Influence of CFH,HTRA1 and ARMS2 polymorphisms in the response to intravitreal ranibizumab treatment for wet age-related macular degeneration in a Spanish population

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.

Temporal pattern of resolution/recurrence of choroidal neovascularization during bevacizumab therapy for wet age-related macular degeneration

AIMTo characterize temporal pattern of resolution and recurrence of naive choroidal neovascularization (CNV) secondary to wet age-related macular degeneration (AMD) treated with intravitreal bevacizumab on as needed regimen, and to analyze baseline risk factors for CNV resolution or recurrence.

Recent Developments in the Treatment of Wet Age-related Macular Degeneration

Age-related macular degeneration(AMD)is the most common cause of irreversible blindness and visual impairment in individuals over the age of 50 years in western societies.More than 25 million people currently suffer from this illness in the world,with an additional 500000 every year,approximately.It is a multifactorial ocular disease that affects the maculae due to a late-onset progressive neurodegeneration and dysfunction of photoreceptors and retinal pigment epithelium(RPE).There are many subtypes of AMD but basically two broad forms:the nonneovascular(dry,nonexudative)and neovascular(wet,exudative).Exudative AMD is the less common form(about 15%)but tends to progress more rapidly.At the moment,wet AMD is treated primarily on the basis of anti-vascular endothelial growth factor(VEGF)agents,which have led to massive improvement in the prognosis of the disease since they were first introduced.This article focuses on the latest treatment approaches to neovascular AMD.An extensive literature review was performed in order to illustrate the effectiveness of current and future anti-VEGF agents as well as the landmark clinical studies that have been carried out to establish these drugs as a gold standard in the therapy of wet AMD.

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.

Health resource utilization and the economic burden of patients with wet age-related macular degeneration in Thailand

AIM: To determine healthcare resource utilization and the economic burden associated with wet age-related macular degeneration(AMD) in Thailand ·METHODS: This study included patients diagnosed with wet AMD that were 60 years old or older,and had best corrected visual acuity(BCVA) measured at least two times during the follow-up period. We excluded patients having other eye diseases. Two separate sub-studies were conducted. The first sub-study was a retrospective cohort study; electronic medical charts were reviewed to estimate the direct medical costs. The second sub-study was a cross-sectional survey estimating the direct non-medical costs based on face-to-face interviews using a structured questionnaire. For the first sub-study,direct medical costs,including the cost of drugs,laboratory,procedures,and other treatments were obtained. For the second sub-study,direct non-medical costs,e.g. transportation,food,accessories,home renovation,and caregiver costs,were obtained from face-to-face interviews with patients and/ or caregivers. ·RESULTS: For the first sub-study,sixty-four medical records were reviewed. The annual average number of medical visits was 11.1 ±6.0. The average direct medical costs were $3 604 ±4 530 per year. No statistically-significant differences of the average direct medical costs among the BCVA groups were detected(P =0.98). Drug costs accounted for 77% of total direct medical costs. For direct non-medical costs,67 patients were included. Forty-eight patients(71.6%) required the accompaniment of a person during the out-patient visit. Seventeen patients(25.4%) required a caregiver at home. The average direct non-medical cost was $2 927 ±6 560 per year. There were no statistically-significant differences in the average costs among the BCVA groups(P =0.74). Care-giver cost accounted for 87% of direct non-medical costs.·CONCLUSION: Our study indicates that wet AMD is associated with a substantial economic burden,especially concerning drug and care-giver costs.

