Search

Purpose To investigate the adjunct efficacy and safety of vitamin supplements, including resveratrol, in patients with diabetic macular edema (DME) treated with intravitreal anti-vascular endothelial factor (anti-VEGF) agents. Methods Participants in this prospective study were 45 patients with DME, who were treated with either intravitreal anti-VEGF injections (n = 23, Group I) or with combination of intravitreal anti-VEGF injections and vitamin supplements, including resveratrol (n = 22, Group II). All patients underwent visual acuity measurement, slit-lamp examination and spectral domain-optical coherence tomography (SD-OCT) at baseline and monthly after the loading phase of three-monthly anti-VEGF injections, following a PRN protocol. Results There was a statistically significant improvement in visual acuity in both groups at month 12 compared to baseline, although the mean change in visual acuity did not differ between the two groups (p = 0.183). Accordingly, there was a statistically significant decrease in central retinal thickness in both groups at month 12 compared to baseline, while the mean difference in central retinal thickness was significantly greater in the “combination” group. The mean number of intravitreal anti-VEGF injection was less in Group II (6.45 ± 1.12 in Group II vs. 7.39 ± 1.31 in Group I, p = 0.018). Conclusions Vitamin supplements with resveratrol was found to be an effective adjunct to intravitreal anti-VEGF injections in patients with DME, offering better anatomic restoration with less injections at the 12-month follow-up.

The beneficial effect of multifactorial treatment of cardiovascular (CV) risk factors (RFs) in type 2 diabetes (T2D) is well established from randomized clinical trials. We prospectively evaluated the impact of such treatment in a real-world setting, on the development of subclinical arterial damage (SAD), as determined by structural/functional noninvasive biomarkers of vascular pathology (atheromatosis, carotid hypertrophy, arteriosclerosis). We prospectively studied 116 persons with T2D, treated with a multifactorial approach for CV RFs at a tertiary medical center, and 324 individuals without diabetes, for 3.2 years. The primary outcome was changes in vascular biomarkers related to SAD. At baseline, participants in the diabetes group had higher prevalence of SAD. At study end, the changes in clinical, biochemical, and lifestyle characteristics, as well as antihypertensive and lipid-lowering treatments, were comparable between the 2 groups. During follow-up, classical CV RFs (smoking, blood pressure, low-density lipoprotein-cholesterol, triglycerides) and behavioral features were significantly improved in both groups. Multivariate analysis, after adjusting for all classic CV RFs and use of antihypertensive/lipid-lowering therapies, demonstrated that all evaluated SAD biomarkers were similarly changed in the 2 groups. In conclusion, implementation of a multimodality approach of T2D treatment is feasible and efficacious in decelerating progression of SAD in routine clinical practice.

The difference in pulse pressure (PP) between peripheral arteries and the aorta, called pulse pressure amplification (PPamp), is a well-described physiological phenomenon independently associated with cardiovascular events. Recent studies suggest that it exhibits circadian variability. Our aim was to detect the factors associated with the circadian variability of PPamp. In 497 consecutive subjects (aged 54 years, 56.7% male, 79.7% hypertensives), we assessed the circadian pattern of peripheral and central arterial hemodynamics by 24-hour evaluation of brachial and aortic blood pressure (BP), augmentation index (AI), and pulse wave velocity (PWV) using a validated oscillometric device (Mobil-O-Graph). All parameters exhibited a circadian variation. Sleep dipping (decrease) pattern was observed for PPamp, brachial and aortic systolic BP, mean BP, and PWV, whereas a rising pattern (higher sleep than wake values) was observed for brachial PP, aortic PP, and AI. The factors independently associated with the less sleep dipping in PPamp were older age, lower height, the use of antihypertensive medication, and sleep decrease in arterial stiffness (PWV), whereas female gender, the presence of hypertension, sleep increase of pressure wave reflections (AI), sleep decrease in heart rate, and mean BP were associated with a greater sleep-dipping in PPamp. These data provide further pathophysiological understanding of the mechanisms leading to PPamp dipping. Several implications regarding the clinical use of the aortic and brachial BP, especially during sleep time, are raised that should be addressed in future research.

