Binocular Dig Rush Game Treatment for Amblyopia (ATS20)

• ClinicalTrials.gov Identifier: NCT02983552
• Recruitment Status: Completed
• First Posted: December 6, 2016
• Results First Posted: June 11, 2021
• Last Update Posted: June 11, 2021
• Sponsor: Jaeb Center for Health Research
• Collaborators: Pediatric Eye Disease Investigator Group; National Eye Institute (NEI)
• Information provided by (Responsible Party): Jaeb Center for Health Research

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	Not Applicable

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 (Clinical Trial)
• 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: March 2, 2017
• Actual Primary Completion Date: April 20, 2020
• Actual Study Completion Date: July 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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

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

Criteria

Inclusion Criteria:

1. Age 4 to <13 years

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

   1. 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)

   2. 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

   3. Criteria for combined-mechanism amblyopia: Both of the following criteria must be met:

      • Criteria for strabismus are met (see above)
      • ≥1.00 D difference between eyes in spherical equivalent OR ≥1.50 D difference in astigmatism between corresponding meridians in the two eyes
3. No amblyopia treatment other than optical correction in the past 2 weeks (patching, atropine, Bangerter, vision therapy, binocular treatment)

4. 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.

   2. 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 2) 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.

5. 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:

   1. VA in the amblyopic eye 20/40 to 20/200 inclusive (ATS-HOTV) or 33 to 72 letters (E-ETDRS)
   2. VA in the fellow eye 20/25 or better (ATS-HOTV) or ≥ 78 letters (E-ETDRS)
   3. Interocular difference ≥ 3 logMAR lines (ATS-HOTV) or ≥ 15 letters (E-ETDRS)
6. 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.)
7. 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%.
8. Investigator is willing to prescribe computer game play, or continued spectacle wear per protocol.
9. Parent understands the protocol and is willing to accept randomization.
10. Parent has phone (or access to phone) and is willing to be contacted by Jaeb Center staff or other study staff.
11. 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

United States, Alabama

UAB Pediatric Eye Care; Birmingham Health Care

Birmingham, Alabama, United States, 35294

United States, Arizona

Midwestern University Eye Institute

Glendale, Arizona, United States, 85308

United States, California

University Eye Center at Ketchum Health

Anaheim, California, United States, 92807

Loma Linda University Health Care, Dept. of Ophthalmology

Loma Linda, California, United States, 92354

Saddleback Eye Medical Associates

Mission Viejo, California, United States, 92691

Western University College of Optometry

Pomona, California, United States, 91766

United States, Connecticut

Yale University

New Haven, Connecticut, United States, 06511

United States, Florida

Nova Southeastern University College of Optometry, The Eye Institute

Fort Lauderdale, Florida, United States, 33382

University of Florida Shands Hospital

Gainesville, Florida, United States, 32608

United States, Georgia

The Emory Eye Center

Atlanta, Georgia, United States, 30322

United States, Idaho

St Luke's Hospital

Boise, Idaho, United States, 83702

United States, Illinois

Ticho Eye Associates

Chicago Ridge, Illinois, United States, 60415

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States, 60611

Illinois College of Optometry

Chicago, Illinois, United States, 60616

Progressive Eye Care

Lisle, Illinois, United States, 60532

Advanced Vision Center

Schaumburg, Illinois, United States, 60194

Pediatric Eye Associates

Wilmette, Illinois, United States, 60091

United States, Indiana

Indiana School of Optometry

Bloomington, Indiana, United States, 47405

United States, Iowa

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States, 52242

Wolfe Eye Clinic

West Des Moines, Iowa, United States, 50266

United States, Maryland

Greater Baltimore Medical Center

Baltimore, Maryland, United States, 21204-5809

Wilmer Eye Institute

Baltimore, Maryland, United States, 21287

United States, Massachusetts

Boston Children's Hospital

Boston, Massachusetts, United States, 02115

United States, Michigan

Michigan College of Optometry at Ferris State Univ

Big Rapids, Michigan, United States, 49307

Helen DeVos Children's Hospital Pediatric Ophthalmology

Grand Rapids, Michigan, United States, 49503

Pediatric Ophthalmology, P.C.

