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 separately.ME...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 separately.METHODS:This was a retrospective and cross-sectional study.Consecutive 25-gauge(25-G)PPV cases operated for PDR from May 2018 to April 2020.According to the FVPMs images outlined after operations,subjects were assigned into three groups:arcade type group,juxtapapillary type group,and central type group.All patients were followed up for over one year.General characteristics,operation-related variables,postoperative parameters and complications were recorded.RESULTS: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 inferior.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 improvement.CONCLUSION:FVPMs are more commonly found in the nasal and inferior mid-peripheral retina in addition to the area of arcade vessels.Performing 25-G PPV for treating PDR eyes with central FVPM have relatively worse prognosis.展开更多
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...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 PDR.METHODS: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 technology.Statistically differentially expressed proteins(DEPs),Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway representation and protein interactions were analyzed.RESULTS:A total of 12 samples were analyzed.The proteomics results showed that a total of 58 proteins were identified as DEPs,of which 47 proteins were up-regulated and 11 proteins were down-regulated.We 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 treatment.GO functional analysis showed that some DEPs are related to changes in inflammatory regulatory pathways caused by PDR.In addition,protein-protein interaction(PPI)network evaluation revealed that TIMP1 plays a central role in neural regulation.In addition,CD47/SIRPαmay become a key target to resolve anti-VEGF drug resistance in PDR.CONCLUSION:Proteomic analysis is an approach of choice to explore the molecular mechanisms of PDR.Our 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.展开更多
AIM:To assess the clinical efficacy and safety of combining panretinal photocoagulation(PRP)with intravitreal conbercept(IVC)injections for patients with high-risk proliferative diabetic retinopathy(HR-PDR)complicated...AIM:To assess the clinical efficacy and safety of combining panretinal photocoagulation(PRP)with intravitreal conbercept(IVC)injections for patients with high-risk proliferative diabetic retinopathy(HR-PDR)complicated by mild or moderate vitreous hemorrhage(VH),with or without diabetic macular edema(DME).METHODS:Patients diagnosed with VH with/without DME secondary to HR-PDR and received PRP combined with IVC injections were recruited in this retrospective study.Upon establishing the patient’s diagnosis,an initial IVC was performed,followed by prompt administration of PRP.In cases who significant bleeding persisted and impeded the laser operation,IVC was sustained before supplementing with PRP.Following the completion of PRP,patients were meticulously monitored for a minimum of six months.Laser therapy and IVC injections were judiciously adjusted based on fundus fluorescein angiography(FFA)results.Therapeutic effect and the incidence of adverse events were observed.RESULTS:Out of 42 patients(74 eyes),29 were male and 13 were female,with a mean age of 59.17±12.74y(33-84y).The diabetic history was between 1wk and 26y,and the interval between the onset of visual symptoms and diagnosis of HR-PDR was 1wk-1y.The affected eye received 2.59±1.87(1-10)IVC injections and underwent 5.5±1.02(4-8)sessions of PRP.Of these,68 eyes received PRP following 1 IVC injection,5 eyes after 2 IVC injections,and 1 eye after 3 IVC injections.Complete absorption of VH was observed in all 74 eyes 5-50wk after initial treatment,with resolution of DME in 51 eyes 3-48wk after initial treatment.A newly developed epiretinal membrane was noted in one eye.Visual acuity significantly improved in 25 eyes.No complications such as glaucoma,retinal detachment,or endophthalmitis were reported.CONCLUSION:The study suggests that the combination of PRP with IVC injections is an effective and safe modality for treating diabetic VH in patients with HR-PDR.展开更多
●AIM:To evaluate the effectiveness and safety of early lens extraction during pars plana vitrectomy(PPV)for proliferative diabetic retinopathy(PDR)compared to those of PPV with subsequent cataract surgery.●METHODS:T...●AIM:To evaluate the effectiveness and safety of early lens extraction during pars plana vitrectomy(PPV)for proliferative diabetic retinopathy(PDR)compared to those of PPV with subsequent cataract surgery.●METHODS:This multicenter randomized controlled trial was conducted in three Chinese hospitals on patients with PDR,aged>45y,with mild cataracts.The participants were randomly assigned to the combined(PPV combined with simultaneously cataract surgery,i.e.,phacovitrectomy)or subsequent(PPV with subsequent cataract surgery 6mo later)group and followed up for 12mo.The primary outcome was the change in best-corrected visual acuity(BCVA)from baseline to 6mo,and the secondary outcomes included complication rates and medical expenses.●RESULTS:In total,129 patients with PDR were recruited and equally randomized(66 and 63 in the combined and subsequent groups respectively).The change in BCVA in the combined group[mean,36.90 letters;95%confidence interval(CI),30.35–43.45]was significantly better(adjusted difference,16.43;95%CI,8.77–24.08;P<0.001)than in the subsequent group(mean,22.40 letters;95%CI,15.55–29.24)6mo after the PPV,with no significant difference between the two groups at 12mo.The overall surgical risk of two sequential surgeries was significantly higher than that of the combined surgery for neovascular glaucoma(17.65%vs 3.77%,P=0.005).No significant differences were found in the photocoagulation spots,surgical time,and economic expenses between two groups.In the subsequent group,the duration of work incapacity(22.54±9.11d)was significantly longer(P<0.001)than that of the combined group(12.44±6.48d).●CONCLUSION:PDR patients aged over 45y with mild cataract can also benefit from early lens extraction during PPV with gratifying effectiveness,safety and convenience,compared to sequential surgeries.展开更多
AIM:To identify the risk factors for postoperative proliferative vitreoretinopathy(PVR)in patients with primary rhegmatogenous retinal detachment(RRD)and develop a nomogram for predicting postoperative PVR-free probab...AIM:To identify the risk factors for postoperative proliferative vitreoretinopathy(PVR)in patients with primary rhegmatogenous retinal detachment(RRD)and develop a nomogram for predicting postoperative PVR-free probability.METHODS:A total of 741 patients(741 eyes)diagnosed with primary RRD who underwent first surgery in the same hospital were retrospectively reviewed and randomly assigned with 521 to the training set and 220 to the validation set.Univariate and multivariate logistic regression analyses were performed in the training cohort to determine risk factors to construct a nomogram for predicting the 3-,4-,5-,and 6-month postoperative PVR-free probabilities.Nomogram performance was estimated by the concordance index(C-index),calibration plot,and the area receiver operating characteristic(ROC)curve.RESULTS:A nomogram was constructed based on the preoperative PVR,silicone oil tamponade time(SOTT),photocoagulation energy(PE),retinal tear size(RTS),and hypertension.In the training set,the C-index of the nomogram was 0.896,0.936,0.961,and 0.972 at 3,4,5,and 6mo,respectively.The C-index values in the validation set were 0.860,0.936,0.951,and 0.965 at 3,4,5,and 6mo,respectively.Decision-curve analysis indicated that only the 4-,5-,and 6-month nomograms had significant net benefits over a large threshold probabilities interval.CONCLUSION:Preoperative PVR,SOTT,PE,RTS,and hypertension are significant risk factors for postoperative PVR formation in patients with primary RRD.The proposed nomogram can effectively predict the 4-,5-,and 6-month PVR-free probabilities after surgery and assist in making clinical decisions during follow-up.展开更多
