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PurposeMethodsResultsConclusionGlucagon-like peptide-1 receptor agonists (GLP-1RA) are used to treat type 2 diabetes mellitus (DM) by augmenting insulin release and sensitivity. We assessed the overall risk for development of vision-threatening diabetic retinopathy (VTDR), proliferative diabetic retinopathy (PDR), and diabetic macular edema (DME), among GLP-1RA users.A retrospective cohort of patients with NPDR newly started on a GLP-1RA from a national insurance claims database was compared to a cohort of patients treated with other oral anti-diabetic agents and matched for age, sex, race, index year, and number of active diabetic medications. Exclusions occurred for < 2 years in the database before diagnosis; prior diagnoses of PDR, DME, vitreous hemorrhage, and/or other retinal vascular diseases; and prior intraocular treatment for VTDR.A total of 6093 users of GLP-1RA were matched to 14,122 controls. In the GLP-1RA cohort, 632 (10.1%), 76 (1.2%), and 544 (8.9%) patients progressed to VTDR, PDR, or DME, respectively. This is compared to 1332 (9.5%) VTDR, 165 (1.2%) PDR, or 1148 (8.1%) DME in the control group. Accounting for underlying DM severity with IPTW, no difference in hazard was seen in the GLP-1RA cohort compared to controls for progression to VTDR (HR = 1.02, 95%CI: 0.92–1.14 p = 0.69), DME (HR = 1.06, 95%CI: 0.95–1.1.9, p = 0.31), or PDR (HR = 0.81, 95%CI: 0.58–1.12, p = 0.20).We found no difference in the risk for vision-threatening diabetic retinopathy, nor for its component diseases, DME or PDR, with GLP-1RA use compared to other oral anti-hyperglycemic agents in patients with NPDR. [ABSTRACT FROM AUTHOR]

Background: We aimed to evaluate microaneurysms (MAs) after treatment with anti-vascular endothelial growth factor (anti-VEGF) therapy to understand causes of chronic edema and anti-VEGF resistance. Methods: Patients with non-proliferative diabetic retinopathy, with or without macular edema were recruited. Optical coherence tomography angiography (OCTA) MAs-related parameters were observed, including the maximum diameter of overall dimensions, material presence, and flow signal within the lumen. OCTA parameters also included central macular thickness (CMT), foveal avascular zone, superficial and deep capillary plexuses, and non-flow area measurements on the superficial retinal slab. Results: Overall, 48 eyes from 43 patients were evaluated. CMT differed significantly between the diabetic macular edema (DME) and non-DME (NDME) groups at 1st, 2nd, 3rd, and 6th months of follow-up (P < 0.001; <0.001; 0.003; <0.001, respectively). A total of 55 and 59 MAs were observed in the DME (mean = 99.40 ± 3.18 μm) and NDME (mean maximum diameter = 74.70 ± 2.86 μm) groups at baseline, respectively (significant between-group difference: P < 0.001). Blood flow signal was measurable for 46 (83.6%) and 34 (59.3%) eyes in the DME and NDME groups, respectively (significant between-group difference: P < 0.001). Conclusions: Compared to the NDME group, the DME group had larger MAs and a higher blood-flow signal ratio. Following anti-VEGF therapy, changes in the diameter of MAs were observed before changes in CMT thickness. Highlights: Microaneurysms (MAs) in diabetic macular edema (DME) are not fully understood. We utilized optical coherence tomography angiography (OCTA) to assess the parameters of MAs. Changes in MAs diameter reflected the therapeutic effects of Anti-Vascular Endothelial Growth Factor (anti-VEGF) therapeutic effects. A limited number of MAs exhibited wall reflex shifts, as well as low content and blood flow signals. Anti-VEGF therapy can enhance rich blood flow signals, however, it does not improved content proportion. [ABSTRACT FROM AUTHOR]

Abstract Background We aimed to evaluate microaneurysms (MAs) after treatment with anti-vascular endothelial growth factor (anti-VEGF) therapy to understand causes of chronic edema and anti-VEGF resistance. Methods Patients with non-proliferative diabetic retinopathy, with or without macular edema were recruited. Optical coherence tomography angiography (OCTA) MAs-related parameters were observed, including the maximum diameter of overall dimensions, material presence, and flow signal within the lumen. OCTA parameters also included central macular thickness (CMT), foveal avascular zone, superficial and deep capillary plexuses, and non-flow area measurements on the superficial retinal slab. Results Overall, 48 eyes from 43 patients were evaluated. CMT differed significantly between the diabetic macular edema (DME ) and non-DME (NDME) groups at 1st, 2nd, 3rd, and 6th months of follow-up (P

Abstract 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.

Abstract 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.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract 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.

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. [ABSTRACT FROM AUTHOR]

