Non-proliferative Diabetic Retinopathy Patients Research Articles

Correlation between vessel density and thickness in the retina and choroid of severe non-proliferative diabetic retinopathy patients.

To explore the correlation between the vessel density (VD) of the retina and choroid vascular plexuses and the thicknesses of their respective retinal layers and choroid membranes in participants with severe non-proliferative diabetic retinopathy (NPDR). We retrospectively analyzed the data of 42 eyes of 42 participants with diabetes mellitus (DM) and severe NPDR. In addition, 41 eyes of 41 healthy controls were evaluated. Measurements were taken for both groups using optical coherence tomography angiography (OCTA), including the area and perimeter of the foveal vascular zone (FAZ) and the vascular density (VD) in the superficial capillary plexus (SCP), deep capillary plexus (DCP), and choroid capillary (CC). These measurements were compared with the retinal thickness (RT) of the inner/intermediate retinal layers and choroidal thickness (CT). The study evaluated the correlation between RT or CT and VD in the respective vascular networks, namely superficial capillary plexus (SCP), deep capillary plexus (DCP), or CC. The inner RT and VD in all plexuses were significantly lower in the severe NPDR group than in the healthy controls. Furthermore, the FAZ area and perimeter were larger in the severe NPDR group. Inner RT was correlated with VD in the SCP group (r=0.67 and r=0.71 in the healthy control and severe NPDR groups, respectively; p<0.05). CT negatively correlated with VD in the CC (r=-0.697 and r=-0.759 in the healthy control and severe NPDR groups, respectively; p<0.05). Intermediate RT significantly correlated with VD in the DCP of the severe NPDR group (r=-0.55, p<0.05), but not in the healthy control group. Retinal or choroidal thickness strongly correlated with VD. Therefore, patients with severe NPDR must consider the distinct anatomical and functional entities of the various retinal layers and the choroid.

Genetic association of TIE2 with diabetic retinopathy and diabetic macular edema

PurposeTo evaluate the associations of the TIE2 gene with diabetic retinopathy (DR) and diabetic macular edema (DME). MethodsThis study included a Chinese cohort of 285 non-proliferative DR patients and 433 healthy controls. The DR patients were classified further into those with or without DME. Thirty haplotype-tagging single-nucleotide polymorphisms (SNPs) in TIE2 were genotyped using TaqMan technology. Associations of DR and subtypes were analyzed by logistic regression adjusted for age and sex. Stratification association analysis by sex was performed. ResultsTIE2 rs625767 showed a nominal but consistent association with DR [odds ratio (OR) = 0.71, P = 0.005] and subtypes (DR without DME: OR = 0.69, P = 0.016; DME: OR = 0.73, P = 0.045). SNP rs652010 was consistently associated with overall DR (OR = 0.74, P = 0.011) and DR without DME (OR = 0.70, P = 0.016), but not with DME. Moreover, SNPs rs669441, rs10967760, rs549099 and rs639225 showed associations with overall DR, whilst rs17761403, rs664461 and rs1413825 with DR without DME. In stratification analysis, three SNPs, rs625767 (OR = 0.62, P = 0.005), rs669441 (OR = 0.63, P = 0.006) and rs652010 (OR = 0.64, P = 0.007), were associated with DR in females, but not in males. Moreover, one haplotype T-T defined by rs625767 and rs669441 was significantly associated with DR in females only. ConclusionsThis study revealed TIE2 as a susceptibility gene for DR and DME in Chinese, with a sex-specific association in females. Further validation should be warranted.

Meta-analysis of the relationship between ocular and peripheral serum IL-17A and diabetic retinopathy.

