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BACKGROUND AND PURPOSE: Diabetic retinopathy (DR) is a prevalent complication of diabetes, with a rising global incidence, and can result in significant vision impairment and potential blindness in adults. Corilagin (COR) has been shown to regulate several pathological processes. However, the specific protective role and mechanism of action of COR in DR remain unknown. EXPERIMENTAL APPROACH: The protective effects and mechanisms of COR in DR were examined using the ARPE-19 cell line and C57BL/6 mice. Intraretinal tissue damage and molecular markers were evaluated to investigate the impact of COR on oxidative stress and cell death pathways. KEY RESULTS: In vitro, COR significantly reduced the cytotoxic effects of high glucose (HG) on ARPE-19 cells. Furthermore, COR also effectively decreased HG-induced lipid peroxidation, iron deposition, and ferroptosis and reduced damage to retinal tight junction proteins. Similarly, an in vivo study of streptozotocin (STZ)-induced DM mice showed that the daily gavage of COR for eight weeks notably alleviated DR. Mechanistically, COR activated the Nrf2 antioxidant signaling pathway both in vivo and in vitro, preventing HG-induced alterations in morphological and biochemical parameters. Notably, our study demonstrated that compared with controls, Nrf2 knockout mice and siNrf2-treated cells were more vulnerable to ferroptosis under HG conditions, and the protective effect of COR on DR was substantially diminished in these models. CONCLUSION AND IMPLICATIONS: These data indicate that COR has a protective effect against HG-induced retinal injury via a mechanism associated with the Nrf2-dependent antioxidant pathway and ferroptosis regulation.

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BACKGROUND: Diabetic retinopathy (DR), a chronic and progressive microvascular complication of diabetes mellitus, substantially threatens vision and is a leading cause of blindness among working-age individuals worldwide. Traditional diagnostic methods, such as ophthalmoscopy and fluorescein angiography are nonquantitative, invasive, and time consuming. Analysis of protein biomarkers in tear fluid offers noninvasive insights into ocular and systemic health, aiding in early DR detection. This study introduces a surface acoustic wave (SAW) microchip that rapidly enhances fluorescence in bead-based immunoassays for the sensitive and noninvasive DR detection from human tear samples. RESULTS: The device facilitated particle mixing for immunoassay formation and particle concentration in the droplet, resulting in an enhanced immunofluorescence signal. This detachable SAW microchip allows the disposal of the cover glass after every use, thereby improving the reusability of the interdigital transducer and minimizing potential cross-contamination. A preliminary clinical test was conducted on a cohort of 10 volunteers, including DR patients and healthy individuals. The results demonstrated strong agreement with ELISA studies, validating the high accuracy rate of the SAW microchip. SIGNIFICANCE: This comprehensive study offers significant insights into the potential application of a novel SAW microchip for the early detection of DR in individuals with diabetes. By utilizing protein biomarkers found in tear fluid, the device facilitates noninvasive, rapid, and sensitive detection, potentially revolutionizing DR diagnostics and improving patient outcomes through timely intervention and management of this vision-threatening condition.

