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Vasoconstrictive effect of topical timolol on human retinal arteries.

Timolol is widely used in glaucoma treatment without sufficient knowledge of its vascular retinal effects. In this study, we measured the retinal vessel diameters before and after instillation of 0.5% timolol twice daily in one eye for 1 week, using photographic enlargements (x44). A total of 12 normal, caucasian subjects aged 25-39 years (average, 30.6 +/- 4.2 years) participated in this study. In all, 75% of the subjects had a diminution of retinal arterial size in the treated eye. The mean arterial diametric decrease was 4.1% in treated eyes compared with both untreated eyes and pretreatment values of treated eyes. These diminutions were statistically significant according to Student's paired t-test (P less than 0.05). No statistical difference was found in venous diameters (t = -0.065). Results showed that 0.5% timolol may have a vasoconstrictive effect on the retinal arteries of normal human subjects after 1 week of unilateral instillation twice daily. We suggest that this arterial vasoconstriction could be caused by the effect of timolol on the vascular beta-2 receptors. Further investigations are warranted to determine whether timolol also acts on ciliary arteries and whether arterial vasoconstriction participates in lowering intraocular pressure.

Adult↗

Intravitreal steroids may facilitate treatment of Eales' disease (idiopathic retinal vasculitis): an interventional case series.

PURPOSE: Eales' disease is an idiopathic peripheral perivasculitis leading to proliferative vascular retinopathy, recurrent vitreous haemorrhages, and tractional retinal detachment. It is an elusive cause of blindness in young, otherwise healthy individuals. We studied the effects of intravitreal triamcinolone acetonide (IVTA) in patients of Eales' disease, which may eventually reduce the side effects and cost of management, with results equivalent to or better than oral steroids. METHODS: Ethics approval and prior patient consent were obtained. Fluorescein fundus angiograms (FFAs) of 12 eyes of 12 Eales' disease patients were taken before enrolment. These patients received 0.1 ml of 40 mg/ml (4 mg) intravitreal triamcinolone through pars plana under topical anaesthesia. Regular weekly follow-ups were initiated to ascertain Snellen visual acuity, intraocular pressure (IOP) with Goldman tonometer, and triple mirror examination. Fluorescein fundus angiography was again performed in the 8th week to monitor response to treatment. Decrease in areas of late perivascular dye extravasation on fluorescein angiography was used as marker for improvement. RESULTS: Ten out of a total of 12 (83.33%) eyes treated with IVTA showed significant reduction of late leakage from retinal vessels on fluorescein fundus angiography. Two out of 12 eyes (16.67%) did not show considerable decrease in late perivascular fluorescein dye leakage after 8 weeks of intravitreal triamcinolone injection. Two patients (16.67%) had a significant rise in IOP after IVTA. CONCLUSION: Intravitreal steroids may be advocated for management of idiopathic retinal vasculitis without complications of systemic steroids, and minimize need for more invasive procedures.

Adult↗

Familial oculoleptomeningeal amyloidosis.

Members of a German family living in Ohio (United States) have been found to have dominantly inherited amyloidosis causing dementia, seizures, strokes, coma and visual deterioration. Pathological examination of affected individuals has shown severe, diffuse amyloidosis of the leptomeninges and subarachnoid vessels associated with patchy fibrosis and obliteration of the subarachnoid space. Amyloid deposits were prominent on the ependymal surfaces and severe and diffuse neuronal loss and generalized subpial gliosis were found in the cerebrum and cerebellum. On occasion superficial brain infarcts were seen. Amyloid was also found in the vitreous, the retinal internal limiting membrane and the retinal vessels, particularly those in the nerve fibre layer. There was only minimal amyloid elsewhere.

Adult↗

Amaurosis congenita (Leber).

