Research

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13 pages, 1564 KiB

Open AccessArticle

The Association between Diabetic Retinopathy and Macular Degeneration: A Nationwide Population-Based Study

by Hsin-Ting Lin, Cai-Mei Zheng, Cheng-Hung Tsai, Ching-Long Chen, Yu-Ching Chou, Jing-Quan Zheng, Yuh-Feng Lin, Chia-Wei Lin, Yong-Chen Chen, Chien-An Sun and Jiann-Torng Chen

Biomedicines 2024, 12(4), 727; https://doi.org/10.3390/biomedicines12040727 - 25 Mar 2024

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Abstract

Objective: Age-related macular degeneration (AMD), particularly its exudative form, is a primary cause of vision impairment in older adults. As diabetes becomes increasingly prevalent in aging, it is crucial to explore the potential relationship between diabetic retinopathy (DR) and AMD. This study aimed [...] Read more.

Objective: Age-related macular degeneration (AMD), particularly its exudative form, is a primary cause of vision impairment in older adults. As diabetes becomes increasingly prevalent in aging, it is crucial to explore the potential relationship between diabetic retinopathy (DR) and AMD. This study aimed to assess the risk of developing overall, non-exudative, and exudative AMD in individuals with DR compared to those without retinopathy (non-DR) based on a nationwide population study in Taiwan. Methods: A retrospective cohort study was conducted using the Taiwan National Health Insurance Database (NHIRD) (2000–2013). A total of 3413 patients were placed in the study group (DR) and 13,652 in the control group (non-DR) for analysis. Kaplan–Meier analysis and the Cox proportional hazards model were used to calculate the hazard ratios (HRs) and adjusted hazard ratios (aHRs) for the development of AMD, adjusting for confounding factors, such as age, sex, and comorbid conditions. Results: Kaplan–Meier survival analysis indicated a significantly higher cumulative incidence of AMD in the DR group compared to the non-DR group (log-rank test, p < 0.001). Adjusted analyses revealed that individuals with DR faced a greater risk of overall AMD, with an aHR of 3.50 (95% CI = 3.10–3.95). For senile (unspecified) AMD, the aHR was 3.45 (95% CI = 3.04–3.92); for non-exudative senile AMD, it was 2.92 (95% CI = 2.08–4.09); and for exudative AMD, the aHR was 3.92 (95% CI = 2.51–6.14). Conclusion: DR is a significant risk factor for both overall, senile, exudative, and non-exudative AMD, even after adjusting for demographic and comorbid conditions. DR patients tend to have a higher prevalence of vascular comorbidities; however, our findings indicate that the ocular pathologies inherent to DR might have a more significant impact on the progression to AMD. Early detection and appropriate treatment of AMD is critically important among DR patients. Full article

(This article belongs to the Special Issue Molecular Research and Recent Advances in Diabetic Retinopathy)

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13 pages, 4542 KiB

Open AccessArticle

Beneficial Effect of Sirolimus-Pretreated Mesenchymal Stem Cell Implantation on Diabetic Retinopathy in Rats

by Nanyoung Kang, Ji Seung Jung, Jiyi Hwang, Sang-Eun Park, Myeongjee Kwon, Haerin Yoon, Jungyeon Yong, Heung-Myong Woo and Kyung-Mee Park

Biomedicines 2024, 12(2), 383; https://doi.org/10.3390/biomedicines12020383 - 07 Feb 2024

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Abstract

Background: Diabetic retinopathy (DR) is a vision-threatening complication that affects virtually all diabetic patients. Various treatments have been attempted, but they have many side effects and limitations. Alternatively, stem cell therapy is being actively researched, but it faces challenges due to a low [...] Read more.

