Efficacy and safety of intravitreal HLX04-O,an anti-VEGF monoclonal antibody,for the treatment of wet age-related macular degeneration

·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.

One-year outcomes of resveratrol supplement with aflibercept versus aflibercept monotherapy in wet agerelated macular degeneration

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.

Tissue factor with age-related macular degeneration

Wet age-related macular degeneration which incidence increases year by year is a blinding eye disease, but current clinical methods of treatment on this disease are limited and the outcome is not ideal. Recent studies have found abnormally high expression of tissue factors which are targets for the treatment of wet age-related macular degeneration to achieve a certain effect in the choroidal neovascularization. Related literatures are reviewed as following.

Mechanism of Mingjing Granules in Treating Wet Age-Related Macular Degeneration Based on Network Pharmacology and Experimental Verification

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.

An efficacy analysis of anti-vascular endothelial growth factor therapy for choroidal neovascularization secondary to multifocal choroiditis and comparison with wet age-related macular degeneration

Objective： To evaluate the effect of anti-vascular endothelial growth factor （VEGF） on juxtafoveal choroidal neovascularization （CNV） secondary to multifocal choroiditis （MFC） and wet age-related macular degeneration （AMD）. Methods： In this retrospective, comparative study, 20 unique eyes with CNV were divided into two groups： 10 patients affected by MFC and 10 patients diagnosed with wet AMD. They all received local intravitreal （Ivr） injections of ranibizumab, with 6 months of follow-up. Retreatment injections were performed based on findings suggestive of active neovascularization. Results： Significant improvements were observed in the juxtafoveal CNV lesions, and average central macular thickness decreased in both groups following the anti-VEGF therapy （P〈0.05）. The average number of injections used in MFC patients was 1.6, while three injections on average were used in wet AMD patients （Z=-2.844, P=0.009）. Best-corrected visual acuity was significantly improved in MFC patients after anti-VEGF therapy （P〈0.05）, and there was no significant difference in wet AMD patients between before anti-VEGF therapy and 6 months later （P〉0.05）. Conclusions： IVT ranibizumab resulted in good clinical outcomes for juxtafoveal CNV secondary to MFC and wet AMD, but the average number of injections used in MFC was fewer than that used in wet AMD over a 6-month observation period. Compared with the wet AMD group, visual acuity was obviously improved in the MFC group at 6 months.

Single-site Baseline and Short-term Outcomes of Clinical Characteristics and Life Quality Evaluation of Chinese Wet Age-related Macular Degeneration Patients in Routine Clinical Practice

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.

Impact of switching from ranibizumab to aflibercept on the number of intravitreous injection and follow up visit in wet AMD:results of real life ELU study

●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.