A case of Leber's amaurosis congenita is presented. The patient was bilaterally and congenitally blind. She had nonrecordable ERG responses and a striking fundus appearance with multiple irregularly shaped yellowish white flecks deep in the retina, peripheraly distributed over an area extending from behind the equator to the ora serrata. No flecks were present in narrow bands on both sides of the retinal vessels and in the whole nasal portion of the fundus. Fine powdery granules of pigment were diffusely spread in the areas that were devoid of flecks. The macula and the optic disc showed no gross abnormality. Although this fundus appearance resembles that of the flecked retina syndrome and Oguchi's disease, retinal function in this case is more profoundly affected than in either of the two.

Blindness↗

Autosomal dominantly inherited optic nerve coloboma.

Four members of three consecutive generations of a family had congenital anomalies of the optic disk: deep excavation of the optic disk containing a mass of white glial tissue at its center, anomalous retinal vessels emerging from the peripheral aspect of the disk, and elevated annulus of peripapillary pigmentary disturbance. These optic disk anomalies occurred bilaterally with some inter- and intra-individual variable expressivity. Five of the eight affected eyes had profound visual loss, but three eyes showed normal vision. Two cases developed unilateral nonrhegmatogenous retinal detachment. There were no other ocular or systemic malformations. This family illustrates an instance of autosomal dominantly inherited optic nerve coloboma.

Adult↗

Central retinal vein and branch artery occlusion associated with inherited plasminogen deficiency and high lipoprotein(a) levels: a case report.

We describe a case of central retinal vein and branch artery occlusion associated with inherited type I plasminogen deficiency (68%) and permanent elevation of Lp(a) (460 mg/l, S2 phenotype) in a 45 year old white woman with no associated local or systemic risk factors. Pedigree analysis revealed inheritance of plasminogen deficiency from the deceased father and of high Lp(a) levels from the mother. Both the patient's sons had plasminogen deficiency, but they had normal Lp(a) levels. In a series of 40 consecutive patients with central retinal vein occlusion we previously reported the observation of high Lp(a) levels--consistently associated with the S2 phenotype--in 30% of the patients as compared to a 10% incidence in controls. This case emphasizes the importance of screening patients with occlusion of the retinal vessels and no associated risk factors for coagulation abnormalities predisposing to thrombosis.

Female↗

Indocyanine green video angiographic findings in acute posterior multifocal placoid pigment epitheliopathy.

The placoid lesions of acute posterior multifocal placoid pigment epitheliopathy consist of two distinct areas: a light yellow area surrounding a dark yellow center. On two occasions, the authors compared indocyanine green video angiographic with fluorescein angiographic findings in a typical case of acute posterior multifocal placoid pigment epitheliopathy. In the acute stage, the multiple placoid lesions observed in the early phase of indocyanine green video-angiography showed hypofluorescent lesions corresponding to those seen with fluorescein angiography which blocked choroidal vessels. Some fluorescent intermediate sized choroidal vessels, which traversed the hypofluorescent areas, were dark due to a slight degree of blocked fluorescence. On both indocyanine green video and fluorescein angiography, hypofluorescent lesions were almost the same size as the light yellow area and the dark yellow center of a placoid lesion. A hypofluorescent lesion, seen on fluorescein angiography, obscured a retinal vessel. When the placoid lesions had disappeared, fewer hypofluorescent lesions, corresponding to some of the hypofluorescent lesions originally observed, were seen in the early phase of indocyanine green video angiography. They were also smaller in size. These hypofluorescent lesions decreased in size and some had completely disappeared in the late phase. No hypofluorescent lesions were seen in the early phase of fluorescein angiography. Findings in the acute stage suggest that the hypofluorescence observed in the early phase of indocyanine green video and fluorescein angiography is mainly blockage due to a light yellow area of placoid. When the placoid lesion disappeared, filling delays, which were detectable on only indocyanine green video angiography, persisted in the choriocapillaris.

Acute Disease↗

Cerebral blood velocity and other cardiovascular responses to 2 days of head-down tilt.

