-
1.
Capillary density and caliber as assessed by optical coherence tomography angiography may be significant predictors of diabetic retinopathy severity.
Kushner-Lenhoff, S, Kogachi, K, Mert, M, Chu, Z, Shahidzadeh, A, Palejwala, NV, Wolfe, J, Itty, S, Drenser, KA, Capone, A, et al
PloS one. 2022;(1):e0262996
Abstract
PURPOSE To validate retinal capillary density and caliber associations with diabetic retinopathy (DR) severity in different clinical settings. METHODS This cross-sectional study assessed retinal capillary density and caliber in the superficial retinal layer of 3-mm OCTA scans centered on the fovea. Images were collected from non-diabetic controls and subjects with mild or referable DR (defined DR worse than mild DR) between February 2016 and December 2019 at secondary and tertiary eye care centers. Vessel Skeleton Density (VSD), a measure of capillary density, and Vessel Diameter Index (VDI), a measure of vascular caliber, were calculated from these images. Discriminatory performance of VSD and VDI was evaluated using multivariable logistic regression models predicting DR severity with adjustments for sex, hypertension, and hyperlipidemia. Area under the curve (AUC) was estimated. Model performance was evaluated in two different cohorts. RESULTS This study included 594 eyes from 385 subjects. Cohort 1 was a training cohort of 509 eyes including 159 control, 155 mild non-proliferative DR (NPDR) and 195 referable DR eyes. Cohort 2 was a validation cohort consisting of 85 eyes including 16 mild NPDR and 69 referable DR eyes. In Cohort 1, addition of VSD and VDI to a model using only demographic data significantly improved the model's AUC for discrimination of eyes with any DR severity from controls (0.91 [95% CI, 0.88-0.93] versus 0.80 [95% CI, 0.76-0.83], p < 0.001) and eyes with referable DR from mild NPDR (0.90 [95% CI, 0.86-0.93] versus 0.69 [95% CI, 0.64-0.75], p < 0.001). The transportability of this regression model was excellent when implemented in Cohort 2 for the referable DR versus mild NPDR comparison. The odds ratio of having any DR compared to control subjects, and referable DR compared to mild DR decreased by 15% (95% CI: 12-18%), and 13% (95% CI: 10-15%), respectively, for every 0.001 unit increase in VSD after adjusting for comorbidities. CONCLUSION OCTA-derived capillary density has real world clinical value for rapidly assessing DR severity.
-
2.
Evaluation of a New Model of Care for People with Complications of Diabetic Retinopathy: The EMERALD Study.
Lois, N, Cook, JA, Wang, A, Aldington, S, Mistry, H, Maredza, M, McAuley, D, Aslam, T, Bailey, C, Chong, V, et al
Ophthalmology. 2021;(4):561-573
Abstract
PURPOSE The increasing diabetes prevalence and advent of new treatments for its major visual-threatening complications (diabetic macular edema [DME] and proliferative diabetic retinopathy [PDR]), which require frequent life-long follow-up, have increased hospital demands markedly. Subsequent delays in patient's evaluation and treatment are causing sight loss. Strategies to increase capacity are needed urgently. The retinopathy (EMERALD) study tested diagnostic accuracy, acceptability, and costs of a new health care pathway for people with previously treated DME or PDR. DESIGN Prospective, multicenter, case-referent, cross-sectional, diagnostic accuracy study undertaken in 13 hospitals in the United Kingdom. PARTICIPANTS Adults with type 1 or 2 diabetes previously successfully treated DME or PDR who, at the time of enrollment, had active or inactive disease. METHODS A new health care pathway entailing multimodal imaging (spectral-domain OCT for DME, and 7-field Early Treatment Diabetic Retinopathy Study [ETDRS] and ultra-widefield [UWF] fundus images for PDR) interpreted by trained nonmedical staff (ophthalmic graders) to detect reactivation of disease was compared with the current standard care (face-to-face examination by ophthalmologists). MAIN OUTCOME MEASURES Primary outcome: sensitivity of the new pathway. SECONDARY OUTCOMES specificity; agreement between pathways; costs; acceptability; proportions requiring subsequent ophthalmologist assessment, unable to undergo imaging, and with inadequate images or indeterminate findings. RESULTS The new pathway showed sensitivity of 97% (95% confidence interval [CI], 92%-99%) and specificity of 31% (95% CI, 23%-40%) to detect DME. For PDR, sensitivity and specificity using 7-field ETDRS images (85% [95% CI, 77%-91%] and 48% [95% CI, 41%-56%], respectively) or UWF images (83% [95% CI, 75%-89%] and 54% [95% CI, 46%-61%], respectively) were comparable. For detection of high-risk PDR, sensitivity and specificity were higher when using UWF images (87% [95% CI, 78%-93%] and 49% [95% CI, 42%-56%], respectively, for UWF versus 80% [95% CI, 69-88%] and 40% [95% CI, 34%-47%], respectively, for 7-field ETDRS images). Participants preferred ophthalmologists' assessments; in their absence, they preferred immediate feedback by graders, maintaining periodic ophthalmologist evaluations. When compared with the current standard of care, the new pathway could save £1390 per 100 DME visits and between £461 and £1189 per 100 PDR visits. CONCLUSIONS The new pathway has acceptable sensitivity and would release resources. Users' suggestions should guide implementation.
