Heyingwuzi formulation alleviates diabetic retinopathy by promoting mitophagy via the HIF-1α/BNIP3/NIX axis.

BACKGROUND: Diabetic retinopathy (DR) is the primary cause of visual problems in patients with diabetes. The Heyingwuzi formulation (HYWZF) is effective against DR. AIM: To determine the HYWZF prevention mechanisms, especially those underlying mitophagy. METHODS: Human retinal capillary endothelial cells (HRCECs) were treated with high glucose (hg), HYWZF serum, PX-478, or Mdivi-1 in vitro. Then, cell counting kit-8, transwell, and tube formation assays were used to evaluate HRCEC proliferation, invasion, and tube formation, respectively. Transmission electron microscopy was used to assess mitochondrial morphology, and Western blotting was used to determine the protein levels. Flow cytometry was used to assess cell apoptosis, reactive oxygen species (ROS) production, and mitochondrial membrane potential. Moreover, C57BL/6 mice were established in vivo using streptozotocin and treated with HYWZF for four weeks. Blood glucose levels and body weight were monitored continuously. Changes in retinal characteristics were evaluated using hematoxylin and eosin, tar violet, and periodic acid-Schiff staining. Protein levels in retinal tissues were determined via Western blotting, immunohistochemistry, and immunostaining. RESULTS: HYWZF inhibited excessive ROS production, apoptosis, tube formation, and invasion in hg-induced HRCECs via mitochondrial autophagy in vitro. It increased the mRNA expression levels of BCL2-interacting protein 3 (BNIP3), FUN14 domain-containing 1, BNIP3-like (BNIP3L, also known as NIX), PARKIN, PTEN-induced kinase 1, and hypoxia-inducible factor (HIF)-1α. Moreover, it downregulated the protein levels of vascular endothelial cell growth factor and increased the light chain 3-II/I ratio. However, PX-478 and Mdivi-1 reversed these effects. Additionally, PX-478 and Mdivi-1 rescued the effects of HYWZF by decreasing oxidative stress and apoptosis and increasing mitophagy. HYWZF intervention improved the symptoms of diabetes, tissue damage, number of acellular capillaries, and oxidative stress in vivo. Furthermore, in vivo experiments confirmed the results of in vitro experiments. CONCLUSION: HYWZF alleviated DR and associated damage by promoting mitophagy via the HIF-1α/BNIP3/NIX axis.

Intraocular lens selection in diabetic patients: How to increase the odds for success.

The incidence of cataracts is significantly higher in diabetic individuals, particularly in younger age groups, with rates quadrupled in those under 65 and doubled in those over 65 compared to non-diabetics. Cataract surgery in diabetic patients poses many challenges: Poor epithelial healing, decreased corneal sensitivity, increased central corneal thickness, decreased endothelial cell count, variable topography, poor pupillary dilatation, anterior capsular phimosis, posterior capsular opacification (PCO), chances of progression of diabetic retinopathy (DR), zonular weakness, and vitreous prolapse and diabetic macular edema. Selection of an appropriate intraocular lens (IOL) is crucial for visual rehabilitation and monitoring DR. The choice of IOL in diabetic cataract patients is a challenging scenario. Square-edge IOLs are favored for their capacity to mitigate PCO, whereas hydrophilic counterparts may incur calcification in the setting of proliferative DR. The advisability of premium IOLs for achieving spectacle independence warrants judicious evaluation, particularly in the presence of advanced retinopathy. Optimal IOL placement within the capsular bag is advocated to minimize postoperative complications. Rigorous preoperative assessment and informed patient counseling regarding IOL options are indispensable for optimizing surgical outcomes. This review article covers various aspects regarding the choice of IOLs in different case scenarios and complications in the diabetic population.

Plasma metabolomics identifies key metabolites and improves prediction of diabetic retinopathy: development and validation across multi-national cohorts.

