Development Of Retinopathy Research Articles

Association between Glucose-lowering Treatments and Risk of Diabetic Retinopathy in People with Type 2 Diabetes: A Nationwide Cohort Study.

Glycaemic variability is possibly linked to the development of diabetic retinopathy, and newer second-line glucose-lowering treatments in type 2 diabetes might reduce glycaemic variability. This study aimed to investigate whether newer second-line glucose-lowering treatments are associated with an alternative risk of developing diabetic retinopathy in people with type 2 diabetes. A nationwide cohort of people with type 2 diabetes on second-line glucose-lowering treatment regimens in 2008-2018 was extracted from the Danish National Patient Registry. Adjusted time to diabetic retinopathy was estimated with a Cox Proportional Hazards model. The model was adjusted for age, sex, diabetes duration, alcohol abuse, treatment start year, education, income, history of late-diabetic complications, history of non-fatal major adverse cardiovascular events, history of chronic kidney disease, and history of hypoglycaemic episodes. Treatment regimens of metformin + basal insulin (HR: 3.15, 95% CI: 2.42-4.10) and metformin + glucagon-like peptide-1 receptor agonist (GLP-1-RA, HR: 1.46, 95% CI: 1.09-1.96) were associated with an increased risk of diabetic retinopathy compared with metformin + dipeptidyl peptidase-4 inhibitors (DPP-4i). Treatment with metformin + sodium-glucose cotransporter-2 inhibitor (SGLT2i, HR: 0.77, 95% CI: 0.28-2.11) was associated with the numerically lowest risk of diabetic retinopathy compared with all regimens investigated. Findings from this study indicate that basal insulin and GLP-1-RA are suboptimal second- line choices for people with type 2 diabetes at risk of developing diabetic retinopathy. However, many other considerations concerning the choice of second-line glucose-lowering treatment for type 2 diabetes patients should be taken into account.

Risk factors for diabetic retinopathy, diabetic macular edema, and sight-threatening diabetic retinopathy

ObjectiveTo identify the risk factors for the development of diabetic retinopathy (DR), diabetic macular edema (DME), and sight-threatening DR (STDR) based on a city-wide diabetes screening program. Research design and methodsDiabetic patients were prospectively recruited between June 2016 and December 2022. All patients underwent dilated fundus photography centered on the disc and macula or macular spectral domain optical coherence tomography (SD-OCT) scan. Complete medical history was documented. Systematic examination, blood analysis, and urinalysis were performed. Multivariate logistic regression analysis adjusting for age and sex was conducted. ResultsOut of 7274 diabetic patients, 6840 had gradable images, among which 3054 (42.0%) were graded as DR, 1153 (15.9%) as DME, and 1500 (20.6%) as STDR. The factors associated with DR, DME, and STDR included younger age (odds ratio [OR]: 0.96, 0.97, and 0.96 respectively), lower BMI (OR: 0.97, 0.95, and 0.95 respectively), longer duration of diabetes (OR: 1.07, 1.03, and 1.05 respectively) and positive of urinary albumin (OR: 2.22, 2.56, and 2.88 respectively). Other associated factors included elevated blood urea nitrogen (OR: 1.22, 1.28, and 1.27 respectively), higher LDL-cholesterol, lower blood hemoglobin (OR: 0.98, 0.98, and 0.98), insulin intake, presence of diabetic foot pathologies and diabetic peripheral neuropathy. We also identified novel risk factors, including high serum potassium (OR: 1.37, 1.46, and 1.55 respectively), high-serum sodium (OR: 1.02, 1.02, and 1.04 respectively). Better family income was a protective factor for DR, DME, and STDR. Alcohol consumption once a week was also identified as a protective factor for DR. ConclusionsSimilar risk factors for DR, DME, and STDR were found in this study. Our data also indicates high serum sodium, high serum potassium, low blood hemoglobin, and level of family income as novel associated factors for DR, DME, and STDR, which can help with DR monitoring and management.

