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

被引：96

作者：

Wallace, David K. ^{[2
]}

Kraker, Raymond T. ^{[1
]}

Freedman, Sharon F. ^{[2
]}

Crouch, Eric R. ^{[3
]}

Hutchinson, Amy K. ^{[4
]}

Bhatt, Amit R. ^{[5
]}

Rogers, David L. ^{[6
]}

Yang, Michael B. ^{[7
]}

Haider, Kathryn M. ^{[8
]}

VanderVeen, Deborah K. ^{[9
]}

Siatkowski, Michael ^{[10
]}

Dean, Trevano W. ^{[1
]}

Beck, Roy W. ^{[1
]}

Repka, Michael X. ^{[11
]}

Smith, Lois E. ^{[9
]}

Good, William V. ^{[12
]}

Hartnett, Mary Elizabeth ^{[13
]}

Kong, Lingkun ^{[14
]}

Holmes, Jonathan M. ^{[15
]}

机构：

[1] Jaeb Ctr Hlth Res, 15310 Amberly Dr,Ste 350, Tampa, FL 33647 USA

[2] Duke Eye Ctr, Durham, NC USA

[3] Eastern Virginia Med Sch, Norfolk, VA 23501 USA

[4] Emory Univ, Sch Med, Atlanta, GA USA

[5] Texas Childrens Hosp, Houston, TX 77030 USA

[6] Pediat Ophthalmol Associates Inc, Columbus, OH USA

[7] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA

[8] Riley Hosp Children, Indianapolis, IN USA

[9] Boston Childrens Hosp, Boston, MA USA

[10] Univ Oklahoma, Dean McGee Eye Inst, Oklahoma City, OK USA

[11] Wilmer Eye Inst, Baltimore, MD 21287 USA

[12] Smith Kettlewell Eye Res Inst, 2232 Webster St, San Francisco, CA 94115 USA

[13] John A Moran Eye Ctr, Salt Lake City, UT USA

[14] Baylor Coll Med, Houston, TX 77030 USA

[15] Mayo Clin, Rochester, MN USA

来源：

JAMA OPHTHALMOLOGY | 2017年 / 135卷 / 06期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1001/jamaophthalmol.2017.1055

中图分类号：

R77 [眼科学];

学科分类号：

100212 ;

摘要：

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 mu L 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.

引用

页码：654 / 656

页数：3

共 6 条

[1] Refractive Outcomes Following Bevacizumab Monotherapy Compared With Conventional Laser Treatment A Randomized Clinical Trial [J].