雷珠单抗球内注射治疗视网膜静脉阻塞并发黄斑水肿血清细胞因子变化及意义的研究

Therapeutic Effects and Serum Cytokine Levels Changing of Intravitreal Ranibizumab Injection for Macular Edema Secondary to Retinal Vein Occlusion

目的通过测定视网膜静脉阻塞继发黄斑水肿(RVO-ME)患者抗VEGF治疗前后血清14种炎症细胞因子浓度的变化,并比较RVO-ME患者与健康对照组患者血清细胞因子水平的差异,分析细胞因子的变化与疗效的关系。方法选取泰州市人民医院眼科2021年1月到6月临床确诊的RVO-ME患者20例20眼,行玻璃体腔内注射雷珠单抗,检测RVO患者治疗前,以及治疗后1周、2周、1月血清中白细胞介素2(IL-2)、IL-4、IL-5、IL-6、IL-8、IL-10、IL-17A、IL-1β、IL-12p70、肿瘤坏死因子-α(TNF-α)、干扰素-γ(IFN-γ)、IFN-α、血管内皮生长因子(VEGF)和血管紧张素II(ANG-II)表达水平的差异以及最佳矫正视力(BCVA)、中央黄斑厚度(CMT)等指标的变化,对照组为体检者中健康人群。结果与健康对照组比较,RVO患者组血清IL-2、IL-4、IL-6、IL-10、TNF-a、IL-17A、IL-1b、IL-5、IL-12p70、IFNa、IL-8、VEGF均显著升高,差异具有统计学差异(P<0.05);IL-8(OR=1.30,95%CI:1.01-1.68)和VEGF(OR=1.16,95%CI:1.00-1.35)是RVO发生的独立危险因素;RVO组在雷珠单抗治疗后视力有明显的提高,CMT也有了明显下降,IL-6、IL-8表达增高,且具有统计学差异。结论RVO-ME患者血清中IL-1β、IL-2、IL-4、IL-5、IL-6、IL-8、IL-10、IL-12p70、IL-17A、TNF-α、IFN-α、VEGF等炎症细胞因子明显增高。玻璃体腔注射雷珠单抗可明显降低血清中VEGF水平,并减轻黄斑水肿,改善视力,但对血清中细胞因子无明显作用。抗VEGF治疗后患者血清中IL-6、IL-8增高,提示球内注射雷珠单抗可能通过诱导炎反应,增加炎症细胞因子的表达。

Objective To determine the changes of serum levels of 14 inflammatory cytokines in patients with macular edema secondary to retinal vein occlusion(RVO-ME)before and after anti-VEGF treatment,and to compare the differences of serum cytokines levels between RVO-ME patients and healthy control group,and to analyze the relationship between the changes of cytokines and the curative effect.Methods Twenty eyes of 20 clinically diagnosed RVO-ME patients were selected from The Department of Ophthalmology of Taizhou People's Hospital from January 2021 to June 2021.They received intravitreal injection of Ranibizumab,and the expression level of serum interleukin-2(IL-2),IL-4,IL-5,IL-6,IL-8,IL-10,IL-17A,IL-1β,IL-12p70,tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),IFN-α,vascular endothelial growth factor(VEGF)and angiotensin II(ANG-II)of RV-ME patients were detected before treatment and 1 week,2 weeks and 1 month after treatment,and the best corrected vision acuity(BCVA)and central macular thickness(CMT)were measured.Results Compared with healthy control group,serum IL-2,IL-4,IL-6,IL-10,TNF-A,IL-17,IL-1B,IL-5,IL-12P70,IFN-A,IL-8 and VEGF levels were significantly increased in RVO-ME patients(P≤0.05).IL-8(OR=1.30,95%CI:1.01-1.68)and VEGF(OR=1.16,95%CI:1.00-1.35)are independent risk factors of RVO.In the RVO group,visual acuity was significantly improved after Ranibizumab treatment,the CMT was also significantly decreased,and the serum levels of IL-6 and IL-8 were significantly increased after anti-VEGF treatment.Conclusion Serum levels of inflammatory-related cytokines in RVO-ME patients were significantly increased compared with control.Intravitreal injection of Ranibizumab can significantly reduce serum VEGF levels,alleviate macular edema,and improve vision,but has no significant effect on serum inflammatory-related cytokines.After anti-VEGF treatment,serum levels of IL-6 and IL-8 in RVO-ME patients are increased,suggesting that intraocular injection of Ranibiizumab may increase the expression of inflammatory cytokines by inducing inflammatory reactions.