A systematic evaluation and Meta-analysis were performed to determine the relationship between IL-17A levels in ocular aqueous and peripheral venous serum samples and diabetic retinopathy (DR). PubMed, Embase, Web of Science, and CNKI databases were searched from the time of library construction to 2023-09-20.The results were combined using a random-effects model, sensitivity analyses were performed to determine whether the arithmetic was stable and reliable, and subgroup analyses were used to look for possible sources of heterogeneity. A total of 7 case-control studies were included. The level of IL-17A was higher in the Nonproliferative DR(NPDR) group than in the Non-DR(NDR) group [SMD=2.07,95%CI(0.45,3.68),P=0.01], and the level of IL-17A in the proliferating DR(PDR) group was higher than that of the NDR group [SMD=4.66,95%CI(1.23,8.08),P<0.00001]. IL-17A levels in peripheral serum and atrial fluid were significantly higher in NPDR and PDR patients than in non-DR patients in subgroup analyses, and detection of peripheral serum IL-17A concentrations could help to assess the risk of progression from NPDR to PDR. Sensitivity analyses suggested that the results of the random-effects arithmetic were stable and reliable. Subgroup analyses based on assay method and sample source showed that the choice of these factors would largely influence the relationship between IL-17A levels and DR. Elevated peripheral serum and ocular aqueous humor IL-17A levels in diabetic patients are associated with the risk of DR, IL-17A may serve as a potential predictor or therapeutic target for DR, and IL-17A may be an important predictor of inflammation for the progression of NPDR to PDR. https://www.crd.york.ac.uk/prospero/, identifier CRD42024532900.

N-glycosylation of disease-specific haptoglobin for the early screening of diabetic retinopathy.

Diabetic retinopathy (DR), as one of the microvascular complications of diabetes, is a leading cause of acquired vision loss. Most DR cases are detected in the advanced stage through fundoscopy, making molecular biomarkers urgently needed for early diagnosis of DR. Serum disease-specific haptoglobin-β (Hp-β) chains of 100 patients with type 2 diabetes mellitus (T2DM) and 156 T2DM patients with non-proliferative diabetic retinopathy (NPDR) were separated using polyacrylamide gel electrophoresis. After in-gel digestion and enrichment, the intact N-glycopeptides were detected by mass spectrometry. Fucosylation of Hp-β was significantly increased and sialylation of Hp-β was significantly decreased in background DR (BDR, an early-stage DR) patients compared with non-diabetic retinopathy patients (p<0.05) and yielded area under curves (AUCs) of 0.801 and 0.829 in training and validation groups, respectively, which had an advantage over glycated hemoglobin A1c (AUC ≤ 0.691). Moreover, a significant increase in sialylated Hp-β was found in severe NPDR patients compared with BDR patients and yielded an AUC of 0.828 to distinguish severe NPDR from BDR. Changes in Hp-β glycosylation are closely related to DR, and may be used for early diagnosis and screening of DR.

Exploring urinary modified nucleosides as biomarkers for diabetic retinopathy: Development and validation of a ultra performance liquid chromatography-tandem mass spectrometry method

The dynamic modification of RNA plays a crucial role in biological regulation and is strongly linked to human disease development and progression. Notably, modified nucleosides in urine have shown promising potential as early diagnostic biomarkers for various conditions. In this study, we developed and validated a rapid, sensitive, and accurate UPLC-MS/MS method for quantifying eight types of modified nucleosides (N1-methyladenosine (m1A), N6-methyladenosine (m6A), 5-methyluridine (m5U), 5-taurinomethyl-2-thiouridine (τm5s2U), 5-methylcytidine (m5C), 2'-O-methylcytidine (Cm), N1-methylguanosine (m1G), and N7-methylguanosine (m7G) in human urine. Using the method, we measured the urinary concentrations of m1A, m6A, m5U, τm5s2U, m5C, Cm, m1G, and m7G in a total of 21 control individuals and 23 patients diagnosed with diabetic retinopathy (DR). Cm levels showed promise as a diagnostic marker for diabetic retinopathy (DR), with a significant value (P < 0.01) and an AUC of 0.735. Other modified nucleosides also exhibited significant differences within specific subpopulations. As non-proliferative diabetic retinopathy (NPDR) signifies the latent early stage of diabetic retinopathy, we developed a multivariate linear model that integrates patients' sex, age, height, and urinary concentration of modified nucleosides which aims to predict and differentiate between healthy individuals, NPDR patients, and proliferative diabetic retinopathy (PDR) patients. Encouragingly, the model achieved satisfactory accuracy rates: healthy (81%), NPDR (75%), and PDR (80%). Our findings provide valuable insights into the development of an early, cost-effective, and noninvasive diagnostic approach for diabetic retinopathy.

