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



Sponsors


Source

National Eye Institute (NEI)

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.

Overall Status

Completed

Start Date

1986-01-01

Completion Date

2003-08-01

Primary Completion Date

N/A

Phase

N/A

Study Type

Interventional


Condition


Intervention

Intervention Type

Procedure

Intervention Name



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.

Gender

All

Minimum Age

N/A

Maximum Age

1 Year

Healthy Volunteers

No


Location

Facility

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

Location Countries

Country

United States


Verification Date

2003-10-01

Lastchanged Date

N/A

Firstreceived Date

N/A

Has Expanded Access

No

Condition Browse


Firstreceived Results Date

N/A

Reference

Citation

Multicenter trial of cryotherapy for retinopathy of prematurity: preliminary results. Cryotherapy for Retinopathy of Prematurity Cooperative Group. Pediatrics. 1988 May;81(5):697-706.

PMID

2895910


Citation

Multicenter trial of cryotherapy for retinopathy of prematurity. Three-month outcome. Cryotherapy for Retinopathy of Prematurity Cooperative Group. Arch Ophthalmol. 1990 Feb;108(2):195-204.

PMID

2405827


Citation

Dobson V, Quinn GE, Biglan AW, Tung B, Flynn JT, Palmer EA. Acuity card assessment of visual function in the cryotherapy for retinopathy of prematurity trial. Invest Ophthalmol Vis Sci. 1990 Sep;31(9):1702-8.

PMID

2211019


Citation

Watzke RC, Robertson JE Jr, Palmer EA, Wallace PR, Evans MS, Soldevilla JE. Photographic grading in the retinopathy of prematurity cryotherapy trial. Arch Ophthalmol. 1990 Jul;108(7):950-5.

PMID

2369354


Citation

Hardy RJ, Davis BR, Palmer EA, Tung B. Statistical considerations in terminating randomization in the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity. Cryotherapy for Retinopathy of Prematurity Cooperative Group. Control Clin Trials. 1991 Apr;12(2):293-303.

PMID

1645641


Citation

Palmer EA, Flynn JT, Hardy RJ, Phelps DL, Phillips CL, Schaffer DB, Tung B. Incidence and early course of retinopathy of prematurity. The Cryotherapy for Retinopathy of Prematurity Cooperative Group. Ophthalmology. 1991 Nov;98(11):1628-40.

PMID

1800923


Citation

Palmer EA, Hardy RJ, Davis BR, Stein JA, Mowery RL, Tung B, Phelps DL, Schaffer DB, Flynn JT, Phillips CL. Operational aspects of terminating randomization in the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity. Cryotherapy for Retinopathy of Prematurity Cooperative Group. Control Clin Trials. 1991 Apr;12(2):277-92.

PMID

1645640


Citation

Phelps DL, Brown DR, Tung B, Cassady G, McClead RE, Purohit DM, Palmer EA. 28-day survival rates of 6676 neonates with birth weights of 1250 grams or less. Pediatrics. 1991 Jan;87(1):7-17.

PMID

1984621


Citation

Quinn GE, Dobson V, Barr CC, Davis BR, Flynn JT, Palmer EA, Robertson J, Trese MT. Visual acuity in infants after vitrectomy for severe retinopathy of prematurity. Ophthalmology. 1991 Jan;98(1):5-13. Erratum in: Ophthalmology. 1991 Jul;98(7):1005.

PMID

2023732


Citation

Gilbert WS, Dobson V, Quinn GE, Reynolds J, Tung B, Flynn JT. The correlation of visual function with posterior retinal structure in severe retinopathy of prematurity. Cryotherapy for Retinopathy of Prematurity Cooperative Group. Arch Ophthalmol. 1992 May;110(5):625-31.

PMID

1580837


Citation

Quinn GE, Dobson V, Repka MX, Reynolds J, Kivlin J, Davis B, Buckley E, Flynn JT, Palmer EA. Development of myopia in infants with birth weights less than 1251 grams. The Cryotherapy for Retinopathy of Prematurity Cooperative Group. Ophthalmology. 1992 Mar;99(3):329-40.

PMID

1565444


Citation

Summers G, Phelps DL, Tung B, Palmer EA. Ocular cosmesis in retinopathy of prematurity. The Cryotherapy for Retinopathy of Prematurity Cooperative Group. Arch Ophthalmol. 1992 Aug;110(8):1092-7.

PMID

1497522


Citation

Trueb L; Evans J; Hammel A; Bartholomew P; Dobson D; Assessing visual acuity of visually impaired children using the Teller acuity cards., Am Orthoptic J 1992;42:149-154


Citation

Multicenter trial of cryotherapy for retinopathy of prematurity. 3 1/2-year outcome--structure and function. Cryotherapy for Retinopathy of Prematurity Cooperative Group. Arch Ophthalmol. 1993 Mar;111(3):339-44.

PMID

8447743


Citation

Evans MS; Wallace PR; Palmer EA; Fundus photography in small infants., J Ophthal Photography 1993;15(1):38-39


Citation

Reynolds J, Dobson V, Quinn GE, Gilbert WS, Tung B, Robertson J, Flynn JT. Prediction of visual function in eyes with mild to moderate posterior pole residua of retinopathy of prematurity. Cryotherapy for Retinopathy of Prematurity Cooperative Group. Arch Ophthalmol. 1993 Aug;111(8):1050-6.

PMID

8352687


Citation

Schaffer DB, Palmer EA, Plotsky DF, Metz HS, Flynn JT, Tung B, Hardy RJ. Prognostic factors in the natural course of retinopathy of prematurity. The Cryotherapy for Retinopathy of Prematurity Cooperative Group. Ophthalmology. 1993 Feb;100(2):230-7.

