Amblyopia Treatment Study: Occlusion Versus Pharmacologic Therapy for Moderate Amblyopia

Purpose | Background | Description | Patient Eligibility | Recruitment Status | Current Status | Results | Publications | Clinical Centers | Resource Centers | NEI Representative

Purpose

• To determine whether the success rate with drug treatment (atropine) of amblyopia due to strabismus or anisometropia in patients less than 7 years old is equivalent to the success rate with occlusion (patching) therapy
• To develop more precise estimates of the success rates of amblyopia treatment
• To identify factors that may be associated with successful treatment of amblyopia
• To collect data on the course of treated amblyopia to provide more precise estimates of treatment effects than are now available

Background

Amblyopia, or lazy eye, is the most common cause of visual impairment in children and often persists in adulthood. It is reported to be the leading cause of vision loss in one eye in the 20-70 year old age group, with a prevalence of 1-4 percent in various studies, indicating that both improved means of detection and treatment are needed.

Most of the available data on the natural history of amblyopia and success rates of its treatment with either patching or drug therapy are retrospective and uncontrolled. Despite the common occurrence of amblyopia, there is little quality data on treatment of this condition. Thus, there is much to be learned about the course of treated amblyopia, to provide more precise estimates of success rates and to identify factors that may be associated with successful and unsuccessful treatment.

Amblyopia, when diagnosed in children, is usually treated with occlusion (patching) of the sound eye. Occlusion therapy is subject to problems of compliance, due to the child's dislike of wearing a patch for visual, skin irritation, and social/psychological reasons. There is evidence that compliance may be one of, if not, the most important determinant of success of amblyopia therapy.

An alternative treatment, drug therapy with a cycloplegic drug (atropine) that dilates the pupils and blurs the image seen by the sound eye, has been known for almost a century. This method has been widely used for the management of occlusion treatment failures and for maintenance therapy. However, it has seen little use as a primary treatment for amblyopia. Clinical experience has found that it has a high acceptability to patients and parents, and hence high compliance. In addition to its acceptability, pharmacologic therapy has the known advantage over occlusion of providing a wider visual field with both eyes, which may have safety and other functional implications. There is also clinical and laboratory evidence suggesting that drug therapy may maintain and improve the ability to see with both eyes (binocularity).

Available data suggest that the success rate with drug therapy is as good as, if not better than, the success rate with occlusion therapy for mild to moderate degrees of amblyopia. If this is true, for many children with amblyopia, drug therapy may be the preferred initial therapy since it appears to be more readily accepted by the children and parents. Despite data to support the use of drug therapy as a primary therapy for amblyopia, it has gained only limited use among pediatric ophthalmologists. A definitive study comparing the outcomes from occlusion therapy and drug therapy is justified in order to determine if new practice guidelines for treatment of amblyopia are needed.

Regardless of whether the trial determines that one therapeutic approach is better than the other, the data that are collected will provide valuable information about the course of amblyopia treatment that is not presently available. The study also is expected to provide data that will help to determine whether factors such as age, refractive status, cause of amblyopia, or fixation pattern should be considered in determining which procedure is best for a given patient.

Description

The study is a randomized trial comparing patching and atropine therapies in the treatment of amblyopia. Patients in the patching group were initially started on 6 to 12 hours per day of occlusion; patching time was increased if the child did not improve. The atropine group received one drop of 1 percent atropine once a day. There were at least three follow-up visits for the first six months, and then at least one visit every six months until the end of two years. Visual acuity is the major study outcome. It is assessed after six months and at two years.

Patient Eligibility

Patients must be less than 7 years old with amblyopia due to strabismus or anisometropia. Visual acuity in the amblyopic eye must be between 20/40 and 20/100, visual acuity in the sound eye or 20/40 or better, and there must be at least 3 lines of acuity difference between the two eyes. Patients must have had no more than two months of amblyopia therapy in the past two years.

Patient Recruitment Status

Completed. Recruitment began in April of 1999 and closed in April 2001 after 419 patients were enrolled.

Current Status of Study

Ongoing. Six-month follow-up (primary outcome exam) was completed in November 2001. Follow up of patients continues through April 2003.

Results

Between April 1999 and April 2001, 419 patients entered the trial, with 215 assigned to the patching group and 204 to the atropine group. The mean visual acuity in the amblyopic eye at enrollment was approximately 20/63, with a mean difference in acuity between eyes of 4.4 lines. The average age of the children was 5.3 years; 47 percent were girls and 83 percent Caucasian.

