PDR Group Research Articles

Relationship between extracellular water to total body water ratio and severe diabetic retinopathy in type 2 diabetes.

Diabetic retinopathy (DR) is a common microvascular complication of diabetes, and identifying the risk factors for severe DR is important. We aimed to investigate the relationship between severe DR and the extracellular water to total body water ratio (ET ratio). Retrospective cross-sectional study. Department of Endocrinology, Metabolism, and Diabetes at Kyushu University Hospital. A total of 205 adults with type 2 diabetes (T2D) were included. The patients were divided into two groups: non-proliferative DR (non-PDR; n = 161, 126 with no DR and 35 with simple DR) and proliferative DR (PDR; n = 44, 18 with pre-proliferative DR and 26 with PDR). The ET ratio was measured using bioelectrical impedance analysis. The ET ratio was significantly higher in the PDR group than in the non-PDR group (0.390 vs. 0.398; P < .0001). Multivariate logistic regression analysis showed that the ET ratio was significantly associated with PDR, independent of known risk factors for DR progression. In the subgroup analysis by age, multivariate logistic regression analysis revealed a significant association between the ET ratio and PDR, independent of known risk factors for DR progression in patients younger than 60 years. However, in patients 60 years and older, only the urinary albumin to creatinine ratio (UACR) showed a significant association with PDR in a model using the UACR and the ET ratio. In patients with T2D younger than 60 years, the ET ratio may be a useful indicator for identifying severe DR.

Nationwide trends and incidence of blindness in patients with diabetic retinopathy identified using an age-period-cohort analysis.

To estimate the epidemiologic trends of blindness in patients with diabetic retinopathy (DR) and investigate the age-, period-, and cohort-specific effects on blindness. A total of 2.5 million patients with DR aged 20 years or older were included from the Korean National Health Claims database from 2005 to 2019. Non-proliferative DR/ proliferative DR (NPDR/PDR) cohorts were constructed separately. Participants were identified as having a blindness in at least one eye. The incidence of blindness were calculated using a log-linear Poisson age-period-cohort (APC) analysis model, each effect on blindness were estimated for each study group. The incidence of blindness was 1326.62 per 100,000 in the NPDR group and 3397.57 in the PDR group. The blindness rate sharply decreased after 2011, with annual decreases of 5.6% and 4.4% in the NPDR and the PDR groups, respectively. People born between 1920 and 1930 had the highest overall risk of blindness, with the risk decreasing rapidly after that. For those born after 1980, the risk started to increase in both sexes. Among the APC models, the combination model of age, period, and cohort effects showed the highest explanatory power (0.96). In this nationwide long-term study, blindness in DR was not due to a single epidemiologic cause but rather a combination of biological age, social determinants, and healthcare policies. The increased risk of blindness in individuals in their 20 s and 30 s may even increase in the future and should not be ignored. Therefore, vigilance of younger patients is recommended.

Gut microbiota induced abnormal amino acids and their correlation with diabetic retinopathy.

To explore the correlation of gut microbiota and the metabolites with the progression of diabetic retinopathy (DR) and provide a novel strategy to elucidate the pathological mechanism of DR. The fecal samples from 32 type 2 diabetes patients with proliferative retinopathy (PDR), 23 with non-proliferative retinopathy (NPDR), 27 without retinopathy (DM), and 29 from the sex-, age- and BMI- matched healthy controls (29 HC) were analyzed by 16S rDNA gene sequencing. Sixty fecal samples from PDR, DM, and HC groups were assayed by untargeted metabolomics. Fecal metabolites were measured using liquid chromatography-mass spectrometry (LC-MS) analysis. Associations between gut microbiota and fecal metabolites were analyzed. A cluster of 2 microbiome and 12 metabolites accompanied with the severity of DR, and the close correlation of the disease progression with PDR-related microbiome and metabolites were found. To be specific, the structure of gut microbiota differed in four groups. Diversity and richness of gut microbiota were significantly lower in PDR and NPDR groups, than those in DM and HC groups. A cluster of microbiome enriched in PDR group, including Pseudomonas, Ruminococcaceae-UCG-002, Ruminococcaceae-UCG-005, Christensenellaceae-R-7, was observed. Functional analysis showed that the glucose and nicotinate degradations were significantly higher in PDR group than those in HC group. Arginine, serine, ornithine, and arachidonic acid were significantly enriched in PDR group, while proline was enriched in HC group. Functional analysis illustrated that arginine biosynthesis, lysine degradation, histidine catabolism, central carbon catabolism in cancer, D-arginine and D-ornithine catabolism were elevated in PDR group. Correlation analysis revealed that Ruminococcaceae-UCG-002 and Christensenellaceae-R-7 were positively associated with L-arginine, ornithine levels in fecal samples. This study elaborates the different microbiota structure in the gut from four groups. The relative abundance of Ruminococcaceae-UCG-002 and Parabacteroides are associated with the severity of DR. Amino acid and fatty acid catabolism is especially disordered in PDR group. This may help provide a novel diagnostic parameter for DR, especially PDR.