Background. A promising direction of modern medicine is to increase the accuracy of predicting the possible outcomes of the disease, its complications or relapses. Several factors are important for the progression of diabetic retinopathy (DR) in type 2 diabetes (T2D), among which glycated hemoglobin, duration of T2D and others are discussed. The purpose was to determine the possibilities of predicting the progression of initial non-proliferative diabetic retinopathy (NPDR) based on the blood glucose, glycated hemoglobin and cholesterol indicators. Materials and methods. Three hundred and fifty-eight patients (358 eyes) with T2D and DR were examined and divided into groups: the first one — with NPDR (189 eyes), the second one — with pre-proliferative DR (96 eyes) and the third one — with proliferative DR (73 eyes). Patients were examined for 2 years using ophthalmological methods; serum fasting glucose, glycated hemoglobin and total cholesterol were determined by colorimetric method. The analysis of the research results was carried out in the EZR v. 1.54 package (Austria). Results. There was no significant difference between the groups at baseline in terms of age and T2D duration; these indicators were not associated with the DR progression (p = 0.512 and p = 0.339, respectively) as well. The independent risk factors for the NPDR progression in the univariate analysis were the content of blood glucose (p = 0.002; odds ratio (OR) = 1.08; 95% confidence interval (CI) 1.03–1.13) and total cholesterol (p < 0.001; OR = 2.02; 95% CI 1.53–2.6 %). Based on the glycated hemoglobin blood level, a logistic model of the NPDR progression was constructed. The area under the receiver operating characteristic curve was 0.84 (95% CI 0.80–0.88), which indicated a strong association with the NPDR progression. The threshold for predicting the glycated hemoglobin level was 8.9 % with a sensitivity of 75.6 % (95% CI 68.6–82 %) and a specificity of 79.9 % (95% CI 73.5–85.4 %). Conclusions. It was found that the content of glycated hemoglobin in the blood above 8.9 % is an independent factor for the NPDR progression, which allowed to build a prognostic model with a very good quality of prognosis. [ABSTRACT FROM AUTHOR]

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

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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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).

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. [ABSTRACT FROM AUTHOR]

Diabetic Retinopathy (DR) has been considered one of the leading causes of blindness or vision loss in the long run. Retinal microvasculature formed due to diabetes mellitus may lead to this sickness case. Therefore, early identification of abnormalities in retinal images will help not only in curing but also in preventing or delaying vision loss. The main objective of this research is to detect and classify the DR stages as non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) via multifractal geometry, as well as automating the classification process by enforcing multistage artificial neural network. Two hundred and seventy eyes have been used for normal, diabetic without DR, non-proliferative diabetic retinopathy (Mild to Moderate), and PDR. The macula superficial capillary plexus of the subjects' images had been imaged using the swept-source optical coherence tomography angiography (SS-OCTA). The proposed classification technique based on a multistage artificial neural network has achieved accuracy with 98.1%. It provides a detecting method for the early diabetic retinopathy stages before the precipitate treatment. [ABSTRACT FROM AUTHOR]

AIM: To assess the reproducibility of macular perfusion parameters in non-proliferative diabetic retinopathy (NPDR) patients measured by different examiners and two different sweep modes of optical coherence tomography angiography (OCTA). METHODS: Ninety-eight (98 eyes) patients with NPDR were included in this study. All participates were performed three times using Cirrus OCTA with Angiography 3×3 mm2 and 6×6 mm2 sweep mode by two examiners. The macular foveal avascular zone (FAZ) and vessel density (VD) in the superficial retinal layer (SRL) were measured. The reproducibility of the measurements was evaluated with intraclass correlation coefficients (ICC) and coefficient of variation (CoV). RESULTS: The intra-mode ICCs of Angiography 3×3 mm2 and 6×6 mm2 sweep mode were 0.957 to 0.959 and 0.964 to 0.977, respectively; and the inter-mode ICCs were 0.962 to 0.970. The intra-examiner ICCs of macular perfusion parameters were >0.950; and the inter-examiner ICCs were 0.928 to 0.969. All CoVs were

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. [ABSTRACT FROM AUTHOR]

PurposeTo evaluate the utility of different optical coherence tomography angiography scan protocols in evaluating retinal changes in non-proliferative diabetic retinopathy.MethodsPatients were imaged with the RTVue XR Avanti OCT 3 mm × 3 mm and 6 mm × 6 mm "Angio Retina" scan protocols. Ability to clearly delineate the foveal avascular zone (FAZ), FAZ remodeling, microaneurysms, capillary nonperfusion, motion, and doubling artifacts were evaluated.ResultsForty-six eyes from 27 patients were enrolled. Eighty-nine percent of 3 mm × 3 mm versus 59% of 6 mm × 6 mm scans clearly delineated the FAZ (P = 0.001). Eighty percent of 3 mm × 3 mm versus 43% of 6 mm × 6 mm scans demonstrated FAZ remodeling (P = 0.0002). Microaneurysms were detected by 57% of 6 mm × 6 mm and 35% of 3 mm × 3 mm scans (P = 0.003). Capillary nonperfusion was detected in 87% of 3 mm × 3 mm scans versus 89% of 6 mm × 6 mm scans (P = 0.99). No significant differences were noted in the incidence of artifacts between the scan sizes (motion artifact P = 0.29 and doubling artifact P = 0.29).Conclusion3 mm × 3 mm scan delineated FAZ and remodeling better than 6 mm × 6 mm scan, likely because of its higher scan density. 6 mm × 6 mm scans detected microaneurysms more readily than 3 mm × 3 mm, likely because of its larger scan area. There were utility for both 3 mm × 3 mm and 6 mm × 6 mm scans when evaluating these patients.

Background: Diabetes mellitus (DM) is a disease characterized by chronic hyperglycemia and a cascade of pathological vascular alterations leading to diabetic retinopathy (DR) and diabetic macular edema (DME). Purpose: To compare clinical characteristics in patients treated with aflibercept only and in those treated with aflibercept plus hyperbaric oxygen (HBO) therapy for DME. Material and Methods: This open-label case-control study involved 91 type 2 diabetic (DM2) patients with non-proliferative DR and DME. Patients of the aflibercept-only group received a monthly intravitreous aflibercept at a dose of 2 mg for 5 months. Patients of the aflibercept-plus-HBO group received a monthly intravitreous aflibercept at a dose of 2 mg for 3 months. In addition, the latter patients received ten HBO sessions in the period between the first and the third injections. All patients underwent a routine general clinical and eye examination. Results: At 3 months and 6 months, patients in the aflibercept-plus-HBO group showed improvements in visual acuity by 28.81% and 7.14%, respectively (р < 0.05), and retinal sensitivity to light by 24.44% and 19.5%, respectively (р < 0.05), with a reduction in the number of patients with DME by 84.56% and 51.13%, respectively (p < 0.05). Conclusion: Intravitreal aflibercept with adjunctive HBO provides improved efficacy of treatment for DME in patients with DM2, with reductions in (a) the number and risk of intravitreal injections, (b) drug load on the patient, and (c) treatment duration.

