Risk Factors For Retinopathy Research Articles

Changes in the Incidence of Retinopathy of Prematurity in Extremely Low Birth Weight Infants in South China From 2004 to 2018

ABSTRACT Purpose: To report the changes in incidence and risk factors of retinopathy of prematurity (ROP) in extremely low birth weight (ELBW) infants over a 15-year period in South China. Methods: The medical records of ELBW infants were retrospectively reviewed through established database of Shenzhen Screening for ROP Cooperative Group. The incidence and severity of ROP were compared among three successive 5-year periods (P1: 2004–2008, P2: 2009–2013, P3: 2014–2018). Gestational age, birth weight, plurality, mode of delivery and gender were analyzed as risk factors for ROP in ELBW infants. Results: Among the 1099 included ELBW infants, 557 (50.7%) had ROP, and 328 (29.9%) had severe ROP. The highest incidence of ROP (87.5%) and severe ROP (82.5%) were seen in P1. From P2 to P3, the incidence of ROP and severe ROP increased from 45.9% to 50.3% for ROP (P < .05) and from 26.4% to 28.3% for severe ROP (P < .05), respectively. Multivariate logistic regression analysis found only gestational age has a significant effect on the incidence of ROP and severe ROP. Conclusions: From 2004 to 2018, the incidence of ROP and severe ROP in ELBW infants in South China was 50.7% and 29.9%, respectively. Controlling for the other risk factors, only gestational age was statistically associated with ROP in ELBW infants.

Deep Neural Network for Predicting Diabetic Retinopathy from Risk Factors

Extracting information from individual risk factors provides an effective way to identify diabetes risk and associated complications, such as retinopathy, at an early stage. Deep learning and machine learning algorithms are being utilized to extract information from individual risk factors to improve early-stage diagnosis. This study proposes a deep neural network (DNN) combined with recursive feature elimination (RFE) to provide early prediction of diabetic retinopathy (DR) based on individual risk factors. The proposed model uses RFE to remove irrelevant features and DNN to classify the diseases. A publicly available dataset was utilized to predict DR during initial stages, for the proposed and several current best-practice models. The proposed model achieved 82.033% prediction accuracy, which was a significantly better performance than the current models. Thus, important risk factors for retinopathy can be successfully extracted using RFE. In addition, to evaluate the proposed prediction model robustness and generalization, we compared it with other machine learning models and datasets (nephropathy and hypertension–diabetes). The proposed prediction model will help improve early-stage retinopathy diagnosis based on individual risk factors.

Bacterial infections as novel risk factors of severe diabetic retinopathy in individuals with type 1 diabetes

Background/AimsDiabetic retinopathy (DR) is associated and shares many risk factors with other diabetic complications, including inflammation. Bacterial infections, potent inducers of inflammation have been associated with the development of diabetic...

Risk factors for retinopathy in hemodialysis patients with type 2 diabetes mellitus

There is limited knowledge on the prevalence and risk factors of diabetic retinopathy (DR) in dialysis patients. We have investigated the association between diabetes mellitus and lipid-related biomarkers and retinopathy in hemodialysis patients. We reviewed 1,255 hemodialysis patients with type 2 diabetes mellitus (T2DM) who participated in the German Diabetes and Dialysis Study (4D Study). Associations between categorical clinical, biochemical variables and diabetic retinopathy were examined by logistic regression. On average, patients were 66 ± 8 years of age, 54% were male and the HbA1c was 6.7% ± 1.3%. DR, found in 71% of the patients, was significantly and positively associated with fasting glucose, HbA1c, time on dialysis, age, systolic blood pressure, body mass index and the prevalence of other microvascular diseases (e.g. neuropathy). Unexpectedly, DR was associated with high HDL cholesterol and high apolipoproteins AI and AII. Patients with coronary artery disease were less likely to have DR. DR was not associated with gender, smoking, diastolic blood pressure, VLDL cholesterol, triglycerides, and LDL cholesterol. In summary, the prevalence of DR in patients with type 2 diabetes mellitus requiring hemodialysis is higher than in patients suffering from T2DM, who do not receive hemodialysis. DR was positively related to systolic blood pressure (BP), glucometabolic control, and, paradoxically, HDL cholesterol. This data suggests that glucose and blood pressure control may delay the development of DR in patients with diabetes mellitus on dialysis.

