Ocular Complications Of Diabetes Mellitus Research Articles

PSAT1 is upregulated by METTL3 to attenuate high glucose-induced retinal pigment epithelial cell apoptosis and oxidative stress

BackgroundDiabetic retinopathy (DR) is a major ocular complication of diabetes mellitus, and a significant cause of visual impairment and blindness in adults. Phosphoserine aminotransferase 1 (PSAT1) is an enzyme participating in serine synthesis, which might improve insulin signaling and insulin sensitivity. Furthermore, it has been reported that the m6A methylation in mRNA controls gene expression under many physiological and pathological conditions. Nevertheless, the influences of m6A methylation on PSAT1 expression and DR progression at the molecular level have not been reported.MethodsHigh-glucose (HG) was used to treat human retinal pigment epithelial cells (ARPE-19) to construct a cell injury model. PSAT1 and Methyltransferase-like 3 (METTL3) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). PSAT1, B-cell lymphoma-2 (Bcl-2), Bcl-2 related X protein (Bax), and METTL3 protein levels were examined by western blot assay. Cell viability and apoptosis were detected by Cell Counting Kit-8 (CCK-8) and TUNEL assays. Reactive oxygen species (ROS), malondialdehyde (MDA), and Glutathione peroxidase (GSH-Px) levels were examined using special assay kits. Interaction between METTL3 and PSAT1 was verified using methylated RNA immunoprecipitation (MeRIP) and dual-luciferase reporter assay.ResultsPSAT1 and METTL3 levels were decreased in DR patients and HG-treated ARPE-19 cells. Upregulation of PSAT1 might attenuate HG-induced cell viability inhibition and apoptosis and oxidative stress promotion in ARPE-19 cells. Moreover, PSAT1 was identified as a downstream target of METTL3-mediated m6A modification. METTL3 might improve the stability of PSAT1 mRNA via m6A methylation.ConclusionMETTL3 might mitigate HG-induced ARPE-19 cell damage partly by regulating the stability of PSAT1 mRNA, providing a promising therapeutic target for DR.

Paquinimod attenuates retinal injuries by suppressing the S100A9/TLR4 signaling in an experimental model of diabetic retinopathy

Diabetic retinopathy (DR), the most common ocular complication of diabetes mellitus (DM), has exhibited an increase in incidence over the past decade. S100 calcium-binding protein A9 (S100A9) plays a significant role in inflammation and cancer. Toll-like receptor 4 (TLR4), a transmembrane receptor, initiates signaling cascades upon ligand binding. S100A9 activates TLR4, and their involvement in various diseases is well-established. We found elevated S100A9/TLR4 pathway proteins in the vitreous of DR patients. Bioinformatics analysis revealed differential gene expression related to this pathway. These proteins were also detected in diabetic rat retinas and induced structural damage. Paquinimod, an S100A9 inhibitor, decreased pathway protein expression and reduced retinal damage. Our study validates the S100A9/TLR4 pathway in diabetic retinas and suggests its potential as a therapeutic target for DR. Targeting S100A9 could offer a novel approach to prevention and treatment.

Racial and Socioeconomic Differences Correlate with Healthcare Disparities in Patients with Diabetic Retinopathy

