scholarly journals Reduced Expression of Erythropoietin After Intravitreal Ranibizumab in Proliferative Diabetic Retinopathy Patients—Retrospective Interventional Study

2021 ◽  
Vol 8 ◽  
Author(s):  
Li Chen ◽  
Jing Feng ◽  
Yanhong Shi ◽  
Fuxiao Luan ◽  
Fang Ma ◽  
...  

Purpose: To evaluate the expressions of erythropoietin (EPO) and vascular endothelial growth factor (VEGF) in the vitreous and fibrovascular membranes (FVMs) of proliferative diabetic retinopathy (PDR) after the intravitreal injection of ranibizumab (IVR) and further explore the relationship between EPO and VEGF.Method: The concentrations of EPO and VEGF levels in the vitreous fluid were measured in 35 patients (24 PDR and 11 non-diabetic patients) using enzyme-linked immunosorbent assay. The patients were divided into three groups: PDR with IVR (IVR group) before par plana vitrectomy (n = 10), PDR without IVR (Non-IVR group) (n = 14) and a control group [macular holes (MHs) or epiretinal membranes (ERM), n = 11]. Fluorescence immunostaining was performed to examine the expressions of VEGF, EPO and CD 105 in the excised epiretinal membranes.Result: The PDR eyes of Non-IVR group had the highest vitreous VEGF and EPO levels (836.30 ± 899.50 pg/ml, 99.29 ± 27.77 mIU/ml, respectively) compared to the control group (10.98 ± 0.98 pg/ml and 18.96 ± 13.30 mIU/ml/ml). Both the VEGF and EPO levels in the IVR group (13.22 ± 2.72 pg/ml and 68.57 ± 41.47 mIU/ml) were significantly lower than the Non-IVR group (P = 0.004 and P = 0.04, respectively). Furthermore, no significant difference was observed for VEGF levels between the control and IVR groups (10.9 ± 0.98 pg/ml and 13.22 ± 2.72 pg/ml, respectively, P = 0.9). Yet the EPO level in the IVR group was significantly higher than that in the Non-diabetic group (68.57 ± 41.47 pg/ml and 18.96 ± 13.30 pg/ml, respectively, P = 0.001). The expressions of EPO, VEGF, and CD105 were significantly reduced in fluorescence immunostaining of FVMs in the IVR group compared with the Non-IVR group. The receiver operating characteristic (ROC) curve of the EPO and VEGF levels were 0.951 and 0.938 in the PDR group.Conclusion: Both of the VEGF and EPO level were significantly increased in PDR patients, which have equal diagnostic value in the prediction of PDR. IVR could reduce the EPO level, but not enough to the normal level.

2020 ◽  
Vol 37 (1) ◽  
Author(s):  
Ali Afzal Bodla ◽  
Syeda Minahil Kazmi ◽  
Noor Tariq ◽  
Ayema Moazzam ◽  
Muhammad Muneeb Aman

Purpose:  To study the effects of Intra-vitreal injection of Bevacizumab as an adjunct during phacoemulsification in patients with diabetic retinopathy. Study Design:  Quasi experimental study. Methods:  Hundred diabetic patients who were scheduled to undergo phacoemulsification were included in the study. They were equally divided into two groups; Bevacizumab and control group. Complete ocular examination and macular thickness and volume were determined using an OPTOVUE-OCT machine. The patients in the Bevacizumab group were given intra-vitreal injection of 1.25 mg/0.05ml of Bevacizumab at the time of Phacoemulsification. A written ethical approval was obtained and the study was conducted according to principles of declaration of Helsinki. Results:  The bevacizumab group manifested low value of CMT one month post-surgery as compared to the control group (262.2 ± 32.2 and 288.5 ± 54.1, respectively) with P = 0.01. The Total Macular volume, and Best-corrected visual acuity in the two groups showed no significant difference one month after surgery. Amongst the patients who developed postsurgical macular edema, four patients did not possess a positive history for diabetic retinopathy and 3 of them had Non Proliferative Diabetic Retinopathy. We found no significant relationship between the post-surgical macula edema with the presence of mild Non Proliferative Diabetic Retinopathy. (Fisher's test, P = 0.321). Conclusion:  The ocular anti-VEGF therapy substantially reduces macular edema secondary to post-surgical inflammation in diabetic patients. It effectively reduces the central macular thickness although the results are not found to be statistically significant when compared with the control group. Key Words:  Diabetes mellitus; diabetic macular edema; diabetic retinopathy: Bevacizumab.