Study on Risk Factors Associated with Severity of Diabetic Retinopathy in Type-2 Diabetic Patients, Attending a Tertiary Care Centre in Kerala

Introduction: Diabetic retinopathy (DR) is a significant public health concern affecting individuals with diabetes mellitus (DM). Despite treatment advances, a substantial proportion of patients do not respond adequately. This study investigates risk factors associated with the progression of non-proliferative diabetic retinopathy (NPDR) to proliferative diabetic retinopathy (PDR) in type-2 diabetes patients. Methods: A retrospective case-control study was conducted on diabetic patients older than 40 years with at least 5 years of Type-2 Diabetes Mellitus history, attending ophthalmology clinic in Government Medical College, Thrissur, a tertiary care hospital. Data from patients with retinal examination showing diabetic retinopathy were analyzed. Records with missing data were excluded. Patients with Proliferative Diabetic Retinopathy (n=153) were compared with those having Non- Proliferative Diabetic Retinopathy (n=230). Various risk factors were assessed using statistical analysis. Results: Among the studied variables, sex, duration of diabetes, serum urea, serum creatinine, serum triglycerides, and chronic kidney disease were significantly different between Proliferative Diabetic Retinopathy and Non-Proliferative Diabetic Retinopathy patients. Binary logistic regression revealed that duration of diabetes (OR = 1.8, 95% CI = 1.1 - 2.39) and serum creatinine (OR =1.8, 95% CI = 1.1 - 2.39) independently influenced Proliferative Diabetic Retinopathy development. Conclusion: This study highlights that longer diabetes duration and elevated serum creatinine levels independently increase the risk of Non- Proliferative Diabetic Retinopathy progressing to Proliferative Diabetic Retinopathy in type-2 diabetic patients. Other factors such as age, gender, hyperlipidemia, systemic hypertension, type of diabetic treatment, and history of ischemic heart disease did not show significant associations with disease progression. These findings emphasize the importance of close monitoring, early detection, and intervention in patients with Non- Proliferative Diabetic Retinopathy, particularly those with a longer diabetic history, to prevent Proliferative Diabetic Retinopathy development. Further research should explore the causal relationship between serum creatinine and diabetic retinopathy progression and evaluate the impact of renal disease management on disease outcomes. Keywords: Diabetic Retinopathy, diabetes mellitus (DM), Type-2 Diabetes Mellitus (T2DM).

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.

Identification of biomarkers associated with immune scores in diabetic retinopathy.

