-
1.
Early Detection of Microvascular Impairments With Optical Coherence Tomography Angiography in Diabetic Patients Without Clinical Retinopathy: A Meta-analysis.
Zhang, B, Chou, Y, Zhao, X, Yang, J, Chen, Y
American journal of ophthalmology. 2021;:226-237
Abstract
PURPOSE To evaluate microvascular impairments with optical coherence tomography angiography (OCTA) in the eyes of diabetic patients with no diabetic retinopathy (NDR). DESIGN Systematic review and meta-analysis. METHODS The PubMed and Embase databases were comprehensively searched to identify studies comparing the microvascular changes between diabetic eyes without clinical retinopathy and healthy controls using OCTA. Data of interest were extracted and analyzed by Review Manager V.5.3 and Stata V.14.0. The weighted mean differences and their 95% confidence intervals were used to assess the strength of the association. RESULTS Forty-five cross-sectional studies involving 2241 diabetic and 1861 healthy eyes were ultimately included. OCTA unambiguously revealed that compared with the healthy control group, the NDR group manifested enlarged areas and increased perimeters of the foveal avascular zone, with decreased perfusion density (PD) in both superficial and deep capillary plexus of the macula (except parafoveal PD of the inner retina and foveal PD) and reduced radial peripapillary capillary PD. In addition, subgroup analyses according to the type of diabetes mellitus indicated that most of those differences became nonsignificant (except parafoveal PD in the deep capillary plexus) in type 1 diabetes mellitus, while in type 2 diabetes mellitus they remained statistically significant. CONCLUSION Our results suggested that retinal microvascular impairments might have occurred antecedent to clinically visible diabetic retinopathy and could be detected early by OCTA. However, those manifestations could be inconsistent according to the types of diabetes mellitus.
-
2.
The Impact of Bariatric Surgery on Diabetic Retinopathy: A Systematic Review and Meta-Analysis.
Yu, CW, Park, LJ, Pinto, A, Ma, ON, Lee, Y, Gupta, R, Chaudhary, V, Doumouras, AG, Hong, D
American journal of ophthalmology. 2021;:117-127
Abstract
OBJECTIVE While bariatric surgery induces remission of type 2 diabetes mellitus and reduces other microvascular complications, its impact on diabetic retinopathy (DR) is unclear. Some trials suggest early worsening of DR postsurgery because of rapid improvements in hyperglycemia. This meta-analysis sought to estimate the impact of bariatric surgery on DR for obese patients compared with medical treatment. DESIGN Systematic review and meta-analysis. METHODS The Medline, Embase, and PubMed Central databases were searched to March 2020. Primary studies comparing DR in patients undergoing bariatric surgery with those undergoing medical management were included. Results were meta-analyzed using a random-effects model. Primary outcomes included prevalence of all DR and sight-threatening DR after surgery. Secondary outcomes included worsening of DR within and beyond 12 months. RESULTS Overall, 14 studies comprised of 110,300 surgical patients and 252,289 control subjects were included. Surgical patients had a statistically significantly lower postoperative prevalence of all DR (relative risk [RR] 0.17 [95% confidence interval {CI} 0.13-0.22]) and sight-threatening DR (RR 0.47 [95% CI 0.27-0.82]). Early worsening of DR and progression to sight-threatening DR had occurred more often in those with more severe DR initially. However, beyond 12 months, bariatric surgery resulted in significantly fewer patients with worsened DR (RR 0.29 [95% CI 0.16-0.54]). The overall risk of bias was low; estimates of relative effects had low to moderate certainty of evidence. CONCLUSION While bariatric surgery was associated with fewer cases of all and sight-threatening DR, early worsening was more severe in patients with existing sight-threatening DR. These findings argue for frequent monitoring during the first postoperative year.
-
3.
Automated Grading of Diabetic Retinopathy with Ultra-Widefield Fluorescein Angiography and Deep Learning.