AIM:To evaluate the effects of intravitreal slow-release dexamethasone on traumatic proliferative vitreoretinopathy(PVR)and Müller cell gliosis and preliminarily explored the possible inflammatory mechanism in a ...AIM:To evaluate the effects of intravitreal slow-release dexamethasone on traumatic proliferative vitreoretinopathy(PVR)and Müller cell gliosis and preliminarily explored the possible inflammatory mechanism in a rabbit model induced by penetrating ocular trauma.METHODS:Traumatic PVR was induced in the right eyes of pigmented rabbits by performing an 8-mm circumferential scleral incision placed 2.5 mm behind the limbus,followed by treatment with a slow-release dexamethasone implant(Ozurdex)or sham injection.Left eyes were used as normal controls.The intraocular pressure(IOP)was monitored using an iCare tonometer.PVR severity was evaluated via anatomical and histopathological examinations every week for 6wk;specific inflammatory cytokine and proliferative marker levels were measured by quantitative real-time polymerase chain reaction,Western blot,protein chip analysis,or immunofluorescence staining.RESULTS:During the observation period,PVR severity gradually increased.Intense Müller cell gliosis was observed in the peripheral retina near the wound and in the whole retina of PVR group.Ozurdex significantly alleviated PVR development and Müller cell gliosis.Post-traumatic inflammation fluctuated and was persistent.The interleukin-1β(IL-1β)mRNA level was significantly upregulated,peaking on day 3 and increasing again on day 21 after injury.The expression of nod-like receptor family pyrin domain containing 3(NLRP3)showed a similar trend that began earlier than that of IL-1βexpression.Ozurdex suppressed the expression of IL-1β,NLRP3,and phosphorylated nuclear factor-kappa B(NF-κB).The average IOP after treatment was within normal limits.CONCLUSION:The present study demonstrates chronic and fluctuating inflammation in a traumatic PVR rabbit model over 6wk.Ozurdex treatment significantly inhibites inflammatory cytokines expression and Müller cell gliosis,and thus alleviates PVR severity.This study highlights the important role of IL-1β,and Ozurdex inhibites inflammation presumably via the NF-κB/NLRP3/IL-1βinflammatory axis.In summary,Ozurdex provides a potential therapeutic option for traumatic PVR.展开更多
Pathological dry skin is a disturbing and intractable healthcare burden,characterized by epithelial hyperplasia and severe itch.Atopic dermatitis(AD)and psoriasis models with complications of dry skin have been studie...Pathological dry skin is a disturbing and intractable healthcare burden,characterized by epithelial hyperplasia and severe itch.Atopic dermatitis(AD)and psoriasis models with complications of dry skin have been studied using single-cell RNA sequencing(scRNA-seq).However,scRNA-seq analysis of the dry skin mouse model(acetone/ether/water(AEW)-treated model)is still lacking.Here,we used scRNA-seq and in situ hybridization to identify a novel proliferative basal cell(PBC)state that exclusively expresses transcription factor CUT-like homeobox 1(Cux1).Further in vitro study demonstrated that Cux1 is vital for keratinocyte proliferation by regulating a series of cyclin-dependent kinases(CDKs)and cyclins.Clinically,Cux1+PBCs were increased in patients with psoriasis,suggesting that Cux1+PBCs play an important part in epidermal hyperplasia.This study presents a systematic knowledge of the transcriptomic changes in a chronic dry skin mouse model,as well as a potential therapeutic target against dry skin-related dermatoses.展开更多
Dear Editor,We are writing to present an uncommon case of a45-year-old woman with bilateral proliferative diabetic retinopathy (PDR) and ocular albinism (OA).Albinism is a group of inherited disorders of tyrosinase ac...Dear Editor,We are writing to present an uncommon case of a45-year-old woman with bilateral proliferative diabetic retinopathy (PDR) and ocular albinism (OA).Albinism is a group of inherited disorders of tyrosinase activities and melanin biosynthesis resulting in little or no production of the pigment melanin。展开更多
BACKGROUND Cerebral proliferative angiopathy(CPA)is a rare subtype of arteriovenous malformation.It is extremely rare in pediatric patients and has serious implications for developing children.However,reports of these...BACKGROUND Cerebral proliferative angiopathy(CPA)is a rare subtype of arteriovenous malformation.It is extremely rare in pediatric patients and has serious implications for developing children.However,reports of these disorders worldwide are limited,and no uniform reference for diagnosis and treatment options exists.We report the case of a 6-year-old with CPA having predominantly neurological dysfunction and review the literature on pediatric CPA.CASE SUMMARY We report the case of a pediatric patient with CPA analyzed using digital subtraction angiography(DSA)who presented initially with a neurological disorder as the main manifestation.This case is the basis for further discussion of the clinical presentation,pathogenesis,diagnosis,and treatment of CPA in children.After the cerebral DSA,the patient was treated conservatively with sedation,fluid replacement,and blood anticoagulation.She could not cooperate with the followup magnetic resonance imaging examination because of her young age,and her family declined further treatment because of the surgery’s high risk.She was followed up for 3 months;her symptoms did not worsen.CONCLUSION This report of rare pediatric CPA can inform and advance clinical research on congenital cerebrovascular diseases.展开更多
AIM: To investigate the pooled prevalence of diabetic retinopathy(DR), proliferative DR(PDR) and nonproliferative DR(NPDR) in Asian type 2 diabetes mellitus(T2 DM) patients. METHODS: We performed a systematic search o...AIM: To investigate the pooled prevalence of diabetic retinopathy(DR), proliferative DR(PDR) and nonproliferative DR(NPDR) in Asian type 2 diabetes mellitus(T2 DM) patients. METHODS: We performed a systematic search online search using PubMed, EMBASE, Web of Science, the Cochrane Library, and China WeiPu Library to identify eligible studies that reported the prevalence of DR, PDR and NPDR in Asian T2 DM patients. Effect size(ES) with 95% confidence interval(CI) was used to evaluate the prevalence of DR, PDR and NPDR in Asian T2 DM patients, respectively. RESULTS: There were 41 references and 48 995 T2 DM patients involved in this study. The prevalence of DR, PDR, and NPDR was 28%, 6%, and 27% in T2 DM patients, respectively; while the prevalence of PDR and NPDR in DR patients was 17% and 83%, respectively. Subgroup analysis showed that prevalence of DR in T2 DM patients from Singaporean, Indian, South Korean, Malaysian, Asian, and Chinese was 33%, 42%, 16%, 35%, 21% and 25%, respectively. In T2 DM patients with NPDR from Indian, South Korean, Malaysian, Asian, Chinese, higher prevalence was found than that in PDR patients(45% vs 17%, 13% vs 3%, 30% vs 5%, 23% vs 2% and 22% vs 3%), as well as in DR patients(74% vs 26%, 81% vs 19%, 86% vs 14%, 92% vs 8% and 85% vs 15%). The prevalence of PDR in T2 DM from India was higher than patients fromother locations of Asia, and the same results were also observed in NPDR patients. CONCLUSION: In either T2 DM Asian patients or DR patients, NPDR is more common than PDR. Based on our results, we should pay more attention to NPDR screening and management in T2 DM patients, and we also recommend suitable interventions to prevent its progression.展开更多