Author(s):  
Shipeng Li ◽  
Jianling Sun ◽  
Wenchao Hu ◽  
Yan Liu ◽  
Dan Lin ◽  
...  

Objective Adropin, a newly identified regulatory protein encoded by Enho gene, is correlated with insulin sensitivity and diabetes. The aim of this study is to determine whether serum and vitreous adropin concentrations are correlated with the presence of diabetic retinopathy. Methods A population of 165 patients with type 2 diabetes mellitus (52 without diabetic retinopathy, 69 with non-proliferative diabetic retinopathy and 44 patients with proliferative diabetic retinopathy) was enrolled in this study. The control group enrolled 68 healthy subjects who had underwent vitrectomy for retinal detachment. Serum and vitreous adropin concentrations were examined using enzyme-linked immunosorbent assay method. Results Control subjects had significantly higher serum and vitreous adropin concentrations compared with diabetic patients. Serum and vitreous adropin concentrations in proliferative diabetic retinopathy patients were significantly reduced compared with those in non-proliferative diabetic retinopathy patients and type 2 diabetes mellitus patients without diabetic retinopathy. In addition, there were lower serum and vitreous adropin concentrations in non-proliferative diabetic retinopathy patients compared with type 2 diabetes mellitus patients without diabetic retinopathy. Logistic regression analysis revealed that serum and vitreous adropin were associated with a decreased risk of type 2 diabetes mellitus and diabetic retinopathy. Conclusion Serum and vitreous adropin concentrations are negatively associated with the presence of diabetic retinopathy.


2020 ◽  
Author(s):  
Hui Wang ◽  
Hui Lou ◽  
Yongrong Li ◽  
Fengtao Ji ◽  
Wei Chen ◽  
...  

Abstract Background Lipocalin-2 (LCN2) is a novel adipokine with potential roles in obesity, insulin resistance, and inflammation. This study aims to assess the concentrations of LCN2 and vascular endothelial growth factor (VEGF) expressed in the vitreous humors of patients with proliferative diabetic retinopathy (PDR). Methods The concentrations of LCN2 and VEGF were measured from the vitreous of 67 patients undergoing vitrectomy (20 controls and 47PDR) via enzyme-linked immunosorbent assay (ELISA). Results The vitreous concentration of LCN2 was statistically significantly higher in the PDR group compared to the control group (63,522 ± 30,009 pg/ml versus 1663 ± 1191 pg/ml, respectively; P<0.001). VEGF level was also significantly higher in the PDR group than in the control group (1038 ± 1326 pg/ml versus 9 pg/ml, respectively; P<0.001). The mean vitreous LCN2 and VEGF levels in active PDR patients were significantly higher than that of the inactive PDR patients. The mean LCN2 concentration in vitreous humor was significantly lower in the 28 PDR patients with a history of complete PRP (37,304 ± 16,651 pg/mL) in comparison with 19 PDR patients without preperformed panretinal photocoagulation or with preperformed incomplete panretinal photocoagulation (79,796 ± 24,391 pg/mL). A significant correlation between the vitreous LCN2 level and VEGF level was found in patients with PDR (R=0.34; P=0.019). Conclusions This report shows a significant increase of LCN2 in the vitreous fluid of patients with PDR and present a significant correlation between LCN2 and VEGF, suggesting LCN2 might be involved in the pathogenesis of PDR.


2021 ◽  
Vol 11 ◽  
Author(s):  
Ahmed M. Abu El-Asrar ◽  
Mohd Imtiaz Nawaz ◽  
Ajmal Ahmad ◽  
Alexandra De Zutter ◽  
Mohammad Mairaj Siddiquei ◽  
...  

