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Quantitative analysis of retinal vessel changes in galactose-fed dogs.

Retinal vessel changes in 36-month 30% galactose-fed beagles treated with or without aldose reductase inhibitors were quantified using an Olympus Cue-3 color image analysis system. Individual maps of the intact retinal vasculature, isolated by trypsin-digestion, were divided into 24 distinct subregions and measurements of either the endothelial cell to pericyte (E/P) ratio or cell densities, expressed as pericytes per mm capillary length or endothelial cells per mm capillary length, were conducted in 0.1 mm2 areas surrounding the midpoints of 12 subregions associated with the highest incidence of microaneurysms. Significantly increased E/P ratios and decreased pericyte densities were observed with the duration of galactose-feeding. These retinal changes were reduced by aldose reductase inhibitor treatment. Correlations between the E/P ratio and either number of microaneurysms or cataract severity were also observed. These data support the dose-dependent effects of aldose reductase inhibitors in preventing pericyte degeneration and subsequent formation of microaneurysms (Archives Ophthalmol. 108:1301, 1990).

Aldehyde Reductase↗

[Correlation between the severity of atherosclerosis of cerebral, coronary and retinal vessels].

As a result of clinico-physiological examinations 643 patients suffering from cerebral atherosclerosis were divided into 3 groups by the severity of atherosclerosis of the cerebral vessels. These patients also exhibited atherosclerosis of the coronary and retinal vessels. Mathematical methods have been used to study the relationship and severity of atherosclerosis of the cerebral, coronary and retinal vessels. The findings obtained indicate that despite a systemic nature of the atherosclerotic process the involvement of various vascular areas is individual and asynchronous. With the development of cerebral atherosclerosis its correlation with atherosclerosis of other localizations becomes closer.

Adult↗

Does glaucoma medication influence the diameter of the retinal arteriole in the human eye? (A pilot study using the retinal vessel analyser).

PURPOSE: To investigate the potential in vivo influence of different topical glaucoma medications on the diameter of the retinal arterioles of healthy volunteers and glaucoma patients. METHODS: The diameter of one pre-selected retinal arteriole per eye was measured using the Retinal Vessel Analyser (RVA), an instrument developed for non-invasive clinical measurement of the diameter of the main retinal vessels. The instrument contains a video system, and the integrated software recognises the boundaries of the retinal vessels by detecting their light-transmission profile. The vessel diameter (in arbitrary units) is plotted against time (seconds) on a separate display screen. In Study I the vessel diameter was measured in 12 eyes of six healthy volunteers (age 21-26 years, mean age 24.0 years) on six occasions each separated by 14 days. In a double-masked fashion, each subject's right eye was treated with one of 5 glaucoma medications (brinzolamide 1%, timolol 0.5%, betaxolol 0.5%, brimonidine 0.2% or latanoprost 0.005%) and the left eye always received balanced salt solution. In Study II, one randomly selected eye of 16 patients (age 50-79 years, mean age 65.2 years) suffering from primary open-angle glaucoma controlled with topical monotherapy was investigated, in an unmasked fashion. Four patients were on betaxolol 0.5% treatment, six subjects were receiving non-selective topical beta receptor blockers and six subjects were being treated with once daily latanoprost 0.005%. RESULTS: The coefficient of variation for the arteriole diameter in the healthy volunteers was less than 12% in each case. No significant post-treatment change of the diameter of the pre-selected arteriole was found for any topical medication investigated, either in the healthy volunteers (Study I) or in the patients suffering from glaucoma (Study II) (p>0.05, paired t-test). In addition, in Study I no difference was observed in the alteration of the arteriole diameter between the baseline and the hour 2 measurements when the values from the drug-treated and placebo treated eyes were compared (p>0.05, two-way ANOVA). CONCLUSION: In the present investigations it was not possible to detect any statistically meaningful change of the arteriole diameter at two hours after the instillation of any of several topical antiglaucoma drugs widely used in clinical practice. Further investigations are necessary to clarify whether the lack of observed change is due to the lack of retinal vascular effects of the drugs investigated, or is due to an inability of the RVA instrument in practice to detect alterations between time-points separated by several hours.