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 mel...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 counts.RESULTS: 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=0.142.CONCLUSION: 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 different populations have different associations for the same polymorphisms.展开更多
AIM:To confirm the role of angiopoietin-like protein 8(Angptl 8) in proliferative diabetic retinopathy(PDR).METHODS:The sera and aqueous humor of 10 PDR patients and 10 non-diabetic retinopathy(NDR) patients(...AIM:To confirm the role of angiopoietin-like protein 8(Angptl 8) in proliferative diabetic retinopathy(PDR).METHODS:The sera and aqueous humor of 10 PDR patients and 10 non-diabetic retinopathy(NDR) patients(idiopathic macular hole patients) were collected and the expression of Angptl 8 was detected by enzyme linked immune-sorbent assay(ELISA).Experimental diabetes mice model was induced with streptozotocin.The expression of glycosylated hemoglobin and Angptl 8 in sera was detected.Recombinant Angptl 8 was re-infused into wild type(WT) diabetic mice and spatial frequency threshold and contrast sensitivity were measured.In vitro retinal pigment epithelium(RPE) were stimulated by recombinant Angptl 8 for 24 h.MMT assay were used to detect cell proliferation.At the same time,q RT-PCR and Western blot was used to measure the expression of proliferation-related factors in PRE cells.RESULTS:The expression of Angptl 8 was markedly increased in the sera and aqueous humor of PDR patients(F=99.02,P〈0.0001 in sera;t=10.42,P〈0.0001 in aqueous).After successfully establishing the diabetic mice model,we found that glycosylated hemoglobin and Angptl 8 expression levels were increased.Re-infusion of recombinant Angptl 8 into WT diabetic mice could further decrease spatial frequency threshold and contrast sensitivity(P〈0.01).In vitro,RPE cells stimulated by recombinant Angptl 8could increase the relative absorbance of MMT assay(1.486±0.042 vs 1.000±0.104,P〈0.05) and proliferating cell nuclear antigen(PCNA) expression(0.55±0.01 vs 0.29±0.03,P〈0.05).The proliferative effect of Angptl 8 is mainly mediated by increasing the expression of proliferation-activating factors cyclin A1(4.973±0.205 vs 2.720±0.197,P〈0.05),cyclin F(5.690±0.219 vs 4.297±0.292,P〈0.05) and E2 F2(2.297±0.102 vs 1.750±0.146,P〈0.05),and reducing the expression of proliferation-inhibiting factors cdkn1(2.370±0.074 vs 3.317±0.135,P〈0.05) and cdkn2(4.793±0.065 vs 5.387±0.149,P〈0.05).CONCLUSION:The expression of Angptl 8 is increased in PDR,and the increased Angptl 8 can promote proliferation and increase proliferation-related factors.展开更多
AIM: To analyze osteopontin (OPN) expression in vitreous and proliferative retinal membranes of patients with proliferative vitreous retinopathy (PVR). METHODS: A total of 54 vitreous fluid samples were obtained betwe...AIM: To analyze osteopontin (OPN) expression in vitreous and proliferative retinal membranes of patients with proliferative vitreous retinopathy (PVR). METHODS: A total of 54 vitreous fluid samples were obtained between 2009 and 2010, which contained 45 with PVR (group A) and 9 without PVR (group B). Enzyme-linked immunosorbent assay was applied to quantify the OPN concentrations in vitreous fluid. Four samples of proliferative retinal membrane were also obtained at the time of vitrectomy, and their contents of OPN were measured by Real-time RT-PCR. RESULTS: The OPN levels in the vitreous fluid were 778.48+/- 62.06ng/mL in group A and 452.99 32.52ng/mL in group B. The vitreous OPN levels in group A were significantly higher than those in group B and to rise by time in the early stages of PVR. The average OPN levels in the proliferative retinal membranes (F =0.14) were also higher than those in the retinal pigment cells (F =0) using Real-time RT-PCR. CONCLUSION: The high vitreous and proliferative retinal membrane OPN levels in PVR suggest that OPN might promote the development of PVR. The vitreous OPN concentrations are rising by the time in the early phases of PVR.展开更多
The underlying effect of different concentrations of neogenin on proliferation, apoptosis and the related proliferative factors in human trophoblasts was explored in order to understand the function of neogenin during...The underlying effect of different concentrations of neogenin on proliferation, apoptosis and the related proliferative factors in human trophoblasts was explored in order to understand the function of neogenin during placentation. TEV-1 cell line was cultured and the expression of netrin-1 was detected by using indirect cellular immunofluorescence. Exponentially growing TEV-1 cells were treated by different concentrations of neogenin (0, 1, 5, 10, 50 ng/mL) for 24 h. Cell viability was measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. TEV-1 cell apoptosis was assessed by flow cytometry (FCM). The expression of netrin-1 mRNA and protein in TEV-1 cells was examined by using real-time PCR and Western blot, respectively. It was found that immunoreactivity for netrin-1 was observed in cytoplasm of the trophoblasts. Immediately after treatment with different concentrations of neogenin for 24 h, the netrin-1 expression began to increase. Real-time PCR revealed that the expression level of netrin-1 mRNA was 37.59±10.25 times higher than control group when TEV-1 cells were exposed to 50 ng/mL neogenin (P<0.01), and the same tendency was seen by using Western blot. MTT results showed that proliferation of TEV-1 cells was independent of neogenin. Meanwhile, apoptosis was significantly increased to (22.15±6.15)% at 50 ng/mL neogenin and (6.55±0.25)% without neogenin (P<0.01). It is suggested that neogenin regulates proliferation and apoptosis of TEV-1 cells. And it can enhance the ability of TEV-1 cells to express netrin-1 in a dose-dependent manner. Neogenin may play an important biological role in the normal human pregnancy and contribute to the physiological pregnancy process.展开更多
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 medica...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.展开更多
AIMTo evaluate the relationship between intravitreal bevacizumab (IVB) treatment and the levels of vitreous vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and vitreous-retina surface ...AIMTo evaluate the relationship between intravitreal bevacizumab (IVB) treatment and the levels of vitreous vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and vitreous-retina surface fibrosis in patients with proliferative diabetic retinopathy (PDR).METHODSThis study was a prospective, open-label, controlled, randomized clinical trial. Sixty-eight eyes of PDR patients (n=53) and macular hole patients (n=15) were enrolled in this study. Thirty-four eyes of the PDR patients received IVB before vitrectomy. Twenty-three of the 34 PDR patients received IVB treatment 5d before vitrectomy (subgroup a), and 11 of the 34 PDR patients received IVB treatment greater than 2wk prior to vitrectomy (subgroup b). Nineteen of the PDR patients did not receive IVB treatment at any time prior to vitrectomy. The levels of bFGF and VEGF in vitreous samples were measured using enzyme-linked immunosorbent assay (ELISA) and the degree of vitreoretinal fibrosis was characterized using clinical data and data obtained intra-operatively.RESULTSIn PDR patients, VEGF and bFGF levels were significantly increased compared to non-PDR (control) subject's eyes (P<0.01). In PDR patients, vitreous VEGF levels were significantly decreased following IVB treatment compared to PDR patients that did not receive IVB treatment (P<0.01). The degree of vitreoretinal fibrosis was significantly increased in subgroup b compared to subgroup a(P<0.05) and to patients that did not receive IVB (P<0.05). Vitreous bFGF levels were significantly greater in subgroup b than subgroup a (P<0.01) or in patients who did not receive IVB treatment (P<0.05). A Spearman's rank correlation test indicated that higher levels of vitreous bFGF, but not VEGF, correlated with the degree of vitreoretinal fibrosis.CONCLUSIONWe found that bFGF levels increase in PDR patient's vitreous after IVB treatment longer than two weeks prior to vitrectomy and correlated with the degree of fibrosis after IVB treatment. These findings suggest vitreous fibrosis is increased in PDR patients after IVB treatment may be due to increased levels of bFGF.展开更多
