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PubMed1999

Retinal capillary changes in Otsuka Long-Evans Tokushima fatty rats (spontaneously diabetic strain). Electron-microscopic study.

The Otsuka Long-Evans Tokushima fatty (OLETF) rat is a spontaneously diabetic strain with polyuria, polydipsia and mild obesity. The pathological features of OLETF rats closely resemble those of patients with non-insulin-dependent diabetes mellitus. The purpose of this study is to investigate the retinal capillary changes in the OLETF rat and to confirm the valuability of the OLETF rat as the model of diabetic retinal disease. One-month-old male OLETF rats and age- and sex-matched Long-Evans Tokushima Otsuka (LETO) controls were supplied by Otsuka Pharmaceutical Co. Ltd. (Tokushima, Japan). Body weight and blood sugar levels were measured monthly. Their eyes were enucleated 14 months after birth. Ultrathin sections were made and examined with a transmission electron microscope. According to their location, two kinds of retinal capillaries were differentiated: those in the nerve fiber layer (NFL) and those in the outer plexiform layer (OPL). The image of each capillary was transferred to a computed image analyzer, and basement membrane thickness and the ratio of the pericyte area to total capillary cross-section area were determined. Corrosion casts of retinal vessels were made and examined with scanning electron microscopy (SEM). OLETF rats gained more weight than LETO rats from the beginning, and the difference increased gradually with age. The blood sugar level of OLETF rats was higher than that of LETO rats after 5 months of age. In the retinal capillaries of 14-month-old OLETF rats, basement membranes were significantly thicker (OLETF: 209 +/- 51 nm in NFL, 132 +/- 23 nm in OPL; LETO: 118 +/- 28 nm in NFL, 79 +/- 14 nm in OPL), and the ratio of pericyte area to the capillary cross-section area was significantly lower than that of the controls (OLETF: 0.131 +/- 0.92 in NFL, 0.111 +/- 0.102 in OPL; LETO: 0.288 +/- 0.142 in NFL, 0.198 +/- 0.136 in OPL). The endothelial cell cytoplasm had degenerated. SEM examination of the vascular corrosion cast of a 14-month-old OLETF rat showed caliber irregularity, narrowing, tortuosity and loop formations of capillaries. The morphological changes in the retinal capillaries of OLETF rats were similar to those seen in diabetic patients. The OLETF rat may be a useful animal model for the study of ocular diabetic complications in humans.

Animals↗
PubMed1975

Retinal changes in Himalayan climbers.

Changes in the fundus of the eye were studied in 15 members of a mountaineering expedition to Dhaulagiri, Nepal (elevation, 8,167 meters [26,795 ft]). Retinal photographs were taken at sea level and at 5,883 meters (19,300) after each climber had descended from his highest point. Five Nepali Sherpas and an additional American climber who came to the base camp late in the climb were also studied. Vascular engorgement with tortuosity, a 24% increase in arterial diameter, and a 23% increase in venous diameter were observed. Retinal hemorrhages were seen in five American climbers (33%), but in none of the Sherpas. The high incidence is striking, but the cause is unknown. We suggest that the hypoxic vasodilatation makes retinal vessels more vulnerable to sudden rises in intravascular pressure.

Adult↗
PubMed1976

Observation of injected fluorescein diffusion after laser treatment of cat fundi. An experimental study with angiography and microscopy.

Argon laser coagulations with a power of 100 mW and 300 mW, exposure time 0.02 and 0.02 sec, and constant spot size of 100 microns were applied on normal cat fundi. From 1 and 2 hrs to 7 days after the coagulation, the treated eyes were observed angiographically and by fluorescence microscopy after dye injection; freeze dried eyes were examined under a fluorescence microscope. Abnormal dye leakages originated from the chorid and from retinal vessels were detected in the specimens examined within 72 hrs after the coagulation.

Animals↗
PubMed2002

Effects of granulocyte colony stimulating factor on retinal leukocyte and erythrocyte flux in the human retina.

