Circulating Biomarkers of Diabetic Retinopathy: An Overview Based on Physiopathology

Diabetic retinopathy (DR) is the main cause of working-age adult-onset blindness. The currently available treatments for DR are applicable only at advanced stages of the disease and are associated with significant adverse effects. In early stages of DR the only therapeutic strategy that physicians can offer is a tight control of the risk factors for DR. Therefore, new pharmacological treatments for these early stages of the disease are required. In order to develop therapeutic strategies for early stages of DR new diagnostic tools are urgently needed. In this regard, circulating biomarkers could be useful to detect early disease, to identify those diabetic patients most prone to progressive worsening who ought to be followed up more often and who could obtain the most benefit from these therapies, and to monitor the effectiveness of new drugs for DR before more advanced DR stages have been reached. Research of biomarkers for DR has been mainly based on the pathogenic mechanism involved in the development of DR (i.e., AGEs, oxidative stress, endothelial dysfunction, inflammation, and proangiogenic factors). This review focuses on circulating biomarkers at both early and advanced stages that could be relevant for the prediction or detection of DR.

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Usefulness of the Vitreous Fluid Analysis in the Translational Research of Diabetic Retinopathy

Mediators of Inflammation ◽

10.1155/2012/872978 ◽

2012 ◽

Vol 2012 ◽

pp. 1-11 ◽

Cited By ~ 47

Author(s):

Olga Simó-Servat ◽

Cristina Hernández ◽

Rafael Simó

Keyword(s):

Diabetic Retinopathy ◽

New Technologies ◽

Vitreoretinal Surgery ◽

Diabetic Patients ◽

Pharmacological Treatments ◽

Vitreous Fluid ◽

Fluid Analysis ◽

Working Age ◽

Advanced Stages ◽

Endothelial Growth Factor

Diabetic retinopathy (DR) is the major cause of acquired blindness in working-age adults. Current treatments for DR (laser photocoagulation, intravitreal corticosteroids, intravitreal antivascular endothelial growth factor (VEGF) agents, and vitreo-retinal surgery) are applicable only at advanced stages of the disease and are associated with significant adverse effects. Therefore, new pharmacological treatments for the early stages of the disease are needed. Vitreous fluid obtained from diabetic patients undergoing vitreoretinal surgery is currently used to explore the events that are taking place in the retina for clinical research. However, several confounding factors such as vitreous haemorrhage and concentration of vitreous proteins should be considered in the analysis of the results. In this paper we will focus on the vitreous fluid as a tool for exploring the mediators of DR and in particular the molecules related to inflammatory pathways. In addition, their role in the pathogenesis of DR will be discussed. The usefulness of new technologies such as flow cytometry and proteomics in identifying new candidates involved in the inflammatory process that occurs in DR will be overviewed. Finally, a more personalized treatment based on vitreous fluid analysis aiming to reduce the burden associated with DR is suggested.

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Stem Cell Therapy for T1 D and T2 D Diabetic patients

International Journal of Scientific and Engineering Research ◽

10.14299/ijser.2020.10.10 ◽

2020 ◽

Vol 11 (10) ◽

pp. 23-25

Author(s):

Nandakumar Ravichandran

Keyword(s):

Diabetic Retinopathy ◽

Beta Cells ◽

Chronic Condition ◽

Major Complication ◽

Limb Ischemia ◽

Diabetic Patients ◽

Insulin Production ◽

Working Age

Diabetes is a chronic condition that causes several diseases. Type 1 and Type 2 dependent diabetes are shown more concern in today’s world. Type1 dependent patients suffers from inability of the Beta cells to produce insulin whereas Type 2 dependent patients suffers from insufficient insulin production. Diabetic Retinopathy, Nephropathy, Critical Limb Ischemia and impaired glucose tolerance are some of the major risk factors of Diabetes. Diabetic Retinopathy is a major complication of Diabetes causing blindness in working age adults. This article discusses some research methods involved in the generation of Beta cells carried out by certain authors, hypothesis and future works in this field.

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Development of Diagnostic Biomarkers for Detecting Diabetic Retinopathy at Early Stages Using Quantitative Proteomics

Journal of Diabetes Research ◽

10.1155/2016/6571976 ◽

2016 ◽

Vol 2016 ◽

pp. 1-22 ◽

Cited By ~ 8

Author(s):

Jonghwa Jin ◽

Hophil Min ◽

Sang Jin Kim ◽

Sohee Oh ◽

Kyunggon Kim ◽

...

