| Part One Research on Choroidal Morphological Changes before and after anti-vascular endothelial growth factor therapy in Patients with Age-Related Macular Degeneration and Polypoidal Choroidal VasculopathySection ? Choroidal Morphological Changes before and after anti-vascular endothelial growth factor therapy in Patients with Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy by Swept-source Optical Coherence TomographyPurpose:To investigate the choroidal morphological characteristics and the changes after anti-vascular endothelial growth factor therapy in patients with polypoidal choroidal vasculopathy(PCV)and wet age-related macular degeneration(wAMD)by swept-source optical coherence tomography(SS-OCT).Design:A prospective,consecutive,case control studyMethod:35 eyes from 35 treatment-naive patients consisting of 11 eyes with wAMD and 24 eyes with PCV were studied from Aug.,2016 to Apr.,2017.22 eyes from 11 more than 50 years old healthy people were selected as control group.Experimental group was given Ranibizumab(Lucentis)via intraocular vitreous injecton every 4 to 6 weeks and last for 3 mouths after be diagnosed as FFA and ICGA.Experimental and controlled groups were both carried in SS-OCT before treatment and follow-up.We use the calipers in SS-OCT to measure central retina thickness(CRT),subfoveal choroidal thickness(SFCT)and choroidal maximal vessel diameter(MVD),and then analyze the difference and changes of all groups before and after therapy by logMAR VA,CRT,SFCT and MVD.Results:Before treatment,average logMAR VA in wAMD group and PCV group is 0.94±0.59 and 0.73±0.40 separately.In addition,the range in control group is 0.06±0.10.There is no difference between PCV and wAMD group.The average CRT in wAMD group is 318.73±101.83?m,in PCV group is 421.38±164.19?m and in control group is 185.48±20.30?m.The CRT in PCV group is significantly larger than that in wAMD 13 group.The average SFCT in wAMD group is 155.45±62.22?m,in PCV group is 305.23±98.5?m and in control group is 246.27±62.78?m.The SFCT of PCV group is significantly larger than that of controlled group.The SFCT in wAMD group is thinner than control group.The average MVD in wAMD group is 139.551±48.96?m,in PCV group is 209.09±68.91?m and in control group is 180.82±47.16?m.The MVD in PCV group is significantly larger than that in wAMD group.SFCT and MVD showed a positive correlation in all groups.After treatment,logMAR VA in PCV group is 0.47±0.28,which is improved significantly compared with before.LogMAR VA in wAMD group is 0.75±0.42,while there is no obvious improvement than that before treatment.CRT in PCV group is 268.06±129.31?m,and in wAMD group is 169.05±90.36?m,both declined significantly than before treatment.SFCT in PCV group is 269.77±93.38?m,while in wAMD group is 120.36±63.33?m,both of them deceased significantly than before treatment.MVD in PCV group is 184.68±63.95?m,while in wAMD group is 120.91±53.50pm,both of them declined significantly than before treatment.Conclusion:SFCT in PCV group is thicker than control group and wAMD group.SFCT in wAMD group is thinner than control group,and MVD in PCV group are thicker than wAMD gourp,so we can conclude that PCV and wAMD groups show significant differences in retina and choroidal topographic,and SFCT and MVD could be applied to distinguish PCV and wAMD,indicating they are capable to evaluate effection of therapy.Section ? Choroidal Thickness Changes in Patients with Age-Related Macular Degeneration and Subtype of Polypoidal Choroidal Vasculopathy by Swept-source Optical Coherence TomographyPurpose:To investigate the response of choroidal morphological characteristics and the changes of anti-vascular endothelial growth factor treatment in patients with thick type of polypoidal choroidal vasculopathy(Thick-PCV),thin type of polypoidal choroidal vasculopathy(Thin-PCV)and wet age-related macular degeneration(wAMD),in order to futher reveal the PCV is an independent disease or the subtype of PCV belongs to a form of wAMD.Method:Classify the PCV patients of section 1 into 2 subgroups according to the thickness