Pregnancy and diabetic retinopathy

Background: An increase in the worldwide prevalence of diabetes, especially among younger populations, has led to a higher prevalence of pre-existing diabetes among pregnant women. The precise mechanisms underlying the development or progression of diabetic retinopathy (DR) during pregnancy are not entirely understood. This narrative review incorporates all available data to offer fresh insights into the pathogenesis and mechanisms of the pregnancy-induced development and/or progression of DR. Moreover, the author aims to offer clinical recommendations for DR both before conception and during pregnancy to appropriately counsel these susceptible patients. Methods: A literature search was performed using various combinations of the following keywords: diabetes, pregnancy, diabetic retinopathy, ocular, eye, retina, microangiopathy, mechanism, pathophysiology, hyperglycemia, hypoxia, neovascularization, growth factors, immune system, blood flow, and recommendations. The search was conducted using PubMed/MEDLINE, ISI Web of Science, Scopus, and Google Scholar, and only English articles published from January 1, 2020, to December 31, 2023, involving human participants, were considered. The International Diabetes Federation Diabetes Atlas website was searched for clinical recommendations. Results: Pregnancy-induced hyperglycemia, blood flow changes, growth factors, and the immune system play important roles in the development and progression of DR. Hyperglycemia leads to significant stress on the capillary endothelium through increased glucose flux via the polyol and hexosamine pathways, activation of protein kinase C, and increased formation of advanced glycation end-products. These pathways act in several ways that may lead to increased oxidative stress, inflammation, and vascular blockage. Thus, eye examinations are crucial before, during, and up to 12 months after pregnancy. Individuals with severe non-proliferative and proliferative DR should gradually decrease their blood glucose levels to near-normal levels over a period of 6 months before conception. Statins and medications inhibiting the renin–angiotensin system should be discontinued before pregnancy or at the initial antenatal visit if they are still being used. Retinal examinations should be performed shortly after conception and during the first trimester using tropicamide eye drops and digital imaging. Subsequent examinations should be scheduled based on DR severity at the initial examination. Conclusions: While the precise mechanism underlying the progression of DR during pregnancy remains uncertain, the available literature suggests that pregnancy-induced hyperglycemia, blood flow changes, growth factors, and the immune system play important roles in its development and progression. Pregnant women with diabetic eye manifestations benefit from the expertise of multidisciplinary teams comprising ophthalmologists, diabetologists, and gynecologists to improve both maternal and perinatal outcomes. Moreover, postpartum follow-up requires special attention.

Predictive role of systemic immune-inflammation index and neutrophil/lymphocyte ratio values in infants with retinopathy of prematurity

PurposeTo search the relationship between serum neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII) values with the development of retinopathy of prematurity (ROP) and the requirement for laser treatment.MethodsThis retrospective cohort study was carried out with 195 preterm infants between 2012 and 2023. The NLR, PLR, LMR, and SII values were calculated on both the first day and at the end of the first month after birth. The association between development of ROP and other risk factors were analyzed using univariate analysis and multivariate logistic regression analysis.ResultsOf patients, 92 infants were diagnosed with ROP. Laser treatment was administered to 36 infants. The postnatal first-day NLR and SII values were higher in infants with ROP than in infants without ROP (p < 0.001 for both). Postnatal first-month NLR, LMR, and SII values were higher in infants with ROP (p < 0.001, p = 0.007, and p < 0.001, respectively). In multivariate analyses, postnatal first-day NLR and first-month LMR values were regarded as independent risk factors for the development of ROP (OR:8.867 and 1.286, p = 0.002 and p = 0.009, respectively). In multivariate analyses performed for laser treatment requirement, postnatal first-month PLR and SII values were determined as independent risk factors (OR:0.951 and 1.011, respectively, p = 0.004 for both).ConclusionsPostnatal first-day NLR and first-month LMR values were determined as independent risk factors for the development of ROP. For the requirement of laser treatment, the postnatal first-month PLR and SII values were determined as independent risk factors.

