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A new model of transient complete obstruction of retinal vessels induced by endothelin-1 injection into the posterior vitreous body in rabbits.

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide produced by vascular endothelial cells. In order to investigate the effects of ET-1 on retinal vessels, ET-1 (1-1000 pmol) was injected into the posterior vitreous body in rabbits. A high dose of ET-1 induced transient complete obstruction of the retinal vessels. In this experimental model of transient complete obstruction of the retinal vessels, the effects of ET-1 on retinal function were further analyzed by means of electroretinograms. The scotopic a-wave was not affected, but the amplitude of the scotopic b-wave was significantly elevated. The amplitude of oscillatory potentials was significantly reduced. These phenomena suggested that retinal ischemia without choroidal ischemia was brought about due to severe vasoconstriction of the retinal arteries. These findings indicate that intravitreal injection of ET-1 causes a transient cessation of blood supply from retinal vessels and that oscillatory potentials in electroretinograms appear to be sensitive for detecting changes of retinal circulation. This new model of transient complete obstruction of retinal vessels might be useful for studying the pathophysiology of severe retinal ischemia.

Animals↗

Morphometry of the optic nerve and retinal vessels in children by computer-assisted image analysis of fundus photographs.

BACKGROUND: The retinal fundus in childhood has a different morphology than in adulthood. Existing methods are not suitable for evaluation of fundus photographs from children. Therefore, a new method for quantitative analysis of fundus morphology utilizing a personal computer-assisted digital mapping system was developed. METHODS: A CCD flatbed scanner is used to digitize fundus photographs, producing computer images which are analyzed on an IBM/AT computer. Area measurements of the optic disc, excavation and peripapillary crescent are made, as well as determinations of the length, branching, tortuosity and distribution of the retinal vessels on the fundus surface. RESULTS: Determination of the inter- and intra-observer variability of the computer-assisted image analysis technique demonstrated good reproducibility. The method is demonstrated using fundus photographs of six normal children and six children with the fetal alcohol syndrome. Typical variations in appearance of optic disc and retinal vessels are seen. CONCLUSION: The system is unique in measuring both the optic nerve head and the retinal vessels and is therefore especially useful for detailed studies of normal and abnormal development of these structures in children.

Adolescent↗

Ultrastructure of retinal vessels in diabetic patients.

The ultrastructure of retinal vessels was examined in three eyes from diabetic patients and two eyes from control subjects. In some of the retinal blood vessels of each of the diabetic eyes, the endothelial cytoplasm was thin and had fenestrae. These fenestrations which were seen in both capillaries and venules, were closed by a thin diaphragm. Transendothelial channels were also observed in the endothelial cytoplasm. The tight junctions between endothelial cells were rarely altered. The junctions were open with short adherent regions in which the junctional membranes showed increased electron density. These morphological changes may account for the characteristic breakdown of the blood-retinal barrier in diabetic patients.

Adult↗

Retinal vessel diameters and the incidence of gross proteinuria and renal insufficiency in people with type 1 diabetes.

Early retinal vessel caliber changes may predict risk of diabetic nephropathy. We examined the association of retinal vessel diameters and the incidence of gross proteinuria and renal insufficiency in a population-based cohort of people with type 1 diabetes (n = 557). Baseline retinal photographs were digitized, and diameters of individual retinal vessels were measured and summarized. Incident cases of gross proteinuria and renal insufficiency were identified over a 16-year period. Larger retinal venular diameter was associated with higher cumulative incidence of gross proteinuria (18.6, 25.4, 37.7, and 50.4%, comparing increasing venular diameter quartiles) and renal insufficiency (10.7, 15.5, 23.2, and 32.8%). After adjusting for age, sex, duration of diabetes, HbA(1c) levels, baseline retinopathy levels, and other factors, larger retinal venular diameter was associated with an increased risk of gross proteinuria (RR 1.53, 95% CI 1.19-1.97, comparing 4th vs. 1st to 3rd quartiles of venular diameter) and renal insufficiency (1.51, 1.05-2.17). Retinal arteriolar diameter was not associated with either gross proteinuria or renal insufficiency. We conclude that in individuals with type 1 diabetes, larger retinal venular diameter is independently associated with the long-term incidence of gross proteinuria and renal insufficiency and may provide additional predictive information regarding risk of nephropathy.

Adult↗

Functional analysis of retinal vessel diameter reaction to artificially raised intraocular pressure in glaucoma patients with and without dorzolamide therapy.