Wang, X, Ji, Z, Ma, X, Zhang, Z, Yi, Z, Zheng, H, Fan, W, Chen, C
Journal of diabetes research. 2021;:2611250
Abstract
PURPOSE The objective of this study was to establish diagnostic technology to automatically grade the severity of diabetic retinopathy (DR) according to the ischemic index and leakage index with ultra-widefield fluorescein angiography (UWFA) and the Early Treatment Diabetic Retinopathy Study (ETDRS) 7-standard field (7-SF). METHODS This is a cross-sectional study. UWFA samples from 280 diabetic patients and 119 normal patients were used to train and test an artificial intelligence model to differentiate PDR and NPDR based on the ischemic index and leakage index with UWFA. A panel of retinal specialists determined the ground truth for our data set before experimentation. A confusion matrix as a metric was used to measure the precision of our algorithm, and a simple linear regression function was implemented to explore the discrimination of indexes on the DR grades. In addition, the model was tested with simulated 7-SF. RESULTS The model classification of DR in the original UWFA images achieved 88.50% accuracy and 73.68% accuracy in the simulated 7-SF images. A simple linear regression function demonstrated that there is a significant relationship between the ischemic index and leakage index and the severity of DR. These two thresholds were set to classify the grade of DR, which achieved 76.8% accuracy. CONCLUSIONS The optimization of the cycle generative adversarial network (CycleGAN) and convolutional neural network (CNN) model classifier achieved DR grading based on the ischemic index and leakage index with UWFA and simulated 7-SF and provided accurate inference results. The classification accuracy with UWFA is slightly higher than that of simulated 7-SF.
-
4.
Glucagon-like peptide-1 (GLP-1) receptor agonists in type 2 diabetes and long-term complications: FOCUS on retinopathy.
Marchand, L, Luyton, C, Bernard, A
Diabetic medicine : a journal of the British Diabetic Association. 2021;(1):e14390
-
5.
Pyroptosis in the Retinal Neurovascular Unit: New Insights Into Diabetic Retinopathy.
Meng, C, Gu, C, He, S, Su, T, Lhamo, T, Draga, D, Qiu, Q
Frontiers in immunology. 2021;:763092
Abstract
Diabetic retinopathy (DR) is prevalent among people with long-term diabetes mellitus (DM) and remains the leading cause of visual impairment in working-aged people. DR is related to chronic low-level inflammatory reactions. Pyroptosis is an emerging type of inflammatory cell death mediated by gasdermin D (GSDMD), NOD-like receptors and inflammatory caspases that promote interleukin-1β (IL-1β) and IL-18 release. In addition, the retinal neurovascular unit (NVU) is the functional basis of the retina. Recent studies have shown that pyroptosis may participate in the destruction of retinal NVU cells in simulated hyperglycemic DR environments. In this review, we will clarify the importance of pyroptosis in the retinal NVU during the development of DR.
-
6.
Diagnostic performance of deep-learning-based screening methods for diabetic retinopathy in primary care-A meta-analysis.
Wewetzer, L, Held, LA, Steinhäuser, J
PloS one. 2021;(8):e0255034
Abstract
BACKGROUND Diabetic retinopathy (DR) affects 10-24% of patients with diabetes mellitus type 1 or 2 in the primary care (PC) sector. As early detection is crucial for treatment, deep learning screening methods in PC setting could potentially aid in an accurate and timely diagnosis. PURPOSE The purpose of this meta-analysis was to determine the current state of knowledge regarding deep learning (DL) screening methods for DR in PC. DATA SOURCES A systematic literature search was conducted using Medline, Web of Science, and Scopus to identify suitable studies. STUDY SELECTION Suitable studies were selected by two researchers independently. Studies assessing DL methods and the suitability of these screening systems (diagnostic parameters such as sensitivity and specificity, information on datasets and setting) in PC were selected. Excluded were studies focusing on lesions, applying conventional diagnostic imaging tools, conducted in secondary or tertiary care, and all publication types other than original research studies on human subjects. DATA EXTRACTION The following data was extracted from included studies: authors, title, year of publication, objectives, participants, setting, type of intervention/method, reference standard, grading scale, outcome measures, dataset, risk of bias, and performance measures. DATA SYNTHESIS AND CONCLUSION The summed sensitivity of all included studies was 87% and specificity was 90%. Given a prevalence of DR of 10% in patients with DM Type 2 in PC, the negative predictive value is 98% while the positive predictive value is 49%. LIMITATIONS Selected studies showed a high variation in sample size and quality and quantity of available data.
