scholarly journals Elevated vitreous Lipocalin-2 levels of patients with proliferative 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.

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.


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 ◽  
pp. 112067212094480
Author(s):  
Yong Hyun Jun ◽  
Seong Taeck Kim

Purpose: To investigate aqueous humor (AH) and serum levels of brain-derived neurotrophic factor (BDNF) in non-proliferative diabetic retinopathy (NPDR) patients with diabetic macular edema (DME). Methods: The prospective study consists of 20 patients with DME NPDR, 20 patients with no-DME NPDR, and 20 healthy control subjects. Serum and AH samples were obtained during cataract surgery and intravitreal injection. Serum and AH levels of BDNF were measured by enzyme-linked immunosorbent assay. Results: The mean serum levels of BDNF were lower in both NPDR groups compared to the control group (DME NPDR group, p = 0.015; no-DME NPDR group, p = 0.024). Furthermore, the mean serum level of BDNF was lower in the DME NPDR group compared to the no-DME NPDR group ( p = 0.041). The mean AH levels of BDNF were significantly reduced in both NPDR groups compared to the control group (DME NPDR group, p < 0.001; no-DME NPDR group, p = 0.006). Further, the mean AH level of BDNF was significantly lower in the DME NPDR group compared to the no-DME NPDR group ( p = 0.037). Conclusion: Serum and AH levels of BDNF were reduced in NPDR patients with DME than without DME.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Murat Okutucu ◽  
Hüseyin Fındık ◽  
Mehmet Gökhan Aslan ◽  
Medeni Arpa

Abstract Background To evaluate alterations in the serum concentrations of vascular endothelial growth factor (VEGF) and netrin-1 after intravitreal bevacizumab (BCZ) injection for the treatment of diabetic macular edema (DME). Methods This prospective case-control study included a total of 50 participants assigned to one of three groups, including 10 individuals with DME and non-proliferative diabetic retinopathy (NPDR), 13 with DME, and proliferative diabetic retinopathy (PDR), and 27 healthy individuals as a control group. Serum VEGF and netrin-1 concentrations were measured by enzyme-linked immunosorbent assays (ELISAs) immediately before, as well as 1 week and 1 month after, intravitreal BCZ injection. Results The mean VEGF serum concentrations in the PDR and NPDR groups were 388.4 and 196.9 pg/mL at baseline, respectively. After 1 week, these concentrations changed to 193.41 and 150.23 pg/mL, respectively (P = 0.001 and P = 0.005, respectively); after 1 month, the concentrations were 97.89 and 76.46 pg/mL, respectively (P = 0.001 and P = 0.009, respectively). The mean netrin-1 serum concentrations in the PDR patients and NPDR groups were 318.2 and 252.7 pg/mL at baseline, respectively. After 1 week, these concentrations increased to 476.6 and 416.3 pg/mL, respectively (P = 0.033 and P = 0.005, respectively), and after 1 month, they were 676.6 and 747.5 pg/mL, respectively (P = 0.001 and P = 0.005, respectively). The correlation analysis revealed a significant inverse relationship between changes in serum VEGF and netrin-1 concentrations in both the PDR and NPDR groups (r = − 0.685, P = 0.029). Conclusions Intravitreal BCZ injections work systemically to significantly decrease serum VEGF levels, leading to a significant upregulation in the concentration of another angiogenic mediator, netrin-1.


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.


2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Hui-Jin Chen ◽  
Zhi-Zhong Ma ◽  
Ying Li ◽  
Chang-Guan Wang

Purpose. To study the change of concentrations of vascular endothelial growth factor (VEGF) in vitreous cavity after vitrectomy in eyes with proliferative diabetic retinopathy (PDR). Methods. In this retrospective study, intravitreal fluid samples were taken at baseline (beginning of the vitrectomy) and postoperatively (several days later after vitrectomy) at the time of prophylactic injection of bevacizumab in forty-eight eyes of forty-eight patients with PDR. Postvitrectomy fluid samples were divided into four groups according to the time interval between the vitrectomy and the injection (group 1, 3–5 days; group 2, 6–10 days; group 3, 11–15 days; group 4, 16–21 days; twelve eyes in each group). Postvitrectomy fluid sample was paired with baseline sample for each eye. VEGF concentrations in the samples were determined by enzyme-linked immunosorbent assay. Recurrent vitreous hemorrhage and neovascular glaucoma within six months postvitrectomy were also analyzed. Results. Overall, the intravitreal VEGF level after vitrectomy (median, 36.95 pg/ml; range, 3.2–1,299.4 pg/ml) was significantly less than the VEGF level at baseline (median, 704.5 pg/ml; range, 30.6–1,981.1 pg/ml). Postoperative and baseline VEGF levels were significantly correlated (r = 0.499, p<0.01). Both the absolute value of postoperative VEGF concentrations and the postop/baseline VEGF ratios declined with time and dramatically decreased in groups 3 and 4. In only two eyes, the postoperative VEGF level was even higher than the baseline VEGF level (postop/baseline VEGF ratio >1), and recurrent vitreous hemorrhage developed within six months in these two eyes. Conclusions. After vitrectomy for PDR, intravitreal VEGF levels decreased substantially in the majority of patients, while persistent high-VEGF level occurred in a few individuals. Postoperative VEGF levels and postop/baseline VEGF ratio declined with time. The postop/preop VEGF ratio may serve as a predictor for late complications.


2018 ◽  
Vol 2 (3) ◽  
pp. 127-137
Author(s):  
Dennis M. Marcus ◽  
Harinderjit Singh ◽  
Davis C. Starnes ◽  
Harveen Walia ◽  
Amina Farooq ◽  
...  

