Progression Of Nonproliferative Diabetic Retinopathy Research Articles

Patterns of Progression of Nonproliferative Diabetic Retinopathy Using Non-Invasive Imaging.

To identify progression of nonproliferative diabetic retinopathy (NPDR) in patients with type 2 diabetes by combining optical coherence tomography angiography (OCTA) metrics and color fundus photography (CFP) images. This study was a post hoc analysis of a prospective longitudinal cohort study (CORDIS, NCT03696810) with 2-year duration. This study enrolled 122 eyes. Ophthalmological examinations included OCTA and CFP. OCTA metrics included skeletonized vessel density (SVD) and perfusion density (PD) at the superficial capillary plexus (SCP) and deep capillary plexus (DCP). Microaneurysm turnover analysis and Early Treatment Diabetic Retinopathy Study (ETDRS) grading for diabetic retinopathy (DR) severity assessment were performed on 7-field CFP. Eyes graded as ETDRS level 20 showed significant capillary nonperfusion predominantly in the inner ring area in the SCP (P < 0.001), whereas eyes graded as ETDRS level 35 and ETDRS levels 43 and 47 showed significant capillary nonperfusion in both the SCP and DCP in both inner and outer rings (P < 0.001). When evaluating rates of progression in capillary nonperfusion for the 2-year period of follow-up, changes were found predominantly in the DCP for SVD and PD and were better identified in the outer ring area. Microaneurysm turnover contributes to the characterization of NPDR progression by discriminating ETDRS level 35 from ETDRS levels 43 and 47 (P < 0.001), which could not be achieved using only OCTA metrics. Patterns of progression of NPDR can be identified combining OCTA examinations of the superficial and deep retinal capillary plexi of central retina and determination of microaneurysm turnover from fundus photographs. Our study reports results from a registered clinical trial that advances understanding of disease progression in NPDR.

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.

Evaluation of Hypoxia and Microcirculation Factors in the Progression of Diabetic Retinopathy.

The purpose of this study was to evaluate comparatively the changes in HIF-1ɑ, EPO, sICAM-1, hemodynamic, and electrophysiological parameters during the progression of non-proliferative diabetic retinopathy (NPDR). This retrospective longitudinal study included 82 patients with NPDR, who were divided into 2 groups: group I (n=40) consisted of patients without progression of NPDR after 1 year and group II (n=42) included patients with the transition of NPDR to proliferative diabetic retinopathy (PDR). The hemodynamics of the eye was assessed by Doppler ultrasonography. The glial hypoxia index Cg was calculated using ERG. The serum levels of hypoxia-inducible factor 1-a (HIF1-α), soluble intercellular adhesion molecule-1 (sICAM-1), and erythropoietin (EPO) were determined by ELISA method. In group II, resistive index (RI), short posterior ciliary arteries (SPCAs) increased significantly from 0.62 ± 0.005 to 0.65 ± 0.007 (P=0.003), being higher than the corresponding parameter in group I (P=0.013). In group II, there was an increase in the hypoxia index Cg (5.56 ± 0.05) relative to the primary indicators and in group I (P<0.001). In group II, HIF1-ɑ, EPO, and sICAM-1 levels after a year significantly increased (0.213 ± 0.02 ng/mL, 37.7 ± 2.4mIU/mL, and 576.3 ± 11.9 ng/mL, respectively) both relative to the main indicators and the values in group I (P<0.001). When EPO exceeds 27.5mIU/mL, a high risk of progression of NPDR to the initial stages of PDR is predicted. The glial Cg index and the level of HIF1-a, EPO in the serum of patients with progression of NPDR were initially higher than in patients without progression of NPDR and have increased during the year, indicating the development of PDR due to more severe hypoxia.

Experimental study on the therapeutic effect and mechanism of erlotinib on non-proliferative diabetic retinopathy

Experimental study on the therapeutic effect and mechanism of erlotinib on non-proliferative 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).

SGLT2 inhibitors and diabetic retinopathy progression.