Diabetic Retinopathy (DR) is a consequence of long-term diabetes which affects the eyes. It causes affliction to the veins in the eyes causing raptures on the retina which can impact vision. If the condition is failed to be detected at an early stage, it can lead to complete vision loss. The conventional diagnosing cycle of DR using fundus images requires very skilled practitioners due to the minute nature of features of the anomalies which can even lead to misdiagnosis and is time consuming. Therefore, devising an automated method for the diagnosis of DR can assist individuals with diabetes to identify symptoms of DR at a very early stage. This research also encompasses the classification of the detected images into its corresponding 3 stages namely No Diabetic Retinopathy (No DR), Non-Proliferative Diabetic Retinopathy (NPDR) and Proliferative Diabetic Retinopathy (PDR) that can greatly aid in monitoring the dynamics of the key features including lesions, hemorrhages, and density of blood vessels. Deep learning algorithms has gotten to become a well-known method that can accomplish a wide variety of classification tasks. However, most of these methods are only efficient in classifying the various stages of DR with low accuracies notably, for the early stages. The devised algorithm in this research uses enriched images processing techniques, automatic hyperparameter tuning and neural network training strategies to provide more emphasis on the minute features for better prediction. The algorithm was tested and compared with modified Resnet50, VGG16, Mobilenetv2, Inceptionv3 and InceptionResnetv2 which gave a classification accuracy of 94.7%, 86.1%, 85.8%, 85.3% and 87% respectively with corresponding detection accuracies of 99.8%, 94%, 94.2%, 94.9% and 98.2% respectively on a test set of 508 images. Using the proposed algorithm, the results indicate Resnet50 based network gave superior performance for both detection and classification tasks. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

AIM: To observe the efficacy of addition and subtraction of Buyang Huanwu decoction in the adjuvant treatment of non-proliferative diabetic retinopathy of Qi-Yin deficiency and blood stasis and its effects on traditional Chinese medicine(TCM)syndromes and visual function level. METHODS: A total of 110 patients with non-proliferative diabetic retinopathy of Qi-Yin deficiency and blood stasis in our hospital between January 2017 and December 2019 were selected and divided into observation group(55 cases, 110 eyes)and control group(55 cases, 110 eyes). Patients in control group received conventional treatment according to the condition of patients with reference to relevant guidelines, and patients in observation group were combined with addition and subtraction of Buyang Huanwu decoction adjuvant therapy on this basis. The clinical efficacy after 3mo of treatment, and TCM syndromes scores, clinical indicators(macular edema score, macular retinal volume, macular foveal retinal thickness), visual function(best corrected visual acuity, average visual field sensitivity)and serum biochemical indicators [vascular endothelial growth factor(VEGF), hypoxia-inducible factor-1(HIF-1)] before treatment and 3mo after treatment were compared between the two groups.RESULTS: After 3mo of treatment, the total effective rate of treatment in observation group was significantly higher than that in control group(P

Non-proliferative diabetic retinopathy is a representative complication of diabetic patients and is known to be a major cause of impaired vision and blindness. There has been ongoing research on automatic detection of diabetic retinopathy, however, there is also a growing need for research on an automatic severity classification system. This study proposes an automatic detection system for pathological symptoms of diabetic retinopathy such as microaneurysms, retinal hemorrhage, and hard exudate by applying the Faster R-CNN technique. An automatic severity classification system was devised by training and testing a Random Forest classifier based on the data obtained through preprocessing of detected features. An experiment of classifying 228 test fundus images with the proposed classification system showed 97.8% accuracy. [ABSTRACT FROM AUTHOR]

Purpose: To identify the biomarkers in the critical period of development in diabetic retinopathy (DR) in Chinese with type 2 diabetes using targeted and untargeted metabolomics, and to explore the feasibility of their clinical application Methods: This case-control study described the differential metabolites between 83 Chinese type 2 diabetes mellitus (T2DM) samples with disease duration = 10 years and 27 controls matched cases. Targeted metabolomics using high-resolution mass spectrometry with liquid chromatography was performed on plasma samples of subjects. The results were compared to our previous untargeted metabolomics study and ELISA was performed to validate the mutual differential metabolites of targeted and untargeted metabolomics on plasma. Multiple linear regression analyses were performed to adjust for the significance of different metabolites between groups. Result: Mean age of the subjects was 66.3 years and mean T2DM duration was 16.5 years. By cross-validating with results from previous untargeted metabolomic assays, we found that L-Citrulline (Cit), indoleacetic acid (IAA), 1-methylhistidine (1-MH), phosphatidylcholines (PCs), hexanoylcarnitine, chenodeoxycholic acid (CDCA) and eicosapentaenoic acid (EPA) were the most distinctive metabolites biomarkers to distinguish the severity of DR for two different metabolomic approaches in our study. We mainly found that samples in the DR stage showed lower serum level of Cit and higher serum level of IAA compared with samples in the T2DM stage, while during the progression of diabetic retinopathy, the serum levels of CDCA and EPA in PDR stage were significantly lower than NPDR stage. Among them, 4 differential key metabolites including Cit, IAA, CDCA and EPA were confirmed with ELISA. Conclusion: This is the first study to compare the results of targeted and untargeted metabolomics via liquid chromatography-mass spectrometry to find the serum biomarkers which could reflect the metabolic variations among different stages of DR in Chinese. The progression of DR in Chinese at different critical stages was related to the serum levels of specific differential metabolites, of which there is a significant correlation between DR progression and increased IAA and decreased Cit, hexanoylcarnitine, CDCA, and EPA. However, larger studies are needed to confirm our results. Based on this study, it could be inferred that the accuracy of targeted metabolomics for metabolite expression in serum is to some extent higher than that of untargeted metabolomics. [ABSTRACT FROM AUTHOR]

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.

