Non-proliferative Diabetic Retinopathy Group Research Articles

Relation between early stages of diabetic retinopathy and early stages of diabetic kidney disease in patients with type 2 diabetes in Egypt

Background. Diabetes mellitus is a pandemic disease. Type 2 diabetes (T2DM) is the most common type. Diabetic retinopathy (DR) and diabetic kidney disease (DKD) are disabling chronic complications. The relation between both is not yet well-established in T2DM. Egypt is considered one of the top ten countries re- garding the prevalence of diabetes that makes diabetes and its complications a major health problem. This encouraged us to conduct this research. Materials and methods. The study included 79 patients with T2DM divided into two groups according to the presence of retinopathy. Both groups were subdivided according to urinary albumin to creatinine ratio (UACR) into normoalbuminuric and albuminuric subgroups. Retinopathy group was further subdivided according to severity of retinopathy into mild, moderate and severe non-proliferative DR (NPDR). Statistical analysis was done and relation between the severity of retinopathy and UACR was studied. Results. Patients with retinopathy had significantly higher diabetes duration and UACR than non retinopathy group. Also in subgroups of normoalbuminuria and albuminuria, retinopathy group was significantly higher regarding the same parameters. On subdividing the retinopathy group according to severity, severe NPDR group had significantly higher UACR. The severity of DR was significantly positively correlated with UACR. Conclusions. The present study identified a significantly positive correlation between early stages of DR and UACR in patients with T2DM in Egypt. Not all cases of DR had DKD especially in early stages and also not all cases of DKD are associated with the presence of DR in T2DM.

Retinal Nonperfusion Characteristics on Ultra-Widefield Angiography in Eyes With Severe Nonproliferative Diabetic Retinopathy and Proliferative Diabetic Retinopathy

Threshold of retinal nonperfusion for the development of proliferative diabetic retinopathy (PDR) is unclear. To identify a threshold of retinal nonperfusion for the presence of retinal neovascularization and the distribution and area of retinal nonperfusion in eyes with severe nonproliferative diabetic retinopathy (NPDR), PDR, neovascularization of the optic disc (NVD), and retinal neovascularization elsewhere (NVE). This cross-sectional image analysis study was performed between September 24, 2018, and October 24, 2018, at a multicenter national study in the United Kingdom. Baseline images were obtained from 2 completed randomized clinical trials (Ranibizumab for Diabetic Macular Edema Panretinal Photocoagulation [RDP] study and Clinical Efficacy of Intravitreal Aflibercept vs Panretinal Photocoagulation for Best Corrected Visual Acuity in Patients With Proliferative Diabetic Retinopathy at 52 Weeks [CLARITY] study). The RDP study recruited eyes with severe NPDR between April 1, 2014, and December 31, 2015, and the CLARITY study recruited eyes with PDR between August 22, 2014, and November 20, 2015. Ultra-widefield angiography images of eyes with no prior panretinal photocoagulation treatment were included. The total area of retinal nonperfusion, the area of posterior pole retinal nonperfusion, and the area of peripheral retinal nonperfusion were measured. A total of 92 patients (92 eyes) were included in the study: 59 in the PDR group (mean [SD] age, 42 [15] years; 20 female [33.9%]) and 33 in the NPDR group (mean [SD] age, 63 [10] years; 3 female [9.1%]). Forty eyes had NVE and 19 had NVD with or without NVE. We identified a retinal nonperfusion threshold of 118.3 disc areas (DA) with a specificity of 84.9% (95% CI, 68.1% to 94.9%) for PDR. The median area of retinal nonperfusion was 67.8 DA (95% CI, 44.2 to 107.3 DA) in the NPDR eyes and 147.9 DA (95% CI, 127.4 to 173.5 DA) for eyes with proliferative changes, with a difference of 69.0 DA (95% CI, 42.2 to 97.7 DA; P < .001). No difference was found in the median area of posterior nonperfusion between NPDR and PDR, with a difference of 0 DA (95% CI, -6.7 to 5.2 DA; P = .56). As for peripheral nonperfusion, NPDR eyes measured 64.1 DA and PDR eyes measured 130.6 DA, with a difference of 70.8 DA (95% CI, 48.4 to 94.9 DA; P < .001). Eyes with NVD had the largest total area of retinal nonperfusion, with a difference of 65.1 DA (95% CI, 28.6 to 95.8 DA; P < .001) compared with eyes with only NVE. These findings suggest eyes with at least 107.3 DA of nonperfusion are at risk of proliferative disease, and eyes with NVD have the largest area of retinal nonperfusion.