PURPOSE: To identify longitudinal metabolomic fingerprints of diabetic retinopathy (DR) and evaluate their utility in predicting DR development and progression. DESIGN: Multicenter, multi-ethnic cohort study. PARTICIPANTS: This study included 17,675 participants with baseline pre-diabetes/diabetes, in accordance with the 2021 American Diabetes Association guideline, and free of baseline DR from the UK Biobank (UKB); and an additional 638 diabetic participants from the Guangzhou Diabetic Eye Study (GDES) for external validation. METHODS: Longitudinal DR metabolomic fingerprints were identified through nuclear magnetic resonance assay in UKB participants. The predictive value of these fingerprints for predicting DR development were assessed in a fully withheld test set. External validation and extrapolation analyses of DR progression and microvascular damage were conducted in the GDES cohort. Model assessments included the C-statistic, net classification improvement (NRI), integrated discrimination improvement (IDI), calibration, and clinical utility in both cohorts. MAIN OUTCOME MEASURES: DR development, progression, and retinal microvascular damage. RESULTS: Of 168 metabolites, 118 were identified as candidate metabolomic fingerprints for future DR development. These fingerprints significantly improved the predictability for DR development beyond traditional indicators (C-statistic: 0.802, 95% CI, 0.760-0.843 vs. 0.751, 95% CI, 0.706-0.796; P = 5.56×10-4). Glucose, lactate, and citrate were among the fingerprints validated in the GDES cohort. Using these parsimonious and replicable fingerprints yielded similar improvements for predicting DR development (C-statistic: 0.807, 95% CI, 0.711-0.903 vs. 0.617, 95% CI, 0.494, 0.740; P = 1.68×10-4) and progression (C-statistic: 0.797, 95% CI, 0.712-0.882 vs. 0.665, 95% CI, 0.545-0.784; P = 0.003) in the external cohort. Improvements in NRIs, IDIs, and clinical utility were also evident in both cohorts (all P <0.05). In addition, lactate and citrate were associated to microvascular damage across macular and optic disc regions (all P <0.05). CONCLUSIONS: Metabolomic profiling has proven effective in identifying robust fingerprints for predicting future DR development and progression, providing novel insights into the early and advanced stages of DR pathophysiology.

Hsa_circ_0004776 regulates the retina neovascularization in progression of diabetic retinopathy via hsa-miR-382-5p/BDNF axis.

The aim of this work was to identify the regulatory function of hsa_circ_0004776 in the progression of diabetic retinopathy (DR). The direct interactions between hsa_circ_0004776 and hsa-miR-382-5p and between hsa-miR-382-5p and BDNF, were confirmed via dual-luciferase reporter assays. Quantitative Real-Time PCR analysis indicated that hsa_circ_0004776 was highly expressed in aqueous humour samples of DR patients and human retinal microvascular epithelial cells (hRECs) under a high-glucose environment, whereas hsa-miR-382-5p showed the opposite trend. Overexpressed hsa_circ_0004776 significantly enhanced DNA synthesis, proliferation, migration, and tube formation in hRECs in hyperglycaemia, while hsa-miR-382-5p mimics reversed these changes. Additionally, in a streptozotocin-induced Sprague-Dawley rat model of DR, vitreous microinjection of rno-miR-382-5p agomir reversed the pathologic features in the progression of DR, including retinal vascular leakage, capillary decellularization, loss of pericytes, fibrosis, and gliosis. Our results indicated that under hyperglycaemic conditions, hsa_circ_0004776 influences the progression of DR via hsa-miR-382-5p and thus represents a potential therapeutic target.

Mechanistic and therapeutic perspectives of non-coding RNA-modulated apoptotic signaling in diabetic retinopathy.

