Clinical serum lipidomic profiling revealed potential lipid biomarkers for early diabetic retinopathy.

Diabetic retinopathy (DR) is a serious complication of diabetes featuring abnormal lipid metabolism. However, the specific lipid molecules associated with onset and progression remain unclear. We used a broad-targeted lipidomics approach to assess the lipid changes that occur before the proliferative retinopathy stage and to identify novel lipid biomarkers to distinguish between patients without DR (NDR) and with non-proliferative DR (NPDR). Targeted lipomics analysis was carried out on serum samples from patients with type I diabetes, including 20 NDRs and 20 NPDRs. The results showed that compared with the NDR group, 102 lipids in the NPDR group showed specific expressions. Four lipid metabolites including TAG58:2-FA18:1 were obtained using the Least Absolute Shrink And Selection Operator (LASSO) and Support Vector Machine Recursive Feature Elimination (SVM-RFE) methods. The four-lipid combination diagnostic models showed good predictive ability in both the discovery and validation sets, and were able to distinguish between NDR patients and NPDR patients. The identified lipid markers significantly improved diagnostic accuracy within the NPDR group. Our findings help to better understand the complexity and individual differences of DR lipid metabolism.

Nuclear proteins and diabetic retinopathy: a review.

Diabetic retinopathy (DR) is an eye disease that causes blindness and vision loss in diabetic. Risk factors for DR include high blood glucose levels and some environmental factors. The pathogenesis is based on inflammation caused by interferon and other nuclear proteins. This review article provides an overview of DR and discusses the role of nuclear proteins in the pathogenesis of the disease. Some core proteins such as MAPK, transcription co-factors, transcription co-activators, and others are part of this review. In addition, some current advanced treatment resulting from the role of nuclear proteins will be analyzes, including epigenetic modifications, the use of methylation, acetylation, and histone modifications. Stem cell technology and the use of nanobiotechnology are proposed as promising approaches for a more effective treatment of DR.

Evaluation of nail fold capillaroscopy changes in patients with diabetic retinopathy and healthy controls, and its correlation with disease duration, HbA1c levels and severity of diabetic retinopathy: An observational study.

Background Diabetic retinopathy (DR) is an important microvascular complication of long-term type 2 diabetes mellitus (T2DM) leading to blindness if not properly diagnosed and managed. It can develop as early as 7 years before the diagnosis of diabetes. Nail fold capillaroscopy (NFC) is a non-invasive technique for observing capillary microvasculature and there are few studies which have explored the use of NFC in diabetes mellitus patients. Objective To study the nail fold capillaroscopic alterations in patients with T2DM having diabetic retinopathy and compare them to healthy controls. The secondary objective was to correlate the NFC findings with the duration of diabetes, haemoglobin A1c (HbA1c) levels and the severity of DR. Materials and methods This cross-sectional observational study enrolled 200 patients - 100 cases with T2DM having diabetic retinopathy (as per the American Diabetes Association criteria and Diabetic Retinopathy Disease Severity Scale) and 100 healthy age and sex-matched controls. All patients were subjected to NFC and ophthalmological assessment. Results NFC revealed that patients with DR showed significantly higher frequencies of tortuous, dilated, bushy, meandering, angulated capillaries, avascular areas and micro-haemorrhages as compared to healthy controls (p < 0.05). In proliferative DR (PDR), the frequency of tortuous, bushy capillaries, and avascular areas was statistically high and the capillary density was reduced as compared to non-proliferative DR. The DR patients with longer disease duration (>20) years had a significantly higher frequency of tortuous capillaries, avascular areas, meandering, angulated and dilated capillaries. The frequency of tortuosity, avascular areas, and bushy areas was significantly higher in patients with poor glycaemic control (HbA1c >11). Limitations A larger sample size study with different demographic populations could have provided a broader picture of NFC changes in T2DM patients with DR. Discussion NFC may act as a surrogate marker of retinal involvement in patients with DM and should be performed at regular intervals. Conclusion NFC is a quick, simple, safe, and non-invasive method to assess the capillaroscopic alterations in diabetic patients which inturn can help in assessing the severity of DR.

The Predictors of Early Treatment Effectiveness of Intravitreal Bevacizumab Application in Patients with Diabetic Macular Edema.

