Arteriovenous Passage Research Articles

Long term results after hemodilution therapy in central retinal vein occlusion

Systemic hemorheologic abnormalities may playa role in the pathogenesis of central retinal vein occlusions. A statistically significant elevation of plasma viscosity was found in patients with acute central retinal vein occlusion compared with control patients. Local retinal blood flow parameters including arteriovenous passage time and mean arterial dye bolus velocity were significantly altered in the central retinal vein occlusion patients versus age matched controls at baseline examination.We performed a randomized, prospective, single-blind clinical investigation to determine the effect of hemorheological manipulation on the clinical course and retinal blood flow of eyes with central vein occlusion. Hemodilution included plasma expansion with hydroxyethyl-starch, withdrawal of whole blood if the hematocrit was above 42%, and rheologic manipulation with parenteral pentoxifylline_ We found a statistically significant improvement in visual acuity at the last follow-up visit 36 months post-treatment for the treated group compared with the control group. The retinal blood flow parameters were markedly improved soon after the institution of therapy and may have contributed to the improved visual prognosis in the treated patient group.

Influence of a single HELP application on hemorheology and retinal hemodynamics.

The heparin-induced extracorporeal low-density lipoprotein precipitation (HELP) eliminates selectively fibrinogen, total cholesterol, low-density lipoproteins (LDL) and triglycerides and improves hemorheology. We investigated the hemodynamic changes in 10 patients without ocular diseases performing a video fluorescein angiography after a single HELP procedure measuring the arm-retina time (ART) and the arteriovenous passage time (AVP). Laboratory parameters such as fibrinogen, cholesterol, LDL, triglycerides, red cell transit time, plasma and whole-blood viscosity were determined and retinal circulation was measured immediately before and after the HELP application. All of the laboratory parameters were lowered significantly. The ART was unaffected by the HELP procedure; however, there was a significant AVP reduction from 2.41 +/- 0.49 to 1.97 +/- 0.47 (p < 0.005). These results support the hemorheological and hemodynamic efficiency of the HELP system in microcirculatory diseases.

CO2 dependence of retinal arterial and capillary blood velocity.

Blood flow to the brain is extremely sensitive to changes in PCO2. While animal studies show a similar potent PCO2 dependence in retinal and choroidal vessels, the PCO2-retinal blood flow relationship has never been adequately studied in humans. Video scanning laser ophthalmoscopy after fluorescein angiography was used to analyze retinal arterial and capillary blood velocity under conditions of mild hypercapnia and hypocapnia. Control conditions (end-tidal PCO2 = 38.3 +/- 0.4 mmHg) were contrasted with hyperventilation-induced hypocapnia (PCO2 = 34.0 +/- 0.4 mmHg) and hypercapnia (PCO2 = 42.3 +/- 0.5 mmHg) created by PCO2 addition to inspired gas. Both larger vessel and macular capillary blood velocity was dependent upon PCO2: arteriovenous passage time fell as PCO2 rose, and both mean arterial dye velocity and capillary blood velocity rose as PCO2 rose (all p < 0.05). These changes in flow velocity occurred despite unchanged heart rate, arterial systolic and diastolic blood pressure, intraocular pressure, and calculated ocular perfusion pressure. Contrast sensitivity was also unchanged by PCO2 variation. The human retinal circulation, like the whole cerebral circulation, may be strongly dependent upon PCO2 in a manner that is unrelated to perfusion pressure and apparently outside strict autoregulatory controls.

