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 explore the effect and mechanism of Lycium barbarum polysaccharide(LBP)inhibiting retinal neovascularization.METHODS:In vitro tests were performed on human retinal microvascular endothelial cells(HRECs)from thr...AIM:To explore the effect and mechanism of Lycium barbarum polysaccharide(LBP)inhibiting retinal neovascularization.METHODS:In vitro tests were performed on human retinal microvascular endothelial cells(HRECs)from three groups,including control group(normal oxygen),hypoxic group(hypoxia at 37℃,1%O_(2),5%CO_(2),and 94%N_(2)),and LBP group(hypoxic group with LBP 100μg/mL).In vivo experiments,C57 mice were divided into three groups:control group(normal rearing group),the oxygen-induced ischemic retinopathy(OIR)group,and the OIR with 50 mg/kg LBP group.Retinal neovascularization was observed by fluorescein angiography and quantified.Retinal thickness was evaluated by Hematoxylin and eosin(HE)stain.The expression of epidermal growth factor receptor(EGFR),phosphatidylinositol 3-kinase(PI3K),mammalian target of rapamycin(mTOR),phosphorylated mammalian target of rapamycin(p-mTOR),protein kinase B(AKT),phosphorylated protein kinase B(p-AKT),interleukin-1β(IL-1β),inducible nitric oxide synthase(iNOS),and tumor necrosis factor-α(TNF-α)in each group were analyzed by Western blot.IL-1βlevel in retina was analyzed using immunohistochemical staining.RESULTS:The increased area of neovascular clusters in OIR mice was significantly decreased by LBP.Retinal thickness of OIR mice was significantly thinner compared with normal oxygenated mice and was increased in LBP group.Compared with those in the hypoxic groups,Western blotting of HRECs and retinal tissues revealed that the expression of EGFR,PI3K,p-mTOR,p-AKT,IL-1β,iNOS,and TNF-αdecreased in the LBP group but was still greater than that in control group.Moreover,IL-1βwas reduced in retinal sections treated with LBP.In the scratch test,the cell migration of the hypoxic group was significantly greater than that of the control group,while LBP treatment attenuated this increase in migration.CONCLUSION:LBP reduces retinal neovascularization and inflammation in vivo and inhibits the migration of HRECs in vitro by regulating the EGFR/PI3K/Akt/mTOR signaling pathway.展开更多
AIM:To repor t the 24mo outcomes of vascular endothelial growth factor(VEGF)inhibitors for myopic choroidal neovascularization(mCNV)in routine clinical practice and simultaneously evaluated the real-world safety.METHO...AIM:To repor t the 24mo outcomes of vascular endothelial growth factor(VEGF)inhibitors for myopic choroidal neovascularization(mCNV)in routine clinical practice and simultaneously evaluated the real-world safety.METHODS:The patients who received intravitreal injections of VEGF inhibitors of either ranibizumab(0.5 mg)or conbercept(0.5 mg)for mCNV were analyzed from 1 January 2017 to 1 January 2022.The primary outcome variables were mean change in best-corrected visual acuity(BCVA)and central macular thickness(CMT)changes.The secondary outcome variables included IOP changes,the period of mCNV re-treatment,and ocular adverse events.RESULTS:Totally 83 patients aged 56.40±15.36y with axial length 29.67±2.09 mm were included.In visual acuity,the mean logMAR BCVA at baseline was 0.81±0.43.After the initial improvement at 1,3,and 6mo(P<0.05),from month 12 onwards,no statistical difference compared to baseline was found.The mean CMT from 1mo onwards had a statistically significant decrease compared with baseline CMT(P<0.05).The regression model showed better baseline BCVA and thicker baseline CMT,significantly associated with the final outcomes.In univariate analysis,choosing 3+pro re nata(PRN)as the initial injection treatment regimen was associated with better BCVA at 24mo[hazard ratio(HR)=-0.65,95%CI:-1.23,-0.07,P=0.048].However,the difference was not significant in multivariate analysis(HR=-0.59,95%CI:-1.21,0.03,P=0.089).Regarding mCNV recurrence,the mean period(P=0.725)and the proportion of mCNV reactivation(P=1.00)were similar between ranibizumab and conbercept.Kaplan-Meier plot also analyzed that the median time of re-injection was not significantly different among gender,drug,and initial injection treatment regimen.No systemic adverse events related to the therapy were observed.CONCLUSION:BCVA gains achieved by the end of our study maintain generally sustained at the 24-mo follow-up.The findings also indicate that ranibizumab and conbercept demonstrate comparable efficacy and safety profiles.Additionally,intravitreal anti-VEGF therapy using 1+PRN regimen,offers certain advantages in both efficacy and cost-effectiveness.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 identify optical coherence tomography(OCT)features present at the diagnosis of neovascular age-related macular degeneration(nAMD)that could predict retinal atrophy(RA)and visual performance in patients treated ...AIM:To identify optical coherence tomography(OCT)features present at the diagnosis of neovascular age-related macular degeneration(nAMD)that could predict retinal atrophy(RA)and visual performance in patients treated with intravitreal aflibercept.METHODS:OCT data collected at the time of nAMD diagnosis(T0),after the first(T1)and third(T2)intravitreal aflibercept injection,and 5y post-diagnosis(T3)were analyzed.The study included 46 eyes from patients undergoing treatment.The association of OCT features with RA and visual acuity(VA)development over time were evaluated.RESULTS:Patients with RA at T3 exhibited worse VA(35.19±5.7 vs 8.90±2.3,P<0.001)and a lower rate of improvement or stability at T2(90.48%vs 56.00%,P=0.019)and T3(85.71%vs 8.00%,P<0.001).The development of RA at T3 was linked with type 2 macular neovascularization(MNV;4.76%vs 36.00%,P=0.013),thinner outer nuclear layer(ONL,88.89±7.82μm vs 71.38±14.14μm,P=0.033),presence of intraretinal fluid(IRF,42.86%vs 80.00%,P=0.014),presence of IRF without subretinal fluid at T0(SRF,4.76%vs 32.00%,P=0.027),and reduced central foveal thickness at T3(CFT,190.14±22.79μm vs 124.32±14.35μm,P<0.001).The presence of SRF with or without IRF at the diagnosis was comparable between the two groups(90.48%vs 68.00%;P=0.084).CONCLUSION:Type 2 MNV,reduces ONL and CFT,and IRF presence at baseline may signal a higher risk of RA in treatment-naive nAMD patients,underscoring the importance of these OCT features in early risk assessment and management strategies.展开更多