Background:Primary Systemic Vasculitides (PSV) constitute a heterogeneous group of rare and potentially life-threatening autoimmune diseases, characterized by a varying degree of inflammatory response, leading to local or generalized vascular disease. Vessel involvement accounts for the micro- and macrovascular complications of the disease, along with the classic risk factors including, among others age and chronic use of steroids (1). Early identification of high-risk patients for cardiovascular disease (CVD) development and the contribution of inflammation towards this adverse outcome are still unmet needs. Alterations of retinal microcirculation have been independently associated with increased CVD risk in the general population (2). The potential changes of retinal vasculature and their association with disease activity and the magnitude of inflammation have not been studied in PSV so far.Objectives:To explore the effect of disease activity and inflammation on retinal microcirculation in PSV, classified according to vessel size as large, medium or small vessel vasculitides (LVV, MVV or SVV respectively), and polymyalgia rheumatica (PMR) without vasculitis.Methods:Fifty-nine patients, 43 with active disease [30 active vasculitis (12 LVV, 4 MVV, 14 SVV) and 13 PMR] and 16 with chronic inactive disease (13 vasculitis, 3 PMR) were studied. All patients were matched at 1:1 ratio with 59 controls, without underlying autoimmune/autoinflammatory disorder, neoplasia or infection, according to age, gender, CVD history, BMI, smoking, arterial hypertension, dyslipidemia, diabetes mellitus and treatment related to comorbidities. A total of 32 rheumatoid arthritis (RA) patients with mild to moderate inflammatory component as defined by standard of care acute phase reactants (ESR and CRP) and 16 chronic RA patients with normal ESR and CRP levels, matched 1:1 according to all the above parameters with 32 active and 16 inactive vasculitis/PMR patients respectively, served as disease controls. Digital retinal images were obtained and retinal vessel calibers were measured with a validated software to determine central retinal arteriolar and venular equivalents ratio (CRAE and CRVE respectively). For 16 patients with active vasculitis/PMR, retinal examination was performed in two time points (baseline and ≤ 6 months later).Results:In the overall population, patients with active Vasculitis/PMR had increased CRVE (213.8±21.7 vs 201.3±17.1, pConclusion:Systemic inflammation alters retinal microcirculation in both a reversible (venules) and irreversible (arterioles) way, independently of PSV form. Thus, common disease specific pathogenetic mechanisms related to inflammation may be implicated in vascular remodeling. Sequential follow-up of PSV patients will address whether retinal vessel calibers may serve as a biomarker of disease activity and CVD development.References:[1]Argyropoulou OD et al. Curr Opin Rheumatol 2017.[2]Shaohua G et al. Current Atherosclerosis reports 2020.Disclosure of Interests:None declared

Background and aims Association of dairy products and meat consumption with macrocirculation is previously described, but such association with microcirculation is poorly investigated. We aimed to test the hypothesis that the consumption of high- and low-fat dairy products as well as red, white, and processed meat is associated with retinal vessel calibers in adults at an increased risk of cardiovascular disease (CVD). Methods and results In consecutive subjects ( n = 181, age: 51.3 ± 12.4 years, 51.4% women) without CVD and diabetes mellitus but with increased CVD risk, we obtained digital left and right retinal images. These images were assessed with validated software to determine central retinal arteriolar and venular equivalents and the arteriolar to venular ratio (CRAE, CRVE, and AVR, respectively). The consumption of dairy products and meat was assessed through 24-h recalls in all volunteers. After adjustment for potential confounders, the following findings were obtained: (i) low-fat milk and yogurt were positively associated with CRAE ( b = 0.145, p = 0.031 left; b = 0.141, p = 0.038 right) and inversely associated with CRVE ( b = − 0.155, p = 0.026 left; b = − 0.146, p = 0.041 right); (ii) low-fat cheese was positively associated with CRAE ( b = 0.164, p = 0.011 left and b = 0.155, p = 0.017 right); and (iii) red meat was inversely associated with CRAE ( b = − 0.143, p = 0.032 left; b = −0.114, p = 0.050 right). High-fat milk, yogurt, and cheese or white and processed meat were not found to be associated with retinal vessel calibers. Conclusions High consumption of low-fat milk, yogurt, and cheese and low consumption of red meat could be beneficial for retinal microvascular health. Prospective studies are needed to verify these findings.

Objective: Aortic (a) systolic blood pressure (SBP) is associated with arterial damage more consistently than brachial (b) SBP. However, it is unknown whether: (i) aSBP is normal in the presence of elevated bSBP, and vice versa; (ii) SBP classification on the basis of proposed bSBP and aSBP cut-off values, improves cardiovascular (CV) risk assessment. We tested (i) the frequency of 4 office SBP phenotypes: type I (both normal bSBP and aSBP); type II (high bSBP but normal aSBP); type III (normal bSBP but high aSBP), and type IV (both high bSBP and aSBP), (ii) the probability of each phenotype (using type I as reference) to be associated with increased arterial damage. Design and method: In a cohort study of 1861 participants (age: years 54 years, 49.1% males), we measured simultaneously bSBP, aSBP and carotid cross-sectional wall area (CSWA) with ultrasound. Results: Depending on the applied aSBP cut-off values, type II and type III phenotypes represented together 5–11 % of the studied population (0.9–3.4% and 1.8–10.3%, respectively). Subgroups with phenotypes II and III had significantly higher probability (by 2.3–3.3 and 3.3–8.9 times, respectively) as assessed by logistic regression analysis to present elevated carotid artery CSWA compared to the reference group, even after adjustment for diastolic blood pressure and other confounders. Conclusions: Defined on the basis of both bSBP and aSBP measurements, type II (i.e. isolated high bSBP) and type III (isolated high aSBP) are commonly observed and refine the detection of subgroups regarding the presence of arterial damage.