The transmembrane chemokine pathways CXCL16/CXCR6 and CX3CL1/CX3CR1 are strongly implicated in inflammation and angiogenesis. We investigated the involvement of these chemokine pathways and their processing metalloproteinases ADAM10 and ADAM17 in the pathophysiology of proliferative diabetic retinopathy (PDR). Vitreous samples from 32 PDR and 24 non-diabetic patients, epiretinal membranes from 18 patients with PDR, rat retinas, human retinal Müller glial cells and human retinal microvascular endothelial cells (HRMECs) were studied by enzyme-linked immunosorbent assay, immunohistochemistry and Western blot analysis. In vitro angiogenesis assays were performed and the adherence of leukocytes to CXCL16-stimulated HRMECs was assessed. CXCL16, CX3CL1, ADAM10, ADAM17 and vascular endothelial growth factor (VEGF) levels were significantly increased in vitreous samples from PDR patients. The levels of CXCL16 were 417-fold higher than those of CX3CL1 in PDR vitreous samples. Significant positive correlations were found between the levels of VEGF and the levels of CXCL16, CX3CL1, ADAM10 and ADAM17. Significant positive correlations were detected between the numbers of blood vessels expressing CD31, reflecting the angiogenic activity of PDR epiretinal membranes, and the numbers of blood vessels and stromal cells expressing CXCL16, CXCR6, ADAM10 and ADAM17. CXCL16 induced upregulation of phospho-ERK1/2, p65 subunit of NF-κB and VEGF in cultured Müller cells and tumor necrosis factor-α induced upregulation of soluble CXCL16 and ADAM17 in Müller cells. Treatment of HRMECs with CXCL16 resulted in increased expression of intercellular adhesion molecule-1 (ICAM-1) and increased leukocyte adhesion to HRMECs. CXCL16 induced HRMEC proliferation, formation of sprouts from HRMEC spheroids and phosphorylation of ERK1/2. Intravitreal administration of CXCL16 in normal rats induced significant upregulation of the p65 subunit of NF-κB, VEGF and ICAM-1 in the retina. Our findings suggest that the chemokine axis CXCL16/CXCR6 and the processing metalloproteinases ADAM10 and ADAM17 might serve a role in the initiation and progression of PDR.


2016 ◽  
Vol 236 (2) ◽  
pp. 61-66 ◽  
Author(s):  
Jun Li ◽  
Wen-chao Hu ◽  
Hui Song ◽  
Jing-na Lin ◽  
Xin Tang

Purpose: To investigate chemerin in the vitreous bodies of patients with proliferative diabetic retinopathy (PDR) and determine the correlation between the levels of vitreous chemerin and vascular endothelial growth factor (VEGF). Methods: This study included 17 patients suffering from PDR and vitreous hemorrhage (VH) (group A), 21 patients with PDR and tractional retinal detachment (TRD) (group B) and 25 patients with idiopathic macular holes or preretinal membranes (control group). All vitreous samples were obtained through pars plana vitrectomy. Enzyme-linked immunosorbent assay and Western blot analysis were performed to evaluate the levels of vitreous chemerin and VEGF. Results: Vitreous concentrations of chemerin were significantly higher in PDR patients with VH and TRD than those in the controls [4.82 ng/ml (3.91-6.13) vs. 5.03 ng/ml (4.01-6.15) vs. 2.53 ng/ml (1.53-5.66), p = 0.025]. The ratio of vitreous chemerin to plasma chemerin concentration significantly differed between groups A and B and the control group [4.93% (4.69-5.34) vs. 4.98% (4.63-5.19) vs. 2.58% (1.78-4.58), p < 0.001]. Western blot results indicated that the levels of vitreous chemerin protein in PDR patients significantly increased compared with those in the controls. Spearman correlation analysis further showed that vitreous chemerin levels in patients with PDR were positively correlated with vitreous VEGF levels (r = -0.542, p < 0.001). Conclusions: Increased vitreous chemerin levels are associated with the development of PDR.


2020 ◽  
Vol 63 (6) ◽  
pp. 517-523
Author(s):  
Feng Jiang ◽  
Liuyun Chong ◽  
Shufang Du ◽  
Yajian Duan ◽  
Ying Wang ◽  
...  

