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Diabetic retinopathy is a complication of diabetes mellitus and a leading cause of blindness and visual impairment globally. Limited information existed on the epidemiology of diabetic retinopathy at the national level in Ethiopia. Thus, the objective of this review was to determine the pooled prevalence of diabetic retinopathy and its associated risk factors in Ethiopia. A systematic review and meta-analysis was conducted using previous primary studies that were found in electronic databases such as Web of Science, Scopus, PubMed, CINHAL, Google Scholar, and online African journals. We evaluated the quality of the included studies using the Newcastle-Ottawa Assessment Scale. The random-effects model was applied because heterogeneity was expected. I-Square and the Cochrane Q statistics were used to evaluate heterogeneity. Publication bias was examined using Egger's test and a funnel plot. A random-effect meta-analysis was applied to pool the odds ratios of risk factors to determine the association between the independent and dependent variables. After 598 articles were found, 22 studies that met the eligibility requirements were included. The pooled prevalence of retinopathy among patients with diabetes in Ethiopia was 24.35% (95% CI: 18.88–29.83), with considerable heterogeneity (I2 = 98.18%, p < 0.001). Ten years and longer with diabetes (AOR = 4.36, 95% CI: 1.71–7.01), hypertension (AOR = 2.54, 95% CI: 1.45–3.63), poor glycemic control (AOR = 3.83, 95% CI: 1.62–6.04), and positive proteinuria (AHR = 1.55, 95% CI: 1.02–2.07) were risk factors for diabetic retinopathy. Retinopathy affects one in four patients with diabetes. Diabetic patients with longer duration, hypertension, poor glycemic control, and positive proteinuria should receive special care. [ABSTRACT FROM AUTHOR]

Prolonged hyperglycemic conditions in type 2 diabetes mellitus (T2DM) cause pathological and functional damage to many organs and tissues, including the kidneys, retina, skin, and neuronal tissues, resulting in the development of microvascular diabetic complications. The altered renin angiotensin aldosterone system (RAAS) pathway has been reported to play an important role in the development of insulin resistance in T2DM and associated complications. The current study was carried out to evaluate the association of risk factors and altered expression of RAAS genes in T2DM patients without complications and T2DM patients with complications (retinopathy, nephropathy, and neuropathy). Four hundred and twenty subjects including 140 healthy controls, 140 T2DM patients with diabetic complications, and 140 T2DM patients without diabetic complications were included in the study. Risk factors associated with the development of T2DM and diabetic complications were evaluated. Further, expression analysis of RAAS genes (AGT, ACE, ACE2, and AGT1R) was carried out using qRTPCR in healthy controls, T2DM patients with complications, and T2DM patients without complications. Various risk factors like urban background, higher BMI, alcoholism, smoking, and family history of diabetes among others were found to be associated with the development of T2DM as well as diabetic complications. The expression level of AGT, ACE, and AGT1R was found to be upregulated whereas ACE2 was found to be downregulated in T2DM patients with complications and T2DM patients without complications as compared to controls. Altered expression of the studied genes of RAAS pathway is associated with the development of microvascular diabetic complications. [ABSTRACT FROM AUTHOR]

Background: Proteinuria is considered as a predictor for cardiovascular complications in diabetes mellitus (DM). However, no study has examined the association between changes in proteinuria and the risk of diabetic microvascular complications. Methods: Study participants were 71,825 DM patients who received urine dipstick test for proteinuria both in 2003–2004 and 2006–2007. They were categorized into four groups according to changes in proteinuria over 3 years (negative: negative → negative, resolved: proteinuria ≥ 1+ → negative, incident: negative → proteinuria ≥ 1+, persistent: proteinuria ≥ 1+ → proteinuria ≥ 1+). Cox-proportional hazard model was used in assessing the adjusted hazard ratios (HR) and 95% confidence interval (CI) for incidence of retinopathy, and neuropathy (adjusted HR [95% CI]). Result: In all of DM patients, risk for comprehensive incidence of retinopathy and neuropathy increased in all types of proteinuria changes. In type 1 DM, HR for retinopathy and neuropathy generally increased in order of negative (reference), resolved (2.175 [1.150–4.114] and 1.335 [0.909–1.961]), incident (2.088 [1.185–3.680] and 1.753 [1.275–2.409]), and persistent proteinuria (1.314 [0.418–4.134] and 2.098 [1.274–3.455]). This pattern of relationship was similarly observed in type 2 DM for retinopathy and neuropathy: negative (reference), resolved (1.490 [1.082–2.051] and 1.164 [0.988–1.371]), incident (1.570 [1.161–2.123] and 1.291 [1.112–1.500]), and persistent proteinuria (2.309 [1.407–3.788] and 1.272 [0.945–1.712]). Conclusion: Risk for diabetic retinopathy and neuropathy generally increased in order of negative, resolved, incident, and persistent proteinuria. Once manifested proteinuria was associated with the increased risk of diabetic retinopathy and neuropathy even after remission of proteinuria. [ABSTRACT FROM AUTHOR]

The development of fetal organs can be impacted by systemic changes in maternal circulation, with the placenta playing a pivotal role in maintaining pregnancy homeostasis and nutrient exchange. In clinical obstetrics, oxytocin (OXT) is commonly used to induce labor. To explore the potential role of OXT in the placental homeostasis of OXT, we compared OXT levels in neonatal cord blood among neonates (23–42 weeks gestation) whose mothers either received prenatal OXT or experienced spontaneous labor. Our previous research revealed that the oxytocin receptor (OXTR), essential in forming the blood–retina barrier, is expressed in the retinal pigment epithelium (RPE). We hypothesized that perinatal OXT administration might influence the development of the neural retina and its vasculature, offering therapeutic potential for retinal diseases such as retinopathy of prematurity (ROP). Plasma OXT levels were measured using a commercial OXT ELISA kit. Human fetal RPE (hfRPE) cells treated with OXT (10 µM) were assessed for gene expression via RNA sequencing, revealing 14 downregulated and 32 upregulated genes. To validate these differentially expressed genes (DEGs), hfRPE cells were exposed to OXT (0.01, 0.1, 1, or 10 µM) for 12 h, followed by RNA analysis via real-time PCR. Functional, enrichment, and network analyses (Gene Ontology term, FunRich, Cytoscape) were performed to predict the affected pathways. This translational study suggests that OXT likely crosses the placenta, altering fetal OXT concentrations. RNA sequencing identified 46 DEGs involved in vital metabolic and signaling pathways and critical cellular components. Our results indicate that the perinatal administration of OXT may affect neural retina and retinal vessel development, making OXT a potential therapeutic option for developmental eye diseases, including ROP. [ABSTRACT FROM AUTHOR]