Diabetic retinopathy (DR), an ocular complication of diabetes mellitus, is the leading cause of permanent blindness in the United States for young adults. Due to biological and environmental factors, diabetes mellitus is well known to disproportionally affect people of color and those of lower socioeconomic status; however, the racial and socioeconomic disparities of DR are less researched. The purpose of this research is to elucidate any differences in DR presentation that arise across racial and socioeconomic lines and to determine if diabetic control can be a predicting factor for DR severity. For this study, a retrospective patient chart analysis was performed on 511 consecutive newly referred patients with diabetes at New England Retina Associates, a vitreo-retinal ophthalmology practice with four locations throughout Connecticut. Our analysis shows that, when compared to their White and Asian counterparts, Black/African American and Hispanic patients present with DR at younger ages, had the higher HbA1c, were uninsured at higher rates, and presented with severe forms of DR in higher rates when compared to their counterparts. Many of these patterns are mirrored in patients that are uninsured or on Medicaid, indicators of lower socioeconomic status. Additionally, regardless of race or socioeconomic status, patients with higher HbA1c tended to present with more severe forms of DR. These findings indicate that DR disproportionately affects racial minority populations and those in socioeconomically disadvantageous positions, but effective glycemic control and routine eye exam screening can improve the outcomes of these patients. It is important for medical providers to recognize the disparities in these vulnerable populations in order to facilitate the timely referrals and the proper care for their long-term ocular health.

PET imaging for the early evaluation of ocular inflammation in diabetic rats by using [18F]-DPA-714

Ocular complications of diabetes mellitus (DM) are the leading cause of vision loss. Ocular inflammation often occurs in the early stage of DM; however, there are no proven quantitative methods to evaluate the inflammatory status of eyes in DM. The 18 kDa translocator protein (TSPO) is an evolutionarily conserved cholesterol binding protein localized in the outer mitochondrial membrane. It is a biomarker of activated microglia/macrophages; however, its role in ocular inflammation is unclear. In this study, fluorine-18-DPA-714 ([18F]-DPA-714) was evaluated as a specific TSPO probe by cell uptake, cell binding assays and micro positron emission tomography (microPET) imaging in both in vitro and in vivo models. Primary microglia/macrophages (PMs) extracted from the cornea, retina, choroid or sclera of neonatal rats with or without high glucose (50 mM) treatment were used as the in vitro model. Sprague-Dawley (SD) rats that received an intraperitoneal administration of streptozotocin (STZ, 60 mg/kg once) were used as the in vivo model. Increased cell uptake and high binding affinity of [18F]-DPA-714 were observed in primary PMs under hyperglycemic stress. These findings were consistent with cellular morphological changes, cell activation, and TSPO up-regulation. [18F]-DPA-714 PET imaging and biodistribution in the eyes of DM rats revealed that inflammation initiates in microglia/macrophages in the early stages (3 weeks and 6 weeks), corresponding with up-regulated TSPO levels. Thus, [18F]-DPA-714 microPET imaging may be an effective approach for the early evaluation of ocular inflammation in DM.

Plasma miR-19b, miR-34a, and miR-146a expression in patients with type 2 diabetes mellitus and cataract: A pilot study.

Cataract is among the most common ocular complications in diabetes mellitus (DM). While microRNA (miRNA) dysregulations in DM have been previously reported, consensus is still lacking concerning miRNA expression in cataract. Furthermore, the miRNA profile in diabetic cataract patients remains largely unexplored, and data on plasma expression levels are limited. Our study aimed to assess the plasma levels of three distinct miRNA species (hsa-miR-19b, hsa-miR-34a, and hsa-miR-146a) implicated in the development of cataract and/or DM.We investigated the circulating miRNA expression in DM patients diagnosed with cataract, compared to a non-DM cataract group. We employed qRT-PCR for relative quantification experiments and subsequently conducted a correlation analysis between miRNA expression levels and clinical characteristics. Our findings reveal that hsa-miR-34a and hsa-miR-146a are differentially expressed in the two cohorts. However, no significant correlation was observed between the clinical variables and miRNA levels. In summary, our results suggest a potential role for hsa-miR-34a and hsa-miR-146a in the biology of diabetic cataract.

