New research from an NIH-funded study suggest 0.004 mg bevacizumab could be an effective treatment for type 1 retinopathy of prematurity.
David Wallace, MD, MPH
A new National Institutes of Health-funded study has uncovered a low-dose version of a common anti-VEGF injection could help prevent blindness in preterm infants.
A trial involving 59 infants found intravitreous injections of 0.004 mg bevacizumab (Avastin) could be an effective treatment for type 1 retinopathy of prematurity (ROP), which clinicians are hopeful might cause less systemic toxicity than the more commonly used 0.25-0.625 mg doses.
"As a faster and easier treatment option, anti-VEGF eye injections were a welcomed alternative to laser therapy for treating severe ROP," said the study protocol chair David Wallace, MD, MPH, chair of ophthalmology at the Indiana University School of Medicine, in a statement. “But we know that anti-VEGF agents injected into the eye also get into the bloodstream, and doctors worry that inhibiting VEGF systemically could interfere with normal development of brain, lung, bone, and kidney tissues.”
In an effort to determine the lowest effective dose of intravitreous bevacizumab for infants with severe ROP, members of the Pediatric Eye Disease Investigator Group designed the current study as a masked phase 1 de-escalation study in preterm infants. Of note, investigators had previously conducted a trial that determined bevacizumab injections were effective with improvement in retinopathy in infants.
In total, investigators enrolled 59 infants in the 4-week study and patients were categorized into 4 groups defined by dose received. Patients were administered doses at either 0.016 mg, 0.008 mg, 0.004 mg, and 0.002 mg, each in 10 μL after dilution with normal saline. Injections to study eye was performed using a 300-μL syringe with a 5/16-inch, 30-gauge fixed needle.
Post-injection follow-up exams were performed at day 1 and weekly for 4 weeks—investigators note examinations were performed between days 3-5 if not at day 1.
For the purpose of the study, successful treatment was defined as an improvement by 4 days and no recurrence of type 1 ROP or severe neovascularization requiring additional treatment within 4 weeks. Investigators planned for each dose to be used in up to 14 infants to ensure at least 10 had data related to 4-week outcomes upon the study’s conclusion.
Of the 59 infants enrolled in the study, 55 had 4-week outcomes. The mean birthweight of this group was 664 (258) grams and the mean gestational age was 24.8 weeks (1.6).
Results of the study indicated a successful 4-week outcome was achieved in 13 of 13 eyes receiving 0.016 mg, 9 of 9 eyes receiving 0.008 mg, 9 of 10 eyes receiving 0.004 mg, and just 17 of 23 eyes receiving 0.002 mg bevacizumab.
"In the current study, we found that 0.004 mg of Avastin—a dose that's merely 0.6% of the dose used in the 2011 study of Avastin for ROP—may be the lower limit to be effective for most infants with ROP," Wallace said.
The aforementioned release notes investigators plan to follow study participants to compare long-term impact of the strategies examined in this study and how they impact vision and organ development.
This study, “Short-term Outcomes After Very Low-Dose Intravitreous Bevacizumab for Retinopathy of Prematurity,” was published in JAMA Ophthalmology.