DME患者黄斑微循环和细胞因子与抗VEGF疗效的关系

Relationship between macular microcirculation,cytokines and anti-VEGF efficacy in DME patients

目的探讨糖尿病黄斑水肿(diabetic macular edema,DME)患者抗血管内皮生长因子(vascular endothelial growth factor,VEGF)治疗后黄斑区微循环和房水细胞因子表达的变化,并分析其与抗VEGF疗效的关系。方法选取2021年10月至2023年8月于南昌市第一医院就诊的DME患者62例(91眼),均行玻璃体腔注射康柏西普治疗。根据黄斑中心厚度(central macular thickness,CMT)的降幅将其分为疗效显著组(CMT降幅≥100μm,59眼)和非疗效显著组(CMT降幅<100μm或增加,32眼)。分析抗VEGF治疗后CMT、黄斑浅层毛细血管丛(superficial capillary plexus,SCP)血管密度(vessel density,VD)、中心凹无血管区(fovea avascular area,FAZ)、VEGF、白细胞介素(interleuki,IL)-6、IL-8、IL-10的变化。采用受试者操作特征曲线(receiver operating characteristic curve,ROC曲线)评估各指标的疗效预测价值。结果治疗前,疗效显著组患眼房水的VEGF、IL-10均显著高于非疗效显著组,IL-8水平显著低于非疗效显著组(P<0.05);治疗后,两组患眼房水的VEGF、IL-6、IL-8、IL-10均显著低于本组治疗前(P<0.05),疗效显著组患眼房水的VEGF、IL-6、IL-8均显著低于非疗效显著组,IL-10水平显著高于非疗效显著组(P<0.05);抗VEGF治疗前后,两组患眼的FAZ面积和SCP-VD均无显著变化(P>0.05)。相关性分析显示,基线房水VEGF(r=0.571,P<0.001)、IL-10(r=0.382,P=0.008)与CMT降幅呈正相关;IL-8与CMT降幅呈负相关性(r=–0.689,P<0.001);IL-6、FAZ面积、SCP-VD与CMT降幅无相关性(P>0.05);细胞因子水平与FAZ面积和SCP-VD无相关性(P>0.05)。ROC曲线结果显示,基线房水IL-8、VEGF和IL-10预测抗VEGF疗效的曲线下面积分别为0.825、0.813和0.676。结论DME患者的基线房水VEGF、IL-8、IL-10水平与抗VEGF疗效相关,且能够预测抗VEGF疗效。

Objective To investigate the changes of macular microcirculation and aqueous humor cytokine expression in patients with diabetic macular edema(DME)after anti-vascular endothelial growth factor(VEGF)treatment,and analyze the relationship with efficacy.Methods A total of 62 patients(91 eyes)with DME who were treated in the First Hospital of Nanchang from October 2021 to August 2023 were selected and treated with intravitreal injection of conbercept.According to the reduction of central macular thickness(CMT),they were divided into efficacy significant group(CMT reduction≥100μm,59 eyes)and non-efficacy significant group(CMT reduction<100μm or increase,32 eyes).The changes of CMT,vessel density(VD)of superficial capillary plexus(SCP),fovea avascular area(FAZ),VEGF,interleuki(IL)-6,IL-8,and IL-10 after anti-VEGF treatment were analyzed.Receiver operating characteristic(ROC)curve was used to evaluate the predictive value of each index.Results Before treatment,the levels of VEGF and IL-10 in aqueous humor in efficacy significant group were significantly higher than those in non-efficacy significant group,and the level of IL-8 was significantly lower than that in non-efficacy significant group(P<0.05).After treatment,levels of VEGF,IL-6,IL-8 and IL-10 in aqueous humor in both groups were significantly lower than before treatment(P<0.05).The levels of VEGF,IL-6 and IL-8 in aqueous humor in efficacy significant group were significantly lower than those in non-efficacy significant group,and the level of IL-10 was significantly higher than that in non-efficacy significant group(P<0.05).Before and after anti-VEGF treatment,there were no significant changes in FAZ area and SCP-VD in both groups(P>0.05).Correlation analysis showed that VEGF(r=0.571,P<0.001)and IL-10(r=0.382,P=0.008)in aqueous humor at baseline were positively correlated with CMT reduction,IL-8 was negatively correlated with CMT reduction(r=–0.689,P<0.001).IL-6,FAZ area and SCP-VD were not correlated with CMT reduction(P>0.05).Cytokine levels were not correlated with FAZ area and SCP-VD(P>0.05).ROC curve results showed that area under the curve of IL-8,VEGF and IL-10 at baseline predicting anti-VEGF efficacy were 0.825,0.813 and 0.676,respectively.Conclusion The levels of VEGF,IL-8,and IL-10 in aqueous humor at baseline in DME patients were correlated with anti-VEGF efficacy and could predict the efficacy of anti-VEGF.