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Diabetes mellitus poses a significant health challenge globally, often leading to debilitating complications, such as neuropathy and retinopathy. Quercetin, a flavonoid prevalent in fruits and vegetables, has demonstrated potential therapeutic effects in these conditions due to its antioxidant, anti-inflammatory, and neuroprotective properties. This review summarizes and provides a comprehensive understanding of the molecular mechanisms underlying the efficacy of quercetin in ameliorating diabetic neuropathy and retinopathy. A thorough search was carried out across scientific databases, such as SciFinder, PubMed, and Google Scholar, to gather pertinent literature regarding the effect of quercetin on diabetic neuropathy and retinopathy till February 2024. Preclinical studies indicate that quercetin mitigates neuropathic pain, sensory deficits, and nerve damage associated with diabetic neuropathy by improving neuronal function, reducing DNA damage, regulating pro-inflammatory cytokines, enhancing antioxidant enzyme levels and endothelial function, as well as restoring nerve injuries. In diabetic retinopathy, quercetin shows the potential to preserve retinal structure and function, inhibiting neovascularization, preventing retinal cell death, reducing pro-inflammatory cytokines, and increasing neurotrophic factor levels. Moreover, through modulating key signaling pathways, such as AMP-activated Protein Kinase (AMPK) activation, Glucose Transporter 4 (GLUT 4) upregulation, and insulin secretion regulation, quercetin demonstrates efficacy in reducing oxidative stress and inflammation, thereby protecting nerve and retinal tissues. Despite promising preclinical findings, challenges, such as limited bioavailability, necessitate further research to optimize quercetin's clinical application in order to establish its optimal dosage, formulation, and long-term efficacy in clinical settings.

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Early detection of diabetic retinopathy (DR) is an urgent ophthalmological problem in Russia and globally. PURPOSE: This study assesses the prevalence of asymptomatic retinopathy and attempts to identify risk groups for its development in patients with type 1 and 2 diabetes mellitus (T1DM and T2DM). MATERIAL AND METHODS: The study involved clinics from 5 cities in the Russian Federation and it included 367 patients with DM, 34.88% men and 65.12% women, aged 50.88±20.55 years. 34.88% of patients suffered from T1DM, 65.12% suffered from T2DM, the average duration of the disease was 9.02±7.22 years. 58.31% of patients had a history of arterial hypertension, 13.08% had a history of smoking. The primary endpoint was the frequency of detection of diabetic changes in the eye fundus of patients with T1DM and T2DM in general; the secondary endpoint - same but separately, and for T2DM patients depending on the duration of the disease. The exploratory endpoint was the assessment of the influence of various factors on the development of DR. The patients underwent visometry (modified ETDRS table), biomicroscopy, mydriatic fundus photography according to the «2 fields¼ protocol. RESULTS: The average detection rate of DR was 12.26%, primarily observed in patients with T2DM (13.81%), women (9.26%), in both eyes (8.17%). Among patients with DR, 26 (19.55%) had glycated hemoglobin (HbA1c) level exceeding 7.5% (p=0.002), indicating a direct relationship between this indicator and the incidence of DR. Logistic regression analysis showed that the duration of diabetes of more than 10 years has a statistically significant effect on the development of DR. In the modified model for odds estimation, the likelihood of developing DR is increased by the duration of DM for more than 10 years; increased blood pressure; HbA1c level >7.5%. CONCLUSION: The obtained results, some of which will be presented in subsequent publications, highlight the effectiveness of using two-field mydriatic fundus photography as a screening for DR.

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OBJECTIVE: To assess the feasibility of using non-mydriatic fundus photography in conjunction with an artificial intelligence (AI) reading platform for large-scale screening of diabetic retinopathy (DR). METHODS: In this study, we selected 120 patients with diabetes hospitalized in our institution from December 2019 to April 2021. Retinal imaging of 240 eyes was obtained using non-mydriatic fundus photography. The fundus images of these patients were divided into two groups based on different interpretation methods. In Experiment Group 1, the images were analyzed and graded for DR diagnosis using an AI reading platform. In Experiment Group 2, the images were analyzed and graded for DR diagnosis by an associate chief physician in ophthalmology, specializing in fundus diseases. Concurrently, all patients underwent the gold standard for DR diagnosis and grading-fundus fluorescein angiography (FFA)-with the outcomes serving as the Control Group. The diagnostic value of the two methods was assessed by comparing the results of Experiment Groups 1 and 2 with those of the Control Group. RESULTS: Keeping the control group (FFA results) as the gold standard, no significant differences were observed between the two experimental groups regarding diagnostic sensitivity, specificity, false positive rate, false negative rate, positive predictive value, negative predictive value, Youden's index, Kappa value, and diagnostic accuracy (X2 = 0.371, P > 0.05). CONCLUSION: Compared with the manual reading group, the AI reading group revealed no significant differences across all diagnostic indicators, exhibiting high sensitivity and specificity, as well as a relatively high positive predictive value. Additionally, it demonstrated a high level of diagnostic consistency with the gold standard. This technology holds potential for suitability in large-scale screening of DR.