Changes of serum vascular endothelial growth factor, apelin and heme oxygenase-1 levels in patients with type 2 diabetes mellitus and their relationship with diabetic retinopathy

Objective To observe the serum vascular endothelial growth factor (VEGF), apelin and heme oxygenase-1 (HO-1) levels in patients with type 2 diabetes mellitus (T2DM) and to explore their their relationship with diabetic retinopathy (DR). Methods A total of 208 patients with T2DM and 50 healthy subjects (control group) from the Central Hospital of Western Hainan during January 2014 and December 2017 were selected in this study. Vision, slit lamp microscope, indirect ophthalmoscope and FFA examinations were performed on all the subjects. According to the results of the examinations combined with the DR clinical staging criteria, the patients were divided into non-DR (NDR) group, non-proliferative DR (NPDR) group, and proliferative DR (PDR) group, with 72, 76 and 60 patients in each, respectively. The clinical data of each group were recorded, and the levels of fasting blood glucose (FPG), HbA1c, total cholesterol (TC), three acylglycerol (TG), high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), VEGF, apelin and HO-1 were detected in each group. The receiver operating characteristic curve (ROC) were used to analyze the value of VEGF, apelin and HO-1 in predicting the occurrence of PDR. Correlation analysis of serum VEGF, Apelin and HO-1 with clinical parameters in PDR patients by Pearson correlation analysis. Results The level of VEGF (56.82±10.16 vs 91.74±22.83, 140.15±36.40, 195.28±42.26 pg/ml) and apelin (2.95±0.53 vs 4.68±0.74, 7.25±1.13, 10.16±1.35 ng/ml) in PDR group were significantly higher than those in NPDR, NDR and control groups (F=17.306, 21.814; P<0.05). The level of HO-1 (50.37±10.14 vs 43.58±8.16, 30.25±6.28, 22.60±4.72 mmol/L) in PDR group was significantly lower than those in NPDR, NDR and control groups (F=15.827, P<0.05). The ROC curve analysis showed that the best cut-off values of serum VEGF, apelin and HO-1 were 162.50 pg/ml, 8.30 ng/ml, 27.13 mmol/L, and the three combined to predict PDR of AUC (95%CI) was 0.906 (0.849−0.962), and their sensitivity (90.3%) and specificity (83%) were better. The correlation analysis showed that the VEGF, apelin and HO-1 of PDR patients were correlated with the course of diabetes (r=0.382, 0.416, −0.36; P<0.05), FPG (r=0.438, 0.460, −0.397; P<0.05) and HbAlc (r=0.375, 0.478, −0.405; P<0.05), and the serum VEGF were correlated with apelin and HO-1 (r=0.793, −0.594; P<0.01). Conclusion Elevated serum VEGF and apelin levels and reduced HO-1 levels are associated with the progression of DR, and the three combination helps predict the occurrence of PDR. Key words: Diabetic retinopathy/etiology; Diabetes mellitus, type 2; Vascular endothelial growth factors; Receptors, angiotensin; Heme oxygenase-1

Sleep-Disordered Breathing Is a Stronger Risk Factor for Proliferative Diabetic Retinopathy than Metabolic Syndrome and the Number of Its Individual Components

ABSTRACTPurpose: To evaluate whether the features of sleep-disordered breathing (SDB) are stronger independent factors for proliferative diabetic retinopathy (PDR) compared to the incidence of metabolic syndrome (MetS) and the number of its individual components.Methods: We studied a cross-sectional total of 132 patients with type 2 diabetes. Thirty-nine patients had non-proliferative diabetic retinopathy (NPDR) and 93 patients had PDR. Pulse oximetry was conducted, and the patients’ mean oxygen saturation (mean SpO2%) and 4% oxygen desaturation index (4% ODI times/hour) were evaluated. We compared the SDB and MetS variables between the NPDR and PDR patients. A logistic regression analysis was used to determine the independent factors for the diagnosis of PDR.Results: The MetS diagnosis was made significantly more often in the PDR group (p = 0.04). The number of individual MetS components was significantly greater in the PDR group compared to the NPDR group (p = 0.01). The mean SpO2 of the NPDR group was not significantly different from that of the PDR group. The 4% ODI in the NPDR group was significantly lower than that in the PDR group (p = 0.01). The logistic regression analysis using the prevalence of MetS and the number of MetS components revealed that younger age and high 4%ODI value were independent factors contributing to the diagnosis of PDR.Conclusion: Our findings confirmed that compared to MetS and the number of its individual components, SDB may be a factor contributing to the progression to PDR. However, further careful longitudinal validation studies are needed.

Do microvascular changes occur preceding neural impairment in early-stage diabetic retinopathy? Evidence based on the optic nerve head using optical coherence tomography angiography.

