Department of Ophthalmology, Jichi Medical University, Shimotsuke, Tochigi, Japan.
Department of Ophthalmology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Br J Ophthalmol. 2018 Apr;102(4):448-454. doi: 10.1136/bjophthalmol-2017-310284. Epub 2017 Aug 1.
To determine changes in multiple cytokine concentrations in the anterior chamber during the induction phase of ranibizumab treatment in patients with neovascular age-related macular degeneration (AMD).
This prospective study included 48 treatment-naïve neovascular AMD eyes of 48 patients who received three consecutive monthly injections of ranibizumab at the Japan Community Health Care Organization Tokyo Shinjuku Medical Center between November 2010 and August 2012. We collected ~0.2 mL aqueous humour before the first and third (2 months later) injections. Controls were 80 eyes with cataracts without retinal disease. The cytokines C-X-C motif chemokine ligand 1 (CXCL1), interferon-γ-induced protein 10 (IP-10), C-X-C motif chemokine ligand 12 (CXCL12), C-X-C motif chemokine ligand 13 (CXCL13), monocyte chemoattractant protein 1 (MCP-1), CCL11, C-C motif chemokine ligand 11 (CCL11), interleukin-6 (IL-6), interleukin-10 (IL-10) and matrix metalloproteinase 9 (MMP-9) were analysed using multiplex cytokine assays.
Mean ages of the patients with AMD and controls were 73 and 75 years, respectively, and 31 (65%) and 37 (46%) subjects were men, respectively. Polypoidal choroidal vasculopathy was found in 27 eyes (56%). Mean concentrations of cytokines in aqueous humour in patients with neovascular AMD before the first and third ranibizumab injections were as follows (in pg/mL): CXCL1, 8.4 and 3.3; IP-10, 110 and 55; CXCL12, 480 and 240; CXCL13, 9.2 and 2.6; MCP-1, 620 and 220; CCL11, 7.1 and 2.8; IL-6, 5.9 and 1.6; IL-10, 0.15 and 0.015 (all p<0.0001), and MMP-9, 0.92 and 1.5 (p=0.0216), respectively. Concentrations of all cytokines decreased significantly after two consecutive ranibizumab injections, except for MMP-9, which increased significantly.
After two monthly consecutive antivascular endothelial growth factor injections, inflammatory cytokine levels in the aqueous humour of the eyes with AMD were strongly suppressed, while MMP-9 levels increased.
在接受抗血管内皮生长因子治疗的新生血管性年龄相关性黄斑变性(AMD)患者的诱导期,确定前房内多种细胞因子浓度的变化。
这项前瞻性研究纳入了 2010 年 11 月至 2012 年 8 月期间在日本社区保健组织东京新宿医疗中心接受连续 3 次每月注射雷珠单抗的 48 例(48 只眼)未经治疗的新生血管性 AMD 患者。我们在首次和第三次(2 个月后)注射前收集了约 0.2ml 的房水。对照组为 80 只无视网膜疾病白内障眼。使用多重细胞因子检测分析细胞因子 C-X-C 基序趋化因子配体 1(CXCL1)、干扰素-γ诱导蛋白 10(IP-10)、C-X-C 基序趋化因子配体 12(CXCL12)、C-X-C 基序趋化因子配体 13(CXCL13)、单核细胞趋化蛋白 1(MCP-1)、CCL11、C-C 基序趋化因子配体 11(CCL11)、白细胞介素 6(IL-6)、白细胞介素 10(IL-10)和基质金属蛋白酶 9(MMP-9)。
AMD 患者和对照组的平均年龄分别为 73 岁和 75 岁,分别有 31 名(65%)和 37 名(46%)男性。27 只眼(56%)发现息肉状脉络膜血管病变。接受新生血管性 AMD 治疗的患者在首次和第三次雷珠单抗注射前的房水细胞因子浓度如下(pg/ml):CXCL1,8.4 和 3.3;IP-10,110 和 55;CXCL12,480 和 240;CXCL13,9.2 和 2.6;MCP-1,620 和 220;CCL11,7.1 和 2.8;IL-6,5.9 和 1.6;IL-10,0.15 和 0.015(均 p<0.0001),和 MMP-9,0.92 和 1.5(p=0.0216)。连续两次雷珠单抗注射后,所有细胞因子的浓度均显著下降,除 MMP-9 外,MMP-9浓度显著升高。
在连续两次每月抗血管内皮生长因子注射后,AMD 眼房水中的炎症细胞因子水平受到强烈抑制,而 MMP-9 水平升高。