Generation of autoantibodies against glycated fibrinogen: Role in diabetic nephropathy and retinopathy.

The process of glycation, characterized by the non-enzymatic reaction between sugars and free amino groups on biomolecules, is a key contributor to the development and progression of both microvascular and macrovascular complications associated with diabetes, particularly due to persistent hyperglycemia. This glycation process gives rise to advanced glycation end products (AGEs), which play a central role in the pathophysiology of diabetes complications, including nephropathy. The d-ribose-mediated glycation of fibrinogen plays a central role in the pathogenesis of diabetes nephropathy (DN) and retinopathy (DR) by the generation and accumulation of advanced glycation end products (AGEs). Glycated fibrinogen with d-ribose (Rb-gly-Fb) induces structural changes that trigger an autoimmune response by generating and exposing neoepitopes on fibrinogen molecules. The present research is designed to investigate the prevalence of autoantibodies against Rb-gly-Fb in individuals with type 2 diabetes mellitus (T2DM), DN & DR. Direct binding ELISA was used to test the binding affinity of autoantibodies from patients' sera against Rb-gly-Fb and competitive ELISA was used to confirm the direct binding findings by checking the bindings of isolated IgG against Rb-gly-Fb and its native conformer. In comparison to healthy subjects, 32% of T2DM, 67% of DN and 57.85% of DR patients' samples demonstrated a strong binding affinity towards Rb-gly-Fb. Both native and Rb-gly-Fb binding by healthy subjects (HS) sera were non-significant (p > 0.05). Furthermore, the early, intermediate, and end products of glycation have been assessed through biochemical and physicochemical analysis. The biochemical markers in the patient groups were also significant (p < 0.05) in comparison to the HS group. This study not only establishes the prevalence of autoantibodies against d-ribose glycated fibrinogen in DN but also highlights the potential of glycated fibrinogen as a biomarker for the detection of DN and/or DR. These insights may open new avenues for research into novel therapeutic strategies and the prevention of diabetes-related nephropathy and retinopathy.

SB431542 partially inhibits high glucose-induced EMT by restoring mitochondrial homeostasis in RPE cells.

BACKGROUND: The epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells participated in the development of retinal fibrosis. SB431542 is a small molecule inhibitor with inhibitory effects on the ALK4, ALK5 and ALK7. Our study aimed to explore the effect of SB431542 on the EMT of RPE cells and to provide new ideas for the treatment of retinal fibrosis. METHODS: We performed fundus fluorescein angiography, optical coherence tomography and hematoxylin-eosin staining in vivo to observe the effect of SB431542 on choroidal neovascularization (CNV)-induced retinopathy. The proliferation, migration, cytoskeleton, adhesion, reactive oxygen species (ROS), mitochondrial morphology and membrane potential of RPE cells were observed in vitro through fluorescein diacetate staining, Cell Counting Kit-8 experiment, wound healing assay, phalloidin staining, immunofluorescence, MitoSOX, DCFH-DA, MitoTracker and JC-10 staining. Western blot, reverse transcription quantitative and immunofluorescence were used to detect the expression of EMT-related markers, pERK1/2, pGSK3ß and ß-catenin. RESULTS: SB431542 significantly alleviated retinopathy in the CNV model. The proliferation, migration and adhesion in RPE cells decreased to a certain extent in SB431542 treatment. SB431542 partially normalized the structure of RPE cells. The expression levels of E-cadherin increased, while the expression levels of laminin and N-cadherin decreased with SB431542 treatment. SB431542 reduced the production of total ROS, mitochondrial SOX and recovered the mitochondrial membrane potential to a certain degree. In addition, our study showed that SB431542 downregulated the phosphorylation of ERK1/2, GSK3ß and the expression of ß-catenin. CONCLUSION: SB431542 improved EMT in RPE cells by maintaining mitochondrial homeostasis via the ERK1/2 and GSK3ß/ß-catenin pathways. Video Abstract SB431542 inhibits EMT in RPE cells under high glucose conditions.

No causal association between serum vitamin D levels and diabetes retinopathy: A Mendelian randomization analysis.

