Existing evidence suggests residential greenness is beneficial to human,while no research to date explored the associations of greenness with age-related macular degeneration(AMD).To evaluate the association of greenn...Existing evidence suggests residential greenness is beneficial to human,while no research to date explored the associations of greenness with age-related macular degeneration(AMD).To evaluate the association of greenness with AMD,modification and mediation effect of air pollution,we conducted this prospective study.We con-structed weighted quantile sum(WQS)index as co-exposure to nitrogen oxides(NO_(x)),particulate matter<2.5μm(PM_(2.5)),particulate matter<10μm(PM10).Stratified Cox regression models were applied to test the effect of exposure.Effect modification of air pollution was assessed.Stratified Cox models through the indirect method and Aalen additive risk models were used in mediation analysis.Over median follow-up of 11.67 years,4596 AMD events were ascertained.Hazard ratios(HRs)and 95%confidence intervals(95%CIs)of incident AMD for pollution per interquartile range(IQR)increment were 1.10(1.04–1.16)for nitrogen dioxide(NO_(2)),1.09(1.03–1.15)for NO_(x),1.14(1.05–1.24)for PM_(2.5),1.13(1.05–1.21)for PM10.The HR(95%CI)of AMD associated with greenness 1000 m buffer per IQR increment was 0.91(0.86–0.97),300 m buffer was 0.94(0.89–0.99).The as-sociation between greenness 1000 m and AMD was 28.59%,44.77%,35.59%,32.31%and 27.08%mediated by the decreased WQS index,NO_(2),NO_(x),PM_(2.5) and PM10,respectively.Increased greenness was associated with lower AMD incidence,and air pollution partly mediate it,which implies that interventions aimed at improving air quality and increasing greenness could have a dual benefit in mitigating AMD risk.展开更多
Age-related macular degeneration is a serious neurodegenerative disease of the retina that significantly impacts vision.Unfortunately,the specific pathogenesis remains unclear,and effective early treatment options are...Age-related macular degeneration is a serious neurodegenerative disease of the retina that significantly impacts vision.Unfortunately,the specific pathogenesis remains unclear,and effective early treatment options are consequently lacking.The microbiome is defined as a large ecosystem of microorganisms living within and coexisting with a host.The intestinal microbiome undergoes dynamic changes owing to age,diet,genetics,and other factors.Such dysregulation of the intestinal flora can disrupt the microecological balance,resulting in immunological and metabolic dysfunction in the host,and affecting the development of many diseases.In recent decades,significant evidence has indicated that the intestinal flora also influences systems outside of the digestive tract,including the brain.Indeed,several studies have demonstrated the critical role of the gut-brain axis in the development of brain neurodegenerative diseases,including Alzheimer’s disease and Parkinson’s disease.Similarly,the role of the“gut-eye axis”has been confirmed to play a role in the pathogenesis of many ocular disorders.Moreover,age-related macular degeneration and many brain neurodegenerative diseases have been shown to share several risk factors and to exhibit comparable etiologies.As such,the intestinal flora may play an important role in age-related macular degeneration.Given the above context,the present review aims to clarify the gut-brain and gut-eye connections,assess the effect of intestinal flora and metabolites on age-related macular degeneration,and identify potential diagnostic markers and therapeutic strategies.Currently,direct research on the role of intestinal flora in age-related macular degeneration is still relatively limited,while studies focusing solely on intestinal flora are insufficient to fully elucidate its functional role in age-related macular degeneration.Organ-on-a-chip technology has shown promise in clarifying the gut-eye interactions,while integrating analysis of the intestinal flora with research on metabolites through metabolomics and other techniques is crucial for understanding their potential mechanisms.展开更多
Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration.It causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central ...Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration.It causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central vision loss of patients with neovascular age-related macular degeneration.The pathogenesis of subretinal fibrosis is complex,and the underlying mechanisms are largely unknown.Therefore,there are no effective treatment options.A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential treatments.The current article reviews several aspects of subretinal fibrosis,including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis;multimodal imaging techniques for subretinal fibrosis;animal models for studying subretinal fibrosis;cellular and non-cellular constituents of subretinal fibrosis;pathophysiological mechanisms involved in subretinal fibrosis,such as aging,infiltration of macrophages,different sources of mesenchymal transition to myofibroblast,and activation of complement system and immune cells;and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis,such as vascular endothelial growth factor,connective tissue growth factor,fibroblast growth factor 2,platelet-derived growth factor and platelet-derived growth factor receptor-β,transforming growth factor-βsignaling pathway,Wnt signaling pathway,and the axis of heat shock protein 70-Toll-like receptors 2/4-interleukin-10.This review will improve the understanding of the pathogenesis of subretinal fibrosis,allow the discovery of molecular targets,and explore potential treatments for the management of subretinal fibrosis.展开更多
AIM:To elucidate causal pathways between oxidative biomarkers and age-related macular degeneration(AMD)phenotypes.METHODS:A bidirectional Mendelian randomization(MR)analytical protocol was implemented,which utilized g...AIM:To elucidate causal pathways between oxidative biomarkers and age-related macular degeneration(AMD)phenotypes.METHODS:A bidirectional Mendelian randomization(MR)analytical protocol was implemented,which utilized genome-wide association study(GWAS)summary statistics derived from the IEU OpenGWAS repositories.The investigation focused on 11 oxidative stress markers and AMD phenotypes,encompassing both wet and dry subtypes.The MR methodology incorporated inverse-variance weighted(IVW)calculations,MR-Egger statistical regression,weighted median approximation,and weighted mode assessments to estimate causative relationships.Sensitivity evaluations were conducted to verify result robustness and identify potential pleiotropy.RESULTS:Genetically predicted elevated catalase(CAT)concentrations demonstrated significant associations with heightened risks of overall AMD(IVW OR=1.084,95%CI:1.021-1.151,P=0.008)and wet AMD phenotype(IVW OR=1.113,95%CI:1.047-1.247,P=0.007).Higher genetically predicted albumin concentrations corresponded with reduced AMD risk(IVW OR=0.827,95%CI:0.715-0.957,P=0.013)but increased wet AMD risk(IVW OR=1.229,95%CI:1.036-1.458,P=0.018).Reverse MR analysis revealed that genetically predicted dry AMD exhibited significant association with reduced albumin levels(IVW OR=0.987,95%CI:0.979-0.996,P=0.004),while wet AMD corresponded with decreased total bilirubin(TBIL)and paraoxonase(PON)activity.CONCLUSION:The results offer strong support for a causal link between markers of oxidative stress and the development of AMD,indicating that oxidative processes play a role in driving the disease progression.展开更多
Age-related macular degeneration(AMD)is a disease that affects the vision of elderly individuals worldwide.Although current therapeutics have shown effectiveness against AMD,some patients may remain unresponsive and c...Age-related macular degeneration(AMD)is a disease that affects the vision of elderly individuals worldwide.Although current therapeutics have shown effectiveness against AMD,some patients may remain unresponsive and continue to experience disease progression.Therefore,in-depth knowledge of the mechanism underlying AMD pathogenesis is urgently required to identify potential drug targets for AMD treatment.Recently,studies have suggested that dysfunction of mitochondria can lead to the aggregation of reactive oxygen species(ROS)and activation of the cyclic GMP-AMP synthase(cGAS)/stimulator of interferon genes(STING)innate immunity pathways,ultimately resulting in sterile inflammation and cell death in various cells,such as cardiomyocytes and macrophages.Therefore,combining strategies targeting mitochondrial dysfunction and inflammatory mediators may hold great potential in facilitating AMD management.Notably,emerging evidence indicates that natural products targeting mitochondrial quality control(MQC)and the cGAS/STING innate immunity pathways exhibit promise in treating AMD.Here,we summarize phytochemicals that could directly or indirectly influence the MQC and the cGAS/STING innate immunity pathways,as well as their interconnected mediators,which have the potential to mitigate oxidative stress and suppress excessive inflammatory responses,thereby hoping to offer new insights into therapeutic interventions for AMD treatment.展开更多