Diabetic retinopathy (DR), a significant and vision-endangering complication associated with diabetes mellitus, constitutes a substantial portion of acquired instances of preventable blindness. The progression of DR appears to prominently feature the loss of retinal cells, encompassing neural retinal cells, pericytes, and endothelial cells. Therefore, mitigating the apoptosis of retinal cells in DR could potentially enhance the therapeutic approach for managing the condition by suppressing retinal vascular leakage. Recent advancements have highlighted the crucial regulatory roles played by non-coding RNAs (ncRNAs) in diverse biological processes. Recent advancements have highlighted that non-coding RNAs (ncRNAs), including microRNAs (miRNAs), circular RNAs (circRNAs), and long non-coding RNAs (lncRNAs), act as central regulators in a wide array of biogenesis and biological functions, exerting control over gene expression associated with histogenesis and cellular differentiation within ocular tissues. Abnormal expression and activity of ncRNAs has been linked to the regulation of diverse cellular functions such as apoptosis, and proliferation. This implies a potential involvement of ncRNAs in the development of DR. Notably, ncRNAs and apoptosis exhibit reciprocal regulatory interactions, jointly influencing the destiny of retinal cells. Consequently, a thorough investigation into the complex relationship between apoptosis and ncRNAs is crucial for developing effective therapeutic and preventative strategies for DR. This review provides a fundamental comprehension of the apoptotic signaling pathways associated with DR. It then delves into the mutual relationship between apoptosis and ncRNAs in the context of DR pathogenesis. This study advances our understanding of the pathophysiology of DR and paves the way for the development of novel therapeutic strategies.

A health economic pilot study comparing two diabetic retinopathy screening strategies.

To compare two screening strategies for diabetic retinopathy (DR), and to determine the health-economic impact of including optical coherence tomography (OCT) in a regular DR screening. This cross-sectional study included a cohort of patients (≥ 18 years) with type 1 or 2 diabetes mellitus (T1D or T2D) from a pilot DR screening program at Oslo University Hospital, Norway. A combined screening strategy where OCT was performed in addition to fundus photography for all patients, was conducted on this cohort and compared to our existing sequential screening strategy. In the sequential screening strategy, OCT was performed on a separate day only if fundus photography indicated diabetic macular edema (DME). The presence of diabetic maculopathy on fundus photography and DME on OCT was determined by two medical retina specialists. Based on the prevalence rate of diabetic maculopathy and DME from the pilot, we determined the health-economic impact of the two screening strategies. The study included 180 eyes of 90 patients. Twenty-seven eyes of 18 patients had diabetic maculopathy, and of these, 7 eyes of 6 patients revealed DME on OCT. When diabetic maculopathy was absent on fundus photographs, OCT could not reveal DME. Accordingly, 18 patients (20%) with diabetic maculopathy would have needed an additional examination with OCT in the sequential screening strategy, 6 (33%) of whom would have had DME on OCT. In an extended healthcare perspective analysis, the cost of the sequential screening strategy was higher than the cost of the combined screening strategy. There was a weak association between diabetic maculopathy on fundus photography and DME on OCT. The health economic analysis suggests that including OCT as a standard test in DR screening could potentially be cost-saving.

Unveiling the Potential: A Comprehensive Review of Artificial Intelligence Applications in Ophthalmology and Future Prospects.

Artificial intelligence (AI) has emerged as a transformative force in healthcare, particularly in the field of ophthalmology. This comprehensive review examines the current applications of AI in ophthalmology, highlighting its significant contributions to diagnostic accuracy, treatment efficacy, and patient care. AI technologies, such as deep learning algorithms, have demonstrated exceptional performance in the early detection and diagnosis of various eye conditions, including diabetic retinopathy (DR), age-related macular degeneration (AMD), and glaucoma. Additionally, AI has enhanced the analysis of ophthalmic imaging techniques like optical coherence tomography (OCT) and fundus photography, facilitating more precise disease monitoring and management. The review also explores AI's role in surgical assistance, predictive analytics, and personalized treatment plans, showcasing its potential to revolutionize clinical practice and improve patient outcomes. Despite these advancements, challenges such as data privacy, regulatory hurdles, and ethical considerations remain. The review underscores the need for continued research and collaboration among clinicians, researchers, technology developers, and policymakers to address these challenges and fully harness the potential of AI in improving eye health worldwide. By integrating AI with teleophthalmology and developing AI-driven wearable devices, the future of ophthalmic care promises enhanced accessibility, efficiency, and efficacy, ultimately reducing the global burden of visual impairment and blindness.

