Incidence Of Proliferative Diabetic Retinopathy Research Articles

Serum VEGF, high-sensitivity CRP, and cystatin-C assist in the diagnosis of type 2 diabetic retinopathy complicated with hyperuricemia

Abstract Elevated serum uric acid (UA) level is related to type 2 diabetic retinopathy (DR). Vascular endothelial growth factor (VEGF), high-sensitivity C-reactive protein (hs-CRP), and cystatin C (Cys-C) have involvement in type 2 DR complicated with hyperuricemia (HUA) (HUDR), and we explored their clinical values in HUDR. Type 2 DR patients were allocated into HUDR/DR groups, with type 2 diabetes mellitus (T2DM) patients as the control group. Serum VEGF and inflammation markers hs-CRP, and Cys-C levels were assessed by ELISA and immunoturbidimetry. The correlations between serum UA level and VEGF/hs-CRP/Cys-C were analyzed by Pearson tests, diagnostic values of VEGF/hs-CRP/Cys-C were analyzed by receiver operating characteristic curves, and the independent risk factors in HUDR were analyzed by logistic multivariate regression. Serum VEGF/hs-CRP/Cys-C level differences among the T2DM/DR/HUDR groups were statistically significant, with the levels in HUDR > DR > T2DM. Serum UA level in HUDR patients was positively correlated with serum VEGF/hs-CRP/Cys-C. Serum VEGF/hs-CRP/Cys-C assisted in HUDR diagnosis, with their combination showing the greatest diagnostic value. UA/FPG/HbA1C/VEGF/hs-CRP/Cys-C were independent risk factors for HUDR. The incidence of proliferative DR was increased in HUDR patients. Collectively, serum VEGF, hs-CRP, and Cys-C levels in HUDR patients were increased, and HUA might promote DR progression.

Current Approaches and Developments in the Surgical Treatment of Proliferative Diabetic Retinopathy Complications

According to World Health Organization data, diabetes mellitus (DM) affects 425 million people in the world today, most of them from low- and middle-income countries and social segments. About a third of diabetic patients have diabetic retinopathy of any stage (DR), and 7% have proliferative diabetic retinopathy (PDR). Even in the ETDRS study, which included cases with timely laser photocoagulation, the 5-year cumulative incidence of vitrectomy was found to be 5.3%. The incidence of PDR and associated blindness has decreased owing to the improvements in diabetes monitoring and treatment. Also, the application of anti-vascular endothelial growth factors (anti-VEGF) and refinement of surgical techniques have greatly improved the management of diabetic eye complications.

Five-Year Incidence of Proliferative Diabetic Retinopathy and Associated Risk Factors in a Nationwide Cohort of 201 945 Danish Patients with Diabetes.

To evaluate the proliferative diabetic retinopathy (PDR) progression rates and identify the demographic and clinical characteristics of patients who later developed PDR compared with patients who did not progress to that state. A national 5-year register-based cohort study including 201 945 patients with diabetes. Patients with diabetes who had attended the Danish national screening program (2013-2018) for diabetic retinopathy (DR). We used the first screening episode as the index date and included both eyes of patients with and without subsequent progression of PDR. Data were linked with various national health registries to investigate relevant clinical and demographic parameters. The International Clinical Retinopathy Disease Scale was used to classify DR, with no DR as level 0, mild DR as level 1, moderate DR as level 2, severe DR as level 3, and PDR as level 4. Hazard ratios (HRs) for incident PDR for all relevant demographic and clinical parameters and 1-, 3-, and 5-year incidence rates of PDR according to baseline DR level. Progression to PDR within 5 years was identified in 2384 eyes of 1780 patients. Proliferative diabetic retinopathy progression rates from baseline DR level 3 at 1, 3 and 5 years were 3.6%, 10.9%, and 14.7%, respectively. The median number of visits was 3 (interquartile range, 1-4). Progression to PDR was predicted in a multivariable model by duration of diabetes (HR, 4.66 per 10 years; 95% confidence interval [CI], 4.05-5.37), type 1 diabetes (HR, 9.61; 95% CI, 8.01-11.53), a Charlson Comorbidity Index score of > 0 (score 1: HR, 4.62; 95% CI, 4.14-5.15; score 2: HR, 2.28; 95% CI, 1.90-2.74; score ≥ 3: HR, 4.28; 95% CI, 3.54-5.17), use of insulin (HR, 5.33; 95% CI, 4.49-6.33), and use of antihypertensive medications (HR, 2.23; 95% CI, 1.90-2.61). In a 5-year longitudinal study of an entire screening nation, we found increased risk of PDR with increasing baseline DR levels, longer duration of diabetes, type 1 diabetes, systemic comorbidity, use of insulin, and blood pressure-lowering medications. Most interestingly, we found lower risk of progression from DR level 3 to PDR compared with that in previous studies. Proprietary or commercial disclosure may be found after the references.

