scholarly journals Update on the Treatment of Diabetic Retinopathy

2008 ◽  
Vol 8 ◽  
pp. 98-120 ◽  
Author(s):  
Jennifer L. Wilkinson-Berka ◽  
Antonia G. Miller
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Vision Loss ◽  
Fibrous Tissue ◽  
Diabetic Macular Oedema ◽  
Renin Angiotensin System ◽  
Neovascular Glaucoma ◽  
Western Society ◽  
Blood Retinal Barrier

Retinopathy is the most feared complication of diabetes, compromising quality of life in most sufferers. Almost all patients with type 1 diabetes will develop retinopathy over a 15- to 20-year period, and approximately 20–30% will advance to the blinding stage of the disease[1]. Greater than 60% of patients with type 2 diabetes will have retinopathy. This situation is highlighted by the frightening statistic that diabetic retinopathy (DR) remains the most common cause of vision impairment in people of working age in Western society. With the global epidemic of type 2 diabetes, this predicament is set to worsen as over 360 million people are projected to suffer from diabetes and its complications by 2030. Vision loss from diabetes is due to a number of factors, including haemorrhage from new and poorly formed blood vessels, retinal detachment due to contraction of deposited fibrous tissue, and neovascular glaucoma resulting in an increase in intraocular pressure. Diabetic macular oedema is now the principal cause of vision loss in diabetes and involves leakage from a disrupted blood-retinal barrier. In terms of treatment, there is clear evidence that strict metabolic and blood pressure control can lower the risk of developing DR and reduce disease progression. Laser photocoagulation and vitrectomy are effective in preventing severe vision loss in DR, particularly in the most advanced stages of the disease. However, both procedures have limitations. This review examines evidence from preclinical and clinical studies that shows that targeting inhibition of the renin-angiotensin system, vascular endothelial growth factor, corticosteroids, protein kinase C, growth hormone, and advanced glycation end-products are potential treatments for DR.

scholarly journals Tofacitinib Ameliorates Retinal Vascular Leakage in a Murine Model of Diabetic Retinopathy with Type 2 Diabetes

2021 ◽  
Vol 22 (21) ◽  
pp. 11876
Author(s):  
Eimear M. Byrne ◽  
María Llorián-Salvador ◽  
Timothy J. Lyons ◽  
Mei Chen ◽  
Heping Xu
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
High Glucose ◽  
Macular Oedema ◽  
Diabetic Macular Oedema ◽  
Janus Kinase ◽  
Blood Retinal Barrier ◽  
Albumin Leakage

We have previously reported that inhibition of the Janus kinase 1 (JAK1) signaling ameliorates IL-17A-mediated blood-retinal barrier (BRB) dysfunction. Higher levels of IL-17A have been observed in the blood and intraocular fluids in patients with diabetic retinopathy (DR), in particular those with diabetic macular oedema. This study aimed to understand whether JAK1 inhibition could prevent BRB dysfunction in db/db mice, a model of type 2 diabetes (T2D). An in vitro study showed that high glucose treatment disrupted the junctional distribution of claudin-5 in bEnd3 cells and ZO-1 in ARPE19 cells and that tofacitinib citrate treatment prevented high glucose-mediated tight junction disruption. Albumin leakage, accompanied by increased levels of the phosphorylated form of JAK1 (pJAK1), was observed in three-month-old db/db mice. Treatment of two-and-a-half-month-old db/db mice with tofacitinib citrate for two weeks significantly reduced retinal albumin leakage and reduced pJAK1 expression. pJAK1 expression was also detected in human DR retina. Our results suggest that JAK1 inhibition can ameliorate BRB dysfunction in T2D, and JAK1 inhibitors such as tofacitinib citrate may be re-purposed for the management of diabetic macular oedema.

scholarly journals Plasma microRNA signature associated with retinopathy in patients with type 2 diabetes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Donato Santovito ◽  
Lisa Toto ◽  
Velia De Nardis ◽  
Pamela Marcantonio ◽  
Rossella D’Aloisio ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Vision Loss ◽  
External Validation ◽  
Diabetic Patients ◽  
Disease Biomarkers ◽  
Response To Stress ◽  
Severity Of The Disease ◽  
Plasma Microrna