The aim of this study was to establish whether multiple blood parameters might predict an early treatment response to intravitreal bevacizumab injections in patients with diabetic macular edema (DME). Seventy-eight patients with non-proliferative diabetic retinopathy (NPDR) and DME were included. The treatment response was evaluated with central macular thickness decrease and best corrected visual acuity increase one month after the last bevacizumab injection. Parameters of interest were the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), vitamin D, and apolipoprotein B to A-I ratio (ApoB/ApoA-I). The NLR (2.03 ± 0.70 vs. 2.80 ± 1.08; p < 0.001), MLR (0.23 ± 0.06 vs. 0.28 ± 0.10; p = 0.011), PLR (107.4 ± 37.3 vs. 135.8 ± 58.0; p = 0.013), and SII (445.3 ± 166.3 vs. 675.3 ± 334.0; p < 0.001) were significantly different between responder and non-responder groups. Receiver operator characteristics analysis showed the NLR (AUC 0.778; 95% CI 0.669-0.864), PLR (AUC 0.628; 95% CI 0.511-0.735), MLR (AUC 0.653; 95% CI 0.536-0.757), and SII (AUC 0.709; 95% CI 0.595-0.806) could be predictors of response to bevacizumab in patients with DME and NPDR. Patients with severe NPDR had a significantly higher ApoB/ApoA-I ratio (0.70 (0.57-0.87) vs. 0.61 (0.49-0.72), p = 0.049) and lower vitamin D (52.45 (43.10-70.60) ng/mL vs. 40.05 (25.95-55.30) ng/mL, p = 0.025). Alterations in the NLR, PLR, MLR, and SII seem to provide prognostic information regarding the response to bevacizumab in patients with DME, whilst vitamin D deficiency and the ApoB/ApoA-I ratio could contribute to better staging.

Impact of anti-VEGF treatment on development of proliferative diabetic retinopathy in routine clinical practice.

BACKGROUND: This study evaluated impact of anti-vascular endothelial growth factor (VEGF) treatment on proliferative diabetic retinopathy (PDR) development among patients with non-proliferative diabetic retinopathy (NPDR) in US real-world clinical practice. METHODS: This was a retrospective analysis of electronic medical records (Vestrum Health; January 2013 to June 2019) of eyes with baseline NPDR, without DME, and naïve to anti-VEGF treatment at index DR diagnosis. Eyes that received anti-VEGF and/or laser treatment over the course of study before development of PDR constituted the treated cohort while the remaining including those treated with laser constituted the anti-VEGF naïve cohort. Survival analysis via Kaplan-Meier method evaluated time to DME and PDR development by baseline NPDR severity, with anti-VEGF treatment as censoring variable. Baseline factors affecting PDR development were analyzed using Cox multivariable regression, censoring for anti-VEGF treatment. RESULTS: Among anti-VEGF-naive eyes, cumulative incidence of DME in eyes with mild (n = 70,050), moderate (n = 39,116), and severe NPDR (n = 10,692) at baseline was 27.1%, 51.2%, and 60.6%. Multivariable regression analysis identified baseline NPDR severity as the most significant predictor of PDR development over 48 months (hazard ratio [HR] [95% confidence interval {CI}] of 2.69 (2.65-2.72) for moderate vs mild NPDR and 6.51 (6.47-6.55) for severe vs mild NPDR). Cumulative incidence (95% CI) of PDR was 7.9% (7.4%-8.3%), 20.9%, (20.0%-21.7%) and 46.8% (44.4%-49.2%) over 48 months in eyes with mild, moderate, and severe NPDR at baseline, respectively. Among treated eyes with baseline severe NPDR, cumulative incidence of PDR at 48 months was 50.1% in eyes treated with laser (n = 546; HR [95% CI] vs no treatment: 0.8 [0.7-1.0]), 27.4% in eyes treated with anti-VEGF (n = 923; HR [95% CI]: 0.4 [0.4-0.5]), and 25.6% in eyes treated with anti-VEGF plus laser (n = 293; HR [95% CI]: 0.5 [0.4-0.7]) compared with 49.9% in eyes with no treatment (n = 8930). CONCLUSIONS: DME and PDR development rates increased with increasing baseline NPDR severity. Approximately half of anti-VEGF‒naive eyes with severe NPDR progressed to PDR within 4 years in US clinical practice. The progression rate from severe NPDR to PDR was approximately halved with anti-VEGF versus no treatment.