BACKGROUND: Examination of the influence of dorzolamide on the autoregulation of retinal vessel diameter in glaucoma patients. PATIENTS AND METHODS: Eleven patients with primary open angle glaucoma (age 60 +/- 11) without medication and four weeks after starting therapy with dorzolamid eye drops three times daily were examined in the study. Short-time rise of intraocular pressure (IOP) was obtained via suction-cup. Functional reaction of the diameter of a segment of a retinal artery and corresponding vein were assessed by retinal vessel analyzer. RESULTS: Dorzolamid lowered the IOP from 23.3 +/- 1.3 to 17.6 +/- 2.2 mmHg (p = 0.004). Therapy did not influence the absolute diameter of retinal vessels regarding maximal dilatation caused by the pressure rising provocation. In eyes with treatment the diameter decreased faster to baseline values (arteries 100 sec, veins 220 sec) compared to those without treatment (arteries 350 sec, veins 480 sec). CONCLUSION: Dorzolamid might possibly be able to accelerate autoregulation of retinal vessels in response to short term artificial IOP increase.

Adult↗

Retinal vessel reaction to short-term IOP elevation in ocular hypertensive and glaucoma patients.

PURPOSE: Regulation of ocular blood flow might be impaired in glaucoma patients. We compared the reaction of retinal vessels to a short-term increase of intraocular pressure (IOP), using a retinal vessel analyzer (RVA), in normal volunteers, ocular hypertensive patients (OH) and primary open angle glaucoma patients (POAG). METHODS: Ten healthy subjects (56+/-8 years, IOP 13.7+/-1.6 mmHg), 10 OH patients (55+/-12 years, IOD 23.4+/-4.1 mmHg) and 11 POAG patients (60+/-11 years, IOP 23.3+/-1.95 mmHg) were evaluated. Arterial and venous retinal vessel diameter was measured continuously before, during and after raising IOP to suprasystolic values by the suction cup method, described as ocular oscillo-dynamography. RESULTS: The change in vessel diameter after the IOP rise differed in its temporal sequence and in absolute values depending on the group examined. In the retinal branch veins the reduction of vessel diameter during the IOP rise was significantly different in POAG (0%+/-6.7) and volunteers (-6.7%+/-8.5; p = 0.06) and in POAG and OH (-6.7%+/-7.0; p = 0.04). At 70-130 sec after IOP increase a dilatation occurred, again differing significantly in POAG (+5.8%+/-3.9) and volunteers (+9.7%+/-4.3; p = 0.03). Systemic blood pressure did not show any significant differences between groups or during the course of the examination. DISCUSSION: At short-term rise in IOP leads to less retinal vessel reaction in POAG patients than in volunteers and OH. This might be due to impaired autoregulation to ocular perfusion changes in POAG patients.

Blood Flow Velocity↗

Association of retinal vessel caliber to optic disc and cup diameters.

PURPOSE: To investigate whether optic disc size is related to retinal venule and arteriole diameters. METHODS: The population of Beaver Dam, Wisconsin, aged 43 to 86 years were invited to participate in a baseline examination from 1988 to 1990. During this examination, photographs, centered on the optic discs, were taken after pupil dilation. Optic discs and cups were measured from stereoscopic photographs, whereas retinal vessel measurements were taken from a single digitized photograph. Central retinal vein and central retinal arterial equivalents were subsequently calculated. Data for 3887 right eyes are included in the analyses. RESULTS: Narrower retinal venules and arterioles were found in the smaller optic discs controlling for optic cup diameter as well as age, systolic and diastolic blood pressure, refraction, and sex. Central retinal artery equivalents ranged from 156.04 +/- 16.82 microm in the smallest optic disc category to 165.93 +/- 15.17 microm in the larger disc category (P < 0.001). Central retinal vein equivalents ranged from 228.93 +/- 21.26 microm in the smallest to 243.18 +/- 22.32 microm in the larger disc categories (P < 0.001). The significant reduction in retinal vessel diameters was only apparent for the smallest optic disc sizes. A reduction in retinal vessel diameters was less consistent and not significant for small optic cup sizes. CONCLUSIONS: Smallest optic discs were associated with smaller central retinal artery and central retinal vein diameters. This anatomic relationship may be useful as an additional associated indicator for nonarteritic anterior ischemic optic neuropathy as well as for retinal vascular events.

Adult↗

Reduced response of retinal vessel diameters to flicker stimulation in patients with diabetes.

