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PubMed1986

Paramacular telangiectasis.

Forty six patients with paramacular retinal telangiectasis were reviewed; unilateral telangiectasis was present in 26 and bilateral disease was present in 20. Patients with unilateral macular telangiectasis had the more extensive vascular involvement associated with exudation and were more likely to have peripheral telangiectasis. Bilateral macular telangiectasis was associated with pigment epithelial changes and sub-retinal scars. Visual acuity was mildly reduced in the majority of patients; severe loss of vision was most frequent in patients with bilateral macular disease. The evolution of vascular changes was very slow and only 5 patients lost vision of two lines or more during an average period of 40 months. The high incidence of peripheral changes in unilaterally involved patients implies the possibility of a primary defect of the retinal vessels in these patients. There is evidence to suggest that there may be a primary defect of the retinal pigment epithelium in some patients with bilateral involvement.

Adult↗

PubMed1986

[Simultaneous study of ocular vascular reactions of the anterior and posterior segments following clonidine and propranolol in normotensive and hypertensive experimental animals].

The influence of clonidine and propranolol on the vessels of the anterior segment and of the fundus, as well as on mean arterial pressure and heart rate, was investigated in normal rabbits, minipigs, and minipigs with experimentally induced hypertension. The vessel reactions were monitored by photography or fluorescein angiography. Following injection of clonidine, constrictions of episcleral and conjunctival vessels occurred in all the animals, but the fundus vessels of the rabbits were not affected. Difficulties were encountered in assessing the condition of the iris vessels. In minipigs, after administering 6-20 micrograms/kg, an average delay of 2 seconds in the inflow into the retinal vessels was recorded, due possibly to a (transitory?) vessel constriction upstream. Mean arterial pressure increased initially in all animals, but to a different extent in the two species. There was less uniformity as regards heart rate. The vessel reactions of the two species to propranolol were different: in rabbits, a reaction was only observed after administering 2.46 mg/kg bodyweight in episcleral and conjunctival vessels, though not in fundus vessels. Minipigs were given doses of 0.16, 0.5, and 0.8 mg/kg; after 0.5 mg/kg a vessel constriction took place in the episclera and the conjunctiva, becoming manifest after 20 minutes and attaining a maximum after 60 minutes. However, there appeared to be no reaction in the fundus vessels. After an abrupt decrease in mean arterial pressure, both this and the heart rate showed an almost identically slow decrease until the 50th minute, followed by a slight increase up to the 60th minute. The comparison of the circulation parameters reveals some interesting parallels, though also some contrasts. The mechanisms of action and characteristics of these two substances are discussed.

Animals↗

PubMed1995

[2-dimensional mapping and retinal and papillary microcirculation using scanning laser Doppler flowmetry].

PURPOSE: To present clinical applications of a new non-invasive method imaging in a high-definition the topography of perfused retinal vessels. METHOD: By a combination of a laser Doppler flowmeter with a scanning laser system the perfusion of the retina and the optic nerve head is visualized and quantified. The principles of measuring blood flow by Laser Doppler Flowmetry are based on the optical Doppler effect: laser light scattered by a moving particle is shifted in frequency by an amount delta f. Our data acquisition and evaluation system is a modified laser scanning tomograph. The technical data are: retinal area of measurement 2.7 mm x 0.7 mm, 10 degree-field with 256 points x 64 lines, measurement accuracy 10 microns, wavelength 670 nm and 790 nm, light power 100 microW, data acquisition time 2,048 s. Every line is scanned 128 times by a line-sampling rate of 4,000 Hz. By performing a discrete Fast Fourier Transformation over 128 intensities of each retinal point the laser Doppler-shift is calculated for each retinal point. With these data a 2-D map with 256 x 64 points of the retinal perfusion is created. The brightness of the picture-point is coded by the value of the Doppler shift. We estimated the reliability and the validity of the method. Perfusion-pictures of the superficial retinal layer and in the optic nerve head were presented. RESULTS: The reliability-coefficients r1 of "Flow", "Volume" and "Velocity" were 0.85, 0.83, and 0.85 respectively. The blood flow measurements by the presented method ("Scanning Laser Doppler Flowmetry") in an artificial capillary gave a linear relationship (r-value 0.973, p < 0.00001) between defined blood velocities and the measured blood flow. By the confocal technique, dependent on the focus, capillaries of the retinal superficial vasculature of the optic nerve head became visible with a high resolution. Off line the blood flow of areas of 110 microns x 110 microns were calculated in terms of laser Doppler flowmetry. CONCLUSION: "Scanning Laser Doppler Flowmetry" facilitates the visualisation of perfused retinal capillaries and vessels in high resolution. The representation of the function of the retinal circulation by SLDF leads to an image similar to the anatomical situation. The 2-dimensional mapping of local blood flow leads to a physiological picture of the retinal perfusion with visible vessels and capillaries.

