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Proteomic study of vitreous in proliferative diabetic retinopathy patients after treatment with aflibercept:a quantitative analysis based on 4D label-free technique

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International Journal of Ophthalmology(English edition) 2024年第4期17卷 676-685页

作者： Ting-Ting Feng Xiang Gao An-Ran Liang Bo-Wen Zhao Guang-Hui He Song Chen Clinical College of Ophthalmology Tianjin Medical UniversityTianjin 300070China Tianjin Key Laboratory of Ophthalmology and Visual Science Tianjin Eye InstituteTianjin Eye HospitalTianjin 300020China Key Laboratory of Ophthalmology Anyang Eye HospitalAnyang 455000Henan ProvinceChina Department of Ophthalmology Jining No.1 People’s HospitalJining 272011Shandong ProvinceChina

AIM:To identify different metabolites,proteins and related pathways to elucidate the causes of proliferative diabetic retinopathy(PDR)and resistance to anti-vascular endothelial growth factor(VEGF)drugs,and to provide biomarkers for the diagnosis and treatment of ***:Vitreous specimens from patients with diabetic retinopathy were collected and analyzed by Liquid Chromatography-Mass Spectrometry(LC-MS/MS)analyses based on 4D label-free *** differentially expressed proteins(DEPs),Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway representation and protein interactions were ***:A total of 12 samples were *** proteomics results showed that a total of 58 proteins were identified as DEPs,of which 47 proteins were up-regulated and 11 proteins were *** found that C1q and tumor necrosis factor related protein 5(C1QTNF5),Clusterin(CLU),tissue inhibitor of metal protease 1(TIMP1)and signal regulatory protein alpha(SIRPα)can all be specifically regulated after aflibercept *** functional analysis showed that some DEPs are related to changes in inflammatory regulatory pathways caused by *** addition,protein-protein interaction(PPI)network evaluation revealed that TIMP1 plays a central role in neural *** addition,CD47/SIRPαmay become a key target to resolve anti-VEGF drug resistance in ***:Proteomic analysis is an approach of choice to explore the molecular mechanisms of *** data show that multiple proteins are differentially changed in PDR patients after intravitreal injection of aflibercept,among which C1QTNF5,CLU,TIMP1 and SIRPαmay become targets for future treatment of PDR and resolution of anti-VEGF resistance.

关键词： vitreous proliferative diabetic retinopathy proteome 4D label-free

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Differential distribution of fibrovascular proliferative membranes in 25-gauge vitrectomy for proliferative diabetic retinopathy

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International Journal of Ophthalmology(English edition) 2024年第8期17卷 1462-1468页

作者： Nan Lu Shi-Lin Yang Shuo Guo Dong-Ni Yang Li Liu Chun-Hui Fan Ying Guo Jian Liu Wei Zhao Department of Ophthalmology the First Hospital of QinhuangdaoQinhuangdao 066000Hebei ProvinceChina School of Control Engineering Northeastern University at QinhuangdaoQinhuangdao 066004Hebei ProvinceChina

AIM:To analyze the distribution of fibrovascular proliferative membranes(FVPMs)in proliferative diabetic retinopathy(PDR)patients that treated with pars plana vitrectomy(PPV),and to evaluate the outcomes ***:This was a retrospective and cross-sectional *** 25-gauge(25-G)PPV cases operated for PDR from May 2018 to April *** to the FVPMs images outlined after operations,subjects were assigned into three groups:arcade type group,juxtapapillary type group,and central type *** patients were followed up for over one *** characteristics,operation-related variables,postoperative parameters and complications were ***:Among 103 eyes recruited,the FVPMs distribution of nasotemporal and inferiosuperioral was significantly different(both P<0.01),with 95(92.23%)FVPMs located in the nasal quadrants,and 74(71.84%)in the *** eyes with a central FVPM required the longest operation time,with silicon oil used in most patients,generally combined with tractional retinal detachment(RD)and rhegmatogenous RD,the worst postoperative bestcorrected visual acuity(BCVA)and the highest rates of recurrent RD(all P<0.05).FVPM type,age of onset diabetes mellitus,preoperative BCVA,and combined with tractional RD and rhegmatogenous RD were significantly associated with BCVA improvement(all P<0.05).Compared with the central type group,the arcade type group had higher rates of BCVA ***:FVPMs are more commonly found in the nasal and inferior mid-peripheral retina in addition to the area of arcade *** 25-G PPV for treating PDR eyes with central FVPM have relatively worse prognosis.

