许妮;刘从威;董方田;
XU Ni;LIU Cong-wei;DONG Fang-tian;Department of Ophthalmology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences &Peking Union Medical College;Department of Orthopedics,the Second Xiangya Hospital of Central South University;

• 1:中国医学科学院北京协和医学院北京协和医院眼科
• 2:中南大学湘雅二医院骨科

摘要(Abstract)：

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Clinical Trials.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Rev Man 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:-2.07~2.15ETDRS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=135.86μm,95%CI:57.07~214.64μm,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。
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,Pub Med,EMBASE,Ovid Medline,and Clinical Trial. 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 AntiVEGF 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.

关键词(KeyWords)： 视网膜静脉阻塞;黄斑水肿;玻璃体腔地塞米松植入物;抗血管内皮生长因子药物;Meta分析
retinal vein occlusion;macular edema;dexamethasone intravitreal implant;anti-vascular endothelial growth fac tor;Meta-analysis

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金(30973256)

作者(Author): 许妮;刘从威;董方田;
XU Ni;LIU Cong-wei;DONG Fang-tian;Department of Ophthalmology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences &Peking Union Medical College;Department of Orthopedics,the Second Xiangya Hospital of Central South University;

Email:

DOI:

参考文献(References)：

• [1]Rogers S,Mc Intosh RL,Cheung N,et al.The prevalence of retinal vein occlusion:pooled data from population studies from the United States,Europe,Asia,and Australia[J].Ophthalmology,2010,117:313-319.e311.
• [2]Cekic O,Cakir M,Yazici AT,et al.A comparison of three different intravitreal treatment modalities of macular edema due to branch retinal vein occlusion[J].Curr Eye Res,2010,35:925-929.
• [3]Demir M,Dirim B,Acar Z,et al.Comparison of the effects of intravitreal bevacizumab and triamcinolone acetonide in the treatment of macular edema secondary to central retinal vein occlusion[J].Indian J Ophthalmol,2014,62:279-283.
• [4]Ding X,Li J,Hu X,et al.Prospective study of intravitreal triamcinolone acetonide versus bevacizumab for macular edema secondary to central retinal vein occlusion[J].Retina,2011,31:838-845.
• [5]Fan C,Wang Y,Ji Q,et al.Comparison of clinical efficacy of intravitreal ranibizumab with and without triamcinolone acetonide in macular edema secondary to central retinal vein occlusion[J].Curr Eye Res,2014,39:938-943.
• [6]Figueroa MS,Ruiz Moreno JM.BRAVO and CRUISE:ranibizumab for the treatment of macular edema secondary to retinalvein occlusion[J].Arch Soc Esp Oftalmol,2012,87 Suppl1:46-53.
• [7]Higashiyama T,Sawada O,Kakinoki M,et al.Prospective comparisons of intravitreal injections of triamcinolone acetonide and bevacizumab for macular oedema due to branch retinal vein occlusion[J].Acta Ophthalmol,2013,91:318-324.
• [8]Lee K,Jung H,Sohn J.Comparison of injection of intravitreal drugs with standard care in macular edema secondary to branch retinal vein occlusion[J].Korean J Ophthalmol,2014,28:19-25.
• [9]Bezatis A,Spital G,Hohn F,et al.Functional and anatomical results after a single intravitreal Ozurdex injection in retinal vein occlusion:a 6-month follow-up—the SOLO study[J].Acta Ophthalmol,2013,91:e340-e347.
• [10]Ferrini W,Ambresin A.Intravitreal dexamethasone implant for the treatment of macular edema after retinal vein occlusion in a clinical setting[J].Klin Monbl Augenheilkd,2013,230:423-426.
• [11]Haller JA,Bandello F,Belfort R Jr,et al.Randomized,sham-controlled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion[J].Ophthalmology,2010,117:1134-1146.e3.
• [12]Haller JA,Bandello F,Belfort R Jr,et al.Dexamethasone intravitreal implant in patients with macular edema related to branch or central retinal vein occlusion twelve-month study results[J].Ophthalmology,2011,118:2453-2460.
