Development Of Retinopathy Research Articles

Association of SDF-1-3' Gene A Variant with Diabetic Retinopathy in the Hungarian Population.

We investigated the association between the SDF-1-3' (c801G > A) variant and the development of diabetic macular edema (DME) or proliferative diabetic retinopathy (PDR) in a Hungarian cohort. SDF-1-3' (c801G > A) was genotyped in 103 patients with diabetic retinopathy and 31 age- and sex-matched non-diabetic controls. Central retinal and choroidal thickness was measured by swept-source optical coherence tomography. The distribution of heterozygous and homozygous SDF-1-3' (c801G > A) genotypes was similar in diabetic and control subjects. The SDF-3'(c801AA) genotype was associated with DME (n = 94 eyes, allele distribution p = 0.006, genotype distribution p = 0.01 OR: 2.48, 95% CL: 1.21-5.08) in both univariable and multivariable modelling, independent of duration and type of diabetes, HbA1C, hypertension and microalbuminuria (p = 0.03). DME occurred earlier in patients carrying the SDF-1 (c801A) allele (Kaplan-Meier analysis, log-rank test p = 0.02). A marginally significant association was found between the presence of the SDF-1 (c801A) allele and the development of PDR (n = 89 eyes, p = 0.06). The SDF-1-3' (c801A) allele also showed a correlation with central retinal (p = 0.006) and choroidal (p = 0.08) thickness. SDF-1-3' (c801G > A) is involved in the development of macular complications in DM independent of critical clinical factors, suggesting that SDF-1 may be a future therapeutic target for high-risk patients, especially those carrying the SDF-1 (c801A) allele.

Incidence and progression of diabetic retinopathy in patients treated with glucagon-like peptide-1 receptor agonists versus sodium-glucose cotransporter 2 inhibitors: A population-based cohort study.

Glucagon-like peptide 1 receptor agonists (GLP1RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) are both recommended for patients with diabetes, yet their effects on the development or progression of diabetic retinopathy (DR) are largely unknown. In this retrospective cohort study, data were collected from a nationwide database. Patients with diabetes who initiated treatment with a GLP1RA or SGLT2i between 1 May 2016 and 31 December 2017, were identified. Patients were divided into those with or without a previous diagnosis of DR and then categorized into the GLP1RA and the SGLT2i groups according to drug use. The primary outcome of interest in the DR group was the composite of new-onset proliferative DR, vitreous haemorrhage and tractional retinal detachment (RD). In the non-DR group, the primary outcome was the composite of newly diagnosed DR of any severity, vitreous haemorrhage and RD. In total, 97 413 patients were identified. After matching, 1517 patients were treated with a GLP1RA and 3034 with an SGLT2i in the DR cohort. In the non-DR cohort, 9549 initiated a GLP1RA and 19 098 initiated an SGLT2i. In patients with pre-existing DR, the incidence of any DR progression event was significantly higher in the GLP1RA group than the SGLT2i group (subdistribution hazard ratio 1.50, 95% confidence interval 1.01-2.23), primarily because of the increased risk of tractional RD. In patients without DR at baseline, the risks of all ocular outcomes were similar between the GLP1RA and SGLT2i groups. In patients with diabetes mellitus and established DR, GLP1RA treatment was associated with increased risks of DR progression compared with SGLT2i use.

Measurement of retinal blood flow precision in the human eye with multimodal adaptive optics imaging.

Impaired retinal blood flow (RBF) autoregulation plays a key role in the development and progression of several ocular diseases, including glaucoma and diabetic retinopathy. Clinically, reproducible RBF quantitation could significantly improve early diagnosis and disease management. Several non-invasive techniques have been developed but are limited for retinal microvasculature flow measurements due to their low signal-to-noise ratio and poor lateral resolution. In this study, we demonstrate reproducible vessel caliber and retinal blood flow velocity measurements in healthy human volunteers using a high-resolution (spatial and temporal) multimodal adaptive optics system with scanning laser ophthalmoscopy and optical coherence tomography.