Современные аспекты патогенеза, диагностики и лечения диабетической ретинопатии

The article discusses current ideas about the pathogenesis, risk factors, and new methods of diagnosis and treatment of diabetic retinopathy. This disease is a specific microvascular ocular complication of diabetes mellitus and is part of the group of ischemic retinopathies, which are characterized by a significant violation of capillary perfusion, the development of intraocular newly formed vessels and retinal edema. Statistics show that almost 366 million people in the world suffer from diabetes mellitus (IDF Atlas, 2011). According to forecasts, this number is expected to double by 2030, and this global growth will have a huge impact on the prevalence of diabetic retinopathy. Over the past decade, advances in medical technology and the development of new treatment methods have significantly improved the diagnosis and treatment of patients, but nevertheless, diabetic macular edema and proliferative diabetic retinopathy remain the leading causes of vision loss.

Role of hyperhomocysteinemia in the progression of diabetic retinopathy

: The aim of this study was to determine the role of hyperhomocysteinemia in the progression of diabetic retinopathy and to determine the association of hyperhomocysteinemia with various grades of diabetic retinopathy.Diabetic retinopathy is the most common ocular complication of Diabetes mellitus. Various studies have shown that mild elevations of homocysteine in plasma are associated with an increased risk of vaso-occlusive disease, thrombosis, and stroke.: A total of 97 patients who were diagnosed with diabetic retinopathy from October 2018 to September 2019 were included in our study. Written informed consent was taken from all the participants. Best corrected visual acuity (BCVA), anterior segment examination using slit lamp biomicroscopy examination(SLE), fundoscopy using indirect ophthalmoscope and using 90D lens on slit lamp was done in all patients. Serum homocysteine was assessed in all. The data was analysed using SPSS version 17.0. Results were expressed as mean, frequency and percentage. Out of 97 patients, mean serum homocysteine seen in mild non proliferative diabetic retinopathy, moderate non proliferative diabetic retinopathy, severe non proliferative diabetic retinopathy and proliferative diabetic retinopathy was 13.8 ± 0.33, 14.6 ± 0.44, 14.64 ± 0.41 and 15.78 ± 1.33 respectively.: In our study we found serum homocysteine levels was elevated in proliferative diabetic retinopathy when compared to non-proliferative diabetic retinopathy.

Diabetes and high-glucose could upregulate the expression of receptor for activated C kinase 1 in retina.

Diabetic retinopathy (DR) is a major ocular complication of diabetes mellitus, leading to visual impairment. Retinal pigment epithelium (RPE) injury is a key component of the outer blood retinal barrier, and its damage is an important indicator of DR. Receptor for activated C kinase 1 (RACK1) activates protein kinase C-ε (PKC-ε) to promote the generation of reactive oxygen species (ROS) in RPE cells, leading to apoptosis. Therefore, we hypothesize that the activation of RACK1 under hypoxic/high-glucose conditions may promote RPE cell apoptosis by modulating PKC-ε/ROS, thereby disrupting the barrier effect of the outer blood retinal barrier and contributing to the progression of DR. To investigate the role and associated underlying mechanisms of RACK1 in the development of early DR. In this study, Sprague-Dawley rats and adult RPE cell line-19 (ARPE-19) cells were used as in vivo and in vitro models, respectively, to explore the role of RACK1 in mediating PKC-ε in early DR. Furthermore, the impact of RACK1 on apoptosis and barrier function of RPE cells was also investigated in the former model. Streptozotocin-induced diabetic rats showed increased apoptosis and up-regulated expression of RACK1 and PKC-ε proteins in RPE cells following a prolonged modeling. Similarly, ARPE-19 cells exposed to high glucose and hypoxia displayed elevated mRNA and protein levels of RACK1 and PKC-ε, accompanied by an increases in ROS production, apoptosis rate, and monolayer permeability. However, silencing RACK1 significantly downregulated the expression of PKC-ε and ROS, reduced cell apoptosis and permeability, and protected barrier function. RACK1 plays a significant role in the development of early DR and might serve as a potential therapeutic target for DR by regulating RPE apoptosis and barrier function.