Background: Diabetic retinopathy (DR) is a vision-threatening complication that affects virtually all diabetic patients. Various treatments have been attempted, but they have many side effects and limitations. Alternatively, stem cell therapy is being actively researched, but it faces challenges due to a low cell survival rate. In this study, stem cells were pretreated with sirolimus, which is known to promote cell differentiation and enhance the survival rate. Additionally, the subconjunctival route was employed to reduce complications following intravitreal injections. Methods: Diabetes mellitus was induced by intraperitoneal injection of 55 mg/kg of streptozotocin (STZ), and DR was confirmed at 10 weeks after DM induction through electroretinogram (ERG). The rats were divided into four groups: intact control group (INT), diabetic retinopathy group (DR), DR group with subconjunctival MSC injection (DR-MSC), and DR group with subconjunctival sirolimus-pretreated MSC injection (DR-MSC-S). The effects of transplantation were evaluated using ERG and histological examinations. Results: The ERG results showed that the DR-MSC-S group did not significantly differ from the INT in b-wave amplitude and exhibited significantly higher values than the DR-MSC and DR groups (p < 0.01). The flicker amplitude results showed that the DR-MSC and DR-MSC-S groups had significantly higher values than the DR group (p < 0.01). Histological examination revealed that the retinal layers were thinner in the DR-induced groups compared to the INT group, with the DR-MSC-S group showing the thickest retinal layers among them. Conclusions: Subconjunctival injection of sirolimus-pretreated MSCs can enhance retinal function and mitigate histological changes in the STZ-induced DR rat model. Full article

(This article belongs to the Special Issue Molecular Research and Recent Advances in Diabetic Retinopathy)

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14 pages, 2285 KiB

Open AccessArticle

Diagnostic Accuracy of Hand-Held Fundus Camera and Artificial Intelligence in Diabetic Retinopathy Screening

by Martina Tomić, Romano Vrabec, Đurđica Hendelja, Vilma Kolarić, Tomislav Bulum and Dario Rahelić

Biomedicines 2024, 12(1), 34; https://doi.org/10.3390/biomedicines12010034 - 22 Dec 2023

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Abstract

Our study aimed to assess the role of a hand-held fundus camera and artificial intelligence (AI)-based grading system in diabetic retinopathy (DR) screening and determine its diagnostic accuracy in detecting DR compared with clinical examination and a standard fundus camera. This cross-sectional instrument [...] Read more.

Our study aimed to assess the role of a hand-held fundus camera and artificial intelligence (AI)-based grading system in diabetic retinopathy (DR) screening and determine its diagnostic accuracy in detecting DR compared with clinical examination and a standard fundus camera. This cross-sectional instrument validation study, as a part of the International Diabetes Federation (IDF) Diabetic Retinopathy Screening Project, included 160 patients (320 eyes) with type 2 diabetes (T2DM). After the standard indirect slit-lamp fundoscopy, each patient first underwent fundus photography with a standard 45° camera VISUCAM Zeiss and then with a hand-held camera TANG (Shanghai Zhi Tang Health Technology Co., Ltd.). Two retina specialists independently graded the images taken with the standard camera, while the images taken with the hand-held camera were graded using the DeepDR system and an independent IDF ophthalmologist. The three screening methods did not differ in detecting moderate/severe nonproliferative and proliferative DR. The area under the curve, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, kappa (ĸ) agreement, diagnostic odds ratio, and diagnostic effectiveness for a hand-held camera compared to clinical examination were 0.921, 89.1%, 100%, 100%, 91.4%, infinity, 0.11, 0.86, 936.48, and 94.9%, while compared to the standard fundus camera were 0.883, 83.2%, 100%, 100%, 87.3%, infinity, 0.17, 0.78, 574.6, and 92.2%. The results of our study suggest that fundus photography with a hand-held camera and AI-based grading system is a short, simple, and accurate method for the screening and early detection of DR, comparable to clinical examination and fundus photography with a standard camera. Full article

(This article belongs to the Special Issue Molecular Research and Recent Advances in Diabetic Retinopathy)

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10 pages, 988 KiB

Open AccessArticle

SLC22A3 rs2048327 Polymorphism Is Associated with Diabetic Retinopathy in Caucasians with Type 2 Diabetes Mellitus

by Emin Grbić, Mojca Globočnik Petrovič, Ines Cilenšek and Danijel Petrovič

Biomedicines 2023, 11(8), 2303; https://doi.org/10.3390/biomedicines11082303 - 18 Aug 2023

Cited by 3 | Viewed by 1057

Abstract

The Solute Carrier Family 22 Member 3 (SLC22A3) is a high-capacity, low-affinity transporter for the neurotransmitters norepinephrine, epinephrine, dopamine, serotonin, and histamine. SLC22A3 plays important roles in interorgan and interorganism small-molecule communication, and also regulates local and overall homeostasis in the body. Our [...] Read more.