AIM:To quantitatively assess central macular thickness(CMT),macular neovascularization(MNV)area,vascular tortuosity(VT),and vascular dispersion(VDisp)in neovascular age-related macular degeneration(nAMD),type 1 and ty...AIM:To quantitatively assess central macular thickness(CMT),macular neovascularization(MNV)area,vascular tortuosity(VT),and vascular dispersion(VDisp)in neovascular age-related macular degeneration(nAMD),type 1 and type 2 MNV,by means of optical coherence tomography(OCT)and OCT angiography(OCTA)techniques.METHODS:In this retrospective and observational case series,patients were classified into type 1 or type 2 MNV groups.A comprehensive panel of OCT and OCTA metrics was evaluated,including CMT,MNV area,VT,and VDisp.All subjects underwent a standardized intravitreal conbercept(IVC)regimen[3+pro re nata(PRN)]with a 12-month follow-up.MNV area was obtained by manual measurements with OCTA software,and VT and VDisp were calculated by automated analysis with Image J software.RESULTS:A total of 101 participants were included,with 51 patients in the type 1 MNV group(mean age 67.32±9.12y)and 50 patients in the type 2 MNV group(mean age 64.74±5.21y).The mean number of IVC injections was 3.98±1.53 for type 1 MNV and 3.73±0.81 for type 2 MNV.Both subtypes exhibited significant improvements in visual acuity,accompanied by marked reductions in CMT and MNV area(P<0.05)at 12mo after treatment.In type 2 MNV,VT significantly decreased(P<0.05),whereas no significant change was observed in VT for type 1 MNV.VDisp did not significantly changed in either sybtypes.Moreover,in type 1 MNV,final best-corrected visual acuity(BCVA)using logMAR correlated positively with both pre-and post-treatment CMT,while in type 2 MNV,a significant positive correlation was found between the number of injections and final CMT.CONCLUSION:This study shows that conbercept treatment significantly improves visual acuity and macular structure in both type 1 and type 2 MNV with reductions in CMT and MNV area.The significant reduction in VT in type 2 MNV suggests its potential as a biomarker for disease activity.The findings imply the quantitative assessment useful for the stratification,prognostication,and personalized management of MNV in nAMD.展开更多
AIM:To conduct a comprehensive bibliometric analysis of age-related macular degeneration(AMD)research from 2002 to 2022,identifying key contributing countries,institutions,authors,journals,and research hotspots to inf...AIM:To conduct a comprehensive bibliometric analysis of age-related macular degeneration(AMD)research from 2002 to 2022,identifying key contributing countries,institutions,authors,journals,and research hotspots to inform future research directions.METHODS:Publications related to AMD were retrieved from the Web of Science Core Collection(WoSCC)database for the period January 1,2002,to December 31,2022.The search was limited to English-language articles and reviews.Bibliometric analysis was performed using Microsoft Excel 2021 for data management and annual publication analysis.Visualization and network analyses were conducted using VOSviewer,CiteSpace,and the Bibliometrix package in R.Collaboration networks among countries,institutions,authors,and journals were mapped.Keywords were analyzed for co-occurrence to identify research hotspots.Metrics such as H-index,total link strength(TLS),and citation counts were used to assess impact.RESULTS:A total of 16715 publications were analyzed,showing a consistent increase in AMD research output over the past 20y,peaking at 1445 publications in 2021.The United States was the leading contributor with 31.8%of total publications,followed by China and the United Kingdom.The University of Melbourne emerged as the most productive institution with the highest TLS,indicating strong international collaborations.Professor Frank G.Holz was identified as the most influential author based on H-index and publication count.Investigative Ophthalmology&Visual Science was the most prolific journal and had the highest citation impact.Keyword co-occurrence analysis revealed four main research clusters:pathogenesis,therapy,epidemiology,and diagnosis.Emerging research hotspots included anti-vascular endothelial growth factor(VEGF)therapies,optical coherence tomography angiography,and artificial intelligence(AI)applications in diagnosis.CONCLUSION:The bibliometric analysis highlights significant growth and collaborative efforts in AMD research globally.Key contributors have advanced understanding in pathogenesis,therapeutic strategies,epidemiology,and diagnostic technologies.Future research should focus on interdisciplinary collaborations,novel therapeutic targets,personalized medicine,and technological innovations such as AI to effectively address the challenges posed by AMD.展开更多
AIM:To investigate the associations between urinary dialkyl phosphate(DAP)metabolites of organophosphorus pesticides(OPPs)exposure and age-related macular degeneration(AMD)risk.METHODS:Participants were drawn from the...AIM:To investigate the associations between urinary dialkyl phosphate(DAP)metabolites of organophosphorus pesticides(OPPs)exposure and age-related macular degeneration(AMD)risk.METHODS:Participants were drawn from the National Health and Nutrition Examination Survey(NHANES)between 2005 and 2008.Urinary DAP metabolites were used to construct a machine learning(ML)model for AMD prediction.Several interpretability pipelines,including permutation feature importance(PFI),partial dependence plot(PDP),and SHapley Additive exPlanations(SHAP)analyses were employed to analyze the influence from exposure features to prediction outcomes.RESULTS:A total of 1845 participants were included and 137 were diagnosed with AMD.Receiver operating characteristic curve(ROC)analysis evaluated Random Forests(RF)as the best ML model with its optimal predictive performance among eleven models.PFI and SHAP analyses illustrated that DAP metabolites were of significant contribution weights in AMD risk prediction,higher than most of the socio-demographic covariates.Shapley values and waterfall plots of randomly selected AMD individuals emphasized the predictive capacity of ML with high accuracy and sensitivity in each case.The relationships and interactions visualized by graphical plots and supported by statistical measures demonstrated the indispensable impacts from six DAP metabolites to the prediction of AMD risk.CONCLUSION:Urinary DAP metabolites of OPPs exposure are associated with AMD risk and ML algorithms show the excellent generalizability and differentiability in the course of AMD risk prediction.展开更多
AIM:To quantify and compare longitudinal thickness changes of the ganglion cell complex(GCC)and the choroid in patients with different patterns of age-related macular degeneration(AMD)progression.METHODS:Retrospective...AIM:To quantify and compare longitudinal thickness changes of the ganglion cell complex(GCC)and the choroid in patients with different patterns of age-related macular degeneration(AMD)progression.METHODS:Retrospective cohort analysis of anonymized data from participants aged 50y or more and diagnosed with early/intermediate AMD in at least one eye(with no evidence of advanced AMD).A total of 64 participants were included from the Instituto de Retina de Lisboa(IRL)study(IPL/2022/MetAllAMD_ESTeSL)and divided into 4 groups according to the Rotterdam classification for AMD.Spectral domain optical coherence tomography(SD-OCT)was used to assess and quantify GCC and choroid thickness at two time points(first visit vs last visit)with a minimum interval of 3y.RESULTS:In the GCC inner ring,a thinner thickness(P=0.001)was observed in the atrophic AMD group(51.3±21.4μm)compared to the early AMD(84.3±11.5μm),intermediate AMD(77.6±16.1μm)and neovascular AMD(88.9±16.3μm)groups.Choroidal thickness quantification showed a generalized reduction in the central circle(P=0.002)and inner ring(P=0.001).Slight reductions in retinal thickness were more accentuated in the inner ring in the atrophic AMD(-13%;P<0.01).CONCLUSION:The variation of the analyzed structures could be an indicator of risk of progression with neurodegenerative(GCC)or vascular(choroid)pattern in the intermediate and atrophic AMD.The quantification of both structures can provide important information about the risk of disease progression in the early and intermediate stages but also for the evolution pattern into late stages(atrophic or neovascular).展开更多
