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房水细胞因子与糖尿病性黄斑水肿抗VEGF治疗疗效的相关性

张建,关小东,方天敏,雷晓琴   

  1. 陕西省铜川市人民医院,陕西省铜川市人民医院,陕西省铜川市人民医院,陕西省铜川市人民医院
  • 收稿日期:2018-12-18 修回日期:2019-02-20 出版日期:2019-03-25

Correlation between Levels of Cytokines in Aqueous Humor and the Efficacy of Anti-VEGF Therapy of Diabetic Macular Edema Patients

Zhang Jian,Guan Xiaodong,Fang Tianmin and Lei Xiaoqin   

  1. Ophthalmology Department,Tongchuan People''''s Hospital,Shaanxi Province,Tongchuan,Ophthalmology Department,Tongchuan People''''s Hospital,Shaanxi Province,Tongchuan,Ophthalmology Department,Tongchuan People''''s Hospital,Shaanxi Province,Tongchuan,Ophthalmology Department,Tongchuan People''''s Hospital,Shaanxi Province,Tongchuan
  • Received:2018-12-18 Revised:2019-02-20 Online:2019-03-25

摘要: 目的:探究房水细胞因子与糖尿病性黄斑水肿(DME)抗血管内皮生长因子(VEGF)治疗疗效的相关性及其对疗效的预测价值。方法:对2016年2月至2018年2月间于我院行抗VEGF治疗的80例DME患者进行前瞻性分析,根据治疗6个月后黄斑中央厚度(CMT)降幅是否≥100 μm,分为显著组(≥100 μm,52例)和不显著组(<100 μm,28例),比较两组患者的一般资料和房水细胞因子水平,分析房水细胞因子与DME抗VEGF治疗疗效的相关性,应用ROC曲线分析不同因子对抗VEGF治疗疗效的预测价值。结果:不显著组的糖尿病病程长于显著组,差异有统计学意义(t=2.336,P=0.022),两组糖尿病视网膜病变(DR)分级间差异存在统计学意义(Z=2.206, P=0.027)。不显著组的白细胞介素-8(IL-8)和胎盘生长因子(PIGF)水平高于显著组,差异有统计学意义(t=6.707,2.443;P=0.000, 0.017),白细胞介素-10(IL-10)和VEGF水平低于显著组,差异有统计学意义(t=5.260,3.016;P=0.000, 0.003)。多因素Logistic回归分析显示,IL-8(OR=0.473, 95%CI 0.302~0.741)水平是影响抗VEGF治疗疗效的独立危险因素,IL-10(OR=5.065, 95%CI 1.818~14.107)和VEGF(OR=1.045, 95%CI 1.008~1.083)是影响抗VEGF治疗疗效的独立保护因素。 Pearson相关分析显示,IL-8水平与CMT降幅呈显著负相关(r=-0.789,P=0.008),IL-10和VEGF水平与CMT降幅呈显著正相关(r=0.633、0.643, P=0.010、0.010),IL-8水平与CMT降幅的相关性显著高于IL-10和VEGF水平(Z=2.175、2.061,P=0.030、0.039)。ROC曲线显示,房水IL-8水平预测抗VEGF疗效的AUC为0.914,明显高于IL-10、PIGF和VEGF(AUC=0.811、0.641、0.709),其最佳截点为IL-8<18.13 pg·mL-1,此时其敏感性和特异性分别为72.41%和96.43%。结论:房水IL-8、IL-10和VEGF水平与DME患者抗VEGF治疗疗效存在相关性,应用房水IL-8水平预测抗VEGF疗效具有较好的诊断效能。

Abstract: ]Objective: To investigate the correlation between levels of cytokines in aqueous humor and the efficacy of anti-VEGF therapy of diabetic macular edema (DME) patients and their predictive value. Methods: A prospective analysis of 80 DME patients who underwent anti-VEGF therapy in our hospital from February 2016 to February 2018 was performed. According to the reduction of central macular thickness (CMT) after 6 months of treatment, patients were divided into significant group (≥100 μm, 52 cases) and insignificant group (<100 μm, 28 cases). The general data and cytokine levels in aqueous humor of the two groups were compared. The correlation of cytokines levels in aqueous humor and the efficacy of anti-VEGF therapy was analyzed. The ROC curve was used to analyze the predictive value of different factors for anti-VEGF treatment efficacy. Results: The duration of diabetes in the insignificant group was higher than the significant group (t=2.336, P=0.022). There was a statistical difference in the diabetic retinopathy(DR) between the two groups (Z=2.206, P=0.027). The levels of IL-8 and PIGF in the insignificant group were higher than the significant group (t=6.707, 2.443; P=0.000, 0.017), and IL-10 and VEGF levels were lower than the significant group(t=5.260, 3.016; P=0.000, 0.003). Multivariate logistic regression analysis showed that IL-8 (OR=0.473, 95%CI 0.302-0.741) level was independent risk factor for anti-VEGF therapy. The IL-10 (OR=5.065, 95%CI 1.818-14.107) and VEGF(OR=1.045, 95%CI 1.008-1.083) levels were the independent protective factors for anti-VEGF therapy. Pearson correlation analysis showed that IL-8 levels were significantly negatively correlated with CMT decline (r=-0.789, P=0.008), IL-10 and VEGF levels were significantly positively correlated with CMT decline (r=0.633, 0.643; P=0.010, 0.010). The correlation of IL-8 level with CMT decline was significantly higher than that of IL-10 and VEGF levels(Z=2.175, 2.061; P=0.030, 0.039). The ROC curve showed that the AUC of the aqueous humor IL-8 level was 0.914 in predicting anti-VEGF efficacy, which was significantly higher than that of IL-10, PIGF and VEGF(AUC=0.811, 0.641, 0.709). The optimal cut-off point was IL-8<18.13 pg·mL-1, the sensitivity and specificity were 72.41% and 96.43%, respectively. Conclusion: The levels of IL-8, IL-10 and VEGF in aqueous humor are correlated with the efficacy of anti-VEGF therapy in DME patients. The application of aqueous humor IL-8 level in predicting anti-VEGF efficacy has good diagnostic efficiency.