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Locating blood vessels in retinal images by piece-wise threshold probing of a matched filter response.

We describe an automated method to locate and outline blood vessels in images of the ocular fundus. Such a tool should prove useful to eyecare specialists for purposes of patient screening, treatment evaluation, and clinical study. Our method differs from previously known methods in that it uses local and global vessel features cooperatively to segment the vessel network. A comparison of our method against hand-labeled ground truth segmentations of five images yielded 65% sensitivity and 81% specificity. A previously known technique yielded 69% sensitivity and 63% specificity. For a baseline, we also compared the ground truth against a second hand labeling, yielding 80% sensitivity and 90% specificity. These numbers indicate our method improves upon the previously known technique, but that further improvement is still possible.

Algorithms↗

Is lipoprotein(A) a risk factor for atherosclerosis of the retinal arteries?

Elevated plasma Lp(a) has been linked to development of coronary artery disease (CAD). There is no data about plasma Lp(a) and atherosclerosis of the retinal arteries. Therefore the purpose of this study was to assess the risk of retinal vessels atherosclerosis conferred by elevated plasma Lp(a) levels in 73 adult males. The results were compared with those in 45 matched apparently healthy males with no retinal vessel changes. The atherosclerotic changes of the retinal vessels were determined by direct ophthalmoscopy and graded (1-4) according to Scheie. Plasma levels of Lp(a) were measured by radial immunodiffusion. The results were compared using chi-square test. Although a very weak correlation between plasma Lp(a) levels and the incidence of retinal atherosclerosis was found, no significant association between the degree of atherosclerotic changes and plasma Lp(a) levels could be proven. Thus it could be concluded that plasma Lp(a) level is not a significant risk factor for atherosclerosis of the retinal arteries.

Arteriosclerosis↗

Hypertensive retinopathy. Description, classification, and prognosis.

In 1898 Marcus Gunn described the changes in retinal vessels noted with hypertension. Arteriolar narrowing, caliber irregularity, alterations of the light reflex, and hiding of the arterial blood column were noted. Arteriovenous crossing changes and capillary bed abnormalities, such as cotton-wool spots, retinal hemorrhages, and retinal edema were also mentioned, as well as blurred discs. In the 83 intervening years, little has been added to the description of hypertensive retinopathy, but our understanding has increased. Retinal vessels respond to elevations of systemic blood pressure by generalized arteriolar constriction. This can lead to arteriolar necrosis, retinal edema, cotton-wool spots, hemorrhage, and disc edema. If the blood pressure is controlled, or slow rising, or if arteriolar sclerosis is present in the retinal arteries, then a picture of arteriolar irregularity will be noted and, depending upon the ability of the retinal vessels to contract, segmental constriction will be seen. In separating hypertensives from nonhypertensives, the most consistent ophthalmoscopic finding is arteriolar narrowing with focal irregularity. In prognosticating for survival, the best method available is the Keith-Wagener-Barker classification. However, the difficulty in separating Groups 1 and 2 of this classification has lead to numerous modifications that make comparisons from one study to another difficult.

Constriction, Pathologic↗

Ocular amyloid angiopathy associated with familial amyloidotic polyneuropathy caused by amyloidogenic transthyretin Y114C.

PURPOSE: To report the clinicopathological findings for a unique ocular amyloid angiopathy in patients with familial amyloidotic polyneuropathy (FAP) caused by amyloidogenic transthyretin Y114C. DESIGN: Three case reports. METHODS: Retrospective review of clinicopathological findings, course, and treatment of the 3 patients. MAIN OUTCOME MEASURES: Visual acuity, intraocular pressure, fundus photography, fluorescein angiography (FA), indocyanine green angiography, and histopathological analysis. RESULTS: In the 32-year-old patient, in the early stage of FAP, indocyanine green angiography demonstrated multiple sites of hyperfluorescence, with staining along major choroidal veins. Retinal vessels appeared normal clinically and on FA. In the 48-year-old patient, who had late-stage FAP, examination of the fundus revealed pinpoint white amyloid opacities over the retinal surface, sheathing of retinal vessels, and scattered retinal hemorrhages. Fluorescein angiography showed vascular closure, focal staining, and microaneurysms. Indocyanine green angiography revealed multiple sites of hyperfluorescence, with staining along retinal and choroidal vessels. Examination during follow-up revealed that these vascular changes continued to progress. Histopathological study of an eye obtained at autopsy from the 49-year-old patient revealed marked intravascular and extravascular amyloid deposition. CONCLUSIONS: Severe and progressive amyloid angiopathy causing visual disturbance was seen in patients with FAP caused by amyloidogenic transthyretin Y114C.

Adult↗

Bilateral retinal artery and choriocapillaris occlusion following the injection of long-acting corticosteroid suspensions in combination with other drugs: II. Animal experimental studies.