Adrenergic alpha-Antagonists↗

Optic disc size and retinal vessel characteristics in healthy children.

PURPOSE: To characterize the optic disc and retinal vessels in healthy children and adolescents. METHODS: Fundus photographs were evaluated by digital image analysis in one hundred healthy Swedish children and adolescents (3-19 years). RESULTS: Median optic disc area was 2.67 mm2 (range, 1.93 to 4.39), median cup area was 0.41 mm2 (range, 0 to 1.45) and median neuroretinal rim area was 2.24 mm2 (range, 1.60 to 3.05). The size of the cup and neuroretinal rim increased with increasing size of the optic disc. There were no correlations between the measured variables and age, sex or refraction. CONCLUSION: The measurements of optic disc size in healthy children, between 3 and 19 years of age, are in accordance with optic disc values found in most studies on adults. The resulting reference intervals may be helpful in clinical pediatric ophthalmology, to facilitate identification of children with abnormal optic disc and retinal vessel morphology.

Adolescent↗

Retinal vessel diameters and the risk of incident age-related macular disease: the Rotterdam Study.

PURPOSE: To study the relationship between retinal vessel diameters and incident age-related macular disease (iAMD). DESIGN: Prospective population-based cohort study. PARTICIPANTS: Persons (55 years and older) from the Rotterdam Study, who participated at the baseline (1990-1993) and 1 of 2 follow-up examinations (1993-1994 and 1997-1999). METHODS: In the current analysis, 4345 participants who were free of AMD at baseline and had gradable macular transparencies at both baseline and follow-up examination were included. Also, arteriolar and venular diameters were measured on digitized baseline images. Stereoscopic transparencies of the macular region were graded according to the International Classification and Grading System for AMD. Incidence of AMD was defined as the development of soft distinct drusen with pigmentary changes or indistinct or reticular drusen with or without pigmentary changes (early iAMD) or atrophic or neovascular AMD (late iAMD). Logistic regression models were used to assess these associations, adjusting for age, gender, and follow-up time and, additionally, for smoking, body mass index, intima-media thickness, systolic blood pressure, and total and high-density lipoprotein cholesterol levels. MAIN OUTCOME MEASURE: Incidence of AMD. RESULTS: After a mean follow-up time of 5.2 years, a total of 374 persons developed early and late iAMD. Neither arteriolar nor venular diameters were related to the risk of iAMD. The odds ratio (OR) per standard deviation (SD) decrease in arteriolar diameter was 1.03 (95% confidence interval [CI], 0.93-1.15), and the OR per SD increase in venular diameter was 1.04 (95% CI, 0.93-1.16). After categorizing the retinal vessel diameters into quintiles, there was no trend. After stratifying on age, only persons 75 years and older with smaller arteriolar diameters were at a borderline significant increased risk of iAMD: OR/SD decrease in arteriolar diameters adjusted for age, gender, follow-up time, and other cardiovascular risk factors, 1.24 (95% CI, 0.94-1.63). CONCLUSION: Overall retinal vessel diameters were not related to the risk of iAMD in this general elderly population.

Aged↗

[Study of the method to measure the diameter of retinal vessels].

PURPOSE: To estimate the objective and repeatable method for measurements of the retinal vessels' diameter. The direct reason for creating this method was to use it to evaluate the influence of exogenous estrogens on the retinal blood vessels. MATERIAL AND METHODS: Based on modern computer systems, using funduscamera Canon NF 505, the model of active matrix for repeatable method for estimating the changes in vessels' diameter, was elaborated. RESULTS: After statistical analysis of a material of 3000 measurements, the degree of objectiveness and recurrence and the potential scale for errors was acknowledged. This method enables the estimation of the changes in retinal vessels diameter caused by many different factors in comparison to initial observations (set as 100%) in every analysed case. CONCLUSIONS: Presented method can be successfully used for objective, reliable evaluation of changes in the blood vessels diameter caused by many different factors.