To evaluate whether sodium-glucose co-transporter 2 (SGLT2) inhibitors affect progression of non-proliferative diabetic retinopathy (NPDR) compared to standard of care. A retrospective cohort study compared subjects enrolled in a commercial and Medicare Advantage medical claims database who filled a prescription for a SGLT2 inhibitor between 2013 and 2020 to unexposed controls, matched up to a 1:3 ratio. Patients were excluded if they were enrolled for less than 2years in the plan, had no prior ophthalmologic exam, had no diagnosis of NPDR, had a diagnosis of diabetic macular edema (DME) or proliferative diabetic retinopathy (PDR), had received treatment for vision-threatening diabetic retinopathy (VTDR), or were younger than 18years. To balance covariates of interest between the cohorts, an inverse probability treatment weighting (IPTW) propensity score for SGLT2 inhibitor exposure was used. Multivariate Cox proportional hazard regression modeling was employed to assess the hazard ratio (HR) for VTDR, PDR, or DME relative to SGLT2 exposure. A total of 6065 patients who initiated an SGLT2 inhibitor were matched to 12,890 controls. There were 734 (12%), 657 (10.8%), and 72 (1.18%) cases of VTDR, DME, and PDR, respectively, in the SGLT2 inhibitor cohort. Conversely, there were 1479 (11.4%), 1331 (10.3%), and 128 (0.99%) cases of VTDR, DME, and PDR, respectively, among controls. After IPTW, Cox regression analysis showed no difference in hazard for VTDR, PDR, or DME in the SGLT2 inhibitor-exposed cohort relative to the unexposed group [HR = 1.04, 95% CI 0.94 to 1.15 for VTDR; HR = 1.03, 95% CI 0.93 to 1.14 for DME; HR = 1.22, 95% CI 0.89 to 1.67 for PDR]. Exposure to SGLT2 inhibitor therapy was not associated with progression of NPDR compared to patients receiving other diabetic therapies.

26-LB: Identifying the Risk of Diabetic Retinopathy Progression Using Machine Learning on Ultrawide Field Retinal Images

Estimating the risk of diabetic retinopathy (DR) progression is one of the most important and difficult tasks when caring for individuals with diabetic eye disease. Current DR severity scales have informed clinicians on the progression risk and provided recommendations for follow-up and treatment. The use of artificial intelligence (AI) algorithms may improve in this process. In this study, we developed and validated machine learning (ML) models for DR progression from ultrawide field (UWF) retinal images, which were labeled for baseline DR severity and progression based on clinician review of the images and 3-year longitudinal follow-up using the Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale. This dataset has 8 classes: no DR nonprogression (14.62%), Mild nonproliferative DR (NPDR) progression (10.16%) /nonprogression (10.73%), Moderate NPDR progression (10.1%) /nonprogression (15.85%), Severe NPDR progression (11.27%) /nonprogression (10.68%), and proliferative DR (16.55%). A total of 9970 unique images were split into the train, the validation, and the test datasets based on 60-20-20 proportions. The class imbalance was addressed during model building through data augmentation. The ResNet model fine-tuned on this dataset has a classification test accuracy of 81% and an AUC of 0.967 on the test dataset. The objective of the model is to reduce false negatives, which refers to predicting a class that is less progressive than the true label. The predicted labels for 91% of the images were either correct labels or were the labels with greater progression than the original labels. These findings demonstrate the accuracy and feasibility of using machine learning models for identifying DR progression developed using UWF images. Potentially, the use of machine learning algorithms may further refine the risk of disease progression and personalize screening intervals that may reduce costs and improve vision-related outcomes. Disclosure A. Nigam: None. J. Sun: None. V. Subhash: None. P. S. Silva: Research Support; Optos plc., Optomed, Speaker's Bureau; Novartis, Roche Pharmaceuticals, Bayer Inc.

Developing and Validating Models to Predict Progression to Proliferative Diabetic Retinopathy.