Retinal hemodynamics in patients with hyperviscosity syndrome

The hyperviscosity syndrome (e.g. plasmacytoma, cryoglobulinaemia and Waldenström's macroglobulinaemia) leads through the polymerisation of macro-molecules to an increased blood viscosity. This may result in microcirculatory disturbances in various organs. In the retina the hyperviscosity produces a pattern of retinal changes including dot and blot hemorrhages, retinal and optic nerve head edema and increased diameters of the veins. In the present study we quantified the retinal hemodynamic in patients with hyperviscosity syndrome. Fifteen patients aged between 35 and 72 years were included in the study. Ten presented with Waldenström's macroglobulinaemia, two with cryoglobulinaemia and three with plasmacytoma. All patients underwent video fluorescein angiographic studies. The arteriovenous passage time (AVP) representing the retinal microcirculation and the arm retina time (ART) were quantified from the angiograms. In addition, hematocrit (Hct) and the plasma viscosity (ETA) were measured. The AVP was significantly prolonged in patients with hyperviscosity syndrome in comparison to healthy volunteers (AVP: 2.6 +/- 1.5 s vs. 1.6 +/- 0.4 s; p < 0.05). The ART showed no significant differences. Plasma viscosity was doubled in the patients as compared with reference values (ETA: 2.54 +/- 2.23 mPas vs. 1.24 +/- 0.08 mPas; p < 0.01). The simultaneous rising of plasmaviscosity and arteriovenous passage time suggests that the increase of plasmaviscosity causes retinal circulatory disturbance. All this may result in the typical fundus changes in patients with hyperviscosity syndrome.

Retinal circulation times in branch retinal vein occlusion.

To investigate the retinal hemodynamics in branch retinal vein occlusion (BRVO), we measured retinal circulation times using scanning laser ophthalmoscope (SLO) and studied their relationships with clinical findings. Arm-retina time (ART) and arteriovenous passage time (AVP) were measured in 30 eyes of 30 patients. Mean ART was 13.07 seconds. ART showed no difference in relation to sex and systemic diseases, but increased with age. Mean AVPs were 3.00 sec. and 3.39 sec. in superotemporal and inferotemporal BRVO, respectively. AVPs were delayed significantly in occluded branch of retinal veins. AVP was delayed three-fold when the area of capillary nonperfusion was over 6 disc area, but showed no difference according to the duration of disease or macular edema. These results suggest that SLO may be a useful tool for studying retinal hemodynamics in BRVO.

Retinal blood velocities during carbogen breathing using scanning laser ophthalmoscopy.

Hyperoxic-hypercapnic gas mixture ('carbogen': 6% CO2-94% O2) is widely used clinically. Its influence on retinal perfusion remains unclear, since past work suggests that high O2 may reduce and high CO2 may increase retinal blood flow. To examine the changes in retinal blood velocity during 'hyperoxic-hypercapnic' gax mixture breathing, we quantified retinal blood velocity indices. Twenty-eight healthy subjects were studied using scanning laser video fluorescein angiograms at baseline and after gas inhalation. Retinal arteriovenous passage time and mean arterial dye velocity were measured by means of a digital image processing system. Arterial diameter measurements showed no change (4%) during carbogen breathing. Increased arterial Pco2 and Po2 resulted in small but statistically significant increases in systolic and diastolic blood pressure and heart rate (each c. 8%, p < 0.05), and a dramatic increase in mean dye velocity (27%, p < 0.01), with parallel reduction in arteriovenous passage time (40%, p < 0.01). The substantial acceleration of retinal dye velocity and transit under combined hyperoxia and hypercapnia strongly suggests that this clinically standard gas mixture may indeed improve oxygenation without reducing retinal perfusion.

Measurement of retinal hemodynamics with scanning laser ophthalmoscopy: Reference values and variation

High resolution video fluorescein angiography using scanning laser ophthalmoscopy allows the assessment of retinal macro- and microcirculation. Data on the retinal macrocirculation were obtained from 221 healthy subjects. The data were derived from estimations of the arm-retina time, the arteriovenous passage time and mean arterial dye velocity, characterizing the passage of fluorescein to the eye, the mean arterial plasma velocity, and the arteriovenous passage through the entire vascular bed of one segment. Additionally, the transit of hypofluorescent segments in the capillary macular network were measured in 90 healthy subjects. These parameters provide a wide range of information for understanding the physiology of healthy and diseased eyes. Fundamental for all interpretations is the knowledge of the physiological variations. In the present study the inter- and intraindividual variability of retinal hemodynamics in healthy volunteers were assessed. The interindividual variation was 23.8% for the arm-retina time, 20.7% for the arteriovenous passage time, 23.7% for the mean arterial dye velocity, and 14.2% for the capillary flow velocity; the coefficient for variation, characterizing the intraindividual variation, was 26.6%, 15.6%, 16.7%, and 7.9%, respectively. The knowledge of the inter- and intraindividual variation of retinal blood flow indices allows for a priori power estimations for pathophysiologic and pharmacological studies.

