline and 4 weeks]

   The primary objective is to compare the efficacy of 4 weeks of treatment with 1 hour/day of binocular game play 5 days per week plus spectacle correction to treatment with spectacle correction alone (control). 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 younger cohort, the level of VA is measured in logMAR (approximate range: -0.2 to 1.2, lower scores indicate better VA) and change in VA from baseline is measured in logMAR lines (positive values indicate improvement), defined as 10 times the difference in logMAR between enrollment and follow-up. Adjusted values have been adjusted for amblyopic-eye visual acuity at randomization.

6. Mean Visual Acuity (VA) in Amblyopic-eye (Younger Cohort) [4 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 younger cohort, the level of VA is measured in logMAR (approximate range: -0.2 to 1.2, lower scores indicate better VA) and change in VA from baseline is measured in logMAR lines (positive values indicate improvement), defined as 10 times the difference in logMAR between enrollment and follow-up.

7. Mean Change in Amblyopic-eye Visual Acuity (VA) in Younger Cohort [Baseline and 8 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 younger cohort, the level of VA is measured in logMAR (approximate range: -0.2 to 1.2, lower scores indicate better VA) and change in VA from baseline is measured in logMAR lines (positive values indicate improvement), defined as 10 times the difference in logMAR between enrollment and follow-up.

8. Mean Visual Acuity (VA) in Amblyopic-eye (Younger Cohort) [8 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 younger cohort, the level of VA is measured in logMAR (approximate range: -0.2 to 1.2, lower scores indicate better VA) and change in VA from baseline is measured in logMAR lines (positive values indicate improvement), defined as 10 times the difference in logMAR between enrollment and follow-up.

Secondary Outcome Measures

1. VA Improvement at 4 Weeks Defined as a Binary Outcome [At 4 weeks]

   A secondary analysis will estimate the proportion of subjects with amblyopic-eye VA improvement of ≥ 2 logMAR lines (≥ 10 letters if E-ETDRS) at 4 weeks after baseline.

2. VA Improvement at 8 Weeks Defined as a Binary Outcome [At 8 weeks]

   A secondary analysis will estimate the proportion of subjects with amblyopic-eye VA improvement of ≥ 2 logMAR lines (≥ 10 letters if E-ETDRS) at 8 weeks after baseline.

3. Distribution of Stereoacuity Scores at 4 Weeks [4 weeks]

   Stereoacuity will be tested at near in current refractive correction using the Randot Butterfly and Randot Preschool stereoacuity tests. 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.

4. Distribution of Change in Stereoacuity Scores From Baseline [4 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 4-week stereoacuity scores.

5. Distribution of Stereoacuity Scores at 8 Weeks [8 weeks]

   Stereoacuity will be tested at near in current refractive correction using the Randot Butterfly and Randot Preschool stereoacuity tests. 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.

6. Distribution of Change in Stereoacuity Scores From Baseline [8 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 8-week stereoacuity scores.

7. Distribution of Stereoacuity Scores (Participants With no History of Strabismus) [4 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.

8. Distribution of Change in Stereoacuity Scores From Baseline (Participants With no History of Strabismus) [4 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 4-week stereoacuity scores.

9. Distribution of Stereoacuity Scores (Participants With no History of Strabismus) [8 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.

10. Distribution of Change in Stereoacuity Scores From Baseline (Participants With no History of Strabismus) [8 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 4-week stereoacuity scores.

11. Binocular Therapy: Treatment Compliance and Fellow-Eye Contrast [4 weeks]

    Data from the automated iPad log files will be used to provide an objective measure of compliance with binocular treatment (participants completion of >75% of prescribed game play). The total amount of game play will be computed for the initial 4 weeks of treatment for the binocular treatment group, as well as throughout 8 weeks. Secondary analyses will evaluate the relationship between the total amount of game play with (1) change in VA and (2) change in stereoacuity after the first 4 weeks of binocular treatment. Data from the automated iPad log files will also be used to assess game performance as measured by the fellow-eye contrast.

12. Binocular Therapy: Treatment Compliance and Fellow-Eye Contrast [8 weeks]

    Data from the automated iPad log files will be used to assess game performance as measured by the fellow-eye contrast. The level and change in fellow-eye contrast will be computed for the initial 4 weeks of treatment for the binocular treatment group. Secondary analyses will evaluate the relationship between the change in fellow-eye contrast with (1) change in VA and (2) change in stereoacuity after the first 8 weeks of binocular treatment. Data from the automated iPad log files will also be used to assess game performance as measured by the fellow-eye contrast.

13. Treatment Compliance With Spectacle Wear [4 weeks]

    Parent-reported adherence with spectacle wear (excluding participants with reported compliance of 'N/A') for the initial 4 weeks. Patient reported to have completed >75% of spectacle wear at 4 weeks.

14. Treatment Compliance With Spectacle Wear [8 weeks]

    Parent-reported adherence with spectacle wear (excluding participants with reported compliance of 'N/A') across 8 weeks. Patient reported to have completed >75% of spectacle wear at 8 weeks.

15. Mean Change in Fellow Eye Visual Acuity at 4 Weeks (Older Cohort) [Baseline and 4 weeks]

    The mean change in fellow-eye VA from baseline to 4 weeks will be calculated and compared between treatment groups using ANCOVA with adjustment for baseline VA.

16. Mean Change in Fellow Eye VA at 8 Weeks (Older Cohort) [Baseline and 8 weeks]

    The mean change in fellow-eye VA from baseline to 8 weeks will be calculated and compared between treatment groups using ANCOVA with adjustment for baseline VA.

17. Ocular Alignment at 4 Weeks [4 weeks]

    The proportion of subjects with development of new strabismus (no heterotropia at baseline and the presence of near and/or distance heterotropia at 4 weeks) or an increase from baseline ≥10∆ in a pre-existing strabismus at 4 weeks will be reported by treatment group and compared using Barnard's exact test. 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 4-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.

18. Ocular Alignment at 8 Weeks [8 weeks]

    The proportion of subjects with development of new strabismus (no heterotropia at baseline and the presence of near and/or distance heterotropia at 8 weeks) or an increase from baseline ≥10∆ in a pre-existing strabismus at 8 weeks will be reported by treatment group and compared using Barnard's exact test. 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 8-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.

19. Distribution of Diplopia Frequency at 4 Weeks (Participant-reported) [4 weeks]

    The proportion of subjects with each level of diplopia frequency will be reported by treatment group at 4 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.

20. Distribution of Diplopia Frequency at 8 Weeks (Participant-reported) [8 weeks]

    The proportion of subjects with each level of diplopia frequency will be reported by treatment group at 8 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.

21. Change in Diplopia Frequency From Baseline to 4 Weeks (Participant-reported) [4 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. Change in diplopia frequency from baseline to 4 weeks was reported categorically.

22. Change in Diplopia Frequency From Baseline to 8 Weeks (Participant-reported) [8 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. Change in diplopia frequency from baseline to 8 weeks was reported categorically.

23. Distribution of Diplopia Frequency at 4 Weeks (Parent-reported) [4 weeks]

    The proportion of subjects with each level of diplopia frequency will be reported by treatment group at 4 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.

24. Distribution of Diplopia Frequency at 8 Weeks (Parent-reported) [8 weeks]

    The proportion of subjects with each level of diplopia frequency will be reported by treatment group at 8 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.

25. Change in Diplopia Frequency From Baseline to 4 Weeks (Parent-reported) [4 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. Change in diplopia frequency from baseline to 4 weeks was reported categorically.

26. Change in Diplopia Frequency From Baseline to 8 Weeks (Parent-reported) [8 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. Change in diplopia frequency from baseline to 8 weeks was reported categorically.

27. Frequency of Adverse Symptoms (Symptom Survey) [4 weeks]

    The child and parent(s) will complete a 5-item symptom survey regarding the presence of various ocular symptoms within the past 2 weeks at enrollment and at each visit. The distribution of scores on each symptom survey item will be described for the enrollment exam and the 4-week exam for each treatment group. The distribution of change in scores on each symptom survey item will also be described for each treatment group.

28. Frequency of Adverse Symptoms (Symptom Survey) at 8 Weeks [8 weeks]

    The child and parent(s) will complete a 5-item symptom survey regarding the presence of various ocular symptoms within the past 2 weeks at enrollment and at each visit. The distribution of scores on each symptom survey item will be described for the enrollment exam and the 4-week exam for each treatment group. The distribution of change in scores on each symptom survey item will also be described for each treatment group.

29. Distribution of Change in Adverse Symptom Frequency (Symptom Survey) From Baseline to 4 Weeks [4 weeks]

    The child and parent(s) will complete a 5-item symptom survey regarding the presence of various ocular symptoms within the past 2 weeks at enrollment and at each visit. The distribution of scores on each symptom survey item will be described for the enrollment exam and the 4-week exam for each treatment group. The distribution of change in scores on each symptom survey item will also be described for each treatment group.

30. Distribution of Change in Adverse Symptom Frequency (Symptom Survey) From Baseline to 8 Weeks [8 weeks]

    The child and parent(s) will complete a 5-item symptom survey regarding the presence of various ocular symptoms within the past 2 weeks at enrollment and at each visit. The distribution of scores on each symptom survey item will be described for the enrollment exam and the 8-week exam for each treatment group. The distribution of change in scores on each symptom survey item will also be described for each treatment group.

31. Mean Change in Fellow Eye Visual Acuity at 4 Weeks (Younger Cohort) [Baseline and 4 weeks]

    The mean change in fellow-eye VA from baseline to 4 weeks will be calculated and compared between treatment groups using ANCOVA with adjustment for baseline VA.

32. Mean Change in Fellow Eye VA at 8 Weeks (Younger Cohort) [baseline and 8 weeks]

    The mean change in fellow-eye VA from baseline to 8 weeks will be calculated and compared between treatment groups using ANCOVA with adjustment for baseline VA.

