The Early Treatment for Retinopathy of Prematurity Study (ETROP)
Retinopathy of Prematurity
Retinopathy of prematurity (ROP) is a potentially blinding eye disease that primarily affects premature infants weighing about 2.75 pounds (1250 grams) or less that are born before 31 weeks of gestation. (A full-term pregnancy has a gestation of 3842 weeks.) The smaller the baby at birth, the more likely that baby is to develop ROP, although not all babies who are premature develop ROP. This disease, which usually develops in both eyes, is one of the most common causes of visual loss in childhood and can lead to lifelong vision impairment and blindness.
Several complex factors may be responsible for the development of ROP. The eye starts to develop early in pregnancy, and the blood vessels of the retina begin to form at the optic nerve in the back of the eye. The blood vessels grow gradually toward the edges of the developing retina, supplying oxygen and nutrients. During the last 12 weeks of a pregnancy, the eye develops rapidly. When a baby is born full-term, the retinal blood vessel growth is mostly complete. But if a baby is born prematurely, before these blood vessels have reached the edges of the retina, normal vessel growth may stop. The edges of the retina, called the periphery, may not get enough oxygen and nutrients.
Scientists believe that the periphery of the retina then sends out signals to other areas of the retina for nourishment. As a result, new abnormal vessels begin to grow and spread throughout the retina. The new blood vessels are fragile and weak and can bleed, leading to retinal scarring. When these scars shrink, they can pull the retina out of position and cause it to detach from the back of the eye. Retinal detachment is the main cause of visual impairment and blindness in ROP.
Previous ROP Research
ROP first became prevalent in the 1940s and 1950s with the introduction of oxygen-rich incubators for premature infants. During this time, ROP was the leading cause of blindness in children in the US. In 1954, scientists funded by the NIH determined that the high levels of oxygen routinely given to premature infants at that time were an important risk factor, and that reducing oxygen levels decreased the incidence of ROP. With newer technology and methods to monitor the oxygen levels of infants, oxygen use as a risk factor for ROP has diminished in importance.
In the 1970s, advances in neonatal care enabled the survival of smaller and very low birthweight babies, and ROP reemerged as an important public health problem. In 1988, scientists funded by the NEI discovered that briefly freezing a portion of the surface of the eye can protect many premature infants against blindness from ROP. This procedure, called cryotherapy, stops the growth of abnormal blood vessels.
In the last five years, continuing advances in neonatal care allow smaller and more premature infants to survive. These infants are at a much higher risk for ROP. In 1998, NEI-supported researchers determined that lighting levels in hospital nurseries has no effect on the development of ROP. In 2000, NEI-funded researchers discovered that modest supplemental oxygen given to premature infants with moderate cases of ROP may not significantly improve ROP but definitely does not make it worse, which had been a concern in the medical community.
Early Treatment for Retinopathy of Prematurity Study
Despite advances in our understanding of ROP, retinal detachments and visual impairment continue to be one of the major disabilities occurring in premature infants. Those involved with the care of premature infants with ROP have sought more effective ways to treat the disease.
Prior to publication of this study, ROP treatment was administered to infants when the severity of the disease indicates that a retinal detachment was 50 percent likely. This degree of severity is called the "threshold" for treatment of the disease. However, over the past several years, some doctors believed early treatment would be more beneficial. The Early Treatment for Retinopathy of Prematurity (ETROP) study was designed to find out if early treatment of premature infants might improve both their vision and the health of the treated eye. This multicenter clinical trial was supported by the NEI.
Infants who received the early treatment were slightly more likely to experience certain complications, such as breathing difficulties and slower heart rate, because they were younger and more fragile. However, none of these side effects were permanent for infants who received treatment at the standard time or early treatment. Also, because timely identification of high-risk eyes with ROP is important to the success of an early treatment program, neonatal nurseries may need to increase the number of examinations in their screening programs to identify eyes that need treatment.