·AIM:To evaluate the efficacy and safety of HLX04-O,an investigational ophthalmic formulation of HLX04(bevacizumab biosimilar)for intravitreal injection,as a treatment for wet age-related macular degeneration(wAM...·AIM:To evaluate the efficacy and safety of HLX04-O,an investigational ophthalmic formulation of HLX04(bevacizumab biosimilar)for intravitreal injection,as a treatment for wet age-related macular degeneration(wAMD)in a phase 1/2 clinical trial(NCT04993352).·METHODS:Eligible patients with wAMD were enrolled to receive HLX04-O intravitreal injections at a dose of1.25 mg/0.05 mL every four weeks.Efficacy and adverse events were evaluated every month during study visits.·RESULTS:A 76-year-old male with wAMD in his left eye participated in the trial and completed six cycles of HLX04-O intravitreal injections.Changes were observed in macular center point thickness(baseline vs last study visit,437 vs 255μm)and best-corrected visual acuity letter score(baseline vs last study visit,36 vs 77)of the affected eye,which indicated an improvement in wAMD over treatment.No adverse events were reported by the data cutoff date.·CONCLUSION:HLX04-O at 1.25 mg/0.05 mL every four weeks is well tolerated in this patient,demonstrating promising safety and efficacy in wAMD treatment.Largescale studies are required to confirm the outcomes.展开更多
AIM:To determine the one-year outcomes of resveratrol oral supplement in patients suffering from wet age-related macular degeneration(AMD).METHODS:Fifty naïve and previously untreated patients suffering from wet ...AIM:To determine the one-year outcomes of resveratrol oral supplement in patients suffering from wet age-related macular degeneration(AMD).METHODS:Fifty naïve and previously untreated patients suffering from wet AMD,were randomly assigned in two subgroups of 25 patients each.All the participants were treated with 3 monthly intravitreal injections of 2.0 mg aflibercept(IAIs)followed by injections“according to need”,while in one group the patients also received daily two tablets of resveratrol oral supplement.Prior to treatment initiation,a complete ophthalmological examination,including best corrected visual acuity(BCVA)and contrast sensitivity evaluation,optical coherence tomography(OCT)scans,fundus autofluorescence(FAF),fluorescein angiography,indocyanine green angiography,and OCT angiography(OCTA),was performed to every participant,while all of them completed the Hospital Anxiety and Depression Scale(HADS)questionnaire,in order to assess their quality of life(QoL)status.The patients were assessed monthly for 1y with FAF,and OCT or OCTA;the main endpoints were the number IAIs,the changes in BCVA,in contrast sensitivity,and in patients’QoL status.RESULTS:No significant differences were present between the groups regarding the baseline demographic and clinical data.Over the 12-month period,a similar number of IAIs was applied in both groups(4.52±1.00 vs 4.28±0.90,P=0.38),while the rest of the clinical data also did not differ significantly after the completion of the study period.However,for HADS Depression(11.88±2.51 vs 8.28±1.54,P<0.001)and HADS Anxiety(11.92±2.52 vs 7.76±1.51,P<0.001)questionnaires values,the score was significantly better in patients who received resveratrol supplements.Moreover,a statistically significant difference was detected in the mean change from baseline values of contrast sensitivity(0.17±0.19 vs 0.35±0.24,P=0.005),HADS Depression(0.08±1.38 vs-3.88±1.48,P<0.001),and HADS Anxiety(0.36±1.98 vs-5.12±2.70,P<0.001)scores,in favour of the patients treated with resveratrol supplements.CONCLUSION:The resveratrol oral supplement is a complementary treatment in cases of wet AMD,highlighting its effectiveness in improving patients’QoL status.展开更多