AIM: To evaluate serum concentrations of angiogenesis-related cytokines in proliferative diabetic retinopathy (PDR) before and after vitrectomy. METHODS: Serum samples were collected from 30 PDR patients with varying ...AIM: To evaluate serum concentrations of angiogenesis-related cytokines in proliferative diabetic retinopathy (PDR) before and after vitrectomy. METHODS: Serum samples were collected from 30 PDR patients with varying severity before and after vitrectomy. Serum concentrations of vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), interleukin-8 (IL-8) and interferon-inducible protein-10 (IP-10) were determined by enzyme-linked immunosorbent assays(ELISA). RESULTS: Serum concentrations of VEGF, PEDF, IL-8 and IP-10 were significantly higher in PDR patients than that in controls, respectively (P<0.05). VEGF concentration decreased significantly in postoperative samples than that in preoperative samples (P<0.05). The concentrations of PEDF, IL-8 and IP-10 did not exhibit significant changes after vitrectomy. CONCLUSION: Elevated cytokines levels in serum may be diagnostically useful in PDR. Angiogenesis-related cytokines play important roles in the development of PDR, and would instruct the risk assessment of pathogenetic condition in PDR patients.展开更多
AIM: To evaluate the effects of panretinal photocoagulation (PRP) compared with PRP plus intravitreal bevacizumab (IVB) in patients with high-risk proliferative diabetic retinopathy (PDR) according to the Early...AIM: To evaluate the effects of panretinal photocoagulation (PRP) compared with PRP plus intravitreal bevacizumab (IVB) in patients with high-risk proliferative diabetic retinopathy (PDR) according to the Early Treatment Diabetic Retinopathy Study criteria.METHODS: The data were collected retrospectively from the eyes of high-risk PDR patients, which were divided into two groups. After treated with standard PRP, the eyes were randomly assigned to receive only PRP (PRP group) or PRP plus intravitreal injection of 1.25 mg of bevacizumab (PRP-Plus group). Patients underwent complete ophthalmic evaluation, including best corrected visual acuity (BCVA), intraocular pressure (IOP), and new vessel size in fluorescein angiography (FA) and optical coherence tomography for the assessment of central subfield macular thickness (CSMT) at baseline and at weeks 12 (±2), 16 (±2), 24 (±2) and 48 (±2). Main outcome measures also included vitreous clear-up time and neovascularization on the disc (NVD) regression time. Adverse events associated with intravitreal injection were investigated.RESULTS: Thirty consecutive patients (n=36 eyes) completed the 48-week follow-up. There was no significant difference between the PRP and PRP-Plus groups with respect to age, gender, type or duration of diabetes, area of fluorescein leakage from active neovascularizations (NVs), BCVA or CSMT at baseline. The mean vitreous clear-up time was 12.1±3.4wk after PRP and 8.4±3.5wk after PRP combined with IVB. The mean time interval from treatment to complete NVD regression on FA examination was 15.2±3.5wk in PRP group and 12.5±3.1wk in PRP-Plus group. No significant difference in CSMT was observed between the groups throughout the study period. However, the total area of actively leaking NVs was significantly reduced in the PRP-Plus group compared with the PRP group (P〈0.05). Patients received an average of 1.3 injections (range: 1-2). Ten eyes (27.8%) underwent 2 injections. Two eyes had ocular complication of PDR progression to dense vitreous hemorrhage (VH). No major adverse events were identified.CONCLUSION: The adjunctive use of IVB with PRP is associated with a greater reduction in the area of active leaking NVs than PRP alone in patients with high-risk PDR. Short-term results suggest combined IVB and PRP achieved rapid clearance of VH and regression of retinal NV in the treatment of high-risk PDR. Further studies are needed to determine the effect of repeated intravitreal bevacizumab injections and the proper number of bevacizumab injections as an adjuvant.展开更多
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 o...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 microscopy.METHODS: 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 microscopy.RESULTS: The NDR group exhibited significantly declined corneal sensitivity and Schirmer I test value, as compared to the non-diabetic controls(P 【0.001). The PDR group showed significantly reduced corneal sensitivity, Schirmer I test value, and NIBUT in comparison to the non-diabetic controls(P 【0.001).Corneal fluorescein staining revealed the progressively injured corneal epithelia in the PDR patients. Moreover,significant decrease in the corneal epithelial density andmorphological abnormalities in the corneal epithelia and nerve fibers were also observed in the PDR patients.CONCLUSION: Ocular surface changes, including blunted corneal sensitivity, reduced tear secretion, tear film dysfunction, progressive loss of corneal epithelia and degeneration of nerve fibers, are common in type II 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 the duration of diabetes. Therefore, ocular surface of the patients with PDR should be examined regularly by conventional approaches and confocal microscopy to facilitate early diagnosis and treatment of keratopathy.展开更多
AIM: To investigate the efficacy of non-buckled vitrectomy with classical endotamponade agents in the treatment of primary retinal detachment (RD) complicated by inferior breaks and proliferative vitreoretinophathy (P...AIM: To investigate the efficacy of non-buckled vitrectomy with classical endotamponade agents in the treatment of primary retinal detachment (RD) complicated by inferior breaks and proliferative vitreoretinophathy (PVR). METHODS: A retrospective, consecutive and case series study of 40 patients with inferior break RD and PVR >= C1 was conducted. All patients underwent a standard 3-port 20-gauge pars plana vitrectomy (PPV) with gas or silicone oil tamponade without supplementary scleral buckling. The vitreous and all proliferative membrane were completely removed, and retinectomy was performed when necessary. The mean follow-up was 12.5 months. The primary and final anatomic success rate, visual acuity and complications were recorded and analyzed. RESULTS: Primary anatomic success rate was achieved in 35 of 40 eyes (87.5%) and the final anatomic success rate was 100%. The most common cause of redetachment was recurrent PVR. The best-corrected visual acuity (BCVA) at final follow-up was improved in 34 eyes (85%), remained stable in 1 eye (2.5%), and worsened in 5 eyes (12.5%). The mean visual acuity at final follow-up was improved significantly (P=0.000). CONCLUSION: This retrospective study provides evidence that vitrectomy without scleral buckling seemed to be an effective treatment for inferior break RD with PVR. With complete removal of vitreous and proliferative membranes and timing of retinectomy, the inferior breaks which complicated with PVR could be dosed successfully without additional sclera! buckling.展开更多
基金Supported by the Program for Qinhuangdao Self-financing Science and Technology Plan of 2008 (No.201805A143).