Physiological perturbation of ocular and cerebral blood flow as measured by scanning laser ophthalmoscopy and color doppler imaging

Retinal blood flow regulation in health remains poorly described. We hypothesized that retinal perfusion is controlled to provide constant O 2 delivery to that tissue, and that changes in retinal blood flow in response to chemical stimuli parallel changes in carotid and retrobulbar perfusion. Accordingly, in 11 young adults with normal eye examinations, we measured retinal blood flow indices (via scanning laser ophthalmoscopy [SLO] during fluorescein angiography) and carotid, ophthalmic, and central retinal arterial blood flow indices (via Doppler imaging [CDI]) under control, hypoxic (alveolar PO 2 = 55 ± 3 mmHg) and hyperoxic (alveolar PO 2 = 655 ± 18 mmHg) conditions. The three conditions were counterbalanced in order and isocapnia was maintained in each. Retinal arterial mean dye velocity and arteriovenous passage time, as measured by SLO, were slowed by hyperoxia and accelerated by hypoxia, in rough proportion to the changes in arterial O 2 content (± 10%; p < 0.05). In the seven subjects in which relative measurements of retinal arterial diameters were obtained, neither hypoxia nor hyperoxia significantly altered vessel diameter. At the same time, mean retinal capillary transit velocity was independent of PO 2, suggesting that, in health, retinal capillaries may be recruited as PO 2 falls. O 2-induced changes in carotid, ophthalmic, or central retinal arterial blood flow velocities (via CDI) were not found, though a wide coefficient of variation (30% for CDI vs. 14% for SLO) may have contributed to this failure. We conclude that, under isocapnic conditions, retinal perfusion may be regulated to provide constant O 2 delivery. The lack of precision of CDI in this study leaves open the possiblity that chemical regulation of the retinal flow may parallel that of other brain regions.

Hemodilution therapy in central retinal vein occlusion

Systemic hemorheologic abnormalities may play a part in the pathogenesis of central retinal vein occlusions. A statistically significant elevation of plasma viscosity was found in patients with acute central retinal vein occlusion compared with control patients. Local retinal blood flow parameters including arteriovenous passage time and mean arterial dye bolus velocity were significantly altered in the central retinal vein occlusion patients compared with age-matched controls at baseline examination. We performed a randomized, prospective, single-blind clinical investigation to determine the effect of hemorheological manipulation on the clinical course and retinal blood flow of eyes with central vein occlusion. Hemodilution included plasma expansion with hydroxyethyl-starch, withdrawal of whole blood if the hematocrit was above 42%, and rheologic manipulation with parenteral pentoxifylline. We found a statistically significant improvement in visual acuity at 1 year post-treatment for the treated group compared with the control group (increase of visual acuity of 1.5 lines vs decrease of 1.5 lines). The retinal blood flow parameters were markedly improved soon after the institution of therapy, and this may have contributed to the improvement in visual acuity in the treated group. There was no statistically significant difference between the two groups in the progression to ischemic central vein occlusion.

Lacunar infarcts and white matter attenuation. Ophthalmologic and microcirculatory aspects of the pathophysiology.