DIABETES DURATION AND RETINAL NERVE FIBER LAYER THICKNESS RELATED DEGREE OF DIABETIC RETINOPATHY

Introduction & ObjectivesDiabetic retinopathy is an ocular complication of diabetes mellitus (DM). Several studies have shownthat neurodegenerative changes in the retina occur earlier than microvascular changes.Measurement of retinal nerve fiber layer thickness can detect neurodegeneration at an early stage.This study aims to analyze the relationship of diabetes duration and retinal nerve fiber layerthickness with degree of diabetic retinopathy in type 2 diabetes mellitus patients.
 MethodsThis research was analytic observational research with cross-sectional design. The sample was type2 diabetes mellitus patients with diabetic retinopathy who visited the eye clinic at the University ofSumatera Utara General Hospital. The sample were then analyzed with the Kruskal Wallis test tofind relationship of diabetes duration and retinal nerve fiber layer thickness with degree of diabeticretinopathy in type 2 diabetes mellitus patients.
 ResultsThe sample of this study were 20 subjects with diabetic retinopathy and 20 subjects without diabeticretinopathy as the control group. The mean duration of having DM in the group of patients with mildNPDR was 5.33 years, with moderate NPDR was 9.13 years and with PDR was 15.33 years. Usingthe Kruskal Wallis test revealed that there was no significant relationship between degree ofdiabetic retinopathy with Avg RNFL (p=0.495), superior RNFL (p=0.385), inferior RNFL (p=0.111),temporal RNFL (p=0.064), nasal RNFL (p=0.535).
 ConclusionThere was a significant difference between diabetes duration with degree of diabetic retinopathy butno significant between retinal nerve fiber layer thickness with degree of diabetic retinopathy.

Fenofibrate and diabetic retinopathy.

Diabetic retinopathy (DR), a sight-threatening ocular complication of diabetes mellitus, is one of the main causes of blindness in the working-age population. Dyslipidemia is a potential risk factor for the development or worsening of DR, with conflicting evidence in epidemiological studies. Fenofibrate, an antihyperlipidemic agent, has lipid-modifying and pleiotropic (non-lipid) effects that may lessen the incidence of microvascular events. Relevant studies were identified through a PubMed/MEDLINE search spanning the last 20 years, using the broad term "diabetic retinopathy" and specific terms "fenofibrate" and "dyslipidemia". References cited in these studies were further examined to compile this mini-review. These pivotal investigations underwent meticulous scrutiny and synthesis, focusing on methodological approaches and clinical outcomes. Furthermore, we provided the main findings of the seminal studies in a table to enhance comprehension and comparison. Growing evidence indicates that fenofibrate treatment slows DR advancement owing to its possible protective effects on the blood-retinal barrier. The protective attributes of fenofibrate against DR progression and development can be broadly classified into two categories: lipid-modifying effects and non-lipid-related (pleiotropic) effects. The lipid-modifying effect is mediated through peroxisome proliferator-activated receptor-α activation, while the pleiotropic effects involve the reduction in serum levels of C-reactive protein, fibrinogen, and pro-inflammatory markers, and improvement in flow-mediated dilatation. In patients with DR, the lipid-modifying effects of fenofibrate primarily involve a reduction in lipoprotein-associated phospholipase A2 levels and the upregulation of apolipoprotein A1 levels. These changes contribute to the anti-inflammatory and anti-angiogenic effects of fenofibrate. Fenofibrate elicits a diverse array of pleiotropic effects, including anti-apoptotic, antioxidant, anti-inflammatory, and anti-angiogenic properties, along with the indirect consequences of these effects. Two randomized controlled trials-the Fenofibrate Intervention and Event Lowering in Diabetes and Action to Control Cardiovascular Risk in Diabetes studies-noted that fenofibrate treatment protected against DR progression, independent of serum lipid levels. Fenofibrate, an oral antihyperlipidemic agent that is effective in decreasing DR progression, may reduce the number of patients who develop vision-threatening complications and require invasive treatment. Despite its proven protection against DR progression, fenofibrate treatment has not yet gained wide clinical acceptance in DR management. Ongoing and future clinical trials may clarify the role of fenofibrate treatment in DR management.