Keyword(s):

Diabetic Retinopathy ◽

Quantitative Proteomics ◽

Multiple Reaction Monitoring ◽

Diabetic Patients ◽

Reaction Monitoring ◽

Protein Marker ◽

Diagnostic Biomarkers ◽

Stable Isotope Dilution ◽

Early Stages ◽

Larger Sample

Diabetic retinopathy (DR) is a common microvascular complication caused by diabetes mellitus (DM) and is a leading cause of vision impairment and loss among adults. Here, we performed a comprehensive proteomic analysis to discover biomarkers for DR. First, to identify biomarker candidates that are specifically expressed in human vitreous, we performed data-mining on both previously published DR-related studies and our experimental data; 96 proteins were then selected. To confirm and validate the selected biomarker candidates, candidates were selected, confirmed, and validated using plasma from diabetic patients without DR (No DR) and diabetics with mild or moderate nonproliferative diabetic retinopathy (Mi or Mo NPDR) using semiquantitative multiple reaction monitoring (SQ-MRM) and stable-isotope dilution multiple reaction monitoring (SID-MRM). Additionally, we performed a multiplex assay using 15 biomarker candidates identified in the SID-MRM analysis, which resulted in merged AUC values of 0.99 (No DR versus Mo NPDR) and 0.93 (No DR versus Mi and Mo NPDR). Although further validation with a larger sample size is needed, the 4-protein marker panel (APO4, C7, CLU, and ITIH2) could represent a useful multibiomarker model for detecting the early stages of DR.

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Diabetic Retinopathy Detection using Retinal Images and Deep Learning Model

International Journal of Innovative Technology and Exploring Engineering - Special Issue ◽

10.35940/ijitee.i9296.0710921 ◽

2021 ◽

Vol 10 (9) ◽

pp. 35-39

Author(s):

Vani Ashok ◽

◽

Navneet Hosmane ◽

Ganesh Mahagaonkar ◽

Aditya Gudigar ◽

...

Keyword(s):

Diabetic Retinopathy ◽

Deep Learning ◽

Retinal Images ◽

Kappa Score ◽

Early Stages ◽

Proposed Model ◽

Learning Capabilities ◽

Working Age ◽

Color Fundus Images ◽

Deep Learning Model

Diabetic Retinopathy (DR) is one of the serious problems caused by diabetes and a leading source of blindness in the working-age population of the advanced world. Detecting DR in the early stages is crucial since the disease generally shows few symptoms until it is too late to provide an effective cure. But detecting DR requires a skilled clinician to examine and assess digital color fundus images of the retina. By simplifying the detection process, severe damages to the eyes can be prevented. Many deep learning models particularly Convolutional Neural Networks (CNNs) have been tested in similar fields as well as in the detection of DR in early stages. In this paper, we propose an automatic model for detecting and suggesting different stages of DR. The work has been carried out on APTOS 2019 Blindness Detection Benchmark Dataset which contains around 3600 retinal images graded by clinicians for the severity of diabetic retinopathy on a range of 0 to 4. The proposed method uses ResNet50 (Residual Network that is 50 layers deep) CNN model along with pre-trained weights as the base neural network model. Due to its depth and better transfer learning capabilities, the proposed model with ResNet50 achieved 82% classification accuracy. The classification ability of the model was further analysed with Cohen Kappa score. The optimized validation Cohen Kappa score of 0.827 indicate that the proposed model didn’t predict the outputs by chance.

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Glyoxalase System as a Therapeutic Target against Diabetic Retinopathy

Antioxidants ◽

10.3390/antiox9111062 ◽

2020 ◽

Vol 9 (11) ◽

pp. 1062 ◽

Cited By ~ 2

Author(s):

Gemma Aragonès ◽

Sheldon Rowan ◽

Sarah G Francisco ◽

Wenxin Yang ◽

Jasper Weinberg ◽

...

Keyword(s):

Oxidative Stress ◽

Diabetic Retinopathy ◽

Therapeutic Strategy ◽

Diabetic Complication ◽

Wild Type ◽

Glyoxalase System ◽

Age Related ◽

Glycation End Products ◽

Working Age ◽

Stress Formation

Hyperglycemia, a defining characteristic of diabetes, combined with oxidative stress, results in the formation of advanced glycation end products (AGEs). AGEs are toxic compounds that have adverse effects on many tissues including the retina and lens. AGEs promote the formation of reactive oxygen species (ROS), which, in turn, boost the production of AGEs, resulting in positive feedback loops, a vicious cycle that compromises tissue fitness. Oxidative stress and the accumulation of AGEs are etiologically associated with the pathogenesis of multiple diseases including diabetic retinopathy (DR). DR is a devastating microvascular complication of diabetes mellitus and the leading cause of blindness in working-age adults. The onset and development of DR is multifactorial. Lowering AGEs accumulation may represent a potential therapeutic approach to slow this sight-threatening diabetic complication. To set DR in a physiological context, in this review we first describe relations between oxidative stress, formation of AGEs, and aging in several tissues of the eye, each of which is associated with a major age-related eye pathology. We summarize mechanisms of AGEs generation and anti-AGEs detoxifying systems. We specifically feature the potential of the glyoxalase system in the retina in the prevention of AGEs-associated damage linked to DR. We provide a comparative analysis of glyoxalase activity in different tissues from wild-type mice, supporting a major role for the glyoxalase system in the detoxification of AGEs in the retina, and present the manipulation of this system as a therapeutic strategy to prevent the onset of DR.