Estrogens↗

Retinal vessel diameter and open-angle glaucoma: the Blue Mountains Eye Study.

PURPOSE: To examine the relationship between open-angle glaucoma (OAG) and retinal vessel diameter among baseline participants in the Blue Mountains Eye Study. DESIGN: Population-based cross-sectional study. PARTICIPANTS: The study included 3654 persons older than 49 years, representing 82.4% of permanent residents living in an area west of Sydney. METHODS: Participants had a detailed eye examination, including automated perimetry and stereo optic disc photography. A computer-assisted program measured retinal vessel diameters from digitized photographs of right eyes. MAIN OUTCOME MEASURES: Open-angle glaucoma was diagnosed from matching visual field defects and optic disc cupping, without reference to intraocular pressure (IOP) level. Ocular hypertension was defined as IOP of >21 mmHg in either eye, without matching glaucomatous optic disc and field changes. Average retinal vessel diameters, measured from right eyes, were summarized as arteriolar and venular equivalents. The lowest quintile of the arteriolar equivalent or arteriole-to-venule ratio was used to define generalized retinal arteriolar narrowing. RESULTS: The study included 3314 participants, after excluding those with incomplete data or nonglaucomatous optic nerve disease. Of persons included, 59 (1.8%) had evidence of glaucomatous damage affecting the right eye, 3065 (92.5%) had no damage to either eye, and 163 (4.9%) had ocular hypertension. Right eyes with glaucomatous damage had significantly narrower retinal arteriolar diameters (183+/-2.6 microm) than eyes without glaucoma (194+/-0.4 microm, P = 0.0001) or eyes with ocular hypertension (195+/-1.6 microm, P = 0.0002), after adjusting for age, mean arterial blood pressure, and other confounding variables, including refraction. Right eyes with glaucomatous damage were at least 2 times more likely to have generalized retinal arteriolar narrowing than eyes without glaucoma (odds ratio, 2.7; 95% confidence interval, 1.5-4.8). CONCLUSIONS: These population-based data suggest that generalized retinal arteriolar narrowing, an indicator of localized vascular change, is significantly associated with optic nerve damage caused by OAG. It is not clear whether such a retinal arteriolar change reflects an ischemic process leading to optic nerve damage or results from loss of retinal neurons secondary to glaucoma.

Aged↗

Early retinal vessel development and iris vessel dilatation as factors in retinopathy of prematurity. Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) Cooperative Group.

OBJECTIVE: To determine whether the extent of retinal vessel development present on early screening examinations for retinopathy of prematurity has prognostic value? DESIGN: The prospectively collected data from the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity were used to compare the development of acute retinopathy of prematurity and long-term structural and visual outcomes for eyes with differing extents of retinal vessel development. PATIENT: Study patients had eyes with the following vessel development. In zone I eyes, vessels extended from the disc less than twice the distance from the disc to the macula. In zone II eyes, vessels extended beyond zone I but not to the nasal ora serrata. Transitional eyes had vessels partly in zone I and partly in zone II. RESULTS: The chance of developing threshold retinopathy of prematurity was inversely related to the early degree of vessel development: 54% for zone I eyes, 25% for transitional eyes, and 8% for zone II eyes. The presence of prominent iris vessels at 34 to 35 weeks of postmenstrual age was associated with increased risk for all three groups; zone I eyes almost always needed treatment (94%). The chance of having an unfavorable anatomic alteration of the posterior fundus, or poor vision at the ages of 1 year and 3 1/2 years, was also inversely related to the degree of early vessel development. Vessel development was an independently important factor even when birth weight, gestational age, and race were considered. CONCLUSIONS: The degree of early retinal vessel development is a significant predictor of outcome from retinopathy of prematurity. Iris vessel dilatation is an important indication for greater vigilance in following these infants.

Cryosurgery↗

Course of disturbance of EOG in retinal vessel occlusions.

