Wallace David K, Kraker Raymond T, Freedman Sharon F, Crouch Eric R, Hutchinson Amy K, Bhatt Amit R, Rogers David L, Yang Michael B, Haider Kathryn M, VanderVeen Deborah K, Siatkowski R Michael, Dean Trevano W, Beck Roy W, Repka Michael X, Smith Lois E, Good William V, Hartnett Mary Elizabeth, Kong Lingkun, Holmes Jonathan M
Duke Eye Center, Durham, North Carolina.
Jaeb Center for Health Research, Tampa, Florida.
JAMA Ophthalmol. 2017 Jun 1;135(6):654-656. doi: 10.1001/jamaophthalmol.2017.1055.
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.
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.
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.
玻璃体内注射贝伐单抗（0.25至0.625毫克）越来越多地用于治疗1型早产儿视网膜病变（ROP），但人们仍担心其全身毒性。更低的剂量可能有效，同时降低全身风险。
找到一种低于先前用于治疗严重ROP的剂量的玻璃体内贝伐单抗，在本研究中有效，并可在未来更大规模的研究中进行测试。
设计、地点和参与者：2015年5月至2016年9月期间，61名单眼或双眼患有1型ROP的早产儿参加了一项双盲、多中心、1期剂量递减研究。10至14名婴儿的一只眼睛接受了0.25毫克的玻璃体内贝伐单抗注射。如果成功，下一组婴儿的剂量将降低（降至0.125毫克，然后是0.063毫克，最后是0.031毫克）。使用配有5/16英寸、30号固定针头的300微升注射器注射稀释后的贝伐单抗。
分别注射0.25毫克、0.125毫克、0.063毫克和0.031毫克的贝伐单抗。
成功定义为注射后5天或更早时，注射前疾病或I区3期ROP有所改善，且4周内1型ROP无复发或无需额外治疗的严重新生血管形成。
61名登记婴儿中有58名完成了4周的随访；平均出生体重为709克，平均胎龄为24.9周。0.25毫克组的11只眼中有11只成功，0.125毫克组的14只眼中有14只成功，0.063毫克组的24只眼中有21只成功，0.031毫克组的9只眼中有9只成功。
在这项1期研究中，低至0.031毫克的贝伐单抗剂量在9只眼中的9只有效，值得进一步研究。确定更低的贝伐单抗有效剂量可能会降低神经发育障碍风险或对其他器官的有害影响。
