Clinical Trial: Augmenting Atropine Treatment for Amblyopia in Children 3 to < 8 Years Old

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Augmenting Atropine Treatment for Amblyopia in Children 3 to < 8 Years Old

Brief Summary: This study is designed to evaluate the effectiveness of adding a plano lens to weekend atropine after visual acuity has stabilized with weekend atropine but amblyopia is still present. Children ages 3 to <8 years with visual acuity of 20/50 to 20/400 in the amblyopic eye will be enrolled in a run-in phase with weekend atropine until no improvement, followed by randomization of eligible patients to weekend atropine treatment with a plano lens over the sound eye versus without a plano lens over the sound eye. The primary objective is to determine if adding a plano lens to weekend atropine will improve visual acuity in patients with amblyopia still present after visual acuity has stabilized with initial treatment.

Detailed Summary: 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.1 Many practitioners prescribe weekend atropine as initial therapy for amblyopia. However, many children fail to achieve normal visual acuity in the amblyopic eye after treatment with this regimen. In a randomized trial conducted by PEDIG comparing atropine regimens, 58 of 83 patients with moderate amblyopia (70%) had amblyopic eye visual acuity of 20/32 or worse after 4 months of treatment with weekend atropine.2 In another PEDIG randomized trial comparing atropine with a plano lens versus without a plano lens for initial treatment of amblyopia, 60 of 84 patients with moderate amblyopia (71%) had amblyopic eye visual acuity of 20/32 or worse after 16 weeks of treatment with weekend atropine.3 When improvement stops after initial therapy and amblyopia is still present, treatment options include increasing the dosage of current treatment, switching to another treatment, maintaining the same treatment and dosage, or combining treatments. Many clinicians will add a plano lens over the sound eye to atropine treatment, in part because families using atropine have become comfortable with its use. This option is limited to children with hypermetropia in the sound eye. However, it is unknown whether adding a plano lens over the sound eye will improve amblyopic eye visual acuity more than continuing atropine alone in patients who have shown no improvement after initial treatment with atropine. In a PEDIG randomized trial comparing patching to atropine for initial treatment of amblyopia, a plano lens was prescribed for the sound eye for 55 patients who had not improved to 20/30 or at least 3 lines after 4 months of daily atropine use.1, 4 Their mean acuity improvement prior to using the plano lens was 1.0 line, compared with 1.6 lines after prescrib
Sponsor: Jaeb Center for Health Research

Current Primary Outcome:

  • Distribution of 10-week Amblyopic-Eye Visual Acuity [ Time Frame: 10 weeks after randomization ]

    The masked 10-week amblyopic eye visual acuity scores were tabulated for both treatment groups, and included data from 10-week visual acuity exams completed between 8 to 15 weeks (inclusive) with no imputation for missing data.

    The primary outcome analysis followed the "intent-to-treat" principle. Therefore, data from randomized participants were included in the analysis regardless of whether the assigned treatment was actually received or whether they deviated from treatment against protocol. In addition, randomized participants who were found to be ineligible upon subsequent review of enrollment data were included in the primary outcome analysis.

  • Mean 10-week Amblyopic-Eye Visual Acuity [ Time Frame: 10 weeks after randomization ]

    The primary outcome analysis was a treatment group comparison of the masked 10-week amblyopic eye visual acuity using an analysis of covariance (ANCOVA) model, adjusting for visual acuity at randomization. The analysis included data from 10-week visual acuity exams completed between 8 to 15 weeks (inclusive) with no imputation for missing data.

    The primary outcome analysis followed the "intent-to-treat" principle. Therefore, data from randomized participants were included in the analysis regardless of whether the assigned treatment was actually received or whether they deviated from treatment against protocol. In addition, randomized participants who were found to be ineligible upon subsequent

    Original Primary Outcome: Amblyopic eye visual acuity [ Time Frame: 10 weeks after randomization ]

    Current Secondary Outcome:

    • Treatment Group Comparison of the Proportion of Participants Who Achieved 20/25 or Better Visual Acuity at 10 Weeks Since Randomization [ Time Frame: 10 weeks after randomization ]

      The proportion of participants who achieved 20/25 or better visual acuity since randomization was computed at the 10-week outcome.

      The secondary outcome analysis was a treatment group comparison of the proportion of participants whose 10-week masked amblyopic eye visual acuity was 20/25 or better since randomization. The analysis included data from 10-week visual acuity exams completed between 8 to 15 weeks (inclusive) according to the principles specified in the primary outcome analysis.

