Importance: 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. Objective: 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. Interventions: 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. Results: 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.
Importance: 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. Objective: 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. Interventions: 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. Results: 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.
Authors: Julie Morin; Thuy Mai Luu; Rosanne Superstein; Luis H Ospina; Francine Lefebvre; Marie-Noëlle Simard; Vibhuti Shah; Prakesh S Shah; Edmond N Kelly Journal: Pediatrics Date: 2016-03-17 Impact factor: 7.124
Authors: Megan M Geloneck; Alice Z Chuang; W Lloyd Clark; Michael G Hunt; Alan A Norman; Eric A Packwood; Khaled A Tawansy; Helen A Mintz-Hittner Journal: JAMA Ophthalmol Date: 2014-11 Impact factor: 7.389
Authors: David K Wallace; Trevano W Dean; Mary Elizabeth Hartnett; Lingkun Kong; Lois E Smith; G Baker Hubbard; Mary Lou McGregor; Catherine O Jordan; Iason S Mantagos; Edward F Bell; Raymond T Kraker Journal: Ophthalmology Date: 2018-06-07 Impact factor: 12.079
Authors: Andreas Stahl; Tim U Krohne; Nicole Eter; Isabel Oberacher-Velten; Rainer Guthoff; Synke Meltendorf; Oliver Ehrt; Sabine Aisenbrey; Johann Roider; Heinrich Gerding; Claudia Jandeck; Lois E H Smith; Johanna M Walz Journal: JAMA Pediatr Date: 2018-03-01 Impact factor: 16.193
Authors: Dana Darwish; Ru-Ik Chee; Samir N Patel; Karyn Jonas; Susan Ostmo; J Peter Campbell; Michael F Chiang; R V Paul Chan Journal: Asia Pac J Ophthalmol (Phila) Date: 2018-05-29
Authors: Eric R Crouch; Raymond T Kraker; David K Wallace; Jonathan M Holmes; Michael X Repka; Janine E Collinge; Don L Bremer; Michael E Gray; Heather A Smith; Paul G Steinkuller Journal: JAMA Ophthalmol Date: 2020-01-01 Impact factor: 7.389
Authors: Lois E H Smith; Ann Hellström; Andreas Stahl; Alistair Fielder; Wiley Chambers; Jane Moseley; Cynthia Toth; David Wallace; Brian A Darlow; Jacob V Aranda; Boubou Hallberg; Jonathan M Davis Journal: JAMA Ophthalmol Date: 2019-03-01 Impact factor: 7.389