Observation on the quality of life before and after the injection of antiangiogenic drug in the vitreous cavity of patients with wet age-related macular degeneration

Objective: To explore the vision-related quality of life ( VRQL) before and after the injection of antiangiogenic drug into the vitreous cavity of patients with wet age-related macular degeneration ( AMD) . Methods: The 2000 edition of the Visual Functioning Questionnaire 25 that was issued by the Na-tional Eye Institute was applied, and the VRQL evaluation was conducted on the initially diagnosed patients with wet-AMD before and after the injection of ranibizumab into the vitreous cavity. Results: Among the wet-AMD patients, patients with better distance visual acuity before the in-travitreal injection had a lower VFQ-25 score. After the vitreous cavity injection, the VFQ-25 questionnaire score was related to patient care and education from the doctors and nurses; specific-ally, the better the nursing, the higher the score. Conclusions: Before the vitreous cavity injection, the degree of distance visual acuity is an im-portant factor affecting the VRQL of wet-AMD patients. In addition, patient care and education from the doctors and nurses toward patients during the pre-, intra-and post-operation of the intrav-itreal injection are also important factors affecting the VRQL.

Matrix γ-carboxyglutamate protein and Fetuin-A, in wet type age-related macular degeneration

AIM: To evaluate the high sensitivity C-reactive protein(hs CRP), Fetuin-A and matrix γ-carboxyglutamate protein(MGP) as the main factors for vascular calcification and inflammation in serum of patients with advanced age-related macular degeneration(ARMD) in comparison to healthy controls. METHODS: The subjects were 40 patients with choroidal neovascularization(CNV) having a mean age of70.9 ±9.1y and a matched group of 49 apparently healthy control subjects. The ARMD was diagnosed using a slitlamp with superfield lens, fundus photography and fluorescein angiography. Measurement of hs CRP was done by nephelometry method. Levels of Fetuin-A and MGP were measured by enzyme-linked immunosorbent assay(ELISA) technique.RESULTS: hs CRP [0.45(0.07-2.63) mg/L vs 0.25(0.03-1.2) mg/L, P =0.02)] and Fetuin-A levels(50.27 ±5.04 vs44.99±10.28 ng/m L, P =0.009) were higher in the patients than in the control groups. We could not find significant difference in MGP level between two groups(P =0.08).There was not a significant correlation between MGP with Fetuin-A and hs CRP among the patients(P =0.7, P =0.9respectively). A significant negative correlation of hs CRP with Fetuin-A was observed in both case and control groups(P =0.004, r =-0.33 and P =0.001, r =-0.54,respectively).CONCLUSION: Although our study shows that serum hs CRP and Fetuin-A is increased in CNV patients as well as negatively correlated with both study groups, their direct role on pathogenesis of ARMD required future studies.

The gut-eye axis:from brain neurodegenerative diseases to age-related macular degeneration

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.

Subretinal fibrosis secondary to neovascular age-related macular degeneration:mechanisms and potential therapeutic targets

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.

Therapeutic effect of Ranibizumab combined with Triamcinolone Acetonide on wet age-related macular degeneration and its effect on interleukin