At six months, visual acuity was improved from baseline by about 3 lines of vision in both the atropine and patching groups. Improvement initially was faster in the patching group, but after six months, the difference in acuity between treatment groups was small. The mean visual acuity (Snellen approximation) at six months was 20/32 in the patching group and 20/32^-2 the atropine group. This small difference between groups was considered clinically inconsequential.

Both treatments were well tolerated, although atropine had a slightly higher degree of acceptability on a parental questionnaire. More patients in the atropine group than in the patching group had reduced acuity in the sound eye at six months but this did not persist with further follow up.

Both atropine and patching are effective treatments for moderate amblyopia in children in the age range of 3 to less than 7 years old. Patching has the potential advantage of a more rapid improvement in visual acuity and possibly a slightly better acuity outcome, whereas atropine has the potential advantage of easier administration and lower cost. Our data are inconclusive about whether atropine may cause a transient treatment-related reduction of acuity in the sound eye more often than does patching. However, we are reasonably confident that in our cohort atropine did not have a lasting adverse effect on acuity of the sound eye. Since incomplete responders to one treatment could later be given the other treatment, our results indicate that the initial choice of patching or atropine can be made by the eye care provider and parent. Both patching and atropine are appropriate treatment modalities for the initial management of moderate amblyopia in children.

Publications

Pediatric Eye Disease Investigator Group: A randomized trial of atropine vs patching for treatment of moderate amblyopia in children. Arch Ophthalmol 120: 268-278, 2002.

Pediatric Eye Disease Investigator Group: The clinical profile of moderate amblyopia in children younger than age 7 years. Arch Ophthalmol 120: 281-287, 2002.

Cole SR, Beck RW, Moke PS, Celano MP, Drews CD, Repka MX, Holmes JM, Birch EE, Kraker RT, Kip KE, for the Pediatric Eye Disease Investigator Group: The amblyopia treatment index. J AAPOS 5: 250-4, 2001.

Holmes JM, Beck RW, Repka MX, Leske DA, Kraker RT, Blair RC, Moke PS, Birch EE, Saunders RA, Hertle RW, Quinn GE, Simons KA, Miller JM, for the Pediatric Eye Disease Investigator Group: The Amblyopia Treatment Study visual acuity testing protocol. Arch Ophthalmol 119: 1345-53, 2001.

Clinical Centers

Alabama
Frederick J. Elsas, M.D.
Thomas H. Metz, Jr., M.D.
Alabama Ophthalmology Associates, P.C.
1000 South 19th Street
Birmingham, AL 35205

Wendy L. Marsh-Tootle, O.D.
Robert P. Rutstein, O.D.
University of Alabama at Birmingham
School of Optometry
1716 University Boulevard
Birmingham, AL 35294

Alaska
Robert W. Arnold, M.D.
Ophthalmic Associates
542 Second Avenue
Anchorage, AK 99501-2242

Arizona
Joseph M. Miller, M.D.
University of Arizona
Department of Ophthalmology
655 N. Alvernon Way, Suite 108
Tucson, AZ 85711-1824

California
Susan M. Shin, O.D.
Raymond H. Chu, O.D.
Carmen Barnhardt, O.D.
Susan A. Cotter, O.D.
Southern California College of Optometry
2575 Yorba Linda Boulevard
Fullerton, CA 92831

James B. Ruben, M.D.
The Permanente Medical Group
1650 Response Road
Sacramento, CA 95815

Canada
William F. Astle, M.D.
Anna L. Ells, M.D.
Alberta Children's Hospital
1820 Richmond Road, SW
Calgary, Alberta T2T 5C7 Canada

Connecticut
Andrew J. Levada, M.D.
Ophthalmic Surgical Associates
1201 West Main Street, Suite 100
Waterbury, CT 06708

District of Columbia
Marijean Michele Miller, M.D.
Children's National Medical Center
Department of Ophthalmology
111 Michigan Avenue N.W.
Washington, DC 20010

Florida
Susanna M. Tamkins, O.D.
NOVA Southeastern University
3200 S. University Drive
Ft. Lauderdale, FL 33328

Magda Barsoum-Homsy, M.D.
Christine L. Burns, M.D.
Specialty Eye Care
34911 U.S. Highway 19 North, Suite 525
Palm Harbor, FL 34684

Georgia
Scott R. Lambert, M.D.
The Emory Eye Center
Department of Ophthalmology
1365-B Clifton Road, N.E.
Atlanta, GA 30322

