| Part1 Analysis of the Efficacy of Three Anti-VEGF Drugs in the Treatment in BRVO-ME and Changs of Inflammatory Factors in Human Aqueous HumorObjective:To compare the therapeutic effect on BRVO-ME of three anti-VEGF drugs:ranibizumab,conbercept and aflibercept.To analyze the changes of inflammatory cytokines in human aqueous humor during treatment.Methods:This is a prospective study.Methods from April 2017 to December 2018,81 patients(81 eyes)were selected in the people Hospital of Zhengzhou.After clinical slit lamp,OCT,fundus angiography and other specialized examinations,the patients were diagnosed as with superior temporal or sub-temporal branch retinal vein occlusion(BRVO).The related data of patients before treatment were recorded in detail,and the factors that may affect the study were excluded.60 patients(60 eyes)completed the follow-up.The patients were randomly divided into ranibizumab group,conbercept group,aflibercept group.The patients were randomly divided into ranibizumab group,conbercept group,the aflibercept group.All patients were followed up after the first treatment with slit lamp to examine the fundus,Best correct visual acuity was recorded by Log MAR.The thickness of fovea was recorded by OCT.After treatment,patients were tested for aqueous humor every month(before injection).The levels of VEGF,PIGF,MCP-1 and IL-6 in aqueous humor were detected by enzyme-linked immunosorbent assay(ELISA).When the follow-up patients had decreased vision or increased central macular thickness,Anti-VEGF drugs(ranibizumab,conbercept,aflibercept)will be injected again.The injection interval should be at least 4 weeks,FFA was performed at the first visit and 6 months after treatment to determine the condition of fundus ischemia.Results:1.The average number of injections was 3.38±0.59,3.15±0.36 and 3.07±0.24 times in ranibizumab group,conbercept group and aflibercept group respectively,There was no significant difference among the three groups;2.BCVA of all three anti-VEGF drugs were significantly improved at all follow-up times compared to baseline,Compared with baseline,the thickness of macular fovea of all three anti-VEGF drugs decreased significantly too.No significant difference was observed in the thickness of macular fovea and BCVA among the three groups.In the ranibizumab group,the best corrected visual acuity was 0.51±0.25,0.52±0.20,0.48±0.21,0.47±0.24,and the fovea thickness was 305.7±188.4 μm,289.0±201.5 μm,301.2±211.9μm,246±178.3 μm,respectively.Significantly lower than baseline.In the conbercept group,the best corrected visual acuity was 0.55±0.36,0.50±0.12,0.52±0.17,0.42±0.13,and the fovea thickness was 310.6±108.4 μ m,300.6±98.1 μ m,280.9±97.6 μm,261.4±93.2 μ m,respectively.Significantly lower than baseline.The best corrected visual acuity(BCVA)was 0.51±.29,0.49±0.26,0.49±0.22,0.5±0.15,and the fovea thickness was 298.2±104.2μm,280.4±109.5 μ m,289.5±91.2 μm,241.4±99.6 μm,respectively,in the arbacicept group.;3.All three VEGF drugs significantly reduced the VEGF,PIGF and IL-6 in the aqueous humor of patients with BRVO during follow-up compared to baseline.At 1 month,2 months and 3 months after treatment,VEGF concentration in aqueous humor of ranibizumab group was 41.4± 12.6 pg/ml,33.1± 13.7 pg/ml and 31.5±9.7 pg/ml.The concentration of PIGF was 5.1±1.3pg/ml,3.7±1.8pg/ml,3.6±1.3pg/ml,and the concentration of IL-6 was 25.1±9.2pg/ml,20.9±11.3pg/ml and 20.8±9.9pg/ml.The concentrations of MCP-1 were 1721.3±219.5pg/ml,1699.1±257.2pg/ml and 1655.5±227.9pg/ml.At 1 month,2 months and 3 months after treatment,VEGF concentration in aqueous humor of conbercept group was 46.2± 10.1pg/ml,31.8±9.9pg/ml,30.1±8.7pg/ml.The concentration of PIGF was 4.5±1.9pg/ml 3.2±1.3pg/ml,3.3± 1.4pg/ml,and the concentration of IL-6 was 23.4±12.2pg/ml,19.3±10.7pg/ml and 20.0± 11.8pg/ml.The concentrations of MCP-1 were 1877.3±230.2pg/ml,1769.7±334.1pg/ml,1693.5±234.6pg/ml.At the first month after the start of treatment,ranibizumab did not decrease MCP-1 in the aqueous humor of patients with BRVO,while 2 and 3 months after treatment,concentration of MCP-1 was decreased.No significant changes of MCP-1 were observed in conbercept and aflibercept groups during the first and second months of treatment.There was a statistically significant decrease in the third