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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.
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Effects of Rosuvastatin and Aspirin on Retinal Vascular Structures in Hypercholesterolemic Patients with Low-to-Moderate Risk of Coronary Artery Disease.
Li, L, Wang, S, Huang, H, Cai, Y, Xi, Y, Bai, Y, Ma, C
American journal of cardiovascular drugs : drugs, devices, and other interventions. 2019;(4):415-420
Abstract
INTRODUCTION Atherosclerosis erodes large elastic arteries and damages peripheral small vessels. Evaluating retinal vessel caliber enables exploration of the effect of improving microcirculation with statins. OBJECTIVE We investigated whether rosuvastatin therapy improves retinal vasculature in hypercholesterolemic patients with a low-to-moderate risk of coronary artery disease (CAD). METHODS This was a prospective, open-label, randomized study in which 127 patients were enrolled and randomized (ratio 1:1) into rosuvastatin and control groups. RESULTS Rosuvastatin increased retinal arteriolar calibers by 3.560 µm at 12 months, decreased retinal venular calibers by 3.110 µm at 6 months and by 5.860 µm at 12 months, and increased the artery-vein ratio (AVR) by 2.68% at 6 months and by 5.90% at 12 months. Meanwhile, in the control group, retinal arteriolar calibers decreased by 1.110 µm at 12 months, retinal venular calibers increased by 1.020 µm at 6 months and by 1.04 µm at 12 months, and AVR decreased by 1.12% at 6 months and by 1.73% at 12 months. All the above parameters were statistically significant between groups, but there was no significant change in retinal arteriolar calibers at 6 months. The increased AVR correlated significantly with decreased C-reactive protein (CRP) at 6 months and decreased low-density lipoprotein and CRP at 12 months. DISCUSSION For patients with a low-to-moderate risk of CAD, we found a significant effect of rosuvastatin on retinal microvasculature, including AVR increase, venular constriction, and arteriolar dilation after 6-12 months of treatment. CLINICAL TRIAL REGISTRATION Chinese Clinical Trial Registry identifier number ChiCTR-IOR-15006664.
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Topical Treatment With Brimonidine and Somatostatin Causes Retinal Vascular Dilation in Patients With Early Diabetic Retinopathy From the EUROCONDOR.
Grauslund, J, Frydkjaer-Olsen, U, Peto, T, Fernández-Carneado, J, Ponsati, B, Hernández, C, Cunha-Vaz, J, Simó, R, ,
Investigative ophthalmology & visual science. 2019;(6):2257-2262
Abstract
PURPOSE Structural retinal microvascular changes have been identified as risk markers of diabetic retinopathy (DR). In order to estimate the retinal response of neuroprotective eye drops, we aimed to evaluate the effect of topical retinal neuroprotection on retinal microvascular changes in early DR. METHODS Patients with type 2 diabetes with no or early DR were randomized 1:1:1 to topical treatment with placebo, brimonidine, or somatostatin in a 96-week prospective, phase II to III, European multicenter trial. Retinal vascular calibers were measured semiautomatically in digital fundus images by certified graders at baseline and follow-up and summarized as central retinal arteriolar and venular equivalent (CRAE and CRVE). RESULTS Of 449 patients originally included, 297 completed the study with gradable retinal images. Median age and duration of diabetes was 64.5 and 9.9 years, and 65.7% were male. At baseline, Early Treatment Diabetic Retinopathy Study levels were 10 (no DR, 42.8%), 20 (minimal DR, 28.3%), and 35 (mild DR, 29.0%), and CRAE and CRVE did not differ between groups. As opposed to patients with no or minimal DR at baseline, patients with mild DR in the active groups developed a larger retinal arteriolar (brimonidine: +6.2 μm, P = 0.006; somatostatin: +7.2 μm, P = 0.006) and venular (brimonidine: +13.9 μm, P = 0.01; somatostatin: +14.3 μm, P = 0.0001) caliber in contrast to those in the placebo group. CONCLUSIONS Topical treatment with brimonidine and somatostatin causes retinal arteriolar and venular dilation in patients with type 2 diabetes and preexisting early DR. Upcoming studies should elaborate on the potential of these findings in arresting early DR.
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Efficacy of Ranibizumab in Eyes with Diabetic Macular Edema and Macular Nonperfusion in RIDE and RISE.