    • Treatment Group Comparison of the Proportion of Participants Who Have Improved by 2 or More logMAR Visual Acuity Lines at 10 Weeks Since Randomization [ Time Frame: 10 weeks after randomization ]

      The proportion of participants who improved at least 2 logMAR lines since randomization was computed at the 10-week outcome.

      The secondary outcome analysis was a treatment group comparison of the proportion of participants whose 10-week masked amblyopic eye visual acuity improved at least 2 logMAR lines since randomization using logistic regression, adjusting for visual acuity at randomization. The analysis included data from 10-week visual acuity exams completed between 8 to 15 weeks (inclusive) according to the principles specified in the primary outcome analysis.

    • Spectacle Compliance at 10 Weeks by Treatment Group [ Time Frame: 10 weeks after randomization ]
      The distribution of compliance with prescribed treatment was tabulated for the 10-week outcome. Compliance was evaluated as excellent (>75%), good (51%-75%), fair (26%-50%), or poor (<26%) based on discussions with the parent and by reviewing study calendars maintained by the parent, who recorded the frequency of atropine administration.
    • Average Spectacle Compliance by Treatment Group [ Time Frame: 10 weeks after randomization or later (until no further VA improvement, up to maximum of 84 weeks for one subject) ]
      The distribution of compliance with prescribed treatment was tabulated for the 10-week outcome and as averaged scores across all study follow-up visits. Compliance was evaluated as excellent (>75%), good (51%-75%), fair (26%-50%), or poor (<26%) based on discussions with the parent and by reviewing study calendars maintained by the parent, who recorded the frequency of atropine administration.
    • Atropine Compliance at 10 Weeks by Treatment Group [ Time Frame: 10 weeks after randomization ]
      The distribution of compliance with prescribed treatment was tabulated for the 10-week outcome. Compliance was evaluated as excellent (>75%), good (51%-75%), fair (26%-50%), or poor (<26%) based on discussions with the parent and by reviewing study calendars maintained by the parent, who recorded the frequency of atropine administration.
    • Average Atropine Compliance by Treatment Group [ Time Frame: 10 weeks after randomization or later (until no further VA improvement, up to maximum of 84 weeks for one subject) ]
      The distribution of compliance with prescribed treatment was tabulated for the 10-week outcome and as averaged scores across all study follow-up visits. Compliance was evaluated as excellent (>75%), good (51%-75%), fair (26%-50%), or poor (<26%) based on discussions with the parent and by reviewing study calendars maintained by the parent, who recorded the frequency of atropine administration.
    • Distribution of Interocular Difference at 12-week Exam [ Time Frame: 12 weeks after randomization ]
      Distribution of Interocular Difference Between Eyes at 12-week Exam
    • Mean Interocular Difference at 12-week Exam [ Time Frame: 12 weeks after randomization ]
      Mean Interocular Difference Between Eyes at 12-week Exam
    • Distribution of 12-week Fellow-Eye Visual Acuity [ Time Frame: 12 weeks after randomization ]
      Following the 10-week primary outcome exam, participants discontinued the randomized treatment and returned 2 weeks later for a 12-week visit to measure off-treatment fellow-eye visual acuity.
    • Mean Fellow-Eye Visual Acuity at 12-week Exam [ Time Frame: 12 weeks after randomization ]
    • Distribution of Change in Fellow-Eye Visual Acuity at 12 Weeks From Randomization [ Time Frame: 12 weeks after randomization ]
    • Mean Change in Fellow-Eye Visual Acuity at 12 Weeks From Randomization [ Time Frame: 12 weeks after randomization ]
    • Distribution of Baseline Characteristics at the 10-week Outcome [ Time Frame: 10 weeks after randomization ]
      The number of participants w

      Original Secondary Outcome:

      • Sound eye visual acuity [ Time Frame: 12 weeks after randomization ]
      • Differences between treatment groups in stereoacuity [ Time Frame: 12 weeks after randomization ]
      • Ocular alignment [ Time Frame: 12 weeks after randomization ]
      • Treatment group comparison of the proportion of patients who have improved by 2 or more logMAR visual acuity lines [ Time Frame: 10 weeks after randomization ]
      • Patients in both groups who have improved by 1 or more lines from baseline to the 10-week outcome exam will have a treatment group comparison of the proportion of patients with at least 2 logMAR lines of visual acuity improvement [ Time Frame: Last study visit ]
      • Patients in both groups who have improved by 1 or more lines from baseline to the 10-week outcome exam will have a treatment group comparison of logMAR visual acuity scores in the amblyopic eye [ Time Frame: Last study visit ]


      Information By: Jaeb Center for Health Research

      Dates:
      Date Received: July 21, 2009
      Date Started: August 2009
      Date Completion:
      Last Updated: July 7, 2016
      Last Verified: July 2016