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Combination Approaches Targeting Neurodegeneration, Oxidative stress and Inflammation in the Treatment of Diabetic Retinopathy

Current Drug Targets ◽

10.2174/1389450122666210319113136 ◽

2021 ◽

Vol 22 ◽

Author(s):

Siddhi Dilip Chalke ◽

Pravin Popatrao Kale

Keyword(s):

Oxidative Stress ◽

Diabetic Retinopathy ◽

Vision Loss ◽

Treatment Options ◽

Treatment Strategies ◽

Early Stages ◽

Advanced Stages ◽

Severe Vision Loss ◽

Angiopoietin 2 ◽

Endothelial Growth Factor

: Diabetic Retinopathy (DR) is one of the most severe ocular problems of diabetes. It is a microvascular complication that impairs the vision of diabetic individuals and can cause acquired blindness. Currently available treatment options like laser therapy, vitrectomy, intravitreal anti-vascular endothelial growth factor (VEGF) agents, and glucocorticoids help to reduce vision loss at advanced stages. In spite of the available therapies, patients with severe vision loss face difficulty in achieving normal vision. There is a need for development of newer treatment strategies to address the condition from the early stages. Multiple factors owing to complex pathophysiological events are responsible for this long-term complication. Neurodegeneration, inflammation, and oxidative stress are the three important factors associated with the development of DR. Oxidative stress is a major contributor to the onset and progression of DR. Pathological events like retinal neurodegeneration and inflammation damage the retina right in the early stages of DR. Different combinations of treatments targeting these pathological events are discussed in the present review. The first combination discussed is citicoline and resveratrol. The second combination is duloxetine and N-acetyl cysteine (NAC). These combinations may help in the early stages of DR. CD5-2 and angiopoietin-2 inhibitors is the third combination. This combination may help to manage diabetic macular edema. The main purpose of this article is to discuss the link between these pathologies and the three combination approaches with the objective of consideration of newer therapeutic approaches in research related to DR treatment.

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Molecular Implications of the PPARs in the Diabetic Eye

PPAR Research ◽

10.1155/2013/686525 ◽

2013 ◽

Vol 2013 ◽

pp. 1-11 ◽

Cited By ~ 13

Author(s):

Andreea Ciudin ◽

Cristina Hernández ◽

Rafael Simó

Keyword(s):

Diabetic Retinopathy ◽

Molecular Mechanisms ◽

Vitreoretinal Surgery ◽

Developed Countries ◽

Peroxisome Proliferator ◽

New Approach ◽

New Strategy ◽

Working Age ◽

Ppar Agonists ◽

Advanced Stages

Diabetic retinopathy (DR) remains as the leading cause of blindness among working age individuals in developed countries. Current treatments for DR (laser photocoagulation, intravitreal corticosteroids, intravitreal anti-VEGF agents, and vitreoretinal surgery) are applicable only at advanced stages of the disease and are associated with significant adverse effects. Therefore, new pharmacological treatments for the early stages of the disease are needed. Emerging evidence indicates that peroxisome proliferator-activator receptors (PPARs) agonists (in particular PPARα) are useful for the treatment of DR. However, the underlying molecular mechanisms are far from being elucidated. This paper mainly focuses on PPARs expression in the diabetic eye, its molecular implications, and the effect of PPAR agonists as a new approach for the treatment of DR. The availability of this new strategy will not only be beneficial in treating DR but may also result in a shift towards treating earlier stages of diabetic retinopathy, thus easing the burden of this devastating disease (Cheung et al. (2010)).

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Hodgkin's Disease in Patients with HIV Infection

Advances in Hematology ◽

10.1155/2011/402682 ◽

2011 ◽

Vol 2011 ◽

pp. 1-7 ◽

Cited By ~ 10

Author(s):

Michele Spina ◽

Antonino Carbone ◽

Annunziata Gloghini ◽

Diego Serraino ◽

Massimiliano Berretta ◽

...

