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[Experimental study of nimodipine and vascular endothelial growth factor in proliferative retinopathy].

OBJECTIVE: To study the therapeutic effect of the calcium channel antagonist nimodipine on the proliferative retinopathy and it's interaction with vascular endothelial growth factor (VEGF). METHODS: A proliferative retinopathy model (OIR) of newborn Sprague-Dawley (SD) rats was induced by hyperoxia. Different dosages of nimodipine were injected to the rats through retrobulbar or intraperitoneal routes. Both eyeballs of newborn rats were enucleated for performing pathological sections and were studied by immunohistochemical method, in order to count the nuclei of proliferative retinal vessels and to investigate the expression of VEGF in the retina. RESULTS: The number of nuclei of proliferative retinal vessels and the expression of VEGF in non-treatment group increased significantly as compared with normal control group (P < 0.01). Both parameters decreased significantly in high dosage and medium dosage of retrobulbar injection group as compared with the non-treatment group (P < 0.01) and there was no significant decrease in low dosage group (P > 0.05). In each dosage group of intraperitoneal injection, there was a significant decrease of the expression of VEGF (P > 0.01). CONCLUSION: VEGF can induce cell proliferation by activating the calcium channel in cell membrane through which the influx of calcium is increased. The calcium channel antagonist nimodipine can inhibit proliferative retinopathy by blocking the influx of calcium. Nimodipine can inhibit the expression of VEGF at certain degrees.

Animals↗

Small vessel disease in vasectomized diabetic monkeys: light microscopic study.

The following four groups of rhesus monkeys were studied for small vessel pathology of the heart, kidney and retina: sham-vasectomized, vasectomized, sham-vasectomized diabetic and vasectomized diabetic. A significant increase was observed in the frequency of pathological changes in small vessels (less than 60 micron diameter), of the heart muscle of nondiabetic vasectomized monkeys, and in sham-vasectomized and vasectomized diabetic monkeys. Further, the thickness of the glomerular capillary basement membrane was also significantly increased in the three experimental groups. In vasectomized diabetic monkeys, the vascular lesions were much greater than in the other two groups. Moreover, in this group one animal had a microaneurysm of a retinal vessel and another had distortion of retinal veins. The monkeys subjected to vasectomy or diabetes alone did not develop these changes. However, the ratio of mural to endothelial cells in retinal vessels was markedly altered in vasectomized and nonvasectomized diabetic monkeys.

Animals↗

An unusual retinal vascular morphology in connection with a novel AIPL1 mutation in Leber's congenital amaurosis.

AIMS: To report a case of an unusual retinal vascular morphology in connection with a novel AIPL1 mutation in a patient with Leber's congenital amaurosis (LCA). METHODS: A patient with LCA and no light perception from birth had both eyes enucleated at the age of 22 years because of excruciating pain. Mutation analysis was performed on known LCA genes. The eyes were processed for casts of the vascular tree, routine histopathology, and electron microscopy. RESULTS: A novel H82Y (244C-->T) mutation and a H90D (286G-->C) polymorphism were detected in exon 2 of the AIPL1 gene. Both the cast and the histopathological examination showed dilated retinal vessels, mainly venules, primarily localised in the posterior pole. In the mid-peripheral retina the density of capillaries on the arteriolar side of the microcirculatory units was significantly decreased. The vascular system was seen to gradually attenuate towards the retinal periphery, and to stop at a zone located approximately 4 mm from the ora serrata along the whole circumference. In this zone pigmented aggregates characteristic of retinitis pigmentosa were seen to ensheath the retinal vessels. The photoreceptors were almost totally absent and retinal gliosis was present. A decreased number of ganglion cells and an increased vacuolisation of the nerve fibre layer were observed. The retinal pigment cells and Bruch's membrane appeared normal in all regions. CONCLUSION: An unusual retinal vascular morphology in an LCA patient is presented and possible pathogenic mechanisms of the findings are discussed.

Adaptor Proteins, Signal Transducing↗

Effects of soft X-ray irradiation on ocular development in Sprague-Dawley rats.