BACKGROUND AND AIM: Diabetes retinopathy (DR) is a common microvascular complication of diabetes, and it is the main cause of global vision loss. The current observational research results show that the causal relationship between Vitamin D and DR is still controversial. Therefore, we conducted a Mendelian randomization study to determine the potential causal relationship between serum 25-hydroxyvitamin D 25(OH)D and DR. METHODS AND RESULTS: In this study, we selected aggregated data on serum 25(OH)D levels (GWAS ID: ebi-a-GCST90000615) and DR (GWAS ID: finn-b-DM_RETINOPATHY) from a large-scale GWAS database. Then use MR analysis to evaluate the possible causal relationship between them. We mainly use inverse variance weighted (IVW), supplemented by MR Egger and weighted median methods. Sensitivity analysis is also used to ensure the stability of the results, such as Cochran's Q-test, MR-PRESSO, MR-Egger interception test, and retention method. The MR analysis results showed that there was no significant causal relationship between 25(OH)D and DR (OR = 1.0128, 95%CI=(0.9593,1.0693), P = 0.6447); Similarly, there was no significant causal relationship between DR and serum 25 (OH) D levels (OR = 0.9900, 95% CI=(0.9758,1.0045), P = 0.1771). CONCLUSION: Our study found no significant causal relationship between serum 25(OH)D levels and DR, and vice versa. A larger sample size randomized controlled trial is needed to further reveal its potential causal relationship.

Improving diabetic retinopathy screening at the point of care: integrating telemedicine to overcome current challenges.

OBJECTIVE: To investigate the utility of point of care screening of diabetic retinopathy (DR) and the impact of a telemedicine program to overcome current challenges. METHODS: This was a retrospective study on people with type 2 diabetes mellitus (T2DM) who were screened for DR using the single-field non-mydriatic fundus photography at the point of care during routine follow-up visits at endocrinology clinic. Retinal images were uploaded and sent to a retina specialist for review. Reports indicating retinopathy status and the need for direct retinal examination were transmitted back to the endocrinology clinic. All patients were informed about DR status and, if needed, referred to the retina specialist for direct retinal examination. RESULTS: Of the 1159 individuals screened for DR, 417 persons (35.98%) were screen-positive and referred to the retina specialist for direct retinal examination. A total of 121 individuals (29.01%) underwent direct retinal examination by the specialist. Diabetes macular edema (DME) was detected in 12.1%. In addition, non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) were detected in 53.4% and 2.6% of the patients, respectively. CONCLUSION: Integrating DR screening program at the point of care at the secondary care services improves the rate of DR screening as well as detection of sight threatening retinopathy and provides the opportunity for timely intervention in order to prevent advanced retinopathy in people with T2DM.

A case report: co-occurrence of probable Vogt-Koyanagi-Harada disease and diabetic retinopathy.

BACKGROUND: Bilateral retinal detachment and choroidal detachment in a patient are rare occurrences. The presence of bilateral diabetic retinopathy (DR) in such a case is even rarer and complicates the condition. CASE PRESENTATION: In this study, we document a case of unconventional VKH. Manifestations in this patient included intense peripheral retinal detachment and choroidal detachment, along with vitreous opacities akin to cotton wool spots, concurrent with DR. The diagnosis was considered as probable VKH with DR. Treatment according to VKH protocols, including high-dose corticosteroids, yielded positive results. CONCLUSIONS: VKH can co-occurrence with DR. VKH manifestations vary, and early, aggressive, and long-term treatment is essential. The complexity of treatment increases with concurrent DR, necessitating the use of immunosuppressants.

Ferroptosis contributes to diabetes-induced visual pathway neuronal damage via iron accumulation and GPX4 inactivation.

The damage of the diabetic visual pathway is one of the main causes of blindness in diabetic patients. Visual pathways include anatomic parts from the retina to the occipital lobe. This study investigated the involvement of ferroptosis, a planned cell death brought on by the buildup of free iron in cells, in the impairment of visual pathways in diabetes mellitus. Streptozotocin (STZ) was used to construct a diabetic rat model. Pathological and ultrastructural changes of the occipital lobe, retina, and optic nerve were observed by Hematoxylin-Eosin (HE) staining and transmission electron microscopy (TEM). The expressions of Neuronal nuclei (NeuN), Glial fibrillary acidic protein (GFAP), and Glutathione Peroxidase 4 (GPX4) in the occipital lobe and retina were detected by immunofluorescence, and Western Blotting was used to identify the NeuN GFAP and GPX4 expressions in the occipital lobe. Iron content in the occipital lobe and retina was detected by Iron Assay Kit. The success rate of the diabetic rat model was 93.3%. In the diabetic group, the cells of the occipital lobe and retina were arranged disorderly, and the boundaries were unclear. The membrane of the occipital lobe, retina, and optic nerve was broken, some vacuoles were observed, mitochondrial morphology was changed, swelling was observed, and the mitochondrial ridge disappeared. There was a large increase in GFAP expression and iron concentration and a significant decrease in the expression of NeuN, and GPX4 in the retina and occipital lobe. Ferroptosis plays an important role in visual pathway damage in diabetes, and GPX4 regulates this process.

