RESUMO
Aim: To investigate the association between intravitreal ranibizumab therapy and serum cytokine concentrations in patients with diabetic macular edema (DME). Methods: Twenty-five patients with center-involved DME were recruited prospectively. Serum samples were collected from the patients before and 4 weeks after two ranibizumab injections. The levels of 32 cytokines at these two time points were assessed using a multiplex array assay. Results: Following two ranibizumab injections, there was a statistically significant decrease in the median [interquartile range] levels of Interleukin 1-1beta (IL-1ß) from 5.56 [3.6, 8.75] to 2.33 [1.51, 2.89], Interleukin 13 (IL-13) from 4.30 [1.84, 18.55] to 0.38 [0.38, 0.78], granulocyte-colony stimulating factor (G-CSF) from 64.65 [42.9, 108] to 37.8 [27.3, 46.37], Interferon gamma (IFN-γ) from 241 [103.33, 753.4] to 94.4626 [42.04, 118.58], Interferon gamma-induced protein 10 (IP-10) from 234.68 [144.16, 285.98] to 158.73 [94.71, 198.64], Macrophage Inflammatory Protein-1 alpha (MIP-1α) from 3.65 [2.62, 11.02] to 1.41 [0.94, 1.88], and Tumor necrosis factor- alpha (TNF-α) from 131.09 [100.68,28 240.27] to 45.19 [24.04, 68.55]. There was a statistically significant increase in the levels of Interleukin 9 (IL-9) from 0.76 [0.76, 7.03] to 19.67 [5.36 27.76], Macrophage Inflammatory Protein-1 beta (MIP-1ß) from 0.28 [0.28, 30 0.28] to 6.79 [I3.74, 14.16], Vascular endothelial growth factor (VEGF) from 2.55 [2.55, 2.55] to 25.24 [14.51, 41.73], and soluble vascular endothelial growth factor -1 (sVEGFR-1) from 333.92 [204.99, 440.43] to 500.12 [38.7, 786.91]. A Bonferroni-corrected p value of 0.00156 was considered statistically significant. Conclusions: In patients with DME, intravitreal ranibizumab therapy appears to influence the serum levels of a range of cytokines. After two injections, intravitreal ranibizumab therapy appears to be associated with a significant decrease in inflammatory mediators and a rise in VEGF and sVEGFR1.
Assuntos
Inibidores da Angiogênese/administração & dosagem , Citocinas/sangue , Retinopatia Diabética/sangue , Edema Macular/sangue , Ranibizumab/administração & dosagem , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Idoso , Retinopatia Diabética/tratamento farmacológico , Feminino , Humanos , Injeções Intravítreas , Edema Macular/tratamento farmacológico , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The Diabetes Management Project is investigating the clinical, behavioural and psychosocial barriers to optimal diabetes care in individuals with and without diabetic retinopathy. DESIGN: Prospective cohort. PARTICIPANTS: Two hundred and twenty-three and 374 patients without and with diabetic retinopathy, respectively. METHODS: All individuals underwent a comprehensive dilated eye test, anthropometric measurements, blood and urine samples, and psychosocial questionnaires. MAIN OUTCOME MEASURES: Good glycaemic control was defined as glycosylated haemoglobin < 7%, good blood pressure control as systolic and diastolic values ≤130 and 80 mmHg, respectively, and good diabetes control as glycosylated haemoglobin < 7% and blood pressure values ≤130 and 80 mmHg. RESULTS: Four hundred and one males (65.4%) and 212 females (34.6%) aged 26-90 years (mean age ± standard deviation = 64.6 ± 11.6) were examined. The median glycosylated haemoglobin for all participants was 7.5% (interquartile range = 1.7%). Average systolic and diastolic blood pressure values were 139.7 mmHg (standard deviation = 18.8) and 92.7 mmHg (standard deviation = 30.9), respectively. Initial data analyses indicate that over two-thirds of participants with diabetes have poor glycaemic control, which was worse in those with diabetic retinopathy compared with those without (76.3% vs. 49.3%; P < 0.001). Blood pressure control was similar for those with and without diabetic retinopathy, with almost a third (28.5%) of the total sample having poor blood pressure control. Overall, those with diabetic retinopathy had poorer diabetes control than those without (24.3% vs. 13.7%; P = 0.002). CONCLUSIONS: Our findings substantiate the implementation of the Diabetes Management Project, developed to assess factors associated with suboptimal diabetes care.
