Effect on fellow eye
After recognizing fellow eye effects when first exploring the use of bevacizumab for proliferative diabetic retinopathy (PDR), Dr. Avery reasoned that if these observed effects were real, the dose of bevacizumab being administered was much higher than that needed to produce a change in retinal neovascularization in the treated eye. Therefore, he sequentially used lower doses of bevacizumab in PDR and found that 6.25 mcg (1/200th the usual clinical dose) could cause an effect on retinal neovascularization of PDR.
“Injection of 6.25 mcg into the vitreous corresponds to an intravitreal concentration of about 1 mcg/mL,” Dr. Avery said. “That is also the maximum concentration that Kong et al found circulating in the blood in their study. Therefore, it is no surprise to see fellow eye effects in babies treated for ROP.
“Assuming that bevacizumab is circulating at physiologically active levels might also explain why it seems to have a longer duration of effect than ranibizumab when used to treat ROP,” he added.
Dr. Avery explained that although both anti-VEGF agents have a similar intravitreal half-life of roughly 1 week, bevacizumab persists in the bloodstream with a half-life of 3 weeks whereas ranibizumab is rapidly cleared with a 2-hour serum half-life.
“It would seem unusual for the persistently higher concentration of bevacizumab in the blood to be responsible for the longer duration of efficacy in the treated eye,” Dr. Avery pointed out. “However, in an animal model of VEGF-induced exudative retinal detachment, Miki et al found that bevacizumab had a greater effect on the fellow eye than direct injection of ranibizumab. The only way to explain that result would be if circulating bevacizumab was affecting the fellow eye.”
In a similar fashion, he proposed that it is conceivable that circulating bevacizumab could contribute to controlling ROP neovascularization once intravitreal levels have decreased significantly.