Keyword(s):

Hiv Infection ◽

Highly Active Antiretroviral Therapy ◽

High Dose Chemotherapy ◽

New Drugs ◽

Diagnostic Tools ◽

High Dose ◽

Stem Cell Rescue ◽

Highly Active ◽

Phase Ii Studies ◽

Advanced Stages

Hodgkin lymphoma (HL) represents one of the most common non-AIDS-defining cancers with an increasing incidence overtime. Clinically, patients present advanced stages of disease with extranodal involvement in the majority of cases. In the last years, significant improvements in the treatment of patients with HL and HIV infection have been achieved. In the lack of randomized trials, several phase II studies have showed that in the era of highly active antiretroviral therapy (HAART) the same regimens employed in HIV-negative patients with HL can be used in HIV setting with similar results. Moreover, in the last years the feasibility of high dose chemotherapy and peripheral stem cell rescue has allowed to save those patients who failed the upfront treatment. Finally, in the near future, a better integration of diagnostic tools (including PET scan), chemotherapy (including new drugs), radiotherapy, HAART, and supportive care will significantly improve the outcome of these patients.

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Association of periodontitis and diabetic macular edema in various stages of diabetic retinopathy

Clinical Oral Investigations ◽

10.1007/s00784-021-04028-x ◽

2021 ◽

Author(s):

Marlene Lindner ◽

Behrouz Arefnia ◽

Domagoj Ivastinovic ◽

Harald Sourij ◽

Ewald Lindner ◽

...

Keyword(s):

Diabetic Retinopathy ◽

Macular Edema ◽

Diabetic Macular Edema ◽

Cross Sectional Study ◽

Diabetic Patients ◽

Pocket Depth ◽

Cross Sectional ◽

Early Stages ◽

Surface Areas ◽

Late Stages

Abstract Objectives Periodontitis and diabetes are known to have a bidirectional relationship. Diabetic macular edema is a complication of diabetes that is strongly influenced by inflammatory pathways. However, it remains to be established whether inflammation at other locations, such as periodontitis, affects diabetic macular edema. Here, we investigated the prevalence of periodontitis in patients treated for diabetic macular edema. Materials and methods Patients with diabetic macular edema were recruited for this cross-sectional study at the Medical University of Graz. Macular edema was documented by optical coherence tomography. Periodontal status was assessed by computerized periodontal probing and panoramic X-ray imaging. Bleeding on probing, clinical attachment level, probing pocket depth, and plaque index were compared between different stages of diabetic retinopathy. Results Eighty-three eyes of 45 patients with diabetic macular edema were enrolled. Forty-four eyes (53.0%) had early stages of diabetic retinopathy (mild and moderate), and 39 eyes (47.0%) had late stages (severe and proliferative). Patients with mild or moderate DR were more likely to have more severe periodontal conditions than patients with severe or proliferative DR. Fourteen patients with mild DR (82.4%), 7 patients with moderate DR (87.5%), 4 patients with severe DR (100.0%), and 15 patients with proliferative DR (93.8%) had some degree of PD. The periodontal inflamed surface areas and the percentages of tooth sites that bled on probing were significantly higher in patients with early stages of diabetic retinopathy than in those with late stages of the disease (p < 0.05). Patients with periodontal inflamed surface areas of more than 500 mm2 required significantly more intravitreal injections in the last year than those with milder forms of periodontitis (n = 6.9 ± 3.1 versus n = 5.0 ± 3.5, p = 0.03). Conclusion In patients with diabetic macular edema, periodontitis is more prevalent in early stages of diabetic retinopathy. We suggest regular dental check-ups for diabetic patients, especially when diabetic macular edema is already present. Clinical relevance Patients with diabetic macular edema should be screened for periodontitis and vice versa, particularly early in the course of diabetes.

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Cost-Effectiveness of the Screening and Treatment of Diabetic Retinopathy: What Are the Costs of Underutilization?

International Journal of Technology Assessment in Health Care ◽

10.1017/s0266462300002385 ◽

1992 ◽

Vol 8 (4) ◽

pp. 694-707 ◽

Cited By ~ 19

Author(s):

A. Mark Fendrick ◽

Jonathan C. Javitt ◽

Yen Pin Chiang

Keyword(s):

Diabetic Retinopathy ◽

Retinal Disease ◽

Medical Expenditures ◽

Diabetic Patients ◽

Controlled Trials ◽

Type I ◽

Visual Disability ◽

Annual Screening ◽

Working Age ◽

Photocoagulation Treatment

AbstractDiabetic retinal disease remains a leading cause of visual disability among those of working age. Controlled trials have demonstrated that timely diagnosis and photocoagulation treatment can reduce significantly the likelihood of visual impairment in affected diabetic patients. Using a prospective simulation model, we show that an annual screening and treatment program saves thousands of years of vision and reduces medical expenditures over the lifetime of a cohort of Swedish Type I diabetic patients.

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