Associations between urinary 6-sulfatoxymelatonin excretion and diabetic vascular complications or arteriosclerosis in patients with type2 diabetes.

Aims/IntroductionThere are limited reports on the association between melatonin levels and vascular complications in patients with type 2 diabetes. The aim of this study was to determine the association between urinary 6‐sulfatoxymelatonin, which is a urinary metabolite of melatonin, and diabetic vascular complications or arteriosclerosis in patients with type 2 diabetes.Materials and MethodsThis retrospective study included patients (167 patients with type 2 diabetes and 27 patients without diabetes adjusted for age and sex) admitted to the hospital who underwent measurement of urinary 6‐sulfatoxymelatonin. The urinary 6‐sulfatoxymelatonin/creatinine ratio (6‐SMT) was calculated.ResultsThe natural logarithmically scaled 6‐SMT level (Ln 6‐SMT) was significantly lower in type 2 diabetes patients (1.9 ± 1.1) compared with patients without diabetes (2.8 ± 1.0, P < 0.001). Multivariate linear regression analysis identified duration of diabetes, smoking status, urinary albumin‐to‐creatinine ratio, retinopathy and coronary heart disease as factors that could influence Ln 6‐SMT levels in type 2 diabetes patients (R 2 = 0.232, P < 0.001). Ln 6‐SMT was associated with decreased odds of diabetic retinopathy, even after adjustment for various confounding factors (odds ratio 0.559, 95% confidence interval 0.369–0.846, P = 0.006). Similarly, Ln 6‐SMT was associated with decreased odds of coronary heart disease (odds ratio 0.442, P = 0.030).ConclusionsOur results showed the presence of low levels of Ln 6‐SMT in type 2 diabetes patients relative to patients without diabetes. Furthermore, Ln 6‐SMT is an independent risk factor of diabetic retinopathy and coronary heart diseases. These findings suggest that 6‐SMT could be a useful biomarker for the prediction of micro‐ and macrovasculopathies in patients with type 2 diabetes.

Внутрижелудочковые кровоизлияния как факторы риска ретинопатии недоношенных

Внутрижелудочковые кровоизлияния как факторы риска ретинопатии недоношенных

Retinopathy of prematurity in a tertiary facility: an initial report of a screening programme

Background: Retinopathy of prematurity (ROP) screening in Nigeria is at a nascent stage and at the moment there are no National guidelines for ROP screening in Nigeria. Thus it is desirable for screening programs to report findings amongst screened preterm infants in order to facilitate the development of national ROP screening criteria and guidelines. The aim of this report is to describe the frequency, severity and risk factors for retinopathy of prematurity (ROP) among preterm and very low-birth-weight babies screened within the first year of initiating an ROP screening program at a Nigerian tertiary facility.&#x0D; Methods: A cross-sectional study of infants born at less than 34 weeks gestational age; or with birth weight less than 1500g between May 2016 and May 2017. ROP screening examinations were performed by ophthalmologists with the use of an indirect ophthalmoscope, after pupillary dilation, in collaboration with the neonatology team. Information on gestational age at birth, birth weight, oxygen therapy and presence of other risk factors were recorded and analyzed.&#x0D; Results: A total of 74 infants were screened during the period. There were 36 (48.6%) males. Mean gestational age at birth was 29.6 (±2.35) weeks. Mean birth weight was 1.26 (±0.27) kg with a range of 800 to 1950g. ROP was detected in 9 (12.2%) infants. Two (22.2%) of these had Threshold ROP. There was no significant difference between the mean birth weight and mean gestational age of the infants who had ROP compared to those without ROP. The two infants with Threshold ROP were treated with intravitreal Bevazicumab and had regression of ROP.&#x0D; Conclusion: Retinopathy of prematurity was diagnosed in at risk infants in this facility. There is, therefore, a need to establish ROP screening programs in all neonatal units across the country. In addition, established programs need to evaluate their screening criteria with a view towards developing country-specific screening guidelines.&#x0D; Keywords: Retinopathy; Prematurity; Preterm; Neonates; Nigeria; Africa

Possible Modifying Effect of Hemoglobin A1c on Genetic Susceptibility to Severe Diabetic Retinopathy in Patients With Type 2 Diabetes.