-
3.
Four-Year Screening Interval and Vision-Threatening Retinopathy in Type 2 Diabetes Patients With Good Glycemic Control.
Tsujimoto, T, Kajio, H
Mayo Clinic proceedings. 2021;(2):322-331
Abstract
OBJECTIVE To assess whether vision-threatening retinopathy developed after 4 years in patients with type 2 diabetes with good glycemic control during follow-up. PATIENTS AND METHODS Using data from the Action to Control Cardiovascular Risk in Diabetes and Action to Control Cardiovascular Risk in Diabetes Follow-on studies (conducted from January 1, 2001, to October 14, 2014), we investigated the incidence of vision-threatening retinopathy after 4 years in patients with type 2 diabetes with good or poor glycemic control. Patients with proliferative diabetic retinopathy at baseline were excluded. Vision-threatening retinopathy was defined as severe nonproliferative diabetic retinopathy, proliferative diabetic retinopathy, laser photocoagulation, or vitrectomy. Good and poor glycemic control was defined as mean glycated hemoglobin level less than 7% and 7% or greater during follow-up, respectively. RESULTS This study included 2285 patients. Among patients with no retinopathy at baseline, the 4-year incidence of vision-threatening retinopathy was 0% (0 of 386) and 0.8% (6 of 721) in those with good and poor glycemic control, respectively (P=.54). Similarly, severe retinopathy was not observed at 8 years in patients who did not have retinopathy at 4 years. Among patients with mild to moderate nonproliferative diabetic retinopathy at baseline, the 4-year incidence of vision-threatening retinopathy was significantly higher in those with poor glycemic control than in those with good glycemic control (9.7% [77 of 790] vs 4.4% [13 of 297]; P=.004). Additionally, the remission rate of diabetic retinopathy was low in patients with a long duration of diabetes. Four-year incidences of vision-threatening retinopathy were higher in patients with retinopathy at baseline who had poorer glycemic control and longer durations of diabetes. CONCLUSION It may be safe to extend screening intervals for diabetic retinopathy to 4 years or longer in patients with type 2 diabetes with no retinopathy.
-
4.
Detection of Diabetic Retinopathy from Ultra-Widefield Scanning Laser Ophthalmoscope Images: A Multicenter Deep Learning Analysis.
Tang, F, Luenam, P, Ran, AR, Quadeer, AA, Raman, R, Sen, P, Khan, R, Giridhar, A, Haridas, S, Iglicki, M, et al
Ophthalmology. Retina. 2021;(11):1097-1106
Abstract
PURPOSE To develop a deep learning (DL) system that can detect referable diabetic retinopathy (RDR) and vision-threatening diabetic retinopathy (VTDR) from images obtained on ultra-widefield scanning laser ophthalmoscope (UWF-SLO). DESIGN Observational, cross-sectional study. PARTICIPANTS A total of 9392 UWF-SLO images of 1903 eyes from 1022 subjects with diabetes from Hong Kong, the United Kingdom, India, and Argentina. METHODS All images were labeled according to the presence or absence of RDR and the presence or absence of VTDR. Labeling was performed by retina specialists from fundus examination, according to the International Clinical Diabetic Retinopathy Disease Severity Scale. Three convolutional neural networks (ResNet50) were trained with a transfer-learning procedure for assessing gradability and identifying VTDR and RDR. External validation was performed on 4 datasets spanning different geographical regions. MAIN OUTCOME MEASURES Area under the receiver operating characteristic curve (AUROC); area under the precision-recall curve (AUPRC); sensitivity, specificity, and accuracy of the DL system in gradability assessment; and detection of RDR and VTDR. RESULTS For gradability assessment, the system achieved an AUROC of 0.923 (95% confidence interval [CI], 0.892-0.947), sensitivity of 86.5% (95% CI, 77.6-92.8), and specificity of 82.1% (95% CI, 77.3-86.2) for the primary validation dataset, and >0.82 AUROCs, >79.6% sensitivity, and >70.4% specificity for the geographical external validation datasets. For detecting RDR and VTDR, the AUROCs were 0.981 (95% CI, 0.977-0.984) and 0.966 (95% CI, 0.961-0.971), with sensitivities of 94.9% (95% CI, 92.3-97.9) and 87.2% (95% CI, 81.5-91.6), specificities of 95.1% (95% CI, 90.6-97.9) and 95.8% (95% CI, 93.3-97.6), and positive predictive values (PPVs) of 98.0% (95% CI, 96.1-99.0) and 91.1% (95% CI, 86.3-94.3) for the primary validation dataset, respectively. The AUROCs and accuracies for detecting both RDR and VTDR were >0.9% and >80%, respectively, for the geographical external validation datasets. The AUPRCs were >0.9, and sensitivities, specificities, and PPVs were >80% for the geographical external validation datasets for RDR and VTDR detection. CONCLUSIONS The excellent performance achieved with this DL system for image quality assessment and detection of RDR and VTDR in UWF-SLO images highlights its potential as an efficient and effective diabetic retinopathy screening tool.
