Binocular Dig Rush Game Treatment for Amblyopia (ATS20)

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 Overview

• Status: Completed
• Conditions: Amblyopia
• Intervention / Treatment: Other: iPad®; Other: Spectacle correction

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 Type: Interventional
• Enrollment (Actual): 320
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • Alberta Children's Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • UAB Pediatric Eye Care; Birmingham Health Care
  • Arizona
    • Glendale, Arizona, United States, 85308
      • Midwestern University Eye Institute
  • California
    • Anaheim, California, United States, 92807
      • University Eye Center at Ketchum Health
    • Loma Linda, California, United States, 92354
      • Loma Linda University Health Care, Dept. of Ophthalmology
    • Mission Viejo, California, United States, 92691
      • Saddleback Eye Medical Associates
    • Pomona, California, United States, 91766
      • Western University College of Optometry
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale University
  • Florida
    • Fort Lauderdale, Florida, United States, 33382
      • Nova Southeastern University College of Optometry, The Eye Institute
    • Gainesville, Florida, United States, 32608
      • University of Florida Shands Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • The Emory Eye Center
  • Idaho
    • Boise, Idaho, United States, 83702
      • St Luke's Hospital
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago
    • Chicago, Illinois, United States, 60616
      • Illinois College of Optometry
    • Chicago Ridge, Illinois, United States, 60415
      • Ticho Eye Associates
    • Lisle, Illinois, United States, 60532
      • Progressive Eye Care
    • Schaumburg, Illinois, United States, 60194
      • Advanced Vision Center
    • Wilmette, Illinois, United States, 60091
      • Pediatric Eye Associates
  • Indiana
    • Bloomington, Indiana, United States, 47405
      • Indiana School of Optometry
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
    • West Des Moines, Iowa, United States, 50266
      • Wolfe Eye Clinic
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Wilmer Eye Institute
    • Baltimore, Maryland, United States, 21204-5809
      • Greater Baltimore Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Michigan
    • Big Rapids, Michigan, United States, 49307
      • Michigan College of Optometry at Ferris State Univ
    • Grand Rapids, Michigan, United States, 49503
      • Helen DeVos Children's Hospital Pediatric Ophthalmology
    • Grand Rapids, Michigan, United States, 49546
      • Pediatric Ophthalmology, P.C.
  • Minnesota
    • Minneapolis, Minnesota, United States, 55454
      • University of Minnesota-Minnesota Lions Children's Eye Clinic
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospitals and Clinics
    • Saint Louis, Missouri, United States, 63103
      • Saint Louis University Institute
    • Saint Louis, Missouri, United States, 63110
      • St. Louis Children's Hospital Eye Center
    • Saint Louis, Missouri, United States, 63121
      • U of MO St. Louis College of Optometry
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • University of Nebraska Medical Center
  • New Hampshire
    • Concord, New Hampshire, United States, 03301
      • Concord Ophthalmologic Associates
  • New Jersey
    • Marlton, New Jersey, United States, 08053
      • Michael F. Gallaway, O.D., P.C.
  • New York
    • New York, New York, United States, 10036
      • State University of New York, College of Optometry
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7040
      • University of North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Eye Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital
    • Columbus, Ohio, United States, 43205
      • Pediatric Ophthalmology Associates, Inc.
    • Columbus, Ohio, United States, 43210-1280
      • The Ohio State University College of Optometry
    • Poland, Ohio, United States, 44514
      • Eye Care Associates, Inc.
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Dean A. McGee Eye Institute, University of Oklahoma
  • Oregon
    • Portland, Oregon, United States, 97239
      • OHSU Casey Eye Institute
    • Portland, Oregon, United States, 97205
      • Pacific University College of Optometry
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16501
      • Pediatric Ophthalmology of Erie
    • Lancaster, Pennsylvania, United States, 17601
      • Conestoga Eye
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • Pediatric Eye Specialists
    • Memphis, Tennessee, United States, 38104
      • Southern College of Optometry
  • Texas
    • Houston, Texas, United States, 77204
      • University of Houston College of Optometry
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital - Dept. Of Ophthalmology
    • Lubbock, Texas, United States, 79430
      • Texas Tech University Health Science Center
    • San Antonio, Texas, United States, 78215
      • San Antonio Eye Center
    • The Woodlands, Texas, United States, 77381
      • Houston Eye Associates
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Virginia Pediatric Eye Center
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital, University of Washington
    • Spokane, Washington, United States, 99204
      • Spokane Eye Clinical Research
    • Spokane, Washington, United States, 99202
      • Northwest Pediatric Ophthalmology, P.S.
  • West Virginia
    • Huntington, West Virginia, United States, 25755
      • Marshall University
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin, University Station
  • Wyoming
    • Laramie, Wyoming, United States, 82070
      • Snowy Range Vision Center