Lower Hemoglobin Levels as a Risk Factor for the Development of Retinopathy of Prematurity.

Retinopathy of prematurity (ROP) is an important cause of visual morbidity among preterm infants. The objective of the study was to assess the relationship between the initial hematological parameters of the complete blood count (CBC) and ROP development in preterm neonates. This retrospective cohort study was conducted in a neonatal intensive care unit in Odisha. The hematological parameters of the CBC conducted within the first 48 hours of age, demographic characteristics, neonatal morbidities, and ROP screening findings of preterm neonates (gestational age <34 weeks) were analyzed. Independent risk factors associated with ROP development were identified in a multivariate logistic regression model. A total of 43 (29.1%) out of 148 neonates had any of the ROP stages (stage 1-26, 2-08, and 3-09). Birth weight (aOR 0.003; 95% CI 0.00, 0.11);hemoglobin (Hb) level (aOR 0.70; 95% CI 0.54, 0.90); presence of respiratory distress syndrome (RDS) (aOR 7.61; 95% CI 1.5, 36.39); and need for packed red blood cell (PRBC) transfusion (aOR 4.26; 95% CI 1.1, 16.44) were independently associated withROP development. The odds of ROP were higher among the neonates with initial Hb 10.5-15.4 g/dL (OR (95% CI) 3.7(1.5, 8.9), p=0.003) and for neonates with Hb 15.4-17.3 g/dL (OR (95% CI)2.5(1.01, 6.16), p=0.047) in comparison to neonates with initial Hb >17.3 g/dL. Preterm neonates with a lower level of Hb during the early postnatal days are at higher risk for ROP development and need to be prioritized for screening.

Causal relationships of lifestyle behaviours and body fat distribution on diabetic microvascular complications: a Mendelian randomization study.

To determine the causal correlations of lifestyle behaviours and body fat distribution on diabetic microvascular complications through a Mendelian Randomization (MR). Genetic variants significantly associated with lifestyle behaviours, abdominal obesity, generalized obesity and diabetic microvascular complications were extracted from the UK Biobank (UKB) and FinnGen. The inverse variance weighted (IVW) method was regarded as the primary method. The main results were presented in odds ratio (OR) per standard deviation (SD) increase, and a series of sensitivity analyses were also conducted to validate the stability of the results. There was a positive causal correlation between smoking and the development of diabetic retinopathy (OR = 1.16; 95%CI: 1.04-1.30; p = 0.01). All of the indicators representing abdominal obesity had a statistically significant causal association with diabetic microvascular complications. Concerning generalized obesity, there were significant causal associations of body mass index (BMI) on diabetic nephropathy (OR = 1.92; 95%CI: 1.58-2.33; p < 0.001), diabetic retinopathy (OR = 1.27; 95%CI: 1.15-1.40; p < 0.001), and diabetic neuropathy (OR = 2.60; 95%CI: 1.95-3.45; p < 0.001). Other indicators including leg fat mass (left), and arm fat mass (left) also had a significant positive causality with diabetic microvascular complications. Our findings suggested that smoking has a genetically causal association with the development of diabetic retinopathy rather than diabetic nephropathy and diabetic neuropathy. In addition, both abdominal obesity and generalized obesity are risk factors for diabetic microvascular complications. To note, abdominal obesity represented by waist circumference (WC) is the most significant risk factor.

Toxic Advanced Glycation End-Products Inhibit Axonal Elongation Mediated by β-Tubulin Aggregation in Mice Optic Nerves.

