Clinical trial NCT00000133: Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) - Outcome Study of Cryotherapy for Retinopathy of Prematurity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Retinopathy of Prematurity
Lead sponsor: National Eye Institute (NEI)
Sponsor class: NIH
First posted: 1999-09-24
Sex: ALL
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED

Brief summary: 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.

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.

Eligibility criteria: 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.

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