Indiana
Derek T. Sprunger, M.D.
Indiana Medical Center
Department of Ophthalmology
Methodist Medical Plaza
201 Pennsylvania Parkway
Indianapolis, IN 46280

Daniel E. Neely, M.D.
David A. Plager, M.D.
Indiana University Medical Center
702 Rotary Circle
Indianapolis, IN 46202

Iowa
William E. Scott, M.D.
University of Iowa
200 Hawkins Drive
Iowa City, IA 52242-1091

Kansas
David A. Johnson, M.D.
The Grene Vision Group
655 North Woodlawn
Wichita, KS 67208

Maryland
Stephen R. Glaser, M.D.
101 Lakeforest Boulevard, Suite 380
Gaithersburg, MD 20877

Mary Louise Z. Collins, M.D.
Greater Baltimore Medical Center
6569 North Charles Street, Suite 505
Baltimore, MD 21204

Richard W. Hertle, M.D.
National Eye Institute
Building 49, Room 2A36
Bethesda, MD 20892-4435

David G. Hunter, M.D.,Ph.D.
Michael X. Repka, M.D.
Wilmer Ophthalmological Institute
233 Wilmer Institute
600 N. Wolfe Street
Baltimore, MD 21287-9028

Massachusetts
Erik M. Weissberg, O.D.
Bruce Moore, O.D.
New England College of Optometry
New England Eye Institute
1255 Boylston Street
Boston, MA 02215

Mexico
Miguel Paciuc, M.D.
Paseo de las Palmas 735-1102
Lomas de Chapultepec
Mexico City 11000 Mexico

Michigan
Patrick J. Droste, M.D.
Robert J. Peters, O.D.
Pediatric Ophthalmology, P.C
1000 East Paris SE #250
Grand Rapids, MI 49546

Minnesota
Jonathan M. Holmes, M.D.
Mayo Clinic
200 First Street, SW
Rochester, MN 55905

Stephen P. Christiansen, M.D.
C. Gail Summers, M.D.
University of Minnesota
Department of Ophthalmology
Box 493
420 Delaware Street, SE
Minneapolis, MN 55455

Missouri
Oscar A. Cruz, M.D.
Bradley V. Davitt, M.D.
Carnidal Glennon Children's Hospital
1465 South Grand Boulevard
St. Louis, MO 63104

New York
Steven Awner, M.D.
Children's Hospital of Buffalo
219 Bryant Street
Buffalo, NY 14222

Robert H. Duckman, O.D.
David E. FitzGerald, O.D.
State University of New York
College Of Optometry
100 East 24th Street
New York, NY 10010

North Carolina
Robert E. Wiggins, Jr., M.D.
Asheville Eye Medical & Surgical Associates
8 Medical Park Drive
Sweeten Creek Road
Asheville, NC 28803

David K. Wallace, M.D.
University of North Carolina
Eye Clinic
Ambulatory Care Center, 2nd Floor
CB #7720
Chapel Hill, NC 27599

Ohio
Constance E. West, M.D.
Children's Hospital Medical Center
3333 Burnet Avenue
Cincinnati, OH 45229

Elbert H. Magoon, M.D.
Eye Centers of Ohio, Inc.
800 McKinley Avenue, NW
Canton, OH 44703

Marjean T. Kulp, O.D.
The Ohio State University College of Optometry
P. O. Box 182342
Columbus, OH 43218

Oregon
David T. Wheeler, M.D.
Casey Eye Institute
3375 SW Terwilliger Boulevard
Portland, OR 97201-4197

Pennsylvania
Brian J. Forbes, Ph.D.,M.D.
Graham E. Quinn, M.D.
Children's Hospital of Philadelphia
Wood Center, 1st Floor
Philadelphia, PA 19104

David I. Silbert, M.D.
Family Eye Group
2110 Harrisburg Pike, Suite 215
Lancaster, PA 17604

Nicholas A. Sala, D.O.
Pediatric Ophthalmology of Erie
2201 W. 38th Street
Erie, PA 16506

Jo Ann T. Bailey, O.D.
Mitchell M. Scheiman, O.D.
Pennsylvania College Of Optometry
1200 West Godfrey Avenue
Philadelphia, PA 19141

Rhode Island
Glenn E. Bulan, M.D.
D. Robbins Tien, M.D.
Pediatric Ophthalmology and Strabismus Associates
2 Dudley Street, Suite 505
Providence, RI 02905