Participation Criteria

Eligibility Criteria

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

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change in Amblyopic-eye Visual Acuity (VA) Older Cohort	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.	Baseline and 4 weeks
Mean Visual Acuity (VA) in Amblyopic-eye (Older Cohort)	Monocular distance visual acuity (VA) in current refractive correction (if required) in each eye by a certified examiner using the Electronic Early Treatment Diabetic Retinoscopy Study (E-ETDRS) visual acuity protocol for children ≥ 7 years on a study-certified acuity tester displaying single surrounded optotypes. For the analyses in the older cohort, the level of VA is measured as letter scores (approximate range: 0 to 97 letters, lower scores indicate poorer VA) and change in VA from baseline is measured in letters (positive values indicate improvement), defined as the difference in letter scores between enrollment and follow-up.	4 weeks
Mean Change in Amblyopic-eye Visual Acuity (VA) in Older Cohort	Monocular distance visual acuity (VA) in current refractive correction (if required) in each eye by a certified examiner using the Electronic Early Treatment Diabetic Retinoscopy Study (E-ETDRS) visual acuity protocol for children ≥ 7 years on a study-certified acuity tester displaying single surrounded optotypes. For the analyses in the older cohort, the level of VA is measured as letter scores (approximate range: 0 to 97 letters, lower scores indicate poorer VA) and change in VA from baseline is measured in letters (positive values indicate improvement), defined as the difference in letter scores between enrollment and follow-up.	Baseline and 8 weeks
Mean Visual Acuity (VA) in Amblyopic-eye (Older Cohort)	Monocular distance visual acuity (VA) in current refractive correction (if required) in each eye by a certified examiner using the Electronic Early Treatment Diabetic Retinoscopy Study (E-ETDRS) visual acuity protocol for children ≥ 7 years on a study-certified acuity tester displaying single surrounded optotypes. For the analyses in the older cohort, the level of VA is measured as letter scores (approximate range: 0 to 97 letters, lower scores indicate poorer VA) and change in VA from baseline is measured in letters (positive values indicate improvement), defined as the difference in letter scores between enrollment and follow-up.	8 weeks
Mean Change in Amblyopic-eye Visual Acuity (VA) Younger Cohort	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.	baseline and 4 weeks
Mean Visual Acuity (VA) in Amblyopic-eye (Younger Cohort)	Monocular distance visual acuity (VA) in current refractive correction (if required) in each eye by a certified examiner using the Electronic Early Treatment Diabetic Retinoscopy Study (E-ETDRS) visual acuity protocol for children ≥ 7 years on a study-certified acuity tester displaying single surrounded optotypes. For the analyses in the 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.	4 weeks
Mean Change in Amblyopic-eye Visual Acuity (VA) in Younger Cohort	Monocular distance visual acuity (VA) in current refractive correction (if required) in each eye by a certified examiner using the Electronic Early Treatment Diabetic Retinoscopy Study (E-ETDRS) visual acuity protocol for children ≥ 7 years on a study-certified acuity tester displaying single surrounded optotypes. For the analyses in the 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.	Baseline and 8 weeks
Mean Visual Acuity (VA) in Amblyopic-eye (Younger Cohort)	Monocular distance visual acuity (VA) in current refractive correction (if required) in each eye by a certified examiner using the Electronic Early Treatment Diabetic Retinoscopy Study (E-ETDRS) visual acuity protocol for children ≥ 7 years on a study-certified acuity tester displaying single surrounded optotypes. For the analyses in the 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 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
VA Improvement at 4 Weeks Defined as a Binary Outcome	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.	At 4 weeks
VA Improvement at 8 Weeks Defined as a Binary Outcome	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.	At 8 weeks
Distribution of Stereoacuity Scores at 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 weeks
Distribution of Change in Stereoacuity Scores From Baseline	Stereoacuity was tested at near in current refractive correction. Stereoacuity scores (seconds of arc) were calculated based on the Randot Butterfly (scores: 2000, Nil) and Randot Preschool stereoacuity (scores: 800, 400, 200, 100, 60 and 40) test methods. Lower scores indicate better stereoacuity. Results of the Randot Butterfly test were analyzed as 2000 (if correct response). Nil (4000) was defined as (1) an incorrect response on the butterfly in absence of a correct response on the 800 seconds of arc level of the Randot Preschool stereoacuity test or (2) an incorrect response on the 800 seconds of arc level if the butterfly was not attempted. For each visit, stereoacuity scores were ordered and assigned a rank score. Change in stereoacuity was calculated as the difference in ranked score between the enrollment and 4-week stereoacuity scores.	4 weeks