Diabetic retinopathy (DR) causes irreversible visual impairment in diabetes mellitus (DM) patients. Immunity played a crucial role in DR. Nevertheless, the triggering mechanism of DR was not yet thorough enough. Herein, we aim to identify the immune-associated genes as biomarkers associated with immune scores that can distinguish early DR from DM without DR. In this study, total RNA of peripheral blood mononuclear cell (PBMC) samples from 15 non-proliferative DR patients and 15 DM patients without DR were collected and the transcriptome sequencing data were extracted. Firstly, the target genes were obtained by intersecting the differentially expressed genes (DEGs), which were screened by "limma", and the module genes (related to immune scores), which were screened by "WGCNA". In order to screen for the crucial genes, three machine learning algorithms were implemented, and a receiver operating characteristic (ROC) curve was used to obtain the diagnostic genes. Moreover, the gene set enrichment analysis (GSEA) was performed to understand the function of diagnostic genes, and analysis of the proportions of immune cells and their association with diagnostic genes was performed to analyze the pathogenesis of DR. Furthermore, the regulatory network of TF-mRNA-miRNA was built to reveal the possible regulation of diagnostic genes. Finally, the quantitative real-time polymerase chain reaction (qRT-PCR) was performed to verify the mRNA level of diagnostic genes. A total of three immune-associated diagnostic genes, namely, FAM209B, POM121L1P, and PTGES, were obtained, and their expression was increased in PBMC samples of DR, and qRT-PCR results confirmed these results. Moreover, the functions of these genes were associated with immune response. The expression of POM121L1P and PTGES was significantly negatively associated with naive B cells, and the expression of FAM209B was significantly negatively associated with immature dendritic cells. Moreover, ESR1 could regulate both FAM209B and PTGES. This study identified three immune-associated diagnostic genes, FAM209B, POM121L1P, and PTGES, as biomarkers associated with immune scores in DR for the first time. This finding might proffer a novel perspective of the triggering mechanism of DR, and help to understand the role of immune-associated genes in the molecular mechanism of DR more deeply.

Novel risk score model for non-proliferative diabetic retinopathy based on untargeted metabolomics of venous blood.

Nonproliferative diabetic retinopathy (NPDR) occurs in the early stages of Diabetic retinopathy (DR), and the study of its metabolic markers will help to prevent DR. Hence, we aimed to establish a risk score based on multiple metabolites through untargeted metabolomic analysis of venous blood from NPDR patients and diabetic non-DR patients. Untargeted metabolomics of venous blood samples from patients with NPDR, diabetes melitus without DR were performed using high-performance liquid chromatography-mass spectrometry. Detailed metabolomic evaluation showed distinct clusters of metabolites in plasma samples from patients with NPDR and diabetic non-DR patients. NPDR patients had significantly higher levels of phenylacetylglycine, L-aspartic acid, tiglylglycine, and 3-sulfinato-L-alaninate, and lower level of indolelactic acid, threonic acid, L-arginine (Arg), and 4-dodecylbenzenesulfonic acid compared to control. The expression profiles of these eight NPDR risk-related characteristic metabolites were analyzed using Cox regression to establish a risk score model. Subsequently, univariate and multivariate Cox regression analyses were used to determine that this risk score model was a predictor of independent prognosis for NPDR. Untargeted metabolome analysis of blood metabolites revealed unreported metabolic alterations in NPDR patients compared with those in diabetic non-DR patients or MH. In the venous blood, we identified depleted metabolites thA and Arg, indicating that they might play a role in NPDR development.

Erythropoiesis-Stimulating Agents and the Risk of Vision-Threatening Diabetic Retinopathy

ABSTRACT Purpose Animal studies have suggested that Erythropoiesis-Stimulating Agents (ESAs) may increase vascular endothelial growth factor (VEGF)-related retinopathies, but this effect is unclear in humans. This study evaluates the risk of vision-threatening diabetic retinopathy (VTDR), defined as either diabetic macular edema (DME) or proliferative diabetic retinopathy (PDR), in patients exposed to an ESA. Methods Two analyses were performed. First, a retrospective matched-cohort study was designed using a de-identified commercial and Medicare Advantage medical claims database. The ESA cohort of non-proliferative diabetic retinopathy patients who were new users of an ESA from 2000 to 2022 was matched to controls up to a 3:1 ratio. Exclusion criteria included less than 2 years in the plan, history of VTDR or history of other retinopathy. Multivariable Cox proportional hazards regression with inverse proportional treatment weighting (IPTW) was used to assess the hazard of developing VTDR, DME, and PDR. The second analysis was a self-controlled case series (SCCS) evaluating the incidence rate ratios (IRR) of VTDR during 30-day periods before and after initiating an ESA. Results After inclusion of 1502 ESA-exposed patients compared with 2656 controls, IPTW-adjusted hazard ratios found the ESA cohort had an increased hazard of progressing to VTDR (HR = 3.0 95%CI:2.3–3.8;p < .001) and DME (HR = 3.4,95%CI:2.6–4.4,p < .001), but not PDR (HR = 1.0,95%CI:0.5–2.3,p = .95). Similar results were found within the SCCS which demonstrated higher IRRs for VTDR (IRRs = 1.09–1.18;p < .001) and DME (IRRs = 1.16–1.18;p < .001), but not increased IRRs in PDR (IRR = 0.92–0.97,p = .02–0.39). Conclusion ESAs are associated with higher risks for VTDR and DME, but not PDR. Those studying ESAs as adjunctive therapy for DR should be cautious of possible unintended effects.