Introduction: The objective of this study is to evaluate diabetic patients with either normal fundus or non-proliferative diabetic retinopathy (NPDR) changes, examine retinal alterations during follow-up, and propose follow-up guidelines within a tertiary eye care setting., Methods: A five-year prospective longitudinal study is being conducted at the Diabetic Clinic of Al Ibrahim Eye Hospital/Isra Postgraduate Institute of Ophthalmology, Karachi. Induction for the research took place from October 2021 to March 2022, and a two-year preliminary report is presented here. Newly diagnosed type II diabetic patients with normal fundus or NPDR of any stage, irrespective of age, gender, or glycemic status, who were willing to participate and agreed to follow-ups, were included. Patients with proliferative diabetic retinopathy (PDR), diabetic macular edema (DME), fundus non-visibility, or systemic complications of diabetes were excluded., Results: A total of 251 patients were enrolled, consisting of 80 individuals with a normal fundus and 171 with different stages of NPDR, including mild (N=59), moderate (N=91), and severe (N=21) retinopathy. The incidence of progression from mild to moderate NPDR was noted to be 52.5%, with a median time of 3.5 months. Progression from moderate to severe NPDR occurred in 37.1% of cases, with a median time of 4.5 months. Similarly, DME developed in 5% of patients with mild NPDR over eight months, in 22.2% with moderate NPDR over seven months, and in 37.5% with severe NPDR over 4.4 months., Conclusion: This study emphasizes the urgent need to revise diabetic retinopathy (DR) monitoring protocols for our Pakistani (Southeast Asian) population. The rapid progression of NPDR and the high rates of DME development demand more frequent screenings. Current guidelines recommending annual screenings are inadequate. Biannual screenings for patients with a normal fundus or mild NPDR, and quarterly assessments for those with moderate or severe NPDR, are necessary., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Research Ethical Committee of Isra Postgraduate Institute of Ophthalmology issued approval REC/IPIO/2021/040-A. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Mahar et al.)

Background: Diabetes mellitus (DM) is a disease characterized by chronic hyperglycemia and a cascade of pathological vascular alterations leading to diabetic retinopathy (DR) and diabetic macular edema (DME). Purpose: To compare clinical characteristics in patients treated with aflibercept only and in those treated with aflibercept plus hyperbaric oxygen (HBO) therapy for DME. Material and Methods: This open-label case-control study involved 91 type 2 diabetic (DM2) patients with non-proliferative DR and DME. Patients of the aflibercept-only group received a monthly intravitreous aflibercept at a dose of 2 mg for 5 months. Patients of the aflibercept-plus-HBO group received a monthly intravitreous aflibercept at a dose of 2 mg for 3 months. In addition, the latter patients received ten HBO sessions in the period between the first and the third injections. All patients underwent a routine general clinical and eye examination. Results: At 3 months and 6 months, patients in the aflibercept-plus-HBO group showed improvements in visual acuity by 28.81% and 7.14%, respectively (p < 0.05), and retinal sensitivity to light by 24.44% and 19.5%, respectively (p < 0.05), with a reduction in the number of patients with DME by 84.56% and 51.13%, respectively (p < 0.05). Conclusion: Intravitreal aflibercept with adjunctive HBO provides improved efficacy of treatment for DME in patients with DM2, with reductions in (a) the number and risk of intravitreal injections, (b) drug load on the patient, and (c) treatment duration. [ABSTRACT FROM AUTHOR]

Background and Objectives: The aim of this study was to evaluate choroidal structure and vascularity indices in patients with non-proliferative diabetic retinopathy (NPDR). Materials and Methods: Sixty-three eyes from sixty-three patients were evaluated: 21 from healthy subjects, 20 with diabetes mellitus (DM) and no diabetic retinopathy (DR), and 22 with DM and non-proliferative diabetic retinopathy without diabetic macular edema (DME). Each patient underwent ocular examination, macular swept-source ocular coherence tomography (SS-OCT) imaging, glycemic control, and systemic high blood pressure (HBP) evaluation. Subfoveal choroidal thickness (SF-CT) was manually assessed on a line scan. Line scan OCT images were exported to ImageJ program. The areas under a 1.5, 3 and 6 mm horizontal line centered on the fovea were assessed by converting the OCT images to binary images, and total choroidal area (TCA), luminal area (LA), stromal area (SA), LA:SA ratio, and choroidal vascularity index (CVI) were evaluated. SF-CT and choroidal parameters were compared between groups, and correlations with ocular and systemic factors were analyzed. Results: SF-CT, TCA, LA, and SA were similar between groups. CVIs were significantly different between groups for all three studied areas (CVI-1.5: 66.21% vs. 66.06% vs. 63.74%, p = 0.003; CVI-3: 65.88% vs. 66.46% vs. 63.79%, p = 0.008; CVI-6: 64.79% vs. 65.40% vs. 63.61%, p = 0.032). NPDR patients had significantly lower CVIs compared to DM patients (p < 0.05). No association of choroidal parameters with glycemic control, DM duration and HBP was found significant (p < 0.05). Conclusions: Choroidal assessment by SS-OCT and image binarization in healthy subjects, subjects with DM without DR, and subjects with DM and NPDR indicated that CVI changes were identifiable and significant in early DR. The lack of association with ocular and systemic factors suggest that CVIs are reliable assessment parameters of choroidal vascular structure. [ABSTRACT FROM AUTHOR]