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PURPOSE: This study aimed to investigate longitudinal changes in choroidal thickness (CT) and ganglion cell-inner plexiform layer thickness (GC-IPLT) across distinct phenotypes of type 2 diabetes mellitus (T2DM) patients. DESIGN: Prospective observational cohort study. METHODS: T2DM patients were categorized into five groups (SAID, SIDD, SIRD, MOD, and MARD) using K-means clustering based on ß-cell function and insulin resistance. Swept-source optical coherence tomography measured baseline and 4-year follow-up CT and GC-IPLT. Linear mixed-effects models assessed absolute and relative changes in CT and GC-IPLT across subtypes. RESULTS: Over a median 4.11-year follow-up, CT and GC-IPLT decreased significantly across all groups. Choroidal thinning rates were most pronounced in SIDD (-6.5±0.53 µm/year and -3.5±0.24%/year) and SAID (-6.27±0.8 µm/year and -3.19±0.37%/year), while MARD showed the slowest thinning (-3.63±0.34 µm/year and -1.98±0.25%/year). SIRD exhibited the greatest GC-IPLT loss (-0.66±0.05 µm/year and -0.91±0.07%/year), with the least in SIDD (-0.36±0.05 µm/year and -0.49±0.07%/year), all statistically significant (Ps < 0.001). Adjusted for variables, SIDD and SAID groups showed faster CT thinning than MARD [-2.57 µm/year (95% CI: -4.16 to -0.97; P=0.002) and -2.89 µm/year (95% CI: -4.12 to -1.66; P<0.001), respectively]. GC-IPLT thinning was notably accelerated in SIRD versus MARD, but slowed in SIDD relative to MARD [differences of -0.16 µm/year (95% CI: -0.3 to -0.03; P=0.015) and 0.15 µm/year (95% CI: 0.03 to 0.27; P=0.015), respectively]. Stratified analysis revealed significant differences among non-DR groups. CONCLUSIONS: Microvascular damage in the choroid is associated with SIDD patients, whereas early signs of retinal neurodegeneration are evident in SIRD patients. All these changes may precede the onset of DR.

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Computer-aided diagnosis (CAD) system assists ophthalmologists in early diabetic retinopathy (DR) detection by automating the analysis of retinal images, enabling timely intervention and treatment. This paper introduces a novel CAD system based on the global and multi-resolution analysis of retinal images. As a first step, we enhance the quality of the retinal images by applying a sequence of preprocessing techniques, which include the median filter, contrast limited adaptive histogram equalization (CLAHE), and the unsharp filter. These preprocessing steps effectively eliminate noise and enhance the contrast in the retinal images. Further, these images are represented at multi-scales using discrete wavelet transform (DWT), and center symmetric local binary pattern (CSLBP) features are extracted from each scale. The extracted CSLBP features from decomposed images capture the fine and coarse details of the retinal fundus images. Also, statistical features are extracted to capture the global characteristics and provide a comprehensive representation of retinal fundus images. The detection performances of these features are evaluated on a benchmark dataset using two machine learning models, i.e., SVM and k-NN, and found that the performance of the proposed work is considerably more encouraging than other existing methods. Furthermore, the results demonstrate that when wavelet-based CSLBP features are combined with statistical features, they yield notably improved detection performance compared to using these features individually.