South Carolina
Richard A. Saunders, M.D.
Medical University of South Carolina
Storm Eye Institute
171 Ashley Avenue
Charleston, SC 29425-2236

Tennessee
Sean Donahue, Ph.D., M.D.
Vanderbilt Eye Center
8016 Medical Center East
Nashville, TN 37232

Texas
Priscilla M. Berry, M.D.
David R. Stager, Sr., M.D.
David R. Stager, Jr., M.D.
Pediatric Ophthalmology, P.A.
8201 Preston Road, Suite 140A
Dallas, TX 75225-6203

David C. Dries, M.D.
Scott and White Ophthalmology
2401 S. 31st Street
Temple, TX 76508

Kathryn M. Brady-McCreery, M.D.
David K. Coats, M.D.
Evelyn A. Paysse, M.D.
Texas Children's Hospital
6621 Fannin, MC3-2700
Houston, TX 77030

David R. Weakley, Jr., M.D.
University of Texas Southwestern Medical Center
5323 Harry Hines Boulevard
Dallas, TX 75235-9057

Utah
Robert O. Hoffman, M.D.
Richard J. Olson, M.D.
University of Utah
50 N. Medical Drive
Salt Lake City, UT 84132

Virginia
Earl R. Crouch, Jr., M.D.
Eastern Virginia Medical School
Department of Ophthalmology
880 Kempsville Road, Suite 2500
Norfolk, VA 23502-3931

Wisconsin
Jane D. Kivlin, M.D.
Mark S. Ruttum, M.D.
Medical College of Wisconsin
The Eye Institute
925 N. 87th Street
Milwaukee, WI 53226-4812

Resource Centers

Chairman's Office
Michael X. Repka, M.D.
Wilmer Eye Institute
Johns Hopkins University School of Medicine
600 N. Wolfe Street
Baltimore, MD 21287-9028
Telephone: (410) 955-8314
Fax: (410) 955-0809
E-mail: mrepka@jhmi.edu

Coordinating Center
Roy W. Beck, M.D., Ph.D.
Pamela S Moke, M.S.P.H
R. Clifford Blair, Ph.D.
Stephen R. Cole, Ph.D.
Raymond T. Kraker, M.S.P.H.
Heidi A. Gillespie
Nicole M. Boyle
Alisha N. Lawson
Julie A. Gillett
Shelly T. Mares
Brian B. Dale
Jaeb Center for Health Research
3010 East 138th Avenue
Suite 9
Tampa, FL 33613
Telephone: (813) 975-8690
Fax: (813) 975-8761
E-mail: pedig@jaeb.org
http://ats.jaeb.org

NEI Representative

Maryland
Donald F. Everett, M.A.
National Eye Institute
6120 Executive Boulevard, MSC 7164
Executive Plaza South, Suite 350
Bethesda, MD 20892-7164
Telephone: (301) 496-5983
Fax: (301) 402-0528

Steering Committee
Michael X. Repka, M.D. (Protocol Chair)
Johns Hopkins University
Baltimore, MD

Eileen Birch, Ph.D.
Retina Foundation of the Southwest
Dallas, TX

Roy W. Beck, M.D., Ph.D.
Jaeb Center for Health Research
Tampa, FL

Pamela S. Moke, M.S.P.H.
Jaeb Center for Health Research
Tampa, FL

Donald F. Everett, M.A.
National Eye Institute
National Institutes of Health
Bethesda, MD

Richard W. Hertle, M.D.
Pediatric Ophthalmology Associates, Inc.
Columbus, OH

Jonathan M. Holmes, M.D.
Mayo Clinic
Rochester, MN

Mitchell M. Scheiman, O.D.
Pennsylvania College of Optometry
Philadelphia, PA

Susan A. Cotter, O.D.
Southern California College of Optometry
Fullerton,, CA

Data and Safety Monitoring Committee

William Barlow, Ph.D.
Group Health Cooperative
Seattle, WA

Edward G. Buckley, M.D.
Duke University Medical Center
Durham, NC

Barry Davis, M.D., Ph.D.
University of Texas
Houston, TX

Velma Dobson, Ph.D.
University of Arizona
Tucson, AZ

John L. Keltner, M.D.
University of California, Davis
Sacramento, CA

Hana Osman, Ph.D.
University of South Florida
Tampa, FL

Earl A. Palmer, M.D.
Casey Eye Institute
Portland, OR

Dale L. Phelps, M.D.
University of Rochester
Rochester, NY

Last Updated: 3/13/02