SAN FRANCISCO — Retinopathy of prematurity appears to respond equally well to either aflibercept injection or laser photocoagulation when treated infants reach age 2, according to results of a European study of 100 children with the disease.
The FIREFLEYE Next trial treated 66 children with 0.4 mg 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 the treatment of vascular growth in retinopathy of prematurity (ROP). , a retinal disease in premature infants caused by abnormal growth of blood vessels 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,” said Andreas Stahl, MD, director of the ophthalmology clinic at Greifswald University Medicine in Germany. Medscape Medical News. “If you laser an infant, you laser the eye and expect it to have no effect on the child’s overall development; maybe the anesthesia has a systemic effect, but laser therapy shouldn’t.”
Stahl presented the findings on the study subjects at age 2 at the 2023 annual scientific meeting of the American Academy of Ophthalmology.
In premature infants, the retinal vasculature is not mature and the blood vessels cover only a limited area of the retina. ROP develops when these vessels fail to grow in the affected area of the retina. About 14,000 premature infants in the United States develop ROP, with up to 1,500 of them progressing to a moderate or severe stage that requires treatment, according to 2017 article.
The goal of either anti-VEGF or laser therapy is to remove the excess VEGF that drives the abnormal blood vessel growth that can cause vision-threatening retinal detachment.
Laser photocoagulation, the established treatment since the 1990s, essentially creates a cycle of scarring with a laser to isolate the abnormal growth of the vessel and allow normal growth out of the area.
“The laser can scar the retina in the periphery; it saves the central aspect of the retina, but you lose the periphery,” Stahl said. “With anti-VEGF therapy you can remove excess vascular endothelial growth factor, but still allow normal vasculature to continue in the periphery.”
The challenge with treatment with a drug like aflibercept is that it can enter the circulation, he said. One injection is usually enough, although some patients may need re-treatment and these patients should be monitored continuously for reactivation of their ROP.
Test results
Children in FIREFLEYE Next were treated at an average age of 9 months. At 2 years of age, 97% of children who received aflibercept and 94% of those who received laser therapy were free of ROP. In the aflibercept arm, 6% (n = 4) were treated for ROP at interim, two for end-stage disease, and two for reactivated bilateral disease. Two children in each arm were unable to fixate and follow a 5 cm toy, which is used to assess vision in non-verbal children.
“We found no differences in growth – body weight, height, head circumference,” Stahl added. “Also, we did not find delayed reactivations beyond the first year that resulted in new retinal detachments. There were some retinal detachments (RDs) in the early post-treatment phase, but it was reassuring that we found no new detachments in the second year of the trial.”
The next phase for FIREFLEYE The next trial is to evaluate children treated at age 5, he said.
Pros and cons of Anti-VEGF
Dr. John Campbell
John P. Campbell, MD, MPH, a pediatric retina specialist at the Casey Eye Institute of Oregon Health & Science University in Portland, called the new results “reassuring,” though they cannot be generalized to other drug treatments for ROP. “Although we’ve been using anti-VEGF for ROP for almost 10 years regularly, we don’t have systematic long-term studies to understand the risk of delayed reactivation and detachment,” he told Medscape.
He recognized the potential benefits of aflibercept over laser — the drug is easier to administer and requires less anesthesia — but also its drawbacks.
“There are remaining questions about long-term visual outcomes that we hope larger studies will help answer,” Campbell said. “There are also legitimate questions about the relative risks of systemic adverse events among anti-VEGF agents, to which we do not yet know the answers.”
It also emphasized the need for long-term follow-up in ROP treated with anti-VEGF. “We don’t know the long-term risk of persistent nonvascular retinitis in this population, but it is an area of active discussion that parents should be involved in as we consider the risks and benefits of repeat exams versus a second laser treatment.” 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.