AIM:To investigate cuproptosis-related molecular and immune infiltration in age-related macular degeneration(AMD)development and establish a predictive model.METHODS:The expression profiles of cuproptosisrelated genes...AIM:To investigate cuproptosis-related molecular and immune infiltration in age-related macular degeneration(AMD)development and establish a predictive model.METHODS:The expression profiles of cuproptosisrelated genes and immune signature in AMD based on the microarray dataset GSE29801 were analyzed.A total of 142 AMD samples were used to identify the cuproptosisrelated differentially expressed genes(Cu-DEGs),together with the immune cell infiltration.To further refine the list of potential genes for AMD diagnosis,three machine learning techniques were used,and an external dataset were applied for confirming the accuracy of the predictive performance.Reverse transcription polymerase chain reaction(RT-PCR)were also performed to examine the level of mRNA of hub genes.The activated immune responses and Cu-DEGs were assessed between AMD and controls.RESULTS:Six genes,including ATP7A,DBT,VEGFA,UBE2D3,CP,SLC31A1,were screened as cuproptosissignature in AMD via three machine learning methods.Next,SLC31A1 and VEGFA was selected as hub genes by performance evaluation in an external dataset GSE160011,further analysis showed that SLC31A1 and VEGFA were associated with pathways related to immune signaling and immune function,which were then observed in relation to infiltrating immune cells.Finally,the mRNA expression levels of SLC31A1 and VEGFA were significantly higher in laser induced choroidal neovascularization(CNV)group than in control group detected by RT-PCR.CONCLUSION:In this study,the possible relationship between cuproptosis and AMD is expounded systematically.A predictive model is developed to assess the risk of cuproptosis-related genes and their clinical prognostic value in AMD patients.展开更多
AIM:To examine effects of switching intravitreal aflibercept to bevacizumab in neovascular age-related macular degeneration(nAMD).METHODS:Data from patients treated for nAMD with anti-vascular endothelial growth facto...AIM:To examine effects of switching intravitreal aflibercept to bevacizumab in neovascular age-related macular degeneration(nAMD).METHODS:Data from patients treated for nAMD with anti-vascular endothelial growth factor(VEGF)injections atÖrebro University Hospital between January 2014 and June 2020,were extracted from the Swedish macular register(SMR).A total of 230 eyes were included in the study:116 in the study/bevacizumab switch group and 114 in the control/aflibercept group.Central retinal thickness(CRT)was measured at baseline and after 2y.Primary outcome was mean change in best corrected visual acuity(BCVA)between baseline and 2y.Secondary outcome variables included proportion of patients with a clinically significant change in BCVA[increase or decrease of≥15 Early Treatment Diabetic Retinopathy Study(ETDRS)letters],mean change in CRT,number of anti-VEGF injections,number of visits assessing disease activity and number of visits with active disease.RESULTS:The mean difference in BCVA between baseline and 2y was 1.13±14.47 ETDRS letters in the bevacizumab switch group and 1.81±13.01 ETDRS letters in the aflibercept group.The lower bound of the 95%confidence interval of the difference in BCVA was-4.25,indicating non-inferiority within a 5 ETDRS letter limit.No significant differences in mean change of CRT between baseline and 2y were detected(study-185.9±167.0 versus control-149.4±193.1μm,P=0.127).The distribution of clinically significant improvement(P=0.598)or worsening(P=0.508)of BCVA during follow-up did not show statistically significant differences between groups.The number of anti-VEGF injections administered(study 12.76±2.20 versus control 13.10±4.20,P=0.442),the number of visits assessing disease activity(P=0.301),and the number of visits with active disease(P=0.065)did not show differences between subjects receiving bevacizumab and aflibercept treatment.No significant differences were detected in baseline characteristics between the study and control groups,including age,BCVA,CRT,neovascular membrane type or location,duration of symptoms or prior cataract surgery.CONCLUSION:Switching to off-label bevacizumab in patients responding to initial aflibercept treatment is noninferior to continued aflibercept treatment with respect to change in visual acuity at 2y.Switching anti-VEGF from aflibercept to bevacizumab may be a viable option in clinical settings with limited resources.展开更多
Introduction Late age-related macular degeneration(AMD)is one of the leading causes of blindness globally(1).In their recent study published in JAMA Ophthalmology,Hallak et al.explore the potential of an emerging ther...Introduction Late age-related macular degeneration(AMD)is one of the leading causes of blindness globally(1).In their recent study published in JAMA Ophthalmology,Hallak et al.explore the potential of an emerging therapeutic opportunity of Janus kinase inhibitor(JAKi)in the role of systemic inflammation in AMD pathogenesis(2).This study offers a real-world examination of the relationship between JAKi and AMD,comparing the incidence of AMD in patients treated with JAKi and those receiving other immunotherapies for existing autoimmune diseases.展开更多
Background: Exudative, or “wet” age-related macular degeneration (wAMD), characterized by choroidal neovascularization and consequent accumulation of subretinal fluid, is the leading cause of visual loss in elderly ...Background: Exudative, or “wet” age-related macular degeneration (wAMD), characterized by choroidal neovascularization and consequent accumulation of subretinal fluid, is the leading cause of visual loss in elderly patients in Western countries. Objective: To compare the effectiveness of aflibercept vs. ranibizumab for treatment-naive wAMD patients in the real world. Methods: PubMed, Web of Science and Cochrane Library were searched to compare aflibercept with ranibizumab. 21 studies with a total of 13,004 eyes were selected and assessed in this meta-analysis. Results: Compared to ranibizumab, aflibercept was more effective in improving best-corrected visual acuity (BCVA) at 12 months (WMD: −0.04;95% CI: −0.07 to 0.00;p = 0.04). At 3 months, aflibercept was superior to ranibizumab in reducing central retinal thickness in patients with worse baseline BCVA (WMD: −36.19;95% CI: −71.47 to −0.92;p = 0.04), reducing subfoveal choroidal thickness in patients with better baseline BCVA (WMD: −12.67;95% CI: −21.33 to −4.02;p = 0.004), reducing height of subfoveal pigment epithelial detachment (WMD: −43.88;95% CI: −73.88 to −13.87;p = 0.004) and improving the incidence of “dry macula” occurrence (OR: 2.26;95% CI: 1.33 to 3.82;p = 0.003). Conclusions: Compared with ranibizumab, aflibercept showed better efficacy in improving morphological changes at 3 months and visual acuity at 12 months post treatment initiation in community clinical setting.展开更多
Dry age-related macular degeneration(AMD)is a progressive blinding disease that currently affects millions of people worldwide with no successful treatment available.Significant research efforts are currently underway...Dry age-related macular degeneration(AMD)is a progressive blinding disease that currently affects millions of people worldwide with no successful treatment available.Significant research efforts are currently underway to develop therapies aimed at slowing the progression of this disease or,more notably,reversing it.Here the therapies which have reached clinical trial for treatment of dry AMD were reviewed.A thorough search of Pub Med,Embase,and Clinicaltrials.gov has led to a comprehensive collection of the most recent strategies being evaluated.This review also endeavors to assess the status and future directions of therapeutics for this debilitating condition.展开更多
Age-related macular degeneration(AMD)is a leading cause of blindness worldwide.AMD most commonly affects older individuals and is characterized by irreversible degeneration of the retinal pigment epithelium and neuros...Age-related macular degeneration(AMD)is a leading cause of blindness worldwide.AMD most commonly affects older individuals and is characterized by irreversible degeneration of the retinal pigment epithelium and neurosensory retina.Currently,there are limited treatment options for dry AMD outside of lifestyle modification and nutrient supplementation.Risuteganib[Luminate(ALG-1001),Allegro Ophthalmics,CA,USA]is an intravitreally administered inhibitor of integrin heterodimersαVβ3,αVβ5,α5β1,andαMβ2.It is currently undergoing clinical trials for the treatment of dry AMD and diabetic macular edema(DME).Preclinical studies have shown that risuteganib has an effect on the pathways for angiogenesis,inflammation,and vascular permeability.Ongoing clinical trials have had promising results showing improvements in patient best corrected visual acuity(BCVA)and reduced central macular thickness measured by optical coherence tomography(OCT).There is a pressing need for treatments for dry AMD and while risuteganib appears to have a potential benefit for patients,more data are needed before one can truly evaluate its efficacy.This narrative review provides a concise summary of the most up to date data regarding the proposed mechanism of action of risuteganib in the treatment of nonexudative AMD and DME as well as the results from recent phase 1 and phase 2 clinical trials.展开更多
