Diabetic Retinopathy Subjects Research Articles

Serum Total Bilirubin and Oxidative Stress Status in Diabetic Retinopathy – A Hospital-Based Observational Study

Diabetic retinopathy (DR) is one of the common microvascular complications of Type 2 Diabetes Mellitus (T2DM). As an antioxidant, the serum total bilirubin is associated with vaso-occlusive disorders. Oxidative stress parameters such as Erythrocyte Glutathione (GSH) as an antioxidant and Malondialdehyde (MDA) as an oxidant are critical in the pathogenesis of diabetic complications. This study aimed to explore the possibilities of the endogenous protective role of serum total bilirubin on the retinal vasculature in DR patients by estimating and correlating the levels of serum total bilirubin, GSH, and MDA in DR cases. In this hospital-based case-control study, 288 participants were selected from R.L. Jalappa Hospital and Research Centre, Kolar, divided into three groups with 96 subjects per group. Group I: Controls, Group II: T2DM, and Group III: DR subjects. The fasting blood sugar, glycated hemoglobin, liver function test, and lipid profiles were estimated by standard methods. Oxidative stress parameters viz, GSH and MDA were assayed by chromogen 5,5'- di thiobis 2-nitrobenzoic acid (DTNB) and thiobarbituric acid reactive substances (TBARS) methods, respectively. The prevalence of DR was significantly lower among subjects with the highest bilirubin quartile than those with the lowest. There was a significant mean difference with p<0.001 between the groups for total bilirubin, FBS, HbA1c, GGT, TC, TG, LDL, GSH, and MDA. A Negative correlation of serum total bilirubin with FBS (r = - 0.375), HbA1c (r = -0.351), and MDA(r=-0.323), and a positive correlation with GSH (r = 0.335) was observed in DR group with a significant p-value. T2DM subjects with higher levels of bilirubin within biological reference intervals were less likely to develop retinopathy. The severity of DR was inversely proportional to the total bilirubin levels. Therefore, serum total bilirubin levels could be a biomarker to predict the risk of developing retinopathy in people with T2DM.

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.

Study of Foveal Avascular Zone Growth in Individuals With Mild Diabetic Retinopathy by Optical Coherence Tomography.

The purpose of this study was to investigate the association between foveal vessels and retinal thickness in individuals with diabetic retinopathy (DR) and control subjects, and to reveal foveal avascular zone (FAZ) growth in early individuals with DR. The regions with a thickness less than 60µm were marked from the intima thickness maps and named FAZThic. The avascular zones extracted from the deep vascular plexus were designated as FAZAngi. The boundary of the two FAZ forms a ring region, which we called FAZRing. The FAZ growth rate was defined as the ratio of the FAZRing area to the FAZThic area. Thirty healthy controls and 30 individuals with mild nonproliferative DR were recruited for this study. The FAZThic area in individuals with mild DR and control subjects showed similar distribution. The FAZAngi area in individuals with mild DR are higher than that in control subjects on the whole, but there was no significant difference (P > 0.05). The FAZRing area in individuals with mild DR was significantly higher than that in control subjects (P < 0.001). However, there is still a small amount of overlap data between the two groups. For the FAZ growth rate, the individuals with mild DR were also significantly larger than the control subjects (P < 0.001). But there were no overlapping data between the two groups. The growth of FAZ in individuals with mild DR can be inferred by comparing FAZAngi with FAZThic. This method minimizes the impact of individual variations and helps researchers to understand the progression mechanism of DR more deeply.

25-LB: Oral APX3330 Reduces the DRSS Worsening after 24-weeks of Daily Treatment—Efficacy and Safety Results of the ZETA-1 Phase 2 Trial in Diabetic Retinopathy

