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Author Notes:

Corresponding author: David K. Wallace, MD, MPH, c/o Jaeb Center for Health Research, 15310 Amberly Drive, Suite 350, Tampa, FL 33647; Phone: (813) 975-8690, Fax: (813) 975-8761, david.wallace@duke.edu

Mr Kraker and Mr Dean had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Wallace, Kraker, Crouch, Hutchinson, Rogers, VanderVeen, Siatkowski, Beck, Repka, Smith, Good, Kong, Holmes.

Acquisition, analysis, or interpretation of data: Wallace, Kraker, Freedman, Crouch, Hutchinson, Bhatt, Rogers, Yang, Haider, VanderVeen, Siatkowski, Dean, Repka, Hartnett, Kong, Holmes. Drafting of the manuscript: Wallace, Kraker, Crouch, Rogers, VanderVeen, Siatkowski.

Critical revision of the manuscript for important intellectual content: Wallace, Kraker, Freedman, Crouch, Hutchinson, Bhatt, Rogers, Yang, Haider, VanderVeen, Siatkowski, Dean, Beck, Repka, Smith, Good, Hartnett, Kong, Holmes.

Statistical analysis: Kraker, Dean, Kong. Obtained funding: Wallace, Kraker, Holmes. Administrative, technical, or material support: Kraker, Crouch, Bhatt, Rogers, Yang, VanderVeen, Beck, Repka, Good, Holmes, Kong.

Study supervision: Kraker, Crouch, Hutchinson, Rogers, Yang, VanderVeen, Siatkowski, Repka.

The funding organization had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.

Dr Freedman has served as a scientific advisor for Pfizer.

No other disclosures were reported.

Subjects:

Research Funding:

This study was supported by grants EY011751, EY023198, and EY018810 from the National Eye Institute, National Institutes of Health, Department of Health and Human Services.

Dr Wallace has received grants from the National Eye Institute and other compensation from FocusROP.

Mr Kraker has received grants from the National Institutes of Health.

Dr Yang has received grants from the Jaeb Center for Health Research and National Eye Institute, National Institutes of Health.

Drs Rogers, Haider, VanderVeen, Repka, and Kong and Mr Dean have received grants from the National Eye Institute, National Institutes of Health.

Dr Hartnett has received a grant from the National Eye Institute and consulting fees from San Bio.

Dr Holmes has received grants from the National Institutes of Health.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Ophthalmology

Assessment of Lower Doses of Intravitreous Bevacizumab for Retinopathy of Prematurity A Phase 1 Dosing Study

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Journal Title:

JAMA Ophthalmology

Volume:

Volume 135, Number 6

Publisher:

, Pages 654-656

Type of Work:

Article | Post-print: After Peer Review

Abstract:

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 achievedin 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 aslow as 0.031 mgwas effectivein 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.

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© 2017 American Medical Association. All rights reserved.

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