The Threshold of the Severity of Diabetic Retinopathy below Which Intensive Glycemic Control Is Beneficial in Diabetic Patients: Estimation Using Data from Large Randomized Clinical Trials.
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SUBMITTER: Liu Y
PROVIDER: S-EPMC6988671 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
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The Threshold of the Severity of Diabetic Retinopathy below Which Intensive Glycemic Control Is Beneficial in Diabetic Patients: Estimation Using Data from Large Randomized Clinical Trials.
Liu Yuqi Y Li Juan J Ma Jinfang J Tong Nanwei N
Journal of diabetes research 20200117
Intensive glucose therapy can protect the retina of individuals with diabetes, but it is unknown if it provides the same protection to patients with different severity of diabetic retinopathy (DR). We finally included DR-related studies involving intensive glucose control with large sample size and long follow-up time, including five large and high-quality randomized clinical trials (RCTs): DCCT, UKPDS, ACCORD, AdRem, and VADT. With DCCT as a reference, we supposed a DR severity threshold that i ...[more]
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Project description:ObjectivesTo compare the effects of intensive and standard statin therapy on severity of diabetic retinopathy (DR) complicated by hypercholesterolaemia in a prespecified substudy of the standard vs. intEnsive statin therapy for hypercholesteroleMic Patients with diAbetic retinopaTHY (EMPATHY) study.MethodsAmong 5144 patients in the multicentre, prospective, randomized EMPATHY study, this substudy considered 157 patients with seven-field fundus photographs of sufficient quality taken during study enrolment and at the 3-year visit. Eighty-five and seventy-two patients received intensive and standard statin treatments, respectively, in a treat-to-target manner. The primary endpoint was a two-step change in the Early Treatment Diabetic Retinopathy Study (ETDRS) DR severity scale at 36 months. Surrogate markers included changes in hard exudates, changes in visual acuity, and additional ocular treatments during study follow-up.ResultsIntensive and standard treatment groups did not differ significantly in terms of changing two or more steps on the DR severity scale (P = 0.4380). In patients with severe DR, defined as ≥47 on the severity scale, exploratory analysis showed more frequent improvement of DR, by at least one step, with intensive vs. standard treatment (83.3% vs. 40.0%; P = 0.0346). The intensive and standard groups did not differ in changes on the hard exudates severity scale (P = 0.3460), logarithm of minimum angle of resolution visual acuity (P = 0.5500), or additional ocular treatment during follow-up.ConclusionsIntensive and standard statin treatment may have similar effects on DR in the population of all patients with DR and hypercholesterolaemia, but intensive therapy may be more beneficial in patients with severe DR.
| S-EPMC8302652 | biostudies-literature
Project description:To identify genetic variants associated with diabetic retinopathy (DR), we performed a large multiethnic genome-wide association study. Discovery included eight European cohorts (n = 3,246) and seven African American cohorts (n = 2,611). We meta-analyzed across cohorts using inverse-variance weighting, with and without liability threshold modeling of glycemic control and duration of diabetes. Variants with a P value <1 × 10-5 were investigated in replication cohorts that included 18,545 European, 16,453 Asian, and 2,710 Hispanic subjects. After correction for multiple testing, the C allele of rs142293996 in an intron of nuclear VCP-like (NVL) was associated with DR in European discovery cohorts (P = 2.1 × 10-9), but did not reach genome-wide significance after meta-analysis with replication cohorts. We applied the Disease Association Protein-Protein Link Evaluator (DAPPLE) to our discovery results to test for evidence of risk being spread across underlying molecular pathways. One protein-protein interaction network built from genes in regions associated with proliferative DR was found to have significant connectivity (P = 0.0009) and corroborated with gene set enrichment analyses. These findings suggest that genetic variation in NVL, as well as variation within a protein-protein interaction network that includes genes implicated in inflammation, may influence risk for DR.
