Early Treatment for Retinopathy of Prematurity Study (ETROP), The

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

Purpose

The goal of the Early Treatment for Retinopathy of Prematurity Study (ETROP) is to test the hypothesis that earlier treatment in carefully selected cases will result in an overall better visual outcome than treatment at the conventional CRYO-ROP threshold point in the disease.

Background

At age 5 1/2 years, the oldest age for which follow-up data are available, children with threshold ROP who were enrolled in the Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) -- Outcome Study showed fewer treated eyes (31.5 percent) than control eyes (48 percent) that were blind (P<0.001). of those eyes that had a favorable structural outcome, with or without retinal ablation (cryotherapy to destroy the fringe of the retina through freezing), only a small percentage had best corrected visual acuity better than or equal to 20/40 at age 5 1/2 years (13 percent in the treated group; 17 percent in the untreated control group (p=0.19)). among the 1398 followed from the 5 large natural history centers of the cryo-rop follow-up study, children with retinal residua of rop (structural changes) had measurable visual acuity that was severly affected and tended to worsen with age. the cryo-rop study proved conclusively that peripheral retinal ablation improves the chances of avoiding blindness, but at least 80 percent of eyes are left with acuity less than 20/40.

Two concerns emerged from the CRYO-ROP extensive study on the natural history of ROP and treatment of threshold ROP. The first of these is failure of peripheral retinal ablation to eliminate all, or nearly all cases, of retinal detachment due to ROP. In the CRYO-ROP Study, 26 percent of eyes with threshold disease in zone II and 78 percent of eyes with zone I threshold disease had an unfavorable structural outcome despite treatment. The second concern is that most children who developed threshold ROP disease had visual acuity worse than 20/40 even if the eye had a favorable structural outcome.

Since no other treatment has yet been shown to be effective in preventing blindness from ROP, retinal ablation remains the treatment of choice. The ETROP Study will test whether earlier treatment is more effective than treatment at threshold in improving functional (visual acuity) outcome following ROP, as well as determining whether earlier treatment decreases the probability of an unfavorable structural outcome.

Description

Earlier treatment is defined as retinal ablation administered to the avascular retina when an eye reaches high risk prethreshold retinopathy of prematurity (ROP). Prethreshold indicates any Zone I ROP; or Zone II stage 2 with plus disease, or stage 3; or Zone II with less than 5 contiguous or 8 cumulative clock hours of stage 3 ROP with plus disease. Recognizing that a substantial number of eyes undergo spontaneous resolution of ROP, eyes will be randomized to early treatment only when high risk for an unfavorable visual acuity outcome is identified. High risk will be determined using a risk model analysis program based on longitudinal natural history data obtained from the CRYO-ROP study. This model integrates risk factors to assign a risk of progression to blindness without treatment. These factors include birth weight, gestational age, ethnicity, singleton/multiple status, outborn status, Zone on first exam, severity of ROP and rate of progression of ROP. When an infant develops prethreshold ROP and greater than or equal to 15 percent risk of unfavorable outcome, randomization to early treatment of one eye will occur. Visual acuity outcome will be measured by masked observers after wearing best corretion using the Teller Acuity Card Procedure at 9 months corrected age.

Patient Eligibility

Infants <1251 grams birthweight born at participating centers and/or examined by 42 days of life are eligible. the early treatment trial requires that an infant have prethreshold retinopathy of prematurity (rop).

Patient Recruitment Status

Completed. A total of 317 infants with birth weights less than 1251 g and birth dates between October 1, 2000, and September 30, 2002, were enrolled at 26 participating centers.

Current Status of Study

Ongoing.

Results

Grating acuity results showed a reduction in unfavorable visual acuity outcomes with earlier treat-ment, from 19.5% to 14.5% (P = .01). Unfavorable structural outcomes were reduced from 15.6% to 9.1% (P<.001) at 9 months. further analysis supported retinal ablative therapy for eyes with type 1 rop, defined as zone i, any stage rop with plus disease (a degree of dilation and tortuosity of the posterior retinal blood vessels meeting or exceeding that of a standard photograph); zone i, stage 3 rop without plus disease; or zone ii, stage 2 or 3 rop with plus disease. the analysis supported a wait-and-watch approach to type 2 rop, defined as zone i, stage 1 or 2 rop without plus disease or zone ii, stage 3 rop without plus disease. these eyes should be considered for treatment only if they progress to type 1 or threshold rop.

Early treatment of high-risk prethreshold ROP significantly reduced unfavorable outcomes to a clinically important degree. Additional analyses led to modified recommendations for the use of peripheral retinal ablation in eyes with ROP. Long-term follow-up is being conducted to learn whether the benefits noted in the first year after birth will persist into childhood.

Publications

Early Treatment for Retinopathy of Prematurity Cooperative Group: Revised Indications for the Treatment of Retinopathy of Prematurity: Results of the Early Treatment for Retinopathy of Prematurity Randomized Trial . Arch Ophthalmol 121: 1684-1694, 2003.