Terapia cukrzycowego obrzęku plamki

Diabetic macular edema is an ocular complication of diabetes mellitus, leading to significant visual impairment. The pathogenesis of diabetic macular edema occurs through the interaction of multiple molecular mediators, including the overexpression of several growth factors, including vascular endothelial growth factor, angiopoietin-1, and -2, insulin-like growth factor-1, etc. These growth factors mediate endothelial cell proliferation, angiogenesis, protease production. Treatment for diabetic macular edema involves primary management of diabetes mellitus, laser photocoagulation, and pharmacotherapeutics targeting mediators, namely, the anti-vascular endothelial growth factor pathway. The introduction of anti-vascular endothelial growth factor therapies has resulted in significant clinical improvements compared to laser photocoagulation alone. However, the presence of anti-vascular endothelial growth factor non-responders and multiple factors influencing the visual outcome after anti-vascular endothelial growth factor treatment have necessitated the development of new therapeutic approaches. In this review, we provide an analysis of current management strategies to the treatment of diabetic macular edema

Quantitative Parameters Relevant for Diabetic Macular Edema Evaluation by Optical Coherence Tomography Angiography.

Diabetic macular edema (DME) is one of the main ocular complications of diabetes mellitus (DM) that can lead to important vision loss in diabetic patients. In clinical practice, there are cases of DME with unsatisfying treatment responses, despite adequate therapeutic management. Diabetic macular ischemia (DMI) is one of the causes suggested to be associated with the persistence of fluid accumulation. Optical coherence tomography angiography (OCTA) is a non-invasive imaging modality, able to give in-depth information about retinal vascularization in a 3-dimensional manner. The OCTA devices currently available can provide various OCTA metrics that quantitatively assess the retinal microvasculature. In this paper, we reviewed the results of multiple studies that investigated the changes in OCTA metrics in the setting of DME and their possible contribution to the diagnosis, therapeutic management, follow-up and prognosis of patients with DME. We analyzed and compared relevant studies that investigated OCTA parameters related to changes in macular perfusion in the setting of DME and we evaluated the correlations between DME and several quantitative parameters, such as vessel density (VD), perfusion density (PD), foveal avascular zone (FAZ)-related parameters, as well as complexity indices of retinal vasculature. The results of our research showed that OCTA metrics, evaluated especially at the level of the deep vascular plexus (DVP), are useful instruments that can contribute to the assessment of patients with DME.

The Role of Swedakarma in the Manifestation of Ocular Pathological Findings Among Diabetic Patients- A Prospective Observational Study

Diabetes mellitus (DM) is a chronic metabolic disorder involving almost all systems with delayed complications. Ophthalmic complications of diabetes rapidly cause blindness and are preventable with early screening and timely management. There are many modifiable risk factors for ocular complications associated with DM. It is very much essential to identify such risk factors to prevent complications. Swedana (Sudation therapy), the prerequisite for Panchakarma (fivefold purification therapy in Ayurveda) is contraindicated in Prameha and explained as an etiological factor of eye diseases. Swedana can become a risk factor for diabetic eye diseases. Repeated Swedakarma is a common practice to treat neurological complications in diabetic patients. Diabetic patients exposed to Swedakarma are more vulnerable to ocular complications. Aim: To analyse the role of Swedakarma in the manifestation of ocular pathological findings among diabetic patients. Methodology: This hospital-based, prospective observational study was conducted at Government Ayurveda College, Tripunithura. The study participants included 108 diabetic patients with matched cases and controls. The Chi-square test was used to analyze various sudation factors and ocular complications. Result: There is a 3.74-fold increase in ocular complications in patients exposed to Swedakarma, compared to patients who did not receive Swedakarma. Conclusion: There is a significant association between Swedakarma and ocular complications in DM.

