Bidirectional Laser Doppler Velocimetry Research Articles

315. Retinal Vascular Photography as a Window into the Cardiovascular Burden of Adolescent Bipolar Disorder

To investigate the retinal hemodynamic changes occurring in patients with retinitis pigmentosa (RP).Bidirectional laser Doppler velocimetry and monochromatic fundus photography were used to determine retinal venous diameter (D), maximum erythrocyte velocity (Vmax), and volumetric blood flow (Q) in the major retinal veins of eight patients with RP and eight age-matched normal controls. The retinal vascular regulatory responses to hyperoxia, defined as the percent decreases in D (RD), Vmax, and Q (RQ) at four to six minutes of breathing 100% oxygen, were determined in eight normal subjects and five RP patients.Average D, Vmax, and Q ± S.D. in the largest retinal vein of each subject were 106 ± 14 μm, 1.01 ± 0.20 cm/sec, and 3.5 ±1.3 μl/min, respectively, in RP patients, and 166 ± 12 μm, 1.79 ± 0.14 cm/sec, and 14.7 ± 2.6 μl/min, respectively, in normal subjects. This corresponded to significant decreases from normal of 36% in D, 44% in Vmax, and 76% in Q in RP patients (Wilcoxon's rank sum test, P < .001). Average total retinal volumetric blood flow rate was 8.2 ± 2.9 μl/min in RP patients and 37 ± 4.9 μl/min in normal subjects, corresponding to a significant decrease from normal of 78% (Wilcoxon's rank sum test, P < .001). In RP patients, the regulatory responses to hyperoxia were similar to those observed in normal subjects.Retinal blood flow is significantly decreased in patients with RP, probably as a result of vascular remodeling in response to reduced metabolic demand. The regulatory responses to hyperoxia are similar to those of normal subjects. Measurements of retinal blood flow may help assess the progression of the disease and the effects of treatment.

Evaluation of Retinal Circulation Using Segmental-Scanning Doppler Optical Coherence Tomography in Anesthetized Cats.

To study retinal blood flow (RBF) measurement reproducibility using segmental-scanning Doppler optical coherence tomography (DOCT) in vitro in glass capillaries and in vivo in anesthetized cats. As a preliminary study, the flow rates of human blood through glass capillaries were changed by using an infusion pump and measured at 13 preset velocities by DOCT. For in vivo measurement, the cats were anesthetized using sevoflurane. The flow in the parent vessel was compared with the sum of the flow values in the two daughter vessels. The RBF was measured using two different instruments: bidirectional laser Doppler velocimetry (LDV) and DOCT. The reproducibility of the measurements was assessed by calculating the coefficients of variation (CVs) for repeated measurements of RBF at the superior retinal arterioles and venules. In vitro, the flow velocities measured by DOCT agreed well with the preset velocities. In vivo, the flow in the parent vessel agreed with the sum of the flow values in the two daughter vessels. In addition, there were no significant differences in the mean averaged CVs of the RBF in both the arterioles and venules between LDV and DOCT. The newly developed segmental-scanning DOCT revealed the accuracy of the measurement in in vitro glass capillaries and reproducibility of the measurements of blood velocity in both the retinal arterioles and venules in anesthetized cats.

Regulation of retinal oxygen metabolism in humans during graded hypoxia.

Animal experiments indicate that the inner retina keeps its oxygen extraction constant despite systemic hypoxia. For the human retina no such data exist. In the present study we hypothesized that systemic hypoxia does not alter inner retinal oxygen extraction. To test this hypothesis we included 30 healthy male and female subjects aged between 18 and 35 years. All subjects were studied at baseline and during breathing 12% O₂ in 88% N₂ as well as breathing 15% O₂ in 85% N₂. Oxygen saturation in a retinal artery (SO₂art) and an adjacent retinal vein (SO₂vein) were measured using spectroscopic fundus reflectometry. Measurements of retinal venous blood velocity using bidirectional laser Doppler velocimetry and retinal venous diameters using a Retinal Vessel Analyzer (RVA) were combined to calculate retinal blood flow. Oxygen and carbon dioxide partial pressure were measured from earlobe arterialized capillary blood. Retinal blood flow was increased by 43.0 ± 23.2% (P < 0.001) and 30.0 ± 20.9% (P < 0.001) during 12% and 15% O₂ breathing, respectively. SO₂art as well as SO₂vein decreased during both 12% O₂ breathing (SO₂art: -11.2 ± 4.3%, P < 0.001; SO₂vein: -3.9 ± 8.5%, P = 0.012) and 15% O₂ breathing (SO₂art: -7.9 ± 3.6%, P < 0.001; SO₂vein: -4.0 ± 7.0%, P = 0.010). The arteriovenous oxygen difference decreased during both breathing periods (12% O2: -28.9 ± 18.7%; 15% O₂: -19.1 ± 16.7%, P < 0.001 each). Calculated oxygen extraction did, however, not change during our experiments (12% O₂: -2.8 ± 18.9%, P = 0.65; 15% O₂: 2.4 ± 15.8%, P = 0.26). Our results indicate that in healthy humans, oxygen extraction of the inner retina remains constant during systemic hypoxia.