Adult↗

PubMed2006

Automatic retinal oximetry.

PURPOSE: To measure hemoglobin oxygen saturation (SO(2)) in retinal vessels and to test the reproducibility and sensitivity of an automatic spectrophotometric oximeter. METHODS: Specialized software automatically identifies the retinal blood vessels on fundus images, which are obtained with four different wavelengths of light. The software calculates optical density ratios (ODRs) for each vessel. The reproducibility was evaluated by analyzing five repeated measurements of the same vessels. A linear relationship between SO(2) and ODR was assumed and a linear model derived. After calibration, reproducibility and sensitivity were calculated in terms of SO(2). Systemic hyperoxia (n = 16) was induced in healthy volunteers by changing the O(2) concentration in inhaled air from 21% to 100%. RESULTS: The automatic software enhanced reproducibility, and the mean SD for repeated measurements was 3.7% for arterioles and 5.3% venules, in terms of percentage of SO(2) (five repeats, 10 individuals). The model derived for calibration was SO(2) = 125 - 142 . ODR. The arterial SO(2) measured 96% +/- 9% (mean +/- SD) during normoxia and 101% +/- 8% during hyperoxia (n = 16). The difference between normoxia and hyperoxia was significant (P = 0.0027, paired t-test). Corresponding numbers for venules were 55% +/- 14% and 78% +/- 15% (P < 0.0001). SO(2) is displayed as a pseudocolor map drawn on fundus images. CONCLUSIONS: The retinal oximeter is reliable, easy to use, and sensitive to changes in SO(2) when concentration of O(2) in inhaled air is changed.

Humans↗

PubMed2000

High-altitude retinopathy and retinal vascular dysregulation.

PURPOSE: (a) To show that high-altitude retinopathy (HAR) is common at high altitudes even in well-acclimatised climbers and that it should not be regarded as part of the spectrum of benign mountain sickness but rather as a clinical sign with a separate aetiology. (b) To test the hypothesis that HAR could be interpreted as a clinical expression of 'ocular vascular dysregulation'. METHODS: Both eyes of the 8 mountaineers of the First Vienna Himalayan Expedition in May/June 1996 were examined 2 weeks before departure to and 2 weeks after descent from a high altitude. Retinal blood flow was measured in the right eyes of 7 climbers, using the Heidelberg Retina Flowmeter (HRF). RESULTS: Two of the 8 climbers had bilateral retinal haemorrhage after the expedition. In 5 climbers chronic hypoxic exposure caused an increase in retinal blood flow between +18% and +96%, and in 2 climbers a decrease in retinal blood flow between -21% and -31%. The 2 climbers (climbers 1 and 2) with bilateral retinal haemorrhage showed a significant increase in HRF parameters. CONCLUSIONS: HAR may be a clinical sign of mountaineers with a tendency towards ocular vascular dysregulation. The pronounced increase in all haemodynamic parameters in the 2 climbers with retinal haemorrhage combined with a dilated epipapillary network 2 weeks after the exposure reflects a retinal vessel configuration, as might be expected at high altitudes under acute hypoxic stress. An inadequate autoregulatory response of the retinal circulation under conditions of chronic hypoxia may play an important part in the pathogenesis of HAR.