To evaluate the microvascular and neural differences of the optic nerve head (ONH) between type 2 diabetes mellitus (T2DM) subjects and controls. This was a cross-sectional observational study. One hundred and eight eyes of 108 T2DM subjects with or without diabetic retinopathy (DR) (54 preclinical DR and 54 mild-to-moderate DR) were included. Fifty-two eyes of 52 healthy subjects were included as controls. The 4.5-mm Angio Disc scan mode and the ganglion cell complex scan mode were performed with all participants using AngioVue software 2.0 of the optical coherence tomography angiography (OCTA) device. Regarding ONH radial peripapillary capillary (RPC) density, the peripapillary region was mainly significantly reduced in the No-DR (NDR) group. Moreover, the RPC density of the peripapillary region and the inside optic disc area were significantly reduced in the non-proliferative DR (NPDR) group. When compared to the controls, significantly reduced peripapillary capillary density in six sections was observed in the NPDR group. However, reduced density was observed in only two sections in the NDR group. The NPDR group had significantly increased focal loss volume (FLV) and reduced peripapillary RNFL thickness in the inferior nasal section compared to those in the controls, but similar changes were not observed in the NDR group. A regression model identified RPCs inside the optic disc as a significant parameter in early-stage DR detection. In the NPDR group, BCVA showed a significantly negative correlation with RPCs inside the optic disc and a significantly positive correlation with FLV. OCTA findings of the ONH area may provide evidence that microvascular changes occur preceding neural impairment in early-stage DR. However, further researches are still needed to support the statement. Reduced ONH perfusion inside the optic disc may be one of the crucial biomarkers in early-stage DR detection and is a possible sensitive visual acuity predictor in early-stage DR subjects. With the ONH mode, OCTA may be a more promising tool in DR screening.

The Optimal Cutoff Value of Neutrophil/Lymphocyte Ratio for Severe Grades of Diabetic Retinopathy.

Objectives:The aim of this study was to define the optimal cutoff value of the neutrophil/lymphocyte ratio (NLR) to predict severe grades of diabetic retinopathy (DR).Methods:A total of 40 patients with proliferative DR (PDR) and 40 patients with severe non-proliferative DR (NPDR) were included this prospective, case control study, and 35 age- and sex-matched healthy subjects were recruited as a control group. White blood cell (WBC) count mean values and ratios were compared between the groups.Results:The groups were statistically similar in terms of age and sex. The neutrophil, lymphocyte, monocyte, platelet counts, and main platelet volume (MPV) values were similar in all 3 groups (all p values >0.05). The mean NLR was 2.67±1.02 in the PDR cases, 2.16±0.58 in severe NPDR, and 1.85±0.49 in the control group, which represented a statistically significant difference between the 3 groups (p=0.003). In post-hoc analysis, the NLR of the PDR and severe NPDR groups was statistically significantly greater than that of the control group (p=0.002 and p=0.048, respectively), but there was no statistically significant difference between the PDR and severe NPDR groups (p=0.083). The monocyte/lymphocyte, platelet/lymphocyte, and MPV/lymphocyte ratios were also similar in all 3 groups (all p values >0.05).Conclusion:An NLR value of 2.11 or more predicted DR (PDR or severe NPDR) with a sensitivity of 76% and a specificity of 80%.

Serum microRNA-221 as a biomarker for diabetic retinopathy in patients associated with type 2 diabetes.

To investigate the candidate microRNA (miRNA), miR-221 as a novel biomarker for diabetic retinopathy (DR) in patients associated with type 2 diabetes (T2D). The subjects involved were divided into four groups: healthy control (HC), no diabetic retinopathy (NDR), non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) group. Serum miR-221 was validated by real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Also, serum angiotensin II (Ang II) and vascular endothelial growth factor (VEGF) were examined by enzyme-linked immunosorbent assay. In addition, receiver operating characteristic (ROC) curve was performed to explore the diagnostic accuracy of miR-221, Ang II and VEGF for DR in patients with T2D. Spearman's rank correlation coefficient was executed to estimate the correlations of serum miR-221 with metabolic parameters and serum markers in patients with T2D. Primarily, serum miR-221, Ang II and VEGF were increased significantly in T2D patients compared to HC participant respectively, and progressive up-regulated in NDR, NPDR and PDR groups (P<0.001). Additionally, miR-221 in serum was remarkably positively correlated with metabolic parameters such as glycated hemoglobin (r=0.310, P=0.002) and homeostasis model assessment for insulin resistance (r=0.413, P<0.001), as well as serum markers for instance Ang II (r=0.667, P<0.001) and VEGF (r=0.499, P<0.001). Furthermore, serum miR-221 (AUC, 0.894; 95%CI, 0.833-0.955; P<0.001), Ang II (AUC, 0.888; 95%CI, 0.828-0.949; P<0.001) and VEGF (AUC, 0.785; 95%CI, 0.695-0.875; P<0.001) had evidently diagnostic efficiency in DR, and miR-221 is the most effective among them. Serum miR-221 as a potential biomarker could be related to not only occurrence but also progression for DR in patients with T2D. However, a prospective clinical trial is warranted.

Correlation between dyslipidemia and diabetic retinopathy in diabetic patients aged 80 years and over