PURPOSE: The blue-field entoptic technique was introduced more than 20 years ago to quantify perimacular white blood cell flux. However, a final confirmation that the perceived corpuscles represent leukocytes is still unavailable. METHODS: The study design was randomized, placebo-controlled, and double masked with two parallel groups. Fifteen healthy male subjects received a single dose of granulocyte colony stimulating factor (G-CSF, 300 microg) and 15 other subjects received placebo. The following parameters were assessed at baseline and at 12 minutes and 8 hours after administration: retinal white blood cell flux, with the blue-field entoptic technique; retinal blood velocities, with bidirectional laser Doppler velocimetry; retinal venous diameter determined with a retinal vessel analyzer; and blood pressure and pulse rate determined by automated oscillometry and pulse oxymetry, respectively. RESULTS: After 12 minutes, G-CSF reduced total leukocyte count from 5.5 +/- 1.4 10(9)/L at baseline to 1.9 +/- 0.4 10(9)/L. This was paralleled by a 35% +/- 11% decrease in retinal white blood cell density. After 8 hours G-CSF increased total leukocyte counts to 20.0 +/- 4.4 10(9)/L. Again, this increase in circulating leukocytes was reflected by an increase in retinal white blood cell density (110% +/- 48%). All effects were significant at P < 0.001. By contrast, none of the other hemodynamic parameters was changed by administration of G-CSF. CONCLUSIONS: The results clearly indicate that the blue-field entoptic technique assesses leukocyte movement in the perimacular capillaries of the retina. Moreover, white blood cell density appears to adequately reflect the number of circulating leukocytes within the retinal microvasculature. Hence, an increase in retinal white blood cell density does not necessarily reflect retinal vasodilatation.

Adult↗
PubMed1982

A revised classification of retinopathy of prematurity.

We have developed a classification system for the acute phases of retinopathy of prematurity based on more than 13,000 ophthalmoscopic examinations of more than 3,400 premature infants between 1968 and 1982. Two forms of the active disease exist. Retinopathy of prematurity is a relatively common mild disease and retinopathy of prematurity plus is characterized by rapid progression and posterior pole vascular tortuosity and dilation. The five grades progress from peripheral vascular abnormalities (Grade 1) through a demarcation line (Grade 2) and extraretinal neovascularization (Grade 3) to partial (Grade 4) or total (Grade 5) retinal detachment. The persistence of abnormal retinal vessels during the first year of life is considered "transitional" retinopathy of prematurity unless unequivocal cicatricial changes with macular distortion develop.

Humans↗
PubMed1993

Evolution of morphologic changes after intravitreous injection of gentamicin.

Gentamicin shows retinal toxicity in rabbits, monkeys, and humans, but its mechanism of toxicity is not understood. Pig eyes, which are anatomically similar to human eyes, were examined with ophthalmoscopy, fluorescein angiography, and light and electron microscopy at time points ranging from 3 to 72 hours after intravitreous injection of 3 mg of gentamicin or vehicle to observe the sequence of toxicity-related changes that occur in the retina. The first ophthalmoscopic changes were retinal hemorrhages at 3 hours, followed by retinal whitening and thickening and vascular nonperfusion detected by fluorescein angiography 48 hours after injection. Vacuolization in the nerve fiber layer and perivascular swelling were seen at 6 hours, and subsequently, extended deeper into the retina. Vascular endothelial cells, photoreceptors, and the retinal pigment epithelium appeared to be spared from the toxic effects of gentamicin. At 48 and 72 hours after injection, numerous large and small retinal vessels showed congestion and leukocyte margination. These changes could not be prevented by increasing the pH of gentamicin to 7.2. These data suggest that gentamicin toxicity is not simply a pH-related phenomenon, that the primary targets of gentamicin toxicity are neurons and glia of the inner retina, and that retinal infarction occurs secondarily, possibly due to leukocytic plugging.

Animals↗
PubMed1979

[Patients on dialysis--late fundus controls (author's transl)].

