贝伐单抗联合曲安奈德与单独贝伐单抗玻璃体腔内注射治疗糖尿病性黄斑水肿的Meta分析

Comparison of clinical efficacy between bevacizumab combined with triamcinolne acetonide and versus bevacizumab via intraovitreal injection for diabetic macular edema： A Meta-analysis

背景临床上贝伐单抗（bevacizumab）和曲安奈德（TA）已广泛用于糖尿病性黄斑水肿（DME）的治疗，但由于二者单独治疗都存在一些弊端，因此一些学者尝试二者联合治疗，但其疗效存在争议。目的系统评价玻璃体腔内注射bevacizumab联合TA与单独注射bevacizumab治疗DME短期疗效的差异。方法用循证医学方法检索美国国立医学图书馆、荷兰医学文摘、循证医学数据库、中国期刊全文数据库中有关bevacizumab联合TA与单独注射bevacizumab治疗DME短期疗效的随机对照临床试验（RCTs）文献进行二次分析，遵循Cochrane Handbook 5．0质量评价原则评价纳入研究的质量。分析的疗效结局指标包括中央黄斑厚度（CMT）及最佳矫正视力（BCVA）变化，安全性评价指标为局部和全身不良事件。连续变量的计量资料采用加权均数差（WMD）作为合并效应量，计数资料采用相对危险度（RR）为疗效分析统计量，采用Cochrane协作网的Revman 5．0软件对效应合并量进行统计学处理。结果共纳入9篇RCTs文献，共665眼。Meta分析结果显示，治疗后12周、18周时bevacizumab联合TA组CMT改善程度优于单独注射bevacizumab组，差异均有统计学意义（WMD=-44．69，95％CI：25．27～64．11，P〈0．000001；WMD=-66．86，95％CI：40．67—93．05，P〈0．000001），而在治疗后6周及6个月时两组间差异无统计学意义（WMD=-15．40，95％CI：-4．04—34．85，P=0．12；WMD=-2．57，95％CI：-19．62—24．75，P=0．82）。治疗后6周时bevacizumab联合TA组BCVA（LogMAR值）的改善值优于单独注射bevacizumab组，差异有统计学意义（WMD=-0．04，95％CI：-0．08--0．00，P=0．05），而在治疗后12周、18周及6个月时两组间差异均无统计学意义（WMD=-0．04，95％CI：-0．12～0．05，P：0．36；WMD=-0．04，95％CI：-0．11～0．03，P=0．28；WMD=0．03，95％CI：-0．05～0．12，P=0．45）。两种治疗方式间术后一过性前房反应的发生率差异无统计学意义（RR=0．89，95％CI：0．49～1．60，P=0．70），bevacizumab联合TA组继发性高眼压的发生率为（30／327），单独注射bevacizumab组治疗眼未发生继发性高眼压。结论Bevacizumab联合TA玻璃体腔内注射治疗DME在减轻黄斑水肿方面疗效明显优于单独注射bevacizumab组，但两种方法在改善BCVA方面效果无明显差异。Bevacizumab联合TA玻璃体腔内注射后发生继发性高眼压的风险高于单独注射bevacizumab应用组，但用降眼压药物后眼压能够控制。

Background Bevacizumab and triamcinolone acetonide （TA） has been widely used in the treatment of diabetic macular edema （DME） clinically, but the effectiveness of both treatment has disadvantage. Therefore,some researchers try to combine bevacizumab with TA for the management of DME, but its efficacy is controversial. Objective This study was to evaluate the efficacy and safety of intraovitreal injection of bevacizumab combined with TA versus bevacizumab for DME. Methods The randomized controlled trials （RCTs） of bevacizumab combined with TA versus bevacizumab via intraovitreal injection for DME were searched from Pubmed, EMbase, Coehrane Library, CNKI. The methodological quality of the literature was evaluated according to evidence- based medicine （EBM） , and the quality of the RCTs was appraised based on the Cochrane Handbook for Systematic Reviews of Interventions Version 5.0. The outcome indicators including the change values of central macular thickness （CMT） and best-corrected visual acuity （BCVA） as well as the safety indicators including topical and system adverse response of RCTs were analyzed with Cochrane Collaboration＇ s software RevMan 5.0. Results Nine RCTs were included with 665 eyes. The decrease value of CMT was more remarkable in the bevacizumab combined with TA group than that of the only bevacizumab group 12 weeks and 18 weeks after intravitreal injection （WMD =-44. 69,95% CI： 25.27- 64. 11, P 〈 0. 000 001 ; WMD = - 66.86,95 % CI ： 40. 67 - 93.05, P 〈 0. 000 001 ）. However, no significant differences were found in the change value of CMT in 6 weeks and 6 months after injection between the two groups （WMD- - 15.40,95% CI： -4. 04-34. 85, P = 0. 12; WMD = -2.57,95% CI： - 19.62-24.75, P = 0. 82）. The improvement value of BCVA （LogMAR） in the bevacizumab combined with TA group was superior to that of the only bevacizumab group 6 weeks after injection （ WMD = -0.04,95% CI： -0. 08 --0. 00, P = 0.05 ） , but there were no significant differences between the two groups at 12weeks, 18 weeks and 6 months after treatment （WMD =-0.04, 95% CI：-0. 12-0.05,P= 0.36;WMD = -0.04,95% CI： -0. 11 -0. 03,P = 0. 28; WMD = 0. 03,95% （31： -0.05- 0. 12,P= 0.45 ）. The incidence rate of transient anterior response after injection was not significantly different between the two groups （ RR = 0. 89,95% CI： 0. 49 - 1.60, P = 0.70 ）. Secondary ocular hypertension after injection occurred in 30 eyes in the bevacizumab combined with TA group, but no hypertension was seen in the only bevacizumab group. Conclusions Compared with only bevacizumab, intravitreal injection of bevacizumab combined with TA has a better efficacy in improving CMT but no obvious dominant in increasing BCVA for early DME. Intravitreal injection of bevacizumab combined with TA seemingly has a higher risk of inducing controllable ocular hypertension than administration of only bevacizumab.