| S-EPMC6341299 | biostudies-literature
Project description:Summary We described a challenge named “Diabetic Retinopathy (DR)—Grading and Image Quality Estimation Challenge” in conjunction with ISBI 2020 to hold three sub-challenges and develop deep learning models for DR image assessment and grading. The scientific community responded positively to the challenge, with 34 submissions from 574 registrations. In the challenge, we provided the DeepDRiD dataset containing 2,000 regular DR images (500 patients) and 256 ultra-widefield images (128 patients), both having DR quality and grading annotations. We discussed details of the top 3 algorithms in each sub-challenges. The weighted kappa for DR grading ranged from 0.93 to 0.82, and the accuracy for image quality evaluation ranged from 0.70 to 0.65. The results showed that image quality assessment can be used as a further target for exploration. We also have released the DeepDRiD dataset on GitHub to help develop automatic systems and improve human judgment in DR screening and diagnosis. Graphical abstract Highlights • Provides the DeepDRiD dataset, performance evaluation, top methods and results• Presents deep learning approaches in DR image quality assessment and grading• Discusses the future work of DR automatic screening The bigger picture Diabetic retinopathy (DR) is the most common disease caused by diabetes. Challenges are held to address real-world issues encountered in the design of DR automated screening systems to advance the technology in this area. Thus, we described a challenge named "Diabetic Retinopathy (DR)—Grading and Image Quality Estimation Challenge" in conjunction with the IEEE International Symposium on Biomedical Imaging (ISBI 2020) for fundus image assessment and DR grading. The scientific community responded positively to the challenge. In the challenge, we provided a deep DR image dataset (DeepDRiD) containing regular DR images and ultra-widefield (UWF) DR images, both having image quality and DR grading diagnosis. We discussed details of the three best algorithms in each sub-challenges. The results by the top algorithms showed that image quality assessment can be used as a target for further exploration. In DeepDRiD challenge, organizers hold a real-world exploration in diabetic retinopathy (DR) auto-screening systems using regular fundus images from 500 participants and ultra-widefield fundus images from 128 participants. Among the 34 participating teams, we summarized the top 3 teams in the three sub-challenges involved in DR grading and image quality assessment. In addition to providing new insights into image quality assessment strategy, these models can enhance the judgment of healthcare workers in DR screening and bring precise screening results.
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Project description:Recently, several study designs incorporating treatment effect assessment in biomarker-based subpopulations have been proposed. Most statistical methodologies for such designs focus on the control of type I error rate and power. In this paper, we have developed point estimators for clinical trials that use the two-stage adaptive enrichment threshold design. The design consists of two stages, where in stage 1, patients are recruited in the full population. Stage 1 outcome data are then used to perform interim analysis to decide whether the trial continues to stage 2 with the full population or a subpopulation. The subpopulation is defined based on one of the candidate threshold values of a numerical predictive biomarker. To estimate treatment effect in the selected subpopulation, we have derived unbiased estimators, shrinkage estimators, and estimators that estimate bias and subtract it from the naive estimate. We have recommended one of the unbiased estimators. However, since none of the estimators dominated in all simulation scenarios based on both bias and mean squared error, an alternative strategy would be to use a hybrid estimator where the estimator used depends on the subpopulation selected. This would require a simulation study of plausible scenarios before the trial.
