A Randomized Trial to Evaluate Sequential vs Simultaneous Patching
- Conditions
- Amblyopia
- Interventions
- Other: PatchingOther: Glasses
- Registration Number
- NCT04378790
- Lead Sponsor
- Jaeb Center for Health Research
- Brief Summary
A randomized trial to determine whether simultaneous treatment with spectacles and patching has an equivalent VA outcome compared with sequential treatment, first with spectacles alone followed by patching (if needed), for previously untreated amblyopia in children 3 to \<13 years of age.
- Detailed Description
At an enrollment visit, distance VA will be measured in trial frames with or without cycloplegia based on a cycloplegic refraction performed within 30 days. If still apparently eligible, children will be prescribed spectacles and will then return for a spectacle baseline visit, where they will wear their new spectacles for the first time for at least 10 minutes (but no more than 24 hours) and will be tested in those new spectacles to confirm final eligibility prior to randomization.
Participants not found to be eligible in their new spectacles will end study participation. Participants eligible for the study will be randomly allocated to one of two treatment groups: Sequential (spectacles alone) and then patching if needed (monitored by ODM), or Simultaneous (spectacles and patching monitored by ODM).
After randomization, follow-up visits will occur at 8-week intervals through 56 weeks. At each visit on or after the 8-week visit, participants will be classified as either: stable/worsening or improving; those stable/worsening are then classified as having either resolved or residual amblyopia, provided that the current and most recent previous visit were completed at least 6-weeks apart (target 8 weeks) and provided the required test and retest VA testing was completed. Participants who are stable/worsening and have residual amblyopia in the sequential group will start patching (monitored by ODM) and continue to be followed every 8 weeks. Participants in the simultaneous group, or in the sequential group after having advanced to patching, who are stable/worsening but have residual amblyopia will be released to treatment at investigator discretion.
All participants continue 8-weekly visits until 56 weeks when Study participation ends.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 544
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Age 3 to <13 years at the time of randomization
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Amblyopia associated with anisometropia, strabismus, or both
o Criteria for strabismic amblyopia: At least one of the following must be met:
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Presence of a heterotropia on examination at distance or near fixation (with or without optical correction)
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Documented history of strabismus which is no longer present (which in the judgment of the investigator could have caused amblyopia)
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Criteria for anisometropia: At least one of the following criteria must be met:
- 1.00 D difference between eyes in spherical equivalent (SE)
- 1.50 D difference in astigmatism between corresponding meridians in the two eyes
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Criteria for combined-mechanism amblyopia: Both of the following criteria must be met:
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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
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No previous treatment for amblyopia, including no more than 24 hours of spectacle wear.
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Investigator planning to initiate spectacle correction of refractive error meeting the following criteria based on a cycloplegic refraction that has been performed within 30 days:
- Full correction of anisometropia
- Full correction of astigmatism with the same axis found by the cycloplegic refraction
- Full correction of any myopia
- Hyperopia must not be under corrected by more than 1.50 D, and reduction in plus sphere must be symmetric in the two eyes.
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At enrollment, single VA measured in each eye assessed in trial frames with the spectacle correction the investigator plans to prescribe, using the investigator's routine method as follows:
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VA in the amblyopic eye 20/40 to 20/200 inclusive.
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Age-normal VA in the fellow eye:40,41
- 3 years: 0.4 logMAR (20/50) or better
- 4 years: 0.3 logMAR (20/40) or better
- 5-6 years: 0.2 logMAR (20/32) or better
- 7-12 years: 0.12 logMAR (78 letters) or better
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Interocular difference ≥ 3 logMAR lines (0.3 logMAR) or ≥ 15 letters o When participants return for the Spectacle Baseline / Randomization Visit with their new spectacles, they will need to meet the same criteria as above using the ATS-HOTV or E-ETDRS protocol after wearing the new spectacles for at least 10 minutes (based upon the mean of a test and retest of VA in those new spectacles).
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Investigator is willing to prescribe spectacle wear followed sequentially by patching or simultaneous spectacles and patching treatment per protocol.
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Parent understands the protocol and is willing to accept randomization.
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Parent has phone (or access to phone) and is willing to be contacted by Jaeb Center staff or other study staff.
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Relocation outside of area of an active PEDIG site for this study within the next 56 weeks is not anticipated.
- Myopia greater than -6.00 D spherical equivalent in either eye.
- Previous intraocular or refractive surgery.
- Planned strabismus surgery in the next 56 weeks.
- Any previous treatment for amblyopia (patching, atropine, Bangerter filter, vision therapy, or binocular treatment).
- Previous spectacle or contact lens wear for more than 24 hours.
- Parent and participant willing to forego option of contact lens wear for the duration of the study.
- 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 participant if the above VA criteria are met).
- Severe developmental delay that would interfere with treatment or evaluation (in the opinion of the investigator). Participants with mild speech delay or reading and/or learning disabilities or attention deficit hyperactivity disorder (ADHD) are not excluded.
- Known allergy to adhesive patches.
