Clinical trial NCT02200211: Study of Binocular Computer Activities for Treatment of Amblyopia
Official title: Study of Binocular Computer Activities for Treatment of 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: 2014-07-25
Enrollment: 485
Sex: ALL
Minimum age (years): 5
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to compare the effectiveness of 1 hour/day of binocular game play 7 days per week with 2 hours/day patching 7 days per week in children 5 to \<17

Detailed description: The purpose of the study is to 1) compare the effectiveness of 1 hour/day of binocular game play 7 days per week (minimum of 4 days per week) with 2 hours/day patching 7 days per week, in children 5 to \<13 years of age (younger cohort), as a non-inferiority study; and 2) to compare the effectiveness of 1 hour/day of binocular game play 7 days per week (minimum of 4 days per week) with 2 hours/day patching 7 days per week, in children 13 to \<17 years of age (older cohort), as a superiority study.

Eligibility criteria: Inclusion Criteria:

1. Age 5 to \<17 years
2. Amblyopia associated with strabismus, anisometropia, or both (previously treated or untreated)

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

      * Presence of a heterotropia on examination at distance or near fixation (with or without spectacles)
      * 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:

      * ≥0.50 diopter (D) difference between eyes in spherical equivalent
      * ≥1.50 D difference between eyes in astigmatism in any meridian
   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 between eyes in astigmatism in any meridian
      * Note: the spherical equivalent requirement differs from that in the definition for refractive/anisometropic amblyopia
3. No amblyopia treatment in the past 2 weeks (patching, atropine, Bangerter, vision therapy)
4. Refractive correction (spectacles or contact lenses, if applicable) must meet the following criteria at enrollment and be based on a cycloplegic refraction that is not more than 7 months old.

   1. Requirements for Correction of Refractive Error:

      1. For subjects meeting criteria for strabismic (only) amblyopia (see 2.2.1 #2 above):

         • Hypermetropia, if corrected, must not be under-corrected by more than +1.50 D spherical equivalent, and the reduction in plus sphere must be symmetric in the two eyes.
      2. For subjects meeting criteria for anisometropic or combined-mechanism amblyopia (see 2.2.1 #2 above):

         * Spherical equivalent must be within 0.50 D of fully correcting the anisometropia
         * Hypermetropia must not be under-corrected by more than +1.50 D spherical equivalent, and reduction in plus must be symmetric in the two eyes
         * Cylinder power in both eyes must be within 0.50 D of fully correcting the astigmatism
         * Cylinder axis for both eyes must be within 6 degrees of the axis of the cycloplegic refraction when cylinder power is ≥1.00 D
   2. Refractive corrections meeting the above criteria must be worn for either:

      * 16 weeks or more or
      * Until visual acuity in amblyopic eye is stable (defined as 2 consecutive visual acuity measurements by the same testing method at least 4 weeks apart with \<1 line change (\<5 letters if E-ETDRS))
   3. Monocular or binocular contact lens wear is allowed provided the contact lenses meet the above refractive requirements at the corneal plane. The same form of correction must be worn throughout the entire study during study procedures (i.e., no changing between contacts and spectacles while patching or while game-playing or study testing). Safety glasses are not required for subjects wearing contact lenses, but investigators are encouraged to suggest safety glasses be worn over contact lenses.
5. Visual acuity, measured in each eye without cycloplegia in current refractive correction (if applicable) within 7 days prior to randomization using the Amblyopia Treatment Study single-surround HOTV (ATS-HOTV) visual acuity protocol for children \< 7 years and the Electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) visual acuity protocol for children ≥ 7 years on a study-approved device displaying single surrounded optotypes, as follows:

   1. Visual acuity in the amblyopic eye 20/40 to 20/200 inclusive (33 to 72 letters if E-ETDRS)
   2. Visual acuity in the fellow eye 20/25 or better (≥ 78 letters if E-ETDRS)
   3. Interocular difference ≥ 3 logMAR lines (≥ 15 letters if E-ETDRS) (i.e., amblyopic-eye acuity at least 3 logMAR lines worse than fellow-eye acuity)
6. Heterotropia or heterophoria with a total near deviation of ≤ 10∆ (measured by PACT).
7. Ability to align the nonius cross on the binocular game system (angles of ocular deviation \>10∆ would require the nonius cross to be adjusted to such an extent that playing of the game would be compromised).
8. Subject is able to play Hess Falling Blocks game on the study iPad® (on easy setting) under binocular conditions (with red-green glasses), as demonstrated by scoring at least 1 line in the office.
9. Investigator is willing to prescribe computer game play or patching per protocol.
10. Parent understands the protocol and is willing to accept randomization.
11. Parent has phone (or access to phone) and is willing to be contacted by Jaeb Center staff.
12. Relocation outside of area of an active Pediatric Eye Disease Investigator Group (PEDIG) site for this study within the next 16 weeks is not anticipated.

Exclusion Criteria:

A subject is excluded for any of the following reasons:

1. Prism in the refractive correction at time of enrollment (eligible only if prism is discontinued 2 weeks prior to enrollment).
2. Myopia greater than -6.00 D spherical equivalent in either eye.
3. Previous intraocular or refractive surgery.
4. Any treatment for amblyopia (patching, atropine, Bangerter filter, or vision therapy) during the past 2 weeks. Previous amblyopia therapy is allowed regardless of type, but must be discontinued at least 2 weeks immediately prior to enrollment.
5. Ocular co-morbidity that may reduce visual acuity determined by an ocular examination performed within the past 7 months (Note: nystagmus per se does not exclude the subject if the above visual acuity 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. Heterotropia or heterophoria with a total ocular deviation \>10∆ (phoria plus tropia \>10∆) at near (measured by PACT).