The m6A-ncRNAs axis in diabetes complications: novel mechanism and therapeutic potential.

Diabetes, a multifaceted metabolic disorder, poses a significant global health burden with its increasing prevalence and associated complications, such as diabetic nephropathy, diabetic retinopathy, diabetic cardiomyopathy, and diabetic angiopathy. Recent studies have highlighted the intricate interplay between N6-methyladenosine (m6A) and non-coding RNAs (ncRNAs) in key pathways implicated in these diabetes complications, like cell apoptosis, oxidative stress, and inflammation. Thus, understanding the mechanistic insights into how m6A dysregulation impacts the expression and function of ncRNAs opens new avenues for therapeutic interventions targeting the m6A-ncRNAs axis in diabetes complications. This review explores the regulatory roles of m6A modifications and ncRNAs, and stresses the role of the m6A-ncRNA axis in diabetes complications, providing a therapeutic potential for these diseases.

Prostanoid signaling in retinal vascular diseases.

The vasculature of the retina is exposed to systemic and local factors that have the capacity to induce several retinal vascular diseases, each of which may lead to vision loss. Prostaglandin signaling has arisen as a potential therapeutic target for several of these diseases due to the diverse manners in which these lipid mediators may affect retinal blood vessel function. Previous reports and clinical practices have investigated cyclooxygenase (COX) inhibition by nonsteroidal anti-inflammatory drugs (NSAIDs) to address retinal diseases with varying degrees of success; however, targeting individual prostanoids or their distinct receptors affords more signaling specificity and poses strong potential for therapeutic development. This review offers a comprehensive view of prostanoid signaling involved in five key retinal vascular diseases: retinopathy of prematurity, diabetic retinopathy, age-related macular degeneration, retinal occlusive diseases, and uveitis. Mechanistic and clinical studies of these lipid mediators provide an outlook for therapeutic development with the potential to reduce vision loss in each of these conditions.

Effect of a self-care promoting program on engagement in self-care behaviors and health-related outcomes among persons with type 2 diabetes and diabetic retinopathy: A single-blind randomized controlled trial.

Background: Diabetic retinopathy (DR) is the most common microvascular complication of diabetes, leading to visual impairment and eventual blindness. Promoting self-care behaviors is crucial in controlling DR progression and preventing blindness. Objective: This study aimed to investigate the effects of a Self-Care Promoting Program (SCPP) on engagement in self-care behaviors, HbA1c levels, visual acuity (VA), severity of DR, and vision-related quality of life (VRQoL) among individuals with type 2 diabetes and DR. Methods: This study employed a single-blind randomized controlled trial design to compare SCPP with conventional diabetic care interventions (standard care). The SCPP was based on the Self-Care of Chronic Illness Theory, Self-efficacy theory, and the Association of Diabetic Care and Education Specialist (ADCES) guidelines incorporating health education, self-care maintenance, monitoring, and management skills training over 12 weeks. Ninety-eight participants were randomly allocated to the experimental or control group (n = 49 per group). While the experimental group received SCPP alongside standard care, the control group received standard care alone. Data collection occurred between May 2022 and March 2023 and included demographic information, the Self-Care of Diabetes Index questionnaire (SCODI), the self-care for diabetes eye care questionnaire (SCFDE), the impact of visual impairment questionnaire (IVI-Thai version), and retinal images for DR severity grading. Data analysis utilized descriptive statistics, Chi-Square tests, t-tests, and MANOVA. Results: Following 8 and 16 weeks of SCPP, the experimental group had significantly higher mean scores in engagement with self-care and eye-care behaviors compared to the control group (p <0.001). The highest scores were observed in self-care and eye-care confidence behaviors, followed by maintenance, monitoring, and management. Furthermore, HbA1c levels and VRQoL significantly decreased and were lower than those of the control group at week 16 (p <0.001 and p <0.05, respectively). However, there were no significant differences in VA, and DR severity increased in both groups by week 16. Conclusion: SCPP benefits individuals with DR, enhancing their confidence and ability to perform, monitor, and manage self-care behaviors. These strategies contribute to improved diabetes management, enhanced quality of life, and reduced DR-related blindness. Integrating SCPP into routine DR management is recommended, with nurses playing a pivotal role in overseeing and driving this integration, highlighting the critical role of nurses in managing this widespread global disease. Trial Registry Number: Thai Clinical Trials Registration (TCTR20230302002).