Adult↗

PubMed1995

Clinical pathology and retinal vascular structure in the Bardet-Biedl syndrome.

A comparative study of clinical pathology and retinal vascular structure is described as studied by vascular casting in an eye of a patient with the Bardet-Biedl syndrome. At the time of examination the eye had been almost blind for at least 4 years. The histopathological examination showed a largely uniform loss of the outer retinal layers. The gross pathological examination of the cast ocular fundus showed three distinct zones, an inner zone inside the temporal vascular arcades where retinal vessels had been cast, a mid peripheral zone with bone spicules, and a peripheral zone with neither cast vessels nor bone spicules. The findings are discussed in relation to possible pathophysiological mechanisms involved in the development of retinal dystrophy in the Bardet-Biedl syndrome.

Female↗

PubMed2005

Microvasculature of the retina, ciliary processes and choroid in the North American raccoon (Procyon lotor) eye: a scanning electron microscopic study of corrosion casts.

We have studied the vasculature of the retina, ciliary processes and choroid in the North American raccoon (Procyon lotor), a nocturnal mammal, using light and scanning electron microscopic examination of corrosion casts. We carried out an identical study in the crab-eating macaque (Macaca fascicularis), which forages only during the daytime, in order to compare the ocular vasculature with that of nocturnal mammals. Our observations in raccoons demonstrated a photoreceptor layer associated with rich lymph and a poorly vascularized retina. The meridian region of the eye, which lies in the horizontal plane and pass around the optic disc, had a markedly sparse capillary network. This horizontal sparse vascular band may correspond to a visual streak. Ciliary process capillaries were delicate, and formed a well-developed and compact network. Choriocapillaries were quite thin and formed a coarse capillary network. This contrasted with the dense retinal and well-extended choroidal capillary networks noted in the macaques. Our findings suggest that the sparse retinal capillary network in raccoons is extremely beneficial for photon capture, thereby allowing the raccoon to see well at night, as the retinal vessels restrict the inflow of photons toward the photoreceptors. The well-developed lymph probably compensates for the sparse retinal capillaries and choriocapillaries and nourishes the retina in the nocturnal raccoon.

Animals↗

PubMed1975

[Hydrostatic pressures within the eye (author's transl)].

In the eye all membranes are more or less under tension, as elsewhere in the body. Hence the hydrostatic pressure in the choroid is less than in the retina. The available pressure difference within the bloodvessels would be less for the retina than for the choroid, if the arteries to the retina did not have a much larger bore than those to the choroid. Hence the bloodstream for the retina is slower and fluorescein appears later in the retina than in the choroid. There is a flow of tissue fluid from the choroid to the retina. It is absorbed by the retinal vessels. The larger the flow, the larger are the retinal veins, till retinal oedema occurs. Then the tissue pressure within the retina rises sharply and the capillaries become strangulated. But a few capillaries remain open and are blown up to arterio-venular shunts. Micro-aneurysmata arise as abortive vessel sprouts. It is plausible that lightcoagulation sticks the lamellae of Bruch's membrane together, to the extent that the development of oedema is arrested.

Choroid↗

PubMed2000

Bax is increased in the retina of diabetic subjects and is associated with pericyte apoptosis in vivo and in vitro.

Diabetes of even short duration accelerates the death of capillary cells and neurons in the inner retina by a process consistent with apoptosis. We examined whether the process is accompanied by changes in the expression of endogenous regulators of apoptosis. In postmortem retinas of 18 diabetic donors (age 67 +/- 6 years, diabetes duration 9 +/- 4 years) the levels of pro-apoptotic Bax were slightly, but significantly, increased when compared with levels in 20 age-matched nondiabetic donors (P = 0.04). In both groups, Bax localized to vascular and neural cells of the inner retina. Neither pro-apoptotic Bcl-X(S), nor pro-survival Bcl-X(L) appeared affected by diabetes. The levels of these molecules could not be accurately quantitated in lysates of retinal vessels because of variable degrees of glial contamination. However, studies in situ showed in several pericytes, the outer cells of retinal capillaries, intense Bax staining often in conjunction with DNA fragmentation. Bovine retinal pericytes exposed in vitro to high glucose levels for 5 weeks showed elevated levels of Bax (P = 0.03) and increased frequency of annexin V binding, indicative of early apoptosis. Hence, human diabetes selectively alters the expression of Bax in the retina and retinal vascular pericytes at the same time as it causes increased rates of apoptosis. The identical program induced by high glucose in vitro implicates hyperglycemia as a causative factor in vivo, and provides a model for establishing the role of Bax in the accelerated death of retinal cells induced by diabetes.