-
5.
Effect of Intravitreous Aflibercept vs Vitrectomy With Panretinal Photocoagulation on Visual Acuity in Patients With Vitreous Hemorrhage From Proliferative Diabetic Retinopathy: A Randomized Clinical Trial.
Antoszyk, AN, Glassman, AR, Beaulieu, WT, Jampol, LM, Jhaveri, CD, Punjabi, OS, Salehi-Had, H, Wells, JA, Maguire, MG, Stockdale, CR, et al
JAMA. 2020;(23):2383-2395
-
-
Free full text
-
Abstract
IMPORTANCE Vitreous hemorrhage from proliferative diabetic retinopathy can cause loss of vision. The best management approach is unknown. OBJECTIVE To compare initial treatment with intravitreous aflibercept vs vitrectomy with panretinal photocoagulation for vitreous hemorrhage from proliferative diabetic retinopathy. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial at 39 DRCR Retina Network sites in the US and Canada including 205 adults with vison loss due to vitreous hemorrhage from proliferative diabetic retinopathy who were enrolled from November 2016 to December 2017. The final follow-up visit was completed in January 2020. INTERVENTIONS Random assignment of eyes (1 per participant) to aflibercept (100 participants) or vitrectomy with panretinal photocoagulation (105 participants). Participants whose eyes were assigned to aflibercept initially received 4 monthly injections. Both groups could receive aflibercept or vitrectomy during follow-up based on protocol criteria. MAIN OUTCOMES AND MEASURES The primary outcome was mean visual acuity letter score (range, 0-100; higher scores indicate better vision) over 24 weeks (area under the curve); the study was powered to detect a difference of 8 letters. Secondary outcomes included mean visual acuity at 4 weeks and 2 years. RESULTS Among 205 participants (205 eyes) who were randomized (mean [SD] age, 57 [11] years; 115 [56%] men; mean visual acuity letter score, 34.5 [Snellen equivalent, 20/200]), 95% (195 of 205) completed the 24-week visit and 90% (177 of 196, excluding 9 deaths) completed the 2-year visit. The mean visual acuity letter score over 24 weeks was 59.3 (Snellen equivalent, 20/63) (95% CI, 54.9 to 63.7) in the aflibercept group vs 63.0 (Snellen equivalent, 20/63) (95% CI, 58.6 to 67.3) in the vitrectomy group (adjusted difference, -5.0 [95% CI, -10.2 to 0.3], P = .06). Among 23 secondary outcomes, 15 showed no significant difference. The mean visual acuity letter score was 52.6 (Snellen equivalent, 20/100) in the aflibercept group vs 62.3 (Snellen equivalent, 20/63) in the vitrectomy group at 4 weeks (adjusted difference, -11.2 [95% CI, -18.5 to -3.9], P = .003) and 73.7 (Snellen equivalent, 20/40) vs 71.0 (Snellen equivalent, 20/40) at 2 years (adjusted difference, 2.7 [95% CI, -3.1 to 8.4], P = .36). Over 2 years, 33 eyes (33%) assigned to aflibercept received vitrectomy and 34 eyes (32%) assigned to vitrectomy received subsequent aflibercept. CONCLUSIONS AND RELEVANCE Among participants whose eyes had vitreous hemorrhage from proliferative diabetic retinopathy, there was no statistically significant difference in the primary outcome of mean visual acuity letter score over 24 weeks following initial treatment with intravitreous aflibercept vs vitrectomy with panretinal photocoagulation. However, the study may have been underpowered, considering the range of the 95% CI, to detect a clinically important benefit in favor of initial vitrectomy with panretinal photocoagulation. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02858076.