Grand Rapids, Michigan, United States, 49546

United States, Minnesota

University of Minnesota-Minnesota Lions Children's Eye Clinic

Minneapolis, Minnesota, United States, 55454

Mayo Clinic

Rochester, Minnesota, United States, 55905

United States, Missouri

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, United States, 64108

Saint Louis University Institute

Saint Louis, Missouri, United States, 63103

St. Louis Children's Hospital Eye Center

Saint Louis, Missouri, United States, 63110

U of MO St. Louis College of Optometry

Saint Louis, Missouri, United States, 63121

United States, Nebraska

University of Nebraska Medical Center

Omaha, Nebraska, United States, 68114

United States, New Hampshire

Concord Ophthalmologic Associates

Concord, New Hampshire, United States, 03301

United States, New Jersey

Michael F. Gallaway, O.D., P.C.

Marlton, New Jersey, United States, 08053

United States, New York

State University of New York, College of Optometry

New York, New York, United States, 10036

United States, North Carolina

University of North Carolina

Chapel Hill, North Carolina, United States, 27599-7040

Duke University Eye Center

Durham, North Carolina, United States, 27710

United States, Ohio

Cincinnati Children's Hospital

Cincinnati, Ohio, United States, 45229

Pediatric Ophthalmology Associates, Inc.

Columbus, Ohio, United States, 43205

The Ohio State University College of Optometry

Columbus, Ohio, United States, 43210-1280

Eye Care Associates, Inc.

Poland, Ohio, United States, 44514

United States, Oklahoma

Dean A. McGee Eye Institute, University of Oklahoma

Oklahoma City, Oklahoma, United States, 73104

United States, Oregon

Pacific University College of Optometry

Portland, Oregon, United States, 97205

OHSU Casey Eye Institute

Portland, Oregon, United States, 97239

United States, Pennsylvania

Pediatric Ophthalmology of Erie

Erie, Pennsylvania, United States, 16501

Conestoga Eye

Lancaster, Pennsylvania, United States, 17601

United States, Tennessee

Pediatric Eye Specialists

Chattanooga, Tennessee, United States, 37421

Southern College of Optometry

Memphis, Tennessee, United States, 38104

United States, Texas

Texas Children's Hospital - Dept. Of Ophthalmology

Houston, Texas, United States, 77030

University of Houston College of Optometry

Houston, Texas, United States, 77204

Texas Tech University Health Science Center

Lubbock, Texas, United States, 79430

San Antonio Eye Center

San Antonio, Texas, United States, 78215

Houston Eye Associates

The Woodlands, Texas, United States, 77381

United States, Virginia

Virginia Pediatric Eye Center

Norfolk, Virginia, United States, 23502

United States, Washington

Seattle Children's Hospital, University of Washington

Seattle, Washington, United States, 98105

Northwest Pediatric Ophthalmology, P.S.

Spokane, Washington, United States, 99202

Spokane Eye Clinical Research

Spokane, Washington, United States, 99204

United States, West Virginia

Marshall University

Huntington, West Virginia, United States, 25755

United States, Wisconsin

University of Wisconsin, University Station

Madison, Wisconsin, United States, 53705

United States, Wyoming

Snowy Range Vision Center

Laramie, Wyoming, United States, 82070

Canada, Alberta

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)

Documents provided by Jaeb Center for Health Research:

Study Protocol  [PDF] April 30, 2018

Statistical Analysis Plan  [PDF] September 16, 2020

Informed Consent Form  [PDF] November 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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Manny RE, Holmes JM, Kraker RT, Li Z, Waters AL, Kelly KR, Kong L, Crouch ER, Lorenzana IJ, Alkharashi MS, Galvin JA, Rice ML, Melia BM, Cotter SA; Pediatric Eye Disease Investigator Group. A Randomized Trial of Binocular Dig Rush Game Treatment for Amblyopia in Children Aged 4 to 6 Years. Optom Vis Sci. 2022 Mar 1;99(3):213-227. doi: 10.1097/OPX.0000000000001867.

• Responsible Party: Jaeb Center for Health Research
• ClinicalTrials.gov Identifier: NCT02983552
• Other Study ID Numbers: ATS20; 2U10EY011751 ( U.S. NIH Grant/Contract )
• First Posted: December 6, 2016
• Results First Posted: June 11, 2021
• Last Update Posted: June 11, 2021
• Last Verified: June 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: In accordance with the NIH data sharing policy, a de-identified database is placed in the public domain on the PEDIG public website after the completion of each protocol and publication of the primary manuscript.
• Time Frame: Data will be made available after publication of each primary manuscript.
• Access Criteria: Users accessing the data must enter an email address.

• 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; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vision Disorders; Sensation Disorders; Neurologic Manifestations; Eye Diseases