Published June 1, 2017
JAMA Ophthalmology

Intravitreous bevacizumab has become an increasingly common way to treat retinopathy of prematurity (ROP) in infants, but systemic toxicity remains one of its potentially dangerous side effects.

However, a new Phase 1 study suggests that significantly lower doses can be equally effective while minimizing risk of toxicity. Researchers say future studies could investigate reducing risks for neurodevelopmental disability and other potential organ dam-age.

The paper involved scientists from 14 institutions across the U.S., including Michael Yang, MD, of the Division of Ophthalmology at Cincinnati Children’s.

Bevacizumab is injected into the eye and works by slowing the growth of new blood vessels. In ROP patients, the abnormal vessel growth can lead to retinal fluid leak, potentially causing blindness by causing the retina to detach from the back of the eye.

The standard dose is 0.625 milligrams. Between May 2015 and September 2016, 61 premature infants with type 1 ROP in one or both eyes were enrolled in the study. Researchers initially reduced treatment to 0.25 mg, then to 0.125 mg, 0.063 mg, and finally 0.031 mg in the study eye, while the fellow or contralateral eye, if affected, received the next higher dose.

“There was some expectation that a reduction to 40 percent of the standard dose would be effective,” Yang says. “Finding that 5 percent of the standard was still effective, and that we could potentially go lower, was a pleasant surprise.”

The team has received permission to extend the study to establish the lowest effective dose. Multi-institutional collaboration is crucial, Yang says, because the number of patients treated at any one center is statistically small.

“Without multi-center involvement,” he says, “it was probably difficult for treating physicians to take the risk of even decreasing the dose to the first lower level of 0.25 mg.”