A Randomized Trial to Evaluate Sequential vs Simultaneous Patching (ATS22)

February 9, 2026 updated by: Jaeb Center for Health Research

A Randomized Trial to Evaluate Sequential vs Simultaneous Spectacles Plus Patching for Amblyopia in Children 3 to <13 Years Old

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

544

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Raymond T Kraker, MSPH
  • Phone Number: 813-975-8690
  • Email: rkraker@jaeb.org

Study Contact Backup

  • Name: Brooke P Fimbel
  • Phone Number: 813-975-8690

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • Recruiting
        • University of Alabama at Birmingham
        • Contact:
          • Katherine Weise, OD, MBA
          • Phone Number: 205-934-6739
          • Email: kweise@uab.edu
      • Birmingham, Alabama, United States, 35294
        • Recruiting
        • UAB Pediatric Eye Care; Birmingham Health Care
        • Principal Investigator:
          • Kristine Hopkins, O.D.
    • Arizona
      • Glendale, Arizona, United States, 85308
        • Recruiting
        • Midwestern University Eye Institute
        • Contact:
        • Sub-Investigator:
          • Christina A Esposito, OD
      • Phoenix, Arizona, United States, 85006
      • Tucson, Arizona, United States, 85711
        • Recruiting
        • University of Arizona
        • Contact:
    • California
      • Berkeley, California, United States, 94720
        • Recruiting
        • Univ. of California- Berkeley
        • Contact:
      • Fullerton, California, United States, 92831
        • Recruiting
        • Marshall B. Ketchum University
        • Contact:
        • Principal Investigator:
          • Angela Chen, O.D., M.S.
      • Irvine, California, United States, 92697
        • Recruiting
        • Univ of California, Irvine- Gavin Herbert Eye Institute
        • Contact:
      • Loma Linda, California, United States, 92354
        • Recruiting
        • Loma Linda University Health Care, Dept. of Ophthalmology
        • Contact:
      • Los Angeles, California, United States, 90027
        • Recruiting
        • Children's Hospital of Los Angeles (CHLA)
        • Contact:
      • Palo Alto, California, United States, 94303
        • Recruiting
        • Stanford University
        • Contact:
      • Pomona, California, United States, 91766
        • Recruiting
        • Western University College of Optometry
        • Contact:
      • Sacramento, California, United States, 95817
        • Recruiting
        • University of California, Davis
        • Contact:
      • San Francisco, California, United States, 94143
        • Recruiting
        • University of California San Francisco Department of Ophthalmology
        • Contact:
    • Connecticut
      • Milford, Connecticut, United States, 06460
        • Recruiting
        • Eye Physicians & Surgeons, PC
        • Contact:
    • Florida
      • Fort Lauderdale, Florida, United States, 33382
        • Recruiting
        • Nova Southeastern University College of Optometry, The Eye Institute
        • Contact:
      • Jacksonville, Florida, United States, 32207
        • Recruiting
        • Nemours Children's Clinic
        • Contact:
      • Tampa, Florida, United States, 33620
        • Recruiting
        • University of South Florida (USF) Eye
        • Contact:
    • Idaho
      • Boise, Idaho, United States, 83702
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Ann & Robert H. Lurie Children's Hospital of Chicago
        • Contact:
      • Chicago Ridge, Illinois, United States, 60415
        • Recruiting
        • Ticho Eye Associates
        • Contact:
      • Downers Grove, Illinois, United States, 60515
        • Recruiting
        • Midwestern U Chicago College of Optometry
        • Contact:
      • Lisle, Illinois, United States, 60532
        • Recruiting
        • Progressive Eye Care
        • Contact:
    • Indiana
      • Bloomington, Indiana, United States, 47405
        • Recruiting
        • Indiana School of Optometry
        • Contact:
        • Principal Investigator:
          • Don W. Lyon, O.D.
      • Indianapolis, Indiana, United States, 47405
        • Recruiting
        • Indiana University School of Optometry
        • Contact:
        • Principal Investigator:
          • Kathyrn M Haider, MD
        • Sub-Investigator:
          • Heather A Smith, MD
        • Sub-Investigator:
          • Charline S Boente, MD
        • Sub-Investigator:
          • David K Wallace, MD
    • Iowa
      • West Des Moines, Iowa, United States, 50266
        • Recruiting
        • Wolfe Eye Clinic
        • Contact:
    • Maryland
      • Baltimore, Maryland, United States, 21287-9028
        • Recruiting
        • Wilmer Eye Institute
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02118
        • Recruiting
        • Boston Medical Center
        • Contact:
          • Stephen Christiansen, MD