Objective:To observe the clinical efficacy of ranibizumab combined with triamcinolone acetonide on wet age-related macular degeneration(AMD)and explore the effect of this method on the levels of IL-1β,IL-2,IL-6 and IL-8.Methods:Prospective study was conducted in this research.86 cases of patients with wet AMD(102 eyes)admitted in Baogang Hospital of Inner Mongolia from November 2017 to October 2018 were chosen and randomly divided into the ranibizumab group(43 cases,50 eyes)and the combination group(43 cases,52 eyes).The ranibizumab group of patients were given intravitreal injection of ranibizumab,and the combination group was additionally given triamcinolone acetonide on the basis of the ranibizumab group.The intraocular pressure values of the two groups before treatment,in 2 weeks,1 month and 3 months after treatment were compared.The central macular thickness(CMT)and visual acuity of the two groups before treatment as well as in 1 month,3 months and 6 months after treatment were compared.The levels of IL-1β,IL-2,IL-6 and IL-8 in the serum were compared between the two groups before treatment and in 1 month after treatment.The incidences of complications during treatment in the two groups were recorded and compared.The data were analyzed by use of t-test,repeated measures ANOVA andχ^(2) test.Results:There were no statistically significant differences in intraocular pressure value between the two groups(Fgroups=1.275,p=.496;Ftime=1.810,p=.211;Finteraction=1.772,p=.335).There were no statistically significant differences in CMT and visual acuity before treatment between the two groups(t=0.042,p=.967;t=0.720,p=.473).In one month,three months and six months after treatment,CMT in the combined group was lower than that in the ranibizumab group(t=2.086,p=.039;t=3.398,p=.001;t=2.987,p=.004),and the visual acuity of the combined group was higher than that of the ranibizumab group(t=3.265,p=.001;t=2.217,p=.029;t=2.519,p=.013).CMT showed a decreasing tendency(tbefore treatment vs.t1 month after treatment=6.210,4.218,p<.001;t1 month after treatment vs.t3months after treatment=16.772,15.865,p<.001;t3 months after treatment vs.t6 months after treatment=4.472,4.848,p<.001)and the visual acuity showed an increasing trend(tbefore treatment vs.t1 month after treatment=4.527,8.395,p<.001;t1 month after treatment vs.t3 months after treatment=5.369,5.349,p<.001;t3 months after treatment vs.t6 months after treatment=3.335,3.730,p<.001)with the time going by in the two groups.Compared with the indicators before treatment,the levels of IL-1β,IL-6 and IL-8 in the serum in 1 month after treatment were lower in both two groups(tcombination group=10.544,32.169,33.156,all p<.001;tranibizumab group=8.996,25.687,30.754,all p<.001),and these indicators in the combination group were lower than those in the ranibizumab group(t=2.894,p=.005;t=5.997,p<.001;t=3.934,p<.001).Compared with the indicators before treatment,the levels of IL-2 in the serum in 3 months after treatment in the two groups were higher(t=20.067,9.091,all p<.001),and the indicator in the combination group was higher than that in the ranibizumab group(t=7.705,p<.001).There were no statistically significant differences in the incidences of bleeding,intraocular foreign body sensation and transient high IOP and the total incidence of complications between the two groups(correctionχ^(2)=0.001,p=.972;correctionχ^(2)=0.221,p=.638;Fisher’s exact test p=.116;correctionχ^(2)=0.004,p=.951).Conclusions:Intravitreal injection of ranibizumab combined with triamcinolone acetonide can effectively improve the visual function of wet AMD,reduce CMT and the levels of IL-1β,IL-6 and IL-8 in the serum,increase the level of IL-2 in the serum and relieve the degree of inflammatory responses.

Treatment options for the wet form of age-related macular degeneration--a perspective

Treatment of the wet form of age-related macular degeneration(wet AMD) has been revolutionized a decade ago with the introduction of vascular endothelial growth factor(VEGF) blockers that reduce neovascularization and macular edema. Two approved drugs are marketed for the treatment of wet AMD—ranibizumab and aflibercept, but there is a third drug, bevacizumab, which is widely used offlabel; a cancer drug that also blocks VEGF but was never tested in pivotal trials and never approved for ophthalmic indications including wet AMD. Similarity of bevacizumab to ranibizumab led to off-label use and even to government-sponsored studies comparison the approved ranibizumab head-to-head to the offlabel cancer drug bevacizumab in wet AMD, like the Comparison of Age-related Macular Degeneration Treatments Trials(CATT) study, discussed in this perspective paper. Recent publication of 5-year follow-up from the initial 2-year CATT study provided the occasion to discuss the similarities and differences between these two drugs and the lessons learned from the last decade of anti-VEGF therapy for wet AMD. Clinical efficacy is comparable, with an advantage for ranibizumab. Likewise, safety finding favor ranibizumab over bevacizumab in some aspects. The latest addition of approved anti-VEGF drugs for wet AMD, aflibercept, may provide even more benefit to patients. In this perspective we discuss results of CATT and other longterm follow-up and comparative studies. While all demonstrate clinical benefit of anti-VEGF, all reveal that most patients' loose visual acuity(VA) in real-life situations over 5–7 years. This loss is based on—what we believe—significant under-treatment of wet AMD patients, due to economic or practical limitations and overestimation of perceived risks as geographic atrophy. We compare own data that showed more intensive treatment(more than twice the CATT-follow-up injections) with ranibizumab or aflibercept can maintain a sustained gain in VA in wet AMD patients after 6 years. We encourage retina specialists to treat wet AMD patients more aggressively and frequently in order to provide the maximum benefit for their patients.