关键词： proliferative diabetic retinopathy fibrovascular proliferative membrane 25-gauge pars plana vitrectomy

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Non-linear relationship between age and subfoveal choroidal thickness in Chinese patients with proliferative diabetic retinopathy

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World Journal of Diabetes 2024年第9期15卷 1903-1915页

作者： Chun-Yan Lei Jiang-Ying Xie Qi-Bo Ran Mei-Xia Zhang Department of Ophthalmology and Research Laboratory of Macular Disease West China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina Sichuan University Operating Room Department of AnesthesiologyWest China HospitalSichuan University/West China School of NursingSichuan UniversityChengdu 610041Sichuan ProvinceChina

BACKGROUND No study has investigated the change regularity between age and subfoveal choroidal thickness(SFCT)in proliferative diabetic retinopathy(PDR).AIM To investigate the relationship between the SFCT and age in Chinese patients with *** This was a cross-sectional retrospective *** participants were hospitalized individuals with type 2 diabetes who underwent vitrectomy for *** eyes that met the criteria were included in the *** necessary laboratory tests were performed at the time of *** macular thickness(CMT)and SFCT were two quantitative assessments made using enhanced depth imaging optical coherence *** was measured automatically and SFCT was measured manually with digital calipers provided by the Heidelberg Eye Explorer *** The final analysis included a total of 234 individuals with *** average age was 55.60 years old±10.03 years old,and 57.69%of the population was *** analysis revealed a significant negative connection between age and SFCT in patients with PDR[β=-2.44,95%confidence interval(95%CI):-3.46 to-1.42;P<0.0001].In the fully adjusted model,the correlation between SFCT and age remained steady(β=-1.68,95%CI:-2.97 to-0.39;P=0.0117).Spline smoothing showed that the relationship between SFCT and age in patients with PDR was non-linear,with an inflection point at 54 years of *** Our findings suggest that age is a key determinant of choroidal *** non-linear link between SFCT and age in PDR patients should be taken into account.

关键词： Age Subfoveal choroidal thickness proliferative diabetic retinopathy Optical coherence tomography Central macular thickness

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Ocular surface changes in type II diabetic patients with proliferative diabetic retinopathy

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International Journal of Ophthalmology(English edition) 2015年第2期8卷 358-364页

作者： Yan Gao Yan Zhang Yu-Sha Ru Xiao-Wu Wang Ji-Zhong Yang Chun-Hui Li Hong-Xing Wang Xiao-Rong Li Bing Li Shanxi Eye Hospital College of Optometry and Ophthalmology Tianjin Medical University Tianjin Medical University Eye Institute Tianjin Medical University Eye Hospital Department of Ophthalmology Shanxi Medical University First Hospital Department of Ophthalmology Beijing Chuiyangliu Hospital Affiliated to Tsinghua University

AIM: To detect and analyze the changes on ocular surface and tear function in type II diabetic patients with proliferative diabetic retinopathy(PDR), an advanced stage of diabetic retinopathy(DR), using conventional ophthalmic tests and the high-resolution laser scanning confocal ***: Fifty-eight patients with type II diabetes were selected. Based on the diagnostic criteria and stage classification of DR, the patients were divided into the non-DR(NDR) group and the PDR group. Thirty-six patients with cataract but no other ocular and systemic disease were included as non-diabetic controls. All the patients were subjected to the conventional clinical tests of corneal sensitivity, Schirmer I test, and corneal fluorescein staining. The non-invasive tear film break-up time(NIBUT) and tear interferometry were conducted by a Tearscope Plus. The morphology of corneal epithelia and nerve fibers was examined using the high-resolution confocal ***: The NDR group exhibited significantly declined corneal sensitivity and Schirmer I test value, as compared to the non-diabetic controls(P diabetic controls(P diabetic patients, particularly in the diabetic patients with PDR. The corneal sensitivity, fluorescein staining scores,and the density of corneal epithelial cells and nerve fibers in the diabetic patients correlate with

关键词： type II diabetes proliferative diabetic retinopathy ocular surface corneal sensitivity confocal microscopy tear film break-up time

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Bimodal imaging of proliferative diabetic retinopathy vascular features using swept source optical coherence tomography angiography

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International Journal of Ophthalmology(English edition) 2018年第9期11卷 1528-1533页

作者： Amal M Elbendary Hossam Youssef Abouelkheir Mansoura Ophthalmic Center Mansoura University

