Clinical trial NCT02983552: Binocular Dig Rush Game Treatment for Amblyopia
Official title: Binocular Dig Rush Game Treatment for Amblyopia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Amblyopia
Keywords: Amblyopia
Lead sponsor: Jaeb Center for Health Research
Sponsor class: OTHER
Collaborators: name: Pediatric Eye Disease Investigator Group
name: National Eye Institute (NEI)
First posted: 2016-12-06
Enrollment: 320
Sex: ALL
Minimum age (years): 4
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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)

Primary outcomes:
measure: Mean Change in Amblyopic-eye Visual Acuity (VA) Older Cohort
timeFrame: Baseline and 4 weeks
measure: Mean Visual Acuity (VA) in Amblyopic-eye (Older Cohort)
timeFrame: 4 weeks
measure: Mean Change in Amblyopic-eye Visual Acuity (VA) in Older Cohort
timeFrame: Baseline and 8 weeks
measure: Mean Visual Acuity (VA) in Amblyopic-eye (Older Cohort)
timeFrame: 8 weeks
measure: Mean Change in Amblyopic-eye Visual Acuity (VA) Younger Cohort
timeFrame: baseline and 4 weeks
measure: Mean Visual Acuity (VA) in Amblyopic-eye (Younger Cohort)
timeFrame: 4 weeks
measure: Mean Change in Amblyopic-eye Visual Acuity (VA) in Younger Cohort
timeFrame: Baseline and 8 weeks
measure: Mean Visual Acuity (VA) in Amblyopic-eye (Younger Cohort)
timeFrame: 8 weeks
Secondary outcomes:
measure: VA Improvement at 4 Weeks Defined as a Binary Outcome
timeFrame: At 4 weeks
measure: VA Improvement at 8 Weeks Defined as a Binary Outcome
timeFrame: At 8 weeks
measure: Distribution of Stereoacuity Scores at 4 Weeks
timeFrame: 4 weeks
measure: Distribution of Change in Stereoacuity Scores From Baseline
timeFrame: 4 weeks
measure: Distribution of Stereoacuity Scores at 8 Weeks
timeFrame: 8 weeks
measure: Distribution of Change in Stereoacuity Scores From Baseline
timeFrame: 8 weeks
measure: Distribution of Stereoacuity Scores (Participants With no History of Strabismus)
timeFrame: 4 weeks
measure: Distribution of Change in Stereoacuity Scores From Baseline (Participants With no History of Strabismus)
timeFrame: 4 weeks
measure: Distribution of Stereoacuity Scores (Participants With no History of Strabismus)
timeFrame: 8 weeks
measure: Distribution of Change in Stereoacuity Scores From Baseline (Participants With no History of Strabismus)
timeFrame: 8 weeks
measure: Binocular Therapy: Treatment Compliance and Fellow-Eye Contrast
timeFrame: 4 weeks
measure: Binocular Therapy: Treatment Compliance and Fellow-Eye Contrast
timeFrame: 8 weeks
measure: Treatment Compliance With Spectacle Wear
timeFrame: 4 weeks
measure: Treatment Compliance With Spectacle Wear
timeFrame: 8 weeks
measure: Mean Change in Fellow Eye Visual Acuity at 4 Weeks (Older Cohort)
timeFrame: Baseline and 4 weeks
measure: Mean Change in Fellow Eye VA at 8 Weeks (Older Cohort)
timeFrame: Baseline and 8 weeks
measure: Ocular Alignment at 4 Weeks
timeFrame: 4 weeks
measure: Ocular Alignment at 8 Weeks
timeFrame: 8 weeks
measure: Distribution of Diplopia Frequency at 4 Weeks (Participant-reported)
timeFrame: 4 weeks
measure: Distribution of Diplopia Frequency at 8 Weeks (Participant-reported)
timeFrame: 8 weeks
measure: Change in Diplopia Frequency From Baseline to 4 Weeks (Participant-reported)
timeFrame: 4 weeks
measure: Change in Diplopia Frequency From Baseline to 8 Weeks (Participant-reported)
timeFrame: 8 weeks
measure: Distribution of Diplopia Frequency at 4 Weeks (Parent-reported)
timeFrame: 4 weeks
measure: Distribution of Diplopia Frequency at 8 Weeks (Parent-reported)
timeFrame: 8 weeks
measure: Change in Diplopia Frequency From Baseline to 4 Weeks (Parent-reported)
timeFrame: 4 weeks
measure: Change in Diplopia Frequency From Baseline to 8 Weeks (Parent-reported)
timeFrame: 8 weeks
measure: Frequency of Adverse Symptoms (Symptom Survey)
timeFrame: 4 weeks
measure: Frequency of Adverse Symptoms (Symptom Survey) at 8 Weeks
timeFrame: 8 weeks
measure: Distribution of Change in Adverse Symptom Frequency (Symptom Survey) From Baseline to 4 Weeks
timeFrame: 4 weeks
measure: Distribution of Change in Adverse Symptom Frequency (Symptom Survey) From Baseline to 8 Weeks
timeFrame: 8 weeks
measure: Mean Change in Fellow Eye Visual Acuity at 4 Weeks (Younger Cohort)
timeFrame: Baseline and 4 weeks
measure: Mean Change in Fellow Eye VA at 8 Weeks (Younger Cohort)
timeFrame: baseline and 8 weeks
Other outcomes:
measure: Exploratory Analysis: Subgroup VA Change Analysis at 4 Weeks
timeFrame: Baseline and 4 weeks
Locations:
city: Birmingham
country: United States
facility: UAB Pediatric Eye Care; Birmingham Health Care
state: Alabama
city: Glendale
country: United States
facility: Midwestern University Eye Institute
state: Arizona
city: Anaheim
country: United States
facility: University Eye Center at Ketchum Health
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Health Care, Dept. of Ophthalmology
state: California
city: Mission Viejo
country: United States
facility: Saddleback Eye Medical Associates
state: California
city: Pomona
country: United States
facility: Western University College of Optometry