To develop models for progression of nonproliferative diabetic retinopathy (NPDR) to proliferative diabetic retinopathy (PDR) and determine if incorporating updated information improves model performance. Retrospective cohort study. Electronic health record (EHR) data from a tertiary academic center, University of California San Francisco (UCSF), and a safety-net hospital, Zuckerberg San Francisco General (ZSFG) Hospital were used to identify patients with a diagnosis of NPDR, age ≥ 18 years, a diagnosis of type 1 or 2 diabetes mellitus, ≥ 6 months of ophthalmology follow-up, and no prior diagnosis of PDR before the index date (date of first NPDR diagnosis in the EHR). Four survival models were developed: Cox proportional hazards, Cox with backward selection, Cox with LASSO regression and Random Survival Forest. For each model, three variable sets were compared to determine the impact of including updated clinical information: Static0 (data up to the index date), Static6m (data updated 6 months after the index date), and Dynamic (data in Static0 plus data change during the 6-month period). The UCSF data were split into 80% training and 20% testing (internal validation). The ZSFG data were used for external validation. Model performance was evaluated by the Harrell's concordance index (C-Index). Time to PDR. The UCSF cohort included 1130 patients and 92 (8.1%) patients progressed to PDR. The ZSFG cohort included 687 patients and 30 (4.4%) patients progressed to PDR. All models performed similarly (C-indices ∼ 0.70) in internal validation. The random survival forest with Static6m set performed best in external validation (C-index 0.76). Insurance and age were selected or ranked as highly important by all models. Other key predictors were NPDR severity, diabetic neuropathy, number of strokes, mean Hemoglobin A1c, and number of hospital admissions. Our models for progression of NPDR to PDR achieved acceptable predictive performance and validated well in an external setting. Updating the baseline variables with new clinical information did not consistently improve the predictive performance. Proprietary or commercial disclosure may be found after the references.

IL-17A Enhances Retinal Neovascularization.

Retinal neovascularization occurs in proliferative diabetic retinopathy, neovascular glaucoma, and age-related macular degeneration. This type of retinal pathology normally occurs in the later stages of these ocular diseases and is a prevalent cause of vision loss. Previously, we determined that Interleukin (IL)-17A plays a pivotal role in the onset and progression of non-proliferative diabetic retinopathy in diabetic mice. Unfortunately, none of our diabetic murine models progress to proliferative diabetic retinopathy. Hence, the role of IL-17A in vascular angiogenesis, neovascularization, and the onset of proliferative diabetic retinopathy was unclear. In the current study, we determined that diabetes-mediated IL-17A enhances vascular endothelial growth factor (VEGF) production in the retina, Muller glia, and retinal endothelial cells. Further, we determined that IL-17A can initiate retinal endothelial cell proliferation and can enhance VEGF-dependent vascular angiogenesis. Finally, by utilizing the oxygen induced retinopathy model, we determined that IL-17A enhances retinal neovascularization. Collectively, the results of this study provide evidence that IL-17A plays a pivotal role in vascular proliferation in the retina. Hence, IL-17A could be a potentially novel therapeutic target for retinal neovascularization, which can cause blindness in multiple ocular diseases.

Fenofibrate for the prevention of progression of non-proliferative diabetic retinopathy: review, consensus recommendations and guidance for clinical practice.

The prevalence of diabetic retinopathy (DR), and associated morbidity is high in the Asia-Pacific region. Emerging evidence suggests a potential role for fenofibrate in the prevention of progression of DR, especially in patients with cardiovascular risk, and pre-existing mild-to-moderate DR. Fenofibrate has also been found to reduce maculopathy, and the need for laser treatment in these patients. Considering these benefits of fenofibrate, a group of experts from the fields of endocrinology and ophthalmology convened in May 2017, to discuss on the the mechanism of action, and clinical efficacy of fenofibrate in DR. The findings from key clinical studies on fenofibrate in DR were reviewed by the experts, and consensus statements were derived to define the role of fenofibrate in the prevention and treatment of DR. The statements were rated based on the GRADE criteria. An algorithm was also developed for the screening and treatment of DR in patients with type 2 diabetes (T2D), and the place of fenofibrate was defined in the algorithm. The expert recommendations, and the algorithm provided in this review will serve as a guide to the clinicians to reconsider the adjunctive use of fenofibrate for preventing the progression of DR in selected T2D patients.