Primary outcomes:
measure: Change in Distance Visual Acuity From Baseline in the Younger Cohort (5 to <13 Years)
timeFrame: Baseline and 16 weeks
measure: Mean Amblyopic Eye Visual Acuity (Younger Cohort)
timeFrame: 16 Weeks from baseline
measure: Mean Change in Amblyopic-eye Visual Acuity in the Older Cohort (13 to <17 Years)
timeFrame: Baseline and 16 weeks
measure: Mean Amblyopic-eye Visual Acuity in the Older Cohort (13 to <17 Years)
timeFrame: 16 weeks
measure: Distribution of Change in Amblyopic-eye Visual Acuity
timeFrame: Baseline and 16 weeks
measure: Distribution of Amblyopic-eye Visual Acuity
timeFrame: At 16 weeks
Secondary outcomes:
measure: Number of Participants With Amblyopic-eye VA Improvement of 2 or More logMAR Lines (10 or More Letters if E-ETDRS) From Baseline
timeFrame: Baseline and 16-week visit
measure: Number of Participants With Resolution of Amblyopia
timeFrame: 16-week visit
measure: Time Course of Visual Acuity Improvement
timeFrame: Baseline, 4 weeks, 8 weeks, 12 weeks and 16 weeks
measure: Younger Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups
timeFrame: Baseline and 16 weeks
measure: Older Cohort: Change in Distance Visual Acuity From Baseline According to Subgroups
timeFrame: Baseline and 16 weeks
measure: Distribution of Stereoacuity Scores
timeFrame: 16 weeks
measure: Median Stereoacuity Score (Seconds of Arc)
timeFrame: 16 weeks
measure: Distribution of Stereoacuity Scores (Participants With no History of Strabismus)
timeFrame: 16 weeks
measure: Distribution of Change in Stereoacuity Scores From Baseline
timeFrame: Baseline and 16 weeks
measure: Distribution of Change in Stereoacuity Scores From Baseline (Participants With no History of Strabismus)
timeFrame: Baseline and 16 weeks
measure: Binocular Treatment Group: Adherence and Fellow-eye Contrast (iPad Log File Data)
timeFrame: Entire study period, up to 16 weeks
measure: Binocular Treatment Group: Median Adherence With Prescribed Game Play (iPad Log File Data)
timeFrame: Entire study period, up to 16 weeks
Other outcomes:
measure: Percentage of Participants Reporting >75% of Prescribed Treatment Completed (Subjective Measures of Adherence)
timeFrame: 16 Weeks from baseline
measure: Participants Who Received Non-protocol, Alternative Treatment During the Study
timeFrame: Entire study period, up to 16 weeks
measure: Safety Analysis: Distribution of the Change in Fellow-eye Visual Acuity From Baseline
timeFrame: 16-week visit
measure: Safety Analysis: Change in Fellow-eye Visual Acuity From Baseline (Younger Cohort)
timeFrame: 16-week visit
measure: Safety Analysis: Change in Fellow-eye Visual Acuity From Baseline (Older Cohort)
timeFrame: 16-week visit
measure: Safety Analysis: Development of a New Tropia and/or Worsening of a Pre-existing Deviation by 10 pd
timeFrame: 16 weeks
measure: Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Parent-reported)
timeFrame: 16 weeks
measure: Safety Analysis: Distribution of Diplopia Frequency at 16 Weeks (Participant-reported)
timeFrame: 16 weeks
measure: Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Follow-up (Parent-reported)
timeFrame: Across study follow-up visits, up to 16 weeks
measure: Safety Analysis: Distribution of Maximum Frequency of Diplopia Reported Across Study Follow-up (Participant-reported)
timeFrame: Across study follow-up visits, up to 16 weeks
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Seattle
country: United States
facility: Seattle Children's Hospital, University of Washington
state: Washington
Study officials:
affiliation: Mayo Clinic
name: Jonathan Holmes, MD
role: STUDY_CHAIR
affiliation: University of Washington
name: Vivan Manh, OD
role: STUDY_CHAIR
References:
citation: Holmes JM, Manh VM, Lazar EL, Beck RW, Birch EE, Kraker RT, Crouch ER, Erzurum SA, Khuddus N, Summers AI, Wallace DK; Pediatric Eye Disease Investigator Group. Effect of a Binocular iPad Game vs Part-time Patching in Children Aged 5 to 12 Years With Amblyopia: A Randomized Clinical Trial. JAMA Ophthalmol. 2016 Dec 1;134(12):1391-1400. doi: 10.1001/jamaophthalmol.2016.4262.
citation: Tailor V, Ludden S, Bossi M, Bunce C, Greenwood JA, Dahlmann-Noor A. Binocular versus standard occlusion or blurring treatment for unilateral amblyopia in children aged three to eight years. Cochrane Database Syst Rev. 2022 Feb 7;2(2):CD011347. doi: 10.1002/14651858.CD011347.pub3.