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Fort Lauderdale
country: United States
facility: Nova Southeastern University College of Optometry, The Eye Institute
state: Florida
city: Gainesville
country: United States
facility: University of Florida Shands Hospital
state: Florida
city: Atlanta
country: United States
facility: The Emory Eye Center
state: Georgia
city: Boise
country: United States
facility: St Luke's Hospital
state: Idaho
city: Chicago Ridge
country: United States
facility: Ticho Eye Associates
state: Illinois
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Chicago
country: United States
facility: Illinois College of Optometry
state: Illinois
city: Lisle
country: United States
facility: Progressive Eye Care
state: Illinois
city: Schaumburg
country: United States
facility: Advanced Vision Center
state: Illinois
city: Wilmette
country: United States
facility: Pediatric Eye Associates
state: Illinois
city: Bloomington
country: United States
facility: Indiana School of Optometry
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: West Des Moines
country: United States
facility: Wolfe Eye Clinic
state: Iowa
city: Baltimore
country: United States
facility: Greater Baltimore Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Wilmer Eye Institute
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Big Rapids
country: United States
facility: Michigan College of Optometry at Ferris State Univ
state: Michigan
city: Grand Rapids
country: United States
facility: Helen DeVos Children's Hospital Pediatric Ophthalmology
state: Michigan
city: Grand Rapids
country: United States
facility: Pediatric Ophthalmology, P.C.
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota-Minnesota Lions Children's Eye Clinic
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Hospitals and Clinics
state: Missouri
city: Saint Louis
country: United States
facility: Saint Louis University Institute
state: Missouri
city: Saint Louis
country: United States
facility: St. Louis Children's Hospital Eye Center
state: Missouri
city: Saint Louis
country: United States
facility: U of MO St. Louis College of Optometry
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Concord
country: United States
facility: Concord Ophthalmologic Associates
state: New Hampshire
city: Marlton
country: United States
facility: Michael F. Gallaway, O.D., P.C.
state: New Jersey
city: New York
country: United States
facility: State University of New York, College of Optometry
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Durham
country: United States
facility: Duke University Eye Center
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Columbus
country: United States
facility: Pediatric Ophthalmology Associates, Inc.
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University College of Optometry
state: Ohio
city: Poland
country: United States
facility: Eye Care Associates, Inc.
state: Ohio
city: Oklahoma City
country: United States
facility: Dean A. McGee Eye Institute, University of Oklahoma
state: Oklahoma
city: Portland
country: United States
facility: Pacific University College of Optometry
state: Oregon
city: Portland
country: United States
facility: OHSU Casey Eye Institute
state: Oregon
city: Erie
country: United States
facility: Pediatric Ophthalmology of Erie
state: Pennsylvania
city: Lancaster
country: United States
facility: Conestoga Eye
state: Pennsylvania
city: Chattanooga
country: United States
facility: Pediatric Eye Specialists
state: Tennessee
city: Memphis
country: United States
facility: Southern College of Optometry
state: Tennessee
city: Houston
country: United States
facility: Texas Children's Hospital - Dept. Of Ophthalmology
state: Texas
city: Houston
country: United States
facility: University of Houston College of Optometry
state: Texas
city: Lubbock
country: United States
facility: Texas Tech University Health Science Center
state: Texas
city: San Antonio
country: United States
facility: San Antonio Eye Center
state: Texas
city: The Woodlands
country: United States
facility: Houston Eye Associates
state: Texas
city: Norfolk
country: United States
facility: Virginia Pediatric Eye Center
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Hospital, University of Washington
state: Washington
city: Spokane
country: United States
facility: Northwest Pediatric Ophthalmology, P.S.
state: Washington
city: Spokane
country: United States
facility: Spokane Eye Clinical Research
state: Washington
city: Huntington
country: United States
facility: Marshall University
state: West Virginia
city: Madison
country: United States
facility: University of Wisconsin, University Station
state: Wisconsin
city: Laramie
country: United States
facility: Snowy Range Vision Center
state: Wyoming
city: Calgary
country: Canada
facility: Alberta Children's Hospital
state: Alberta
Study officials:
affiliation: University of Houston College of Optometry
name: Ruth Manny, OD, PhD
role: STUDY_CHAIR
affiliation: Mayo Clinic
name: Jonathan Holmes, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.