Other Outcome Measures

1. Exploratory Analysis: Subgroup VA Change Analysis at 4 Weeks [Baseline and 4 weeks]

   The treatment effect after 4 weeks in subgroups based on baseline factors will be assessed in exploratory analyses and used to suggest hypotheses for further investigation in future studies. The following baseline factors are of interest: amblyopic-eye VA, stereoacuity, the presence of a tropia at near, and prior amblyopia treatment (other than spectacle correction). In accordance with NIH guidelines, subgroup analyses of treatment effect according to gender and race/ethnicity will be conducted. Positive values for visual acuity change indicate improvement.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 4 Years to 12 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Age 4 to <13 years

2. Amblyopia associated with strabismus, anisometropia, or both (previously treated or untreated)

3. Criteria for strabismic amblyopia: At least one of the following must be met:

• Presence of a heterotropia on examination at distance or near fixation (with or without optical correction, must be no more than 5pd by SPCT at near fixation (see #6 below)

• Documented history of strabismus which is no longer present (which in the judgment of the investigator could have caused amblyopia)

1. Criteria for anisometropia: At least one of the following criteria must be met:

• ≥1.00 D difference between eyes in spherical equivalent

• ≥1.50 D difference in astigmatism between corresponding meridians in the two eyes

1. 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 in astigmatism between corresponding meridians in the two eyes

1. No amblyopia treatment other than optical correction in the past 2 weeks (patching, atropine, Bangerter, vision therapy, binocular treatment)

2. Requirements for required refractive error correction (based on a cycloplegic refraction completed within the last 7 months):

• Hypermetropia of 2.50 D or more by spherical equivalent (SE)

• Myopia of amblyopic eye of 0.50D or more SE

• Astigmatism of 1.00D or more

• Anisometropia of more than 0.50D SE

NOTE: Subjects with cycloplegic refractive errors that do not fall within the requirements above for spectacle correction may be given spectacles at investigator discretion but must follow the study-specified prescribing guidelines, as detailed below.

1. Spectacle prescribing instructions referenced to the cycloplegic refraction completed within the last 7 months:

• SE must be within 0.50D of fully correcting the anisometropia.

• SE must not be under corrected by more than 1.50D SE, and reduction in plus sphere must be symmetric in the two eyes.

• Cylinder power in both eyes must be within 0.50D of fully correcting the astigmatism.

• Axis must be within +/- 10 degrees if cylinder power is ≤1.00D, and within +/- 5 degrees if cylinder power is >1.00D.

• Myopia must not be undercorrected by more than 0.25D or over corrected by more than 0.50D SE, and any change must be symmetrical in the two eyes.

1. Spectacle correction meeting the above criteria must be worn:

• For at least 16 weeks OR until VA stability is documented (defined as <0.1 logMAR change by the same testing method measured on 2 consecutive exams at least 8 weeks apart).

• For determining VA stability (non-improvement):

• The first of two measurements may be made 1) in current spectacles, or

1. in trial frames with or without cycloplegia or 3) without correction (if new correction is prescribed),

• The second measurement must be made without cycloplegia in the correct spectacles that have been worn for at least 8 weeks.

• Note: since this determination is a pre-study procedure, the method of measuring VA is not mandated.

1. VA, measured in each eye without cycloplegia in current spectacle correction (if applicable) within 7 days prior to randomization using the ATS-HOTV VA protocol for children < 7 years and the E-ETDRS VA protocol for children ≥ 7 years on a study-approved device displaying single surrounded optotypes, as follows:

2. VA in the amblyopic eye 20/40 to 20/200 inclusive (ATS-HOTV) or 33 to 72 letters (E-ETDRS)

3. VA in the fellow eye 20/25 or better (ATS-HOTV) or ≥ 78 letters (E-ETDRS)

4. Interocular difference ≥ 3 logMAR lines (ATS-HOTV) or ≥ 15 letters (E-ETDRS)

5. Heterotropia with a near deviation of ≤ 5∆ (measured by SPCT) in habitual correction (Angles of ocular deviation >5∆ are not allowed because large magnitudes of the deviation would compromise successful playing of the game.)

6. Subject is able to play the Dig Rush game (at least level 3) on the study iPad under binocular conditions (with red-green glasses). Subject must be able to see both the red "diggers" and blue "gold carts" when contrast for the non-amblyopic eye is at 20%.

7. Investigator is willing to prescribe computer game play, or continued spectacle wear per protocol.

8. Parent understands the protocol and is willing to accept randomization.

9. Parent has phone (or access to phone) and is willing to be contacted by Jaeb Center staff or other study staff.

10. Relocation outside of area of an active PEDIG site for this study within the next 8 weeks is not anticipated.

Exclusion Criteria:

1. Prism in the spectacle correction at time of enrollment (eligible only if prism is discontinued 2 weeks prior to enrollment).

2. Myopia greater than -6.00D spherical equivalent in either eye.

3. Previous intraocular or refractive surgery.

4. Any treatment for amblyopia (patching, atropine, Bangerter filter, vision therapy or previous binocular treatment) during the past 2 weeks. Previous amblyopia therapy is allowed regardless of type, but must be discontinued at least 2 weeks prior to enrollment.

5. Ocular co-morbidity that may reduce VA determined by an ocular examination performed within the past 7 months (Note: nystagmus per se does not exclude the subject if the above VA 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. Subject has demonstrated previous low compliance with binocular treatment and/or spectacle treatment (as assessed informally by the investigator)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UAB Pediatric Eye Care; Birmingham Health Care	Birmingham	Alabama	United States	35294
2	Midwestern University Eye Institute	Glendale	Arizona	United States	85308
3	University Eye Center at Ketchum Health	Anaheim	California	United States	92807
4	Loma Linda University Health Care, Dept. of Ophthalmology	Loma Linda	California	United States	92354
5	Saddleback Eye Medical Associates	Mission Viejo	California	United States	92691
6	Western University College of Optometry	Pomona	California	United States	91766
7	Yale University	New Haven	Connecticut	United States	06511
8	Nova Southeastern University College of Optometry, The Eye Institute	Fort Lauderdale	Florida	United States	33382
9	University of Florida Shands Hospital	Gainesville	Florida	United States	32608
10	The Emory Eye Center	Atlanta	Georgia	United States	30322
11	St Luke's Hospital	Boise	Idaho	United States	83702
12	Ticho Eye Associates	Chicago Ridge	Illinois	United States	60415
13	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois	United States	60611
14	Illinois College of Optometry	Chicago	Illinois	United States	60616
15	Progressive Eye Care	Lisle	Illinois	United States	60532
16	Advanced Vision Center	Schaumburg	Illinois	United States	60194
17	Pediatric Eye Associates	Wilmette	Illinois	United States	60091
18	Indiana School of Optometry	Bloomington	Indiana	United States	47405
19	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
20	Wolfe Eye Clinic	West Des Moines	Iowa	United States	50266
21	Greater Baltimore Medical Center	Baltimore	Maryland	United States	21204-5809
22	Wilmer Eye Institute	Baltimore	Maryland	United States	21287
23	Boston Children's Hospital	Boston	Massachusetts	United States	02115
24	Michigan College of Optometry at Ferris State Univ	Big Rapids	Michigan	United States	49307
25	Helen DeVos Children's Hospital Pediatric Ophthalmology	Grand Rapids	Michigan	United States	49503
26	Pediatric Ophthalmology, P.C.	Grand Rapids	Michigan	United States	49546
27	University of Minnesota-Minnesota Lions Children's Eye Clinic	Minneapolis	Minnesota	United States	55454
28	Mayo Clinic	Rochester	Minnesota	United States	55905
29	Children's Mercy Hospitals and Clinics	Kansas City	Missouri	United States	64108
30	Saint Louis University Institute	Saint Louis	Missouri	United States	63103
31	St. Louis Children's Hospital Eye Center	Saint Louis	Missouri	United States	63110
32	U of MO St. Louis College of Optometry	Saint Louis	Missouri	United States	63121
33	University of Nebraska Medical Center	Omaha	Nebraska	United States	68114
34	Concord Ophthalmologic Associates	Concord	New Hampshire	United States	03301
35	Michael F. Gallaway, O.D., P.C.	Marlton	New Jersey	United States	08053
36	State University of New York, College of Optometry	New York	New York	United States	10036
37	University of North Carolina	Chapel Hill	North Carolina	United States	27599-7040
38	Duke University Eye Center	Durham	North Carolina	United States	27710
39	Cincinnati Children's Hospital	Cincinnati	Ohio	United States	45229
40	Pediatric Ophthalmology Associates, Inc.	Columbus	Ohio	United States	43205
41	The Ohio State University College of Optometry	Columbus	Ohio	United States	43210-1280
42	Eye Care Associates, Inc.	Poland	Ohio	United States	44514
43	Dean A. McGee Eye Institute, University of Oklahoma	Oklahoma City	Oklahoma	United States	73104
44	Pacific University College of Optometry	Portland	Oregon	United States	97205
45	OHSU Casey Eye Institute	Portland	Oregon	United States	97239
46	Pediatric Ophthalmology of Erie	Erie	Pennsylvania	United States	16501
47	Conestoga Eye	Lancaster	Pennsylvania	United States	17601
48	Pediatric Eye Specialists	Chattanooga	Tennessee	United States	37421
49	Southern College of Optometry	Memphis	Tennessee	United States	38104
50	Texas Children's Hospital - Dept. Of Ophthalmology	Houston	Texas	United States	77030
51	University of Houston College of Optometry	Houston	Texas	United States	77204
52	Texas Tech University Health Science Center	Lubbock	Texas	United States	79430
53	San Antonio Eye Center	San Antonio	Texas	United States	78215
54	Houston Eye Associates	The Woodlands	Texas	United States	77381
55	Virginia Pediatric Eye Center	Norfolk	Virginia	United States	23502
56	Seattle Children's Hospital, University of Washington	Seattle	Washington	United States	98105
57	Northwest Pediatric Ophthalmology, P.S.	Spokane	Washington	United States	99202
58	Spokane Eye Clinical Research	Spokane	Washington	United States	99204
59	Marshall University	Huntington	West Virginia	United States	25755
60	University of Wisconsin, University Station	Madison	Wisconsin	United States	53705
61	Snowy Range Vision Center	Laramie	Wyoming	United States	82070
62	Alberta Children's Hospital	Calgary	Alberta	Canada

Sponsors and Collaborators

• Jaeb Center for Health Research
• Pediatric Eye Disease Investigator Group
• National Eye Institute (NEI)

Investigators

• Study Chair: Ruth Manny, OD, PhD, University of Houston College of Optometry
• Study Chair: Jonathan Holmes, MD, Mayo Clinic

Study Documents (Full-Text)

• Study Protocol - Apr 30, 2018
• Statistical Analysis Plan - Sep 16, 2020
• Informed Consent Form - Nov 5, 2018

More Information

Publications

• Pediatric Eye Disease Investigator Group, Holmes JM, Manny RE, Lazar EL, Birch EE, Kelly KR, Summers AI, Martinson SR, Raghuram A, Colburn JD, Law C, Marsh JD, Bitner DP, Kraker RT, Wallace DK. A Randomized Trial of Binocular Dig Rush Game Treatment for Amblyopia in Children Aged 7 to 12 Years. Ophthalmology. 2019 Mar;126(3):456-466. doi: 10.1016/j.ophtha.2018.10.032. Epub 2018 Oct 22.