AbstractDiabetic retinopathy (DR) is a leading cause of vision loss and disability. Effective management of DR depends on prompt treatment and would benefit from biomarkers for screening and pre-symptomatic detection of retinopathy in diabetic patients. MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression which are released in the bloodstream and may serve as biomarkers. Little is known on circulating miRNAs in patients with type 2 diabetes (T2DM) and DR. Here we show that DR is associated with higher circulating miR-25-3p (P = 0.004) and miR-320b (P = 0.011) and lower levels of miR-495-3p (P < 0.001) in a cohort of patients with T2DM with DR (n = 20), compared with diabetic subjects without DR (n = 10) and healthy individuals (n = 10). These associations persisted significant after adjustment for age, gender, and HbA1c. The circulating levels of these miRNAs correlated with severity of the disease and their concomitant evaluation showed high accuracy for identifying DR (AUROC = 0.93; P < 0.001). Gene ontology analysis of validated targets revealed enrichment in pathways such as regulation of metabolic process (P = 1.5 × 10–20), of cell response to stress (P = 1.9 × 10–14), and development of blood vessels (P = 2.7 × 10–14). Pending external validation, we anticipate that these miRNAs may serve as putative disease biomarkers and highlight novel molecular targets for improving care of patients with diabetic retinopathy.

Association of a Pro-Inflammatory Axis Comprised By TSP1-TGF-CTGF/CCN2 with a Decrease in Mir-19a-3p in the Pathophysiology of Diabetic Retinopathy

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5552-5552
Author(s):  
Philippe Alexander Alvarez Dela Cadena ◽  
Jose Francisco Calva Moreno ◽  
Fabiola Elizabeth Del Carpio-Cano ◽  
Rao Ajaykumar ◽  
William J Foster ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Growth Factor ◽  
Differential Expression ◽  
Proliferative Diabetic Retinopathy ◽  
Vision Loss ◽  
The United States ◽  
Control Group ◽  
Down Regulation

Abstract Diabetic retinopathy (DR) is the leading cause of legal blindness in working age adults in the United States with about 18 thousand new cases of blindness each year. Approximately 75% of patients with type-2 diabetes will develop some sign of retinopathy after 15 years. The healthcare costs associated with diabetes related vision loss has been estimated at $500 million annually and the cost rises significantly with the severity of DR. Therefore, preventing the progression of DR from mild non-progressive diabetic retinopathy (NPDR) to progressive diabetic retinopathy (PDR) could ameliorate the economic burden related to diabetes and vision loss. Our laboratory has focused on a pro-inflammatory axis comprised by thrombospondin-1 (TSP1), transforming growth factor β (TGFb) and connective tissue growth factor (CTGF/CCN2) in the pathophysiology of DR. Furthermore, the regulation of this pro-inflammatory axis during disease states in humans associated with acute and chronic inflammation such as type-2 diabetes has not been elucidated. The current prospective study documents a potential regulatory mechanism, namely a microRNA associated with the up-regulation of the pro-inflammatory axis. Patients were recruited between February 2013 to May 2014. In May of 2015 it was determined by this research team that the data was mature for final analysis and, thus the results are the topic of this abstract. The participants were patients with type-2 diabetes (n=36) with either evidence of non-proliferative diabetic retinopathy (NPDR Group, n=16), or with evidence of proliferative diabetic retinopathy (PDR Group, n=20) as well as non-diabetic human subjects (Control Group, n=21). Each patient's history and duration of diabetes was obtained from the medical electronic records. TSP1 was found significantly increased in the NPDR (502±145.03 ng/ml, p<0.05) and PDR (1033.9±136 ng/ml, p<0.001) groups when compared to control group (167±41.9 ng/ml). TGF-β was found significantly increased in the NPDR (32.0±4.49 pg/ml, p<0.001) and PDR (7.75±1.7 pg/ml, p<0.05) groups when compared to control (0.75±0.05 pg/ml). CTGF/CCN2 was found significantly increased in the NPDR and PDR groups, namely 3.69±1.52 ng/ml (p<0.001) and 1.69±0.4 ng/ml (p<0.05) respectively when compared to the control group (0.25±0.049 ng/ml). Tumor necrosis factor-α was found significantly increased (17.3±2.1 pg/ml, p<0.05) in the NPDR group but not in the PDR group (trend for higher levels) when compared to control group (9.61±0.74 pg/ml). Interleukin-4 was found decreased in both the NPDR (1.54±0.23 pg/ml, p<0.05) and the PDR (2.02±0.26, p<0.05) groups when compared with the control group (5.42±1.63 pg/ml). IL-4 recently has been documented as an important regulator of lipid metabolism. When comparing the three groups using an ANOVA, one microRNA, namely miR-19a-3p was found to be the most strongly differentially expressed using a cutoff p-value ≤ 0.05 after a Benjamini-Hochberg correction for multiple testing, recommended when doing panel or array profiling. Figure 1 panel A shows the expression level centered to assay average for miR-19a-3p detected in most samples. Panel B clearly illustrates a significant decrease in miR-19a-3p in both groups, namely NPDR (p<0.0012) and PDR (p<0.049). Interestingly down-regulation of miR-19a was found independent of progression of disease suggesting that the differential expression seen in our study in the NPDR and PDR groups is inherent to the underlying disease. These last observations including the mechanistic steps involved are currently under investigation in our laboratory, since understanding, how the down-regulation of miR-19a leads to up-regulation of TSP1-TGFb-CTGF/CCN2, might have a two-fold potential value in type-2 diabetes. First, it can be used as a biomarker for early diagnosis, prognosis and therapeutic response. Second, a therapeutic approach would be able to restore the mature miRNA levels in the proper tissue/cells. In summary our results support the role of a pro-inflammatory axis in the pathophysiology of type-2 diabetes as a result of differential expression of miR-19a. Figure 1. Panel A and Panel B Figure 1. Panel A and Panel B Disclosures No relevant conflicts of interest to declare.

