Stages Of Diabetic Retinopathy Research Articles

Deer Hunting Optimization with 3D-Convolutional Neural Network for Diabetic Retinopathy Classification Model

A retina disease caused by high glucose levels in the blood is called Diabetic Retinopathy (DR) and is the world’s leading cause of blindness. To avoid or delay vision degradation and loss, early diagnosis and treatment are required. As a result, the creation of an automated method for accurate DR identification is essential. For this, in this paper, a 3D-Convolution Neural Network (3D-CNN) with Deer Hunting Optimization (DHO) algorithm is proposed for detecting and classifying DR images. The proposed 3D-CNN-DHO approach includes four phases such as pre-processing, segmentation, feature extraction, and classification. The contrast of the DR image is first improved using a Contrast-Limited Adaptive Histogram Equalization (CLAHE) approach. Subsequently, the threshold-based effective segmentation is carried out. Then, the Resnet50 model is implemented to extract the features from the image. Finally, 3D-CNN-DHO-based classifier model is implemented to categorize the various DR stages. The experiments are carried out in detail and evaluated on the Messidor DR benchmark dataset. The acquired experimental result demonstrated the 3D-CNN-DHO model’s outstanding qualities by achieving optimal specificity, sensitivity, recall, precision, and accuracy.

Reduced serum magnesium is associated with the occurrence of diabetic macular edema in patients with diabetic retinopathy: A retrospective study.

Serum magnesium levels have been reported to reflect the risk of diabetic retinopathy (DR); however, the effect of serum magnesium level on diabetic macular edema (DME) remains unclear. Here, we investigated the association between the serum magnesium levels and DME in patients with DR. Patients with DR were recruited between January 2018 and June 2021. A total of 519 such patients were included in this study. All patients underwent a standardized clinical ophthalmic examination by an experienced ophthalmologist, and an assay was conducted to determine the serum magnesium concentration. Compared with the non-DME group, the DME group had a higher proportion of insulin use and a higher level of serum ischemia-modified albumin and fasting plasma glucose. The serum magnesium and calcium levels were lower in the DME group than in the non-DME group (P < 0.05). Higher magnesium levels were negatively associated with DME after adjustment for relevant covariates. Compared with the participants in the lowest magnesium quartile, those in the fourth quartile showed a significantly lower risk of DME after adjustment [odds ratio (OR), 0.294; 95% confidence interval, 0.153–0.566; P < 0.0001]. Considering the potentially different effects of serum magnesium on the development of DME in patients with DR based on age, DR staging and insulin use, stratified analysis was performed by considering these factors. Among insulin-using patients with non-proliferative DR who were < 66 years of age, those in the third and fourth quartile of serum magnesium were less likely to develop DME than those in the lowest quartile of serum magnesium [OR (95% CI), 0.095 (0.014–0.620), 0.057 (0.011–0.305); P = 0.014, 0.001]. Overall, a higher serum magnesium level was associated with a lower risk of DME in patients with DR. Furthermore, patients with DR who used insulin were more likely to develop DME. Long-term studies on oral magnesium supplements are needed to determine whether maintaining the serum magnesium levels in a higher physiological range can reduce the risk of DME in patients with DR.

Peripapillary vessel density and retinal nerve fiber layer thickness changes in early diabetes retinopathy.