Purpose: For proliferative diabetic retinopathy (PDR) eyes not requiring vitrectomy, Diabetic Retinopathy Clinical Research Protocol S and the CLARITY trial demonstrated better visual function and anatomical outcomes with less proliferative and diabetic macular edema consequences in the antivascular endothelial growth factor groups compared to the panretinal photocoagulation groups. Intravitreal aflibercept injection (IAI) may represent a useful therapy with vitrectomy for PDR-related vitreous hemorrhage (VH) as a viable alternative to intraoperative endolaser during vitrectomy. We will determine the safety and efficacy when aflibercept is used for PDR-related VH with endolaserless vitrectomy. Methods: Evaluation of endolaserless vitrectomy and 2 mg IAI for PDR-related VH. Eyes receive 1 preoperative and intraoperative IAI followed by randomization to a q8week group receiving 4 postoperative q4week IAI followed by q8week IAI or q16week group receiving 2 postoperative q4week IAI followed by q16week IAI. Main Outcome Measures: Herein, we present pooled safety and efficacy outcomes through 4 months. Results: Twenty-one of 24 eyes were randomized. Preoperative average visual acuity (VA) was 36 letters (20/200). At 4-month follow-up, 18 of 21 randomized eyes showed an average VA of 72 letters (20/40) with an average visual gain of 38 (range, 0-84 gain) letters. Average optical coherence tomography (OCT) central subfield thickness (CST) at 1-month postoperative follow-up was 311 µm. Average OCT CST at 4-month follow-up was 272 µm (average thinning of 38 µm). No significant short-term ocular or systemic adverse events were observed through 4 months. Conclusions: Endolaserless vitrectomy with IAI for PDR-related VH demonstrates short-term safety with significant VA improvement.


2021 ◽  
Author(s):  
Ming-Chieh Hsieh ◽  
Chieh-Yin Cheng ◽  
Kun-Hsien Li ◽  
Chih-Chun Chuang ◽  
Jian-Sheng Wu ◽  
...  

Abstract The purpose of this retrospective interventional case series is to compare the functional and anatomical outcomes in eyes with diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) treated intravitreally with aflibercept or ranibizumab under the Taiwan National Insurance Bureau reimbursement policy. 84 eyes were collected and all eyes were imaged with spectral-domain optical coherence tomography (SD-OCT), color fundus photographs (CFPs), and fluorescein angiography (FA). At 24 months after therapy initiation, the logMAR BCVA improved from 0.58 ± 0.33 to 0.47 ± 0.38 (p < 0.01), the CRT decreased from 423.92 ± 135.84 to 316.36 ± 90.02 (p < 0.01), and the number of microaneurysms decreased from 142.14 ± 57.23 to 75.32 ± 43.86 (p < 0.01). The mean injection count was 11.59 ± 6.54. There was no intergroup difference in logMAR BCVA (p = 0.96), CRT (p = 0.69), or injection count (p = 0.81). However, the mean number of microaneurysms was marginally reduced (p = 0.06) in eyes treated with aflibercept at the end of the follow-up, and the incidence rates of supplementary panretinal photocoagulation (PRP) (p = 0.04) and subthreshold micropulse laser (SMPL) therapy sessions (p = 0.01) were also reduced. Multivariate analysis revealed that only initial logMAR BCVA influenced the final VA improvements (odds ratio (OR) 0.49, 95% confidence interval (CI) 0.21 ~ 0.93, p < 0.01); in contrast, age (OR -0.38, 95% CI -6.97~-1.85, p < 0.01) and initial CRT (OR 0.56, 95% CI 0.34 ~ 0.84, p < 0.01) both influenced the final CRT reduction at 24 months. To sum up, both aflibercept and ranibizumab are effective in managing DME with PDR in terms of VA, CRT and MA count. Eyes receiving aflibercept required less supplementary PRP and SMPL treatment than those receiving ranibizumab. The initial VA influenced the final VA improvements at 24 months, while age and initial CRT were prognostic predictors of 24-month CRT reduction.


2020 ◽  
Vol 9 (5) ◽  
pp. 1462
Author(s):  
Ho Ra ◽  
Jae Hyun Park ◽  
Jin Uk Baek ◽  
Jiwon Baek

Purpose: To investigate the relationships among the retinal nonperfusion (NP) area, neovascularization (NV) area, and aqueous humor vascular endothelial growth factor (VEGF) levels in quiescent proliferative diabetic retinopathy (PDR). Methods: Forty-seven eyes from 47 patients with treatment-naïve PDR that did not show macular edema or vitreous hemorrhage were enrolled. NP area, NV number, and NV area were quantitatively measured using ultra-widefield fluorescein angiography in an automated manner. Aqueous humor VEGF level was measured using a bead assay. Results: The NP areas of the total, posterior pole, peripheral retinae, and NV area positively correlated with each other (all p < 0.034). NV number correlated with total NP area, peripheral NP area, and NV area (all p ≤ 0.001). VEGF levels were significantly positively correlated with total, posterior polar, and peripheral NP areas and NV area (r = 0.575, 0.422, 0.558, and 0.362, respectively; all p ≤ 0.012). In eyes with NV in the disc area, the VEGF level was higher compare to eyes without NV in the disc area (208.89 ± 192.77 pg/mL vs. 103.34 ± 132.66, p = 0.010). A multiple linear regression model using NP area, NV area, and NVD demonstrated good prediction for VEGF level (R2 = 0.417, p < 0.001) and revealed a significant contribution of the peripheral NP area in predicting the VEGF level (β = 0.497, p = 0.002). Conclusions: Aqueous humor VEGF levels in quiescent PDR eyes were associated with NP and NV areas, which had positive correlations with each other. In addition, the NP area of the peripheral retina was the most important predictor of VEGF level.


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