文摘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 separately.METHODS:This was a retrospective and cross-sectional study.Consecutive 25-gauge(25-G)PPV cases operated for PDR from May 2018 to April 2020.According to the FVPMs images outlined after operations,subjects were assigned into three groups:arcade type group,juxtapapillary type group,and central type group.All patients were followed up for over one year.General characteristics,operation-related variables,postoperative parameters and complications were recorded.RESULTS: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 inferior.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 improvement.CONCLUSION:FVPMs are more commonly found in the nasal and inferior mid-peripheral retina in addition to the area of arcade vessels.Performing 25-G PPV for treating PDR eyes with central FVPM have relatively worse prognosis.
基金Supported by Tianjin Key Medical Discipline Specialty Construction Project(No.TJYXZDXK-016A)Henan Provincial Department of Science and Technology(No.LHGJ20200802).
文摘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 PDR.METHODS: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 technology.Statistically differentially expressed proteins(DEPs),Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway representation and protein interactions were analyzed.RESULTS:A total of 12 samples were analyzed.The proteomics results showed that a total of 58 proteins were identified as DEPs,of which 47 proteins were up-regulated and 11 proteins were down-regulated.We 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 treatment.GO functional analysis showed that some DEPs are related to changes in inflammatory regulatory pathways caused by PDR.In addition,protein-protein interaction(PPI)network evaluation revealed that TIMP1 plays a central role in neural regulation.In addition,CD47/SIRPαmay become a key target to resolve anti-VEGF drug resistance in PDR.CONCLUSION:Proteomic analysis is an approach of choice to explore the molecular mechanisms of PDR.Our 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.
基金Supported by Research Grants from the fund of Suzhou Kowloon Hospital(No.SZJL202106).
文摘AIM:To assess the clinical efficacy and safety of combining panretinal photocoagulation(PRP)with intravitreal conbercept(IVC)injections for patients with high-risk proliferative diabetic retinopathy(HR-PDR)complicated by mild or moderate vitreous hemorrhage(VH),with or without diabetic macular edema(DME).METHODS:Patients diagnosed with VH with/without DME secondary to HR-PDR and received PRP combined with IVC injections were recruited in this retrospective study.Upon establishing the patient’s diagnosis,an initial IVC was performed,followed by prompt administration of PRP.In cases who significant bleeding persisted and impeded the laser operation,IVC was sustained before supplementing with PRP.Following the completion of PRP,patients were meticulously monitored for a minimum of six months.Laser therapy and IVC injections were judiciously adjusted based on fundus fluorescein angiography(FFA)results.Therapeutic effect and the incidence of adverse events were observed.RESULTS:Out of 42 patients(74 eyes),29 were male and 13 were female,with a mean age of 59.17±12.74y(33-84y).The diabetic history was between 1wk and 26y,and the interval between the onset of visual symptoms and diagnosis of HR-PDR was 1wk-1y.The affected eye received 2.59±1.87(1-10)IVC injections and underwent 5.5±1.02(4-8)sessions of PRP.Of these,68 eyes received PRP following 1 IVC injection,5 eyes after 2 IVC injections,and 1 eye after 3 IVC injections.Complete absorption of VH was observed in all 74 eyes 5-50wk after initial treatment,with resolution of DME in 51 eyes 3-48wk after initial treatment.A newly developed epiretinal membrane was noted in one eye.Visual acuity significantly improved in 25 eyes.No complications such as glaucoma,retinal detachment,or endophthalmitis were reported.CONCLUSION:The study suggests that the combination of PRP with IVC injections is an effective and safe modality for treating diabetic VH in patients with HR-PDR.
文摘●AIM:To evaluate the effectiveness and safety of early lens extraction during pars plana vitrectomy(PPV)for proliferative diabetic retinopathy(PDR)compared to those of PPV with subsequent cataract surgery.●METHODS:This multicenter randomized controlled trial was conducted in three Chinese hospitals on patients with PDR,aged>45y,with mild cataracts.The participants were randomly assigned to the combined(PPV combined with simultaneously cataract surgery,i.e.,phacovitrectomy)or subsequent(PPV with subsequent cataract surgery 6mo later)group and followed up for 12mo.The primary outcome was the change in best-corrected visual acuity(BCVA)from baseline to 6mo,and the secondary outcomes included complication rates and medical expenses.●RESULTS:In total,129 patients with PDR were recruited and equally randomized(66 and 63 in the combined and subsequent groups respectively).The change in BCVA in the combined group[mean,36.90 letters;95%confidence interval(CI),30.35–43.45]was significantly better(adjusted difference,16.43;95%CI,8.77–24.08;P<0.001)than in the subsequent group(mean,22.40 letters;95%CI,15.55–29.24)6mo after the PPV,with no significant difference between the two groups at 12mo.The overall surgical risk of two sequential surgeries was significantly higher than that of the combined surgery for neovascular glaucoma(17.65%vs 3.77%,P=0.005).No significant differences were found in the photocoagulation spots,surgical time,and economic expenses between two groups.In the subsequent group,the duration of work incapacity(22.54±9.11d)was significantly longer(P<0.001)than that of the combined group(12.44±6.48d).●CONCLUSION:PDR patients aged over 45y with mild cataract can also benefit from early lens extraction during PPV with gratifying effectiveness,safety and convenience,compared to sequential surgeries.
文摘AIM:To identify the risk factors for postoperative proliferative vitreoretinopathy(PVR)in patients with primary rhegmatogenous retinal detachment(RRD)and develop a nomogram for predicting postoperative PVR-free probability.METHODS:A total of 741 patients(741 eyes)diagnosed with primary RRD who underwent first surgery in the same hospital were retrospectively reviewed and randomly assigned with 521 to the training set and 220 to the validation set.Univariate and multivariate logistic regression analyses were performed in the training cohort to determine risk factors to construct a nomogram for predicting the 3-,4-,5-,and 6-month postoperative PVR-free probabilities.Nomogram performance was estimated by the concordance index(C-index),calibration plot,and the area receiver operating characteristic(ROC)curve.RESULTS:A nomogram was constructed based on the preoperative PVR,silicone oil tamponade time(SOTT),photocoagulation energy(PE),retinal tear size(RTS),and hypertension.In the training set,the C-index of the nomogram was 0.896,0.936,0.961,and 0.972 at 3,4,5,and 6mo,respectively.The C-index values in the validation set were 0.860,0.936,0.951,and 0.965 at 3,4,5,and 6mo,respectively.Decision-curve analysis indicated that only the 4-,5-,and 6-month nomograms had significant net benefits over a large threshold probabilities interval.CONCLUSION:Preoperative PVR,SOTT,PE,RTS,and hypertension are significant risk factors for postoperative PVR formation in patients with primary RRD.The proposed nomogram can effectively predict the 4-,5-,and 6-month PVR-free probabilities after surgery and assist in making clinical decisions during follow-up.
