Newly published research details a different approach to treating premature infants at risk for retinopathy of prematurity (ROP)鈥攖he leading cause of childhood vision loss and blindness.
In normally developing infants, blood vessels grow in the back of the eye to deliver oxygen and nutrition to the retina. ROP causes abnormal blood vessels to grow into the vitreous, a gel-like fluid between the retina and the front of the eye.
One way doctors can treat ROP is by injecting the eye with a drug that inhibits vascular endothelial growth factor (VEGF), a protein that signals cells to grow blood vessels. However, research from John A. Moran Eye Center surgeon-scientist Mary Elizabeth Hartnett, MD, has shown too much anti-VEGF can affect the structure of an infant鈥檚 developing retina or leak into the bloodstream where it can potentially harm developing organs. Using unique models of ROP, has determined a more targeted regulation of VEGF could strike a better balance to preserve vision.
on March 3, a study conducted at 10 U.S. hospitals between 2015 and 2019 aimed to find the safest low dose of the anti-VEGF drug bevacizumab. Doctors gave different doses of the drug to 83 infants with type 1 ROP and no previous treatment. They collected blood samples three days before initial injection and at two and four weeks after injection. The study determined bevacizumab doses as low as 0.002 mg reduced VEGF levels by half at two and four weeks after injection. However, no association was observed between the different doses administered into the eyes and the amount of VEGF that was reduced in the blood at two weeks or four weeks.
"While additional studies are needed to measure long-term effects of this drug, this is an important first step," said Hartnett, MD, lead author of the JAMA study. "The new studies will help us understand if the most effective low dose of bevacizumab has associated adverse effects on the retina, and we鈥檒l learn about its effects on the developing brain of the infant. The findings also raise the question if the major contribution of VEGF in the blood is from the eye, since ocular VEGF can leak into the blood stream. Once the VEGF in the eye is bound by bevacizumab, the amount that leaks into the blood stream and can be measured is reduced. We are still learning more about this, but other studies have found evidence supporting such a hypothesis."
If an effective dose of anti-VEGF leads to neural or retinal issues for the infant it would suggest a more targeted approach aligned with Hartnett鈥檚 research may be the future of treating ROP.
The study is "Plasma Levels of Bevacizumab and Vascular Endothelial Growth Factor After Low-Dose Bevacizumab Treatment for Retinopathy of Prematurity in Infants," authored by the Writing Committee for the Pediatric Eye Disease Investigator Group. It was funded by National Institute of Health R01 grants EY015130 and R01 EY017011 and by an Unrestricted Grant from Research to Prevent Blindness, New York, NY, to the Department of Ophthalmology & Visual Sciences, University of Utah.
About the John A. Moran Eye Center
The John A. Moran Eye Center at the University of Utah serves as the largest ophthalmology clinical care and research facility in the Mountain West, with more than 60 faculty members and 10 satellite clinics. Physicians provide comprehensive care in all ophthalmic subspecialties, making the Moran Eye Center a major referral center for complex cases with over 157,000 patient visits and about 9,000 surgeries annually. Moran supports 16 research laboratories and centers. Its Sharon Eccles Steele Center for Translational Medicine uses public-private partnerships to turn lab discoveries into therapies quickly. Moran CEO and Chair of Ophthalmology and Visual Sciences Randall J Olson, MD, leads more than 500 employees working to achieve the Moran Eye Center鈥檚 vision that no person with a blinding condition, eye disease, or visual impairment should be without hope, understanding, and treatment.