Factors associated with development of retinopathy in patients with type 2 diabetes mellitus at onset and within three years after diagnosis

Objective To investigate the prevalence of diabetes retinopathy and evaluate the factors influencing its occurrence both at the onset of type 2 diabetes (T2D) and three years into its duration. Design Retrospective population-based study. Setting Data was retrieved from Regional Healthcare Information Platform in Region Halland 2016–2020. Subjects Patients 35-75 years old in Region Halland receiving first-time diabetes diagnosis according to ICD-code E11-14 in 2016–17. The total cohort consisted of 1659 patients. Main outcome measures The main outcome measure of the study was the occurrence of diabetes retinopathy at onset and within three years from the diabetes diagnosis. Multivariate logistic regression analysis was conducted for diabetes retinopathy at onset and within three years, adjusted for age, gender, comorbidities, levels of HbA1c, cholesterol, kidney functional and blood pressure. Results At onset, there were 12% with diabetes retinopathy and after three years, 32% of the patients had developed diabetes retinopathy. In the study cohort, 71 of patients who were examined with fundus photography within three years after onset, and 8% had had dietary recommendation without pharmacotherapy. High HbA1c levels, blood pressure values and impaired renal function already at onset were associated with development of diabetes retinopathy at onset and this association persisted after three years. The odds ratio for diabetes retinopathy was increased adjusted for HbA1c elevations, renal impairment, and increased blood pressure at index and when adjusted for these variables three years from index. Conclusion These findings indicate that the risk of developing diabetes retinopathy is present early on at onset and within the first three years of diabetes diagnosis. This highlights the importance of promptly regulating glucose- and blood-pressure levels and follow up kidney dysfunction to mitigate the risk of diabetes retinopathy.

The association between endometrial cancer and subsequent diabetic retinopathy severity: A retrospective nationwide study.

The endometrial cancer is a disorder with elevated oxidative stress. The high oxidative stress resulting from hyperglycemia can lead to diabetic retinopathy (DR) development which is a complication of type 2 diabetes mellitus. Accordingly, we aim to evaluate the potential relationship between the endometrial cancer and following DR development. A retrospective cohort study was conducted using the National Health Insurance Research Database (NHIRD) of Taiwan. Individuals diagnosed with endometrial cancer were matched to the non-endometrial cancer patients in a 1:4 ratio. The major outcomes are the presence of DR, diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) according to diagnostic codes. Cox proportional hazard regression was used to show the adjusted hazard ratio (aHR) with 95% confidence interval (CI) of major outcomes between groups. There were 99 (2.3%), 20 (0.5%), and 14 (0.3%) cases with DR, DME and PDR in the endometrial cancer group, respectively. Another 303 (1.8%), 35 (0.2%), and 27 (0.2%) with DR, DME and PDR were observed in the control group, respectively. The endometrial cancer group revealed a significantly higher incidence of DR compared with the control group (aHR 1.51, 95% CI 1.20-1.90, P < 0.001). The cumulative probability of DR was also higher in the endometrial cancer group than in the control group (P < 0.001). The relationship between endometrial cancer and DR was significantly higher in patients aged over 70 years (P = 0.008). In addition, a higher incidence of DR was found during the first 5 years after the endometrial cancer diagnosis (P < 0.001). The endometrial cancer correlates to a higher incidence of subsequent DR, especially within first 5 years of endometrial cancer diagnosis.

Ocular Effects of MEK Inhibitor Therapy: Literature Review, Clinical Presentation, and Best Practices for Mitigation.

MEK signaling pathway targeting has emerged as a valuable addition to the options available for the treatment of advanced cancers including melanoma and non-small cell lung cancer. Ophthalmologic monitoring of patients taking part in clinical trials of MEK inhibitors has shown that while ocular effects are common, generally emerging during the first days to weeks of treatment, the majority are either asymptomatic or have minimal visual impact and are benign, resolving without intervention or the need to reduce or stop MEK inhibitor therapy. However rare cases of serious, potentially vision-threatening ocular toxicities have been reported during MEK inhibitor therapy. There is currently no recommendation for routine ophthalmologic screening or monitoring of patients with advanced cancer who are initiating MEK inhibitor therapy. However, baseline ophthalmologic examination may be useful for all patients initiating MEK inhibitor therapy to allow the differentiation of preexisting pathology versus the development of MEK inhibitor-associated retinopathy in the event of the emergence of symptomatic ocular events. Regular ophthalmologic examination may be appropriate for patients at increased risk for ocular events, such as patients with a history of ocular inflammation, infection, or underlying macular/retinal disease. All patients reporting visual disturbance should be referred for prompt ophthalmologic review to determine the potential seriousness of any underlying abnormalities and whether there is a need for treatment modification or specific intervention. Understanding the potential consequences of ocular toxicities is of particular importance in the context of decision-making for the continuation of potentially life-prolonging medications such as MEK inhibitors.

