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Assessment of capillary dropout in the superficial retinal capillary plexus by optical coherence tomography angiography in the early stage of diabetic retinopathy.
Shen, C, Yan, S, Du, M, Zhao, H, Shao, L, Hu, Y
BMC ophthalmology. 2018;(1):113
Abstract
BACKGROUND To assess capillary dropout in the superficial retinal capillary plexus (SCP) by optical coherence tomography angiography (OCTA) in the early stage of diabetic retinopathy (DR). METHODS This study was a cross-sectional observational study. Patients that underwent OCTA examinations in our hospital between November 2015 and May 2016 were included in the study. The subjects were divided into two groups: A) normal controls (41 eyes of 41 subjects) and B) the DR patients (49 eyes of 49 patients with mild non-proliferative DR (NPDR)). The retinal thickness and SCP vessel density were analyzed using built-in software in nine sections of the macular area; whole scan area; fovea; parafovea; and sub-sections of the parafovea, superior-hemi, inferior-hemi, temporal, superior, nasal, and inferior. The correlation between vessel density and retinal thickness was also analyzed. RESULTS The SCP density was significantly lower (P < 0.05) in mild NPDR patients than in normal controls in all areas, with the exception of the fovea (P > 0.05). In the parafovea, superior-hemi, inferior-hemi, temporal, and nasal sectors of group B, the SCP density was negatively correlated with the corresponding retinal thickness (P < 0.05). Specifically, as the SCP density decreased, retinal thickness increased. CONCLUSIONS In the early stage of NPDR, retinal capillary dropout and retinal thickness changes can be clearly captured and analyzed by OCTA. The results confirm a negative correlation between vessel density and retinal thickness in diabetic patients. This noninvasive technique could be applied for DR detection and monitoring. Further study with a larger sample size is warranted.
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Effects of a cluster-randomized school-based prevention program on physical activity and microvascular function (JuvenTUM 3).
Siegrist, M, Hanssen, H, Lammel, C, Haller, B, Koch, AM, Stemp, P, Dandl, E, Liestak, R, Parhofer, KG, Vogeser, M, et al
Atherosclerosis. 2018;:73-81
Abstract
BACKGROUND AND AIMS It is unknown whether a school-based prevention program has the potential to improve microvascular health in children. This study investigates the impact of the school-based lifestyle intervention program JuvenTUM 3 on physical activity, physical fitness, serum biomarkers and microvascular function. METHODS We studied 434 children (10-11 years) in a cluster-randomized setting (8 intervention schools, IG; 7 control schools, CG) over 18 months. The school-based prevention program included weekly lifestyle lessons for children with the aim to increase physical activity in and outside of school, physical fitness as well as health behavior. Anthropometric measurements and blood sampling were conducted using standard protocols, physical activity by use of a questionnaire and physical fitness by a 6-item-test battery. Central retinal arteriolar (CRAE) and venular (CRVE) vessel diameters as early marker of vascular dysfunction, as well as the arteriolar-to-venular diameter ratio (AVR), were investigated with a non-mydriatic vessel analyser. RESULTS School-based physical activity increased in 41% of children in IG (19% in CG, p = 0.038). Improvements in vascular parameters were observed for AVR (increase in 83% of children in IG versus 50% in CG; p < 0.001) and for CRVE (43% of children with retinal venular widening in IG versus 58% in CG, p = 0.019). These vascular improvements were also seen in overweight children for CRAE (p = 0.021) and AVR (p < 0.001). CONCLUSIONS The school-based prevention program JuvenTUM 3 increased physical activity at school inducing favourable effects on retinal microvasculature function. These findings underline the importance of early lifestyle interventions in children for primary prevention of cardiovascular disease.
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Region-specific ischemia, neovascularization and macular oedema in treatment-naïve proliferative diabetic retinopathy.