基金Supported by National Natural Science Foundation of China(No.81974135,No.81900851)。
文摘AIM:To evaluate the effects of intravitreal slow-release dexamethasone on traumatic proliferative vitreoretinopathy(PVR)and Müller cell gliosis and preliminarily explored the possible inflammatory mechanism in a rabbit model induced by penetrating ocular trauma.METHODS:Traumatic PVR was induced in the right eyes of pigmented rabbits by performing an 8-mm circumferential scleral incision placed 2.5 mm behind the limbus,followed by treatment with a slow-release dexamethasone implant(Ozurdex)or sham injection.Left eyes were used as normal controls.The intraocular pressure(IOP)was monitored using an iCare tonometer.PVR severity was evaluated via anatomical and histopathological examinations every week for 6wk;specific inflammatory cytokine and proliferative marker levels were measured by quantitative real-time polymerase chain reaction,Western blot,protein chip analysis,or immunofluorescence staining.RESULTS:During the observation period,PVR severity gradually increased.Intense Müller cell gliosis was observed in the peripheral retina near the wound and in the whole retina of PVR group.Ozurdex significantly alleviated PVR development and Müller cell gliosis.Post-traumatic inflammation fluctuated and was persistent.The interleukin-1β(IL-1β)mRNA level was significantly upregulated,peaking on day 3 and increasing again on day 21 after injury.The expression of nod-like receptor family pyrin domain containing 3(NLRP3)showed a similar trend that began earlier than that of IL-1βexpression.Ozurdex suppressed the expression of IL-1β,NLRP3,and phosphorylated nuclear factor-kappa B(NF-κB).The average IOP after treatment was within normal limits.CONCLUSION:The present study demonstrates chronic and fluctuating inflammation in a traumatic PVR rabbit model over 6wk.Ozurdex treatment significantly inhibites inflammatory cytokines expression and Müller cell gliosis,and thus alleviates PVR severity.This study highlights the important role of IL-1β,and Ozurdex inhibites inflammation presumably via the NF-κB/NLRP3/IL-1βinflammatory axis.In summary,Ozurdex provides a potential therapeutic option for traumatic PVR.
基金supported by Technological Innovation 2030-Major Projects of Brain Science and Brain-like Research(Grant No.:2022zD0206200)the Natural Science Foundation of China(Grant Nos.:31872796,82030108 to W.Yang,32071102 to P.Yu)+3 种基金the National Major Special Project on New Drug Innovation of China(Grant No.:2018ZX09711001-004-005)the key research and development program of Ningxia Hui Autonomous Region(Grant No.:2019BFH02003)Fundamental Research Funds for the Central Universities of China(Grant No.:2016QNA7002 to P.Yu)Zhejiang Provincial Natural Science Foundation(Grant No.:LR16H090001 to W.Yang).
文摘Pathological dry skin is a disturbing and intractable healthcare burden,characterized by epithelial hyperplasia and severe itch.Atopic dermatitis(AD)and psoriasis models with complications of dry skin have been studied using single-cell RNA sequencing(scRNA-seq).However,scRNA-seq analysis of the dry skin mouse model(acetone/ether/water(AEW)-treated model)is still lacking.Here,we used scRNA-seq and in situ hybridization to identify a novel proliferative basal cell(PBC)state that exclusively expresses transcription factor CUT-like homeobox 1(Cux1).Further in vitro study demonstrated that Cux1 is vital for keratinocyte proliferation by regulating a series of cyclin-dependent kinases(CDKs)and cyclins.Clinically,Cux1+PBCs were increased in patients with psoriasis,suggesting that Cux1+PBCs play an important part in epidermal hyperplasia.This study presents a systematic knowledge of the transcriptomic changes in a chronic dry skin mouse model,as well as a potential therapeutic target against dry skin-related dermatoses.
文摘Dear Editor,We are writing to present an uncommon case of a45-year-old woman with bilateral proliferative diabetic retinopathy (PDR) and ocular albinism (OA).Albinism is a group of inherited disorders of tyrosinase activities and melanin biosynthesis resulting in little or no production of the pigment melanin。
文摘BACKGROUND Cerebral proliferative angiopathy(CPA)is a rare subtype of arteriovenous malformation.It is extremely rare in pediatric patients and has serious implications for developing children.However,reports of these disorders worldwide are limited,and no uniform reference for diagnosis and treatment options exists.We report the case of a 6-year-old with CPA having predominantly neurological dysfunction and review the literature on pediatric CPA.CASE SUMMARY We report the case of a pediatric patient with CPA analyzed using digital subtraction angiography(DSA)who presented initially with a neurological disorder as the main manifestation.This case is the basis for further discussion of the clinical presentation,pathogenesis,diagnosis,and treatment of CPA in children.After the cerebral DSA,the patient was treated conservatively with sedation,fluid replacement,and blood anticoagulation.She could not cooperate with the followup magnetic resonance imaging examination because of her young age,and her family declined further treatment because of the surgery’s high risk.She was followed up for 3 months;her symptoms did not worsen.CONCLUSION This report of rare pediatric CPA can inform and advance clinical research on congenital cerebrovascular diseases.
文摘AIM: To investigate the pooled prevalence of diabetic retinopathy(DR), proliferative DR(PDR) and nonproliferative DR(NPDR) in Asian type 2 diabetes mellitus(T2 DM) patients. METHODS: We performed a systematic search online search using PubMed, EMBASE, Web of Science, the Cochrane Library, and China WeiPu Library to identify eligible studies that reported the prevalence of DR, PDR and NPDR in Asian T2 DM patients. Effect size(ES) with 95% confidence interval(CI) was used to evaluate the prevalence of DR, PDR and NPDR in Asian T2 DM patients, respectively. RESULTS: There were 41 references and 48 995 T2 DM patients involved in this study. The prevalence of DR, PDR, and NPDR was 28%, 6%, and 27% in T2 DM patients, respectively; while the prevalence of PDR and NPDR in DR patients was 17% and 83%, respectively. Subgroup analysis showed that prevalence of DR in T2 DM patients from Singaporean, Indian, South Korean, Malaysian, Asian, and Chinese was 33%, 42%, 16%, 35%, 21% and 25%, respectively. In T2 DM patients with NPDR from Indian, South Korean, Malaysian, Asian, Chinese, higher prevalence was found than that in PDR patients(45% vs 17%, 13% vs 3%, 30% vs 5%, 23% vs 2% and 22% vs 3%), as well as in DR patients(74% vs 26%, 81% vs 19%, 86% vs 14%, 92% vs 8% and 85% vs 15%). The prevalence of PDR in T2 DM from India was higher than patients fromother locations of Asia, and the same results were also observed in NPDR patients. CONCLUSION: In either T2 DM Asian patients or DR patients, NPDR is more common than PDR. Based on our results, we should pay more attention to NPDR screening and management in T2 DM patients, and we also recommend suitable interventions to prevent its progression.