AIM:To investigate the choroidal vascular index(CVI)and the choroidal structural changes beyond the subfoveal area(analyzed across a 20 mm×24 mm scanning area)in eyes with chronic central serous chorioretinopathy...AIM:To investigate the choroidal vascular index(CVI)and the choroidal structural changes beyond the subfoveal area(analyzed across a 20 mm×24 mm scanning area)in eyes with chronic central serous chorioretinopathy(cCSC)eyes with macular neovascularization(MNV)using ultra-widefield swept-source optical coherence tomography angiography(UWF SS-OCTA).METHODS:This retrospective comparative study included 46 cCSC with MNV eyes(With MNV group),52 cCSC without MNV eyes(Without MNV group),and 40 age-matched healthy controls.UWF SS-OCTA imaging with a 20 mm×24 mm protocol was used to quantify CVI across 9 subfields(superotemporal,superior,superonasal,temporal,central,nasal,inferotemporal,inferior,and inferonasal).The CVI was compared among the groups.RESULTS:With MNV group demonstrated significantly older mean age than Without MNV group(56.2±6.1 vs 47.5±8.6y,P<0.001).The CVI was significantly lower in the With MNV group than in the Without MNV group,except in the superotemporal,superior,and temporal regions(all P<0.05).Notably,despite MNV-associated CVI reductions,the With MNV group maintained a higher CVI than the control group in all 5 subfields(superior,temporal,central,inferior,and inferonasal;all P<0.05).In the central region,CONCLUSION:CVI decreases,and choroidal structural changes extend beyond the subfoveal area in cCSC with MNV eyes,providing with an imaging evidence for the important role of choroidal ischemia in the pathogenesis of MNV in cCSC.展开更多
AIM:To present a case series of rapid-onset neovascular glaucoma(NVG)accompanied by vitreous haemorrhage(VH)following cataract surgery in diabetic patients,and to evaluate the efficacy of pars plana vitrectomy(PPV)com...AIM:To present a case series of rapid-onset neovascular glaucoma(NVG)accompanied by vitreous haemorrhage(VH)following cataract surgery in diabetic patients,and to evaluate the efficacy of pars plana vitrectomy(PPV)combined with Ahmed glaucoma valve(AGV)implantation.METHODS:This is a retrospective,single-center,consecutive case series.All patients underwent 23-gauge PPV with AGV implantation 2–3d after intravitreal ranibizumab injection(IVR).The minimum postoperative follow-up period lasted 12mo.The primary outcome measures included bestcorrected visual acuity(BCVA),intraocular pressure(IOP),and topical hypotensive medications.RESULTS:Fifteen diabetic patients(age,46–81y)with rapid-onset NVG and VH following uncomplicated phacoemulsification were included.The median time to the initial NVG diagnosis following cataract surgery was within 4wk.After PPV combined with AGV implantation,the mean BCVA(logMAR)improved from 1.9(range:1.0 to 2.6)preoperatively to 1.2(range:0.2 to 2.6)at the final follow-up.Baseline BCVA and the presence of diabetic nephropathy(DN)were significantly associated with the final BCVA in the multiple regression model.The mean postoperative IOP at all follow-up visits was significantly reduced compared to baseline.At the final follow-up,9 patients required one or two topical ocular hypotensive medications,while the other 6 needed not.Success was achieved in 87%,and the reoperation rate was 20%.The majority of NVG cases(9/15)were primarily attributed to the rapid progression of proliferative diabetic retinopathy.However,a notable subset(6 eyes)was complicated retinal vein occlusion or carotid artery occlusion.CONCLUSION:PPV combined with AGV implantation after adjuvant IVR for rapid-onset NVG with VH following diabetic cataract surgery is one of the safe and effective treatments.Baseline BCVA and preexisting DN may be potential indicators for visual outcomes.展开更多
Retinopathy of prematurity(ROP)is a vision-threatening disorder that leads to pathological growth of the retinal vasculature due to hypoxia.Here,we investigated the potential effects of alamandine,a novel heptapeptide...Retinopathy of prematurity(ROP)is a vision-threatening disorder that leads to pathological growth of the retinal vasculature due to hypoxia.Here,we investigated the potential effects of alamandine,a novel heptapeptide in the renin-angiotensin system(RAS),on hypoxia-induced retinal neovascularization and its underlying mechanisms.In vivo,the C57BL/6J mice with oxygen-induced retinopathy(OIR)were injected intravitreally with alamandine(1.0µmol/kg per eye).In vitro,human retinal microvascular endothelial cells(HRMECs)were utilized to investigate the effects of alamandine(10µg/mL)on proliferation,apoptosis,migration,and tubular formation under vascular endothelial growth factor(VEGF)stimulation.Single-cell RNA sequencing(scRNA-seq)matrix data from the Gene Expression Omnibus(GEO)database and RAS-related genes from the Molecular Signatures Database(MSigDB)were sourced for subsequent analyses.By integrating scRNA-seq data across multiple species,we identified that RAS-associated endothelial cell populations were highly related to retinal neovascularization.The liquid chromatography-tandem mass spectrometry(LC-MS/MS)analysis revealed a significant decrease in alamandine levels in both the serum and retina of OIR mice compared to those in the control group.Next,alamandine ameliorated hypoxia-induced retinal pathological neovascularization and physiologic revascularization in OIR mice.In vitro,alamandine effectively mitigated VEGF-induced proliferation,scratch wound healing,and tube formation of HRMECs primarily by inhibiting the hypoxia-inducible factor-1α(HIF-1α)/VEGF pathway.Further,coincubation with D-Pro7(Mas-related G protein-coupled receptor D(MrgD)antagonist)hindered the beneficial impacts of alamandine on hypoxia-induced pathological angiogenesis both in vivo and in vitro.Our findings suggested that alamandine could mitigate retinal neovascularization by targeting the MrgD-mediated HIF-1α/VEGF pathway,providing a potential therapeutic agent for OIR prevention and treatment.展开更多
Macrophages are involved in angiogenesis, and might also contribute to the pathogenesis of intraocular neovascular diseases. Recent studies indicated that macrophages exert different functions in the process of intrao...Macrophages are involved in angiogenesis, and might also contribute to the pathogenesis of intraocular neovascular diseases. Recent studies indicated that macrophages exert different functions in the process of intraocular neovascularization, and the polarization of M1 and M2 phenotypes plays extremely essential roles in the diverse functions of macrophages. Moreover, a large number of cytokines released by macrophages not only participate in macrophage polarization, but also associate with retinal and choroidal neovascular diseases. Therefore, macrophage might be considered as a novel therapeutic target to the treatment of pathological neovascularization in the eye. This review mainly summarizes diverse roles of macrophages and discusses the possible mechanisms in retinal and choroidal neovascularization.展开更多
Neovascular glaucoma is defined as iris and/or anterior chamber angle neovascularization associated with increased intraocular pressure. It is a secondary glaucoma that is most frequently caused by severe retinal isch...Neovascular glaucoma is defined as iris and/or anterior chamber angle neovascularization associated with increased intraocular pressure. It is a secondary glaucoma that is most frequently caused by severe retinal ischemia. The most common diseases responsible for the development of neovascular glaucoma are diabetic retinopathy, ischemic central retinal vein occlusion,and ocular ischemic syndrome. Uncommon causes include ocular radiation, ocular tumors, uveitis and other miscellaneous conditions. Vascular endothelial growth factor is an important and likely predominant agent involved in the pathogenesis of intraocular neovascularization and neovascular glaucoma. The evolution of clinical and histopathological changes from predisposing conditions to the occurrence of rubeosis iridis and neovascular glaucoma is divided into four stages: prerubeosis, preglaucoma, open angle glaucoma, and angle-closure glaucoma.展开更多