Retinal oxygen metabolism during normoxia and hyperoxia in healthy subjects.

To characterize retinal metabolism during normoxia and hyperoxia in healthy subjects. Forty-six healthy subjects were included in the present study, and data of 41 subjects could be evaluated. Retinal vessel diameters, as well as oxygen saturation in arteries and veins, were measured using the Dynamic Vessel Analyzer. In addition, retinal venous blood velocity was measured using bidirectional laser Doppler velocimetry, retinal blood flow was calculated, and oxygen and carbon dioxide partial pressures were measured from arterialized capillary blood from the earlobe. Measurements were done during normoxia and during 100% oxygen breathing. Systemic hyperoxia caused a significant decrease in retinal venous diameter (-13.0% ± 4.5%) and arterial diameter (-12.1% ± 4.0%), in retinal blood velocity (-43.4% ± 7.7%), and in retinal blood flow (-57.0% ± 5.7%) (P < 0.001 for all). Oxygen saturation increased in retinal arteries (+4.4% ± 2.3%) and in retinal veins (+19.6% ± 6.2%), but the arteriovenous oxygen content difference significantly decreased (-29.4% ± 19.5%) (P < 0.001 for all). Blood oxygen tension in arterialized blood showed a pronounced increase from 90.2 ± 7.7 to 371.3 ± 92.7 mm Hg (P < 0.001). Calculated oxygen extraction in the eye decreased by as much as 62.5% ± 9.5% (P < 0.001). Our data are compatible with the hypothesis that during 100% oxygen breathing a large amount of oxygen, consumed by the inner retina, comes from the choroid, which is supported by previous animal data. Interpretation of oxygen saturation data in retinal arteries and veins without quantifying blood flow is difficult. (ClinicalTrials.gov number, NCT01692821.).

Retinal blood flow and vascular reactivity in chronic smokers.

The aim of this study was to investigate the impact of cigarette smoking in otherwise healthy young individuals on retinal blood flow (RBF) and vascular reactivity (RVR). An automated gas flow controller (RespirAct) was used to achieve normoxic hypercapnia in 10 nonsmokers (mean age 28.9; SD 4.6 years) and nine smokers (mean age 27.55; SD 4.7 years). Retinal blood flow measurements were obtained using a prototype Doppler spectral-domain optical coherence tomographer (SD-OCT) and bidirectional laser Doppler velocimetry and simultaneous vessel densitometry during baseline, normoxic hypercapnia, and recovery. Group mean PETCO2 (end-tidal partial pressure of CO2) was increased by 15.9% in the nonsmoking group and by 15.7% in the smoking group, with a concomitant increase in PETO2 (end-tidal partial pressure of O2) by approximately 1.5% to 2% in both groups. In nonsmokers, retinal arteriolar diameter (P < 0.0001), centerline velocity (P = 0.0004), and blood flow (P < 0.0001) significantly increased during normoxic hypercapnia. Similarly, the venous area (P = 0.0418), venous velocity (P = 0.0068), and total venous RBF (P < 0.0001), as measured by the prototype Doppler SD-OCT, significantly increased. In smokers, normoxic hypercapnia resulted in a significant increase in velocity (P = 0.0019), flow (P = 0.0029), and total venous RBF (P = 0.002). Comparing smokers and nonsmokers, the percentage change in arteriolar diameter (P = 0.0379) and blood flow (P = 0.0101) was significantly lower in the smoking group. There was no significant difference in baseline PETCO2 level between smokers and nonsmokers. Retinal vascular reactivity in response to normoxic hypercapnia is significantly reduced in young, healthy smokers compared with nonsmokers.