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AIMS: Diabetic nephropathy, vision loss and diabetic retinopathy (DR) are frequent comorbidities among individuals with type 2 diabetes (T2D). The Retinopathy in People Currently On Renal Dialysis (RiPCORD) study sought to examine the epidemiology and risk of vision impairment (VI) and DR among a cohort of Indigenous and non-Indigenous Australians with T2D currently receiving haemodialysis for end-stage renal failure (ESRF). METHODS: A total of 106 Indigenous and 109 non-Indigenous Australians were recruited in RiPCORD across five haemodialysis centres in urban and remote settings. Clinical assessments, questionnaires and medical record data determined the rates of ocular complications and risk factor profiles. RESULTS: Prevalence rates include unilateral VI, 23.5 %; bilateral VI, 11.7 %; unilateral blindness, 14.2 %; and bilateral blindness, 3.7 %, with no significant differences between sub-cohorts (p=0.30). DR prevalence rates were 78.0 % among non-Indigenous Australians and 93.1 % among Indigenous Australians (p=<0.001). Non-Indigenous ethnicity (OR: 0.28) and pre-dialysis diastolic blood pressure (OR: 0.84 per 10-mmHg) were protective, while peripheral vascular disease (OR: 2.79) increased DR risk. CONCLUSIONS: Ocular complications among individuals with T2D and ESRF are disproportionately high, especially for Indigenous Australians, and beyond what can be accounted for by risk factor variation. Findings suggest a need to improve screening and preventative efforts within this high-risk population group.

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Because of its rapid progression and frequently poor prognosis, stroke is the third major cause of death in Europe and the first one in China. Many independent studies demonstrated sufficient space for prevention interventions in the primary care of ischemic stroke defined as the most cost-effective protection of vulnerable subpopulations against health-to-disease transition. Although several studies identified molecular patterns specific for IS in body fluids, none of these approaches has yet been incorporated into IS treatment guidelines. The advantages and disadvantages of individual body fluids are thoroughly analyzed throughout the paper. For example, multiomics based on a minimally invasive approach utilizing blood and its components is recommended for real-time monitoring, due to the particularly high level of dynamics of the blood as a body system. On the other hand, tear fluid as a more stable system is recommended for a non-invasive and patient-friendly holistic approach appropriate for health risk assessment and innovative screening programs in cost-effective IS management. This article details aspects essential to promote the practical implementation of highlighted achievements in 3PM-guided IS management. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-024-00376-2.

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Objective: This study aimed to assess the efficacy and safety of QiMing granules (QM) in the treatment of patients with diabetic retinopathy (DR). Methods: We systematically searched multiple databases, including Pubmed, Embase, Web of Science, Cochrane Library, SinoMed, Chinese National Knowledge Infrastructure (CNKI), Wanfang database, and VIP database. Randomized controlled trials (RCTs) of QM in the treatment of DR were collected, and the search time limit was from the establishment of the database to 27 March 2024. Two independent researchers were involved in literature screening, data extraction, and bias risk assessment. The risk of bias in the included studies was assessed using the Risk of Bias Assessment tool for randomized controlled trials of Cochrane Collaboration 2.0 (RoB 2.0). The main outcomes were the overall efficacy, visual acuity, retinal circulation time, macular thickness. The secondary outcomes were the levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and glycated hemoglobin (HbA1c). The adverse events was considered the safety outcome. Review Manager 5.4.1 and Stata 15.1 were used for meta-analysis. Data were pooled by random-effects or fixed-effects model to obtain the mean difference (MD), risk ratio (RR), and 95% confidence interval (CI). Results: A total of 33 RCTs involving 3,042 patients were included in this study. Overall, we demonstrated that QM had a significant clinical effect on DR. QM alone was superior to conventional treatment (CT) in terms of overall efficacy [RR = 1.45, 95% CI: (1.34, 1.58), p < 0.00001, moderate certainty], retinal circulation time [MD = -0.56, 95% CI: (-1.01, -0.12), p = 0.01] and macular thickness [MD = -11.99, 95% CI: (-23.15, -0.83), p = 0.04]. QM plus CT was superior to CT in terms of overall efficacy [RR = 1.29, 95% CI: (1.24, 1.33), p < 0.00001], visual acuity [MD = 0.14, 95% CI: (0.11, 0.17), p < 0.00001], macular thickness [MD = -14.70, 95% CI: (-21.56, -7.83), p < 0.0001], TG [MD = -0.20, 95% CI: (-0.33, -0.08), p = 0.001, moderate certainty], TC [MD = -0.57, 95% CI: (-1.06, -0.07), p = 0.02], and LDL-C [MD = -0.36, 95% CI: (-0.70, -0.03), p = 0.03]. In terms of safety, the incidence of adverse events in the experimental group was less than that in the control group. The results of the GRADE evidence quality evaluation showed that the evidence quality of outcome indicators was mostly low. Conclusion: QM can effectively improve overall efficacy, visual acuity, macular thickness, retinal circulation time, and reduce the levels of TG, TC, and LDL-C. However, due to the limited number of studies included, a small sample size, and a lack of high-quality literature, the possibility of publication bias cannot be excluded. Moreover, biases are present due to differences in study design, such as the absence of placebo use in the control group and a predominant use of combined intervention designs in the control group, along with deficiencies in allocation concealment and blinding methods. Therefore, more multi-center, large-sample, and rigorously designed studies are needed to substantiate this conclusion. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42023465165.