Advanced glycation end-products (AGEs) form through non-enzymatic glycation of various proteins. Optic nerve degeneration is a frequent complication of diabetes, and retinal AGE accumulation is strongly linked to the development of diabetic retinopathy. Type 2 diabetes mellitus is a major risk factor for Alzheimer's disease (AD), with patients often exhibiting optic axon degeneration in the nerve fiber layer. Notably, a gap exists in our understanding of how AGEs contribute to neuronal degeneration in the optic nerve within the context of both diabetes and AD. Our previous work demonstrated that glyceraldehyde (GA)-derived toxic advanced glycation end-products (TAGE) disrupt neurite outgrowth through TAGE-β-tubulin aggregation and tau phosphorylation in neural cultures. In this study, we further illustrated GA-induced suppression of optic nerve axonal elongation via abnormal β-tubulin aggregation in mouse retinas. Elucidating this optic nerve degeneration mechanism holds promise for bridging the knowledge gap regarding vision loss associated with diabetes mellitus and AD.

مدى إنتشار عوامل الخطر وارتباطها في تطور إعتلال الشبكية السكري في قسم طب العيون، مركز طبرق الطبي، ليبيا

Diabetic retinopathy is a condition of the eyes that can affect people with diabetes. This is the degree at which the retina's blood vessels are damaged by high blood sugar. These vascular structures can expand and rupture. Additionally, the vessels might close, preventing the circulation of blood. Sometimes, abnormally new blood vessels might grow on the retina. Any of the foregoing changes could impair your vision. The aim of this study is to identify risk factors that may enhance the development of diabetic retinopathy and explore strategies for reducing the possibility of visual impairment caused by this condition. A prospective cross-sectional study of diabetic patients registered at the Eye Department of Tobruk Medical Center in Tobruk, Libya between (01.06.2023 to 29.02.2024). Data was collected using a self-administered questionnaire. Grading of DR (diabetic retinopathy) was done by slit-lamp examination and fundoscopy by an ophthalmologist. Descriptive analysis included percentage, mean of age, and p-value by using SPSS 25. Result: There were 85 diabetic patients, with a mean age of 63.5 and an age range of 31 to 85 years. Of these, 98.8% were of Libyan nationality and 96.4% were place of residencein Tobruk. Forty-three women were present. Compared to individuals with diabetes for less than ten years, those with diabetes for eleven to fifteen years had an almost five-fold increased chance of having diabetic retinopathy disease (DR). Patients with poor diabetes control (HbA1c &gt; 9) had a 25-fold increased chance of developing PR compared to those with adequate control (HbA1c &lt; 7.5). Conclusion: Patients with uncontrolled diabetes and those with the disease for a longer period of time are more likely to develop diabetic retinopathy and experience visual impairment. Key word: Diabetic retinopathy, poor diabetes control, longer period of diabetes, Tobruk, Libya.

Assessment of Risk Factors for the Development of Diabetic Retinopathy in T2D

Objective: To estimate the risk factors that contributes to the incidence of diabetic retinopathy (DR) in type 2 diabetes (T2D). Methodology: We conducted serial fundus photography in individuals at high risk of developing type 2 diabetes, including after the onset of diabetes. The ETDRS (Early Treatment Diabetic Retinopathy Study) grading system was used to evaluate the fundus photographs. Results: A total of 400 participants with a 3:3.6 male-to-female ratio were included in this study. The T2 DM patients with mean age 48.73±9.24 and 47.53±8.53 years with and without retinopathy respectively were observed, which shows that there is a non-significant difference (p=0.801). The differences in weight and BMI in T2 D participants with and without diabetic retinopathy were also not significant. The study found that the history of pregnancy, history of gestational DM, measures of HOMA-B, HOMA-IR, insulin genic inde, oral disposition inde, urine albumin to creatinine ratio, and hs-CRP were not associated with the presence of retinopathy. Association of nonglycemic risk factors in T2D. The study found that mean HbA1c during follow-up was significantly associated (P 0.0001) with the prevalence of retinopathy, The study found that retinopathy was associated with measures of higher blood pressure (systolic blood pressure, diastolic blood pressure, and presence of hypertension) and lipid profile. Conclusions: The development of DR can occur in the early stages of T2D. Hemoglobin A1c was found to be a significant risk factor for the occurrence of DR across the intact glycemic range in patients with T2D.