Calculation of central retinal artery diameters from non‐invasive ocular haemodynamic measurements in type 1 diabetes patients

The aim of the study was to compare the diameter of the central retinal artery (CRA) between patients with diabetes mellitus and healthy subjects in vivo. CRA diameters were calculated from retinal haemodynamic parameters measured with noninvasive measurement techniques. Sixteen patients with type 1 diabetes with no or mild diabetic retinopathy and 16 age-matched healthy controls were included in this study. Total retinal blood flow was assessed by combining bidirectional laser Doppler velocimetry in all veins entering the optic disc with measurements of retinal vessel diameters using a Dynamic Vessel Analyser. Blood flow velocity in the CRA was measured with colour Doppler imaging (CDI). The diameter of the CRA in the optic nerve was then calculated for each subject using the individual ocular haemodynamic data. Calculated CRA diameters were significantly larger in patients with diabetes (180 ± 13 μm) compared with healthy controls (166 ± 10 μm, p = 0.001). No significant differences were found in retinal blood flow, retinal artery or vein diameters or mean flow velocity of the CRA. The data of the present study show increased calculated CRA diameter in patients with type 1 diabetes with no or mild retinopathy. Blood flow velocity measurements in retrobulbar vessels using CDI need to be interpreted with caution in terms of retinal blood flow, because no information about vessel diameters is obtained by this technique.

Retinal Blood Flow in Healthy Young Subjects

To characterize total retinal blood flow in a group of healthy subjects. Included in this study were 64 healthy volunteers. Retinal venous diameters were measured using a dynamic vessel analyzer. Retinal blood velocities were measured using bidirectional laser Doppler velocimetry. All vessels with a diameter of >60 μm entering the optic nerve head were measured. Total retinal blood flow was measured by summing up all data from the individually measured vessels. In a subgroup of 10 healthy subjects measurements were also taken from the arterioles, and results obtained for total retinal blood flow as measured both from retinal venules and from retinal arterioles were compared. Total retinal blood flow was 44.0 ± 13.3 μL/min. Retinal blood flow was highest in the temporal inferior quadrant, followed by the temporal superior quadrant, the nasal inferior quadrant, and the nasal superior quadrant (P < 0.001 each). In all quadrants retinal blood velocities were linearly correlated to vessel diameters. Retinal blood flow as measured in retinal venules (42.1 ± 13.0 μL/min) and in retinal arterioles (43.3 ± 12.1 μL/min) was similar (P = 0.16). The present study provides reference values for total retinal blood flow in 64 healthy subjects. The interindividual variability in retinal blood flow is high, making it unlikely that individual diagnostics can be based on measurements of retinal blood flow. Total retinal blood flow, however, may be important in risk stratification, which needs to be proven in future studies.

Relative magnitude of vascular reactivity in the major arterioles of the retina

The relative magnitude of vascular reactivity to inhaled gas stimuli in the major retinal arterioles has not been systematically investigated. The purpose of this study was to compare the magnitude of retinal vascular reactivity in response to inhaled gas provocation at equivalent measurement sites in the superior-, and inferior-, temporal retinal arterioles (STA, ITA). One randomly selected eye of each of 17 healthy volunteers (age 24.4 ± 4.7) was prospectively enrolled. Volunteers were connected to a sequential gas delivery circuit and a computer-controlled gas blender (RespirAct™, Thornhill Research Inc., Canada) and underwent an isocapnic hyperoxic challenge i.e. P(ET)O(2) of 500 mm Hg with P(ET)CO(2) maintained at 38 mm Hg during baseline and hyperoxia. Four retinal hemodynamic measurements were acquired using bi-directional laser Doppler velocimetry and simultaneous vessel densitometry (Canon Laser Blood Flowmeter, CLBF-100, Japan) at equivalent positions on the STA and ITA. Statistical analysis was performed using linear mixed-effect models. During the hyperoxic phase, the vessel diameter (STA p=0.004; ITA p=0.003), blood velocity (STA p<0.001; ITA p<0.001) and flow (STA p<0.001; ITA p<0.001) decreased in both the STA and the ITA relative to baseline. The diameter, velocity and flow were equivalent between STA and ITA at baseline and during hyperoxia; and their magnitude of change remained comparable with hyperoxia (p>0.05). The magnitude of retinal arteriolar vascular reactivity in response to isocapnic hyperoxic inhaled gas challenge was not significantly different between the STA and ITA. However, the correlation analysis did not reveal a significant relationship between the percentage changes in diameter, velocity and flow of the STA and ITA and did not demonstrate equal responses from the STA and ITA to gas provocation.