• Responsible Party: Jaeb Center for Health Research
• ClinicalTrials.gov Identifier: NCT02983552
• Other Study ID Numbers: ATS20; 2U10EY011751
• First Posted: Dec 6, 2016
• Last Update Posted: Jun 11, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Jaeb Center for Health Research: Amblyopia
• Additional relevant MeSH terms: Amblyopia

Study Results

Participant Flow

Recruitment Details	138 is the number of subjects from the older cohort study. 182 is the number of subjects from the younger cohort.

Arm/Group Title	Binocular Computer Game Treatment- Older Cohort	Continued Spectacle Correction- Older Cohort	Binocular Computer Game Treatment- Younger Cohort	Continued Spectacle Correction- Younger Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Period Title: Overall Study
STARTED	69	69	92	90
4 Week Visit	69	67	85	84
8 Week Visit	67	68	85	84
16 Week Visit	0	66	0	72
COMPLETED	69	67	92	90
NOT COMPLETED	0	2	0	0

Baseline Characteristics

Arm/Group Title	Binocular Computer Game Treatment Older Cohort	Continued Spectacle Correction Older Cohort	Binocular Computer Game Treatment Younger Cohort	Continued Spectacle Correction Younger Cohort	Total
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week	Total of all reporting groups
Overall Participants	69	69	92	90	320
Age (Count of Participants)
<=18 years	69 100%	69 100%	92 100%	90 100%	320 100%
Between 18 and 65 years	0 0%	0 0%	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	9.6 (1.6)	9.6 (1.5)	5.8 (0.7)	5.7 (0.7)	7.4 (2.2)
Age, Customized (Count of Participants)
7 to <10 years	45 65.2%	45 65.2%	0 0%	0 0%	90 28.1%
10 to <13 years	24 34.8%	24 34.8%	0 0%	0 0%	48 15%
4 to <5 years	0 0%	0 0%	12 13%	17 18.9%	29 9.1%
5 to <6 years	0 0%	0 0%	39 42.4%	41 45.6%	80 25%
6 to <7 years	0 0%	0 0%	41 44.6%	32 35.6%	73 22.8%
Sex: Female, Male (Count of Participants)
Female	30 43.5%	35 50.7%	50 54.3%	46 51.1%	161 50.3%
Male	39 56.5%	34 49.3%	42 45.7%	44 48.9%	159 49.7%
Race/Ethnicity, Customized (Count of Participants)
White	50 72.5%	55 79.7%	75 81.5%	74 82.2%	254 79.4%
Black/African American	3 4.3%	2 2.9%	2 2.2%	5 5.6%	12 3.8%
Hispanic	9 13%	8 11.6%	12 13%	8 8.9%	37 11.6%
Asian	6 8.7%	1 1.4%	1 1.1%	2 2.2%	10 3.1%
More than one race	1 1.4%	2 2.9%	2 2.2%	1 1.1%	6 1.9%
Unknown/not reported	0 0%	1 1.4%	0 0%	0 0%	1 0.3%
Prior Amblyopia Treatment (Count of Participants)
None	4 5.8%	2 2.9%	33 35.9%	32 35.6%	71 22.2%
Patching	34 49.3%	36 52.2%	39 42.4%	40 44.4%	149 46.6%
Atropine	0 0%	1 1.4%	2 2.2%	2 2.2%	5 1.6%
Patching/Atropine	26 37.7%	21 30.4%	15 16.3%	15 16.7%	77 24.1%
Patching/Other	3 4.3%	2 2.9%	1 1.1%	1 1.1%	7 2.2%
Patching/Atropine/Other	2 2.9%	7 10.1%	2 2.2%	0 0%	11 3.4%
Prior Binocular Treatment (Count of Participants)
Count of Participants [Participants]	1 1.4%	4 5.8%	0 0%	0 0%	5 1.6%
Distance Amblyopic-eye VA (Letter Score) (Count of Participants)
20/160	2 2.9%	2 2.9%	2 2.2%	3 3.3%	9 2.8%
20/125	3 4.3%	3 4.3%	7 7.6%	3 3.3%	16 5%
20/100	8 11.6%	8 11.6%	3 3.3%	4 4.4%	23 7.2%
20/80	10 14.5%	17 24.6%	9 9.8%	9 10%	45 14.1%
20/63	19 27.5%	14 20.3%	24 26.1%	24 26.7%	81 25.3%
20/50	11 15.9%	10 14.5%	27 29.3%	26 28.9%	74 23.1%
20/40	16 23.2%	15 21.7%	19 20.7%	19 21.1%	69 21.6%
20/200	0 0%	0 0%	1 1.1%	2 2.2%	3 0.9%
Distance Amblyopic-eye VA (logMAR) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [logMAR]	0.50 (0.16)	0.52 (0.16)	0.48 (0.16)	0.48 (0.17)	0.49 (0.16)
Distance Fellow-eye VA (logMAR) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [logMAR]	-0.058 (0.079)	-0.058 (0.074)	0.002 (0.083)	-0.003 (0.085)	-0.025 (0.086)
Interocular Difference (Lines) (Lines) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Lines]	5.57 (1.83)	5.75 (1.86)	4.80 (4.86)	1.71 (1.70)	5.19 (1.81)
Stereoacuity: Nil (Count of Participants)
Count of Participants [Participants]	33 47.8%	33 47.8%	29 31.5%	28 31.1%	123 38.4%
Stereoacuity (Seconds of Arc) (Seconds of Arc) [Median (Full Range) ]
Median (Full Range) [Seconds of Arc]	2000	2000	800	800	2000
Amblyopia Cause (Count of Participants)
Strabismus	15 21.7%	11 15.9%	15 16.3%	15 16.7%	56 17.5%
Anisometropia	27 39.1%	39 56.5%	61 66.3%	54 60%	181 56.6%
Combined-mechanism	27 39.1%	19 27.5%	16 17.4%	21 23.3%	83 25.9%
Distance SPCT: Maximum angle of deviation (Count of Participants)
Orthotropic	47 68.1%	50 72.5%	73 79.3%	76 84.4%	246 76.9%
1 to 4 prism diopters	18 26.1%	15 21.7%	15 16.3%	11 12.2%	59 18.4%
5 to 9 prism diopters	2 2.9%	2 2.9%	3 3.3%	2 2.2%	9 2.8%
>=10 prism diopters	2 2.9%	2 2.9%	1 1.1%	1 1.1%	6 1.9%
Near SPCT: Maximum angle of deviation (Count of Participants)
Orthotropic	44 63.8%	47 68.1%	72 78.3%	75 83.3%	238 74.4%
1 to 4 prism diopters	25 36.2%	22 31.9%	20 21.7%	15 16.7%	82 25.6%
Amblyopic-eye Spherical Equivalent (Diopters) (Diopters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Diopters]	4.35 (2.42)	4.40 (2.28)	4.49 (1.75)	4.45 (2.76)	4.43 (2.32)
Fellow-eye Spherical Equivalent (Diopters) (Diopters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Diopters]	2.10 (2.12)	2.22 (1.99)	2.41 (1.67)	2.67 (1.99)	2.38 (1.93)
Spherical Equivalent Anisometropia (Diopters) (Diopters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Diopters]	2.29 (1.79)	2.27 (1.62)	2.12 (1.52)	2.25 (1.51)	2.22 (1.59)

Outcome Measures

1. Primary Outcome

Title	Mean Change in Amblyopic-eye Visual Acuity (VA) Older Cohort
Description	The primary objective is to compare the efficacy of 4 weeks of treatment with 1 hour/day of binocular game play 5 days per week plus spectacle correction to treatment with spectacle correction alone (control). 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. Adjusted values have been adjusted for amblyopic-eye visual acuity at randomization.
Time Frame	Baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Binocular Computer Game Treatment Older Cohort	Continued Spectacle Correction Older Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Measure Participants	69	67
Adjusted	1.3	1.7
Unadjusted	1.3	1.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Binocular Computer Game Treatment Older Cohort, Continued Spectacle Correction Older Cohort
	Comments	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 4 weeks. A 2-sided 95% confidence interval (CI) was computed on the adjusted treatment group difference at 4 weeks. There was no imputation for missing data.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.71
	Comments	a priori threshold for statistical significance: 2-sided type I error rate of 5%
	Method	ANOVA
	Comments	Adjusted for baseline amblyopic-eye visual acuity.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -2.2 to 1.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	A 2-sided 95% confidence interval was computed on the adjusted treatment group difference evaluating change in amblyopic-eye visual acuity from baseline to the 4 week visit.

2. Primary Outcome

Title	Mean Visual Acuity (VA) in Amblyopic-eye (Older Cohort)
Description	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	4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Binocular Computer Game Treatment Older Cohort	Continued Spectacle Correction Older Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Measure Participants	69	67
Mean (Standard Deviation) [Letter score]	26.6 (10.5)	28.0 (10.7)

3. Primary Outcome

Title	Mean Change in Amblyopic-eye Visual Acuity (VA) in Older Cohort
Description	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 8 weeks

Outcome Measure Data

Analysis Population Description

Two participants (1 per group) were not included with the 8-week visual acuity data. One participant in the control treatment group had visual acuity tested using a non-protocol method and another participant in the binocular treatment group completed the 8-week exam outside of the analysis window (49 to <105 days from randomization).