Biomaterial engineering strategies for modeling the Bruch's membrane in age-related macular degeneration

Age-related macular degeneration,a multifactorial inflammatory degenerative retinal disease,ranks as the leading cause of blindness in the elderly.Strikingly,there is a scarcity of curative therapies,especially for the atrophic advanced form of age-related macular degeneration,likely due to the lack of models able to fully recapitulate the native structure of the outer blood retinal barrier,the prime to rget tissue of age-related macular degeneration.Standard in vitro systems rely on 2D monocultures unable to adequately reproduce the structure and function of the outer blood retinal barrier,integrated by the dynamic interaction of the retinal pigment epithelium,the Bruch's membrane,and the underlying choriocapillaris.The Bruch's membrane provides structu ral and mechanical support and regulates the molecular trafficking in the outer blood retinal barrier,and therefo re adequate Bruch's membrane-mimics are key for the development of physiologically relevant models of the outer blood retinal barrie r.In the last years,advances in the field of biomaterial engineering have provided novel approaches to mimic the Bruch's membrane from a variety of materials.This review provides a discussion of the integrated properties and function of outer blood retinal barrier components in healt hy and age-related macular degeneration status to understand the requirements to adequately fabricate Bruch's membrane biomimetic systems.Then,we discuss novel materials and techniques to fabricate Bruch's membrane-like scaffolds for age-related macular degeneration in vitro modeling,discussing their advantages and challenges with a special focus on the potential of Bruch's membrane-like mimics based on decellularized tissue.

NLRP3 and autophagy in retinal ganglion cell inflammation in age-related macular degeneration:potential therapeutic implications

Retinal degenerative diseases were a large group of diseases characterized by the primary death of retinal ganglion cells(RGCs).Recent studies had shown an interaction between autophagy and nucleotide-binding oligomerization domain-like receptor 3(NLRP3)inflammasomes,which may affect RGCs in retinal degenerative diseases.The NLRP3 inflammasome was a protein complex that,upon activation,produces caspase-1,mediating the apoptosis of retinal cells and promoting the occurrence and development of retinal degenerative diseases.Upregulated autophagy could inhibit NLRP3 inflammasome activation,while inhibited autophagy can promote NLRP3 inflammasome activation,which leaded to the accelerated emergence of drusen and lipofuscin deposition under the neurosensory retina.The activated NLRP3 inflammasome could further inhibit autophagy,thus forming a vicious cycle that accelerated the damage and death of RGCs.This review discussed the relationship between NLRP3 inflammasome and autophagy and its effects on RGCs in age-related macular degeneration,providing a new perspective and direction for the treatment of retinal diseases.

HCSP-Net:A Novel Model of Age-Related Macular Degeneration Classification Based on Color Fundus Photography

Age-related macular degeneration(AMD)ranks third among the most common causes of blindness.As the most conventional and direct method for identifying AMD,color fundus photography has become prominent owing to its consistency,ease of use,and good quality in extensive clinical practice.In this study,a convolutional neural network(CSPDarknet53)was combined with a transformer to construct a new hybrid model,HCSP-Net.This hybrid model was employed to tri-classify color fundus photography into the normal macula(NM),dry macular degeneration(DMD),and wet macular degeneration(WMD)based on clinical classification manifestations,thus identifying and resolving AMD as early as possible with color fundus photography.To further enhance the performance of this model,grouped convolution was introduced in this study without significantly increasing the number of parameters.HCSP-Net was validated using an independent test set.The average precision of HCSPNet in the diagnosis of AMD was 99.2%,the recall rate was 98.2%,the F1-Score was 98.7%,the PPV(positive predictive value)was 99.2%,and the NPV(negative predictive value)was 99.6%.Moreover,a knowledge distillation approach was also adopted to develop a lightweight student network(SCSP-Net).The experimental results revealed a noteworthy enhancement in the accuracy of SCSP-Net,rising from 94%to 97%,while remarkably reducing the parameter count to a quarter of HCSP-Net.This attribute positions SCSP-Net as a highly suitable candidate for the deployment of resource-constrained devices,which may provide ophthalmologists with an efficient tool for diagnosing AMD.