Mendelian randomization study and mediation analysis about the relation of inflammatory bowel disease and diabetic retinopathy: the further exploration of gut-retina axis.

Background: The concept of the gut-retinal axis proposed by previous scholars primarily focused on the relationship between intestinal microbiota and retinal diseases, and few further expanded the relationship between intestinal diseases and retinal diseases. To further substantiate the concept of the gut-retinal axis, we analyzed inflammatory bowel disease (IBD) and diabetic retinopathy (DR) using Mendelian randomization (MR), and use mediation analysis to further explore the potential substances that influence this causal relationship. Methods: The genome-wide association study's (GWAS) summary statistics for genetic variations were utilized in a Mendelian randomization (MR) investigation. GWAS data on IBD (including ulcerative colitis (UC), Crohn's disease (CD), and IBD) for non-Finnish Europeans (NFE) were sourced from published articles. In contrast, data on DR (including DR and diabetic maculopathy (DMP)) were obtained from FinnGen R9. The causal relationship has been investigated using inverse variance weighted (IVW), MR-Egger, and weighted median and sensitivity analysis was applied to verify the stability of the results. In addition, we applied mediation analysis to investigate whether circulating inflammatory proteins and plasma lipids played a mediating role, and calculated its effect ratio. Results: The causal relationship between IBD and DR was discovered by employing the inverse variance weighted (IVW) method and weighted median method. In forward MR, UC was significantly associated with lower risk of DR (IVW: OR=0.874; 95%CI= 0.835-0.916; P value= 1.28E-08) (Weighted median: OR=0.893; 95%CI= 0.837-0.954; P value= 7.40E-04). In reverse MR, it was shown that DR (IVW: OR=0.870; 95%CI= 0.828-0.914; P value= 2.79E-08)(Weighted median: OR=0.857; 95%CI= 0.801-0.916; P value= 6.40E-06) and DMP (IVW: OR=0.900; 95%CI= 0.865-0.937; P value= 3.34E-07)(Weighted median: OR=0.882; 95%CI= 0.841-0.924; P value= 1.82E-07) could reduce the risk of CD. What's more, DR is associated with a lower risk of IBD according to genetic prediction (IVW: OR=0.922; 95%CI= 0.873-0.972; P value= 0.002) (Weighted median: OR=0.924; 95%CI= 0.861-0.992; P value= 0.029). Fibroblast growth factor 21 (FGF21), phosphatidylcholine (PC), and triacylglycerol (TG) serve as mediators in these relationships. Conclusions: Our research offers novel insights and sources for investigating the gut-retina axis in the genetic relationship between IBD and DR. We discover four mediators and more about the association between the intestine and retinal disorders and provide more evidence for the gut-retinal axis theory.

Health transition and eye care policy planning for people with diabetic retinopathy in south Asia.

The prevalence of type 2 diabetes (T2D), associated systemic disorders, diabetic retinopathy (DR) and current health policies in south Asian countries were analysed to assess country-specific preparedness to meet the 2030 Sustainable Development Goals. The south Asian countries were classified by human development index, socio-demographic index, multidimensional poverty indices, and eye health resources for epidemiological resource-level analysis. In south Asia, the prevalence of diagnosed and undiagnosed T2D in adults aged 40 years or above, was higher in Pakistan (26.3%) and Afghanistan (71.4%), respectively; India has the highest absolute number of people with DR, and Afghanistan has the highest prevalence of DR (50.6%). In this region, out-of-pocket spending is high (∼77%). This Health Policy is a situational analysis of data available on the prevalence of DR and common eye diseases in people with T2D in south Asia and available resources to suggest tailored health policies to local needs. The common issues in the region are insufficient human resources for eye health, unequal distribution of available workforce, and inadequate infrastructure. Addressing these challenges of individuals with T2D and DR, a 10-point strategy is suggested to improve infrastructure, augment human resources, reduce out-of-pocket spending, employ targeted screening, and encourage public-private partnerships.