To perform a quantitative analysis of the peripapillary vessel density (VD) and retinal nerve fiber layer (RNFL) thickness changes in patients with early stage of diabetic retinopathy (DR). In this case-control study, swept-source optical coherence tomography angiography (SS-OCTA) imaging was used to examine diabetic and age-matched healthy subjects. The optic disc HD 6×6 mm2 blood flow imaging scan mode was selected. Automatic software was used to measure the peripapillary VD, capillary vessel density (CVD), and RNLF in an optic nerve head (ONH) filed based on the Garway-Heath map. In addition, the correlation between peripapillary VD, CVD, and RNFL was further investigated. The cohort consisted of 32 healthy individuals and 72 patients with diabetes (34 eyes with no DR and 38 eyes with mild-moderate NPDR). Peripapillary VD decreased in the mild-moderate NPDR group compared to the control group in most regions (P<0.05). Peripapillary CVD and RNFL thickness were significantly lower in the mild-moderate NPDR group in the superior temporal (ST) quadrants (P=0.018, P=0.030). In the correlation analysis of each region, the RNFL thickness in the NS region was positively correlated with the peripapillary VD and CVD (r=0.233, P=0.05; r=0.288, P=0.015). In the TI region, the RNFL thickness was positively correlated with the peripapillary CVD (r=0.237, P=0.047). The measurement based on the ONH topographic map may be helpful in detecting functional and structural impairments in DR. The peripapillary VD, CVD and RNFL decrease in early DR, and the RNFL thickness altered in association with the CVD or/and VD in some regions.

Diabetic Retinopathy Classification Using CNN and Hybrid Deep Convolutional Neural Networks

Diabetic Retinopathy (DR) is an eye condition that mainly affects individuals who have diabetes and is one of the important causes of blindness in adults. As the infection progresses, it may lead to permanent loss of vision. Diagnosing diabetic retinopathy manually with the help of an ophthalmologist has been a tedious and a very laborious procedure. This paper not only focuses on diabetic retinopathy detection but also on the analysis of different DR stages, which is performed with the help of Deep Learning (DL) and transfer learning algorithms. CNN, hybrid CNN with ResNet, hybrid CNN with DenseNet are used on a huge dataset with around 3662 train images to automatically detect which stage DR has progressed. Five DR stages, which are 0 (No DR), 1 (Mild DR), 2 (Moderate), 3 (Severe) and 4 (Proliferative DR) are processed in the proposed work. The patient’s eye images are fed as input to the model. The proposed deep learning architectures like CNN, hybrid CNN with ResNet, hybrid CNN with DenseNet 2.1 are used to extract the features of the eye for effective classification. The models achieved an accuracy of 96.22%, 93.18% and 75.61% respectively. The paper concludes with a comparative study of the CNN, hybrid CNN with ResNet, hybrid CNN with DenseNet architectures that highlights hybrid CNN with DenseNet as the perfect deep learning classification model for automated DR detection.

Retinal Oxygen Metabolism in Patients With Type 2 Diabetes and Different Stages of Diabetic Retinopathy.

The aim of this cross-sectional study was to assess retinal oxygen metabolism in patients with type 2 diabetes and different stages of nonproliferative diabetic retinopathy (DR) (n = 67) compared with healthy control subjects (n = 20). Thirty-four patients had no DR, 15 had mild DR, and 18 had moderate to severe DR. Retinal oxygen saturation in arteries and veins was measured using the oxygen module of a retinal vessel analyzer. Total retinal blood flow (TRBF) was measured using a custom-built Doppler optical coherence tomography system. Retinal oxygen extraction was calculated from retinal oxygen saturation and TRBF. Arteriovenous difference in oxygen saturation was highest in healthy subjects (34.9 ± 7.5%), followed by patients with no DR (32.5 ± 6.3%) and moderate to severe DR (30.3 ± 6.5%). The lowest values were found in patients with mild DR (27.3 ± 8.0%, P = 0.010 vs. healthy subjects). TRBF tended to be higher in patients with no DR (40.1 ± 9.2 μL/min) and mild DR (41.8 ± 15.0 μL/min) than in healthy subjects (37.2 ± 5.7 μL/min) and patients with moderate to severe DR (34.6 ± 10.4 μL/min). Retinal oxygen extraction was the highest in healthy subjects (2.24 ± 0.57 μL O2/min), followed by patients with no DR (2.14 ± 0.6 μL O2/min), mild DR (1.90 ± 0.77 μL O2/min), and moderate to severe DR (1.78 ± 0.57 μL O2/min, P = 0.040 vs. healthy subjects). These results indicate that retinal oxygen metabolism is altered in patients with type 2 diabetes. Furthermore, retinal oxygen extraction decreases with increasing severity of DR.

Topical nerve growth factor prevents neurodegenerative and vascular stages of diabetic retinopathy.

