Young Investigator Award Honors Researcher Studying Improved Blindness Screening
CHOP Research investigator Gil Binenbaum, M.D., M.S.C.E., Division of Ophthalmology, was awarded the 2010 Young Investigator Faculty Award at the Eastern Society for Pediatric Research Meeting for his research on retinopathy of prematurity (ROP).
ROP is a disease that affects the developing blood vessels in the retinas of prematurely born infants. It is a leading cause of childhood blindness, yet it can be successfully treated with retinal laser surgery when an early diagnosis is made. Infants who are considered at risk for ROP must have a series of repeated eye exams, which are physically and emotionally taxing for patients and families and lead to a high cost of care. Current ROP screening, based upon birth weight and gestational age levels, detects severe disease but is not specific; less than 5 percent of infants meeting the screening criteria actually require laser surgery.
In collaboration with Graham Quinn, M.D., M.S.C.E., Division of Ophthalmology, Haresh Kirpalani, M.D., M.Sc., Division of Neonatology, and Gui-shuang Ying, Ph.D., a biostatistician at the University of Pennsylvania, Dr. Binenbaum is leading a multicenter effort to develop and validate a model to more accurately predict ROP risk by incorporating postnatal weight gain measurements into the existing clinical risk assessment method.
ROP develops in two phases, a preclinical phase and the clinically apparent phase that is currently diagnosed with eye exams. Both phases are related to changes in the growth hormone insulin-like growth factor 1 (IGF1). The level of IGF1 in an infant’s blood closely parallels the infant’s postnatal growth. IGF1 levels fall following premature birth and the longer it takes an infant to start producing sufficient IGF1, the greater the risk the infant will develop ROP. Measuring the growth that parallels rising IGF1 levels is a surrogate measure to detect ROP in the preclinical phase and may be used to predict which infants will need ROP treatment in the near future.
To develop a pilot model, the study team analyzed prospective data from the Premature Infants in Need of Transfusion Study, which enrolled infants weighing less than 1,000 grams at birth who were assessed for ROP status. Severe ROP was diagnosed in 67 of 367 patients (18 percent), and infants who gained weight more slowly than other infants had higher risk for severe ROP. Advancing work first done by Swedish researchers, Dr. Binenbaum and his colleagues used an algorithm that includes postnatal weekly weight gain to accurately predict risk of severe ROP in 66 of the 67 infants with severe ROP. The growth-based predictive model reduced the number of infants requiring eye exams by 30 percent in the high-risk group, while correctly identifying all infants requiring laser surgery.
“Growth-based screening guidelines have the potential to reduce the number of exams for infants who do not really need them, direct resources to the infants who really do, and identify infants who might benefit from preventive treatments currently being developed, such as affecting growth with IGF1 supplementation or nutritional changes,” says Dr. Binenbaum. While these preliminary results are very promising, Dr. Binenbaum cautions that further development and validation of the predictive model are required before a growth-based risk system can be used to change ROP screening guidelines. He and his colleagues have organized a collaborative study group of 20 centers across the United States and Canada to pursue these larger studies.