Lower bevacizumab doses, agents with less systemic exposure may be safer options for ROP
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WAIKOLOA, Hawaii — Systemic effects of anti-VEGF in retinopathy of prematurity have not been ruled out, so it may be wise to use bevacizumab in lower doses or switch to agents with less systemic exposure, according to one presenter.
“The BEAT-ROP study demonstrated a beneficial effect for bevacizumab vs. laser in the treatment of zone I, stage 3+ ROP. But one thing I didn’t like was the complete absence of concern about systemic effects,” Robert L. Avery, MD, said at Retina 2022.
Because VEGF plays an important role in neurogenesis and organogenesis in preterm newborns, there is justified concern that VEGF inhibition may have long-term effects on the development of a myriad of different organs, including the brain, lungs, kidneys and bones. Multiple studies in the pediatric literature have investigated the side effects of anti-VEGF in ROP, and some have found an increased risk for severe neurodevelopmental delay and death. However, insufficient data preclude strong conclusions, and at this stage, the jury is still out, Avery said.
Of the anti-VEGF agents, bevacizumab is the most frequently used in ROP but is also the one with a higher penetration and persistence in the bloodstream. While the half-life of ranibizumab is about 2 hours, bevacizumab has an elimination half-life of 3 weeks, and clearance from the bloodstream in premature infants takes at least 2 months, Avery said.
“The risk is out there, and until we know better, there may be reasons to mitigate that risk,” he said.
He focused on two ways to lower systemic exposure: by dose or drug choice.
In a phase 1 dosing study, the Pediatric Eye Disease Investigator Group evaluated the possibility of achieving comparable efficacy in severe ROP using lower doses of bevacizumab and were able to show that a dose as low as 31 µg was effective in nine of nine eyes.
“Identifying a lower effective dose of bevacizumab may reduce the risk for neurodevelopmental disability or detrimental effects on other organs,” Avery said.
Ranibizumab, which flushes through the bloodstream with less effect on serum VEGF levels, might be another option. Larger studies, especially prospective ones, may help answer this safety question, he said.
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Avery RL. What’s the right dose of anti-VEGF for pediatric patients? Presented at: Retina 2022; Jan. 15-21, 2022; Waikoloa, Hawaii.
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