Multimodal dataset using OCTA and fundus images for the study of diabetic retinopathy.

This article presents a Multimodal database consisting of 222 images of 76 people wherein 111 are OCTA images and 111 are color fundus images taken at the Natasha Eye Care and Research Institute of Pune Maharashtra, India. Nonmydriatic fundus images were acquired using a confocal SLO widefield fundus imaging Eidon machine. Nonmydriatic OCTA images were acquired using the Optovue Avanti Edition machine Initially, the clinical approach described in this article was used to obtain the retinal images. Following that, the dataset was categorized by two experienced eye specialists. To identify instances of Non-Proliferative Diabetic Retinopathy (NPDR) with their various stages, medical professionals and scholars can use this data. Research scholars and ophthalmologists can utilize the data created to develop the initial stages of automated identification techniques for diabetic retinopathy (DR).

Optical Coherence Tomography Angiography as a Diagnostic Tool for Diabetic Retinopathy.

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes mellitus, leading to visual impairment if left untreated. This review discusses the use of optical coherence tomography angiography (OCTA) as a diagnostic tool for the early detection and management of DR. OCTA is a fast, non-invasive, non-contact test that enables the detailed visualisation of the macular microvasculature in different plexuses. OCTA offers several advantages over fundus fluorescein angiography (FFA), notably offering quantitative data. OCTA is not without limitations, including the requirement for careful interpretation of artefacts and the limited region of interest that can be captured currently. We explore how OCTA has been instrumental in detecting early microvascular changes that precede clinical signs of DR. We also discuss the application of OCTA in the diagnosis and management of various stages of DR, including non-proliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), diabetic macular oedema (DMO), diabetic macular ischaemia (DMI), and pre-diabetes. Finally, we discuss the future role of OCTA and how it may be used to enhance the clinical outcomes of DR.

Systemic Inflammatory Mediator Levels in Non-Proliferative Diabetic Retinopathy Patients with Diabetic Macular Edema.

PURPOSE: To study the systemic inflammatory mediator levels in non-proliferative diabetic retinopathy (NPDR) patients with diabetic macular edema (DME) and explore the correlation between systemic inflammatory mediators and DME. METHODS: In this prospective study, we included 25 patients without diabetes (control group) and 75 patients with type 2 diabetes mellitus (diabetic group). According to fundus examination, the diabetic group patients were divided into: diabetic patients without diabetic retinopathy (DR) (Non-DR group), NPDR patients without DME (Non-DME group), and NPDR patients with DME (DME group). Serum levels of a broad panel of inflammatory mediators were analysed by multiplex protein quantitative detection technology based on a flow cytometry detection system. RESULTS: The interferon-γ (IFN-γ) levels were significantly higher in DME group and Non-DME group as compared to control group (p = 0.023 and p = 0.033) and Non-DR group (p = 0.009 and p = 0.015). Significantly higher values were obtained in DME group and Non-DME group as compared to control group for the interleukin-8 (IL-8) (p = 0.003 and p = 0.003). The IL-23 levels were significantly elevated in DME group and Non-DR group than in Non-DME group (p = 0.013 and p = 0.004). The diabetic group had significantly higher serum levels of IL-8 and IL-33 (p = 0.001 and p = 0.011), and lower serum levels of tumor necrosis factor-α (TNF-α) (p = 0.027) in comparison with control group. CONCLUSIONS: The changed levels of serum inflammatory mediators suggest that the systemic inflammatory mediators are involved in the pathogenesis of NPDR patients with DME. Such effects can guide clinical monitoring, diagnostic and therapeutic approaches for DME patients at an early stage.

