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ATS11: Combined Patching-Atropine for Residual Amblyopia

Sponsor
Jaeb Center for Health Research (Other)
Overall Status
Terminated
CT.gov ID
NCT00506675
Collaborator
National Eye Institute (NEI) (NIH)
55
Enrollment
1
Location
2
Arms
23
Duration (Months)
2.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is designed to evaluate the effectiveness of treatment of residual amblyopia in children ages 3 to < 10 years with visual acuity of 20/32 to 20/63 in the amblyopic eye. The study is a randomized clinical trial comparing intensive treatment (42 hours per week of patching plus daily atropine) with a control group that will have rapid weaning of existing treatment followed by spectacle correction only (if needed). The primary objective is to determine if this intensive treatment will improve visual acuity in patients with residual amblyopia.

The primary outcome assessment is amblyopic eye visual acuity at 10 weeks.

The primary analytic approach for the amblyopic eye acuity will be a treatment group comparison of the proportion of patients with at least two lines of visual acuity improvement.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

Amblyopia is the most common cause of monocular visual impairment in both children and young and middle-aged adults. Both patching and atropine are accepted treatment modalities for the management of moderate amblyopia in children. Despite best efforts with conventional treatment, some patients fail to achieve normal visual acuity in the amblyopic eye. In a randomized trial conducted by PEDIG comparing atropine versus patching in 3 to 6 year olds with moderate amblyopia (ATS1), 261 of 402 patients (65%) had amblyopic eye visual acuity of 20/32 or worse after 6 months of treatment with patching or atropine. Beyond 6 months, treatment was at investigator discretion, and two years after randomization, 181 of 363 children (50%) still had amblyopic eye visual acuity of 20/32 or worse. In a randomized trial conducted by PEDIG comparing patching regimens, 129 of 181 patients with moderate amblyopia (71%) and 145 of 157 patients with severe amblyopia (92%) had amblyopic eye visual acuity of 20/32 or worse after 4 months of occlusion therapy. Many patients receive treatment beyond 6 months but still fail to achieve normal visual acuity in the amblyopic eye. It is unknown whether an intensive "final push" of combined treatment with daily patching and atropine will improve visual acuity in these patients. Although some clinicians prescribe simultaneous patching and atropine for selected patients, there are no published reports of its effectiveness. Also, we are not aware of reports of response to treatment of residual amblyopia.

The study has been designed as a simple trial that, other than the type of amblyopia therapy being determined through the randomization process, approximates standard clinical practice.

Patients will be randomized to one of two treatment regimens:

  • Intensive treatment: 42 hours per week of patching combined with daily atropine (1%)

  • Control group: Weaning of the current treatment (two hours of daily patching for patients currently using patching and once weekly atropine for patients currently using atropine) for 4 weeks, then no treatment other than spectacles (if needed).

Study Design

Study Type:
Interventional
Actual Enrollment :
55 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized Trial to Evaluate Combined Patching-Atropine for Residual Amblyopia
Study Start Date :
Oct 1, 2007
Actual Primary Completion Date :
Apr 1, 2009
Actual Study Completion Date :
Sep 1, 2009

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Intensive

42 hours per week of patching combined with atropine (1%) once daily in the sound eye, with spectacle correction (if needed)

Device: Patching
42 hours per week of patching
Other Names:
  • Coverlet, 3M Opticlude, Ortopad®

    • Drug: Atropine
    daily atropine (1%)
    Active Comparator: Weaning

    For patients currently patching, reduce patching to two hours daily for four weeks, then no treatment thereafter except spectacle correction (if needed). For patients currently using atropine, reduce atropine to once weekly for 4 weeks, then no treatment thereafter except spectacle correction (if needed)

    Device: Patching
    two hours of daily patching for 4 weeks, then no treatment
    Other Names:
  • Coverlet, 3M Opticlude, Ortopad®

    • Drug: Atropine
    once weekly atropine for 4 weeks, then no treatment

    Outcome Measures

    Primary Outcome Measures

    1. Distribution of Amblyopic Eye Visual Acuity at 10 Weeks [10 Weeks]

      Visual acuity was measured in each eye using the Amblyopia Treatment Study (ATS) visual acuity testing protocol resulting in a Snellen acuity score that can range from 20/16 to 20/800 for ages 3 to <7; or with the electronic early treatment diabetic retinopathy study (E-ETDRS) method for 7 to <10 year olds which resulted in a letter score that could range from 0 to 97 letters, with 0 being the worst and 97 being the best. Scores were converted to log of minimum angle of resolution (logMAR) equivalents for analyses (lower logMAR value is better than higher logMAR).