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Diabetic retinopathy (DR) is a major complication of diabetes worldwide, significantly causing vision loss and blindness in working-age adults, and imposing a substantial socioeconomic burden globally. This review examines the crucial role of genetic factors in the development of DR and highlights the shift toward personalized treatment approaches. Advances in genetic research have identified specific genes and variations involved in angiogenesis, inflammation, and oxidative stress that increase DR susceptibility. Understanding these genetic markers enables early identification of at-risk individuals and the creation of personalized treatment plans. Incorporating these genetic insights, healthcare providers can develop early intervention strategies and tailored treatment plans to improve patient outcomes and minimize side effects. This review emphasizes the transformative potential of integrating genetic information into clinical practice, marking a paradigm shift in DR management and advancing toward a more personalized and effective healthcare model.

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BACKGROUND: Diabetic retinopathy (DR) affects about 25% of people with diabetes in Canada. Early detection of DR is essential for preventing vision loss. OBJECTIVE: We evaluated the real-world performance of an artificial intelligence (AI) system that analyzes fundus images for DR screening in a Quebec tertiary care center. METHODS: We prospectively recruited adult patients with diabetes at the Centre hospitalier de l'Université de Montréal (CHUM) in Montreal, Quebec, Canada. Patients underwent dual-pathway screening: first by the Computer Assisted Retinal Analysis (CARA) AI system (index test), then by standard ophthalmological examination (reference standard). We measured the AI system's sensitivity and specificity for detecting referable disease at the patient level, along with its performance for detecting any retinopathy and diabetic macular edema (DME) at the eye level, and potential cost savings. RESULTS: This study included 115 patients. CARA demonstrated a sensitivity of 87.5% (95% CI 71.9-95.0) and specificity of 66.2% (95% CI 54.3-76.3) for detecting referable disease at the patient level. For any retinopathy detection at the eye level, CARA showed 88.2% sensitivity (95% CI 76.6-94.5) and 71.4% specificity (95% CI 63.7-78.1). For DME detection, CARA had 100% sensitivity (95% CI 64.6-100) and 81.9% specificity (95% CI 75.6-86.8). Potential yearly savings from implementing CARA at the CHUM were estimated at CAD $245,635 (US $177,643.23, as of July 26, 2024) considering 5000 patients with diabetes. CONCLUSIONS: Our study indicates that integrating a semiautomated AI system for DR screening demonstrates high sensitivity for detecting referable disease in a real-world setting. This system has the potential to improve screening efficiency and reduce costs at the CHUM, but more work is needed to validate it.