The Solute Carrier Family 22 Member 3 (SLC22A3) is a high-capacity, low-affinity transporter for the neurotransmitters norepinephrine, epinephrine, dopamine, serotonin, and histamine. SLC22A3 plays important roles in interorgan and interorganism small-molecule communication, and also regulates local and overall homeostasis in the body. Our aim was to investigate the association between the rs2048327 gene polymorphism and diabetic retinopathy (DR) in Slovenian patients with type 2 diabetes mellitus (T2DM). We also investigated SLC22A3 expression in the fibrovascular membranes (FVMs) of patients with proliferative DR (PDR). Our study involved 1555 unrelated Caucasians with T2DM with a defined ophthalmologic status: 577 of them with DR as the study group, and 978 without DR as the control group. The investigated polymorphisms were genotyped using the KASPar genotyping assay. The expression of SLC22A3 (organic cation transporter 3—OCT3) was examined via immunohistochemistry in human FVM from 16 patients with PDR. The C allele and CC genotype frequencies of the rs2048327 polymorphism were significantly higher in the study group compared to the controls. The logistic regression analysis showed that the carriers of the CC genotype in the recessive genetic models of this polymorphism have a 1.531-fold increase (95% CI 1.083–2.161) in the risk of developing DR. Patients with the C allele of rs2048327 compared to the homozygotes for the wild type T allele exhibited a higher density of SLC22A3 (OCT3)-positive cells (10.5 ± 4.5/mm² vs. 6.1 ± 2.7/mm², respectively; p < 0.001). We showed the association of the rs2048327 SLC22A3 gene polymorphism with DR in a Slovenian cohort with type 2 diabetes mellitus, indicating its possible role as a genetic risk factor for the development of this diabetic complication. Full article

(This article belongs to the Special Issue Molecular Research and Recent Advances in Diabetic Retinopathy)

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12 pages, 1485 KiB

Open AccessArticle

Spontaneous Neutrophil Extracellular Traps Release Are Inflammatory Markers Associated with Hyperglycemia and Renal Failure on Diabetic Retinopathy

by Fátima Sofía Magaña-Guerrero, José Eduardo Aguayo-Flores, Beatriz Buentello-Volante, Karla Zarco-Ávila, Paola Sánchez-Cisneros, Ilse Castro-Salas, Enya De la Torre-Galván, José Luis Rodríguez-Loaiza, Aida Jiménez-Corona and Yonathan Garfias

Biomedicines 2023, 11(7), 1791; https://doi.org/10.3390/biomedicines11071791 - 22 Jun 2023

Cited by 2 | Viewed by 1128

Abstract

Diabetic retinopathy (DR) is the major microvascular complication of diabetes and causes vitreous traction and intraretinal hemorrhages leading to retinal detachment and total blindness. The evolution of diabetes is related to exacerbating inflammation caused by hyperglycemia and activation of inflammatory cells. Neutrophils are [...] Read more.

Diabetic retinopathy (DR) is the major microvascular complication of diabetes and causes vitreous traction and intraretinal hemorrhages leading to retinal detachment and total blindness. The evolution of diabetes is related to exacerbating inflammation caused by hyperglycemia and activation of inflammatory cells. Neutrophils are cells able to release structures of extracellular DNA and proteolytic enzymes called extracellular traps (NETs), which are associated with the persistence of inflammation in chronic pathologies. The purpose of the study was to determine the usefulness of neutrophil traps as indicators of DR progression in patients with type 2 diabetes (T2DM). We performed a case–control study of seventy-four cases classified into five groups (non-proliferative DR, mild, moderate, severe, and proliferative) and fifteen healthy controls. We found correlations between NETs and a diagnostic time of T2DM (r = 0.42; p < 0.0001), fasting glucose (r = 0.29; p < 0.01), glycated hemoglobin (HbA1c) (r = 0.31; p < 0.01), estimated glomerular filtration rate (eGFR) (r = −0.29; p < 0.01), and plasma osmolarity (r = 0.25; p < 0.01). These results suggest that due to NETs being associated with clinical indicators, such as HbA1c and eGFR, and that NETs are also associated with DR, clinical indicators might be explained in part through an NET-mediated inflammation process. Full article