Compound anisodine combined with retinal laser photocoagulation for the treatment of severe non-proliferative diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the clinical efficacy of the compound anisodine combined with retinal laser photocoagulation in the treatment of severe non-proliferative diabetic retinopathy(NPDR). METHODS: According to the retrospective study, totally 120 eyes of patients with severe NPDR who admitted to Daxing Teaching Hospital Affiliated to Capital Medical University from May 2023 to July 2023 were selected. The patients were divided into the observation group and the control group according to treatment methods, with 60 eyes in each group. The observation group was treated with panretinal photocoagulation combined with the compound anisodine injection. The control group was only treated with panretinal photocoagulation. The optical coherence tomography angiography(OCTA)and optical coherence tomography(OCT)were used to quantitatively analyze the fundus retinal structure and blood flow. Furthermore, the best corrected visual acuity(BCVA), superficial vascular density(SVD), deep vascular density(DVD), choroidal blood flow density and central macular foveal retinal thickness(CMT)were compared before treatment and at 1 d, 1 and 2 mo after treatment.RESULTS:At 2 mo postoperatively, the rate of visual improvement and the BCVA in the observation group of patients were significantly better than those of the control group, and the incidence of macular edema in the observation group was significantly lower than the control group(P&#x003C;0.05). The BCVA at 1 and 2 mo after treatment were significantly higher than those before treatment in both groups(P&#x003C;0.05). The SVD in the observation group was better than the control group at 1 d, 1 and 2 mo after treatment(all P&#x003C;0.05). The DVD and choroidal flow density in the observation group were better than those of the control group at 1 d after treatment(all P&#x003C;0.05). The CMT of the observation group was smaller than that of the control group at 1 d after treatment(P&#x003C;0.05).CONCLUSION:Compound anisodine can effectively improve the fundus microcirculation after panretinal photocoagulation and reduce the incidence of macular edema, thus promoting the visual function.

Optical coherence tomography angiography manifestations of different degrees of nonproliferative diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the differences in varying stages of non-proliferative diabetic retinopathy(NPDR)using optical coherence tomography angiography(OCTA).METHODS: Cross-sectional study. A total of 77 cases(77 eyes)of diabetic patients were included, and they were divided into non-diabetic retinopathy(NDR; 23 eyes)and non-proliferative diabetic retinopathy(NPDR; 54 eyes)groups, further subdivided into mild NPDR(20 eyes), moderate NPDR(20 eyes), and severe NPDR(14 eyes). Foveal avascular zone(FAZ)area, superficial and deep capillary plexus densities(SSP and DSP), and visual acuity(LogMAR)were compared between NDR and NPDR groups. Furthermore, the visual acuity, FAZ area and levels of SSP and DSP were compared in different degrees of NPDR. Correlation analysis were conducted to elucidate relationships between FAZ area, visual acuity, SSP, DSP, and severity of the disease.RESULTS: Compared with the NDR group, the visual acuity(LogMAR)and macular FAZ area increased, while SSP and DSP were decreased in the NPDR group(P&#x0026;#x003C;0.05); there were significant differences in visual acuity, FAZ area and SSP and DSP levels in different degrees of NPDR(P&#x0026;#x003C;0.05). Visual acuity(LogMAR)and FAZ area displayed a positive correlation with the severity of disease, while SSP and DSP showed a negative correlation.CONCLUSION: With the progression of NPDR, the visual acuity(LogMAR)and FAZ area increased, and the SSP and DSP decreased.

The effect of moderate-intensity aerobic exercise on non-proliferative diabetic retinopathy in type II diabetes mellitus patients: A clinical trial.

INTRODUCTION: Diabetic retinopathy (DR) is one of the most threatening complications of diabetes and a leading cause of visual loss in working-age population. Although exercise is beneficial in diabetes, previous studies have showed contradictory and inconclusive results on how it effects DR. In this study, we aimed to investigate the effect of moderate-intensity aerobic exercise on non-proliferative diabetic retinopathy. MATERIALS & METHODS: In this before-after clinical trial, 40 patients with diabetic retinopathy were enrolled by convenient sampling method in Shahid Labbafinejad Hospital in Tehran during 2021-2022. Before the intervention, central macular thickness (CMT, microns) measured by optical coherence tomography (OCT) and fasting blood sugar (FBS, mg/dl) were obtained. Then, patients took part in a 12-week moderate-intensity aerobic exercise (3 sessions per week, each session 45 min). Data were analyzed using SPSS version 26.0. RESULTS: Out of 40 examined patients, 21 (52.5 %) were male and 19 (47.5 %) were female. The mean age of the patients was 50.8 years. The mean rank of FBS (mg/dl) significantly decreased from 21.12 before the exercise to 8.75 after the exercise (p < 0.001). Also, the mean rank of CMT (microns) showed a significant decrease from 21.11 before the intervention to 16.20 after the exercise (p < 0.001). There was a significant positive correlation between patients' age and FBS (mg/dl) before (rho = 0.457, p = 0.003) and after (rho = 0.365, p = 0.021) the intervention. Also, a significant positive correlation was found between patients' age and CMT (microns) before (rho = 0.525, p = 0.001) and after (rho = 0.461, p = 0.003) moderate exercise. CONCLUSION: Moderate-intensity aerobic exercise leads to lower FBS (mg/dl) and CMT (microns) in patients with diabetic retinopathy, so it may be beneficial for diabetic patients to avoid sedentary lifestyle.