    2. Mean (SD) Distribution of Visual Acuity at 10 Weeks [10 Weeks]

      Visual acuity was measured in each eye using the Amblyopia Treatment Study (ATS) visual acuity testing protocol resulting in a Snellen acuity score that can range from 20/16 to 20/800 for ages 3 to <7; or with the electronic early treatment diabetic retinopathy study (E-ETDRS) method for 7 to <10 year olds which resulted in a letter score that could range from 0 to 97 letters, with 0 being the worst and 97 being the best. Scores were converted to log of minimum angle of resolution (logMAR) equivalents for analyses (lower logMAR value is better than higher logMAR).

    3. Distribution of Amblyopic Eye Visual Acuity Change From Baseline to 10 Weeks [baseline to 10 Weeks]

      Change in logMAR from baseline to 10 weeks was calculated, with positive difference indicating improvement. Note one logMAR line = 5 letters or one Snellen line equivalent.

    4. Mean (SD) Change in Visual Acuity in the Amblyopic Eye at the 10 Week Primary Outcome Exam [baseline to 10 Weeks]

      Change in logMAR from baseline to 10 weeks was calculated, with positive difference indicating improvement. Note one logMAR line = 5 letters or one Snellen line equivalent.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    3 Years to 9 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Age 3 to < 10 years

    • Amblyopia associated with strabismus, anisometropia, or both

    • Visual acuity in the amblyopic eye between 20/32 and 20/63 inclusive

    • Visual acuity in the sound eye 20/32 or better and inter-eye acuity difference >= 2 logMAR lines

    • Current/previous treatment with patching and/or atropine subject to the following stipulations:

    • No simultaneous treatment with patching and atropine in the past 6 months

    • No prior use of atropine in combination with the sound eye spectacle lens reduced by more than 1.50 D

    • Maximum level of any previous treatment:

    • Patching: up to 42 hours per week (averaging 6 hours daily)

    • Atropine: up to once daily

    • Current treatment with 42 hours per week patching or daily atropine

    • No improvement in best-corrected amblyopic eye visual acuity between two consecutive visits at least 6 weeks apart using the same testing method and optimal spectacle correction (if needed), with no improvement defined as follows:

    • No lines of improvement

    • For patients tested using E-ETDRS, letter score that is no more than 4 letters improved

    • Wearing spectacles with optimal correction (if applicable)

    • Investigator ready to wean or stop treatment

    Exclusion Criteria:

    • Current vision therapy or orthoptics

    • Ocular cause for reduced visual acuity

    • Prior intraocular or refractive surgery

    • Strabismus surgery planned within 10 weeks

    • Known allergy to atropine or other cycloplegic drugs

    • Known skin reactions to patch or bandage adhesives

    • Down Syndrome present

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Duke University Eye Center Durham North Carolina United States 27710

    Sponsors and Collaborators

    • Jaeb Center for Health Research
    • National Eye Institute (NEI)

    Investigators

    • Study Chair: David K. Wallace, M.D., Duke University Eye Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Ray Kraker, Director, PEDIG Coordinating Center, Jaeb Center for Health Research
    ClinicalTrials.gov Identifier:
    NCT00506675
    Other Study ID Numbers:
    • NEI-135
    • 2U10EY011751
    First Posted:
    Jul 25, 2007
    Last Update Posted:
    Jul 13, 2016
    Last Verified:
    Jul 1, 2016
    Keywords provided by Ray Kraker, Director, PEDIG Coordinating Center, Jaeb Center for Health Research
    Amblyopia
    Atropine
    Patching
    Additional relevant MeSH terms:
    Amblyopia
    Atropine

