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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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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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3.
Interleukin-6 and Diabetic Retinopathy: A Systematic Review and Meta-Analysis.
Yao, Y, Li, R, Du, J, Long, L, Li, X, Luo, N
Current eye research. 2019;(5):564-574
Abstract
BACKGROUND Interleukin-6 (IL-6) is produced by a variety of cells involved in inflammation and acts as local intensification signals in pathological processes associated with chronic eye inflammation. This meta-analysis was performed to provide a better understanding of the relationship between IL-6 and diabetic retinopathy. METHODS The study was started with systematic search for literatures by using the PubMed, Web of Science and Embase online databases. The standard mean difference (SMD) and its 95% confidence intervals (CIs) were was included and then pooled with a random effects model. RESULTS Thirty-one articles, containing1099 DR patients and 1010 controls, were included in this meta-analysis. The level of IL-6 in the DR group was found to be higher than that in the control group (SMD: 2.12, 95% CI: 1.53-2.70, p < 0.00001).Obvious heterogeneity existed between the studies (p < 0.00001, I2 = 96%). So a subgroup analysis and sensitivity analysis were performed. Removing the sensitivity studies, the stability of the overall treatment effect was good. Subgroup analysis showed that the levels of IL-6 in case group were observed to be higher than those in the control group; and the IL-6 levels in the proliferative diabetic retinopathy (PDR) group were also higher than those in the non-proliferative diabetic retinopathy (NPDR) group. (SMD: 0.78, 95% CI: 0.26-1.31, p= 0.003) Conclusion: The results from this current meta-analysis indicated that increased level of IL-6 generally exist in DR patients. And it may associated with the severity of DR. However, large-scale and high-quality studies in future are required to confirm the present findings.
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4.
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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5.
Tumor necrosis factor-α and diabetic retinopathy: Review and meta-analysis.
Yao, Y, Li, R, Du, J, Li, X, Zhao, L, Long, L, Li, D, Lu, S
Clinica chimica acta; international journal of clinical chemistry. 2018;:210-217
Abstract
BACKGROUND Tumor necrosis factor-alpha (TNF-α) is produced by multinuclear giant cells and acts as local intensification signals in pathological processes associated with chronic eye inflammation. This meta-analysis was performed to provide a better understanding of the relationship between TNF-α and diabetic retinopathy (DR). METHOD Online electric databases were searched to retrieve all relevant articles published before October 2017. The standard mean difference (SMD) and their 95% confidence intervals (CI) were included and then pooled with a random effects model. RESULTS A total of 16 articles with 1286 participants were included in this meta-analysis. No difference in the level of TNF-α was found between DR patients and healthy controls (SMD = 0.39, 95% CI = -0.09 to 0.68, P = 0.01). Subgroup analysis showed that with respect to the level of TNF-α, the association was significant for studies conducted in Europe (SMD: 0.57, 95% CI: 0.11-1.02, P = 0.01), patients with type 1 DM (SMD: 1.06, 95% CI: 0.09-2.04, P = 0.03), studies based on serum samples (SMD: 0.57, 95% CI: 0.12-1.02, P = 0.01) and studies with a sample size >50 (SMD: 0.39, 95% CI: 0.03-0.75, P = 0.04). CONCLUSION The results this meta-analysis indicated that the level of TNF-α in DR patients was significantly different from that in the healthy controls, so TNF-α represents a candidate biomarker for DR.
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6.
Intravitreal bevacizumab combined with/without triamcinolone acetonide in single injection for treatment of diabetic macular edema.
Wang, YS, Li, X, Wang, HY, Zhang, ZF, Li, MH, Su, XN
Chinese medical journal. 2011;(3):352-8
Abstract
BACKGROUND Diabetic macular edema (DME) is a common manifestation of diabetic retinopathy (DR) that forms the main cause of central visual impairment. This study aimed to compare the efficacy and safety of a single intravitreal injection of bevacizumab alone versus bevacizumab combined with triamcinolone acetonide in eyes with diabetic macular edema (DME). METHODS A total of 40 eyes in 40 Chinese patients (22 male and 18 female) diagnosed with diabetic macular edema were enrolled in this prospective, randomized, consecutive study. Among them, 21 patients in group 1 were treated with intravitreal injection of bevacizumab (1.25 mg/0.05 ml), and the other 19 patients in group 2 accepted intravitreal bavacizumab (1.25 mg/0.05 ml) combined with triamcinolone acetonide (2 mg/0.05 ml). All patients were examined at baseline and followed up at 4, 6 and 12 weeks after the injection. Changes in mean best correct visual acuity (BCVA) using ETDRS chart, central retina thickness (CRT) measured by optical coherence tomography (OCT), and intraocular pressure (IOP) were focused on. RESULTS In group 1, mean BCVA improved from (41.76 ± 15.59) letters (baseline) to (56.24 ± 18.56) letters, (52.57 ± 12.31) letters and (48.41 ± 17.90) letters at 4, 6 and 12 weeks post-injection, respectively (P = 0.004, P = 0.011 and P = 0.026, respectively). Mean CRT decreased from (525.76 ± 184.10) µm (baseline) to (270.33 ± 202.67)µm, (303.12 ± 168.43) µm and (402.26 ± 196.21) µm, respectively (P = 0.009, P = 0.016 and P = 0.030, respectively). In group 2, mean BCVA improved from (39.89 ± 12.27) letters (baseline) to (55.31 ± 19.27) letters, (51.25 ± 13.48) letters and (46.97 ± 16.23) letters at 4, 6 and 12 weeks after injection, respectively (P = 0.003, P = 0.010 and P = 0.027, respectively). Mean CRT decreased from (554.50 ± 169.05) µm (baseline) to (292.76 ± 196.05) µm, (323.46 ± 164.05) µm and (426.38 ± 169.05) µm, respectively (P = 0.009, P = 0.014 and P = 0.028, respectively). However, there was no significant difference between these two groups with regard to mean BCVA (F = 1.602, P = 0.216) and CRT (F = 0.412, P = 0.526). At 12 weeks after the injection, 11 of the patients in group 1 and nine patients in group 2 appeared recurrent macular edema and needed repeat injections. There was one patient in group 2 appeared transient intraocular pressure increases. CONCLUSIONS Intravitreal injection of bevacizumab combined with/without triamcinolone acetonide had a beneficial effect on DME. However, the significant effect was not permanent. Our results showed that no significant differences were detected between intravitreal bevacizumab combined with/without triamcinolone acetonide for the eyes with diabetic macular edema in Chinese patients.