month.Conclusion:Lucentis,conbercept and aflibercept have good therapeutic effect on BRVO-ME.They can improve visual acuity and reduce macular edema.three anti-VEGF drugs had no significant difference in VA improvement,macular central macular thickness and injection times.The three anti-VEGF drugs can obviously inhibit the VEGF of aqueous humor in patients,and the inhibitory effect is the same.In addition to inhibiting VEGF,the three anti-VEGF drugs have anti-inflammatory effects,and The anti-inflammatory effect of ranibizumab seems to be stronger than that of the other two.Part 2 Efficacy of Dexamethasone Intravitreal Implant on BRVO-ME and the Level of Inflammatory Factors in Human Aqueous HumorObjective:To study the effect of dexamethasone intravitreal implant on BRVO-ME.Analysis of the changes of relevant cytokines in human aqueous humor during treatment and comparison of therapeutic effect with anti-VEGF drugsMethods:This is a prospective study.Methods from April 2017 to December 2018,33 patients(33 eyes)were selected in the people Hospital of Zhengzhou.After clinical slit lamp,OCT,fundus angiography and other specialized examinations,the patients were diagnosed as with superior temporal or sub-temporal retinal branch vein occlusion.The related data of patients before treatment were recorded in detail,and the factors that may affect the study were excluded.20 patients(20 eyes)completed the follow-up.All patients were followed up after the first treatment with slit lamp to examine the fundus,The best corrected visual acuity(BCVA)was calculated by log Mar.OCT was used to record the thickness of macular fovea of patients.After treatment,patients were tested for aqueous humor every month(before injection).The levels of VEGF,PIGF,MCP-1 and IL-6 in aqueous humor were detected by enzyme-linked immunosorbent assay(ELISA).When the follow-up patients had decreased vision or increased central macular thickness,dexamethasone intravitreal implant would be injected again.The injection interval should be at least 12 weeks.FFA was performed at the first visit and 6 months after treatment to determine the condition of fundus ischemia.Results1.One of the 20 patients who received dexamethasone intravitreal implant developed ocular hypertension requiring treatment,which was recovered without recurrence soon.Two patients developed significant cataract aggravation and eventually underwent cataract surgery.In dexamethasone group,the best corrected visual acuity was 0.61±0.45(p=0.031),0.55±0.38(p=0.008),0.59±0.35(p=0.037),0.52±0.39 respectively and the central macular thickness was 323.1±115.9μm(p=0.003),297.2±112.3 μm(p=0.001),290.5±85.2 μm,(p=0.000),280.7±109.1 μm(p=0.001)respectively at 1 month,2 months,3 months and 6 months after treatment,There was a significant decrease compared with the baseline.The concentrations of VEGF in aqueous humor were 115.2±12.6pg/ml,77.8±12.3pg/ml and 50.2±8.9pg/ml at 1 month,2 months and 3 months after treatment.The concentrations of PIGF and IL-6 were 5.5±1.8pg/inl,21.5±10.3pg/ml、4.1 ±0.9pg/ml,20.7±11.1pg/ml and 3.5±1.1pg/ml,18.1±9.7pg/ml,respectively.The concentrations of MCP-1 were 1496.3±133.9pg/ml,1369.1 ± 227.2pg/ml and 1363.6±247.8pg/ml.These indicators are significantly lower than the baseline;4.best corrected visual acuity and macular central macular thickness were not statistically different between dexamethasone intravitreal implant group and anti-VEGF drug during follow-up period;5.At the first month after treatment,the concentration of MCP-1 in aqueous humor of dexamethasone intravitreal implant group was lower than that of any of the three anti-VEGF groups.While the concentration of VEGF in aqueous humor of dexamethasone intravitreal implant group was higher than that of any of the three anti-VEGF groups.Conclusion:Dexamethasone intravitreal implant has good therapeutic effect on BRVO-ME,which can improve visual acuity and reduce macular edema.Dexamethasone intravitreal implants can significantly inhibit angiogenesis factors(VEGF and PIGF)and inflammatory factors(IL-6 and MCP-1)in patients with aqueous humor.Dexamethasone intravitreal implant showed stronger anti-inflammatory effect than ranibizumab,conbercept and aflibercept,but weaker anti VEGF effect. |
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