Arm/Group Title	Binocular Computer Game Treatment Older Cohort	Continued Spectacle Correction Older Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Measure Participants	67	67
Adjusted	2.3	2.4
Unadjusted	2.3	2.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Binocular Computer Game Treatment Older Cohort, Continued Spectacle Correction Older Cohort
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 98.3%; -2.4 to 2.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	A 2-sided 98.3% confidence interval was computed on the adjusted treatment group difference evaluating change in amblyopic-eye visual acuity from baseline to the 8-week visit.

4. Primary Outcome

Title	Mean Visual Acuity (VA) in Amblyopic-eye (Older Cohort)
Description	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	8 weeks

Outcome Measure Data

Analysis Population Description

Two participants (1 per group) were not included with the 8-week visual acuity data. One participant in the control treatment group had visual acuity tested using a non-protocol method and another participant in the binocular treatment group completed the 8-week exam outside of the analysis window (49 to <105 days from randomization).

Arm/Group Title	Binocular Computer Game Treatment Older Cohort	Continued Spectacle Correction Older Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Measure Participants	67	67
Mean (Standard Deviation) [Letter score]	25.9 (9.9)	27.7 (10.4)

5. Primary Outcome

Title	Mean Change in Amblyopic-eye Visual Acuity (VA) Younger Cohort
Description	The primary objective is to compare the efficacy of 4 weeks of treatment with 1 hour/day of binocular game play 5 days per week plus spectacle correction to treatment with spectacle correction alone (control). 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 younger cohort, the level of VA is measured in logMAR (approximate range: -0.2 to 1.2, lower scores indicate better VA) and change in VA from baseline is measured in logMAR lines (positive values indicate improvement), defined as 10 times the difference in logMAR between enrollment and follow-up. Adjusted values have been adjusted for amblyopic-eye visual acuity at randomization.
Time Frame	baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Binocular Computer Game Treatment Younger Cohort	Continued Spectacle Correction Younger Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Measure Participants	85	84
Adjusted	1.0724	0.6053
Unadjusted	1.0706	0.6071

6. Primary Outcome

Title	Mean Visual Acuity (VA) in Amblyopic-eye (Younger Cohort)
Description	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 younger cohort, the level of VA is measured in logMAR (approximate range: -0.2 to 1.2, lower scores indicate better VA) and change in VA from baseline is measured in logMAR lines (positive values indicate improvement), defined as 10 times the difference in logMAR between enrollment and follow-up.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Binocular Computer Game Treatment Younger Cohort	Continued Spectacle Correction Younger Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Measure Participants	85	84
Mean (Standard Deviation) [LogMAR]	0.38 (0.22)	0.42 (0.21)

7. Primary Outcome

Title	Mean Change in Amblyopic-eye Visual Acuity (VA) in Younger Cohort
Description	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 younger cohort, the level of VA is measured in logMAR (approximate range: -0.2 to 1.2, lower scores indicate better VA) and change in VA from baseline is measured in logMAR lines (positive values indicate improvement), defined as 10 times the difference in logMAR between enrollment and follow-up.
Time Frame	Baseline and 8 weeks

Outcome Measure Data

Analysis Population Description

Two participants (1 per group) were not included with the 8-week visual acuity data. One participant in the control treatment group had visual acuity tested using a non-protocol method and another participant in the binocular treatment group completed the 8-week exam outside of the analysis window (49 to <105 days from randomization).

Arm/Group Title	Binocular Computer Game Treatment Younger Cohort	Continued Spectacle Correction Younger Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Measure Participants	85	84
Adjusted	1.2614	0.9855
Unadjusted	1.2588	0.9981

8. Primary Outcome

Title	Mean Visual Acuity (VA) in Amblyopic-eye (Younger Cohort)
Description	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 younger cohort, the level of VA is measured in logMAR (approximate range: -0.2 to 1.2, lower scores indicate better VA) and change in VA from baseline is measured in logMAR lines (positive values indicate improvement), defined as 10 times the difference in logMAR between enrollment and follow-up.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

Two participants (1 per group) were not included with the 8-week visual acuity data. One participant in the control treatment group had visual acuity tested using a non-protocol method and another participant in the binocular treatment group completed the 8-week exam outside of the analysis window (49 to <105 days from randomization).

Arm/Group Title	Binocular Computer Game Treatment Younger Cohort	Continued Spectacle Correction Younger Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Measure Participants	85	84
Mean (Standard Deviation) [LogMAR]	0.36 (0.22)	0.38 (0.22)

9. Secondary Outcome

Title	VA Improvement at 4 Weeks Defined as a Binary Outcome
Description	A secondary analysis will estimate the proportion of subjects with amblyopic-eye VA improvement of ≥ 2 logMAR lines (≥ 10 letters if E-ETDRS) at 4 weeks after baseline.
Time Frame	At 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Binocular Computer Game Treatment Older Cohort	Continued Spectacle Correction Older Cohort	Binocular Computer Game Treatment Younger Cohort	Continued Spectacle Correction Younger Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Measure Participants	69	67	85	84
Count of Participants [Participants]	2 2.9%	3 4.3%	31 33.7%	16 17.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Binocular Computer Game Treatment Older Cohort, Continued Spectacle Correction Older Cohort
	Comments	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 4-week visit, adjusted for visual acuity at randomization.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2
	Confidence Interval	(2-Sided) 98.3%; -13 to 9
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	VA Improvement at 8 Weeks Defined as a Binary Outcome
Description	A secondary analysis will estimate the proportion of subjects with amblyopic-eye VA improvement of ≥ 2 logMAR lines (≥ 10 letters if E-ETDRS) at 8 weeks after baseline.
Time Frame	At 8 weeks

Outcome Measure Data

Analysis Population Description

Of 68 participants in the continued spectacle correction older cohort, only 67 visits were completed in the analysis window.

Arm/Group Title	Binocular Computer Game Treatment Older Cohort	Continued Spectacle Correction Older Cohort	Binocular Computer Game Treatment Younger Cohort	Continued Spectacle Correction Younger Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Measure Participants	67	67	85	84
Count of Participants [Participants]	5 7.2%	6 8.7%	35 38%	25 27.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Binocular Computer Game Treatment Older Cohort, Continued Spectacle Correction Older Cohort
	Comments	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 8-week visit, adjusted for visual acuity at randomization.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1
	Confidence Interval	(2-Sided) 98.3%; -15 to 12
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		For secondary visual acuity outcomes, which included the 8-week treatment group comparison, a Bonferroni adjustment was used to control for multiple testing (3 outcomes tested) to preserve the overall type I error rate at 5% (2-sided alpha=0.017 per test).

11. Secondary Outcome

Title	Distribution of Stereoacuity Scores at 4 Weeks
Description	Stereoacuity will be tested at near in current refractive correction using the Randot Butterfly and Randot Preschool stereoacuity tests. 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	4 weeks

Outcome Measure Data

Analysis Population Description

Limited to those with follow-up visits completed within the pre-specified analysis window

Arm/Group Title	Binocular Computer Game Treatment Older Cohort	Continued Spectacle Correction Older Cohort	Binocular Computer Game Treatment Younger Cohort	Continued Spectacle Correction Younger Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Measure Participants	69	67	85	84
Missing/Not done	0 0%	0 0%	6 6.5%	8 8.9%
Nil	31 44.9%	25 36.2%	24 26.1%	21 23.3%
2000	11 15.9%	11 15.9%	8 8.7%	10 11.1%
800	9 13%	5 7.2%	13 14.1%	7 7.8%
400	7 10.1%	6 8.7%	10 10.9%	15 16.7%
200	3 4.3%	5 7.2%	9 9.8%	9 10%
100	4 5.8%	12 17.4%	10 10.9%	6 6.7%
60	2 2.9%	2 2.9%	3 3.3%	5 5.6%
40	2 2.9%	1 1.4%	2 2.2%	3 3.3%

12. Secondary Outcome

Title	Distribution of Change in Stereoacuity Scores From Baseline
Description	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 4-week stereoacuity scores.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

Change was only calculated if data was available at both baseline and 4 week time points. Some baseline data was missing in the younger cohort, leading to the numerical inconsistency.

Arm/Group Title	Binocular Computer Game Treatment Older Cohort	Continued Spectacle Correction Older Cohort	Binocular Computer Game Treatment Younger Cohort	Continued Spectacle Correction Younger Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®
Measure Participants	69	67	78	73
2 or more levels worse	8 11.6%	6 8.7%	11 12%	8 8.9%
Within 1 level	53 76.8%	50 72.5%	56 60.9%	57 63.3%
2 or more levels better	8 11.6%	11 15.9%	11 12%	8 8.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Binocular Computer Game Treatment Older Cohort, Continued Spectacle Correction Older Cohort
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.38
	Comments	The exact Wilcoxon rank-sum test was used to compare the change in stereoacuity levels from baseline to the 4-week visit by treatment group.
	Method	Wilcoxon (Mann-Whitney)
	Comments

13. Secondary Outcome

Title	Distribution of Stereoacuity Scores at 8 Weeks
Description	Stereoacuity will be tested at near in current refractive correction using the Randot Butterfly and Randot Preschool stereoacuity tests. 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	8 weeks

Outcome Measure Data

Analysis Population Description

Limited to those with follow-up visits completed within the pre-specified analysis window

Arm/Group Title	Binocular Computer Game Treatment Older Cohort	Continued Spectacle Correction Older Cohort	Binocular Computer Game Treatment Younger Cohort	Continued Spectacle Correction Younger Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Measure Participants	67	68	85	84
Nil	31 44.9%	24 34.8%	28 30.4%	25 27.8%
2000	11 15.9%	10 14.5%	11 12%	8 8.9%
800	5 7.2%	8 11.6%	10 10.9%	15 16.7%
400	4 5.8%	2 2.9%	9 9.8%	12 13.3%
200	5 7.2%	11 15.9%	12 13%	9 10%
100	6 8.7%	9 13%	10 10.9%	7 7.8%
60	2 2.9%	3 4.3%	2 2.2%	3 3.3%
40	3 4.3%	1 1.4%	3 3.3%	5 5.6%

14. Secondary Outcome

Title	Distribution of Change in Stereoacuity Scores From Baseline
Description	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 8-week stereoacuity scores.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

Change was only calculated if data was available at both baseline and 4 week time points. Some baseline data was missing in the younger cohort, leading to the numerical inconsistency.

