Department of Ophthalmology, Chang Gung Memorial Hospital, Guishan, Taoyuan, Taiwan2Department of Medicine, Chang Gung University, College of Medicine, Taoyuan, Taiwan.
Department of Medicine, Chang Gung University, College of Medicine, Taoyuan, Taiwan3Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
JAMA Ophthalmol. 2015 Apr;133(4):391-7. doi: 10.1001/jamaophthalmol.2014.5373.
Intravitreous injections of bevacizumab (IVB) have been found to be effective for the treatment of retinopathy of prematurity (ROP). However, serum levels of vascular endothelial growth factor (VEGF) have been found to be suppressed for 2 weeks after IVB in patients with ROP. Changes in serum VEGF levels after IVB in patients with ROP may be important because VEGF also plays a role in the neurodevelopment of newborns.
To investigate the correlation of levels of VEGF and related growth factors with bevacizumab levels in the systemic circulation after IVB in patients with type 1 ROP.
DESIGN, SETTING, AND PARTICIPANTS: We studied a prospective case series at an institutional referral center from December 1, 2011, through February 28, 2013. We enrolled patients with type 1 ROP who received IVB. We collected blood samples before and for as long as 8 weeks after IVB. The samples were tested for serum levels of bevacizumab and growth factors, including VEGF, VEGF receptor 1 (VEGFR1), VEGFR2, Tie2, erythropoietin, transforming growth factor β1, insulinlike growth factor type 1, angiopoietin 1, angiopoietin 2, angiopoietinlike 3, and angiopoietin 4. The serum concentrations of these factors were measured using enzyme-linked immunosorbent assays.
Serum levels of VEGF, bevacizumab, and the other growth factors before and for as long as 8 weeks after IVB.
We enrolled 8 patients with type 1 ROP. Bevacizumab levels were elevated 1 day after IVB in the 3 patients for whom measurements were available (mean [SD], 1425 [1010 (95% CI, 0-3934)] ng/mL; P = .13) and remained detectable in the serum as long as 8 weeks after IVB (285 ng/mL for the 1 patient with a measurement available). Serum VEGF levels were suppressed for the same period (mean [SD] level at 1 day after IVB, 379 [226 (95% CI, 190-568)] pg/mL for the 3 patients with measurements available; at 8 weeks, 216 pg/mL for the 1 patient with a measurement available). We found a negative correlation between the serum levels of bevacizumab and VEGF in the patients with ROP who received IVB (r = -0.43 [95% CI, -0.67 to -0.10]; P = .01). No changes were identified in the serum levels of any of the other factors after IVB. Bevacizumab may interfere with the actual level of VEGF in the serum, and the total VEGF level in the serum cannot be determined when bevacizumab is present. Wide CIs were noted in the measurement of these factors, probably owing to the small number of patients enrolled in this study.
Serum VEGF levels were suppressed for 2 months after IVB in patients with type 1 ROP owing to the leakage of bevacizumab into the systemic circulation.
已发现玻璃体内注射贝伐单抗（IVB）对治疗早产儿视网膜病变（ROP）有效。然而，在接受 ROP 治疗的患者中，IVB 后 2 周发现血管内皮生长因子（VEGF）的血清水平被抑制。接受 ROP 治疗的患者接受 IVB 后 VEGF 水平的变化可能很重要，因为 VEGF 也在新生儿的神经发育中发挥作用。
调查 1 型 ROP 患者接受 IVB 后，VEGF 水平和相关生长因子与全身循环中贝伐单抗水平的相关性。
设计、地点和参与者：我们在 2011 年 12 月 1 日至 2013 年 2 月 28 日期间，在一家机构转诊中心进行了一项前瞻性病例系列研究。我们纳入了接受 IVB 的 1 型 ROP 患者。我们在 IVB 前后采集血样，最长可达 8 周。采集的样本用于检测血清中的贝伐单抗和生长因子，包括 VEGF、VEGF 受体 1（VEGFR1）、VEGFR2、Tie2、促红细胞生成素、转化生长因子β1、胰岛素样生长因子 1、血管生成素 1、血管生成素 2、血管生成素样 3 和血管生成素 4。使用酶联免疫吸附试验测量这些因子的血清浓度。
IVB 前后最长 8 周的 VEGF、贝伐单抗和其他生长因子的血清水平。
我们纳入了 8 名 1 型 ROP 患者。在可测量的 3 名患者中，IVB 后 1 天贝伐单抗水平升高（平均[标准差]，1425[1010（95%CI，0-3934）]ng/ml；P = .13），并且在 IVB 后最长 8 周仍可在血清中检测到（1 名可测量的患者为 285ng/ml）。同期 VEGF 血清水平受到抑制（3 名可测量患者的 1 天 VEGF 水平平均值[标准差]，379[226（95%CI，190-568）]pg/ml；8 周时，1 名可测量患者的 216pg/ml）。我们发现接受 IVB 的 ROP 患者血清中贝伐单抗和 VEGF 水平呈负相关（r = -0.43[95%CI，-0.67 至 -0.10]；P = .01）。IVB 后其他因子的血清水平没有变化。贝伐单抗可能会干扰血清中 VEGF 的实际水平，并且当存在贝伐单抗时，无法确定血清中 VEGF 的总水平。由于本研究纳入的患者数量较少，因此在这些因子的测量中观察到较宽的置信区间。
由于贝伐单抗渗漏到全身循环中，1 型 ROP 患者在接受 IVB 后 2 个月内 VEGF 血清水平受到抑制。