Segmentation of retinal microaneurysms in fluorescein fundus angiography images by a novel three-step model.

Introduction: Microaneurysms serve as early signs of diabetic retinopathy, and their accurate detection is critical for effective treatment. Due to their low contrast and similarity to retinal vessels, distinguishing microaneurysms from background noise and retinal vessels in fluorescein fundus angiography (FFA) images poses a significant challenge. Methods: We present a model for automatic detection of microaneurysms. FFA images were pre-processed using Top-hat transformation, Gray-stretching, and Gaussian filter techniques to eliminate noise. The candidate microaneurysms were coarsely segmented using an improved matched filter algorithm. Real microaneurysms were segmented by a morphological strategy. To evaluate the segmentation performance, our proposed model was compared against other models, including Otsu's method, Region Growing, Global Threshold, Matched Filter, Fuzzy c-means, and K-means, using both self-constructed and publicly available datasets. Performance metrics such as accuracy, sensitivity, specificity, positive predictive value, and intersection-over-union were calculated. Results: The proposed model outperforms other models in terms of accuracy, sensitivity, specificity, positive predictive value, and intersection-over-union. The segmentation results obtained with our model closely align with benchmark standard. Our model demonstrates significant advantages for microaneurysm segmentation in FFA images and holds promise for clinical application in the diagnosis of diabetic retinopathy. Conclusion: The proposed model offers a robust and accurate approach to microaneurysm detection, outperforming existing methods and demonstrating potential for clinical application in the effective treatment of diabetic retinopathy.

Diabetic retinopathy: New concepts of screening, monitoring, and interventions.

The science of diabetes care has progressed to provide a better understanding of the oxidative and inflammatory lesions and pathophysiology of the neurovascular unit within the retina (and brain) that occur early in diabetes, even prediabetes. Screening for retinal structural abnormalities, has traditionally been performed by fundus examination or color fundus photography; however, these imaging techniques detect the disease only when there are sufficient lesions, predominantly hemorrhagic, that are recognized to occur late in the disease process after significant neuronal apoptosis and atrophy, as well as microvascular occlusion with alterations in vision. Thus, interventions have been primarily oriented toward the later-detected stages, and clinical trials, while demonstrating a slowing of the disease progression, demonstrate minimal visual improvement and modest reduction in the continued loss over prolonged periods. Similarly, vision measurement utilizing charts detects only problems of visual function late, as the process begins most often parafoveally with increasing number and progressive expansion, including into the fovea. While visual acuity has long been used to define endpoints of visual function for such trials, current methods reviewed herein are found to be imprecise. We review improved methods of testing visual function and newer imaging techniques with the recommendation that these must be utilized to discover and evaluate the injury earlier in the disease process, even in the prediabetic state. This would allow earlier therapy with ocular as well as systemic pharmacologic treatments that lower the and neuro-inflammatory processes within eye and brain. This also may include newer, micropulsed laser therapy that, if applied during the earlier cascade, should result in improved and often normalized retinal function without the adverse treatment effects of standard photocoagulation therapy.

Prediction of diabetic retinopathy among type 2 diabetic patients in University of Gondar Comprehensive Specialized Hospital, 2006-2021: A prognostic model.