An experimental dog model was used to reproduce the clinical picture of bilateral arteriole and choriocapillaris occlusion from a unilateral intracarotid injection of long-acting corticosteroids combined with other drugs including lidocaine, epinephrine, and penicillin. All five known long-acting corticosteroids, when combined with 1:1000,000 epinephrine, elicited vasoconstriction followed by dilatation of the retinal vessels with particulate material occlusion of the retinal vessels and choriocapillaris associated with small retinal hemorrhages. The fluorescein picture is described. The particles were identified by polarization as the long-acting corticosteroid.

Animals↗

The three-dimensional architecture of retinal blood vessels in KK mice, with special reference to the smooth muscle cells and pericytes.

In the present study, the three-dimensional architecture of retinal vasculature was studied in KK mice, by combined use of resin injection, chemical treatment and scanning electron microscopy (SEM). In particular, Mercox/methylmethacrylate resin-injected eye tissues were subjected in sequence to NaClO immersion, ultrasonication and HCl treatment. The present technological innovation made possible SEM visualization of deeper retinal vasculature. In KK mice, the tunica media of stem arterioles and of first and second order branches consisted of a single layer of spindle-shaped smooth muscle cells provided with spine-like cytoplasmic processes. In addition, there occurred small triangular smooth muscle cells provided with slender cytoplasmic processes. The processes, giving off tiny secondary processes, overlapped with each other, thus forming assemblages around branching sites. Such a structure was particularly prominent for those branching sites where parent arterioles gave rise to their branches in a side arm-like pattern. The third (and occasionally fourth) order branches were surrounded by atypical smooth muscle cells, with considerable dimension of endothelial surface remaining uncovered. Capillary pericytes consisted of fusiform cell bodies and slender cytoplasmic processes. Smooth muscle cells of retinal venules differed from those of arterioles. They were stellate in shape, exhibiting several cytoplasmic processes.

Animals↗

Accurate vessel width measurement from fundus photographs: a new concept.

Accurate determination of retinal vessel width measurement is important in the study of the haemodynamic changes that accompany various physiological and pathological states. Currently the width at the half height of the transmittance and densitometry profiles are used as a measure of retinal vessel width. A consistent phenomenon of two 'kick points' on the slopes of the transmittance and densitometry profiles near the base, has been observed. In this study, mathematical models have been formulated to describe the characteristic curves of the transmittance and the densitometry profiles. They demonstrate the kick points being coincident with the edges of the blood column. The horizontal distance across the kick points would therefore indicate the actual blood column width. To evaluate this hypothesis, blood was infused through two lengths of plastic tubing of known diameters, and photographed. In comparison with the known diameters, the half height underestimated the blood column width by 7.33% and 6.46%, while the kick point method slightly overestimated it by 1.40% and 0.34%. These techniques were applied to monochromatic fundus photographs. In comparison with the kick point method, the half height underestimated the blood column width in veins by 16.67% and in arteries by 15.86%. The characteristics of the kick points and their practicality have been discussed. The kick point method may provide the most accurate measurement of vessel width possible from these profiles.

Fluorescein Angiography↗

Characterization and ontogeny of PGE2 and PGF2 alpha receptors on the retinal vasculature of the pig.

The vasoconstrictor effects of PGE2 and PGF2 alpha are less pronounced on retinal vessels of the newborn than of the adult pig. We tested the hypothesis that the decreased vasomotor response to these prostaglandins might be due to relatively fewer receptors and/or different receptor subtypes (in the case of PGE2) on retinal vessels of the newborn animal. Binding studies using [3H]PGE2 and [3H]PGF2 alpha revealed that PGE2 (EP) and PGF2 alpha (FP) receptor densities in retinal microvessel membrane preparations from newborn animals were approximately 25% of those found in vessels from the adult. The Kd for PGF2 alpha did not differ; however, the Kd for PGE2 was less in newborn than in adult vessels. Competition binding studies using AH 6809 (EP1 antagonist), butaprost (EP2 agonist), M/+B 28,767 (EP3 agonist), and AH 23848B (EP4 antagonist) suggested that the retinal vessels of the newborn contained approximately equal number of EP1 and EP2 receptor subtypes whereas the main receptor subtype in the adult vessels was EP1. In addition, PGE2 and butaprost produced comparable increases in adenosine 3',5'-cyclic monophosphate synthesis in newborn and adult vessels. PGE2, 17-phenyl trinor PGE2 (EP1 agonist) and PGF2 alpha caused a 2.5 to 3-fold greater increase in inositol 1,4,5-triphosphate (IP3) formation in adult than in newborn preparations. It is concluded that fewer PGF2 alpha receptors and an associated decrease in receptor-coupled IP3 formation in the retinal vessels of the newborn could lead to weaker vasoconstrictor effects of PGF2 alpha on retinal vessels of the newborn than of adult pigs; fewer EP1 receptors (associated with vasoconstriction) and a relatively greater proportion of EP2 receptors (associated with vasodilation) might be responsible for the reduced retinal vasoconstrictor effects of PGE2 in the newborn.