Background and Objectives: Cytokines are cell-signaling proteins whose identification may serve as inflammatory markers or early indicators for progressive disease. The aim of our study was to quantify several cytokines in aqueous humor (AH) and their correlations with biochemical parameters in diabetic eyes with non-proliferative diabetic retinopathy (NPDR). Materials and Methods: A total of 62 eyes from 62 patients were included in the study: 37 eyes from nondiabetic patients (group 1), 13 diabetic eyes with no retinopathy changes (group 2) and 12 diabetic eyes with early and moderate NPDR (group 3). AH samples were collected during uneventful cataract surgery. The cytokines IL-1β, IL-6, IL-8, IL-10, IL-12, IP-10, MCP-1, TNF-α and VEGF were quantified using multiplex bead-based immunoassay. Due to unreliable results, IL-1β, TNF-α, IL-10 and IL-12 were excluded. Concentrations were compared between groups. Biochemical parameters (fasting blood sugar, glycated hemoglobin, C-reactive protein) and the duration of diabetes were recorded. Results: VEGF levels were significantly different between groups (p = 0.001), while levels of IL-6, IL-8, IP-10 and MCP-1 were comparable across all groups (p > 0.05). IL-6 concentration correlated with VEGF in group 1 (rho = 0.651, p = 0.003) and group 3 (rho = 0.857, p = 0.007); no correlation could be proved between IL-6, IL-8, IP-10, MCP-1 or VEGF and biochemical parameters. Duration of diabetes was not correlated with the cytokine levels in groups 2 and 3. The receiver operating characteristic (ROC) curve revealed that VEGF concentrations could discriminate early and moderate NPDR from diabetes, with an area under the curve (AUC) of 0.897 (p = 0.001, 95% CI = 0.74–1.0). Conclusions: Diabetes mellitus induces significant intraocular changes in the VEGF expression in diabetic patients vs. normal subjects, even before proliferative complications appear. VEGF was increasingly expressed once the diabetes progressed from no retinopathy to early or moderate retinopathy. [ABSTRACT FROM AUTHOR]

Abstract Background There have been a major advance made in screening, early diagnosis, and prompt treatment of Diabetic Retinopathy among Person living with diabetes (PLWD). However, screening services remain a challenge in Low-Middle-Income-Countries where access to eye care professionals is inadequate. This study assesses the utilization of Eye Health Service prevalence (UEHS) among PLWD and associated factors and further quantifies its association with Non-Proliferative Diabetic Retinopathy (NPDR). Methods A cross-sectional study design with a random sample of 360 PLWD was conducted at Korle-Bu Teaching Hospital, a National Referral Centre in Ghana from May to July 2019. UEHS and DR were the study outcomes. We adopted Poisson and Probit regression analysis to assess factors associated with UEHS over the past year. We employed pairwise and phi correlation (fourfold correlational analysis) to assess the relationship between UEHS and DR (ordinal and binary respectively). Ordered Logistic and Poisson regression were applied to assess the association between the UEHS and DR. Stata 16.1 was used to perform the analyses and a p-value ≤ 0.05 was deemed significant. Results The prevalence of UEHS over the past year and DR was 21.7 %(95 %CI = 17.7–26.2) and 65.0 %(95 %CI = 59.9–69.8 respectively. The prevalence of severe NPDR with Clinically Significant Macular Edema (CSME) was 23.9 %(19.8–28.6). Type of diabetes, increasing age, educational level, mode of payment for healthcare services, marital status, years since diagnosis, and current blood glucose significantly influenced UEHS. There was a negative relationship between DR and UEHS (Pairwise and φ correlation were − 20 and − 15 respectively; p

Background: Ocular surface disorders and dryness of eye are increasing day-by-day particular among type 2 diabetics. The factors such as autonomic dysfunction and high blood sugar level account for the development of dry eye in diabetes. Although pathogenesis of dry eye syndrome (DES) is not clearly understood, it has been shown that accumulation of sorbitol may cause lacrimal gland structure damage and dysfunction resulting decreased tear secretion. Poor glycemic control affects both the anterior and the posterior segments of the eye and increasing prevalence of diabetes-associated DES has been reported in recent years. Materials and Methods A cross-sectional study was conducted in the department of ophthalmology of a tertiary care hospital. Consecutive 100 patients with type 2 diabetes mellitus (DM) who attended outpatient department were included as per inclusion-exclusion criteria. Results: The majority of the patients (58%) was female with female-to-male ratio of 1.38:1. Most of the patients (43%) were under 50 years followed by 51–60 years (34%). Overall, the mean age was 54.26 ± 10.06 years. More than half (63%) of the patients had duration of diabetes up to 5 years. The result showed 42% prevalence of DES among the patients. Number of patients had been suffering from mild, moderate, and severe dry eye were 21%, 16%, and 5%, respectively. The condition was pronounced with longer duration and poor control of diabetes. Conclusions: DES in patient with type 2 DM was significantly associated with increasing age but not with the sex. The duration of diabetes had a direct influence on dry eye. Poor control of diabetes was associated with higher prevalence of dry eye. Early detection of diabetes and its adequate control is the key measure for prevention of dry eye in diabetes.