Prognostic factors for the development and progression of proliferative diabetic retinopathy in people with diabetic retinopathy.

Prognostic factors for the development and progression of proliferative diabetic retinopathy in people with diabetic retinopathy.

Proliferative Diabetic Retinopathy Events in Patients With Diabetic Macular Edema: Post Hoc Analysis of VISTA and VIVID Trials.

This work aimed to assess the incidence of proliferative diabetic retinopathy (PDR) events and improvement to mild non-PDR (NPDR) or better after intravitreal aflibercept injection (IAI) or laser treatment (control) in diabetic macular edema (DME). PDR events in the VISTA (NCT01363440) and VIVID (NCT01331681) phase 3 clinical trials were evaluated in a combined IAI-treated group (IAI 2 mg every 4 weeks or 2 mg every 8 weeks after 5 initial monthly doses; n = 475) and a macular laser control group (n = 235) through week 100 in eyes without PDR at baseline (Diabetic Retinopathy Severity Scale [DRSS] score ≤ 53). Improvement in the DRSS score to 35 or better was evaluated in those with a baseline DRSS score of 43 or greater. A lower proportion of eyes in the IAI group than in the laser group developed a PDR event through week 100 (4.4% vs 11.1%; adjusted difference, -6.7%; 97.5% CI, -11.7 to -1.6; nominal P = .0008). All PDR events occurred in eyes with a baseline DRSS score of 43, 47, or 53 and not in those with a score of 35 or less. A greater proportion of eyes in the IAI group than in the control group achieved a DRSS score of 35 or less (20.0% vs 3.8%; nominal P < .0001). Fewer eyes with NPDR and DME treated with IAI than eyes treated with a laser had a PDR event. More eyes treated with IAI improved to mild NPDR or better (DRSS score ≤ 35) through 100 weeks.

Trends in diabetic eye disorders and associated comorbidities in Taiwan: a 10-year nationwide population-based cohort study

Background/aimsIn-depth analysis is needed to investigate trends in diabetic retinopathy (DR), diabetic macular oedema (DME) and associated comorbidities in patients with type 2 diabetes mellitus (T2DM) so that we can...

Incidence of Proliferative Diabetic Retinopathy and Other Neovascular Sequelae at 5 Years Following Diagnosis of Type 2 Diabetes.

To determine the incidence and risk factors for developing proliferative diabetic retinopathy (PDR), tractional retinal detachment (TRD), and neovascular glaucoma (NVG) at 5 years after the initial diagnosis of type 2 diabetes. Insured patients aged ≥18 years with newly diagnosed type 2 diabetes and 5 years of continuous enrollment were identified from a nationwide commercial claims database containing data from 2007 to 2015. The incidences of PDR, TRD, and NVG were computed at 5 years following the index diagnosis of type 2 diabetes. Associations between these outcomes and demographic, socioeconomic, and medical factors were tested with multivariable logistic regression. At 5 years following the initial diagnosis of type 2 diabetes, 1.74% (1,249 of 71,817) of patients had developed PDR, 0.25% of patients had developed TRD, and 0.14% of patients had developed NVG. Insulin use (odds ratio [OR] 3.59, 95% CI 3.16-4.08), maximum HbA1c >9% or >75 mmol/mol (OR 2.10, 95% CI 1.54-2.69), renal disease (OR 2.68, 95% CI 2.09-3.42), peripheral circulatory disorders (OR 1.88, 95% CI 1.25-2.83), neurological disease (OR 1.62, 95% CI 1.24-2.11), and older age (age 65-74 years) at diagnosis (OR 1.62, 95% CI 1.28-2.03) were identified as risk factors for development of PDR at 5 years. Young age (age 18-23 years) at diagnosis (OR 0.46, 95% CI 0.29-0.74), Medicare insurance (OR 0.60, 95% CI 0.70-0.76), morbid obesity (OR 0.72, 95% CI 0.59-0.87), and smoking (OR 0.84, 95% CI 0.70-1.00) were identified as protective factors. A subset of patients with type 2 diabetes develop PDR and other neovascular sequelae within the first 5 years following the diagnosis with type 2 diabetes. These patients may benefit from increased efforts for screening and early intervention.