Background: Hypertensive emergency is a critical disease that causes multiple organ injuries. Although the renin-angiotensin-aldosterone system (RAS) is enormously activated in this disorder, whether the RAS contributes to the development of the organ damage has not been fully elucidated. This cross-sectional study was conducted to characterize the association between RAS and the organ damage in patients with hypertensive emergencies. Methods: We enrolled 63 patients who visited our medical center with acute severe hypertension and multiple organ damage between 2012 and 2020. Hypertensive target organ damage was evaluated on admission, including severe kidney impairment (eGFR less than 30 mL/min/1.73 m2, SKI), severe retinopathy, concentric left ventricular hypertrophy (c-LVH), thrombotic microangiopathy (TMA), heart failure with reduced ejection fraction (HFrEF) and cerebrovascular disease. Then, whether each organ injury was associated with blood pressure or a plasma aldosterone concentration was analyzed. Results: Among 63 patients, 31, 37, 43 and 8 cases manifested SKI, severe retinopathy, c-LVH and ischemic stroke, respectively. All populations with the organ injuries except cerebral infarction had higher plasma aldosterone concentrations than the remaining subset but exhibited a variable difference in systolic or diastolic blood pressure. Twenty-two patients had a triad of SKI, severe retinopathy and c-LVH, among whom 5 patients manifested TMA. Furthermore, the number of the damaged organs was correlated with plasma aldosterone levels (Spearman's coefficient = 0.50), with a strong association observed between plasma aldosterone (≥ 250 pg/mL) and 3 or more complications (odds ratio = 9.16 [95%CI: 2.76–30.35]). Conclusion: In patients with hypertensive emergencies, a higher aldosterone level not only contributed to the development of the organ damage but also was associated with the number of damaged organs in each patient. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is a common complication of diabetes characterized by vascular pathology and neuroinflammation. Pentraxin 3 (PTX3) is a soluble pattern recognition molecule that functions at the crossroads between innate immunity, inflammation, and tissue remodeling. DR is known to involve inflammatory pathways, although the potential relevance of PTX3 has not been explored. We found that PTX3 protein levels increased in the retina of diabetic mice. Similarly, evaluation of a publicly available transcriptomic human dataset revealed increased PTX3 expression in DR with diabetic macular edema and proliferative retinopathy, when compared to nondiabetic retinas or diabetic retinas without complications. To further understand the role of PTX3 within DR, we employed the streptozotocin-induced diabetes model in PTX3 knockout mice (PTX3KO), which were followed up for 9 mo to evaluate hallmarks of disease progression. In diabetic PTX3KO mice, we observed decreased reactive gliosis, diminished microglia activation, and reduced vasodegeneration, when compared to diabetic PTX3 wild-type littermates. The decrease in DR-associated pathological features in PTX3KO retinas translated into preserved visual function, as evidenced by improved optokinetic response, restored b-wave amplitude in electroretinograms, and attenuated neurodegeneration. We showed that PTX3 induced an inflammatory phenotype in human retinal macroglia, characterized by GFAP upregulation and increased secretion of IL6 and PAI-1. We confirmed that PTX3 was required for TNF-α-induced reactive gliosis, as PTX3KO retinal explants did not up-regulate GFAP in response to TNF-α. This study reveals a unique role for PTX3 as an enhancer of sterile inflammation in DR, which drives pathogenesis and ultimately visual impairment. [ABSTRACT FROM AUTHOR]

Background: Pathological retinal neovascularization is marked by microvascular lesions manifested initially as endothelial cell dysfunction and metabolic disturbances. However, the regulatory mechanism guiding retinal vascular endothelial cell function remian controversial. Main body: Previous studies have demonstarted that high glucose or oxidative stress can induce premature senescence in endothelial cells, triggering inflammatory responses within the vascular system and promoting the secretion of pro‐inflammatory factors, ultimately leading to pathological angiogenesis. Endothelial cell senescence has thus become a key target for anti‐angiogenic therapies. Conclusion: This review delves into current research on the mechanisms driving senescence‐induced retinal angiogenesis and highlights potential target protein pathways, aiming to provide insights for future investigations. [ABSTRACT FROM AUTHOR]

Background: The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction and failure of various organs, especially the eyes, kidneys, nerves, heart and blood vessels. Present study was aimed to study associated comorbidities and microvascular/macrovascular complications in diabetic patients attending a tertiary care center. Material and Methods: Present study was Cross sectional study, conducted in Type 1 and Type 2 Diabetes mellitus or newly diagnosed diabetes mellitus patients. Results: In present study regarding the eGFR maximum patients 47 (46.54%) were in stage III-B (G3a) followed by 37 (36.63%) were in stage IV (G4), 9 (8.91%) were in stage 5 (G5) and 8 (7.92%) in stage III-A (G3b) of chronic kidney disease. Data revealed that majority of patient's eGFR was moderately decreased. Majority of patients 93 (92.08%) lies in very high risk as per KDIGO classification and remaining 8 (7.92%) were at high risk. In present study out of 101 patients 48 (47.52%) had retinopathy. Among the 48 cases of retinopathy maximum patients 43 (89.58%) were having non-proliferative diabetic retinopathy (NDRP) followed by 4 (8.33%) were having mixed NDRP/PDR and single case was having proliferative retinopathy. Majority 81 (80.20%) not having neuropathy and 20 (19.80%) had neuropathy. Regarding macrovascular complication majority of patients 30 (29.70%) had unstable angina followed by myocardial infarction in 25 (24.75%), Heart failure in 18 (17.82%) and 15 (14.85%) had stroke. In present study maximum patients 97 (96.04%) were discharged and 4 (3.96%) were died during the study period. Further data reveals significant correlation between stages of CKD with outcome as p<0.05. Maximum mortality was seen in progressive stage of CKD. Conclusion: Among diabetic population, advancing age, gender, concomitant hypertension, increasing duration of diabetes and the presence of macrovascular complication were found to be important risk factors. [ABSTRACT FROM AUTHOR]

Worldwide, the number of individuals suffering from visual impairment, as well as those affected by blindness, is about 600 million and it will further increase in the coming decades. These diseases also seriously affect the quality of life in working-age individuals. Beyond the characterization of metabolic, genetic, and environmental factors related to ocular pathologies, it is important to verify how lifestyle may participate in the induction of the molecular pathways underlying these diseases. On the other hand, scientific studies are also contributing to investigations as to whether lifestyle could intervene in modulating pathophysiological cellular responses, including the production of metabolites and neurohormonal factors, through the intake of natural compounds capable of interfering with molecular mechanisms that lead to ocular diseases. Nutraceuticals are promising in ameliorating pathophysiological complications of ocular disease such as inflammation and neurodegeneration. Moreover, it is important to characterize the nutritional patterns and/or natural compounds that may be beneficial against certain ocular diseases. The adherence to the Mediterranean diet (MeDi) is proposed as a promising intervention for the prevention and amelioration of several eye diseases. Several characteristic compounds and micronutrients of MeDi, including vitamins, carotenoids, flavonoids, and omega-3 fatty acids, are proposed as adjuvants against several ocular diseases. In this review, we focus on studies that analyze the effects of MeDi in ameliorating diabetic retinopathy, macular degeneration, and glaucoma. The analysis of knowledge in this field is requested in order to provide direction on recommendations for nutritional interventions aimed to prevent and ameliorate ocular diseases. [ABSTRACT FROM AUTHOR]

Objective: There are very few reports on the prevalence of diabetic retinopathy (DR) in children and youth with type-1 diabetes (T1D). Studies have also found very low rates of referral for DR screening in children and youth with T1D. We conducted this study to determine the prevalence of DR, to study the reliability of ISPAD screening recommendations and to identify predictors of DR, its progression and regression in Indian children and youth with T1D. Methods: This study included 882 children and youth with T1D. Demographic data, anthropometry, blood pressure, sexual maturity rating, ophthalmological examination (slit lamp for cataract) and biochemical measurements were performed using standard protocols. Fundus images were captured using the Forus Health 3netra classic digital non-mydriatic fundus camera by the same experienced operator. De-identified images were assessed by a senior grader and ophthalmologist (Belfast Ophthalmic Reading Center). Severity of DR was graded as per the UK National Health Service (NHS) DR classification scale. Result: We report 6.4% and 0.2% prevalence of DR and cataract in Indian children and youth with T1D, respectively. All the subjects with DR had early non-proliferative DR. We report that amongst subjects with DR, only 2 subjects were aged less than 11 years and had duration of illness less than 2 years. Presence of hypertension and older age were significant predictors of DR (P <.05). Subjects with DR had significantly higher triglyceride concentrations (P <.05), of these, 6.9% had progression and 2.9% had regression at 1 year follow up; the change in glycaemic control was a significant positive predictor of progression of DR (P <.05). None of the participants included in the study progressed to develop sight-threatening DR. Conclusion: DR is not uncommon in Indian children and youth with T1D, thus screening for DR needs to be initiated early, particularly in older individuals with higher disease duration. Controlling blood pressure and triglyceride concentrations may prevent occurrence of DR. Improving glycaemic control may prevent progression of DR in Indian children and youth with T1D. Plain Language Summary: Diabetic retinopathy in Indian children with Type 1 Diabetes We found that 6.4% and 0.2% Indian children and youth with type-1 diabetes had diabetic retinopathy and cataract respectively. We report that amongst subjects with DR, only 2 subjects were aged less than 11 years and had duration of illness less than 2 years. Thus, International Society for Paediatric and Adolescent Diabetes (ISPAD) screening criteria must be implemented by all centres to avoid missing cases. Presence of high blood pressure, high triglyceride levels and older age were significant predictors of DR. Of the subjects with DR, 6.9% had progression and 2.9% had regression at 1 year follow up; the change in glycaemic control was a significant positive predictor of progression of DR. None of the participants included in the study progressed to develop sight-threatening DR. DR is not uncommon in Indian children and youth with T1D, hence, screening for DR needs to be initiated early, particularly in older individuals with higher disease duration. Controlling blood pressure and triglyceride concentrations may prevent occurrence of DR. Improving glycaemic control may prevent progression of DR in Indian children and youth with T1D. [ABSTRACT FROM AUTHOR]