Reddy, RK, Pieramici, DJ, Gune, S, Ghanekar, A, Lu, N, Quezada-Ruiz, C, Baumal, CR
Ophthalmology. 2018;(10):1568-1574
Abstract
PURPOSE To determine whether there are baseline characteristics that distinguish patients with diabetic macular edema (DME) with coexisting macular nonperfusion (MNP) at baseline and assess these patients' potential to achieve favorable visual acuity (VA), anatomic, and diabetic retinopathy (DR) outcomes over 24 months. DESIGN Post hoc analysis of RIDE/RISE, 2 phase 3, parallel, randomized, multicenter, double-masked trials (ClinicalTrials.gov: NCT00473382; NCT00473330). PARTICIPANTS Study eyes with best-corrected VA (BCVA)/fluorescein angiogram (FA) data at baseline. METHODS To measure MNP, the Early Treatment for Diabetic Retinopathy Study (ETDRS) grid was overlaid on FAs of the macula. The MNP area was calculated by estimating the percentage of capillary loss in the central, inner, and outer subfields and converting into disc areas (DAs) using a software algorithm. Summary statistics and P values, respectively, were provided for all outcomes and comparisons of interest. MAIN OUTCOME MEASURES Baseline characteristics; MNP area, BCVA, and central subfield thickness (CST) at months 12 and 24; and incidence of study eyes with ≥2-step DR improvement at months 3, 6, 12, 18, and 24. RESULTS Baseline MNP was detected in 28.2%, 25.8%, and 26.3% of study eyes in the ranibizumab 0.3 mg (n = 213), ranibizumab 0.5 mg (n = 225), and sham (n = 228) arms, respectively. At baseline, patients with MNP were younger and had shorter diabetes duration, worse vision, increased CST, and worse DR severity (P values < 0.01 vs. those without MNP). In the ranibizumab 0.3 mg arm, eyes with baseline MNP had lower mean baseline BCVA (53.4 vs. 57.2 ETDRS letters for those without baseline MNP; P = 0.05), but mean BCVA gain at month 24 was comparable (+15.6 vs. +13.4 ETDRS letters, respectively; P = 0.2). Eyes with baseline MNP had increased CST at baseline, but experienced a greater decrease in CST by month 24. The proportion of eyes with ≥2-step DR improvement was greater for eyes with versus without baseline MNP in each ranibizumab arm. CONCLUSIONS Despite having worse vision/increased CST versus those without baseline MNP, eyes with concurrent DME and baseline MNP entering RIDE/RISE experienced robust VA and anatomic improvement with ranibizumab and therefore should not be excluded from therapy.
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Targeted Retinal Photocoagulation for Diabetic Macular Edema with Peripheral Retinal Nonperfusion: Three-Year Randomized DAVE Trial.
Brown, DM, Ou, WC, Wong, TP, Kim, RY, Croft, DE, Wykoff, CC, ,
Ophthalmology. 2018;(5):683-690
Abstract
PURPOSE To evaluate the effect of targeted retinal photocoagulation (TRP) on visual and anatomic outcomes and treatment burden in eyes with diabetic macular edema (DME). DESIGN Phase I/II prospective, randomized, controlled clinical trial. PARTICIPANTS Forty eyes of 29 patients with center-involved macular edema secondary to diabetes mellitus. METHODS Eyes with center-involved DME and Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) between 20/32 and 20/320 (Snellen equivalent) were randomized 1:1 to monotherapy with 0.3 mg ranibizumab (Lucentis, Genentech, South San Francisco, CA) or combination therapy with 0.3 mg ranibizumab and TRP guided by widefield fluorescein angiography. All eyes received 4 monthly ranibizumab injections followed by monthly examinations and pro re nata (PRN) re-treatment through 36 months. Targeted retinal photocoagulation was administered outside the macula to areas of retinal capillary nonperfusion plus a 1-disc area margin in the combination therapy arm at week 1, with re-treatment at months 6, 18, and 25, if indicated. MAIN OUTCOME MEASURES Mean change in ETDRS BCVA from baseline and number of intravitreal injections administered. RESULTS At baseline, mean age was 55 years, mean BCVA was 20/63 (Snellen equivalent), and mean central retinal subfield thickness (CRT) was 530 μm. Thirty-four eyes (85%) completed month 36, at which point mean BCVA improved 13.9 and 8.2 letters (P = 0.20) and mean CRT improved 302 and 152 μm (P = 0.03) in the monotherapy and combination therapy arms, respectively. The mean number of injections administered through month 36 was 24.4 (range, 10-34) and 27.1 (range, 12-36), with 73% (362/496) and 80% (433/538) of PRN injections administered (P = 0.004) in the monotherapy and combination therapy arms, respectively. Goldmann visual field isopter III-4e area decreased by 2% and 18% in the monotherapy and combination therapy arms, respectively (P = 0.30). CONCLUSIONS In this 3-year randomized trial of 40 eyes with DME, there was no evidence that combination therapy with ranibizumab and TRP improved visual outcomes or reduced treatment burden compared with ranibizumab alone.