Future Therapeutics: Targeting the NLRP3 Inflammasome Pathway to Manage Diabetic Retinopathy Development and Progression

While existing local therapies partially restore vision loss from diabetic retinopathy (DR), there is currently no reliable treatment to prevent the onset or stop the progression of the disease. This review seeks to explore the inflammatory molecular mechanisms underpinning DR pathogenesis, which have not been targeted by current interventions. Specifically, this review explores the role of the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) protein 3 (NLRP3) inflammasome in DR onset and progression. Evidence through clinical trials has begun to note that specific drugs (fenofibrate, metformin) appear effective in slowing DR progression independent of lipid or glucose-lowering, respectively, suggesting that other mechanisms are at play. Novel therapeutics that inhibit the activation of the NLRP3 inflammasome pathway may provide a novel treatment for halting DR progression.

HbA1c and the risk of developing peripheral neuropathy in childhood-onset type 1 diabetes: A follow-up study over 3decades.

We have evaluated long-term weighted mean HbA1c (wHbA1c), HbA1c variability, diabetes duration, and lipid profiles in relation to the development of diabetic peripheral neuropathy (DPN), nephropathy, and retinopathy in childhood-onset type 1 diabetes. In a longitudinal cohort study, 49 patients (21 women) with childhood-onset type 1 diabetes were investigated with neurophysiological measurements, blood tests, and clinical examinations after a diabetes duration of 7.7 (±3.3) years (baseline) and followed with repeated examinations for 30.6 (±5.2) years. We calculated wHbA1c by integrating the area under all HbA1c values since the diabetes diagnosis. Lipid profiles were analysed in relation to the presence of DPN. Long-term fluctuations of HbA1c variability were computed as the standard deviation of all HbA1c measurements. Data regarding the presence of other diabetes complications were retrieved from medical records. In this follow-up study, 51% (25/49) of the patients fulfilled electrophysiological criteria for DPN. In nerve conduction studies, there was a deterioration in the amplitudes and conduction velocities for the median, peroneal, and sural nerves over time. Patients with DPN had a longer duration of diabetes, higher wHbA1c, and increased HbA1c variability. The lowest wHbA1c value associated with the development of DPN was 62mmol/mol (7.8%). The presence of albuminuria and retinopathy was positively correlated with the presence of neuropathy. More than half of the patients had developed DPN after 30years. None of the patients who developed DPN had a wHbA1c of less than 62mmol/mol (7.8%).

Identification of Risk Factors for the Development of Diabetic Retinopathy Among Palestinian Adults With Type 2 Diabetes Mellitus: A Cross-Sectional Study.

Although risk factors linked to diabetic retinopathy (DR) among patients with Type 2 diabetes mellitus (T2DM) have been extensively studied globally, the specific determinants of these factors in relation to DR in Palestine are presently not well understood. This retrospective cross-sectional study included patients who underwent DR screening with a fundus camera (VersaCam a). The study included patients aged ≥18 with T2DM, excluding those with other types of diabetes or a history of malignancies. Univariable and multivariable logistic regressions were used to identify factors associated with DR. A total of 1163 patients with T2DM were included in this study. Of these, 211 (18.1%) patients were classified in the DR group, 761 (65.4%) in the no DR group and 191 (16.4%) were ungradable. Among the included patients, 434 (37.3%) were male. A secondary level of education or higher and a BMI ≥30 kg/m2, compared with <25 kg/m2, were independently and inversely associated with DR, with odds ratios (ORs) of 0.46 (p < 0.001) and 0.58 (p = 0.046), respectively. A 5-year increase in the duration of T2DM correlated with 45% higher odds of having DR (p < 0.001). Patients with DR were more likely to have HbA1c >7%, be physically inactive and use insulin, with ORs of 1.63 (p = 0.02), 2.05 (p < 0.001) and 1.53 (p = 0.03), respectively. Age, gender, occupational status, hypertension and hyperlipidaemia were not independent predictors of DR (p < 0.05). Longer duration of T2DM, HbA1c >7%, physical inactivity and insulin use were all independently associated with the presence of DR. Furthermore, a secondary or higher educational level and obesity demonstrated independent and inverse associations with the development of DR.