Spaceflight induces a cephalad redistribution of fluid volume and blood flow within the human body, and space motion sickness, which is a problem during the first few days of spaceflight, could be related to these changes in fluid status and in blood flow of the cerebrum and vestibular system. To evaluate possible changes in cerebral blood flow during simulated weightlessness, we measured blood velocity in the middle cerebral artery (MCA) along with retinal vascular diameters, intraocular pressure, impedance cardiography, and sphygmomanometry on nine men (26.2 +/- 6.6 yr) morning and evening for 2 days during continuous 10 degrees head-down tilt (HDT). When subjects went from seated to head-down bed rest, their heart rate and retinal diameters decreased, and intraocular pressures increased. After 48 h of HDT, blood flow velocity in the MCA was decreased and thoracic impedance was increased, indicating less fluid in the thorax. Percent changes in blood flow velocities in the MCA after 48 h of HDT were inversely correlated with percent changes in retinal vascular diameters. Blood flow velocities in the MCA were inversely correlated (intersubject) with arterial pressures and retinal vascular diameters. Heart rate, stroke volume, cardiac output, systolic arterial pressure, and at times pulse pressure and blood flow velocities in the MCA were greater in the evening. Total peripheral resistance was higher in the morning. Although cerebral blood velocity is reduced after subjects are head down for 2 days, the inverse relationship with retinal vessel diameters, which have control analogous to that of cerebral vessels, indicates cerebral blood flow is not reduced.

Adult↗

Perifoveal microcirculation in eyes with epiretinal membranes.

BACKGROUND/AIMS: Eyes with epiretinal membranes (ERMs) often have alterations of retinal vessels. The authors studied perifoveal microcirculation in eyes with epiretinal membranes (ERMs) using scanning laser ophthalmoscope (SLO) fluorescein angiography. METHODS: Mean capillary blood flow velocity (CFV) was measured as an index of perifoveal microcirculation by SLO fluorescein angiography in 26 eyes with ERMs (19 eyes with idiopathic epiretinal membranes, seven eyes with epiretinal membranes after retinal detachment surgery) before and 6 months after vitreous surgery, and in 23 healthy control subjects. RESULTS: The mean CFV was significantly reduced in eyes with ERMs compared with healthy controls (p=0.012), and the postoperative mean CFV was significantly increased compared with the preoperative mean CFV (p=0.041). CONCLUSION: Significant changes of capillary blood flow velocity in the perifoveal areas were observed between normal subjects and eyes with epiretinal membranes. This indicates that eyes with ERMs show abnormal haemodynamics in the perifoveal capillaries.

Adult↗

Elevated plasma fibrinogen levels in patients with essential hypertension are related to vascular complications.

AIM: We investigated whether or not fibrinogen is related to the cardiovascular risk profile and complications in hypertensive subjects. METHODS: Plasma fibrinogen and laboratory tests including factor VII, homocysteine and microalbuminuria were evaluated in 127 consecutive hypertensive subjects stratified according to cardiovascular risk. Parameters were age, gender, smoking, cholesterol, diabetes, target organ damage: left ventricular hypertrophy (LVH), carotid atherosclerotic complications and retinical vessels. RESULTS: Fibrinogen levels were significantly different between patients according to risk levels (low 290+/-73, n=20, high 342+/-94 mg/dl, n=39, very high risk 350+/-72, n=29, p=0.01), hypertension grade (II-III) and organ damage. Fibrinogen was significantly higher in patients with more severe carotid atherosclerotic lesions and vascular retinal lesions (grades II-III vs 0 and I). Also in patients, matched for age and sex, without and with carotid atherosclerotic lesions, fibrinogen was significantly higher in the latter group. No significant differences were found on the basis of IVS, creatinine and microalbuminuria. In hypertensive patients, fibrinogen directly correlated with age, by multiple linear regression. In hypertensive patients with diabetes, fibrinogen was significantly higher (466+/-176 mg/dL, n=14) than in those hypertensive without diabetes (333+/-87 mg/dL, n=113, p=0.001) and in all patients there was a a significant correlation (r=0.474, p<0.001) between blood glucose and fibrinogen. CONCLUSION: Hyperfibrinogenemia is a marker of vascular damage and could be an important factor contributing to the evolution of the complications.

