湿性年龄相关性黄斑变性患者抗血管内皮生长因子治疗敏感性的影响因素:基于房水细胞因子分析

Analysis of factors influencing the sensitivity of anti vascular endothelial growth factor therapy in patients with wet age-related macular degeneration based on aqueous humor cytokines

目的通过分析湿性年龄相关性黄斑变性(wAMD)患者抗血管内皮生长因子(VEGF)治疗后房水细胞因子浓度的改变及房水细胞因子与相关指标之间的相关性,探讨影响wAMD患者抗VEGF治疗敏感性的因素。方法选取2019年8月至2020年1月于广州中医药大学第一附属医院就诊的wAMD患者(观察组)和白内障患者(对照组)各30例(30眼),分别收集两组患者研究期间房水,用微球悬浮阵列技术(Luminex200TM)进行房水细胞因子浓度检测。同时分析观察组患者连续2次抗VEGF(雷珠单抗或康柏西普)治疗前后相关指标最佳矫正视力、黄斑中心凹视网膜厚度(CMT)与房水细胞因子之间的相关性。结果抗VEGF治疗前,观察组患者房水中白细胞介素-8(IL-8)、血管生成素样蛋白4(angiopoietin-like protein 4,ANGPTL4)、单核细胞趋化蛋白-1(MCP-1)浓度均明显高于对照组,差异均有统计学意义(均为P<0.05);而两组患者房水中血管内皮生长因子-A(VEGF-A)、白细胞介素-6(IL-6)、血小板源性生长因子-BB(PDGF-BB)细胞因子浓度差异均无统计学意义(均为P>0.05);抗VEGF治疗1个月后,观察组患者房水中VEGF-A浓度明显下降,与治疗前相比差异具有统计学意义(Z=-3.589,P<0.001);连续2个月抗VEGF治疗后,观察组患者视力提高,CMT降低,差异均有统计学意义(均为P<0.05);抗VEGF治疗前后观察组患者房水中PDGF-BB浓度与视力呈负相关(r=-0.413、-0.508,均为P<0.05),治疗1个月后MCP-1、IL-6、ANGPTL4浓度与CMT均呈正相关(r=0.743、0.552、0.566,均为P<0.05)。结论房水细胞因子IL-8、MCP-1、ANGPTL4可能参与wAMD疾病的发生,抗VEGF治疗能有效改善患者视力及减轻黄斑水肿,其中视力恶化可能与房水细胞因子PDGF-BB浓度有关,而房水细胞因子MCP-1、IL-6、ANGPTL4浓度可能与黄斑水肿有关。

Objective To analyze the changes of cytokines in aqueous humor of patients with wet age-related macular degeneration(wAMD)after anti vascular endothelial growth factor(VEGF)treatment and the correlation between cytokines in aqueous humor and related therapeutic indexes,and the factors affecting the sensitivity of anti-VEGF treatment in wAMD patients were discussed.Methods From August 2019 to January 2020,30 patients(30 eyes)with wAMD and 30 patients(30 eyes)with cataract in the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine were selected as the observation group and the control group,respectively.The aqueous humor of the two groups was collected during the study period,and the concentrations of cytokines in aqueous humor were detected by(microsphere)suspension array technology(Luminex 200).At the same time,the correlation between the related indexes best corrected visual acuity(BCVA),macular fovea thickness(CMT)and the cytokines in the aqueous humor before and after two consecutive anti-VEGF(ranibizumab or conbercept)treatment in the observation group was analyzed.Results Before anti-VEGF treatment,the concentrations of interleukin-8(IL-8),angiopoietin-like protein 4(ANGPTL4)and monocyte chemotactic protein-1(MCP-1)in aqueous chamber in observation group were significantly higher than those in control group,with statistical significance(all P<0.05),while the concentrations of vascular endothelial growth factor-A(VEGF-A),interleukin-6(IL-6),IL-8,and platelet-derived growth factor-BB(PDGF-BB)in the aqueous humor of the two groups were not significantly different(all P>0.05).After 1 month of anti-VEGF treatment,the concentration of VEGF-A in aqueous humor of the observation group decreased significantly,the difference was statistically significant(Z=-3.589,P<0.001).After 2 months of anti-VEGF treatment,the visual acuity of the observation group was improved,and CMT was decreased,with statistical significance(all P<0.05).Before anti-VEGF treatment,the concentrations of PDGF-BB cytokines in aqueous humor of the observation group were negatively correlated with the visual acuity(r=-0.413,-0.508,both P<0.05),and the concentrations of MCP-1,IL-6,and ANGPTL4 cytokines were positively correlated with CMT after 1 month of treatment(r=0.743,0.552,0.566,all P<0.05).Conclusion Aqueous humor cytokines IL-8,MCP-1 and ANGPTL4 may be involved in the occurrence of wAMD.Anti-VEGF can effectively improve the vision of patients and reduce macular edema.The deterioration of vision may be related to PDGF-BB,while MCP-1,IL-6 and ANGPTL4 may be related to macular edema.