Haplotype-based association study of TCF7L2 gene variants with the development of diabetic retinopathy in an Iranian population

ABSTRACT Background Diabetic retinopathy (DR) is recognized as one of the most prevalent complications of diabetes and a major cause of morbidity. Transcription factor 7-like 2 (TCF7L2), a pivotal component in the Wnt-signaling pathway, plays a significant role in β-cell development, blood-glucose homeostasis, cell survival, cell migration, and cell proliferation. Thus, this study aimed to assess the association between TCF7L2 variants (rs7903146, rs11196205, and rs12255372) with DR in a population-based association study. Materials and Methods DNA was extracted from whole blood of all subjects by salting-out procedure. Total 524 T2DM patients including 234 T2DM individuals without DR and 290 T2DM individuals with DR were genotyped by TaqMan assay technology. Clinical characteristics of subjects were conducted to evaluate the plausible association between TCF7L2 variants and DR with univariate linear regression analysis. Results Demographic analysis between case and control groups revealed significant differences in FBS, HbA1c, lipidemia, heart disease, and family history of T2DM (p < 0.05). No significant difference was observed in either genotypes distribution or allele frequency (p > 0.05) between T2DM individuals with and without DR in any models of inheritance. Genotype-phenotype association showed no significant association. Result of analysis indicated that HbAlc with adjusted OR of 1.8 (p < 0.0001) and first-degree relatives of family history with adjusted OR of 3.04 (p < 0.0001) were significantly associated with DR. Finally, haplotype analysis showed no noticeable association. Conclusion In conclusion, there was no significant genetic association between rs7903146, rs11196205, and rs12255372 with DR among T2DM Iranians; however, these variants may play unknown roles in other populations.

TCERG1L hypermethylation is a risk factor of diabetic retinopathy in Chinese children with type 1 diabetes.

To identify the differential methylation sites (DMS) and their according genes associated with diabetic retinopathy (DR) development in type 1 diabetes (T1DM) children. This study consists of two surveys. A total of 40 T1DM children was included in the first survey. Because no participant has DR, retina thinning was used as a surrogate indicator for DR. The lowest 25% participants with the thinnest macular retinal thickness were included into the case group, and the others were controls. The DNA methylation status was assessed by the Illumina methylation 850K array BeadChip assay, and compared between the case and control groups. Four DMS with a potential role in diabetes were identified. The second survey included 27 T1DM children, among which four had DR. The methylation patterns of the four DMS identified by 850K were compared between participants with and without DR by pyrosequencing. In the first survey, the 850K array revealed 751 sites significantly and differentially methylated in the case group comparing with the controls (|Δβ|>0.1 and Adj.P<0.05), and 328 of these were identified with a significance of Adj.P<0.01. Among these, 319 CpG sites were hypermethylated and 432 were hypomethylated in the case group relative to the controls. Pyrosequencing revealed that the transcription elongation regulator 1 like (TCERG1L, cg07684215) gene was hypermethylated in the four T1DM children with DR (P=0.018), which was consistent with the result from the first survey. The methylation status of the other three DMS (cg26389052, cg25192647, and cg05413694) showed no difference (all P>0.05) between participants with and without DR. The hypermethylation of the TCERG1L gene is a risk factor for DR development in Chinese children with T1DM.