APX3330 is an oral, novel, small-molecule inhibitor of Ref-1, in diabetic retinopathy (DR) patients. ZETA-1 was a multi-center, placebo-controlled, double-masked Phase 2 trial. Subjects were randomized 1:1 to receive APX3330 (total 600 mg/day) or placebo BID for 24 weeks. Eligible subjects had non-proliferative DR (NPDR) or mild proliferative DR, corresponding to DR severity scale (DRSS) scores of 47, 53, or 61 as confirmed by the Duke reading center. The primary efficacy endpoint was the % of subjects with ≥ 2-step DRSS improvement in the study eye at week 24 compared to baseline. Several key pre-specified endpoints were evaluated. Results: ZETA-1 trial enrolled 103 DR subjects with 90% having NPDR with a baseline DRSS of 47 or 53. The primary endpoint was not met with 8% of study eyes showing ≥ 2-step DRSS improvement in each treatment group. Consistent with its mechanism of action of bringing VEGF and inflammation to physiologic levels, APX3330 demonstrated a statistically significant reduction in binocular ≥ 3-step worsening after 24 weeks, with 16% of placebo subjects worsening compared to 0% of APX3330 subjects (p=0.04). 19% of placebo subjects lost ≥5 BCVA letters compared to 5% of APX3330 subjects (p=0.07). AEs that occurred in ≥5% of subjects were pruritis, rash, and worsening of DR or DME in the placebo group. No subjects withdrew due to rash or pruritis. Disclosure V. H. Gonzalez: Consultant; Alimera, Bausch + Lomb, Research Support; Adverum Biotechnologies, AbbVie Inc., Apellis, Genentech, Inc., IQVIA Inc., Iveric Bio, Regeneron. P. K. Kaiser: Consultant; Ocuphire, AbbVie Inc., Bausch + Lomb, Bayer Inc., Regeneron, Ocular Therapeutix, Novartis, REGENXBIO Inc. D. S. Boyer: Advisory Panel; 3Boehringer Ingelheim Canada Ltd. /Ltée, AbbVie Inc., Adverum Biotechnologies, Alexion Pharmaceuticals, Inc., Alkahest, Allergan, Amgen Inc., Apellis, Bausch + Lomb, Chengdu Pharmaceuticals, F. Hoffmann-La Roche Limited, Genentech, Inc., Iveric Bio, Gyroscope, Janssen Pharmaceuticals, Inc., Kodiak Pharmaceuticals, NGM Biopharmaceuticals, Oxurion, Novartis, ocuphire, Roche Pharmaceuticals, REGENXBIO Inc., Other Relationship; 4D Pharma PLC. M. G. Brigell: Consultant; Ocuphire Pharma, ONL Therapeutics. D. Su: None. R. Patel: Employee; Ocuphire Pharma. B. Withers: Employee; Ocuphire. M. Kelley: None. L. Haddad: None. M. Sooch: Board Member; Ocuphire Pharma, Employee; Ocuphire Pharma, Stock/Shareholder; Ocuphire Pharma. J. S. Pepose: Consultant; Acufocus, Bausch + Lomb, Brim Biotechnology, Johnson &amp; Johnson Medical Devices Companies, Kala Pharmaceuticals, Mimetogen, Ocuphire Pharma, OKYO Pharma, Stuart Therapeutics, Thea Pharma.

Fluorescein videoangiography data analysis protocol for mapping retinal vascular permeability in humans.

Fluorescein video angiographies (FVAs) are a diagnostic tool for eye diseases, such as diabetic retinopathy (DR). Currently, kinetic tracer model methods based on indicator-dilutions theory use FVAs to extract biomarkers (e.g., volumetric blood flow and retinal vascular permeability) via pixel mapping using two-step non-linear least square fitting. Prior to biomarker extraction, the FVAs must attain optimal quality. The objective of this research is to create a program to remove all frames experiencing signal drops (causes include blinking, squinting, and head movement). 15 FVAs (6 healthy control subjects, 6 diabetes mellitus no DR (DMnoDR) subjects, and 3 mild non-proliferative DR (NPDR) subjects) were analyzed for low quality frames. The average signal of each frame was analyzed as top, middle, and bottom thirds. The frame with maximum average signal up to the final frame of a created "Gold Standard" was compared with the raw AVI's frame with maximum average signal and subsequent frames. All frames before maximum average signal and any remaining frames were compared with the previous good-quality raw frame to determine if the frame of interest was of good quality. All remaining frames were subsequently re-evaluated and flagged if they had a local minimum prominence of 10% of the maximum average signal. The flagged frames', as well as former and subsequent frames', quality were subjectively determined. The AVI quality was subsequently tested via pre-DTKM processing and biomarker extraction via DTKM methods. Results displayed that the semi-automated frame removal process provides sufficient quality AVIs.

Flavoprotein fluorescence elevation is a marker of mitochondrial oxidative stress in patients with retinal disease.