Arm/Group Title	Binocular Computer Game Treatment Older Cohort	Continued Spectacle Correction Older Cohort	Binocular Computer Game Treatment Younger Cohort	Continued Spectacle Correction Younger Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Measure Participants	67	68	85	72
2 or more levels worse	6 8.7%	3 4.3%	8 8.7%	3 3.3%
Within 1 level	53 76.8%	51 73.9%	65 70.7%	54 60%
2 or more levels better	8 11.6%	14 20.3%	12 13%	15 16.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Binocular Computer Game Treatment Older Cohort, Continued Spectacle Correction Older Cohort
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.53
	Comments	The exact Wilcoxon rank-sum test was used to compare the change in stereoacuity levels from baseline to the 8-week visit by treatment group.
	Method	Wilcoxon (Mann-Whitney)
	Comments

15. Secondary Outcome

Title	Distribution of Stereoacuity Scores (Participants With no History of Strabismus)
Description	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	4 weeks

Outcome Measure Data

Analysis Population Description

Only participants with no history of strabismus are analyzed, as mentioned in the outcome title.

Arm/Group Title	Binocular Computer Game Treatment Older Cohort	Continued Spectacle Correction Older Cohort	Binocular Computer Game Treatment Younger Cohort	Continued Spectacle Correction Younger Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Measure Participants	27	37	58	51
Missing/Not Done	0 0%	0 0%	4 4.3%	4 4.4%
Nil	8 11.6%	7 10.1%	11 12%	8 8.9%
2000	3 4.3%	5 7.2%	5 5.4%	7 7.8%
800	2 2.9%	3 4.3%	8 8.7%	4 4.4%
400	5 7.2%	4 5.8%	8 8.7%	10 11.1%
200	1 1.4%	4 5.8%	9 9.8%	9 10%
100	4 5.8%	12 17.4%	10 10.9%	4 4.4%
60	2 2.9%	1 1.4%	3 3.3%	4 4.4%
40	2 2.9%	1 1.4%	0 0%	1 1.1%

16. Secondary Outcome

Title	Distribution of Change in Stereoacuity Scores From Baseline (Participants With no History of Strabismus)
Description	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 4-week stereoacuity scores.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

Only participants with no history of strabismus are analyzed, as mentioned in the outcome title. Change was only calculated if data was available at both baseline and 4 week time points. Some baseline data was missing in the younger cohort, leading to the numerical inconsistency.

Arm/Group Title	Binocular Computer Game Treatment Older Cohort	Continued Spectacle Correction Older Cohort	Binocular Computer Game Treatment Younger Cohort	Continued Spectacle Correction Younger Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Measure Participants	27	37	54	45
2 or more levels worse	5 7.2%	2 2.9%	8 8.7%	6 6.7%
Within 1 level	17 24.6%	27 39.1%	37 40.2%	34 37.8%
2 or more levels better	5 7.2%	8 11.6%	9 9.8%	5 5.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Binocular Computer Game Treatment Older Cohort, Continued Spectacle Correction Older Cohort
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.19
	Comments	The exact Wilcoxon rank-sum test was used to compare the change in stereoacuity levels from baseline to the 4-week visit by treatment group for participants without strabismus.
	Method	Wilcoxon (Mann-Whitney)
	Comments

17. Secondary Outcome

Title	Distribution of Stereoacuity Scores (Participants With no History of Strabismus)
Description	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	8 weeks

Outcome Measure Data

Analysis Population Description

Only participants with no history of strabismus are analyzed, as mentioned in the outcome title.

Arm/Group Title	Binocular Computer Game Treatment Older Cohort	Continued Spectacle Correction Older Cohort	Binocular Computer Game Treatment Younger Cohort	Continued Spectacle Correction Younger Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Measure Participants	27	38	57	51
Nil	8 11.6%	8 11.6%	14 15.2%	11 12.2%
2000	3 4.3%	7 10.1%	8 8.7%	4 4.4%
800	1 1.4%	1 1.4%	5 5.4%	8 8.9%
400	1 1.4%	1 1.4%	5 5.4%	8 8.9%
200	5 7.2%	9 13%	11 12%	8 8.9%
100	4 5.8%	9 13%	9 9.8%	6 6.7%
60	2 2.9%	3 4.3%	2 2.2%	2 2.2%
40	3 4.3%	0 0%	3 3.3%	4 4.4%

18. Secondary Outcome

Title	Distribution of Change in Stereoacuity Scores From Baseline (Participants With no History of Strabismus)
Description	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 4-week stereoacuity scores.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

Only participants with no history of strabismus are analyzed, as mentioned in the outcome title.

Arm/Group Title	Binocular Computer Game Treatment Older Cohort	Continued Spectacle Correction Older Cohort	Binocular Computer Game Treatment Younger Cohort	Continued Spectacle Correction Younger Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Measure Participants	27	38	57	51
2 or more levels worse	3 4.3%	0 0%	5 5.4%	4 4.4%
Within 1 level	19 27.5%	31 44.9%	44 47.8%	34 37.8%
2 or more levels better	5 7.2%	7 10.1%	8 8.7%	13 14.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Binocular Computer Game Treatment Older Cohort, Continued Spectacle Correction Older Cohort
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.74
	Comments	The exact Wilcoxon rank-sum test was used to compare the change in stereoacuity levels from baseline to the 8-week visit by treatment group for participants without strabismus.
	Method	Wilcoxon (Mann-Whitney)
	Comments

19. Secondary Outcome

Title	Binocular Therapy: Treatment Compliance and Fellow-Eye Contrast
Description	Data from the automated iPad log files will be used to provide an objective measure of compliance with binocular treatment (participants completion of >75% of prescribed game play). The total amount of game play will be computed for the initial 4 weeks of treatment for the binocular treatment group, as well as throughout 8 weeks. Secondary analyses will evaluate the relationship between the total amount of game play with (1) change in VA and (2) change in stereoacuity after the first 4 weeks of binocular treatment. Data from the automated iPad log files will also be used to assess game performance as measured by the fellow-eye contrast.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

The control group was not prescribed binocular therapy, which is why they were not included here.

Arm/Group Title	Binocular Computer Game Treatment Older Cohort	Binocular Computer Game Treatment Younger Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®
Measure Participants	69	84
Completed >75% prescribed game play	40 58%	37 53.6%
Fellow-eye contrast of 100%	30 43.5%	32 46.4%
Fellow-eye contrast of 20% or worse	1 1.4%	3 4.3%

20. Secondary Outcome

Title	Binocular Therapy: Treatment Compliance and Fellow-Eye Contrast
Description	Data from the automated iPad log files will be used to assess game performance as measured by the fellow-eye contrast. The level and change in fellow-eye contrast will be computed for the initial 4 weeks of treatment for the binocular treatment group. Secondary analyses will evaluate the relationship between the change in fellow-eye contrast with (1) change in VA and (2) change in stereoacuity after the first 8 weeks of binocular treatment. Data from the automated iPad log files will also be used to assess game performance as measured by the fellow-eye contrast.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

Data from automated iPad log files were only able to be retrieved successfully for 81 of 85 participants in the younger cohort.

Arm/Group Title	Binocular Computer Game Treatment Older Cohort	Binocular Computer Game Treatment Younger Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®
Measure Participants	67	81
Completed >75% prescribed game play	38 55.1%	35 50.7%
Fellow-eye contrast of 100%	59 85.5%	50 72.5%
Fellow-eye contrast of 20% or worse	1 1.4%	2 2.9%

21. Secondary Outcome

Title	Treatment Compliance With Spectacle Wear
Description	Parent-reported adherence with spectacle wear (excluding participants with reported compliance of 'N/A') for the initial 4 weeks. Patient reported to have completed >75% of spectacle wear at 4 weeks.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Binocular Computer Game Treatment Older Cohort	Continued Spectacle Correction Older Cohort	Binocular Computer Game Treatment Younger Cohort	Continued Spectacle Correction Younger Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Measure Participants	69	67	85	78
Count of Participants [Participants]	57 82.6%	57 82.6%	66 71.7%	74 82.2%

22. Secondary Outcome

Title	Treatment Compliance With Spectacle Wear
Description	Parent-reported adherence with spectacle wear (excluding participants with reported compliance of 'N/A') across 8 weeks. Patient reported to have completed >75% of spectacle wear at 8 weeks.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Binocular Computer Game Treatment Older Cohort	Continued Spectacle Correction Older Cohort	Binocular Computer Game Treatment Younger Cohort	Continued Spectacle Correction Younger Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Measure Participants	67	68	89	82
Count of Participants [Participants]	61 88.4%	62 89.9%	69 75%	78 86.7%

23. Secondary Outcome

Title	Mean Change in Fellow Eye Visual Acuity at 4 Weeks (Older Cohort)
Description	The mean change in fellow-eye VA from baseline to 4 weeks will be calculated and compared between treatment groups using ANCOVA with adjustment for baseline VA.
Time Frame	Baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Binocular Computer Game Treatment Older Cohort	Continued Spectacle Correction Older Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Measure Participants	69	67
Adjusted	0.1	1.1
Unadjusted	0.1	1.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Binocular Computer Game Treatment Older Cohort, Continued Spectacle Correction Older Cohort
	Comments	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 4 weeks, adjusting for fellow-eye visual acuity at randomization. A 2-sided 99% confidence interval was computed on the adjusted treatment group difference.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.1
	Confidence Interval	(2-Sided) 99%; -2.5 to 0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Statistical significance of the treatment group comparison was based on a 2-sided alpha=0.01.

24. Secondary Outcome

Title	Mean Change in Fellow Eye VA at 8 Weeks (Older Cohort)
Description	The mean change in fellow-eye VA from baseline to 8 weeks will be calculated and compared between treatment groups using ANCOVA with adjustment for baseline VA.
Time Frame	Baseline and 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Binocular Computer Game Treatment Older Cohort	Continued Spectacle Correction Older Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Measure Participants	68	67
Adjusted	0.5	1.5
Unadjusted	0.5	1.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Binocular Computer Game Treatment Older Cohort, Continued Spectacle Correction Older Cohort
	Comments	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 8 weeks, adjusting for fellow-eye visual acuity at randomization. A 2-sided 99% confidence interval was computed on the adjusted treatment group difference.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 99%; -2.3 to 0.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Statistical significance of the treatment group comparison was based on a 2-sided alpha=0.01.