Prevalence and incidence of diabetic retinopathy (DR) in the UK population of Gloucestershire.

PurposeTo estimate prevalence and incidence of diabetic retinopathy (DR) in a UK region by severity between 2012 and 2016 and risk factors for progression to proliferative DR (PDR).MethodsElectronic medical records from people with diabetes (PWD) ≥18 years seen at the Gloucestershire Diabetic Eye Screening Programme (GDESP) and the hospital eye clinic were analysed (HEC). Prevalence and incidence of DR per 100 PWD (%) by calendar year, grade and diabetes type were estimated using log‐linear regression. Progression to PDR and associated risk factors were estimated using parametric survival analyses.ResultsAcross the study period, 35 873 PWD had at least one DR assessment. They were aged 66 (56–75) years (median (interquartile range)), 57% male, 5 (1–10) years since diabetes diagnosis, 93% Type 2 diabetes. Prevalence of DR decreased from 38.9% (95% CI: 38.1%, 39.8%) in 2012 to 36.6% (95% CI: 35.9%, 37.3%) in 2016 (p < 0.001). Incidence of any DR decreased from 10.9% (95% CI: 10.4%, 11.5%) in 2013 to 8.5% (95% CI: 8.1%, 9.0%) in 2016 (p < 0.001). Prevalence of PDR decreased from 3.5% (95% CI: 3.3%, 3.8%) in 2012 to 3.1% (95% CI 2.9%, 3.3%) in 2016 (p = 0.008). Incidence of PDR did not change over time. HbA1c and bilateral moderate–severe NPDR were statistically significant risk factors associated with progression to PDR.ConclusionsIncidence and prevalence of DR decreased between 2012 and 2016 in this well‐characterized population of the UK.

Statin reduces the incidence of diabetic retinopathy and its need for intervention: A systematic review and meta-analysis.

We aimed to perform a systematic literature search on the latest evidence of the role of statin in reducing diabetic retinopathy and its need for intervention. A comprehensive search on cohort studies/clinical trials that assess statins and diabetic retinopathy up until August 2019 was performed. The outcome measured was the incidence of diabetic retinopathy and its need for intervention. There were 558.177 patients from six studies. Statin was associated with a lower incidence of diabetic retinopathy (hazard ratio: 0.68 (0.55, 0.84), p < 0.001; I2: 95%). For the subtypes of diabetic retinopathy, statin lowers the incidence of proliferative diabetic retinopathy (hazard ratio: 0.69 (0.51, 0.93), p = 0.01; I2: 90%), non-proliferative diabetic retinopathy (hazard ratio: 0.80 (0.66, 0.96), p = 0.02; I2: 93%), and diabetic macular edema (hazard ratio: 0.56 (0.39, 0.80), p = 0.002; I2: 82%). Statin was associated with a reduced need for retinal laser treatment with a hazard ratio of 0.70 (0.64, 0.76) (p < 0.001; I2: 0%), intravitreal injection with a hazard ratio of 0.82 (0.79, 0.85) (p < 0.001; I2: 0%), and vitrectomy with a hazard ratio of 0.64 (0.48, 0.85) (p < 0.001; I2: 75%). Overall, statin was associated with a reduced need for intervention for diabetic retinopathy with a hazard ratio of 0.72 (0.64, 0.80) (p < 0.001; I2: 73%). The regression-based Egger's test showed statistically significant small-study effects for non-proliferative diabetic retinopathy (p = 0.011) outcomes. Statin was associated with a decreased risk of diabetic retinopathy and its subtypes. Statin also reduced the need for intervention with retinal laser treatment, intravitreal injection, and vitrectomy.