Recent studies of glaucoma, age-related macular degeneration, and diabetic retinopathy have demonstrated that flavoprotein fluorescence (FPF) can be utilized non-invasively as an indicator of mitochondrial oxidative stress in the retina. However, a comprehensive assessment of the validity and reliability of FPF in differentiating between healthy and diseased eyes across multiple disease states is lacking. Here, we evaluate the sensitivity and specificity of FPF in discriminating between healthy and diseased eyes in four leading causes of visual impairment worldwide, one of which has not been previously evaluated using FPF. We also evaluate the association between FPF and visual acuity. A total of 88 eyes [21 eyes of 21 unaffected controls, 20 eyes from 20 retinal vein occlusion (RVO) patients, 20 eyes from 20 diabetic retinopathy (DR) patients, 17 eyes from 17 chronic exudative age-related macular degeneration (exudative AMD) patients, and 10 eyes from 10 central serous retinopathy (CSR) patients] were included in the present cross-sectional observational study. Eyes were imaged non-invasively using a specially configured fundus camera OcuMet Beacon® (OcuSciences, Ann Arbor, MI). The macula was illuminated using a narrow bandwidth blue light (455 - 470 nm) and fluorescence was recorded using a narrow notch filter to match the peak emission of flavoproteins from 520 to 540 nm. AUROC analysis was used to determine the sensitivity of FPF in discriminating between diseased eyes and healthy eyes. Nonparametric Kruskal-Wallis Tests with post-hoc Mann Whitney U tests with the Holm-Bonferroni correction were performed to assess differences in FPF intensity, FPF heterogeneity, and best corrected visual acuity (BCVA) between the five groups. Spearman rank correlation coefficients were calculated to assess the relationship between FPF and BCVA. AUROC analysis indicated that FPF intensity is highly sensitive for detecting disease, particularly for exudative AMD subjects (0.989; 95% CI = 0.963 - 1.000, p=3.0 x 107). A significant difference was detected between the FPF intensity, FPF heterogeneity, and BCVA in all four disease states compared to unaffected controls (Kruskal-Wallis Tests, p = 1.06 x 10-8, p = 0.002, p = 5.54 x 10-8, respectively). Compared to healthy controls, FPF intensity values were significantly higher in RVO, DR, exudative AMD, and CSR (p < 0.001, p < 0.001, p < 0.001, and p = 0.001, respectively). Spearman rank correlation coefficient between FPF intensity and BCVA was ρ = 0.595 (p = 9.62 x 10-10). Despite variations in structural retinal findings, FPF was found to be highly sensitive for detecting retinal disease. Significant FPF elevation were seen in all four disease states, with the exudative AMD patients exhibiting the highest FPF values compared to DR, CSR, and RVO subjects. This is consistent with the hypothesis that there is elevated oxidative stress in all of these conditions as previously demonstrated by blood studies. FPF intensity is moderately correlated with the late-in disease-marker BCVA, which suggests that the degree of FPF elevation can be used as a metabolic indicator of disease severity.

VEGF Genotype and Allele Frequency of Diabetes Mellitus and Diabetic retinopathy in Lahore, Pakistan

Diabetic retinopathy is characterized as basement membrane (BM) thickening, pericyte loss, endothelial cell (EC) dysfunction, microaneurysms, microvascular infarcts and neovascularization in a patient with diabetic retinopathy. Objectives: To determine the VEGF genotype and allele frequency of diabetes mellitus and diabetic retinopathy in Lahore, Pakistan. Methods: A total of 100 blood samples were taken including diabetes mellitus (50) and diabetic retinopathy patients (50). Diseased and control subjects were selected for blood sampling. Demographic and clinical characteristics was evaluated. The BMI, HbA1c and the blood pressure of both groups were also examined. The VEGF genotype and allele frequency of diabetes mellitus and diabetic retinopathy was done. The statistical analysis was done by chi-square test and SPSS to study significant differences in control and diabetic retinopathy subjects. Results: The normal estimation of DM group was 46.18 ± 1.23 years while of DR class was 52.86 ± 1.36 years. The mean value of BMI of DM group was 26.0±0.62 while of DR group was 26.57±0.70.&#x0D; DD genetic mutation was substantially higher in diabetic retinopathy bunch (p&lt;0.05) relative to the II gene mutation, the huge contrasts (p&lt;0.05) were seen in diabetic group. Conclusions: This study concluded that Vascular endothelial growth factor gene was detected in both group of diabetes. In retinopathy people with T2DM the substantial elevated VEGF DD genetic variation was seen relative to retinopathy people without diabetes.

Evaluation of Macular Thickness Changes after Uncomplicated Phacoemulsification Surgery in Healthy Subjects and Diabetic Patients without Retinopathy by Spectral Domain OCT.