The impact of cataract on the quantitative, non-invasive assessment of retinal blood Flow

The aim of the study was to determine the impact of cataract on the quantitative, non-invasive assessment of retinal blood flow assessed by bidirectional laser Doppler flowmetry and simultaneous vessel densitometry. Ten patients scheduled for extracapsular cataract extraction using phacoemulsification and intraocular lens implantation between the ages of 61 and 84 (mean age 73 years, SD ± 8) were prospectively recruited. Two visits were required to complete the study; one visit prior to extracapsular cataract extraction and one at least 6 weeks after the surgery to allow for sufficient postoperative recovery. The severity of cataract was documented using the Lens Opacity Classification System (LOCS, III) at the first visit. Retinal arteriolar hemodynamics were measured at both visits using the high-intensity setting of the Canon Laser Blood Flowmeter. All eyes showed no clinical signs of postoperative intraocular inflammation. The quantitative assessment of retinal arteriolar diameter and blood flow were reduced following extracapsular cataract extraction (Wilcoxon signed-rank test, p = 0.022 and p=0.028, respectively); however, centreline blood velocity was not significantly changed (Wilcoxon signed-rank test, p=0.074). Intraocular pressure was unchanged pre- and postcataract extraction. Retinal vessel densitometry assessment in the presence of cataract results in the erroneous elevation of the diameter measurement and thereby the calculation of blood flow. The bidirectional Doppler assessment of blood velocity appears to be more robust to light scatter induced by cataract. Care needs to be exercised in the interpretation of studies of retinal vessel diameter or blood flow that utilize similar densitometry techniques.

In Vivo Measurement of Blood Velocity in Human Major Retinal Vessels Using the Laser Speckle Method

To develop a simple, noninvasive method of determining blood velocity and flow through human retinal vessels (RVs), by using the laser speckle method and validating the results by bidirectional laser Doppler velocimetry (LDV). The square blur rate (SBR), a quantitative blurring index of the laser speckle pattern that parallels the velocity of moving substances, obtained from blood flowing through glass capillary tubes (RV analogues), correlated with tube diameter, background reflectance and absorption, flow velocity, and the SBR obtained from blood flowing through underlying glass capillary tubes (choroidal vessel analogues). A nomogram was constructed to calculate the blood velocity in human RVs from the SBR values obtained in vivo. Blood velocities in RVs were determined in 12 normal eyes by using the laser speckle method and bidirectional LDV. Measurements were performed twice at the same site at 1-hour intervals. Measurements from a temporal superior artery (n = 12; mean ± SD) were blood velocity (V(mean)), 41.7 ± 4.2 mm/s; flow, 13.0 ± 3.2 μL/min; and diameter, 119.5 ±15.7 μm and time to complete one measurement, 65 ± 18 seconds, with the laser speckle apparatus; and V(mean), 37.7 ± 6.7 mm/s; flow, 11.7 ±3.0 μL/min; diameter, 111.1 ±16.6 μm; and measurement time, 112 ± 25 seconds, with the bidirectional LDV apparatus. The results obtained by the two methods correlated with each other (V(mean), r = 0.59, P = 0.023; flow, r = 0.83, P = 0.005; and diameter, r = 0.56, P = 0.032). The coefficients of reproducibility for V(mean), blood flow, and diameter measurement were 9.5% ± 2.5%, 10.5% ± 3.2%, and 5.3% ± 2.7% for the former and 15.3% ± 4.2%, 18.5% ± 4.1%, and 6.2% ± 2.2% for the latter, respectively. The laser speckle method accurately and reproducibly determines blood velocity in human RVs in less time than the LDV apparatus requires.

