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1.
Association of VEGF Gene Polymorphisms with Susceptibility to Diabetic Retinopathy: A Systematic Review and Meta-Analysis.
Yang, Q, Zhang, Y, Zhang, X, Li, X, Liu, J
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2020;(5):264-279
Abstract
The associations between vascular endothelial growth factor (VEGF) gene polymorphisms and risk of type 2 diabetic retinopathy (DR) - proliferative diabetic retinopathy (PDR), and nonproliferative diabetic retinopathy (NPDR) - remain unclear. A systematic search and meta-analysis using odds ratio (OR) with 95% confidence interval (CI) was performed to evaluate the association. Our study concluded 26 studies containing 10 single nucleotide polymorphisms (SNPs). In Asian populations, rs3025039 polymorphism was associated with DR risk, while in overall populations and Caucasians, the DR risk was increased by association with rs2010963. There was a significant association between rs25648 and rs833061 and DR risk in Caucasians. DR risks were found to be significantly associated between rs3025021, rs13207351, and rs2146323 in either overall populations, Caucasians or Asians. Besides, in overall and Asian populations, rs699947 and rs3025039 were associated with PDR risk. rs1570360, rs3025039, and rs833061 played a key role in PDR etiology in Caucasians. rs2010963 was associated with increased risk of PDR in overall populations. A significant association between rs699947, rs3025039, and rs833061 and NPDR risk in overall populations and Asians was found. A significant association was observed between rs2010963 and increased NPDR risk in overall and Caucasian populations. This study provides a new insight into the parthenogenesis of diabetic retinopathy. Targeting VEGF SNPs may be a potential of therapeutic approach for the treatment of DR, PDR, and NPDR.
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2.
Association between Normal Thyroid Hormones and Diabetic Retinopathy in Patients with Type 2 Diabetes.
Zou, J, Li, Z, Tian, F, Zhang, Y, Xu, C, Zhai, J, Shi, M, Wu, G, Zhang, Z, Yang, C, et al
BioMed research international. 2020;:8161797
Abstract
The relationship between normal thyroid function and type 2 diabetes mellitus (T2DM) has been a particular focus for concern. The present study determined the relationship between thyroid hormone levels and the prevalence of diabetic retinopathy (DR) in T2DM patients. A cross-sectional study (n = 633) was performed in Xi'an, Shaanxi Province, China. Subjects were evaluated for anthropometric measurements, thyroid function, and diabetic retinopathy. Logistic regression models were used to assess the relationships between thyroid hormones and DR. Of 633 patients, 243 (38.4%) patients suffered from DR. The prevalence of DR showed a significantly decreasing trend across the quartiles based on free triiodothyronine (FT3) (FT3 quartile 1 group [FT3-Q1] <4.35 pmol/L, FT3 quartile 2 group [FT3-Q2] 4.35-4.70 pmol/L, FT3 quartile 3 group [FT3-Q3] 4.70-5.08 pmol/L, and FT3 quartile 4 group [FT3-Q4] ≥5.08 pmol/L) (56.7%, 42.5%, 33.1%, 23.8%, P < 0.001). In comparison with all participants categorized in FT3-Q1, the multivariable adjusted odds ratios (95% confidence interval) of DR in FT3-Q2, FT3-Q3, and FT3-Q4 were 0.587 (0.340-1.012), 0.458 (0.258-0.813), and 0.368 (0.201-0.673), (P = 0.055, P = 0.008, P = 0.001), respectively. FT3 levels within the normal range are negatively associated with DR in euthyroid patients with type 2 diabetes. Further studies should be aimed at clarifying the relationship between thyroid hormones and T2DM.
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The efficacy and safety of aflibercept and conbercept in diabetic macular edema.
Cai, S, Yang, Q, Li, X, Zhang, Y
Drug design, development and therapy. 2018;:3471-3483
Abstract
Diabetic macular edema (DME) has shown an increasing prevalence during the past years and is the leading cause of diabetic retinopathy blindness. Traditional treatment modalities include laser and corticosteroid therapy, which, however, either act through unclear mechanisms or cause cataracts and elevated intraocular pressure. In recent years, as the pathogenic role of VEGF in DME has been well-recognized, the intravitreal injection of anti-VEGF drugs has become the first-line treatment of DME due to their great efficacy in improving visual acuity and mitigating macular edema. Advantages have been shown for aflibercept and conbercept, the two recombinant decoy receptors that can bind VEGF with high specificity and affinity, in DME treatment in clinical trials conducted both worldwide and in People's Republic of China. This review introduces the structural characteristics and molecular mechanisms of action of these two anti-VEGF drugs, and summarizes the clinical trials evaluating their efficacy and safety, with the hope to provide clues for designing optimal and personalized therapeutic regimens for DME patients.
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4.
Body mass index and risk of diabetic retinopathy: A meta-analysis and systematic review.