Longitudinal follow-up study of the retrobulbar and intrarenal hemodynamics in patients with T2DM.

Objective:The primary aim of this study is to examine the hemodynamics of retrobulbar and intrarenal in the changes of early stage of type 2 diabetes mellitus (T2DM) patients from 2000 to 2015 and to assess incidence associated with diabetic kidney disease (DKD) and diabetic retinopathy (DR).Method:Our study contained 60 subjects newly diagnosed of T2DM were divided into 2 groups base on the mean resistive index (RI) (≤0.7 and >0.7) of hemodynamic and to compare between-group differences of the early changes in hemodynamics of retrobulbar and intrarenal and also to conclude the incidences of diabetic kidney disease (DKD) and diabetic retinopathy (DR)subsequently with a long follow-up duration(2000–2015). First, to compare the mean RI of central retinal artery (CRA) between 2 groups. Second, to compare the mean RI of intrarenal hemodynamics in the bilateral interlobular renal arteries, renal function parameters (blood urea nitrogen (BUN), creatinine (Cr), blood glucose parameters (glycosylated hemoglobinA1c (HbA1c), fasting plasma glucose (FBG), and 2-hour postprandial blood glucose (2hPBG)), glomerular filtration rate (GFR), albumin excretion rate (AER), and urine albumin-to-creatinine ratio (UACR) between 2 groups.Results:First part of our follow-up studies was to compare hemodynamic RI index of retrobulbar in years of 2000 and 2015, both renal function and blood glucose parameters were fund significantly enhanced in subject group RIs ≤0.7. Incidence of DKD and DR was notably lower in group RIs ≤0.7 than group RIs > 0.7, difference was statistically significant (P < .05). Incidence of HbA1c ≤7% was higher in group RIs ≤0.7 than group RIs >0.7, but difference was not statistically significant (P > .05). Incidence of proliferative diabetic retinopathy (PDR) was notably lower in group RIs ≤0.7 than group RIs >0.7, but the difference was not statistically significant (P > .05). Second part of our follow-up studies was to compare hemodynamic RI index of interlobular renal in years of 2000 and 2015, both renal function and blood glucose parameters were fund significantly enhanced in subject group RIs ≤0.7. Compared data of various incidences from first part of study were coherent with second part. (Incidence of DKD and DR was notably lower in group RIs ≤0.7 than group RIs >0.7, difference was statistically significant (P < .05). Incidence of HbA1c ≤7% was higher in group RIs ≤0.7 than group RIs >0.7, but difference was not statistically significant (P > .05). Incidence of PDR was notably lower in group RIs ≤0.7 than group RIs >0.7, but the difference was not statistically significant (P > .05).Conclusions:RIs of retrobulbar and interlobular renal which would serve as a good predictors for the hemodynamics changes in retrobulbar and intrarenal would assess incidence of DKD and DR during the preclinical stage in long-term range excluding renal function and HbA1c in T2DM patients.

Could Intensive Blood Pressure Control Really Reduce Diabetic Retinopathy Outcomes? Evidence from Meta-Analysis and Trial Sequential Analysis from Randomized Controlled Trials.

IntroductionTo explore the accumulated evidence concerning the effect of intensive blood pressure control on the incidence and progression of diabetic retinopathy (DR), proliferative diabetic retinopathy (PDR) and macular edema (ME).MethodsA number of electronic databases were searched including PubMed, EMBASE, CINAHL, Cochrane Library, conferences and proceedings. Randomized controlled trials comparing intensive blood pressure targets with conventional blood pressure targets in patients with type 2 diabetes were included. The definition of intensive versus conventional blood pressure targets was from the pertinent original studies. Meta-analyses and trial sequential analyses of randomized trials were analyzed in STATA.ResultsEight trials randomizing 6989 patients were assessed and reviewed in full text; 3749 vs. 3240 were in each arm (intensive vs. conventional). All trials had a low risk of bias. Intensive blood pressure control supported a 17% reduction in the incidence of DR (relative risk 0.83, 95% confidence interval 0.72–0.95). Trial sequential analyses confirmed that sufficient evidence indicated a relative risk reduction above 17% for the incidence of DR when intensive blood pressure control was targeted. Heterogeneity was absent (I2 = 0%; P = 0.56). No statistically significant effect was found for intensive blood pressure targeting on the progress of DR (relative risk 0.94, 95% confidence interval 0.81–1.08). TSA showed that insufficient evidence had been found, although the Z value line appeared to have a tendency of approaching the futility boundaries. There were also no statistically significant effects on the incidence of PDR and ME (TSA-adjusted CI 0.84–1.12).ConclusionIntensive blood pressure control reduced the relative risk of incidence of DR by 17%. The available data were insufficient to prove or refute a relative risk reduction for the progression of DR or incidence of PDR and ME at a magnitude of 15%.