Objective:To analyze the potential mechanism of Mingjing granules in the treatment of wet age-related macular degeneration(wAMD)based on the research methods of network pharmacology and molecular docking approach and ...Objective:To analyze the potential mechanism of Mingjing granules in the treatment of wet age-related macular degeneration(wAMD)based on the research methods of network pharmacology and molecular docking approach and to provide a new reference for the currently limited treatment of wAMD.Materials and Methods:We searched TCMSP,GeneCards,OMIM,PharmGkb,TTD,and DrugBank database to screen the main active ingredients of Mingjing granules and their therapeutic targets of wAMD.The network of active components and targets was constructed using Cytoscape3.6.1 software,which was also used for the topological analysis of target genes.The network of Protein-Protein Interactions(PPI)was mapped using the String platform.We also used R language to do the Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway for additional analysis.Molecular docking studies were finished by Chemoffice,Autodock,and Pymol.Finally,the efficacy of the Mingjing granules was examined in animal experiments,in which we used enzyme-linked immunosorbent assay to the contents of vascular endothelial growth factor(VEGF)and matrix metalloproteinase-9(MMP-9)levels in peripheral blood.Results:Active compounds,including quercetin,lignocaine,and kaempferol,were found.PPI network analysis showed that tumor necrosis factor(TNF),MMP-9,epidermal growth factor(EGF),prostaglandin-endoperoxide synthase 2(PTGS2),and caspase-3(CASP3)were related to both Mingjing granules and wAMD.GO and KEGG pathway analysis showed that these targets were mainly involving lipids and atherosclerosis,TNF,and interleukin-17(IL-17)signaling pathways.Docking studies suggested that quercetin and luteolin can fit in the binding pocket of four target proteins(CASP3,EGF,PTGS2,and TNF).In the vivo experiment,the Mingjing granules were found to be effective on the expression of VEGF and MMP-9 in peripheral blood.Conclusions:This study initially reveals the multi-constituent,multi-target,and multi-pathway mechanism of action of Mingjing granules in the treatment of wAMD and implies the inhibition of choroidal neovascularization may be related to the expression of VEGF and MMP-9.展开更多
Background：Age-related macular degeneration （AMD） is the leading cause of irreversible vision loss among the older population.In China,treatment of age-related ocular diseases is becoming a priority in eye care ser...Background：Age-related macular degeneration （AMD） is the leading cause of irreversible vision loss among the older population.In China,treatment of age-related ocular diseases is becoming a priority in eye care services.This study was to investigate the clinical characteristics and quality of life of Chinese patients with wet AMD and current treatment types,to evaluate short-term gains in different treatments,and to investigate associations between visual function and vision-related quality of life （VRQoL）.Methods：A prospective,observational,noninterventional study was conducted.Basic data were collected from patients with clinical diagnoses of wet AMD before clinical assessments at baseline.VRQoL was measured with the Chinese version of the National Eye Institute Visual Function Questionnaire-25 （NEI VFQ-25）.Correlations of the NEI VFQ-25 subscale scores with best-corrected visual acuity （BCVA） and between-group differences were analyzed.Results：A total of 80 wet AMD patients were enrolled,with the mean age of 68.40 years.About one-quarter ofwetAMD patients received intravitreal （IVT） ranibizumab treatment,and 67％ of them were treated on apro re nata basis.The visual acuity of patients treated with IVT ranibizumab at month 3 after treatment was significantly increased,whereas patients treated with traditional Chinese medicine achieved no significant improvement.Cronbach＇s α for the NEI VFQ-25 subscales ranged from 0.697 to 0.843.Eight subscale and overall composite scores were moderately correlated with the BCVA of the better-seeing eye.Significant differences in the overall NEI VFQ-25 scores and other subscales were observed between patients with BCVA in the better-seeing eye of less than 50 letters and the others.Conclusions：Patients treated with IVT ranibizumab experienced better vision improvement at short-term follow-up.The Chinese version of the NEI VFQ-25 is a valid and reliable tool for assessing the VRQoL of Chinese wet AMD patients.展开更多