Zhou, Y, Zhang, Y, Shi, K, Wang, C
Medicine. 2017;(22):e6754
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Abstract
Diabetic retinopathy (DR) is a frequent cause of acquired blindness worldwide. Various studies have reported the effects of body mass index (BMI) on the risk of DR, but the results remain controversial. Therefore, a meta-analysis was performed to evaluate the relationship between BMI and the risk of DR.A systematic search was performed using the Cochrane Library, PubMed, and Embase databases to obtain articles published through December 2016. Articles regarding the association between BMI and the risk of DR were retrieved. The adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) were included and then pooled with a random effects model.A total of 27 articles were included in this meta-analysis. When BMI was analyzed as a categorical variable, neither being overweight (OR = 0.89, 95% CI 0.75-1.07; P = .21; I = 65%) nor obesity (OR = 0.97, 95% CI 0.73-1.30; P = .86) were associated with an increased risk of DR when compared with normal weight. When BMI was analyzed as a continuous variable, a higher BMI was not associated with an increased risk of DR (OR = 0.99, 95% CI 0.97-1.01; P = .25; I2 = 79%). The pooled results did not significantly change after the sensitivity analysis.Based on the current publications, neither being overweight nor obesity is associated with an increased risk of DR. Further studies should confirm these findings.
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5.
Peripapillary retinal nerve fiber layer changes in preclinical diabetic retinopathy: a meta-analysis.
Chen, X, Nie, C, Gong, Y, Zhang, Y, Jin, X, Wei, S, Zhang, M
PloS one. 2015;(5):e0125919
Abstract
BACKGROUND Diabetic retinopathy is a microvascular neurodegenerative disorder in diabetic patients. Peripapillary retinal nerve fiber layer changes have been described in patients with preclinical diabetic retinopathy, but study results have been inconsistent. OBJECTIVE To assess changes in peripapillary retinal nerve fiber layer thickness in diabetic patients with preclinical diabetic retinopathy. METHODS A literature search was conducted through PubMed, EMBASE, Web of Science and Cochrane Library. Case-control studies on RNFL thickness in preclinical diabetic retinopathy patients and healthy controls were retrieved. A meta-analysis of weighted mean difference and a sensitivity analysis were performed using RevMan 5.2 software. RESULTS Thirteen case-control studies containing 668 diabetic patients and 556 healthy controls were selected. Peripapillary RNFL thickness was significantly reduced in patients with preclinical diabetic retinopathy compared to healthy controls in studies applying Optical Coherence Tomography (-2.88 μm, 95%CI: -4.44 to -1.32, P = 0.0003) and in studies applying Scanning Laser Polarimeter (-4.21 μm, 95%CI: -6.45 to -1.97, P = 0.0002). Reduction of RNFL thickness was significant in the superior quadrant (-3.79 μm, 95%CI: -7.08 to -0.50, P = 0.02), the inferior quadrant (-2.99 μm, 95%CI: -5.44 to -0.54, P = 0.02) and the nasal quadrant (-2.88 μm, 95%CI: -4.93 to -0.82, P = 0.006), but was not significant in the temporal quadrant (-1.22 μm, 95%CI: -3.21 to 0.76, P = 0.23), in diabetic patients. CONCLUSION Peripapillary RNFL thickness was significantly decreased in preclinical diabetic retinopathy patients compared to healthy control. Neurodegenerative changes due to preclinical diabetic retinopathy need more attention.
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Pharmacokinetics of ranibizumab after intravitreal administration in patients with retinal vein occlusion or diabetic macular edema.
Zhang, Y, Yao, Z, Kaila, N, Kuebler, P, Visich, J, Maia, M, Tuomi, L, Ehrlich, JS, Rubio, RG, Campochiaro, PA
Ophthalmology. 2014;(11):2237-46
Abstract
OBJECTIVE To describe the systemic pharmacokinetics of ranibizumab after intravitreal administration in patients with retinal vein occlusion (RVO) or diabetic macular edema (DME). DESIGN A population approach of nonlinear mixed-effect pharmacokinetics modeling based on serum concentrations of ranibizumab measured at various times after intravitreal administration. PARTICIPANTS Patients with RVO (n = 441) and DME (n = 435) from 4 large, randomized, phase 3 clinical trials of monthly ranibizumab intravitreal administration. METHODS A 1-compartment pharmacokinetics model with first-order absorption and elimination rate constants previously developed in patients with age-related macular degeneration (AMD) was fitted separately to RVO and DME data. Population pharmacokinetic parameters and interindividual variability were estimated for each model. Baseline covariates were evaluated for potential effects on systemic pharmacokinetics. Model performance was validated using general diagnostic plots and a visual predictive check. MAIN OUTCOME MEASURES Ranibizumab disposition was determined in RVO and DME patients and compared with that previously seen in AMD patients. RESULTS The AMD pharmacokinetics model correctly predicted the measured serum ranibizumab concentration data for RVO and DME patients. Most observed data points were within the simulated 90% confidence interval, indicating that systemic ranibizumab concentrations were comparable among AMD, RVO, and DME patients. No disease-related covariates were identified by the population pharmacokinetics analysis. CONCLUSIONS The systemic pharmacokinetics of ranibizumab were similar among patients with AMD, RVO, or DME. Disease-related differences and patient demographics, measured in this study, did not lead to variability in ocular elimination or in systemic exposure of ranibizumab after intravitreal administration. In all disease processes tested, ranibizumab exits the eye slowly and then is eliminated rapidly from the circulation, thus minimizing systemic exposure.