Good WV, Hardy RJ, on behalf of the ETROP Multicenter Study Group: The Multicenter Study of Early Treatment for Retinopathy of Prematurity. Ophthalmology Volume 108, Number 6: 1013-1014, 2001.

Clinical Centers

David K. Coats, M.D.
Laura Gonzalez
Baylor College of Medicine
Feigin Center
6621 Fannin Street, MC 3-2700
Houston, TX 77030-2399
Telephone: 832-824-3237
Fax: 713-796-8110
E-mail: dcoats@bcm.tmc.edu

Bradley V. Davitt, M.D.
Linda Breuer
Cardinal Glennon Children's Hospital
Neonatology Office
1465 South Grand Boulevard
St. Louis, MO 63104
Telephone: 314-577-5660
Fax: 314-268-6410
E-mail: davittb@slu.edu

Gary L. Rogers, M.D.
Rae Fellows, M.Ed.
Columbus Children's Hospital
Outpatient Care Center
555 S. 18th Street, Suite 4C
Columbus, OH 43205-2696
Telephone: 614-722-6129
Fax: 614-722-6130
E-mail: garogers@chi.osu.edu

Sharon F. Freedman, M.D.
David Wallace, M.D.
Lori Hutchins
Lora Lake
Duke University Eye Center
Ophthalmology and Pediatrics
Box 3802, Room 111, Erwin Road
Durham, NC 27710
Telephone: 919-684-4584
Fax: 919-684-6096
E-mail: freed003@mc.duke.edu

Pamela Ann Weber, M.D., F.A.A.O.
Marc A. Horowitz, M.D., F.A.C.S.
Adriann Combs, R.N.C.
Natalie Dweck, R.N.
Eastern Long Island Retina Associates
1500 William Floyd Parkway
Shirley, NY 11967
Telephone: 631-924-4300
Fax: 631-924-2525
E-mail: pamela.weber@worldnet.att.net

John T. Flynn, M.D.
Thomas C. Lee, M.D., Ph.D.
Osode Coki
Edward S. Harkness Eye Institute
Department of Ophthalmology
Columbia University College of Physicians and Surgeons
635 West 165th Street
New York, NY 10032
Telephone: 212-305-3908
Fax: 212-342-5293
E-mail: jtf38@columbia.edu

Daniel E. Neely, M.D.
Elizabeth Hynes, R.N.C.
Indiana University Department of Pediatrics
James Whitcomb Riley Hospital for Children
699 West Drive, RR 208
Indianapolis, IN 46002-2119
Telephone: 317-274-4716
Fax: 317-274-2065
E-mail: jlemons@iupui.edu

Robert O. Hoffman, M.D.
Susan Bracken, R.N.
John Moran Eye Center
University of Utah Health Sciences Center
75 North Medical Drive
Salt Lake City, UT 84132
Telephone: 801-581-4955
Fax: 801-585-1295
E-mail: robert.hoffman@hsc.utah.edu

Kenneth P. Cheng, M.D.
Judith G. Jones, R.N.C, B.S.N.
Magee-Women's Hospital
Department of Pediatrics
Division of Neonatology
300 Halket Street
Pittsburgh, PA 15213-3180
Telephone: 724-934-3333
Fax: 724-934-3371
E-mail: kpchengmd@stargate.net

Richard A. Saunders, M.D.
Dilip Purohit, M.D.
Lisa M. Langdale, R.N., M.S.N.
Medical University of South Carolina
Storm Eye Institute
167 Ashley Avenue
P.O. Box 250676
Charleston, SC 29425-2236
Telephone: 843-792-2761
Fax: 843-792-3903
E-mail: saundric@musc.edu

David T. Wheeler, M.D.
Nancy Dolphin, R.N.
Oregon Health Sciences University
Casey Eye Institute
3375 S.W. Terwilliger Boulevard
Portland, OR 97201-4197
Telephone: 503-494-0741
Fax: 503-494-6071
E-mail: wheeleda@ohsu.edu

John D. Baker, M.D.
Kristi I. Cumming, M.S.N.
Pediatric Ophthalmology Associates, PC
2355 Monroe Boulevard
Dearborn, MI 48124
Telephone: 313-561-1777
Fax: 313-561-8044
E-mail: jbaker4051@aol.com

William Good, M.D.
Monica Hubbard
Smith-Kettlewell Eye Research Institute
2318 Fillmore Street
San Francisco, CA 94115-1813
Telephone: 415-345-2000
Fax: 415-345-2095
E-mail: good@ski.org

Michael Gaynon, M.D.
David Stevenson, M.D.
Ashima Madan, M.D.
Bethany Ball
Stanford University School of Medicine
750 Welch Road, #315
Palo Alto, CA 94304
Telephone: 650-321-4121
Fax: 650-853-6086
E-mail: opmed@ix.netcom.com

James D. Reynolds, M.D.
Dawn Gordon
The Children's Hospital of Buffalo
Department of Ophthalmology
219 Bryant Street
Buffalo, NY 14222-2099
Telephone: 716-878-7204
Fax: 716-888-3807
E-mail: jreynold@acsu.buffalo.edu