Aged↗

PubMed2006

Regular aspirin use and retinal microvascular signs: the Blue Mountains Eye Study.

OBJECTIVE: Hypertension is closely related to microvascular abnormalities and there is increasing interest in agents that target the microvasculature. The effect of aspirin on the microvasculature has not been well studied. We examined the cross-sectional and longitudinal associations between regular aspirin use and retinal microvascular signs. DESIGN AND METHODS: We digitized retinal photographs from participants of the Blue Mountains Eye Study cohort (1992-1994, n = 3654, aged over 49 years, and 1997-1999, n = 2335) and used a computer-assisted method to measure average retinal arteriolar and venular diameters. Information on the frequency of aspirin use was collected, with regular aspirin use defined as weekly or daily. RESULTS: Regular aspirin users comprised 21.2% (n = 775) of the baseline population. At baseline and in individuals who were on one or more antihypertensive medication, regular aspirin use was found to be associated with retinal arterioles on average 3.6 mum (95% confidence interval 1.0, 6.2) wider than those of non-users or occasional aspirin users, after adjusting for age, blood pressure, smoking, diabetes, non-steroidal anti-inflammatory drug use and other variables. Increasing frequency of aspirin use was associated with increasing retinal arteriolar diameter (Ptrend < 0.01). At 5-year follow-up, regular users of aspirin and antihypertensive medication(s) had wider retinal arterioles than those who used aspirin less regularly. Neither antihypertensive medication use alone nor aspirin use alone was associated with wider retinal vessels. CONCLUSION: Our finding of a possible association between the combined use of aspirin and antihypertensive agent(s) and wider retinal arteriolar diameter warrants further investigation into the effects of aspirin on the microvasculature.

Aged↗

PubMedDate not supplied

Role of VEGF-A in endothelial phenotypic shift in human diabetic retinopathy and VEGF-A-induced retinopathy in monkeys.

The endothelium-specific antigen PAL-E, associated with transport vesicles in non-barrier endothelium, is almost absent from barrier capillaries in the normal brain and retina. We have recently demonstrated that only leaking retinal capillaries in diabetic retinopathy (DR) in humans characteristically express PAL-E. Here we investigated the relation between the expression of the PAL-E antigen and vascular endothelial growth factor-A (VEGF) in human post-mortem eyes of individuals with diabetes mellitus (DM) and in experimental VEGF-induced retinopathy in cynomolgus monkeys. Cryosections were cut of eyes of 41 individuals with and 30 individuals without DM and eyes of 2 cynomolgus monkeys who received 4 injections of 0.5 microg VEGF in the vitreous of one eye and PBS in the other. The sections were stained with antibodies against VEGF, PAL-E and endogenous markers for microvascular leakage. Specific retinal vascular staining for VEGF was only observed in 10 out of the 41 cases with DM. These 10 cases also had marked uniform PAL-E staining and widespread vascular leakage. In contrast, diabetic patients without microvascular leakage and controls were negative for VEGF and PAL-E. Likewise, PAL-E was found only in the leaky retinal vessels of monkey eyes injected with VEGF. These results indicate that increased expression of the PAL-E antigen in retinal endothelium in conditions with microvascular leakage is related to VEGF and suggest that VEGF directly or indirectly induces PAL-E. PAL-E expression may reflect important endothelial changes involved in the disturbance of the blood-retina barrier in DR.

Adult↗

PubMedDate not supplied

Ultrastructural evaluation of the retina in retinopathy of prematurity and correlations with vitamin E therapy.