- Known allergy to silicone.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Sequential treatment Patching full-time spectacle correction first, with subsequent patching for 2 hours per day/7 days per week only if needed (no improvement (stable/worsening) and residual) Sequential treatment Glasses full-time spectacle correction first, with subsequent patching for 2 hours per day/7 days per week only if needed (no improvement (stable/worsening) and residual) Simultaneous treatment Glasses full-time spectacle correction and part-time patching for 2 hours per day/7 days per week Simultaneous treatment Patching full-time spectacle correction and part-time patching for 2 hours per day/7 days per week
- Primary Outcome Measures
Name Time Method Mean Change in Amblyopic Eye logMAR distance Visual Acuity 56 weeks 1. Amblyopic eye VA (calculated as mean of test and retest) at the last visit that was the basis for a "stable resolved" or "stable residual" determination (in the sequential group, stable residual amblyopia criteria can be reached only after patching has been instituted); or
2. 56-week visit amblyopic-eye VA (calculated as mean of test and retest) in those completing a 56-week visit without ever meeting criteria for "stable resolved" or "stable residual" amblyopia (if retest missing at 56 weeks, the single test value will be used).
- Secondary Outcome Measures
Name Time Method Proportion of participants who achieve Binary distance visual acuity outcomes 56 weeks The proportion of participants who achieve the following binary outcomes will be tabulated by treatment group to aid in the interpretation of the primary outcome:
* The proportion of participants with outcome amblyopic-eye distance VA improvement of ≥ 2 logMAR lines (≥ 10 letters if E-ETDRS) from baseline.
* The proportion of participants with stable resolved VA.
Poisson regression with the log link will be used to estimate the relative risk of each outcome for the sequential versus simultaneous and a multiplicity adjusted two sided P-value and confidence interval. The Poisson models will include an adjustment for baseline amblyopic eye VA.
In the event the number of outcomes is too small for reliable estimation with Poisson regression,43 a treatment group difference and 95% confidence interval will be estimated using the Farrington-Manning Score test or other exact method with no adjustment for baseline VA.Time to Stable Resolved Amblyopia 56 weeks For those participants who are classified as "stable resolved," the time from baseline to the time meeting that classification will be compared between treatment groups, using a Kaplan-Meier analysis with the logrank test. Multiplicity adjusted two sided P-values and confidence intervals will be produced.
Change in binocularity levels 56 Weeks Binocularity will be assessed on an ordered scale combining the results of the Randot Preschool Test, Randot butterfly, and Worth 4-Dot (W4D) at near. Results of each individual test also will be tabulated at baseline and at the final study visit according to treatment group.
The possible levels of binocularity will be 40, 60, 100, 200, 400, 800 seconds of arc (Randot Preschool test), 2000 seconds of arc (Randot butterfly), binocular perception by W4D (4 or 5 lights), or no binocular perception by W4D (2 or 3 lights). This yields an ordered binocularity scale with 9 ordered levels. The change in binocularity levels for each test will be tabulated and compared between treatment groups using the exact Wilcoxon rank-sum test. The proportion of participants in each treatment group unable to perform testing will be tabulated but these participants will not be included in the analysis of change.Pediatric Eye Questionnaire (PedEyeQ) 56 weeks Rasch scores for each questionnaire item will be obtained from published look-up tables available at www.pedig.net, and used to calculate a score for each participant and a separate treatment group mean for the three PedEyeQ domains of the Child, Proxy and Parent PedEyeQ at randomization and at each visit. Scores will also be converted to a 0-100 scale to aid in interpretation. Multiplicity adjusted two sided P-values and confidence intervals will be produced.
Child PedEyeQ: Functional Vision, Bothered by Eyes and Vision, Social, Frustration / Worry Proxy PedEyeQ: Functional Vision, Bothered by Eyes and Vision, Social, Frustration / Worry, Eyecare Parent PedEyeQ: Impact on Parent and Family, Worry about Child's Eye Condition, Worry about Self-perception and Interactions, Worry about Functional VisionProportion Achieving Stable Resolved Outcome with Spectacles Alone 56 Weeks The proportion of participants in the Sequential Spectacles group who achieve "stable resolved" outcome status with spectacles alone will be calculated, along with a multiplicity adjusted two sided P-value and confidence interval.
Difference in Mean Change of Distance Visual Acuity after 8 Weeks on Randomized Treatment 56 Weeks An analysis of covariance (ANCOVA) will be performed to compute the difference in mean change in amblyopic-eye distance logMAR VA after 8 weeks between the sequential and simultaneous treatment groups, adjusted for baseline amblyopic eye distance VA, and a multiplicity adjusted two sided P-value and confidence interval will be constructed on the treatment group difference for each time point.
Difference in mean change in amblyopic-eye log contrast sensitivity 56 weeks Contrast sensitivity scores range from unable (\<0.90), and then from 0.90 to 2.05 (by 0.05 log contrast sensitivity units). An analysis of covariance (ANCOVA) will be performed to compute the difference in mean change in amblyopic-eye log contrast sensitivity units between the sequential and simultaneous treatment groups, adjusted for baseline amblyopic eye contrast sensitivity, and a multiplicity adjusted two sided P-value and confidence interval will be produced.