To assess differences in the evolution of macular thickness after uncomplicated phacoemulsification surgery between non-diabetic subjects and patients with diabetes mellitus (DM) without diabetic retinopathy (DR), using Spectral Domain OCT (SD-OCT). We performed a unicentric prospective study including one hundred and thirty-one eyes of 70 patients divided into two groups-34 well-controlled DM patients without DR and 36 non-diabetic subjects-who underwent phacoemulsification for cataract surgery. Eyes that developed pseudophakic cystoid macular edema (PCME) were excluded from the study, leaving us with 64 patients. Macular thickness was analyzed using Cirrus HD-OCT (Macular Cube 512 × 128 protocol) preoperatively and on postoperative days 7, 30, 90, and 180. For cases with information available for both eyes, one eye was randomly selected for analysis. A total of 64 eyes from 64 patients were analyzed in this study. The mean value of HbA1c in the diabetic group was 7%. After uncomplicated cataract surgery, patients showed no increase of the foveal, parafoveal, and perifoveal retinal thickness on postoperative day 7. However, thickness values increased on days 30, 90, and 180 after surgery in both groups, and peak at 90 days. There was no difference in macular thickness before or after surgery between DM and non-diabetic patients (p = 0.540). Macular thickness increases up to 6 months after uncomplicated cataract surgery in both DM patients without DR and non-diabetic subjects, with no differences between increases in both groups.

Choroidal vascularity profile in diabetic eyes using wide field optical coherence tomography.

To report the wide-field choroidal vascularity up to the mid-equator area in diabetic retinopathy (DR) subjects using wide-field optical coherence tomography (WF-OCT). Prospective, Cross-sectional study. Forty-seven eyes of 25 DR subjects. WF-OCT images (55 degrees) were obtained using Spectralis HRA + OCT (Heidelberg Engineering, Germany) in extremes of gazes in all quadrants and manual montages were created to obtain wide field images up to mid equator. A previously reported semi-automated algorithm was used to calculate choroidal vascularity profile (CVI). Regression analysis was performed to identify the factors influencing CVI. Forty-seven eyes from 25 patients were enrolled in the study. The mean age was 68.4 ± 10.6 years. The refractive error (spherical equivalent) ranged from -2.25 to +3.75 diopters. Most common DR grade among study subjects was moderate NPDR (29.41%) and 74.5% eyes had diabetic macular edema (DME). The mean CVI in the macular area (58.29 ± 3.63) was significantly lower than in any of the other fundus areas (all p ˂ 0.01). The maximum CVI was seen in the nasal region (66.60 ± 5.61), followed by temporal (65.69 ± 3.81), superior (65.01 ± 4.87), and inferior (63.80 ± 5.42). The vertical macular area had the least coefficient of variation (CV) of CVI (0.06) while the inferior quadrant had the highest CV (0.08). The current study describes the CVI profile on WF-OCT in DR eyes up to mid-equator. The significant increase of the CVI compared to healthy subjects and its significant regional variations introduce this novel quantitative parameter as a reliable biomarker of the diabetes-induced choroidal microangiopathy.

Effects of Hydroxychloroquine on Progression of Diabetic Retinopathy in Subjects with Rheumatoid Arthritis and Type 2 Diabetes Mellitus.

The study was conducted to investigate the effects of hydroxychloroquine, an anti-inflammatory drug, which was recently approved and used as an add on oral antidiabetic drug for uncontrolled Type 2 Diabetes Mellitus (DM) on an adequate dose of sulfonylurea and metformin on the progression of diabetic retinopathy (DR) in subjects with Rheumatoid Arthritis and Type 2 Diabetes Mellitus. The primary objective was to evaluate the effect of hydroxychloroquine on the onset of Diabetic Retinopathy (DR) and progression of the disease. Best-corrected visual acuity (BCVA) charts with 3 or more lines worsening of visual acuity and the development of clinically significant macular edema (CSME) were added as secondary objectives as described in the Early Treatment Diabetic Retinopathy Study (ETDRS). This retrospective analysis was done from medical records of all Rheumatoid Arthritis (RA) patients who also had T2DM and were treated with hydroxychloroquine (HCQ) 400 mg OD or 200 mg BID (N=65) and received ophthalmologic care at an endocrinology clinic in India up to a mean follow-up of 3.5±0.5 years and matched subjects taking any other disease-modifying antirheumatic drugs (DMARD) and pioglitazone (N=34). Baseline characteristics were similar in both the groups, with matched glycated haemoglobin (9.1 % and 9.2 % respectively, p=0.127). In both groups, over 3.5 years, HbA1c was reduced significantly. No new cases of DR were detected in the HCQ group, whereas 2 patients had developed DR in the pioglitazone group. At the base line visit, mild non-proliferative Diabetic Retinopathy (NPDR) was present in 18 eyes and 14 eyes in the HCQ and pioglitazone groups, respectively. Progression to moderate NPDR over 3.5 years occurred in 2 out of 18 (11 %) eyes in the HCQ group and 8 out of 14 (57 %) eyes in the pioglitazone group, respectively, representing a significant relative risk reduction (p=.001). No patients had progressed from mild NPDR to severe NPDR in the HCQ group, whereas 2 eyes had progressed from mild NPDR to severe NPDR in the pioglitazone group. None of the patients in either arm developed diabetic macular oedema. Progression of DR from mild to moderate NPDR or severe NPDR may be delayed by HCQ. Large scale randomised prospective clinical trial is required to establish the risk-benefit profiles of HCQ in T2DM.ct.