    Study Results

    Participant Flow

    Recruitment Details Between October 2007 and March 2009, 27 subjects were randomized to the intensive group and 28 randomized to the weaning group.
    Pre-assignment Detail Eligible subjects were aged 3-<10 with strabismic and/or anisometropic amblyopia, best-corrected amblyopic eye acuity of 20/32 to 20/63, interocular acuity difference greater than or equal to 2 lines, and no improvement in amblyopic eye acuity between 2 consecutive visits at least 6 weeks apart.
    Arm/Group Title Intensive Weaning
    Arm/Group Description 6 hours daily patching combined with daily atropine For patients currently patching, a reduction of current treatment for 4 weeks with 2 hours daily patching or once weekly atropine followed by spectacles alone if needed.
    Period Title: Overall Study
    STARTED 27 28
    COMPLETED 27 28
    NOT COMPLETED 0 0

    Baseline Characteristics

    Arm/Group Title Intensive Weaning Total
    Arm/Group Description 6 hours daily patching combined with daily atropine For patients currently patching, a reduction of current treatment for 4 weeks with 2 hours daily patching or once weekly atropine followed by spectacles alone if needed. Total of all reporting groups
    Overall Participants 27 28 55
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    6.9
    (1.1)
    6.9
    (1.3)
    6.9
    (1.2)
    Age, Customized (participants) [Number]
    3 to < 7 years
    15
    55.6%
    13
    46.4%
    28
    50.9%
    7 to < 10 years
    12
    44.4%
    15
    53.6%
    27
    49.1%
    Sex: Female, Male (Count of Participants)
    Female
    14
    51.9%
    11
    39.3%
    25
    45.5%
    Male
    13
    48.1%
    17
    60.7%
    30
    54.5%
    Race/Ethnicity, Customized (participants) [Number]
    White
    18
    66.7%
    22
    78.6%
    40
    72.7%
    African American
    0
    0%
    0
    0%
    0
    0%
    Hispanic or Latino
    7
    25.9%
    4
    14.3%
    11
    20%
    Asian
    0
    0%
    1
    3.6%
    1
    1.8%
    More than one race
    2
    7.4%
    1
    3.6%
    3
    5.5%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    27
    100%
    28
    100%
    55
    100%
    Cause of Amblyopia (participants) [Number]
    Strabismus
    10
    37%
    16
    57.1%
    26
    47.3%
    Anisometropia
    6
    22.2%
    3
    10.7%
    9
    16.4%
    Strabismus and Anisometropia
    11
    40.7%
    9
    32.1%
    20
    36.4%
    Current Treatment for Amblyopia at Enrollment (participants) [Number]
    Patching
    18
    66.7%
    21
    75%
    39
    70.9%
    Atropine
    9
    33.3%
    7
    25%
    16
    29.1%
    Distance Visual Acuity in Amblyopic Eye (Number) [Number]
    20/63 (0.54 to 0.46 logMAR)
    3
    11.1%
    2
    7.1%
    5
    9.1%
    20/50 (0.44 to 0.36 logMAR)
    13
    48.1%
    12
    42.9%
    25
    45.5%
    20/40 (0.34 to 0.26 logMAR)
    7
    25.9%
    10
    35.7%
    17
    30.9%
    20/32 (0.24 to 0.16 logMAR)
    4
    14.8%
    4
    14.3%
    8
    14.5%
    Distance Visual Acuity in Fellow Eye (Number) [Number]
    20/32 (0.24 to 0.16 logMAR)
    2
    7.4%
    4
    14.3%
    6
    10.9%
    20/25 (0.14 to 0.06 logMAR)
    10
    37%
    7
    25%
    17
    30.9%
    20/20 (0.04 to -0.04 logMAR)
    8
    29.6%
    11
    39.3%
    19
    34.5%
    20/16 (-0.06 to -0.14 logMAR)
    7
    25.9%
    6
    21.4%
    13
    23.6%
    Refractive Error in Amblyopic Eye (spherical equivalent/diopters) (participants) [Number]
    < 0.00D
    0
    0%
    3
    10.7%
    3
    5.5%
    0 to < +1.00 D
    1
    3.7%
    0
    0%
    1
    1.8%
    +1.00 to < +2.00D
    3
    11.1%
    1
    3.6%
    4
    7.3%
    +2.00 to < +3.00D
    0
    0%
    2
    7.1%
    2
    3.6%
    +3.00 to < +4.00D
    1
    3.7%
    5
    17.9%
    6
    10.9%
    greater than or equal to +4.00D
    22
    81.5%
    17
    60.7%
    39
    70.9%
    Refractive Error in Fellow Eye (participants) [Number]
    < 0.00D
    1
    3.7%
    0
    0%
    1
    1.8%
    0 to < +1.00D
    2
    7.4%
    2
    7.1%
    4
    7.3%
    +1.00 to < +2.00D
    5
    18.5%
    5
    17.9%
    10
    18.2%
    +2.00 to < +3.00D
    4
    14.8%
    4
    14.3%
    8
    14.5%
    +3.00 to < +4.00D
    6
    22.2%
    7
    25%
    13
    23.6%
    greater than or equal to +4.00D
    9
    33.3%
    10
    35.7%
    19
    34.5%
    Mean (SD) Intereye Acuity Difference (logMAR) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [logMAR]
    0.33
    (0.11)
    0.31
    (0.10)
    0.32
    (0.11)
    Mean (SD) Distance Visual Acuity in Fellow Eye (logMAR) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [logMAR]
    0.02
    (0.09)
    0.03
    (0.10)
    0.03
    (0.09)
    Mean (SD) Spherical Equivalent Refractive Error in Amblyopic Eye (diopters) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [diopters]
    5.39
    (2.33)
    4.24
    (2.15)
    4.81
    (2.29)
    Mean (SD) Spherical Equivalent Refractive Error in Fellow Eye (diopters) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [diopters]
    3.46
    (2.38)
    3.29
    (1.90)
    3.37
    (2.13)
    Mean (SD) Distance Visual Acuity in Amblyopic Eye (logMAR) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [logMAR]
    0.35
    (0.09)
    0.34
    (0.08)
    0.35
    (0.09)