Ischemic and neovascular disease is one of the most difficult ocular diseases to deal with nowadays.Redundancy,poor visual acuity and decreased life quality are bothering patients and ophthalmologists for decades.Afte...Ischemic and neovascular disease is one of the most difficult ocular diseases to deal with nowadays.Redundancy,poor visual acuity and decreased life quality are bothering patients and ophthalmologists for decades.After vascular endothelial growth factor(VEGF)was found to be a primary factor in promoting retinal angiogenesis,intravitreal injection of anti-VEGF drugs has been the firstline treatment.Whereas,some patients are refractory to this therapy and problems of economic burden,local complications and adverse effects promote researches into other possible targets.The vasohibin(VASH)family is a newly-investigated factor in modulating ocular angiogenesis.The family includes VASH1 and VASH2,which show opposite effects of inhibiting and accelerating angiogenesis respectively.Positive results have been reported in cellular and animal experiments.With further researches,it can be a promising future target of treating ocular neovascular diseases.展开更多
AIM:lo evaluate the changes on optical coherence tomography angiography(OCTA) and fluorescein angiography(FA) and their correlation in neovascular agerelated macular degeneration(nAMD) before and after intravitreal af...AIM:lo evaluate the changes on optical coherence tomography angiography(OCTA) and fluorescein angiography(FA) and their correlation in neovascular agerelated macular degeneration(nAMD) before and after intravitreal aflibercept injections(IAIs).METHODS:In 43 treatment-na?ve patients with nAMD,choroidal neovascularization(CNV) in OCTA were morphologically and quantitatively analyzed before and after IAIs to determine whether they are correlated with leakage on FA or not.By combining CNV in OCTA and leakage in FA,lesions were characterized as three types:L+C+(with both CNV and leakage),L-C+(with CNV but without leakage),or L+C-lesion(with leakage outside CNV).RESULTS:Before IAI,while 27 eyes had L+C+lesion only,16 eyes had both L+C+and L-C+lesions simultaneously.Tiny capillaries and anastomosis in CNV were more developed in L+C+lesion,at 86.0% and58.1%,respectively,relative to 9.3% and 9.3% in L-C+lesions(P<0.001).After IAIs in 33 eyes,tiny capillaries and anastomosis were decreased in the lesions with cessation of leakage on FA(P<0.001 and P=0.001,respectively).In quantitative analysis,neovascularization length and numbers of junctions and endpoints were also significantly decreased.CONCLUSION:Leakage on FA is associated with CNV morphology in OCTA and remained so after IAls.Therefore,by carefully assessing the morphological and quantitative changes of CNV in OCTA before and after treatment,activity of nAMD is expected even though CNV on OCTA is not completely matched with fluorescein leakage.展开更多
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 fo...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.展开更多
AIM:To assess neovascularization within human ca-rotid atherosclerotic soft plaques in patients with isch-emic stroke.METHODS:Eighty-one patients with ischemic stroke and 95 patients without stroke who had soft athero...AIM:To assess neovascularization within human ca-rotid atherosclerotic soft plaques in patients with isch-emic stroke.METHODS:Eighty-one patients with ischemic stroke and 95 patients without stroke who had soft athero-sclerotic plaques in the internal carotid artery were studied.The thickest soft plaque in each patient was examined using contrast-enhanced ultrasound.Time-intensity curves were collected from 5 s to 3 min after contrast injection.The neovascularization within the plaques in the internal carotid artery was evaluated using the ACQ software built into the scanner by 2 of the experienced investigators who were blinded to the clinical history of the patients.RESULTS:Ischemic stroke was present in 7 of 33 patients(21%) with grade Ⅰ plaque,in 14 of 51 pa-tients(28%) with grade Ⅱ plaque,in 26 of 43 patients(61%) with grade Ⅲ plaque,and in 34 of 49 patients(69%) with grade Ⅳ plaque(P < 0.001 comparing grade Ⅳ plaque with grade I plaque and with grade Ⅱ plaque and P = 0.001 comparing grade Ⅲ plaque with grade Ⅰ plaque and with grade Ⅱ plaque).Analysis of the time intensity curves revealed that patients with ischemic stroke had a significantly higher intensity of enhancement(IE) than those without ischemic stroke(P < 0.01).The wash-in time(WT) of plaque was signifi-cantly shorter in stroke patients(P < 0.05).The sensi-tivity and specificity for IE in the plaque were 82% and 80%,respectively,and for WT were 68% and 74%,respectively.There was no significant difference in the peak intensity or time to peak between the 2 groups.CONCLUSION:This study shows that the higher the grade of plaque enhancement,the higher the risk of ischemic stroke.The data suggest that the presence of neovascularization is a marker for unstable plaque.展开更多
AIM:To discuss the impact of Lycium Barbarum Polysaccharide (LBP) and Danshensu purified from Traditional Chinese Medicine (TCM) on vascular endothelial growth factor (VEGF) of rabbits with retinal neovascularization....AIM:To discuss the impact of Lycium Barbarum Polysaccharide (LBP) and Danshensu purified from Traditional Chinese Medicine (TCM) on vascular endothelial growth factor (VEGF) of rabbits with retinal neovascularization. METHODS:Forty rabbits were divided into normal control group, model control group, LBP group and Danshensu group. Animals in the normal control group were fed in the normal oxygen environment. Animals in the other three groups were put into the environment with 70% oxygen for 5 days in order to build the model of oxygen-induced vascular proliferation retinopathy. And then different TCM extract was injected into the abdominal cavities of these annimals. After 7 days, the VEGF content of in the serum of rabbit was measured by double antibody sandwich method. RESULTS:Data analysis indicated that VEGF content was as follows:Danshensu group was lower than model control group (12.92 ±3.84ng/L vs 19.32 ±4.15ng/L, P 【 0.05); LBP group and normal control group were lower than model control group (12.92±3.84ng/L, 9.26±1.61ng/L vs 19.32±4.15ng/L, P【0.01); total blood viscosity, plasma viscosity, cholesterol content, fibrinogen content and triacylglycerol content after peritoneal injection of LBP and Danshensu were obviously lower than before injection. CONCLUSION:TCM extract-LBP and Danshensu can prominently reduce the content of VEGF in the process of vascular proliferative retinopathy of rabbit; can prevent the occurrence of retinal microvascular disease by improving partial oxygen -deficient environment or affecting all kinds of new growth factor.展开更多