Regulatory factors of Nrf2 in age-related macular degeneration pathogenesis

Age-related macular degeneration(AMD)is a complicated disease that causes irreversible visual impairment.Increasing evidences pointed retinal pigment epithelia(RPE)cells as the decisive cell involved in the progress of AMD,and the function of anti-oxidant capacity of PRE plays a fundamental physiological role.Nuclear factor erythroid 2 related factor 2(Nrf2)is a significant transcription factor in the cellular anti-oxidant system as it regulates the expression of multiple anti-oxidative genes.Its functions of protecting RPE cells against oxidative stress(OS)and ensuing physiological changes,including inflammation,mitochondrial damage and autophagy dysregulation,have already been elucidated.Understanding the roles of upstream regulators of Nrf2 could provide further insight to the OS-mediated AMD pathogenesis.For the first time,this review summarized the reported upstream regulators of Nrf2 in AMD pathogenesis,including proteins and miRNAs,and their underlying molecular mechanisms,which may help to find potential targets via regulating the Nrf2 pathway in the future research and further discuss the existing Nrf2 regulators proved to be beneficial in preventing AMD.

Comparative study between swept-source and spectraldomain OCTA for imaging of choroidal neovascularization in age-related macular degeneration

AIM:To compare the dif ferences of choroidal neovascularization(CNV)measurements between sweptsource and spectral-domain optical coherence tomography angiography(SS-OCTA and SD-OCTA)in neovascular agerelated macular degeneration(nAMD)and the imaging reliability of the two devices.METHODS:Prospective comparative study.SS-OCTA and SD-OCTA were used to scan the same eye with the modes of 3×3 and 6×6 mm2 centered on the neovascularization.Only qualified images were chosen and the border of CNV was manually delineated by two graders independently.The area of CNV(ACNV),vascular perfusion density(PD),and vessel length density(VLD)within the delineation were calculated using Image J.The differences of CNV measurements between the two OCTA devices were compared using Bland-Altman analysis.The agreement between the two graders on the measurements of each device was compared using the intraclass correlation coefficient(ICC).RESULTS:A total of 18 patients(22 eyes)with nAMD were included.The measurements of ACNV,PD,and VLD were 7.247±4.586 and 4.901±3.741 mm^(2),43.202±9.636 and 34.904±10.489,6.339±1.228 and 5.908±1.741 mm^(-1) for SS-OCTA and SD-OCTA,respectively.The differences between the two devices were 2.346±3.030 mm^(2)(Z=-3.782,P<0.0001),8.298±14.160(Z=-2.419,P=0.016),and 0.431±2.114 mm^(-1)(Z=-0.828,P=0.408)for ACNV,PD and VLD,respectively.The ICC between two graders were 0.893(P<0.001),0.902(P<0.001),0.885(P<0.001)for ACNV,PD,VLD in SS-OCTA,and 0.971(P<0.001),0.976(P<0.001),0.973(P<0.001)in SD-OCTA,respectively.CONCLUSION:Both OCTA devices have high imaging reliability.Compared with SD-OCTA,SS-OCTA has a larger ACNV measurements,but doesn’t show better resolution of internal vessels of CNV and well signal strength.