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OBJECTIVE: The aim of this study is to explore general practice staff perspectives regarding a teaching concept based on instructional videos for conducting DR screenings. Furthermore, this study aims to investigate the competencies acquired by the staff through this teaching concept. DESIGN AND SETTING: Qualitative cross-sectional study conducted in general practice clinics in the North Denmark Region. METHOD: A teaching concept was developed based on instruction videos to teach general practice staff to conduct diabetic retinopathy screenings with automated grading through artificial intelligence. Semi-structured interviews were performed with 16 staff members to investigate their perspectives on the concept and acquired competencies. RESULTS: This study found no substantial resistance to the teaching concept from staff; however, participants' satisfaction with the methods employed in the instruction session, the progression of learning curves, screening competencies, and their acceptance of a known knowledge gap during screenings varied slightly among the participants. CONCLUSION: This study showed that the teaching concept can be used to teach general practice staff to conduct diabetic retinopathy screenings. Staffs' perspectives on the teaching concept and acquired competencies varied, and this study suggest few adjustments to the concept to accommodate staff's preferences and establish more consistent competencies.

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Background: Diabetic retinopathy (DR) is one of the common chronic complications of diabetes mellitus, which has developed into the leading cause of irreversible visual impairment in adults worldwide. Compound Qilian tablets (CQLT) is a traditional Chinese medicine (TCM) developed for treating DR, but its mechanism is still unclear. This study explored the mechanism of action of CQLT in treating DR through metabolomics and intestinal microbiota. Methods: Histopathologic examination of the pancreas and retina of Zucker diabetic fatty (ZDF) rats and immunohistochemistry were used to determine the expression levels of retinal nerve damage indicators ionized calcium binding adaptor molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP). Rat fecal samples were tested by LC-MS metabolomics to search for potential biomarkers and metabolic pathways for CQLT treatment of DR. Characteristic nucleic acid sequences of rat intestinal microbiota from each group were revealed using 16S rDNA technology to explore key microbes and related pathways for CQLT treatment of DR. At the same time, we investigated the effect of CQLT on the gluconeogenic pathway. Results: After CQLT intervention, islet cell status was improved, Iba-1 and GFAP expression were significantly decreased, and abnormal retinal microvascular proliferation and exudation were ameliorated. Metabolomics results showed that CQLT reversed 20 differential metabolites that were abnormally altered in DR rats. Intestinal microbiota analysis showed that treatment with CQLT improved the abundance and diversity of intestinal flora. Functional annotation of metabolites and intestinal flora revealed that glycolysis/gluconeogenesis, alanine, aspartate and glutamate metabolism, starch and sucrose metabolism were the main pathways for CQLT in treating DR. According to the results of correlation analysis, there were significant correlations between Iba-1, GFAP, and intestinal microbiota and metabolites affected by CQLT. In addition, we found that CQLT effectively inhibited the gluconeogenesis process in diabetic mice. Conclusion: In conclusion, CQLT could potentially reshape intestinal microbiota composition and regulate metabolite profiles to protect retinal morphology and function, thereby ameliorating the progression of DR.

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Introduction: Oxidative stress has been identified as a major contributor to the pathogenesis of DR, and many diagnostic and therapeutic strategies have been developed to target oxidative stress. Our aim was to understand the contribution of the country of origin of the publication, the institution, the authors, and the collaborative relationship between them. Methods: We performed a bibliometric analysis to summarize and explore the research hotspots and trends of oxidative stress in the DR. Results: We observe an upward trend in the number of posts on related topics from year to year. Expanding on this, Queens University Belfast is the most influential research institution. Current research hotspots and trends focus on the mechanism of autophagy and NLRP3 inflammasome's role in oxidative stress in DR. Discussion: We conducted a multi-dimensional analysis of the research status of oxidative stress in diabetic retinopathy through bibliometric analysis, and proposed possible future research trends and hotspots.

