曲安奈德联合雷珠单抗治疗对糖尿病性黄斑水肿患者血清VEGF、IL-6、IL-8水平的影响

摘要

目的 探讨曲安奈德联合雷珠单抗玻璃体腔注射对糖尿病性黄斑水肿(DME)的治疗效果,以及对患者血清VEGF、IL-6、IL-8水平的影响.方法 前瞻性临床对照研究.研究对象为2015年1月-2016年12月在我院确诊为DME的患者166例(235只眼),随机分为两组.A组83例(116只眼),采用玻璃体腔注射雷珠单抗,B组83例(119只眼)采用曲安奈德与雷珠单抗联合注射,均每4周注射1次,共注射3次.治疗前及完成最后一次注射后4周检测两组患者血清血管内皮生长因子(VEGF)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)水平,光学相干断层扫描(OCT)测量黄斑中心视网膜厚度.治疗完毕后对所有患者随访6个月,统计并发症发生情况.结果 1.炎症细胞因子水平:治疗前A组血清VEGF、IL-6、IL-8分别为(432.87±98.24) ng/L,(75.12±8.32) ng/L,(62.34±7.12) ng/L,B组分别为(433.05 ±98.74) ng/L,(74.68 ±8.45) ng/L,(63.08±7.25) ng/L,治疗后A组VEGF、IL-6、IL-8分别为(156.31±68.15) ng/L,(54.85±8.66) ng/L,(43.28±7.56)ng/L,B组分别为(102.50±68.34) ng/L,(52.75±8.35) ng/L,(41.34±7.85) ng/L.治疗前两组各指标水平无明显差异(P＞0.05),治疗后各指标数值均较治疗前下降(P＜0.05),B组治疗后的血清VEGF明显低于A组(P＜0.05),IL-6、IL-8水平与A组相当(P＞0.05).2.黄斑中心凹视网膜厚度:治疗前A、B组的黄斑中心视网膜厚度分别为(536.15±86.28)μm,(529.14±84.57) μm,治疗后的结果分别为(386.67±84.11) μm,(321.08±85.16) μm.治疗前两组黄斑中心视网膜厚度接近(P＞0.05),治疗后两组数值均较治疗前降低(P＜0.05),B组的数值低于A组(P＜0.05).3.并发症:A组眼内炎2只眼(1.72％),眼压升高0只眼(0.00％),晶状体混浊加重1只眼(0.86％),出血4只眼(3.45％),总计7只眼(6.03％),B组相应的眼数分别为1只眼(0.84％),5只眼(4.20％),2只眼(1.68％),2只眼(1.68％),总计10只眼(8.40％).组间差异均无统计学意义(P＞0.05).结论 与单独玻璃体腔注射雷珠单抗相比,联合应用曲安奈德对DME的治疗效果更好,并能降低血清VEGF、IL-6、IL-8水平,其安全性总体上与单纯应用雷珠单抗相当,可以根据患者的个体情况选择使用.%OBJECTIVE To investigate the therapeutic effect of intravitreal triamcinolone acetonide combined with rezumab on diabetic macular edema (DME) and its impact on serum levels of vascular endothelial growth factor (VEGF),interleukin-6 (IL-6) and interleukin-8 (IL-8).METHODS It was a prospective controlled clinical study.The subjects were 166 patients (235 eyes) diagnosed as DME in our hospital from January of 2015 to December of 2016,which were randomly divided into two groups.In group A,83 cases (116 eyes) were treated by intravitreal injection of rezumab,and 83 cases (119 eyes) in group B were injected with triamcinolone acetonide combined with rezumab.They were injected 1 times every 4 weeks,3 times in a row.Serum levels of VEGF,IL-6 and IL-8 in two groups were detected before the treatment and 4 weeks after the last injection,while the central retinal thickness was measured by optical coherence tomography (OCT).After the treatment,all patients were followed up for 6 months,and the incidence of complications was statistically analyzed.RESULTS 1.The level of inflammatory cell factor:Before intervention,the serum level of VEGF,IL-6,IL-8 in group A were 432.87+98.24ng/L,75.12+8.32ng/L,62.34+7.12ng/L;These parameters in B group were 433.05 +98.74ng/L,74.68 +8.45ng/L,63.08 +7.25ng/L;After treatment,VEGF,IL-6 and IL-8 in group A were 156.31+68.15ng/L,54.85+8.66ng/L,43.28+7.56ng/L;These indexes in B group were 102.50+68.34ng/L,52.75+8.35ng/L,41.34+7.85ng/L.Before treatment,there were no significant differences in each index level between the two group (P＞0.05).After treatment,the result of each index were all decreased significantly (P＜0.05).Serum VEGF in group B was significantly lower than it in group A (P＜0.05),IL-6 and IL-8 level were similar to counterparts in A group (P＞0.05).2.macular central retinal thickness:Before treatment,the macular central retinal thickness in group A and group B was 536.15+86.28μm and 529.14+84.57μm respectively,and the results after treatment were 386.67 +84.11μm,321.08 +85.16μm.Before treatment,the macular central retinal thickness of the two groups was close (P＞0.05).After treatment,the values of two groups were both dropped significantly (P＜0.05),and the result in group B were lower than counterpart in group A (P＜0.05).3.complications:In group A,7 eyes (8.43％) suffered complications,specifically,2 eyes of endophthalmitis (2.41％),0 eyes of increased intraocular pressure (0％),1 eye of increased lens opacity (0.86％),4 eyes of hemorrhage(4.82％);In group B,complications happened in 10 eyes (12.05％),as 1 eyes of endophthalmitis (1.2％) respectively,5 eyes of increased intraocular pressure (6.03％),2 eyes of increased lens opacity and hemorrhage respectively(2.41％).There was no significant difference between groups (P＞0.05).CONCLUSIONS Compared with the single use of intravitreal ranibizumab injection,combined application of triamcinolone acetonide and ranibizumab injection enjoyed better effects on DME,in addition,it decreased the level of VEGF,IL-6,IL-8 and as safe as ranibizumab alone which meant it was a reliable choose for patients with indications.