of choroid,12 eyes with Thick-PCV(SFCT>=300?m)and 12 eyes with Thin-PCV(SFCT<300?m)were compared with wAMD of section 1 by analyzing the difference and changes logMAR VA,CRT,SFCT and MVD.Results:Before treatment,average logMAR VA in wAMD group is 0.94±0.59,in Thick-PCV group is 0.73±0.41 and in Thin-PCV group is 0.73±0.41.There is no significant difference among these three groups.The average CRT in wAMD group is 318.73±101.83?m,in Thick-PCV group is 338.96±105.81?m and in Thin-PCV group is 503.79±174.21?m.CRT in Thick-PCV group is significantly larger than that in wAMD and Thin-PCV group.There is no significant difference between Thin-PCV and wAMD.The average SFCT in wAMD group is 155.45±62.22?m,in Thick-PCV group is 369.00±87.73?m and in Thin-PCV group is 212.500±50.25?m.SFCT in Thick-PCV group is significantly larger than that in wAWD and Thin-PCV group.There is no significant difference between Thin-PCV and wAMD group.The average MVD in wAMD group is 139.55±48.96?m,in Thick-PCV group is 247.42±62.61?m and in Thin-PCV group is 153.00±47.32?m.MVD inThick-PCV is larger than that in wAMD group and Thin-PCV group(P<0.0001).There is no difference between Thin-PCV and wAMD groups.After treatment,logMAR VA in wAMD group is 0.75±0.42,while there is no obvious improvement compared to before treatment.LogMAR VA in Thick-PCV is 0.43±0.31,which improved significantly compared to before treatment.LogMAR VA in Thin-PCV is 0.50±0.26,which improved significantly compared to before treatment.CRT in wAMD group is 169.05±90.36?m,in Thick-PCV group is 203.12±69.73?m and Thin-PCV group is 333.00±144.57?m.All of them had improved significantly than before treatment.SFCT in wAMD group is 120.36±63.33?m,in Thick-PCV group is 337.17±67.61?m,and Thin-PCV group is 176.00±45.81?m.All of them had improved significantly than before treatment.MVD in wAMD group is 120.91±53.50?m,in Thick-PCV group is 222.33±58.57?m and Thin-PCV group is 129.25±39.35?m.wAMD and Thin-PCV had improved significantly than before treatment,but there is no obvious improvement in Thick-PCV compared to before treatment.Conclusion:SFCT and MVD in Thick-PCV thicker than Thin-PCV group and wAMD group,while there is no obvious difference than before treatment between Thin-PCV and wAMD in choroidal morphology.After anti-VEGF treatment,CRT,SFCT and MVD of the wAMD and Thin-PCV decline.No significant decrease in Thick-PCV MVD,it suggests that Thick-PCV is independent to other diseases.We speculate that Thick-PCV may be an independent disease,Thin-PCV may be a subtype of wAMD.Part ? Detection of Aqueous Humor and Serum Cytokine Levels Before and After Intravitreal Injection of Anti-VEGF Antibody in Patients with wet Age-Related Macular Degeneration and Polypoidal Choroidal VasculopathyPurpose:To investigate the difference and relationship among 45 cytokines from serum and aqueous humor of patients with polypoidal choroidal vasculopathy(PCV)or wet age-related macular degeneration(wAMD).Design:A prospective,consecutive,case control studyMethod:49 eyes from 49 treatment-naive patients consisting of 11 eyes with wAMD,24 eyes with PCV and 14 eyes with senile cataracts were studied from Aug.2016 to Apr.2017 in Peking Union Medical College Hospital.wAMD and PCV group were given Ranibizumab(Lucentis)via intraocular vitreous injecton every 4 to 6 weeks and last for 3 mouths.We extracted 10Oul aqueous humor and 2ml blood before the treatment.We applied luminex method to test 45 cytokines and growth factors,as follows:interleukin-1?(IL-1?),interleukin-1?(IL-1?),interleukin-1RA(IL-1RA),interleukin-2(IL-2),interleukin-4(IL-4),interleukin-5(IL-5),interleukin-6(IL-6),interleukin-7(IL-7),interleukin-8(IL-8),interleukin-9(IL-9),interleukin-10(IL-10),interleukin-13(IL-13),interleukin-15(IL-15),interleukin-17A(IL-17A),interleukin-18(IL-18),interleukin-21(IL-21),interleukin-22(IL-22),interleukin-23(IL-23),interleukin-27(IL-27),interleukin-31(IL-31),VEGF-A,VEGF-D,leukemia inhibitory factor(LIF),stromal-derived factor 1-?