| S-EPMC6175016 | biostudies-literature
Project description:PurposeIncreased oxidative stress and inflammatory mediators are implicated in the development of diabetic retinopathy, and in rats, its development can be prevented by antioxidants. Carotenoids are some of the powerful antioxidants, and diabetes decreases lutein and zeaxanthin levels in the serum and retina. The aim of this study is to investigate the effect of carotenoid containing nutritional supplements (Nutr), which is in clinical trials for 'Diabetes Vision Function', on diabetic retinopathy.MethodsStreptozotocin-induced diabetic rats (Wistar, male) were fed Purina 5001 supplemented with nutritional supplements containing zeaxanthin, lutein, lipoic acid, omega-3 fatty acids and other nutrients, or without any supplementation. Retinal function was analyzed at ~4 months of diabetes by electroretinography. After 11 months of diabetes, capillary cell apoptosis (TUNEL-staining) and histopathology (degenerative capillaries) were quantified in trypsin-digested retinal vasculature. Retina was also analyzed for mitochondrial damage (by quantifying gene expressions of mtDNA-encoded proteins of the electron transport chain), VEGF and inflammatory mediators, interleukin-1β and NF-kB.ResultsDiabetes impaired retinal function decreasing the amplitudes of both a- and b-waves. In the same animals, retinal capillary cell apoptosis and degenerative capillaries were increased by 3-4 fold. Gene expressions of mtDNA encoded proteins were decreased, and VEGF, interleukin-1β and NF-kB levels were elevated. Supplementation with the nutrients prevented increased capillary cell apoptosis and vascular pathology, and ameliorated these diabetes-induced retinal abnormalities.ConclusionsNutritional supplementation prevents diabetic retinopathy, and also maintains normal retinal function, mitochondrial homeostasis and inflammatory mediators. Thus, this supplementation could represent an achievable and inexpensive adjunct therapy to also inhibit retinopathy, a slow progressing disease feared most by diabetic patients.
| S-EPMC3937140 | biostudies-literature
Project description:PurposeWe previously reported European mitochondrial haplogroup H to be a risk factor for and haplogroup UK to be protective against proliferative diabetic retinopathy (PDR) among Caucasian patients with diabetic retinopathy (DR). The purpose of this study was to determine whether these haplogroups are also associated with the risk of having DR among Caucasian patients with diabetes.MethodsDeidentified medical records for 637 Caucasian patients with diabetes (223 with DR) were obtained from BioVU, Vanderbilt University's electronic, deidentified DNA databank. An additional 197 Caucasian patients with diabetes (98 with DR) were enrolled from the Vanderbilt Eye Institute (VEI). We tested for an association between European mitochondrial haplogroups and DR status.ResultsThe percentage of diabetes patients with DR did not differ across the haplogroups (P = 0.32). The percentage of patients with nonproliferative DR (NPDR; P = 0.0084) and with PDR (P = 0.027) significantly differed across the haplogroups. In logistic regressions adjusting for sex, age, diabetes type, duration of diabetes, and hemoglobin A1c, neither haplogroup H nor haplogroup UK had a significant effect on DR compared with diabetic controls. Haplogroup UK was a significant risk factor (OR = 1.72 [1.13-2.59], P = 0.010) for NPDR compared with diabetic controls in the unadjusted analysis, but not in the adjusted analysis (OR = 1.29 [0.79-2.10], P = 0.20).ConclusionsMitochondrial haplogroups H and UK were associated with severity, but not presence, of DR. These data argue that the effect of these haplogroups is related to ischemia and neovascularization, the defining features of PDR.
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Project description:Prolonged diabetes ultimately leads to Diabetic Retinopathy (DR) which is one of the leading causes of preventable blindness in the world. Through advanced image analysis techniques are used for abnormalities detection in retina that define and correlate the severity of DR. A thorough study is done in this area in recent past years and on the basis of these studies we have developed a computer based prediction model that is used to determine the severity of DR. To identify severity DR, we have analyzed the human eye image. We have extracted some important features from human eye image i.e. Blood Artery, Optical disc, Exudates. Based on these image and data we have designed an automated system for the determination of DR severity. This automated DR severity assessment methods can be used to predict the clinical case and conditions when young clinicians would agree or disagree with their more experienced fellow members. The algorithms described in this study may be used in clinical practice to validate or invalidate the diagnoses. Algorithms or method developed here may also be used for pooling diagnostic knowledge for serving mankind. Here we have described a computational based low cost retinal diagnostic approach which can aid an ophthalmologist to quickly diagnose the various stages of DR. This system can accept retinal images and can successfully detect any pathological condition associated with DR.