<b><i>Background:</i></b> Different splicing of vascular endothelial growth factor (VEGF) gene results in 2 families of VEGF, the proangiogenic isoforms (VEGF<sub>xxx</sub>a) and the antiangiogenic isoforms (VEGF<sub>xxx</sub>b). VEGF<sub>165</sub>b is the major antiangiogenic isoform of VEGF and the most studied member of the VEGF<sub>xxx</sub>b family so far. <b><i>Objectives:</i></b> To determine the concentration of VEGF<sub>165</sub>b and VEGF in the aqueous humor (AH) in diabetic eyes with or without diabetic retinopathy (DR) and to address the predictive value of VEGF<sub>165</sub>b/VEGF ratio for progression of DR. <b><i>Methods:</i></b> AH samples from 20 eyes in healthy controls (CON group), 40 eyes in diabetic patients without DR (nDR group), and 30 eyes in diabetic patients with mild nonproliferative DR (DR group) were collected. All of the patients were followed up for at least 5 years. VEGF<sub>165</sub>b and VEGF levels of AH samples were measured by enzyme-linked immunosorbent assay (ELISA). The predictive value of the initial VEGF<sub>165</sub>b/VEGF ratio for progression of DR was studied. <b><i>Results:</i></b> The mean concentration of VEGF<sub>165</sub>b significantly decreased in diabetic eyes vs. controls. The mean concentration of VEGF significantly increased in the DR group vs. the CON group. The VEGF<sub>165</sub>b/VEGF ratio was significantly lower in diabetic patients compared to the CON group. The VEGF<sub>165</sub>b/VEGF ratio was significantly lower in diabetic patients compared to the control group. The mean follow-up was 66.1months (range 60–71 months). The risk of DR progression was greater with a lower VEGF<sub>165</sub>b/VEGF ratio. <b><i>Conclusion:</i></b> The VEGF<sub>165</sub>b/VEGF ratio is lower in the AH of DR patients and the decreased ratio of VEGF<sub>165</sub>b/VEGF predicts DR progression.


2020 ◽  
Vol 17 ◽  
Author(s):  
Van-An Duong ◽  
Jeeyun Ahn ◽  
Na-Young Han ◽  
Jong-Moon Park ◽  
Jeong-Hun Mok ◽  
...  

Background: Diabetic Retinopathy (DR), one of the major microvascular complications commonly occurring in diabetic patients, can be classified into Proliferative Diabetic Retinopathy (PDR) and Non-Proliferative Diabetic Retinopathy (NPDR). Currently available therapies are only targeted for later stages of the disease in which some pathologic changes may be irreversible. Thus, there is a need to develop new treatment options for earlier stages of DR through revealing pathological mechanisms of PDR and NPDR. Objective: The purpose of this study was to characterize proteomes of diabetic through quantitative analysis of PDR and NPDR. Methods: Vitreous body was collected from three groups: control (non-diabetes mellitus), NPDR, and PDR. Vitreous proteins were digested to peptide mixtures and analyzed using LC-MS/MS. MaxQuant was used to search against the database and statistical analyses were performed using Perseus. Gene ontology analysis, related-disease identification, and protein-protein interaction were performed using the differential expressed proteins. Results: Twenty proteins were identified as critical in PDR and NPDR. The NPDR group showed different expressions of kininogen-1, serotransferrin, ribonuclease pancreatic, osteopontin, keratin type II cytoskeletal 2 epidermal, and transthyretin. Also, prothrombin, signal transducer and activator of transcription 4, hemoglobin subunit alpha, beta, and delta were particularly up-regulated proteins for PDR group. The up-regulated proteins related to complement and coagulation cascades. Statherin was down-regulated in PDR and NPDR compared with the control group. Transthyretin was the unique protein that increased its abundance in NPDR compared with the PDR and control group. Conclusion: This study confirmed the different expressions of some proteins in PDR and NPDR. Additionally, we revealed uniquely expressed proteins of PDR and NPDR, which would be differential biomarkers: prothrombin, alpha-2-HS-glycoprotein, hemoglobin subunit alpha, beta, and transthyretin.


2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Xiaochun Yang ◽  
Jianbiao Xu ◽  
Ruili Wang ◽  
Yan Mei ◽  
Huo Lei ◽  
...  

Purpose.To determine the efficacy and safety of preoperative intravitreal conbercept (IVC) injection before vitrectomy for proliferative diabetic retinopathy (PDR).Methods.107 eyes of 88 patients that underwent pars plana vitrectomy (PPV) for active PDR were enrolled. All patients were assigned randomly to either preoperative IVC group or control group. Follow-up examinations were performed for three months after surgery. The primary bioactivity measures were severity of intraoperative bleeding, incidence of early and late recurrent VH, vitreous clear-up time, and best-corrected visual acuity (BCVA) levels. The secondary safety measures included intraocular pressure, endophthalmitis, rubeosis, tractional retinal detachment, and systemic adverse events.Results.The incidence and severity of intraoperative bleeding were significantly lower in IVC group than in the control group. The average vitreous clear-up time of early recurrent VH was significantly shorter in IVC group compared with that in control group. There was no significant difference in vitreous clear-up time of late recurrent VH between the two groups. Patients that received pretreatment of conbercept had much better BCVA at 3 days, 1 week, and 1 month after surgery than control group. Moreover, both patients with improved BCVA were greater in IVC group than in control group at each follow-up.Conclusions.Conbercept pretreatment could be an effective adjunct to vitrectomy in accelerating postoperative vitreous clear-up and acquiring stable visual acuity restoration for PDR.