More than 60 patients with retinal vessel occlusions were examined using the electro-oculogram (EOG) ramp test. In the course of the disease a systematic disturbance of the slow oscillation of the corneoretinal potential occurred. First, the latency of the light peak increased. Then the peak decreased and was reached up to 5 min later than in the healthy eye. In the final stage the basic level dropped to about half of the normal value and light response was absent. During the next few weeks an improvement in the basic level took place, but usually this did not involve improved vision.

Adult↗

Effects of laser wavelengths on experimental retinal detachments and retinal vessels.

We studied the effects of the yellow (577 nm), orange (595 nm) and red (630 nm) dye lasers, the argon blue-green (488, 514.5 nm) and green (514.5 nm) lasers, and the krypton red (647 nm) laser on experimentally produced serous and hemorrhagic retinal detachments and on retinal vessels in rabbits. Retinal detachments were created by either injecting balanced saline solution or partially hemolyzed blood under the retina. All laser wavelengths except the argon blue-green bypassed the sensory retina and produced no damage on either the sensory retina or the underlying retinal pigment epithelium with serous retinal detachment. Each laser wavelength, however, produced a specific effect on the detached retina with hemorrhagic fluid. Blue-green, green, yellow and orange wavelengths damaged the sensory retina more severely than the red wavelengths. Laser coagulation of the retinal vessels with the blue-green, green and orange wavelengths produced vasospasms.

Animals↗

Effects of atropine and propranolol on retinal vessel diameters during isometric exercise.

PURPOSE: There is controversy regarding the nervous control of retinal blood vessels in humans. Most in vitro studies indicate that the intraocular part of the central retinal artery lacks autonomic innervation. We investigated the response of retinal vessels to isometric exercise during blockade of beta-receptors (propranolol) or muscarinic receptors (atropine). METHODS: Twelve healthy subjects performed squatting for 6 min during infusion of either propranolol atropine or placebo. Blood pressure and pulse rate were measured non-invasively. Retinal vessel diameters were measured continuously using the Zeiss Retinal Vessel Analyser. RESULTS: Squatting induced a significant increase in blood pressure and pulse rate, which was paralleled by a decrease in retinal vein and artery diameters. Atropine did not change the retinal vessel response to isometric exercise. Propranolol significantly blunted the exercise-induced vasoconstriction in retinal arteries. CONCLUSION: This result likely indicates propranolol-evoked vasoconstriction in the extraocular parts of the central retinal artery during isometric exercise.

Adrenergic beta-Antagonists↗

Influence of flicker frequency on flicker-induced changes of retinal vessel diameter.

PURPOSE: To investigate the effect of diffuse luminance flicker of different frequencies on retinal vessel diameter in the human eye. METHODS: Nine healthy subjects participated in the study. A retinal vessel analyzer (RVA; Zeiss, Jena, Germany) was modified to allow for continuous measurement of vessel diameter during flicker stimulation. With this technique, the light used for measurement of vessel diameter consists of wavelengths between 567 and 587 nm, whereas the spectrum of the stimulation is low-pass, with a cutoff wavelength at 550 nm. Flicker frequencies ranged from 2 to 64 Hz. RESULTS: In retinal arteries an increase was observed at all flicker frequencies, with a less-pronounced effect at 64 Hz. In retinal veins, all flicker frequencies except 2 and 64 Hz induced vasodilation. Generally, the flicker-induced diameter response was less pronounced in retinal veins than in arteries. CONCLUSIONS: The flicker-induced diameter response of the larger retinal arteries and veins can be continuously measured with a modified RVA system that spectrally separates the flicker stimulation from the fundus illumination light. Vasodilation of retinal arteries was observed in response to short wavelength flicker with frequencies between 2 and 64 Hz, indicating that the parvo- and magnocellular neural pathways are activated with this stimulation.

Adult↗

The poor reactivity of retinal vessels to systemic administration of vasoactive agents in pentobarbital anesthetized rats.