Assuntos
Atitude Frente a Saúde , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 2/terapia , Retinopatia Diabética/terapia , Acessibilidade aos Serviços de Saúde/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Antropometria , Glicemia/metabolismo , Pressão Sanguínea/fisiologia , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Retinopatia Diabética/sangue , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica , Atenção Primária à Saúde , Estudos Prospectivos , Inquéritos e Questionários , Acuidade Visual/fisiologiaRESUMO
PURPOSE: To assess the relationship of retinal vessel diameter and diabetic retinopathy (DR) in a subgroup of participants recruited through the Darwin Region Urban Indigenous Diabetes study. METHODS: Participants were examined as part of the Darwin Region Urban Indigenous Diabetes study. All participants with gradable fundus photographs were included in the current analysis. Assessment of retinal vascular diameter, including arteriolar diameter (central retinal arteriolar equivalent) and venular diameter (central retinal venular equivalent), was undertaken using a semi-automated retinal vascular imaging program. DR was graded according to the modified Early Treatment DR Study scale. RESULTS: A total of 110 participants, 25 men and 85 women, with a mean age of 50.8 years were included in the analysis. The odds ratio for having DR for each standard deviation increase in central retinal venular equivalent was as high as 1.62 (95% confidence intervals 0.94, 2.80); however, this did not reach statistical significance (P = 0.08). Moreover, individuals with severe non-proliferative DR and proliferative DR were found to have narrower arteriolar diameters compared with those with no DR, but this was not statistically significant (-8.1 microm, 95% confidence intervals, -39.3 microm, 23.1 microm; P = 0.612). CONCLUSION: Our data indicate a trend for narrower arteriole diameter and wider venular diameter with DR in this high-risk ethnic group, which concurs with overall trends seen in non-indigenous populations.
Assuntos
Retinopatia Diabética/etnologia , Havaiano Nativo ou Outro Ilhéu do Pacífico/etnologia , Artéria Retiniana/patologia , Veia Retiniana/patologia , População Urbana/estatística & dados numéricos , Pressão Sanguínea , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , Retinopatia Diabética/fisiopatologia , Feminino , Teste de Tolerância a Glucose , Hemoglobinas Glicadas/metabolismo , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Northern Territory/epidemiologia , Razão de Chances , FotografaçãoRESUMO
Purpose: To evaluate the effect of intravitreal ranibizumab injections on aqueous concentrations of angiogenic or inflammatory cytokines in patients with diabetic macular edema (DME). Methods: Thirty eyes of 25 patients with center-involved DME were recruited to the study. All had a central macular thickness (CMT) of >300 µm and best-corrected visual acuity (BCVA) between 28 and 70 logMAR letters (Snellen equivalent 20/320-20/40). At baseline, all eyes had 0.1 mL of aqueous collected before ranibizumab treatment. At week 4, a second ranibizumab injection was administered and at week 8, aqueous sampling was repeated before a third ranibizumab injection. From week 12, all eyes were followed at 4-weekly intervals and the need for ranibizumab treatment was determined by BCVA and CMT measurements. Levels of 32 cytokines were assessed at baseline and at week 8 using a multiplex array assay. Results: Following two consecutive ranibizumab injections, there was a statistically significant reduction in VEGF (P < 0.00001), as well as IL-1ß (P = 0.00006), IL-7 (P = 0.00002), IL-8 (P = 0.00023), IL-10 (P < 0.00001), IL-12 (P < 0.00001), IL-17 (P = 0.00024), MCP-1 (P = 0.00023), and TNF-α (P < 0.00001). There was also an upregulation of soluble VEGF receptor-2 (P = 0.00004). A P < 0.0015 was considered significant in this study. Conclusions: Ranibizumab treatment influences various inflammatory cytokine concentrations in addition to reducing aqueous VEGF concentrations in patients with DME. This may contribute to its therapeutic effect in patients with DME.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Humor Aquoso/metabolismo , Citocinas/metabolismo , Retinopatia Diabética/tratamento farmacológico , Inflamação/metabolismo , Edema Macular/tratamento farmacológico , Ranibizumab/uso terapêutico , Retinopatia Diabética/metabolismo , Feminino , Humanos , Injeções Intravítreas , Edema Macular/metabolismo , Masculino , Pessoa de Meia-Idade , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual/fisiologiaRESUMO
BACKGROUND: The regulation of miR-126 by rs4636297 single nucleotide polymorphism (SNP) has been implicated in the pathogenesis of neovascularisation by promoting vascular endothelial growth factor, suggesting it could be associated with sight threatening diabetic retinopathy (STDR), but has not been previously investigated or reported. MATERIALS AND METHODS: A case control study of 531 individuals with diabetes was genotyped for the rs4636297 SNP, using the Sequenom iPLEX Gold chemistry. STDR included people with severe non-proliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR). Association was tested using logistic regression analysis, adjusting for confounding variables. RESULTS: In an additive model, the A allele of rs4636297 SNP is significantly associated with STDR compared to people with none or mild diabetic retinopathy (DR) (odds ratio (OR) = 2.02, 95% confidence interval (CI) = 1.22-3.35, p = 0.006). CONCLUSION: The A allele of rs4636297, known to be the non-functional allele for post-translational regulation of miR-126, is associated with STDR. This finding suggests that this locus would be a potential therapeutic target for inhibiting the development of DR.