• [13]Kuppermann BD,Haller JA,Bandello F,et al.Onset and duration of visual acuity improvement after dexamethasone intravitreal implant in eyes with macular edema due to retinal vein occlusion[J].Retina,2014,34:1743-1749.
• [14]Schmitz K,Maier M,Clemens CR,et al.Reliability and safety of intravitreal Ozurdex injections.The ZERO study[J].Ophthalmologe,2014,111:44-52.
• [15]Yeh WS,Haller JA,Lanzetta P,et al.Effect of the duration of macular edema on clinical outcomes in retinal vein occlusion treated with dexamethasone intravitreal implant[J].Ophthalmology,2012,119:1190-1198.
• [16]Higgins JP,Green S.Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0[updated March,2011][M/OL].The Cochrane Collaboration,2011.http://handbook.cochrane.org.
• [17]Wells G,Shea B,O'Connell D,et al.The Newcastle-Ottawa Scale(NOS)for assessing the quality of nonrandomised studies in meta analyses[EB/OL].http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.
• [18]Moher D,Liberati A,Tetzlaff J,et al.Preferred reporting items for systematic reviews and meta-analyses:the PRISMA statement[J].J Clin Epidemiol,2009,62:1006-1012.
• [19]Guignier B,Subilia-Guignier A,Fournier I,et al.Prospective pilot study:efficacy of intravitreal dexamethasone and bevacizumab injections in the treatment of macular oedema associated with branch retinal vein occlusion[J].Ophthalmologica,2013,230:43-49.
• [20]Chiquet C,Dupuy C,Bron AM,et al.Intravitreal dexamethasone implant versus anti-VEGF injection for treatment-naive patients with retinal vein occlusion and macular edema:a12-month follow-up study[J].Graefes Arch Clin Exp Ophthalmol,2015,253:2095-2102.
• [21]Novartis(Novartis Pharmaceuticals).Efficacy and Safety of Ranibizumab Intravitreal Injections Versus Dexamethasone Intravitreal Implant in Patients With Branch Retinal Vein Occlusion(BRVO)(COMRADE-B).NCT01396057[EB/OL].(2014-08-04)https://clinicaltrials.gov/ct2/show/NCT01396057?term=NCT01396057&rank=1.
• [22]Novartis(Novartis Pharmaceuticals).Efficacy and Safety of Ranibizumab Intravitreal Injections Versus Dexamethasone Intravitreal Implant in Patients With Central Retinal Vein Occlusion(CRVO)(COMRADE-C).NCT01396083[EB/OL].(2015-02-25)https://clinicaltrials.gov/ct2/show/NCT01396083?term=NCT01396083&rank=1.
• [23]Argon laser photocoagulation for macular edema in branch vein occlusion.The Branch Vein Occlusion Study Group[J].Am J Ophthalmol,1984,98:271-282.
• [24]Central Vein Occlusion Study Group M.Evaluation of grid pattern photocoagulation for macular edema in central vein occlusion.The Central Vein Occlusion Study Group M report[J].Ophthalmology,1995,102:1425-1433.
• [25]Hahn P,Fekrat S.Best practices for treatment of retinal vein occlusion[J].Curr Opin Ophthalmol,2012,23:175-181.
• [26]Edelman JL.Differentiation introcular glucocorticoids[J].Ophthalmologica,2010,224(Suppl 1):25-30.
• [27]Campochiaro PA,Brown DM,Awh CC,et al.Sustained benefits from ranibizumab for macular edema following central retinal vein occlusion:twelve-month outcomes of a phase III study[J].Ophthalmology,2011,118:2041-2049.
• [28]Brown DM,Heier JS,Clark WL,et al.Intravitreal aflibercept injection for macular edema secondary to central retinal vein occlusion:1-year results from the phase 3 COPERNICUS study[J].Am J Ophthalmol,2013,155:429-437.
• [29]Korobelnik JF,Holz FG,Roider J,et al.Intravitreal aflibercept injection for macular edema resulting from central retinal vein occlusion:one-year results of the phase 3 GALILEO study[J].Ophthalmology,2014,121:202-208.
• [30]Fialho SL,Bahar-Cohen F,Silva-Cunha A.Dexamethasone loaded poly(epsiloncaprolactone)intravitreal implnats:a pilot study[J].Eur J Pharm Biopharm,2008,68:637-646.
• [31]Bakri SJ,Omar AF,Iezzi R,et al.Evaluation of multiple dexamethasone intravitreal implants in patients with macular edma associated with retinal vein occlusion[J].Retina,2016,36:552-557.