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玻璃体腔注射地塞米松植入物与抗血管内皮生长因子药物治疗视网膜静脉阻塞并发黄斑水肿比较的Meta分析

许妮,  刘从威,  董方田

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文章导航 > 协和医学杂志  > 2016 >  7(3): 168-175
许妮, 刘从威, 董方田. 玻璃体腔注射地塞米松植入物与抗血管内皮生长因子药物治疗视网膜静脉阻塞并发黄斑水肿比较的Meta分析[J]. 协和医学杂志, 2016, 7(3): 168-175. doi: 10.3969/j.issn.1674-9081.2016.03.002
引用本文: 许妮, 刘从威, 董方田. 玻璃体腔注射地塞米松植入物与抗血管内皮生长因子药物治疗视网膜静脉阻塞并发黄斑水肿比较的Meta分析[J]. 协和医学杂志, 2016, 7(3): 168-175. doi: 10.3969/j.issn.1674-9081.2016.03.002
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Ni XU, Cong-wei LIU, Fang-tian DONG. Dexamethasone Intravitreal Implant Compared with Anti-vascular Endothelial Growth Factor Injection for Macular Edema Secondary to Retinal Vein Occlusion: a Meta-analysis[J]. Medical Journal of Peking Union Medical College Hospital, 2016, 7(3): 168-175. doi: 10.3969/j.issn.1674-9081.2016.03.002
Citation: Ni XU, Cong-wei LIU, Fang-tian DONG. Dexamethasone Intravitreal Implant Compared with Anti-vascular Endothelial Growth Factor Injection for Macular Edema Secondary to Retinal Vein Occlusion: a Meta-analysis[J]. Medical Journal of Peking Union Medical College Hospital, 2016, 7(3): 168-175. doi: 10.3969/j.issn.1674-9081.2016.03.002
shu

玻璃体腔注射地塞米松植入物与抗血管内皮生长因子药物治疗视网膜静脉阻塞并发黄斑水肿比较的Meta分析

doi: 10.3969/j.issn.1674-9081.2016.03.002
  • 1.

    中国医学科学院 北京协和医学院 北京协和医院眼科, 北京 100730

  • 2.

    中南大学湘雅二医院骨科, 长沙 410011

基金项目: 

国家自然科学基金 30973256

详细信息
    通讯作者:

    董方田  电话:010-69156360, E-mail:d_fangtian@sina.com

  • 中图分类号: R774.1

Dexamethasone Intravitreal Implant Compared with Anti-vascular Endothelial Growth Factor Injection for Macular Edema Secondary to Retinal Vein Occlusion: a Meta-analysis

  • 1.

    Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China

  • 2.

    Department of Orthopedics, the Second Xiangya Hospital of Central South University, Changsha 410011, China