The Relationship of Retinal Vessel Geometric Characteristics to the Incidence and Progression of Diabetic Retinopathy

To examine the relationships of retinal vessel geometric characteristics (RVGCs) to the incidence and progression of diabetic retinopathy (DR). Observational, prospective cohort study. Nine hundred ninety-six persons with type 1 diabetes mellitus (T1DM) and 1370 persons with type 2 diabetes mellitus (T2DM) seen at a baseline examination who were eligible for follow-up examinations at subsequent 5-year intervals. A total of 3846 person-interval data from these follow-up examinations are the basis for the analyses. Diabetic retinopathy and macular edema were assessed by grading of 30° stereoscopic color fundus photographs. Retinal vessel geometric characteristics were assessed using the Singapore I Vessel Assessment program from a digitized copy of 1 of the field 1 fundus photographs obtained at baseline and follow-up. The 5-year incidence of any DR, progression of DR, and incidence of proliferative diabetic retinopathy (PDR) and clinically significant macular edema (CSME) in right eyes. Incident DR occurred in 45%, progression in 32%, PDR in 10%, and CSME in 5%. While adjusting for glycated hemoglobin, duration of diabetes, and other factors, retinal arteriolar simple tortuosity was associated significantly with the incidence of any DR (odds ratio [OR], 1.17; 95% confidence interval [CI], 1.01-1.35). Retinal venular branching angle was associated significantly with progression of DR (OR, 1.18; 95% CI, 1.03-1.36), retinal venular curvature tortuosity was associated significantly with the incidence of PDR (OR, 1.15; 95% CI, 1.01-1.30), and retinal venular branching angle (OR, 1.41; 95% CI, 1.10-1.82) was associated significantly with the incidence of CSME. There were no significant associations of other RVGCs with any of the DR outcomes in the full multivariate model. Inclusion of all possible RVGCs did not improve the predictive value of the models that already included retinal vessel diameter and baseline DR severity level. Retinal vessel geometric characteristics of the retinal venules were associated with progression of DR; however, most of the RVGCs measured from digitized fundus photographs added little to the assessment of risk of incidence and progression of DR when other risk factors were considered in T1DM and T2DM.

Oxidized Low-Density Lipoprotein and the Incidence of Proliferative Diabetic Retinopathy and Clinically Significant Macular Edema Determined From Fundus Photographs.

Studies have shown oxidized low-density lipoprotein to be associated with the incidence of proliferative retinopathy and other complications of type 1 diabetes mellitus. Because low-risk interventions are available to modify oxidized low-density lipoprotein, it is important to examine the relationships between this factor and the incidence of proliferative retinopathy and of macular edema, 2 important causes of visual impairment in people with type 1 diabetes. To determine the association of oxidized low-density lipoprotein with the worsening of diabetic retinopathy and the incidence of proliferative retinopathy and of macular edema. Of 996 participants with type 1 diabetes in the Wisconsin Epidemiologic Study of Diabetic Retinopathy, 730 were examined up to 4 times (1990-1992, 1994-1996, 2005-2007, and 2012-2014) over 24 years and had assays of oxidized low-density lipoprotein and fundus photographs gradable for diabetic retinopathy and macular edema. Analyses started July 2014 and ended February 2015. Worsening of diabetic retinopathy, incidence of proliferative diabetic retinopathy, and incidence of macular edema as assessed via grading of color stereo film fundus photographs. The levels of oxidized low-density lipoprotein collected from serum samples at the time of each examination were measured in 2013 and 2014 from frozen serum. The cohort at baseline had a mean (SD) level of oxidized low-density lipoprotein of 30.0 (8.5) U/L. While adjusting for duration of diabetes, glycated hemoglobin A1c level, and other factors, we found that neither the level of oxidized low-density lipoprotein at the beginning of a period nor the change in it over a certain period was associated with the incidence of proliferative diabetic retinopathy (hazard ratio [HR], 1.11 [95% CI, 0.91-1.35], P = .30; odds ratio [OR], 1.77 [95% CI, 0.99-3.17], P = .06), the incidence of macular edema (HR, 1.04 [95% CI, 0.83-1.29], P = .74; OR, 1.08 [95% CI, 0.44-2.61], P = .87), or the worsening of diabetic retinopathy (HR, 0.94 [95% CI, 0.83-1.07], P = .34; OR, 1.32 [95% CI, 0.83-2.09], P = .24). Our findings do not provide evidence for a relationship between increasing levels of serum oxidized low-density lipoprotein and the incidence of macular edema or the worsening of diabetic retinopathy in persons with type 1 diabetes. The potential increase in the HR for incident proliferative retinopathy, with an increase in oxidized low-density lipoprotein level over the preceding period, warrants further investigation of this relationship.

