Trial Comparing Patching Versus Atropine for Amblyopia in 7 to < 13 Year Olds

NCT ID: NCT00315328

Last Updated: 2016-06-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 233 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-08-31
• Study Completion Date: 2008-01-31

Brief Summary

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 treatment.
• To determine whether amblyopia is associated with structural abnormalities of optic nerve fiber layer.

Detailed Description

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.

Conditions

Amblyopia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Patching

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 at least 5 letters)

Group Type: ACTIVE_COMPARATOR

Patching

Intervention Type: DEVICE

Patching 2 hours per day

Near activities

Intervention Type: PROCEDURE

near visual activities for at least one hour per day

Atropine

Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day (with increase to daily atropine at 5 weeks if acuity not improved by at least 5 letters)

Group Type: ACTIVE_COMPARATOR

Atropine

Intervention Type: DRUG

Atropine 1% each weekend day in the sound eye

Near activities

Intervention Type: PROCEDURE

near visual activities for at least one hour per day

Interventions

Atropine

Atropine 1% each weekend day in the sound eye

Intervention Type: DRUG

Patching

Patching 2 hours per day

Intervention Type: DEVICE

Near activities

near visual activities for at least one hour per day

Intervention Type: PROCEDURE

Other Intervention Names

Coverlet, 3M Opticlude, Ortopad®

Eligibility Criteria

Inclusion Criteria

• Age 7 to 12 years old (inclusive)
• Amblyopia associated with strabismus, anisometropia, or both
• Visual acuity in the amblyopic eye 19 to 71 letters on Electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS©) (20/40 to 20/400 inclusive)
• 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 stable

• 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 Central Nervous System (CNS) disease (e.g. intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), meningitis, developmental abnormalities of the brain, hydrocephalus, cerebral palsy, hypoxic ischemic encephalopathy

Exclusion Criteria

• Amblyopia treatment (other than spectacles) in the last 6 months
• Myopia (more than -0.25D spherical equivalent) in either eye

• Minimum Eligible Age: 7 Years
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Eye Institute (NEI)

NIH

Sponsor Role: collaborator

Jaeb Center for Health Research

OTHER

Sponsor Role: lead

Responsible Party

Ray Kraker

Director, PEDIG Coordinating Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Richard W. Hertle, M.D.

Role: STUDY_CHAIR

University of Pittsburgh

Mitchell M. Scheiman, O.D.

Role: STUDY_CHAIR

Pennsylvania College of Optometry

Locations

Pennsylvania College of Optometry

Philadelphia, Pennsylvania, United States

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Countries

United States

References

Repka MX, Kraker RT, Beck RW, Birch E, Cotter SA, Holmes JM, Hertle RW, Hoover DL, Klimek DL, Marsh-Tootle W, Scheiman MM, Suh DW, Weakley DR; Pediatric Eye Disease Investigator Group. Treatment of severe amblyopia with weekend atropine: results from 2 randomized clinical trials. J AAPOS. 2009 Jun;13(3):258-63. doi: 10.1016/j.jaapos.2009.03.002.

Reference Type: BACKGROUND

PMID: 19541265 (View on PubMed)

Repka MX, Kraker RT, Tamkins SM, Suh DW, Sala NA, Beck RW; Pediatric Eye Disease Investigator Group. Retinal nerve fiber layer thickness in amblyopic eyes. Am J Ophthalmol. 2009 Jul;148(1):143-7. doi: 10.1016/j.ajo.2009.01.015. Epub 2009 Mar 27.

Reference Type: BACKGROUND

PMID: 19327749 (View on PubMed)

Pediatric Eye Disease Investigator Group. Pharmacological plus optical penalization treatment for amblyopia: results of a randomized trial. Arch Ophthalmol. 2009 Jan;127(1):22-30. doi: 10.1001/archophthalmol.2008.520.

Reference Type: BACKGROUND

PMID: 19139333 (View on PubMed)

Felius J, Chandler DL, Holmes JM, Chu RH, Cole SR, Hill M, Huang K, Kulp MT, Lazar EL, Matta NS, Melia M, Wallace DK; Pediatric Eye Disease Investigator Group. Evaluating the burden of amblyopia treatment from the parent and child's perspective. J AAPOS. 2010 Oct;14(5):389-95. doi: 10.1016/j.jaapos.2010.07.009.

Reference Type: BACKGROUND

PMID: 21035063 (View on PubMed)

Scheiman MM, Hertle RW, Kraker RT, Beck RW, Birch EE, Felius J, Holmes JM, Kundart J, Morrison DG, Repka MX, Tamkins SM; Pediatric Eye Disease Investigator Group. Patching vs atropine to treat amblyopia in children aged 7 to 12 years: a randomized trial. Arch Ophthalmol. 2008 Dec;126(12):1634-42. doi: 10.1001/archophthalmol.2008.107.

Reference Type: RESULT

PMID: 19064841 (View on PubMed)

Wallace DK, Lazar EL, Melia M, Birch EE, Holmes JM, Hopkins KB, Kraker RT, Kulp MT, Pang Y, Repka MX, Tamkins SM, Weise KK; Pediatric Eye Disease Investigator Group. Stereoacuity in children with anisometropic amblyopia. J AAPOS. 2011 Oct;15(5):455-61. doi: 10.1016/j.jaapos.2011.06.007.

Reference Type: DERIVED

PMID: 22108357 (View on PubMed)

Repka M, Simons K, Kraker R; Pediatric Eye Disease Investigator Group. Laterality of amblyopia. Am J Ophthalmol. 2010 Aug;150(2):270-4. doi: 10.1016/j.ajo.2010.01.040. Epub 2010 May 8.

Reference Type: DERIVED

PMID: 20451898 (View on PubMed)

Related Links

https://www.ncbi.nlm.nih.gov/pubmed/19064841

PubMed Abstract

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2846774/

PubMed Central HHS Public Access - Full Text

Other Identifiers

2U10EY011751

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NEI-119

Identifier Type: -

Identifier Source: org_study_id