Ischemia modified albumin as a useful marker for diagnoses and management of diabetic retinopathy.

Objectives: Ischemia modified albumin (IMA) may aid in the early detection and management of diabetic retinopathy (DR). In this study, we examined the relationship between IMA and DR, and the effect of intravitreal anti-vascular endothelial growth factor (anti-VEGF) on IMA levels in patients with DR. Methods: This Quasi-experimental study was conducted from March-December 2018 at a Al-Ibrahim Eye Hospital in Karachi, Pakistan. Adult patients (age ≥ 18 year) with Type-2 diabetes mellitus (T2DM) presenting to the Diabetic Clinic were categorized as control (Group-A n=30: DM without DR) or case (Group-B n=59: DM with DR). Patients in Group-B received an intravitreal injection of bevacizumab (anti-VEGF). Visual acuity, retinoscopy and serum IMA were recorded at baseline and at a 30-day follow-up for both groups. Results: A significant drop in IMA levels was seen one month after bevacizumab (IMA baseline: 1590.82±121.22 and follow up: 940.8±91.26; p<0.01) in Group-B subjects. Visual acuity (VA) of patient in Group-B also improved one month after bevacizumab injection in both eyes (p<0.001). Whereas, the IMA levels in Group-A showed an upward rising trend after one month (baseline 448.80±22.4ng/ml and follow up 522.21±33.15 ng/ml; p>0.05) indicating disease progression. Conclusion: Ischemia modified albumin may be used as an effective and novel screening biomarker for assessing oxidative stress associated with DR, and to quantify response to and prognosis after intravitreal bevacizumab injection for DR.

HbA1c variability as an independent predictor of diabetes retinopathy in patients with type 2 diabetes.

AIMS: To evaluate the association of both mean HbA1c and HbA1c variability with DR development in patients with type 2 diabetes. METHODS: Patients with type 2 diabetes who received dilated funduscopic examination annually and who underwent at least 2-year follow-up were included in this longitudinal study. Subjects were excluded if they took less than five HbA1c measurements during the follow-up period. HbA1C variability was expressed as A1c-SD, and the mean of HbA1c (A1c-Mean) was calculated. In addition, medical history and clinical data of all subjects were collected and analyzed. According to A1c-Mean above or below the value 7% and A1c-SD above or below the population mean value 0.76%, subjects were divided into four quartiles: Q1(A1c-Mean < 7%, A1c-SD < 0.76%); Q2(A1c-Mean < 7%, A1c-SD ≥ 0.76%); Q3(A1c-Mean ≥ 7%, A1c-SD < 0.76%); Q4(A1c-Mean ≥ 7%, A1c-SD ≥ 0.76%). RESULTS: 3152 participants were included in the study analysis with a median follow-up period of 3.95 years (2-5 years), 17.6% (n = 556) were found to have DR, and these patients also had higher HbA1c levels (P < 0.001). Linear mixed-effect models were performed after adjusting for the characteristics of participants and the results showed that HbA1c variability is an independent risk factor for DR. Cox regression revealed that patients in Q4 group had the highest DR prevalence (HR = 1.624, P < 0.001) while Q1 group had the lowest. In addition, patients in Q2 group (HR = 1.429, P = 0.006) had a higher risk of DR than those in Q3 group (HR = 1.334, P < 0.001). CONCLUSIONS: HbA1c variability is an independent predictor of DR in patients with type 2 diabetes in Asia. It may play a greater role in DR development than mean HbA1c does when the mean value of HbA1c variability index is above 0.75%, indicating that aggressive A1c lowering strategies may, in fact, contribute excessively to risk of DR in patients with type 2 diabetes; steady decline of A1c should be taken into consideration.