Serum Lipids and Proliferative Diabetic Retinopathy and Macular Edema in Persons With Long-term Type 1 Diabetes Mellitus: The Wisconsin Epidemiologic Study of Diabetic Retinopathy.

Total serum and high-density lipoprotein cholesterol have been considered risk factors for severe vascular outcomes in persons with type 1 diabetes mellitus. To examine the long-term relationships between these 2 serum lipids and the incidence and prevalence of proliferative diabetic retinopathy and macular edema. Nine-hundred three persons with younger-onset type 1 diabetes mellitus who participated in the Wisconsin Epidemiologic Study of Diabetic Retinopathy. Serum total and high-density cholesterol and history of statin use during the course of 5 visits spanning approximately 30 years (April 10, 1984, to February 13, 2014). Prevalence and incidence of proliferative diabetic retinopathy and macular edema. A modest association was found for higher levels of high-density lipoprotein cholesterol and decreased prevalence of proliferative diabetic retinopathy (odds ratio per 10 mg/dL, 0.87; 95% CI, 0.82-0.93), adjusting for duration of diabetes mellitus, glycosylated hemoglobin A1c, statin use, and end-stage renal disease. While adjusting for covariates, no associations of serum total or high-density lipoprotein cholesterol and incident proliferative diabetic retinopathy or macular edema, nor of statin use with decreased incidence of proliferative diabetic retinopathy or macular edema, were identified. In the course of long-duration diabetes mellitus during a time of changing medical care, there appeared to be little effect of serum lipids or statins on the incidence of proliferative diabetic retinopathy and macular edema.

The 16-year incidence, progression and regression of diabetic retinopathy in a young population-based Danish cohort with type 1 diabetes mellitus: The Danish cohort of pediatric diabetes 1987 (DCPD1987)

The aim was to investigate the long-term incidence of proliferative diabetic retinopathy (PDR), and progression and regression of diabetic retinopathy (DR) and associated risk factors in young Danish patients with Type 1 diabetes mellitus. In 1987-89, a pediatric cohort involving approximately 75% of all children with Type 1 diabetes in Denmark <19years of age was identified (n=720). In 1995, 339 (47.1%) were re-studied with retinopathy graded and all relevant diabetic parameters assessed. Of those, 185 (54.6%) were evaluated again in 2011 for the same clinical parameters. All retinal images were graded using modified early treatment of DR study for 1995 and 2011. In 1995, mean age was 21.0years and mean diabetes duration 13.5years. The 16-year incidence of proliferative retinopathy, 2-step progression and 2-step regression of DR was 31.0, 64.4 and 0.0%, respectively, while the incidence of DR was 95.1%. In a multivariate logistic regression model, progression to PDR was significantly associated with 1995 HbA1c (OR 2.61 per 1% increase, 95% CI 1.85-3.68) and 1995 diastolic blood pressure (OR 1.79 per 10mmHg increase, 95% CI 1.04-3.07). Two-step progression of DR was associated with male gender (OR 2.37 vs. female, 95% CI 1.07-5.27), 1995 HbA1c (OR 3.02 per 1% increase, 95% CI 2.04-4.48) and 1995 vibration perception threshold (OR 1.19 per 1Volt increase, 95% CI 1.02-1.40). In conclusion, one in three progressed to PDR and two in three had 2-step progression despite young age and increased awareness of the importance of metabolic control. After 30years duration of diabetes, the presence of DR is almost universal.