PurposeGlycemic control has been recognized as an important modifiable risk factor for diabetic retinopathy (DR). Whether hemoglobin A1c (HbA1c), as an indicator of glycemic control, could modify the genetic susceptibility to severe DR remains to be investigated. This study aimed to investigate whether HbA1c could modulate the genetic susceptibility to severe DR in Chinese patients with type 2 diabetes.MethodsA total of 3,093 Chinese individuals with type 2 diabetes were included in the cross-sectional case-control study: 1,051 with sight-threatening DR (STDR) and 2,042 without STDR. Sixty-nine top-ranked single nucleotide polymorphisms (SNPs) identified from previous genome-wide association studies were examined for their associations with STDR and proliferative DR as a subgroup analysis. SNPs showing suggestive associations with DR were examined in the stratified analysis by dichotomized HbA1c (<7% vs. ≥7%). An interaction analysis was performed by including an interaction term of SNP × HbA1c in the regression model.ResultsFour SNPs showed suggestive associations with STDR. In the stratified analysis, patients with adequate glycemic control (HbA1c <7%) had a 42% lower risk of STDR for carrying each additional protective C allele of COL5A1 rs59126004 (P = 1.76 × 10−4; odds ratio, 0.58; 95% confidence interval, 0.44–0.77). rs59126004 demonstrated a significant interaction with dichotomized HbA1c on the risk of STDR (Pinteraction = 1.733 × 10−3). In the subgroup analysis for proliferative DR, the protective effect of rs59126004 was even more pronouncedly demonstrated (P = 8.35 × 10−5; odds ratio, 0.37; 95% confidence interval, 0.22–0.60) and it showed similar interactions with dichotomized HbA1c (Pinteraction = 1.729 × 10−3).ConclusionsOur data provided evidence for possible interactions between HbA1c and COL5A1 rs59126004 on the risk of severe DR. These findings may provide new insight into the pathophysiologic mechanism of DR.

Incidence and risk factors of retinopathy of prematurity in Korle-Bu Teaching Hospital: a baseline prospective study

ObjectiveTo determine the incidence of retinopathy of prematurity (ROP) and any associated risk factors among preterm infants at the Neonatal Intensive Care Unit (NICU) of Korle-Bu Teaching Hospital (KBTH).DesignProspective study.SettingLevel...

Perinatal Risk Factors for Retinopathy of Prematurity in Preterm and Low Birth Weight Neonates.

Retinopathy of prematurity (ROP) is emerging as a leading cause of childhood blindness. The incidence of ROP is likely to increase after improvement in neonatal care unit in premature neonates. This study is conducted to determine the perinatal risk factors for ROP in preterm and low birth weight neonates. This is a prospective, descriptive and clinical; hospital based study. A total of 92 preterm neonates with gestational age of 36 weeks or less and birth weight of 2000 grams or less admitted in Neonatal Intensive Care Unit (NICU) were screened. Detailed antenatal, perinatal and neonatal history; birth asphyxia and subsequent oxygen support records were noted. All the neonates underwent detailed anterior and posterior segment eye examination with indirect binocular ophthalmoscope after pupil dilatation within 4 weeks of life. Retinal vascular changes were classified according to the International Classification of Retinopathy of Prematurity. The Chi-square test with odds ratio was performed to derive the association between ROP and antenatal, perinatal and neonatal factors. A p-value was considered significant at 0.05. Out of 92 neonates, 21(22.8%) developed ROP. Twelve neonates (13%) had stage-1 ROP, 6(6.5%) had stage-2 and 3(3.3%) had stage-3 ROP. Birth weight (OR=2.9; p=0.04; 95% CI=1.0-8.3), gestational age (OR=3.9; p=0.01; 95% CI=1.3-11.8) and time span of oxygen exposure (OR=2.9; p=0.05; 95% CI=1.0-8.4) had a strong association with ROP. The incidence of ROP is significantly high among preterm low birth weight neonates. The risk of developing ROP becomes even greater with lower gestational age and more duration of oxygen exposure.