The Effect of Cardiometabolic Control and Malnutrition on the Prevalence and Prognosis of Diabetic Retinopathy in Type 2 Diabetes

Purpose:It is estimated that type 2 diabetes mellitus affects 530 million people worldwide and 10.5 per cent of these patients have diabetic retinopathy. This study aims to investigate the predictive value of cardiometabolic control, GGT and malnutrition-related inflammation markers for predicting Diabetic retinopathy prevalence and prognosis.&#x0D; Materials and Methods:Type 2 Diabetes Mellitus patients who were consecutively admitted to Internal and Ophthalmology outpatient clinics were included in this study. Clinical, haematological and biochemical data were recorded. Cut-off values of GGT, PNI, NRI and HALP scores were determined by receiver operator characteristic curve analysis. Univariate and multivariate analyses were performed to determine the association of all variables with Diabetic retinopathy. As a result, we evaluated which of these tests were predictive and prognostic for the development of diabetic retinopathy.&#x0D; Results:This study included 166 patients. Fasting blood glucose(p

TGF-β Signaling Pathways in the Development of Diabetic Retinopathy.

Diabetic retinopathy (DR), a prevalent complication of diabetes mellitus affecting a significant portion of the global population, has long been viewed primarily as a microvascular disorder. However, emerging evidence suggests that it should be redefined as a neurovascular disease with multifaceted pathogenesis rooted in oxidative stress and advanced glycation end products. The transforming growth factor-β (TGF-β) signaling family has emerged as a major contributor to DR pathogenesis due to its pivotal role in retinal vascular homeostasis, endothelial cell barrier function, and pericyte differentiation. However, the precise roles of TGF-β signaling in DR remain incompletely understood, with conflicting reports on its impact in different stages of the disease. Additionally, the BMP subfamily within the TGF-β superfamily introduces further complexity, with BMPs exhibiting both pro- and anti-angiogenic properties. Furthermore, TGF-β signaling extends beyond the vascular realm, encompassing immune regulation, neuronal survival, and maintenance. The intricate interactions between TGF-β and reactive oxygen species (ROS), non-coding RNAs, and inflammatory mediators have been implicated in the pathogenesis of DR. This review delves into the complex web of signaling pathways orchestrated by the TGF-β superfamily and their involvement in DR. A comprehensive understanding of these pathways may hold the key to developing targeted therapies to halt or mitigate the progression of DR and its devastating consequences.

Association of Oxygen Therapy Concentration and Duration with Retinopathy of Prematurity Incidence at Naresuan University Hospital

Objective: This study aimed to evaluate the association between the concentration and duration of oxygen therapy and the development and severity of retinopathy of prematurity (ROP). Additionally, it sought to examine the incidence of ROP at Naresuan University Hospital. Materials and Methods: A retrospective observational cohort study was conducted, utilizing data from the medical records of infants admitted to the Neonatal Intensive Care Unit at Naresuan University Hospital, Phitsanulok, Thailand, from January 1, 2016, to December 31, 2022. The duration of various oxygen therapies was recorded in hours, and the concentration of oxygen administered per hour was calculated as the average fraction of inspired oxygen for each infant. These data were subsequently analyzed using STATA version 11.0. Results: Out of 100 eligible infants, 27 (27%) were diagnosed with ROP at different severity levels: 17 infants (62.96%) with ROP stage 1, 9 infants (33.33%) with stage 2, and 1 infant (3.70%) with stage 3. There were no cases of Stage 4 or 5 ROP. The adjusted risk ratio revealed that infants receiving an average FiO2 of 0.3 or higher had a 1.64 times greater risk of developing ROP [95%CI 1.03-2.62], (P-value=0.038). Further analysis using mean difference regression showed a significant correlation between the duration of oxygen therapy and the severity of ROP. Conclusion: This study suggests that regulating oxygen therapy to not exceed an FiO2 of 0.3 and administering it strictly as needed may mitigate the risk of developing ROP and its severe manifestations.

USP48 deubiquitination stabilizes SLC1A5 to inhibit retinal pigment epithelium cell inflammation, oxidative stress and ferroptosis in the progression of diabetic retinopathy.

