Venules In Patients Research Articles

Vascular Endothelial Effects of Sacubitril/Valsartan in Heart Failure With Reduced Ejection Fraction: Randomized Controlled Trial

BackgroundThe mechanism of how sacubitril/valsartan improves outcomes in heart failure with reduced ejection fraction (HFrEF) is still incompletely understood. ObjectivesThe aim of this trial was to delineate the effects of sacubitril/valsartan on endothelial function, retinal microvascular function, and arterial stiffness in HFrEF. MethodsThis double-blind controlled trial randomized 79 stable HFrEF patients with NYHA class II-IV on guideline-recommended therapy (mean age: 59.4 ± 12 years, left ventricular ejection fraction: 30% ± 7%) to sacubitril/valsartan or valsartan alone for 3 months. The primary endpoint was flow-mediated vasodilation (FMD). Secondary outcomes included flicker-induced dilatation of retinal arterioles and venules (FIDv), retinal arteriovenous ratio, and surrogate markers of arterial stiffness (pulse wave velocity and augmentation index). ResultsThe primary outcome FMD did not significantly differ between sacubitril/valsartan and valsartan alone (FMD 6.6% ± 3.9% vs 6.7% ± 2.8%; ANCOVA coefficient adjusted for baseline values 0.36, 95% CI: −0.78 to 1.51, P = 0.53). The secondary outcomes flicker-induced dilatation of retinal arterioles, arteriovenous ratio, pulse wave velocity, and augmentation index showed no significant differences. FIDv was lower after sacubitril/valsartan versus valsartan alone (FIDv 2.4% ± 1.3% vs 3.1% ± 2.1%; ANCOVA coefficient −0.7, 95% CI: −1.4 to −0.02, P = 0.04). Systolic blood pressure was lower after sacubitril/valsartan versus valsartan alone (ANCOVA coefficient −6.5 mm Hg, 95% CI: −12.7 to −0.3 mm Hg, P = 0.04). There were numerically fewer serious adverse events with sacubitril/valsartan versus valsartan alone. ConclusionsIn this randomized double-blind clinical trial addressing mechanisms, sacubitril/valsartan lowered blood pressure and flicker-induced dilatation of retinal venules in patients with symptomatic HFrEF but did not improve endothelial function, retinal microvascular function, or arterial stiffness compared to valsartan monotherapy. (Differential Vascular and Endocrine Effects of Valsartan/​Sacubitril in Heart Failure With Reduced Ejection Fraction [VASCEND]; NCT03168568)

Alterations in Retinal Vessel Diameters in Patients with Retinal Vein Occlusion before and after Treatment with Intravitreal Ranibizumab

Purpose: To investigate the alterations of retinal vessel diameters in patients with macular edema secondary to retinal vein occlusion (RVO), before and after treatment with intravitreal ranibizumab. Methods: Digital retinal images were obtained from 16 patients and retinal vessel diameters were measured before and three months after treatment with intravitreal ranibizumab with validated software to determine central retinal arteriolar and venular equivalents, as well as arteriolar to venular ratio. Results: In 17 eyes of 16 patients with macular edema secondary to RVO (10 with branch RVO and 6 with central RVO) aged 67 ± 10.2 years, we found that diameters of both retinal arterioles and venules were significantly decreased after intravitreal ranibizumab treatment. Specifically, the central retinal arteriolar equivalent was 215.2 ± 11.2 μm at baseline and 201.2 ± 11.1 μm at month 3 after treatment (p < 0.001), while the central retinal venular equivalent was 233.8 ± 29.6 μm before treatment versus 207.6 ± 21.7 μm at month 3 after treatment (p < 0.001). Conclusions: A significant vasoconstriction in both retinal arterioles and venules in patients with RVO was found at month 3 after intravitreal ranibizumab treatment compared to baseline. This could be of clinical importance, since the degree of vasoconstriction might be an early marker of treatment efficacy, compatible with the idea that hypoxia is the major trigger of VEGF in RVO. Further studies should be conducted to confirm our findings.