PurposeTo correlate angiogenic cytokines in the aqueous humour with total retinal blood flow in subjects with type 2 diabetes with non-proliferative diabetic retinopathy (NPDR).MethodsA total of 17 controls and 16 NPDR patients were recruited into the study. Aqueous humour was collected at the start of cataract surgery to assess the concentration of 14 angiogenic cytokines. Aqueous humour was analysed using the suspension array method. Six images were acquired to assess total retinal blood flow (TRBF) using the prototype RTVue™ Doppler Fourier domain optical coherence tomography (Doppler FD-OCT) (Optovue, Inc., Fremont, CA) using a double circular scan protocol, 1 month postsurgery. At the same visit, forearm blood was collected to determine glycosylated haemoglobin (A1c).ResultsTransforming growth factor beta (TGF-β1, TGF-β2) and PLGF were increased while FGF-1 was reduced in NPDR compared to controls (Bonferroni corrected, p

Purpose: To reveal molecular mechanisms of diabetic retinopathy (DR) in Asians and facilitate the identification of new therapeutic targets through untargeted metabolomics. To determine the differences in serum metabolites and metabolic pathways between different stages of diabetic retinopathy in patients with type 2 diabetic mellitus (T2DM) and proliferative DR (PDR) and non-proliferative DR (NPDR) and identify differential metabolites between T2DM and DR (NPDR and PDR) patients.Methods: This prospective observational registration study described the differential metabolites between 45 T2DM patients and 15 control cases with no significant differences in clinical characteristics. Their biospecimens and clinical information were collected and recorded in their medical reports. DR phenotypes of the subjects were verified by retina specialists. Serum metabolites were analyzed using high-resolution mass spectrometry with liquid chromatography. Untargeted metabolomics was performed on serum samples from 15 T2DM patients, 15 non-proliferative diabetic retinopathy patients, 15 proliferative diabetic retinopathy patients, and 15 diabetic controls. Discriminatory metabolic features were identified through partial least squares discriminant analysis (PLS-DA), hierarchical clustering analysis (HCA), and generalized linear regression models.Result: Through untargeted metabolomics, 931 features (523 in positive and 408 in negative modes) with 102 common metabolites highly relevant to the presence of DR were detected. In the adjusted analysis, 67 metabolic features differed significantly between T2DM and NPDR patients. Pathway analysis revealed alterations in metabolisms of amino acids and fatty acids. Glutamate, phosphatidylcholine, and 13-hydroperoxyoctadeca-9,11-dienoic acid (13-PHODE) were key contributors to these pathway differences. A total of 171 features distinguished PDR patients from T2DM patients, and pathway analysis revealed alterations in amino acid metabolism, fatty acid metabolism, nitrogen metabolism, and tricarboxylic acid cycle. Aspartate, glutamate, glutamine, ornithine, N-acetyl-l-glutamate, N-acetyl-l-aspartate, citrate, succinate, N-(L-arginino)succinate, 2-oxoglutarate, 13-hydroperoxyoctadeca-9,11-dienoic acid, methionine, lysine, threonine, phenylalanine, N(pi)-methyl-l-histidine, phosphatidylcholine, and linoleate were major contributors to the pathway differences. Between NPDR patients and PDR patients, there were 79 significant differential metabolites. Enrichment pathway analysis showed changes in amino acid metabolism, fatty acid metabolism, pantothenate, and CoA biosynthesis. Aspartate, glutamine, N-acetyl-l-glutamate, N-acetyl-l-aspartate, pantothenate, dihomo-gamma-linolenate, docosahexaenoic acid, and icosapentaenoic acid were key factors for the differences of these pathways.Conclusion: This study demonstrated that the pathways of arginine biosynthesis metabolism, linoleic acid metabolism, alanine, aspartate, and glutamate metabolism, as well as d-glutamine and d-glutamate metabolism, were dysregulated in DR patients of the Asian population. Increased levels of glutamate, aspartate, glutamine, N-acetyl-l-glutamate, and N-acetyl-l-aspartate and decreased levels of dihomo-gamma-linolenate, docosahexaenoic, and icosapentaenoic were considered as the metabolic profile that could distinguish PDR from NPDR in Asians. Phosphatidylcholine and 13-PHODE were identified as two major novel metabolite markers in advanced stages of DR in our study.

Abstract Background Diabetic retinopathy (DR), a microvascular complication of diabetes, is the leading cause of visual impairment in people aged 20–65 years and can go undetected until vision is irreversibly lost. There is a need for treatments for non-proliferative diabetic retinopathy (NPDR) which, in comparison with current intravitreal (IVT) injections, offer an improved risk–benefit ratio and are suitable for the treatment of early stages of disease, during which there is no major visual impairment. Efficacious systemic therapy for NPDR, including oral treatment, would be an important and convenient therapeutic approach for patients and physicians and would reduce treatment burden. In this article, we review the rationale for the investigation of amine oxidase copper-containing 3 (AOC3), also known as semicarbazide-sensitive amine oxidase and vascular adhesion protein 1 (VAP1), as a novel target for the early treatment of moderate to severe NPDR. AOC3 is a membrane-bound adhesion protein that facilitates the binding of leukocytes to the retinal endothelium. Adherent leukocytes reduce blood flow and in turn rupture blood vessels, leading to ischemia and edema. AOC3 inhibition reduces leukocyte recruitment and is predicted to decrease the production of reactive oxygen species, thereby correcting the underlying hypoxia, ischemia, and edema seen in DR, as well as improving vascular function. Conclusion There is substantial unmet need for convenient, non-invasive treatments targeting moderately severe and severe NPDR to reduce progression and preserve vision. The existing pharmacotherapies (IVT corticosteroids and IVT anti-vascular endothelial growth factor-A) target inflammation and angiogenesis, respectively. Unlike these treatments, AOC3 inhibition is predicted to address the underlying hypoxia and ischemia seen in DR. AOC3 inhibitors represent a promising therapeutic strategy for treating patients with DR and could offer greater choice and reduce treatment burden, with the potential to improve patient compliance.