Graham E. Quinn, M.D.
Jamie Koh, R.N., M.S.N.
The Children's Hospital of Philadelphia
Division of Pediatric Ophthalmology
The Richard D. Wood Building, First Floor
34th Street and Civic Center Boulevard
Philadelphia, PA 19104-4399
Telephone: 215-590-2791
Fax: 215-590-4325
E-mail: quinn@email.chop.edu

R. Michael Siatkowski, M.D.
Karen Corff, M.S., A.R.N.P.
The Dean A. McGee Eye Institute
608 Stanton L. Young Boulevard
Oklahoma City, OK 73104
Telephone: 405-271-1094
Fax: 405-271-3013
E-mail: rmichael_siatkowski@ouhsc.edu

Michael J. Shapiro, M.D.
Jeffrey Parker
The University of Illinois at Chicago
UIC Eye Center Department of Ophthalmology and Visual Sciences
The Lions of Illinois Eye Research Institute
1905 West Taylor Street
Chicago, IL 60612-7245
Telephone: 312-416-7319
Fax: 312-996-7770
E-mail: michshap@uic.edu

Michael X. Repka, M.D.
Jennifer A. Shepard, C.R.N.P.
The Zanvyl Krieger Children's Eye Center
The Wilmer Institute, 233
The Johns Hopkins Hospital
600 North Wolfe Street
Baltimore, MD 21287
Telephone: 410-955-8314
Fax: 410-955-0809
E-mail: mrepka@jhmi.edu

Cynthia H. Cole, M.D., M.P.H.
Brenda MacKinnon, R.N.C.
Tufts University School of Medicine
Department of Pediatrics
750 Washington Street, NEMC #84
Boston, MA 02111
Telephone: 617-636-5322
Fax: 617-636-1456
E-mail: ccole@lifespan.org

Robert A. Gordon, M.D.
Deborah S. Neff, L.P.N.
Tulane University Medical Center
School of Medicine
Department of Ophthalmology SL69
1430 Tulan Avenue
New Orleans, LA 70112-2699
Telephone: 504-588-5804
Fax: 504-584-2684
E-mail: deborah.neff@hcahealthcare.com

Paul Rychwalski, M.D.
Greg Whittington
University of Louisville Health Sciences Center
Department of Ophthalmology and Visual Sciences
301 East Muhammad Ali Boulevard
Louisville, KY 40202-1594
Telephone: 502-852-5466
Fax: 502-852-7393

Ira H. Gewolb, M.D.
Rani Kalsi
University of Maryland School of Medicine
22 South Green Street, Room N5W68
University Center
Baltimore, MD 21201-1595
Telephone: 410-328-6356
Fax: 410-328-1076
E-mail: igewolb@peds.umaryland.edu

Stephen P. Christiansen, M.D.
Sally M. Cook
University of Minnesota
Department of Ophthalmology
Mayo Mail Code 493
420 Delaware Street, SE
Minneapolis, MN 55455-0591
Telephone: 612-625-4400
Fax: 612-626-3119
E-mail: chris196-@tc.umn.edu

Dale L. Phelps, M.D.
Cassandra Horihan
University of Rochester Medical Center
601 Elmwood Avenue, Box 651
Rochester, NY 14642
Telephone: 716-275-2972
Fax: 716-461-3614
E-mail: dale_phelps@urmc.rochester.edu

W.A.J. van Heuven, M.D.
Alice K. Gong, M.D.
Yolanda Trigo
University of Texas Health Science Center at San Antonio
Department of Ophthalmology, MC 6230
7703 Floyd Curl Drive
San Antonio, TX 78229-3900
Telephone: 210-567-8402
Fax: 210-567-8413
E-mail: vanheuven@uthscsa.edu

Resource Centers

Coordinating Center
Robert J. Hardy, Ph.D.
Betty Tung, M.S.
University of Texas Health Science Center
School of Public Health
Coordinating Center for Clinical Trials
1200 Herman Pressler, E833
Houston, TX 77030
Telephone: 713-500-9524
Fax: 713-500-9530
E-mail: bhardy@utsph.sph.uth.tmc.edu

Study Headquarters
William V. Good, M.D.
Michelle Quintos
Smith-Kettlewell Eye Research Institute
2318 Fillmore Street
San Francisco, CA 94115-1813
Telephone: 415-345-2055
Fax: 415-345-2095
E-mail: good@ski.org

Vision Center
Velma Dobson, Ph.D.
University of Arizona, SOM
Department of Ophthalmology
655 N. Alvernon Way, Suite 108
Tucson, AZ 85711
Telephone: 520-322-3800 x238
Fax: 520-321-3665
E-mail: vdobson@eyes.arizona.edu

NEI Representative

NEI Representative
Maryann Redford, D.D.S., M.P.H.
National Eye Institute
Eexecutive Plaza Sosuth, Suite 350
6120 Executive Boulevard, MSC 7164
Bethesda, MD 20892-7164
Telephone: 301-496-5983
Fax: 301-402-0528
E-mail: maryann.redford@nei.nih.gov

Last Updated: 12/8/2003