Is primary open-angle glaucoma a risk factor for diabetic retinopathy?

To compare the prevalences of diabetic retinopathy in diabetes mellitus patients, with and without primary open-angle glaucoma, with a view to determine if glaucoma is a risk factor for the development of diabetic retinopathy. Cross-sectional, comparative study consisting of 86 diabetic patients with glaucoma matched with 86 diabetic patients without glaucoma. The two groups were matched by age, sex and duration of diabetes mellitus. Demographic data were obtained via patient medical records and self-administered questionnaires. Participants underwent a standardized examination protocol including blood pressure measurement and ocular examination. Main outcome measure was the presence of diabetic retinopathy. Two hundred and ninety-two eyes (144 glaucomatous eyes and 148 non-glaucomatous eyes) of 172 participants with diabetes mellitus were assessed. The prevalence of diabetic retinopathy among 86 participants with glaucoma comorbidity was 23.6%, while the prevalence among 86 non-glaucomatous participants was 33.8% (p = 0.06). After the regression analysis, controlling for systemic and ocular risk factors for diabetic retinopathy, the odds of developing diabetic retinopathy were significantly higher in the glaucomatous eyes compared with eyes without glaucoma (OR: 2.75; p = 0.03; 95% CI: 1.10-6.87). This study demonstrated that glaucomatous diabetic eyes were almost three times more likely to develop diabetic retinopathy compared to non-glaucomatous diabetic eyes. Prospective studies may be required to establish a risk-cause relationship. Ocular perfusion pressure control should be considered in patients with diabetes mellitus and glaucoma.

Retrospective Analysis of Risk factors in Aggressive Posterior Retinopathy of Prematurity (APROP)

This is a retrospective, observational study to analyse the risk factors contributing in the pathogenesis of Aggressive Posterior retinopathy of prematurity (AP-ROP). Case record of 30 babies were analysed. All these babies had received supplemental oxygen for 2 days or longer after birth and had several other systemic co-morbidities. The mean gestational age was 30.3+/-3.03 weeks and mean birth weight was 1.27+/- 0.283 kgs. Examination revealed 35 eyes (61.4%) had zone II posterior AP-ROP and 22 eyes (38.5%) had zone I APROP.

Cholestasis after very preterm birth was associated with adverse neonatal outcomes but no significant long-term liver disease: A population-based study.

To describe outcome linked to neonatal cholestasis in a defined cohort of very preterm infants. Population-based retrospective case-control study of preterm infants, gestational age <30weeks, surviving for 28days, in Stockholm County. Cholestasis was defined as conjugated bilirubin ≥30μmol/L exceeding 20% of total level at least twice and graded as high if exceeding 100μmol/L. Cholestatic cases were matched on gestational week with two non-cholestatic controls. The incidence rate of cholestasis was 37/250 (14.8%), with increasing rates in lower gestational weeks. Perinatal factors associated with cholestasis were pre-eclampsia and being born small for gestational age. Cholestatic infants had three times more bronchopulmonary dysplasia and eight times more retinopathy of prematurity. The mortality was 13.5% in cholestatic infants versus 2.7% in controls (P=.040). All deceased cholestatic infants had high-grade cholestasis. No surviving infants developed chronic liver disease by 10years of age. Cholestasis was common in very preterm infants and linked to disease severity and adverse outcome. Cholestasis may be an independent risk factor for bronchopulmonary dysplasia and retinopathy of prematurity and more severe cholestasis associated with increased mortality. Cholestasis was not associated with chronic liver disease later in childhood.