Different Risk Profiles for Progression of Nonproliferative Diabetic Retinopathy: A 2-Year Study.

Characterization of 2-year progression of different risk phenotypes in eyes with mild and moderate nonproliferative diabetic retinopathy (NPDR) in type 2 diabetes (T2D). A 2-year prospective longitudinal cohort study (CORDIS, NCT03696810) was conducted. Ophthalmological examinations were performed including best corrected visual acuity, color fundus photography and optical coherence tomography (OCT and OCTA). OCT metrics, central retinal thickness and ganglion cell layer + inner plexiform layer (GCL + IPL) thickness were analyzed. OCTA metrics, vessel density (VD), perfusion density (PD) and area of intercapillary spaces (AIS) were obtained from superficial and deep capillary plexus (SCP, DCP). Only phenotype C identified by decreased VD ≥ 2 SD of healthy controls and phenotype B identified by subclinical macular edema with decreased VD < 2 SD of healthy controls were included. One hundred twenty-two eyes from T2D individuals were included in study; 65 eyes (53%) were classified as phenotype B and 57 eyes (47%) as phenotype C. For phenotype B, progression was associated with thinning of the GCL + IPL (ETDRS 35, 1 year p = 0.013, 2 year p < 0.001; ETDRS 43-47, 2 year p = 0.003) and vessel closure involving mainly the DCP for both ETDRS grades (ETDRS 35, 1 year p = 0.025, 2 year p = 0.034; ETDRS 43-47, 1 year p = 0.011). For phenotype C there was also progressive thinning of the GCL + IPL (ETDRS 35, in both years p ≤ 0.001; ETDRS 43-47, 1 year p = 0.002, 2 year p = 0.001), with vessel closure involving mainly SCP (ETDRS 35, 1 year p = 0.012, 2 year p = 0.023 in full-retina), which appeared to stabilize at maximal values in ETDRS grade 43-47 at the end of 2 years. ETDRS severity changes at the end of the 2-year period showed that worsening was associated with phenotype C with changes involving predominantly the SCP (VD, p = 0.005; PD, p = 0.008; AIS, p = 0.005). Association between ETDRS classification of NPDR severity and identification of different risk phenotypes offers new perspective to predict disease progression in T2D individuals with NPDR.

Supplementation with a Highly Concentrated Docosahexaenoic Acid (DHA) in Non-Proliferative Diabetic Retinopathy: A 2-Year Randomized Double-Blind Placebo-Controlled Study.

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.

Association of glycation markers with the progression of the initial stages of diabetic non-proliferative retinopathy in type 2 diabetes mellitus

Relevance. In the development and progression of non-proliferative diabetic retinopathy (NPDR) in type 2 diabetes mellitus (DM2), an important role belongs to the activity of the protein glycation process and the formation of advanced glycation end products (AGE).Objective: To link glycation markers carboxymethyl lysine (AGE-CML) and circulating AGE receptor (sRAGE) to the progression of early-stage of nonproliferative diabetic retinopathy in patients with type 2 diabetes.Material and methods. 91 patients (182 eyes) with diabetes mellitus aged 42 to 80 years were examined. The control group included 25 people of the appropriate age. At the time of the initial examination and 1 year later, the NPDR stage was established according to the modified ETDRS system of clinical signs Airlie House. The content of glycation markers was determined by enzyme-linked immunosorbent assay in blood plasma. MedStat and MedCalc v.15.1 (MedCalc Software bvba) software packages were used for statistical research.Results. The initial manifestations of diabetic retinal lesions occurred in 27.5% of patients, began after 7.16 ± 1.11 years and were accompanied by higher glycemia. The content of AGE-CML in diabetes mellitus was significantly increased compared to the control, which was more pronounced in the presence of initial retinal changes - was 1.3 times higher than in patients without such changes (p = 0.015). The content of sRAGE decreased several times, which was also associated with the presence of diabetic retinal changes - in their presence it was 2.2 times lower (p &lt;0.001). The content of AGE-CML was significantly higher (1.5 times; p &lt;0.001) in the presence of NPDR progression during 1 year of observation than without it. The content of sRAGE in the presence of progression was 1.6 times (p &lt;0.001) lower. Conclusion. Thus, accumulation of blood AGE-CML and sRAGE reduction is connected with the occurrence and progression of NPDR.Key words: nonproliferative diabetic retinopathy, type 2 diabetes mellitus, Advanced Glicated End Products, AGE-CML, sRAGE