The occurrence and development of ophthalmic diseases are related to the dysfunction of eye tissues. Ubiquitin is an important form of protein post-translational modification, which plays an essential role in the occurrence and development of diseases through specific modification of target proteins. Ubiquitination governs a variety of intracellular signal transduction processes, including proteasome degradation, DNA damage repair, and cell cycle progression. Studies have found that ubiquitin can play a role in eye diseases such as cataracts, glaucoma, keratopathy, retinopathy, and eye tumors. In this paper, the role of protein ubiquitination in eye diseases was reviewed. [ABSTRACT FROM AUTHOR]

Purpose: To report a case of bilateral exudative retinal detachments and panuveitis in a patient with multiple myeloma (MM). Case Report: A 54-year-old patient with non-proliferative diabetic retinopathy was referred with blurred vision and scotomas in both eyes (OU). Three months prior to the onset of ocular symptoms, he was diagnosed with systemic MM and was receiving chemotherapy. Clinical examination revealed best-corrected visual acuities of 20/80 OU, rare anterior chamber cell, 2+ vitreous cell, diffuse intraretinal hemorrhages, and exudative retinal detachments (RD). Optical coherence tomography of the macula showed central subretinal fluid with cystic intraretinal fluid OU. The findings were consistent with panuveitis and exudative RD in the setting of MM. He reported symptomatic improvement after plasmapheresis and oral prednisone initiation. Conclusion: Extensive, bilateral exudative RD and panuveitis are rare but potentially sight-threatening findings in patients with MM. [ABSTRACT FROM AUTHOR]

Background: Diabetes is a rapidly growing health challenge and potential epidemic across low-and-middle-income countries like India. Diabetic retinopathy (DR) is a consequence of diabetic microangiopathy, which may cause visual deterioration due to macular edema in any stage and vitreous hemorrhage or tractional retinal detachment in the advanced proliferative retinopathy stages. Aims and Objectives: The aim was to study the retinopathy status in diabetic patients with a risk of diabetic foot syndrome (DFS) visiting a western regional hospital in India. Materials and Methods: In this cross-sectional study, all patients with diabetes mellitus (DM) with a risk of DFS, visiting a tertiary care hospital during the study period, underwent an ophthalmological evaluation for documentation of their retinopathy status. Results: One hundred and fourteen patients diagnosed to have a risk profile for DFS were included in the study. Their mean age was 61.22 years and 81.6% were males. The mean duration of DM was 12.24 years, respectively. Of the 114 patients, 72 had DR. An increased presence of retinopathy in patients with an increased risk grade of diabetic foot (DF) was found significant by the Chi-square test. (P<0.001). Conclusion: Our study found an increased presence of DR in Western Indian cohort with DFS. The severity of retinopathy was greater in patients with higher grades of risk for DF, therefore establishment of an association between DR and DFS will help in developing an integrated management strategy for these two grave consequences of diabetes. [ABSTRACT FROM AUTHOR]

Diabetes Mellitus (DM) is on the rise making it a major concern for global health. DM can be classified into type 1 or type 2, and both can lead to changes in brain metabolites. These can result in serious complications like cognitive decline, particularly if not managed properly by diabetic patients. Magnetic Resonance Spectroscopy (MRS) is a non-invasive technique that allows us to study the brain metabolite levels. The present review utilises available Magnetic Resonance Imaging (MRI) data to understand how brain metabolites are affected in both type 1 and type 2 diabetes (T2DM). Research shows that in individuals with diabetes, there are changes in important brain chemicals such as creatine (Cr), N-Acetyl Aspartate (NAA), Myo-Inositol (MI), choline (Cho), glutamate, and glutamine. A consistent finding across multiple studies showed a reduction in NAA levels, which is a key indicator of brain neuron health. This suggests that diabetes negatively impacts the function of neurons in the brain. Changes were seen in other metabolites indicating potential disruptions in energy regulation and membrane function. This review concludes that alterations in brain metabolites as measured using MRS, could serve as a non-invasive biomarker for tracking the progression of DM and its related complications. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is a leading cause of blindness, yet its molecular mechanisms are unclear. Extracellular vesicles (EVs) contribute to dysfunction in DR, but the characteristics and functions of vitreous EVs are unclear. This study investigated the inflammatory properties of type 2 diabetic (db) vitreous EVs. EVs isolated from the vitreous of db and non-db donors were used for nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), immunogold staining, Western blotting, and proteomic analysis by mass spectrometry. Intracellular uptake of vitreous EVs by differentiated macrophages was evaluated using ExoGlow membrane labeling, and the impact of EVs on macrophage (THP-1) activation was assessed by cytokine levels using RT-qPCR. NTA and TEM analysis of db and non-db vitreous EVs showed non-aggregated EVs with a heterogeneous size range below 200 nm. Western blot detected EV markers (Alix, Annexin V, HSP70, and Flotillin 1) and an upregulation of Cldn5 in db EVs. While the db EVs were incorporated into macrophages, treatment of THP-1 cells with db EVs significantly increased mRNA levels of TNFα and IL-1β compared to non-db EVs. Proteomic and gene enrichment analysis indicated pro-inflammatory characteristics of db EVs. Our results suggest a potential involvement of EC-derived Cldn5+ EVs in triggering inflammation, offering a novel mechanism involved and presenting a possible therapeutic avenue for DR. [ABSTRACT FROM AUTHOR]

Diabetes is a metabolic disorder whose prevalence has become a worrying condition in recent decades. Chronic diabetes can result in serious health conditions such as impaired kidney function, stroke, blindness, and myocardial infarction. Despite a variety of currently available treatments, cases of diabetes and its complications are on the rise. This review article provides a comprehensive account of the ameliorative effect of prebiotics and probiotics individually or in combination i.e. synbiotics on health complications induced by Type 2 Diabetes Mellitus (T2DM). Recent advances in the field underscore encouraging outcomes suggesting the consumption of synbiotics leads to favorable changes in the gut microbiota. These changes result in the production of bioactive metabolites such as short-chain fatty acids (crucial for lowering blood sugar levels), reducing inflammation, preventing insulin resistance, and encouraging the release of glucagon-like peptide-1 in the host. Notably, novel strategies supplementing synbiotics to support gut microbiota are gaining attraction as pivotal interventions in mitigating T2DM-induced health complications. Thus, by nurturing a symbiotic relationship between prebiotics and probiotics i.e. synbiotics, these interventions hold promise in reshaping the microbial landscape of the gut thereby offering a multifaceted approach to managing T2DM and its associated morbidities. Supporting the potential of synbiotics underscores a paradigm shift toward holistic and targeted interventions in diabetes management, offering prospects for improved outcomes and enhanced quality of life for affected individuals. Nevertheless, more research needs to be done to better understand the single and multispecies pre/pro and synbiotics in the prevention and management of T2DM-induced health complications. [ABSTRACT FROM AUTHOR]