AIM: To compare visual acuity (VA) outcomes between intravitreal injection of bevacizumab and ranibizumab in the treatment of neovascular age-related macular degeneration (AMD). METHODS: We conducted a consecutive, re...AIM: To compare visual acuity (VA) outcomes between intravitreal injection of bevacizumab and ranibizumab in the treatment of neovascular age-related macular degeneration (AMD). METHODS: We conducted a consecutive, retrospective case series study in patients with newly diagnosed all type choroidal neovascularization (CNV) secondary to AMD who received an intravitreal injection of bevacizumab (1.25mg) or ranibizumab (0.3mg) at Lions Eye Institute, Western Australia from Mar. 2006 to May 2008. All patients received injection at baseline with additional monthly injections given at the discretion of the treating physician. Main outcome measures were changes in VA. RESULTS: There were 371 consecutive patients received injection at least in one eye with at least 6 months of follow up (median of 12.0 months). Bevacizumab treatment prevented 221 out of 278 (79.5%) patient from losing < 15 letters in VA compared with 79 out of 93 (84.9%) of ranibizumab treated patients (P=0.25). While 68 (24.5%) of bevacizumab treated patients gained 15 letters of VA compared with 24 (25.8%) of ranibizumab treated patients (P=0.79). 75.3% and 66.2% patients benefited from ranibizumab and bevacizumab respectively with final VA better than 6/60 (P=0.10). Multivariate analysis showed that pre-treatment VA was negatively associated with benefit outcome. Assignment of injection was not associated with VA outcome of benefit after adjusting the covariate (P=0.857). CONCLUSION: There are no difference in treatment efficacy in terms of VA between bevacizumab and ranibizumab in routine clinical condition.展开更多
AIM: To compare the clinical efficacy of intravitreal injections of bevacizumab and ranibizumab for treating Chinese patients with neovascular age-related macular degeneration (AMD).METHODS: Among 60 Chinese patients ...AIM: To compare the clinical efficacy of intravitreal injections of bevacizumab and ranibizumab for treating Chinese patients with neovascular age-related macular degeneration (AMD).METHODS: Among 60 Chinese patients with exudative AMD (60 eyes), 28 received intravitreal bevacizumab injections (1.25mg) and 32 received intravitreal ranibizumab injections (0.5mg), once a month for 3 months and were followed for a total of 6 months. Monthly optical coherence tomography (OCT) was used to determine whether the patients received additional treatments during the follow-up. We compared the baseline and 6 -month follow-up values of mean best-corrected visual acuity (BCVA) and central retinal thickness (CRT) in both groups of patients. We also compared the occurrence of adverse events.RESULTS: At the 6-month follow-up, the mean BCVA (logMAR) of the bevacizumab and ranibizumab treatment groups improved from the baseline measurements of 0.72 ±0.23 and 0.73 ±0.22 to 0.47 ±0.14 and 0.45 ±0.20, respectively (P 【0.05 for both groups). However, the change was not significantly different between the two groups. As evaluated by OCT, CRT decreased from 366.71 ±34.72μm and 352 ±36.9μm at baseline to 250.86 ± 41.51μm and 243.22 ±41.38μm in the bevacizumab and ranibizumab groups, respectively (P 【0.05 for both groups). However, the change was not significantly different between the two groups. There were no severe local adverse reactions or systemic adverse events.CONCLUSION:Intravitreal bevacizumab and ranibizumab have equivalent effects on BCVA and CRT and appeare safe over the short-term.展开更多
The retina may suffer neurodegenerative damages,as other tissues of the central nervous system do,and serious eye diseases may develop.One of them is age-related macular degeneration,which causes progressive loss of v...The retina may suffer neurodegenerative damages,as other tissues of the central nervous system do,and serious eye diseases may develop.One of them is age-related macular degeneration,which causes progressive loss of vision due to retina degeneration.Treatment of age-related macular degeneration focuses on antioxidant agents and anti-vascular endothelial growth factor compounds,among others,that prevent/diminish oxidative stress and reduce neovascularisation respectively.The phytochemicals,medicinal plants and/or plant-diet supplements might be a useful adjunct in prevention or treatment of age-related macular degeneration owing to their antioxidant and anti-vascular endothelial growth factor properties.This review article presents the most investigated plants and natural products in relation to age-related macular degeneration,such as saffron,ginkgo,bilberry and blueberry,curcuma or turmeric,carotenoids,polyphenols,and vitamins C and E.This study provides up-to-date information on the effects,treatments,safety and efficiency of these phytotherapy products.展开更多
AIM：To investigate the place of neutrophil-to-lymphocyte ratio（NLR） and platelet-to-lymphocyte ratio（PLR） in the diagnosis of and prognosis for neovascular age-related macular degeneration（AMD）. METHODS：One hu...AIM：To investigate the place of neutrophil-to-lymphocyte ratio（NLR） and platelet-to-lymphocyte ratio（PLR） in the diagnosis of and prognosis for neovascular age-related macular degeneration（AMD）. METHODS：One hundred AMD patients and 100 healthy controls were included in the study. Blood samples were obtained from the venous blood, which is used for routine analysis, and these samples were subjected to complete blood count. NLR was defined as the neutrophil count divided by the number of lymphocytes, and PLR was defined as the platelet count divided by the number of lymphocytes. RESULTS：No statistically significant difference was observed between the two groups under consideration in terms of demographic features（P〉0.05）. The average NLR in the patient group was found to be significantly higher than that in the healthy control group（P〈0.05）. The average PLR was significantly higher in the patient group as compared to the control group（P〈0.05）. As best corrected visual acuity（BCVA） increased, both NLR and PLR decreased（significant negative correlations at 49.8% and 63.0%, respectively）, whereas as central macular thickness（CMT） increased, both NLR and PLR increased（significant positive correlations at 59.3% and 70.0%, respectively）.CONCLUSION：NLR and PLR levels are higher among neovascular AMD patients as compared to healthy control group. NLR and PLR levels were found to be inversely proportional to BCVA and directly proportional to CMT.展开更多
AIM：To determine whether gene polymorphisms of the major genetic risk loci for age-related macular degeneration（AMD）：ARMS2（rs10490923）,the complement factor H（CFH）（rs1410996） and HTRA1（rs11200638） influenc...AIM：To determine whether gene polymorphisms of the major genetic risk loci for age-related macular degeneration（AMD）：ARMS2（rs10490923）,the complement factor H（CFH）（rs1410996） and HTRA1（rs11200638） influence the response to a treatment regimen with ranibizumab for exudative AMD.METHODS：This study included 100 patients（100 eyes）with exudative AMD.Patients underwent a treatment with ranibizumab injections monthly during three months.Reinjections were made when the best corrected visual acuity（BCVA） decrease five letters（ETDRS） or central subfield retinal thickness gained 100 pm in optical coherence tomography image.Genotypes（rs10490923,rs1410996 and rs11200638） were analyzed using TaqMan probes or polymerase chain reaction-restricted fragment length polymorphisms analysis.RESULTS：There were no statistically significant differences in allelic distribution of CFH（rs1410996）,ARMS2（rs10490923） and HTRA1（rs11200638）polymorphisms regarding to response to ranibizumab treatment.CONCLUSION：Ranibizumab treatment response is not related to CFH（rs1410996）,ARMS2（rs10490923） and HTRA1（rs11200638） poymorphisms.展开更多
基金supported by the High-level Talents Introduction Plan from Central South University(No.502045003)the National Natural Science Foundation of China(No.42277438)Hunan Provincial Natural Science Foundation for Distinguished Young Scholars(No.2024JJ2082)to Fang Xiao,and the Postgraduate Independent Exploration and Innovation Project of Central South University,China(Nos.2024ZZTS0557 and 2023ZZTS0993)。
文摘Existing evidence suggests residential greenness is beneficial to human,while no research to date explored the associations of greenness with age-related macular degeneration(AMD).To evaluate the association of greenness with AMD,modification and mediation effect of air pollution,we conducted this prospective study.We con-structed weighted quantile sum(WQS)index as co-exposure to nitrogen oxides(NO_(x)),particulate matter<2.5μm(PM_(2.5)),particulate matter<10μm(PM10).Stratified Cox regression models were applied to test the effect of exposure.Effect modification of air pollution was assessed.Stratified Cox models through the indirect method and Aalen additive risk models were used in mediation analysis.Over median follow-up of 11.67 years,4596 AMD events were ascertained.Hazard ratios(HRs)and 95%confidence intervals(95%CIs)of incident AMD for pollution per interquartile range(IQR)increment were 1.10(1.04–1.16)for nitrogen dioxide(NO_(2)),1.09(1.03–1.15)for NO_(x),1.14(1.05–1.24)for PM_(2.5),1.13(1.05–1.21)for PM10.The HR(95%CI)of AMD associated with greenness 1000 m buffer per IQR increment was 0.91(0.86–0.97),300 m buffer was 0.94(0.89–0.99).The as-sociation between greenness 1000 m and AMD was 28.59%,44.77%,35.59%,32.31%and 27.08%mediated by the decreased WQS index,NO_(2),NO_(x),PM_(2.5) and PM10,respectively.Increased greenness was associated with lower AMD incidence,and air pollution partly mediate it,which implies that interventions aimed at improving air quality and increasing greenness could have a dual benefit in mitigating AMD risk.