scholarly journals The relationship between ACE/AGT gene polymorphisms and the risk of diabetic retinopathy in Chinese patients with type 2 diabetes

2018 ◽  
Vol 19 (1) ◽  
pp. 147032031775295 ◽  
Author(s):  
Yong-chao Qiao ◽  
Min Wang ◽  
Yan-hong Pan ◽  
Xiao-xi Zhang ◽  
Fang Tian ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Gene Polymorphisms ◽  
Renin Angiotensin System ◽  
Binary Logistic Regression ◽  
Albumin Excretion Rate ◽  
Chinese Patients ◽  
Significant Difference ◽  
Agt Gene

Aims: This study aims to investigate the association between renin-angiotensin system gene polymorphism and diabetic retinopathy (DR) in Chinese patients with type 2 diabetes. Methods: We consecutively included 1491 patients for the assessment of ACE I/D and AGT M/T gene polymorphisms in 345 DR cases and 1146 patients without retinopathy (DNR). Albuminuria was defined by urine albumin creatinine ratio and albumin excretion rate. Results: Compared with the NDR patients, the DR cases displayed a higher proportion of diabetic nephropathy (32.68% vs. 6.52%, χ2 = 150.713, p < 0.001). The DR cases and DNR individuals did not differ in the frequency of genotypes and alleles of ACE I/D and AGT M/T (all p > 0.05). Intriguingly, DR patients with obesity showed higher frequency of DD (χ2 = 4.181, p = 0.041), but no significant difference exists in the other stratified BMI and hypertension analyses (all p > 0.05). Binary logistic regression displays that the association of the ACE and AGT gene polymorphisms in DR patients is not significant after adjusting for confounding covariates in all the comparisons. Conclusions: The ACE and AGT gene polymorphisms are not associated with the progress of diabetes developing into retinopathy in Chinese patients with type 2 diabetes. However, more investigations are needed to further prove the association.

scholarly journals Incidence of Proliferative Diabetic Retinopathy and Other Neovascular Sequelae at 5 Years Following Diagnosis of Type 2 Diabetes

2021 ◽  
Author(s):  
William S. Gange ◽  
Khristina Lung ◽  
Jennifer Lopez ◽  
Benjamin Y. Xu ◽  
Seth A. Seabury ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Proliferative Diabetic Retinopathy ◽  
Neovascular Glaucoma ◽  
Initial Diagnosis ◽  
Age At Diagnosis ◽  
Insured Patients ◽  
Diagnosis Age

