Retinopathy of Prematurity: An Important Cause of Blindness in Children - October 2004
Retinopathy of prematurity (ROP) remains a leading cause of bilateral vision impairment in low birthweight children. In this issue of Pediatric Page, we describe the disorder, its causes and treatment. Doctors at California Pacific Medical Center have been at the forefront of ROP research. Some recent findings will lead to a reduction in blindness from this condition, not only locally, but also worldwide.
History
First described in the 1940s, ROP was originally termed “retrolental fibroplasia.” Literally, the first cases of this disease became apparent when a white pupil was noticed in infants. Scarring of the retina and detachment—both visible as whitening and scarring behind the lens—cause this white pupil. Roughly simultaneous to this discovery, pediatricians learned that oxygen supplementation improved survival rates in premature infants. No wonder, then, that a link between oxygen supplementation and ROP was suspected and proven in a randomized trial in 1954. But results of this trial failed to take into consideration the additional morbidity and even mortality imposed on premature infants as a consequence of oxygen restriction. Subsequent trials conducted with transcutaneous oxygen saturation monitoring, which was not available in the 1950s, have failed to show any alterable significant effect of oxygen on the disease.
Risk Factors
Instead, what has become apparent in the past 20 years is that extreme prematurity is the most significant risk factor for developing ROP. The lowest birthweight infants are the ones most likely to develop the condition. Approximately 60% of infants with birthweights less than 1251 grams develop ROP, and the risk for acquiring the disease increases with declining birthweight. Nearly 10% of infants less than 1251 grams at birth require treatment in the form of peripheral retinal ablation, with 75% of those treated cured. However, the “cured” 75% frequently need glasses or amblyopia management, and there is a lifelong risk of later retinal detachment.
Screening
ROP usually develops after 5-6 weeks of age, and thus screening programs are commenced when infants are 4-6 weeks old. Ophthalmologists will follow infants until it is clear that there is no risk to the infant’s vision from the disease, or until the disease requires treatment. Screening exams are performed at least every other week and sometimes more often in high-risk situations. When children are discharged from the hospital, it is imperative that frequent and diligent screening continues until the ophthalmologist signs off on the patient. Some infants will require screening until 45 weeks gestational age. If the opportunity to treat a child is missed, there is no turning back. The consequences may be devastating.
New Research Advocates Earlier Treatment
Even with timely detection of treatable ROP, 25% of infants with advanced disease are blinded by it. A group of doctors at California Pacific Medical Center organized a National Institutes of Health, National Eye Institute-funded project to study risk factors for ROP and whether earlier treatment would reduce the rate of blindness. The study was called the Early Treatment for Retinopathy of Prematurity Study (ETROP). Study results were published in the Archives of Ophthalmology, December 2003 and showed that earlier treatment—when the disease is severe, but not as severe as was the current standard for treatment—further reduces the incidence of blindness. Now, with treatment at high-risk, so-called pre-threshold disease, the risk of blindness is less than 10%. Not every child with ROP requires treatment, and the ETROP Study showed that a computer-based risk model could be used successfully to identify those infants who should be treated and those who can be observed without treatment.
ROP is fundamentally a disease of retinal blood vessel development and growth. An arrest in development of retinal vessels, triggered by extreme prematurity, sets off a cascade of molecular events which can culminate in ROP leading to scarring and retinal detachment. Doctors at California Pacific have also been involved in studies of blood vessel biology and have discovered a novel protein which plays an important role in modifying angiogenesis in this disease. Results of these studies will be published in Investigative Ophthalmology and Visual Sciences in October 2004. These advances in the basic science of ROP will lead to medical models to treat the disease, instead of the retinal ablation required currently.
The Department of Pediatrics at California Pacific Medical Center offers state-of-the-art clinical care for premature infants and has pioneered research in ROP. With continued effort, we hope that ROP will fade as an important cause of blindness in children and that findings from these studies will have ramifications for managing other pediatric low-vision conditions.