Objective To explore the correlations of dyslipidemia and hypertension with diabetic retinopathy in diabetic patients aged 80 years and over. Methods The 487 diabetic patients admitted to endocrine department of our hospital from January 2013 to June 2017 were recruited and their medical records were retrospectively analyzed.According to the results of examination, they were divided into three groups: non-diabetic retinopathy group(n=306), non-proliferative diabetic retinopathy group(n=143)and proliferative diabetic retinopathy group(n=38). The course of diabetes, levels of blood glucose and lipids, and the course of hypertension were compared among the three groups. Results Prevalence of diabetic retinopathy was 37.2%(181/487), and was increased along with the prolongation of diabetes duration, and occurrence of coexisted hypertension and dyslipidemia.Statistically significant differences were found among the 3 groups(all P<0.05)in the levels of glycosylated hemoglobin A1c, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, apolipoprotein A, apolipoprotein B and the ratio of apolipoprotein A over apolipoprotein B. Multivariate analysis showed that the levels of glycosylated hemoglobin A1c, low-density lipoprotein cholesterol and the ratio of apolipoprotein A and apolipoprotein B were correlated with the development and progression of diabetic retinopathy(OR=3.00, 0.22 and 2.96, respectively). Conclusions The incidence of diabetic retinopathy is higher in diabetic patients aged 80 years and over.Dyslipidemia is correlated with development and progression of diabetic retinopathy. Key words: Aged, 80 and over; Diabetic retinopathy; Dyslipidemia

Diagnostic and prognostic role of serum miR-20b, miR-17-3p, HOTAIR, and MALAT1 in diabetic retinopathy.

Noncoding RNAs are emerging biomarkers for many diseases including diabetic retinopathy (DR). This study aimed to measure the expression levels of serum miR-20b, miR-17-3p, HOTAIR, and MALAT1 in DR patients. A total of 80 patients diagnosed as type 2 diabetes (T2D) and 81 healthy subjects were recruited in this study. T2D patients were divided into three groups: nondiabetic retinopathy (NDR) group (30 patients), nonproliferative diabetic retinopathy (NPDR) group (30 patients), and proliferative diabetic retinopathy (PDR) group (20 patients). Quantitative real-time polymerase chain reaction (PCR) was used to assess the expression of serum miR-20b, miR-17-3p, HOTAIR, and MALAT1. We found a significant decrease in serum miR-20b and a significant increase in serum HOTAIR and MALAT1 in NDR patients compared to healthy subjects. Also, we revealed a significant decrease in serum miR-20b and miR-17-3p and a significant increase in serum HOTAIR and MALAT1 in each of NPDR and PDR groups when compared with healthy subjects. Furthermore, we reported a significant decrease in miR-20b and miR-17-3p and a significant increase in HOTAIR and MALAT1in DR as well as in PDR patients when compared with NDR patients. However, on comparing NPDR with NDR patients, no significant difference was observed regarding the expression levels of miR-20b and miR-17-3p, in contrast, significant elevation of serum HOTAIR and MALAT1 was found in NPDR. Moreover, we observed a significant decrease in serum miR-20b and miR-17-3p and a significant increase in serum HOTAIR and MALAT1 in PDR group relative to NPDR group. Receiver operating characteristic (ROC) curve was used for evaluating the diagnostic value of the examined serum noncoding RNAs as novel biochemical indicators detecting severity of DR. Our analyses suggested that the examined serum noncoding RNAs may discriminate DR (PDR and NPDR) from NDR. Furthermore, these noncoding RNAs (less importantly miR-17) can be used as promising novel biomarkers for prediction DR severity, distinguishing PDR from NPDR patients. We can conclude that serum miR-20b, miR-17-3p, HOTAIR, and MALAT1 may be used as noninvasive biomarkers for screening of DR and early diagnosis of PDR. © 2018 IUBMB Life, 71(3):310-320, 2019.

Expression and significance of miR-126 and VEGF in proliferative diabetic retinopathy

Objective To investigate the expression and clinical significance of miR-126 and vascular endothelial growth factor (VEGF) in proliferative diabetic retinopathy (PDR). Methods 226 cases of diabetic retinopathy (DR) patients admitted in our hospital were studied, including 110 cases of PDR (group PDR), 116 non proliferative diabetic retinopathy (NPDR) (group NPDR). 80 patients with diabetes mellitus without retinopathy (NDR) were enrolled in DR group at the same period, another 80 healthy subjects (control group) were selected as control group. The plasma miR-126 level of all subjects was detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). The enzyme linked im-munosorbent assay (ELISA) method was used to detect plasma VEGF level. The clinical diagnostic value of miR-126 and VEGF in PDR patients was further analyzed. Results Plasma levels of miR-126 in PDR group, NPDR group and NDR group were lower than those in control group (P<0.05), PDR group was lower than NPDR group and NDR group (P<0.05); plasma levels of VEGF in PDR group, NPDR group and NDR group were higher than those in control group (P<0.05), PDR group was higher than NPDR group and NDR group (P<0.05). Total cholesterol (TC), triglyceride (TG) and glycated hemoglobin (HbA1c) in PDR group were higher than those in NPDR group and NDR group (P<0.05), low density lipoprotein cholesterol (LDL-C) in PDR group, NPDR group and NDR group were higher than those in control group (P<0.05), and LDL-C in PDR group was higher than that in NPDR group and NDR group (P<0.05). High density lipoprotein cholesterol (HDL-C) in PDR group and NDR group was lower than that in control group (P<0.05), C-reactive protein (CRP) in PDR group, NPDR group and NDR group was higher than that in control group (P<0.05); plasma miR-126 levels in PDR group were negatively correlated with TC, LDL-C, CRP and HbA1c (P<0.05), but positively correlated with HDL-C (P<0.05), and no correlation with TG; the plasma levels of VEGF in PDR patients were positively correlated with TC, TG, LDL-C, CRP and HbA1c (P<0.05), but negatively correlated with the expressions of miR-126 (r=-0.573, P=0.000); the AUC of miR-126 was 0.861, and when the cut-off value was <0.64, the diagnostic sensitivity and specificity were 82.50% , 83.64%; the area under curve (AUC) of VEGF was 0.889, and when the cut-off value was <7.000, the sensitivity and specificity of diagnosis were 82.73%, 86.25%; 0.847 for the AUC of HbA1c, and the sensitivity and specificity 81.82%, 87.50% respectively. Conclusions Plasma miR-126 is low-expressed and VEGF is high-expressed in PDR patients, there is a negative correlation between the two indexes. They may be involved in the course of PDR through abnormal lipid metabolism and inflammatory reaction and may be a potential biomarker for early diagnosis of PDR. Key words: Diabetic retinopathy/BL; MicroRNAs/BL; Vascular endothelial growth factors/BL