(This article belongs to the Special Issue Molecular Research and Recent Advances in Diabetic Retinopathy)

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16 pages, 596 KiB

Open AccessArticle

Relationship between Diabetic Nephropathy and Development of Diabetic Macular Edema in Addition to Diabetic Retinopathy

by Yukihisa Suzuki and Motohiro Kiyosawa

Biomedicines 2023, 11(5), 1502; https://doi.org/10.3390/biomedicines11051502 - 22 May 2023

Cited by 4 | Viewed by 1875

Abstract

This study aimed to examine the relationship between diabetic retinopathy (DR) and systemic factors. We evaluated 261 patients (143 men, 118 women, aged 70.1 ± 10.1 years) with type 2 diabetes. All participants underwent a fundus examination, fundus photography using spectral domain optical [...] Read more.

This study aimed to examine the relationship between diabetic retinopathy (DR) and systemic factors. We evaluated 261 patients (143 men, 118 women, aged 70.1 ± 10.1 years) with type 2 diabetes. All participants underwent a fundus examination, fundus photography using spectral domain optical coherence tomography (SD-OCT), and blood tests. For glycated hemoglobin (HbA1c) levels, the average and highest values in the past were used. We observed DR in 127 (70 men and 57 women) of 261 patients. Logistic regression analyses revealed a significant correlation between DR development and the duration of diabetes (OR = 2.40; 95% CI: 1.50), average HbA1c level (OR = 5.57; 95% CI: 1.27, 24.4), highest HbA1c level (OR = 2.46; 95% CI: 1.12, 5.38), and grade of diabetic nephropathy (DN) (OR = 6.23; 95% CI: 2.70, 14.4). Regression analyses revealed a significant correlation between the severity of DR and duration of diabetes (t = –6.66; 95% CI: 0.21, 0.39), average HbA1c level (t = 2.59; 95% CI: 0.14, 1.02), and severity of DN (t = 6.10; 95% CI: 0.49, 0.97). Logistic regression analyses revealed a significant correlation between diabetic macular edema (DME) development and DN grade (OR = 2.22; 95% CI: 1.33, 3.69). DN grade correlates with the development of DR and DME, and decreased renal function predicts the onset of DR. Full article

(This article belongs to the Special Issue Molecular Research and Recent Advances in Diabetic Retinopathy)

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11 pages, 494 KiB

Open AccessArticle

A Pilot Study of Implementing Diabetic Retinopathy Screening in the Oslo Region, Norway: Baseline Results

by Ellen Steffenssen Sauesund, Øystein Kalsnes Jørstad, Cathrine Brunborg, Morten Carstens Moe, Maja Gran Erke, Dag Sigurd Fosmark and Goran Petrovski

Biomedicines 2023, 11(4), 1222; https://doi.org/10.3390/biomedicines11041222 - 19 Apr 2023

Cited by 1 | Viewed by 1531

Abstract

Purpose: to gain insight into the baseline parameters of a population with diabetes mellitus (DM) included in a pilot diabetic retinopathy (DR) screening program at Oslo University Hospital (OUH), Norway. Methods: This was a cross-sectional study of a cohort of adult patients (≥18 [...] Read more.