Incidence of diabetic retinopathy in anti-tnf treated rheumatic disease patients with type 2 diabetes.

This study aimed to evaluate the impact of anti-TNF (biological) therapies on the incidence and progression of diabetic retinopathy. A cross-sectional analysis of 50 diabetic patients with rheumatic diseases (group 1) was performed. An age-, sex-, and HbA1c-matched control group (group 2) was formed from a pool of diabetic patients who underwent regular eye examinations. The presence or absence of diabetic retinopathy was also assessed. Comorbidities such as hypertension, coronary artery disease, and hyperlipidemia were also evaluated as possible confounding factors. Hundred eyes of 50 patients were evaluated in each group. Only three patients in group 1 had non-proliferative retinopathy. The median duration of rheumatic disease was 9 years, whereas that of diabetes was 11 years. The mean duration of anti-TNF therapy was 4 years. In the control group of diabetes-only patients, 13 patients developed some form of newly diagnosed diabetic retinopathy during the last five years. The calculated retinopathy occurrence between the groups was statistically significant (p < 0.05). In this study, the incidence rate ratio for patients receiving anti-TNF treatment was calculated as 0.4 in the study. TNF inhibitors, with their anti-inflammatory effects, positively impact diabetic complications by reducing the incidence of retinopathy. To our knowledge, this is the first study to evaluate retinopathy development after anti-TNF therapy.

Protective Effects of Bioactive Compound-Derived Nanoparticle Against Diabetic Retinopathy Through the Modulation of the NF-κB Signaling Pathway.

Diabetic retinopathy is a prevalent and severe microvascular complication of diabetes, often causing visual impairment and blindness in adults. This condition significantly impacts the quality of life for many diabetes patients worldwide. Berberine (BBR), a bioactive compound known for its effects on blood glucose levels, has shown promise in managing diabetic complications. However, the exact mechanism of how BBR influences the development of diabetic retinopathy remains unclear. In this study, we focused on synthesizing a formulation derived from BBR and assessing its protective effects against diabetic retinopathy. The formulation was created using a green synthesis method and thoroughly characterized. In vitro studies demonstrated the antioxidant activity of the formulation against 2,2-diphenyl-1-picryl-hydrazyl-hydrate. We also examined the NF-κB signaling pathway at a molecular level using real-time polymerase chain reaction. To mimic diabetic retinopathy in a controlled setting, a diabetic rat model was established through streptozotocin injection. The rats were divided into normal, diabetic, and treatment groups. The treatment group received the formulated treatment via intragastric administration for several weeks, while the other groups received normal saline. Evaluation of histopathological characteristics and microstructural changes in the retina using hematoxylin and eosin staining revealed that the bioactive compound-derived nanoparticle exhibited favorable biological, chemical, and physical properties. Treatment with the formulation effectively reduced oxidative stress induced by diabetes and inhibited the NF-κB signaling pathway in the diabetic rat model. Under high glucose conditions, oxidative stress was heightened, leading to mitochondria-dependent cell apoptosis in Müller cells via the activation of the NF-κB signaling pathway. The bioactive compound-derived formulation counteracted these effects by decreasing IκB phosphorylation, preventing NF-κB nuclear translocation, and deactivating the NF-κB signaling pathway. Furthermore, treatment with the bioactive compound-derived formulation mitigated retinal micro- and ultrastructural changes associated with diabetic retinopathy. These results indicate that the formulation protects against diabetic retinopathy by suppressing oxidative stress, reducing cell apoptosis, and deactivating the NF-κB signaling pathway. This suggests that the bioactive compound-derived formulation could be a promising therapeutic option for diabetic retinopathy.