AIM: To evaluate the risk factors associated with retinal neovascularization of diabetic retinopathy in northern Chinese Han patients with type 2 diabetes mellitus (T2DM). METHODS: The clinical characteristics of 200 ...AIM: To evaluate the risk factors associated with retinal neovascularization of diabetic retinopathy in northern Chinese Han patients with type 2 diabetes mellitus (T2DM). METHODS: The clinical characteristics of 200 patients with proliferative diabetic retinopathy (PDR) and 100 age-matched healthy individuals were compared. The univariate and multivariate logistic regression analysis were performed in the patients with PDR. RESULTS: Fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), blood urea nitrogen (BUN), uric acid (UA), white blood cell count (WBC), absolute neutrophil count, hematocrit (HCT) and mean platelet volume (MPV) and mean platelet volume (MPV) were all significantly higher in patients with PDR than in the control group (P<0.05). The univariate and multivariate logistic regression analysis showed that risk factors independently associated with retinal neovascularization of DR were duration of diabetes mellitus (OR=1.112; P=0.000), BUN (OR=1.277; P=0.000), smoking (OR=3.967; P=0.000) and MPV (OR=2.472; P=0.000). On the other hand, panretinal photocoagulation was associated with reduced risk of retinal neovascularization (OR=0.983; P=0.000). CONCLUSION: Preventing and controlling T2DM in terms of risk factors, including duration of diabetes, BUN, smoking and MPV, might offer novel approaches to prevent or delay the onset of retinal neovascularization in patients with PDR.展开更多
A large subset of corneal pathologies involves the formation of new vessels(neovascularization), leading to compromised visual acuity. This article aims to review the clinical causes and presentations of corneal neova...A large subset of corneal pathologies involves the formation of new vessels(neovascularization), leading to compromised visual acuity. This article aims to review the clinical causes and presentations of corneal neovascularization(CNV) by examining the mechanisms behind common CNV-related corneal pathologies, with a particular focus on herpes simplex stromal keratitis,contact lenses-induced keratitis and CNV secondary to keratoplasty. Moreover, we reviewed CNV in the context of different types of corneal transplantation and keratoprosthesis, and summarized the most relevant treatment available so far.展开更多
Endothelial progenitor cells are resident in the bone marrow blood sinusoids and circulate in the peripheral circulation. They mobilize from the bone marrow after vascular injury and home to the site of injury where t...Endothelial progenitor cells are resident in the bone marrow blood sinusoids and circulate in the peripheral circulation. They mobilize from the bone marrow after vascular injury and home to the site of injury where they differentiate into endothelial cells. Activation and mobilization of endothelial progenitor cells from the bone marrow is induced via the production and release of endothelial progenitor cell-activating factors and includes specific growth factors and cytokines in response to peripheral tissue hypoxia such as after acute ischemic stroke or trauma. Endotheli- al progenitor cells migrate and home to specific sites following ischemic stroke via growth factor/ cytokine gradients. Some growth factors are less stable under acidic conditions of tissue isch- emia, and synthetic analogues that are stable at low pH may provide a more effective therapeutic approach for inducing endothelial progenitor cell mobilization and promoting cerebral neovascularization following ischemic stroke.展开更多
AIM:To explore the efficacy of preoperative intravitreal bevacizumab(IVB) injection combined with Ahmed glaucoma valve(AGV) implantation in the treatment of neovascular glaucoma(NVG).METHODS:This retrospective study i...AIM:To explore the efficacy of preoperative intravitreal bevacizumab(IVB) injection combined with Ahmed glaucoma valve(AGV) implantation in the treatment of neovascular glaucoma(NVG).METHODS:This retrospective study included 35 eyes from 35 patients who underwent preoperative IVB and AGV implantation for treatment of NVG. Findings such as intraocular pressure(IOP) number of anti-glaucoma medications, visual acuity(VA), surgical success rates,and complications were recorded.RESULTS:AfterAGVimplantation,IOPwas18.2±4.0mmHg,15.5±3.3 mm Hg and 9.8±2.6 mm Hg at 6, 12 and 36 mo,significantly decreased compared with pre-IOP(P 【0.01).The number of anti-glaucoma medications was 0.9 ±0.5,0.8 ±0.9 and 0.8 ±0.6 at 6, 12 and 36 mo, significantly decreased compared to pre-treatment(P 【0.01). At last visit, there were 19 eyes with stable VA, 4 with VA improvement, 12 with diminished VA and 3 with complete loss light perception. There were 7 cases that failed during 3-year fellow up period. Cumulative probabilities of valve survival by Kaplan-Meier analysis were 82.9%,74.1% and 71.0% at 12, 24 and 36 mo, respectively. Cox stepwise regression analysis found that the survival time was significant associated with the pre-visual acuity 【2/400(P 【0.05). Post-operative complications occurred in 8eyes, of which hyphema presented in 2 eyes, choroidal effusion in 2 eyes.CONCLUSION:The procedure of preoperative IVB andAGV implantation should be one of treatments for NVG because of its safety and effectiveness.展开更多
AIM: To compare the efficacies of subconjunctival bevacizumab, ranibizumab, and pegaptanib sodium injections for the inhibition of corneal neovascularization in an experimental rat model. METHODS: Sixteen corneas of 1...AIM: To compare the efficacies of subconjunctival bevacizumab, ranibizumab, and pegaptanib sodium injections for the inhibition of corneal neovascularization in an experimental rat model. METHODS: Sixteen corneas of 16 rats were chemically cauterized and randomized into four groups: bevacizumab group that treated with 0.05mL/1.25mg bevacizumab, ranibizumab group that treated with 0.05mL/0.5mg ranibizumab, pegaptanib group that treated with 0.05mL/0.15mg pegaptanib sodium, and control group that treated with 0.05mL saline solution. Digital photographs of the corneas were taken and analyzed using an image analysis software program. All corneas were excised and examined histologically on the 15 th day. RESULTS: Each treatment group had significantly less neovascularized corneal areas and fewer blood vessels than the control group (all P 【0.05). In addition, bevacizumab group had significantly less neovascu-larized corneal areas and fewer blood vessels than ranibizumab and pegaptanib groups (both P 【0.05). However, there was no significant difference between the ranibizumab and pegaptanib groups regarding percentage of neovascularized corneal areas and number of blood vessels (both P 】0.05). CONCLUSION: Subconjunctival bevacizumab, ranibiz-umab, and pegaptanib sodium were effective with no corneal epitheliopathy for inhibiting corneal neovascularization after corneal burn in rats .Bevacizumab was more effective than ranibizumab and pegaptanib sodium.展开更多
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 the Tianjin Health Research Project(No.ZC20069No.TJWJ2022MS040)+1 种基金the Foundation of the Committee of Integrated Traditional Chinese and Western Medicine(No.2021011)the Science and Technology Foundation of Tianjin Eye Hospital(No.YKYB1901).