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.

Background: Diabetic retinopathy (DR), one of the commonest microvascular complications in diabetic patients, is featured by a series of fundus lesions. Conventional Western medicine therapies for DR are always with modest treatment outcome. This paper is to assess the ocular fundus signs, vision and safety of Chinese patent medicines (CPMs) as an add-on treatment for DR. Method: 7 electronic databases were searched to determine eligible trials. Randomized controlled trials (RCTs) of non-proliferative diabetic retinopathy (NPDR) in which the intervention group received CPMs combined with calcium dobesilate (CD), and the control group received only CD were included for analysis. Two reviewers extracted the data independently. Results expressing as mean differences (MD) and relative risks (RR) were analyzed with a fixed-effects or random-effects models. Results: 19 RCTs involved 1568 participants with 1622 eyes met our inclusion criteria. The results suggested that compared with CD alone, CPMs plus CD for NPDR was superior at reducing the microaneurysm volume (MD -3.37; 95% confidence interval [CI], -3.59 to -3.14), microaneurysm counts (MD -2.29; 95%CI -2.97 to -1.61), hemorrhage area (MD -0.79; 95%CI -0.83 to -0.75), and macular thickness (MD -59.72; 95%CI -63.24 to -56.20). Participants in CPMs plus CD group also achieved a better vision. No obvious adverse events occurred. Conclusion: CPMs as an add-on therapy for NPDR have additional benefits and be generally safe. This meta‐analysis demonstrated that CPMs combined with CD could improve retinal microaneurysm, hemorrhage, macular thickness, visual acuity, fasting blood glucose (FBG), and glycosylated hemoglobin (HbAlc) compared with CD alone. Further studies are needed to provide more conclusive evidence. Systematic Review Registration: PROSPERO https://www.crd.york.ac.uk/prospero/ , identifier CRD42021257999. [ABSTRACT FROM AUTHOR]

BackgroundThe relationship between uric acid (UA) and diabetic retinopathy (DR) remains ambiguous, and the results of current studies on the UA levels in patients with DR are conflicting. A meta-analysis was performed to provide a better understanding of the relationship between UA levels and DR.MethodsPubMed, Web of Science, Embase, and the Cochrane Library databases were searched until December 11, 2021 to identify eligible studies, that compared the UA levels of the case group (patients with DR) and control group (controls with diabetes and healthy participants). The weighted mean difference (WMD) with a 95% confidence interval (CI) was used to evaluate the difference in UA levels between the case and control groups.ResultsTwenty-one studies involving 4,340 patients with DR and 8,595 controls (8,029 controls with diabetes and 566 healthy participants) were included in this meta-analysis. We found that patients with DR had significantly higher UA levels than those in the controls with diabetes (WMD = 36.28; 95% CI: 15.68, 56.89; P < 0.001) and healthy participants (WMD = 70.80; 95% CI: 19.85, 121.75; P = 0.006). There was an obvious heterogeneity among the 21 studies (I2 = 97%, P < 0.001). Subgroup analyses of different phases of DR showed that UA levels were significantly increased in participants with proliferative diabetic retinopathy (PDR) (WMD = 46.57; 95% CI: 28.51, 64.63; P < 0.001) than in controls with diabetes; however, the difference is not statistically significant when comparing UA levels in patients with non-proliferative diabetic retinopathy (NPDR) and controls with diabetes (WMD = 22.50; 95% CI: −6.07, 51.08; P = 0.120). In addition, UA levels were higher in participants with a body mass index (BMI) ≥25.0 kg/m2 and over 15 years of diabetes. Univariate meta-regression analysis revealed that BMI (P = 0.007, Adj R2 = 40.12%) and fasting blood glucose (FBG) (P = 0.040, Adj R2 = 29.72%) contributed to between-study heterogeneity.ConclusionsIn conclusion, our study provides evidence that UA levels are higher in patients with DR than those in the controls, but this difference is not statistically significant in the early phases. UA might be a potential biomarker for identifying disease severity in patients with DR, rather than predicting the onset of DR among patients with diabetes. However, more prospective and high-quality clinical evidence is required to confirm these present findings.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=297708.

BackgroundDiabetic retinopathy (DR), one of the commonest microvascular complications in diabetic patients, is featured by a series of fundus lesions. Conventional Western medicine therapies for DR are always with modest treatment outcome. This paper is to assess the ocular fundus signs, vision and safety of Chinese patent medicines (CPMs) as an add-on treatment for DR.Method7 electronic databases were searched to determine eligible trials. Randomized controlled trials (RCTs) of non-proliferative diabetic retinopathy (NPDR) in which the intervention group received CPMs combined with calcium dobesilate (CD), and the control group received only CD were included for analysis. Two reviewers extracted the data independently. Results expressing as mean differences (MD) and relative risks (RR) were analyzed with a fixed-effects or random-effects models.Results19 RCTs involved 1568 participants with 1622 eyes met our inclusion criteria. The results suggested that compared with CD alone, CPMs plus CD for NPDR was superior at reducing the microaneurysm volume (MD -3.37; 95% confidence interval [CI], -3.59 to -3.14), microaneurysm counts (MD -2.29; 95%CI -2.97 to -1.61), hemorrhage area (MD -0.79; 95%CI -0.83 to -0.75), and macular thickness (MD -59.72; 95%CI -63.24 to -56.20). Participants in CPMs plus CD group also achieved a better vision. No obvious adverse events occurred.ConclusionCPMs as an add-on therapy for NPDR have additional benefits and be generally safe. This meta‐analysis demonstrated that CPMs combined with CD could improve retinal microaneurysm, hemorrhage, macular thickness, visual acuity, fasting blood glucose (FBG), and glycosylated hemoglobin (HbAlc) compared with CD alone. Further studies are needed to provide more conclusive evidence.Systematic Review RegistrationPROSPERO https://www.crd.york.ac.uk/prospero/, identifier CRD42021257999.