Detection of Diabetic Retinopathy Using KNN &amp; SVM Algorithm

Diabetic Retinopathy (DR) is a medical condition caused by diabetes. The development of retinopathy significantly depends on how long a person has had diabetes. Initially, there may be no symptoms or just a slight vision problem due to impairment of the retinal blood vessels. Later, it may lead to blindness. Recognizing the early clinical signs of DR is very important for intervening in and effectively treating DR. Thus, regular eye check-ups are necessary to direct the person to a doctor for a comprehensive ocular examination and treatment as soon as possible to avoid permanent vision loss. Nevertheless, due to limited resources, it is not feasible for screening. As a result, emerging technologies, such as artificial intelligence, for the automatic detection and classification of DR are alternative screening methodologies and thereby make the system cost-effective. People have been working on artificial- intelligence-based technologies to detect and analyze DR in recent years. This study aimed to investigate different machine learning styles that are chosen for diagnosing retinopathy. Thus, a bibliometric analysis was systematically done to discover different machine learning styles for detecting diabetic retinopathy. The data were exported from popular databases, namely, Web of Science (WoS) and Scopus. These data were analyzed using Biblioshiny and VOS viewer in terms of publications, top countries, sources, subject area, top authors, trend topics, co-occurrences, thematic evolution, factorial map, citation analysis, etc., which form the base for researchers to identify the research gaps in diabetic retinopathy detection and classification

Impact of anti-VEGF treatment on development of proliferative diabetic retinopathy in routine clinical practice

BackgroundThis study evaluated impact of anti–vascular endothelial growth factor (VEGF) treatment on proliferative diabetic retinopathy (PDR) development among patients with non-proliferative diabetic retinopathy (NPDR) in US real-world clinical practice.MethodsThis was a retrospective analysis of electronic medical records (Vestrum Health; January 2013 to June 2019) of eyes with baseline NPDR, without DME, and naïve to anti-VEGF treatment at index DR diagnosis. Eyes that received anti-VEGF and/or laser treatment over the course of study before development of PDR constituted the treated cohort while the remaining including those treated with laser constituted the anti-VEGF naïve cohort. Survival analysis via Kaplan–Meier method evaluated time to DME and PDR development by baseline NPDR severity, with anti-VEGF treatment as censoring variable. Baseline factors affecting PDR development were analyzed using Cox multivariable regression, censoring for anti-VEGF treatment.ResultsAmong anti-VEGF–naive eyes, cumulative incidence of DME in eyes with mild (n = 70,050), moderate (n = 39,116), and severe NPDR (n = 10,692) at baseline was 27.1%, 51.2%, and 60.6%. Multivariable regression analysis identified baseline NPDR severity as the most significant predictor of PDR development over 48 months (hazard ratio [HR] [95% confidence interval {CI}] of 2.69 (2.65–2.72) for moderate vs mild NPDR and 6.51 (6.47–6.55) for severe vs mild NPDR). Cumulative incidence (95% CI) of PDR was 7.9% (7.4%–8.3%), 20.9%, (20.0%–21.7%) and 46.8% (44.4%–49.2%) over 48 months in eyes with mild, moderate, and severe NPDR at baseline, respectively. Among treated eyes with baseline severe NPDR, cumulative incidence of PDR at 48 months was 50.1% in eyes treated with laser (n = 546; HR [95% CI] vs no treatment: 0.8 [0.7–1.0]), 27.4% in eyes treated with anti-VEGF (n = 923; HR [95% CI]: 0.4 [0.4–0.5]), and 25.6% in eyes treated with anti-VEGF plus laser (n = 293; HR [95% CI]: 0.5 [0.4–0.7]) compared with 49.9% in eyes with no treatment (n = 8930).ConclusionsDME and PDR development rates increased with increasing baseline NPDR severity. Approximately half of anti-VEGF‒naive eyes with severe NPDR progressed to PDR within 4 years in US clinical practice. The progression rate from severe NPDR to PDR was approximately halved with anti-VEGF versus no treatment.