文摘AIM:To explore the effect and mechanism of Lycium barbarum polysaccharide(LBP)inhibiting retinal neovascularization.METHODS:In vitro tests were performed on human retinal microvascular endothelial cells(HRECs)from three groups,including control group(normal oxygen),hypoxic group(hypoxia at 37℃,1%O_(2),5%CO_(2),and 94%N_(2)),and LBP group(hypoxic group with LBP 100μg/mL).In vivo experiments,C57 mice were divided into three groups:control group(normal rearing group),the oxygen-induced ischemic retinopathy(OIR)group,and the OIR with 50 mg/kg LBP group.Retinal neovascularization was observed by fluorescein angiography and quantified.Retinal thickness was evaluated by Hematoxylin and eosin(HE)stain.The expression of epidermal growth factor receptor(EGFR),phosphatidylinositol 3-kinase(PI3K),mammalian target of rapamycin(mTOR),phosphorylated mammalian target of rapamycin(p-mTOR),protein kinase B(AKT),phosphorylated protein kinase B(p-AKT),interleukin-1β(IL-1β),inducible nitric oxide synthase(iNOS),and tumor necrosis factor-α(TNF-α)in each group were analyzed by Western blot.IL-1βlevel in retina was analyzed using immunohistochemical staining.RESULTS:The increased area of neovascular clusters in OIR mice was significantly decreased by LBP.Retinal thickness of OIR mice was significantly thinner compared with normal oxygenated mice and was increased in LBP group.Compared with those in the hypoxic groups,Western blotting of HRECs and retinal tissues revealed that the expression of EGFR,PI3K,p-mTOR,p-AKT,IL-1β,iNOS,and TNF-αdecreased in the LBP group but was still greater than that in control group.Moreover,IL-1βwas reduced in retinal sections treated with LBP.In the scratch test,the cell migration of the hypoxic group was significantly greater than that of the control group,while LBP treatment attenuated this increase in migration.CONCLUSION:LBP reduces retinal neovascularization and inflammation in vivo and inhibits the migration of HRECs in vitro by regulating the EGFR/PI3K/Akt/mTOR signaling pathway.
基金Supported by Tianjin Key Medical Discipline(Specialty)Construction Project(No.TJYXZDXK-037A).
文摘AIM:To repor t the 24mo outcomes of vascular endothelial growth factor(VEGF)inhibitors for myopic choroidal neovascularization(mCNV)in routine clinical practice and simultaneously evaluated the real-world safety.METHODS:The patients who received intravitreal injections of VEGF inhibitors of either ranibizumab(0.5 mg)or conbercept(0.5 mg)for mCNV were analyzed from 1 January 2017 to 1 January 2022.The primary outcome variables were mean change in best-corrected visual acuity(BCVA)and central macular thickness(CMT)changes.The secondary outcome variables included IOP changes,the period of mCNV re-treatment,and ocular adverse events.RESULTS:Totally 83 patients aged 56.40±15.36y with axial length 29.67±2.09 mm were included.In visual acuity,the mean logMAR BCVA at baseline was 0.81±0.43.After the initial improvement at 1,3,and 6mo(P<0.05),from month 12 onwards,no statistical difference compared to baseline was found.The mean CMT from 1mo onwards had a statistically significant decrease compared with baseline CMT(P<0.05).The regression model showed better baseline BCVA and thicker baseline CMT,significantly associated with the final outcomes.In univariate analysis,choosing 3+pro re nata(PRN)as the initial injection treatment regimen was associated with better BCVA at 24mo[hazard ratio(HR)=-0.65,95%CI:-1.23,-0.07,P=0.048].However,the difference was not significant in multivariate analysis(HR=-0.59,95%CI:-1.21,0.03,P=0.089).Regarding mCNV recurrence,the mean period(P=0.725)and the proportion of mCNV reactivation(P=1.00)were similar between ranibizumab and conbercept.Kaplan-Meier plot also analyzed that the median time of re-injection was not significantly different among gender,drug,and initial injection treatment regimen.No systemic adverse events related to the therapy were observed.CONCLUSION:BCVA gains achieved by the end of our study maintain generally sustained at the 24-mo follow-up.The findings also indicate that ranibizumab and conbercept demonstrate comparable efficacy and safety profiles.Additionally,intravitreal anti-VEGF therapy using 1+PRN regimen,offers certain advantages in both efficacy and cost-effectiveness.
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.
文摘AIM:To identify optical coherence tomography(OCT)features present at the diagnosis of neovascular age-related macular degeneration(nAMD)that could predict retinal atrophy(RA)and visual performance in patients treated with intravitreal aflibercept.METHODS:OCT data collected at the time of nAMD diagnosis(T0),after the first(T1)and third(T2)intravitreal aflibercept injection,and 5y post-diagnosis(T3)were analyzed.The study included 46 eyes from patients undergoing treatment.The association of OCT features with RA and visual acuity(VA)development over time were evaluated.RESULTS:Patients with RA at T3 exhibited worse VA(35.19±5.7 vs 8.90±2.3,P<0.001)and a lower rate of improvement or stability at T2(90.48%vs 56.00%,P=0.019)and T3(85.71%vs 8.00%,P<0.001).The development of RA at T3 was linked with type 2 macular neovascularization(MNV;4.76%vs 36.00%,P=0.013),thinner outer nuclear layer(ONL,88.89±7.82μm vs 71.38±14.14μm,P=0.033),presence of intraretinal fluid(IRF,42.86%vs 80.00%,P=0.014),presence of IRF without subretinal fluid at T0(SRF,4.76%vs 32.00%,P=0.027),and reduced central foveal thickness at T3(CFT,190.14±22.79μm vs 124.32±14.35μm,P<0.001).The presence of SRF with or without IRF at the diagnosis was comparable between the two groups(90.48%vs 68.00%;P=0.084).CONCLUSION:Type 2 MNV,reduces ONL and CFT,and IRF presence at baseline may signal a higher risk of RA in treatment-naive nAMD patients,underscoring the importance of these OCT features in early risk assessment and management strategies.