25. Secondary Outcome

Title	Ocular Alignment at 4 Weeks
Description	The proportion of subjects with development of new strabismus (no heterotropia at baseline and the presence of near and/or distance heterotropia at 4 weeks) or an increase from baseline ≥10∆ in a pre-existing strabismus at 4 weeks will be reported by treatment group and compared using Barnard's exact test. 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 4-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	4 weeks

Outcome Measure Data

Analysis Population Description

As this was a safety outcome, all visit information was recorded, regardless of whether or not it was collected in the analysis window.

Arm/Group Title	Binocular Computer Game Treatment Older Cohort	Continued Spectacle Correction Older Cohort	Binocular Computer Game Treatment Younger Cohort	Continued Spectacle Correction Younger Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Measure Participants	69	67	88	84
Count of Participants [Participants]	10 14.5%	6 8.7%	7 7.6%	7 7.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Binocular Computer Game Treatment Older Cohort, Continued Spectacle Correction Older Cohort
	Comments	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 4-week visit.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.37
	Comments
	Method	Fisher Exact
	Comments

26. Secondary Outcome

Title	Ocular Alignment at 8 Weeks
Description	The proportion of subjects with development of new strabismus (no heterotropia at baseline and the presence of near and/or distance heterotropia at 8 weeks) or an increase from baseline ≥10∆ in a pre-existing strabismus at 8 weeks will be reported by treatment group and compared using Barnard's exact test. 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 8-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	8 weeks

Outcome Measure Data

Analysis Population Description

As this was a safety outcome, all visit information was recorded, regardless of whether or not it was collected in the analysis window.

Arm/Group Title	Binocular Computer Game Treatment Older Cohort	Continued Spectacle Correction Older Cohort	Binocular Computer Game Treatment Younger Cohort	Continued Spectacle Correction Younger Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Measure Participants	67	68	86	84
Count of Participants [Participants]	9 13%	9 13%	6 6.5%	7 7.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Binocular Computer Game Treatment Older Cohort, Continued Spectacle Correction Older Cohort
	Comments	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 8-week visit.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.99
	Comments
	Method	Fisher Exact
	Comments

27. Secondary Outcome

Title	Distribution of Diplopia Frequency at 4 Weeks (Participant-reported)
Description	The proportion of subjects with each level of diplopia frequency will be reported by treatment group at 4 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.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

As this was a safety outcome, all visit information was recorded, regardless of whether or not it was collected in the analysis window.

Arm/Group Title	Binocular Computer Game Treatment Older Cohort	Continued Spectacle Correction Older Cohort	Binocular Computer Game Treatment Younger Cohort	Continued Spectacle Correction Younger Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Measure Participants	69	67	87	84
Never	62 89.9%	64 92.8%	78 84.8%	79 87.8%
Less than once a week	1 1.4%	0 0%	2 2.2%	2 2.2%
Once a week	2 2.9%	2 2.9%	4 4.3%	0 0%
Once a day	2 2.9%	1 1.4%	3 3.3%	3 3.3%
Up to 10 times a day	2 2.9%	0 0%	0 0%	0 0%
More than 10 times a day	0 0%	0 0%	0 0%	0 0%
All the time	0 0%	0 0%	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Binocular Computer Game Treatment Older Cohort, Continued Spectacle Correction Older Cohort
	Comments	The frequency of diplopia, across categories of diplopia, was compared between the treatment groups using the Cochran-Armitage trend test.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.20
	Comments
	Method	Cochran-Armitage trend test
	Comments

28. Secondary Outcome

Title	Distribution of Diplopia Frequency at 8 Weeks (Participant-reported)
Description	The proportion of subjects with each level of diplopia frequency will be reported by treatment group at 8 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.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

As this was a safety outcome, all visit information was recorded, regardless of whether or not it was collected in the analysis window.

Arm/Group Title	Binocular Computer Game Treatment Older Cohort	Continued Spectacle Correction Older Cohort	Binocular Computer Game Treatment Younger Cohort	Continued Spectacle Correction Younger Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Measure Participants	68	68	86	84
Never	63 91.3%	65 94.2%	78 84.8%	78 86.7%
Less than once a week	5 7.2%	2 2.9%	4 4.3%	4 4.4%
Once a week	0 0%	0 0%	1 1.1%	1 1.1%
Once a day	0 0%	1 1.4%	2 2.2%	0 0%
Up to 10 times a day	0 0%	0 0%	1 1.1%	0 0%
More than 10 times a day	0 0%	0 0%	0 0%	0 0%
All the time	0 0%	0 0%	0 0%	1 1.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Binocular Computer Game Treatment Older Cohort, Continued Spectacle Correction Older Cohort
	Comments	The frequency of diplopia, across categories of diplopia, was compared between the treatment groups using the Cochran-Armitage trend test.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	>0.99
	Comments
	Method	Cochran-Armitage trend test
	Comments

29. Secondary Outcome

Title	Change in Diplopia Frequency From Baseline to 4 Weeks (Participant-reported)
Description	A standardized questionnaire was administered to participants and their parents to assess the presence and frequency of any diplopia since the last study visit. Change in diplopia frequency from baseline to 4 weeks was reported categorically.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

As this was a safety outcome, all visit information was recorded, regardless of whether or not it was collected in the analysis window. There was 1 missing participant-reported diplopia frequency at baseline in the Binocular Younger cohort.

Arm/Group Title	Binocular Computer Game Treatment Older Cohort	Continued Spectacle Correction Older Cohort	Binocular Computer Game Treatment Younger Cohort	Continued Spectacle Correction Younger Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Measure Participants	69	67	86	84
Increased frequency (≥ 2 levels)	3 4.3%	2 2.9%	6 6.5%	2 2.2%
Similar frequency (within 1 level)	64 92.8%	64 92.8%	79 85.9%	80 88.9%
Reduced frequency (≥ 2 levels)	2 2.9%	1 1.4%	1 1.1%	2 2.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Binocular Computer Game Treatment Older Cohort, Continued Spectacle Correction Older Cohort
	Comments	The exact Wilcoxon rank-sum test was used to compare the change in diplopia frequency levels from baseline to the 4-week visit by treatment group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.44
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

30. Secondary Outcome

Title	Change in Diplopia Frequency From Baseline to 8 Weeks (Participant-reported)
Description	A standardized questionnaire was administered to participants and their parents to assess the presence and frequency of any diplopia since the last study visit. Change in diplopia frequency from baseline to 8 weeks was reported categorically.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

As this was a safety outcome, all visit information was recorded, regardless of whether or not it was collected in the analysis window. There was 1 missing participant-reported diplopia frequency at baseline in the Binocular Younger cohort.

Arm/Group Title	Binocular Computer Game Treatment Older Cohort	Continued Spectacle Correction Older Cohort	Binocular Computer Game Treatment Younger Cohort	Continued Spectacle Correction Younger Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Measure Participants	68	68	85	84
Increased frequency (≥ 2 levels)	0 0%	1 1.4%	2 2.2%	1 1.1%
Similar frequency (within 1 level)	64 92.8%	66 95.7%	82 89.1%	80 88.9%
Reduced frequency (≥ 2 levels)	4 5.8%	1 1.4%	1 1.1%	3 3.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Binocular Computer Game Treatment Older Cohort, Continued Spectacle Correction Older Cohort
	Comments	The exact Wilcoxon rank-sum test was used to compare the change in diplopia frequency levels from baseline to the 8-week visit by treatment group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	>0.99
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

31. Secondary Outcome

Title	Distribution of Diplopia Frequency at 4 Weeks (Parent-reported)
Description	The proportion of subjects with each level of diplopia frequency will be reported by treatment group at 4 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.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

As this was a safety outcome, all visit information was recorded, regardless of whether or not it was collected in the analysis window.

Arm/Group Title	Binocular Computer Game Treatment Older Cohort	Continued Spectacle Correction Older Cohort	Binocular Computer Game Treatment Younger Cohort	Continued Spectacle Correction Younger Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Measure Participants	69	66	88	83
Never	65 94.2%	66 95.7%	87 94.6%	83 92.2%
Less than once a week	3 4.3%	0 0%	1 1.1%	0 0%
Once a week	1 1.4%	0 0%	0 0%	0 0%
Once a day	0 0%	0 0%	0 0%	0 0%
Up to 10 times a day	0 0%	0 0%	0 0%	0 0%
More than 10 times a day	0 0%	0 0%	0 0%	0 0%
All the time	0 0%	0 0%	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Binocular Computer Game Treatment Older Cohort, Continued Spectacle Correction Older Cohort
	Comments	The frequency of diplopia, across categories of diplopia, was compared between the treatment groups using the Cochran-Armitage trend test.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.12
	Comments
	Method	Cochran-Armitage trend test
	Comments

32. Secondary Outcome

Title	Distribution of Diplopia Frequency at 8 Weeks (Parent-reported)
Description	The proportion of subjects with each level of diplopia frequency will be reported by treatment group at 8 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.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

As this was a safety outcome, all visit information was recorded, regardless of whether or not it was collected in the analysis window.

Arm/Group Title	Binocular Computer Game Treatment Older Cohort	Continued Spectacle Correction Older Cohort	Binocular Computer Game Treatment Younger Cohort	Continued Spectacle Correction Younger Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Measure Participants	67	68	86	84
Never	66 95.7%	67 97.1%	84 91.3%	84 93.3%
Less than once a week	1 1.4%	1 1.4%	2 2.2%	0 0%
Once a week	0 0%	0 0%	0 0%	0 0%
Once a day	0 0%	0 0%	0 0%	0 0%
Up to 10 times a day	0 0%	0 0%	0 0%	0 0%
More than 10 times a day	0 0%	0 0%	0 0%	0 0%
All the time	0 0%	0 0%	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Binocular Computer Game Treatment Older Cohort, Continued Spectacle Correction Older Cohort
	Comments	The frequency of diplopia, across categories of diplopia, was compared between the treatment groups using the Cochran-Armitage trend test.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	>0.99
	Comments
	Method	Cochran-Armitage trend test
	Comments

33. Secondary Outcome

Title	Change in Diplopia Frequency From Baseline to 4 Weeks (Parent-reported)
Description	A standardized questionnaire was administered to participants and their parents to assess the presence and frequency of any diplopia since the last study visit. Change in diplopia frequency from baseline to 4 weeks was reported categorically.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

As this was a safety outcome, all visit information was recorded, regardless of whether or not it was collected in the analysis window.