More Information

    摘要
  • 摘要:   目的  比较玻璃体腔注射地塞米松植入物(dexamethasone implant, DEX)与抗血管内皮生长因子(anti-vascular epithelial growth factor, anti-VEGF)药物在治疗视网膜静脉阻塞(retinal vein occlusion, RVO)并发黄斑水肿(macular edema, ME)时的有效性及安全性。  方法  以"retinal vein occlusion"、"macular edema"、"anti-VEGF"、"pegaptanib"、"Macugen"、"bevacizumab"、"Avastin"、"ranibizumab"、"Lucentis"、"aflibercept"、"Trap-eye"、"Ozurdex"、"dexamethasone invitreal implant"、"clinical trial"为关键词, 检索1948年1月至2015年6月外文生物医学数据库Cochrane图书馆、Pubmed、EMBASE、Ovid Medline及ClinicalTrials.gov关于两种药物对RVO并发ME比较治疗的临床试验。采用Cochrane或Newcastle-Ottawa scale评价方法评价所纳入研究的文献质量, 并提取有效数据后用RevMan 5.3软件进行Meta分析。  结果  随访1个月时, 玻璃体腔注射DEX与anti-VEGF治疗前后最佳矫正视力差值的差异无统计学意义[MD=0.04糖尿病视网膜病变早期治疗研究字母视力表(Early Treatment Diabetic Retinopathy Study, ETDRS)字母, 95% CI:-2.07~2.15 ETDRS字母, P=0.97]。但在随访3、4、6个月时, anti-VEGF药物能获得更好的治疗前后最佳矫正视力差值, 两组间差异有统计学意义(MD=-6.98, -12.18, -11.84 ETDRS字母, 95% CI:-10.39~-3.58, -20.34~-4.03, -19.66~-4.02 ETDRS字母, P < 0.0001, P=0.003, P=0.003)。随访6个月时, anti-VEGF药物较DEX能更有效地降低中央视网膜厚度变化值(MD=135.86 μm, 95% CI:57.07~214.64 μm, P=0.0007)。anti-VEGF组眼压升高的人数比例也较DEX组低(OR=3.54, 95% CI:1.64~7.66, P=0.001)。  结论  在治疗RVO引起的ME时, anti-VEGF药物较DEX可更有效改善最佳矫正视力、减少ME, 同时对眼内压的影响较小, 其有效性及安全性均优于DEX。
    Abstract:   Objective  To compare the efficacy and safety of intravitreal injections of dexamethasone implants (DEX) with anti-vascular endothelial growth factor (VEGF) in the treatment of macular edema (ME)secondary to retinal vein occlusion (RVO).  Methods  The databases of Cochrane Library, PubMed, EMBASE, Ovid Medline, and ClinicalTrial.gov between January 1948 and June 2015 were searched for studies comparing DEX with anti-VEGF for the treatment of ME caused by RVO with key words "retinal vein occlusion", "macular edema", "anti-VEGF", "pegaptanib", "Macugen", "bevacizumab", "Avastin", "ranibizumab", "Lucentis", "aflibercept", "Trap-eye", "Ozurdex", "dexamethasone invitreal implant", and "clinical trial". We evaluated the quality of selected studies using Cochrane or Newcastle-Ottawa scale. Data were extracted and analyzed by RevMan 5.3 for Meta-analysis.  Results  The mean difference in the mean changes of best corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Study (ETDRS) letters comparing DEX with anti-VEGF was 0.04[95% confidence interval (CI):-2.07~2.15; P=0.97] at 1 month, -6.98(95% CI:-10.39~-3.58; P < 0.0001) at 3 months, -12.18(95% CI:-20.34~-4.03; P=0.003) at 4 months, and -11.84(95% CI:-19.66~-4.02; P=0.003) at 6 months. A greater reduction of central retinal thickness at 6 months was observed in the anti-VEGF group than in the DEX group (mean difference 135.86 μm; 95% CI:57.07~214.64 μm; P=0.0007). The incidence of intraocular pressure increase in the DEX group was significantly higher than that in the anti-VEGF group (OR=3.54, 95% CI:1.64~7.66, P=0.001).  Conclusions  Anti-VEGF showed better effect than DEX in improving BCVA, reducing ME, and less influence on intraocular pressure for ME secondary to RVO. Therefore, anti-VEGF may have higher efficacy and safety than DEX for this condition.
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  • 图  1  DEX组与anti-VEGF组最佳矫正视力比较的Meta分析结果

    DEX、anti-VEGF：同表 1

    下载: 全尺寸图片 幻灯片

    图  2  DEX组与anti-VEGF组视力提高≥15个ETDRS字母人数比例的Meta分析结果

    DEX、anti-VEGF：同表 1；ETDRS：同表 2

    下载: 全尺寸图片 幻灯片

    图  3  DEX组与anti-VEGF组视力下降≥15个ETDRS字母人数比例的Meta分析结果

    DEX、anti-VEGF：同表 1；ETDRS：同表 2

    下载: 全尺寸图片 幻灯片

    图  4  DEX组与anti-VEGF组中央视网膜厚度变化值的Meta分析结果

    DEX、anti-VEGF：同表 1

    下载: 全尺寸图片 幻灯片

    图  5  DEX组与anti-VEGF组眼内压升高的人数比例的Meta分析结果

    DEX、anti-VEGF：同表 1

    下载: 全尺寸图片 幻灯片

    表  1  纳入Meta分析研究的基本特征

    研究 研究设计 时间及国家 RVO类型 随访终点 研究眼数(DEX组/ anti-VEGF组)
    Guignier等[19] 前瞻性预期试验 2013年，法国 BRVO 6个月 11/ 8
    Chiquet等[20] 回顾性研究 2015年，法国 CRVO/BRVO 12个月 38/64
    COMRADE-B[21] 随机对照试验 2014年，美国、德国 BRVO 6个月 118/126
    COMRADE-C[22] 随机对照试验 2015年，美国、德国 CRVO 6个月 119/124
    研究 患者年龄(x±s, 岁) 患者性别(男/女) 纳入患者特征
    DEX组 anti-VEGF组 DEX组 anti-VEGF组
    Guignier等[19] 67 ±7 61 ±12 7/4 3/5 (1)RVO并发ME≤3个月；(2)视力范围20/400~20/32；(3)中央视网膜厚度≥350 μm
    Chiquet等[20] 69 ±12 70 ±11 14/24 36/28 (1) logMAR视力表视力≤+0.30；(2)中央视网膜厚度≥250 μm(TD-OCT)或295 μm(SD-OCT)
    COMRADE-B[21] 65.6±10.0 65.7±10.9 61/57 50/76 (1)年龄＞18岁；(2)RVO持续时间≤6个月；(3)视力范围20/400~20/40；(4)中央视网膜厚度≥250 μm
    COMRADE-C[22] 66.9±12.4 65.3±11.4 73/46 72/52 (1)年龄＞18岁；(2)RVO持续时间≤6个月；(3)视力范围20/400~20/40；(4)中央视网膜厚度≥250 μm
    RVO：视网膜静脉阻塞；BRVO：视网膜分支静脉阻塞；CRVO：中央视网膜静脉阻塞；DEX：地塞米松植入物；anti-VEGF：抗血管内皮生长因子；ME：黄斑水肿；OCT：光学相干断层扫描；TD-OCT：时域OCT；SD-OCT：谱域OCT
    下载: 导出CSV