Specific and effective preventive treatment for diabetic retinopathy (DR) is presently unavailable, mostly because the early stages of the complication have been, until recently, poorly understood. The recent demonstration that the vascular phase of DR is preceded and possibly caused by the neurodegeneration of retinal ganglion cells suggests that DR could, at least theoretically, be prevented through an early neuroprotective approach. The aims of our study were to clarify the natural history of diabetes-driven retinal neurodegeneration and to verify the possibility to prevent DR using topical nerve growth factor (NGF). The results of the study show that retinal neurodegeneration, characterized by the loss of retinal ganglion cells represents a relatively early phenomenon of diabetes (between 5 and 16 weeks of age), which tends to be self-limiting in the long run. Neurodegeneration is followed by the development of DR-related vascular dysfunctions, as confirmed by the development of acellular capillaries and the loss of retinal pericytes. Both retinal neurodegeneration and subsequent vascular dysfunction can be successfully prevented by topical NGF administration. These findings suggest that: 1) The first stage of DR consists in a self-limiting retinal neurodegeneration 2) The demonstrated effectiveness of topical NGF in the prevention of DR could be rapidly translated into clinical practice.

Metabolomic comparison followed by cross-validation of enzyme-linked immunosorbent assay to reveal potential biomarkers of diabetic retinopathy in Chinese with type 2 diabetes.

PurposeTo identify the biomarkers in the critical period of development in diabetic retinopathy (DR) in Chinese with type 2 diabetes using targeted and untargeted metabolomics, and to explore the feasibility of their clinical applicationMethodsThis case-control study described the differential metabolites between 83 Chinese type 2 diabetes mellitus (T2DM) samples with disease duration ≥ 10 years and 27 controls matched cases. Targeted metabolomics using high-resolution mass spectrometry with liquid chromatography was performed on plasma samples of subjects. The results were compared to our previous untargeted metabolomics study and ELISA was performed to validate the mutual differential metabolites of targeted and untargeted metabolomics on plasma. Multiple linear regression analyses were performed to adjust for the significance of different metabolites between groups.ResultMean age of the subjects was 66.3 years and mean T2DM duration was 16.5 years. By cross-validating with results from previous untargeted metabolomic assays, we found that L-Citrulline (Cit), indoleacetic acid (IAA), 1-methylhistidine (1-MH), phosphatidylcholines (PCs), hexanoylcarnitine, chenodeoxycholic acid (CDCA) and eicosapentaenoic acid (EPA) were the most distinctive metabolites biomarkers to distinguish the severity of DR for two different metabolomic approaches in our study. We mainly found that samples in the DR stage showed lower serum level of Cit and higher serum level of IAA compared with samples in the T2DM stage, while during the progression of diabetic retinopathy, the serum levels of CDCA and EPA in PDR stage were significantly lower than NPDR stage. Among them, 4 differential key metabolites including Cit, IAA, CDCA and EPA were confirmed with ELISA.ConclusionThis is the first study to compare the results of targeted and untargeted metabolomics via liquid chromatography-mass spectrometry to find the serum biomarkers which could reflect the metabolic variations among different stages of DR in Chinese. The progression of DR in Chinese at different critical stages was related to the serum levels of specific differential metabolites, of which there is a significant correlation between DR progression and increased IAA and decreased Cit, hexanoylcarnitine, CDCA, and EPA. However, larger studies are needed to confirm our results. Based on this study, it could be inferred that the accuracy of targeted metabolomics for metabolite expression in serum is to some extent higher than that of untargeted metabolomics.