Evaluation of choroidal thickness in different stages of diabetic retinopathy

Purpose: to assess changes of choroidal thickness (CT) in diabetic patients in different stages of diabetic retinopathy and diabetic macular edema using spectral domain optical coherence tomography. Patients and methods: One hundred and sixty three subjects were enrolled: 113 diabetic patients (186 eyes) and 50 normal individuals as controls. Eyes were divided into two groups according to age; group A from 35 to 50 years and group B from 51 to 65 years. Both groups classified according to retinopathy grade: DR1 (no DR), DR2 (mild- moderate nonproliferative diabetic retinopathy (NPDR)), DR3 (severe NPDR), DR4 (untreated proliferative diabetic retinopathy (PDR)) and DR5 (previously treated PDR). All participants underwent full ophthalmic examination, stereoscopic color fundus photography, and spectral domain optical coherence tomography (RS-3000; Nidek). Spectral domain optical coherence tomography examination consisted of linear scans, 6 mm in length, centered onto the fovea, and macula multi scans. Choroidal thickness was measured manually at the fovea and at 500, 1000, and 1500 um distance along all scans in the macula. Results: Mean age was not significantly different between patients with diabetes and controls. In the macular area, CT was significantly lower in the nasal quadrant versus all other quadrants (P, 0.0001), in both groups. No significant CT difference was found between controls and diabetic eyes without detectable DR. Diabetic macular edema did not influence CT. In early NPDR (mild and moderate) and treated PDR the mean choroidal thickness was significantly decreased than control. In severe NPDR and treated PDR, the mean subfoveal choroidal thickness was not different than control. There was a statistically significant increase in choroidal thickness in PDR when compared with the mild NPDR group (P=0.027). DME was associated with a non-statistically significant increase in choroidal thickness compared with eyes without DME (P=0.13). Conclusion: Choroidal thickness is reduced in diabetic eyes. Subfoveal choroidal thickness increased with the severity of diabetic retinopathy but showed no statistically significant association with the presence of DME. Spectral domain optical coherence tomography clearly confirms in vivo previously reported histopathologic observations. The role of choroid in the pathophysiology of DR needs to be adequately investigated.

Expression levels of aldose reductase enzyme, vascular endothelial growth factor, and intercellular adhesion molecule-1 in the anterior lens capsule of diabetic cataract patients

To compare the levels of aldose reductase (ALR) enzyme, intercellular adhesion molecule-1 (ICAM-1), and vascular endothelial growth factor (VEGF) in the anterior lens capsule of diabetic versus nondiabetic patients. Alexandria Main University Hospital, Alexandria, Egypt. Prospective case-control study. The study enrolled patients undergoing cataract extraction and divided them into 3 groups: eyes that had proliferative diabetic retinopathy (PDR), eyes that had nonproliferative diabetic retinopathy (NPDR), and nondiabetic eyes. The anterior lens capsules were obtained by performing femtosecond laser-assisted capsulorhexis. Concentrations of ALR, ICAM-1, and VEGF in the lens capsule specimens were measured using human enzyme-linked immunosorbent assay. This study comprised 200 patients (200 eyes); 51 eyes had PDR, 49 eyes had NPDR, and 100 eyes were nondiabetic. The mean ALR, ICAM-1, and VEGF levels in the anterior capsule of diabetic group were 2.84nanogram (ng)/mL±0.51 (SD), 87.73±22.84picogram (pg)/mL, and 75.53±14.95 pg/mL, respectively; whereas, in the nondiabetic group, they were 1.44±0.17ng/mL, 35.45±2.8 pg/mL, and 33.55±5.47 pg/mL, respectively. In comparing the concentrations of these mediators, both the PDR and NPDR groups had significantly higher levels compared with the nondiabetic eyes (P<.001). In addition, eyes with PDR had significantly higher levels of these mediators than eyes with NPDR (P<.001). The concentrations of ALR, ICAM-1, and VEGF in the anterior lens capsule of diabetic patients are significantly higher than those of nondiabetics. A significantly higher level of 3 mediators in eyes with PDR compared with those with NPDR might allow the use of them as a biomarker for severity of diabetic retinopathy.