Background/Aim: Although nutritional risk factors for developing complications in type 2 diabetes mellitus (T2DM) have been examined, the effect of protein intake on nephropathy is debated, and there is little research on retinopathy. This cross-sectional case-series study aimed to examine the risk factors, including nutritional status, for complications in patients newly diagnosed with T2DM. Patients and Methods: Fifty-four patients were recruited, based on the results of examinations of blood glucose and/or glycated hemoglobin level for T2DM. To evaluate nutritional status, blood and urine examinations were performed and the Food Frequency Questionnaire was administered. Two-way analysis of variance, Fisher’s exact test and logistic regression analyses were performed. Results: The patients were categorized into four groups: 24 without albuminuria and without retinopathy, four without albuminuria with retinopathy, 21 with albuminuria without retinopathy, and five with albuminuria with retinopathy. Logistic analysis of albuminuria revealed that estimated sodium intake was significantly independent as the explanatory factors of age, sex, and body mass index. Patients with retinopathy had significantly higher blood urea nitrogen, and significantly lower plasma total protein levels than patients without retinopathy, suggesting that retinopathy is related to a higher catabolic state. Through a questionnaire on food intake, patients with retinopathy had a significantly lower intake of fat and monounsaturated fatty acids and a significantly higher intake of iodine based on intake of seaweed, corrected for energy intake, than patients without retinopathy. Conclusion: The present study may lead to planning a large cohort study for examining nutritional risk factors related to complications in patients newly diagnosed with T2DM in Japan. [ABSTRACT FROM AUTHOR]

This study aimed to assess the prevalence and selected correlates of dry eye disease (DED) among patients with type 2 diabetes in Kosovo. A case-series study was conducted in Kosovo from July 2023 to July 2024, including a consecutive sample of 400 patients with type 2 diabetes aged =18 years seeking healthcare services at the Eye Clinic of the Clinical University Center of Kosovo in Prishtina (51% females; overall mean age: 62.4±9.7 years; response rate: 80%). Data collection consisted of a detailed clinical examination and a structured questionnaire. Almost 70% of the patients had DED (standalone or combined with retinopathy, which, in turn, had a separate prevalence of 3%). Significant positive correlates of autonomous and/or combined DED and retinopathy included older age, unhealthy dietary patterns, sedentary lifestyle, high blood pressure, and treatment of diabetes with insulin and pills. Our findings indicate a high prevalence of DED among type 2 diabetes patients in Kosovo. DED and retinopathy were strongly associated with a range of demographic factors, behavioral characteristics, and preexisting conditions pertinent to type 2 diabetes patients in this population. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to evaluate intraretinal microvascular abnormalities (IRMA) in eyes with advanced nonproliferative diabetic retinopathy (NPDR) using multimodal approach in co-located areas focusing on central retina (up to 50°) and to look at possible correlations between IRMA and other structural changes, like ischemia and presence of microaneurysms. Methods: The RICHARD study (NCT05112445) included 60 eyes from 60 patients with type 2 diabetes with moderate-severe NPDR, diabetic retinopathy severity levels 43, 47, and 53 (DRSS). IRMA were defined as capillary tortuosity covering a minimum circular area of 300 µm (calculated to correspond to the Early Treatment Diabetic Retinopathy Study standard photo 8A) and were identified using multimodal imaging with distinct fields of view (FoV): color fundus photography (CFP) using a Topcon TRC-50DX camera (Topcon Medical Systems, Japan), Optos California ultra wide field fundus fluorescein angiography (UWF-FFA) (Optos plc, UK), and swept-source optical coherence tomography angiography (SS-OCTA) (PLEX® Elite 9000, ZEISS, USA). Different areas of the retina were examined: central macula (up to 20°) and posterior pole (between 20° and 50°). Results: Multimodal imaging was used to identify IRMA in co-located areas (FoV < 50°) including UWF-FFA, CFP, and SS-OCTA. In eyes with DRSS levels 47 and 53, IRMA were identified in both areas of the retina, while in eyes with DRSS level 43, IRMA were detected only outside of the central macula (FoV > 20°). Our results show that when evaluating the presence of IRMA (FoV < 50°), UWF-FFA detected 203 IRMA, SS-OCTA detected 133 IRMA, and CFP detected 104 IRMA. Our results also show that the presence of IRMA was positively associated with presence of microaneurysms. Conclusions: Identification of IRMA in eyes with advanced NPDR is better achieved by UWF-FFA than CFP and SS-OCTA. A statistically significant correlation was found between the presence of IRMA and the increase in number of microaneurysms. Trial Registration: ClinicalTrials.gov, identifier NCT05112445. [ABSTRACT FROM AUTHOR]

Deep learning algorithms effectively work with, a significant amount of data. trained on small datasets tend to have poor generalization. Data augmentation techniques can be used to make better use of existing training data, improving the applicability of deep learning methods. However, traditional data augmentation methods often produce limited additional credible data. The deep learning approach's performance can be enhanced by generating new data by employing generative adversarial networks (GANs). Although GANs have been extensively used to improve the performance of convolutional neural networks (CNNs), there has been relatively less research on data augmentation methods specifically for GAN training. This study focuses on using a Wasserstein GAN (WGAN) architecture for generating synthetic optical coherence tomography angiography (OCTA) images of diabetic retinopathy to aid in the detection of different types of diabetic retinopathy diseases, including proliferative diabetic retinopathy (PDR), Severe non-PDR (NPDR), Moderate NPDR, and Mild NPDR. WGAN, provides the generator with a more informative learning signal, making training more stable, particularly in high-dimensional spaces. The trained WGAN model is saved in .h5 file format (HDF), converted to portable network graphics (PNG) image format, and then classified into different categories of diabetic retinopathy using a ResNet50 model with various fine-tuning methods. The proposed model has demonstrated better results than the previous study. 99.95% accuracy is exhibited. [ABSTRACT FROM AUTHOR]

This review explored the role of mitochondria in retinal ganglion cells (RGCs), which are essential for visual processing. Mitochondrial dysfunction is a key factor in the pathogenesis of various vision-related disorders, including glaucoma, hereditary optic neuropathy, and age-related macular degeneration. This review highlighted the critical role of mitochondria in RGCs, which provide metabolic support, regulate cellular health, and respond to cellular stress while also producing reactive oxygen species (ROS) that can damage cellular components. Maintaining mitochondrial function is essential for meeting RGCs' high metabolic demands and ensuring redox homeostasis, which is crucial for their proper function and visual health. Oxidative stress, exacerbated by factors like elevated intraocular pressure and environmental factors, contributes to diseases such as glaucoma and age-related vision loss by triggering cellular damage pathways. Strategies targeting mitochondrial function or bolstering antioxidant defenses include mitochondrial-based therapies, gene therapies, and mitochondrial transplantation. These advances can offer potential strategies for addressing mitochondrial dysfunction in the retina, with implications that extend beyond ocular diseases. [ABSTRACT FROM AUTHOR]

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Human embryonic stem cells and human induced pluripotent stem cells may be used to create 3D tissues called brain organoids. They duplicate the physiological and pathological characteristics of human brain tissue more faithfully in terms of both structure and function, and they more precisely resemble the morphology and cellular structure of the human embryonic brain. This makes them valuable models for both drug screening and in vitro studies on the development of the human brain and associated disorders. The technical breakthroughs enabled by brain organoids have a significant impact on the research of different brain regions, brain development and sickness, the connections between the brain and other tissues and organs, and brain evolution. This article discusses the development of brain organoids, their use in diabetes research, and their progress. [ABSTRACT FROM AUTHOR]

Aim: To assess clinical and biochemical measurements that can identify people with dysglycaemia (i.e. diabetes or pre‐diabetes) who remain free of serious outcomes during follow‐up. Materials and Methods: We conducted exploratory analyses using data from the Outcomes Reduction with an Initial Glargine Intervention (ORIGIN) study to identify independent determinants of outcome‐free status in 12 537 middle‐aged and older adults with prediabetes and early type 2 diabetes from 40 countries. Serious outcome‐free status was defined as the absence of major cardiovascular outcomes, kidney or retinal outcomes, peripheral artery disease, dementia, cancer, any hospitalization, or death during follow‐up. Results: In total, 3328 (26.6%) participants remained free of serious outcomes during a median follow‐up of 6.2 years (IQR 5.8, 6.7). Independent clinical determinants of outcome‐free status included younger age, female sex, non‐White ethnicity, shorter diabetes duration, absence of previous cardiovascular disease, current or former smokers, higher grip strength, Mini‐Mental State Examination score, and ankle‐brachial index, lower body mass index and kidney disease index, and non‐use of renin‐angiotensin system drugs and beta‐blockers. In a subset of 8401 people with baseline measurements of 238 biomarkers, growth differentiation factor 15, kidney injury molecule‐1, N‐terminal pro‐brain natriuretic peptide, uromodulin, C‐reactive protein, factor VII and ferritin were independent determinants. The combination of clinical determinants and biomarkers best identified participants who remained outcome‐free (C‐statistics 0.71, 95% confidence interval 0.70‐0.73; net reclassification improvement 0.55, 95% confidence interval 0.48‐0.58). Conclusions: A set of routinely measured clinical characteristics and seven protein biomarkers identify middle‐aged and older people with prediabetes or early type 2 diabetes as least likely to experience serious outcomes during follow‐up. [ABSTRACT FROM AUTHOR]