Epigallocatechin-3-gallate stimulates autophagy and reduces apoptosis levels in retinal Müller cells under high-glucose conditions.

Retinal neurodegeneration is an early feature in the pathogenesis of diabetic retinopathy (DR). Autophagy is an intracellular catabolic process involved in protein and organelle degradation that has been linked in DR. Epigallocatechin gallate (EGCG) is a major polyphenol in green tea that has beneficial effects in diabetic. however, it is not currently known whether EGCG can regulate Müller cell autophagy. Here, we showed that EGCG increased autophagy by promoting the formation of autophagosomes, increasing lysosomal acidification, and stimulating autophagic flux in Müller cells, while high glucose (HG) induced a decrease in autophagy and an increase in apoptosis. However, retinal Müller cells in HG treated with EGCG showed autophagy machinery activation and reestablishment of cargo degradation, protecting the cells from apoptosis. EGCG could increase the ability of cells to proliferate by increasing autophagy. In an experimental model of diabetic retinopathy, EGCG reduced the reactive gliosis of Müller cells and decreased retinal damage. These results highlight that HG downregulates autophagy and accumulates P62 cargo due to lysosomal dysfunction and then increases apoptosis, which was reversed by treatment with EGCG. This finding might be valuable for developing a novel therapeutic strategy to treat DR.

Pemafibrate Protects Against Retinal Dysfunction in a Murine Model of Diabetic Retinopathy.

Diabetic retinopathy (DR) is one of the leading causes of blindness globally. Retinal neuronal abnormalities occur in the early stage in DR. Therefore, maintaining retinal neuronal activity in DR may prevent vision loss. Previously, pemafibrate, a novel selective peroxisome proliferator-activated receptor alpha modulator, was suggested as a promising drug in hypertriglyceridemia. However, the role of pemafibrate remains obscure in DR. Therefore, we aimed to unravel systemic and retinal changes by pemafibrate in diabetes. Adult mice were intraperitoneally injected with streptozotocin (STZ) to induce diabetes. After STZ injection, diet supplemented with pemafibrate was given to STZ-induced diabetic mice for 12 weeks. During the experiment period, body weight and blood glucose levels were examined. Electroretinography was performed to check the retinal neural function. After sacrifice, the retina, liver, and blood samples were subjected to molecular analyses. We found pemafibrate mildly improved blood glucose level as well as lipid metabolism, boosted liver function, increased serum fibroblast growth factor21 level, restored retinal functional deficits, and increased retinal synaptophysin protein expression in STZ-induced diabetic mice. Our present data suggest a promising pemafibrate therapy for the prevention of early DR by improving systemic metabolism and protecting retinal function.

Pemafibrate Prevents Retinal Pathological Neovascularization by Increasing FGF21 Level in a Murine Oxygen-Induced Retinopathy Model.

Large-scale clinical trials, such as the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) and the Action to Control Cardiovascular Risk in Diabetes (ACCORD) studies, have shown that the administration of fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARα) agonist, suppresses the progression of diabetic retinopathy. In this paper, we reveal a therapeutic effect of a selective PPARα modulator (SPPARMα), pemafibrate, against pathological angiogenesis in murine models of retinopathy. Oxygen-induced retinopathy (OIR) was induced in C57BL/6J mice by exposure to 85% oxygen from postnatal day eight (P8) for 72 h. Vehicle, pemafibrate or fenofibrate was administrated by oral gavage from P12 to P16 daily. Administration of pemafibrate, but not fenofibrate, significantly reduced pathological angiogenesis in OIR. After oral pemafibrate administration, expression levels of downstream PPARα targets such as acyl-CoA oxidase 1 (Acox1), fatty acid binding protein 4 (Fabp4), and fibroblast growth factor 21 (Fgf21) were significantly increased in the liver but not in the retina. A significant increase in plasma FGF21 and reduced retinal hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor A (Vegfa) were also observed after this treatment. In an in vitro HIF-luciferase assay, a long-acting FGF21 analogue, but not pemafibrate, suppressed HIF activity. These data indicate that SPPARMα pemafibrate administration may prevent retinal pathological neovascularization by upregulating FGF21 in the liver.