Azelaic acid and guanosine in tears improve discrimination of proliferative from non-proliferative diabetic retinopathy in type-2 diabetes patients: A tear metabolomics study

BackgroundDiabetic retinopathy (DR) is the microvascular ocular complication of diabetes mellitus (DM), which can lead to irreversible blindness and visual impairment if not properly treated. Tears can be collected non-invasively, and the compositions of tears could be the potential biomarkers for ocular diseases. Here we aimed to delineate the metabolomics signature in tears collected from Chinese type-2 DM patients with DR. MethodsThe metabolomics profiles of tear samples from 41 Chinese type-2 DM patients with DR and 21 non-diabetic subjects were determined by the untargeted liquid chromatography-mass spectrometry. The associated pathways of the differentially abundant metabolites were delineated, and the receiver operating characteristic curve analysis was conducted to identify the metabolites differentiating non-proliferative DR (NPDR) from proliferative DR (PDR). ResultsTotal 14 differentially abundant metabolites were identified between total DR and non-diabetic subjects, and 17 differentially abundant metabolites were found between the NPDR and PDR subjects. Moreover, total 18 differentially abundant metabolites were identified between the NPDR and PDR subjects with stratification in DR duration and blood glucose level. d-Glutamine and d-glutamate metabolism was significantly highlighted in the PDR group as compared to the non-diabetic group. For the predictive performance, azelaic acid combined with guanosine achieved the area under receiver operating characteristic curve of 0.855 in the comparison between NPDR and PDR groups. ConclusionThis study revealed the metabolomics changes in tear samples of DR patients. The metabolites in tears could be the potential biomarkers in the DR analysis.

Diabetic retinopathy: Looking forward to 2030.

Diabetic retinopathy (DR) is the major ocular complication of diabetes mellitus, and is a problem with significant global health impact. Major advances in diagnostics, technology and treatment have already revolutionized how we manage DR in the early part of the 21st century. For example, the accessibility of imaging with optical coherence tomography, and the development of anti-vascular endothelial growth factor (VEGF) treatment are just some of the landmark developments that have shaped the DR landscape over the last few decades. Yet, there are still more exciting advances being made. Looking forward to 2030, many of these ongoing developments are likely to further transform the field. First, epidemiologic projections show that the global burden of DR is not only increasing, but also shifting from high-income countries towards middle- and low-income areas. Second, better understanding of disease pathophysiology is placing greater emphasis on retinal neural dysfunction and non-vascular aspects of diabetic retinal disease. Third, a wealth of information is becoming available from newer imaging modalities such as widefield imaging systems and optical coherence tomography angiography. Fourth, artificial intelligence for screening, diagnosis and prognostication of DR will become increasingly accessible and important. Fifth, new pharmacologic agents targeting other non-VEGF-driven pathways, and novel therapeutic strategies such as gene therapy are being developed for DR. Finally, the classification system for diabetic retinal disease will need to be continually updated to keep pace with new developments. In this article, we discuss these major trends in DR that we expect to see in 2030 and beyond.

Ocular complications of diabetes mellitus in a pediatric population and proposals for screening and follow-up programs.