BACKGROUND: There has been a paucity of evidence for the development of a prediction model for diabetic retinopathy (DR) in Ethiopia. Predicting the risk of developing DR based on the patient's demographic, clinical, and behavioral data is helpful in resource-limited areas where regular screening for DR is not available and to guide practitioners estimate the future risk of their patients. METHODS: A retrospective follow-up study was conducted at the University of Gondar (UoG) Comprehensive Specialized Hospital from January 2006 to May 2021 among 856 patients with type 2 diabetes (T2DM). Variables were selected using the Least Absolute Shrinkage and Selection Operator (LASSO) regression. The data were validated by 10-fold cross-validation. Four ML techniques (naïve Bayes, K-nearest neighbor, decision tree, and logistic regression) were employed. The performance of each algorithm was measured, and logistic regression was a well-performing algorithm. After multivariable logistic regression and model reduction, a nomogram was developed to predict the individual risk of DR. RESULTS: Logistic regression was the best algorithm for predicting DR with an area under the curve of 92%, sensitivity of 87%, specificity of 83%, precision of 84%, F1-score of 85%, and accuracy of 85%. The logistic regression model selected seven predictors: total cholesterol, duration of diabetes, glycemic control, adherence to anti-diabetic medications, other microvascular complications of diabetes, sex, and hypertension. A nomogram was developed and deployed as a web-based application. A decision curve analysis showed that the model was useful in clinical practice and was better than treating all or none of the patients. CONCLUSIONS: The model has excellent performance and a better net benefit to be utilized in clinical practice to show the future probability of having DR. Identifying those with a higher risk of DR helps in the early identification and intervention of DR.

Positive and Negative Associations of Myopia with Ocular Diseases in Population-Based Studies.

OBJECTIVE: Prevalence of myopia and vision impairment due to myopic macular degeneration and myopia-related optic neuropathies have markedly increased worldwide. We evaluated whether myopia is associated with the prevalence of other ocular disorders in a positive or negative sense. DESIGN: Population-based studies conducted in Russia, China and India. PARTICIPANTS: The Russian Ural Eye and Medical Study (UEMS) and the Beijing Eye Study (BES) included 5899 individuals and 4439 individuals (all aged 40+ years), respectively, and the Central India Eye and Medical Study (CIEMS) consisted of 4711 individuals, aged 30+ years. The studies were conducted in rural and urban regions in Bashkortostan/Russia, Nagpur/India, and Beijing/China. METHODS: The participants underwent a series of ophthalmological and general medical examinations. MAIN OUTCOME MEASURES: Axial length as surrogate for myopia, and prevalence of diabetic retinopathy (DR), age-related macular degeneration (AMD), angle-closure glaucoma (ACG), and open-angle glaucoma (OAG). RESULTS: In the UEMS, DR prevalence (OR:0.73;95%CI:0.56,0.96), AMD prevalence (OR:0.85;95%CI:0.74,0.98) and ACG prevalence (OR:0.72;95%CI:0.55,0.95) decreased, and OAG prevalence (OR:1.65;95%CI:1.45,1.88) increased with longer axial length in multivariable analyses. In the CIEMS, lower AMD prevalence (OR:0.81;95%CI:0.69,0.95) and lower ACG prevalence (OR:0.55;95%CI:0.36,0.83), and higher OAG prevalence (OR:1.45;95%CI:1.15,1.83) were associated with longer axial length. DR prevalence (0.33%;95%CI:0.16,0.50) was too low for statistical analysis in the CIEMS. In the BES, prevalence (OR:0.64;95%CI:0.50,0.81) and 10-year incidence of DR (OR:0.48;95%CI:0.33,0.71) and prevalence (OR:0.83;95%CI:0.77,0.89) and 5-year incidence of AMD (OR:0.996;95%CI:0.993,0.999) decreased, and prevalence (OR:1.35;95% CI:1.17,1.56) and 10-year incidence of OAG (OR:1.40;95%CI:1.22,1.61) increased with longer axial length. In all three studies, the association between higher OAG prevalence and longer axial length was nonlinear with a slight increase for the moderate myopia range, and a steep increase in the highly myopic range. CONCLUSIONS AND RELEVANCE: Myopia is associated with a lower prevalence of DR, AMD and ACG and lower incidence of DR and AMD, while high myopia more than moderate myopia is associated with a higher prevalence and incidence of OAG. Future studies may assess whether in myopia, in particular in moderate myopia, the myopia-related advantages, i.e., lower prevalence of DR, AMD and ACG, may outweigh the increased risks for OAG and other myopia-related disorders.