Analyzing the changing trend of corneal biomechanical properties under different influencing factors in T2DM patients

To analyze the changing trend of CH and CRF values under different influencing factors in T2DM patients. A total of 650 patients with T2DM were included. We discovered that the course of T2DM, smoking history, BMI, and FBG, DR, HbA1c, TC, TG, and LDL-C levels were common risk factors for T2DM, while HDL-C levels were a protective factor. Analyzing the CH and CRF values according to the course of diabetes, we discovered that as T2DM continued to persist, the values of CH and CRF gradually decreased. Moreover, with the increase in FBG levels and the accumulation of HbA1c, the values of CH and CRF gradually decreased. In addition, in patients with HbA1c (%) > 12, the values of CH and CRF decreased the most, falling by 1.85 ± 0.33 mmHg and 1.28 ± 0.69 mmHg, respectively. Compared with the non-DR group, the CH and CRF values gradually decreased in the mild-NPDR, moderate-NPDR, severe-NPDR and PDR groups, with the lowest CH and CRF values in the PDR group. In patients with T2DM, early measurement of corneal biomechanical properties to evaluate the change trend of CH and CRF values in different situations will help to identify and prevent diabetic keratopathy in a timely manner.

The association in diabetic retinopathy and stroke finding from NHANES evidence.

Diabetic retinopathy and stroke are both vascular pathologies, and this study intends to investigate the relationship between diabetic retinopathy and stroke. The NHANES database was used to find the relationship between diabetic retinopathy and stroke with 1948 individuals aged 40years or older. The sensitivity of the data was verified by multiple interpolation, further analysis was done by subgroup analyses, and possible links were investigated with mediation studies. Diabetes retinopathy was found to be closely associated with stroke, with the PDR group having a higher stroke incidence than the NPDR group. After controlling for covariates, there were still substantial differences in the risk of stroke among patients with NPDR and PDR. Overall, subgroup analysis revealed DR group showed an important distinction, compared to the non-DR (OR = 1.76, 95% CI 1.15-2.64). The results of the mediation research indicated that the connection between DR and stroke was mediated by the frailty index and hypertension. This study demonstrated a statistically significant correlation between DR and stroke, which persisted even after DR staging and was more prevalent in PDR patients than in NPDR patients. Stroke prevention may benefit from DR health management.

Mean Platelet Volume As Retinopathy Diabetic Predictive Factor in Peripheral Hospital: Could it be?

Introduction &amp; ObjectivesSeveral studies conducted that diabetic retinopathy (DR) pathogenesis may be linked tomicrocirculation disorders and microvascular damage. Platelets have a significant role inmicrocirculation changes that lead to microvascular injury. Mean Platelet Volume (MPV) is used as amarker to indicate the platelet’s average size and activity. The association between MPV and DR in apatient’s blood sample has been established. Aim of this study is to evaluate the association of MPVwith DR in our population.&#x0D; MethodsThis was a cross-sectional study in Brigjend H. Hasan Hospital within 183 patients which classifiedinto three groups including: I. DM without DR (n=61), II. DM with Non-proliferative DR (n=61), andIII. DM with proliferative DR (n=61). Data about gender, age and laboratory markers (MVP, HbA1C,fasting blood glucose) were collected, then analyzed using SPSS.&#x0D; ResultsMPV value was significantly higher in group II and III compared to group I (p&lt;0.001). The MPVvalue was also significantly higher in PDR Group compared to NPDR Group (adj. OR 7.91, 95% CI:3.79-16.5). The FBG value also significantly higher in group II and III compared to group I(p=0.012). On the other hand, HbA1C value mean was higher in group II and III but not statisticallysignificant (p=0.052).&#x0D; ConclusionThis study demonstrated relationship between higher MPV with DR and its severity. Consideringthat MPV can be easily measured and suitable as parameter reflective platelet function, DR and itsprogressivity can be clinically monitored using this method.