●AIM:To study if one of the two molecules could lead to a lower number of follow up visits and intra-vitreous injection(IVI)with the same efficacy.●METHODS:ELU(or"elected"in French)study is a retrospective...●AIM:To study if one of the two molecules could lead to a lower number of follow up visits and intra-vitreous injection(IVI)with the same efficacy.●METHODS:ELU(or"elected"in French)study is a retrospective study conducted in real life in patients presenting suboptimal response after ranibizumab IVI(phase 1)and secondary switched to aflibercept(phase 2).The number of follow up visits and IVI were compared in both phases.Visual acuity(VA)evolution and"switching"reasons were secondary analyzed.●RESULTS:We retrospectively included data of 33 patients(38 eyes)with age-related macular degeneration(AMD;mean age:77±7.7 y).The number of monthly follow up visits[median(Q1;Q3)]:was significantly lower with aflibercept(phase 2),respectively 1.0(0.81;1.49)visits in phase 1,versus 0.79(0.67;0.86)visits in phase 2.The median number of monthly IVI also significantly decreased in phase 2,respectively 0.67(0.55;0.90)IVI in phase 1,versus 0.55(0.45;0.67)IVI in phase 2.The mean VA evolution(VA final-VA initial)was similar in both phases,(P>0.05).Whatever the reason for"switching"(loss of efficacy,tachyphylaxis,tolerance problems),there was no incidence on VA evolution over the time.●CONCLUSION:Our results show that switching from ranibizumab to aflibercept in"suboptimal"patients significantly reduce the number of follow up visits and IVI,with a comparable efficacy.This decrease in visit number could improve patients’quality of life and reduce surgical risk by reducing the number of injections.展开更多
目的:评价中药联合玻璃体腔内注射抗血管内皮生长因子(VEGF)与单纯抗VEGF药物治疗湿性年龄相关性黄斑变性(wAMD)的疗效。方法:检索中国知网、万方、维普、中国生物医学库CBM、Pubmed、Web of Science、Cochrane Library、Embase八大数据...目的:评价中药联合玻璃体腔内注射抗血管内皮生长因子(VEGF)与单纯抗VEGF药物治疗湿性年龄相关性黄斑变性(wAMD)的疗效。方法:检索中国知网、万方、维普、中国生物医学库CBM、Pubmed、Web of Science、Cochrane Library、Embase八大数据库,发表于建库以来至2022-04-20所有中英文文献。选取研究对象为wAMD患者,研究方法为比较中药联合抗VEGF药物与单纯抗VEGF药物治疗的临床随机对照实验研究。采用的结局指标为最佳矫正视力(BCVA),黄斑中心凹厚度(CMT)。采用传统Meta和网状Meta分析对数据进行统计。结果:在617项确定的研究中,39项纳入分析,涉及28种口服中药,2757名参与者。在提高BCVA方面,中药联合抗VEGF药物治疗优于单纯抗VEGF药物治疗(MD=0.07,95%CI:0.05~0.09)。生蒲黄汤(SPD)在治疗后1、2mo最佳,血府逐瘀胶囊(XZC)在治疗后3mo最佳。在降低CMT方面,中药联合治疗效果更好(MD=-25.32μm,95%CI:-30.06~-20.57)。当归明目汤(DMD)在治疗1mo后效果最好。补肾活血汤(BHD)在2mo时疗效最好。二陈二黄汤(EED)在3mo时疗效最好。结论:与单纯抗VEGF治疗相比,中药联合治疗可改善BCVA,降低CMT。然而,纳入的文献多为小样本、单中心、单盲随机对照试验,文献质量总体较低。展开更多
文摘·AIM:To evaluate the efficacy and safety of HLX04-O,an investigational ophthalmic formulation of HLX04(bevacizumab biosimilar)for intravitreal injection,as a treatment for wet age-related macular degeneration(wAMD)in a phase 1/2 clinical trial(NCT04993352).·METHODS:Eligible patients with wAMD were enrolled to receive HLX04-O intravitreal injections at a dose of1.25 mg/0.05 mL every four weeks.Efficacy and adverse events were evaluated every month during study visits.·RESULTS:A 76-year-old male with wAMD in his left eye participated in the trial and completed six cycles of HLX04-O intravitreal injections.Changes were observed in macular center point thickness(baseline vs last study visit,437 vs 255μm)and best-corrected visual acuity letter score(baseline vs last study visit,36 vs 77)of the affected eye,which indicated an improvement in wAMD over treatment.No adverse events were reported by the data cutoff date.·CONCLUSION:HLX04-O at 1.25 mg/0.05 mL every four weeks is well tolerated in this patient,demonstrating promising safety and efficacy in wAMD treatment.Largescale studies are required to confirm the outcomes.
基金Supported by unrestricted Grant from Laboratoires Thea^(■),France.