Association of Irisin Circulating Level with Diabetic Retinopathy: A Case-Control Study.

Obesity and obesity induced type 2 diabetes development and progression have been associated with sedentary lifestyle. Irisin, a newly discovered myokine, has been demonstrated at lower levels in obese and type 2 diabetes patients compared to controls. The main aim of this study is to explore association of Irisin with diabetic retinopathy (DR). A total of 233 healthy and adults participated in this study. Participants were divided into four categories: a healthy control group and an age-match subset of patients with type 2 diabetes; a positive control group of patients with type 2 diabetes not affected by DR (No DR); and patients with type 2 diabetes affected by DR (non-proliferative DR (NPDR) and proliferative DR (PDR)). Plasma samples were quantified for Irisin measurement, lipid profile and HbA1c. Comparison of the age-matched groups of healthy controls and patients with type 2 diabetes revealed lower Irisin plasma level in type 2 diabetes group. Analyses revealed negative correlations of Irisin to HbA1c and LDL levels and positive correlation to HDL level. Comparing Irisin level in No DR and DR groups revealed a higher level in No DR group and analysis per DR classification indicated higher Irisin level in NPDR group. Our results demonstrate not only correlation of plasma Irisin level with DR stages, but also significantly different Irisin level among them. This is promising in terms of researching Irisin as a potential associating marker for type 2 diabetes and DR development and progression.

Analysis of the quality of life and the influencing factors in patients with diabetic retinopathy before and after receiving pan-retinal photocoagulation

Objective: Quality of life and the influencing factors in patients with diabetic retinopathy before and after receiving treatment of pan-retinal photocoagulation (PRP) were studied. Methods: Prospective study. A total of 55 diabetic retinopathy patients were collected at Beijing Friendship Hospital, Capital Medical University from November 2016 to August 2017 and were surveyed using Vision Function Questionaire (VFQ-25) to evaluate their quality of life before and 3 months after treatment with PRP. According to diagnostic criteria, the patients were divided into two groups: severe nonproliferative diabetic retinopathy(NPDR) and proliferative diabetic retinopathy group(PDR). SPSS was used for statistical analysis. Results: The score of VFO-25 general health before PRP treatment was 62.73±14.20, obviously lower the other sub scale scores of VFO-25. The results of variance analysis there was significant statistical difference between the composite score and the different educational levels (F=2.94, P<0.05), but there was no statistical difference for diabetes duration (F=3.01, P<0.05). The composite score was significantly significance between the severe NPDR and PDR group(t=8.95, P<0.05). The patients with hyperlipidemia (t=-3.21, P<0.05), hypertension(t=-2.32, P<0.05) and renal insufficiency(t=-2.05, P=0.045) has lower composite score. There was high relationship for age among the factors of worse logMAR vision, better logMAR vision and age (r=-0.47, P<0.05; r=-0.38, P<0.05; r=-0.26, P<0.05). The scores of VFQ-25 subscale of social function (t=-2.07, P<0.05) , role limitations (t=-2.38, P<0.05) , dependency (t=-2.99, P<0.05) and mental health (t=-2.26, P<0.05) was significantly increased after treatment of PRP. The score of ocular pain was obviously decreased (t=4.19, P<0.001) ; there were no significance in other sub scale scores. Conclusions: This study showed that the degree of visual acuity, the severity of DR and age were an important factor affecting the quality of life in DR patients. PRP therapy could improve the mental health and social field of DR patients, but failed to improve the scores of other visual functions in the patients. (Chin J Ophthalmol, 2018, 54:611-616).

Changes in the expressions of E-selectin, adiponectin and serum ferritin in patients with diabetic retinopathy, and their correlations

Purpose: To study changes in the expressions of E-selectin, adiponectin (APN) and serum ferritin in patients with diabetes retinopathy (DN) and their correlations with DN.Methods: Diabetes patients (180) in Tangshan City Workers Hospital Group Rehabilitation Hospital from February 2014 to February 2015 were recruited and divided into three groups: 56 non-diabetic retinopathy (NDR) cases, 60 non-proliferative diabetic retinopathy (NPDR) cases and 64 proliferative diabetic retinopathy (PDR) cases. Serum levels of E-selectin, adiponectin (APN), ferritin (SF), fasting plasma glucose (FPG) and fasting insulin (FINS) were separately assayed, and their correlations analyzed.Results: There were no significant differences between patients in the three groups with respect to sex, age, blood pressure and blood lipids (p &gt; 0.05). Serum E-selectin, APN and SF levels gradually and significantly increased in the order: NDR group ˂ NPDR group ˂ PDR group (p &lt; 0.05).Conclusion: E-selectin, APN and SF levels of patients with DN increase with aggravation of the disease. The decrease in E-selectin, APN and SF levels may have a positive effect on the improvement of the status of DN patients.Keywords: Diabetic retinopathy, E-selectin, Adiponectin, Serum ferritin

The macular capillary morphology in diabetic patients by optical coherence tomography angiography