BACKGROUND/AIM: Stimulation of the retina with flickering light increases retinal arterial and venous diameters in animals and humans, indicating a tight coupling between neural activity and blood flow. The aim of the present study was to investigate whether this response is altered in patients with insulin dependent diabetes mellitus. METHODS: 26 patients with diabetes mellitus with no or mild non-proliferative retinopathy and 26 age and sex matched healthy volunteers were included in the study. Retinal vessel diameters were measured continuously with the Zeiss retinal vessel analyser. During these measurements three episodes of square wave flicker stimulation periods (16, 32, and 64 seconds; 8 Hz) were applied through the illumination pathway of the vessel analyser. RESULTS: In retinal arteries, the response to stimulation with diffuse luminance flicker was significantly diminished in diabetic patients compared to healthy volunteers (ANOVA, p<0.0031). In non-diabetic controls flicker stimulation increased retinal arterial diameters by +1.6% (1.8%) (mean, p<0.001 v baseline), +2.8% (SD 2.2%) (p<0.001) and +2.8% (1.6%) (p<0.001) during 16, 32, and 64 seconds of flicker stimulation, respectively. In diabetic patients flicker had no effect on arterial vessel diameters: +0.1% (3.1%) (16 seconds, p = 0.9), +1.1% (2.7%) (32 seconds, p = 0.07), +1.0% (2.8%) (64 seconds, p = 0.1). In retinal veins, the response to flicker light was not significantly different in both groups. Retinal venous vessel diameters increased by +0.7% (1.6%) (16 seconds, p<0.05), +1.9% (2.3%) (32 seconds, p<0.001) and 1.7% (1.8%) (64 seconds, p<0.001) in controls during flicker stimulation. Again, no increase was observed in the patients group: +0.6% (2.4%), +0.5% (1.5%), and +1.2% (3.1%) (16, 32, and 64 seconds, respectively). CONCLUSION: Flicker responses of retinal arteries and veins are abnormally reduced in patients with IDDM with no or mild non-proliferative retinopathy. Whether this diminished response can be attributed to altered retinal vascular reactivity or to decreased neural activity has yet to be clarified.

Analysis of Variance↗

ETa-receptor blockade, but not ACE inhibition, blunts retinal vessel response during isometric exercise.

Angiotensin II and endothelin-1 are potent vasoconstrictors that appear to play a role in retinal blood flow regulation. In the present study, we investigated the possible role of the angiotensin and the endothelin system in the regulation of retinal vessel diameters during isometric exercise in healthy humans. The study design was randomized, double-masked, placebo-controlled, and three-way cross over. Twelve healthy subjects performed squatting exercises for 6 min during infusion of either an angiotensin-converting enzyme inhibitor (enalapril), an ET(A)-receptor antagonist (BQ-123), or placebo. Retinal vessel diameters were measured continuously with the Zeiss retinal vessel analyzer. Systemic hemodynamics were assessed noninvasively, and intraocular pressure was measured with applanation tonometry. Squatting induced a significant increase in blood pressure and pulse rate, which was paralleled by a vasoconstriction in retinal arteries and veins. Intraocular pressure was only slightly increased during the squatting periods. BQ-123 significantly blunted the exercise-induced decrease in venous (P < 0.01) and arterial (P < 0.02, ANOVA) vessel diameters but had no effect on basal retinal diameters. By contrast, enalapril did neither influence vessel diameter at baseline conditions nor in response to isometric exercise. The data of the present study indicate that retinal vasoconstriction during isometric exercise is modified by ET(A)-receptor blockade, whereas it is not altered by angiotensin-converting enzyme inhibition. Hence, the present data indicate that endothelin-1, but not angiotensin II, is involved in retinal blood flow regulation during isometric exercise.

Adult↗

Reliability of computer-assisted retinal vessel measurementin a population.

The purpose of the study was to assess the intergrader and intragrader reliability of computer-assisted retinal vessel dia-meter measurement in a defined, community-based population. Retinal photographs from participants in the Blue Mountains Eye Study were digitized using standard techniques. A grader identified all retinal vessels located 0.5-1.0 disc diameter from the optic disc margin,and a computer program measured the width of these vessels. Intergrader and intragrader reliability was assessed on a random sub-sample of 184 and 97 images, respectively, using quadratic weighted kappa(kappa) and correlation analysis (R2). Intergrader reliability was high for summary indices of retinal arteriolar (kappa = 0.85, R2 = 0.88)and venular (kappa = 0.90, R2 = 0.90)diameters, and their ratio, the arteriole-to-venule ratio (kappa = 0.75, R2 = 0.79).Intragrader reliability was also high, with kappa values ranging from 0.80 to 0.93 and from 0.80 to 0.92 for graders 1 and 2, respectively. It is concluded that the retinal vessel diameters could be reliably measured using computer-assisted software and may be used for population-based research.

Aged↗

The temporal retinal vessel angle and infants born preterm.