基金Supported by General Program of National Natural Science Foundation of China(No.82471110)National Key Research and Development Program of China(No.2022YFC2502805)Postdoctoral Foundation of General Hospital of Central Theater Command(No.20210517KY04).
文摘AIM:To investigate the choroidal vascular index(CVI)and the choroidal structural changes beyond the subfoveal area(analyzed across a 20 mm×24 mm scanning area)in eyes with chronic central serous chorioretinopathy(cCSC)eyes with macular neovascularization(MNV)using ultra-widefield swept-source optical coherence tomography angiography(UWF SS-OCTA).METHODS:This retrospective comparative study included 46 cCSC with MNV eyes(With MNV group),52 cCSC without MNV eyes(Without MNV group),and 40 age-matched healthy controls.UWF SS-OCTA imaging with a 20 mm×24 mm protocol was used to quantify CVI across 9 subfields(superotemporal,superior,superonasal,temporal,central,nasal,inferotemporal,inferior,and inferonasal).The CVI was compared among the groups.RESULTS:With MNV group demonstrated significantly older mean age than Without MNV group(56.2±6.1 vs 47.5±8.6y,P<0.001).The CVI was significantly lower in the With MNV group than in the Without MNV group,except in the superotemporal,superior,and temporal regions(all P<0.05).Notably,despite MNV-associated CVI reductions,the With MNV group maintained a higher CVI than the control group in all 5 subfields(superior,temporal,central,inferior,and inferonasal;all P<0.05).In the central region,CONCLUSION:CVI decreases,and choroidal structural changes extend beyond the subfoveal area in cCSC with MNV eyes,providing with an imaging evidence for the important role of choroidal ischemia in the pathogenesis of MNV in cCSC.
基金Supported by Shanghai Municipal Health Commission(No.202140183).
文摘AIM:To present a case series of rapid-onset neovascular glaucoma(NVG)accompanied by vitreous haemorrhage(VH)following cataract surgery in diabetic patients,and to evaluate the efficacy of pars plana vitrectomy(PPV)combined with Ahmed glaucoma valve(AGV)implantation.METHODS:This is a retrospective,single-center,consecutive case series.All patients underwent 23-gauge PPV with AGV implantation 2–3d after intravitreal ranibizumab injection(IVR).The minimum postoperative follow-up period lasted 12mo.The primary outcome measures included bestcorrected visual acuity(BCVA),intraocular pressure(IOP),and topical hypotensive medications.RESULTS:Fifteen diabetic patients(age,46–81y)with rapid-onset NVG and VH following uncomplicated phacoemulsification were included.The median time to the initial NVG diagnosis following cataract surgery was within 4wk.After PPV combined with AGV implantation,the mean BCVA(logMAR)improved from 1.9(range:1.0 to 2.6)preoperatively to 1.2(range:0.2 to 2.6)at the final follow-up.Baseline BCVA and the presence of diabetic nephropathy(DN)were significantly associated with the final BCVA in the multiple regression model.The mean postoperative IOP at all follow-up visits was significantly reduced compared to baseline.At the final follow-up,9 patients required one or two topical ocular hypotensive medications,while the other 6 needed not.Success was achieved in 87%,and the reoperation rate was 20%.The majority of NVG cases(9/15)were primarily attributed to the rapid progression of proliferative diabetic retinopathy.However,a notable subset(6 eyes)was complicated retinal vein occlusion or carotid artery occlusion.CONCLUSION:PPV combined with AGV implantation after adjuvant IVR for rapid-onset NVG with VH following diabetic cataract surgery is one of the safe and effective treatments.Baseline BCVA and preexisting DN may be potential indicators for visual outcomes.
基金supported by the National Natural Science Foundation of China(Nos.82200379 and 82300309)the Shanghai Sailing Program(No.22YF1443100)+1 种基金the Academy Talent Special Fund of The First Affiliated Hospital of Nanjing Medical University(Nos.YNRCQN0312 and MXJL202208)the Jiangsu Funding Program for Excellent Postdoctoral Talent(No.2023ZB592),China.
文摘Retinopathy of prematurity(ROP)is a vision-threatening disorder that leads to pathological growth of the retinal vasculature due to hypoxia.Here,we investigated the potential effects of alamandine,a novel heptapeptide in the renin-angiotensin system(RAS),on hypoxia-induced retinal neovascularization and its underlying mechanisms.In vivo,the C57BL/6J mice with oxygen-induced retinopathy(OIR)were injected intravitreally with alamandine(1.0µmol/kg per eye).In vitro,human retinal microvascular endothelial cells(HRMECs)were utilized to investigate the effects of alamandine(10µg/mL)on proliferation,apoptosis,migration,and tubular formation under vascular endothelial growth factor(VEGF)stimulation.Single-cell RNA sequencing(scRNA-seq)matrix data from the Gene Expression Omnibus(GEO)database and RAS-related genes from the Molecular Signatures Database(MSigDB)were sourced for subsequent analyses.By integrating scRNA-seq data across multiple species,we identified that RAS-associated endothelial cell populations were highly related to retinal neovascularization.The liquid chromatography-tandem mass spectrometry(LC-MS/MS)analysis revealed a significant decrease in alamandine levels in both the serum and retina of OIR mice compared to those in the control group.Next,alamandine ameliorated hypoxia-induced retinal pathological neovascularization and physiologic revascularization in OIR mice.In vitro,alamandine effectively mitigated VEGF-induced proliferation,scratch wound healing,and tube formation of HRMECs primarily by inhibiting the hypoxia-inducible factor-1α(HIF-1α)/VEGF pathway.Further,coincubation with D-Pro7(Mas-related G protein-coupled receptor D(MrgD)antagonist)hindered the beneficial impacts of alamandine on hypoxia-induced pathological angiogenesis both in vivo and in vitro.Our findings suggested that alamandine could mitigate retinal neovascularization by targeting the MrgD-mediated HIF-1α/VEGF pathway,providing a potential therapeutic agent for OIR prevention and treatment.