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Background: Diabetes mellitus (DM) is tightly associated with the increased prevalence of diabetic kidney disease (DKD). Nonetheless, severe renal function impairment and/or nephrotic range-proteinuria could also result from non-diabetic renal disease (non-DRD) among patients with DM. The 'Gold standard' for the differential diagnosis between DKD and non-DRD is kidney biopsy, although no real consensus exists. Thus, this study intends to associate the clinical and biochemical profile of patients with DM and renal disease with the histopathological data of kidney biopsy.In addition, we aimed to evaluate the role of kidney biopsy, especially when other causes, other than DM, are highly suspected among patients with DM and kidney disease. Methods: Thirty two patients with T2DM and nephrotic range levels of proteinuria or with co-existing factors pointing towards a non-diabetic origin of kidney disease were studied, retrospectively. All 32 patients underwent kidney biopsy and were classified according to histopathological findings into 3 groups: a) isolated diabetic kidney disease (DKD), b) non-diabetic kidney disease (NDKD) and c) mixed kidney disease (MKD). Results: Fifteen out of the 32 patients had findings of an isolated DKD, while 17 out of 32 patients suffered from NDKD (13 patients) or MKD (4 patients). DKD patients were younger (p = 0.016) and had a higher HbA1c value (p = 0.069, borderline statistical significance), while the NDKD patients had significantly shorter disease duration (p = 0.04). Furthermore, the incidence of diabetic retinopathy (DR) was lower among the NDKD patients (p < 0.001), who had also significantly less interstitial fibrosis (p = 0.02). Finally, the presence of DR, higher levels of interstitial fibrosis and longer T2DM duration were recognized as factors, which were positively associated with DKD. Conclusion: This study advocates the usefulness of kidney biopsy in patients with T2DM and nephrotic range levels of proteinuria, especially when DR is absent and shorter disease duration is observed.

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PURPOSE: To compare differences in the foveal avascular zone (FAZ) area, measured in the Superficial Vascular Complex (SVC), Deep Vascular Complex (DVC) and a combined analysis of both (SDVC), using two Spectral Domain OCT angiography (OCT-A) protocols, High Speed (HS) and High Resolution (HR). METHODS: A total of 26 eyes of diabetic patients, with and without macular oedema, were examined with two different fovea centered OCT-A volume scans. The two protocols were HS and HR volume scans, and the foveal avascular zone was manually measured in the SVC, DVC, and SDVC slabs by two masked investigators. Inter and intraoperator variability was analysed using Intraclass Correlation Coefficient (ICC) and differences were compared between the HR and HS acquisitions throughout the different vascular slabs. RESULTS: Intraoperator variability was low in all slabs (ICC > 0.9) and interoperator variability was lower for HR (ICC 0.835-0.911) compared to HS (ICC between 0.604 and 0.865). Comparing HS and HR measurements for the same slab, the correlation was only moderate in SVC and DVC (ICC was 0.640 and 0.568 respectively) but was good in the SDVC (ICC = 0.823). FAZ area measurement in SDVC also showed the smallest bias (mean difference 0.009 mm2) and the narrowest limits of agreement (-0.175 to 0.193 mm2). CONCLUSIONS: Even in cases of diabetic macular oedema, when measuring the FAZ area, the reproducibility was better between HS and HR protocols when using the SDVC slab, compared to the SVC or DVC slabs alone. Further studies should evaluate the use of the combined SDVC slab for the FAZ assessment, compared to the SVC and DVC slabs alone, in the detection and progression of different retinal diseases.