Distribution of Stereoacuity Scores at 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.	8 weeks
Distribution of Change in Stereoacuity Scores From Baseline	Stereoacuity was tested at near in current refractive correction. Stereoacuity scores (seconds of arc) were calculated based on the Randot Butterfly (scores: 2000, Nil) and Randot Preschool stereoacuity (scores: 800, 400, 200, 100, 60 and 40) test methods. Lower scores indicate better stereoacuity. Results of the Randot Butterfly test were analyzed as 2000 (if correct response). Nil (4000) was defined as (1) an incorrect response on the butterfly in absence of a correct response on the 800 seconds of arc level of the Randot Preschool stereoacuity test or (2) an incorrect response on the 800 seconds of arc level if the butterfly was not attempted. For each visit, stereoacuity scores were ordered and assigned a rank score. Change in stereoacuity was calculated as the difference in ranked score between the enrollment and 8-week stereoacuity scores.	8 weeks
Distribution of Stereoacuity Scores (Participants With no History of Strabismus)	Stereoacuity was tested at near in current refractive correction. Stereoacuity scores (measure as seconds of arc) were calculated based on the Randot Butterfly (scores: 2000, Nil) and Randot Preschool stereoacuity (scores: 800, 400, 200, 100, 60 and 40) test methods. Lower scores indicate better stereoacuity. Results of the Randot Butterfly test were analyzed as 2000 seconds of arc (if correct response). Nil was assigned a score of 4000 seconds of arc and was defined as (1) an incorrect response on the butterfly in absence of a correct response on the 800 seconds of arc level of the Randot Preschool stereoacuity test or (2) an incorrect response on the 800 seconds of arc level if the butterfly was not attempted.	4 weeks
Distribution of Change in Stereoacuity Scores From Baseline (Participants With no History of Strabismus)	Stereoacuity was tested at near in current refractive correction. Stereoacuity scores (seconds of arc) were calculated based on the Randot Butterfly (scores: 2000, Nil) and Randot Preschool stereoacuity (scores: 800, 400, 200, 100, 60 and 40) test methods. Lower scores indicate better stereoacuity. Results of the Randot Butterfly test were analyzed as 2000 (if correct response). Nil (4000) was defined as (1) an incorrect response on the butterfly in absence of a correct response on the 800 seconds of arc level of the Randot Preschool stereoacuity test or (2) an incorrect response on the 800 seconds of arc level if the butterfly was not attempted. For each visit, stereoacuity scores were ordered and assigned a rank score. Change in stereoacuity was calculated as the difference in ranked score between the enrollment and 4-week stereoacuity scores.	4 weeks
Distribution of Stereoacuity Scores (Participants With no History of Strabismus)	Stereoacuity was tested at near in current refractive correction. Stereoacuity scores (measure as seconds of arc) were calculated based on the Randot Butterfly (scores: 2000, Nil) and Randot Preschool stereoacuity (scores: 800, 400, 200, 100, 60 and 40) test methods. Lower scores indicate better stereoacuity. Results of the Randot Butterfly test were analyzed as 2000 seconds of arc (if correct response). Nil was assigned a score of 4000 seconds of arc and was defined as (1) an incorrect response on the butterfly in absence of a correct response on the 800 seconds of arc level of the Randot Preschool stereoacuity test or (2) an incorrect response on the 800 seconds of arc level if the butterfly was not attempted.	8 weeks
Distribution of Change in Stereoacuity Scores From Baseline (Participants With no History of Strabismus)	Stereoacuity was tested at near in current refractive correction. Stereoacuity scores (seconds of arc) were calculated based on the Randot Butterfly (scores: 2000, Nil) and Randot Preschool stereoacuity (scores: 800, 400, 200, 100, 60 and 40) test methods. Lower scores indicate better stereoacuity. Results of the Randot Butterfly test were analyzed as 2000 (if correct response). Nil (4000) was defined as (1) an incorrect response on the butterfly in absence of a correct response on the 800 seconds of arc level of the Randot Preschool stereoacuity test or (2) an incorrect response on the 800 seconds of arc level if the butterfly was not attempted. For each visit, stereoacuity scores were ordered and assigned a rank score. Change in stereoacuity was calculated as the difference in ranked score between the enrollment and 4-week stereoacuity scores.	8 weeks
Binocular Therapy: Treatment Compliance and Fellow-Eye Contrast	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.	4 weeks