Purpose: to gain insight into the baseline parameters of a population with diabetes mellitus (DM) included in a pilot diabetic retinopathy (DR) screening program at Oslo University Hospital (OUH), Norway. Methods: This was a cross-sectional study of a cohort of adult patients (≥18 years) with type 1 or 2 DM (T1D and T2D). We measured the best-corrected visual acuity (BCVA), blood pressure (BP), heart rate (HR), intraocular pressure (IOP), height and weight. We also collected HbA1c, total serum cholesterol and urine-albumin, -creatinine and -albumin-to-creatinine ratio (ACR), as well as socio-demographic parameters, medications and previous screening history. We obtained color fundus photographs, which were graded by two experienced ophthalmologists according to the International Clinical Disease Severity Scale for DR. Results: The study included 180 eyes of 90 patients: 12 patients (13.3%) had T1D and 78 (86.7%) had T2D. In the T1D group, 5 patients (41.7%) had no DR, and 7 (58.3%) had some degree of DR. In the T2D group, 60 patients (76.9%) had no DR, and 18 (23.1%) had some degree of DR. None of the patients had proliferative DR. Of the 43 patients not newly diagnosed (time of diagnosis > 5 years for T1D and >1 years for T2D), 37.5% of the T1D patients and 5.7% of the T2D patients had previously undergone regular screening. Univariate analyses found for the whole cohort significant associations between DR and age, HbA1c, urine albumin-to-creatinine ratio, body mass index (BMI) and duration of DM. For the T2D group alone, there were significant associations between DR and HbA1c, BMI, urine creatinine, urine albumin-to-creatinine ratio and duration of DM. The analysis also showed three times higher odds for DR in the T1D group than the T2D group. Conclusions: This study underscores the need for implementing a systematic DR screening program in the Oslo region, Norway, to better reach out to patients with DM and improve their screening adherence. Timely and proper treatment can prevent or mitigate vision loss and improve the prognosis. A considerable number of patients were referred from general practitioners for not being followed by an ophthalmologist.Among patients not newly diagnosed with DM, 62.8% had never had an eye exam, and the duration of DM for these patients was up to 18 years (median: 8 years). Full article

(This article belongs to the Special Issue Molecular Research and Recent Advances in Diabetic Retinopathy)

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Review

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17 pages, 958 KiB

Open AccessReview

Aldose Reductase as a Key Target in the Prevention and Treatment of Diabetic Retinopathy: A Comprehensive Review

by Alexandra-Ioana Dănilă, Laura Andreea Ghenciu, Emil Robert Stoicescu, Sorin Lucian Bolintineanu, Roxana Iacob, Mihai-Alexandru Săndesc and Alexandra Corina Faur

Biomedicines 2024, 12(4), 747; https://doi.org/10.3390/biomedicines12040747 - 27 Mar 2024

Viewed by 487

Abstract

The escalating global prevalence of diabetes mellitus (DM) over the past two decades has led to a persistent high incidence of diabetic retinopathy (DR), necessitating screening for early symptoms and proper treatment. Effective management of DR aims to decrease vision impairment by controlling [...] Read more.

The escalating global prevalence of diabetes mellitus (DM) over the past two decades has led to a persistent high incidence of diabetic retinopathy (DR), necessitating screening for early symptoms and proper treatment. Effective management of DR aims to decrease vision impairment by controlling modifiable risk factors including hypertension, obesity, and dyslipidemia. Moreover, systemic medications and plant-based therapy show promise in advancing DR treatment. One of the key mechanisms related to DR pathogenesis is the polyol pathway, through which aldose reductase (AR) catalyzes the conversion of glucose to sorbitol within various tissues, including the retina, lens, ciliary body and iris. Elevated glucose levels activate AR, leading to osmotic stress, advanced glycation end-product formation, and oxidative damage. This further implies chronic inflammation, vascular permeability, and angiogenesis. Our comprehensive narrative review describes the therapeutic potential of aldose reductase inhibitors in treating DR, where both synthetic and natural inhibitors have been studied in recent decades. Our synthesis aims to guide future research and clinical interventions in DR management. Full article

(This article belongs to the Special Issue Molecular Research and Recent Advances in Diabetic Retinopathy)

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23 pages, 734 KiB

Open AccessReview

The Impact of Modern Anti-Diabetic Treatment on Endothelial Progenitor Cells

by Velimir Altabas, Jelena Marinković Radošević, Lucija Špoljarec, Stella Uremović and Tomislav Bulum

Biomedicines 2023, 11(11), 3051; https://doi.org/10.3390/biomedicines11113051 - 14 Nov 2023

Cited by 1 | Viewed by 1117

Abstract

Diabetes is one of the leading chronic diseases globally with a significant impact on mortality. This condition is associated with chronic microvascular and macrovascular complications caused by vascular damage. Recently, endothelial progenitor cells (EPCs) raised interest due to their regenerative properties. EPCs are [...] Read more.