基金supported by the National Natural Science Foundation of China,No.82171080Nanjing Medical Science and Technology Development Project,No.YKK23264Postgraduate Research&Practice Innovation Program of Jiangsu Province,Nos.JX10414151,JX10414152(all to KL)。
文摘Age-related macular degeneration is a serious neurodegenerative disease of the retina that significantly impacts vision.Unfortunately,the specific pathogenesis remains unclear,and effective early treatment options are consequently lacking.The microbiome is defined as a large ecosystem of microorganisms living within and coexisting with a host.The intestinal microbiome undergoes dynamic changes owing to age,diet,genetics,and other factors.Such dysregulation of the intestinal flora can disrupt the microecological balance,resulting in immunological and metabolic dysfunction in the host,and affecting the development of many diseases.In recent decades,significant evidence has indicated that the intestinal flora also influences systems outside of the digestive tract,including the brain.Indeed,several studies have demonstrated the critical role of the gut-brain axis in the development of brain neurodegenerative diseases,including Alzheimer’s disease and Parkinson’s disease.Similarly,the role of the“gut-eye axis”has been confirmed to play a role in the pathogenesis of many ocular disorders.Moreover,age-related macular degeneration and many brain neurodegenerative diseases have been shown to share several risk factors and to exhibit comparable etiologies.As such,the intestinal flora may play an important role in age-related macular degeneration.Given the above context,the present review aims to clarify the gut-brain and gut-eye connections,assess the effect of intestinal flora and metabolites on age-related macular degeneration,and identify potential diagnostic markers and therapeutic strategies.Currently,direct research on the role of intestinal flora in age-related macular degeneration is still relatively limited,while studies focusing solely on intestinal flora are insufficient to fully elucidate its functional role in age-related macular degeneration.Organ-on-a-chip technology has shown promise in clarifying the gut-eye interactions,while integrating analysis of the intestinal flora with research on metabolites through metabolomics and other techniques is crucial for understanding their potential mechanisms.
基金supported by grants from National Key R&D Program of China,No.2023YFC2506100(to JZ)the National Natural Science Foundation of China,No.82171062(to JZ).
文摘Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration.It causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central vision loss of patients with neovascular age-related macular degeneration.The pathogenesis of subretinal fibrosis is complex,and the underlying mechanisms are largely unknown.Therefore,there are no effective treatment options.A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential treatments.The current article reviews several aspects of subretinal fibrosis,including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis;multimodal imaging techniques for subretinal fibrosis;animal models for studying subretinal fibrosis;cellular and non-cellular constituents of subretinal fibrosis;pathophysiological mechanisms involved in subretinal fibrosis,such as aging,infiltration of macrophages,different sources of mesenchymal transition to myofibroblast,and activation of complement system and immune cells;and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis,such as vascular endothelial growth factor,connective tissue growth factor,fibroblast growth factor 2,platelet-derived growth factor and platelet-derived growth factor receptor-β,transforming growth factor-βsignaling pathway,Wnt signaling pathway,and the axis of heat shock protein 70-Toll-like receptors 2/4-interleukin-10.This review will improve the understanding of the pathogenesis of subretinal fibrosis,allow the discovery of molecular targets,and explore potential treatments for the management of subretinal fibrosis.
基金Supported by National Natural Science Foundation of China(No.82371033)Tianjin Health Bureau Fund(No.ZC20030)+4 种基金Tianjin Eye Hospital Fund Project(No.YKYB1911)Tianjin Key Medical Discipline(Specialty)Construction Project(No.TJYXZDXK-016A)Nankai University Institute of Optometry Science Research Open Fund(No.YKPY2208)Tianjin Eye Hospital Science and Technology Fund(No.NKSGY202405)Xianyang Science and Technology Plan Project(No.L2022ZDYFSF038).
文摘AIM:To elucidate causal pathways between oxidative biomarkers and age-related macular degeneration(AMD)phenotypes.METHODS:A bidirectional Mendelian randomization(MR)analytical protocol was implemented,which utilized genome-wide association study(GWAS)summary statistics derived from the IEU OpenGWAS repositories.The investigation focused on 11 oxidative stress markers and AMD phenotypes,encompassing both wet and dry subtypes.The MR methodology incorporated inverse-variance weighted(IVW)calculations,MR-Egger statistical regression,weighted median approximation,and weighted mode assessments to estimate causative relationships.Sensitivity evaluations were conducted to verify result robustness and identify potential pleiotropy.RESULTS:Genetically predicted elevated catalase(CAT)concentrations demonstrated significant associations with heightened risks of overall AMD(IVW OR=1.084,95%CI:1.021-1.151,P=0.008)and wet AMD phenotype(IVW OR=1.113,95%CI:1.047-1.247,P=0.007).Higher genetically predicted albumin concentrations corresponded with reduced AMD risk(IVW OR=0.827,95%CI:0.715-0.957,P=0.013)but increased wet AMD risk(IVW OR=1.229,95%CI:1.036-1.458,P=0.018).Reverse MR analysis revealed that genetically predicted dry AMD exhibited significant association with reduced albumin levels(IVW OR=0.987,95%CI:0.979-0.996,P=0.004),while wet AMD corresponded with decreased total bilirubin(TBIL)and paraoxonase(PON)activity.CONCLUSION:The results offer strong support for a causal link between markers of oxidative stress and the development of AMD,indicating that oxidative processes play a role in driving the disease progression.
基金funded by Chinese NSFC(Grant Nos.:82373336,82303238,and U22A20311,Sichuan Science and Technology Department,China(GrantNos.:2024NSFSC1945,,and 2023NSFSC0667)the Third People's Hospital of Chengdu Clinical Research Program,China(Grant Nos.:CSY-YN-01-2023-013,CSYYN-01-2023-005,and CSY-YN-03-2024-003)+1 种基金Sichuan University“From O to 1”Innovative Research Project,China(Project No.:2023SCUH0024)Health Commission of Chengdu,China(Grant No.:2024291).