We assessed the effect of a 2-year supplementation with a highly concentrated docosahexaenoic acid (DHA) product with antioxidant activity on non-proliferative diabetic retinopathy (NPDR) in a randomized double-blind placebo-controlled study. A total of 170 patients with diabetes were randomly assigned to the DHA group (n = 83) or the placebo group (n = 87). NPDR was diagnosed using non-contact slit lamp biomicroscopy examination, and classified into mild, moderate, and severe stages. Patients in the DHA group received a high rich DHA triglyceride (1050 mg/day) nutritional supplement, and those in the placebo group received olive oil capsules. The percentages of mild NPDR increased from 61.7% at baseline to 75.7% at the end of the study in the DHA group, and from 61.9% to 73.1% in the placebo group. Moderate NPDR stages decreased from 35.1% at baseline to 18.7% at the end of the study in the DHA group, and from 36.8% to 26.0% in the placebo group. In the DHA group, there were five eyes with severe NPDR at baseline, which increased to one more at the end of the study. In the placebo group, of two eyes with severe NPDR at baseline, one eye remained at the end of the study. Changes in visual acuity were not found. There were improvements in the serum levels of HbA1c in both groups, but significant differences between the DHA and the placebo groups were not found. In this study, the use of a DHA triglyceride nutraceutical supplement for 2 years did not appear to influence the slowing of the progression of NPDR. [ABSTRACT FROM AUTHOR]

Elizabeth Pearce,1 Sobha Sivaprasad1,2 1Department of Ocular Biology, Institute of Ophthalmology, University College London, London, UK; 2Medical Retina Department, NIHR Moorfields Biomedical Research Centre, Moorfields Eye Hospital, London, UKCorrespondence: Sobha SivaprasadNIHR Moorfields Biomedical Research Centre, Moorfields Eye Hospital, NHS Foundation Trust, 162 City Road, London EC1V 2PD, UKTel +44 20 7253 3411Email senswathi@aol.comAbstract: Diabetic retinopathy (DR) is a microvascular complication of diabetes with a prevalence of ∼ 35%, and is one of the leading causes of visual impairment in people of working age in most developed countries. The earliest stage of DR, non-proliferative DR (NPDR), may progress to sight-threatening DR (STDR). Thus, early detection of DR and active regular screening of patients with diabetes are necessary for earlier intervention to prevent sight loss. While some countries offer systematic DR screening, most nations are reliant on opportunistic screening or do not offer any screening owing to limited healthcare resources and infrastructure. Currently, retinal imaging approaches for DR screening include those with and without mydriasis, imaging in single or multiple fields, and the use of conventional or ultra-wide-field imaging. Advances in telescreening and automated detection facilitate screening in previously hard-to-reach communities. Despite the heterogeneity in approaches to fit local needs, an evidence base must be created for each model to inform practice. In this review, we appraise different aspects of DR screening, including technological advances, identify evidence gaps, and propose several studies to improve DR screening globally, with a view to identifying patients with moderate-to-severe NPDR who would benefit if a convenient treatment option to delay progression to STDR became available.Keywords: telescreening, non-proliferative diabetic retinopathy, risk-stratification, systematic, opportunistic

AIM: To analyse the characteristic of macular microcirculation detected by optical coherence tomography angiography(OCTA)in nonproliferative diabetic retinopathy(NPDR).METHODS: Vessel density of 3mm×3mm centered on the fovea(3mm×3mm VD), parafoveal vessel density(parafoveal VD)and foveal vessel density(foveal VD)were measured by OCTA in healthy people, NDR, mild NPDR, moderate NPDR, and severe NPDR groups. RESULTS: Deep 3mm×3mm VD, deep parafoveal VD and deep foveal VD were decreased gradually in groups. There was statistically significant difference between moderate NPDR, severe NPDR and others in deep 3mm×3mm VD and parafoveal VD(PP=0.006). Superficial 3mm×3mm VD and superficial parafoveal VD are statistically significant in groups. There was statistically significant difference between moderate NPDR group and control group in superficial 3mm×3mm VD and parafoveal VD(PPCONCLUSION: Deep vessel density decreased more significantly in moderate NPDR and severe NPDR groups and deep parafoveal vessel density might be a potential biomarker of DR.

Abstract Background Diabetic retinopathy (DR) is the leading cause of blindness in many countries. The current treatment for non-proliferative DR (NPDR) using Western medicine (WM) alone is insufficient. At present, the combination of NPDR treatment with traditional Chinese medicine (TCM) and WM is universally applied. We aimed to evaluate the effectiveness and safety of TCM as an add-on for NPDR using a systematic review and meta-analysis. Method Data from randomized controlled trials (RCTs) of TCM for NPDR treatment along with WM before July 6, 2019, were collected from the China National Knowledge Infrastructure, Wanfang Database, China Biomedical Database, Pubmed, Embase, and Cochrane Library. Relevant data were extracted by two reviewers. I 2 statistics was adopted to appraise heterogeneity. If I 2