Highly Selective Purification of Plasma Extracellular Vesicles Using Titanium Dioxide Microparticles for Depicting the Metabolic Signatures of Diabetic Retinopathy.

Extracellular vesicle (EV) cargos with regular fluctuations hold the potential for providing chemical predictors toward clinical diagnosis and prognosis. A plasma sample is one of the most important sources of circulating EVs, yet the technical barrier and cost consumption in plasma-EV isolation still limit its application in disease diagnosis and biomarker discovery. Here, we introduced an easy-to-use strategy that allows selectively purifying small EVs (sEVs) from human plasma and detecting their metabolic alternations. Fe3O4@TiO2 microbeads with a rough island-shaped surface have proven the capability of performing efficient and reversible sEV capture owing to the phospholipid affinity, enhanced binding sites, and size-exclusion-like effect of the rough TiO2 shell. The proposed system can also shorten the separation procedure from hours to 20 min when compared with the ultracentrifugation method and yield approximately 108 sEV particles from 100 μL of plasma. Metabolome variations of sEVs among progressive diabetic retinopathy subjects were finally studied, observing a cluster of metabolites with elevated levels and suggesting potential roles of these sEV chemicals in diabetic retinopathy onset and progression. Such a scalable and flexible EV capture system can be seen as an effective analytical tool for facilitating plasma-based liquid biopsies.

Beneficial Actions of Essential Fatty Acids in Streptozotocin-Induced Type 1 Diabetes Mellitus.

The essential fatty acids (EFA), n3 alpha-linolenic acid (ALA), and n6 linoleic acid (LA) are of benefit in diabetes mellitus, but their mechanisms of action are unknown. We, therefore, examined the effects of EFAs on the metabolism, gut microbiota, and inflammatory and retinal histopathology indices in streptozotocin (STZ)-induced type 1 diabetes mellitus (T1DM) animals, and we assessed the levels of vitreal lipoxin A4 (LXA4)—derived from LA—in subjects with diabetic retinopathy (DR). STZ-induced T1DM rats received LA or ALA 100 μg/day intraperitoneally on alternate days for 21 days, and their blood glucose; lipid profile; plasma, hepatic, and retinal fatty acid profiles (by gas chromatography); retinal histology; activities of hepatic and retinal desaturases; and inflammatory markers (by qRT-PCR) were evaluated. Gut microbiota composition was assayed by 16S rDNA sequencing technology of the fecal samples, and their short-chain fatty acids and bile acids were assayed by gas chromatography, liquid chromatography coupled with tandem mass spectrometry, respectively. The human vitreal fatty acid profiles of subjects with proliferative DR and LXA4 levels were measured. LA and ALA significantly improved the plasma glucose and lipid levels; increased the abundance of Ruminococcaceae (the ALA-treated group), Alloprevotella, Prevotellaceae_Ga6A1_group, Ruminococcaceae_UCG_010, and Ruminococcus_1 (the LA-treated group) bacteria; enhanced acetate and butyrate levels; and augmented fecal and hepatic concentrations of cholic acid, chenodeoxycholic acid, and tauro ursodeoxycholic acid in ALA- and LA-treated animals. Significant STZ-induced decreases in plasma LA, gamma-linolenic acid, arachidonic acid, and ALA levels reverted to near normal, following LA and ALA treatments. Significant changes in the expression of desaturases; COX-2, 5-LOX, and 12-LOX enzymes; and cytokines in T1DM were reverted to near normal by EFAs. DR subjects also had low retinal LXA4 levels. The results of the present study show that ALA and LA are of significant benefit in reversing metabolism, gut microbiota, and inflammatory and retinal index changes seen in T1DM, suggesting that EFAs are of benefit in diabetes mellitus.

Non-invasive technique to detect diabetic retinopathy based on Electrooculography signal using machine learning classifiers.