Pregnant rats were irradiated with soft x-rays at a dose of 1.6, 3.2, 6.3 or 12.6 Gy on Day 9 of gestation, and the eyes of F1 offspring were examined using indirect ophthalmoscopy and biomicroscopy during Postnatal Week 5. Ophthalmoscopic examination revealed iris and choroidal coloboma, microphthalmia and anophthalmia in the 3.2, 6.3 and 12.6 Gy groups. In addition to those anomalies, lens luxation and associated anterior displacement of the vitreous face, and retinal vascular anomalies were observed in the 12.6 Gy group. Histological examination revealed agenesis of retinal vessels. Ophthalmoscopic examination using biomicroscopy and indirect ophthalmoscopy detected choroidal coloboma, lens and vitreous luxation and defect in retinal vessels which could not be detected by external observation, demonstrating the usefulness of this technique in the postnatal stage of teratology studies.

Animals↗

Analysis of retinal vasodilation after flicker light stimulation in relation to vasospastic propensity.

PURPOSE: To explore the maximum retinal vasodilation in response to repeated flicker light stimulation in relation to vasospastic propensity in healthy subjects. METHODS: Twenty-four young healthy women were grouped as vasospastic and nonvasospastic, based on their history of cold extremities and on the results of nailfold capillaroscopy. A retinal vessel analyzer was used to obtain recordings of the ocular fundus during still illumination and three flicker light stimulations. Retinal vessels were analyzed in the immediate vicinity of the optic nerve head and 2 to 3 disc diameters away from the disc. The maximum dilatory amplitudes were always the highest 1-second mean vessel diameter in response to each of the three flicker light stimuli. RESULTS: Maximum dilatory amplitude (in percent) was, in the proximal measurement site in the arterioles, 6.2 +/- 2.6, 4.8 +/- 2.1, and 6.6 +/- 3.9 in the vasospastic group, and 7.9 +/- 3.2, 8.6 +/- 4.1, and 9.1 +/- 4.7 in the nonvasospastic group in three repeated flicker stimulations. Corresponding values for distal measurement sites were 6.7 +/- 2.5, 4.8 +/- 3.4, and 4.7 +/- 4.4 and 9.0 +/- 3.7, 11.0 +/- 5.2, and 12.3 +/- 7.7. The maximum amplitude was significantly lower in the vasospastic group (P = 0.001). The maximum venule dilation was also significantly lower in the vasospastic group (P = 0.037). Vessel diameters failed to stabilize at the original baseline level during the 80-second recovery period, and this baseline offset had opposite signs in the arterioles in the vasospastic (remained below the original baseline) and nonvasospastic (remained above the original baseline) groups. CONCLUSIONS: The maximum dilatory amplitude was significantly lower in vessels in the vasospastic group. An augmentation of the maximum vasodilation was observed in the nonvasospastic group after repeated flicker stimulations, a phenomenon that was missing in arterioles of vasospastic subjects. It seems that such different behavior is due to the opposite baseline offsets in interflicker periods in the two groups.

Adult↗

Ophthalmodynamometry in eyes with dilated episcleral veins.

PURPOSE: To determine the central retinal vessel collapse pressure in patients with dilated episcleral veins. METHODS: This clinical noninterventional comparative study included a study group of 10 eyes (6 patients) with dilated episcleral veins, and a control group consisting of 50 eyes of 40 patients with cataract or refractive problems. With topical anesthesia, a Goldmann contact lens fitted with a pressure sensor in its holding ring was placed onto the cornea. Pressure was asserted onto the globe by pressing the contact lens, and the pressure value at the time when the central retinal artery and vein started pulsating was noted as central retinal artery and vein collapse pressure. RESULTS: Central retinal vein collapse pressure was significantly higher (P<0.001) in the study group with dilated episcleral veins than in the control group (37.9 +/- 33.8 vs 5.1 +/- 8.4 relative units [RU]). In the central retinal artery, there was not significant difference in diastolic collapse pressure measured between the study and control groups (78.2 +/- 22.8 vs 74.2 +/- 18.8 RU, respectively; P = 0.74). CONCLUSIONS: As measured by a new ophthalmodynamometer with biomicroscopic visualization of the central retinal vessels during the examination, the central retinal vein collapse pressure measurements were significantly higher in eyes with dilated episcleral veins than in control eyes. Ophthalmodynamometric estimation of the central retinal vein collapse pressure may be helpful in the assessment of patients with dilated episcleral veins.

Adult↗

Central retinal artery and vein collapse pressure in eyes with chronic open angle glaucoma.