(SDF1-?),brain-derived neurotrophic factor(BDNF),interferon inducible protein 10(IP-10),hepatocyte Growth Factor(HGF),interleukin-12p70(IL-12p70),PIGF,basic fibroblast growth factor(FGF-basic),granulocyte macrophage colony stimulating Factor(GMCSF),epidermal growth factor(EGF),macrophage inflammatory protein 1?(MIP-1?),eotaxin,regulated upon activation normal T cell expressed and secreted(RANTES),platelet-derived growth factor-BB(PDGF-BB),MCP-1,nerve growth factor b(NGFb),stem cell factor(SCF),macrophage inflammatory protein-1?(MIP-1?),growth-related gene product ?(GRO?),interferon-?(IFN-?),interferon-a(IFNa),tumor necrosis factor a(TNFa)and tumor necrosis factor ?(TNF?).First,we compared concentration among PCV,wAMD and control group,and then compared the changes of concentration among different groups before and after anti-VEGF treatment.Results:Before treatment,in aqueous humor,the concentration of IL-8,IL-18,IL-21,IL-31,LIF,SDF1-?,FGF-basic,VEGF-A,VEGF-D in wAMD and PCV had increased significantly.And,the concentration of BDNF,HGF,IP-10,MCP-1,IL-13 in wAMD and PCV had decreased significantly.IL-17A has a significant decrease in wAMD group,but there is no significant change in PCV group.GMCSF,IL-12p70 has significant decrease in PCV group,but there is no significant change in wAMD group.The concentrations of IL-8 and IL-12p70 in wAMD group were significantly higher than PCV group.Before treatment,in serum,the concentration of EGF,Eotaxin,GMCSF,MCP-1,MIP-1p,IL-8,IL-21,IL-31,LIF,SDF1-?,VEGF-A,VEGF-D in wAMD and PCV had increased significantly.PDGF-BB has a significant decrease in wAMD and PCV group.And,FGF-basic has significant increase in wAMD,while there is no obvious change in PCV.HGF,IL-5 have a significant decrease in wAMD group,but there is no significant change in PCV group.IL-18 has obvious decrease in PCV.The concentration of LIF in wAMD group was significantly higher than this in group PCV.After treatment,in aqueous humor,the concentration of HGF,IL-12p70 in wAMD and PCV had increased significantly.The concentration of IL-18,IL-21,LIF,SDF1-?,VEGF-A,VEGF-D in wAMD and PCV group had decreased significantly.Second,the concentration of IL-8,IL-23,PDGF-BB only had decreased in wAMD group,but there is no significant change in PCV group.MCP-1,IL-13 only had increased in wAMD group,but there is no significant change in PCV group.After treatment,in serum,HGF concentration of HGF had increased significantly in wAMD and PCV group.And,the concentration of IL-21,LIF,SCF,SDF1-?,VEGF-A,VEGF-D had decreased significantly.IL-8 only had decreased in wAMD group,but there is no significant change in PCV group.IL-2,IL-6,NGF? only had decreased in PCV group,but there is no significant change in wAMD group.Compared with the controlled group,HGF,IP-10,MCP-1,IL-13,IL-31,LIF,SDF1-?,VEGF-A,VEGF-D have positive correlation with wAMD and PCV.GROa,IL-1?,IL-1?,IFN?,IFN?,IL-7,IL-9,IL-10,IL-22,TNF? and TNF? below detection limit.Conclusion:The concentrations of IL-8 and IL-12p70 in aqueous homour and LIF in serum are significantly higher in wAMD group than in PCV.It indicated that concentrations of IL-8,IL-12p70 and LIF may be used to identify wAMD and PCV.The changes in concentrations of VEGF-A,VEGF-D,IL-13,IL-31,LIF,SDF1-?,HGF,IP-10,MCP-1 in aqueous humour and MCP-1,PDGF-BB,VEGF-A,VEGF-D in serum can be used to identify wAMD and PCV with control group.The concentrations of VEGF-A and VEGF-D in aqueous and serum of wAMD and PCV patients were equally higher than control group,and shown no difference between them,suggesting that the changes after anti-VEGF therapy could be used to evaluate the treatment effect.Pro-angiogenesis factor and anti-angiogenesis cytokines,pro-inflammatory cytokines and anti-inflammatory cytokines all participated in the pathogenesis of wAMD and PCV.It is necessary for us to attach importance to the vital role of immunity dysfunction and chronic inflammation in the development and progression of wAMD and PCV.The functions of some cytokines in eyes were not so clear,The change trends is not consistent with past studies and systemic mechanism,further research is still needed. |
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