Lange, J, Hadziahmetovic, M, Zhang, J, Li, W
Clinical & experimental ophthalmology. 2018;(7):757-766
Abstract
IMPORTANCE Region-specific pathology in proliferative diabetic retinopathy enhances our understanding and management of this disease. BACKGROUND To investigate non-perfusion, neovascularization and macular oedema. DESIGN A cross-sectional, observational, non-randomized study. PARTICIPANTS Consecutive 43 eyes of 27 treatment-naïve patients. METHODS Ultra-widefield fluorescein angiography for studying specific zones, that is, far-peripheral zone, mid-peripheral zone and central retina (cr), and spectral-domain optical coherence tomography for analysing thickness of macular layers. MAIN OUTCOME MEASURES Non-perfusion index (NPI) and neovascularization index (NVI) in different zones, thickness of cr, retinal nerve fibre layer, ganglion cell layer (GCL), inner nuclear layer (INL) and outer plexiform layer in parafoveal regions. RESULTS The NPI of far-periphery and NVI of mid-periphery were the highest by one-way analysis of variance testing. Ischemic retina defined as high NPI in far-periphery was significantly related to macular oedema via a binary classification approach (P < 0.05). The ischemic retina was correlated with a decreased thickness of both retinal nerve fibre and GCL (P < 0.05); macular oedema was correlated with increased INL thickness (P < 0.0001). CONCLUSIONS AND RELEVANCE The region-specific correlation of NPI of far-periphery and NVI of mid-periphery, but not with central retinal thickness, suggests different pathogeneses of neovascularization and macular oedema. Retinal nerve fibre layer and GCL, both biomarkers of diabetic retinal neuronopathy, are associated with retinal ischemia, but not with macular oedema, suggesting that diabetic microangiopathy and neuronopathy possess distinct pathogenic pathways. The strong correlation between macular oedema and INL indicates that intracellular oedema is a determining factor of diabetic macular oedema.
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Retinal complications of gout: a case report and review of the literature.
Jiang, Y, Brenner, JE, Foster, WJ
BMC ophthalmology. 2018;(1):11
Abstract
BACKGROUND There have been few reported findings of posterior segment complications of gout. While exudative lesions, an increased risk of macular degeneration, and vascular occlusions have been previously reported, to our knowledge, refractile macular lesions have not been reported in a patient with chronic uncontrolled gout. CASE PRESENTATION Highly refractile, crystal-like lesions were found in the macula of a 62 year old male patient with chronically uncontrolled gout. The lesions appeared at the termination of retinal arterioles and were located at the level of the retinal pigment epithelium. The lesions did not stain with fluorescein and were associated with larger areas geographic atrophy. Review of the patient's blood tests revealed well-controlled vasculopathic risk factors. Fundus appearance and best-corrected visual acuity remained stable over 12 months of follow-up during which the uric acid levels were well controlled. CONCLUSION Retinopathy may be associated with chronically uncontrolled gout and patients with visual complaints should undergo a dilated examination in addition to the typical anterior segment slit-lamp exam.
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Visualization of microaneurysms using optical coherence tomography angiography: comparison of OCTA en face, OCT B-scan, OCT en face, FA, and IA images.
Hamada, M, Ohkoshi, K, Inagaki, K, Ebihara, N, Murakami, A
Japanese journal of ophthalmology. 2018;(2):168-175
Abstract
PURPOSE To compare the visualization of microaneurysms (MAs) in patients with diabetic retinopathy (DR) using optical coherence tomography angiography (OCTA) with that using fluorescein angiography (FA). STUDY DESIGN Prospective, clinical, and experimental. METHODS This study was a prospective evaluation of imaging technology. Thirty-seven eyes of 33 patients with DR were scanned using an OCTA instrument. The 83 MAs that were confirmed on OCT B-scan and OCT en face images were evaluated using OCTA, and these findings were compared with those evaluated using FA. RESULTS Of the 83 MAs confirmed on OCT B-scan images, 73 (88%) were clearly visualized on the OCTA en face images as nodular or comma-shaped structures, while the remaining 12% did not present with a typical MA or vascular structure on the OCTA en face images at the relevant positions. Seventy-four of the 83 MAs (87%) confirmed on the OCT B-scan images presented as punctate hyperfluorescent spots on the FA images. On the FA images, 8 of 9 (88%) MAs absent on the OCTA en face images presented as hyperfluorescent spots. Visualization of the MAs on the OCTA en face images did not correlate with the OCT B-scan images of the MA lumens (open, closed, or heterogeneous). CONCLUSIONS For diabetic maculopathy, OCTA en face images do not present with comprehensive MAs images, indicating that some MAs might be overlooked with OCTA en face images.
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Correlation Analysis between Foveal Avascular Zone and Peripheral Ischemic Index in Diabetic Retinopathy: A Pilot Study.