Quantification of vascular and neuronal changes in the peripapillary retinal area secondary to diabetic retinopathy

PurposeTo investigate and quantify peripapillary vascular and neuronal changes secondary to diabetic retinopathy, using spectral-domain optical coherence tomography (OCT) and OCT angiography (OCTA).DesignThis was a cross-sectional study.Methods51 eyes of 51...

CASE OF IDIOPATHIC UVEAL EFFUSION THAT DEVELOPED PROLIFERATIVE DIABETIC RETINOPATHY AFTER SCLERAL RESECTION SURGERY

To report a diabetic patient with uveal effusion that developed proliferative diabetic retinopathy after unsuccessful scleral resection for the uveal effusion. A 50-year-old Japanese man with nonproliferative diabetic retinopathy and uveal effusion in his right eye underwent partial thickness sclerectomies at the four quadrants to treat the uveal effusion. These procedures reduced the amount of subretinal fluid and thus the choroidal and retinal detachment. However, the retinal detachment recurred and proliferative diabetic retinopathy developed with pre- and subretinal proliferation at 5 months after the surgery. The patient then underwent pars plana vitrectomy combined with phacoemulsification and implantation of an intraocular lens. During the surgery, the vasoproliferative membrane was removed, panretinal photocoagulation was performed, and intraocular tamponade with silicone oil was performed. After the removal of the silicone oil, the retina remained attached but the visual acuity was 2/20 because of macular atrophy. Clinicians should be aware that treatment of a uveal effusion by scleral resection can lead to a progression of nonproliferative diabetic retinopathy to proliferative diabetic retinopathy.

Anaemia and the risk of progression from non-proliferative diabetic retinopathy to vision threatening diabetic retinopathy

To determine if anaemia and oxygen delivery-related co-morbidities (ODCs) affect progression from non-proliferative diabetic retinopathy (NPDR) to vision-threatening diabetic retinopathy (VTDR). This is a retrospective cohort study using medical claims data from a large US insurer. Cohorts were created from all NPDR patients between 2002 and 2016. Primary exclusion criteria consisted of any previous diagnosis of proliferative diabetic retinopathy (PDR), diabetic macular oedema (DME) or treatment used in the care of VTDR. The main outcome was a new diagnosis of VTDR (DME or PDR), PDR, or DME. A time-dependent, multivariate Cox proportional hazard regression was used to determine the association between anaemia and other ODCs with NPDR progression. Of the total 69,982 NPDR patients included for analysis, 12,270, 2,162, and 10,322 progressed to VTDR, PDR and DME, respectively. Both mild and moderate/severe (mod/sev) anaemia were associated with an increased hazard for progression to VTDR (mild HR:1.10, 95% CI:1.04-1.16, p < 0.001; mod/sev HR:1.20, 95% CI:1.12-1.29, p < 0.001), PDR (mild HR:1.29, 95% CI:1.13-1.46, p < 0.001; mod/sev HR:1.43, 95% CI:1.21-1.69, p < 0.001), and DME (mild HR:1.06, 95% CI:1.00-1.13, p < 0.001; mod/sev HR:1.14, 95% CI:1.05-1.24, p < 0.001). ODCs such as chronic pulmonary disease and history of blood disorder/cancer were also significantly associated with an increased hazard for NPDR progression (HR > 1.00, p < 0.001 for all comparisons). Anaemia, independent of kidney disease, appears to play a significant role in progression from NPDR to VTDR, PDR, or DME. Concurrently, association of ODCs with NPDR progression lends support to the underlying mechanisms of anaemia in the pathogenesis of diabetic retinopathy.