Relationship between visual acuity and OCT angiography parameters in diabetic retinopathy eyes after treatment.

To assess the relationship between visual acuity and OCT angiography parameters in diabetic retinopathy eyes after treatment, and to analyze the relative factors in PDR eyes. A total of 89 eyes, including 42 eyes with non-PDR (NPDR), and 47 eyes after vitrectomy with PDR were included and underwent OCTA. All images were processed by Python or FIJI. Multivariable linear regression models were used to analyze the associations between postoperative BCVA and OCTA parameters in PDR patients. Postoperative OCTA parameters including deep capillary plexus (DCP) parafoveal and perifoveal vessel density (VD), DCP parafoveal and perifoveal vessel length density (VLD), DCP fractal dimension (FD), choriocapillaris plexus (CCP) VD, CCP VLD, were significantly lower in the PDR group than in the NPDR group. In the superficial capillary plexus (SCP), we found a negative correlation between the postoperative BCVA and VD (parafovea: β coefficient = -0.351, p = 0.023; perifovea: β coefficient = -0.338, p = 0.036). Perifoveal VLD (β coefficient = -0.343, p = 0.031) and FD (β coefficient = -0.375, p = 0.016) of the SCP were also negatively correlated with postoperative BCVA. Regarding the DCP, perifoveal VD (β coefficient = -0.396, p = 0.008), perifoveal VLD (β coefficient = -0.334, p = 0.025), vessel tortuosity (VT) (β coefficient = -0.369, p = 0.015) were negatively correlated with postoperative BCVA. In CCP, VLD (β coefficient = -0.373, p = 0.023) and number of flow voids (β coefficient = -0.334, p = 0.036) exhibited a negative association with postoperative BCVA. Postoperative BCVA of PDR patients was related to OCTA parameters of the SCP (parafoveal and perifoveal VD, perifoveal VLD and FD), DCP (perifoveal VD, VLD, and VT) and CCP (VLD and number of flow voids).

Single-session associative protocol for dentin hypersensitivity management: a 1-year randomized, blinded clinical study.

This study aimed to establish a single-session associative protocol for non-restorative management of dentin hypersensitivity (DH). Twenty-four individuals with DH and a minimum sensitivity level of 4 on the visual analog scale (VAS) were selected. The study was conducted in a split-mouth design, with each participant (n = 20) having at least 1 affected tooth in all quadrants. The management protocols consisted of control group: universal adhesive, Neural Desensitizing Protocol group: 5% potassium nitrate, Mixed Desensitizing Protocol (PAM) group: 5% sodium fluoride and 5% potassium nitrate, Remineralizing Desensitizing Protocol (PDR) group: surface-partially reacted glass technology photopolymerizable varnish. Evaluations were performed immediately after application, at 1 week, 1 month, 2 months, and 12 months using the VAS sensitivity test. The scores were subjected to statistical analysis using the Friedman test (p < 0.05), Durbin-Conover test (p < 0.05), and Wilcoxon test (p < 0.05). At the 12-month evaluation, all groups showed statistically significant differences compared to the initial assessment. For the evaluation after 12 months, there was a statistically significant difference between the PAM group, the control group, and the PDR group. It can be concluded that all groups were effective in controlling DH, but there were significant results in the control group and PDR group. The clinical relevance of this study is to demonstrate that the application of single-session desensitizing protocols can be effective in controlling DH for up to 12 months. Brazilian Clinical Trials Registry Identifier: RBR-4r63d7s.