Correlation between HbA1c Levels and Severity of Diabetic Retinopathy

Background: In recent years, Diabetes Mellitus (DM) has emerged as the world's leading cause of death with the potential to develop micro vascular complications in the form of retinopathy. HbA1c is an indicator to identify hyperglycemia and plays an important role in monitoring the development of complications due to DM. This study is undertaken determine the relationship between HbA1C levels and the severity of diabetic retinopathy in DM patients.&#x0D; Aim: To identify the relationship between HbA1c levels and different stages of diabetic retinopathy.&#x0D; Method: An analytic observational, cross sectional design, using patients’ medical record. Patient data consisted of gender, age, DM duration, HbA1c levels, and stages of diabetic retinopathy. Non parametric correlation Spearman’s rho was chosen for statistical analysis. &#x0D; Result: A total of 72 DM patients consisted of 29 men and 43 women with a mean DM duration 10.4 years. A total of 37 patients were diagnosed with diabetic retinopathy with 30 NPDR respondents (41.7%) and 7 PDR respondents (9.7%). The average HbA1C levels based on the patient's diabetic retinopathy stages, as follows; normal attained 6.49% (SD ± 0.95), NPDR 8.17% (SD ± 1.77), and PDR 8.47% (SD ± 1, 10). Spearman's non-parametric test showed a strong and significant relationship (p

Prediction of a reliable method for the estimation of central corneal thickness in diabetic patients with and without diabetic retinopathy

ABSTRACT Background This study aimed to analyze the central corneal thickness (CCT) in diabetic patients with and without diabetic retinopathy (DR) by investigating the impacts of other CCT factors such as hemoglobin A1c (HbA1c) levels, diabetes mellitus (DM) duration, and the DR stages. The study also compared the results of two measuring devices – anterior segment-optical coherence tomography (AS-OCT) and ultrasound pachymetry (UP). However, the existing research possesses bias in revealing the precise measurement of CCT. Research design and methods The study enrolled 300 participants who were segregated into three equal groups: group A with DR, group B without DR, and the control group. The study tested the following formulated hypothesis, like the correlation between the age, duration, and HbA1c level of diabetic patients with DR and without DR. The effectiveness of the AS-OCT and UP was assessed through statistical analysis. Results The experiment revealed a considerable statistical difference in the formulated hypothesis and observed that AS-OCT had higher efficacy than UP in estimating CCT in all the groups. Conclusions The study recommends the prompt utilization of devices such as AS-OCT to precisely predict CCT. This could greatly benefit DM patients with retinopathy conditions for better decision-making and reliable measures during glaucoma surgery.

A Cross-Sectional Study of Various Imaging and Biochemical Biomarkers in Patients with Diabetic Macular Edema in Different Stages of Diabetic Retinopathy.

PurposeTo compare which imaging and biochemical biomarkers are associated with different stages of diabetic retinopathy (DR) in type 2 diabetes mellitus patients with diabetic macular edema (DME).Patients and MethodsIt was a cross-sectional, observational study that included 100 patients of DME with different stages of DR. Patients were divided into two groups: Group A – DME with non-proliferative diabetic retinopathy (NPDR) and Group B - DME with proliferative diabetic retinopathy (PDR). Group A was further subdivided into three subgroups: A (1) – DME with mild NPDR, A (2) – DME with moderate NPDR, and A (3) – DME with severe NPDR. The primary outcome measure was the association of imaging and biochemical biomarkers with different stages of DR in patients with DME.ResultsOut of 100 patients, Group A (1) had 1, Group A (2) 44, Group A (3) 29, and group: B had 29 patients. As Group A (1) had only one patient, we did not include it in the calculation. The overall mean age of the study population was 54.84+9.87 years, with a male preponderance (76%). The HbA1c levels, serum triglyceride level, serum cholesterol level, and microalbuminuria level showed no significant association with different stages of DR (P>0.05). Still, we found high serum urea levels (p=0.027) in Group B patients. The optical coherence tomography (OCT)-based imaging biomarkers – central subfield thickness (CST), cystoid macular edema (CME), subretinal fluid (SRF), and hyperreflective foci (HRF) – showed no significant association with various stages of DR. The presence of diffuse retinal thickness (DRT) (p=0.04) and the epiretinal membrane (ERM) (p=0.04) showed significant association with Group B patients.ConclusionThe essential biochemical biomarkers such as serum urea levels and DRT and ERM may be considered an important imaging biomarker for the advanced stage of DR.

A Paradigm Shift in the Management Approaches of Proliferative Diabetic Retinopathy: Role of Anti-VEGF Therapy.