-
7.
Safety and cost-effectiveness of individualised screening for diabetic retinopathy: the ISDR open-label, equivalence RCT.
Broadbent, DM, Wang, A, Cheyne, CP, James, M, Lathe, J, Stratton, IM, Roberts, J, Moitt, T, Vora, JP, Gabbay, M, et al
Diabetologia. 2021;(1):56-69
-
-
Free full text
-
Abstract
AIMS/HYPOTHESIS Using variable diabetic retinopathy screening intervals, informed by personal risk levels, offers improved engagement of people with diabetes and reallocation of resources to high-risk groups, while addressing the increasing prevalence of diabetes. However, safety data on extending screening intervals are minimal. The aim of this study was to evaluate the safety and cost-effectiveness of individualised, variable-interval, risk-based population screening compared with usual care, with wide-ranging input from individuals with diabetes. METHODS This was a two-arm, parallel-assignment, equivalence RCT (minimum 2 year follow-up) in individuals with diabetes aged 12 years or older registered with a single English screening programme. Participants were randomly allocated 1:1 at baseline to individualised screening at 6, 12 or 24 months for those at high, medium and low risk, respectively, as determined at each screening episode by a risk-calculation engine using local demographic, screening and clinical data, or to annual screening (control group). Screening staff and investigators were observer-masked to allocation and interval. Data were collected within the screening programme. The primary outcome was attendance (safety). A secondary safety outcome was the development of sight-threatening diabetic retinopathy. Cost-effectiveness was evaluated within a 2 year time horizon from National Health Service and societal perspectives. RESULTS A total of 4534 participants were randomised. After withdrawals, there were 2097 participants in the individualised screening arm and 2224 in the control arm. Attendance rates at first follow-up were equivalent between the two arms (individualised screening 83.6%; control arm 84.7%; difference -1.0 [95% CI -3.2, 1.2]), while sight-threatening diabetic retinopathy detection rates were non-inferior in the individualised screening arm (individualised screening 1.4%, control arm 1.7%; difference -0.3 [95% CI -1.1, 0.5]). Sensitivity analyses confirmed these findings. No important adverse events were observed. Mean differences in complete case quality-adjusted life-years (EuroQol Five-Dimension Questionnaire, Health Utilities Index Mark 3) did not significantly differ from zero; multiple imputation supported the dominance of individualised screening. Incremental cost savings per person with individualised screening were £17.34 (95% CI 17.02, 17.67) from the National Health Service perspective and £23.11 (95% CI 22.73, 23.53) from the societal perspective, representing a 21% reduction in overall programme costs. Overall, 43.2% fewer screening appointments were required in the individualised arm. CONCLUSIONS/INTERPRETATION Stakeholders involved in diabetes care can be reassured by this study, which is the largest ophthalmic RCT in diabetic retinopathy screening to date, that extended and individualised, variable-interval, risk-based screening is feasible and can be safely and cost-effectively introduced in established systematic programmes. Because of the 2 year time horizon of the trial and the long time frame of the disease, robust monitoring of attendance and retinopathy rates should be included in any future implementation. TRIAL REGISTRATION ISRCTN 87561257 FUNDING The study was funded by the UK National Institute for Health Research. Graphical abstract.
-
8.
The Role of HIF1α-PFKFB3 Pathway in Diabetic Retinopathy.
Min, J, Zeng, T, Roux, M, Lazar, D, Chen, L, Tudzarova, S
The Journal of clinical endocrinology and metabolism. 2021;(9):2505-2519
-
-
Free full text
-
Abstract
Diabetic retinopathy (DR) is the leading cause of blindness for adults in developed countries. Both microvasculopathy and neurodegeneration are implicated in mechanisms of DR development, with neuronal impairment preceding microvascular abnormalities, which is often underappreciated in the clinic. Most current therapeutic strategies, including anti-vascular endothelial growth factor (anti-VEGF)-antibodies, aim at treating the advanced stages (diabetic macular edema and proliferative diabetic retinopathy) and fail to target the neuronal deterioration. Hence, new therapeutic approach(es) intended to address both vascular and neuronal impairment are urgently needed. The hypoxia-inducible factor 1α (HIF1α)-6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) pathway is critically implicated in the islet pathology of diabetes. Recent evidence highlighted the pathway relevance for pathologic angiogenesis and neurodegeneration, two key aspects in DR. PFKFB3 is key to the sprouting angiogenesis, along with VEGF, by determining the endothelial tip-cell competition. Also, PFKFB3-driven glycolysis compromises the antioxidative capacity of neurons leading to neuronal loss and reactive gliosis. Therefore, the HIF1α-PFKFB3 signaling pathway is unique as being a pervasive pathological component across multiple cell types in the retina in the early as well as late stages of DR. A metabolic point-of-intervention based on HIF1α-PFKFB3 targeting thus deserves further consideration in DR.