The responsiveness of retinal vasculature to i.v. administration of several potent vasoactive agents was studied in pentobarbital anesthetized rats by taking fundus photographs. Since cerebral vasculature had been claimed to react in a similar manner but less liably than retinal vessels to some vasoactive substances, the findings were applied to the problem of reactivity of brain vessels. Sublethal doses of noradrenaline, adrenaline, 5-hydroxytryptamine, angiotensin amide and arginine orlysine vasopressin caused no marked acute ( less than or equal to 2 min) vasoconstriction in retinal vessels. Nor did any of these agents or bradykinin elicit vasodilatation. The late vasoconstriction (greater than 2 min) found in succumbing animals was most likely unspecific, since it did not occur until severe toxic symptoms appeared. The findings support the concept that intracerebral vessels are quite resistant to the direct action of many vasoactive agents given i.v.

Animals↗

Effects of inhibition of glycation and oxidative stress on the development of cataract and retinal vessel abnormalities in diabetic rats.

PURPOSE: To study effects of inhibition of glycation, and oxidative stress on the development of cataract and retinal vessel abnormalities in diabetic rats. METHODS: Diabetes was induced in male Wistar rats with streptozocin (STZ; 60 mg/kg BW, i.p.). Diabetic as well as strain matched control rats were fed 1) a normal diet, 2) addition of aminoguanidine in the drinking water (0.5 g/l for diabetic rats and 1.0 g/l for control rats) or 3) probucol in the pellets (1% w/w). After 6 months, the number of acellular vessels, endothelial cells and pericytes were counted in trypsin digested retinal vessel preparations, and the total retinal tissue amount of glutathione (GSH) and cysteine was measured with HPLC. RESULTS: Cataract formation occurred after 13 weeks in diabetic animals compared with 17 weeks for those treated with aminoguanidine, and 16 weeks for those treated with probucol (p < 0.001 in both cases). Aminoguanidine inhibited the formation of acellular collapsed capillary strands, 9 (3-14) vs. 18 (12-262) (median, range) per quadrant in untreated diabetic rats (p = 0.004), while probucol did not have any effect. Neither aminoguanidine, nor probucol influenced the endothelial/pericyte ratio. Diabetes caused a reduction in the GSH/cysteine ratio (10.7 +/- 0.6 vs. 15.3 +/- 1. 5) (mean +/- SD; p < 0.001). Probucol partly restored this imbalance (p < 0.05) whereas aminoguanidine did not. CONCLUSIONS: The results indicate that cataract formation in diabetes involves both glycation and oxidative stress processes. The reduced formation of acellular collapsed capillary strands by aminoguanidine suggests a potential role for glycation in vascular damage. The positive effect of probucol on cysteine/GSH metabolism imbalance indicates that derangements of one of the retinal defense systems against oxidative stress can be normalized by antioxidants.

Animals↗

Reproducible estimation of retinal vessel width by computerized microdensitometry.

An objective method for reliably estimating the width of retinal vessels is presented. A computerized microdensitometer scans film negatives of fundus photographs and reconstructs black and white images of the fundus on a visual display terminal. After this initial scan, a desired region of a retinal vessel is selected with moveable cursors, and a cross-sectional density profile through the vessel is plotted. Vessel width is determined by the half-height width of the profile of the minimum (least transmitting) and average background film densities. Measurement sites can be accurately reproduced on different negatives by landmark mapping. A series of ten fundus photographs were taken of three healthy human eyes, and the width of the superior temporal vein was measured in two places on alle negatives. The coefficient of variation of the six sets ranged from 1.2 and 3.4% with an average of 2.2%.

Analysis of Variance↗

Optic disk neovascularization and retinal vessel diameter in diabetic retinopathy.

We measured retinal vessel diameter before and after panretinal photocoagulation in 59 eyes with diabetic retinopathy and moderate to severe optic disk neovascularization. Treatment significantly reduced mean arteriolar and venular diameter. The diameter of the retinal arterioles after treatment correlated significantly with the amount of regression in disk neovascularization. Eyes with large diameter vessels after treatment usually had little or no regression of proliferative retinopathy, whereas regression was more frequently seen in eyes with smaller diameter vessels after treatment.

Arterioles↗