文摘AIM:To determine the one-year outcomes of resveratrol oral supplement in patients suffering from wet age-related macular degeneration(AMD).METHODS:Fifty naïve and previously untreated patients suffering from wet AMD,were randomly assigned in two subgroups of 25 patients each.All the participants were treated with 3 monthly intravitreal injections of 2.0 mg aflibercept(IAIs)followed by injections“according to need”,while in one group the patients also received daily two tablets of resveratrol oral supplement.Prior to treatment initiation,a complete ophthalmological examination,including best corrected visual acuity(BCVA)and contrast sensitivity evaluation,optical coherence tomography(OCT)scans,fundus autofluorescence(FAF),fluorescein angiography,indocyanine green angiography,and OCT angiography(OCTA),was performed to every participant,while all of them completed the Hospital Anxiety and Depression Scale(HADS)questionnaire,in order to assess their quality of life(QoL)status.The patients were assessed monthly for 1y with FAF,and OCT or OCTA;the main endpoints were the number IAIs,the changes in BCVA,in contrast sensitivity,and in patients’QoL status.RESULTS:No significant differences were present between the groups regarding the baseline demographic and clinical data.Over the 12-month period,a similar number of IAIs was applied in both groups(4.52±1.00 vs 4.28±0.90,P=0.38),while the rest of the clinical data also did not differ significantly after the completion of the study period.However,for HADS Depression(11.88±2.51 vs 8.28±1.54,P<0.001)and HADS Anxiety(11.92±2.52 vs 7.76±1.51,P<0.001)questionnaires values,the score was significantly better in patients who received resveratrol supplements.Moreover,a statistically significant difference was detected in the mean change from baseline values of contrast sensitivity(0.17±0.19 vs 0.35±0.24,P=0.005),HADS Depression(0.08±1.38 vs-3.88±1.48,P<0.001),and HADS Anxiety(0.36±1.98 vs-5.12±2.70,P<0.001)scores,in favour of the patients treated with resveratrol supplements.CONCLUSION:The resveratrol oral supplement is a complementary treatment in cases of wet AMD,highlighting its effectiveness in improving patients’QoL status.
基金funded by the National Natural Science Foundation of China(Grant No.81973912)Capital Health Research and Development of Special Fund(Grant No.2020-2-4183)+2 种基金Project commissioned by China Academy of Chinese Medical Sciences(Grant No.ZZ13-036-1)“Special Project of Director of Business Laboratory”China Center for Evidence-based Medicine of Traditional Chinese Medicine(Grant No.2020YJSZX-2)。
文摘Objective:To analyze the potential mechanism of Mingjing granules in the treatment of wet age-related macular degeneration(wAMD)based on the research methods of network pharmacology and molecular docking approach and to provide a new reference for the currently limited treatment of wAMD.Materials and Methods:We searched TCMSP,GeneCards,OMIM,PharmGkb,TTD,and DrugBank database to screen the main active ingredients of Mingjing granules and their therapeutic targets of wAMD.The network of active components and targets was constructed using Cytoscape3.6.1 software,which was also used for the topological analysis of target genes.The network of Protein-Protein Interactions(PPI)was mapped using the String platform.We also used R language to do the Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway for additional analysis.Molecular docking studies were finished by Chemoffice,Autodock,and Pymol.Finally,the efficacy of the Mingjing granules was examined in animal experiments,in which we used enzyme-linked immunosorbent assay to the contents of vascular endothelial growth factor(VEGF)and matrix metalloproteinase-9(MMP-9)levels in peripheral blood.Results:Active compounds,including quercetin,lignocaine,and kaempferol,were found.PPI network analysis showed that tumor necrosis factor(TNF),MMP-9,epidermal growth factor(EGF),prostaglandin-endoperoxide synthase 2(PTGS2),and caspase-3(CASP3)were related to both Mingjing granules and wAMD.GO and KEGG pathway analysis showed that these targets were mainly involving lipids and atherosclerosis,TNF,and interleukin-17(IL-17)signaling pathways.Docking studies suggested that quercetin and luteolin can fit in the binding pocket of four target proteins(CASP3,EGF,PTGS2,and TNF).In the vivo experiment,the Mingjing granules were found to be effective on the expression of VEGF and MMP-9 in peripheral blood.Conclusions:This study initially reveals the multi-constituent,multi-target,and multi-pathway mechanism of action of Mingjing granules in the treatment of wAMD and implies the inhibition of choroidal neovascularization may be related to the expression of VEGF and MMP-9.
