Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) - Outcome Study of Cryotherapy for Retinopathy of Prematurity

February 3, 2014 updated by: National Eye Institute (NEI)

To determine the safety and efficacy of trans-scleral cryotherapy of the peripheral retina in certain low birth-weight infants with retinopathy of prematurity (ROP) for reducing blindness from ROP.

To determine the long-term outcome for eyes that had severe ("threshold") ROP, both with and without cryotherapy.

Study Overview

Status

Completed

Detailed Description

ROP is a disease of the eyes of prematurely born infants in which the retinal blood vessels increase in number and branch excessively, sometimes leading to hemorrhage or scarring. Before the establishment of this study in 1985, more than 500 infants annually were blinded by ROP in the United States alone.

More than 30 years ago, the National Institutes of Health sponsored a clinical trial that showed that if premature babies are given oxygen only as needed, the number of infants who develop ROP drops dramatically. Subsequently, hospitals cut back on giving excessive oxygen routinely to premature babies. But, with improvements in neonatal care over the last two decades, the number of babies at risk is increasing as survival rates for smaller premature infants improve. The lower the birth weight, the higher the incidence and severity of ROP.

In a more recent NEI-supported study at the University of Miami, blood oxygen levels of very low birth-weight infants were monitored continuously by use of transcutaneous measurements as long as oxygen therapy was needed. The study showed that there is no statistically significant difference between the rates of ROP in infants monitored on continuous oxygen therapy and in those monitored only when they were receiving oxygen in excess of 40 percent.

The Supplemental Therapeutic Oxygen for Prethreshold ROP (STOP-ROP) trial, also funded by the NEI, studied whether a slight increase in oxygen therapy would prevent the progression of moderate ROP to ROP severe enough to require surgical treatment. This intervention made little or no difference in outcomes.

Likewise, another NEI-sponsored clinical trial (LIGHT-ROP) demonstrated absence of protective effect on ROP by limiting light exposure to newborn premature infants. These studies have led to the conclusion that factors other than oxygen or light exposure must be involved in causing ROP.

In most infants who develop ROP, the disease spontaneously subsides, permitting development of normal vision. But other infants who progress to a severe form of ROP are in danger of becoming permanently blind. Although the cause of ROP is not fully explained, scientists are seeking ways to treat ROP successfully and to find the right time in the progression of the disease to use treatment. Cryotherapy, which destroys the fringe of the retina through freezing, is the only treatment so far that has been demonstrated to provide substantial benefit to these eyes.

The multicenter trial of cryotherapy for ROP enrolled more than 4,000 premature infants who weighed no more than 1,250 grams at birth. This category of infants is at the greatest risk of developing ROP. The eyes of the infants enrolled in the study were examined at predetermined intervals while the subjects were still in the intensive care nursery. After the pupils were dilated with eye drops, the eyes were examined by an ophthalmologist using a binocular indirect ophthalmoscope to visualize the developing retina. The natural history of the condition of each infant's retina was recorded. When examination disclosed the severe form of ROP (threshold ROP) in both eyes, and the parents gave informed consent, one of the infant's eyes was randomly selected to receive cryotherapy. In this technique, a cryoprobe was used to freeze and thus destroy the peripheral extent of the retina, thereby arresting the development of the blood vessels growing wildly toward it.

Outcome of the therapy was assessed at 3 months and 12 months following randomization by an extensive examination that included photography of the interior of both the treated and the control eyes. The 12-month exam also measured visual function with preferential-looking techniques. Such measurements allowed correlations between fundus photographs and visual function and a comparison of visual function for treated versus control eyes. Neither the trained photograph readers who evaluated the pictures from both eyes nor the specially trained vision testers knew which eyes had received cryotherapy. Additional assessments of visual acuity and retinal status have been made approximately each year up to the present. Currently (2001), preparations are being made for a 15-year outcome study that will conclude by 2003.

Study Type

Interventional

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Alabama
      • Birmingham, Alabama, United States
        • Alabama Ophthalmology Associates, P.C.
    • District of Columbia
      • Washington, District of Columbia, United States
        • Private practice of David Plotsky, MD
      • Washington, District of Columbia, United States
        • Retina Group of Washington
    • Florida
      • Miami, Florida, United States
        • Bascom Palmer Eye Institute, University of Miami School of Medicine
    • Illinois
      • Chicago, Illinois, United States
        • University of Illinois Eye and Ear Infirmary
    • Indiana
      • Indianapolis, Indiana, United States
        • Department of Ophthalmology, Indiana University School of Medicine
    • Kentucky
      • Louisville, Kentucky, United States
        • Kentucky Lions Eye Research Institute, University of Louisville
    • Louisiana
      • New Orleans, Louisiana, United States
        • Department of Ophthalmology, Tulane University School of Medicine
    • Maryland
      • Baltimore, Maryland, United States
        • Wilmer Eye Institute, The Johns Hopkins Medical Institutions
    • Michigan
      • Dearborn, Michigan, United States
        • Private practice of John D. Baker, MD
      • Royal Oak, Michigan, United States
        • Associated Retinal Consultants, P.C.
    • Minnesota
      • Minneapolis, Minnesota, United States
        • Department of Ophthalmology, University of Minnesota
    • New York
      • Rochester, New York, United States
        • Strong Children's Hospital, University of Rochester Medical Center
    • North Carolina
      • Durham, North Carolina, United States
        • Duke University Medical Center
    • Ohio
      • Cincinnati, Ohio, United States
        • Private Practice of Miles J. Burke, MD
      • Columbus, Ohio, United States
        • Columbus Children's Hospital
    • Oregon
      • Portland, Oregon, United States
        • Oregon Health & Science University, Casey Eye Institute
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States
        • Children's Hospital of Philadelphia, Division of Pediatric Ophthalmology
      • Pittsburgh, Pennsylvania, United States
        • Pediatric Ophthalmology and Strabismus, Inc.
    • South Carolina
      • Charleston, South Carolina, United States
        • Storm Eye Institute, Medical University of South Carolina
    • Tennessee
      • Nashville, Tennessee, United States
        • Department of Ophthalmology, Vanderbilt University Medical Center
    • Texas
      • Dallas, Texas, United States
        • Private practice of Rand Spencer, M.D.
      • San Antonio, Texas, United States
        • University of Texas Health Science Center, San Antonio, Department of Ophthalmology
    • Utah
      • Salt Lake City, Utah, United States
        • John Moran Eye Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 1 year (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Premature infants of either gender who were eligible for the natural history study had weighed less than 1,251 grams at birth and had survived the first 28 days of life. They had no major ocular or systemic congenital anomalies. Infants who met these criteria and also had a threshold level of ROP (defined as stage 3+ of the International Classification of Retinopathy of Prematurity occupying five or more contiguous or eight cumulative 30 degree sectors [clock hours] of stage 3 ROP in zone I or II in the presence of plus disease) could be referred for examination to determine eligibility for entry to the cryotherapy trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Randomized

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 1986

Study Completion (Actual)

August 1, 2003

Study Registration Dates

First Submitted

September 23, 1999

First Submitted That Met QC Criteria

September 23, 1999

First Posted (Estimate)

September 24, 1999

Study Record Updates

Last Update Posted (Estimate)

February 4, 2014

Last Update Submitted That Met QC Criteria

February 3, 2014

Last Verified

October 1, 2003

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Retinopathy of Prematurity

Clinical Trials on Trans-scleral Cryotherapy

Subscribe