Objective To observe the macular capillary morphology in diabetic patients. Methods A total of 61 patients (104 eyes) with diabetes mellitus (DM group) and 31 healthy controls (41 eyes) were enrolled in the study. According to the degree of diabetic retinopathy (DR), the DM group was divided into non-DR (NDR) group, non-proliferative DR (NPDR) group, and proliferative DR (PDR) group. There were 13 patients (23 eyes), 21 patients (34 eyes) and 27 patients (47 eyes) in each group, respectively. According to whether there was diabetic macular edema (DME), the DM patients were divided into DME group and non-DME group, each had 20 patients (28 eyes) and 41 patients (76 eyes), respectively. The age (F=2.045) and sex (χ2=2.589) between the control group, the NDR group, the NPDR group and PDR group were not statistically significant (P=0.908, 0.374). The 3 mm × 3 mm region in macula was scanned by optical coherence tomography angiography (OCTA), and the retinal capillary morphological changes of superficial capillary layer (SCL) and deep capillary layer (DCL) were observed. Chi-square test and t test were used to compare data among different groups. Results There was no abnormal change of retinal capillary morphology in control group. Microaneurysms and foveal avascular zone (FAZ) integrity erosion can be found in NDR group. There were microaneurysms, FAZ integrity erosion, vascular tortuosity bending, capillary non-perfusion and venous beading in NPDR and PDR groups. The microaneurysms of DCL were significantly more than that of the SCL (t=4.759, P<0.001). The eyes with microaneurysms in NDR group, NPDR group, and PDR group showed significant differences (χ2=44.071, P<0.001), and the eyes with FAZ integrity erosion among these three groups also showed significant differences (χ2=30.759, P<0.001). Compared with NPDR group and PDR group, there were significant differences in vascular tortuosity bending and capillary non-perfusion (vascular tortuosity bending: OR=0.213, 95%CI 0.070−0.648, P=0.004; capillary non-perfusion: OR=0.073, 95%CI 0.022−0.251, P<0.001), and there was no significant difference in venous beading (OR=0.415, 95%CI 0.143−1.208, P=0.102). SCL blood flow density in the 4 groups (control, NDR, NPDR and PDR group) was 49.233±1.694, 48.453±2.581, 45.020±4.685 and 40.667±4.516, respectively. While the difference between the control and NDR group was not significant, the differences between other pairs (control vs NPDR/PDR, NDR vs NPDR/PDR, NPDR vs PDR) were significant. The ratio of FAZ integrity erosion and non-perfusion of DME group was significantly higher than those of non-DME group (vascular tortuosity bending: OR=7.719, 95%CI 1.645−36.228, P=0.004; capillary non-perfusion: OR=14.560, 95%CI 3.134−67.646, P<0.001). Conclusions OCTA can distinctively detect the abnormal retinal capillary changes of SCL and DCL in diabetic patients. Even in DM patients without diabetic retinopathy, OCTA can detect abnormal blood vessels. Key words: Diabetic retinopathy; Regional blood flow; Tomography, optical coherence; Foveal avascular zone

Quantitative Analysis of Retinal Microvascular Changes in Optical Coherence Tomography Angiography Of Diabetic Retinopathy

Introduction: Diabetic Retinopathy (DR) is a common microvascular complication in patients with Diabetes Mellitus (DM) that can cause visual impairment and blindness in adult populations. Retinal microvascular changes, reflecting capillary drop out, non perfusion, and retinal ischemia seen in patients with DM can be assessed not only qualitatively, but also quantitatively with the introduction of a new, non invasive imaging modality Optical Coherence Tomography Angiography (OCTA), avoiding potential advese risks that can occur with the use of dye-injection imaging technique. We quantified retinal microvascular changes in healthy control eyes and Diabetic Retinopathy using OCTA.&#x0D; Methods: A cross sectional study included 13 eyes of 9 patients with DR, consists of 11 eyes with Non Proliferative Diabetic Retinopathy (NPDR) and 2 eyes with Proliferative Diabetic Retinopathy (PDR) and 5 eyes of 5 age-matched controls. Participants were imaged with commercial OCTA device (CIRRUS HD-OCT 5000 Angioplex). We analyzed in the Superficial Capillary Plexus (SCP) the following OCTA parameters : Vessel Density (VD), Foveal Avascular Zone (FAZ) area, and FAZ circularity.&#x0D; Result: Normal eyes had a higher mean VD, FAZ circularity (p &gt;0.05) and lower mean FAZ area ( p &lt;0.05) in the SCP compared with the DR (NPDR + PDR) group. If we excluded the PDR eyes from the analytic data, mean VD and FAZ area were found to be lower in control group, and mean FAZ circularity was higher. However, no quantitative parameters were statistically significant between control group and NPDR group.&#x0D; Conclusion: Microvascular changes in DR can be assessed with the use of Optical Coherence Tomography Angioraphy, which is non invasive and provides high quality of images acquired from the chosen level of retina.

Parafoveal Nonperfusion Analysis in Diabetic Retinopathy Using Optical Coherence Tomography Angiography.