In 102 patients on dialysis for renal failure late fundus controls have been done to studie the response of retinal vessels to blood pressure reduction. In 52 patients follow up studies were possible. Only 4 patients showed reversible changes of the vessels, in 4 other patients changes increased. In the majority of the patients hypertensive vascular changes (stage I or II) remained unchanged. Young age and deep diastolic pressure seems to be necessary for normalization of the fundus vessels. Vessel changes did not improve if the diastolic pressure was 90--100 mmHg and more.

Adult↗
PubMed2003

Retinal microvascular abnormalities and 10-year cardiovascular mortality: a population-based case-control study.

PURPOSE: Retinal microvascular abnormalities reflect persistent arteriolar damage from hypertension and independently predict stroke. We examined their associations with long-term cardiovascular mortality. DESIGN: Population-based, nested, case-control study. POPULATION: Cases were Beaver Dam Eye Study participants (age range, 43-84 years) who died of coronary heart disease or stroke between the baseline examination in 1988 to 1990 and 1999 (n = 413). Nearly 3 controls per case were selected from the baseline cohort, frequency-matched on 5-year age intervals and gender (n = 1198). METHODS: Retinal photographs of cases and controls at baseline were evaluated for retinopathy, focal arteriolar narrowing, and arteriovenous nicking by graders masked to case-control status using standardized protocols. To obtain an estimate of generalized arteriolar narrowing, photographs were digitized and diameters of individual retinal vessels were measured and summarized by a computer program. MAIN OUTCOME MEASURE: Ten-year cardiovascular mortality. RESULTS: After controlling for systolic blood pressure, diabetes, glycosylated hemoglobin levels, and other risk factors, retinopathy was associated with increased cardiovascular mortality, with odds ratios of 1.8 (95% confidence interval [CI], 1.2, 2.7). For other retinal abnormalities, associations with cardiovascular mortality were present only in younger people, with odds ratios of 2.7 (95% CI, 1.0, 7.4) for focal arteriolar narrowing, 1.8 (95% CI, 0.8, 4.5) for arteriovenous nicking, and 1.9 (95% CI, 1.2, 2.9) for generalized arteriolar narrowing in persons 43 to 74 years of age but odds ratios of 1.1, 0.4, and 1.0 for the corresponding retinal abnormalities in persons 75 years and older. CONCLUSIONS: Retinopathy is independently associated with cardiovascular mortality. Associations for other retinal abnormalities were only observed in middle-aged persons. These data support recent studies that suggest retinal microvascular abnormalities provide independent information regarding cardiovascular risk.

Adult↗
PubMedDate not supplied

Yield of fluorescence from indocyanine green in plasma and flowing blood.

The purpose of this work was to obtain more quantitative knowledge about the yield of fluorescence from retinal vessels during indocyanine green angiography (ICG). The yield of fluorescence from blood was investigated for various shear rates, concentrations of ICG, and layer thicknesses. Measurements were performed in vitro on samples of human blood in a cone-plate shear chamber using frontal illumination as in scanning laser angiography. In blood and in plasma, the yield of fluorescence of ICG increased with concentration up to 0.05 and 0.1 mg/ml, respectively. At higher concentrations, the yield decreased for all layer thicknesses. For increasing layer thicknesses, both in plasma and in blood, the yield of ICG fluorescence increased nonlinearly for concentrations higher than 0.012 mg/ml. Saturation occurred for layers thicker than 200 microns in combination with ICG concentrations of 0.4 mg/ml and higher. Application of shear rates within the physiological range of the microcirculation (88/sec and 528/sec) increased the yield of fluorescence from the blood sample compared with stasis. The high transparency of blood for the excitation and emission light of ICG that was demonstrated will lead to superposition of fluorescence from superficial and deeper layers. This superposition precludes quantitative indocyanine angiography of ocular vessels.

Biomechanical Phenomena↗
PubMed1993

Microvascular retinopathy in the Zucker diabetic fatty rat.