Potential impact of epicardial fat thickness, pentraxin-3, and high-sensitive C-reactive protein on the risk of non-proliferative diabetic retinopathy.

Purpose: We tried to clarify the potential association between systemic inflammatory markers like high-sensitive C-reactive protein (Hs-CRP), pentraxin-3 (PTX3), and epicardial fat thickness (EFT) with the non-proliferative diabetic retinopathy (NPDR) in patients with type 2 diabetes mellitus (T2D). Previous studies dealt with diabetic retinopathy as a whole entity rather than early stages of diabetic retinopathy. Early detection of various determinants of NPDR is prioritized in clinical practice. Methods: A case-control study was conducted at Mansoura University Hospital, included 207 Egyptian subjects divided into 3 groups; 69 diabetic patients without retinopathy, 69 diabetic patients with NPDR, and 69 healthy control subjects. Participants were subjected to clinical history taking, physical examination, and laboratory assessment of Hs-CRP and plasma PTX3. Transthoracic echocardiography was applied to estimate EFT. Results: Hs-CRP, PTX3, and EFT were significantly higher in patients with T2D without retinopathy than control cohort (p = 0.033, p < 0.00 and p < 0.00, respectively). Moreover, patients with NPDR showed significantly higher values of Hs-CRP, PTX3, and EFT than diabetic comparators without retinopathy (p = 0.002, p = 0.012, and p < 0.001, respectively). Although, NPDR was positively correlated with Hs-CRP, PTX3, and EFT (p < 0.001), Hs-CRP was not an independent determinant of NPDR meanwhile, EFT (OR = 1.094, 95%CI: 1.036-1.154, P = 0.001) and PTX3 (OR = 16.145, 95%CI: 1.676-155.551, P = 0.016) were. Conclusion: Plasma pentraxin-3 and epicardial fat thickness showed more significant association with NPDR than high-sensitive C-reactive protein in patients with type 2 diabetes mellitus.

The comparative effects of oral Chinese patent medicines in non-proliferative diabetic retinopathy: A Bayesian network meta-analysis of randomized controlled trials.

Background: Non-proliferative diabetic retinopathy (NPDR), a common diabetic complication with high morbidity, is featured by impaired visual function and fundus lesions. It has been reported that oral Chinese patent medicines (OCPMs) may improve visual acuity and fund signs. However, the best possible OCPMs for NPDR remain questionable and merit further investigation. Methods: From inception to October 20, 2022, seven databases were searched for eligible randomized controlled trials (RCTs). The outcomes were clinical effective rate, visual acuity, visual field gray value, microaneurysm volume, hemorrhage area, macular thickness, and adverse events rate. The revised Cochrane risk-of-bias tool (ROB 2) was used to assess the quality of the included studies. Network meta-analysis was performed using R 4.1.3 and STATA 15.0 software. Results: We included 42 RCTs with 4,858 patients (5,978 eyes). The Compound Danshen Dripping Pill (CDDP) combined with calcium dobesilate (CD) had the most improvement in clinical efficacy rate (SUCRA, 88.58%). The Compound Xueshuantong Capsule (CXC) combined with CD may be the best intervention (SUCRA, 98.51%) for the improvement of visual acuity. CDDP alone may be the most effective treatment option (SUCRA, 91.83%) for improving visual field gray value. The Hexuemingmu Tablet (HXMMT) and Shuangdan Mingmu Capsule (SDMMC) combined with CD may be the most effective treatment for reducing microaneurysm volume and hemorrhage area (SUCRA, 94.48%, and 86.24%), respectively. Referring to reducing macular thickness, CXC combined with CD ranked first (SUCRA, 86.23%). Moreover, all OCPMs did not cause serious adverse reactions. Conclusion: OCPMs are effective and safe for NPDR. CDDP alone, and combined with CD, may be the most effective in improving visual field gray value and clinical efficacy rate, respectively; CXC combined with CD may be the best in enhancing BCVA and reducing macular thickness; HXMMT and SDMMC combined with CD, maybe the most effective regarding microaneurysm volume and hemorrhage area, respectively. However, the reporting of methodology in the primary study is poor, potential biases may exist when synthesizing evidence and interpreting the results. The current findings need to be confirmed by more large-sample, double-blind, multi-center RCTs of rigorous design and robust methods in the future. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022367867.