The KL-VS polymorphism of KLOTHO gene is protective against retinopathy incidence in patients with type 1 diabetes.

BACKGROUND AND AIMS: KLOTHO is an anti-ageing circulating hormone involved in insulin signaling, inflammation and vascular homeostasis through its protective effects on the endothelium and antioxidant actions. The common functional "KL-VS" variant of the KLOTHO gene is reproducibly associated with longevity in humans. Large number of studies have evaluated close relationship between KLOTHO protein and diabetes but the association between KL-VS variant and retinopathy in type 1 diabetes mellitus (T1D) is unknown. Therefore, in the present study we examined the association between the KL-VS polymorphism and the risk of diabetic retinopathy (DR) in patients with T1D. METHODS: We examined 400 patients with T1D and 350 healthy age-matched controls. The analysis concerned KL-VS polymorphism along with the levels of serum inflammatory (CRP, TNF-α) and anti-inflammatory (IL-10) markers, pro-angiogenic (angiogenin) and anti-angiogenic interferon gamma-induced protein 10 (IP-10) factors as well as adhesion molecules (ICAM-1, ICAM-3). RESULTS: We did not find significant association between T1D and KL-VS alleles. However, we observed that the incidence of KL-VS genotype is lower in a group with retinopathy in comparison to diabetic patients without this complication. Moreover, we established that KL-VS carriers had the lowest levels of inflammatory markers, pro-angiogenic factors and adhesion molecules. Simultaneously, the KL-VS carriers had increased serum levels of anti-inflammatory and anti-angiogenic cytokines than holders bearing wild type genotype. CONCLUSIONS: In conclusion, the findings of our studies suggest that the functional KL-VS variant of the KLOTHO gene protects against the development of retinopathy in patients with T1D.

[Study of Resting-state Functional Magnetic Resonance Imaging of T2DR].

OBJECTIVES: To explore the changes and meaning of bilateral posterior cingulate cortex, hippocampus, precuneus, posterior cerebellum lobe to all the other parts of the whole brain for T2DM and T2DR patients. METHODS: The differences of functional connectivity strengthen expressed were calculated and analyzed between seed points to all the other parts of the whole brain after rs-fMRI scan by two sample t-test. Also The correlations of the functional connectivity with clinical parameters were discussed. RESULTS: The functional connectivity had changed between some seed points and other brain regions comparing T2DM to controls and T2DR to T2DM. The changed functional connectivity were also correlated with clinical parameters. CONCLUSIONS: The changed brain regions of T2DM and T2DR were relevant to emotion, memory, cognitive and visual control.

Lactate Transport and Receptor Actions in Retina: Potential Roles in Retinal Function and Disease.

In retina, like in brain, lactate equilibrates across cell membranes via monocarboxylate transporters and in the extracellular space by diffusion, forming a basis for the action of lactate as a transmitter of metabolic signals. In the present paper, we argue that the lactate receptor GPR81, also known as HCAR1, may contribute importantly to the control of retinal cell functions in health and disease. GPR81, a G-protein coupled receptor, is known to downregulate cAMP both in adipose and nervous tissue. The receptor also acts through other down-stream mechanisms to control functions, such as excitability, metabolism and inflammation. Recent publications predict effects of the lactate receptor on neurodegeneration. Neurodegenerative diseases in retina, where the retinal ganglion cells die, notably glaucoma and diabetic retinopathy, may be linked to disturbed lactate homeostasis. Pilot studies reveal high GPR81 mRNA in retina and indicate GPR81 localization in Müller cells and retinal ganglion cells. Moreover, monocarboxylate transporters are expressed in retinal cells. We envision that lactate receptors and transporters could be useful future targets of novel therapeutic strategies to protect neurons and prevent or counteract glaucoma as well as other retinal diseases.

Effect of propylene glycol mannate sulfate on non-proliferative diabetic retinopathy.