Serum disease-specific IgG Fc glycosylation as potential biomarkers for nonproliferative diabetic retinopathy using mass spectrometry

ObjectiveTo explore the potential of serum disease-specific immunoglobulin G (DSIgG) glycosylation as a biomarker for the diagnosis of nonproliferative diabetic retinopathy (NPDR). MethodsA total of 387 consecutive diabetic patients presenting in an eye clinic without proliferative diabetic retinopathy (DR) were included and divided into those with nondiabetic retinopathy (NDR) (n = 181) and NPDR (n = 206) groups. Serum was collected from all patients for DSIgG separation. The enriched glycopeptides of the tryptic digests of DSIgG were detected using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Patients were randomly divided into discovery and validation sets (1:1). The differences in glycopeptide ratios between the groups were compared by using Student's t-test or the Mann–Whitney U test. The predictive ability of the model was assessed using the area under the receiver operating characteristic curve (AUC). ResultsDSIgG1 G1FN/G0FN, G2N/G2, G2FN/G2N and DSIgG2 G1F/G0F, G1FN/G0FN, G2N/G1N, G2S/G2 were significantly different between NDR and NPDR patients (p < 0.05) in both the discovery and validation sets. The prediction model that was built comprising the seven glycopeptide ratios showed good NPDR prediction performance with an AUC of 0.85 in the discovery set and 0.87 in the validation set. ConclusionDSIgG Fc N-glycosylation ratios were associated with NPDR and can be used as potential biomarkers for the early diagnosis of DR.

Short time effect of sodium fluorescein on chorodial vascularity index

Purpose This study aimed to investigate the effect of sodium fluorescein on the choroidal vascularity index (CVI). Materials and Methods In this cross-sectional study, a total of 27 eyes of 27 mild nonproliferative diabetic retinopathy patients (without maculopathy and any systemic disease) who performed fluorescein angiography (FA) procedure were included. Choroidal parameters such as choroidal thickness (CT), total choroidal area (TCA), luminal area (LA), stromal area (SA), LA/SA, and CVI were examined with the optical coherence tomography and binarization technique at baseline and 5th, 15th, and 30th minutes after FA. The values of the parameters before and after the procedure were compared. Results At baseline, the mean values of the TCA, LA, SA, LA/SA, and CVI were 0.44 ± 0.14mm2, 0.29 ± 0.09 mm2, 0.15 ± 0.05 mm2, 1.87 ± 0.19. Five minutes later to FA, the mean values of the TCA, LA, SA, LA/SA, and CVI were 0.43 ± 0.13 mm2, 0.28 ± 0.08 mm2, 0.15 ± 0.05 mm2, 1.82 ± 0.20, and 0.64 ± 0.03, respectively. There was a significant decrease in LA and CVI values 5 minutes after FA (p:0.002 and p:0.021, respectively). On the other hand, the mean, nasal, subfoveal, and temporal CT were 279.22 ± 93.40 μm, 289.78 ± 91.17 μm, 267.44 ± 95.71 μm before FA and 270.33 ± 90.34 μm, 279.67 ± 90.01 μm, 261.82 ± 95.82 μm 5 minutes after FA (p = 0.960, p = 0.952, and p = 0.991, respectively). Although there was a reduction in the value of CT, there was not a statistically significant difference between before and after FA. Conclusions This study shows that there was a significant decrease in LA and CVI values 5 minutes after FA in patients with mild nonproliferative diabetic retinopathy.