Evaluation of retinal macular oxygen saturation in healthy controls can aid in understanding the pathological changes seen in similar locations of those with vascular diseases like diabetes. The aim of this study was to determine the test-retest repeatability of localised retinal oximetry measurements in the macula on the Zilia Oximeter within healthy subjects of different races, 18–40 years old. Oxygen saturation was measured between three time points within the same locations of the right eye. Twenty seven subjects were included (aged 26.3 ± 3.6 years). All were confirmed to have healthy retinas and at least 6/9 vision. Oximetry measurements were taken using the Zilia to acquire local oxygen saturation measurements (300 µm diameter) at four points 3.1 degrees from the fovea in the superior/temporal, superior/nasal, inferior/temporal, and inferior/nasal locations. Oximetry measurements were taken twice on the same day 20 minutes apart and then again 1–2 weeks later. Oximetry data was analysed with intraclass correlation between visits. To assess intrasubject repeatability, the Bland-Altman repeatability coefficient and coefficient of variation were calculated. Average Intraclass correlation for the three acquisition times of the right eye was 0.78. The averaged intrasubject repeatability coefficient for the three acquisition times was 8.4. The averaged coefficient of variation was 5.4%. The Zilia oximeter has good macular test-retest repeatability; however, multiple measurements may be needed to ensure accuracy. [ABSTRACT FROM AUTHOR]

Purpose: This study describes how the diagnosis of Usher syndrome was revised to PRPS1-associated retinopathy and Charcot—Marie—Tooth disease type 5. Case Report: A 38-year-old female with bilaterally subnormal vision and non-congenital hearing loss was initially diagnosed with Usher syndrome, based on finding variants in three genes (MYO7A, USH2A, and PCDH15), was re-evaluated at the inherited retinal disorders clinic. She had asymmetric retinopathy and right macular pseudocoloboma. She was also found to have myopathic facies, poor grip strength and atrophy of the calf muscles. Whole exome sequencing including variants in PRPS1 showed a variant (NM_002764.4:c.287 G > A; p.Arg96Gln), which was not detected by targeted Sanger sequencing of the DNA from her mother and sister. Conclusion: The constellation of asymmetric retinopathy and non-congenital hearing impairment should prompt the clinician to search for other diagnoses that may not be covered by an Usher syndrome next generation sequencing panel. Interpretation of genetic testing results should be correlated with a detailed clinical phenotype. [ABSTRACT FROM AUTHOR]

Copyright of Balikesir Health Sciences Journal / Balıkesir Sağlık Bilimleri Dergisi is the property of Balikesir Health Sciences Journal (BAUN Health Sci J) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background The initiation of type-2 diabetes mellitus (T2DM) is frequently asymptomatic and gradual. One reason newly diagnosed type-2 diabetes mellitus patients have a higher risk of microvascular problems is untreated long-standing hyperglycemia. The objective of our study was to evaluate the frequency of microvascular problems in recently diagnosed patients with type 2 diabetes mellitus at a tertiary care hospital in India. Material and Methods: A cross-sectional study was undertaken in the medicine department of a tertiary care hospital. The study included a cohort of 100 patients who were recently diagnosed with type 2 diabetes mellitus. Microvascular complications were diagnosed after a thorough study of the patient's medical history, clinical assessment, and pertinent diagnostic tests. Results: Subjects who had an IDRS score of 60 or higher showed a higher occurrence of peripheral neuropathy (86.5% vs 13.5%, p=0.371), retinopathy (91.7% vs 8.3%, p=0.157), and nephropathy (77.8% vs 22.2%, p=0.410) compared to subjects with an IDRS score below 60. However, there was no statistically significant difference in the occurrence of microvascular problems between the two IDRS subgroups. Those diagnosed with nephropathy exhibit a statistically significant higher average IDRS score compared to those without nephropathy (65.00±17.32 vs 62.66±12.50, p-value = 0.037). However, no statistically significant difference was detected in the mean values of the IDRS scores of the other two microvascular complications. Conclusion: IDRS is a valuable tool for predicting newly diagnosed type 2 diabetes mellitus. However, further large, multi-centric studies will be required to detect its usefulness in microvascular complications. [ABSTRACT FROM AUTHOR]

Background: Prior case reports and animal studies have reported on potential ophthalmologic complications of babesiosis, but this issue has not previously been addressed in a cohort of patients with babesiosis. This cross-sectional descriptive pilot study evaluated the retinas of patients with acute babesiosis to determine if retinal abnormalities are a feature of the disease. Methods: We screened all patients admitted to Yale New Haven Hospital with laboratory confirmed babesiosis during the summer of 2023 and obtained informed consent. Patients were interviewed and underwent pupil dilation and a retinal examination using an indirect ophthalmoscope. Demographic and clinical information were obtained by questionnaire and through chart review. Results: Ten patients underwent retinal eye exams with results that were generally unremarkable. No study patients showed any signs of retinal inflammation, infection, retinal bleeding, retinal tears, or abnormal vessel formation that could be attributed to infection. Conclusion: This small study did not find evidence of retinopathy in patients with babesiosis. Further studies with larger populations, repeated exams, and long term follow up will further elucidate the potential small vessel complications of human babesiosis. [ABSTRACT FROM AUTHOR]

Many diseases produce pathological changes in the fundus; analyzing the retinopathy of the fundus could help diagnose diseases in time. A fundus camera is a medical imaging device that specializes in taking fundus images to diagnose hypertension, coronary heart disease, diabetes, and others. The fundus optical imaging system is the core part of it. Nevertheless, the conventional fundus optical imaging system is large and not suitable for mobile examination and follow-up use. So, it has not been widely used in medical institutions. In this paper, a miniaturized fundus optical imaging system based on aspheric technology and non-coaxial illumination is proposed. The length of the imaging system is only 34.6   mm , the field of view is 50°, and the MTF curve is greater than 0.2 at 100 lp / mm , which can resolve the structure of 5   um . The illumination system adopts a non-coaxial annular array illumination structure to avoid occlusion of the imaging system. Our study effectively tackles the pressing predicament of fundus optical system miniaturization. This innovative paradigm harbors the potential to revolutionize fundus image data acquisition, propelling the field of fundus diagnosis forward and efficiently catering to crucial applications, improving the versatility of fundus examination, and providing technical support for the intelligent diagnosis system. [ABSTRACT FROM AUTHOR]