Neurodegeneration in diabetic retinopathy: An insight on its main signalling pathways

Aims/Purpose: In the latest years neurodegeneration has been considered as one of the main pathological processes involved in proliferative diabetic retinopathy's (PDR) onset and progression. We aimed to increase the understanding on the role of the main signalling molecules that participate in this phenomenon, including apoptotic, excitotoxic and neurotrophic factor pathways.Methods: Participants of both sexes were selected and programmed for vitrectomy by its diabetes mellitus 2 (DM2)‐derived vitreoretinal complications (PDR group, PDRG; n = 20), or by suffering macular hole, epiretinal membrane or rhegmatogenous retinal detachment (as the surrogate control group, SCG; n = 26). Vitreous body (VIT) and plasma (PLS) samples were collected and processed to determine the glutamate, caspase‐3 (CAS‐3) and brain‐derived neurotrophic factor (BDNF) levels. Next‐Generation Sequencing (NGS) techniques were applied to characterize the miRNA expression pattern in both groups.Results: Significantly higher VIT glutamate (p &lt; 0.05) and CAS‐3 (p &lt; 0.05), and significantly lower BDNF (p &lt; 0.05) levels were detected in the PDRG. Significantly higher PLS glutamate (p &lt; 0.05) and CAS‐3 (p &lt; 0.05) levels were found in diabetics. However, PLS levels of BDNF showed no differences between groups (p = 0.80). NGS analysis showed a different miRNA expression pattern between both groups.Conclusions: Diabetes‐induced changes in retinal neurons/glia may be the key to discover preclinical biomarkers for better managing diabetic eyes. Glutamate, caspase‐3 and BDNF, playing important roles in the neurodegenerative processes occurring in PDR, are pivotal candidates to identify diabetics at high risk of sight‐threatening complications. Additionally, certain miRNAs could be playing an important role in these signalling pathways, being involved in PDR's neurodegenerative phenomenon.

Retinal and choroidal microvascular characterization and density changes in different stages of diabetic retinopathy eyes.

The purpose of this study was to evaluate the changes in fundus vascular density and micromorphological structure of all vascular plexuses during the different stages of diabetic retinopathy (DR), and the correlation between fundus blood flow and the DR severity. This observational cross-sectional study was conducted of 50 eyes with different stages of DR, 25 diabetes mellitus (DM) patients without clinical signs of DR and 41 healthy eyes. The foveal avascular zone (FAZ), vessel density of superficial capillary plexus (SCP), and deep retinal capillary plexus (DCP) were acquired by RTVue XR Avanti OCTA device. The perfusion density (PD), skeleton vessel density (SVD) was manually calculated using ImageJ. The area under receiver operating characteristic (ROC) curve was used to determine the diagnostic value of OCTA parameters in distinguishing DR and healthy eyes. The choroidal VD were significantly higher in the healthy group than in the DM without DR, NPDR, and PDR groups (p < 0.001). The mean retinal parafovea VD, PD, and retinal SVD were higher in healthy and DM without DR eyes compared with NPDR and DR eyes in all vascular layers (p < 0.001). The parafoveal VD of SCP, and DCP decreased, and FAZ area increased with the exacerbation of DR. The OCTA parameters, including FAZ area, parafovea VD, PD, and SVD in all vascular layers showed significant correlation with DR severity (all p < 0.001). ROC curves of OCTA parameters (FAZ area, retinal parafovea VD, retinal PD, and SVD in all vascular layers) for had high sensitivity and specificity in distinguishing DR versus healthy eyes. The choroidal parafovea VD, retinal parafovea VD, retinal PD, and SVD in the two plexuses decreased, and retinal FAZ area increased significantly with worsening DR. VD, PD, and SVD might be potential early biomarkers indicating the progression of DR before appearance of clinically PDR in patients with DM. In this study, OCTA parameters had high sensitivity and specificity in distinguishing DR and healthy eyes.