Retinopathy severity correlates with RANTES concentrations and CCR 5-positive microvesicles in diabetes.

RANTES regulates leukocyte recruitment to areas affected by the inflammatory process. Microvesicles (MVs) belong to a subpopulation of extracellular vesicles and show proangiogenic potential by transferring bioactive molecules to target cells. the aim of this study was to determine the relationship between circulating proangiogenic factors (MVs and RANTES) and diabetes complications in patients with different severities of diabetic retinopathy (DR). CCR5 (CD195) receptors transported by annexin V-labeled MVs were also investigated. Diabetic patients (n = 61), among whom 35 had confirmed DR classified according to guidelines, and controls (n = 25) were included. MVs were isolated by centrifugation and analyzed using flow cytometry, RANTES was assessed by ELISA. the study group differed from the control group with respect to BMI, age, heart rate and systolic blood pressure. Additionally, glucose and creatinine concentrations were significantly increased: 5.30 [5.09-5.62] vs. 9.38 [7.48-11.55] (p <0.0001) mmol/l and 74.59 [64-84] vs. 89.00 [77.11-105.44] μmol/l (p = 0.0005), respectively. RANTES concentrations were significantly increased in diabetic patients compared to those of controls (15.5 (9.7-18.1) vs. 8.9 (0.9-14.6) μg/ml (p = 0.011)), and RANTES concentration significantly increased with respect to nonproliferative DR progression. Moreover, the number of CCR5-positive MVs was significantly increased in patients with heavy nonproliferative diabetic retinopathy (HNPDR) compared to those with so nonproliferative DR (SNPDR): 1178 [836-2254] vs. 394 [275-799] counts/μl. Correlation of RANTES concentrations with the stage of nonproliferative DR and the statistically significant dependence of CCR5-positive MVs with disease progression suggest that MVs and RANTES can be considered new biomarkers.

Progression of diabetic retinopathy severity after treatment with dexamethasone implant: a 24-month cohort study the 'DR-Pro-DEX Study'.

Intravitreal anti-vascular endothelial growth factor agents have been shown to reduce diabetic retinopathy (DR) progression; data on the effects of intravitreal corticosteroids on modifying disease severity are limited. This study evaluates the long-term effect of intravitreal dexamethasone implant (DEX) on the severity and progression of non-proliferative DR (NPDR). This was a retrospective cohort study. Sixty eyes from 60 consecutive patients with NPDR and diabetic macular edema (DME) treated with dexamethasone implant (DEX group) and 49 eyes from consecutive 49 patients without DME requiring observation only. Fundus angiography images from baseline and after 24months were graded by two masked assessors into mild, moderate and severe NPDR and PDR, according to the ETDRS classification. Patients were followed up 1-3 and 4-6months after each DEX implant. Re-treatment with DEX implant was on a pro re nata basis. Records were reviewed for performance of panretinal photocoagulation. Main outcome was as follows: change of DR≥1 grade and progression to proliferative diabetic retinopathy (PDR). Three eyes (5%) in the DEX group and 43 (87.8%) eyes in the control group progressed to PDR (P<0.0001). Twenty-five eyes (41.7%) in the DEX group but none in the control group demonstrated an improvement in DR severity (P<0.0001). This study provides the first long-term evidence that DEX implant has the potential to not only delay progression of DR and PDR development, but may also improve DR severity over 24months. Better understanding of the effects of corticosteroids will help guide its use in the treatment pathway of DR.