Incidence, Risk Factors and Development of Retinopathy of Prematurity in Mid-Preterm and Late-Preterm Infants.

To evaluate the incidence, risk factors, and development of retinopathy of prematurity (ROP) in midpreterm and late-preterm infants born at 32 to 36 6/7 weeks of gestational age. The ophthalmic examination findings and risk factors of 5,477 preterm infants who underwent ophthalmological examination were evaluated retrospectively. The rates of any stage and severe ROP (requiring treatment) development and treatment options were recorded. The risk factors were analyzed by using logistic regression analysis. A total of 5,477 infants were included in the study, of whom 2,715 (49.57%) were mid-preterm and 2,762 (50.43%) were late-preterm. The rates of any stage and severe ROP were 8.2% (n = 223) and 0.6% (n = 15) in mid-preterm infants, respectively. In late-preterm infants, the rate of any stage ROP was 2.1% (n = 59), and no severe ROP was detected. There was no significant difference in mean birth weight in mid-preterm infants between infants with any stage ROP and severe ROP (P = .104). Of the 15 infants (0.3%) who required treatment, 14 (0.2%) infants had laser photocoagulation, 1 (0.01%) had intravitreal bevacizumab, and 2 (0.03%) had additional therapy (laser photocoagulation and intravitreal bevacizumab). In logistic regression analysis, a significant association was found between treatment requirement and transport from an external center (P < .001, ß = 0.04). Although ROP development rates decrease as birth weight and gestational age increase, late-preterm infants should be examined for ROP at least once, especially those born in low-income countries because ROP development can still be observed. [J Pediatr Ophthalmol Strabismus. 20XX;X(X):XX-XX.].

Presence and development of diabetic retinopathy in 16 999 patients with type 1 diabetes in the Danish Registry of Diabetic Retinopathy.

To evaluate the five-year incidence of diabetic retinopathy (DR) and associated risk markers in patients with type 1 diabetes in the national Danish DR-screening programme. Based on national data, we included all 16 999 patients with type 1 diabetes in the Danish Registry of Diabetic Retinopathy, who attended the national screening programme in the period 2013-2018. According to the worse eye at first screening, DR was classified (levels 0-4) and linked with various national health registries to retrieve information on diabetes duration, systemic comorbidity, and medication. At first screening, median age and duration of diabetes were 45.0 and 16.7 years, and 57.5% were males. The prevalence and five-year incidences for DR and progression to proliferative DR (PDR) were 44.2%, 8.9% and 2.0%, respectively. In multivariable Cox models, the incidence endpoints were associated with duration of diabetes (hazard ratio [HR] 1.76, 95% confidence interval [CI] 1.63-1.89, and HR 2.04, 95% CI 1.73-2.40 per 10 years), moderately low Charlson Comorbidity Index score (HR 1.27, 95% CI 1.10-1.47, and HR 2.80, 95% CI 2.23-3.51), and use of blood pressure lowering medication (HR 1.20, 95% CI 1.05-1.36, and HR 1.98, 95% CI 1.53-2.57). In a study of all patients with type 1 diabetes from the Danish DR-screening programme, we identified duration of diabetes, systemic disease and use of anti-hypertensive treatment as consistent risk markers for incident and progressive DR.