-
9.
Clinical efficacy and acceptability of panretinal photocoagulation combined with conbercept for patients with proliferative diabetic retinopathy: A protocol for systematic review and meta-analysis.
Wang, L, Chen, Z, Wang, X
Medicine. 2021;(17):e25611
-
-
Free full text
-
Abstract
BACKGROUND Although conbercept has been used for other diseases associated with new vascular formation, the effect of single-dose conbercept in combination with proliferative diabetic retinopathy (PDR) have not been established. We thus conducted this protocol for systematic review and meta-analysis to compare the efficacy and acceptability of panretinal photocoagulation (PRP) associated with intravitreal conbercept injections versus PRP alone in the treatment of patients with PDR. METHODS The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols reporting guidelines and the recommendations of the Cochrane Collaboration were followed to conduct this study. Reviewers will search the PubMed, Cochrane Library, Web of Science, and EMBASE online databases using the key phrases "panretinal photocoagulation," "conbercept," and "proliferative diabetic retinopathy" for all cohort studies published up to May 2021. The studies on cohort study focusing on PRP + conbercept and PRP alone for PDR patients will be included in our meta-analysis. At least one of the following outcomes should have been measured: PRP completion rate, proportion of eyes with visual gain/loss, central macular thickness, and incidence of complication. Review Manager software (v 5.4; Cochrane Collaboration) is used for the meta-analysis. RESULTS It was hypothesized that intravitreal conbercept plus PRP was more effective than PRP alone. OSF REGISTRATION NUMBER 10.17605/OSF.IO/HCQ2S.
-
10.
Characteristics Associated with Early Worsening of Retinopathy in Patients with Type 2 Diabetes Diagnosed with Retinopathy at Their First Visit: A Retrospective Observational Study.
Sugawa, SW, Yoshida, Y, Hikima, Y, Sato, H, Shimada, A, Noda, M, Kushiyama, A
Journal of diabetes research. 2021;:7572326
Abstract
MATERIALS AND METHODS Our study design was a retrospective observational study. Subjects with type 2 diabetes diagnosed with either simple or preproliferative diabetic retinopathy by ophthalmologists at their first visit and followed up for 6-18 months thereafter were included and divided into worsening and nonworsening groups. Thereafter, baseline characteristics and changes in HbA1c and therapy over a year were investigated. RESULTS Among the 88 subjects with simple diabetic retinopathy, 16% improved to no retinopathy, 65% retained their simple diabetic retinopathy, 18% worsened to preproliferative diabetic retinopathy, and 1% worsened to proliferative diabetic retinopathy. Among the 47 subjects with preproliferative diabetic retinopathy, 9% improved to simple diabetic retinopathy, 72% retained their preproliferative diabetic retinopathy, and 19% worsened to proliferative diabetic retinopathy. Patients with simple diabetic retinopathy had an odds ratio of 1.44 for worsening retinopathy with a 1% increase in baseline HbA1c. Meanwhile, the odds ratios for worsening retinopathy with a 1% decrease in HbA1c from baseline at 3, 6, and 12 months were 1.34, 1.31, and 1.38, respectively. Among patients with simple diabetic retinopathy, significantly more new interventions were introduced in the worsening group than in the nonworsening group. CONCLUSIONS Increased baseline HbA1c, a substantial decrease in HbA1c, and intensified therapy were identified as risk factors for early worsening of diabetic retinopathy in patients with simple diabetic retinopathy at the first visit. Patients should therefore be intimately followed for retinopathy after their first visit.