文摘Age-related macular degeneration(AMD)is a disease that affects the vision of elderly individuals worldwide.Although current therapeutics have shown effectiveness against AMD,some patients may remain unresponsive and continue to experience disease progression.Therefore,in-depth knowledge of the mechanism underlying AMD pathogenesis is urgently required to identify potential drug targets for AMD treatment.Recently,studies have suggested that dysfunction of mitochondria can lead to the aggregation of reactive oxygen species(ROS)and activation of the cyclic GMP-AMP synthase(cGAS)/stimulator of interferon genes(STING)innate immunity pathways,ultimately resulting in sterile inflammation and cell death in various cells,such as cardiomyocytes and macrophages.Therefore,combining strategies targeting mitochondrial dysfunction and inflammatory mediators may hold great potential in facilitating AMD management.Notably,emerging evidence indicates that natural products targeting mitochondrial quality control(MQC)and the cGAS/STING innate immunity pathways exhibit promise in treating AMD.Here,we summarize phytochemicals that could directly or indirectly influence the MQC and the cGAS/STING innate immunity pathways,as well as their interconnected mediators,which have the potential to mitigate oxidative stress and suppress excessive inflammatory responses,thereby hoping to offer new insights into therapeutic interventions for AMD treatment.
基金Supported by Natural Science Foundation of Shandong Province(No.ZR2023MH363)Bethune Langmu Young Scholars Research Fund Project(No.BJ-LM2021007J).
文摘AIM:To quantitatively assess central macular thickness(CMT),macular neovascularization(MNV)area,vascular tortuosity(VT),and vascular dispersion(VDisp)in neovascular age-related macular degeneration(nAMD),type 1 and type 2 MNV,by means of optical coherence tomography(OCT)and OCT angiography(OCTA)techniques.METHODS:In this retrospective and observational case series,patients were classified into type 1 or type 2 MNV groups.A comprehensive panel of OCT and OCTA metrics was evaluated,including CMT,MNV area,VT,and VDisp.All subjects underwent a standardized intravitreal conbercept(IVC)regimen[3+pro re nata(PRN)]with a 12-month follow-up.MNV area was obtained by manual measurements with OCTA software,and VT and VDisp were calculated by automated analysis with Image J software.RESULTS:A total of 101 participants were included,with 51 patients in the type 1 MNV group(mean age 67.32±9.12y)and 50 patients in the type 2 MNV group(mean age 64.74±5.21y).The mean number of IVC injections was 3.98±1.53 for type 1 MNV and 3.73±0.81 for type 2 MNV.Both subtypes exhibited significant improvements in visual acuity,accompanied by marked reductions in CMT and MNV area(P<0.05)at 12mo after treatment.In type 2 MNV,VT significantly decreased(P<0.05),whereas no significant change was observed in VT for type 1 MNV.VDisp did not significantly changed in either sybtypes.Moreover,in type 1 MNV,final best-corrected visual acuity(BCVA)using logMAR correlated positively with both pre-and post-treatment CMT,while in type 2 MNV,a significant positive correlation was found between the number of injections and final CMT.CONCLUSION:This study shows that conbercept treatment significantly improves visual acuity and macular structure in both type 1 and type 2 MNV with reductions in CMT and MNV area.The significant reduction in VT in type 2 MNV suggests its potential as a biomarker for disease activity.The findings imply the quantitative assessment useful for the stratification,prognostication,and personalized management of MNV in nAMD.
基金Supported by the National Natural Science Foundation of China(No.82371033)the Tianjin Natural Science Foundation(No.21JCZDJC01250)the Tianjin Key Medical Discipline(Specialty)Construction Project(No.TJYXZDXK-016A).
文摘AIM:To conduct a comprehensive bibliometric analysis of age-related macular degeneration(AMD)research from 2002 to 2022,identifying key contributing countries,institutions,authors,journals,and research hotspots to inform future research directions.METHODS:Publications related to AMD were retrieved from the Web of Science Core Collection(WoSCC)database for the period January 1,2002,to December 31,2022.The search was limited to English-language articles and reviews.Bibliometric analysis was performed using Microsoft Excel 2021 for data management and annual publication analysis.Visualization and network analyses were conducted using VOSviewer,CiteSpace,and the Bibliometrix package in R.Collaboration networks among countries,institutions,authors,and journals were mapped.Keywords were analyzed for co-occurrence to identify research hotspots.Metrics such as H-index,total link strength(TLS),and citation counts were used to assess impact.RESULTS:A total of 16715 publications were analyzed,showing a consistent increase in AMD research output over the past 20y,peaking at 1445 publications in 2021.The United States was the leading contributor with 31.8%of total publications,followed by China and the United Kingdom.The University of Melbourne emerged as the most productive institution with the highest TLS,indicating strong international collaborations.Professor Frank G.Holz was identified as the most influential author based on H-index and publication count.Investigative Ophthalmology&Visual Science was the most prolific journal and had the highest citation impact.Keyword co-occurrence analysis revealed four main research clusters:pathogenesis,therapy,epidemiology,and diagnosis.Emerging research hotspots included anti-vascular endothelial growth factor(VEGF)therapies,optical coherence tomography angiography,and artificial intelligence(AI)applications in diagnosis.CONCLUSION:The bibliometric analysis highlights significant growth and collaborative efforts in AMD research globally.Key contributors have advanced understanding in pathogenesis,therapeutic strategies,epidemiology,and diagnostic technologies.Future research should focus on interdisciplinary collaborations,novel therapeutic targets,personalized medicine,and technological innovations such as AI to effectively address the challenges posed by AMD.
基金Supported by the National Key Research and Development Program of China(No.2022YFC2502800)the National Natural Science Foundation of China(No.82171076)the Shanghai Municipal Education Commission(No.2023KJ05-67).
文摘AIM:To investigate the associations between urinary dialkyl phosphate(DAP)metabolites of organophosphorus pesticides(OPPs)exposure and age-related macular degeneration(AMD)risk.METHODS:Participants were drawn from the National Health and Nutrition Examination Survey(NHANES)between 2005 and 2008.Urinary DAP metabolites were used to construct a machine learning(ML)model for AMD prediction.Several interpretability pipelines,including permutation feature importance(PFI),partial dependence plot(PDP),and SHapley Additive exPlanations(SHAP)analyses were employed to analyze the influence from exposure features to prediction outcomes.RESULTS:A total of 1845 participants were included and 137 were diagnosed with AMD.Receiver operating characteristic curve(ROC)analysis evaluated Random Forests(RF)as the best ML model with its optimal predictive performance among eleven models.PFI and SHAP analyses illustrated that DAP metabolites were of significant contribution weights in AMD risk prediction,higher than most of the socio-demographic covariates.Shapley values and waterfall plots of randomly selected AMD individuals emphasized the predictive capacity of ML with high accuracy and sensitivity in each case.The relationships and interactions visualized by graphical plots and supported by statistical measures demonstrated the indispensable impacts from six DAP metabolites to the prediction of AMD risk.CONCLUSION:Urinary DAP metabolites of OPPs exposure are associated with AMD risk and ML algorithms show the excellent generalizability and differentiability in the course of AMD risk prediction.
基金Supported by FCT/MCTES UIDB/05608/2020(https://doi.org/10.54499/UIDB/05608/2020)UIDP/05608/2020(https://doi.org/10.54499/UIDP/05608/2020)+1 种基金IDI&CA grant IPL/2022/MetAllAMD_ESTeSL by H&TRC-Health&Technology Research Center,ESTeSL-Escola Superior de Tecnologia da Saúde,Instituto Politécnico de Lisboaby Retina Institute of Lisbon(IRL).