By means of neurological and ophthalmologic examinations we considered whether there is a microcirculatory disorder not related to hypertension and diabetes in patients with lacunar infarcts and whether there are microcirculatory differences in patients with lacunar infarcts compared with those with white matter attenuation. Eighty neurological patients with a lacunar infarct underwent computed tomography and, based on the results, were prospectively assigned to subgroups as follows: (1) patients without changes; (2) patients with white matter attenuation but without lacunar infarcts; (3) patients with lacunar infarcts alone; and (4) patients with both lacunar infarcts and white matter attenuation. Clinical and ophthalmologic parameters were monitored. The retinal microcirculation was studied by videofluorescence angiography. These neurological patients were compared with control ophthalmologic patients matched for age, sex, hypertensive and diabetic ocular fundus changes, and smoking habits. On average, the 80 patients with lacunar infarcts had a significantly (P = .0001) slower arteriovenous passage time (2.6 +/- 0.7 seconds) than the ophthalmologic control subjects (1.6 +/- 0.6 seconds). Arteriovenous dye passage time through the retinal microcirculation was nearly normal (2.2 +/- 0.8 seconds) in patients with white matter attenuation alone, but was significantly prolonged in patients with lacunar infarcts (2.9 +/- 0.8 seconds, P = .00085) or both white matter attenuation and lacunar infarcts (2.8 +/- 0.4 seconds, P = .008). Patients with lacunar infarcts are characterized by an additional disorder of retinal microcirculation independent of arterial hypertension and diabetes. Our data suggested that white matter attenuation and lacunar infarcts may be phenomena with only weak interdependence.

Retinal Hemodynamics Using Scanning Laser Ophthalmoscopy and Hemorheology in Chronic Open-angle Glaucoma

Recent studies suggest that elevated intraocular pressure is not the only causative factor for the development of visual field loss and optic nerve damage in glaucomatous eyes. The authors determine whether retinal hemodynamics or blood fluidity are alternated in eyes of patients with open-angle glaucoma compared with those of age- and sex-matched healthy subjects. High-quality video fluorescein angiograms were obtained from single eyes of 51 patients with chronic open-angle glaucoma. From these angiograms, the arm-retina time, mean dye velocity, and arteriovenous passage time were quantified. The data from patients were compared with those of an age- and sex-matched group of healthy subjects. In patients with chronic open-angle glaucoma, an 11% reduction of the mean dye velocity (P < 0.05) and a 41% prolongation of the arteriovenous passage time (P < 0.01) was observed relative to the values obtained among the control subjects. Among hematocrit values, plasma viscosity, and erythrocyte aggregation, only plasma viscosity showed a significant increase (4%; P < 0.01) in patients with chronic open-angle glaucoma. These results indicate that a pronounced circulatory deficit exists within the retinal vasculature of glaucomatous eyes, which may coexist with, but cannot be fully attributed to, an increase in plasma viscosity.

Retinal circulation and current blood glucose value in diabetic retinopathy

In 42 type II diabetic patients with nonproliferative diabetic retinopathy the arm-retina time (ART) and arteriovenous passage time (AVP) were measured by means of videofluorescein angiography. Glycosylated hemoglobin (HbAlc) as a parameter of longterm diabetic control and the blood glucose level were determined. The ART in the diabetics was similar to the ART of normals and the AVP was significantly prolonged. HbAlc level ranged between 5.6 and 12.2% (8.6 +/- 1.7%) and the blood glucose level between 4.5 and 22.9 mmol/l (11.4 +/- 4.5 mmol/l). Significant correlations were found between AVP and blood glucose (r = 0.37) and between AVP and HbAlc (r = 0.49). No correlation was found neither between ART and blood glucose nor between ART and HbAlc. A multiple stepwise regression analysis shows that of both investigated parameters HbAlc is the predicting variable for AVP. These results show that in diabetic patients the retinal blood flow is more influenced by the longterm diabetic control than by the blood glucose level at the time of examination.

Videofluoreszenzangiographische Untersuchungen bei akuter vorderer ischämischer Opticoneuropathie

Acute anterior ischemic optic neuropathy (AION) is a circulatory disorder of the short posterior ciliary arteries and their branches. 74 patients with AION were examined with video fluorescein angiography for disturbance of the retinal circulation. The armretina time (ART) was slightly (15%, p less than 0.01) increased in patients with AION (12.9 +/- 3.9 s) as compared to healthy persons (11.2 +/- 3.3 s). The prolonged ART was more prominent in the 26 (35.1%) diabetic patients (14.2 +/- 3.9 s). Because of the ART being only moderately prolonged and since the Doppler ultrasonography of the carotid arteries showed in only 3 patients an occlusion or a hemodynamically relevant stenosis of greater than or equal to 50%, prolonged ART may play a considerable role in the course of AION in only few patients. The retinal arteriovenous passage time (AVP) is considerably (77%, p less than 0.01) increased in AION (2.57 +/- 0.89 s) as compared to healthy persons (1.45 +/- 0.40 s). In patients with duration of symptoms less than 10 days (2.78 +/- 0.96 s) the AVP was increased (p less than 0.01) as compared to patients with duration of symptoms between 11 and 30 days (2.11 +/- 0.46 s). The comparison between the eye with AION and the not affected eye showed no difference in ART but an increase of AVP in the eye with AION. The AVP in AION patients without and with diabetes was not different. No differences in ART and in AVP were found between arteriitic and non-arteriitic patients with AION. The results indicate that the retinal microcirculation is disturbed in patients with arteriitic and non-arteriitic AION. This condition may worsen the in AION affected microcirculation of the optic nerve head through the mechanism of decreased blood flow in the retinociliary anastomoses.