AIM： To categorize neovessels morphology and to detect response to anti-angiogenic therapy by using structural and angiographic modes of swept source optical coherence tomography（SS-OCT）.METHODS： Thirty-two eyes with neovessels at disc（NVD） and neovessels elsewhere（NVE）-as diagnosed by fluorescein angiography-were included. Cross sectional OCT images of disc and macular regions were registered to enface OCT angiography（OCTA）, B-scan blood flow over lay and density maps. Three eyes received antiangiogenic ***： Pin point registration of cross-sectional OCT and OCTA images differentiated active NVD with vascular elements from fibrous or equivalent fibrovascular elements. En face images delineated NVE as vascular tufts or area of filling while cross-sectional images differentiated NVE from microvascular intraretinal abnormality（IRMA）. All cases were associated with enlargement of foveal avascular zone and or areas of capillary non perfusion. Regressed NVD appeared as ghost vessel or pruned vascular loops after ***： Structural and angiographic modes of SS-OCT can detect, characterize and categorize the pattern of wide spectrum of neovessels based on blood flow data and density maps. It is potentially useful to detect ischemic changes in the vascular bed and regression of NVD after therapeutic regimens providing substitute for invasive techniques.

关键词： optical coherence tomography angiography swept proliferative diabetic retinopathy

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Phosphorylation of alphaB-crystallin in epiretinal membrane of human proliferative diabetic retinopathy

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International Journal of Ophthalmology(English edition) 2016年第8期9卷 1100-1105页

作者： Yoko Dong Zhenyu Dong Satoru Kase Ryo Ando Junichi Fukuhara Satoshi Kinoshita Saori Inafuku Yoshiaki Tagawa Erdal Tan Ishizuka Wataru Saito Miyuki Murata Atsuhiro Kanda Kousuke Noda Susumu Ishida Laboratory of Ocular Cell Biology and Visual Science Department of Ophthalmology Hokkaido University Graduate School of Medicine

AIMTo examine phosphorylation of alphaB-crystallin (p-αBC), a vascular endothelial growth factor (VEGF) chaperone, and immunohistochemically investigate relationship between p-αBC, VEGF and phosphorylated p38-mitogen-activated protein kinase (p-p38 MAPK) in the epiretinal membrane of human proliferative diabetic retinopathy (PDR).METHODSEleven epiretinal membranes of PDR surgically excised were included in this study. Two normal retinas were also collected from enucleation tissues due to choroidal melanoma. Paraformaldehyde-fixed, paraffin-embedded tissue sections were processed for immunohistochemistry with anti-p-αBC, VEGF, CD31, and p-p38 MAPK *** for p-αBC was observed in all of the epiretinal membranes examined, where phosphorylation on serine (Ser) 59 showed strongest immunoreactivity in over 70% of the membranes. The immunolocalization of p-αBC was detected in the CD31-positive endothelial cells, and co-localized with VEGF and p-p38 MAPK in PDR membranes. Immunoreactivity for p-αBC, however, was undetectable in endothelial cells of the normal retinas, where p-p38 MAPK immunoreactivity was less marked than PDR *** of αBC, in particular, phosphorylation on Ser59 by p-p38 MAPK may play a potential role as a molecular chaperon for VEGF in the pathogenesis of epiretinal membranes in PDR.

关键词： phosphorylated alphaB-crystallin vascular endothelial growth factor neovascularization proliferative diabetic retinopathy

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Optimal timing of preoperative intravitreal anti-VEGF injection for proliferative diabetic retinopathy patients

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International Journal of Ophthalmology(English edition) 2022年第10期15卷 1619-1626页

作者： Yue Xu Chi Xie Yan Fang Yan Yu Cui Qiu Department of Ophthalmology the First Affiliated Hospital of Anhui University of Science&TechnologyHuainan 232001Anhui ProvinceChina Institute of Ophthalmology Anhui University of Science&TechnologyHuainan 232001Anhui ProvinceChina