To assess the differences among seven different methods for the calculation of mean arterial pressure (MAP) and to identify the formula that provides MAP values that are more closely associated with target organ deterioration as expressed by the carotid cross-sectional area (CSA), carotid-to-femoral pulse-wave velocity (cf-PWV) and left ventricular mass (LVM). The study population consisted of 1878 subjects who underwent noninvasive cardiovascular risk assessment. Blood pressure (BP) was assessed in all subjects, and MAP was calculated by direct oscillometry and six different formulas. Carotid artery ultrasound imaging was performed in 1628 subjects. The CSA of the right and left common carotid artery (CCA) were calculated and used as surrogates of arterial wall mass and hypertrophy. Aortic stiffness was evaluated in 1763 subjects by measuring the cf-PWV. Finally, 218 subjects underwent echocardiographic examination for the assessment of LVM. Among the examined methods of MAP calculation, the formula MAP1=[diastolic BP]+0.412 × [pulse pressure] yielded the strongest correlations with the LVM, cf-PWV and CSA of the right and left CCA, even after adjusting for age and gender. The MAP calculation using the 0.412 was superior compared with the traditional formula that uses the 0.33 for the discrimination of subjects with left ventricular and carotid wall hypertrophy, as well as subjects with increased aortic stiffness. MAP estimated with the 0.412 is better correlated with target organ deterioration compared with other formulas. Future studies are needed to explore the accuracy of these formulas for MAP estimation compared with direct intra-arterial BP measurement.

Background Arterial stiffness measured under static conditions reclassifies significantly cardiovascular (CV) risk and associates with narrower retinal arterioles. However, arterial stiffness exhibits circadian variation, thus single static stiffness recordings do not correspond to the "usual" 24 hr, awake, and asleep average arterial stiffness. We aimed to test the hypothesis that ambulatory 24 hr, awake, and asleep aortic (a) pulse wave velocity (PWV) associate with retinal vessel calibers, independently of confounders and of static arterial stiffness, in hypertensive individuals free from diabetes and CV disease. Methods Digital retinal images were obtained (181 individuals, age: 53.9±10.7 years, 55.2% men) and retinal vessel calibers were measured with validated software to determine central retinal arteriolar and venular equivalents (CRAE and CRVE, respectively); ambulatory (24 hr, awake, asleep) and static office aPWV were estimated by Mobil-O-Graph; and static office carotid to femoral (cf) PWV by SphygmoCor. Results Regression analysis performed in 320 gradable retinal images showed that, after adjustment for confounders: (i) ambulatory aPWV was significantly associated with narrower retinal arterioles but not with venules; (ii) asleep aPWV had stronger associations with CRAE than awake aPWV; (iii) both ambulatory aPWV and cfPWV were associated mutually independently with narrower retinal arterioles; aPWV introduction in the model of cfPWV, improved model's R2 (P = 0.012). Similar discriminatory ability of 24 hr aPWV and of cfPWV to detect the presence of retinal arteriolar narrowing was found. Conclusion Ambulatory aPWV, estimated by an operator-independent method, provides additional information to cfPWV regarding the associations of arterial stiffness with the retinal vessel calibers.

Purpose The aim of this study was to evaluate the morphological properties of corneal endothelial cells and central corneal thickness (CCT) in patients with neurofibromatosis type 1 (NF1) and to compare them with age-matched healthy controls. Methods Nineteen NF1 patients and 38 healthy individuals were recruited. All participants underwent complete ophthalmological examination as well as noncontact specular microscopy to measure endothelial cell density (ECD), average cell area (AVG), coefficient of variation of cell area (CV), the percentage of hexagonal cells, and CCT. Eyes with previous ocular trauma, inflammation or surgery, and preexisting corneal and ocular surface diseases were excluded. Results NF1 patients had higher ECD compared to healthy controls of the same age (2764.2 ± 270.4 versus 2570.4 ± 449.2 cells/mm, respectively), although at a borderline level (P = 0.051). Patients with NF1 presented significantly lower CV and AVG when compared to controls (32.9 ± 4.6 versus 37.8 ± 9.5%, P = 0.011 and 364.9 ± 34.4 versus 406.0 ± 107.4 µm, P = 0.038, respectively). The NF1 group had significantly higher hexagonality in comparison with controls (55.7 ± 6.5 versus 50.5 ± 9.9%, P = 0.025). CCT was similar between the two groups (P = 0.955). Conclusion Our results show that corneal endothelium has more favorable morphological characteristics in NF1 patients compared to healthy individuals of the same age.