Effect of diabetic macular oedema on serum iron status indicators

ABSTRACT Clinical relevance The role of subclinical inflammation in the pathophysiology of diabetic macular oedema (DME), which is known to be quite complex, is of much interest. Serum ferritin level, which is an indicator of body iron stores, is both an inflammatory marker for various neurodegenerative diseases and an important indicator in the evaluation of iron-induced oxidative stress. Background Iron metabolism indicators play a role in the formation and development of diabetic retinopathy, which is known to be associated with subclinical inflammation, and may also play a role in the pathogenesis of DME. The aim of this study was to investigate the role of serum iron metabolism markers in the pathogenesis of DME. Materials and methods The files of all nonproliferative diabetic retinopathy (NPDR) patients who were scheduled for the first intravitreal injection for DME in the eye clinic between January 2019 and January 2020 were reviewed retrospectively. By examining the files of all diabetes mellitus patients who attended the outpatient eye clinic on the same dates, those without retinopathy and those with NPDR but not DME were recorded. All results, including a comprehensive ophthalmological examination, laboratory data of fasting blood tests, and an internal medicine outpatient examination were collected for analysis. Results Of the 157 participants, 44 were NPDR patients with oedema, 50 were NPDR patients without oedema, and 63 were patients without retinopathy. There was a significant difference between the groups in respect of creatinine, high-density lipoprotein, mean corpuscular volume, serum iron and ferritin, total iron binding capacity and transferrin saturation (p < 0.050). Ferritin values were found to be significantly higher in patients with macular oedema. Other iron status markers were found to be significantly lower (p < 0.050). Conclusion Evaluation of serum iron status indicators in the routine follow-up of diabetic patients may be of diagnostic and/or prognostic benefit in terms of DME.

Characteristics of Unexposed Proliferative Diabetic Retinopathy: An Optical Coherence Tomography Angiography Study

Purpose: To compare optical coherence tomography angiography (OCTA) findings between severe non-proliferative diabetic retinopathy (NPDR) and unexposed proliferative diabetic retinopathy (PDR), and identify predictive factors.Methods: Patients newly diagnosed with severe NPDR or unexposed PDR between January 2018 and December 2021 were reviewed retrospectively. Unexposed PDR was diagnosed using fluorescein fundus angiography, because new vessels could not be observed in the poster pole or clearly distinguished in the retinal periphery on wide fundus photography. Clinical features at the time of diagnosis, and OCTA measurements (mean vascular density, superficial capillary plexus (SCP) foveal avascular zone (FAZ) area, and mean retinal thickness), were compared between the two groups. Factors that could predict unexposed PDR were investigated using multivariate analysis with a generalized estimating equation.Results: A total of 61 severe NPDR and 23 unexposed PDR eyes were included. The unexposed PDR had significantly larger SCP-FAZ areas (&lt;i&gt;p&lt;/i&gt; = 0.031) and lower total and parafoveal mean inner retinal thicknesses (&lt;i&gt;p&lt;/i&gt; = 0.014 and &lt;i&gt;p&lt;/i&gt; &lt; 0.001, respectively). However, there were no differences in mean vascular density between the groups (&lt;i&gt;p&lt;/i&gt; &gt; 0.05). Multivariate analysis showed that SCP-FAZ area and parafoveal mean inner retinal thickness were significant predictors of unexposed PDR (&lt;i&gt;p&lt;/i&gt; = 0.027 and &lt;i&gt;p&lt;/i&gt; = 0.001, respectively).Conclusions: In severe NPDR patients, unexposed PDR may be considered a differential diagnosis when the SCP-FAZ area is large or the parafoveal mean inner retinal thickness is small.