Diabetes mellitus (DM) is one of the world's greatest health emergencies of the 21st century. Ocular complications of DM are commonly chronic and progressive, but vision loss can be effectively prevented or delayed with early detection and timely treatment. Therefore, regular comprehensive ophthalmologic examinations are mandatory. Ophthalmic screening and dedicated follow-up for adults with DM are well established, whereas, there is no consensus on optimal recommendations for the pediatric population, reflecting the lack of clarity about the current burden of disease in this age group. To determine the epidemiology of ocular complications of diabetes and to assess optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) macular features in a pediatric population with DM. To review ophthalmological screening and follow-up plans for the diabetic pediatric population. Observational study. Retrospective consecutive cohort study of all 165 diabetic patients (330 eyes) aged 0-18 years, examined between January 2006 and September 2018 at the Pediatric Department of 'S. Maria della Misericordia' Udine Hospital who underwent at least one complete ophthalmologic examination at the Ophthalmology University Clinic at the Udine Hospital. OCT and OCTA data were available for 37 patients (72 eyes, 2 excluded). The associations between ocular complications and selected potential risk factors were evaluated by univariate analyses. No patient had signs of ocular diabetic complications or any macular morphological or micro-vascular impairment, regardless of any potential risk factor. The prevalence of strabismus and refractive errors in the study group, was found to be similar to non-diabetic pediatric populations. Screening and follow-up of ocular diabetic complications in children and adolescents could be performed less frequently than in adults with diabetes. There is no need to screen potentially treatable visual disorders in diabetic children earlier or more frequently than in the healthy children thus reducing time spent in hospital and permitting a better tolerance to medical examinations in diabetic pediatric patients. We described the OCT and OCTA patterns in a pediatric population with DM.

Prevalence of ocular findings and their association with glycemia in dogs with diabetes mellitus: A 10-year clinical study (2009-2019).

Although ocular findings in diabetic patients are well described, prevalence data for those is unknown. To describe the prevalence of ocular findings and their association with glycemia in dogs with diabetes mellitus. Medical records from diabetic dogs assessed by the ophthalmology and the internal medicine services at the Veterinary Teaching Hospital of the Autonomous University of Barcelona were reviewed (2009-2019). Seventy-five dogs (150 eyes) of both genders (51/75 females; 68% and 24/75 males; 32%) and a mean age of 9.37 ± 2.43 years, were included. The most common ocular findings were cataracts (146/150; 97.3%), vitreous degeneration (45/98; 45.9%), anterior uveitis (47/150; 31.3%), aqueous deficiency dry eye (ADDE) (33/150; 22%), diffuse corneal edema (31/150; 20.7%), non-proliferative retinopathy (13/98; 13.3%), and lipid keratopathy (9/150; 6%). The most prevalent type of cataracts observed (78/146; 53.4%) was intumescent, which was commonly accompanied by non-proliferative retinopathy (p = 0.003). Among the diabetic dogs, blood glucose levels were statistically higher in dogs with non-proliferative retinopathy or anterior uveitis (p < 0.005). Ocular complications of diabetes mellitus in dogs are numerous, being the most frequent intumescent cataracts, vitreous degeneration, anterior uveitis, ADDE, diffuse corneal edema, and non-proliferative retinopathy. This high prevalence warrants a more detailed ophthalmic evaluation in diabetic dogs especially for those undergoing cataract surgery. Furthermore, a predisposition for anterior segment inflammation and non-proliferative retinopathy is suggested when fasting plasma glucose is higher than 600 mg/dl..

The Relationship Between Diabetic Retinopathy Degree With Visual Acuity And Retinal Nerve Fiber Layer Thickness In Type 2 Diabetes Mellitus Patients