Doppler ocular ultrasound in patients with type 2 diabetes mellitus

Purpose: To determine ocular blood flow parameters by Doppler ultrasound scanning in type 2 diabetic patients with different stages of diabetic retinopathy. Material and Methods: In this prospective study, forty-five patients (90 eyes) with type 2 diabetes mellitus were divided into three groups of 15 patients each: no diabetic retinopathy group (DR0), non-proliferative retinopathy (NPDR), and proliferative retinopathy (PDR) groups. Doppler indices such as systolic blood flow velocity (Vs), diastolic blood flow velocity (Vd), time-averaged maximum velocity (TAMXV), pulsatility index (PI) and resistivity index (RI) in the ophthalmic artery (OA), central retinal artery (CRA) and short posterior ciliary arteries (SPCA) were determined. ANOVA was used for quantitative comparisons between the three groups. Results: There was a significant (р less 0.05) decrease in (a) the Vs from 71.1 +- 20.6 cm/s in the DR0 group to 59.9 +- 16.7 cm/s in the NPDR group and 47.4 +- 16.4 cm/s in the PDR group, (b) Vd from 22.1 +- 6.9 cm/s to 17.0 +- 6.6 cm/s and 12.3 +- 5.9 cm/s, respectively; and (c) TAMXV from 37.2 +- 11.3 cm/s to 31.9 +- 9.1 cm/s and 25.3 +- 9.7 cm/s, respectively, and an increase in the RI from 0.69 +- 0.06 cm/s to 0.71 +- 0.09 cm/s and 0.75 +- 0.08 cm/s, respectively, in the OA. In addition, there was a significant decrease in the Vd from 9.9 +- 5.4 cm/s in the DR0 group to 8.1 +- 3.8 cm/s in the NPDR group and 5.5 +- 3.1 cm/s in the PDR group, and an increase in the PI from 1.34 +- 0.16 cm/s to 1.46 +- 0.28 cm/s and 1.54 +- 0.24 cm/s, respectively, and in the RI from 0.71 +- 0.06 cm/s to 0.75 +- 0.07 cm/s and 0.80 +- 0.05 cm/s, respectively, in the CRA. Moreover, there was a significant decrease in the Vd from 4.3 +- 1.6 cm/s in the DR0 group to 3.2 +- 2.0 cm/s in the NPDR group and 3.1 +- 2.2 cm/s in the PDR group, and an increase in the PI from 1.32 +- 0.21 cm/s to 1.37 +- 0.24 cm/s and 1.54 +- 0.26 cm/s, respectively, and in the RI from 0.76 +- 0.04 cm/s to 0.82 +- 0.06 cm/s and 0.82 +- 0.06 cm/s, respectively, in the SPCA. Conclusion: We found that the arteries examined in patients with diabetic retinopathy tended to have decreased blood flow velocities and increased resistivity and pulsatility indices, with the greatest changes observed in patients with PDR. In addition, the difference in mean values of most Doppler indices between the PDR and NPDR groups was larger than that between the NPDR and DR0 groups.

Investigation of the Role of Carcinoembryonic Antigen-Related Cell Adhesion Molecule-1 in Diabetic Retinopathy

ABSTRACT Purpose Diabetic retinopathy (DR) has become a major cause of blindness with increased prevalence of diabetic mellitus. Carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1) plays a part in pathological neovascularization. This study aimed to investigate the role of CEACAM1 in the progression of DR. Methods Aqueous and vitreous samples were collected from proliferative or non-proliferative DR and the control group. Multiplex fluorescent bead-based immunoassays were used to detect the levels of Cytokines. Expression of CEACAM1, VEGF, VEGF receptor 2 (VEGFR2) and hypoxia-induced factor-1α (HIF-1α) were detected in human retinal microvascular endothelial cells (HRECs). Results CEACAM1 and VEGF levels were significantly upregulated in PDR group and positively correlated with PDR progression. Expression CEACAM1 and VEGFR2 were increased in HRECs under hypoxic conditions. The HIF-1α/VEGFA/VEGFR2 pathway was blocked by CEACAM1 siRNA in vitro. Conclusions CEACAM1 might play a role in the pathology of PDR. CEACAM1 might be a therapeutic target for retinal neovasculariztion.

Downregulation of plasma microRNA-29c-3p expression may be a new risk factor for diabetic retinopathy