Age Factors↗

Congenital bilateral arterial anastomosis between the choroid and peripheral retina.

A healthy 26-year-old woman, had a decrease of vision in her left eye caused by a macular pucker, showed deformed retinal vessels, small exudative detachments of the neuroretina, and retinal exudates and hemorrhages in both fundi peripheral to the equator at the 6-o'clock position. Fluorescein angiography and stereoscopic photographs clearly showed an anastomosis of a recurrent ciliary artery with periphral retinal vessels and localized absence of the choriocapillaris under the detached retina in both eyes. The anastomosis probably developed in the last month of fetal life as the result of a localized absence of Bruch's membrane caused by an incomplete coloboma of the choroid that originated during the second month of gestation.

Adult↗

[TalkingEyes-and-more].

To avoid the clinical manifestation of a vascular disease like stroke it is necessary to detect early vascular signs, to begin a therapy before the outbreak of the vascular disease happens. "TalkingEyes-and-more" is an interdisciplinary and quality-assessed program for prevention of vascular diseases. In several "screening-centers" in Germany interested citized were examined by non-invasive and fast methods to estimate the vascular risk. The examinations were performed on site, the medical evaluation of the data and images were performed centrally in the reading center of the Private Center of Preventive Medicine and Eye Diagnostics" in Erlangen by medical doctors. Alterations of the microvessels become often at first visible in retinal vessels. "TalkingEyes-and-more" examined telemedically the retinal vessels by a patented approach regarding microangiopathic abnormalities. In addition other risk factors like arterial blood pressure, intima media thickness of the carotid artery, cholesterol, fasting glucose, extended bodymass index, and others were documented. By these data a risk index is calculated and a proposal for improving the risk factors is generated.

Adult↗

Abnormal retinal vascular development in IL-18 knockout mice.

Recent studies have indicated that interleukin 18 (IL-18) might act as either an angiogenic or an angiostatic factor, but the true function of this protein in vascular development is unclear. We therefore investigated the role of IL-18 in the formation of retinal vessels. Development of the retinal vasculature was compared in IL-18 knockout (KO) and wild-type (WT) mice at several different time points. The formation of vessels was evaluated using angiography of flat-mounted retinal samples after inoculation with fluorescein dextran. Retinal samples from both groups were also evaluated through histological examinations, and the expression of angiogenic factors was examined using the reverse-transcription-polymerase chain reaction. The capillary retinal vessels in both WT and IL-18 KO mice had reached the peripheral retina by postnatal day (P) 7. However, IL-18 KO mice showed angiectasis and vascular leakage at P7, especially in the mid-peripheral retina. These symptoms were not observed in WT mice at any stage. Histopathological analysis confirmed abnormal vascular formation in IL-18 KO mice at P14. Interestingly, these abnormalities regressed over time and had disappeared by P84. Several angiogenesis-associated factors, including vascular endothelial growth factor (VEGF), basic fibroblast-growth factor (bFGF), platelet-derived growth factor (PDGF) and pigment epithelium-derived factor (PEDF), were overexpressed in the retinas of IL-18 KO mice compared with those of WT mice at P14. Interferon-gamma was detected only in WT mouse retinas at P14. These results provide new evidence for the role of IL-18 in retinal vascular development.

Angiogenic Proteins↗

Inhibition of pathologic retinal neovascularization by alpha-defensins.

Proliferative retinopathies, such as those complicating prematurity and diabetes, are major causes of blindness. A prominent feature of these retinopathies is excessive neovascularization, which is orchestrated by the hypoxia-induced vascular endothelial growth factor (VEGF) stimulating endothelial cells and the integrin-mediated adhesive interactions of endothelial cells with extracellular matrix components such as fibronectin (FN). Recently, we demonstrated that alpha-defensins interfere with alpha5beta1-FN interactions and dependent endothelial cell functions. Here, alpha-defensins were studied in hypoxia-induced proliferative retinopathy. In vitro, alpha-defensins specifically inhibited alpha5beta1-integrin-dependent migration of bovine retinal endothelial cells (BRECs) to FN, attenuated the VEGF-stimulated increase in endothelial permeability, and blocked BREC proliferation and capillary sprout formation in 3-dimensional fibrin-matrices. An up-regulation of beta1-integrin and FN was observed in the retinal vessels in the mouse model of hypoxia-induced retinal angiogenesis. Systemic and local administration of alpha-defensins reduced retinal neovascularization by 45% and 60%, respectively, and this effect was comparable to the inhibitory effect of alpha5beta1-blocking antibody. alpha-Defensins were detected in human diabetic retinas associated with normal retinal vessels but were absent from proliferative lesions. Together, these data show that alpha-defensins inhibit pathologic retinal neovascularization in vivo and may provide a clinically efficient strategy against proliferative retinopathies.

Animals↗