文摘AIM:To quantify and compare longitudinal thickness changes of the ganglion cell complex(GCC)and the choroid in patients with different patterns of age-related macular degeneration(AMD)progression.METHODS:Retrospective cohort analysis of anonymized data from participants aged 50y or more and diagnosed with early/intermediate AMD in at least one eye(with no evidence of advanced AMD).A total of 64 participants were included from the Instituto de Retina de Lisboa(IRL)study(IPL/2022/MetAllAMD_ESTeSL)and divided into 4 groups according to the Rotterdam classification for AMD.Spectral domain optical coherence tomography(SD-OCT)was used to assess and quantify GCC and choroid thickness at two time points(first visit vs last visit)with a minimum interval of 3y.RESULTS:In the GCC inner ring,a thinner thickness(P=0.001)was observed in the atrophic AMD group(51.3±21.4μm)compared to the early AMD(84.3±11.5μm),intermediate AMD(77.6±16.1μm)and neovascular AMD(88.9±16.3μm)groups.Choroidal thickness quantification showed a generalized reduction in the central circle(P=0.002)and inner ring(P=0.001).Slight reductions in retinal thickness were more accentuated in the inner ring in the atrophic AMD(-13%;P<0.01).CONCLUSION:The variation of the analyzed structures could be an indicator of risk of progression with neurodegenerative(GCC)or vascular(choroid)pattern in the intermediate and atrophic AMD.The quantification of both structures can provide important information about the risk of disease progression in the early and intermediate stages but also for the evolution pattern into late stages(atrophic or neovascular).
文摘AIM:To investigate cuproptosis-related molecular and immune infiltration in age-related macular degeneration(AMD)development and establish a predictive model.METHODS:The expression profiles of cuproptosisrelated genes and immune signature in AMD based on the microarray dataset GSE29801 were analyzed.A total of 142 AMD samples were used to identify the cuproptosisrelated differentially expressed genes(Cu-DEGs),together with the immune cell infiltration.To further refine the list of potential genes for AMD diagnosis,three machine learning techniques were used,and an external dataset were applied for confirming the accuracy of the predictive performance.Reverse transcription polymerase chain reaction(RT-PCR)were also performed to examine the level of mRNA of hub genes.The activated immune responses and Cu-DEGs were assessed between AMD and controls.RESULTS:Six genes,including ATP7A,DBT,VEGFA,UBE2D3,CP,SLC31A1,were screened as cuproptosissignature in AMD via three machine learning methods.Next,SLC31A1 and VEGFA was selected as hub genes by performance evaluation in an external dataset GSE160011,further analysis showed that SLC31A1 and VEGFA were associated with pathways related to immune signaling and immune function,which were then observed in relation to infiltrating immune cells.Finally,the mRNA expression levels of SLC31A1 and VEGFA were significantly higher in laser induced choroidal neovascularization(CNV)group than in control group detected by RT-PCR.CONCLUSION:In this study,the possible relationship between cuproptosis and AMD is expounded systematically.A predictive model is developed to assess the risk of cuproptosis-related genes and their clinical prognostic value in AMD patients.
文摘AIM:To examine effects of switching intravitreal aflibercept to bevacizumab in neovascular age-related macular degeneration(nAMD).METHODS:Data from patients treated for nAMD with anti-vascular endothelial growth factor(VEGF)injections atÖrebro University Hospital between January 2014 and June 2020,were extracted from the Swedish macular register(SMR).A total of 230 eyes were included in the study:116 in the study/bevacizumab switch group and 114 in the control/aflibercept group.Central retinal thickness(CRT)was measured at baseline and after 2y.Primary outcome was mean change in best corrected visual acuity(BCVA)between baseline and 2y.Secondary outcome variables included proportion of patients with a clinically significant change in BCVA[increase or decrease of≥15 Early Treatment Diabetic Retinopathy Study(ETDRS)letters],mean change in CRT,number of anti-VEGF injections,number of visits assessing disease activity and number of visits with active disease.RESULTS:The mean difference in BCVA between baseline and 2y was 1.13±14.47 ETDRS letters in the bevacizumab switch group and 1.81±13.01 ETDRS letters in the aflibercept group.The lower bound of the 95%confidence interval of the difference in BCVA was-4.25,indicating non-inferiority within a 5 ETDRS letter limit.No significant differences in mean change of CRT between baseline and 2y were detected(study-185.9±167.0 versus control-149.4±193.1μm,P=0.127).The distribution of clinically significant improvement(P=0.598)or worsening(P=0.508)of BCVA during follow-up did not show statistically significant differences between groups.The number of anti-VEGF injections administered(study 12.76±2.20 versus control 13.10±4.20,P=0.442),the number of visits assessing disease activity(P=0.301),and the number of visits with active disease(P=0.065)did not show differences between subjects receiving bevacizumab and aflibercept treatment.No significant differences were detected in baseline characteristics between the study and control groups,including age,BCVA,CRT,neovascular membrane type or location,duration of symptoms or prior cataract surgery.CONCLUSION:Switching to off-label bevacizumab in patients responding to initial aflibercept treatment is noninferior to continued aflibercept treatment with respect to change in visual acuity at 2y.Switching anti-VEGF from aflibercept to bevacizumab may be a viable option in clinical settings with limited resources.
基金supported by Health Education England/National Institute for Health Research(NIHR)(Clinical Lectureship CL-2020-18-009 for C.H.).
文摘Introduction Late age-related macular degeneration(AMD)is one of the leading causes of blindness globally(1).In their recent study published in JAMA Ophthalmology,Hallak et al.explore the potential of an emerging therapeutic opportunity of Janus kinase inhibitor(JAKi)in the role of systemic inflammation in AMD pathogenesis(2).This study offers a real-world examination of the relationship between JAKi and AMD,comparing the incidence of AMD in patients treated with JAKi and those receiving other immunotherapies for existing autoimmune diseases.
文摘Background: Exudative, or “wet” age-related macular degeneration (wAMD), characterized by choroidal neovascularization and consequent accumulation of subretinal fluid, is the leading cause of visual loss in elderly patients in Western countries. Objective: To compare the effectiveness of aflibercept vs. ranibizumab for treatment-naive wAMD patients in the real world. Methods: PubMed, Web of Science and Cochrane Library were searched to compare aflibercept with ranibizumab. 21 studies with a total of 13,004 eyes were selected and assessed in this meta-analysis. Results: Compared to ranibizumab, aflibercept was more effective in improving best-corrected visual acuity (BCVA) at 12 months (WMD: −0.04;95% CI: −0.07 to 0.00;p = 0.04). At 3 months, aflibercept was superior to ranibizumab in reducing central retinal thickness in patients with worse baseline BCVA (WMD: −36.19;95% CI: −71.47 to −0.92;p = 0.04), reducing subfoveal choroidal thickness in patients with better baseline BCVA (WMD: −12.67;95% CI: −21.33 to −4.02;p = 0.004), reducing height of subfoveal pigment epithelial detachment (WMD: −43.88;95% CI: −73.88 to −13.87;p = 0.004) and improving the incidence of “dry macula” occurrence (OR: 2.26;95% CI: 1.33 to 3.82;p = 0.003). Conclusions: Compared with ranibizumab, aflibercept showed better efficacy in improving morphological changes at 3 months and visual acuity at 12 months post treatment initiation in community clinical setting.
基金Supported by the Gates Family Fundthe Doni Solich Family Chair in Ocular Stem Cell Research,the Cell Sight Fundan Unrestricted Research Award from Research to Prevent Blindness to the Department of Ophthalmology at the University of Colorado。
文摘Dry age-related macular degeneration(AMD)is a progressive blinding disease that currently affects millions of people worldwide with no successful treatment available.Significant research efforts are currently underway to develop therapies aimed at slowing the progression of this disease or,more notably,reversing it.Here the therapies which have reached clinical trial for treatment of dry AMD were reviewed.A thorough search of Pub Med,Embase,and Clinicaltrials.gov has led to a comprehensive collection of the most recent strategies being evaluated.This review also endeavors to assess the status and future directions of therapeutics for this debilitating condition.