Investigating the causal link between gut microbiota and dry age-related macular degeneration:a bidirectional Mendelian randomization study

AIM:To assess the causal link between 211 gut microbiota(GM)taxa and dry age-related macular degeneration(dAMD)risk.METHODS:Mendelian randomization using instrumental factors taken from a genome-wide association study(GWAS)were used.Inverse variance weighted(IVW)analysis and sensitivity analysis were performed on the FinnGen project,which included 5095 cases and 222590 controls.RESULTS:The IVW analysis showed substantial genusand family-level relationships between GM taxa and dAMD risk.Specifically,the family Peptococcaceae(P=0.03),genus Bilophila(P=3.91×10^(-3)),genus Faecalibacterium(P=6.55×10^(-3)),and genus Roseburia(P=0.04)were linked to a higher risk of developing dAMD,while the genus Candidatus Soleaferrea(P=7.75×10^(-4)),genus Desulfovibrio(P=0.04)and genus Eubacterium ventriosum group(P=0.04)exhibited a protective effect against dAMD.No significant causal relationships were observed at higher taxonomic levels.Additionally,in the reverse IVW analysis,no meaningful causal effects of the 7 GM taxa.CONCLUSION:These findings give support for the gutretina axis participation in dAMD and shed light on putative underlying processes.Investigations on the connection between GM and dAMD have not yet revealed the underlying mechanism.

RNA-sequencing expression profile and functional analysis of retinal pigment epithelium in atrophic age-related macular degeneration

The retinal pigment epithelium(RPE)is fundamental to sustaining retinal homeostasis.RPE abnormality leads to visual defects and blindness,including age-related macular degeneration(AMD).Although breakthroughs have been made in the treatment of neovascular AMD,effective intervention for atrophic AMD is largely absent.The adequate knowledge of RPE pathology is hindered by a lack of the patients'RPE datasets,especially at the single-cell resolution.In the current study,we delved into a large-scale single-cell resource of AMD donors,in which RPE cells were occupied in a substantial proportion.Bulk RNA-seq datasets of atrophic AMD were integrated to extract molecular characteristics of RPE in the pathogenesis of atrophic AMD.Both in vivo and in vitro models revealed that carboxypeptidase X,M14 family member 2(CPXM2),was specifically expressed in the RPE cells of atrophic AMD,which might be induced by oxidative stress and involved in the epithelial-mesenchymal transition of RPE cells.Additionally,silencing of CPXM2 inhibited the mesenchymal phenotype of RPE cells in an oxidative stress cell model.Thus,our results demonstrated that CPXM2 played a crucial role in regulating atrophic AMD and might serve as a potential therapeutic target for atrophic AMD.

Nomogram for predicting short-term response to anti-vascular endothelial growth factor treatment in neovascular age-related macular degeneration:An observational study

BACKGROUND Anti-vascular endothelial growth factor(anti-VEGF)therapy is critical for managing neovascular age-related macular degeneration(nAMD),but understanding factors influencing treatment efficacy is essential for optimizing patient outcomes.AIM To identify the risk factors affecting anti-VEGF treatment efficacy in nAMD and develop a predictive model for short-term response.METHODS In this study,65 eyes of exudative AMD patients after anti-VEGF treatment for≥1 mo were observed using optical coherence tomography angiography.Patients were classified into non-responders(n=22)and responders(n=43).Logistic regression was used to determine independent risk factors for treatment response.A predictive model was created using the Akaike Information Criterion,and its performance was assessed with the area under the receiver operating characteristic curve,calibration curves,and decision curve analysis(DCA)with 500 bootstrap re-samples.RESULTS Multivariable logistic regression analysis identified the number of junction voxels[odds ratio=0.997,95%confidence interval(CI):0.993-0.999,P=0.010]as an independent predictor of positive anti-VEGF treatment outcomes.The predictive model incorporating the fractal dimension,number of junction voxels,and longest shortest path,achieved an area under the curve of 0.753(95%CI:0.622-0.873).Calibration curves confirmed a high agreement between predicted and actual outcomes,and DCA validated the model's clinical utility.CONCLUSION The predictive model effectively forecasts 1-mo therapeutic outcomes for nAMD patients undergoing anti-VEGF therapy,enhancing personalized treatment planning.

Progress of clinical therapies for dry age-related macular degeneration

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.