Diabetic retinopathy (DR) is considered one of the leading causes of vision loss globally. It principally causes upregulation of pro-angiogenic, proinflammatory, and vascular permeability factors such as vascular endothelial growth factor (VEGF), leading to neovascularisation. The advanced stage of DR or proliferative diabetic retinopathy (PDR) is of more concern, as it leads to vitreous haemorrhage and traction retinal detachment. Various risk factors associated with PDR include hyperglycemia, hypertension, neuropathy, dyslipidemia, anaemia, nephropathy, and retinal complications of drugs used for diabetes. Current management approaches for PDR have been stratified and involve pan-retinal photocoagulation, vitrectomy, and anti-VEGF agents. Given the emerging role of anti-VEGF agents as a favourable adjunct or alternative therapy, they have a critical role in the management of PDR. The review emphasises current management approaches for PDR focusing on anti-VEGF therapy. The review also highlights the risk/benefit evaluation of the various approaches employed for PDR management in various clinical scenarios.

Relationship of proliferative diabetic retinopathy and severe stages of chronic renal failure

Diabetic nephropathy, as a frequent complication in patients with diabetes mellitus (DM), is increasing due to the rapid increase in the prevalence of diabetes, which is considered one of the leading causes of chronic renal failure (CRF). Diabetic retinopathy (DR) and diabetic nephropathy are the two main microvascular complications of DM. Studies show that the prevalence and severity of visual pathology is significantly higher among patients with severe stages of CRF, which is associated with the following risk factors: hypertension, metabolic disorders, uremia, anemia, and the use of anticoagulant therapy. The leading forms of eye pathology in patients with DR and CRF are proliferative DR, macular edema, and vitreous hemorrhage. The main structural changes in the choroid and retina in patients with CRF are the thickness of the choroid, accompanied by a decrease in the density of vessels and the volume of perfusion in the surface capillary layer of the choriocapillaries, which is aggravated with the aggravation of the stage of the disease and is interconnected with impaired renal function. Literature data indicate a positive effect of the hemodialysis procedure on DR. It should be borne in mind that in patients with end-stage chronic renal failure, a hemodialysis session may be accompanied by pain in the eye associated with an increase in blood pressure. Interdisciplinary collaboration between nephrologists and ophthalmologists will ensure improved and adequate treatment of patients with CRF and proliferative DR.

Therapeutic effect of cataract surgery with simultaneous intravitreal injection of aflibercept on diabetic macular edema: An observational study.

This study aimed to investigate the therapeutic effect of cataract surgery along with simultaneous intravitreal injection (IVI) of aflibercept on diabetic macular edema (DME). This cohort study enrolled 106 patients aged >40 years with type 2 diabetes mellitus and DME who received cataract surgery from January 1, 2016, to October 31, 2020. The baseline and mean data of the following parameters were collected: age, sex, glycated hemoglobin level, diabetic retinopathy (DR) grading, previous DR treatments including IVI of anti–vascular endothelial growth factor and pan-retinal photocoagulation, intraocular pressure, use of intraocular pressure-lowering medication, central subfield thickness (CST), and log MAR visual acuity (VA). Patients were categorized into 2 groups based on whether they received aflibercept IVI or not during cataract surgery and were compared using the t test and Fisher exact test for continuous and discrete variables, respectively. Beta coefficient and standard error were calculated using multiple linear regression analysis to identify the explanatory variables predictive of the net change of CST and log MAR VA. There was no difference in the net change in CST (15.24 ± 45.07 μm vs 18.62 ± 33.84 μm, P = .772) and log MAR VA (−0.27 ± 0.29 vs −0.37 ± 0.31, P = .215). Gender, glycated hemoglobin level, aflibercept IVI during cataract surgery, and baseline CST did not interfere with the morphological and functional outcomes of DME in cataract surgery. Older age was significantly and independently associated with a greater net change in log MAR VA. Proliferative DR was significantly and independently associated with a greater net change in CST and log MAR VA. A greater baseline log MAR VA was significantly and independently associated with lower net change in log MAR VA. Simultaneous aflibercept IVI for treating DME may not interfere with the functional and tomographic parameters of cataract surgery relative to cataract surgery alone. Factors influencing the outcomes of patients with DME undergoing cataract surgery are as follows: age, baseline DR staging, and baseline VA. Identifying these factors of DME preoperatively may be an important consideration in preventing it from progressing and for improving the overall visual prognosis.