Background The usefulness of the hypertensive retinopathy classification by Keith-Wagener-Barker (KWB) in clinical practice remains controversial. The simplified Mitchell-Wong grading, combining the two initial KWB' grades in one stage, is proposed as an alternative method; both systems are poorly validated regarding their association with target organ damage. Objective In a population free of cardiovascular disease and diabetes, we aimed to investigate the interobserver and intraobserver agreement of both grading systems, their association with aortic stiffness, carotid hypertrophy or plaques and the role of age and sex on this association. Methods Digital retinal images were obtained and graded - according to both classifications - by two independent and blinded observers; aortic stiffness (carotid-femoral pulse wave velocity, m/s) and common carotid hypertrophy (cross-sectional area, mm) or plaques were assessed by tonometry and ultrasound, respectively. Results From the gradable retinal photos obtained by 200 eyes of 107 consecutive patients (age: 54 ± 13 years, 51% men, 79% hypertensive patients) and after adjustments for confounders, the intraobserver and interobserver level of agreement was as following: KWB 88/64% and Mitchell-Wong 91/71%, respectively; exclusively in younger, not older, individuals aortic stiffness, carotid hypertrophy, but not plaques, were significantly associated with both systems, independently from confounders; no differences regarding target organ damage were found between stages 1 and 2 of KWB. Conclusion Detecting early signs of hypertensive retinopathy may be of value in young individuals; the Mitchell-Wong seems preferable to the KWB classification system only for reasons of simplifying clinical practice.

OBJECTIVE The current general population study explored the prognostic value of home blood pressure (HBP) average and variability (BPV) versus office measurements (OBP). METHODS In 1997, 665 adults of Didima, Argolida, Greece were evaluated with OBP (two visits, six readings) and HBP (3 days, 12 readings) measurements. Total mortality and cardiovascular morbidity and mortality (CVD) were assessed after 19.0 ± 1.4 years. BPV was quantified by using SD and coefficient of variation. RESULTS During follow-up, 216 deaths (124 cardiovascular) and 146 cardiovascular events (fatal and nonfatal) were documented. Hazard ratios for total mortality were 1.39/1.20 (P

Relapsing ocular inflammation occurs in about 70% of patients with Behçet's disease (BD) and can lead to permanent loss of vision. Neovascularization of the optic disc (NVD) or elsewhere in the retina (NVE) is a relatively uncommon but severe complication that lacks standardized treatment.We report on the therapeutic use of anti-TNF monoclonal antibodies for BD-associated NVD and NVE in one pediatric patient (subcutaneous adalimumab) and one young man (intravenous infliximab). Also, we review the previously published experience on biologic therapeutic options, namely anti-TNF agents and interferon-alpha in a total of three and eight patients, respectively.A fast-onset therapeutic effect was observed in both patients leading to complete regression of neovascularizations.Both options may lead to regression of neovascularization, thus preventing loss of vision, but comparative studies need to determine the optimal treatment for this sight-threatening complication of BD.

Background: Chronic systemic inflammatory diseases (CSID) are associated with increased cardiovascular morbidity and mortality. Widening of retinal venular calibers has been independently associated with systemic inflammation and cardiovascular risk in the general population. We aimed to test the hypothesis that retinal vessel calibers are altered in a population with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and spondyloarthropathies (SpA) compared to a reference group (RG).Methods: Between 2012 and 2014 digital retinal images were obtained from consecutive individuals and retinal vessel calibers were measured with validated software to determine central retinal arteriolar and venular equivalents.Results: One hundred eighty-eight patients with CSID [(74 RA, 75 SLE, 39 SpA), (70.2% females, mean age 50.4 +/- 12.5 years)] and 512 non-CSID individuals [(187 normotensives and 325 hypertensives, 90 of whom untreated; RG), (43.7% females, mean age 52.3 +/- 11.7)] were recruited. Logistic regression analysis after adjustment for all factors associated with retinal vessel calibers in univariate analysis (age, sex, body mass index, blood pressure, anti-hypertensive/lipid modifying drugs and disease duration), showed that both arteriolar and venular retinal vessel calibers were comparable between CSID patients and the RG. No significant differences were found regarding retinal vessel calibers between each patient subgroup and the RG.Conclusions: Retinal vessel calibers were not significantly altered in patients with CSID. Well-controlled disease, as indicated by inflammatory indices, may be an explanation of our results suggesting that sufficient control of inflammation could improve microvascular abnormalities in these populations. (C) 2017 Association for Research into Arterial Structure and Physiology. Published by Elsevier B.V. All rights reserved.