USP5 facilitates diabetic retinopathy development by stabilizing ROBO4 via deubiquitination

Ubiquitin-specific proteases (USPs) have been proved to play important roles in the progression of diabetic retinopathy. In this study, we explored the role of USP5 and its possible mechanisms in diabetic retinopathy development. Cell proliferation, apoptosis, inflammation and oxidative stress were determined using CCK-8 assay, EdU staining assay, flow cytometry, and ELISA, respectively. The mRNA and protein expression of ROBO4 and USP5 were measured through RT-qPCR and western blot, respectively. Co-IP and deubiquitination assay were conducted to evaluate the interaction between ROBO4 and USP5. The results showed that high glucose (HG) stimulation significantly led to HRPE cell damage as described by suppressing proliferation, and promoting oxidative stress, inflammation and apoptosis. ROBO4 was markedly increased in diabetic retinopathy plasma samples and HG-triggered HRPE cells. Depletion of ROBO4 could alleviate HG-caused HRPE cell damage. USP5 was also significantly elevated in diabetic retinopathy plasma samples and HG-triggered HRPE cells. USP5 overexpression aggravated HG-induced HRPE cell damage. USP5 stabilized ROBO4 through deubiquitination. Moreover, USP5 knockdown decreased ROBO4 expression to mitigate HG-triggered cell damage in HRPE cells. USP5 stabilized ROBO4 via deubiquitination to repress cell proliferation, and facilitate inflammation, cell apoptosis and oxidative stress in HG-treated HRPE cells, thereby promoting the development of diabetic retinopathy.

Diabetic retinopathy is a ceramidopathy reversible by anti-ceramide immunotherapy

Diabetic retinopathy is a microvascular disease that causes blindness. Using acid sphingomyelinase knockout mice, we reported that ceramide generation is critical for diabetic retinopathy development. Here, in patients with proliferative diabetic retinopathy, we identify vitreous ceramide imbalance with pathologic long-chain C16-ceramides increasing and protective very long-chain C26-ceramides decreasing. C16-ceramides generate pro-inflammatory/pro-apoptotic ceramide-rich platforms on endothelial surfaces. To geo-localize ceramide-rich platforms, we invented a three-dimensional confocal assay and showed that retinopathy-producing cytokines TNFα and IL-1β induce ceramide-rich platform formation on retinal endothelial cells within seconds, with volumes increasing 2-logs, yielding apoptotic death. Anti-ceramide antibodies abolish these events. Furthermore, intravitreal and systemic anti-ceramide antibodies protect fromdiabetic retinopathy in standardized rodent ischemia reperfusion and streptozotocin models. These data support (1) retinal endothelial ceramide as a diabetic retinopathy treatment target, (2) early-stage therapy of non-proliferative diabetic retinopathy to prevent progression, and (3) systemic diabetic retinopathy treatment; and they characterize diabetic retinopathy as a "ceramidopathy" reversible by anti-ceramide immunotherapy.

Effect of High-Sucrose Diet on the Occurrence and Progression of Diabetic Retinopathy and Dietary Modification Strategies.

As the most serious of the many worse new pathological changes caused by diabetes, there are many risk factors for the occurrence and development of diabetic retinopathy (DR). They mainly include hyperglycemia, hypertension, hyperlipidemia and so on. Among them, hyperglycemia is the most critical cause, and plays a vital role in the pathological changes of DR. High-sucrose diets (HSDs) lead to elevated blood glucose levels in vivo, which, through oxidative stress, inflammation, the production of advanced glycation end products (AGEs) and vascular endothelial growth factor (VEGF), cause plenty of pathological damages to the retina and ultimately bring about loss of vision. The existing therapies for DR primarily target the terminal stage of the disease, when irreversible visual impairment has appeared. Therefore, early prevention is particularly critical. The early prevention of DR-related vision loss requires adjustments to dietary habits, mainly by reducing sugar intake. This article primarily discusses the risk factors, pathophysiological processes and molecular mechanisms associated with the development of DR caused by HSDs. It aims to raise awareness of the crucial role of diet in the occurrence and progression of DR, promote timely changes in dietary habits, prevent vision loss and improve the quality of life. The aim is to make people aware of the importance of diet in the occurrence and progression of DR. According to the dietary modification strategies that we give, patients can change their poor eating habits in a timely manner to avoid theoretically avoidable retinopathy and obtain an excellent prognosis.