AIM: To analyze concentrations of vascular endothelial growth factor(VEGF) and fibrosis-related factors in vitreous fluid of proliferative diabetic retinopathy(PDR) patients pretreated with intravitreal anti-VEGF injections(IVI) at different time periods prior to pars plana vitrectomy(PPV), and their correlation with the degree of vitreoretinal fibrosis and explore the optimal timing of preoperative ***: The prospective case-control study from January 2019 to July 2020 included 31 eyes with PDRrelated complications(PDR group) and 21 eyes with nondiabetic ocular disease(control group) requiring PPV. PDR eyes were divided into four groups based on timing of PPV: 3 d after IVI(3-day group);5 d after IVI(5-day group);7 or more days after IVI(≥7-day group);and no IVI. Vitreous fluid samples(0.5-1.0 m L) were collected prior to switching on the infusion before routine 23-G PPV. Concentrations of VEGF, basic fibroblast growth factor(b FGF), periostin(PN), interleukin(IL)-6, IL-8, and tumor necrosis factor(TNF)-α were measured by immunoassay, and concentration differences for each cytokine were compared among the groups. The degree of vitreoretinal fibrosis was graded intraoperatively, and the correlation between the changes in cytokine levels and the severity of vitreoretinal fibrosis was analyzed by univariate ordinal logistic regression ***: PDR eyes without IVI had significantly higher VEGF, b FGF, PN, and IL-6 concentrations than nondiabetic eyes(all P<0.05), and had a significantly higher concentration of VEGF(P<0.05) and a significantly lower concentration of IL-8(P<0.05) than PDR eyes with IVI. Statistically significant differences were also observed for concentrations of VEGF, b FGF, PN, IL-6, and IL-8 among 3-day, 5-day, and ≥7-day groups(all P<0.05);meanwhile there was no significant difference in TNF-α among groups(P=0.226). The 5-day group had the lowest concentration of VEGF and the ≥7-day group had the highest concentration of b FGF and P

关键词： preoperative timing intravitreal anti-VEGF injection angio-fibrosis switch proliferative diabetic retinopathy

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Effect of intravitreal ranibizumab on fibrovascular membranes in patients with proliferative diabetic retinopathy

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International Journal of Ophthalmology(English edition) 2022年第10期15卷 1577-1585页

作者： Ze-Yu Liang Yi-Peng Wang Jing Li Wen-Chao Yang Yong-Fang Tu Yue Zhang Song Chen Tianjin Eye Hospital Tianjin Eye InstituteTianjin Key Lab of Ophthalmology and Visual ScienceNankai University Affiliated Eye HospitalTianjin 300020China Anyang Eye Hospital Anyang 455000Henan ProvinceChina

AIM: To assess the effects of intravitreal ranibizumab(IVR) on angiogenesis and glial activity of the fibrovascular membrane(FVM) in patients with proliferative diabetic retinopathy(PDR). METHODS: Forty-two eyes from 42 patients with PDR requiring vitrectomy were included and divided into two groups: control group(n=16) did not receive IVR, while IVR group(n=26) underwent IVR 5 d before vitrectomy. FVM specimens were collected by the same surgeon during the interventions. Histopathological morphology was examined by hematoxylin-eosin(H-E) staining and cell densities in the FVM was assessed. Microvessels were outlined by immunohistochemical staining of CD31 and microvessel density(MVD) assessed as an index of FVM angiogenesis. Dual-color immunofluorescence staining, and confocal microscopy was used to detect co-localization and relative expression levels of glial fibrillary acidic protein(GFAP) and α-smooth muscle actin(α-SMA) as markers of glialmesenchymal transition(GMT). The GMT index(GI;ratio of relative GFAP/α-SMA expression) was used to semi-quantify the degree of GMT or glial activity of FVMs. RESULTS: H-E staining showed similar vascularization in both groups, with microvessels and scattered stromal cells in the matrix. Infiltrated cell densities did not differ significantly between the two groups(P>0.05). The MVD of the IVR group(130.62±15.46/mm~2) was significantly lower than that of the controls(142.25±19.16/mm~2, P<0.05). In both groups, all sections were strongly immunostained for GFAP and α-SMA. The Pearson’s correlation coefficients(PCC) of intensity of automated pixel count of two markers indicated GFAP and α-SMA co-stained well and GMT participated in the remolding of FVMs in PDR. The mean relative GFAP expression in the IVR group was significantly lower, whereas that of α-SMA was significantly higher than in controls(P<0.05). GI in the IVR group(1.10±0.10) was significantly lower than in the controls(1.21±0.12, P<0.05). CONCLUSION: IVR can reduce an

关键词： proliferative diabetic retinopathy ranibizumab fibrovascular membranes glial-mesenchymal transition microvessel density

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Newly diagnosed diabetes mellitus patients presenting with proliferative diabetic retinopathy as an initial sign

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International Journal of Ophthalmology(English edition) 2014年第1期7卷 173-178页

作者： Hoon Park Young Gyun Kim Jong Wook Lee Jong Seok Park Department of Ophthalmology Eulji Hospital