Tortuosity of Retinal Main and Branching Arterioles, Venules in Patients With Type 2 Diabetes and Diabetic Retinopathy in China

The epidemic studies have demonstrated an excessively increase of diabetic patients in recent years, who are at high risk of developing microvascular complications. Those microvascular complications usually lead to chronic health problems, e.g. diabetic retinopathy (DR), thus early and regular screening is indeed necessary. Retinal vascular tortuosity, which is one of geometrical parameters related to microvascular morphological changes, has been investigated in many studies related to diabetes, diabetic risk factors and diabetic complications. However, the global tortuosity of retinal vessels in DR progression is quantified either subjectively or imprecisely in those previous studies. Furthermore, to our best knowledge, the association of tortuosity, diabetes and DR has never been investigated based on a Chinese population-based cohort, even though it accounts for more than 30% of diabetic patients worldwide. Therefore, it is of great necessary and clinical significance to extract retinal tortuosity in a more reliable way and explore its associations with diabetic risk factors and DR severity in China. In this study, high contrast retinal images from 495 Chinese patients with type 2 diabetes were acquired by confocal scanning laser ophthalmoscope and the global tortuosity was extracted from main and branching arterioles, venules in the whole retinal image based on the theory of best-fit exponential curves in the roto-translation group SE(2). The statistical analysis results show that retinal arteriolar and venular tortuosity might be remarkable indices for assessing retinopathy severity and identifying individuals with high-risk of renal disease in diabetes, which may provide additional insights on microvascular changes for diabetic retina and kidney diseases.

Impaired retinal microcirculation in patients with Alzheimer's disease.

The goal of this study was to determine the retinal blood flow rate (BFR) and blood flow velocity (BFV) of pre-capillary arterioles and post-capillary venules in patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Forty patients (20 AD and 20 MCI) and 21 cognitively normal (CN) controls with a similar age range (± 5 yrs) were recruited. A retinal function imager (RFI) was used to measure BFRs and BFVs of arterioles and venules in the macular region. The thickness of the ganglion cell-inner plexiform layer (GCIPL) was measured using Zeiss Cirrus optical coherence tomography. Macular BFRs in AD group were 2.64 ± 0.20 nl/s (mean ± standard deviation) in arterioles and 2.23 ± 0.19 nl/s in venules, which were significantly lower than in MCI and CN groups (P < 0.05). In addition, BFRs in MCI were lower than in CN in both arterioles and venules (P < 0.05). The BFV of the arterioles was 3.20 ± 1.07 mm/s in AD patients, which was significantly lower than in CN controls (3.91 ± 0.77 mm/s, P = 0.01). The thicknesses of GCIPL in patients with AD and MCI were significantly lower than in CN controls (P < 0.05). Neither BFV nor BFR in arterioles and venules was related to age, GCIPL thickness, mini mental state examination (MMSE) score and disease duration in patients with AD and MCI (P > 0.05). The lower BFR in both arterioles and venules in AD and MCI patients together with the loss of GCIPL were evident, indicating the impairment of the two components in the neurovascular-hemodynamic system, which may play a role in disease progression.

Retinal oximetry imaging in Alzheimer's disease.

Structural and physiological abnormalities have been reported in the retina in Alzheimer's disease (AD). Retinal oximetry detects changes in retinal oxygen metabolism in many eye diseases, where structural changes are seen. To compare oxygen saturation in retinal blood vessels in patients with AD and a healthy cohort. Oxygen saturation of hemoglobin was measured in retinal blood vessels, using imaging with spectrophotometric noninvasive retinal oximeter. 18 individuals with mild to moderate dementia of the Alzheimer-type (stage 3-5 according to the Global Deterioration Scale) and 18 healthy subjects underwent retinal oximetry in a case control study. Retinal oxygen saturation in arterioles and venules in patients with moderate AD was significantly elevated compared to healthy individuals. Retinal arterioles have 94.2 ± 5.4% oxygen saturation in moderate AD compared with 90.5 ± 3.1% in healthy subjects (mean ± SD, n = 10, p = 0.028). Retinal venules were 51.9 ± 6.0% saturated in moderate AD compared with 49.7 ± 7.0% in healthy subjects (mean ± SD, n = 10, p = 0.02). This is the first study of retinal oxygen metabolism in any central nervous system disease. It discovers abnormalities in retinal oxygen metabolism in AD. The findings are similar to those seen in age-related macular degeneration and diabetic retinopathy. Noninvasive retinal oximetry may offer new insights into pathophysiology of AD. Further studies are needed to confirm and expand these findings.