Single-channel Electrooculogram (EOG) is proposed for detecting diabetic retinopathy. The Corneal-retinal potential of the eyes plays a vital role in the acquisition of Electrooculography. Diabetes is the most prevalent disease and for one out of three people with diabetes above 40 years, diabetic retinopathy occurs. It is necessary for the early detection of diabetic retinopathy as it is one of the primary reasons for blindness in the population. The potential difference between cornea and retina leads to the acquisition of EOG signal. The proposed study aims to design a low-cost miniaturized hardware circuit to obtain EOG signal using second order filters without compromising in accuracy of the outcome signal and to classify the signal into normal and diabetic retinopathy subjects by extracting the statistical features like kurtosis, mean, median absolute deviation, standard deviation, and range from software filtered EOG signal. Among the classifiers used, Support vector machine (SVM) shows a higher accuracy of 93.33%. The sensitivity, specificity and Area Under Curve (AUC) values of SVM are 96.43%, 90.625%, 0.93% is considered as more favorable outcome for the proposed method and it supports the developed prototype and processing methodology. The novelty of the research is based on proposing and exploring a non-invasive methodology for Diabetic retinopathy diagnosis based on EOG signal. Thus, the designed hardware is simple in operation and cost effective, provides an affordable and non-invasive diagnostic tool for diabetic retinopathy patients.

Association of Long Non-Coding RNA Growth Arrest-Specific 5 Genetic Variants with Diabetic Retinopathy.

The aim of this work was to appraise the potential associations of single nucleotide polymorphisms (SNPs) of long non-coding RNA growth arrest-specific 5 (GAS5) with diabetic retinopathy (DR) in a diabetes mellitus (DM) population. Two loci of the GAS5 SNPs (rs55829688 and rs145204276) were genotyped via TaqMan allelic discrimination in 449 non-DR patients and 273 DR subjects. The SNP rs145204276 Del/Del showed a significantly higher distribution in the DR group compared to the non-DR group (AOR: 2.487, 95% CI: 1.424–4.344, p = 0.001). During subgroup analyses, the non-proliferative diabetic retinopathy (NPDR) subgroup demonstrated a significantly higher ratio of the SNP rs145204276 Del/Del (AOR: 2.917, 95% CI: 1.574–5.406, p = 0.001) and Ins/Del + Del/Del (AOR: 1.242, 95% CI: 1.016–1.519, p = 0.034) compared to the non-DR population, while the proliferative diabetic retinopathy (PDR) subgroup did not reveal significant differences in either SNP rs145204276 or rs55829688 distributions compared to the non-DR group. Furthermore, patients with a GAS5 SNP rs145204276 Del/Del showed a significantly shorter DM duration than the wild type (Ins/Ins) (p = 0.021). In conclusion, our findings demonstrate that the GAS5 SNP rs145204276 Del/Del variant is associated with an increased susceptibility to DR in DM patients, particularly in those patients with NPDR.

Assessment of Knowledge, Attitude, and Practice Regarding Diabetic Retinopathy in an Urban Population in Northeast China.

ObjectiveThis study aimed to assess the knowledge, attitude, and practice (KAP) of diabetic subjects with diabetic retinopathy (DR) and those without DR (NDR) in an urban community in Northeast China, as well as their risk factors in subjects with DR and NDR.MethodsA community-based survey involving 1,662 subjects was conducted in Fushun, China, between July 2012 and May 2013. The subjects included diabetics with DR (n = 783) and those NDR (n = 879), and questionnaires were completed to collect information about their sociodemographic and healthcare characteristics. A Chi-square test and multiple logistic analyses were performed to analyze the data.ResultsAmong the DR group, 21.88% had a good knowledge of DR, 94.15% had a positive attitude, and 68.07% followed good practice, whereas 20.98% of the NDR group had a good knowledge of DR, 94.18% had a positive attitude, and 66.92% followed good practice. There was no significant difference in the KAP of the two groups of subjects. In the NDR group, a good level of knowledge was associated with a high-level of education (OR = 0.1, 0.2; p < 0.05), a good attitude was associated with retirement (OR = 0.2; p < 0.05), and good practice was associated with being female, having a high-level of education, and the type of treatment (OR = 0.5, 0.4, 2.3, 3.1; p < 0.05). In the DR group, good practice was associated with older age and retirement (OR = 0.6, 0.4; p < 0.05).ConclusionsThere was no significant difference between the DR and NDR subjects in the overall levels of KAP, but both groups showed a poor level of knowledge. Age, gender, education, occupation, and type of treatment were the main factors associated with the KAP scores, more risk factors in the NDR group than in the DR group. There is an urgent need for coordinated educational campaigns with a prioritized focus on the northeast region of China, especially NDR group.