Inflammatory Biomarkers and Progression of Diabetic Retinopathy in African Americans With Type 1 Diabetes

We examined whether baseline plasma levels of markers of inflammation and endothelial dysfunction are associated with the incidence of diabetic retinopathy (DR) in African Americans with type 1 insulin-dependent diabetes mellitus (T1DM). At baseline and follow-up examinations, detailed ocular examination, structured clinical interview, venous blood specimens, and masked grading of seven standard field retinal photographs were obtained. Baseline plasma levels of 28 inflammatory biomarkers, measured using multiplex bead analysis system, were measured in the participants. After adjusting for age, glycemic control, and other potential confounders, baseline plasma levels of E-selectin were associated significantly with progression of DR, E-selectin and tumor necrosis factor-α (TNF-α) levels with incidence of proliferative DR (PDR), and soluble intercellular adhesion molecule-1 (sICAM-1) and TNF-α levels with incidence of macular edema (ME). In African Americans with T1DM, inflammation and endothelial dysfunction precede the development of DR, thus supporting the notion that inflammation may influence progression/incidence of disease.

Changes in Retinal Vessel Diameter and Incidence and Progression of Diabetic Retinopathy

To describe the relationship of change in retinal vessel diameters to the subsequent 6-year incidence and progression of diabetic retinopathy (DR) and incidence of proliferative diabetic retinopathy (PDR) and macular edema (ME) in persons with diabetes mellitus. A total of 1098 persons with diabetes who had DR graded from fundus photographs and had computer-assisted measurements of the central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent(CRVE) participated in examinations in 1980-1982, 1984-1986, and 1990-1992. During the first 4-year period, the mean change in CRAE and CRVE was −0.37 and 2.54 μm, respectively.The 6-year incidence and progression of DR and the incidence of PDR and ME from 1984-1986 to 1990-1992 were 56%, 39%, 15%, and 11%, respectively. In multivariate analyses, while controlling for duration, diabetes type, and other factors, an increase of 10 μm in CRVE from 1980-1982 to 1984-1986 was associated with increases in the 6-year incidence of DR (odds ratio [OR],1.26; 95% CI, 1.10-1.43), progression of DR (OR, 1.21;95% CI, 1.12-1.30), incidence of PDR (OR, 1.19; 95%CI, 1.07-1.32), and incidence of ME (OR, 1.16; 95% CI,1.03-1.31). No interactions of these associations by diabetes type were found (data not shown). Change in CRAE was unrelated to the incidence or progression of DR (data not shown). Independent of DR severity level, glycemic control, and other factors, widening of the retinal venular but not arteriolar diameter was associated with subsequent incidence and progression of DR. The CRVE may provide additional information regarding the risk of incidence and progression of DR beyond traditional risk factors.

The Relation of Markers of Inflammation and Endothelial Dysfunction to the Prevalence and Progression of Diabetic Retinopathy

To determine the relation of glycemia, blood pressure, and serum total cholesterol level as systemic markers of inflammation and endothelial dysfunction to the prevalence and incidence of diabetic retinal outcomes in persons with long-duration type 1 diabetes mellitus. Longitudinal population-based study of persons with type 1 diabetes mellitus who received care for their diabetes in south central Wisconsin from July 1, 1979, to June 30, 1980. Data for this investigation were obtained from the 1990-1992 through the 2005-2007 follow-up examinations. Main outcome measures included the severity of diabetic retinopathy (DR) and macular edema (ME). In the 1990-1992 prevalence data, soluble vascular cell adhesion molecule, tumor necrosis factor, and homocysteine levels were associated with increased odds of more severe DR (odds ratios [highest vs lowest quartile], 3.95 [95% confidence interval, 1.66-9.39], 5.46 [2.38-12.52], and 7.46 [2.91-19.16], respectively) in those with kidney disease while controlling for relevant confounders. Similar odds were found for proliferative DR. Only total homocysteine level was associated with increased odds of ME (3.80 [95% confidence interval, 1.91-7.54]), irrespective of kidney disease. None of the markers were associated with incidence of proliferative DR, ME, or progression of DR 15 years later. A limited number of markers are associated with increased odds of prevalent retinal outcomes in persons with type 1 diabetes mellitus and kidney disease. Only homocysteine level is associated with ME in those with and without kidney disease. In the absence of kidney disease, the markers do not add to the more conventional descriptors and predictors of DR in persons with type 1 diabetes mellitus. This may reflect the close association of DR and kidney disease in diabetic persons.