Arm/Group Title	Binocular Computer Game Treatment Older Cohort	Continued Spectacle Correction Older Cohort	Binocular Computer Game Treatment Younger Cohort	Continued Spectacle Correction Younger Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Measure Participants	69	66	88	83
Increased frequency (≥ 2 levels)	0 0%	0 0%	0 0%	0 0%
Similar frequency (within 1 level)	69 100%	66 95.7%	88 95.7%	82 91.1%
Reduced frequency (≥ 2 levels)	0 0%	0 0%	0 0%	1 1.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Binocular Computer Game Treatment Older Cohort, Continued Spectacle Correction Older Cohort
	Comments	The exact Wilcoxon rank-sum test was used to compare the change in diplopia frequency levels from baseline to the 4-week visit by treatment group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.12
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

34. Secondary Outcome

Title	Change in Diplopia Frequency From Baseline to 8 Weeks (Parent-reported)
Description	A standardized questionnaire was administered to participants and their parents to assess the presence and frequency of any diplopia since the last study visit. Change in diplopia frequency from baseline to 8 weeks was reported categorically.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

As this was a safety outcome, all visit information was recorded, regardless of whether or not it was collected in the analysis window.

Arm/Group Title	Binocular Computer Game Treatment Older Cohort	Continued Spectacle Correction Older Cohort	Binocular Computer Game Treatment Younger Cohort	Continued Spectacle Correction Younger Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Measure Participants	67	68	86	84
Increased frequency (≥ 2 levels)	0 0%	0 0%	0 0%	0 0%
Similar frequency (within 1 level)	67 97.1%	68 98.6%	86 93.5%	83 92.2%
Reduced frequency (≥ 2 levels)	0 0%	0 0%	0 0%	1 1.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Binocular Computer Game Treatment Older Cohort, Continued Spectacle Correction Older Cohort
	Comments	The exact Wilcoxon rank-sum test was used to compare the change in diplopia frequency levels from baseline to the 8-week visit by treatment group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	>0.99
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

35. Secondary Outcome

Title	Frequency of Adverse Symptoms (Symptom Survey)
Description	The child and parent(s) will complete a 5-item symptom survey regarding the presence of various ocular symptoms within the past 2 weeks at enrollment and at each visit. The distribution of scores on each symptom survey item will be described for the enrollment exam and the 4-week exam for each treatment group. The distribution of change in scores on each symptom survey item will also be described for each treatment group.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

There were 3 participants in the older cohort control treatment group with responses of 'Not wearing spectacles'. These participants were excluded from the percentage tabulations (only the number is reported) in the table and any analyses specific to these Symptom Survey items.

Arm/Group Title	Binocular Computer Game Treatment Older Cohort	Continued Spectacle Correction Older Cohort	Binocular Computer Game Treatment Younger Cohort	Continued Spectacle Correction Younger Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Measure Participants	69	67	88	83
Never	61 88.4%	57 82.6%	72 78.3%	71 78.9%
Almost Never	3 4.3%	8 11.6%	10 10.9%	6 6.7%
Sometimes	5 7.2%	1 1.4%	5 5.4%	4 4.4%
Often	0 0%	1 1.4%	1 1.1%	2 2.2%
Almost Always	0 0%	0 0%	0 0%	0 0%
Never	50 72.5%	46 66.7%	53 57.6%	58 64.4%
Almost Never	7 10.1%	13 18.8%	15 16.3%	19 21.1%
Sometimes	9 13%	7 10.1%	17 18.5%	6 6.7%
Often	2 2.9%	1 1.4%	3 3.3%	0 0%
Almost Always	1 1.4%	0 0%	0 0%	0 0%
Never	38 55.1%	38 55.1%	60 65.2%	68 75.6%
Almost Never	20 29%	14 20.3%	14 15.2%	13 14.4%
Sometimes	8 11.6%	12 17.4%	9 9.8%	1 1.1%
Often	3 4.3%	3 4.3%	5 5.4%	1 1.1%
Almost Always	0 0%	0 0%	0 0%	0 0%
Never	44 63.8%	39 56.5%	44 47.8%	40 44.4%
Almost Never	11 15.9%	9 13%	17 18.5%	19 21.1%
Sometimes	13 18.8%	11 15.9%	19 20.7%	17 18.9%
Often	1 1.4%	5 7.2%	6 6.5%	6 6.7%
Almost Always	0 0%	0 0%	2 2.2%	1 1.1%
Never	43 62.3%	41 59.4%	43 46.7%	46 51.1%
Almost Never	13 18.8%	14 20.3%	26 28.3%	24 26.7%
Sometimes	12 17.4%	9 13%	15 16.3%	11 12.2%
Often	1 1.4%	0 0%	4 4.3%	1 1.1%
Almost Always	0 0%	0 0%	0 0%	1 1.1%

36. Secondary Outcome

Title	Frequency of Adverse Symptoms (Symptom Survey) at 8 Weeks
Description	The child and parent(s) will complete a 5-item symptom survey regarding the presence of various ocular symptoms within the past 2 weeks at enrollment and at each visit. The distribution of scores on each symptom survey item will be described for the enrollment exam and the 4-week exam for each treatment group. The distribution of change in scores on each symptom survey item will also be described for each treatment group.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

There were 3 participants in the control treatment group with responses of 'Not wearing spectacles'. These participants were excluded from the percentage tabulations (only the number is reported) in the table and any analyses specific to these Symptom Survey items.

Arm/Group Title	Binocular Computer Game Treatment Older Cohort	Continued Spectacle Correction Older Cohort	Binocular Computer Game Treatment Younger Cohort	Continued Spectacle Correction Younger Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Measure Participants	67	68	86	84
Never	58 84.1%	61 88.4%	74 80.4%	62 68.9%
Almost Never	7 10.1%	4 5.8%	5 5.4%	17 18.9%
Sometimes	2 2.9%	2 2.9%	7 7.6%	5 5.6%
Often	0 0%	1 1.4%	0 0%	0 0%
Almost Always	0 0%	0 0%	0 0%	0 0%
Never	48 69.6%	47 68.1%	58 63%	58 64.4%
Almost Never	9 13%	13 18.8%	16 17.4%	20 22.2%
Sometimes	9 13%	7 10.1%	12 13%	6 6.7%
Often	1 1.4%	1 1.4%	0 0%	0 0%
Almost Always	0 0%	0 0%	0 0%	0 0%
Never	44 63.8%	44 63.8%	62 67.4%	65 72.2%
Almost Never	13 18.8%	17 24.6%	13 14.1%	17 18.9%
Sometimes	8 11.6%	6 8.7%	10 10.9%	2 2.2%
Often	2 2.9%	1 1.4%	1 1.1%	0 0%
Almost Always	0 0%	0 0%	0 0%	0 0%
Never	42 60.9%	41 59.4%	38 41.3%	40 44.4%
Almost Never	15 21.7%	11 15.9%	16 17.4%	17 18.9%
Sometimes	9 13%	10 14.5%	26 28.3%	23 25.6%
Often	1 1.4%	2 2.9%	5 5.4%	2 2.2%
Almost Always	0 0%	1 1.4%	1 1.1%	2 2.2%
Never	40 58%	43 62.3%	45 48.9%	44 48.9%
Almost Never	16 23.2%	17 24.6%	28 30.4%	30 33.3%
Sometimes	10 14.5%	4 5.8%	8 8.7%	7 7.8%
Often	0 0%	1 1.4%	5 5.4%	3 3.3%
Almost Always	1 1.4%	0 0%	0 0%	0 0%

37. Secondary Outcome

Title	Distribution of Change in Adverse Symptom Frequency (Symptom Survey) From Baseline to 4 Weeks
Description	The child and parent(s) will complete a 5-item symptom survey regarding the presence of various ocular symptoms within the past 2 weeks at enrollment and at each visit. The distribution of scores on each symptom survey item will be described for the enrollment exam and the 4-week exam for each treatment group. The distribution of change in scores on each symptom survey item will also be described for each treatment group.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

There were 3 participants in the control treatment group with responses of 'Not wearing spectacles'. These participants were excluded from the tabulations in the table and any analyses specific to these Symptom Survey items.

Arm/Group Title	Binocular Computer Game Treatment Older Cohort	Continued Spectacle Correction Older Cohort	Binocular Computer Game Treatment Younger Cohort	Continued Spectacle Correction Younger Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Measure Participants	69	67	88	83
Increased frequency (≥ 2 levels)	1 1.4%	1 1.4%	4 4.3%	0 0%
Similar frequency (within 1 level)	62 89.9%	59 85.5%	73 79.3%	72 80%
Reduced frequency (≥ 2 levels)	6 8.7%	7 10.1%	11 12%	11 12.2%
Increased frequency (≥ 2 levels)	1 1.4%	3 4.3%	9 9.8%	0 0%
Similar frequency (within 1 level)	61 88.4%	52 75.4%	73 79.3%	73 81.1%
Reduced frequency (≥ 2 levels)	7 10.1%	12 17.4%	6 6.5%	10 11.1%
Increased frequency (≥ 2 levels)	2 2.9%	2 2.9%	7 7.6%	0 0%
Similar frequency (within 1 level)	60 87%	58 84.1%	76 82.6%	72 80%
Reduced frequency (≥ 2 levels)	7 10.1%	7 10.1%	5 5.4%	11 12.2%
Increased frequency (≥ 2 levels)	2 2.9%	5 7.2%	4 4.3%	2 2.2%
Similar frequency (within 1 level)	60 87%	46 66.7%	72 78.3%	73 81.1%
Reduced frequency (≥ 2 levels)	7 10.1%	13 18.8%	12 13%	8 8.9%
Increased frequency (≥ 2 levels)	0 0%	0 0%	1 1.1%	0 0%
Similar frequency (within 1 level)	64 92.8%	54 78.3%	78 84.8%	80 88.9%
Reduced frequency (≥ 2 levels)	5 7.2%	10 14.5%	9 9.8%	3 3.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Binocular Computer Game Treatment Older Cohort, Continued Spectacle Correction Older Cohort, Binocular Computer Game Treatment Younger Cohort, Continued Spectacle Correction Younger Cohort
	Comments	For each Symptom Survey item, the exact Wilcoxon rank-sum test was used to compare the change in symptom frequency level from baseline to the 4-week visit by treatment group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.07
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

38. Secondary Outcome

Title	Distribution of Change in Adverse Symptom Frequency (Symptom Survey) From Baseline to 8 Weeks
Description	The child and parent(s) will complete a 5-item symptom survey regarding the presence of various ocular symptoms within the past 2 weeks at enrollment and at each visit. The distribution of scores on each symptom survey item will be described for the enrollment exam and the 8-week exam for each treatment group. The distribution of change in scores on each symptom survey item will also be described for each treatment group.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

There were 3 participants in the control treatment group with responses of 'Not wearing spectacles'. These participants were excluded from the tabulations in the table and any analyses specific to these Symptom Survey items. One participant in the binocular treatment group did not have a completed Symptom Survey at the 8-week visit.