Blood Coagulation Disorders↗

[Ocular function in beta-thalassemia patients].

The eyes were examined in 118 inpatients with various thalassemia forms. The examinations included viso- and perimetry, biomicro- and ophthalmoscopy, fluorescent angiography of the fundus oculi and retinophotography. Patients with thalassemia were found to develop a variety of changes in the eye, whose manifestations depended on the length and severity of the underlying disease and on the treatment administered. Changes in the conjunctival and retinal vessels develop as early as in the initial stages of thalassemia, presenting as twisting, dilatation, and irregular calibre of the veins, dilatation of the arteries and reduction of their light reflex. Later dystrophic and atrophic changes develop: obliteration of the iris pattern and thinning of its peripheral zone, deterioration of blood circulation in the central retinal zone. Multiple blood transfusions and hemosiderosis lead to the development of hyperpigmentation of the limb, sclera, fundus oculi and appearance of retinal angioid strips. These findings should be taken into consideration when assessing the ocular status of thalassemia patients and defining the indications for treatment for angiopathic and dystrophic processes in the eye.

Adolescent↗

The eye in accelerated hypertension. I. Elschnig's spots in nonhuman primates.

The acute form of Elschnig's spots was produced in a rhesus monkey with experimentally induced accelerated hypertension. Clinically, Elschnig's spots appeared within 24 hours of hypertension as discrete, whitish, subretinal lesions located in the temporal posterior poles of both fundi. The lesions leaked fluorescein. Morphologically, they consisted of complete obstruction of terminal choroidal arterioles and choriocapillaris by fibrin thrombi, necrosis of the retinal pigment epithelium, and fibrinous exudation into Bruch's membrane and into the subpigment epithelial and subretinal spaces. Most of the neurosensory retina was spared from morphologic damage. The differential susceptibility between choroidal and retinal vessels is explained by differences in anatomy and in autonomic nervous control.

Animals↗

Evidence of chronic inflammation in retina excised after relaxing retinotomy for anterior proliferative vitreoretinopathy.

BACKGROUND: Epiretinal membranes from eyes with proliferative vitreoretinopathy (PVR) frequently express molecules associated with chronic inflammation. To investigate the extent to which inflammation may compromise the detached retina, we determined the expression of inflammatory molecules in anterior retina removed after relaxing retinotomy for retinal detachment complicated by anterior PVR. METHODS: Surgical retinal specimens were studied immunohistochemically for the distribution of the vascular cell adhesion molecules VCAM, E-selectin, P-selectin, ICAM and PECAM and for the presence of the cytokine TNF alpha and of T lymphocytes (CD3-positive cells), macrophages (CD68-positive cells) and HLA-DR molecules. The findings were compared with those in control cadaveric retina. RESULTS: Aberrant expression of ICAM-1 was observed in four of nine retinal specimens from eyes with PVR, whereas its expression in control retinas was confined to the external limiting membrane and ganglion cell layers. PECAM was observed in seven of nine surgical retinal specimens and in four of five controls. E-selectin and P-selectin were expressed within the luminal aspects of four of nine retinal specimens from eyes with PVR, and VCAM was present in three of nine surgical specimens investigated. All cadaveric control retinas were negative for E-selectin and VCAM, whilst one was positive for P-selectin. Staining for TNF alpha was observed within luminal aspects and walls of retinal vessels from eight of nine surgical specimens, but was not seen in any of the cadaveric controls. T lymphocytes and cells expressing the macrophage marker CD68 were identified in two and seven of nine diseased retinas respectively, but not in any of the controls. Cells staining for HLA-DR were observed in eight of nine surgical retinal specimens and in three of five controls. CONCLUSION: The present findings indicate that retina from eyes with advanced PVR may itself be subject to inflammatory changes, and indicate that the PVR process is not limited to retinal membranes, but involves a more widespread distribution of inflammation than is generally appreciated.