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Project description:Diabetic retinopathy (DR) is more prevalent in blacks than whites because, compared to whites, blacks on average have worse glycemic control. Both of these racial disparities reflect differences in sociocultural determinants of health, including physician mistrust. This randomized, controlled 6-month pilot trial compared the efficacy of a culturally tailored behavioral health/ophthalmologic intervention called Collaborative Care for Depression and Diabetic Retinopathy (CC-DDR) to enhanced usual care (EUC) for improving glycemic control in black patients with DR (n = 33). The mean age of participants was 68 years (SD 6.1 years), 76% were women, and the mean A1C was 8.7% (SD 1.5%). At baseline, 14 participants (42%) expressed mistrust about ophthalmologic diagnoses. After 6 months, CC-DDR participants had a clinically meaningful decline in A1C of 0.6% (SD 2.1%), whereas EUC participants had an increase of 0.2% (SD 1.1%) (f[1, 28] = 1.9; P = 0.176). Within CC-DDR, participants with trust had a reduction in A1C (1.4% [SD 2.5%]), whereas participants with mistrust had an increase in A1C (0.44% [SD 0.7%]) (f[1, 11] = 2.11; P = 0.177). EUC participants with trust had a reduction in A1C (0.1% [SD 1.1%]), whereas those with mistrust had an increase in A1C (0.70% [SD 1.1%]) (f[1, 16] = 2.01; P = 0.172). Mistrust adversely affected glycemic control independent of treatment. This finding, coupled with the high rate of mistrust, highlights the need to target mistrust in new interventions to improve glycemic control in black patients with DR.
| S-EPMC6528393 | biostudies-literature
Project description:ImportanceModerate to substantial agreement between Early Treatment Diabetic Retinopathy Study (ETDRS) 7-field imaging and ultrawide-field (UWF) imaging has been suggested in single-center studies. Comparing images obtained by multiple centers could increase confidence that UWF images can be used reliably in place of ETDRS imaging in future clinical trials.ObjectiveTo compare diabetic retinopathy (DR) severity from modified ETDRS 7-field imaging and UWF imaging.Design, setting, and participantsThis preplanned, cross-sectional analysis included modified ETDRS 7-field images obtained using the Diabetic Retinopathy Clinical Research Network acquisition protocol and UWF images obtained captured with the Optos 200Tx system (Optos, PLC) from adult participants (≥18 years old) with type 1 or type 2 diabetes. Both image types were evaluated by trained graders masked to clinical data. Data collection occurred from February 2015 to December 2015, and data analysis from June 2016 to December 2017.Main outcomes and measuresAgreement between UWF images, UWF images masked to include only the ETDRS 7-field area, and ETDRS 7-field images were calculated using κ statistics.ResultsA total of 764 eyes from 385 participants were included; participants had a median (IQR) age of 62.2 (53.6-69.2) years, 194 (50.4%) were women, and 256 (66.5%) were white. Of 742 eyes with both ETDRS 7-field images and UWF masked images graded, 359 (48.4% [95% CI, 44.4%-52.4%]) eyes had exact agreement, and 653 eyes (88.0% [95% CI, 85.2%-90.3%]) agreed within 1 step (weighted κ, 0.51 [95% CI, 0.44-0.58]). After open adjudication by an independent senior grader of all images with more than a 2-step discrepancy, perfect agreement was found in 435 eyes (59.0% [95% CI, 55.1%-62.8%]) and agreement within 1 step in 714 eyes (96.9% [95% CI, 95.1%-98.0%]; κ, 0.77 [95% CI, 0.73-0.82]). Ability of the imaging modalities to detect retinopathy severity in an individual eye was considered similar in 59 eyes (50.9% [95% CI, 41.3%-60.4%]), better for ETDRS 7-field imaging in 22 eyes (19.0% [95% CI, 12.5%-27.7%]), and better for UWF-masked images in 31 eyes (26.7% [95% CI 18.8%-36.5%]). Comparing UWF masked and unmasked images, 94 of 751 eyes (12.5%) had DR graded as at least 1 step more severe on UWF unmasked images vs UWF masked images. Predominantly peripheral DR lesions were present in 308 of 751 eyes (41.0%); this suggested increased DR severity by 2 or more steps in 34 eyes (11.0%).Conclusions and relevanceImaging by the ETDRS 7-field and UWF imaging systems have moderate to substantial agreement when determining the severity of DR within the 7 standard fields. Disparities in an individual eye are equivalently distributed between imaging modalities and can be better or worse on 1 or the other. Longitudinal follow-up will evaluate the primary outcome of this study to determine if peripheral retinal findings are associated with future retinopathy outcomes.