          • Phone Number: 617-414-2020
          • Email: spchris@bu.edu
      • Boston, Massachusetts, United States, 02453
    • Michigan
      • Grand Rapids, Michigan, United States, 49503
      • Grand Rapids, Michigan, United States, 49546
        • Recruiting
        • Pediatric Ophthalmology, P.C.
        • Contact:
    • Minnesota
      • Duluth, Minnesota, United States, 55811
      • Rochester, Minnesota, United States, 55905
      • Sartell, Minnesota, United States, 56377
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Recruiting
        • Children's Mercy Hospitals and Clinics
        • Contact:
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • St. Louis Children's Hospital Eye Center
        • Contact:
      • St Louis, Missouri, United States, 63121
        • Recruiting
        • U of MO St. Louis College of Optometry
        • Contact:
    • Nebraska
      • Omaha, Nebraska, United States, 68114
    • New York
      • Buffalo, New York, United States, 14209
        • Recruiting
        • Ross Eye Institute, University of Buffalo, Med School Dept Ophthalmology
        • Contact:
      • New York, New York, United States, 10017
      • New York, New York, United States, 10036
        • Recruiting
        • State University of New York, College of Optometry
        • Contact:
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
      • Durham, North Carolina, United States, 27710
    • Ohio
      • Akron, Ohio, United States, 44308
        • Recruiting
        • Akron Children's Hospital
        • Contact:
      • Cincinnati, Ohio, United States, 45229
        • Recruiting
        • Cincinnati Children's Hospital
        • Contact:
      • Columbus, Ohio, United States, 43210-1280
        • Recruiting
        • Ohio State University College of Optometry
        • Principal Investigator:
          • Marjean T Kulp, O.D.
        • Contact:
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
    • Oregon
      • Albany, Oregon, United States, 97321
        • Recruiting
        • River View Family Eyecare
        • Contact:
      • Portland, Oregon, United States, 97239
        • Recruiting
        • Casey Eye Institute
        • Contact:
    • Pennsylvania
      • Erie, Pennsylvania, United States, 16501
        • Recruiting
        • Pediatric Ophthalmology of Erie
        • Contact:
      • Lancaster, Pennsylvania, United States, 17601
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • Wills Eye Hospital
        • Contact:
      • Philadelphia, Pennsylvania, United States, 19141
        • Recruiting
        • Salus University/Pennsylvania College of Optometry
        • Contact:
      • Pittsburgh, Pennsylvania, United States, 15224
        • Recruiting
        • UPMC Children's Eye Center of Children's Hospital of Pittsburgh
        • Contact:
    • South Carolina
    • Tennessee
      • Memphis, Tennessee, United States, 38104
        • Recruiting
        • Southern College of Optometry
        • Contact:
      • Nashville, Tennessee, United States, 37232
        • Recruiting
        • Vanderbilt University Medical Center - Vanderbilt Eye Institute
        • Contact:
    • Texas
      • Fort Worth, Texas, United States, 76014
        • Recruiting
        • Pediatric Eye Specialists, LLP
        • Contact:
          • Michael G Hunt, MD
      • Houston, Texas, United States, 77030
        • Recruiting
        • Baylor College of Medicine
        • Contact:
          • Irene T Tung, MD
          • Phone Number: 832-822-3230
      • Lubbock, Texas, United States, 79430
        • Recruiting
        • Texas Tech University Health Science Center
        • Contact:
      • San Antonio, Texas, United States, 78215
        • Recruiting
        • San Antonio Eye Center
        • Contact:
      • San Antonio, Texas, United States, 78229
        • Recruiting
        • University of Incarnate Word Rosenberg School of Optometry
        • Contact:
      • San Antonio, Texas, United States, 78209
        • Recruiting
        • University of the Incarnate Word
        • Contact:
    • Utah
      • Salt Lake City, Utah, United States, 84107
        • Recruiting
        • Rocky Mountain Eye Care Associates
        • Contact:
        • Principal Investigator:
          • David Petersen, MD
    • Virginia
      • Norfolk, Virginia, United States, 23502
        • Recruiting
        • Virginia Pediatric Eye Center
        • Contact:
    • Washington
      • Seattle, Washington, United States, 98105
        • Recruiting
        • Seattle Children's Hospital, University of Washington
        • Contact:
          • Vivian Manh, O.D., M.S.
          • Phone Number: 206-987-4950
          • Email: vmanh@uw.edu
        • Principal Investigator:
          • Vivian Manh, O.D., M.S>
      • Spokane, Washington, United States, 99204
        • Recruiting
        • Spokane Eye Clinical Research
        • Contact:
    • Wyoming
      • Laramie, Wyoming, United States, 82070