PURPOSE: To determine if quantifiable morphometric signs of retinopathy occur in the Zucker diabetic fatty rat (ZDF/Gmi-fa, formerly designated ZDF/Drt), a partially inbred strain in which the genetic propensity for diabetes is only expressed in obese males. METHODS: Retired diabetic (ZDF/Gmi-fa) and control lean Zucker (fa/+) breeder rats were examined for quantifiable evidence of microvascular changes of the retinal capillaries by gross examination, trypsin digestion of retinal vessels, and transmission electron microscopy. RESULTS: Gross examination of retinas and trypsin digestion of capillaries revealed no differences. Quantitative assessment of capillary cell nuclear density showed that diabetic retinas were hypercellular compared to lean rats (3.888 +/- 0.041 versus 3.304 +/- 0.046 nuclei per 100 microns (mean +/- SE), P = 0.0042). Transmission electron microscopic analysis of retinal capillary basement membrane thickness demonstrated thicker measurements in diabetic animals (mean thickness 21% greater in diabetic rats, P = 0.0307). CONCLUSIONS: This model may be useful for pharmacologic intervention studies because it is naturally and severely non-insulin-dependent diabetic, there are quantifiable retinal vascular changes, and same-sex litter mates can be used as controls.

Animals↗
PubMed1997

Ocular blood flow velocities in patients with proliferative diabetic retinopathy after panretinal photocoagulation.

Color Doppler imaging allows for simultaneous two-dimensional anatomical imaging and Doppler measurement of blood-flow velocity. Because hemodynamic changes have been seen in diabetic patients after photocoagulation by other techniques, the author compared 25 eyes of 25 patients with proliferative diabetic retinopathy before and 6 months and 1 year after panretinal photocoagulation with a matched control group of 30 eyes of 30 healthy volunteers. The ophthalmic artery, short posterior ciliary artery, central retinal vessels, and vortex veins of all patients were examined, and the systolic, diastolic, and mean arterial velocities were measured. Panretinal photocoagulation was performed with these parameters: 800-1000 spots, 0.1 second, 500 microm argon laser. The blood velocity was significantly lower in diabetic patients than in normals in the ophthalmic artery and the central retinal artery. After treatment, blood-flow velocities were significantly lower than before photocoagulation in the ophthalmic artery, the central retinal artery and the central retinal vein. No statistically significant differences were found between 6 months and 1 year after panretinal photocoagulation. No significant correlations were found between age and blood velocities in diabetics and healthy volunteers. Eyes with proliferative diabetic retinopathy showed lower ocular perfusion velocities than normals in the ophthalmic artery and the central retinal artery. Photocoagulation resulted in a reduction in ocular blood-flow velocities in the ophthalmic artery, the central retinal artery and the central retinal vein; these values did not change significantly during 1 year of follow-up.

Adolescent↗
PubMed1997

[High altitude retinopathy after Himalayan ascent].

BACKGROUND: Visual disturbances after high altitude exposure were first reported in 1969. Later, the term "High Altitude Retinal Hemorrhage-HARH" has been used for the ensuing retinal hemorrhages and vascular engorgement. CASE REPORT: A 31-year-old Caucasian male presented to our outpatient department 1 week after climbing Mt. Gosainthan in the Himalayas. He had spent 25 days without oxygen supply above 5000 meters, with a maximum of 8046 meters. He now complained of glare and decreased vision in twilight. Visual acuity was 20/25 OD and 20/20 OS. Ophthalmoscopy revealed intraretinal hemorrhages and tortuosity of dilated arterioles and venoles. After 6 weeks of gradual improvement, visual acuity was 20/20 OD and 20/16 OS with normal visual fields. DISCUSSION: The hypoxia at high altitude causes increased retinal blood flow and blood volume possibly via autoregulatory mechanisms. Furthermore, retinal venous pressure can be increased by extreme physical exertion and Valsalva maneuvers during mountain climbing. A hypoxic retinal capillary bed exposed to increased retinal venous pressure predisposes to intraretinal hemorrhage. Retinal changes include marked increase of retinal vessel diameter with tortuosity of arterioles and venoles and hyperemia or edema of the optic disc. The intra- or preretinal hemorrhages often spare the macular area. These patients do not experience debilitating symptoms unless vitreous hemorrhage occurs. This may be potentially hazardous when the patient is still in the high mountains. Clinically, all these retinal changes are reversible within weeks. To prevent high altitude retinopathy, ascending slowly and use of supplemental oxygen is recommended.