基金Supported by National Natural Science Foundation of China(No.81371036No.81700837)+2 种基金Department of Science and Technology,Hunan(No.2015TP2007)Japan Society for the Promotion of Science KAKENHI Grants(No.26293374No.16K15734)
文摘Macrophages are involved in angiogenesis, and might also contribute to the pathogenesis of intraocular neovascular diseases. Recent studies indicated that macrophages exert different functions in the process of intraocular neovascularization, and the polarization of M1 and M2 phenotypes plays extremely essential roles in the diverse functions of macrophages. Moreover, a large number of cytokines released by macrophages not only participate in macrophage polarization, but also associate with retinal and choroidal neovascular diseases. Therefore, macrophage might be considered as a novel therapeutic target to the treatment of pathological neovascularization in the eye. This review mainly summarizes diverse roles of macrophages and discusses the possible mechanisms in retinal and choroidal neovascularization.
文摘Neovascular glaucoma is defined as iris and/or anterior chamber angle neovascularization associated with increased intraocular pressure. It is a secondary glaucoma that is most frequently caused by severe retinal ischemia. The most common diseases responsible for the development of neovascular glaucoma are diabetic retinopathy, ischemic central retinal vein occlusion,and ocular ischemic syndrome. Uncommon causes include ocular radiation, ocular tumors, uveitis and other miscellaneous conditions. Vascular endothelial growth factor is an important and likely predominant agent involved in the pathogenesis of intraocular neovascularization and neovascular glaucoma. The evolution of clinical and histopathological changes from predisposing conditions to the occurrence of rubeosis iridis and neovascular glaucoma is divided into four stages: prerubeosis, preglaucoma, open angle glaucoma, and angle-closure glaucoma.
基金Supported by Natural Science Fund Project in Jiangsu Province(No.BK20180380)Nanjing Health Commission(No.YKK18260)。
文摘Ischemic and neovascular disease is one of the most difficult ocular diseases to deal with nowadays.Redundancy,poor visual acuity and decreased life quality are bothering patients and ophthalmologists for decades.After vascular endothelial growth factor(VEGF)was found to be a primary factor in promoting retinal angiogenesis,intravitreal injection of anti-VEGF drugs has been the firstline treatment.Whereas,some patients are refractory to this therapy and problems of economic burden,local complications and adverse effects promote researches into other possible targets.The vasohibin(VASH)family is a newly-investigated factor in modulating ocular angiogenesis.The family includes VASH1 and VASH2,which show opposite effects of inhibiting and accelerating angiogenesis respectively.Positive results have been reported in cellular and animal experiments.With further researches,it can be a promising future target of treating ocular neovascular diseases.
基金Supported in part by the Bio&Medical Technology Development Program of the NRF funded in part by the Korean government and the Ministry of Science and ICT (MSIP,NRF-2017M3A9E2056458,No.2020R1A2C1005729)。
文摘AIM:lo evaluate the changes on optical coherence tomography angiography(OCTA) and fluorescein angiography(FA) and their correlation in neovascular agerelated macular degeneration(nAMD) before and after intravitreal aflibercept injections(IAIs).METHODS:In 43 treatment-na?ve patients with nAMD,choroidal neovascularization(CNV) in OCTA were morphologically and quantitatively analyzed before and after IAIs to determine whether they are correlated with leakage on FA or not.By combining CNV in OCTA and leakage in FA,lesions were characterized as three types:L+C+(with both CNV and leakage),L-C+(with CNV but without leakage),or L+C-lesion(with leakage outside CNV).RESULTS:Before IAI,while 27 eyes had L+C+lesion only,16 eyes had both L+C+and L-C+lesions simultaneously.Tiny capillaries and anastomosis in CNV were more developed in L+C+lesion,at 86.0% and58.1%,respectively,relative to 9.3% and 9.3% in L-C+lesions(P<0.001).After IAIs in 33 eyes,tiny capillaries and anastomosis were decreased in the lesions with cessation of leakage on FA(P<0.001 and P=0.001,respectively).In quantitative analysis,neovascularization length and numbers of junctions and endpoints were also significantly decreased.CONCLUSION:Leakage on FA is associated with CNV morphology in OCTA and remained so after IAls.Therefore,by carefully assessing the morphological and quantitative changes of CNV in OCTA before and after treatment,activity of nAMD is expected even though CNV on OCTA is not completely matched with fluorescein leakage.
基金the Longyan First Affiliated Hospital of Fujian Medical University(approval No.202014).
文摘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.
基金Supported by The Science and Technology Department of Zhejiang Province,No.2008C33012Zhejiang Nature Science Foundation,No.Y2080718
文摘AIM:To assess neovascularization within human ca-rotid atherosclerotic soft plaques in patients with isch-emic stroke.METHODS:Eighty-one patients with ischemic stroke and 95 patients without stroke who had soft athero-sclerotic plaques in the internal carotid artery were studied.The thickest soft plaque in each patient was examined using contrast-enhanced ultrasound.Time-intensity curves were collected from 5 s to 3 min after contrast injection.The neovascularization within the plaques in the internal carotid artery was evaluated using the ACQ software built into the scanner by 2 of the experienced investigators who were blinded to the clinical history of the patients.RESULTS:Ischemic stroke was present in 7 of 33 patients(21%) with grade Ⅰ plaque,in 14 of 51 pa-tients(28%) with grade Ⅱ plaque,in 26 of 43 patients(61%) with grade Ⅲ plaque,and in 34 of 49 patients(69%) with grade Ⅳ plaque(P < 0.001 comparing grade Ⅳ plaque with grade I plaque and with grade Ⅱ plaque and P = 0.001 comparing grade Ⅲ plaque with grade Ⅰ plaque and with grade Ⅱ plaque).Analysis of the time intensity curves revealed that patients with ischemic stroke had a significantly higher intensity of enhancement(IE) than those without ischemic stroke(P < 0.01).The wash-in time(WT) of plaque was signifi-cantly shorter in stroke patients(P < 0.05).The sensi-tivity and specificity for IE in the plaque were 82% and 80%,respectively,and for WT were 68% and 74%,respectively.There was no significant difference in the peak intensity or time to peak between the 2 groups.CONCLUSION:This study shows that the higher the grade of plaque enhancement,the higher the risk of ischemic stroke.The data suggest that the presence of neovascularization is a marker for unstable plaque.