Diabetic retinopathy is one of the complications of diabetes mellitus. The aim of this study was to explore the effects of ubiquitin-specific protease 48 (USP48) and its underlying mechanisms in the development of diabetic retinopathy. CCK-8 assay, EdU assay, and flow cytometry were used to measure the proliferative ability and the apoptotic rate of ARPE-19 cells, respectively. ELISA kits were utilized to assess the levels of inflammatory cytokines. The levels of Fe2+, ROS and MDA were detected using the corresponding biochemical kits. The protein expression of USP48 and SLC1A5 was examined through western blot. The mRNA level of SLC1A5 was determined using RT-qPCR. The interaction relationship between USP48 and SLC1A5 was evaluated using Co-IP assay. High glucose (HG) treatment significantly inhibited cell proliferation and elevated cell apoptosis, inflammation, ferroptosis and oxidative stress in ARPE-19 cells. HG treatment-caused cell damage was hindered by USP48 or SLC1A5 overexpression in ARPE-19 cells. Fer-1 treatment improved HG-caused cell damage in ARPE-19 cells, which was blocked by USP48 knockdown. Moreover, USP48 knockdown decreased SLC1A5 expression. SLC1A5 downregulation reversed the improvement effects of USP48 upregulation on cell damage in HG-treated ARPE-19 cells. USP48 overexpression deubiquitinated SLC1A5 to elevate cell proliferation and suppress cell apoptosis, inflammation, ferroptosis and oxidative stress in HG-triggered ARPE-19 cells, thereby inhibiting the progression of diabetic retinopathy.

Melatonin and its bioisosteres as potential therapeutic agents for the treatment of retinopathy of prematurity.

We conducted a study on the impact of intraperitoneal injections of melatonin and its three bioisosteres (compounds 1-3) on the development of oxygen-induced retinopathy in newborn rats during a 21-day experiment. It was demonstrated that melatonin and its analogues 1-3 effectively reduce the total protein concentration in the vitreous body of rat pups, decrease concentration of VEGF-A, and lower the level of oxidative stress (as indicated by normalization of antioxidant activity in the vitreous body). Melatonin and its analogues 1-3 equally normalize the level of VEGF-A. Analogues 1 and 2 even exceed melatonin in their ability to reduce protein influx into the vitreous body. However, analogue 2 had no effect on antioxidant activity, while analogues 1 and 3 caused a significant increase in this parameter, with analogue 3 even slightly exceeding melatonin. Thus, it can be concluded that analogues 1-3 are comparable to melatonin and can be utilized as potential therapeutic agents for the treatment of retinopathy of prematurity.

Advanced Glycation End Products Upregulate CD40 in Human Retinal Endothelial and Müller Cells: Relevance to Diabetic Retinopathy.

CD40 induces pro-inflammatory responses in endothelial and Müller cells and is required for the development of diabetic retinopathy (DR). CD40 is upregulated in these cells in patients with DR. CD40 upregulation is a central feature of CD40-driven inflammatory disorders. What drives CD40 upregulation in the diabetic retina remains unknown. We examined the role of advanced glycation end products (AGEs) in CD40 upregulation in endothelial cells and Müller cells. Human endothelial cells and Müller cells were incubated with unmodified or methylglyoxal (MGO)-modified fibronectin. CD40 expression was assessed by flow cytometry. The expression of ICAM-1 and CCL2 was examined by flow cytometry or ELISA after stimulation with CD154 (CD40 ligand). The expression of carboxymethyl lysine (CML), fibronectin, and laminin as well as CD40 in endothelial and Müller cells from patients with DR was examined by confocal microscopy. Fibronectin modified by MGO upregulated CD40 in endothelial and Müller cells. CD40 upregulation was functionally relevant. MGO-modified fibronectin enhanced CD154-driven upregulation of ICAM-1 and CCL2 in endothelial and Müller cells. Increased CD40 expression in endothelial and Müller cells from patients with DR was associated with increased CML expression in fibronectin and laminin. These findings identify AGEs as inducers of CD40 upregulation in endothelial and Müller cells and enhancers of CD40-dependent pro-inflammatory responses. CD40 upregulation in these cells is associated with higher CML expression in fibronectin and laminin in patients with DR. This study revealed that CD40 and AGEs, two important drivers of DR, are interconnected.