Binocular Therapy: Treatment Compliance and Fellow-Eye Contrast	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.	8 weeks
Treatment Compliance With Spectacle Wear	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.	4 weeks
Treatment Compliance With Spectacle Wear	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.	8 weeks
Mean Change in Fellow Eye Visual Acuity at 4 Weeks (Older Cohort)	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.	Baseline and 4 weeks
Mean Change in Fellow Eye VA at 8 Weeks (Older Cohort)	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.	Baseline and 8 weeks
Ocular Alignment at 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.	4 weeks
Ocular Alignment at 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.	8 weeks
Distribution of Diplopia Frequency at 4 Weeks (Participant-reported)	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.	4 weeks
Distribution of Diplopia Frequency at 8 Weeks (Participant-reported)	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.	8 weeks
Change in Diplopia Frequency From Baseline to 4 Weeks (Participant-reported)	A standardized questionnaire was administered to participants and their parents to assess the presence and frequency of any diplopia since the last study visit. Change in diplopia frequency from baseline to 4 weeks was reported categorically.	4 weeks
Change in Diplopia Frequency From Baseline to 8 Weeks (Participant-reported)	A standardized questionnaire was administered to participants and their parents to assess the presence and frequency of any diplopia since the last study visit. Change in diplopia frequency from baseline to 8 weeks was reported categorically.	8 weeks
Distribution of Diplopia Frequency at 4 Weeks (Parent-reported)	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.	4 weeks
Distribution of Diplopia Frequency at 8 Weeks (Parent-reported)	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.	8 weeks
Change in Diplopia Frequency From Baseline to 4 Weeks (Parent-reported)	A standardized questionnaire was administered to participants and their parents to assess the presence and frequency of any diplopia since the last study visit. Change in diplopia frequency from baseline to 4 weeks was reported categorically.	4 weeks
Change in Diplopia Frequency From Baseline to 8 Weeks (Parent-reported)	A standardized questionnaire was administered to participants and their parents to assess the presence and frequency of any diplopia since the last study visit. Change in diplopia frequency from baseline to 8 weeks was reported categorically.	8 weeks
Frequency of Adverse Symptoms (Symptom Survey)	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.	4 weeks
Frequency of Adverse Symptoms (Symptom Survey) at 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.	8 weeks
Distribution of Change in Adverse Symptom Frequency (Symptom Survey) From Baseline to 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.	4 weeks
Distribution of Change in Adverse Symptom Frequency (Symptom Survey) From Baseline to 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.	8 weeks
Mean Change in Fellow Eye Visual Acuity at 4 Weeks (Younger Cohort)	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.	Baseline and 4 weeks
Mean Change in Fellow Eye VA at 8 Weeks (Younger Cohort)	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.	baseline and 8 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Analysis: Subgroup VA Change Analysis at 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.	Baseline and 4 weeks

Collaborators and Investigators

• Sponsor: Jaeb Center for Health Research
• Collaborators: National Eye Institute (NEI); Pediatric Eye Disease Investigator Group
• Investigators: Study Chair: Ruth Manny, OD, PhD, University of Houston College of Optometry; Study Chair: Jonathan Holmes, MD, Mayo Clinic

Publications and helpful links

General 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2017
• Primary Completion (Actual): April 20, 2020
• Study Completion (Actual): July 10, 2020

Study Registration Dates

• First Submitted: November 16, 2016
• First Submitted That Met QC Criteria: December 5, 2016
• First Posted (Estimate): December 6, 2016

Study Record Updates

• Last Update Posted (Actual): June 11, 2021
• Last Update Submitted That Met QC Criteria: June 10, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Amblyopia
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Eye Diseases; Neurologic Manifestations; Sensation Disorders; Vision Disorders; Amblyopia
• Other Study ID Numbers: ATS20; 2U10EY011751 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD 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.
• IPD Sharing Time Frame: Data will be made available after publication of each primary manuscript.
• IPD Sharing Access Criteria: Users accessing the data must enter an email address.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No