Both brachial blood pressure (BP) level and its variability (BPV) significantly associate with left ventricular (LV) structure and function. Recent studies indicate that aortic BP is superior to brachial BP in the association with LV abnormalities. However, it remains unknown whether aortic BPV better associate with LV structural and functional abnormalities. We therefore aimed to investigate and compare aortic versus brachial BPV, in terms of the identification of LV abnormalities. Two hundred and three participants who underwent echocardiography were included in this study. Twenty-four-hour aortic and brachial ambulatory BP was measured simultaneously by a validated BP monitor (Mobil-O-Graph, Stolberg, Germany) and BPV was calculated with validated formulae. LV mass and LV diastolic dysfunction (LVDD) were evaluated by echocardiography. The prevalence of LV hypertrophy (LVH) and LVDD increased significantly with BPV indices (P⩽0.04) in trend tests. After adjustment to potential confounders, only aortic average real variability (ARV), but not brachial ARV or weighted s.d. (wSD, neither aortic nor brachial) significantly associated with LV mass index (P=0.02). Similar results were observed in logistic regression. After adjustment, only aortic ARV significantly associated with LVH (odds ratio (OR) and 95% confidence interval (CI): 2.28 (1.08, 4.82)). As for LVDD, neither the brachial nor the aortic 24-hour wSD, but the aortic and brachial ARV, associated with LVDD significantly, with OR=2.28 (95% CI: (1.03, 5.02)) and OR=2.36 (95% CI: (1.10, 5.05)), respectively. In summary, aortic BPV, especially aortic ARV, seems to be superior to brachial BPV in the association of LV structural and functional abnormalities.

Objectives The association of caffeinated and alcoholic drinks with microcirculation is poorly investigated. The aim of the study was to investigate the associations of daily consumption of caffeinated and alcoholic drinks with retinal vessel calibers. Methods In consecutive adults at increased risk but free of cardiovascular disease (CVD) and diabetes mellitus, (n=181, age: 51.32±12.42 years, 51.4% women), we determined central retinal arteriolar and venular equivalents and arteriolar to venular ratio (CRAE, CRVE and AVR, respectively). Daily consumption of caffeinated and alcoholic drinks was assessed through 24hour recalls. Results After adjustment for potential confounders: (i) caffeine was positively associated with CRVE (b= 0.177, p=0.006 for left, b= 0.208, p=0.002 for right eye respectively) (ii) decaffeinated coffee was positively associated with CRAE (b= 0.141, p=0.035 for left eye) and negatively associated with CRVE (b= -0.234, p

Objective.A primary endothelial cell dysfunction is thought to be involved in systemic sclerosis (SSc)-associated fibroproliferative vasculopathy of the microcirculation and small arterioles, even in sites not affected by fibrosis. Because the role of fibroblasts in pathologic modifications and vascular wall remodeling is relatively unclear, and because the retina provides a unique opportunity to assess microcirculation in the absence of resident fibroblasts, we systematically evaluated retinal vessels in patients with SSc.Methods.Digital retinal images were obtained from both eyes of 93 consecutive patients with fully characterized SSc and 29 healthy controls matched 1:1 for age and sex with selected patients without diabetes, hypertension history, or antihypertensive treatment. Internal microvascular calibers (erythrocyte column width in μm) by central retinal arteriolar and venular equivalents and arteriolar to venular ratio were measured using validated software.Results.Arteriolar and venular calibers were similar in patients and their matched controls (mean ± SEM; 187 ± 2 vs 184 ± 3, p = 0.444, and 211 ± 2 vs 216 ± 3, p = 0.314, respectively). Both arteriolar and venular calibers and their ratio in patients with SSc were not associated with disease duration, extent of skin involvement, pulmonary fibrosis, digital ulcers or pitting scars, amputations, digital capillaroscopic findings, inflammatory indices, or autoantibodies.Conclusion.The evidence that retinal microcirculation is spared in SSc suggests that fibroproliferative vasculopathy may depend on specific cellular or soluble factors not present in the retinal environment.