Artificial intelligence in diabetic retinopathy screening: from idea to a medical device in clinical practice.

With the growing significance of artificial intelligence in healthcare, new perspectives are emerging in primary care. Diabetic retinopathy, a microvascular complication of diabetes mellitus, often remains unnoticed until patient is facing complications. Artificial intelligence presents a promising solution that can enhance the accessibility of diabetic retinopathy screening for a broader range of patients. The key challenge lies in successfully integrating the solution into clinical practice, a demanding process with multiple phases to ensure the resulting medical device is effective and safe for patient use. Aireen software uses artificial intelligence to perform diabetic retinopathy screening on retinal images captured by optical fundus cameras. The medical device complies with European Medical Device Regulation 2017/745 and was introduced to the market in 2023. Collaboration between physicians and the development team played a crucial role throughout the entire lifecycle of the medical device. Physicians were engaged in defining the intended use of the medical device, risk analysis, data annotation for training and software validation, as well as throughout a clinical trial. A clinical trial was conducted on 1,274 patients with type 1 and type 2 diabetes mellitus, where Aireen medical device achieved a sensitivity of 94.0% and a specificity of 90.7% compared to the reference evaluation. This clinical trial confirmed the potential of Aireen to enhance the availability of diabetic retinopathy screening and early disease detection.

The circular RNA circSLC16A10 alleviates diabetic retinopathy by improving mitochondrial function via the miR-761-5p/MFN2 axis.

It has been demonstrated that circular RNAs (circRNAs) are associated with the development of diabetic retinopathy (DR). Nevertheless, the function of circSLC16A10 in the development of DR remains unclear. In order to investigate the role of circSLC16A10, we employed cell and animal models of DR. An analysis of a public database revealed that hsa_circSLC16A10 was expressed at lower levels in DR patients than in diabetic patients without DR or healthy controls. Additionally, the level of hsa_circSLC16A10 was lower in high glucose (HG)-exposed ARPE-19 cells and diabetic mice. hsa_circSLC16A10 was observed to be mainly distributed in the cytoplasm. Moreover, overexpression of hsa_circSLC16A10 alleviated HG-induced endoplasmic reticulum stress and cell apoptosis in vitro. Furthermore, overexpression of hsa_circSLC16A10 ameliorated HG-induced mitochondrial dysfunction, as evidenced by improvements in mitochondrial structure and function. Hsa_circSLC16A10 acted as a hsa-miR-761-5p sponge to increase MFN2 expression. MFN2 knockdown or hsa-miR-761-5p overexpression partially reversed the protective effect of hsa_circSLC16A10 in vitro. The protective effect of mmu_circSLC16A10 against DR was confirmed in an animal model of DR. These findings indicate that circSLC16A10 may regulate DR progression by improving mitochondrial function via the miR-761-5p/MFN2 axis.

Insulin resistance in the retina: possible implications for certain ocular diseases.

Insulin resistance (IR) is becoming a worldwide medical and public health challenge as an increasing prevalence of obesity and metabolic disorders. Accumulated evidence has demonstrated a strong relationship between IR and a higher incidence of several dramatically vision-threatening retinal diseases, including diabetic retinopathy, age-related macular degeneration, and glaucoma. In this review, we provide a schematic overview of the associations between IR and certain ocular diseases and further explore the possible mechanisms. Although the exact causes explaining these associations have not been fully elucidated, underlying mechanisms of oxidative stress, chronic low-grade inflammation, endothelial dysfunction and vasoconstriction, and neurodegenerative impairments may be involved. Given that IR is a modifiable risk factor, it may be important to identify patients at a high IR level with prompt treatment, which may decrease the risk of developing certain ocular diseases. Additionally, improving IR through the activation of insulin signaling pathways could become a potential therapeutic target.