文摘Age-related macular degeneration(AMD)is a leading cause of blindness worldwide.AMD most commonly affects older individuals and is characterized by irreversible degeneration of the retinal pigment epithelium and neurosensory retina.Currently,there are limited treatment options for dry AMD outside of lifestyle modification and nutrient supplementation.Risuteganib[Luminate(ALG-1001),Allegro Ophthalmics,CA,USA]is an intravitreally administered inhibitor of integrin heterodimersαVβ3,αVβ5,α5β1,andαMβ2.It is currently undergoing clinical trials for the treatment of dry AMD and diabetic macular edema(DME).Preclinical studies have shown that risuteganib has an effect on the pathways for angiogenesis,inflammation,and vascular permeability.Ongoing clinical trials have had promising results showing improvements in patient best corrected visual acuity(BCVA)and reduced central macular thickness measured by optical coherence tomography(OCT).There is a pressing need for treatments for dry AMD and while risuteganib appears to have a potential benefit for patients,more data are needed before one can truly evaluate its efficacy.This narrative review provides a concise summary of the most up to date data regarding the proposed mechanism of action of risuteganib in the treatment of nonexudative AMD and DME as well as the results from recent phase 1 and phase 2 clinical trials.
文摘AIM: To compare visual acuity (VA) outcomes between intravitreal injection of bevacizumab and ranibizumab in the treatment of neovascular age-related macular degeneration (AMD). METHODS: We conducted a consecutive, retrospective case series study in patients with newly diagnosed all type choroidal neovascularization (CNV) secondary to AMD who received an intravitreal injection of bevacizumab (1.25mg) or ranibizumab (0.3mg) at Lions Eye Institute, Western Australia from Mar. 2006 to May 2008. All patients received injection at baseline with additional monthly injections given at the discretion of the treating physician. Main outcome measures were changes in VA. RESULTS: There were 371 consecutive patients received injection at least in one eye with at least 6 months of follow up (median of 12.0 months). Bevacizumab treatment prevented 221 out of 278 (79.5%) patient from losing < 15 letters in VA compared with 79 out of 93 (84.9%) of ranibizumab treated patients (P=0.25). While 68 (24.5%) of bevacizumab treated patients gained 15 letters of VA compared with 24 (25.8%) of ranibizumab treated patients (P=0.79). 75.3% and 66.2% patients benefited from ranibizumab and bevacizumab respectively with final VA better than 6/60 (P=0.10). Multivariate analysis showed that pre-treatment VA was negatively associated with benefit outcome. Assignment of injection was not associated with VA outcome of benefit after adjusting the covariate (P=0.857). CONCLUSION: There are no difference in treatment efficacy in terms of VA between bevacizumab and ranibizumab in routine clinical condition.
文摘AIM: To compare the clinical efficacy of intravitreal injections of bevacizumab and ranibizumab for treating Chinese patients with neovascular age-related macular degeneration (AMD).METHODS: Among 60 Chinese patients with exudative AMD (60 eyes), 28 received intravitreal bevacizumab injections (1.25mg) and 32 received intravitreal ranibizumab injections (0.5mg), once a month for 3 months and were followed for a total of 6 months. Monthly optical coherence tomography (OCT) was used to determine whether the patients received additional treatments during the follow-up. We compared the baseline and 6 -month follow-up values of mean best-corrected visual acuity (BCVA) and central retinal thickness (CRT) in both groups of patients. We also compared the occurrence of adverse events.RESULTS: At the 6-month follow-up, the mean BCVA (logMAR) of the bevacizumab and ranibizumab treatment groups improved from the baseline measurements of 0.72 ±0.23 and 0.73 ±0.22 to 0.47 ±0.14 and 0.45 ±0.20, respectively (P 【0.05 for both groups). However, the change was not significantly different between the two groups. As evaluated by OCT, CRT decreased from 366.71 ±34.72μm and 352 ±36.9μm at baseline to 250.86 ± 41.51μm and 243.22 ±41.38μm in the bevacizumab and ranibizumab groups, respectively (P 【0.05 for both groups). However, the change was not significantly different between the two groups. There were no severe local adverse reactions or systemic adverse events.CONCLUSION:Intravitreal bevacizumab and ranibizumab have equivalent effects on BCVA and CRT and appeare safe over the short-term.
文摘The retina may suffer neurodegenerative damages,as other tissues of the central nervous system do,and serious eye diseases may develop.One of them is age-related macular degeneration,which causes progressive loss of vision due to retina degeneration.Treatment of age-related macular degeneration focuses on antioxidant agents and anti-vascular endothelial growth factor compounds,among others,that prevent/diminish oxidative stress and reduce neovascularisation respectively.The phytochemicals,medicinal plants and/or plant-diet supplements might be a useful adjunct in prevention or treatment of age-related macular degeneration owing to their antioxidant and anti-vascular endothelial growth factor properties.This review article presents the most investigated plants and natural products in relation to age-related macular degeneration,such as saffron,ginkgo,bilberry and blueberry,curcuma or turmeric,carotenoids,polyphenols,and vitamins C and E.This study provides up-to-date information on the effects,treatments,safety and efficiency of these phytotherapy products.
文摘AIM：To investigate the place of neutrophil-to-lymphocyte ratio（NLR） and platelet-to-lymphocyte ratio（PLR） in the diagnosis of and prognosis for neovascular age-related macular degeneration（AMD）. METHODS：One hundred AMD patients and 100 healthy controls were included in the study. Blood samples were obtained from the venous blood, which is used for routine analysis, and these samples were subjected to complete blood count. NLR was defined as the neutrophil count divided by the number of lymphocytes, and PLR was defined as the platelet count divided by the number of lymphocytes. RESULTS：No statistically significant difference was observed between the two groups under consideration in terms of demographic features（P〉0.05）. The average NLR in the patient group was found to be significantly higher than that in the healthy control group（P〈0.05）. The average PLR was significantly higher in the patient group as compared to the control group（P〈0.05）. As best corrected visual acuity（BCVA） increased, both NLR and PLR decreased（significant negative correlations at 49.8% and 63.0%, respectively）, whereas as central macular thickness（CMT） increased, both NLR and PLR increased（significant positive correlations at 59.3% and 70.0%, respectively）.CONCLUSION：NLR and PLR levels are higher among neovascular AMD patients as compared to healthy control group. NLR and PLR levels were found to be inversely proportional to BCVA and directly proportional to CMT.
基金Supported by a Grant from Gerencia Regional de Salud de Castillay Leon GRS 957/A/14
文摘AIM：To determine whether gene polymorphisms of the major genetic risk loci for age-related macular degeneration（AMD）：ARMS2（rs10490923）,the complement factor H（CFH）（rs1410996） and HTRA1（rs11200638） influence the response to a treatment regimen with ranibizumab for exudative AMD.METHODS：This study included 100 patients（100 eyes）with exudative AMD.Patients underwent a treatment with ranibizumab injections monthly during three months.Reinjections were made when the best corrected visual acuity（BCVA） decrease five letters（ETDRS） or central subfield retinal thickness gained 100 pm in optical coherence tomography image.Genotypes（rs10490923,rs1410996 and rs11200638） were analyzed using TaqMan probes or polymerase chain reaction-restricted fragment length polymorphisms analysis.RESULTS：There were no statistically significant differences in allelic distribution of CFH（rs1410996）,ARMS2（rs10490923） and HTRA1（rs11200638）polymorphisms regarding to response to ranibizumab treatment.CONCLUSION：Ranibizumab treatment response is not related to CFH（rs1410996）,ARMS2（rs10490923） and HTRA1（rs11200638） poymorphisms.