PURPOSE: To evaluate the effect of propylene glycol mannate sulfate (PGMS) on retinopathy in non-proliferative diabetic patients. METHODS: Eighty patients (111 eyes) with non-proliferative diabetic retinopathy were selected and retrospectively analyzed. Patients were divided into a control group (40 cases, 56 eyes) and an experimental group (40 cases, 55 eyes) using a random number table method. The control group continued had routine blood glucose management, while the experimental group received PGMS 100 mg additionally TID for 60 days. Changes in visual acuity, fundus conditions including hemorrhage points and exudation in each quadrant, and non-perfusion area were revealed through fundus angiography before and after the treatment period. RESULTS: After PGMS treatment, the experimental group demonstrated significant improvements compared to the control group in terms of eyesight improvement (P=0.002), the macular edema and macular retinal thickness (P=0.008). The total clinical efficacy rate of the experimental group was 67.86%, which was higher than 38.18% of the control group (P=0.032). Notably, there was a significant reduction in macular hemorrhage and hard extrusion. CONCLUSION: Oral administration of PGMS is an effective treatment for non-proliferative diabetic retinopathy.

A Narrative Review of the Advances in Screening Methods for Diabetic Retinopathy: Enhancing Early Detection and Vision Preservation.

Diabetes mellitus (DM) is putting a great burden worldwide. This rise in DM cases, both type 1 and 2, significantly impacts public health. India has grappled with a diabetes epidemic for several years, leading to many misdiagnosed and untreated diabetes cases. Diabetes remains a significant factor in adult-onset blindness despite improvements in diabetes management. This increases the danger of diabetic retinopathy (DR) with permanent loss of sight for those affected. The screening for DR aims to identify those persons with complications arising from diabetes or DR, which could potentially result in blindness, so that treatment can be started immediately and blindness can be avoided. A comprehensive health system approach is required to ensure that the public sector in India effectively screens for DR. Improving patient outcomes and avoiding visual loss depends significantly on early identification and treatment. This article discusses the actions that should be implemented to establish a national effort for systematic DR screening. It also highlights the importance of screening in DR and its impact on treatment effectiveness. Regular screenings enable the early detection of retinopathy, allowing for timely intervention and treatment. Early screening helps prevent complications associated with DR, such as macular edema or retinal detachment. Screening also assists healthcare providers in planning, optimizing treatment approaches, and monitoring treatment effectiveness. Meanwhile, early intervention is essential for enhancing treatment outcomes, thus enhancing the chances of preserving vision and preventing further progression of the disease. This helps in improving the overall management of this sight-threatening complication.

Development and external validation of a predictive model for type 2 diabetic retinopathy.

Diabetes retinopathy (DR) is a critical clinical disease with that causes irreversible visual damage in adults, and may even lead to permanent blindness in serious cases. Early identification and treatment of DR is critical. Our aim was to train and externally validate a prediction nomogram for early prediction of DR. 2381 patients with type 2 diabetes mellitus (T2DM) were retrospective study from the First Affiliated Hospital of Xinjiang Medical University in Xinjiang, China, hospitalised between Jan 1, 2019 and Jun 30, 2022. 962 patients with T2DM from the Suzhou BenQ Hospital in Jiangsu, China hospitalised between Jul 1, 2020 to Jun 30, 2022 were considered for external validation. The least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression was performed to identify independent predictors and establish a nomogram to predict the occurrence of DR. The performance of the nomogram was evaluated using a receiver operating characteristic curve (ROC), a calibration curve, and decision curve analysis (DCA). Neutrophil, 25-hydroxyvitamin D3 [25(OH)D3], Duration of T2DM, hemoglobin A1c (HbA1c), and Apolipoprotein A1 (ApoA1) were used to establish a nomogram model for predicting the risk of DR. In the development and external validation groups, the areas under the curve of the nomogram constructed from the above five factors were 0.834 (95%CI 0.820-0.849) and 0.851 (95%CI 0.829-0.874), respectively. The nomogram demonstrated excellent performance in the calibration curve and DCA. This research has developed and externally verified that the nomograph model shows a good predictive ability in assessing DR risk in people with type 2 diabetes. The application of this model will help clinicians to intervene early, thus effectively reducing the incidence rate and mortality of DR in the future, and has far-reaching significance in improving the long-term health prognosis of diabetes patients.

CSANet: a lightweight channel and spatial attention neural network for grading diabetic retinopathy with optical coherence tomography angiography.