AIM: To determine the temporal retinal vessel angle in babies and its relation to preterm birth. METHODS: Digital images were obtained during routine screening for retinopathy of prematurity (ROP). The temporal retinal vessel angle was measured in 164 eyes of 82 babies born "very preterm" (24-27 weeks gestational age (GA)), "preterm" (28-31 weeks GA), and "near term" (>/=32 weeks GA). RESULTS: Mean temporal vessel angle (TVA) for all three GA groups together is 80.0 degrees (SD 17.0 degrees ) for the right eye and 80.5 degrees (16.7 degrees ) for the left eye. The range is right eye 59-106 degrees , left eye 69-97 degrees , with 95% data above 67 degrees for the right and 63 degrees for the left eye. For babies born near term, TVA is 82 degrees in each eye. There is a high degree of interocular symmetry between right and left eyes and a statistically insignificant trend for increasing TVA with increasing GA. The presence and stage of ROP affected one parameter of the left eye alone. CONCLUSIONS: These data provide normative data on the TVA in babies and will facilitate, especially if there is interocular asymmetry, determining whether there is macular displacement.

Fovea Centralis↗

Cryocoagulation of retinal vessels: an experimental model of intravascular coagulation.

Various amounts of cryothermy were applied to the posterior pole of rabbit eyes to determine changes in retinal tissue and vasculature. Four consecutive freezing and refreezing applications of -60 degrees was the most effective technique for achieving central retinal vessel occlusion. Electron microscopic observations of sequentially sectioned occlusion. Electron microscopic observations of sequentially sectioned occluded vessels showed that the vessels were occluded by a platelet plug distally and packed erythrocytes proximally. Fibrin formation was not found in the occluded retinal vessels but was seen within platelet plugs in choroidal vessels. Because cryocoagulation simulates the normal physiologic means of coagulation more closely than other vessel occluding techniques, cryocoagulation of the primary retinal vessels is suggested as an experimental model for intravascular coagulation.

Animals↗

The active transport of fluorescein by the retinal vessels and the retina.

1. The movement of fluorescein across the retinal surface of the rabbit's eye was estimated by measuring the concentration gradient of the dye in the vitreous body. These measurements were made in vivo by means of a slit-lamp fluorophotometer, or were taken from frozen sections of enucleated eyes.2. In the normal eye, fluorescein does not pass from the blood to the vitreous body across any part of the retina. When injected into the vitreous body it passes rapidly out across the entire retinal surface, even against a very large concentration gradient.3. A variety of metabolic and competitive inhibitors, effective in blocking organic anion transport in the kidney and liver, tend to abolish this unidirectional movement of fluorescein across the retina.4. The region occupied by the retinal vessels is more sensitive to inhibition than other areas of the retina. Occlusion of the vessels by diathermy prevents the exchange of fluorescein in this region.5. It appears, then, that there is an active transport of organic anions out of the vitreous body, both by the retinal capillaries and by the retina itself. The latter system is probably located in the pigment epithelium and seems to be carried forward to the rear surface of the iris.6. Since the walls of the retinal vessels of the rabbit are freely in contact with the vitreous body, the active transport must take place across the capillary endothelial cells themselves. These vessels have structural and permeability characteristics found only in the central nervous system and it is to be presumed that the anion transport system is shared by the capillaries of the brain.7. The function of the transport in the retina may be to protect the nervous tissue from toxic materials by preventing their entry from the blood or by removing products of metabolism conjugated as organic anions. Alternatively, the mechanism may be concerned in maintaining the normal adhesion of the retina to the choroid, since retinal detachment was observed to follow its total inhibition.

Animals↗

Retinal vessel diameters and incident open-angle glaucoma and optic disc changes: the Rotterdam study.

PURPOSE: It remains unclear whether reduced retinal blood flow and smaller arterioles, reported to exist in patients with open-angle glaucoma (OAG), are a cause or a consequence of ganglion cell loss. We examined whether baseline retinal vessel diameters were related to incident (i)OAG or incident optic disc changes in a population-based sample. METHODS: In the prospective population-based Rotterdam Study, baseline diameters of retinal arterioles and venules (1990-1993) were measured in digitized images of 3469 persons (aged 55 years and older) at risk for OAG. The follow-up examinations took place from 1997 to 1999. iOAG was based on the presence of incident glaucomatous visual field loss and/or incident glaucomatous optic neuropathy. Changes in neuroretinal rim, cup area, or vertical cup-to-disc ratio were calculated with a semiautomated image analyzer in 2782 persons. RESULTS: After a mean follow-up time of 6.5 years, 74 participants had iOAG. At baseline, the mean arteriolar diameter was 147.5 +/- 14.2 microm (SD) and the venular, 222.9 +/- 20.0 microm. Neither arteriolar diameters (odds ratio [OR] per SD decrease: 0.82; 95% confidence interval [CI]: 0.66-1.03) nor venular ones (OR per SD increase: 1.20; 95% CI: 0.95-1.53) were significantly related to iOAG. Baseline retinal vessel diameters did not predict changes in the optic disc. Additional adjustment for cardiovascular risk factors did not alter these results. CONCLUSIONS: The data show that baseline retinal vessel diameters did not influence the risk of iOAG or incident optic disc changes. These data provide no evidence for a retinal vascular role in the pathogenesis of OAG.