Diabetes is one of the leading chronic diseases globally with a significant impact on mortality. This condition is associated with chronic microvascular and macrovascular complications caused by vascular damage. Recently, endothelial progenitor cells (EPCs) raised interest due to their regenerative properties. EPCs are mononuclear cells that are derived from different tissues. Circulating EPCs contribute to regenerating the vessel’s intima and restoring vascular function. The ability of EPCs to repair vascular damage depends on their number and functionality. Diabetic patients have a decreased circulating EPC count and impaired EPC function. This may at least partially explain the increased risk of diabetic complications, including the increased cardiovascular risk in these patients. Recent studies have confirmed that many currently available drugs with proven cardiovascular benefits have beneficial effects on EPC count and function. Among these drugs are also medications used to treat different types of diabetes. This manuscript aims to critically review currently available evidence about the ways anti-diabetic treatment affects EPC biology and to provide a broader context considering cardiovascular complications. The therapies that will be discussed include lifestyle adjustments, metformin, sulphonylureas, gut glucosidase inhibitors, thiazolidinediones, dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor analogs, sodium-glucose transporter 2 inhibitors, and insulin. Full article

(This article belongs to the Special Issue Molecular Research and Recent Advances in Diabetic Retinopathy)

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21 pages, 2079 KiB

Open AccessReview

Advances and Perspectives in Relation to the Molecular Basis of Diabetic Retinopathy—A Review

by Michał Błaszkiewicz, Agata Walulik, Kamila Florek, Ignacy Górecki, Olga Sławatyniec and Krzysztof Gomułka

Biomedicines 2023, 11(11), 2951; https://doi.org/10.3390/biomedicines11112951 - 01 Nov 2023

Cited by 1 | Viewed by 1237

Abstract

Diabetes mellitus (DM) is a growing problem nowadays, and diabetic retinopathy (DR) is its predominant complication. Currently, DR diagnosis primarily relies on fundoscopic examination; however, novel biomarkers may facilitate that process and make it widely available. In this current review, we delve into [...] Read more.

Diabetes mellitus (DM) is a growing problem nowadays, and diabetic retinopathy (DR) is its predominant complication. Currently, DR diagnosis primarily relies on fundoscopic examination; however, novel biomarkers may facilitate that process and make it widely available. In this current review, we delve into the intricate roles of various factors and mechanisms in DR development, progression, prediction, and their association with therapeutic approaches linked to the underlying pathogenic pathways. Specifically, we focus on advanced glycation end products, vascular endothelial growth factor (VEGF), asymmetric dimethylarginine, endothelin-1, and the epigenetic regulation mediated by microRNAs (miRNAs) in the context of DR. Full article

(This article belongs to the Special Issue Molecular Research and Recent Advances in Diabetic Retinopathy)

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16 pages, 680 KiB

Open AccessReview

Suppressing Inflammation for the Treatment of Diabetic Retinopathy and Age-Related Macular Degeneration: Dazdotuftide as a Potential New Multitarget Therapeutic Candidate

by Brice Nguedia Vofo and Itay Chowers

Biomedicines 2023, 11(6), 1562; https://doi.org/10.3390/biomedicines11061562 - 27 May 2023

Cited by 2 | Viewed by 2305

Abstract

Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are major causes of blindness globally. The primary treatment option for DME and neovascular AMD (nAMD) is anti-vascular endothelial growth factor (VEGF) compounds, but this treatment modality often yields insufficient results, and monthly injections can [...] Read more.

Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are major causes of blindness globally. The primary treatment option for DME and neovascular AMD (nAMD) is anti-vascular endothelial growth factor (VEGF) compounds, but this treatment modality often yields insufficient results, and monthly injections can place a burden on the health system and patients. Although various inflammatory pathways and mediators have been recognized as key players in the development of DR and AMD, there are limited treatment options targeting these pathways. Molecular pathways that are interlinked, or triggers of multiple inflammatory pathways, could be promising targets for drug development. This review focuses on the role of inflammation in the pathogenesis of DME and AMD and presents current anti-inflammatory compounds, as well as a potential multitarget anti-inflammatory compound (dazdotuftide) that could be a candidate treatment option for the management of DME and AMD. Full article

(This article belongs to the Special Issue Molecular Research and Recent Advances in Diabetic Retinopathy)

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