Status and correlation of 25-hydroxy Vitamin D in diabetes mellitus Type II patients with and without retinopathy

Background: Emerging data from in vivo and in vitro investigations have proven that Vitamin D deficiency may be a risk factor for the etiology of diabetes and its consequences; however, individual published studies have yielded conflicting results. The current study’s goal was to evaluate and correlate Vitamin D levels in the blood of diabetic patients with and without diabetic retinopathy (DR), as well as to correlate Vitamin D with duration of diabetes, age and HbA1C. Aim and Objectives: The aim of the study was to evaluate and correlate Vitamin D levels in the blood of diabetic patients with and without DR, and to correlate Vitamin D levels with age, duration of diabetes, and HbA1C. Materials and Methods: A cross-sectional case-control study of 150 Type 2 diabetes mellitus (T2DM) patients (aged 35–70 years) was included. The 150 Type 2 Diabetic patients were separated into three groups: Group 1 (no DR, n = 52), Group 2 (non-proliferative DR [NPDR], n = 58), and Group 3 (PDR, n = 42). Enrolled participants were subjected to a thorough physical examination to rule out the occurrence of microvascular problems, which included microfilament testing and a thorough fundus examination. Serum samples were used to test fasting blood sugar, HbA1C, and serum Vitamin D. Results: T2DM subjects with DR had lower mean serum 25 (OH) D concentrations than patients without DR (21.5 ± 9.5 vs. 17.7 ± 10.2 vs. 14.4 ± 5.9; P = 0.04). Mean HbA1C concentration was significantly lower in No DR (NDR) in comparison to NPDR and PDR (7.6 ± 1.5; vs. 8.5 ± 1.9; vs. 9.3 ± 1.8; P = 0.037. In addition, there was a significant negative correlation between the blood 25 (OH) D level and age (–0.165; P = 0.015), diabetes duration (–0.172; P = 0.014), and HbA1C (–0.148; P = 0.040). Conclusion: The current investigation showed that patients with DR have lower levels of 25 [OH] D than those with non DR subjects. 25 [OH] D levels were negatively associated with age, duration of diabetes, and HbA1C.

Decorin Concentrations in Aqueous Humor of Patients with Diabetic Retinopathy.

Diabetic retinopathy (DR) is a microvascular complication of diabetes in the retina. Chronic hyperglycemia damages retinal microvasculature embedded into the extracellular matrix (ECM), causing fluid leakage and ischemic retinal neovascularization. Current treatment strategies include intravitreal anti-vascular endothelial growth factor (VEGF) or steroidal injections, laser photocoagulation, or vitrectomy in severe cases. However, treatment may require multiple modalities or repeat treatments due to variable response. Though DR management has achieved great success, improved, long-lasting, and predictable treatments are needed, including new biomarkers and therapeutic approaches. Small-leucine rich proteoglycans, such as decorin, constitute an integral component of retinal endothelial ECM. Therefore, any damage to microvasculature can trigger its antifibrotic and antiangiogenic response against retinal vascular pathologies, including DR. We conducted a cross-sectional study to examine the association between aqueous humor (AH) decorin levels, if any, and severity of DR. A total of 82 subjects (26 control, 56 DR) were recruited. AH was collected and decorin concentrations were measured using an enzyme-linked immunosorbent assay (ELISA). Decorin was significantly increased in the AH of DR subjects compared to controls (p = 0.0034). AH decorin levels were increased in severe DR groups in ETDRS and Gloucestershire classifications. Decorin concentrations also displayed a significant association with visual acuity (LogMAR) measurements. In conclusion, aqueous humor decorin concentrations were found elevated in DR subjects, possibly due to a compensatory response to the retinal microvascular changes during hyperglycemia.