Aged↗

[Oxygen saturation of retinal vessels. Studies for measuring with polarized light].

UNLABELLED: The accuracy of the spectrometric measurement of the oxygen saturation in retinal vessels is limited by its signal-to-noise ratio. The aim of this study was to investigate the possibility of enhancement of the reflection signal by the use of polarized light. MATERIALS AND METHODS: The Jena ophthalmospectrometer was equipped with two polarizing filters: one in the illumination and the other in front of the detector. Reflection spectra of erythrocytes streaming through a cuvette in the focus of an artificial eye were recorded. The influence of the polarization on the reflection spectra was investigated by rotating the polarizer in front of the detector. Furthermore, the degree of polarization of the light reflected from retinal vessels in vivo was determined. RESULTS: The degree of polarization of the light reflected from the erythrocytes was 0.6-0.8, whereas the polarization of light reflected by a standard white reflectance target was virtually zero. CONCLUSION: Polarized light can be used for the reduction of error in retinal vessel oximetry.

Blood Flow Velocity↗

Retinal vessel responses to passive tilting.

Alterations in retinal vessel calibre on changing posture may indicate an autoregulatory response to changing perfusion pressure. The effect of passive tilting on retinal response in healthy individuals was investigated. Subjects were supported on a specially constructed tilting table. The control measurements were taken with the body in a 30 degrees head up position. Red-free fundus photographs were taken before, during and after a three minute period of 30 degrees head down tilting. Ten subjects were assessed (mean age 29 years: range 18-38). A total of 92 arteriolar and 86 venular sites were measured. On tilting to the head down position arterioles showed an early and significant decrease in calibre: mean -3.1% (p less than 0.001). Venules showed an increase of 3.7% (p less than 0.001). The response was not sustained throughout the period of tilting despite a maintained increase in ocular perfusion pressure, which was estimated in six of the subjects.

Adolescent↗

Doppler ultrasonography of the ophthalmic and central retinal vessels.

B-Scan-guided, pulsed Doppler ultrasonography of central retinal vessels and ophthalmic arteries of 72 normal subjects gave the following average peak flow velocities: central retinal artery, 9.5 +/- 3.1 cm/s; central retinal vein, 5.7 +/- 1.5 cm/s; and ophthalmic artery, 31.6 +/- 9.0 cm/s. Doppler shifts in the central retinal vessels were absent at intraocular pressures above 80 mm Hg. Ophthalmic artery systolic, middiastolic, and end-diastolic velocities significantly declined as a function of age. The technique is independent of the status of the ocular media, is noninvasive, requires little time, and causes minimal discomfort.

Adult↗

Shear rate and hematocrit dependence of fluorescence from retinal vessels in fluorescein angiography.

The purpose of this work was to obtain more quantitative knowledge about the yield of fluorescence from retinal vessels during fluorescein angiography. The influence of shear rate, concentration of sodium fluorescein, hematocrit, and layer thickness on the yield of fluorescence from blood were investigated. Measurements were performed in vitro on samples of human blood in a cone-plate shear chamber using frontal illumination. Application of physiologically relevant levels of shear (> 88/sec) decreased the yield of fluorescence from the blood sample considerably as compared with stasis. The yield of fluorescence was proportionally related to the logarithm of the sodium fluorescein concentration in blood up to a sodium fluorescein concentration of 1.2 mg/ml. Above that concentration quenching occurred. An increase in layer thickness at a hematocrit of 45% resulted only in an increase of the yield of fluorescence up to a layer thickness of 25 microns. In conclusion, the sodium fluorescein concentration in blood is the only important factor that determines the yield of fluorescence from the larger retinal vessels in the successive phases of the fluorescein angiogram in a subject with a given hematocrit and hemoglobin concentration. The yield of fluorescence from retinal vessels (> 25 microns) is proportionally related to the logarithm of the sodium fluorescein concentration over a broad range of concentrations.

Biophysical Phenomena↗