Association of Predominantly Peripheral Lesions on Ultra-Widefield Imaging and the Risk of Diabetic Retinopathy Worsening Over Time

Ultra-widefield (UWF) imaging improves the ability to identify peripheral diabetic retinopathy (DR) lesions compared with standard imaging. Whether detection of predominantly peripheral lesions (PPLs) better predicts rates of disease worsening over time is unknown. To determine whether PPLs identified on UWF imaging are associated with increased disease worsening beyond the risk associated with baseline Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) score. This cohort study was a prospective, multicenter, longitudinal observational study conducted at 37 US and Canadian sites with 388 participants enrolled between February and December 2015. At baseline and annually through 4 years, 200° UWF-color images were obtained and graded for DRSS at a reading center. Baseline UWF-color and UWF-fluorescein angiography (FA) images were evaluated for the presence of PPL. Data were analyzed from May 2020 to June 2022. Treatment of DR or diabetic macular edema was at investigator discretion. Predominantly peripheral lesions were defined as DR lesions with a greater extent outside vs inside the 7 standard ETDRS fields. Primary outcome was disease worsening defined as worsening 2 steps or more on the DRSS or receipt of DR treatment. Analyses were adjusted for baseline DRSS score and correlation between 2 study eyes of the same participant. Data for 544 study eyes with nonproliferative DR (NPDR) were analyzed (182 [50%] female participants; median age, 62 years; 68% White). The 4-year disease worsening rates were 45% for eyes with baseline mild NPDR, 40% for moderate NPDR, 26% for moderately severe NPDR, and 43% for severe NPDR. Disease worsening was not associated with color PPL at baseline (present vs absent: 38% vs 43%; HR, 0.78; 95% CI, 0.57-1.08; P = .13) but was associated with FA PPL at baseline (present vs absent: 50% vs 31%; HR, 1.72; 95% CI, 1.25-2.36; P < .001). Although no association was identified with color PPL, presence of FA PPL was associated with greater risk of disease worsening over 4 years, independent of baseline DRSS score. These results suggest that use of UWF-FA to evaluate retinas peripheral to standard ETDRS fields may improve the ability to predict disease worsening in NPDR eyes. These findings support use of UWF-FA for future DR staging systems and clinical care to more accurately determine prognosis in NPDR eyes.

Optimal Frequency of Retinopathy Screening in Adolescents With Type 1 Diabetes: Markov Modeling Approach Based on 30 Years of Data.

Current guidelines recommend biennial diabetic retinopathy (DR) screening commencing at the age of 11 years and after 2-5 years' duration of type 1 diabetes. Growing evidence suggests less frequent screening may be feasible. Prospective data were collected from 2,063 youth with type 1 diabetes who were screened two or more times between 1990 and 2019. Baseline (mean ± SD) age was 13.3 ± 1.8 years, HbA1c was 8.6 ± 1.3% (70.1 ± 14.7 mmol/mol), diabetes duration was 5.6 ± 2.8 years, and follow-up time was 4.8 ± 2.8 years. DR was manually graded from 7-field retinal photographs using the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. Markov chain was used to calculate probabilities of DR change over time and hazard ratio (HR) of DR stage transition. The incidence of moderate nonproliferative DR (MNPDR) or worse was 8.6 per 1,000 patient-years. Probabilities of transition to this state after a 3-year interval were from no DR, 1.3%; from minimal DR, 5.1%; and from mild DR, 22.2%, respectively. HRs (95% CIs) for transition per 1% current HbA1c increase were 1.23 (1.16-1.31) from no DR to minimal NPDR, 1.12 (1.03-1.23) from minimal to mild NPDR, and 1.28 (1.13-1.46) from mild to MNPDR or worse. HbA1c alone explained 27% of the transitions between no retinopathy and MNPDR or worse. The addition of diabetes duration into the model increased this value to 31% (P = 0.03). Risk was also increased by female sex and higher attained age. These results support less frequent DR screening in youth with type 1 diabetes without DR and short duration. Although DR progression to advanced stages is generally slow, higher HbA1c greatly accelerates it.