Circulation miRNAs have emerged as new biomarkers for identifying and monitoring the microvascular complications of diabetes. The aim of this study is to evaluate the levels of five candidate miRNAs (miR-29c-3p, miR-18a, miR-31, miR-181 and miR-20a) in patients with diabetic retinopathy (DR) and their relationship with disease severity. The study included 31 diabetes patients without DR (NDR group), 68 patients with DR (DR group) and 30 healthy controls (HC group). Twenty-five of patients with DR were proliferative DR (PDR group) and 43 were non-proliferative DR (NPDR group) patients. Metabolic parameters and serum vascular endothelial growth factor (VEGF) levels of all participants were measured. Circulating miRNAs levels were determined by quantitative real-time PCR. Fundus examinations of all patients were performed by a single ophthalmologist. VEGF levels were significantly higher in the NDR, and DR groups compared to HC group (P=0.011 and P=0.014, respectively). Plasma miR-29c-3p was downregulated in diabetic patients with retinopathy and without retinopathy. This downregulation was more prominent in diabetic patients without retinopathy compared to those with retinopathy (P=0.016). There was no significant difference in plasma levels of miR-18a, miR-20a, miR-18a and miR-31 between diabetic subjects with and without retinopathy (P>0.05). There was no correlation between DR severity and the levels of miRNAs (P>0.05). In multivariate logistic regression analysis, it was found that changes in plasma miR-29c-3p expression of diabetic patients increased DR risk independent of other risk factors. Plasma miR-29c-3p expression is downregulated in diabetic patients with and without retinopathy, and changes in this miRNA are an independent risk factor for the development of DR.

Serum brain-derived neurotrophic factor and macular perfusion in type 2 diabetes mellitus using optical coherence tomography angiography.

To investigate the relationship between serum brain-derived neurotrophic factor (BDNF) and changes in macular perfusion in different stages of diabetic retinopathy (DR) using optical coherence tomography angiography (OCTA). The study was conducted on 72 eyes of people with type 2 diabetes mellitus (DM). They were divided into five groups based on their DR stage: no DR (nDR), mild and moderate nonproliferative DR, severe nonproliferative DR, active proliferative DR (aPDR), and stable PDR. The presence or absence of diabetic maculopathy was also used to categorize the cases. All patients underwent a complete history, ophthalmological examination, OCTA imaging, and evaluation of BDNF and glycated hemoglobin A1c levels. The mean blood BDNF levels in the aPDR group were considerably lower than those in the nDR group (P = 0.023). In comparison to eyes without maculopathy, eyes with maculopathy had considerably decreased mean blood BDNF levels (P = 0.0004). Comparing NPDR and PDR groups to nDR as well as NPDR and PDR, a substantial decrease in average and parafoveal vessel density (VD) of the retina and choriocapillaries was seen (P = 0.02). The Foveal Avascular Zone (FAZ) acircularity index and VD were found to be significantly impacted by deteriorating DR (P = 0.001 and 0.017, respectively). It was discovered that there is a positive correlation between BDNF and the FAZ fractal dimension (P = 0.03). In diabetic eyes, there was a statistically favorable correlation between BDNF levels and best corrected visual acuity (P = 0.002). Furthermore, there was a negative relationship between DM duration and BDNF (P = 0.021). Serum BDNF levels decreased with the progression of DR and in patients with maculopathy. BDNF was found to be related to macular perfusion, particularly in the fovea.

Abnormal Levels of Serum Ferroptosis-Related Biomarkers in Diabetic Retinopathy.

This study aimed to measure the concentrations of ferroptosis-related biomarkers, namely, iron (Fe), lipid peroxide (LPO), reactive oxygen species (ROS), glutathione peroxidase-4 (GPX4), and glutathione (GSH) in DR in the attempt to evaluate the diagnostic performance of these biomarkers. This study included 30 NPDR patients, 30 PDR patients, and 30 healthy subjects matched in age and sex. The concentrations of Fe, LPO, ROS, GPX4, and GSH in serum of the subjects were measured. Compared with the normal group, GPX4 and GSH concentrations were significantly lower, and LPO, Fe, and ROS concentrations were significantly higher in DR patients. Compared with the PDR group, the NPDR group had higher concentrations of LPO, Fe, and ROS and lower concentrations of GPX4 and GSH, but there was no statistical difference in Fe, GPX4, and GSH. ROC curve shows that ferroptosis-related biomarkers have accumulated accuracy in NPDR and PDR. This study shows that ferroptosis-related biomarkers may be involved in the pathological process of DR and can be used as one of the biomarkers of DR.

Changes in serum lipids with the onset and progression of Diabetic Retinopathy in Type-II Diabetes Mellitus.