PMID

8437832


Citation

The natural ocular outcome of premature birth and retinopathy. Status at 1 year. Cryotherapy for Retinopathy of Prematurity Cooperative Group. Arch Ophthalmol. 1994 Jul;112(7):903-12.

PMID

8031269


Citation

Dobson V, Quinn GE, Summers CG, Saunders RA, Phelps DL, Tung B, Palmer EA. Effect of acute-phase retinopathy of prematurity on grating acuity development in the very low birth weight infant. The Cryotherapy for Retinopathy of Prematurity Cooperative Group. Invest Ophthalmol Vis Sci. 1994 Dec;35(13):4236-44.

PMID

8002243


Citation

Dobson V, Quinn GE, Saunders RA, Spencer R, Davis BR, Risser J, Palmer EA. Grating visual acuity in eyes with retinal residua of retinopathy of prematurity. The Cryotherapy for Retinopathy of Prematurity Cooperative Group. Arch Ophthalmol. 1995 Sep;113(9):1172-7.

PMID

7661752


Citation

Dobson V, Quinn GE, Tung B, Palmer EA, Reynolds JD. Comparison of recognition and grating acuities in very-low-birth-weight children with and without retinal residua of retinopathy of prematurity. Cryotherapy for Retinopathy of Prematurity Cooperative Group. Invest Ophthalmol Vis Sci. 1995 Mar;36(3):692-702.

PMID

7890499


Citation

Kivlin JD, Biglan AW, Gordon RA, Dobson V, Hardy RA, Palmer EA, Tung B, Gilbert W, Spencer R, Cheng KP, Buckley E. Early retinal vessel development and iris vessel dilatation as factors in retinopathy of prematurity. Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) Cooperative Group. Arch Ophthalmol. 1996 Feb;114(2):150-4.

PMID

8573016


Citation

Quinn GE, Dobson V, Biglan A, Evans J, Plotsky D, Hardy RJ. Correlation of retinopathy of prematurity in fellow eyes in the cryotherapy for retinopathy of prematurity study. The Cryotherapy for Retinopathy of Prematurity Cooperative Group. Arch Ophthalmol. 1995 Apr;113(4):469-73.

PMID

7710397


Citation

Bartholomew PA; Chao J; Evans JL; Hammel AM; Trueb AL; Verness JL; Dobson V; Quinn GE; Acceptance/Use of the Teller acuity card procedure in the clinic., Am Orthoptic J 1996;46:100-106


Citation

Cryotherapy for Retinopathy of Prematurity Cooperative Group. Multicenter trial of cryotherapy for retinopathy of prematurity. Snellen visual acuity and structural outcome at 5 1/2 years after randomization. Arch Ophthalmol. 1996 Apr;114(4):417-24.

PMID

8602778


Citation

Dobson V, Quinn GE, Abramov I, Hardy RJ, Tung B, Siatkowski RM, Phelps DL. Color vision measured with pseudoisochromatic plates at five-and-a-half years in eyes of children from the CRYO-ROP study. Invest Ophthalmol Vis Sci. 1996 Nov;37(12):2467-74.

PMID

8933763


Citation

Gilbert WS, Quinn GE, Dobson V, Reynolds J, Hardy RJ, Palmer EA. Partial retinal detachment at 3 months after threshold retinopathy of prematurity. Long-term structural and functional outcome. Multicenter Trial of Cryotherapy for Retinopathy of Prematurity Cooperative Group. Arch Ophthalmol. 1996 Sep;114(9):1085-91.

PMID

8790093


Citation

Quinn GE, Dobson V, Barr CC, Davis BR, Palmer EA, Robertson J, Summers CG, Trese MT, Tung B. Visual acuity of eyes after vitrectomy for retinopathy of prematurity: follow-up at 5 1/2 years. The Cryotherapy for Retinopathy of Prematurity Cooperative Group. Ophthalmology. 1996 Apr;103(4):595-600.

PMID

8618758


Citation

Quinn GE, Dobson V, Hardy RJ, Tung B, Phelps DL, Palmer EA. Visual fields measured with double-arc perimetry in eyes with threshold retinopathy of prematurity from the cryotherapy for retinopathy of prematurity trial. The CRYO-Retinopathy of Prematurity Cooperative Group. Ophthalmology. 1996 Sep;103(9):1432-7.

PMID

8841302


Citation

Hardy RJ, Palmer EA, Schaffer DB, Phelps DL, Davis BR, Cooper CJ. Outcome-based management of retinopathy of prematurity. Multicenter Trial of Cryotherapy for Retinopathy of prematurity Cooperative Group. J AAPOS. 1997 Mar;1(1):46-54. Erratum in: J AAPOS 1997 Sep;1(3):137.

PMID

10530985


Citation

Saunders RA, Donahue ML, Christmann LM, Pakalnis AV, Tung B, Hardy RJ, Phelps DL. Racial variation in retinopathy of prematurity. The Cryotherapy for Retinopathy of Prematurity Cooperative Group. Arch Ophthalmol. 1997 May;115(5):604-8.

PMID

9152127


Citation

Multicenter trial of cryotherapy for retinopathy of prematurity. Preliminary results. Cryotherapy for Retinopathy of Prematurity Cooperative Group. Arch Ophthalmol. 1988 Apr;106(4):471-9.

PMID

2895630



Firstreceived Results Disposition Date

N/A

Study Design Info

Allocation

Randomized


Study First Submitted

September 23, 1999

Study First Submitted Qc

September 23, 1999

Study First Posted

September 24, 1999

Last Update Submitted

February 3, 2014

Last Update Submitted Qc

February 3, 2014

Last Update Posted

February 4, 2014


ClinicalTrials.gov processed this data on August 24, 2018

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These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.



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