A Randomized Trial Comparing Daily Atropine Versus Weekend Atropine

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

Purpose

• To compare the visual acuity outcome in the amblyopic eye after 17 weeks of daily use of atropine versus weekend-only use of atropine.
• To compare the proportion of patients achieving a complete treatment response (defined as amblyopic eye acuity >20/25 or equal to that of the sound eye in the absence of a reduction in the sound eye acuity from baseline) with daily atropine versus weekend-only atropine.

Background

Amblyopia is the most common cause of monocular visual impairment in both children and young and middle-aged adults. Patching has been the mainstay of amblyopia therapy. It is generally held that the response to treatment is best when it is instituted at an early age and is poor when attempted after eight years of age.

The study ‘Occlusion versus Pharmacologic Therapy for Moderate Amblyopia', a randomized trial of 419 children meeting entry criteria similar to the current study, found that both atropine 1% (one drop daily) and patching (6 hours to full time daily) produced visual acuity improvement of similar magnitude and that both are appropriate treatment modalities for the management of moderate amblyopia in children. 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.

Through its cycloplegic effect, atropine prevents accommodation, blurring the sound eye at near fixation. The blurring effect can be augmented by reducing the spectacle correction of hyperopia in the sound eye. The cycloplegic effect lasts at least partially for a week or longer. Therefore, some pediatric eye care providers believe that daily use of atropine is unnecessary and treatment may be effective at a dosage of as little as once a week. One advantage of less frequent dosing is a potential reduction in side effects, including any potential adverse effect on the vision in the sound eye (reverse amblyopia), on ocular alignment, and on binocularity. The current study will assess whether prescribing atropine once a day produces a better visual outcome than does atropine used only on the two weekend days.

In the ‘Occlusion versus Pharmacologic Therapy for Moderate Amblyopia' study, the 6-month outcome data showed that more patients treated with atropine had a reduction in visual acuity of 1 or more lines in the sound eye than did patients treated with patching. Visual acuity was decreased from baseline by 1 line in 15% of the atropine group compared with 7% of the patching group and by 2 or more lines in 9% of the atropine group and 1% of the patching group. Only one patient (in the atropine group) was actively treated for a presumed treatment-related decrease in sound eye acuity, with return of acuity to its baseline level. Some of the cases of reduced acuity were unequivocally due to the use of improper refractive correction for the sound eye testing (including nine cases in which the testing was done with a plano lens prescribed for therapeutic effect rather than the proper corrective lens). In other cases, we speculated that there was a residual cycloplegic effect of atropine combined with improper refractive correction related to previously latent hyperopia becoming manifest hyperopia during the period of atropine treatment, although there were not data to fully document this in all cases. All 47 atropine group patients with a decrease of one or more lines at six months have had subsequent follow-up exams. Acuity on the subsequent testing was the same or better than that at baseline in 42 of the 47 patients: 22 while still on atropine treatment (11 with the same refractive correction and 11 with a different refractive correction) and 20 after atropine was discontinued (6 with the same refractive correction and 14 with a different refractive correction). In the other five patients, acuity on subsequent testing was decreased from baseline by one line (3 on atropine, 2 off atropine). Thus, there did not appear to be a long-term safety concern for atropine, but the data were inconclusive as to whether atropine caused an actual, though transient, treatment-related decrease in sound eye acuity. One of the objectives of the current study will be to provide additional data on the effect of atropine on the sound eye.

Description

The study is a randomized trial comparing atropine regimes for children moderate amblyopia. It will consist of about 160 children. Patients in the daily atropine group receive atropine 1% one drop daily in the sound eye. Patients in the weekend atropine group will receive atropine 1% twice a week (Saturday and Sunday) in the sound eye. Visual acuity is the major study outcome. It is measured after 17 weeks of treatment with either daily or weekend atropine.

Patient Eligibility

• Age < 7 years
• Able to measure surrounded single optotype visual acuity using the ATS single-surround HOTV protocol (this will in effect exclude all patients <2 years old and many <3 years old)
• Amblyopia associated with strabismus, anisometropia, or both
• If anisometropia present (as per protocol definition), refractive error corrected with spectacles for a minimum of 4 weeks
• Visual acuity in the amblyopic eye < 20/40 and >20/80
• Visual acuity in the sound eye > 20/40 and inter-eye acuity difference >3 logMAR lines
• No amblyopia treatment (other than spectacles) in the past month and no more than one month of amblyopia treatment in the past 6 months
• No myopia more than a spherical equivalent of -6.00 D in the amblyopic eye
• No myopia more than a spherical equivalent of -0.50 D in the sound eye

Patient Recruitment Status

Completed. Recruitment began in June 2002 and closed in April 2003 after 168 patients were enrolled.

Current Status of Study

Completed.

Results

None. Manuscript submitted to Ophthalmology in February 2004.

Publications

None.