Chronic Disease↗

Fluorescein angiography in hypertensive pregnancies.

A retrospective study in two university hospitals investigating retinal changes in pregnancies complicated by hypertension, seldom revealed retinal vascular changes in pre-eclamptic toxemia. Fluorescein angiography was performed on 16 severe pre-eclamptic toxemias and 14 chronic hypertension pregnancies. Normal caliber retinal vessels and normal filling time, with no subretinal or subepithelium leakage, was found in all pre-eclamptic toxemic patients. Four out of the 14 chronic hypertensive patients showed signs of mild hypertensive retinopathy. A review of the literature on fluorescein angiography in pregnancy showed that vascular changes in pre-eclamptic toxemia are choroidal rather than retinal.

Adult↗

Sickle cell retinopathy in Jamaican children: a search for prognostic factors.

Children with homozygous sickle cell (SS) disease and with sickle cell-haemoglobin C (SC) disease, aged 6 1/2 to 8 1/2 years, were examined by fluorescein angiography/angioscopy to determine the presence of retinal nonperfusion. The haematological and clinical features of children with and without nonperfusion were compared. Retinal vessel closure was significantly correlated with low total haemoglobin, and high fetal haemoglobin, reticulocyte, and irreversibly sickled cell counts in SS disease, and with high reticulocyte count in SC disease. No relationships were apparent between vessel closure and other haematological indices or clinical events in either genotype.

Anemia, Sickle Cell↗

Excitation and emission spectra of fluorescein dye in the human ocular fundus.

The excitation and emission spectra of fluorescein dye were determined during angiography from different sites in the human ocular fundus. All spectra were markedly shifted toward longer wavelengths relative to the spectra of fluorescein in aqueous solution. This effect is most pronounced for the macular area; however, it decreases for the choroidal background and even more for the retinal vessels. The results are relevant to the selection of optical filter combinations for fluorescein angiography.

Adolescent↗

Retinal vasculitis.

Retinal vasculitis is a sight-threatening intraocular inflammation affecting the retinal vessels. It may occur as an isolated ocular condition, as a manifestation of infectious or neoplastic disorders, or in association with a systemic inflammatory disease. The search for an underlying etiology should be approached in a multidisciplinary fashion based on a thorough history, review of systems, physical examination, and laboratory evaluation. Discrimination between infectious and noninfectious etiologies of retinal vasculitis is important because their treatment is different. This review is based on recently published articles on retinal vasculitis and deals with its clinical diagnosis, its link with systemic diseases, and its laboratory investigation.

Diagnosis, Differential↗

The effect of hypoxia on the central light reflex of retinal arteries and veins.

Computerized scanning microdensitometry was used on fundus photographs of 40 men (aged 18-23 years) and effects of hypoxia on intensity profiles of the 'light reflex' in 140 arteries and 138 veins were analysed. Changes from sea level to four levels of acute hypoxia of simulated altitude were studied: 8000 feet (ft) (2438 meters) (m), 10,000 ft (3048 m), 12,500 ft (3810 m), and 15,000 ft (4572 m) using a low-pressure chamber. The intensity of the reflex increased at 12,500 ft and 15,000 ft by 24% (P less than 0.05) and 39% (P less than 0.01) in arteries and 50% and 33% in veins (P less than 0.05), respectively. As an overall response from sea level to all four altitudes, the width of the reflex was reduced. The reduction in width was negatively correlated to the diameter of the arteries (P less than 0.0001) and veins (P less than 0.001) at sea level, and the variability of changes was larger in veins (P less than 0.01). Funduscopic light reflected from intravascular blood columns of retinal vessels is thus influenced by hypoxic stress, and 12,500 ft of simulated altitude represents a threshold value of circulatory interest.

Adolescent↗