ADIPOCYTE FATTY ACID BINDING PROTEIN (A-FABP) AS A NOVEL BIOCHEMICAL MARKER OF DIABETIC RETINOPATHY

Introduction: Diabetes mellitus is acomplex metabolic disorder associated with increased risk of microvascular and macrovascular disease characterized by chronic hyperglycaemia resulting from defect in insulin secretion, insulin action, or both. Diabetic retinopathy (DR) causes visual impairment as a result of long term accumulated damaged to the small blood vessels in the retina.Adipocyte fatty acid binding protein(AFABP), been suggested as a third adipokine, in addition to leptin and adiponectin. AFABP might have a role in the proliferation of endothelial cells, as well as in angiogenesis. A-FABP levels were determined in subjects witout diabetes mellitus, with type 2 diabetes mellitus without DR and with DR at admission in order to investigate a possible association of A-FABP to the increased risk of incidence of DR. Material and methods: This study was done on non-diabetic (n=25) and Type 2 diabetes subjectswith(n=25) and without retinopathy (n=25) who visited HAHC hospital. Blood glucose (fasting and post prandial), glycated hemoglobin(HbA1c), urea, creatinine, uric acid, total protein, serum albumin,serum electrolytes (sodium, potassiumand chloride), totalcholesterol,triglyceride, high density lipoprotein(HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL) and and AFABP were measured . Result: The mean values of blood glucose (fasting and post prandial),HbA1C,urea, creatinine , TG, LDL VLDL and AFABP were higher in diabetic subjectswith diabetic retinopathy in comparison to diabetic subjects without retinopathy and subjects without diabetes mellitus and were highly significant statistically.(p&lt;0.01). The mean value of HDL was lower in diabetic subjects with diabetic retinopathy in comparison to diabetic subjects without retinopathy and subjects without diabetes mellitus and was highly significant statistically. Conclusion:The study helps in associating AFABP as an early biochemical marker for identifying onset of diabetic retinopathy in subjects with diabetes mellitus at an early stage.

Quantifying the pattern of retinal vascular orientation in diabetic retinopathy using optical coherence tomography angiography

Quantitative imaging using optical coherence tomography angiography (OCTA) could provide objective tools for the detection and characterization of diabetic retinopathy (DR). In this study, an operator combining the second derivative and Gaussian multiscale convolution is applied to identify the retinal orientation at each pixel in the OCTA image. We quantified the pattern of retinal vascular orientation and developed three novel quantitative metrics including vessel preferred orientation, vessel anisotropy, and vessel area. Each of eight 45º sectors of the circular disk centered at the macular region was defined as the region of interest. Significant sectoral differences were observed in the preferred orientation (p < 0.0001) and vessel area (p < 0.0001) in the 34 healthy subjects, whereas vessel anisotropy did not demonstrate a significant difference among the eight sectors (p = 0.054). Differential retinal microvascular orientation patterns were observed between healthy controls (n = 34) and the DR subjects (n = 7). The vessel area characterized from the vascular orientation pattern was shown to be strongly correlated with the traditionally reported vessel density (Pearson R > 0.97, p < 0.0001). With three metrics calculated from the vascular orientation pattern simultaneously and sectorally, our quantitative assessment for retinal microvasculature provides more information than vessel density alone and thereby may enhance the detection of DR. These preliminary results suggest the feasibility and advantage of our vessel orientation-based quantitative approach using OCTA to characterize DR-associated changes in retinal microvasculature.

SILICONE OIL VERSUS PERFLUOROPROPANE GAS TAMPONADE DURING VITRECTOMY FOR TRACTIONAL RETINAL DETACHMENT OR FIBROUS PROLIFERATION: A Randomized Clinical Trial.

To compare vitreous substitution with silicone oil to perfluoropropane gas in proliferative diabetic retinopathy subjects undergoing pars plana vitrectomy (PPV) for the treatment of tractional retinal detachment or extensive fibrous proliferation. Randomized clinical trial. Three hundred and two proliferative diabetic retinopathy subjects with tractional retinal detachment or extensive fibrous proliferation requiring PPV were enrolled into the trial. Subjects were prospectively randomized into one of two vitreous substitution groups during PPV: Group A subjects underwent 1,000 centistoke silicone oil tamponade, whereas Group B subjects underwent 14% to 16% silicone oil to perfluoropropane gas tamponade. The principal outcome was the best-corrected visual acuity at 6-month follow-up. Secondary outcomes were postoperative complications and unplanned PPV during the 6-month trial interval. Two hundred and fifty-eight subjects were randomized to receive a vitreous substitute and completed 6-month follow-up. Group B had better best-corrected visual acuity, more subjects ending up with 0.4 logarithm of the minimum angle of resolution (20/50) or better visual acuity, and more subjects ending up with 1 logarithm of the minimum angle of resolution (20/200) or better visual acuity at 6 months compared with Group A (P < 0.001, P = 0.02, P < 0.001, respectively). There were no significant differences in baseline characteristics, intraoperative or postoperative complications, or incidence of unplanned PPV between groups. This trial demonstrated that vitreous substitution with silicone oil to perfluoropropane gas resulted in better visual acuity at 6 months compared with silicone oil tamponade in proliferative diabetic retinopathy patients undergoing PPV for tractional retinal detachment or extensive fibrous proliferation. Surgeons should consider silicone oil to perfluoropropane gas tamponade as the first-line vitreous substitute in this patient population.