Intraretinal Microvascular Abnormalities and Venous Beading Have Different Genetic Profiles in Caucasian Patients with Non-Proliferative Diabetic Retinopathy.

Diabetic Retinopathy (DR) is a leading cause of preventable visual impairment in the working age population. Despite the increasing prevalence of DR, there remain gaps in our understanding of its pathophysiology. This is a prospective case-control study comparing the genetic profiles of patients with no DR vs. non-proliferative DR (NPDR) focusing on intraretinal microvascular abnormalities (IRMA) and venous beading (VB) in Caucasians. A total of 596 participants were recruited to the study; 199 with moderate/severe NPDR and 397 with diabetes for at least 5 years without DR. Sixty-four patients were excluded due to technical issues. In total, 532 were analysed; 181 and 351 were in the NPDR group and no DR group, respectively. Those with severe IRMA and VB had distinctly different genetic profiles from each other and from the no DR group, which further supports the theory that these two features of DR might have different etiologies. This also suggests that IRMA and VB are independent risk factors for the development of PDR and may have different pathophysiologies. If these findings are confirmed in larger studies, this could pave the way for personalised treatment options for those more at risk of developing different features of NPDR.

A Regression-Based Approach to Diabetic Retinopathy Diagnosis Using Efficientnet.

The aim of this study is to develop a computer-assisted solution for the efficient and effective detection of diabetic retinopathy (DR), a complication of diabetes that can damage the retina and cause vision loss if not treated in a timely manner. Manually diagnosing DR through color fundus images requires a skilled clinician to spot lesions, but this can be challenging, especially in areas with a shortage of trained experts. As a result, there is a push to create computer-aided diagnosis systems for DR to help reduce the time it takes to diagnose the condition. The detection of diabetic retinopathy through automation is challenging, but convolutional neural networks (CNNs) play a vital role in achieving success. CNNs have been proven to be more effective in image classification than methods based on handcrafted features. This study proposes a CNN-based approach for the automated detection of DR using Efficientnet-B0 as the backbone network. The authors of this study take a unique approach by viewing the detection of diabetic retinopathy as a regression problem rather than a traditional multi-class classification problem. This is because the severity of DR is often rated on a continuous scale, such as the international clinical diabetic retinopathy (ICDR) scale. This continuous representation provides a more nuanced understanding of the condition, making regression a more suitable approach for DR detection compared to multi-class classification. This approach has several benefits. Firstly, it allows for more fine-grained predictions as the model can assign a value that falls between the traditional discrete labels. Secondly, it allows for better generalization. The model was tested on the APTOS and DDR datasets. The proposed model demonstrated improved efficiency and accuracy in detecting DR compared to traditional methods. This method has the potential to enhance the efficiency and accuracy of DR diagnosis, making it a valuable tool for healthcare professionals. The model has the potential to aid in the rapid and accurate diagnosis of DR, leading to the improved early detection, and management, of the disease.

Automated machine learning-based classification of proliferative and non-proliferative diabetic retinopathy using optical coherence tomography angiography vascular density maps.

PURPOSE: The study aims to classify the eyes with proliferative diabetic retinopathy (PDR) and non-proliferative diabetic retinopathy (NPDR) based on the optical coherence tomography angiography (OCTA) vascular density maps using a supervised machine learning algorithm. METHODS: OCTA vascular density maps (at superficial capillary plexus (SCP), deep capillary plexus (DCP), and total retina (R) levels) of 148 eyes from 78 patients with diabetic retinopathy (45 PDR and 103 NPDR) was used to classify the images to NPDR and PDR groups based on a supervised machine learning algorithm known as the support vector machine (SVM) classifier optimized by a genetic evolutionary algorithm. RESULTS: The implemented algorithm in three different models reached up to 85% accuracy in classifying PDR and NPDR in all three levels of vascular density maps. The deep retinal layer vascular density map demonstrated the best performance with a 90% accuracy in discriminating between PDR and NPDR. CONCLUSIONS: The current study on a limited number of patients with diabetic retinopathy demonstrated that a supervised machine learning-based method known as SVM can be used to differentiate PDR and NPDR patients using OCTA vascular density maps.