| S-EPMC6439787 | biostudies-literature
Project description:ImportanceStudies have not yet determined whether the distribution of lesions in the retinal periphery alters the association between the severity of diabetic retinopathy (DR) and macular vessel density.ObjectiveTo evaluate the association of DR lesion distribution with optical coherence tomography angiography (OCTA) metrics and DR severity.Design, setting, and participantsThis cross-sectional observational study was conducted at a tertiary care center for diabetic eye disease among 225 patients with type 1 or 2 diabetes who had undergone imaging between February 15, 2016, and December 31, 2019.ExposuresOptical coherence tomography angiography 3 × 3-mm macular scans and ultra-widefield color imaging.Main outcomes and measuresOptical coherence tomography angiography vessel density in the superficial capillary plexus, intermediate capillary plexus, and deep capillary plexus and choriocapillaris flow density. The severity of DR and the predominantly peripheral lesions (PPL) were evaluated from ultra-widefield color imaging.ResultsThe study evaluated 352 eyes (225 patients; 125 men [55.6%]; mean [SD] age, 52.1 [15.1] years), of which 183 eyes (52.0%) had mild nonproliferative diabetic retinopathy (NPDR), 71 eyes (20.2%) had moderate NPDR, and 98 eyes (27.8%) had severe NPDR or proliferative diabetic retinopathy (PDR). In eyes with no PPL (209 [59.4%]), the mean (SD) vessel density in the superficial capillary plexus (mild NPDR, 38.1% [4.7%]; moderate NPDR, 36.4% [4.6%]; severe NPDR or PDR, 34.1% [4.1%]; P < .001) and the deep capillary plexus (mild NPDR, 45.8% [3.0%]; moderate NPDR, 45.8% [2.2%]; severe NPDR or PDR, 44.5% [1.9%]; P = .002), as well as the mean (SD) choriocapillaris flow density (mild NPDR, 69.7% [6.2%]; moderate NPDR, 67.6% [5.6%]; severe NPDR or PDR, 67.1% [5.6%]; P = .01), decreased with increasing DR severity. These associations remained statistically significant even after correcting for age, signal strength index, spherical equivalent, duration of diabetes, type of diabetes, and correlation between eyes of the same patient. In eyes with PPL (143 [40.6%]), mean (SD) vessel density in the superficial capillary plexus (mild NPDR, 34.1% [4.1%]; moderate NPDR, 35.2% [4.1%]; severe NPDR or PDR, 36.0% [4.3%]; P = .42) and the deep capillary plexus (mild NPDR, 44.5% [1.7%]; moderate NPDR, 45.4% [1.4%]; severe NPDR or PDR, 44.9% [1.5%]; P = .81), as well as the mean (SD) choriocapillaris flow density (mild NPDR, 67.1% [5.6%]; moderate NPDR, 69.3% [4.6%]; severe NPDR or PDR, 68.3% [5.6%]; P = .49), did not appear to change with increasing DR severity.Conclusions and relevanceThese results suggest that central retinal vessel density is associated with DR severity in eyes without, but not with, PPL. These findings suggest a potential need to stratify future optical coherence tomography angiography studies of eyes with DR by the presence or absence of PPL. If DR onset and worsening are associated with the location of retinal nonperfusion, assessment of global retinal nonperfusion using widefield angiography may improve the ability to evaluate DR severity and risk of DR worsening over time.
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