Rabiolo, A, Cicinelli, MV, Corbelli, E, Baldin, G, Carnevali, A, Lattanzio, R, Querques, L, Bandello, F, Querques, G
Ophthalmology. Retina. 2018;(1):46-52
Abstract
PURPOSE To investigate the foveal avascular zone (FAZ) by OCT angiography (OCT-A) in patients affected by diabetic retinopathy and its correlation with peripheral retinal ischemic index. DESIGN Observational, cross-sectional study, prospectively designed. PARTICIPANTS Consecutive patients with treatment-naïve diabetic retinopathy were prospectively recruited between October 2015 and January 2017. METHODS All patients underwent a comprehensive ocular examination including OCT, OCT-A, ultra-widefield (UWF) color fundus images, and UWF fluorescein angiography. MAIN OUTCOME MEASURES Variables analyzed included best-corrected visual acuity (BCVA) expressed in logarithm of the minimal angle of resolution (logMAR); diabetic retinopathy grading; FAZ area at full-thickness (internal limiting membrane to Bruch's membrane) OCT-A angiogram; superficial capillary plexus; deep capillary plexus; ischemic index; and central macular thickness (CMT). RESULTS Twenty-two eyes of 22 patients (11 male, mean age 54.9±15.8 years) were included. Mean FAZ areas at full thickness, superficial plexus, and deep plexus were 0.331±0.137 mm2, 0.340±0.140 mm2, and 1.028±0.447 mm2, respectively. Mean ischemic index was 13.6% (range, 0%-50.2%). A significant correlation was found between ischemic index and FAZ area at both full-thickness (r = 0.60, P = 0.0035) and superficial (r = 0.68, P = 0.0005) layers. Disease severity correlated to ischemic index (r = 0.49, P = 0.0204), and FAZ area at full-thickness (r = 0.53, P = 0.0108) and superficial (r = 0.47, P = 0.0292) plexuses. No significant correlation between ischemic index and FAZ at deep plexus was found. BCVA correlated only to CMT (r = 0.66, P = 0.0008). CONCLUSIONS The association between peripheral and macular perfusion found in this study supports the hypothesis that both conditions share a common pathogenic mechanism that leads to capillary nonperfusion.
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The Adolescent Cardio-Renal Intervention Trial (AdDIT): retinal vascular geometry and renal function in adolescents with type 1 diabetes.
Benitez-Aguirre, PZ, Wong, TY, Craig, ME, Davis, EA, Cotterill, A, Couper, JJ, Cameron, FJ, Mahmud, FH, Jones, TW, Hodgson, LAB, et al
Diabetologia. 2018;(4):968-976
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Abstract
AIMS/HYPOTHESIS We examined the hypothesis that elevation in urinary albumin creatinine ratio (ACR) in adolescents with type 1 diabetes is associated with abnormal retinal vascular geometry (RVG) phenotypes. METHODS A cross-sectional study at baseline of the relationship between ACR within the normoalbuminuric range and RVG in 963 adolescents aged 14.4 ± 1.6 years with type 1 diabetes (median duration 6.5 years) screened for participation in AdDIT. A validated algorithm was used to categorise log10 ACR into tertiles: upper tertile ACR was defined as 'high-risk' for future albuminuria and the lower two tertiles were deemed 'low-risk'. RVG analysis, using a semi-automated computer program, determined retinal vascular calibres (standard and extended zones) and tortuosity. RVG measures were analysed continuously and categorically (in quintiles: Q1-Q5) for associations with log10 ACR and ACR risk groups. RESULTS Greater log10 ACR was associated with narrower vessel calibres and greater tortuosity. The high-risk group was more likely to have extended zone vessel calibres in the lowest quintile (arteriolar Q1 vs Q2-Q5: OR 1.67 [95% CI 1.17, 2.38] and venular OR 1.39 [0.98, 1.99]) and tortuosity in the highest quintile (Q5 vs Q1-Q4: arteriolar OR 2.05 [1.44, 2.92] and venular OR 2.38 [1.67, 3.40]). The effects of retinal vascular calibres and tortuosity were additive such that the participants with the narrowest and most tortuous vessels were more likely to be in the high-risk group (OR 3.32 [1.84, 5.96]). These effects were independent of duration, blood pressure, BMI and blood glucose control. CONCLUSIONS/INTERPRETATION Higher ACR in adolescents is associated with narrower and more tortuous retinal vessels. Therefore, RVG phenotypes may serve to identify populations at high risk of diabetes complications during adolescence and well before onset of clinical diabetes complications.