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Smartphone-Based Accurate Analysis of Retinal Vasculature towards Point-of-Care Diagnostics.
Xu, X, Ding, W, Wang, X, Cao, R, Zhang, M, Lv, P, Xu, F
Scientific reports. 2016;:34603
Abstract
Retinal vasculature analysis is important for the early diagnostics of various eye and systemic diseases, making it a potentially useful biomarker, especially for resource-limited regions and countries. Here we developed a smartphone-based retinal image analysis system for point-of-care diagnostics that is able to load a fundus image, segment retinal vessels, analyze individual vessel width, and store or uplink results. The proposed system was not only evaluated on widely used public databases and compared with the state-of-the-art methods, but also validated on clinical images directly acquired with a smartphone. An Android app is also developed to facilitate on-site application of the proposed methods. Both visual assessment and quantitative assessment showed that the proposed methods achieved comparable results to the state-of-the-art methods that require high-standard workstations. The proposed system holds great potential for the early diagnostics of various diseases, such as diabetic retinopathy, for resource-limited regions and countries.
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Correlation between Retinal Vessel Calibre and Neurodegeneration in Patients with Type 2 Diabetes Mellitus in the European Consortium for the Early Treatment of Diabetic Retinopathy (EUROCONDOR).
Frydkjaer-Olsen, U, Soegaard Hansen, R, Simó, R, Cunha-Vaz, J, Peto, T, Grauslund, J, ,
Ophthalmic research. 2016;(1):10-6
Abstract
PURPOSE To investigate the correlation between retinal vessel calibre and measurements of neurodegeneration in patients with type 2 diabetes (T2D) and no or early diabetic retinopathy (DR). METHODS Baseline data on 440 patients with T2D from the EUROCONDOR clinical trial were used. DR was graded according to the Early Treatment of Diabetic Retinopathy Study (ETDRS) scale, and patients with ETDRS levels 10-35 were included. Retinal vessel diameters were measured by semi-automatic software. Calibres were summarized into central retinal artery and vein equivalents (CRAE and CRVE). RESULTS Median age and diabetes duration were 64.0 and 10.3 years, respectively. ETDRS levels were 10 (42.3%), 20 (27.5%) and 35 (30.2%). The median CRAE and CRVE were 146.7 and 215.3 µm, respectively. CRAE did not differ according to ETRDS level (p = 0.12), but wider CRVE were found in patients with higher ETDRS levels (p = 0.04). In a multivariable linear regression model, CRAE was associated with macular ganglion cell layer thickness (coefficient 0.27 per micrometre, p < 0.01), and CRVE was correlated with macular retinal thickness (coefficient -0.07 per micrometre, p = 0.04) and retinal nerve fibre layer thickness at the optic disc (coefficient 0.32 per micrometre, p < 0.01). CONCLUSION Retinal vessel calibre was independently associated with structural changes of the neuroretina in patients with no or early DR.
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Three-dimensional vascular imaging of proliferative diabetic retinopathy by Doppler optical coherence tomography.
Miura, M, Hong, YJ, Yasuno, Y, Muramatsu, D, Iwasaki, T, Goto, H
American journal of ophthalmology. 2015;(3):528-38.e3
Abstract
PURPOSE To evaluate the 3-dimensional architecture of neovascularization in proliferative diabetic retinopathy using Doppler optical coherence tomography (OCT). DESIGN Prospective, nonrandomized clinical trial. METHODS Seventeen eyes of 14 patients with proliferative diabetic retinopathy were prospectively studied. Prototype Doppler OCT was used to evaluate the 3-dimensional vascular architecture at vitreoretinal adhesions. RESULTS Proliferative membranes were detected in all eyes with proliferative diabetic retinopathy by standard OCT images. Doppler OCT images detected blood flow by neovascularization of the disc in 12 eyes and neovascularization elsewhere in 11 eyes. Doppler OCT images showed the 3-dimensional extent of new vessels at various stages of neovascularization, and the extent of new vessels could be clearly confirmed at vitreoretinal adhesions. CONCLUSIONS Doppler OCT is useful for the detection and evaluation of the 3-dimensional vascular structure of neovascularization, and can assist in the noninvasive assessment of proliferative diabetic retinopathy.
