A Meta-analysis Comparing Intravitreal Ranibizumab And Intravitreal Dexamethasone Implant For Treating Macular Edema Secondary To Retinal Vein Occlusion

BACKGROUND:Retinal vein occlusion is a common retinal vascular disease resulting in permanent loss of vision despite available treatment options.Main vision impending complication of retinal vein occlusion is macular edema.Laser photocoagulation has been an established method for treating macular edema for many years but nowadays intravitreal injection of Anti-vascular endothelial growth factors like ranibizumab,aflibercept bevacizumab and pegaptanib sodium are the treatment of choice for macular edema from retinal vein occlusion.Intra-vitreal corticosteroids like triamcinolone acetonide and dexamethasone implant,are also being used to treat in some macular edema cases but with higher rates of side effects.However,ranibizumab has not been previously compared to dexamethasone implant efficacy.OBJECTIVE:The main aim of our meta-analysis is to compare the efficacy of intra vitreal ranibizumab and intra vitreal dexamethasone implant in treating macular edema secondary to retinal vein occlusion.METHOD:A systematic search of articles was conducted electronically up to the year 2018 in databases such as PubMed,Embase,Cochrane Library,Web of Science.Therapeutic effects were estimated using best-corrected visual acuity(BCVA),central retinal thickness(CRT)and intraocular pressure(IOP).All values were extracted as mean±standard deviation(SD).Weighted mean difference(WMD)and the corresponding 95%confidence intervals(95%CI)were used as a measure of effect size.Revman 5.3 was used for meta-analysis.RESULT:In total 10 studies with total number of 1274 RVO(BRVO and CRVO)patients were identified from literature search.One group was treated with intravitreal ranibizumab and other group was treated with intravitreal dexamethasone implant.The result of the meta-analysis showed the following.1.Best Corrected Visual Acuity(BCVA):For eyes with BRVO,ranibizumab improved BCVA(log MAR)significantly more than dexamethasone implant at 1months(WMD:0.10,95%CI:0.04-0.16,P=0.0004 and 3 months(WMD:0.06,95%CI:0.00-0.11,P=0.03)with no heterogeneity(At 1month P=.70,I~2=0%and At3months P=.89,I~2=0%).For eyes with CRVO,BCVA(ETDRS letters)difference was only significant at 6 months(WMD:9.51,95%CI:6.20-12.82,P<.00001)with no heterogeneity(P=.68,I~2=0%).For eyes with RVO,the effect of ranibizumab on BCVA over time was significantly better at 6 months than 3months(WMD:-0.02,95%CI:-0.03 to-0.00,P=0.03)without heterogeneity(P=.72,I~2=0%).BCVA was similar between 6 and 12 months following therapy.The effect of dexamethasone implant on BCVA over time between 3 and 6 months was also statistically significant,BCVA being worse at 6 months than 3 months.(WMD:0.16,95%CI:0.14-0.18,P<.00001)with no heterogeneity(P=.78,I~2=0%).BCVA progressively increased from 6 to 12 months following therapy.2.Central Retinal Thickness(CRT):For BRVO patients,ranibizumab reduced CRT significantly than dexamethasone implant at 3 months(WMD:-92.10,95%CI:-123.12 to-61.08,P<.00001)without heterogeneity(P=.31,I~2=1%)and at 6months(WMD:-67.02,95%CI:-133.43 to-20.60,P=0.0005;Figure 5C)with substantial heterogeneity(P=.01,I~2=72%).In CRVO patients ranibizumab reduced CRT significantly more than dexamethasone implant at 6 months(WMD:-158.83,95%CI:-270.08to-47.57,P=0.005 with heterogeneity(P=.009,I~2=66%).3.Intra Ocular Pressure(IOP):Eyes treated with ranibizumab had significantly lower IOP changes than eyes treated with dexamethasone implant at 3months(WMD:-1.94,95%CI:-2.46 to-1.42,P<.00001)and 6 months(WMD:-1.04,95%CI:-2.02to-0.05,P=0.04)after initiating therapy.None results had identifiable heterogeneities(3 months:P=.49,I~2=0%;6 months:P=.0002,I~2=83%).4.Number of Injections:The number of injections used in treatment of RVO eyes was statistically higher in ranibizumab group than in the dexamethasone implant group at 6 months(WMD:1.97,95%CI:1.38to-2.55,P<0.00001)and 12months(WMD:2.21,95%CI:1.33 to 3.09,P<.00001)after initiating therapy.None of these results had identifiable heterogeneities(6 month:P=0.21,I~2=37%;12 months:P<.00001,I~2=58%).CONCLUSION:Ranibizumab is more effective than dexamethasone for improving BCVA and decreasing CRT in patients with macular edema secondary to RVO.However,the number of ranibizumab injections used in patients with macular edema secondary to RVO was higher than in the dexamethasone implant group.Ranibizumab also has a lower risk of elevating IOP.Additionally,Ranibizumab is more effective for improving BCVA and reducing CRT in BRVO early than CRVO which took time.However,it should be noted that dexamethasone implant has also shown improvement BCVA and decreasing CRT in patients with macular edema secondary to RVO but for short period of time.So,in clinical practice,dexamethasone implant retreatment may be required earlier than 6 months to increase its efficacy.Similar efficacy of ranibizumab and dexamethasone implant is seen at 12 months in terms of improvement of BCVA and reduction of CRT in both CRVO and BRVO patients.However,care should be taken when using dexamethasone because of high possibility of elevated IOP than with ranibizumab therapy,as demonstrated by our meta-analysis.