Regional factors of somatic pathologies in pregnant women and predelivery risk factors for retinopathy in premature infants of the Altai region

Despite progress in medicine, the number of preterm births as a result of the use of new reproductive technologies is increasing. Preterm birth is a multifactorial process. The success of neonatal resuscitation in nursing children with extremely low birth weight leads to an increase in the number of surviving children with various ophthalmic pathologies. Retinopathy in premature infants remains one of the urgent problems of pediatric ophthalmology, being one of the leading causes of blindness and low vision in preterm neonates. Premature retinopathy is a multifactorial disease, the incidence and severity of which are due to the influence of many risk factors that adversely affect the immature retina of a premature infant and lead to a violation of its normal vasculogenesis.&#x0D; Aim. To evaluate the state of health of pregnant women and the connection of this factor with the development of retinopathy among retinopathy prematurity in the Altai Region.&#x0D; Material and methods. To achieve this aim, statistical compendiums of the Demographic Yearbook in the Altai Region over an 11-year period (from 2005 to 2016) were analyzed, as were the medical histories of infants hospitalized inThe Altai Regional Clinical Childrens Hospital during the same period.&#x0D; Results. Statistically significant differences (p 0.05) in the incidence of hepatitis and diabetes were discovered. In addition, the most apparent variations, confirming the existence of prenatal risk factors leading to retinopathy in premature infants, were obtained on such indicators as anemia among pregnant women, fetoplacental deficiency, gestational toxicosis, pyelonephritis among pregnant women, and others.&#x0D; Сonclusions. We detected a significant number of somatic pathologies in pregnant women in the Altai Region, which was considerably higher than the average rates in the Russian Federation. The most remarkable antenatal risk factors for the birth of premature babies developing retinopathy of the premature were highlighted, and these should be taken into account when organizing prophylactic screening measures for the early identification of retinopathy of prematurity in the Altai Region.

Early Results of Stereotactic Radiosurgery in Uveal Melanoma and Risk Factors for Radiation Retinopathy

Objectives:To report treatment results and complications of stereotactic radiosurgery in uveal malignant melanoma and to identify risk factors for development of radiation retinopathy.Materials and Methods:This was a retrospective study of 36 patients diagnosed with uveal melanoma between 2014 and 2019. Best corrected visual acuity, funduscopic findings, basal tumor diameter and tumor thickness were recorded at baseline and at follow-up visits at 3-month intervals. The response of tumors to stereotactic radiosurgery and complications were determined.Results:The mean basal diameter of tumor was 10.2 (range: 4.0-19.4, standard deviation [SD]: ±3.3) mm x 9.7 (range: 4.5-18.0, SD: ±3.3), tumor thickness was 5.1 (range: 2.0-11.0, ±2.4) mm at baseline. The mean follow-up period was 17.2 (range: 6-48, SD: ±10.43) months. The mean visual acuity was 0.5 (SD: ±0.3) logMAR before treatment and 0.6 (SD: ±0.3) logMAR after the mean follow-up period. The most common complications after stereotactic radiosurgery were cataract (38.9%) and radiation retinopathy (27.7%). There was a statistically significant relation between radiation retinopathy development and tumor distance from the optic disc (p=0.04). The rate of eye salvage was 83.3% in this study.Conclusion:Our short-term results show stereotactic radiosurgery was an effective and sustained treatment modality among the other eye conservation therapies.

Risk factors for hydroxychloroquine retinopathy in systemic lupus erythematosus: a case-control study with hydroxychloroquine blood-level analysis.