Histological evidence of retinal damage associated with the clinical observation of Retinopathy of Prematurity (ROP) grade III was documented in preterm infants receiving the minimum dosage of vitamin E recommended by the American Academy of Pediatrics (5 mg/kg/day), and exposed to high concentration/duration of oxygen at birth. Matched infants that were provided a higher oral dosage of vitamin E (100 mg/kg/day) did not develop the serious grade of retinopathy (grade III) (1,2). In this paper cytological correlates are described which substantiate pre-existing theories concerning the pathological changes associated with the development of the disease at a light microscopic level. Moreover, observations made at the electronmicroscopic level permit distinctions to be made concerning the newly formed retinal vessels, in treated versus non-treated infants, that have not been noted in the history of this disease. These retinal distinctions suggest that vitamin E may be efficacious in reducing the severity of ROP. Lastly, a mechanism is suggested for the action of vitamin E in reducing the severity of ROP.

Humans↗

PubMed1996

Fibronectin overexpression in retinal microvessels of patients with diabetes.

PURPOSE: To examine whether fibronectin is synthesized in the adult human retina and whether diabetes alters its amount, level of expression, and pattern of splicing. METHODS: Retinas were obtained after death from 24 patients (age, 64 +/- 6 years) with 8 +/- 5 years of diabetes and 24 age-matched control subjects. Retinal localization of fibronectin and its amount in retinal vessels were examined with the immunoperoxidase technique. Fibronectin mRNA in the total retina was studied with reverse transcriptase-polymerase chain reaction using primers encompassing the alternatively spliced exon ED-A. The levels of fibronectin mRNA were measured relative to an internal standard (beta-actin mRNA). To detect and measure fibronectin expression in microvessels, retinal trypsin digests were studied by in situ hybridization. RESULTS: In the adult human retina, fibronectin is present exclusively in the walls of the vessels, including capillaries, and in the internal limiting membrane. In diabetic vessels, immunoreactive fibronectin was increased 1.4-fold over levels in control vessels (P = 0.05). Fibronectin is synthesized locally, and the predominant mRNA species excludes the ED-A region. The splicing pattern was not altered by diabetes. However, in the retinas of patients with diabetes, the levels of fibronectin mRNA were increased 1.3-fold over levels in control retinas (P = 0.028), whereas actin mRNA levels were similar in the two groups. Levels of fibronectin mRNA showed a substantial increase in the microvessels of patients with diabetes (0.49 +/- 0.18 grains/cell versus 0.15 +/- 0.12 grains/cell in control microvessels; P = 0.009. CONCLUSIONS: Fibronectin is synthesized in the adult human retina. Diabetes increases the amount of fibronectin in retinal vessels and upregulates its expression without changing the splicing pattern of the ED-A segment. Increased synthesis and deposition of fibronectin by microvascular cells may modify the interactions of cells and matrix with functional consequences relevant to the lesions of retinopathy.

Aged↗

PubMed1978

Glaucoma-inducing mechanisms in eyes with retinoblastoma.

A total of 149 eyes with retinoblastomas were examined histopathologically to determine the types and frequencies of mechanisms inducing glaucoma. The most common mechanism was iris neovascularization with secondary peripheral anterior synechiae formation. In such cases, the tumor was almost always located at the posterior pole with involvement of central retinal vessels and with growth of a highly vascularized tumor mass into the vitreous. The second most common mechanism was massive exudative retinal detachment causing pupillary block and angle closure. In such cases, tumor growth was present within and under the retina. The third most common mechanism was a combination of the aforementioned mechanisms. Uveitis and/or necrotic tumor tissue in the anterior chamber as the sole mechanism inducing glaucoma was infrequently seen.

Cornea↗

PubMed2003

Retinal vascular abnormalities in neurofibromatosis type 1.

Microvascular retinal abnormalities, presenting in a corkscrew configuration, have been very recently described in patients with neurofibromatosis type 1 (NF-1). We report one more patient with NF-1 who had distinctive corkscrew retinal vessels superior and inferior to the fovea. This patient further supports the existence of a true association between this recently described retinal finding and NF-1.