Arm/Group Title	Binocular Computer Game Treatment Older Cohort	Continued Spectacle Correction Older Cohort	Binocular Computer Game Treatment Younger Cohort	Continued Spectacle Correction Younger Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Measure Participants	67	68	86	84
Increased frequency (≥ 2 levels)	1 1.4%	2 2.9%	4 4.3%	2 2.2%
Similar frequency (within 1 level)	61 88.4%	57 82.6%	67 72.8%	71 78.9%
Reduced frequency (≥ 2 levels)	5 7.2%	9 13%	15 16.3%	11 12.2%
Increased frequency (≥ 2 levels)	1 1.4%	1 1.4%	5 5.4%	1 1.1%
Similar frequency (within 1 level)	60 87%	55 79.7%	75 81.5%	72 80%
Reduced frequency (≥ 2 levels)	6 8.7%	12 17.4%	6 6.5%	11 12.2%
Increased frequency (≥ 2 levels)	2 2.9%	0 0%	5 5.4%	0 0%
Similar frequency (within 1 level)	60 87%	59 85.5%	76 82.6%	77 85.6%
Reduced frequency (≥ 2 levels)	5 7.2%	9 13%	5 5.4%	7 7.8%
Increased frequency (≥ 2 levels)	3 4.3%	0 0%	6 6.5%	3 3.3%
Similar frequency (within 1 level)	54 78.3%	50 72.5%	70 76.1%	76 84.4%
Reduced frequency (≥ 2 levels)	10 14.5%	15 21.7%	10 10.9%	5 5.6%
Increased frequency (≥ 2 levels)	0 0%	0 0%	0 0%	2 2.2%
Similar frequency (within 1 level)	62 89.9%	55 79.7%	76 82.6%	77 85.6%
Reduced frequency (≥ 2 levels)	5 7.2%	10 14.5%	10 10.9%	5 5.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Binocular Computer Game Treatment Older Cohort, Continued Spectacle Correction Older Cohort, Binocular Computer Game Treatment Younger Cohort, Continued Spectacle Correction Younger Cohort
	Comments	For each Symptom Survey item, the exact Wilcoxon rank-sum test was used to compare the change in symptom frequency level from baseline to the 8-week visit by treatment group. This was utilized for each item in the survey.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.06
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

39. Secondary Outcome

Title	Mean Change in Fellow Eye Visual Acuity at 4 Weeks (Younger Cohort)
Description	The mean change in fellow-eye VA from baseline to 4 weeks will be calculated and compared between treatment groups using ANCOVA with adjustment for baseline VA.
Time Frame	Baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Binocular Computer Game Treatment Younger Cohort	Continued Spectacle Correction Younger Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Measure Participants	88	84
Adjusted	0.0536	0.1939
Unadjusted	0.0682	0.1786

40. Secondary Outcome

Title	Mean Change in Fellow Eye VA at 8 Weeks (Younger Cohort)
Description	The mean change in fellow-eye VA from baseline to 8 weeks will be calculated and compared between treatment groups using ANCOVA with adjustment for baseline VA.
Time Frame	baseline and 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Binocular Computer Game Treatment Younger Cohort	Continued Spectacle Correction Younger Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Measure Participants	86	84
Adjusted	0.3160	0.2122
Unadjusted	0.3256	0.2024

41. Other Pre-specified Outcome

Title	Exploratory Analysis: Subgroup VA Change Analysis at 4 Weeks
Description	The treatment effect after 4 weeks in subgroups based on baseline factors will be assessed in exploratory analyses and used to suggest hypotheses for further investigation in future studies. The following baseline factors are of interest: amblyopic-eye VA, stereoacuity, the presence of a tropia at near, and prior amblyopia treatment (other than spectacle correction). In accordance with NIH guidelines, subgroup analyses of treatment effect according to gender and race/ethnicity will be conducted. Positive values for visual acuity change indicate improvement.
Time Frame	Baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

Analyses were limited to participants who completed the 4-week visit within the pre-defined analysis window (21 to <49 days after randomization).

Arm/Group Title	Binocular Computer Game Treatment Older Cohort	Continued Spectacle Correction Older Cohort	Binocular Computer Game Treatment Younger Cohort	Continued Spectacle Correction Younger Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®	Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
Measure Participants	69	67	85	84
Overall	1.3 (5.3)	1.7 (5.5)	1.1 (1.4)	0.6 (1.3)
Sex: Female	1.5 (4.6)	1.8 (6.0)	1.2 (1.4)	0.7 (1.4)
Sex: Male	1.2 (5.8)	1.6 (4.9)	1.0 (1.4)	0.5 (1.1)
Age at Randomization: 4 to <5	0.8 (1.2)	0.8 (1.2)
Age at Randomization: 5 to <7	1.1 (1.5)	0.6 (1.3)
Age at Randomization: 7 to <10	1.6 (6.0)	2.0 (5.4)
Age at Randomization: 10 to <13	0.9 (3.8)	1.2 (5.6)
Race: Non-white/Hispanic	2.5 (6.8)	3.7 (7.2)	1.1 (1.3)	0.5 (0.8)
Race: White/Non-Hispanic	0.9 (4.6)	1.2 (4.8)	1.1 (1.5)	0.6 (1.3)
Baseline VA: 20/080 to 20/200	3.2 (5.9)	1.3 (6.5)	1.0 (1.3)	0.7 (1.4)
Baseline VA: 20/063	1.5 (3.7)	2.5 (5.5)	0.9 (1.5)	0.5 (1.2)
Baseline VA: 20/050	1.6 (4.2)	0.9 (3.3)	1.4 (1.5)	0.5 (1.1)
Baseline VA: 20/040	-1.7 (5.9)	2.2 (4.5)	1.1 (1.5)	0.9 (1.4)
Prior Amblyopia Treatment: No	0.5 (3.0)	5.0 (5.7)	0.9 (1.1)	0.6 (1.1)
Prior Amblyopia Treatment: Yes	1.4 (5.4)	1.6 (5.5)	1.2 (1.6)	0.6 (1.4)
Prior Binocular Treatment: No	1.3 (5.3)	2.2 (5.2)
Prior Binocular Treatment: Yes	3.0 (0)	-5.8 (3.1)
Baseline stereoacuity at near: Nil	1.6 (5.5)	0.7 (5.6)	0.9 (1.6)	0.3 (1.2)
Baseline stereoacuity at near: Better than Nil	1.1 (5.2)	2.5 (5.2)	1.2 (1.4)	0.8 (1.3)
Near Heterotropia at Randomization: No	2.0 (5.2)	2.2 (5.6)	1.1 (1.5)	0.7 (1.3)
Near Heterotropia at Randomization: Yes	0.1 (5.4)	0.7 (5.1)	1.1 (1.2)	0.4 (1.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Binocular Computer Game Treatment Older Cohort, Continued Spectacle Correction Older Cohort
	Comments	An analysis of covariance (ANCOVA) was performed to test the 2-way interaction between treatment group with each factor (baseline age and visual acuity were treated as continuous factors), adjusting for baseline amblyopic-eye visual acuity and the nested terms from the interaction term. Formal subgroup analyses were only performed if there was a minimum of 20 participants in every subgroup category across both treatment groups for factors treated as categorical variables in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	>0.01
	Comments	Statistical significance of the interaction term was based on a 2-sided alpha=0.01.
	Method	ANCOVA
	Comments

Adverse Events

Time Frame	8 weeks
Arm/Group Title	Binocular Computer Game Treatment Older Cohort		Continued Spectacle Correction Older Cohort		Binocular Computer Game Treatment Younger Cohort		Continued Spectacle Correction Younger Cohort
Arm/Group Description	Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®		Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week		Binocular computer game treatment is defined as playing a Dig Rush application on an iPad® 1 hour per day, 5 days per week for 8 weeks in addition to continued spectacle correction (if required) iPad®: Binocular therapy using a Dig Rush application on an iPad®		Continued spectacle correction is defined as wearing appropriate spectacle correction (if required) for all waking hours, 7 days per week for 8 weeks. Spectacle correction: Spectacle correction for all waking hours, 7 days per week
All Cause Mortality
	Binocular Computer Game Treatment Older Cohort		Continued Spectacle Correction Older Cohort		Binocular Computer Game Treatment Younger Cohort		Continued Spectacle Correction Younger Cohort
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/69 (0%)		0/69 (0%)		0/92 (0%)		0/90 (0%)
Serious Adverse Events
	Binocular Computer Game Treatment Older Cohort		Continued Spectacle Correction Older Cohort		Binocular Computer Game Treatment Younger Cohort		Continued Spectacle Correction Younger Cohort
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/69 (0%)		0/69 (0%)		0/92 (0%)		0/90 (0%)
Other (Not Including Serious) Adverse Events
	Binocular Computer Game Treatment Older Cohort		Continued Spectacle Correction Older Cohort		Binocular Computer Game Treatment Younger Cohort		Continued Spectacle Correction Younger Cohort
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/69 (0%)		0/69 (0%)		0/92 (0%)		0/90 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.