基金Supported by a grant from the Asociation to Prevent Blindness in Mexico(No.RE-14-02)
文摘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 counts.RESULTS: 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=0.142.CONCLUSION: 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 different populations have different associations for the same polymorphisms.
文摘AIM:To confirm the role of angiopoietin-like protein 8(Angptl 8) in proliferative diabetic retinopathy(PDR).METHODS:The sera and aqueous humor of 10 PDR patients and 10 non-diabetic retinopathy(NDR) patients(idiopathic macular hole patients) were collected and the expression of Angptl 8 was detected by enzyme linked immune-sorbent assay(ELISA).Experimental diabetes mice model was induced with streptozotocin.The expression of glycosylated hemoglobin and Angptl 8 in sera was detected.Recombinant Angptl 8 was re-infused into wild type(WT) diabetic mice and spatial frequency threshold and contrast sensitivity were measured.In vitro retinal pigment epithelium(RPE) were stimulated by recombinant Angptl 8 for 24 h.MMT assay were used to detect cell proliferation.At the same time,q RT-PCR and Western blot was used to measure the expression of proliferation-related factors in PRE cells.RESULTS:The expression of Angptl 8 was markedly increased in the sera and aqueous humor of PDR patients(F=99.02,P〈0.0001 in sera;t=10.42,P〈0.0001 in aqueous).After successfully establishing the diabetic mice model,we found that glycosylated hemoglobin and Angptl 8 expression levels were increased.Re-infusion of recombinant Angptl 8 into WT diabetic mice could further decrease spatial frequency threshold and contrast sensitivity(P〈0.01).In vitro,RPE cells stimulated by recombinant Angptl 8could increase the relative absorbance of MMT assay(1.486±0.042 vs 1.000±0.104,P〈0.05) and proliferating cell nuclear antigen(PCNA) expression(0.55±0.01 vs 0.29±0.03,P〈0.05).The proliferative effect of Angptl 8 is mainly mediated by increasing the expression of proliferation-activating factors cyclin A1(4.973±0.205 vs 2.720±0.197,P〈0.05),cyclin F(5.690±0.219 vs 4.297±0.292,P〈0.05) and E2 F2(2.297±0.102 vs 1.750±0.146,P〈0.05),and reducing the expression of proliferation-inhibiting factors cdkn1(2.370±0.074 vs 3.317±0.135,P〈0.05) and cdkn2(4.793±0.065 vs 5.387±0.149,P〈0.05).CONCLUSION:The expression of Angptl 8 is increased in PDR,and the increased Angptl 8 can promote proliferation and increase proliferation-related factors.
基金National Natural Science Foundation of China(No. 30973257and 81070743)Research Found of Jiangsu Health Department, China (No. H200908)
文摘AIM: To analyze osteopontin (OPN) expression in vitreous and proliferative retinal membranes of patients with proliferative vitreous retinopathy (PVR). METHODS: A total of 54 vitreous fluid samples were obtained between 2009 and 2010, which contained 45 with PVR (group A) and 9 without PVR (group B). Enzyme-linked immunosorbent assay was applied to quantify the OPN concentrations in vitreous fluid. Four samples of proliferative retinal membrane were also obtained at the time of vitrectomy, and their contents of OPN were measured by Real-time RT-PCR. RESULTS: The OPN levels in the vitreous fluid were 778.48+/- 62.06ng/mL in group A and 452.99 32.52ng/mL in group B. The vitreous OPN levels in group A were significantly higher than those in group B and to rise by time in the early stages of PVR. The average OPN levels in the proliferative retinal membranes (F =0.14) were also higher than those in the retinal pigment cells (F =0) using Real-time RT-PCR. CONCLUSION: The high vitreous and proliferative retinal membrane OPN levels in PVR suggest that OPN might promote the development of PVR. The vitreous OPN concentrations are rising by the time in the early phases of PVR.
基金supported by a grant from National Natural Sciences Foundation of China (No. 30872776)
文摘The underlying effect of different concentrations of neogenin on proliferation, apoptosis and the related proliferative factors in human trophoblasts was explored in order to understand the function of neogenin during placentation. TEV-1 cell line was cultured and the expression of netrin-1 was detected by using indirect cellular immunofluorescence. Exponentially growing TEV-1 cells were treated by different concentrations of neogenin (0, 1, 5, 10, 50 ng/mL) for 24 h. Cell viability was measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. TEV-1 cell apoptosis was assessed by flow cytometry (FCM). The expression of netrin-1 mRNA and protein in TEV-1 cells was examined by using real-time PCR and Western blot, respectively. It was found that immunoreactivity for netrin-1 was observed in cytoplasm of the trophoblasts. Immediately after treatment with different concentrations of neogenin for 24 h, the netrin-1 expression began to increase. Real-time PCR revealed that the expression level of netrin-1 mRNA was 37.59±10.25 times higher than control group when TEV-1 cells were exposed to 50 ng/mL neogenin (P<0.01), and the same tendency was seen by using Western blot. MTT results showed that proliferation of TEV-1 cells was independent of neogenin. Meanwhile, apoptosis was significantly increased to (22.15±6.15)% at 50 ng/mL neogenin and (6.55±0.25)% without neogenin (P<0.01). It is suggested that neogenin regulates proliferation and apoptosis of TEV-1 cells. And it can enhance the ability of TEV-1 cells to express netrin-1 in a dose-dependent manner. Neogenin may play an important biological role in the normal human pregnancy and contribute to the physiological pregnancy process.
文摘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.