Diabetic retinopathy as a predictor of cardiovascular morbidity and mortality in subjects with type 2 diabetes.

This study aimed to evaluate the predictive value of diabetic retinopathy (DR) and its stages with the incidence of major cardiovascular events and all-cause mortality in type 2 diabetes mellitus (T2DM) persons in our large primary healthcare database from Catalonia (Spain). A retrospective cohort study with pseudo-anonymized routinely collected health data from SIDIAP was conducted from 2008 to 2016. We calculated incidence rates of major cardiovascular events [coronary heart disease (CHD), stroke, or both—macrovascular events] and all-cause mortality for subjects with and without DR and for different stages of DR. The proportional hazards regression analysis was done to assess the probability of occurrence between DR and the study events. About 22,402 T2DM subjects with DR were identified in the database and 196,983 subjects without DR. During the follow-up period among the subjects with DR, we observed the highest incidence of all-cause mortally. In the second place were the macrovascular events among the subjects with DR. In the multivariable analysis, fully adjusted for DR, sex, age, body mass index (BMI), tobacco, duration of T2DM, an antiplatelet or antihypertensive drug, and HbA1c, we observed that subjects with any stage of DR had higher risks for all of the study events, except for stroke. We observed the highest probability of all-cause death events (adjusted hazard ratios, AHRs: 1.34, 95% CI: 1.28; 1.41). In conclusion, our results show that DR is related to CHD, macrovascular events, and all-cause mortality among persons with T2DM.

Effect of troxerutin in counteracting hyperglycemia-induced VEGF upregulation in endothelial cells: a new option to target early stages of diabetic retinopathy?

Diabetic retinopathy (DR), one of the most common complications of diabetes mellitus, is characterized by degeneration of retinal neurons and neoangiogenesis. Until today, the pharmacological approaches for DR are limited and focused on counteracting the end-stage of this neurodegenerative disease, therefore efforts should be carried out to discover novel pharmacological targets useful to prevent DR development. Hyperglycemia is a major risk factor for endothelial dysfunction and vascular complication, which subsequently may trigger neurodegeneration. We previously demonstrated that, in the rat retina, hyperglycemia activates a new molecular cascade implicating, up-stream, protein kinase C βII (PKC βII), which in turn leads to a higher expression of vascular endothelial growth factor (VEGF), via the mRNA-binding Hu-antigen R (HuR) protein. VEGF is a pivotal mediator of neovascularization and a well-known vasopermeability factor. Blocking the increase of VEGF via modulation of this cascade can thus represent a new pharmacological option to prevent DR progression. To this aim, proper in vitro models are crucial for drug discovery, as they allow to better identify promising effective molecules. Considering that endothelial cells are key elements in DR and that hyperglycemia triggers the PKCβII/HuR/VEGF pathway, we set up two distinct in vitro models applying two different stimuli. Namely, human umbilical vein endothelial cells were exposed to phorbol 12-myristate 13-acetate, which mimics diacylglycerol whose synthesis is triggered by diabetic hyperglycemia, while human retinal endothelial cells were treated with high glucose for different times. After selecting the optimal experimental conditions able to determine an increased VEGF production, in search of molecules useful to prevent DR development, we investigated the capability of troxerutin, an antioxidant flavonoid, to counteract not only the rise of VEGF but also the activation of the PKCβII/HuR cascade in both in vitro models. The results show the capability of troxerutin to hinder the hyperglycemia-induced increase in VEGF in both models through PKCβII/HuR pathway modulation. Further, these data confirm the key engagement of this cascade as an early event triggered by hyperglycemia to promote VEGF expression. Finally, the present findings also suggest the potential use of troxerutin as a preventive treatment during the early phases of DR.