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Association of tumor necrosis factor alpha promoter polymorphism (TNF-α 238 G/A and TNF-α 308 G/A) with diabetic mellitus, diabetic retinopathy and diabetic nephropathy: a meta-analysis.
Meng, N, Zhang, Y, Li, H, Ma, J, Qu, Y
Current eye research. 2014;(2):194-203
Abstract
AIM: To examine the association between tumor necrosis factor alpha (TNF-α) polymorphism and risk for diabetic mellitus (DM), diabetic retinopathy (DR) and diabetic nephropathy (DN). METHODS Systematic searches of electronic databases such as PubMed, Medline, Web of knowledge and CNKI, as well as hand searching of the references of identified articles were performed. A total of 8979 subjects in 14 studies from 12 eligible publications were included in this meta-analysis (6 of 12 eligible studies were analyzed for TNF 238 G/A polymorphism and Type 1 DM (T1DM), 5 of 12 were analyzed for TNF 308 G/A polymorphism and DR in Type 2 DM (T2DM), and 3 of 12 were analyzed for TNF 308 G/A polymorphism and DN in T2DM). Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed or random effects model. The I(2) statistics were used to evaluate between-study heterogeneity. Sensitivity analysis was also performed. RESULTS The results showed no evidence for significant association between TNF 238 G/A polymorphism and T1DM (for AA + GA versus GG: OR = 0.95, 95% CI = 0.48-1.88, p = 0.89), and also no association between TNF 308 G/A polymorphism and DR and DN risk in T2DM (for AA + GA versus GG: OR = 1.04, 95% CI = 0.87-1.25, p = 0.68; OR = 0.88, 95% CI = 0.71-1.08, p = 0.21; respectively). In addition, the similar results were obtained in the subgroup analysis based on the ethnicity. CONCLUSIONS In summary, results from this meta-analysis suggest that the TNF 238 G/A polymorphism was not associated with T1DM. No association between TNF 308 G/A polymorphism and DR and DN in T2DM was detected.
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Comparison of intravitreal triamcinolone acetonide with intravitreal bevacizumab for treatment of diabetic macular edema: a meta-analysis.
Zhang, Y, Ma, J, Meng, N, Li, H, Qu, Y
Current eye research. 2013;(5):578-87
Abstract
PURPOSE To compare the effects of intravitreal triamcinolone acetonide (IVTA) and intravitreal bevacizumab (IVB) injections for the treatment of diabetic macular edema (DME). METHODS A literature search was conducted using PUBMED, the Cochrane Central Register of Controlled Trials, Web of Science and the Chinese Biomedical Database. Pooled mean differences (MDs) for changes in visual acuity (VA) and central macular thickness (CMT) were calculated between groups receiving a single TA (4 mg) and bevacizumab (1.25 or 1.5 mg) from baseline to 4, 8, 12 and 24 weeks after treatment, respectively. Changes in intraocular pressure (IOP) were calculated between the two groups from baseline to 4, 8 and 12 weeks after treatment. RESULTS Eight trials (n = 434 eyes) comparing the efficacy of IVTA with IVB were included in the meta-analysis. Patients in the IVTA group demonstrated significant post-treatment improvement in VA compared with those in the IVB group at 4 (MD = -0.08; 95% confidence interval [CI]: -0.12 to -0.03; p = 0.0008), 8 (MD = -0.15; 95% CI: -0.20 to -0.11; p < 0.00001), 12 (MD = -0.11; 95% CI: -0.15 to -0.06; p < 0.0001) and 24 (MD = -0.05; 95% CI: -0.10 to -0.01; p = 0.02) weeks. After receiving IVTA, MDs in CMT decreased significantly at 4 weeks (MD = -40.05 μm; 95% CI: -75.29 to -4.81; p = 0.03). No significant differences in CMT were seen between the two groups at 8, 12 and 24 weeks post-treatment. Fluctuations of IOP were within normal range for both groups throughout the entire observation period. CONCLUSIONS Results of this meta-analysis suggest that IVTA is more effective for improving VA in DME. However, the CMT reduction with IVTA was unsustainable. Additional well-designed studies are needed to further investigate optimal interventions.