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"Up to now, there have been tight restrictions on the amount of oxygen low birthweight infants were permitted to have," said Carl Kupfer, MD, director of the National Eye Institute (NEI), which funded the study in collaboration with the National Institute of Child Health and Human Development (NICHD) and the National Institute of Nursing Research (NINR). "This is because doctors have been concerned about a possible adverse effect of supplemental oxygen on the eyes of infants with ROP. While the benefits and risks of supplemental oxygen must be individually considered for each infant, doctors need no longer worry that supplemental oxygen, as used in this study, will harm eyes with moderate ROP."
Many premature infants need supplemental oxygen soon after birth because their lungs are not sufficiently mature to efficiently transfer oxygen into their bodies. Doctors have long known that supplemental oxygen, while helping infants survive, might increase cases of ROP. They have also been concerned that it might allow the disease to progress from a moderate stage, when surgery is not needed, to a severe stage, which usually requires surgery and sometimes permanently damages sight. However, recent research had suggested that controlled amounts of supplemental oxygen might actually keep ROP from progressing from moderate to severe. If controlled amounts of supplemental oxygen could help prevent the progression of ROP, then infants could avoid this threat to their sight and consequently the invasive surgery for severe ROP, with its possible long-term side effects.
Retinopathy of prematurity develops when abnormal blood vessels grow and spread throughout the retina, the nerve tissue that lines the back of the eye. The scarring and bleeding caused by the excess growth of these blood vessels can lead to retinal detachment, resulting in vision loss. ROP develops in about 14,000-16,000 infants each year who weigh less than 2¾ pounds (1250 grams) at birth. In most cases (80 percent), the disease improves and leaves no permanent damage. However, about 1,100-1,500 infants annually develop ROP that is severe enough to require surgical treatment.
The most effective proven treatments for severe ROP are cryotherapy and laser therapy, which usually will stop the growth of abnormal blood vessels and prevent retinal detachment. The effectiveness of cryotherapy - a freezing treatment - was demonstrated several years ago through another NEI-sponsored clinical trial. However, even with these therapies, about 400-600 infants with ROP become legally blind each year. Cryotherapy and laser therapy are considered invasive surgeries on the eye, and doctors don't know their long-term side effects.
"Of the infants in the study with moderate ROP who received the supplemental oxygen, 41 percent progressed to severe ROP," said study chair Dale Phelps, MD, professor of Pediatrics and Ophthalmology at Children's Hospital at Strong at the University of Rochester School of Medicine and Dentistry. "Of the infants with moderate ROP who did not receive the supplemental oxygen, 48 percent progressed to severe ROP. Statistically, there is no difference.
"However, we found something we did not expect," Dr. Phelps said. "The infants in the study
fell into two groups - those whose moderate ROP was complicated with dilated eye blood
vessels, and those whose blood vessels were not dilated. Modest supplemental oxygen
significantly reduced the need for surgery in the second group. This finding needs to be
confirmed with additional research before we can recommend modest supplemental oxygen as
a treatment for infants with moderate ROP without dilated blood vessels."
Dr. Phelps said there were side effects in some infants who received the supplemental oxygen, including a temporary worsening of their chronic lung disease. "In addition, we examined the infants three months after their due dates, when they were no longer on the treatment," Dr. Phelps said. "We found, at the three-month exam, that the children who received the supplemental oxygen were more likely than those who did not receive the extra oxygen to be either in the hospital, on oxygen, and/or on medications for chronic lung disease. However, these side effects themselves are not life-threatening, and are acceptable risks for infants who require extra oxygen for cardiopulmonary reasons."
The clinical trial, called the Supplemental Therapeutic Oxygen for Prethreshold ROP (STOP-ROP) study, initially enrolled 649 infants; 597 completed the study. The clinical trial was conducted at 30 study centers involving 71 hospitals across the US.
Related photos are available in downloadable, camera-ready format on the NEI website at http://www.nei.nih.gov/photo/eye_exam/eye_exam.htm and at http://www.nei.nih.gov/photo/eyedis/index.htm, or by calling 301-496-5248.
The NEI, NICHD, and NINR are part of the National Institutes of Health, an agency of the U.S. Department of Health and Human Services.