    Outcome Measures

    1. Primary Outcome
    Title Distribution of Amblyopic Eye Visual Acuity at 10 Weeks
    Description Visual acuity was measured in each eye using the Amblyopia Treatment Study (ATS) visual acuity testing protocol resulting in a Snellen acuity score that can range from 20/16 to 20/800 for ages 3 to <7; or with the electronic early treatment diabetic retinopathy study (E-ETDRS) method for 7 to <10 year olds which resulted in a letter score that could range from 0 to 97 letters, with 0 being the worst and 97 being the best. Scores were converted to log of minimum angle of resolution (logMAR) equivalents for analyses (lower logMAR value is better than higher logMAR).
    Time Frame 10 Weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Intensive Weaning
    Arm/Group Description 6 hours daily patching combined with daily atropine For patients currently patching, a reduction of current treatment for 4 weeks with 2 hours daily patching or once weekly atropine followed by spectacles alone if needed.
    Measure Participants 27 28
    20/125 (0.84 to 0.76 logMAR)
    0
    0%
    1
    3.6%
    20/100 (0.74 to 0.66 logMAR)
    0
    0%
    0
    0%
    20/80 (0.64 to 0.56 logMAR)
    1
    3.7%
    1
    3.6%
    20/63 (0.54 to 0.46 logMAR)
    1
    3.7%
    4
    14.3%
    20/50 (0.44 to 0.36 logMAR)
    4
    14.8%
    0
    0%
    20/40 (0.34 to 0.26 logMAR)
    13
    48.1%
    9
    32.1%
    20/32 (0.24 to 0.16 logMAR)
    7
    25.9%
    7
    25%
    20/25 (0.14 to 0.06 logMAR)
    1
    3.7%
    3
    10.7%
    20/20 (0.04 to -0.04 logMAR)
    0
    0%
    2
    7.1%
    20/16 (-0.16 to -0.24 logMAR)
    0
    0%
    0
    0%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Intensive, Weaning
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.30
    Comments
    Method ANCOVA
    Comments
    2. Primary Outcome
    Title Mean (SD) Distribution of Visual Acuity at 10 Weeks
    Description Visual acuity was measured in each eye using the Amblyopia Treatment Study (ATS) visual acuity testing protocol resulting in a Snellen acuity score that can range from 20/16 to 20/800 for ages 3 to <7; or with the electronic early treatment diabetic retinopathy study (E-ETDRS) method for 7 to <10 year olds which resulted in a letter score that could range from 0 to 97 letters, with 0 being the worst and 97 being the best. Scores were converted to log of minimum angle of resolution (logMAR) equivalents for analyses (lower logMAR value is better than higher logMAR).
    Time Frame 10 Weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Intensive Weaning
    Arm/Group Description 6 hours daily patching combined with daily atropine For patients currently patching, a reduction of current treatment for 4 weeks with 2 hours daily patching or once weekly atropine followed by spectacles alone if needed.
    Measure Participants 27 28
    Mean (Standard Deviation) [logMAR]
    0.30
    (0.10)
    0.29
    (0.18)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Intensive, Weaning
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.30
    Comments
    Method ANCOVA
    Comments
    3. Primary Outcome
    Title Distribution of Amblyopic Eye Visual Acuity Change From Baseline to 10 Weeks