To investigate the role of serum lipids in the onset and progression of Diabetic Retinopathy (DR) in Type-II diabetes (T2DM) individuals. This cross-sectional study was conducted at the National Institute of Diabetes and Endocrinology (NIDE), Dow University of Health Sciences (DUHS) from March to May 2019. After signing the informed consent, healthy controls (n=30), T2DM patients (diabetic n=30), proliferative (PDR n=30) and non-proliferative (NPDR n= 30) of age 18 to 65 years were selected by convenient sampling. Background information was gathered through interviews and the fundoscopy was done. Fasting five ml venous blood samples were collected and analysed for triglycerides (TGs), cholesterol, HDL, LDL, VLDL and the HbA1c using commercially available assays. The SPSS, version 24.0, was used for data analysis. The HbA1c level was high in the diabetes, NPDR and PDR groups than control (p<0.05). The serum TGs and cholesterol were raised while the HDL was low in the diabetes group than in control (p<0.05). The cholesterol and LDL were high in the diabetes group compared to NPDR and PDR groups (p<0.05). The cholesterol and VLDL showed a positive moderately strong correlation with HbA1c in the PDR group (p<0.05). The serum lipid levels vary with the HbA1c levels and greater degree of derangement is observed with increasing mean HbA1C independent of diabetic retinopathy. For this reason, strict control of HbA1c and serum lipid level by lifestyle and/or pharmacologic intervention is recommended in diabetes with or without retinopathy.

Oct biomarkers of treatment-naive diabetic macular edema in patients with non-proliferative and proliferative diabetic retinopathy.

To evaluate and compare the retinal and choroidal spectral-domain optic coherence tomography (SD-OCT) findings of treatment-naïve diabetic macular edema (DME) secondary to non-proliferative and proliferative diabetic retinopathy (NPDR-PDR). A hundred and thirty-eight eyes of 138 patients with DME were evaluated. Best-corrected visual acuity was recorded, biomicroscopic anterior and posterior segment examination, SD-OCT imaging, and fundus fluorescein angiography (FFA) were performed. Demographic features, OCT characteristics, FFA, and visual acuity measurements were evaluated and compared between the two groups. Sixteen eyes were excluded from the study due to the lack of FFA images. Data of 122 eyes were analyzed for the study. Sixty-five eyes with NPDR (Group 1) and 57 eyes with PDR (Group 2) were enrolled in the study. There was no significant difference in central macular thicknesses (CMT) between the two groups. The eyes with DME + PDR showed a higher rate of the diffuse type of macular edema with more para and peri-foveal extension accompanied by larger cysts than the eyes with DME + NPDR. Disorganization of retinal inner layers, disrupted ellipsoid zone, and the epiretinal membrane were more prominent in the eyes with PDR. Also, there were more prominent macular ischemia on FFA and worse initial visual acuity measurements in the eyes with PDR than those with NPDR. Choroidal thickness (CT) was significantly reduced in the PDR group. SD-OCT features of treatment-naïve DME in patients with NPDR and PDR presented some differences. These variations may be related to diabetic retinopathy severity and may provide information about prognosis.

The association of AGER and ALDH2 gene polymorphisms with diabetic retinopathy.

To evaluate the possible associations between AGER (rs1051993, rs2070600) and ALDH2 (rs671) gene polymorphisms with nonproliferative (NPDR) and proliferative (PDR) diabetic retinopathy, in a well-defined Greek population. 66 NPDR patients and 57 PDR patients participated in our study, along with 156 age- and gender-matched healthy-control subjects (CL). All the participants underwent a complete ophthalmological examination, while clinical and demographic data were collected. Furthermore, they were genotyped for the studied polymorphisms. No significant differences were detected among the studied groups regarding the participants' age and gender status. We found that the ALDH2 AA genotype was significantly more frequent in PDR patients than in CL (p = 0.014). Furthermore, between NPDR and PDR groups, the AGER rs1051993 GT and TT genotype frequencies were significantly elevated in PDR patients (p < 0.0001 and 0.04, respectively). Moreover, we demonstrated that the heterozygous GT genotype in DR patients is accompanied by 71.11 times higher risk of developing PDR (OR = 71.11: 95% CI- 4.14-1215.2), while the homozygous TT genotype is associated with 12.71 times elevated risk for PDR development (OR = 12.71: 95% CI- 0.63-254.1). We documented that the ALDH2 AA and AGER rs1051993 GT and TT genotypes were observed significantly more frequently in PDR Greek diabetic patients. Our findings also support the genetic theory, suggesting that heritability is significantly implicated in the development of DR, providing additional evidence in the understanding of DR pathogenesis.