文摘Background：Age-related macular degeneration （AMD） is the leading cause of irreversible vision loss among the older population.In China,treatment of age-related ocular diseases is becoming a priority in eye care services.This study was to investigate the clinical characteristics and quality of life of Chinese patients with wet AMD and current treatment types,to evaluate short-term gains in different treatments,and to investigate associations between visual function and vision-related quality of life （VRQoL）.Methods：A prospective,observational,noninterventional study was conducted.Basic data were collected from patients with clinical diagnoses of wet AMD before clinical assessments at baseline.VRQoL was measured with the Chinese version of the National Eye Institute Visual Function Questionnaire-25 （NEI VFQ-25）.Correlations of the NEI VFQ-25 subscale scores with best-corrected visual acuity （BCVA） and between-group differences were analyzed.Results：A total of 80 wet AMD patients were enrolled,with the mean age of 68.40 years.About one-quarter ofwetAMD patients received intravitreal （IVT） ranibizumab treatment,and 67％ of them were treated on apro re nata basis.The visual acuity of patients treated with IVT ranibizumab at month 3 after treatment was significantly increased,whereas patients treated with traditional Chinese medicine achieved no significant improvement.Cronbach＇s α for the NEI VFQ-25 subscales ranged from 0.697 to 0.843.Eight subscale and overall composite scores were moderately correlated with the BCVA of the better-seeing eye.Significant differences in the overall NEI VFQ-25 scores and other subscales were observed between patients with BCVA in the better-seeing eye of less than 50 letters and the others.Conclusions：Patients treated with IVT ranibizumab experienced better vision improvement at short-term follow-up.The Chinese version of the NEI VFQ-25 is a valid and reliable tool for assessing the VRQoL of Chinese wet AMD patients.
文摘●AIM:To study if one of the two molecules could lead to a lower number of follow up visits and intra-vitreous injection(IVI)with the same efficacy.●METHODS:ELU(or"elected"in French)study is a retrospective study conducted in real life in patients presenting suboptimal response after ranibizumab IVI(phase 1)and secondary switched to aflibercept(phase 2).The number of follow up visits and IVI were compared in both phases.Visual acuity(VA)evolution and"switching"reasons were secondary analyzed.●RESULTS:We retrospectively included data of 33 patients(38 eyes)with age-related macular degeneration(AMD;mean age:77±7.7 y).The number of monthly follow up visits[median(Q1;Q3)]:was significantly lower with aflibercept(phase 2),respectively 1.0(0.81;1.49)visits in phase 1,versus 0.79(0.67;0.86)visits in phase 2.The median number of monthly IVI also significantly decreased in phase 2,respectively 0.67(0.55;0.90)IVI in phase 1,versus 0.55(0.45;0.67)IVI in phase 2.The mean VA evolution(VA final-VA initial)was similar in both phases,(P>0.05).Whatever the reason for"switching"(loss of efficacy,tachyphylaxis,tolerance problems),there was no incidence on VA evolution over the time.●CONCLUSION:Our results show that switching from ranibizumab to aflibercept in"suboptimal"patients significantly reduce the number of follow up visits and IVI,with a comparable efficacy.This decrease in visit number could improve patients’quality of life and reduce surgical risk by reducing the number of injections.
文摘目的:评价中药联合玻璃体腔内注射抗血管内皮生长因子(VEGF)与单纯抗VEGF药物治疗湿性年龄相关性黄斑变性(wAMD)的疗效。方法:检索中国知网、万方、维普、中国生物医学库CBM、Pubmed、Web of Science、Cochrane Library、Embase八大数据库,发表于建库以来至2022-04-20所有中英文文献。选取研究对象为wAMD患者,研究方法为比较中药联合抗VEGF药物与单纯抗VEGF药物治疗的临床随机对照实验研究。采用的结局指标为最佳矫正视力(BCVA),黄斑中心凹厚度(CMT)。采用传统Meta和网状Meta分析对数据进行统计。结果:在617项确定的研究中,39项纳入分析,涉及28种口服中药,2757名参与者。在提高BCVA方面,中药联合抗VEGF药物治疗优于单纯抗VEGF药物治疗(MD=0.07,95%CI:0.05~0.09)。生蒲黄汤(SPD)在治疗后1、2mo最佳,血府逐瘀胶囊(XZC)在治疗后3mo最佳。在降低CMT方面,中药联合治疗效果更好(MD=-25.32μm,95%CI:-30.06~-20.57)。当归明目汤(DMD)在治疗1mo后效果最好。补肾活血汤(BHD)在2mo时疗效最好。二陈二黄汤(EED)在3mo时疗效最好。结论:与单纯抗VEGF治疗相比,中药联合治疗可改善BCVA,降低CMT。然而,纳入的文献多为小样本、单中心、单盲随机对照试验,文献质量总体较低。