    Description Change in logMAR from baseline to 10 weeks was calculated, with positive difference indicating improvement. Note one logMAR line = 5 letters or one Snellen line equivalent.
    Time Frame baseline to 10 Weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Intensive Weaning
    Arm/Group Description 6 hours daily patching combined with daily atropine For patients currently patching, a reduction of current treatment for 4 weeks with 2 hours daily patching or once weekly atropine followed by spectacles alone if needed.
    Measure Participants 27 28
    greater than or equal to 3 lines
    0
    0%
    1
    3.6%
    2 to < 3 lines worse
    1
    3.7%
    0
    0%
    1 to < 2 lines worse
    2
    7.4%
    4
    14.3%
    Within 1 logMAR line
    12
    44.4%
    8
    28.6%
    1 to < 2 lines better
    9
    33.3%
    8
    28.6%
    2 to < 3 lines better
    3
    11.1%
    5
    17.9%
    greater than or equal to 3 lines better
    0
    0%
    1
    3.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Intensive, Weaning
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.30
    Comments
    Method ANCOVA
    Comments
    4. Primary Outcome
    Title Mean (SD) Change in Visual Acuity in the Amblyopic Eye at the 10 Week Primary Outcome Exam
    Description Change in logMAR from baseline to 10 weeks was calculated, with positive difference indicating improvement. Note one logMAR line = 5 letters or one Snellen line equivalent.
    Time Frame baseline to 10 Weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Intensive Weaning
    Arm/Group Description 6 hours daily patching combined with daily atropine For patients currently patching, a reduction of current treatment for 4 weeks with 2 hours daily patching or once weekly atropine followed by spectacles alone if needed.
    Measure Participants 27 28
    Mean (Standard Deviation) [logMAR]
    0.056
    (0.096)
    0.053
    (0.150)

    Adverse Events

    Time Frame 10 weeks
    Adverse Event Reporting Description
    Arm/Group Title Intensive Weaning
    Arm/Group Description 6 hours daily patching combined with daily atropine For patients currently patching, a reduction of current treatment for 4 weeks with 2 hours daily patching or once weekly atropine followed by spectacles alone if needed.
    All Cause Mortality
    Intensive Weaning
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Intensive Weaning
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/27 (0%) 0/28 (0%)
    Other (Not Including Serious) Adverse Events
    Intensive Weaning
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 6/27 (22.2%) 0/28 (0%)
    General disorders
    Light sensitivity 6/27 (22.2%) 6 0/28 (0%) 0

    Limitations/Caveats

    This trial was stopped after 18 months due to inadequate recruitment.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Raymond Kraker, MSPH
    Organization Jaeb Center for Health Research
    Phone 813-975-8690
    Email pedig@jaeb.org
    Responsible Party:
    Ray Kraker, Director, PEDIG Coordinating Center, Jaeb Center for Health Research
    ClinicalTrials.gov Identifier:
    NCT00506675
    Other Study ID Numbers:
    • NEI-135
    • 2U10EY011751
    First Posted:
    Jul 25, 2007
    Last Update Posted:
    Jul 13, 2016
    Last Verified:
    Jul 1, 2016