2014 ◽  
Vol 142 (9-10) ◽  
pp. 529-534 ◽  
Author(s):  
Ivan Sencanic ◽  
Miroslav Stamenkovic ◽  
Vesna Jovanovic ◽  
Sinisa Babovic ◽  
Vesna Jaksic ◽  
...  

Introduction. Ultrastructural changes in corneas of patients with diabetes mellitus have been previously described. Objective. The aim of this study was to compare central corneal thickness (CDR) values in diabetic patients without retinopathy at the stage of diabetic nonproliferative and proliferative retinopathy and CDR in a control group of healthy subjects. Methods. The study included 121 diabetic patients and 125 healthy subjects matched according to gender and age. Each patient underwent ophthalmological examination involving a dilated fundus examination and CDR measurement using the ultrasound pachymeter. The eyes of diabetic patients were classified according to Early Treatment Diabetic Retinopathy Study into three groups: without diabetic retinopathy (NDR), with nonproliferative diabetic retinopathy (NPDR) and a group with proliferative diabetic retinopathy (PDR). Only one eye of each subject was chosen for the study. Results. The mean CDR value was significantly higher in the diabetic group (570.52?31.81 ?m) compared with the control group (541.42?27.82 ?m). The difference between the two groups was statistically significant (p<0.0001). The highest mean CDR value was recorded in the PDR group (585.97?28.58 ?m), followed by the NPDR group (570.84?30.27 ?m), whereas the lowest mean CDR value was recorded in the NDR group (559.80?31.55 ?m). There was a statistically significant difference in CDR between the NDR and PDR groups, as well as between the NPDR and PDR groups (p<0.001, p<0.05 respectively). No significant difference was recorded between the NDR and NPDR groups (p>0.05). Conclusion. CDR of diabetic patients was higher compared to healthy subjects. The highest mean value of CDR was registered in the PDR group, followed by the NPDR and the NDR groups.


2021 ◽  
Vol 8 ◽  
Author(s):  
Li Lu ◽  
Gaocheng Zou ◽  
Li Chen ◽  
Qianyi Lu ◽  
Mian Wu ◽  
...  

Purpose: This study aims to determine vitamin D concentrations in the vitreous and serum, as well as the expression levels of NLRP3 inflammasome pathway in the vitreous of patients with proliferative diabetic retinopathy (PDR). In addition, we investigated the possible correlation between NLRP3 inflammasome levels and vitamin D concentrations.Methods: We obtained vitreous samples before vitrectomy from 55 PDR patients, 25 non-diabetic patients with idiopathic macular hole (IMH), and 10 non-proliferative diabetic retinopathy (NPDR) patients. We also collected serum samples from the same patients. Enzyme-linked immunosorbent assay (ELISA) was used to examine NLRP3 inflammasome pathway proteins, including NLRP3, caspase-1, IL-1β, and VEGF. In addition, vitamin D concentrations were analyzed in Roche Cobas 6000's module e601 platform using electrochemiluminescence immune assay.Results: The levels of NLRP3 inflammasome pathway and VEGF increased dramatically in PDR vitreous. However, vitamin D concentrations in vitreous and serum followed the opposite trend. Meanwhile, vitreous and serum vitamin D concentrations were significantly negatively correlated with vitreous NLRP3 expression in PDR patients. Moreover, serum and vitreous vitamin D concentrations were positively correlated and demonstrated discriminatory ability in DR. The subgroup analysis of PDR group revealed that eyes with tractional retinal detachment (TRD) had higher NLRP3 inflammasome pathway and VEGF levels but lower vitamin D concentrations. Conversely, eyes that received preoperative pan-retinal photocoagulation (PRP) exhibited lower levels of NLRP3 inflammasome pathway, but vitamin D concentrations were irrelevant to laser treatment.Conclusions: Our results demonstrate a strong correlation between increased NLRP3 inflammasome pathway and decreased vitamin D concentrations in the vitreous of PDR patients, which may be linked to PDR pathogenesis. In addition, vitamin D supplementation may play a key role in preventing, treating, and improving PDR prognosis due to its inhibitory impact on NLRP3 inflammasome pathway and VEGF.


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