Application of the Full-Width-at-Half-Maximum Image Segmentation Method to Analyse Retinal Vascular Changes in Patients with Diabetic Retinopathy.

This study used spectral domain optical coherence tomography (SD-OCT) and full-width-at-half-maximum image segmentation to investigate the morphological changes of retinal blood vessels in patients with diabetic retinopathy (DR). Seventy-five patients with type 2 diabetes mellitus (T2DM) without DR and 65 patients with DR were studied. Vascular images of superior temporal region B of the retina were obtained by SD-OCT. The edges of retinal vessels were identified by the full-width-at-half-maximum image segmentation method. The lumen diameter, wall thickness (WT), wall cross-sectional area (WCSA), and wall-to-lumen ratio (WLR) were investigated. We found that, compared with the no diabetic retinopathy (NDR) group, patients in the DR group had an increased retinal arteriolar lumen diameter (RALD), retinal arteriolar outer diameter (RAOD), and WT (128.80 μm versus 104.88 μm; 147.01 μm versus 135.60 μm; 18.29 μm versus 15.26 μm, P < 0.05, respectively). The retinal venular lumen diameter (RVLD), retinal venular outer diameter (RVOD), and venular WT in the DR group were also increased (146.17 μm versus 133.66 μm; 180.20 μm versus 156.43 μm; 17.01 μm versus 11.38 μm, P < 0.05, respectively). The morphological changes in retinal vessels were significantly correlated with DR stage. In conclusion, in diabetic patients with DR, both retinal arteries and veins are widened and exhibit increased vascular thickness.

The Role of Medical Image Modalities and AI in the Early Detection, Diagnosis and Grading of Retinal Diseases: A Survey

Traditional dilated ophthalmoscopy can reveal diseases, such as age-related macular degeneration (AMD), diabetic retinopathy (DR), diabetic macular edema (DME), retinal tear, epiretinal membrane, macular hole, retinal detachment, retinitis pigmentosa, retinal vein occlusion (RVO), and retinal artery occlusion (RAO). Among these diseases, AMD and DR are the major causes of progressive vision loss, while the latter is recognized as a world-wide epidemic. Advances in retinal imaging have improved the diagnosis and management of DR and AMD. In this review article, we focus on the variable imaging modalities for accurate diagnosis, early detection, and staging of both AMD and DR. In addition, the role of artificial intelligence (AI) in providing automated detection, diagnosis, and staging of these diseases will be surveyed. Furthermore, current works are summarized and discussed. Finally, projected future trends are outlined. The work done on this survey indicates the effective role of AI in the early detection, diagnosis, and staging of DR and/or AMD. In the future, more AI solutions will be presented that hold promise for clinical applications.

Prevalence, characteristics and risk factors of diabetic retinopathy in type 2 diabetes mellitus patients in Jordan: a cross-sectional study.

ObjectivesTo measure the prevalence of diabetic retinopathy in patients with type 2 diabetes, to define their characteristics, and identify the associated risk factors.MethodsWe performed a cross sectional study of 1316 adult patients with type 2 diabetes mellitus who attended an ophthalmology clinic. Demographic, clinical, and laboratory data were analyzed. Diabetic retinopathy (DR) was diagnosed using a complete ophthalmic evaluation, including a fundic examination. Two regression models were constructed to identify the risk factors associated with DR and the parameters associated with the stage of retinopathy.ResultsMen accounted for 774 (58.8%) of the participants. The prevalence of DR was 28.2% (371 participants). DR was significantly more common in participants who were ≥60 years old, were women, had had diabetes for >10 years, were taking insulin, were not taking metformin, had a body mass index >30 kg/m2, were current smokers, or had a history of hypertension. Advanced stages of DR were more common in participants in the later stages of nephropathy and with albuminuria.ConclusionsPoor glycemic control, smoking, and advanced diabetic kidney disease are most closely associated with retinopathy. Further longitudinal studies are necessary to identify the mechanisms underlying these relationships and to guide community-based interventions.