Hämodynamische Befunde bei Patienten mit Retinitis pigmentosa

The hemodynamic status of 26 patients with retinitis pigmentosa was examined using video fluorescein angiography. The hemorheological parameters hematocrit, plasma viscosity, erythrocyte aggregation and erythrocyte rigidity were determined. The results were compared to a matched pairs-group. Video angiography showed for retinitis pigmentosa patients a normal arm-retina time and a significant increase of the arteriovenous passage time. The rheological parameters for both groups were within the reference range. Interestingly the hemodynamic disturbance of microcirculation could be demonstrated already in early stages with no ophthalmoscopic symptoms and no atrophy of retinal vessels detectable at the time. The results indicate that disturbance of the retinal hemodynamics in early stages of retinitis pigmentosa may play a role in the pathogenesis of the disease.

Bestimmung der arteriovenösen Passagezeit der Aderhaut mit Indozyaningrün

We present a very sensitive, yet light-weight videosystem for infrared angiography with Indocyanine green. This system was used to quantify for the first time the choroidal arteriovenous passage time (chAVP) in eight healthy volunteers and eight patients with retinal detachment pre- and postoperatively. The mean normal value of the chAVP was measured to be 3,46 + 0,59 sec. Patients with retinal detachment could be divided into two groups. The chAVP did not change significantly (p = 0,298) from 3,37 + 0,55 sec. to 3,48 + 0,54 sec. in six patients (mean age 49,7 + 5,4 years), who had a simple scleral buckling procedure. In two further patients (63 and 70 years), who had been operated with an encircling band, a postoperative chAVP-delay of 0,72 and 1,48 sec. was detected. This verification of the clinically expected obstruction of choroidal venous outflow after encircling bands emphasizes the validity of the method. Nevertheless, since the procedure is time consuming and detects only marked disturbances, it must be taken as one basic step in the search for the quantification of the choroidal circulation.

Retinal circulation times in diabetes mellitus type 1.

Video fluorescein angiography was performed in 124 patients between 18 and 65 years of age (mean 35.0, SD 12.3 years) with juvenile-onset, insulin-dependent diabetes mellitus (type 1). The arm-retina time (ART) and the retinal arteriovenous passage time (AVP) were measured by means of a picture analysis system to quantify the retinal microcirculation. Glucose metabolism was assessed by the blood level of haemoglobin A1c. The ART 11.5, SD 3.4 s) was similar to that in normal persons (11.2, SD 3.3 s), while the AVP was significantly longer in the diabetics (AVP = 2.35, SD 0.87 s) than in normal persons (AVP = 1.45, SD 0.40 s). The patients with severe diabetic retinopathy showed the most impressive change in AVP. The diabetics with good glycaemic control, that is, with glycosylated haemoglobin (HbA1c) less than or equal to 8.0 g/dl, had a shorter AVP than patients with bad glycaemic control (HbA1c greater than or equal to 9.5 g/dl). The group with a history of diabetes for less than five years showed circulation parameters similar to those of normal persons. The AVP in this group was significantly shorter than in groups with a history of diabetes for five or more years.