Prevalence of Diabetic Retinopathy in Diabetic Subjects Visiting Diabetic Centers of Lahore, Pakistan

One of the chronic illnesses with the highest rate of growth in the globe and a major contributor to acquired visual loss is diabetes mellitus (DM). Globally, diabetic retinopathy (DR), a particular microvascular consequence of DM, continues to be the primary cause of acquired visual loss. Objective: To ascertain the percentage prevalence of diabetic retinopathy in diabetic subjects and the relationship between diabetic retinopathy and potential risk factors. Methods: This study was conducted at Services Hospital, Lahore. The time duration of study was from November 2018 to June 2019. The patients were asked to fill a designed questionnaire which contained questions regarding patient’s demographic data, habits and history about the disease. Results: A total of 1000 diabetic patients were enrolled and among them 511 (51.1%) had diabetic retinopathy. Among 369 males, 173 (46.9%) males had diabetic retinopathy and among 631 females, 338 (53.6%) females had diabetic retinopathy. The mean age of studied population was 53.77±0.35 years. Logistic regression model indicated that age (years), gender, systolic blood pressure (mmHg), diastolic blood pressure (mmHg), HbA1c level (mmol/L), span of diabetes (years), family history of diabetes, sedentary lifestyle were the risk factors for incidence of diabetic retinopathy in this study. Conclusions: The occurrence of DR is high in the studied population. Age (years), span of diabetes (years), HbA1c level (mmol/L) and not doing exercise were seen to be exhibiting more important role towards the development of diabetic retinopathy.

Deep-VEGF: deep stacked ensemble model for prediction of vascular endothelial growth factor by concatenating gated recurrent unit with two-dimensional convolutional neural network

Vascular endothelial growth factor (VEGF) is involved in the development and progression of various diseases, including cancer, diabetic retinopathy, macular degeneration and arthritis. Understanding the role of VEGF in various disorders has led to the development of effective treatments, including anti-VEGF drugs, which have significantly improved therapeutic methods. Accurate VEGF identification is critical, yet experimental identification is expensive and time-consuming. This study presents Deep-VEGF, a novel computational model for VEGF prediction based on deep-stacked ensemble learning. We formulated two datasets using primary sequences. A novel feature descriptor named K-Space Tri Slicing-Bigram position-specific scoring metrix (KSTS-BPSSM) is constructed to extract numerical features from primary sequences. The model training is performed by deep learning techniques, including gated recurrent unit (GRU), generative adversarial network (GAN) and convolutional neural network (CNN). The GRU and CNN are ensembled using stacking learning approach. KSTS-BPSSM-based ensemble model secured the most accurate predictive outcomes, surpassing other competitive predictors across both training and testing datasets. This demonstrates the potential of leveraging deep learning for accurate VEGF prediction as a powerful tool to accelerate research, streamline drug discovery and uncover novel therapeutic targets. This insightful approach holds promise for expanding our knowledge of VEGF's role in health and disease. Communicated by Ramaswamy H. Sarma

Vasoactive peptides as biomarkers for the prediction of retinopathy of prematurity

BackgroundRetinopathy of prematurity (ROP) is a major complication in preterm infants. We assessed if plasma levels of midregional pro-atrial natriuretic peptide (MR-proANP) and C-terminal pro-endothelin-1 (CT-proET1) serve as early markers for subsequent ROP development in preterm infants <32 weeks gestation.MethodsProspective, two-centre, observational cohort study. MR-proANP and CT-proET1 were measured on day seven of life. Associations with ROP ≥ stage II were investigated by univariable and multivariable logistic regression models.ResultsWe included 224 infants born at median (IQR) 29.6 (27.1–30.8) weeks gestation and birth weight of 1160 (860–1435) g. Nineteen patients developed ROP ≥ stage II. MR-proANP and CT-proET1 levels were higher in these infants (median (IQR) 864 (659–1564) pmol/L and 348 (300–382) pmol/L, respectively) compared to infants without ROP (median (IQR) 299 (210–502) pmol/L and 196 (156–268) pmol/L, respectively; both P < 0.001). MR-proANP and CT-proET1 levels were significantly associated with ROP ≥ stage II in univariable logistic regression models and after adjusting for co-factors, including gestational age and birth weight z-score.ConclusionsMR-proANP and CT-proET1 measured on day seven of life are strongly associated with ROP ≥ stage II in very preterm infants and might improve early prediction of ROP in the future.ImpactPlasma levels of midregional pro-atrial natriuretic peptide and C-terminal pro-endothelin-1 measured on day seven of life in very preterm infants show a strong association with development of retinopathy of prematurity ≥ stage II.Both biomarkers have the potential to improve early prediction of retinopathy of prematurity.Vasoactive peptides might allow to reduce the proportion of screened infants substantially.