    表  2  纳入Meta分析研究中各组用药及处理方案

    研究 组别 用药 处理方案
    Guignier等[19] DEX组(n=8) IVD 700 μg 患者接受1次IVD注射，当中央视网膜厚度≥50 μm或视力下降≥5个ETDRS字母时进行重复注射
    anti-VEGF组(n=11) IVB 1.25 mg 患者接受每月1次、共3次的IVB注射, 当中央视网膜厚度≥50 μm或视力下降≥5个ETDRS字母时进行重复注射
    Chiquet等[20] DEX组(n=38) IVD 700 μg 患者至少4个月后再次重新注射IVD
    anti-VEGF组(n=64) IVR 0.5 mg或IVB 患者在前3个月接受3次IVR或IVB注射
    COMRADE-B[21] DEX组(n=118) IVD 700 μg 700 μg长效持续释放激素IVD注射至玻璃体腔，维持6个月
    anti-VEGF组(n=126) IVR 0.5 mg 注射浓度为0.5 mg/0.05 ml，6个月内每月注射1次
    COMRADE-C[22] DEX组(n=119) IVD 700 μg 700 μg长效持续释放激素IVD注射至玻璃体腔，维持6个月
    anti-VEGF组(n=124) IVR 0.5 mg 注射浓度为0.5 mg/0.05 ml，6个月内每月注射1次
    DEX、anti-VEGF：同表 1；IVD：玻璃体腔注射地塞米松；IVB：玻璃体腔注射贝伐单抗；IVR：玻璃体腔注射雷珠单抗；ETDRS：糖尿病视网膜病变早期治疗研究字母视力表
    下载: 导出CSV

    表  3  COMRADE-B [21]及COMRADE-C [22]研究中的眼部不良反应

    眼部不良反应 COMRADE-B研究(NCT 01396057) COMRADE-C研究(NCT01396083)
    IVR IVD IVR IVD
    眼部不适感 5/126(3.97%) 3/118(2.54%) 6/124(4.84%) 8/119(6.72%)
    结膜下出血 12/126(9.52%) 14/118(11.86%) 16/124(12.9%) 13/119(10.92%)
    眼部刺激征 3/126(2.38%) 6/118(5.08%) 4/124(3.23%) 3/119(2.52%)
    眼痛 9/126(7.14%) 13/118(11.02%) 15/124(12.10%) 14/119(11.76%)
    眼部异物感 8/126(6.35%) 4/118(3.39%) 6/124(4.84%) 6/119(5.04%)
    青光眼 1/126(0.79%) 3/118(2.54%) 0/124(0.00%) 5/119(4.20%)
    流泪增加 7/126(5.56%) 4/118(3.39%) 6/124(4.84%) 8/119(6.72%)
    黄斑水肿 4/126(3.17%) 7/118(5.93%) 13/124(10.48%) 19/119(15.97%)
    眼部充血 16/126(12.70%) 21/118(17.80%) 14/124(11.29%) 15/119(12.61%)
    高眼压 0/126(0) 6/118(5.08%) 0/124(0) 6/119(5.04%)
    视网膜渗出 7/126(5.56%) 3/118(2.54%) 2/124(1.61%) 4/119(3.36%)
    视力下降 4/126(3.17%) 6/118(5.08%) 8/124(6.45%) 19/119(15.97%)
    玻璃体后脱离 3/126(2.38%) 7/118(5.93%) 5/124(4.03%) 3/119(2.52%)
    玻璃体浮游体 3/126(2.38%) 3/118(2.54%) 5/124(4.03%) 11/119(9.24%)
    白内障 1/126(0.79%) 4/118(3.39%) N/A N/A
    IVR、IVD：同表 2；N/A：无
    下载: 导出CSV
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  • 收稿日期:  2016-01-13
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