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OBJECTIVE: To investigate the correlation between glucose and lipid metabolism, renal function, and retinopathy in patients with diabetic retinopathy (DR) based on optical coherence tomography angiography (OCTA). METHODS: A total of 584 diabetic patients who underwent treatment at The Second Affiliated Hospital of Dalian Medical University from March 2022 to June 2023 were retrospectively selected as research participants. They were categorized into a NDR group (n=366) and a DR group (n=218) based on the presence or absence of DR. Relevant indexes of glucose and lipid metabolism, renal function, and OCTA findings were collected. Logistic regression analysis was applied to identify the influencing factors of diabetes mellitus complicated with DR. ROC curves were drawn to examine the diagnostic value of the screened influencing factors for diabetes mellitus complicated with DR. Finally, Spearman correlation coefficients were calculated to examine the relevance between influencing factors and the severity of DR Lesions. RESULTS: Logistic regression showed that high levels of angiography 3 × 3 inner vascular density (IVD_33) and angiography 3 × 3 inner perfusion density (IPD_33) were protective factors for diabetes mellitus complicated with DR, and diabetic peridiabetic vascular disease (DPVD), elevated blood urea nitrogen (BUN), and urea levels were risk factors for diabetes mellitus complicated with DR (all P<0.05). ROC curve displayed that the areas under the curve (AUC) of IVD_33, DPVD, BUN, IPD_33, and Urea in predicting diabetes mellitus with DR were 0.779, 0.705, 0.621, 0.723, and 0.632, respectively. The AUC of combined prediction with OCTA index was higher than that of combined prediction without OCTA index (0.781 VS 0.84, P<0.05). Spearman correlation coefficient displayed that IVD_33 and IPD_33 were negatively correlated with the severity of DR, whereas DPVD and Urea showed a positive correlation (P<0.05). CONCLUSION: Our findings provide valuable insights for the initial clinical assessment of diabetic patients with DR and aid in the early determination of DR severity. Corresponding intervention measures should be formulated as early as possible to remedy patients' outcomes.

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Purpose: Retinal ischemia is a major feature of diabetic retinopathy (DR). Traditional nonperfused areas measured by OCT angiography (OCTA) measure blood supply but not ischemia. We propose a novel 3-dimensional (3D) quantitative method to derive ischemia measurements from OCTA data. Design: Cross-sectional study. Participants: We acquired 223 macular OCTA volumes from 33 healthy eyes, 33 diabetic eyes without retinopathy, 7 eyes with nonreferable DR, 17 eyes with referable but nonvision-threatening DR, and 133 eyes with vision-threatening DR. Methods: Each eye was scanned using a spectral-domain OCTA system (Avanti RTVue-XR, Visionix/Optovue, Inc) with 1.6-mm scan depth in a 3 × 3-mm region (640 × 304 × 304 voxels) centered on the fovea. For each scanned OCTA volume, a custom algorithm removed flow projection artifacts. We then enhanced, binarized, and skeletonized the vasculature in each OCTA volume and generated a 3D oxygen tension map using a zero-order kinetics oxygen diffusion model. Each volume was scaled to the average retina thickness in healthy controls after foveal registration and flattening of the Bruch's membrane. Finally, we extracted 3D ischemia maps by comparison with a reference map established from scans of healthy eyes using the same processing. To assess the ability of the ischemia maps to grade DR severity, we constructed receiver operating characteristic curves for diagnosing diabetes, referable DR, and vision-threatening DR. Main Outcome Measures: Spearman correlation coefficient and area under receiver operating characteristic curve (AUC) were used to quantify the ability of the ischemia maps to DR. Results: The ischemia maps showed that the ischemic tissues were at or near pathologically nonperfused areas, but not the normally nonvascular tissue, such as the foveal avascular zone. We found multiple novel metrics, including inferred 3D-oxygen tension, ischemia index, and ischemic volume ratio, were strongly correlated with DR severity. The AUCs of ischemia index measured were 0.94 for diabetes, 0.89 for DR, 0.88 for referable DR, and 0.85 for vision-threatening DR. Conclusions: A quantitative method to infer 3D oxygen tension and ischemia using OCTA in diabetic eyes can identify ischemic tissue that are more specific to pathologic changes in DR. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.