Bevacizumab Injection in Patients with Neovascular Age-Related Macular Degeneration Increases Angiogenic Biomarkers.
Bevacizumab Injection in Patients with Neovascular Age-Related Macular Degeneration Increases Angiogenic Biomarkers.
复制标题
新血管年龄相关的黄斑变性患者的贝伐单抗注射会增加血管生成生物标志物。
DOI：
10.1016/j.oret.2017.04.004
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发表时间：
2018-01
期刊：
影响因子：
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通讯作者：
Belfort R Jr
中科院分区：
文献类型：
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作者：
Cabral T;Lima LH;Mello LGM;Polido J;Correa ÉP;Oshima A;Duong J;Serracarbassa P;Regatieri CV;Mahajan VB;Belfort R Jr
评估新生血管性年龄相关性黄斑变性 (AMD) 眼玻璃体内注射贝伐单抗 (IVB) 前后房水中 19 种血管生成生物标志物的表达。前瞻性、非比较性、干预性病例系列。 23 名初治患者的 23 只眼睛患有继发于新生血管性 AMD 的脉络膜新生血管 (CNV)。眼睛被诊断为继发于新生血管性 AMD 的 CNV，并接受了 3 个月的 IVB 治疗。在基线时和每次玻璃体内注射贝伐单抗之前立即通过前房穿刺术获得房水样本。 19 种血管生成生物标志物（血管生成素 2、骨形态发生蛋白 9 [BMP-9]、表皮生长因子 [EGF]、内皮糖蛋白、内皮素 1、成纤维细胞生长因子 [FGF]-1 和 FGF-2、卵泡抑素、粒细胞集落刺激因子 [GCSF]、肝素结合 EGF 样生长因子 [HB-EGF]、肝细胞生长因子的房水水平测量了[HGF]、白细胞介素8、瘦素、胎盘生长因子[PLGF]、血管内皮生长因子[VEGF]-A、VEGF-C、VEGF-D和金属蛋白酶组织抑制剂[TIMP]-1和TIMP-2）。还评估了最佳矫正视力 (BCVA)、频域 OCT 参数和眼压。在治疗开始前，所有研究眼的基线水性 VEGF-A 表达均升高。在 1 个月和 2 个月的随访中观察到 VEGF-A 的统计学显着下降。 7 种生物标志物浓度出现统计学显着性增加：VEGF-C、血管生成素 2、内皮素 1、卵泡抑素、HB-EGF、HGF 和白细胞介素 8。其他 11 种研究生物标志物水平（VEGF-D、BMP-9、EGF、内皮糖蛋白、FGF-1、FGF-2、GCSF、瘦素、PLGF、TIMP-1 和 TIMP-2）没有增加。在随访期间显示任何显着差异。 2 个月时 BCVA 统计显着改善。在所有随访中，谱域 OCT 参数均显着改善。研究期间平均眼压值没有统计学差异。玻璃体内注射贝伐单抗后，尽管 VEGF-A 降低，但 VEGF-C、血管生成素 2、内皮素 1、卵泡抑素、HB-EGF、HGF 和白介素 8 的房水水平显着升高。这些上调的血管生成生物标志物可能代表渗出性 AMD 的新治疗靶点。
To evaluate the expression of 19 angiogenic biomarkers in the aqueous humor before and after intravitreal bevacizumab injection (IVB) in eyes with neovascular age-related macular degeneration (AMD). Prospective, noncomparative, interventional case series. Twenty-three eyes of 23 treatment-naïve patients with choroidal neovascularization (CNV) secondary to neovascular AMD. Eyes were diagnosed with CNV secondary to neovascular AMD and were treated with 3 monthly IVBs. Aqueous humor samples were obtained by anterior chamber paracentesis at baseline and immediately before each intravitreal bevacizumab injection. Aqueous humor levels of 19 angiogenic biomarkers (angiopoietin 2, bone morphogenetic protein 9 [BMP-9], epidermal growth factor [EGF], endoglin, endothelin 1, fibroblast growth factor [FGF]-1 and FGF-2, follistatin, granulocyte colony-stimulating factor [GCSF], heparin-binding EGF-like growth factor [HB-EGF], hepatocyte growth factor [HGF], interleukin 8, leptin, placental growth factor [PLGF], vascular endothelial growth factor [VEGF]-A, VEGF-C, VEGF-D, and tissue inhibitor of metalloproteinases [TIMP]-1 and TIMP-2) were measured. Best-corrected visual acuity (BCVA), spectral-domain OCT parameters, and intraocular pressure also were evaluated. Baseline aqueous VEGF-A expression was elevated in all study eyes before treatment initiation. A statistically significant decrease of VEGF-A was observed at the 1- and 2-month follow-ups. A statistically significant increased concentration was observed in 7 biomarkers: VEGF-C, angiopoietin 2, endothelin 1, follistatin, HB-EGF, HGF, and interleukin 8. The other 11 study biomarker levels (VEGF-D, BMP-9, EGF, endoglin, FGF-1, FGF-2, GCSF, leptin, PLGF, TIMP-1, and TIMP-2) did not show any significant difference during follow-up. The BCVA statistically improved significantly at 2 months. Spectral-domain OCT parameters improved significantly at all follow-ups. Mean intraocular pressure values were not statistically different during the study period. Despite a decrease in VEGF-A, the aqueous levels of VEGF-C, angiopoietin 2, endothelin 1, follistatin, HB-EGF, HGF, and interleukin 8 increased significantly after intravitreal injection of bevacizumab. These upregulated angiogenic biomarkers may represent new therapeutic targets in exudative AMD.