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Association of retinal vessel calibre and visual outcome in eyes with diabetic macular oedema treated with ranibizumab.
Moradi, A, Sepah, YJ, Ibrahim, MA, Sophie, R, Moazez, C, Bittencourt, MG, Annam, RE, Hanout, M, Liu, H, Ferraz, D, et al
Eye (London, England). 2014;(11):1315-20
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Abstract
PURPOSE The study aims to identify the association between the baseline retinal vascular calibre and visual outcome of patients with diabetic macular oedema (DMO) treated with intravitreal ranibizumab. METHODS The 1-M field (as defined in the ETDRS study) of the digital colour fundus photographs of DMO patients who had been treated primarily with ranibizumab in a clinical trial was assessed. Of the 84 patients, 25 had gradable retinal photographs that could be subjected to analyses by the Interactive Vessel Analysis (IVAN) software at baseline. The average retinal vascular calibre of the six largest venules (CRVE) and the six largest arterioles (CRAE) in the peripapillary area (0.5 and 1 disc diameter from the optic disc margin) was measured. The relationship between CRVE and CRAE at baseline and the change in visual acuity at month 12 was assessed using the Mann-Whitney U test. RESULTS Ten eyes from 10 patients who had shown an improvement of ≥2 lines of best corrected visual acuity (BCVA) at month 12 had a wider baseline CRVE (248.3±24.5 μm) compared with the 15 eyes from 15 patients who did not show the improvement of ≥2 lines (226.6±44.8 μm, P<0.05). The baseline CRAE did not differ significantly in these patients (156.1±22.7 vs 142±17.5 μm, P=0.17). CONCLUSIONS A wider baseline retinal venular calibre may be a predictor of better visual outcome in DMO eyes treated with ranibizumab. Further prospective studies with a larger sample size and a broader range of disease severity and visual acuity are needed to confirm this finding.
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Healthy obese and post bariatric patients - metabolic and vascular patterns.
Bachmayer, C, Lammert, A, Hasenberg, T, Hammes, HP
Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 2013;(8):483-7
Abstract
OBJECTIVE Obesity and the metabolic syndrome (MetS) are associated with endothelial dysfunction (ED). An established method to determine ED is retinal vessel analysis. Obesity is associated with MetS, but obese patients not matching all criteria of the MetS and therefore defined as metabolically healthy obese subjects (MHOS) exist. Bariatric surgery may be an appropriate option to treat morbid obesity. The aim of this study was to compare MetS, MHOS and post bariatric patients in adipocytokine -patterns and ED. METHODS Arterio-venous ratio (AVR) and vessel diameters from retinal photographs (IMEDOS™), parameters of MetS (IDF) and obesity-associated factors (hsCRP, TNF, Il-6, MCP-1, sICAM, sVCAM, IGF-BP3, RBP 4 and adiponectin) were assessed in 51 obese patients with MetS, 20 obese patients without MetS and 21 patients pre and post bariatric surgery. RESULTS Bariatric surgery improved ED as reflected by AVR and venous diameters (p<0.05 for both). These improvements were associated with lower levels of fasting plasma glucose, insulin, HOMA-IR, LDL-C, triglycerides, cholesterol, hsCRP, sICAM, and higher levels of adiponectin and RBP4 (p<0.05 for each parameter). MHOS differed from MetS by neck circumference, fasting plasma glucose, HOMA-IR, triglycerides, HDL-C, sICAM, and adiponectin (p<0.05), but not by RRs, RRd, insulin, LDL-C, hsCRP, Il-6, TNF, MCP-1, sVCAM, RBP-4, IGF-BP3, and retinal ED. CONCLUSION These data indicate that improved insulin-sensitivity and reduced inflammatory mediators characterize the metabolic outcome of postbariatric patients in comparison to MHOS. Thus, MHOS characterizes an intermediate state between MetS and postbariatric patients.