-
6.
Microvascular retinal changes in pre-clinical diabetic retinopathy as detected by optical coherence tomographic angiography.
Yang, JY, Wang, Q, Yan, YN, Zhou, WJ, Wang, YX, Wu, SL, Yuan, MX, Wei, WB, Jonas, JB
Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 2020;(3):513-520
Abstract
PURPOSE To investigate microvascular abnormalities in diabetic patients without conventional clinical signs of diabetic retinopathy (DR). METHODS In this cross-sectional observational cohort study, the study group included randomly chosen participants of a community-based cohort with diabetes type 2 without DR, and the control group consisted of non-diabetic individuals from a population-based study. All participants underwent optical coherence tomographic angiography (OCTA). RESULTS Upon OCTA, 118 (40.4%) eyes of the study group (n = 292 eyes) showed microvascular abnormalities including foveal avascular zone erosion (95 (32.5%) eyes), non-perfusion areas in the superficial and deep retinal layers (39 (13.4%) eyes and 19 (6.5%) eyes, respectively), and microaneurysms in the superficial and deep retinal layers (22 (7.5%) eyes and 31 (10.6%) eyes, resp.). None of these abnormalities was detected in the control group (n = 80). The study group showed a lower vessel density in the superficial retinal vascular layer in all regions except for the foveal region (P < 0.001), and higher vessel density in the parafoveal region in the deep retinal vascular layer (P = 0.01). Higher diabetes prevalence was associated with lower superficial retinal vascular density (P = 0.005) in multivariable analysis. A lower radial peripapillary capillary flow density was correlated (regression coefficient r, 0.62) with higher fasting blood concentration of glucose (P < 0.001) in multivariable analysis. CONCLUSIONS OCTA revealed microvascular abnormalities in 40% of eyes of diabetic patients without ophthalmoscopically detectable diabetic fundus changes in a community-based population. The early stage of DR may be re-defined upon OCTA.
-
7.
A Randomized, Double-Masked, Multicenter, Phase III Study Assessing the Efficacy and Safety of Brolucizumab versus Aflibercept in Patients with Visual Impairment due to Diabetic Macular Edema (KITE).
Garweg, JG
Klinische Monatsblatter fur Augenheilkunde. 2020;(4):450-453
Abstract
BACKGROUND Brolucizumab is a single-chain variable antibody fragment (scVF) that specifically binds to VEGF-A. The results of two large phase III, multicentre, randomized clinical trials comparing intravitreal treatment with Brolucizumab and Aflibercept in neovascular age-related degeneration demonstrated its potency in the treatment of neovascular age-related macular degeneration (nAMD). METHODS The currently tested injected dose of 6 mg Brolucizumab results in a 11.2 - 13.3 times higher equivalent molar dose compared to Aflibercept 2 mg. Thus, it is conceivable that the effect of Brolucizumab in DME exceeds that of other currently used anti-VEGF agents with regards to effect durability; this was confirmed for nAMD in a phase I/II study. RESULTS Approved anti-VEGF drugs have shown unprecedented success compared to laser treatment with regards to restoration of visual acuity and improvement of diabetic retinopathy severity scores for up to 5 years. The visual gains were sustained after the loading phase and a reduced number of injections were required after the first year independent of the treatment strategy. Compared to pan-retinal laser photocoagulation, the time to progression of DRP was markedly extended and was proven by better preservation of the visual field, prevention of severe vision loss, hemorrhagic complications, and the need for intraocular surgery. CONCLUSIONS The ongoing prospective, randomized, phase III clinical studies in DME, KITE, and KESTREL aim to confirm the non-inferiority of Brolucizumab 6 mg compared to Aflibercept 2 mg on a functional and morphological level as well as durability effect over 2 years.
-
8.
Long-term follow-up of diabetic macular edema treated with dexamethasone implant: a real-life study.