Clinical Centers

Alabama
Wendy L. Marsh-Tootle, O.D.
Katherine K. Niemann, 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 W 2nd Ave
Anchorage, AK 99501-2242

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

California
Henry S. O'Halloran, M.D.
Yvette M. Jockin, M.D.
Colin A. Scher, M.D.
Childrens Specialists of San Diego
3030 Children's Way, Suite #109
San Diego, CA 92123

Carmen N. Barnhardt, O.D.
Raymond H. Chu, O.D.
Susan A. Cotter, O.D.
Susan M. Shin, O.D.
Southern California College of Optometry
2575 Yorba Linda Blvd
Fullerton, CA 92831-1699

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

Connecticut
Darron A. Bacal, M.D.
Eye Physicians & Surgeons, PC
202 Cherry Street
Milford, CT 06460

Andrew J. Levada, M.D.
The Eye Care Group, PC
1201 W Main Street, Suite 100
Waterbury, CT 06708

Florida
Susanna M. Tamkins, O.D., F.A.A.O.
Bascom Palmer Eye Institute
900 NW 17th Street
Miami, FL 33136

Lee S. Friedman, M.D.
Palm Beach Eye Foundation
Visual Health and Surgical Center
2889 10th Avenue North
Lake Worth, FL 33461

Christine L. Burns, M.D.
Specialty Eye Care
34911 U.S. Highway 19 N, Suite 525
Palm Harbor, FL 34684-1967

Illinois
Deborah R. Fishman, M.D.
Lisa C. Verderber, M.D.
Pediatric Eye Associates
3612 Lake Ave Unit 3
Wilmette, IL 60091-1000

Indiana
Don W. Lyon, O.D.
Indianapolis Eye Care Center
501 Indian Ave Suite 100
Indianapolis, IN 46202

Iowa
Donny W. Suh, M.D.
Wolfe Clinic
6000 University Ave
West Des Moines, IA 50266-8203

Kansas
David A. Johnson, M.D., Ph.D.
Eye Clinic of Wichita
655 North Woodlawn
Wichita, KS 67208

Maryland
Stephen R. Glaser, M.D.
15235 Shady Grove Road Suite 101
Rockville, MD 20850

Michael X. Repka, M.D.
Wilmer Institute
600 N Wolfe St
Baltimore, MD 21287-9028

Michigan
Patrick J. Droste, M.D.
Robert J. Peters, O.D.
Pediatric Ophthalmology, P.C.
5050 Cascade Road SE
Grand Rapids, MI 49546

Minnesota
Evan A. Ballard, M.D.
Susan Schloff, M.D.
Associated Eye Care
280 Smith Ave N STE 840
Saint Paul, MN 55102-2454

Jonathan M. Holmes, M.D.
Brian G. Mohney, M.D.
Melissa L. Rice, O.D.
Mayo Clinic
200 1st St SW
Rochester, MN 55905-0002

Stephen P. Christiansen, M.D.
C. Gail Summers, M.D.
University of Minnesota
420 Delaware Street SE, Mayo Mail Code 493
Minneapolis, MN 55455-0501

Missouri
Oscar A. Cruz, M.D.
Bradley V. Davitt, M.D.
Cardinal Glennon Children's Hospital
1755 S Grand Blvd
St. Louis, MO 63104-1095

New Jersey
Michael F. Galloway, O.D.
2401 Route 130 S
Cinnaminson, NJ 08077-3020

New Mexico
Frank Durso, M.D.
Eye Associates of New Mexico & Southwest Colorado
101 Hospital Loop, NE; Suite 203
Albuquerque, NM 87109

New York
Stanley W. Hatch, O.D.
Associates in Ophthalmology, PC
450 Margaret St
Plattsburgh, NY 12901-1793

Robert H. Duckman, O.D.
State University of New York, College of Optometry
33 W 42nd St
New York, NY 10036-8003

North Carolina
David K. Wallace, M.D.
UNC Dept. of Ophthalmology
2nd Floor, CB# 7720
Chapel Hill, NC 27599-7720

Ohio
Don L. Bremer, M.D.
Richard W. Hertle, M.D.
Pediatric Ophthalmology Associates, Inc.
555 S 18th St STE 4C
Columbus, OH 43025

Marjean T. Kulp, O.D.
The Ohio State University
P.O. Box 182342
Columbus, OH 43218-2342

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

Pennsylvania
Don D. Blackburn, O.D.
David I. Silbert, M.D.
Eric L. Singman, M.D., Ph.D.
Family Eye Group
2110 Harrisburg Pike, Suite 215
Lancaster, PA 17604

Nicholas A. Sala, D.O.
Pediatric Ophthalmology of Erie
2201 W 38th St
Erie, PA 16506-4501

Jo Ann T. Bailey, O.D.
Mitchell M. Scheiman, O.D.
Brandy J. Scombordi, O.D.
Kathleen T. Zinzer, O.D.
Pennsylvania College of Optometry
1200 West Godfrey Ave.
Philadelphia, PA 19141

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

John P. Donahue, M.D., Ph.D.
Rhode Island Eye Institute
150 East Manning Street
Providence, RI 02906

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

David R. Weakley, Jr., M.D.
UT Southwestern Med Ctr
5323 Harry Hines Blvd Stop 9057
Dallas, TX 75235-9057

Virginia
Earl R. Crouch, Jr., M.D.
Eastern Virginia Medical School
880 Kempsville Rd STE 2500
Norfolk, VA 23502-3942

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

Resource Centers

Co-Chairman
Jonathan M. Holmes, M.D.
Mayo Clinic
Department of Ophthalmology W7
200 First Street Southwest
Rochester, MN 55905
Telephone: (507) 284-3760
Fax: (507) 284-8566
E-mail: holmes.jonathan@mayo.edu

Michael X. Repka, M.D.
Wilmer Eye Institute
233 N. Wolfe Street
Baltimore, MD 21287-9028
Telephone: (410) 955-8314
Fax: (410) 955-0809
E-mail: mrepka@jhmi.edu

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

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
Sacramento, CA

Hana Osman, Ph.D.
Louis de la Parte Florida Mental Health Institute
Tampa, FL

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

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

NEI Representative

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

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

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

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

Donald F. Everett
National Eye Institute
Bethesda, MD

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

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

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

Graham E. Quinn, M.D.
Children's Hospital of Philadelphia
Philadelphia, PA

Michael X. Repka, M.D.
Johns Hopkins University
Baltimore, MD

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

Last Updated: 3/15/2004