Association of Diabetic Retinopathy and Sleep Quality

Sleep disorders are more common in diabetes mellitus (DM) cases rather than normal ones. In addition, this condition could be associated with diabetic retinopathy (DR) development with more inflammatory indices in circulation. In the present study, we have evaluated the association between DR and sleep quality. This cross-sectional study is a part of the second phase of the study of the elderly cohort of Amirkola City, which was conducted in 2015-2016 on all people aged 60 and higher. Of all diabetic cases, 44 cases had retinopathy and were selected as the case group. To compare two control groups, 135 diabetic patients without retinopathy and 135 people without diabetes were randomly selected. The presence and type of retinopathy were determined based on an eye physical examination by an ophthalmologist. In addition, sleep quality was evaluated based on the Pittsburgh Questionnaire. The obtained data were analyzed by ANOVA, t-test, and linear regression tests. In the present study, there was a significant difference in the score of the Pittsburgh questionnaire between people with DR (45.5±68.2) compared to diabetic people without retinopathy (76.5±48.2) and people without diabetes (95.4±36.2) (P=0.470), but diabetic people without retinopathy had significantly worse sleep quality than people without diabetes (P=0.019). Also, sleep quality in women with DR was worse than in men (P=014). In the linear regression analysis, it was observed that age, gender, diabetes, and history of depression significantly affect the sleep quality of the evaluated cases (P&lt;0.05 for all). According to the results of the present study, DR does not negatively influence the quality of sleep, and DR is not related to sleep disorders.

The serum thioredoxin-1 levels are not associated with bronchopulmonary dysplasia and retinopathy of prematurity

BackgroundWe hypothesized that the serum TRX-1 in extremely preterm infants (EPIs) after birth was associated with the development of severe bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP).MethodsThis single-centered retrospective study enrolled EPIs treated at our institution. Serum TRX-1 concentrations of the residual samples taken on admission, day 10–20 of life, and 36–40 weeks of postmenstrual age (PMA) were measured with an enzyme-linked immunosorbent assay.ResultsThe serum TRX-1 levels on admission were not different between the severe BPD (n = 46) and non-severe BPD groups (n = 67): [median (interquartile range) 147 (73.0–231) vs. 164 (80.5–248) ng/mL] (P = 0.57). These had no significant difference between the severe ROP (n = 47) and non-severe ROP groups (n = 66): [164 (71.3–237) vs. 150 (80.9–250) ng/mL] (P = 0.93). The TRX-1 levels at 10–20 days of life and 36–40 weeks of PMA also had no association with the development of severe BPD and ROP.ConclusionThe serum TRX-1 levels after birth are not predictive of severe BPD and ROP.ImpactSerum thioredoxin-1 levels in extremely preterm infants on the day of birth are lower than those in term or near-term infants hospitalized for transient tachypnea of the newborn.In extremely preterm infants, the serum thioredoxin-1 levels on the day of birth, at 10–20 days of life, and at postmenstrual age of 36–40 weeks were not associated with severe bronchopulmonary dysplasia and retinopathy of prematurity.The thioredoxin system is under development in extremely preterm infants; however, the serum thioredoxin-1 level is not predictive for severe bronchopulmonary dysplasia and retinopathy of prematurity.