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 years to 13 years (Child)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age 3 to <13 years at the time of randomization

  2. Amblyopia associated with anisometropia, strabismus, or both

    o 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)

    • Documented history of strabismus which is no longer present (which in the judgment of the investigator could have caused amblyopia)

      • 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
      • 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 previous treatment for amblyopia, including no more than 24 hours of spectacle wear.

  4. 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:

    1. Full correction of anisometropia
    2. Full correction of astigmatism with the same axis found by the cycloplegic refraction
    3. Full correction of any myopia
    4. Hyperopia must not be under corrected by more than 1.50 D, and reduction in plus sphere must be symmetric in the two eyes.

  5. 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:

    • VA in the amblyopic eye 20/40 to 20/200 inclusive.

    • 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
    • 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).
  6. Investigator is willing to prescribe spectacle wear followed sequentially by patching or simultaneous spectacles and patching treatment per protocol.
  7. Parent understands the protocol and is willing to accept randomization.
  8. Parent has phone (or access to phone) and is willing to be contacted by Jaeb Center staff or other study staff.
  9. Relocation outside of area of an active PEDIG site for this study within the next 56 weeks is not anticipated.

Exclusion Criteria:

  1. Myopia greater than -6.00 D spherical equivalent in either eye.
  2. Previous intraocular or refractive surgery.
  3. Planned strabismus surgery in the next 56 weeks.
  4. Any previous treatment for amblyopia (patching, atropine, Bangerter filter, vision therapy, or binocular treatment).
  5. Previous spectacle or contact lens wear for more than 24 hours.
  6. Parent and participant willing to forego option of contact lens wear for the duration of the study.
  7. 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).
  8. 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.
  9. Known allergy to adhesive patches.
  10. Known allergy to silicone.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Sequential treatment
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)
Other: Patching
Procedure in which the eye is covered utilizing a patch to increase the strength of the uncovered eye.
Other Names:
  • Eye Patch
Other: Glasses
Eye Glasses are created and worn by patient to improve vision
Other Names:
  • Spectacles
Experimental: Simultaneous treatment
full-time spectacle correction and part-time patching for 2 hours per day/7 days per week
Other: Patching
Procedure in which the eye is covered utilizing a patch to increase the strength of the uncovered eye.
Other Names:
  • Eye Patch
Other: Glasses
Eye Glasses are created and worn by patient to improve vision
Other Names:
  • Spectacles

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean Change in Amblyopic Eye logMAR distance Visual Acuity
Time Frame: 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).
56 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pediatric Eye Questionnaire (PedEyeQ)
Time Frame: 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 Vision
56 weeks
Proportion Achieving Stable Resolved Outcome with Spectacles Alone
Time Frame: 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.
56 Weeks
Proportion of participants who achieve Binary distance visual acuity outcomes
Time Frame: 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.
56 weeks
Time to Stable Resolved Amblyopia
Time Frame: 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.
56 weeks
Difference in Mean Change of Distance Visual Acuity after 8 Weeks on Randomized Treatment
Time Frame: 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.
56 Weeks
Change in binocularity levels
Time Frame: 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.
56 Weeks
Difference in mean change in amblyopic-eye log contrast sensitivity
Time Frame: 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.
56 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jaeb Center for Health Research

Collaborators

National Eye Institute (NEI)
Pediatric Eye Disease Investigator Group

Investigators

  • Study Chair: Vivian Manh, Seattle Children's Hospital, University of Washington
  • Study Chair: Michael Gray, Children's Hospital Medical Center, Cincinnati

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 8, 2020

Primary Completion (Estimated)

May 1, 2028

Study Completion (Estimated)

May 1, 2028

Study Registration Dates

First Submitted

May 5, 2020

First Submitted That Met QC Criteria

May 5, 2020

First Posted (Actual)

May 7, 2020

Study Record Updates

Last Update Posted (Actual)

February 11, 2026

Last Update Submitted That Met QC Criteria

February 9, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ATS22
  • 2UG1EY011751 (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 Pediatric Eye Disease Investigator Group (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.

IPD Sharing Access Criteria

Users accessing the data must enter an email address.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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