Assuntos
Retinopatia Diabética/genética , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Visão Ocular/genética , Idoso , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/fisiopatologia , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Fatores de RiscoRESUMO
PURPOSE: Recent genome-wide association studies for diabetic retinopathy (DR) have identified novel single nucleotide polymorphisms (SNPs) associated with this potentially blinding disease. These markers could prove useful in risk profiling, if the association are validated by replication. To date, these associations have not been well assessed in independent cohorts. The objective of this study was to ascertain any association of these polymorphisms with advanced stages of DR. METHODS: A total of 463 patients who had either type 1 (n = 46) or 2 (n = 417) diabetes were genotyped for 24 SNPs previously implicated in DR. Cases (n = 163) were defined as people with severe nonproliferative DR or proliferative DR. Control participants (n = 300) with a confirmed duration of diabetes of at least 5 years had either no evidence of DR or only mild DR. RESULTS: Two SNPs (rs1073203 and rs4838605) were found to be significantly associated with DR in patients with diabetes after adjusting for covariants; rs1073203-G (P = 0.012, odds ratio [OR] = 0.317, 95% confidence interval [95% CI]: 0.129-0.778), rs1073203 in a dominant model (P = 0.005, OR = 0.251, 95% CI: 0.096-0.655), rs4838605 in an additive model (P = 0.047, OR = 1.650, 95% CI: 1.007-2.703), In a dominant model rs1073203 (P = 0.027, OR = 1.400, 95% CI: 0.101-0.857), was significantly associated with DR in type 2 diabetes after adjustment for covariants. This study was sufficiently powered to replicate previous findings. CONCLUSIONS: This study confirmed that two variants (rs1073203 and rs4838605) are associated with advanced stages of DR in our cohort. The underlying genes in these candidate regions provide interesting future gene association targets for understanding the pathogenesis of DR.
Assuntos
Retinopatia Diabética/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Idoso , Estudos Transversais , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/epidemiologia , Feminino , Seguimentos , Frequência do Gene , Loci Gênicos , Genótipo , Humanos , Masculino , Prevalência , Estudos Retrospectivos , Vitória/epidemiologiaRESUMO
The aim of this study was to perform a systematic meta-analysis of biomarkers investigated with diabetic retinopathy (DR) in the vitreous, and to explore the molecular pathway interactions of these markers found to be consistently associated with DR. Relevant databases [PubMed and ISI web of science] were searched for all published articles investigating molecular biomarkers of the vitreous associated with DR. Based on set exclusion/inclusion criteria available data from studies with human vitreous samples were extracted and used for our meta-analysis. The interactions of significant biomarkers in DR were investigated via STRING and KEGG pathway analysis. Our meta-analysis of DR identifies eleven biomarkers as potential therapeutic candidates alternate to current anti-VEGF therapy. Four of these are deemed viable therapeutic targets for PDR; ET receptors (ET A and ET B), anti-PDGF-BB, blocking TGF-ß using cell therapy and PEDF. The identification of supplementary or synergistic therapeutic candidates to anti VEGF in the treatment of DR may aid in the development of future treatment trials.