Simple Summary: Diabetes is a worldwide epidemic that affects the retina, kidneys, and peripheral nerves. More recent findings indicate that brain changes also occur and are associated with dementia and/or cognitive deficits. As both the retina and the brain have blood–tissue barriers that are sensitive to high blood sugar levels, it has been proposed that complications in the retina, an extension of the brain, could be used to predict subsequent brain pathology. In this review, we summarize published data about the disease-associated changes in the retina and brain reported in animal models (rodents and zebrafish) to assess specific cellular and/or behavioral mechanisms associated with vision and cognitive function loss in diabetes. Diabetes is prevalent worldwide, with >90% of the cases identified as Type 2 diabetes. High blood sugar (hyperglycemia) is the hallmark symptom of diabetes, with prolonged and uncontrolled levels contributing to subsequent complications. Animal models have been used to study these complications, which include retinopathy, nephropathy, and peripheral neuropathy. More recent studies have focused on cognitive behaviors due to the increased risk of dementia/cognitive deficits that are reported to occur in older Type 2 diabetic patients. In this review, we collate the data reported from specific animal models (i.e., mouse, rat, zebrafish) that have been examined for changes in both retina/vision (retinopathy) and brain/cognition, including db/db mice, Goto-Kakizaki rats, Zucker Diabetic Fatty rats, high-fat diet-fed rodents and zebrafish, and hyperglycemic zebrafish induced by glucose immersion. These models were selected because rodents are widely recognized as established models for studying diabetic complications, while zebrafish represent a newer model in this field. Our goal is to (1) summarize the published findings relevant to these models, (2) identify similarities in cellular mechanisms underlying the disease progression that occur in both tissues, and (3) address the hypothesis that hyperglycemic-induced changes in retina precede or predict later complications in brain. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is one of the significant disabling outcomes of diabetes mellitus characterized by retinal microvascular damage, inflammation, and neuronal dysfunction. Allicin (Alc), a natural compound found in garlic, has garnered attention for its antioxidant and anti-inflammatory properties, positioning it as a potential therapeutic agent for DR. The aim of the present study was to investigate the therapeutic efficacy of Alc in DR management and elucidate its underlying mechanisms of action. We established a DR model in male Sprague–Dawley rats (n = 50, 200–250 g, 12 weeks old) using a high-fat diet for 8 weeks plus a low dose of streptozotocin administered at the start of the 4th week. The diabetic (Diab) animals were administered Alc (16 mg/kg/day, orally), either alone or in combination with mitochondrial division inhibitor-1 (Mdivi-1) as a mitophagy inhibitor, starting 28 days before tissue sampling. We evaluated histopathological changes, metabolic abnormalities associated with type 2 diabetes mellitus (T2DM), the expression of proteins regulating pyroptosis (NOD-like receptor family pyrin domain containing 3, cleaved-caspase 1, and gasdermin D-N terminal) and mitophagy (phosphatase and tensin homolog-induced kinase 1 [PINK1] and Parkin), as well as the levels of oxidative stress mediators and proinflammatory cytokines. Alc treatment effectively ameliorated histopathological changes and metabolic abnormalities associated with T2DM. It downregulated pyroptosis-related proteins, upregulated mitophagy-related proteins, reduced proinflammatory cytokine levels, and attenuated oxidative stress. Treatment with Mdivi-1 suppressed the beneficial effects of Alc. Our findings highlight the therapeutic potential of Alc in managing DR by targeting multiple pathophysiological pathways, including pyroptosis, inflammation, and oxidative stress. The observed antipyroptotic effects of Alc were partially mediated by the activation of the PINK1/parkin-mediated mitophagy pathway. Additional studies are necessary to thoroughly understand the therapeutic mechanisms of Alc and its viability as a treatment choice for DR. [ABSTRACT FROM AUTHOR]

Introduction and Objectives: Type 2 Diabetes Mellitus (T2DM), a prevalent metabolic disorder, often coexists with a range of complications, with retinopathy being particularly common. Recent studies have shed light on a potential connection between diabetic retinopathy (DR) and hepatic fibrosis, indicating a possible shared pathophysiological foundation in T2DM. This study investigates the correlation between retinopathy and hepatic fibrosis among individuals with T2DM, as well as evaluates the diagnostic value of DR for significant hepatic fibrosis. Materials and Methods: Our cross-sectional analysis incorporated 5413 participants from the National Health and Nutrition Examination Survey (NHANES) 2005-2008. The Fibrosis-4 score (FIB-4) classified hepatic fibrosis into different grades (F0-F4), with significant hepatic fibrosis marked as F2 or higher. Retinopathy severity was determined using retinal imaging and categorized into four levels. The analysis of variance or Chi-square tests facilitated group comparisons. Additionally, the receiver operating characteristic (ROC) analysis appraised the predictive accuracy of retinopathy for significant hepatic fibrosis in the T2DM population. Results: Among 5413 participants, the mean age was 59.56 § 12.41, with 50.2% male. And 20.6% were diagnosed with T2DM. Hepatic fibrosis grading was positively associated with retinopathy severity (OR [odds ratio]: 1.521, 95%CI [confidence interval]: 1.152-2.008, P = 0.003) across the entire population. The association was amplified in the T2DM population according to Pearson’s analysis results. The ROC curve demonstrated retinopathy’s diagnostic capacity for significant hepatic fibrosis in the T2DM population (AUC [area under curve] = 0.72, 95%CI: 0.651-0.793, P < 0.001). Conclusions: Retinopathy could serve as an independent predictor of significant hepatic fibrosis in T2DM population. Ophthalmologists are advised to closely monitor T2DM patients with retinopathy. [ABSTRACT FROM AUTHOR]

Background: Retinopathy of prematurity (ROP) is one of the common complications in premature neonates. ROP examination is one of the most important examinations for premature babies, which is associated with pain and can be very annoying. This study aimed to compare the effectiveness of pharmacological and nonpharmacological methods in reducing the pain of ROP examination. Materials and Methods: This study was conducted as a double-blind, randomized control trial on 300 ROP examinations of patients who were hospitalized in the NICU department of Mahdieh Hospital in Tehran. The neonates were randomly selected into three groups, and ketamine 2mg/kg nasally, fentanyl two µg/kg nasally10minutes before an examination, and acetaminophen 2drop/kg orally 30 minutes before each examination were given to each neonate as two pharmacological groups. In the non-pharmacological group, infants received saddling-pacifier oral sucrose 25% 0.5cc 2 minutes before examination. Pain was assessed based on PIPP (premature infant pain index). Results: The amount of pain after using oral sucrose was significantly lower than the ketamine-acetaminophen (P-value=0.011) and fentanyl-acetaminophen (P-value=0.027) groups, but there was not a statistically significant difference between the two groups of ketamine-acetaminophen and fentanyl-acetaminophen (Pvalue= 0.953). The hypoxia was more prevalent in the ketamine-acetaminophen group (18.8%), and the least hypoxia occurred in the oral sucrose treatment group (7%) (P-value=0.028). Conclusion: It is concluded that the effect of non-pharmacological drugs is greater than pharmacological drugs in reducing the pain of neonates during ROP examination. The effect of oral sucrose in reducing pain was more significant than ketamine-acetaminophen and fentanyl-acetaminophen. However, there was no significant difference between the two groups of ketamine-acetaminophen and fentanyl-acetaminophen. [ABSTRACT FROM AUTHOR]

Background: An increasing amount of people are globally affected by retinal diseases, such as diabetes, vascular occlusions, maculopathy, alterations of systemic circulation, and metabolic syndrome. Aim: This review will discuss novel technologies in and potential approaches to the detection and diagnosis of retinal diseases with the support of cutting-edge machines and artificial intelligence (AI). Methods: The demand for retinal diagnostic imaging exams has increased, but the number of eye physicians or technicians is too little to meet the request. Thus, algorithms based on AI have been used, representing valid support for early detection and helping doctors to give diagnoses and make differential diagnosis. AI helps patients living far from hub centers to have tests and quick initial diagnosis, allowing them not to waste time in movements and waiting time for medical reply. Results: Highly automated systems for screening, early diagnosis, grading and tailored therapy will facilitate the care of people, even in remote lands or countries. Conclusion: A potential massive and extensive use of AI might optimize the automated detection of tiny retinal alterations, allowing eye doctors to perform their best clinical assistance and to set the best options for the treatment of retinal diseases. [ABSTRACT FROM AUTHOR]