AIMS: To determine central retinal vessel collapse pressure in chronic open angle glaucoma. METHODS: For 19 eyes with chronic open angle glaucoma and 27 eyes of a control group, central retinal vessel collapse pressure was measured by a Goldmann contact lens fitted with a pressure sensor in its holding grip. RESULTS: Central retinal vein collapse pressure was significantly (p=0.001) higher in the glaucoma group than in the control group (26.1 (SD 26.4) relative units versus 6.1 (8.4) relative units). CONCLUSIONS: Measured by a new ophthalmodynamometer, central retinal vein collapse pressure measurements may be abnormally high in eyes with chronic open angle glaucoma.

Adult↗

Ocular findings in homozygous sickle cell disease in Jos, Nigeria.

Ophthalmological examinations were performed in 78 homozygous sickle cell (Hb SS) patients, aged 4-42 years attending the sickle cell clinic of the Jos University Teaching Hospital, and the University Clinic, Jos, in Nigeria. Conjunctival signs present in about 77% of cases were observed in all ages and sexes. White without pressure present in 62.8% of the cases was the commonest retinal sign and in 56.3% of the cases was associated with peripheral retinal vessel disease. Salmon patches (6.4%), iridescent spots (10.3%), mottled brown areas (16.7%) and black sunbursts (7.7%) were seen as early as 10 years of age but showed an upward trend with age. Peripheral retinal vessel disease present in 52.5% of the cases was the second commonest retinal sign and with the exception of arteriolar occlusion showed no sex predilection, but an upward trend with age. Arterio-venous anastomosis (7.7%), vitreous haemorrhages and veils (3.8%) were the only severe proliferative signs noted. There were no cases of retinal neovascularization, retinal detachment or of angoid streaks, and the posterior poles were normal. Retinal signs were present as early as 8 years of age and showed an upward trend with age.

Adolescent↗

Combining surgical ablation of retinal inflow and outflow vessels with photodynamic therapy for retinal angiomatous proliferation.

PURPOSE: To evaluate short-term efficacy of combining surgical ablation of retinal inflow and outflow vessels and photodynamic therapy (PDT) for stage 3 retinal angiomatous proliferation (RAP). DESIGN: Prospective interventional case series. METHODS: Five eyes (five patients) underwent surgical ablation of inflow and outflow vessels and PDT for stage 3 RAP. RESULTS: Inflow and outflow vessels were ablated in four eyes, and only inflow was ablated in one eye. In four eyes starting PDT within six weeks of surgical ablation, choroidal neovascularization (CNV) disappeared or shrank after one PDT session (three months follow-up). However, CNV enlarged again in three of the four (final follow-up) because of reperfusion from newly formed inflow vessels. In one eye starting PDT seven months after ablation, a new retinal inflow vessel feeding the CNV appeared by the time of the first PDT session. The CNV continued to expand, despite two PDT sessions. CONCLUSIONS: Combining surgical ablation and PDT was not useful on account of a high frequency of reperfusion from retinal inflow vessels.

Arterioles↗

[In vivo and in vitro study of experimental occlusion of choroidal and retinal blood vessels in the miniature pig].

Experimental occlusion of ocular blood vessels was performed in 25 eyes of 20 adult miniature pigs. The hyperacute, acute, subacute and chronic effects of these occlusions were studied by photography and fluorescein angiography of the ocular fundus in the living animals, and post-mortem by microscopic examination of histologic sections and stereomicroscopic study of vascular corrosion casts. Transection of the lateral posterior ciliary arteries was performed in eleven eyes and resulted in manifest chorioretinal ischaemic atrophy in confined areas of the ocular fundus. One month and longer after arterial transection, revascularization was found in the areas in which hypoperfusion had been induced, but no indications of neovascularization were observed. In one eye the lateral vortex veins were occluded by ligation. The subsequent fluorescein angiograms demonstrated only an insignificant local retardation of the choroidal filling. Filling defects of the choroidal vasculature and chorioretinal ischaemic lesions were not observed in the living animal nor in the vascular corrosion cast. Transection of the lateral posterior ciliary arteries was combined with ligation of the lateral vortex veins in seven eyes. These experiments resulted in lesions which were less severe than the sequels caused by transection of the lateral posterior ciliary arteries only. This observation was explained by the retrograde flow of venous blood which is rich in oxygen from the medial to the lateral choroidal quadrants. Consequently, ligation of the lateral vortex veins has a protective influence on the acute ischaemic lesions provoked by transection of the lateral posterior ciliary arteries. Simultaneous transection of the lateral posterior ciliary arteries and lateral chorioretinal arteries was performed in eight eyes. In the subacute and chronic stages, 1 and 4 months respectively after the vascular transection, proliferation of the retinal pigment epithelium and intraretinal neovascularization were observed in three out of five eyes examined. A fibrogliotic tissue mass containing newly formed blood vessels was found in between the reduplicated retinal pigment epithelium and the external layers of the sensory retina. The miniature pig offers an interesting ophthalmologic model because the ischaemic chorioretinal lesions and intraretinal gliovascular membranes which can be induced experimentally in this species present numerous similarities with the sequels of chorioretinal vascular occlusions in man.