REDUCED RETINAL BLOOD FLOW VELOCITY IN DIABETIC RETINOPATHY

The purpose of this study was to compare the retinal blood flow velocities of patients with diabetes and healthy control subjects. We used a novel device offering a noninvasive diagnostic of retinal function. Flow velocities in retinal arterioles and venules were quantitatively analyzed by retinal function imager scanning in 58 eyes of 42 patients with nonproliferative diabetic retinopathy and 51 eyes of 32 normal subjects. Group differences were assessed by the mixed-model effect. Average velocity in arterial compartments (in mm/s) was 3.74 +/- 1.09 for the diabetic group and 4.19 +/- 0.99 for the control subjects. The average velocity of all segments, taking associated heart rate and individual segment widths into account, was 17% slower in the diabetic group (P < 0.0001). In both groups, average venous compartment velocity was lower than the arterial velocity (2.61 +/- 0.65 for the diabetic group; 3.03 +/- 0.59 for the control subjects). Individual vein velocities, taking heart rate and segment widths into account, was 17% slower, on average, in the diabetic group (P < 0.0001). Our measurement showed significantly decreased flow velocities in the retinal arterioles and venules of patients with diabetes compared with healthy control subjects, supporting the view of abnormal vessel function in eyes with nonproliferative diabetic retinopathy.

Retinal microvasculature in acute lacunar stroke

In their interesting and novel study in this issue of The Lancet Neurology, Lindley and colleagues1 report microvascular abnormalities in the retinal vessels of patients who have had ischaemic small vessel stroke (lacunar stroke). These retinal changes, which include a smaller arteriole:venule ratio, arteriovenous crossing abnormalities, enhanced arteriolar light reflex, and wider retinal venules in patients without diabetes, support an underlying mechanism of intracerebral vessel narrowing in lacunar infarction that has a non-atherothrombotic origin.

Intravascular oxygen saturation in retinal vessels in normal subjects and open‐angle glaucoma subjects

To measure the oxygen saturation (SO(2)) in retinal arterioles and venules in patients with glaucomatous optic neuropathy. We examined SO(2) in retinal arterioles and venules simultaneously by imaging spectrometry. Oxygen saturation was evaluated according to the difference of the extinction spectra of haemoglobin and oxyhaemoglobin. The arterio-venous difference (avD) was calculated by (SO(2art) - SO(2ven)). The optic nerve head topography was estimated by Heidelberg retinal tomography and the visual field using the Octopus G1. We examined one eye in each of 58 healthy persons (mean age 58.6 +/- 10.7 years; mean rim area 1.52 +/- 0.33 mm(2); mean defect 0.65 +/- 1.31 dB; mean intraocular pressure [IOP] 18.5 +/- 2.7 mmHg), 49 patients with normal-tension primary open-angle glaucoma (NTG) (mean age 63.0 +/- 8.5 years; mean rim area 0.89 +/- 0.34 mm(2); mean defect 5.4 +/- 4.1 dB; mean IOP 19.2 +/- 2.9 mmHg), and 45 patients with high-tension primary open-angle glaucoma (POAG) (mean age 62.6 +/- 10.3 years; mean rim area 0.97 +/- 0.47 mm(2); mean defect 7.1 +/- 6.4 dB; mean IOP 31.6 +/- 10.8 mmHg). The intraclass correlation coefficients of the SO(2) measurement were 0.82 (arteriole) and 0.59 (venule). In normal eyes, the SO(2art), SO(2ven) and avD were 92.3 +/- 3.4%, 55.7 +/- 6.8% and 36.6 +/- 7.0%, respectively. Equivalent data were 89.7 +/- 5.4%, 56.0 +/- 8.3% and 33.7 +/- 10.6%, respectively, in NTG eyes and 91.4 +/- 4.0%, 58.3 +/- 10.5% and 33.1 +/- 11.5%, respectively, in POAG eyes. Over all examined eyes, the arteriolar SO(2) and the retinal arterio-venous difference correlated significantly with the rim area. Eyes with NTG showed significantly decreased arteriolar SO(2). These changes were not seen in POAG patients.