Objectives: To determine the prevalence of retinal lesions and describe the fundoscopic findings of retinopathy in Greyhound dogs in the Manawatu/Whanganui region of New Zealand. To examine possible associations between sex, age, and racing variables with retinopathy in the study population. To describe retinal histologic findings in seven Greyhounds with retinopathy in New Zealand. Methods: Two hundred Greyhound dogs from the Manawatu/Whanganui region of New Zealand underwent fundoscopy and fundic photography to identify and score the degree of retinopathy. Associations between retinopathy and age, sex, as well as racing variables, were examined. Histologic examination of the retina was undertaken on the eyes of seven Greyhounds from the Manawatu and Canterbury regions previously diagnosed with retinopathy by fundoscopy. Results: Fifty dogs (25.1%) were identified with retinopathy of varying degrees of severity. In at least one eye, 7.5% of dogs had mild retinopathy, 11.6% moderate retinopathy, and 6.0% severe retinopathy. Males were more likely to be affected in both eyes and with moderate or severe grades, than females. Increasing age was not associated with increased prevalence of retinopathy, nor increased grade of severity. Retinal histology identified multifocal retinal detachment in 5 of the 7 cases examined and other common lesions included choroidal necrosis and outer to full‐thickness retinal atrophy in the absence of significant inflammation. Conclusions: Retinopathy is prevalent in Greyhounds in the Manawatu/Whanganui region of New Zealand, but more research is required to elucidate the etiopathogenesis. Consideration should be made to include mandatory eye health examination in racing Greyhound dogs. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: A protective role of sodium–glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP1-ra) in the development of diabetic retinopathy and diabetic macular oedema has been described in some recent studies, which may extend beyond glycaemic control. We aimed to review the clinical impact of SGLT2i and GLP1-ra therapy on the risk of diabetic retinopathy and diabetic macular oedema in individuals with type 2 diabetes taking insulin. Methods: This is a retrospective cohort analysis of approximately two million people with type 2 diabetes receiving insulin across 97 healthcare organisations using a global federated health research network (TriNetX, Cambridge, USA). Two intervention cohorts (SGLT2i + insulin, n=176,409; GLP1-ra + insulin, n=207,034) were compared against a control cohort (insulin with no SGLT2i/GLP1-ra, n=1,922,312). Kaplan–Meier survival analysis was performed and estimated HRs were reported for each outcome. Propensity score was used to 1:1 match for age, sex, ischaemic heart disease, hypertension, microvascular complications, chronic kidney disease, HbA1c, BMI and use of pioglitazone, lipid modifying agents, antilipemic agents, ACE inhibitors, angiotensin II inhibitors and metformin. A sub-analysis comparing the two intervention cohorts was also performed. Results: SGLT2i with insulin was associated with a reduced HR (95% CI) for diabetic macular oedema compared with the control cohort (0.835; 0.780, 0.893), while GLP1-ra with insulin demonstrated a lack of signal with no statistical significance to the HR (1.013; 0.960, 1.069). SGLT2i with insulin was not associated with a clinically significant increase in the risk of developing diabetic retinopathy (1.076; 1.027, 1.127), while GLP1-ra with insulin increased diabetic retinopathy risk (1.308; 1.261, 1.357). Compared with SGLT2i with insulin, GLP1-ra with insulin was associated with higher risk of diabetic retinopathy (1.205; 1.153, 1.259) and diabetic macular oedema (1.130; 1.056, 1.208). Conclusions/interpretation: Our study suggests that the combination of SGLT2i and insulin is associated with lower risk of developing diabetic macular oedema. However, the use of GLP1-ra was associated with an increased risk of diabetic retinopathy in individuals with type 2 diabetes also taking insulin. A comparative analysis showed favourable outcomes with SGLT2i and insulin in the development of diabetic macular oedema and diabetic retinopathy. RCTs using dedicated retinal imaging are required to determine the causal relationship with these therapies. [ABSTRACT FROM AUTHOR]

Background: The purpose of this review was to examine if dipeptidyl peptidase-4 inhibitor (DPP4i) use affects the risk of diabetic retinopathy (DR). Methods: Cohort studies published up to 20th July 2023 in the databases of PubMed, CENTRAL, Embase, Scopus, and Web of Science were searched. The adjusted effect size was pooled to calculate the odds ratio (OR). Results: Seven studies were included. Meta-analysis showed that the use of DPP4i was not associated with any significant change in the risk of DR (OR: 0.86 95% CI: 0.70, 1.06 I2 = 78%). The pooled analysis also found that DPP4i use was not associated with any significant risk of progression of DR (OR: 0.87 95% CI: 0.47, 1.59 I2 = 86%). The results did not change during sensitivity analysis. Conclusion: Present evidence from a limited number of real-world studies shows that DPP4i may not affect the incidence and progression of DR. There is a need for further studies from different countries using accurate definitions of DR and its progression to validate the current results. [ABSTRACT FROM AUTHOR]

Purpose: To assess the quality of hydroxychloroquine (HCQ)-induced retinopathy screening at a Canadian tertiary center, we concentrate on risk factor documentation within the electronic health record, in accordance with the 2016 AAO guidelines. Methods: We performed a retrospective quality assessment study based on chart review of patients who underwent screening for HCQ-induced retinopathy at the Centre Hospitalier de l'Université de Montréal (CHUM) from 2016 to 2019. We evaluated four key risk factors for HCQ-induced retinopathy: daily dose, duration of use, renal disease, and tamoxifen use, using a three-tier grading system (ideal, adequate, inadequate) for documentation assessment. Pareto and root cause analyses were conducted to identify potential improvement solutions. Results: Documentation quality varied in our study: daily dosage was 33% ideal, 31% appropriate, and 36% inappropriate. Duration of use documentation was 75% ideal, 2% adequate, and 24% inadequate. Renal disease documentation was only 6% ideal, with 62% adequate and 32% of charts lacking any past medical history. Among women's charts, tamoxifen use wasn't documented at all, with 65% adequately documenting medication lists. Pareto analysis indicated that improving renal disease and tamoxifen documentation could reduce 64% of non-ideal records, and enhancing daily dose documentation could decrease this by up to 90%. Conclusion: Accurate documentation of key risk factors is critical for HCQ-induced retinopathy screening, impacting both exam initiation and frequency. Our study identifies potential improvements in the screening process at the hospital, referring physician, and ophthalmologist levels. Implementing integrated pathways could enhance patient experience and screening effectiveness. [ABSTRACT FROM AUTHOR]

Background: Gowing number of studies have demonstrated the association between gut microbiome and T2DM microvascular complications, however the causal relationship remains unclear. Therefore, we using the Mendelian randomization (MR) approach to investigate this causal relation. Methods: Using gut microbiome data from the International MiBioGen Consortium genome-wide association study (GWAS) and T2DM microvascular complications data from the FinnGen Consortium GWAS to perform MR analyses. Single nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs), the inverse variance weighting (IVW) method was used as the primary analysis method, and the results were tested for heterogeneity and horizontal pleiotropy. Results: Our research identified that there are 5 known microbial species and 2 unknown microbial species in the gut microbiome that were causally related to T2DM retinopathy. Besides, three and seven known microbial species causal relationships between the gut microbiome and T2DM neuropathy and T2DM nephropathy, respectively. Conclusions: Using MR methods, we demonstrated the causal relationship between gut microbiome and microvascular complications in T2DM, providing a new strategy for the prevention and treatment of it. [ABSTRACT FROM AUTHOR]

We hypothesize that the injection of JP4-039, a mitochondria-targeted nitroxide, prior to irradiation of the mouse retina may decrease apoptosis and reduce neutrophil and macrophage migration into the retina. In our study, we aimed to examine the effects of JP4-039 in the mouse retina using fluorescent microscopy, a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and flow cytometry. Forty-five mice and one eye per mouse were used. In Group 1, fluorescent microscopy was used to determine retinal uptake of 10 µL (0.004 mg/µL) of intravitreally injected BODIPY-labeled JP4-039 at 0, 15, and 60 min after injection. In Group 2, the TUNEL assay was performed to investigate the rate of apoptosis after irradiation in addition to JP4-039 injection, compared to controls. In Group 3, flow cytometry was used to determine the extent of inflammatory cell migration into the retina after irradiation in addition to JP4-039 injection, compared to controls. Maximal retinal uptake of JP4-039 was 15 min after intravitreal injection (p < 0.0001). JP4-039-treated eyes had lower levels of retinal apoptosis (35.8 ± 2.5%) than irradiated controls (49.0 ± 2.7%; p = 0.0066) and demonstrated reduced migration of N1 cells (30.7 ± 11.7% vs. 77.7 ± 5.3% controls; p = 0.004) and M1 cells (76.6 ± 4.2 vs. 88.1 ± 3.7% controls, p = 0.04). Pretreatment with intravitreally injected JP4-039 reduced apoptosis and inflammatory cell migration in the irradiated mouse retina, marking the first confirmed effect of this molecule in retinal tissue. Further studies may allow for safety profiling and potential use for patients with radiation retinopathy. [ABSTRACT FROM AUTHOR]