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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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Wide-field en face swept-source optical coherence tomography angiography using extended field imaging in diabetic retinopathy.
Hirano, T, Kakihara, S, Toriyama, Y, Nittala, MG, Murata, T, Sadda, S
The British journal of ophthalmology. 2018;(9):1199-1203
Abstract
AIMS: To examine the feasibility of wide-field en face swept-source optical coherence tomography angiography (SS-OCTA) with extended field imaging (EFI) for evaluation of the retinal vasculature in diabetic retinopathy (DR). METHODS This study included 37 eyes of 27 patients (age, 65±10 years; male patients, 18; female patients, 9) with DR. All patients underwent comprehensive ophthalmological examination, including OCTA and fluorescein angiography (FA). The imaging methods were compared for visible field of view, presence and extent of non-perfused areas (NPAs), presence and number of new blood vessels (NVs), vessel density (VD) and patient comfort level measured by Visual Analogue Scale. RESULTS SS-OCTA with EFI allowed capture of larger areas (by 1.80±0.18 times on average) of the fundus than SS-OCTA without EFI. Compared with FA, the sensitivities of SS-OCTA with EFI for detection of NPAs and NVs were 96% and 79%, respectively, with specificities of 100% and 96%, respectively. There was no significant difference in extent of NPAs (61.2±45.8 vs 61.5±55.0 disc areas, P=0.99) or number of NVs (1.5±3.3 vs 0.9±1.8, P=0.68) between FA and SS-OCTA with EFI. VD showed significantly lower values in EFI SS-OCTA than in those acquired without EFI (31.6%±4.3% vs 34.2%±4.3%, P<0.001). Wide-field OCTA with EFI was significantly more comfortable for patients than FA (P<0.001). CONCLUSIONS SS-OCTA with EFI allows acquisition of wide-field en face images of the retinal vasculature in patients with DR, with greater patient comfort than FA.
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A spectrum of retinal vasculature measures and coronary artery disease.
Wang, SB, Mitchell, P, Liew, G, Wong, TY, Phan, K, Thiagalingam, A, Joachim, N, Burlutsky, G, Gopinath, B
Atherosclerosis. 2018;:215-224
Abstract
BACKGROUND AND AIMS We aimed to comprehensively describe a spectrum of retinal vessel measures including fractal dimension (Df) and their associations with indices of coronary artery disease (CAD) extent and severity, as well as hypertension and diabetes. METHODS The Australian Heart Eye Study (AHES) is an observational study that surveyed 1680 participants presenting to a tertiary referral hospital for the evaluation of potential CAD by coronary angiography. A range of newer retinal vessel geometric measures (Df, curvature tortuosity, and branching angle) were quantified from retinal photographs using semi-automated software, the Singapore 'I' Vessel Assessment (SIVA) tool. A combined retinal score was constructed, aiming to assess the joint effect of multiple retinal vessel parameters on CAD, comprising of those variables that were most strongly significant in multivariate analysis - Df, arteriolar curvature tortuosity, and retinal arteriolar calibre. CAD was objectively quantified using a range of measures obtained from coronary angiography. RESULTS A total of 1187 participants had complete data on retinal vessel measurements and coronary vessel evaluation. Retinal vascular Df and curvature tortuosity decreased with increasing age; women had significantly lower Df than men (p<0.003). Straighter retinal vessels were associated with CAD extent and Gensini scores in multivariable analysis (p<0.02). Accounting for media opacity by sub-group analysis in pseudophakic patients, the combined retinal score was associated with stenosis greater than 50% in any coronary artery segment (vessel score) and obstructive coronary stenosis in all three main coronary arteries (segment score) (p = 0.01). Lower Df and narrower arteriolar branching angle were associated with CAD vessel score (p<0.03). In sex-stratified multivariate analyses, straighter arterioles were associated with greater odds of CAD in men, and narrower venular branching angle was associated with CAD in women. CONCLUSIONS A range of retinal vessel measures were associated with CAD extent and severity. A sparser retinal microvascular network (smaller Df) was associated with older age and female gender. After accounting for the impact of media opacity, retinal vessel measures were associated with more diffuse and severe CAD.