Adult↗

PubMed1984

Comparison of retinal and cerebral vasculature in trypsin digest preparations.

The trypsin digestion technique for preparing flat mounts of the retinal capillary system was modified for comparable mounts of the cerebrocortical capillaries. These preparations, supplemented by electron microscopy, showed a basic similarity between the 2 systems, but the cortical capillaries have larger diameters, more abundant collateral channels, and less regularly spaced mural cells (intramural pericytes). The cortical capillaries did not show the right-angle branching of the precapillary arteriole characteristic of some retinal vessels, but they did show in the crotches of the branches an excess basement membrane that was not present in the retinal capillaries.

Capillaries↗

PubMed2003

Upregulation of P-selectin and intercellular adhesion molecule-1 after retinal ischemia-reperfusion injury.

PURPOSE: Vascular endothelial cells and leukocytes express several inflammatory adhesion receptors, such as selectins and cell adhesion molecules, after retinal ischemia. They mediate the transmigration process of leukocytes. For further understanding of the role of leukocytes after retinal ischemia-reperfusion injury, the responses of the leukocyte-endothelial cell adhesion molecules P-selectin and intercellular adhesion molecule (ICAM)-1 during retinal ischemia and reperfusion were examined. METHODS: Male pigmented rats were subjected to retinal ischemia by a 1-hour ligation of the optic nerve followed by reperfusion. Gene and protein expression of P-selectin and ICAM-1 were studied at 0.5, 1, 6, 12, and 24 hours after the onset of reperfusion with semiquantitative polymerase chain reaction and Western blot analysis. Immunohistochemical methods were used to detect specific lesions expressing ICAM-1. RESULTS: Significant upregulation of P-selectin and ICAM-1 mRNA (at 6, 12, and 24 hours of reperfusion) were observed, with the expression peaks of both P-selectin and ICAM-1 mRNA occurring at 12 hours after reperfusion. P-selectin protein gradually increased and reached a maximum 6 hours after reperfusion, whereas ICAM-1 protein increased until 24 hours after reperfusion. Immunostaining with ICAM-1 antibodies was positive in endothelial cells after ischemia-reperfusion injury. CONCLUSIONS: Retinal ischemia-reperfusion stimulates P-selectin and ICAM-1 expression. Endothelial ICAM-1 expression in retinal vessels was observed. Upregulation of P-selectin and ICAM-1, which contribute to leukocyte rolling and adhesion, were observed after retinal ischemia.

Animals↗

PubMed2004

Diabetic retinopathy: VEGF, bFGF and retinal vascular pathology.

BACKGROUND: Previous research indicated that the development of diabetic retinopathy (DR) is closely related to the excessive expression of growth factors. This paper was to study the relationship of DR with vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and the retinal vascular pathological change. METHODS: Fifty-five Wistar rats, weighing 100 - 200 g, were selected and randomly divided into four groups: control group (no streptozocin injection, n = 10), M1 group (streptozocin induced diabetes for 1 month, n = 15), M3 group (streptozocin induced diabetes for 3 months, n = 15), and M5 group (streptozocin induced diabetes for 5 months, n = 15). In situ hybridization and immunohistochemistry were used to investigate the expressions of bFGF and VEGF on retinal vascular, and retinal vessels were observed by transmission electron microscope. RESULTS: There was no difference in the number of pericytes between M1 and control group (P > 0.05), but the number of pericytes decreased obviously in M3 and M5 groups compared with the control group (P < 0.01, P < 0.001, respectively). Capillary embolization and non-cell capillary were seen in M5 group. Positive expression of VEGF was found in M5 group using in situ hybridization and immunohistochemistry respectively. Positive expression of bFGF could be seen in M3 (78%) and M5 group (89%). Most remarkable changes of vessels were observed in M5 group including fragmental thickness, split of basement membrane, swelling and distortion of endothelial cells. CONCLUSIONS: In retinal vascular of the streptozocin (STZ) rats, there shows the expression of bFGF at the third month and that of VEGF at the fifth month.

Animals↗