基金Supported by Public Interest Research on Social Development Projects in Zhejiang Province (No.2011c23019)
文摘AIMTo evaluate the relationship between intravitreal bevacizumab (IVB) treatment and the levels of vitreous vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and vitreous-retina surface fibrosis in patients with proliferative diabetic retinopathy (PDR).METHODSThis study was a prospective, open-label, controlled, randomized clinical trial. Sixty-eight eyes of PDR patients (n=53) and macular hole patients (n=15) were enrolled in this study. Thirty-four eyes of the PDR patients received IVB before vitrectomy. Twenty-three of the 34 PDR patients received IVB treatment 5d before vitrectomy (subgroup a), and 11 of the 34 PDR patients received IVB treatment greater than 2wk prior to vitrectomy (subgroup b). Nineteen of the PDR patients did not receive IVB treatment at any time prior to vitrectomy. The levels of bFGF and VEGF in vitreous samples were measured using enzyme-linked immunosorbent assay (ELISA) and the degree of vitreoretinal fibrosis was characterized using clinical data and data obtained intra-operatively.RESULTSIn PDR patients, VEGF and bFGF levels were significantly increased compared to non-PDR (control) subject's eyes (P<0.01). In PDR patients, vitreous VEGF levels were significantly decreased following IVB treatment compared to PDR patients that did not receive IVB treatment (P<0.01). The degree of vitreoretinal fibrosis was significantly increased in subgroup b compared to subgroup a(P<0.05) and to patients that did not receive IVB (P<0.05). Vitreous bFGF levels were significantly greater in subgroup b than subgroup a (P<0.01) or in patients who did not receive IVB treatment (P<0.05). A Spearman's rank correlation test indicated that higher levels of vitreous bFGF, but not VEGF, correlated with the degree of vitreoretinal fibrosis.CONCLUSIONWe found that bFGF levels increase in PDR patient's vitreous after IVB treatment longer than two weeks prior to vitrectomy and correlated with the degree of fibrosis after IVB treatment. These findings suggest vitreous fibrosis is increased in PDR patients after IVB treatment may be due to increased levels of bFGF.
文摘AIM: To evaluate serum concentrations of angiogenesis-related cytokines in proliferative diabetic retinopathy (PDR) before and after vitrectomy. METHODS: Serum samples were collected from 30 PDR patients with varying severity before and after vitrectomy. Serum concentrations of vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), interleukin-8 (IL-8) and interferon-inducible protein-10 (IP-10) were determined by enzyme-linked immunosorbent assays(ELISA). RESULTS: Serum concentrations of VEGF, PEDF, IL-8 and IP-10 were significantly higher in PDR patients than that in controls, respectively (P<0.05). VEGF concentration decreased significantly in postoperative samples than that in preoperative samples (P<0.05). The concentrations of PEDF, IL-8 and IP-10 did not exhibit significant changes after vitrectomy. CONCLUSION: Elevated cytokines levels in serum may be diagnostically useful in PDR. Angiogenesis-related cytokines play important roles in the development of PDR, and would instruct the risk assessment of pathogenetic condition in PDR patients.
文摘AIM: To evaluate the effects of panretinal photocoagulation (PRP) compared with PRP plus intravitreal bevacizumab (IVB) in patients with high-risk proliferative diabetic retinopathy (PDR) according to the Early Treatment Diabetic Retinopathy Study criteria.METHODS: The data were collected retrospectively from the eyes of high-risk PDR patients, which were divided into two groups. After treated with standard PRP, the eyes were randomly assigned to receive only PRP (PRP group) or PRP plus intravitreal injection of 1.25 mg of bevacizumab (PRP-Plus group). Patients underwent complete ophthalmic evaluation, including best corrected visual acuity (BCVA), intraocular pressure (IOP), and new vessel size in fluorescein angiography (FA) and optical coherence tomography for the assessment of central subfield macular thickness (CSMT) at baseline and at weeks 12 (±2), 16 (±2), 24 (±2) and 48 (±2). Main outcome measures also included vitreous clear-up time and neovascularization on the disc (NVD) regression time. Adverse events associated with intravitreal injection were investigated.RESULTS: Thirty consecutive patients (n=36 eyes) completed the 48-week follow-up. There was no significant difference between the PRP and PRP-Plus groups with respect to age, gender, type or duration of diabetes, area of fluorescein leakage from active neovascularizations (NVs), BCVA or CSMT at baseline. The mean vitreous clear-up time was 12.1±3.4wk after PRP and 8.4±3.5wk after PRP combined with IVB. The mean time interval from treatment to complete NVD regression on FA examination was 15.2±3.5wk in PRP group and 12.5±3.1wk in PRP-Plus group. No significant difference in CSMT was observed between the groups throughout the study period. However, the total area of actively leaking NVs was significantly reduced in the PRP-Plus group compared with the PRP group (P〈0.05). Patients received an average of 1.3 injections (range: 1-2). Ten eyes (27.8%) underwent 2 injections. Two eyes had ocular complication of PDR progression to dense vitreous hemorrhage (VH). No major adverse events were identified.CONCLUSION: The adjunctive use of IVB with PRP is associated with a greater reduction in the area of active leaking NVs than PRP alone in patients with high-risk PDR. Short-term results suggest combined IVB and PRP achieved rapid clearance of VH and regression of retinal NV in the treatment of high-risk PDR. Further studies are needed to determine the effect of repeated intravitreal bevacizumab injections and the proper number of bevacizumab injections as an adjuvant.
基金Supported by Shanxi China Scientific and Technological Project(No.2007031096-1)Ph.D.Program Foundation of Ministry of Education of China(No.20111202110008)
文摘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 microscopy.METHODS: 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 microscopy.RESULTS: The NDR group exhibited significantly declined corneal sensitivity and Schirmer I test value, as compared to the non-diabetic controls(P 【0.001). The PDR group showed significantly reduced corneal sensitivity, Schirmer I test value, and NIBUT in comparison to the non-diabetic controls(P 【0.001).Corneal fluorescein staining revealed the progressively injured corneal epithelia in the PDR patients. Moreover,significant decrease in the corneal epithelial density andmorphological abnormalities in the corneal epithelia and nerve fibers were also observed in the PDR patients.CONCLUSION: Ocular surface changes, including blunted corneal sensitivity, reduced tear secretion, tear film dysfunction, progressive loss of corneal epithelia and degeneration of nerve fibers, are common in type II 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 the duration of diabetes. Therefore, ocular surface of the patients with PDR should be examined regularly by conventional approaches and confocal microscopy to facilitate early diagnosis and treatment of keratopathy.
基金supported by the Health Bureau of Zhejiang Province, China (No.20100580)
文摘AIM: To investigate the efficacy of non-buckled vitrectomy with classical endotamponade agents in the treatment of primary retinal detachment (RD) complicated by inferior breaks and proliferative vitreoretinophathy (PVR). METHODS: A retrospective, consecutive and case series study of 40 patients with inferior break RD and PVR >= C1 was conducted. All patients underwent a standard 3-port 20-gauge pars plana vitrectomy (PPV) with gas or silicone oil tamponade without supplementary scleral buckling. The vitreous and all proliferative membrane were completely removed, and retinectomy was performed when necessary. The mean follow-up was 12.5 months. The primary and final anatomic success rate, visual acuity and complications were recorded and analyzed. RESULTS: Primary anatomic success rate was achieved in 35 of 40 eyes (87.5%) and the final anatomic success rate was 100%. The most common cause of redetachment was recurrent PVR. The best-corrected visual acuity (BCVA) at final follow-up was improved in 34 eyes (85%), remained stable in 1 eye (2.5%), and worsened in 5 eyes (12.5%). The mean visual acuity at final follow-up was improved significantly (P=0.000). CONCLUSION: This retrospective study provides evidence that vitrectomy without scleral buckling seemed to be an effective treatment for inferior break RD with PVR. With complete removal of vitreous and proliferative membranes and timing of retinectomy, the inferior breaks which complicated with PVR could be dosed successfully without additional sclera! buckling.