Copyright of Progress in Modern Biomedicine is the property of Publishing House of Progress in Modern Biomedicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Diabetes is a multifactorial disorder that involves several molecular mechanisms and is still one of the key global health challenges with increasing prevalence and incidence. Gut microbiome dysbiosis could activate and recognize receptors that trigger the inflammation response and modulation of insulin sensitivity. In addition, the intricate role of gut microbiota dysbiosis in the onset and development of T2D (Type 2 diabetes mellitus) and associated microvascular complications was identified. These complications include diabetic nephropathy (DN) and diabetic retinopathy (DR), diabetic neuropathy, cerebrovascular disorders, and coronary heart disease. A recent interesting strategy to improve these complications is probiotics administration. The safety and health effects of probiotics against various diseases have been validated by various in vitro, in vivo and clinical studies. In this review, the related mechanisms between the gut microbiome, initiation, and progression of T2D and its common microvascular complications (DN and DR) have been discussed. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is a major complication of diabetes mellitus and is a leading cause of vision loss globally. A prompt and accurate diagnosis is crucial for ensuring favorable visual outcomes, highlighting the need for increased access to medical care. The recent remarkable advancements in artificial intelligence (AI) have raised high expectations for its role in disease diagnosis and prognosis prediction across various medical fields. In addition to achieving high precision comparable to that of ophthalmologists, AI-based diagnosis of DR has the potential to improve medical accessibility, especially through telemedicine. In this review paper, we aim to examine the current role of AI in the diagnosis of DR and explore future directions. [ABSTRACT FROM AUTHOR]

The Crumbs protein (CRB) family plays a crucial role in maintaining the apical–basal polarity and integrity of embryonic epithelia. The family comprises different isoforms in different animals and possesses diverse structural, localization, and functional characteristics. Mutations in the human CRB1 or CRB2 gene may lead to a broad spectrum of retinal dystrophies. Various CRB-associated experimental models have recently provided mechanistic insights into human CRB-associated retinopathies. The knowledge obtained from these models corroborates the importance of CRB in retinal development and maintenance. Therefore, complete elucidation of these models can provide excellent therapeutic prospects for human CRB-associated retinopathies. In this review, we summarize the current animal models and human-derived models of different CRB family members and describe the main characteristics of their retinal phenotypes. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Contemporary Pediatrics is the property of Xiangya Medical Periodical Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: The duration of type 2 diabetes mellitus (T2DM) and blood glucose levels have a significant impact on the development of T2DM complications. However, currently known risk factors are not good predictors of the onset or progression of diabetic retinopathy (DR). Therefore, we aimed to investigate the differences in the serum lipid composition in patients with T2DM, without and with DR, and search for potential serological indicators associated with the development of DR. Methods: A total of 622 patients with T2DM hospitalized in the Department of Endocrinology of the First Affiliated Hospital of Xi'an JiaoTong University were selected as the discovery set. One-to-one case–control matching was performed according to the traditional risk factors for DR (i.e., age, duration of diabetes, HbA1c level, and hypertension). All cases with comorbid chronic kidney disease were excluded to eliminate confounding factors. A total of 42 pairs were successfully matched. T2DM patients with DR (DR group) were the case group, and T2DM patients without DR (NDR group) served as control subjects. Ultra-performance liquid chromatography–mass spectrometry (LC–MS/MS) was used for untargeted lipidomics analysis on serum, and a partial least squares discriminant analysis (PLS-DA) model was established to screen differential lipid molecules based on variable importance in the projection (VIP) > 1. An additional 531 T2DM patients were selected as the validation set. Next, 1:1 propensity score matching (PSM) was performed for the traditional risk factors for DR, and a combined 95 pairings in the NDR and DR groups were successfully matched. The screened differential lipid molecules were validated by multiple reaction monitoring (MRM) quantification based on mass spectrometry. Results: The discovery set showed no differences in traditional risk factors associated with the development of DR (i.e., age, disease duration, HbA1c, blood pressure, and glomerular filtration rate). In the DR group compared with the NDR group, the levels of three ceramides (Cer) and seven sphingomyelins (SM) were significantly lower, and one phosphatidylcholine (PC), two lysophosphatidylcholines (LPC), and two SMs were significantly higher. Furthermore, evaluation of these 15 differential lipid molecules in the validation sample set showed that three Cer and SM(d18:1/24:1) molecules were substantially lower in the DR group. After excluding other confounding factors (e.g., sex, BMI, lipid-lowering drug therapy, and lipid levels), multifactorial logistic regression analysis revealed that a lower abundance of two ceramides, i.e., Cer(d18:0/22:0) and Cer(d18:0/24:0), was an independent risk factor for the occurrence of DR in T2DM patients. Conclusion: Disturbances in lipid metabolism are closely associated with the occurrence of DR in patients with T2DM, especially in ceramides. Our study revealed for the first time that Cer(d18:0/22:0) and Cer(d18:0/24:0) might be potential serological markers for the diagnosis of DR occurrence in T2DM patients, providing new ideas for the early diagnosis of DR. [ABSTRACT FROM AUTHOR]

Purpose: In this extensive review work, the important role of AMP-activated protein kinase (AMPK) in causing of diabetes mellitus has been highlighted. Structural feature of AMPK as well its regulations and roles are described nicely, and the association of AMPK with the diabetic complications like nephropathy, neuropathy and retinopathy are also explained along with the connection between AMPK and β-cell function, insulin resistivity, mTOR, protein metabolism, autophagy and mitophagy and effect on protein and lipid metabolism. Methods: Published journals were searched on the database like PubMed, Medline, Scopus and Web of Science by using keywords such as AMPK, diabetes mellitus, regulation of AMPK, complications of diabetes mellitus, autophagy, apoptosis etc. Result: After extensive review, it has been found that, kinase enzyme like AMPK is having vital role in management of type II diabetes mellitus. AMPK involve in enhance the concentration of glucose transporter like GLUT 1 and GLUT 4 which result in lowering of blood glucose level in influx of blood glucose into the cells; AMPK increases the insulin sensitivity and decreases the insulin resistance and further AMPK decreases the apoptosis of β-cells which result into secretion of insulin and AMPK is also involve in declining of oxidative stress, lipotoxicity and inflammation, owing to which organ damage due to diabetes mellitus can be lowered by activation of AMPK. Conclusion: As AMPK activation leads to overall control of diabetes mellitus, designing and developing of small molecules or peptide that can act as AMPK agonist will be highly beneficial for control or manage diabetes mellitus. [ABSTRACT FROM AUTHOR]

Background and aims: Type 2 diabetes mellitus (T2DM) is a chronic condition associated with various microvascular complications, including neuropathy, retinopathy, and nephropathy. Recent studies have suggested a potential association between serum omentin levels and the risk of developing microvascular complications in patients with T2DM. However, the existing evidence remains inconclusive. Therefore, we conducted a systematic review and meta-analysis to examine the association between serum omentin levels and microvascular complications in T2DM patients. Methods: A comprehensive search was conducted in PubMed, Scopus, and Google Scholar databases to retrieve relevant articles published up to May 2023. Observational studies investigating omentin levels association with microvascular complications in T2DM patients were included. Data was extracted and hence analyzed. Results: A total of seven cross-sectional articles met the inclusion criteria, with a total population of 1587 participants. The meta-analysis revealed a significant association between serum omentin levels and microvascular complications in patients with T2DM. Serum omentin levels were lower in patients with microvascular complications than in those without complications (Mean difference, 95% confidence interval: -1.31 [-2.50, -0.13], I2 = 99.62%). Conclusion: This systematic review and meta-analysis provides evidence supporting an association between serum omentin levels and microvascular complications in patients with T2DM. The findings suggest that Omentin may be lower in T2DM patients with microvascular complications. Further research is warranted to elucidate the underlying mechanisms and explore the clinical implications of these findings. [ABSTRACT FROM AUTHOR]