Simulation of long-term impact of intravitreal anti-VEGF therapy on patients with severe non-proliferative diabetic retinopathy

ObjectiveA simulation model was constructed to assess long-term outcomes of proactively treating severe non-proliferative diabetic retinopathy (NPDR) with anti-vascular endothelial growth factor (anti-VEGF) therapy versus delaying treatment until PDR develops.Methods...

Novel optical coherence tomography angiography biomarkers in the diagnosis and assessment of diabetic macular edema and diabetic macular ischemia in patients with non-proliferative diabetic retinopathy.

The present study aims to determine the macular and choroidal optical coherence tomography angiography (OCTA) biomarkers in the assessment and monitoring of diabetic macular edema (DME) and diabetic macular ischemia (DMI) in patients with non-proliferative diabetic retinopathy (NPDR). In this cohort study, a total of 176 eyes of 110 patients with NPDR were investigated at our institute over a period of 10 months. Eyes were divided into four groups based on the severity of NPDR. Each eye was subjected to OCTA (Topcon 3D OCT-1 Maestro2) macula 6 × 6 mm2 en face. It features IMAGEnet 6 software for dynamic viewing of OCTA and imaging data. Four OCTA biomarkers for the macula were identified: foveal avascular zone area (FAZ area), foveal avascular zone contour irregularity (FAZ-CI), capillary dropout areas (CDA), and perifoveal intercapillary areas (PICA). The choroidal OCTA biomarker was the number of choroidal circulation flow voids (CCFV). For all analyses, P < 0.05 was considered statistically significant. Increase in FAZ area and number of CDA were statistically significant (p < 0.0001) with an increase in central foveal thickness, suggesting a correlation of ischemic changes with an increase in DME. FAZ-CI, enlarged PICA, and CCFV were significantly associated with more severe NPDR patients. A correlation between DME and DMI in a patient of NPDR and its progression can be evaluated in a single visit. A unique feature of our study is it revealed novel diagnostic biomarkers of OCTA for DMI and DME.

Rates of choroidal loss and ganglion cell–inner plexiform layer thinning in type 2 diabetes mellitus and healthy individuals: a 2-year prospective study

AimsTo investigate longitudinal choroid and ganglion cell–inner plexiform layer (GCIPL) changes in type 2 diabetes mellitus (T2DM) patients and healthy populations across 2 years.MethodsThis prospective cohort study included T2DM patients...

Proteomic profiling and correlations with clinical features reveal biomarkers indicative of diabetic retinopathy with diabetic kidney disease.

Diabetic retinopathy (DR) and diabetic kidney disease (DKD) are complications of diabetes and place serious health and economic burdens on society. However, the identification and characterization of early biomarkers for DKD, especially for nonproliferative DR (NPDR) patients with DKD, are still needed. This study aimed to demonstrate the plasma proteomic profiles of NPDR+DKD and NPDR patients and identify potential biomarkers for early diagnosis of DKD. Fifteen plasma samples from the NPDR group and nine from the NPDR+DKD group were analyzed by LC−MS/MS to identify the differentially expressed proteins between the two groups. Functional enrichment, protein−protein interaction and clinical feature correlation analyses revealed the target protein candidates, which were verified using ELISA and receiver operating characteristic (ROC) analysis. In total, 410 proteins were detected in plasma; 15 were significantly upregulated and 7 were downregulated in the NPDR+DKD group. Bioinformatics analysis suggested that DKD is closely related to cell adhesion and immunity pathways. β-2-Microglobulin (B2M) and vimentin (VIM) were upregulated in NPDR+DKD, enriched as hub proteins and strongly correlated with clinical features. ELISA showed that B2M (p<0.001) and VIM (p<0.0001) were significantly upregulated in NPDR+DKD compared with NPDR. In ROC analysis, B2M and VIM could distinguish DKD from NPDR with area under the curve values of 0.9000 (p < 0.0001) and 0.9950. Our proteomic study revealed alterations in the proteomic profile and identified VIM and B2M as early biomarkers of DKD, laying the foundation for the prevention, diagnosis and treatment of DKD.