<b>Objective:</b> To determine the incidence and risk factors for developing proliferative diabetic retinopathy (PDR), tractional retinal detachment (TRD), and neovascular glaucoma (NVG) at 5 years after initial diagnosis of type 2 diabetes. <p><b>Research Design and Methods: </b>Insured patients age 18 or older with newly-diagnosed type 2 diabetes and 5 years of continuous enrollment were identified from a nationwide commercial claims database containing data from 2007-2015.<b> </b>The<b> </b>incidences of PDR, TRD, and NVG were computed at 5 years following index diagnosis of type 2 diabetes.<b> </b>Associations between these outcomes and demographic, socioeconomic, and medical factors were tested with multivariable logistic regression.</p> <p><b>Results:</b> At 5 years following initial diagnosis of type 2 diabetes, 1.74% (1,249/71,817) of patients had developed PDR. Additionally, 0.25% of patients had developed TRD, and 0.14% of patients had developed NVG. Insulin use (OR 3.59, 95% CI 3.16-4.08), maximum HbA1c >9% or 75mmol/mol (OR 2.10, 95% CI 1.54-2.69), renal disease (OR 2.68, 95% CI 2.09-3.42), peripheral circulatory disorders (OR 1.88, 95% CI 1.25-2.83), neurological disease (OR 1.62, 95% CI 1.24-2.11), and older age at diagnosis (age 65-74, OR 1.62, 1.28-2.03) were identified as risk factors for development of PDR at 5 years. Young age at diagnosis (age 18-34, OR 0.46, 95% CI 0.29-0.74), Medicare insurance (OR 0.60, 95% CI 0.70-0.76), morbid obesity (OR 0.72, 95% CI 0.59-0.87), and smoking (OR 0.84, 95% CI 0.70-1.00) were identified as protective factors. </p> <p><b>Conclusions:</b> A subset of patients with type 2 diabetes develop PDR and other neovascular sequelae within the first 5 years following diagnosis with type 2 diabetes. These patients may benefit from increased efforts for screening and early intervention.</p>

scholarly journals Prevalence and associated risk factors of diabetic retinopathy and macular oedema in patients recently diagnosed with type 2 diabetes

2020 ◽  
Vol 5 (1) ◽  
pp. e000304
Author(s):  
Enrique O Graue-Hernandez ◽  
David Rivera-De-La-Parra ◽  
Sergio Hernandez-Jimenez ◽  
Carlos A Aguilar-Salinas ◽  
David Kershenobich-Stalnikowitz ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Plasma Glucose ◽  
Macular Oedema ◽  
Diabetic Macular Oedema ◽  
Diabetes Duration ◽  
Haemoglobin A1c ◽  
Associated Risk Factors

ObjectiveTo determine the prevalence of diabetic retinopathy (DR) and diabetic macular oedema (DME) and their associated risk factors in patients recently diagnosed with type 2 diabetes.Methods and analysisWe carried out a cross-sectional study from April 2014 to August 2017. We included patients aged ≥18 years. Diabetes was defined as fasting plasma glucose of >7.8 mmol/L or 2-hour postload plasma glucose of >11.1 mmol/L. Non-mydriatic fundus examination with a digital-fundus camera was performed. Three images centred in the macula, optic disc and temporal to the macula were obtained and graded according to the Scottish Scale Classification of Diabetic Retinopathy.Results1232 patients (mean age 51.5 years) with a diabetes duration of 0–5 years were examined. Age-adjusted and sex-adjusted prevalence of DR and DME was 17.4% (95% CI 15.3% to 19.6%) and 6.6% (95% CI 5.4% to 8.2%), respectively. DR was associated with diabetes duration (OR per year=1.20, p<0.001), haemoglobin A1c (HbA1c) from 7.0 to 8.9 (OR=2.19, p<0.001), HbA1c≥9 (OR=2.98, p<0.001) and systolic blood pressure (SBP) (OR=1.16 per 5 mm Hg, p<0.001). DME was associated with diabetes duration (OR per year=1.26, p<0.01), HbA1c from 7.0 to 8.9 (OR=2.26, p<0.05), HbA1c≥9 (OR=2.38, p<0.01), SBP (OR per mm Hg=1.15, p<0.001) and albuminuria (OR=2.45, p<0.01).ConclusionOur study contributes to the evidence of progressive increase in DR and DME risk in early stages of diabetes, supporting the urgent need for early screening.