Introduction: Diabetic retinopathy is an ocular complication of diabetes mellitus (DM), and is one of the leading causes of visual impairment and blindness worldwide.. More than one third of people with diabetes have signs of diabetic retinopathy.&#x0D; &#x0D; Methods: This was an analytic observational study with cross-sectional design. The sample was type 2 diabetes mellitus patients with diabetic retinopathy who visited the eye clinic at the University of Sumatera Utara General Hospital from September 2021-December 2021. The sample were then analyzed with the Mann-Whitney and Kruskal Wallis test to find the relationship between diabetic retinopathy degree with visual acuity and retinal nerve fiber layer thickness in type 2 diabetes mellitus patients.&#x0D; &#x0D; Results: The sample of this study were 20 subjects with diabetic retinopathy and 20 subjects without diabetic retinopathy as the control group. The mean visual acuity in subjects with mild diabetic retinopathy was 0.65+0.48. Average visual acuity in subjects with the degree of moderate diabetic retinopathy was 0.83+0.46. The mean visual acuity in subjects with a proliferative degrees diabetic retinopathy was 0.77+0.64. Mann Whitney test revealed no statistically significant relationship between the degree of diabetic retinopathy and visual acuity (p=0.734). Using the Kruskal Wallis test revealed that there was no significant relationship between the degree of retinopathy diabetic with Avg RNFL (p=0.495), superior RNFL (p=0.385), inferior RNFL (p=0.111), temporal RNFL (p=0.064), nasal RNFL (p=0.535).&#x0D; &#x0D; Discussion: Controlling blood glucose levels becomes more important than the duration of diabetes in preventing the development of retinopathy. Most patients are advised to have an HbA1c of 7% or lower, and for certain patients it is recommended to be lower than6.5%. Diabetic retinopathy slowly damages the retinal blood vessels or the optic nerve layer, leading to leakage, thus resulting in accumulation of fluid containing lipid and blood in the retina which will gradually lead to visual impairment, and even blindness.&#x0D; &#x0D; Conclusion: There is no significant relationship between diabetic retinopathy degree with visual acuity and retinal nerve fiber layer thickness in type 2 diabetes mellitus patients.

Current and Novel Therapeutic Approaches for Treatment of Diabetic Macular Edema.

Diabetic macular edema (DME) is a major ocular complication of diabetes mellitus (DM), leading to significant visual impairment. DME’s pathogenesis is multifactorial. Focal edema tends to occur when primary metabolic abnormalities lead to a persistent hyperglycemic state, causing the development of microaneurysms, often with extravascular lipoprotein in a circinate pattern around the focal leakage. On the other hand, diffusion edema is due to a generalized breakdown of the inner blood–retinal barrier, leading to profuse early leakage from the entire capillary bed of the posterior pole with the subsequent extravasation of fluid into the extracellular space. The pathogenesis of DME occurs through the interaction of multiple molecular mediators, including the overexpression of several growth factors, including vascular endothelial growth factor (VEGF), insulin-like growth factor-1, angiopoietin-1, and -2, stromal-derived factor-1, fibroblast growth factor-2, and tumor necrosis factor. Synergistically, these growth factors mediate angiogenesis, protease production, endothelial cell proliferation, and migration. Treatment for DME generally involves primary management of DM, laser photocoagulation, and pharmacotherapeutics targeting mediators, namely, the anti-VEGF pathway. The emergence of anti-VEGF therapies has resulted in significant clinical improvements compared to laser therapy alone. However, multiple factors influencing the visual outcome after anti-VEGF treatment and the presence of anti-VEGF non-responders have necessitated the development of new pharmacotherapies. In this review, we explore the pathophysiology of DME and current management strategies. In addition, we provide a comprehensive analysis of emerging therapeutic approaches to the treatment of DME.

Diabetic Retinopathy: From Animal Models to Cellular Signaling.

Diabetic retinopathy (DR) is an ocular complication of diabetes mellitus (DM), a metabolic disorder characterized by elevation in blood glucose level. The pathogenesis of DR includes vascular, neuronal, and inflammatory components leading to activation of complex cellular molecular signaling. If untreated, the disease can culminate in vision loss that eventually leads to blindness. Animal models mimicking different aspects of DM complications have been developed to study the development and progression of DR. Despite the significant contribution of the developed DR models to discovering the mechanisms of DR and the recent achievements in the research field, the sequence of cellular events in diabetic retinas is still under investigation. Partially, this is due to the complexity of molecular mechanisms, although the lack of availability of models that adequately mimic all the neurovascular pathobiological features observed in patients has also contributed to the delay in determining a precise molecular trigger. In this review, we provide an update on the status of animal models of DR to help investigators choose an appropriate system to validate their hypothesis. We also discuss the key cellular and physiological events of DR in these models.