Plasma and vitreous selenium concentrations in patients with type 2 diabetes and diabetic retinopathy.

Background:This work aimed to determine and compare plasma and vitreous selenium (Se) concentrations in patients with type 2 diabetes and diabetic retinopathy (DR).Methods:A total of 60 type-2-diabetes patients including 20 without DR, 20 with non-proliferative DR (NPDR), and 20 with proliferative diabetic retinopathy (PDR), were involved in this study. Blood plasma samples were collected from above 60 patients and 20 normal controls (without diabetes). Twenty control vitreous samples were obtained from the eyes presenting a macular hole and epimacular membrane. Vitreous samples were also collected from PDR patients receiving one-week intravitreal anti-VEGF therapy or not. Plasma and vitreous Se concentrations were determined by inductively coupled plasma mass spectrometry.Results:Plasma Se concentrations in PDR patients (163.74 ± 32.68 μg/L) were significantly higher than those in normal control patients (121.59 ± 28.33 μg/L), NPDR patients (130.34 ± 29.11 μg/L), and the patients without DR (81.23 ± 20.59 μg/L) (all P < .001). Similarly, Se concentrations in vitreous samples of PDR patients (56.30 ± 12.03 μg/L) were consistently higher than those in control vitreous samples (26.26 ± 6.53 μg/L). In addition, vitreous Se concentrations in PDR patients decreased to 47.76 ± 9.72 μg/L after intravitreal injection of the anti-VEGF drug ranibizumab for one week, which was significantly lower than those before injection (P = .02). Plasma VEGF levels of diabetic patients were lower than those of the normal controls (P < .001). On the contrary, the vitreous VEGF level in the PDR group (913.61 ± 193.32 pg/mL) was significantly higher than that of the normal control group (101.23 ± 21.33 pg/mL) (P < .001).Conclusion:The elevation of Se concentrations may be an important risk factor in plasma and vitreous with diabetic retinopathy among type-2-diabetes patients. The elevated VEGF may be also closely related to the intraocular Se concentration in PDR patients.

Postoperative complications of combined phacoemulsification and pars plana vitrectomy in diabetic retinopathy patients.

PurposeTo compare intra- and postoperative complications in combined phacoemulsification and pars plana vitrectomy surgeries performed in patients with non-proliferative diabetic retinopathy (NPDR) vs. proliferative diabetic retinopathy (PDR).MethodsRetrospective, case series of patients with diabetic retinopathy who underwent combined phacovitrectomy surgery between 2008 and 2017. We compared intraoperative complications including posterior capsular rupture and retinal tear, and postoperative complications including corneal edema, macular edema (ME), epiretinal membrane (ERM), neovascular glaucoma and persistent inflammation.ResultsA total of 104 eyes of 104 patients were included in this study. Twenty-four eyes (23.1%) were categorized as NPDR and 80 eyes (76.9%) as PDR. The most common indications for surgery in the NPDR group were ERM (67%) and rhegmatogenous retinal detachment (12.5%), while in the PDR group, indications were vitreous hemorrhage (56%) and tractional retinal detachment (19%). The most common intraoperative complication was retinal tear (8% in NPDR and 19% in PDR, p = 0.195) and postoperative complication was ME (29% in NPDR and 26% in PDR, p = 0.778). There were no statistically significant differences in intra- and postoperative complication rates between the NPDR and PDR groups, even after adjusting for confounders; patient age at surgery and indication for surgery.ConclusionAfter combined phacovitrectomy in NPDR and PDR patients, new-onset ME was found in about a quarter of eyes in both groups. Intraoperative anti-VEGF or steroid administration, and intense postoperative anti-inflammatory medication and follow-up should be regarded after phacovitrectomy regardless of the DR level.