scholarly journals Incidence of Proliferative Diabetic Retinopathy and Other Neovascular Sequelae at 5 Years Following Diagnosis of Type 2 Diabetes

2021 ◽  
Author(s):  
William S. Gange ◽  
Khristina Lung ◽  
Jennifer Lopez ◽  
Benjamin Y. Xu ◽  
Seth A. Seabury ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Proliferative Diabetic Retinopathy ◽  
Neovascular Glaucoma ◽  
Initial Diagnosis ◽  
Age At Diagnosis ◽  
Insured Patients ◽  
Diagnosis Age

<b>Objective:</b> To determine the incidence and risk factors for developing proliferative diabetic retinopathy (PDR), tractional retinal detachment (TRD), and neovascular glaucoma (NVG) at 5 years after initial diagnosis of type 2 diabetes. <p><b>Research Design and Methods: </b>Insured patients age 18 or older with newly-diagnosed type 2 diabetes and 5 years of continuous enrollment were identified from a nationwide commercial claims database containing data from 2007-2015.<b> </b>The<b> </b>incidences of PDR, TRD, and NVG were computed at 5 years following index diagnosis of type 2 diabetes.<b> </b>Associations between these outcomes and demographic, socioeconomic, and medical factors were tested with multivariable logistic regression.</p> <p><b>Results:</b> At 5 years following initial diagnosis of type 2 diabetes, 1.74% (1,249/71,817) of patients had developed PDR. Additionally, 0.25% of patients had developed TRD, and 0.14% of patients had developed NVG. Insulin use (OR 3.59, 95% CI 3.16-4.08), maximum HbA1c >9% or 75mmol/mol (OR 2.10, 95% CI 1.54-2.69), renal disease (OR 2.68, 95% CI 2.09-3.42), peripheral circulatory disorders (OR 1.88, 95% CI 1.25-2.83), neurological disease (OR 1.62, 95% CI 1.24-2.11), and older age at diagnosis (age 65-74, OR 1.62, 1.28-2.03) were identified as risk factors for development of PDR at 5 years. Young age at diagnosis (age 18-34, OR 0.46, 95% CI 0.29-0.74), Medicare insurance (OR 0.60, 95% CI 0.70-0.76), morbid obesity (OR 0.72, 95% CI 0.59-0.87), and smoking (OR 0.84, 95% CI 0.70-1.00) were identified as protective factors. </p> <p><b>Conclusions:</b> A subset of patients with type 2 diabetes develop PDR and other neovascular sequelae within the first 5 years following diagnosis with type 2 diabetes. These patients may benefit from increased efforts for screening and early intervention.</p>

scholarly journals Modern aproaches to diabetic macular edema diagnosticks

2020 ◽  
Vol 23 (3) ◽  
pp. 260-266
Author(s):  
A. V. Doga ◽  
P. L. Volodin ◽  
E. V. Ivanova ◽  
D. A. Buryakov ◽  
O. I. Nikitin ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Early Diagnosis ◽  
Macular Edema ◽  
Diabetic Macular Edema ◽  
Vision Loss ◽  
Diagnostic Methods ◽  
Diabetic Patients ◽  
Timely Treatment

Diabetic macular edema (DME) continues to be an important problem of modern ophthalmology and endocrinology. Therisk of edema is higher in patients with type 2 diabetes. Thus, this is the main cause of irreversible vision loss in these patients. DME is one of the prognostically unfavorable and difficult to treat manifestations of diabetic retinopathy. As themain cause of vision loss in diabetic patients, diabetic macular edema is often not diagnosed immediately, which causes difficulties in the treatment of pathology. Thus, early diagnosis and timely treatment of this disease is the key to successfully counteract the uncontrolled decline in the patients visual functions. In this article, the team of authors highlighted the possibilities of informative instrumental research methods available in the Arsenal of modern ophthalmological services. Based on the analysis of modern literature, the main principles of these diagnostic methods were indicated, their key capabilities and limitations compared to each other were highlighted. Knowledge of these characteristics is, in our opinion, an integral and most important tool in the Arsenal of a practicing ophthalmologist who supervises patients with this pathology.

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