Could a lower dose of intravitreous bevacizumab effectively treat severe retinopathy of prematurity?
In this masked phase 1 dose de-escalation study, premature infants with type 1 retinopathy of prematurity were treated with bevacizumab. Success, defined as improvement by 5 days and no recurrence requiring additional treatment within 4 weeks, was achieved in 11 of 11 eyes at 0.25 mg, 14 of 14 eyes at 0.125 mg, 21 of 24 eyes at 0.063 mg, and 9 of 9 eyes at 0.031 mg of bevacizumab.
A dose of bevacizumab as low as 0.031 mg was effective in this study, and further investigation is needed to determine the optimal dose and assess effectiveness and systemic safety.
Intravitreous bevacizumab (0.25 to 0.625 mg) is increasingly used to treat type 1 retinopathy of prematurity (ROP), but there remain concerns about systemic toxicity. A much lower dose may be effective while reducing systemic risk.
To find a dose of intravitreous bevacizumab that was lower than previously used for severe ROP, was effective in this study, and could be tested in future larger studies.
Design, Setting, and Participants
Between May 2015 and September 2016, 61 premature infants with type 1 ROP in 1 or both eyes were enrolled in a masked, multicenter, phase 1 dose de-escalation study. One eye of 10 to 14 infants received 0.25 mg of intravitreous bevacizumab. If successful, the dose was reduced for the next group of infants (to 0.125 mg, then 0.063 mg, and finally 0.031 mg). Diluted bevacizumab was delivered using 300 µL syringes with 5/16-inch, 30-gauge fixed needles.
Bevacizumab injections at 0.25 mg, 0.125 mg, 0.063 mg, and 0.031 mg.
Main Outcomes and Measures
Success was defined as improvement in preinjection plus disease or zone I stage 3 ROP by 5 days after injection or sooner, and no recurrence of type 1 ROP or severe neovascularization requiring additional treatment within 4 weeks.
Fifty-eight of 61 enrolled infants had 4-week outcomes completed; mean birth weight was 709 g and mean gestational age was 24.9 weeks. Success was achieved in 11 of 11 eyes at 0.25 mg, 14 of 14 eyes at 0.125 mg, 21 of 24 eyes at 0.063 mg, and 9 of 9 eyes at 0.031 mg.
Conclusions and Relevance
A dose of bevacizumab as low as 0.031 mg was effective in 9 of 9 eyes in this phase 1 study and warrants further investigation. Identifying a lower effective dose of bevacizumab may reduce the risk for neurodevelopmental disability or detrimental effects on other organs.
Wallace DK, Kraker RT, Freedman SF, et al. Assessment of Lower Doses of Intravitreous Bevacizumab for Retinopathy of Prematurity: A Phase 1 Dosing Study . JAMA Ophthalmol. 2017;135(6):654–656. doi:10.1001/jamaophthalmol.2017.1055
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