Differential oral microbiome in nonhuman primates from periodontitis-susceptible and periodontitis-resistant matrilines.

Rhesus monkeys (n=36) exhibiting a healthy periodontium at baseline were used to induce progressing periodontitis through ligature placement around premolar/molar teeth. Bacterial samples were collected at baseline, 0.5, 1, and 3 months of disease and at 5 months for disease resolution. The animals were distributed into two groups (18/group): 3-7 years (young) and 12-23 years (adult) and stratified based upon matriline susceptibility to periodontitis (PDS, susceptible; PDR, resistant). A total of 444 operational taxonomic units (OTUs) with 100 microbes representing a core microbiome present in ≥75% of the samples were identified. Only 48% of the major phylotypes overlapped in the PDS and PDR samples. Different OTU abundance patterns were seen in young animals from the PDS and PDR matrilines, with qualitative similarities during disease and the relative abundance of phylotypes becoming less diverse. In adults, 23 OTUs were increased during disease in PDS samples and 24 in PDR samples; however, only five were common between these groups. Greater diversity of OTU relative abundance at baseline was observed with adult compared to young oral samples from both the PDS and PDR groups. With disease initiation (2weeks), less diversity of relative abundance and some distinctive increases in specific OTUs were noted. By 1 month, there was considerable qualitative homogeneity in the major OTUs in both groups; however, by 3 months, there was an exacerbation of both qualitative and quantitative differences in the dominant OTUs between the PDS and PDR samples. These results support that some differences in disease expression related to matriline (familial) periodontitis risk may be explained by microbiome features.

Association study of HIF-1α rs11549465 and VEGF rs3025039 genetic variants with diabetic retinopathy in Egyptian patients: crosslinks with angiogenic, inflammatory, and anti-inflammatory markers

BackgroundGenetic factors are implicated in the progression of DR—a global cause of blindness. Hence, the current work investigated the association of HIF-1α rs11549465 and VEGF rs3025039 genetic variants with the different stages of retinopathy among T2DM Egyptian patients. The crosslinks of these variants were explored with angiogenesis (VEGF), inflammation (AGEP and VCAM-1), and anti-inflammation (CTRP3) markers. Two hundred eighty-eight subjects were recruited in this study: 72 served as controls and 216 were having T2DM and were divided into diabetics without retinopathy (DWR), diabetics with non-proliferative retinopathy (NPDR), and diabetics with proliferative retinopathy (PDR). The genetic variants were analyzed using PCR-RFLP and their associations with NPDR and PDR were statistically tested. The circulating levels of AGEP, VCAM-1, HIF-1α, VEGF, and CTRP3 were assayed followed by analyzing their associations statistically with the studied variants. ResultsOnly HIF-1α rs11549465 genetic variant (recessive model) was significantly associated with the development of NPDR among T2DM patients (p < 0.025) with a significant correlation with the circulating HIF-1α level (p < 0.0001). However, this variant was not associated with PDR progression. Neither HIF-1α rs11549465 nor VEGF rs3025039 genetic variants were associated with the PDR progression. The circulating AGEP, VCAM-1, HIF-1α, and VEGF were significantly elevated (p < 0.0001) while the CTRP3 was significantly decreased (p < 0.0001) in NPDR and PDR groups. The HIF-1α rs11549465 CT and/or TT genotype carriers were significantly associated with AGEP and VCAM-1 levels in the NPDR group, while it showed a significant association with the CTRP3 level in the PDR group. The VEGF rs3025039 TT genotype carriers showed only a significant association with the CTRP3 level in the PDR group. ConclusionThe significant association of HIF-1α rs11549465 other than VEGF rs3025039 with the initiation of NPDR in T2DM Egyptian patients might protect them from progression to the proliferative stage via elevating circulating HIF-1α. However, this protective role was not enough to prevent the development of NPDR because of enhancing angiogenesis and inflammation together with suppressing anti-inflammation. The non-significant association of HIF-1α rs11549465 with PDR among T2DM patients could not make this variant a risk factor for PDR progression.