Changes in Visual Impairment Prevalence by Period of Diagnosis of Diabetes: The Wisconsin Epidemiologic Study of Diabetic Retinopathy

To examine relationships of period of diagnosis of type 1 diabetes mellitus (T1DM) to the prevalence of visual impairment (VI). Population-based longitudinal study. Nine hundred fifty-five persons (3719 participant visits) 4 to 80 years of age at baseline who lived in an 11-county area in southern Wisconsin who were diagnosed with T1DM before 30 years of age contributed to the prevalence of VI. Five eye examination visits occurred in the following periods: 1980 through 1982, 1984 through 1986, 1990 through 1992, 1995 through 1996, and 2005 through 2007. Age of diagnosis of T1DM was grouped as before 1960, 1960 through 1969, 1970 through 1974, and 1975 through 1979. Best-corrected visual acuity (VA) using a modification of the Early Treatment Diabetic Retinopathy protocol was measured. Visual impairment was defined as best-corrected VA in the better eye of 20/40 or worse. While controlling for duration of T1DM, there was a lower prevalence of VI for more recent periods of diagnosis of diabetes (odds ratio per category, 0.91; 95% confidence interval, 0.88-0.93; P<0.001). This remained while controlling for glycosylated hemoglobin, blood pressure, and other related factors. More recently diagnosed T1DM was associated with a lower prevalence of VI. This is likely because of the diminishing incidence of proliferative diabetic retinopathy (PDR) and clinically significant macular edema (CSME) resulting from better glycemic control and more timely interventions with photocoagulation for CSME and PDR in those with more recently diagnosed T1DM.

Retinal Vessel Caliber and Microvascular and Macrovascular Disease in Type 2 Diabetes: XXI: The Wisconsin Epidemiologic Study of Diabetic Retinopathy

To describe the relationship of retinal arteriolar and venular calibers to the long-term incidence of microvascular and macrovascular complications in people with type 2 diabetes. Population-based prospective study. One thousand three hundred seventy persons diagnosed to have diabetes at > or =30 years of age in south central Wisconsin participated in the baseline examination from 1980 to 1982, 987 in the 4-year follow-up, and 533 in the 10-year follow-up. Computer-assisted grading was used to determine the average caliber of retinal arterioles (central retinal arteriolar equivalent [CRAE]) and retinal venules (central retinal venular equivalent [CRVE]) at all examinations. Incidence and progression of diabetic retinopathy; incidence of proliferative diabetic retinopathy and macular edema; incidence of nephropathy, neuropathy, and lower extremity amputation; and ischemic heart disease, stroke, and overall mortality. While adjusting for other factors, smaller CRAE was associated with the 14-year cumulative incidence of lower extremity amputation (odds ratio [OR], first vs. second to fourth quartiles, 2.20; 95% confidence interval [CI], 1.14-4.24; P = 0.02), 22-year all-cause mortality (hazard ratio [HR], 1.18; 95% CI, 1.02-1.38; P = 0.03), and 22-year stroke mortality (HR, 1.47; 95% CI, 1.04-2.07; P = 0.03) but not with the other end points. Larger CRVE was associated with the 14-year incidence of diabetic nephropathy (OR, fourth vs. first to third quartiles, 2.08; 95% CI, 1.47-2.94; P<0.001) and 22-year stroke mortality (HR, 1.71; 95% CI, 1.20-2.44; P = 0.003) but with none of the other end points. Retinal vessel caliber is independently associated with risk of incident nephropathy, lower extremity amputation, and stroke mortality in persons with type 2 diabetes. Measurement of retinal vessel caliber from photographs may provide additional information for the prediction of these events.