Preliminary clinical application of Keluoxin capsule for treatment of moderate and severe non-proliferative diabetic retinopathy / 中华眼底病杂志

Objective:To observe the safety and efficacy of Keluoxin capsules in the treatment of moderate to severe non-proliferative diabetic retinopathy (NPDR).Methods:An open-label, multi-center, single-arm, phase Ⅱa clinical trial. From May 2014 to December 2016, the patients diagnosed with moderate to severe NPDR who received Keroxin treatment in General Hospital of Central Theater Command, Affiliated Eye Hospital to Nanchang University, Xiyuan Hospital of China Academy of Chinese Medical Sciences, and Eye Hospital China Academy of Chinese Medical Sciences were divided into moderate NPDR group and severe NPDR group. The baseline data of the patients were obtained, best-corrected visual acuity (BCVA), optical coherence tomography, fundus fluorescein angiography and fundus photography were performed. On the basis of maintaining the original diabetes treatment, all patients took Keluoxin capsules orally for 24 weeks; 24 weeks after treatment was used as the time point for evaluating the efficacy. BCVA letters, central macular thickness (CMT) and 6 mm diameter total macular volume (TMV), retinal vascular leakage area, and retinal non-perfusion (RNP) area within an average diameter of 6 mm were compared between the two groups at baseline and 24 weeks after treatment. Independent sample Mann-Whitney U test was used to compare continuous variables between groups. Categorical data were compared by χ2 test. Results:A total of 60 NPDR patients and 60 eyes were included, 9 cases were lost to follow-up, and 51 cases and 51 eyes were finally included, including 37 eyes in the moderate NPDR group and 14 eyes in the severe NPDR group, respectively. At baseline, BCVA in moderate NPDR group and severe NPDR group were (80.1±6.8), (81.4±6.3) letters, respectively. CMT were (249.5±32.1), (258.9±22.2) μm, respectively. TMV were (8.79±1.09), (8.95±1.31) mm 3, respectively. Retinal vascular leakage areas were (7.69±10.63), (10.45±7.65) mm 2, respectively. RNP area were (2.48±5.74), (10.63±20.06) mm 2, respectively. There were 11 (29.7%, 11/37) and 4 (28.6%, 4/14) eyes with diabetic macular edema (DME), respectively; 24 weeks after treatment, BCVA in moderate NPDR group and severe NPDR group increased by (1.3±5.2), (3.2±3.0) letters, respectively. Compared with baseline, there was a statistically significant difference in the severe NPDR group ( t=-3.986, P=0.033). CMT were (252.1±45.6), (269.8± 57.2) μm, respectively. There were no significant differences compared with baseline ( t=-0.567, -0.925; P>0.05). TMV were (9.96±1.16), (10.09±1.32) mm 3, respectively. There were no significant differences compared with baseline ( t=-0.996, -1.304; P>0.05). Retinal vascular leakage area decreased (0.19±6.90), (1.98±7.52) mm 2, respectively. There were no significant differences compared with baseline ( t=0.168, 0.983; P>0.05). RNP area were (3.01±6.47), (10.36±19.57) mm 2, respectively. Compared with baseline, the differences were statistically significant ( t=-1.267, 0.553; P>0.05). There were 8 (21.6%, 8/37) and 3 (21.4%, 3/14) eyes with DME, respectively. Compared with baseline, the difference was statistically significant ( χ2=11.919, 4.571; P=0.001, 0.033). Conclusion:Keluoxin capsules can stabilize or improve BCVA, CMT, TMV and RNP area in patients with moderate and severe NPDR, and reduce the area of retinal vascular leakage.