基金National"Eleventh Five-year Plan"Science and Technology Support Project,China(No.2006BAI06A15-3)
文摘AIM:To discuss the impact of Lycium Barbarum Polysaccharide (LBP) and Danshensu purified from Traditional Chinese Medicine (TCM) on vascular endothelial growth factor (VEGF) of rabbits with retinal neovascularization. METHODS:Forty rabbits were divided into normal control group, model control group, LBP group and Danshensu group. Animals in the normal control group were fed in the normal oxygen environment. Animals in the other three groups were put into the environment with 70% oxygen for 5 days in order to build the model of oxygen-induced vascular proliferation retinopathy. And then different TCM extract was injected into the abdominal cavities of these annimals. After 7 days, the VEGF content of in the serum of rabbit was measured by double antibody sandwich method. RESULTS:Data analysis indicated that VEGF content was as follows:Danshensu group was lower than model control group (12.92 ±3.84ng/L vs 19.32 ±4.15ng/L, P 【 0.05); LBP group and normal control group were lower than model control group (12.92±3.84ng/L, 9.26±1.61ng/L vs 19.32±4.15ng/L, P【0.01); total blood viscosity, plasma viscosity, cholesterol content, fibrinogen content and triacylglycerol content after peritoneal injection of LBP and Danshensu were obviously lower than before injection. CONCLUSION:TCM extract-LBP and Danshensu can prominently reduce the content of VEGF in the process of vascular proliferative retinopathy of rabbit; can prevent the occurrence of retinal microvascular disease by improving partial oxygen -deficient environment or affecting all kinds of new growth factor.
基金Tianjin Science and Technology Project,China (No.08ZCGYSF01700)
文摘AIM: To evaluate the risk factors associated with retinal neovascularization of diabetic retinopathy in northern Chinese Han patients with type 2 diabetes mellitus (T2DM). METHODS: The clinical characteristics of 200 patients with proliferative diabetic retinopathy (PDR) and 100 age-matched healthy individuals were compared. The univariate and multivariate logistic regression analysis were performed in the patients with PDR. RESULTS: Fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), blood urea nitrogen (BUN), uric acid (UA), white blood cell count (WBC), absolute neutrophil count, hematocrit (HCT) and mean platelet volume (MPV) and mean platelet volume (MPV) were all significantly higher in patients with PDR than in the control group (P<0.05). The univariate and multivariate logistic regression analysis showed that risk factors independently associated with retinal neovascularization of DR were duration of diabetes mellitus (OR=1.112; P=0.000), BUN (OR=1.277; P=0.000), smoking (OR=3.967; P=0.000) and MPV (OR=2.472; P=0.000). On the other hand, panretinal photocoagulation was associated with reduced risk of retinal neovascularization (OR=0.983; P=0.000). CONCLUSION: Preventing and controlling T2DM in terms of risk factors, including duration of diabetes, BUN, smoking and MPV, might offer novel approaches to prevent or delay the onset of retinal neovascularization in patients with PDR.
文摘A large subset of corneal pathologies involves the formation of new vessels(neovascularization), leading to compromised visual acuity. This article aims to review the clinical causes and presentations of corneal neovascularization(CNV) by examining the mechanisms behind common CNV-related corneal pathologies, with a particular focus on herpes simplex stromal keratitis,contact lenses-induced keratitis and CNV secondary to keratoplasty. Moreover, we reviewed CNV in the context of different types of corneal transplantation and keratoprosthesis, and summarized the most relevant treatment available so far.
文摘Endothelial progenitor cells are resident in the bone marrow blood sinusoids and circulate in the peripheral circulation. They mobilize from the bone marrow after vascular injury and home to the site of injury where they differentiate into endothelial cells. Activation and mobilization of endothelial progenitor cells from the bone marrow is induced via the production and release of endothelial progenitor cell-activating factors and includes specific growth factors and cytokines in response to peripheral tissue hypoxia such as after acute ischemic stroke or trauma. Endotheli- al progenitor cells migrate and home to specific sites following ischemic stroke via growth factor/ cytokine gradients. Some growth factors are less stable under acidic conditions of tissue isch- emia, and synthetic analogues that are stable at low pH may provide a more effective therapeutic approach for inducing endothelial progenitor cell mobilization and promoting cerebral neovascularization following ischemic stroke.
文摘AIM:To explore the efficacy of preoperative intravitreal bevacizumab(IVB) injection combined with Ahmed glaucoma valve(AGV) implantation in the treatment of neovascular glaucoma(NVG).METHODS:This retrospective study included 35 eyes from 35 patients who underwent preoperative IVB and AGV implantation for treatment of NVG. Findings such as intraocular pressure(IOP) number of anti-glaucoma medications, visual acuity(VA), surgical success rates,and complications were recorded.RESULTS:AfterAGVimplantation,IOPwas18.2±4.0mmHg,15.5±3.3 mm Hg and 9.8±2.6 mm Hg at 6, 12 and 36 mo,significantly decreased compared with pre-IOP(P 【0.01).The number of anti-glaucoma medications was 0.9 ±0.5,0.8 ±0.9 and 0.8 ±0.6 at 6, 12 and 36 mo, significantly decreased compared to pre-treatment(P 【0.01). At last visit, there were 19 eyes with stable VA, 4 with VA improvement, 12 with diminished VA and 3 with complete loss light perception. There were 7 cases that failed during 3-year fellow up period. Cumulative probabilities of valve survival by Kaplan-Meier analysis were 82.9%,74.1% and 71.0% at 12, 24 and 36 mo, respectively. Cox stepwise regression analysis found that the survival time was significant associated with the pre-visual acuity 【2/400(P 【0.05). Post-operative complications occurred in 8eyes, of which hyphema presented in 2 eyes, choroidal effusion in 2 eyes.CONCLUSION:The procedure of preoperative IVB andAGV implantation should be one of treatments for NVG because of its safety and effectiveness.
文摘AIM: To compare the efficacies of subconjunctival bevacizumab, ranibizumab, and pegaptanib sodium injections for the inhibition of corneal neovascularization in an experimental rat model. METHODS: Sixteen corneas of 16 rats were chemically cauterized and randomized into four groups: bevacizumab group that treated with 0.05mL/1.25mg bevacizumab, ranibizumab group that treated with 0.05mL/0.5mg ranibizumab, pegaptanib group that treated with 0.05mL/0.15mg pegaptanib sodium, and control group that treated with 0.05mL saline solution. Digital photographs of the corneas were taken and analyzed using an image analysis software program. All corneas were excised and examined histologically on the 15 th day. RESULTS: Each treatment group had significantly less neovascularized corneal areas and fewer blood vessels than the control group (all P 【0.05). In addition, bevacizumab group had significantly less neovascu-larized corneal areas and fewer blood vessels than ranibizumab and pegaptanib groups (both P 【0.05). However, there was no significant difference between the ranibizumab and pegaptanib groups regarding percentage of neovascularized corneal areas and number of blood vessels (both P 】0.05). CONCLUSION: Subconjunctival bevacizumab, ranibiz-umab, and pegaptanib sodium were effective with no corneal epitheliopathy for inhibiting corneal neovascularization after corneal burn in rats .Bevacizumab was more effective than ranibizumab and pegaptanib sodium.
