Trial Comparing Patching Versus Atropine for Amblyopia in 7 to < 13 Year Olds
Information source: National Eye Institute (NEI)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Amblyopia
Intervention: Atropine (Drug); Patching (Device); Near activities (Procedure)
Phase: Phase 3
Status: Active, not recruiting
Sponsored by: National Eye Institute (NEI)
Official(s) and/or principal investigator(s):
Richard W. Hertle, M.D., Study Chair, Affiliation: Children's Hospital of Pittsburgh
Mitchell M. Scheiman, O.D., Study Chair, Affiliation: Pennsylvania College of Optometry
The purpose of this study is:
- To compare the effectiveness of weekend atropine plus near activities and daily patching
plus near activities for moderate amblyopia (20/40 to 20/100) and severe amblyopia
(20/125 to 20/400) in improving vision in the amblyopic eye of 7 to <13 year olds.
- To determine the maximum improvement in vision of the amblyopic eye with each
- To determine whether amblyopia is associated with structural abnormalities of optic
nerve fiber layer.
Official title: A Randomized Trial Comparing Patching Versus Atropine for Amblyopia in 7 to < 13 Year Olds
Study design: Treatment, Randomized, Open Label, Uncontrolled, Parallel Assignment, Efficacy Study
Primary outcome: Visual acuity for both amblyopic and sound eyes
Although there is consensus that amblyopia can be treated effectively in young children, many
eye care practitioners believe that treatment beyond a certain age is ineffective. Some
clinicians have believed that a treatment response is unlikely after the age of 6 or 7 years,
while others have considered age 9 or 10 years to be the upper age limit for successful
treatment. The American Academy of Ophthalmology Preferred Practice Pattern for amblyopia
recommends treatment up to age 10 years. The opinion that amblyopia treatment is ineffective
in older children may have arisen because the age of 6 to 7 years is thought to be the end of
the "critical period" for visual development in humans. This belief, however, was not based
on adequate prospectively-collected data.
To address this issue of the response of amblyopia to treatment in children 7 years and
older, the Pediatric Eye Disease Investigator Group (PEDIG) conducted a randomized trial of
507 patients (aged 7 to <18 years) with amblyopic eye visual acuity ranging from 20/40 to
20/400. Patients were provided with optimal optical correction and then randomized to a
Treatment Group (2 to 6 hours per day of prescribed patching of the sound eye combined with
near visual activities for all patients plus atropine one drop per day in the sound eye for 7
to <13 year olds) or an Optical Correction Group (optical correction alone). Patients whose
amblyopic eye acuity improved 10 or more letters (2 lines) by 24 weeks were considered
responders. In the 7 to <13 year olds (N=404), 53% of the Treatment Group were responders
compared with 25% of the Optical Correction Group (P<0. 001). In the 13 to <18 year olds
(N=103), the responder rates were 25% and 23% respectively overall (adjusted P=0. 22), but 47%
and 20% respectively among patients not previously treated with patching and/or atropine for
amblyopia (adjusted P=0. 03). Most patients, including responders, were left with a residual
visual acuity deficit.
The use of multiple modalities (patching, atropine, near visual activities) in the treatment
regimen for the 7 to <13 year olds in this trial (ATS3) was an effort to maximize the
therapeutic response. Patients age 13 years and older were prescribed patching but not
atropine because of concern that the continual optical blur from the atropine could have a
deleterious effect on their ability to drive and perform other activities. Prescribed
patching was 2 to 6 hours a day to limit patch wear to non-school hours and because our prior
studies of 3 to <7 year olds demonstrated that as little as two hours of patching a day (when
combined with near visual activities) is as effective as a greater number of hours.
Instructing patients to perform at least one hour of near activities while wearing the patch
was based on the unproven clinical opinion that near activities can augment the effect of the
occlusion therapy. A PEDIG pilot study suggested that near activities are beneficial and this
question of benefit of near activities is currently being studied in another randomized
clinical trial. Atropine placed in the sound eye once a day and two days a week has been
demonstrated in younger children to be beneficial to the acuity of the amblyopic eye,
presumably due to its cycloplegic effect of blurring vision in the sound eye especially at
near fixation. In a study comparing daily and weekend atropine, daily atropine was not found
to be superior.
The unanswered question from this completed clinical trial is whether prescribing patching or
atropine alone could have produced a response similar to the combination therapy, or whether
in this age group, one treatment is better than the other. A poll of PEDIG investigators at
an investigator meeting on January 15, 2005 indicated that very few are following the
treatment regimen used in the prior study (ATS3); rather, most are prescribing
monotherapy—either patching or atropine—as the initial treatment for amblyopia in the 7 to
<13 year age range. Thus, a trial comparing atropine and patching as amblyopia treatments in
7 to <13 year olds is needed.
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.
The two treatment regimes are: 1) Atropine 1% once each weekend day in the sound eye plus
near activities for at least one hour every day without the aid of reading glasses (with
increase to daily atropine at 5 weeks if acuity not improved by at least 5 letters) and 2)
Patching 2 hours per day plus near activities for one hour while patching (with increase to 4
hours per day for moderate amblyopes and > 4 hours per day for severe amblyopes at 5 weeks if
acuity not improved by at least 5 letters).
Optional Ancillary Study As part of the optic nerve imaging ancillary study, retinal nerve
fiber layer imaging using optical coherence tomography will be performed on some patients.
This will be optional for patients at participating sites. The procedure is not part of
standard care. The subject's pupils will need to be dilated, if not already dilated as part
of the exam. Testing of both eyes can be completed in about 15 minutes.
Minimum age: 7 Years.
Maximum age: 12 Years.
- Age 7 to <13 years
- Amblyopia associated with strabismus, anisometropia, or both
- Visual acuity in the amblyopic eye 19 to 71 letters on E-ETDRS (20/40 to 20/400
- Visual acuity in the sound eye 79 letters or better on E-ETDRS (20/25 or better)
- Interocular difference >=15 letters (3 lines)
- Spectacles, if needed, worn for at least 16 weeks or visual acuity documented to be
Inclusion Criteria for Optional Ancillary Study:
- Enrolled into the main study
- Refractive error in both eyes between -0. 25 and +5. 00D, inclusive (to avoid the need
to adjust for refractive error)
- Birth weight >1500 grams
- No history of CNS disease (e. g. IVH, PVL, meningitis, developmental abnormalities of
the brain, hydrocephalus, cerebral palsy, hypoxic ischemic encephalopathy
- Amblyopia treatment (other than spectacles) in the last 6 months
- Myopia (more than -0. 25D spherical equivalent) in either eye
Locations and Contacts
Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States
Pennsylvania College of Optometry, Philadelphia, Pennsylvania 19141, United States
NEI Clinical Studies Database
PEDIG public website
Starting date: August 2005
Ending date: February 2008
Last updated: December 21, 2007