Adult↗
PubMedDate not supplied

Fundus angiography with fluorescein-labelled peptide fraction from bovine factor VIII: correlation with histologic findings.

A peptide fraction (VUEFFE) obtained from bovine factor VIII, with a high affinity for vessel endothelium, was bound to fluorescein and used for angiography in rabbits. Several eyes had undergone laser photocoagulation on the retina. The location of the dye was studied histologically with fluorescence microscopy on the enucleated, freeze-dried eyes. The angiographic and histologic findings were compared with findings obtained using sodium fluorescein. Fluorescein-labelled VUEFFE gave a longer lasting fluorescence of the retinal vessels with histologic evidence of dye deposition on the vessel wall. It also showed marked affinity for the photocoagulated tissues, giving intense and prolonged staining of the laser burns. Possible clinical applications are discussed.

Amino Acid Sequence↗
PubMed1994

[Exudation of indocyanine green from subretinal neovascularization and its significance].

Owing to its tight binding to protein, exudation of indocyanine green from subretinal new vessels would not normally be expected, but it has been demonstrated. We investigated 102 subretinal new vessels to find out how often exudation develops and to understand the reason for it. Exudation was found in 29 (28.4%) of the cases examined; 37 (36.6%) were stained, which means that these membranes became hyperfluorescent but not lighter than other, definitively non-exuding, structures on the fundus. In 26 (25.5%) no hyperfluorescence was seen in the late phase, and in 10, or 9.8%, neovascularization remained occult. The correlation of indocyanine green exudation with retinal blood or lipid deposits was significant (r = 0.77, p = 0.0001). Histological examinations showed a correlation of lipid deposits with a severe disintegration of retinal vessels. This finding, in combination with others, indicates that the exudation of indocyanine green reflects severe destruction of vessel walls, which does not seem to occur consistently in all neovascular membranes. The exudation of indocyanine green might be of prognostic value.

Adult↗
PubMed1983

Vascular leakage, neovascularization, and vitreous hemorrhage in senile bullous retinoschisis.

Retinal detachment is the primary complication of bullous retinoschisis, a benign abnormality of the peripheral retina. We examined three patients (all women, 43, 55, and 56 years old) with typical bullous retinoschisis who had vitreous hemorrhage. In each case, there were sclerotic retinal vessels over the surface of the schisis cavity along with neovascularization above the central portion of the cyst. In one case there was also neovascularization of the peripheral retina in an area distant from the schisis. These findings were confirmed by fluorescein angiography in one case; the other two cases demonstrated similar changes by fluorescein angioscopy. Fluorescein angiography, also demonstrated intraretinal dye leakage from vessels along the posterior extent of the schisis, as well as from an adjacent area of white without pressure.

Female↗
PubMed1998

Entoptic image quality of the retinal vasculature.

Spatial details of entoptically visible retinal vessels were investigated using transcleral and Maxwellian-view stimulators. Nine normal subjects provided detailed drawings of the entoptic images which were digitized and superimposed onto digitized fundus photographs and fluorescein angiograms from the same eyes. Subjects also used a tracing method to locate visible entoptic features. The trans-scleral method provided images similar in detail to standard fundus photography (lacking capillary detail, but capturing larger arteries, veins, arterioles and venules) in the macula and around the disk. The Maxwellian-view method illuminated the fovea (7.7 degree field) and provided foveola capillary detail (capillaries traversing the foveola, the capillary arcade forming the FAZ) as well as the larger foveal vessels supplying the foveola, and often contained more foveal detail that available with fluorescein angiography.

Adult↗
PubMed1988

[Unusual course of Goodpasture syndrome].

Description of a case of Goodpasture's syndrome with vasculitis of the retinal vessels and macular edema. Unusually, the ocular signs became manifest some time before the appearance of hemoptysis and renal insufficiency.

Adult↗