Retinal blood flow in diabetic children and adolescents

A total of 209 diabetic children and adolescents aged 6-17 years (mean, 12.6 +/- 2.3 years) were examined by ophthalmoscopy, video fluorescein angiography and hemoglobin (HbA1c) test. Microaneurysms were found in 26% of the children (ophthalmoscopy, 11%; angiography, 23%). The prevalence of retinopathy was 16% in patients aged 6-10 years, 27% in those aged 11-13 years and 36% in those aged 14-17 years. Only five diabetics aged 11-17 years showed lesions other than microaneurysms (hard exudates, intraretinal hemorrhages or retinal capillar leakage). Retinal blood flow was quantified using video fluorescein angiography. The arm-retina time (ART) and the arteriovenous passage time (AVP) as parameters of the retinal microcirculation were obtained using an image analysing system. The mean value for ART was 9.7 +/- 2.5 s and that for AVP was 1.43 +/- 0.52 s. AVP was significantly shorter in diabetic children and adolescents with good glycemic control (HbA1c, less than 7%; AVP, 1.35 +/- 0.44 s) than in those with bad glycemic control (HbA1c, greater than or equal to 9%; AVP, 1.65 +/- 0.51 s).

Video fluorescein angiography follow-up of patients with retinal artery occlusion

Forty patients (age 67 +/- 9 years) with acute central artery obstruction (CAO; n = 20) or branch artery occlusion (BAO; n = 20) of the retina were examined in a prospective study. All patients received a hypervolemic or isovolemic hemodilution, depending on their hematocrit values, for a period of ten days. Clinical, hemodynamic, and rheological data of these patients were recorded before therapy, after ten days, and after six weeks. Under this therapy the central vision of 24 patients (CAO: n = 10; BAO: n = 14) improved by two or more stages. The extent of the circulatory disturbance was determined by arteriovenous passage time and dye bolus velocity. Compared with a control group, a significantly increased arteriovenous passage time and decreased dye bolus velocity were observed initially. The values after ten days of therapy and after six weeks were significantly improved (P less than 0.01) as compared to the initial values. Patients with longer latency showed almost normal retinal hemodynamics, even without therapy, after some weeks. However, in most cases the spontaneous improvement occurred too late. Therefore, it appears important to achieve early reperfusion by therapy.

Video fluorescein angiography: method and clinical application.

Video fluorescein angiography, combined with a picture analyzing system, is a clinically applicable, objective method of evaluating the retinal blood-flow parameters. Optical density measurements were performed on videorecordings of fluorescence angiograms by means of a picture-analyzing system in order to determine the circulation parameters of the retina. These included: the arm-retina time (ART), the arteriovenous passage time (AVP), and the mean arterial dye-bolus velocity (MDV). Normal values for these parameters were derived from measurements in 75 healthy volunteers. The mean arm-retina time (ART) was 11.2 +/- 3.3 s, the mean arteriovenous passage time (AVP) 1.45 +/- 0.4 s and the mean arterial dye-bolus velocity (MDV) 6.39 +/- 1.7 mm/s. No significant correlation could be shown between pulse or blood pressure and one of the retinal circulation parameters. A group of ten healthy volunteers was examined twice in order to obtain the intraindividual variation for the measuring parameters. The coefficient of variation for the ART was 18%, 10% for the AVP, and 26% for the MDV.

Video fluorescence angiography follow-up of patients with retinal stasis syndrome

Forty-four patients were examined by video-fluorescein angiography. With the onset of the first symptoms a significant decrease in retinal blood flow was determined by prolonged arteriovenous passage time (AVP) and diminution of mean dye bolus velocity (MDV). No correlation could be found between the extent of impeded retinal perfusion in the acute phase and the severity of the clinical appearance. In 35 of the 44 patients a favorable clinical course was observed. An initially markedly reduced retinal perfusion improved under treatment by isovolemic or hypervolemic hemodilution, fibrinolysis, and panretinal laser coagulation, and remained stationary during the further course of time. Complete normalization of the AVP and the MDV could not be found in any of these patients. Sixteen percent of the patients with retinal stasis syndrome developed hemorrhagic central venous thrombosis. In the authors' opinion videoangiographic follow-up of patients with retinal stasis syndrome is essential for early detection of further-reduced retinal perfusion. It may thus be possible to prevent the transition to hemorrhagic central retinal vein occlusion in these cases by early treatment.