Application of OCTA in screening microvascular changes in non-proliferative diabetic retinopathy / 西安交通大学学报(医学版)

【Objective】 To investigate the clinical effect of optical coherence tomography angiograph (OCTA) applied in retinal microvascular screening in patients with non-proliferative diabetic retinopathy (NPDR). 【Methods】 Thirty patients with NPDR (NPDR group) diagnosed at The Third Affiliated Hospital of Soochow University and 30 healthy volunteers (control group) were selected to receive OCTA examination. The area, perimeter, and circularity of the fovea avascular zone (FAZ) were measured and blood flow density in the superior, inferior, nasal, temporal quadrants of the macular superficial retinal capillary layer (SCP) and the peripapillary radial capillary layer (RPC) of the optic disc were quantified. 【Results】 In NPDR group, blood flow density in the four quadrants of macular SCP and RPC were decreased significantly compared with that in control group (43.68±3.03 vs. 46.98±3.04, 42.79±3.17 vs. 50.45±2.25, 43.21±2.67 vs. 47.44±2.42, 44.21±3.22 vs. 51.72±5.32, 46.43±3.54 vs. 53.02±2.62, 45.97±3.67 vs. 52.53±2.82, 44.63±2.73 vs. 48.19±3.67, 41.73±3.15 vs. 45.12±3.31) (all P<0.01). The area and perimeter of FAZ in NPDR group were significantly higher than those in control group [(0.50±0.06 vs. 0.43±0.47) mm2, (3.10±0.21 vs. 2.87±0.22) mm]. The circularity of FAZ was significantly lower in NPDR group than in control group [(0.63±0.05 vs. 0.67±0.05)%, P<0.01]. 【Conclusion】 OCTA can detect early retinal microstructure changes in NPDR, and thus can be used as an auxiliary screening of NPDR to provide information for early diagnosis and treatment.

Factors affecting the risk of non-proliferative diabetic retinopathy among patients with type 2 diabetic mellitus / 预防医学

Objective@#To investigate the factors affecting the development of non-proliferative diabetic retinopathy (NPDR) among patients with type 2 diabetic mellitus (T2DM), so as to provide insights into manangement of NPDR.@*Methods@#T2DM patients without obvious eye discomfort at ages of 18 years and older admitted to Department of Endocrinology, Jining No. 1 People's Hospital during the period from December 2019 to May 2021 were enrolled. Participants' demographics, smoking, alcohol consumption, medical history of diabetes and use of medicines were collected, and the height, weight and blood pressure were measured. The levels of glycosylated hemoglobin (HbA1c), fasting blood glucose, blood C-peptide, lipid and creatinine were tested, and retinopathy was examined with a non-mydriatic fundus camera. The factors affecting the development of NPDR were identified among T2DM patients using a multivariable logistic regression model.@*Results@#A total of 486 T2DM patients were enrolled, including 354 men (72.84%), with a median age of 48.00 (15.25) years, and median diabetes duration of 35.00 (104.25) months. The prevalence of NPDR was 19.34% among the participants. multivariable logistic regression analysis identified an educational level of senior high school and above (OR=0.546, 95%CI: 0.325-0.918), duration of diabetes (OR=1.008, 95%CI: 1.005-1.012), HbA1c (OR=1.183, 95%CI: 1.034-1.354) and use of non-sulfonylurea insulin secretagogues (OR=1.859, 95%CI: 1.082-3.196) as factors affecting the risk of NPDR among T2DM patients.@*Conclusion@#A high risk of NPDR is found among T2DM patients with a low educational level, long duration of diabetes, poor HbA1c control and use of non-sulfonylurea insulin secretagogues.

Integrated Analysis of Metabolomics and Lipidomics in Plasma of T2DM Patients with Diabetic Retinopathy.

Diabetic retinopathy (DR) is a major cause of blindness worldwide and may be non-proliferative (NPDR) or proliferative (PDR). To Investig.gate the metabolomic and lipidomic characteristics of plasma in DR patients, plasma samples were collected from patients with type 2 diabetes mellitus (DR group) with PDR (n = 27), NPDR (n = 18), or no retinopathy (controls, n = 21). Levels of 54 and 41 metabolites were significantly altered in the plasma of DR patients under positive and negative ion modes, respectively. By subgroup analysis, 74 and 29 significantly changed plasma metabolites were detected in PDR patients compared with NPDR patients under positive and negative ion modes, respectively. KEGG analysis indicated that pathways such as biosynthesis of amino acids and neuroactive ligand-receptor interaction were among the most enriched pathways in altered metabolites in the DR group and PDR subgroup. Moreover, a total of 26 and 41 lipids were significantly changed in the DR group and the PDR subgroup, respectively. The panel using the 29-item index could discriminate effectively between diabetic patients with and without retinopathy, and the panel of 22 items showed effective discrimination between PDR and NPDR. These results provide a basis for further research into the therapeutic targets associated with these metabolite and lipid alterations.