AIM: To investigate the clinical features of newly diagnosed diabetes mellitus(NDM) patients showing proliferative diabetic retinopathy(PDR) as an initial sign. ·METHODS: As a retrospective case series,the medical records of a total of four hundred and thirty-two patients who underwent a vitrectomy due to PDR were reviewed to find the subjects. Of 432 patients,six cases of NDM patients showing PDR as an initial sign were included and analyzed with their systemic and ocular features. Main outcome measures: the systemic features and ocular features [preoperative and postoperative best corrected visual acuity(BCVA),intraoperative findings]. ·RESULTS: The mean onset age of visual symptoms was 36.3 years old. The mean serum insulin and C-peptide titer was below the normal range. The mean fasting plasma glucose was 178mg/dL and the mean postprandial 2h plasma glucose was 306mg/dL. The mean HbA1c at diagnosis was 11.02%. In all cases,an acute progressive fibrovascular proliferation was observed. Intraoperative retinal tears were found in three cases of six. The mean preoperative BCVA was +0.67 ± 0.58 logMAR and the mean BCVA at postoperative 6 months was +0.20±0.30 logMAR. ·CONCLUSION: All patients were considered to have latent autoimmune diabetes in adults(LADA). A rapid deterioration of kidney function as well as poor diabetic control status at diagnosis was observed in all six cases. The ocular features of the patients showed acute progressive fibrovascular proliferation and relatively favorable postoperative visual acuity.

关键词： fibrovascular proliferation latent autoimmune diabetes in adults diabetes mellitus proliferative diabetic retinopathy

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Evaluation of VEGF gene polymorphisms and proliferative diabetic retinopathy in Mexican population

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International Journal of Ophthalmology(English edition) 2017年第1期10卷 135-139页

作者： Roberto Gonzalez-Salinas Maria C Garcia-Gutierrez Gerardo Garcia-Aguirre Virgilio Morales-Canton Raul Velez-Montoya Vidal R Soberon-Ventura Victoria Gonzalez Rodrigo Lechuga Pablo Garcia-Solis David G Garcia-Gutierrez Marco Vinicio Garcia-Solis Manuel Saenz de Viteri Juan C Solis-S Biomedical Research Department Autonomous University of QueretaroQueretaro 76170Mexico Retina Department Asociation to Prevent Blindness in MexicoMexico City 04030Mexico Research Department Asociation to Prevent Blindness in MexicoMexico City 04030Mexico Retina Department General Hospital of Queretaro(ISSSTE)Queretaro 76000Mexico Universidad La Salle School of Medicine Mexico City 06140Mexico

AIM： To assess if the included vascular endothelial growth factor （VEGF） polymorphisms rs3025035, rs3025021 and rs2010963 are associated to proliferative retinopathy in a Mexican population with type 2 diabetes mellitus （T2DM）. METHODS： A case-control study was conducted in adult individuals with T2DM associated to proliferative retinopathy or non-proliferative retinopathy from Oct. 2014 to Jun. 2015 from the Retina Department of the Asociation to Prevent Blindness in Mexico. The selected patients were adults with a diagnosis of T2DM ≥5y. All subjects had a comprehensive ocular examination and the classification of the retinopathy severity was made considering the Early Treatment diabetic retinopathy Study （ETDRS） standardization protocols. Genomic DNA was extracted from whole fresh blood. All samples were genotyped by qPCR for selected VEGF polymorphisms. Hardy-Weinberg equilibrium was calculated by comparing Chi-square values between the expected and the observed values for genotype ***： In total 142 individuals were enrolled, 71 individuals with T2DM and associated proliferative retinopathy and 71 individuals with non-proliferative retinopathy. One-sided Fisher’s exact test was performed for rs3025021 [OR （95% CI）=0.44（0.08-2.2）; P=0.25] and rs2010963 [OR （95% CI）=0.63（0.25-1.6）; P=0.23]. The minor allelic frequencies obtained were 26% for rs3025021, 10% for rs3025035 and 61% for rs2010963. The pairwise linkage disequilibrium between the three SNP was assessed, and was as follows： rs3025021 vs rs3025035： D’=1.0, r2=0.1043, P≤0.0001; rs3025021 vs rs2010963： D’=0.442, r2=0.0446, P=0.149; rs3025035 vs rs2010963： D’=0.505, r2=0.0214, P=***： This is the first analysis involving VEGF polymorphisms and proliferative diabetic retinopathy in a Mexican population. A major finding of the present study is that none of the polymorphisms studied was significantly associated with proliferative retinopathy. Based on these results, we can infer that differ

关键词： vascular endothelial growth factor polymor-phism proliferative diabetic retinopathy non-proliferative diabetic retinopathy rs3025021 rs3025035 rs2010963

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