Angiography↗

[Branch artery occlusion due to focal necrotizing retinitis -- probably caused by toxoplasmosis (author's transl)].

A case of necrotizing retinitis, probably due to toxoplasma gondii, is described in a 21-year-old man. Transient occlusion of the arteriole lying over the lesions was confirmed angiographically. The presence of inflammatory chorioretinal foci in the vicinity of retinal vessels was documented photographically in three other cases. The fundus changes and the field defects in these patients suggested that retinal perfusion had been temporarily impaired. The customary administration of steroids combined with antibiotics appears justified in order to minimise the occurrence of retinal vascular damage in the presence of necrotizing retinitis.

Adolescent↗

Morphology of intraretinal new vessels in the PETH rat.

The mature stages of retinal dystrophy in PETH rats are characterised by loss of the photoreceptor layer and invasion of the retinal pigment epithelium by new capillaries derived from the retinal vessels. The new capillaries are fenestrated where they are adjacent to the basement membrane of the retinal pigment epithelium and are surrounded by cells of the disrupted pigment epithelium, which follow the course of the capillaries into the inner retina. Abnormal basement membrane deposits are common within the retinal pigment epithelium.

Animal Husbandry↗

Ocular findings in homozygous sickle cell disease in Nigeria.

We report the ocular findings in 124 Nigerians with homozygous sickle cell disease. None had ocular symptoms. In order of frequency conjunctival vessel anomalies, tortuosity of the major retinal vessels and chorioretinal scars were found. The resemblance of sickle cell chorioretinal scars to toxoplasmic choroiditis is remarkable and should lead to the exclusion of sickle cell disease whenever such lesions are encountered. Angioid streaks, retinitis proliferans, retinal detachment and arteriovenous fans were not observed.

Adolescent↗

Detection of paravascular retinal cysts before using OCT in a highly myopic patient.

PURPOSE: We describe a case of high myopia who developed paravascular retinal rarefaction generated by vitreoretinal adhesion on retinal vessels detected using optical coherence tomography (OCT). METHODS: A 31-year-old man received a regular ophthalmologic examination for high myopia including detailed fundus examination and OCT. RESULTS: Detailed fundus examination revealed retinal rarefaction and fissure-like findings alongside the superior temporal retinal artery and vein in the right eye. OCT images revealed vitreoretinal adhesions on the retinal artery and a paravascular cystoid space in the inner retina. There was no retinal detachment. The axial length had increased by 1.50 mm over 15 years. CONCLUSION: Paravascular retinal rarefaction as well as pseudohole formation caused by vitreoretinal adhesion on retinal vessels was detected in this patient using OCT. OCT might be useful to detect early-stage retinal pathologies caused by paravascular vitreoretinal traction in highly myopic patients.

Adult↗

Imaging of chorioretinal anastomoses in vascularized retinal pigment epithelium detachments.

OBJECTIVE: To identify specific features of pigment epithelium detachments with limited hyperfluorescent lesions (hot spots). DESIGN: One hundred eighty-two consecutive patients (186 eyes) who had vascularized pigment epithelium detachments and recent onset of symptoms were examined with indocyanine green and fluorescein videoangiography using the scanning laser ophthalmoscope. The choroidal neovascularization complex and macular retinal vessels were studied. The natural history and the effect of laser treatment were evaluated. RESULTS: Fifty-four eyes had hot spots on indocyanine green angiography. In 50 of these 54 eyes, the video analysis showed an anastomosis of one or more retinal vessels, with the choroidal neovascularization within the hot spot. One or two retinal veins or arteries or both filled with both dyes and were seen to enter into the hot spot. Results of indocyanine green-guided photocoagulation of the hot spot in 28 eyes were disappointing. CONCLUSION: Continuous recording of the early phases of fluorescein and indocyanine green angiography allowed identification of chorioretinal anastomoses in vascularized pigment epithelium detachments with hot spots at an early exudative stage of age-related macular degeneration in 50 (26.8%) of 186 eyes. The poor outcome of laser photocoagulation could be related not only to the development of an overlying pigment epithelium detachment, but also to the retinal and choroidal vascularization of the lesion.