ObjectiveHCQ is an essential medication in SLE, proven to lengthen survival and reduce flares. Its use, however, is limited by its rare but severe ophthalmological complications. Here, we aimed to analyse factors associated with HCQ retinopathy including HCQ blood levels.MethodsThis case–control study compared SLE patients with and without HCQ retinopathy, defined by abnormal results for at least two of the following ophthalmological tests: automated visual fields, spectral-domain optical coherence tomography (SD-OCT), multifocal electroretinogram (mfERG) and fundus autofluorescence. We compared clinical and laboratory findings to assess risk factors for HCQ retinopathy.ResultsThe study included 23 patients with confirmed retinopathy (cases) and 547 controls. In the univariate analysis, age (P < 0.001), height (P = 0.045), creatinine clearance (P < 0.001), haemoglobin concentration (P = 0.01), duration of HCQ intake, (P < 0.001), higher cumulative HCQ dose (P < 0.001) and geographical origin (West Indies and sub-Saharan Africa) (P = 0.007) were associated with the risk of retinopathy, while HCQ blood levels were not. In the multivariate analysis, only cumulative dose (P = 0.016), duration of intake (P = 0.039), creatinine clearance (P = 0.002) and geographical origin (P < 0.0001, odds ratio 8.7) remained significantly associated with retinopathy.ConclusionSLE patients on HCQ should be closely monitored for retinopathy, especially those from the West Indies or sub-Saharan Africa, or with renal insufficiency, longer HCQ intake or a high cumulative dose. Although reducing the daily dose of HCQ in patients with persistently high HCQ blood levels seems logical, these concentrations were not associated with retinopathy in this study with controls adherent to treatment.

Prevalence of and Risk Factors for Diabetic Retinopathy and Diabetic Macular Edema in Patients with Early- and Late-Onset Diabetes Mellitus

Purpose: The aim of this study was to compare the prevalence of diabetic retinopathy (DR) and diabetic macular edema (DME), as well as their risk factors in patients with early-onset diabetes (EOD, ≤40 years) and late-onset diabetes (LOD, >40 years). Methods: Patients were recruited from a community-based study, Fushun Diabetic Retinopathy Cohort Study (FS-DIRECT), conducted between July 2012 and May 2013 in China. The presence and severity of DR and DME were determined by a modified Early Treatment Diabetic Retinopathy Study (ETDRS) retinopathy scale of six-field fundus photographs. Results: A total of 1,932 patients (796 male, 41.2%) with gradable fundus photography were included. The prevalence of any DR and DME was 67.0% (95% confidence interval [CI]: 60.3–73.7%) and 39.3% (95% CI: 32.1–46.5%) in the EOD patients, respectively, which were both significantly higher than that in the LOD patients (DR: 41.9%, 39.6–44.2%, p < 0.001; DME: 14.4%, 12.7–16.1%, p < 0.001). Insulin use was associated with both the presence of DR and DME in both EOD and LOD patients. Besides insulin use, a high level of income (odds ratio [OR], 95% CI: 0.05, 0.01–0.51) was negatively associated with DR, and higher high-density lipoprotein (OR, 95% CI: 4.14, 1.44–11.91) was associated with DME among EOD patients. Conclusion: In this sample of patients with type 2 diabetes, both prevalence of DR and DME were apparently higher in patients who developed diabetes ≤40 years of age than those who developed it later.

Differences in Risk Factors for Diabetic Retinopathy in Type 1 and Type 2 Diabetes Mellitus Patients in North-East Poland.

Background and Objective: Nowadays, diabetes is one of the main causes of blindness in the world. Identification and differentiation of risk factors for diabetic retinopathy depending on the type of diabetes gives us the opportunity to fight and prevent this complication. Aim of the research: To assess differences in the risk factors for diabetic retinopathy in type 1 and type 2 diabetes mellitus patients in Warmia and Mazury Region, Poland. Materials and Methods: Risk factors for diabetic retinopathy (DR) were assessed on the basis of an original questionnaire, which included: personal data, clinical history of diabetes and eye disease. Elements of clinical examination: blood pressure, BMI, waist circumference. Indicators of diabetes metabolic control: mean glycemia, glycated hemoglobin (HbA1c), total cholesterol and triglycerides, creatinine, glomerular filtration rate (GFR), albumin–creatinine ratio in urine. Results: The study group included 315 (26%) patients with DM1 and 894 (74%) patients with DM2. Risk factors were estimated on the basis of logistic regression and verified with Student’s t-test. Statistically significant dependencies were found in both groups between the occurrence of diabetic retinopathy and diabetes duration, HbA1c, triglyceride concentrations, indicators of kidney function and cigarette smoking status. In the DM2 group, the development of DR was significantly influenced by the implemented models of diabetic treatment. Conclusions: In the whole study group, the risk of DR was associated with the duration of diabetes, HbA1c, triglyceride concentrations and smoking. In DM1 patients, the risk of DR was associated with diabetic kidney disease in the G1A1/A2 stage of chronic kidney disease, and in DM2 patients with the G2 stage of chronic kidney disease. An important risk factor for DR in DM2 patients was associated with late introduction of insulin therapy.