Plasma metabolic profile reveals PGF2α protecting against non-proliferative diabetic retinopathy in patients with type 2 diabetes

Diabetic retinopathy (DR) is the most frequent microvascular complications of diabetes and the leading cause of blindness in adults worldwide. Non-proliferative DR (NPDR) is the first stage of DR but currently has few recommended intervention. Eicosanoids play important roles in maintaining vessel homeostasis. However, the functions of eicosanoids in NPDR are still unknown. In this study, we investigated the eicosanoids profile difference in plasma between type 2 diabetes with NPDR or not. A total of 50 patients with type 2 diabetes were recruited and divided into non-DR (NDR) group and NPDR group based on fundus photographs. The eicosanoids profiles in plasma were determined by LC-MS/MS. Adhesion and transwell assay were used to detect the adhesion and migration effects of metabolites on primary bovine retinal pericyte cells (BRPC), respectively. Streptomycin (STZ)-induced diabetic mouse model was used to test the protective effects of selected metabolites according to retinal immunofluorescence staining and fluorescence confocal microscopy. Prostaglandin 2α (PGF2α) was decreased significantly in NPDR group compared to NDR group and negatively correlated with NPDR. In vitro, PGF2α was found to accelerate adhesion and migration by activating prostaglandin F receptor (FP receptor) and subsequent increasing RhoA activity in primary bovine retinal pericyte. Administration of PGF2α analogue diminished the damage on retinal capillary in an STZ-induced diabetic mouse model. Our results suggested that PGF2α may be a protective factor in the progression of NPDR in T2D patients. The protective mechanism of PGF2α was to increase pericyte mobility through FP receptor/RhoA pathway.

Proliferative retinopathy during hyperbaric oxygen treatment

A 43-year-old male with type 2 diabetes mellitus, treated with insulin for 28 years and with an HbA1c of 7.9% six months prior, suffered from bilateral plantar ulcers refractory to specialised wound care. He underwent a planned 40 sessions of treatment (HBOT) at 243 kPa for 90 minutes. Consent was given for this report. The patient's ophthalmic history included bilateral proliferative diabetic retinopathy (PDR) identified on routine diabetic eye screening three years previously. This was treated with pan-retinal photocoagulation (PRP). Three months before starting HBOT, he underwent phacoemulsification and intra-ocular lens insertion of his left eye, having had the same procedure done to his right eye a year prior, without complication. He was reviewed again one week prior to his first HBOT and fundoscopy confirmed non-proliferative diabetic retinopathy (NPDR) without evidence of PDR. The patient had a routine follow up by the ophthalmologist following his fifth HBOT when fundoscopic examination revealed pre-retinal a form of PDR, in his left eye. This was treated with PRP at the time. His visual acuity, 6⁄9 bilaterally, had not changed, nor did he describe any changes in his visual field despite these findings. He was seen three weeks later (following 12 further HBOT) when fundoscopy showed worsening proliferative changes, this time in both eyes. Bevacizumab was injected at the time and fill-in PRP performed the following week. His visual acuity remained unchanged in both eyes. At this point, HBOT was withheld to allow the proliferative phase of the patients' retinopathy to remit. The potentially effects of to the retinal vasculature of diabetic patients was postulated in 1994 following a similar experience, albeit without a baseline fundoscopic examination. In particular, the concern was of accelerating the proliferative process of retinopathy with subsequent irreversible loss of vision. Thereafter, routine screening and treatment of all diabetic patients for PDR was adopted at our facility. Until now, there have been no further cases of NPDR evolving into PDR at three-month review following HBOT. Indeed, a brief literature search using the terms retinopathy, complications, adverse effects, vitreous, hemorrhage, haemorrhage, hyperbaric and oxygen has not found any other cases described. In a double blind, randomised trial (meeting abstract only) of 15 diabetic patients with both NPDR and PDR, patients in neither the HBOT (243 kPa for 90 min) nor the control arm had evidence of neovascularisation nor worsening of their proliferative retinopathy at three-month follow up. The significance of PDR following cataract surgery has also been considered. A review article consistently found that NPDR progression occurred in up to a third of such patients. Despite this, there were no cases of NPDR progressing to PDR at 12-month follow up. Whether this patient's sudden progression to PDR was related to HBOT, recent cataract surgery or another unknown factor is unclear. However, the temporal relationship to 17 HBOT is difficult to explain and appears more rapid than available data regarding vascular regrowth in wound healing would suggest.