Aged↗

Complete avulsion of the optic nerve. A clinical, angiographic, and electrodiagnostic study.

A case of traumatic complete avulsion of the optic nerve is reported together with fluorescein angiography and electrodiagnostic findings. Despite the disappearance of the central vessels, circulation remained in the branch retinal vessels and angiography demonstrated communication between peripapillary choroidal vessels and the superior temporal artery. The visually-evoked cortical response was abolished. Electroretinography showed a normal a-wave but reduced amplitude b-wave, not supporting the theory of the existence of centrifugal retino-suppressive fibres in the optic nerve of man.

Adult↗

Blood-ocular barrier breakdown in eyes with ocular melanoma. A potential role for vascular endothelial growth factor/vascular permeability factor.

A series of 130 eyes with ocular melanomas, 19 normal eyes, and 18 eyes affected with other disorders leading to blood-ocular barrier (BOB) breakdown were immunohistochemically stained for albumin to localize sites of BOB failure within the retina, ciliary body, and iris. Thirty-nine of the eyes containing melanomas and all of the other eyes were also immunohistochemically stained for vascular endothelial growth factor (VEGF), to investigate its potential role as a mediator for BOB failure. Eyes with melanomas showed widespread leakage through the retinal pigment epithelium, and 58% demonstrated leakage from retinal vessels in the proximity of the tumor. BOB failure remote from the tumor also occurred in retina (50%), optic nerve head (77%), ciliary body (51%), and iris (51%), suggesting that a soluble mediator may be involved. VEGF was demonstrated intraretinally in the proximity of (46%) and remote from (24%) melanomas and in eyes affected by other disease processes, particularly those involving neoplasia or retinal detachments, usually within particular cell populations (ie, retinal vessel walls, ganglion cells, inner or outer nuclear layers, retinal pigment epithelium). VEGF localization in retina, ciliary body, and iris often coincided with sites of extravasated albumin. Preincubation of albumin or VEGF antibodies with normal serum or VEGF peptide, respectively, eliminated or markedly reduced all immunoreactivity. Only 1 of 14 normal postmortem eyes and 0 of 5 normal surgically removed eyes showed VEGF positivity in the retina, 5 of 19 normal eyes had weak positivity in the ciliary body, and VEGF was not demonstrated in the iris of normal eyes. VEGF cannot account for all of the BOB failure associated with ocular melanomas, but appears likely to play a contributing role in many cases.

Blood-Retinal Barrier↗

[Ocular changes in tropical malaria with cerebral involvement--results from the Blantyre Malaria Project].

INTRODUCTION: Malaria is a tropical disease causing an estimated 300 million infections and one million deaths per year. In sub-Saharan Africa, most infections are due to Plasmodium falciparum. The hallmark of the clinical syndrome of cerebral malaria is coma, and the associated mortality rate, even in appropriately treated patients, is 15 - 50 %. Funduscopy plays a major role for the ophthalmologist in the differential diagnosis because of the characteristic changes. METHODS: To date more than 1000 children who satisfied the standard clinical case definition of cerebral malaria were admitted to the Blantyre Malaria Project (Malawi, Africa) for inpatient treatment and examined using indirect ophthalmoscopy through fully dilated pupils. The gender distribution was homogeneous and the children were between 2 and 14 years old. The optic nerve head, central and peripheral retina and central and peripheral vessels were described and photographed using a hand-held fundus camera (KOWA). RESULTS: The spectrum and severity of findings of the ocular fundus in children with CM include the following distinct entities: haemorrhages (with and without a white centre), cotton wool spots, papilloedema, retinal whitening and retinal vessel abnormalities that may appear to be orange or white. Most of the retinal haemorrhages (in 40 %) have white centres and resemble Roth spots. Cotton wool spots were seen in only 5 %. Papilloedema was also not commonly seen (8 %) but is a poor prognostic sign. Retinal whitening (in 50 %) is seen more commonly at the posterior pole than in the periphery. 20 % of patients show retinal vessel abnormalities that may be orange or white in colour. CONCLUSION: Ocular fundus changes in CM can be detected by the ophthalmologist using simple means and are decisive for the prognosis and timely therapy for this potentially lethal disease.

Adolescent↗