Homocysteine Disrupts Balance between MMP-9 and Its Tissue Inhibitor in Diabetic Retinopathy: The Role of DNA Methylation.

High homocysteine is routinely observed in diabetic patients, and this non-protein amino acid is considered as an independent risk factor for diabetic retinopathy. Homocysteine biosynthesis from methionine forms S-adenosyl methionine (SAM), which is a major methyl donor critical in DNA methylation. Hyperhomocysteinemia is implicated in increased oxidative stress and activation of MMP-9, and in diabetic retinopathy, the activation of MMP-9 facilitates capillary cell apoptosis. Our aim was to investigate the mechanism by which homocysteine activates MMP-9 in diabetic retinopathy. Human retinal endothelial cells, incubated with/without 100 μM homocysteine, were analyzed for MMP-9 and its tissue inhibitor Timp1 expressions and interactions, and ROS levels. Timp1 and MMP-9 promoters were analyzed for methylated and hydroxymethylated cytosine levels (5mC and 5hmC respectively) by the DNA capture method, and DNA- methylating (Dnmt1) and hydroxymethylating enzymes (Tet2) binding by chromatin immunoprecipitation. The results were confirmed in retinal microvessels from diabetic rats receiving homocysteine. Homocysteine supplementation exacerbated hyperglycaemia-induced MMP-9 and ROS levels and decreased Timp1 and its interactions with MMP-9. Homocysteine also aggravated Dnmts and Tets activation, increased 5mC at Timp1 promoter and 5hmC at MMP-9 promoter, and suppressed Timp1 transcription and activated MMP-9 transcription. Similar results were obtained from retinal microvessels from diabetic rats receiving homocysteine. Thus, hyperhomocysteinemia in diabetes activates MMP-9 functionally by reducing Timp1-MMP-9 interactions and transcriptionally by altering DNA methylation-hydroxymethylation of its promoter. The regulation of homocysteine could prevent/slow down the development of retinopathy and prevent their vision loss in diabetic patients.

Genomic ancestry as a risk factor for diabetic retinopathy in patients with type 1 diabetes from an admixed population: a nested case-control study in Brazil.

The influence of genetic factors on the development and progression of diabetic retinopathy is still unclear. Previous studies showed controversial results. We aimed to characterize the relationship between genomic ancestry and self-reported color/race with severe diabetic retinopathy in patients with type 1 diabetes belonging to a highly admixed population. This study was a nested case-control based on data collected from a large cross-sectional, nationwide survey conducted in clinics from all five geographic regions of Brazil. For the present study, we included 414 individuals. Cases (n = 176) were considered if they had severe non-proliferative or proliferative diabetic retinopathy, and controls (n = 238) were type 1 diabetes patients without retinopathy, matched for diabetes duration by a range of 5years. Indirect ophthalmoscopy was performed, and individual genomic ancestry was inferred using a panel of 46 ancestry informative markers. The backward stepwise logistic regression analysis showed that African genomic ancestry (OR 3.9, p = 0.045), HbA1c (OR 1.24, p = 0.001), glomerular filtration rate (OR 0.98, p < 0.001) and hypertension (OR 2.52, p < 0.001) were associated with severediabetic retinopathy after adjusting for clinical and demographic data. Self-reported color/race was not statistically associated with diabetic retinopathy. Genomic ancestry, as well as clinical variables such as hypertension, impaired glomerular filtration rate and poor diabetes control (HbA1c), was important risk factor for the development of severe diabetic retinopathy. Further studies are needed, especially in highly admixed populations, to better understand the role of genomic ancestry and possible genes that might be associated with the development and/or progression of diabetic retinopathy.