At 2 Years, Anti-VEGF Treatment, Laser Equal for ROP: Study

SAN FRANCISCO — Retinopathy of prematurity seems to respond equally to either an injection with aflibercept or laser photocoagulation when infants who were treated reached age 2 years, according to results from a European study of 100 children with the disease.

The FIREFLEYE Next trial treated 66 children with 0.4 mg of intravitreal aflibercept  and 34 with laser photocoagulation. Aflibercept (Eylea), an anti-vascular endothelial growth factor (VEGF), is commonly used to treat age-related macular degeneration or diabetic macular edema, but is also indicated for treatment of vascular growth in retinopathy of prematurity (ROP), a retinal disease in premature infants that’s caused by abnormal blood vessel growth in the back of the eye that can lead to blindness.

Dr Andreas Stahl

“The most important findings are comparable neurodevelopmental outcomes in the laser and anti-VEGF treatment arm,” Andreas Stahl, MD, ophthalmology clinic director at Greifswald University Medicine in Germany, told Medscape Medical News. “If you laser an infant, you laser the eye, and you expect not to have any impact on the overall development of the child; maybe the anesthesia might have a systemic effect but laser treatment shouldn’t.”

Stahl presented the findings in the study subjects at age 2 years at the 2023 annual scientific meeting of the American Academy of Ophthalmology.

In premature infants, the retinal vasculature is not mature and blood vessels cover only a limited area of the retina. ROP develops when those vessels fail to grow into the affected area of the retina. About 14,000 premature infants in the United States develop ROP, with up to 1500 of them progressing to a moderate or severe stage that requires treatment, according to a 2017 article.

The goal of either anti-VEGF or laser treatment is to remove the excessive VEGF that drives the pathologic blood vessel growth that can cause sight-threatening retinal detachment.

Laser photocoagulation, the standard treatment since the 1990s, essentially creates a circle of laser scarred to sequester the pathologic vessel growth and allow normal development outside the area.

“Lasering can cause scarring of retina in the periphery; it saves the central view of the retina, but you lose the periphery,” Stahl said. “With anti-VEGF treatment you can remove the excessive vascular endothelial growth factor but still allow normal vascularization to continue into the periphery.”

The challenge of treatment with a drug such as aflibercept is that it can enter in the circulation, he said. One injection typically is sufficient, although some patients may need retreatment, and these patients have to be monitored continuously for reactivation of their ROP.

Trial Results

Children in FIREFLEYE Next were treated at an average age of 9 months. At age 2 years, 97% of the children who received aflibercept and 94% of those treated with lasers had no ROP. In the aflibercept arm, 6% (n = 4) received treatment for ROP in the interim, two for end-stage disease and two for reactivated bilateral disease. Two children in each arm were not able to fixate on and follow a 5-cm toy, which is used to evaluate vision in nonverbal children.

“We found no differences in growth — body weight, height, head circumference,” Stahl added. “We also did not find any late reactivations beyond year one that led to new retinal detachments. There had been some retinal detachments (RDs) in the early posttreatment phase, but it was reassuring that we didn’t find any new detachments coming on in the second year of the trial.”

The next phase for the FIREFLEYE Next trial is to evaluate the treated children at age 5 years, he said.

Benefits and Drawbacks of Anti-VEGF

Dr John Campbell

John P. Campbell, MD, MPH, a pediatric retina specialist at Casey Eye Institute of Oregon Health & Science University in Portland, called the new results “reassuring,” although they are not generalizable to other drug treatments for ROP. “Although we have been using anti-VEGF for ROP for nearly 10 years routinely, we lack systematic long-term studies to understand the risk of late reactivation and detachment,” he told Medscape.

He acknowledged the potential benefits of aflibercept vs laser — the drug is easier to administer and needs less anesthesia — but also its drawbacks.

“There are remaining questions regarding long-term visual outcomes that hopefully larger studies will help answer,” Campbell said. “There are also legitimate questions being asked about the relative risks of systemic adverse events between the anti-VEGF agents that we do not yet know the answers to.”

He also emphasized the need for long-term follow-up in anti-VEGF–treated ROP. “We do not know the long-term risk of persistent avascular retina in this population, but it is an area of active discussion that parents should be part of as we consider the risks and benefits of repeated exams vs a second treatment with laser,” he said.

Stahl disclosed relationships with Allergan/AbbVie, Apellis Pharmaceuticals, Bayer, Hoffman La Roche, and Novartis. Campbell disclosed relationships with Boston AI Labs, Genentech/Roche and Siloam Vision.

Richard Mark Kirkner is a medical journalist based in the Philadelphia area.

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