Trial Locations
- Locations (66)
Snowy Range Vision Center
🇺🇸Laramie, Wyoming, United States
UAB Pediatric Eye Care; Birmingham Health Care
🇺🇸Birmingham, Alabama, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Midwestern University Eye Institute
🇺🇸Glendale, Arizona, United States
Arizonia Pediatric Eye Specialists
🇺🇸Phoenix, Arizona, United States
University of Arizona
🇺🇸Tucson, Arizona, United States
Univ. of California- Berkeley
🇺🇸Berkeley, California, United States
Marshall B. Ketchum University
🇺🇸Fullerton, California, United States
Univ of California, Irvine- Gavin Herbert Eye Institute
🇺🇸Irvine, California, United States
Loma Linda University Health Care, Dept. of Ophthalmology
🇺🇸Loma Linda, California, United States
Children's Hospital of Los Angeles (CHLA)
🇺🇸Los Angeles, California, United States
Stanford University
🇺🇸Palo Alto, California, United States
Western University College of Optometry
🇺🇸Pomona, California, United States
University of California, Davis
🇺🇸Sacramento, California, United States
University of California San Francisco Department of Ophthalmology
🇺🇸San Francisco, California, United States
Eye Physicians & Surgeons, PC
🇺🇸Milford, Connecticut, United States
Nova Southeastern University College of Optometry, The Eye Institute
🇺🇸Fort Lauderdale, Florida, United States
Nemours Children's Clinic
🇺🇸Jacksonville, Florida, United States
University of South Florida (USF) Eye
🇺🇸Tampa, Florida, United States
St Luke's Hospital
🇺🇸Boise, Idaho, United States
Ticho Eye Associates
🇺🇸Chicago Ridge, Illinois, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
Midwestern U Chicago College of Optometry
🇺🇸Downers Grove, Illinois, United States
Progressive Eye Care
🇺🇸Lisle, Illinois, United States
Indiana School of Optometry
🇺🇸Bloomington, Indiana, United States
Indiana University School of Optometry
🇺🇸Indianapolis, Indiana, United States
Wolfe Eye Clinic
🇺🇸West Des Moines, Iowa, United States
Wilmer Eye Institute
🇺🇸Baltimore, Maryland, United States
Boston Medical Center
🇺🇸Boston, Massachusetts, United States
Boston Children's Hospital Waltham
🇺🇸Boston, Massachusetts, United States
Helen DeVos Children's Hospital Pediatric Ophthalmology
🇺🇸Grand Rapids, Michigan, United States
Pediatric Ophthalmology, P.C.
🇺🇸Grand Rapids, Michigan, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
PineCone Vision Center
🇺🇸Sartell, Minnesota, United States
Children's Mercy Hospitals and Clinics
🇺🇸Kansas City, Missouri, United States
St. Louis Children's Hospital Eye Center
🇺🇸Saint Louis, Missouri, United States
U of MO St. Louis College of Optometry
🇺🇸Saint Louis, Missouri, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Ross Eye Institute, University of Buffalo, Med School Dept Ophthalmology
🇺🇸Buffalo, New York, United States
NYU Langone Health
🇺🇸New York, New York, United States
State University of New York, College of Optometry
🇺🇸New York, New York, United States
University of North Carolina
🇺🇸Chapel Hill, North Carolina, United States
Duke University Eye Center
🇺🇸Durham, North Carolina, United States
Akron Children's Hospital
🇺🇸Akron, Ohio, United States
Cincinnati Children's Hospital
🇺🇸Cincinnati, Ohio, United States
Ohio State University College of Optometry
🇺🇸Columbus, Ohio, United States
Dean A. McGee Eye Institute
🇺🇸Oklahoma City, Oklahoma, United States
River View Family Eyecare
🇺🇸Albany, Oregon, United States
Casey Eye Institute
🇺🇸Portland, Oregon, United States
Pediatric Ophthalmology of Erie
🇺🇸Erie, Pennsylvania, United States
Conestoga Eye
🇺🇸Lancaster, Pennsylvania, United States
Wills Eye Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Salus University/Pennsylvania College of Optometry
🇺🇸Philadelphia, Pennsylvania, United States
Prisma Health
🇺🇸Columbia, South Carolina, United States
Southern College of Optometry
🇺🇸Memphis, Tennessee, United States
Vanderbilt University Medical Center - Vanderbilt Eye Institute
🇺🇸Nashville, Tennessee, United States
Pediatric Eye Specialists, LLP
🇺🇸Fort Worth, Texas, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Texas Tech University Health Science Center
🇺🇸Lubbock, Texas, United States
University of the Incarnate Word
🇺🇸San Antonio, Texas, United States
San Antonio Eye Center
🇺🇸San Antonio, Texas, United States
University of Incarnate Word Rosenberg School of Optometry
🇺🇸San Antonio, Texas, United States
Rocky Mountain Eye Care Associates
🇺🇸Salt Lake City, Utah, United States
Virginia Pediatric Eye Center
🇺🇸Norfolk, Virginia, United States
Seattle Children's Hospital, University of Washington
🇺🇸Seattle, Washington, United States
Spokane Eye Clinical Research
🇺🇸Spokane, Washington, United States