PurposeTo describe a new technique for mapping parafoveal intercapillary areas (PICAs) using optical coherence tomography angiography (OCTA), and demonstrate its utility for quantifying parafoveal nonperfusion in diabetic retinopathy (DR).MethodsNineteen controls, 15 diabetics with no retinopathy (noDR), 15 with nonproliferative diabetic retinopathy (NPDR), and 15 with proliferative diabetic retinopathy (PDR) were imaged with 10 macular OCTA scans. PICAs were automatically delineated on the averaged superficial OCTA images. Following creation of an eccentricity-specific reference database from the controls, all PICAs greater than 2 SD above the reference means for PICA area and minor axis length were identified as nonperfused areas. Regions of interest (ROI) at 300 μm and 1000 μm from the foveal avascular zone (FAZ) margin were analyzed. Percent nonperfused area was defined as summed nonperfused areas divided by ROI area. Values were compared using Kruskal-Wallis and post-hoc Mann-Whitney U tests.ResultsMedian values for total percent nonperfused area at the 300-μm ROI were 2.09, 2.44, 18.08, and 27.55 in the control, noDR, NPDR, and PDR groups, respectively. Median values at the 1000-μm ROI were 3.10, 3.31, 13.42, and 23.00. While there were no significant differences between the control and noDR groups, significant differences were observed between all other groups at both ROIs.ConclusionsPercent nonperfused area can quantify parafoveal nonperfusion in DR and can be calculated through automatic delineation of PICAs in an eccentricity-specific manner using a standard deviation mapping approach.Translational RelevancePercent nonperfused area shows promise as a metric to measure disease severity in diabetic retinopathy.

Reduced Contrast Sensitivity is Associated With Elevated Equivalent Intrinsic Noise in Type 2 Diabetics Who Have Mild or No Retinopathy.

PurposeTo evaluate explanations for contrast sensitivity (CS) losses in subjects who have mild nonproliferative diabetic retinopathy (NPDR) or no diabetic retinopathy (NDR) by measuring and modeling CS in luminance noise.MethodsTen diabetic subjects with NDR, 10 with mild NPDR, and 10 age-equivalent nondiabetic controls participated. Contrast threshold energy (Et) was measured for letters presented in the absence of noise (Et0) and in four levels of luminance noise. Data were fit with the linear amplifier model to estimate inferred noise level within the visual pathway (Neq) and sampling efficiency (ability to use stimulus information optimally). Et0, Neq, and efficiency were compared to clinical characteristics.ResultsNeq was correlated with Et0 for the diabetic subjects (r = 0.93, P < 0.001) and ranged from normal to 12-times the upper limit of normal. ANOVA indicated significant differences among the subject groups for Et0 and Neq (both F > 11.92, P < 0.001). Et0 and Neq were elevated for the mild NPDR group compared to the control and NDR groups (all t > 3.89, P ≤ 0.001); the NDR and control groups did not differ significantly (all t < 0.61, P > 0.55). There were no significant efficiency differences among the groups (F = 1.29, P = 0.29). Neq was correlated significantly with disease duration, microperimetric sensitivity, and Pelli-Robson CS.ConclusionsElevated contrast threshold may be associated with increased intrinsic noise in early-stage diabetic subjects. Results suggest that noise-based CS measurements can provide important information about early neural dysfunction in these individuals.

Combining ODR and Blood Vessel Tracking for Artery-Vein Classification and Analysis in Color Fundus Images.

PurposeThis study aims to develop a fully automated algorithm for artery–vein (A-V) and arteriole-venule classification and to quantify the effect of hypertension on A-V caliber and tortuosity ratios of nonproliferative diabetic retinopathy (NPDR) patients.MethodsWe combine an optical density ratio (ODR) analysis and blood vessel tracking (BVT) algorithm to classify arteries and veins and arterioles and venules. An enhanced blood vessel map and ODR analysis are used to determine the blood vessel source nodes. The whole vessel map is then tracked beginning from the source nodes and classified as vein (venule) or artery (arteriole) using vessel curvature and angle information. Fifty color fundus images from NPDR patients are used to test the algorithm. Sensitivity, specificity, and accuracy metrics are measured to validate the classification method compared to ground truths.ResultsThe combined ODR-BVT method demonstrates 97.06% accuracy in identifying blood vessels as vein or artery. Sensitivity and specificity of A-V identification are 97.58%, 97.81%, and 95.89%, 96.68%, respectively. Comparative analysis revealed that the average A-V caliber and tortuosity ratios of NPDR patients with hypertension have 48% and 15.5% decreases, respectively, compared to that of NPDR patients without hypertension.ConclusionsAutomated A-V classification has been achieved by combined ODR-BVT analysis. Quantitative analysis of color fundus images verified robust performance of the A-V classification. Comparative quantification of A-V caliber and tortuosity ratios provided objective biomarkers to differentiate NPDR groups with and without hypertension.Translational RelevanceAutomated A-V classification can facilitate quantitative analysis of retinal vascular distortions due to diabetic retinopathy and other eye conditions and provide increased sensitivity for early detection of eye diseases.