Mathis, T, Lereuil, T, Abukashabah, A, Voirin, N, Sudhalkar, A, Bilgic, A, Denis, P, Dot, C, Kodjikian, L
Acta diabetologica. 2020;(12):1413-1421
Abstract
AIMS: To evaluate the efficacy and safety of intravitreal dexamethasone implant (DEX-implant) for diabetic macular edema (DME) in real-life practice with an extended follow-up for up to 5 year. METHODS This multicentric retrospective study reviewed 227 eyes of 152 patients with DME treated by DEX-implant. Main outcome measures included changes in best corrected visual acuity (BCVA), central macular thickness (CMT), time to retreatment and incidence of adverse effects. RESULTS The mean number of DEX-implant received by patients was 2.6 (± 2.2) with a mean (SD) follow-up of 20.1 (± 15.8) months, median [IQR] 15.8 [7.4-30.1]. The mean time of retreatment was 6.9 months. The mean maximal BCVA gain during follow-up was 12.3 (± 12.7) letters. A gain of ≥ 5, ≥ 10 and ≥ 15 letters from baseline BCVA was obtained for 71.8%, 48.9% and 34.8% of eyes, respectively. A total of 62.6% of eyes presented a significant anatomical response (decrease of CMT ≥ 20%), and DME was resolved (absence of cystoid macular spaces on OCT) in 37% of cases at the end of the follow-up. A transient increase in intraocular pressure ≥ 25 mmHg occurred in 14.1% of eyes, and cataract surgery was performed for 49.1% of the phakic eyes during the follow-up. Four eyes developed a proliferative diabetic retinopathy. CONCLUSION This large cohort study showed favorable long-term outcomes when using DEX-implant, which provides substantial long-term benefits in the treatment of DME in real life.
-
9.
Complete Posterior Vitreous Detachment Reduces the Need for Treatment of Diabetic Macular Edema.
Anderson, W, Piggott, K, Bao, YK, Pham, H, Kavali, S, Rajagopal, R
Ophthalmic surgery, lasers & imaging retina. 2019;(11):e266-e273
-
-
Free full text
-
Abstract
BACKGROUND AND OBJECTIVE To evaluate the vitreomacular interface and its relation to treatment burden for diabetic macular edema (DME) in patients without overt vitreomacular traction (VMT). PATIENTS AND METHODS A retrospective cohort study of 494 eyes from 274 patients who had macular spectral-domain optical coherence tomography (SD-OCT) and did not have proliferative diabetic retinopathy, DME, or VMT at the initial visit. Posterior vitreous detachment (PVD) was categorized at the initial visit into five stages (0-4) using SD-OCT parameters alone. RESULTS Two of 34 eyes (6.9%) presenting with a complete PVD required DME treatment during follow-up, whereas 144 of 460 eyes (31.3%) without a complete PVD at baseline required treatment (P = .001, Chi-squared). After adjusting for age, ethnicity, gender, and HbA1c, complete PVD at baseline was associated with a significant reduction in risk of DME therapy (hazard ratio: 0.18; 95% confidence interval, 0.05-0.73; P = .02). CONCLUSION Complete PVD is independently associated with a reduced need for DME treatment. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e266-e273.].
-
10.
Association of non-alcoholic fatty liver disease with microvascular complications of type 2 diabetes.
Afarideh, M, Aryan, Z, Ghajar, A, Ganji, M, Ghaemi, F, Saadat, M, Heidari, B, Mechanick, JI, Esteghamati, A
Primary care diabetes. 2019;(6):505-514
Abstract
INTRODUCTION Non-alcoholic fatty liver disease (NAFLD) affects risks of type 2 diabetes (T2D), diabetes-related complications, and cardiovascular disease in a complex manner. This study is designed to clarify associations of sonographically-detected NAFLD and serum liver enzymes with diabetes-related microvascular complications. METHODS A matched case-contorl study was designed for 440 patients with T2D and at least one of the chronic diabetes-related microvascular complications and 495 age- and gender-matched control patients with T2D. RESULTS Considering pre-existing and newly developed chronic microvascular complications, diabetic peripheral neuropathy was found in 347 out of 935 (37.1%) study patients, diabetic retinopathy in 141/935 (15.1%), and diabetic nephropathy in 103/935 (11.0%). Diagnosis of diabetic retinopathy and diabetic nephropathy were inversely associated with the presence of NAFLD in the crude logistic regressions (OR [95% CI] = 0.18 [0.05-0.63], p value = 0.007; OR [95% CI] = 0.17 [0.04-0.59], p value = 0.011, respectively). The subgroup of NAFLD with elevated liver enzymes had lower odds of having diabetic peripheral neuropathy in the fully adjusted model (OR [95% CI] = 0.34 [0.12-0.98], p value = 0.048). CONCLUSION Diagnosis of NAFLD with or without elevated serum liver enzymes was inversely correlated with certain chronic diabetes microvascular complications. Possible explanations for this counter-intuitive and unexpected finding are discussed and center on reverse-causality, wherein sicker patients may develop beneficial compensatory physiological and behavioral adaptations. Diversity of studied patients, in particular with regards to the ethnic and racial differences among the Western and Asian populations may also partly account for contrasting findings of the relationship between NAFLD and microvascular complications of diabetes.