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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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Prognosis value of Chinese Ocular Fundus Diseases Society classification for proliferative diabetic retinopathy on postoperative visual acuity after pars plana vitrectomy in type 2 diabetes

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International Journal of Ophthalmology(English edition) 2022年第10期15卷 1627-1633页

作者： Tie-Zhu Lin Yan Kong Cheng Shi Emmanuel Eric Pazo Guang-Zheng Dai Xian-Wei Wu Ling Xu Li-Jun Shen Eye Hospital and School of Ophthalmology and Optometry Wenzhou Medical UniversityWenzhou 325000Zhejiang ProvinceChina He Eye Specialist Hospital Shenyang 110034Liaoning ProvinceChina Ophthalmology Department Zhejiang Provincial People’s HospitalHangzhou 310000Zhejiang ProvinceChina

AIM: To compare the postoperative visual acuity among eyes with proliferative diabetic retinopathy(PDR) of different stages after pars plana vitrectomy(PPV) in type 2 diabetic patients. METHODS: A retrospective study was conducted for PDR eyes undergoing PPV in type 2 diabetic patients. All patients were divided into three groups based on Chinese Ocular Fundus Diseases Society(COFDS) classification for PDR: Group A(primary vitreous hemorrhage), Group B(primary fibrovascular proliferation) and Group C(primary vitreous hemorrhage and/or fibrovascular proliferative combined with retinal detachment). The postoperative visual acuity and the change between postoperative and preoperative visual acuity were compared among three groups. The associated risk factors for postoperative visual acuity were analyzed in the univariate and multiple linear aggression. RESULTS: In total, 195 eyes of 195 patients were collected in this study, including 71 eyes of 71 patients in Group A, 75 eyes of 75 patients in Group B and 49 eyes of 49 patients in Group C. The eyes in Group A got better postoperative best-corrected visual acuity(BCVA) compared to the eyes in Group B and C(0.48±0.48 vs 0.89±0.63, Pproliferative type(β=0.194, 95%CI=0.060-0.447, P=0.01), retinal detachment type(β=0.244, 95%CI=0.132-0.579, P=0.02), baseline log MAR BCVA(β=0.192, 95%CI=0.068-0.345, P=0.004), silicone oil tamponade(β=0.272, 95%CI=0.173-0.528, P<0.001) was positively correlated with postoperative log MAR BCVA. Eyes undergoing phacovitrectomy had better postoperative BCVA(β=-0.144, 95%CI=-0.389 to-0.027, P=0.025). CONCLUSION: PDR eyes of primary vitreous hemorrhage type usually have better visual acuity prognosis compared to primary fib

关键词： proliferative diabetic retinopathy pars plana vitrectomy postoperative visual acuity best-corrected visual acuity Chinese Ocular Fundus Diseases Society

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Inner limiting membrane peeling prevents secondary epiretinal membrane after vitrectomy for proliferative diabetic retinopathy

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International Journal of Ophthalmology(English edition) 2022年第9期15卷 1496-1501页

作者： Rong-Han Wu Ming-Na Xu Ke Lin Ming-Xue Ren Han Wen Ke-Mi Feng Hong-Jia Zhou Nived Moonasar Zhong Lin Eye Hospital and School of Ophthalmology and Optometry Wenzhou Medical UniversityWenzhou 325027Zhejiang ProvinceChina National Clinical Research Center for Ocular Diseases Wenzhou 325027Zhejiang ProvinceChina Caribbean Eye Institute ValsaynTrinidad and Tobago

·AIM:To evaluate the role of internal limiting membrane(ILM)peeling in preventing secondary epiretinal membrane(ERM)formation in pars plana vitrectomy(PPV)for proliferative diabetic retinopathy(PDR).·METHODS:This retrospective study analyzed the medical records of patients who underwent PPV for PDR and were followed up for minimum 3 *** peeling was performed based on the intraoperative surgeons’*** was assessed by optical coherence tomography *** relationship between ILM peeling and postoperative ERM was analyzed.·RESULTS:In total,212 eyes from 197 patients were included in this *** incidence of secondary ERM in the ILM non-peeling group was significantly higher than that in the ILM peeling group(37.0%vs 14.0%;P<0.001).Multivariate logistical regression revealed that ILM peeling was highly associated with the prevention of secondary ERM development[odds ratio 0.38;95%confidence interval0.17-0.86;P<0.05].·CONCLUSION:ILM peeling during PPV for PDRs can effectively reduce the incidence of secondary ERM development and is worth consideration by vitreoretinal surgeons.

关键词： internal limiting membrane secondary epiretinal membrane 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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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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Comprehensive assessment of growth factors,inflammatory mediators, and cytokines in vitreous from patients with proliferative diabetic retinopathy

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International Journal of Ophthalmology(English edition) 2022年第11期15卷 1736-1742页

作者： Qiao-Yun Gong Guang-Yi Hu Su-Qin Yu Tian-Wei Qian Xun Xu Department of Ophthalmology Shanghai General HospitalShanghai Jiao Tong UniversityShanghai 200080China National Clinical Research Center for Eye Diseases Shanghai 200080China Shanghai Key Laboratoryof Ocular Fundus Diseases Shanghai 200080China Shanghai Engineering Center for Visual Science and Photomedicine Shanghai 200080China Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Disease Shanghai 200080China

AIM: To assess alterations in growth factors, inflammatory mediators, and cytokines associated with vitreous-retinal diseases in vitreous humor from patients with proliferative diabetic retinopathy(PDR), and to identify potential new treatment targets and ***: Control vitreous samples were collected from patients with macular hole, epiretinal membranes, or rhegmatogenous retinal detachments, and PDR samples from patients with complications of PDR, who required pars plana vitrectomy. Specimens were stored at-80℃ and then investigated by Luminex multi-factor assay. Parametric and nonparametric analyses of demographic characteristics and cytokine expression levels were conducted using ***: There were no significant differences in demographic characteristics between patients with and without PDR. Expression levels of growth factors [plateletderived growth factor(PDGF)-AA, glial cell line-derived neurotrophic factor(GDNF), and vascular endothelial growth factor A(VEGFA)], inflammatory mediators [interleukin(IL)-8, IL-11, and tumor necrosis factor-α(TNF-α)] and cytokines [chemokine C-X-C ligand(CXCL)10, interferon-γ(IFN-γ), and granulocyte macrophage-colony stimulating factor(GM-CSF)] were significantly elevated in vitreous humor from patients with PDR compared with those in the control group(all P0.05).CONCLUSION: This proof-of-concept study demonstrates the potential for combinational therapeutic strategies to ameliorate diabetic retinopathy progression by targeting growth factors, inflammatory factors, and cytokines, in addition to VEGFA.

关键词： vitreous proliferative diabetic retinopathy growth factors inflammation cytokines

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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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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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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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