Background: Diabetic retinopathy (DR) is one of the most common eye diseases. Convolutional neural networks (CNNs) have proven to be a powerful tool for learning DR features; however, accurate DR grading remains challenging due to the small lesions in optical coherence tomography angiography (OCTA) images and the small number of samples. Methods: In this article, we developed a novel deep-learning framework to achieve the fine-grained classification of DR; that is, the lightweight channel and spatial attention network (CSANet). Our CSANet comprises two modules: the baseline model, and the hybrid attention module (HAM) based on spatial attention and channel attention. The spatial attention module is used to mine small lesions and obtain a set of spatial position weights to address the problem of small lesions being ignored during the convolution process. The channel attention module uses a set of channel weights to focus on useful features and suppress irrelevant features. Results: The extensive experimental results for the OCTA-DR and diabetic retinopathy analysis challenge (DRAC) 2022 data sets showed that the CSANet achieved state-of-the-art DR grading results, showing the effectiveness of the proposed model. The CSANet had an accuracy rate of 97.41% for the OCTA-DR data set and 85.71% for the DRAC 2022 data set. Conclusions: Extensive experiments using the OCTA-DR and DRAC 2022 data sets showed that the proposed model effectively mitigated the problems of mutual confusion between DRs of different severity and small lesions being neglected in the convolution process, and thus improved the accuracy of DR classification.

5-Bromo-3,4-dihydroxybenzaldehyde stabilizes diabetic retinal neurovascular units by inhibiting the inflammatory microenvironment.

BACKGROUND: Diabetic retinopathy (DR) is a leading cause of blindness characterized by damage to the retinal neurovascular unit, which is caused by hyperglycemia-induced metabolic and inflammatory responses. 5-Bromo-3,4-dihydroxybenzaldehyde (BDB) is a compound derived from marine red algae and known for its anti-inflammatory effects. METHODS: This study aimed to investigate the potential protective effects of BDB on DR using primary human retinal vascular endothelial cells and retinal tissue explants. The analysis involved assessing vascular integrity, expression of tight junction protein, hyperglycemia-induced permeability, and retinal ganglion cell (RGC) apoptosis. The protective effect of BDB in maintaining the diabetic retinal neurovascular units was verified using type 1 diabetic mouse models. Additionally, the inhibitory effect of BDB on the levels of inflammatory cytokines TNF-α, IL-1ß, and IL-6 were examined. RESULTS: In vitro experiments revealed that BDB promoted vascular integrity, inhibited the transcription of pro-inflammatory factors, and alleviated hyperglycemia-induced permeability. BDB also protected RGC from hyperglycemia-induced apoptosis. In diabetic mice models, BDB treatment maintained the integrity of diabetic retinal neurovascular units and inhibited the secretion of TNF-α, IL-1ß, and IL-6. CONCLUSION: BDB demonstrated a protective effect on DR by inhibiting the secretion of inflammatory factors, suggesting its potential as a therapeutic agent for the treatment of DR. Further research is warranted to validate its safety and efficacy for clinical application.

Variability in Grading Diabetic Retinopathy Using Retinal Photography and Its Comparison with an Automated Deep Learning Diabetic Retinopathy Screening Software.

BACKGROUND: Diabetic retinopathy (DR) screening using colour retinal photographs is cost-effective and time-efficient. In real-world clinical settings, DR severity is frequently graded by individuals of different expertise levels. We aim to determine the agreement in DR severity grading between human graders of varying expertise and an automated deep learning DR screening software (ADLS). METHODS: Using the International Clinical DR Disease Severity Scale, two hundred macula-centred fundus photographs were graded by retinal specialists, ophthalmology residents, family medicine physicians, medical students, and the ADLS. Based on referral urgency, referral grading was divided into no referral, non-urgent referral, and urgent referral to an ophthalmologist. Inter-observer and intra-group variations were analysed using Gwet's agreement coefficient, and the performance of ADLS was evaluated using sensitivity and specificity. RESULTS: The agreement coefficient for inter-observer and intra-group variability ranged from fair to very good, and moderate to good, respectively. The ADLS showed a high area under curve of 0.879, 0.714, and 0.836 for non-referable DR, non-urgent referable DR, and urgent referable DR, respectively, with varying sensitivity and specificity values. CONCLUSION: Inter-observer and intra-group agreements among human graders vary widely, but ADLS is a reliable and reasonably sensitive tool for mass screening to detect referable DR and urgent referable DR.