Twelve‐hour reproducibility of retinal and optic nerve blood flow parameters in healthy individuals

The aim of the present study was to investigate the reproducibility and potential diurnal variation of optic nerve head and retinal blood flow parameters in healthy individuals over a period of 12 hr. We measured optic nerve head and retinal blood flow parameters in 16 healthy male non-smoking individuals at five time-points during the day (08:00, 11:00, 14:00, 17:00 and 20:00 hr). Outcome parameters were perimacular white blood cell flux (as assessed with the blue field entoptic technique), blood velocities in retinal veins (as assessed with bi-directional laser Doppler velocimetry), retinal arterial and venous diameters (as assessed with the retinal vessel analyser), optic nerve head blood flow, volume and velocity (as assessed with single point and scanning laser Doppler flowmetry) and blood velocities in the central retinal artery (as assessed with colour Doppler imaging). The coefficient of variation and the maximum change from baseline in an individual were calculated for each outcome parameter. No diurnal variation in optic nerve head or retinal blood flow was observed with any of the techniques employed. Coefficients of variation were between 1.6% and 18.5% for all outcome parameters. The maximum change from baseline in an individual was much higher, ranging from 3.7% to 78.2%. Our data indicate that in healthy individuals the selected techniques provide adequate reproducibility to be used in clinical studies. However, in patients with eye diseases and reduced vision the reproducibility may be considerably worse.

Effect of systemic moxaverine on ocular blood flow in humans

A number of common eye diseases are associated with ocular perfusion abnormalities. The present study aimed to investigate whether systemically administered moxaverine improves ocular blood flow. Sixteen healthy volunteers were studied in this randomized, double-masked, placebo-controlled, two-way crossover study. Moxaverine in a dose of 150 mg was administered i.v. Ocular haemodynamic parameters were measured before and after drug administration. Retinal arterial and venous diameters were measured with a retinal vessel analyser. Retinal blood velocity was assessed using laser Doppler velocimetry and choroidal and optic nerve head blood flow was measured with laser Doppler flowmetry. Moxaverine increased choroidal blood flow (22.6 ± 27.9%), an effect which was significant versus placebo (p = 0.015). Red blood cell velocity in retinal veins tended to increase by 13.6 ± 13.3% after infusion of moxaverine, but this effect was not significant compared with placebo (p = 0.25). In the optic nerve head moxaverine also tended to increase blood flow (11.8 ± 12.7%), but, again, this effect was not significant versus placebo (p = 0.12). Neither moxaverine nor placebo had an effect on retinal arterial diameters. In retinal veins moxaverine tended to induce vasodilation (2.6 ± 2.8%) and to increase blood flow (19.6 ± 16.5%), but these effects were not significant (both p = 0.12). The present study indicates an increase in choroidal blood flow after systemic infusion of a single dose of moxaverine in healthy subjects. Further studies are warranted to investigate whether these effects are also seen after longterm treatment in patients with ocular vascular disease.

Effects of dopamine on retinal and choroidal blood flow parameters in humans

Aim:To investigate the effect of dopamine on retinal and choroidal blood flow in humans.Methods:We investigated the effect of two doses of intravenous dopamine (5 and 10 µg/kg/min) via a randomised...

Effects of Pentoxifylline and Alprostadil on Ocular Hemodynamics in Healthy Humans

Alprostadil, a prostaglandin (PG)E(1) analogue and pentoxifylline, an alkylxanthine derivate, have been shown to exert vasodilatory effects in several vascular beds. The purpose of the present study was to investigate the effect of PGE(1) and pentoxifylline on the ocular circulation. A placebo-controlled, double-masked, three-way, crossover study was performed in 15 healthy male subjects. Subjects received pentoxifylline (300 mg), PGE(1) (alprostadil 60 mug), or placebo intravenously over 2 hours on three trial days. Choroidal red blood cell flow was assessed with laser Doppler flowmetry and pulsatile choroidal blood flow with laser interferometric measurement of fundus pulsation amplitude (FPA). Retinal blood cell flow was calculated based on the measurements of maximum erythrocyte velocity in a retinal vein assessed with bidirectional laser Doppler velocimetry, and diameter measurements of retinal vessels were obtained with a retinal vessel analyzer. Pentoxifylline increased FPA by 15.4% +/- 1.1% (P < 0.001 versus placebo and baseline). Alprostadil tended to increase FPA, but this effect did not reach the level of significance (P = 0.07 versus placebo). Choroidal blood flow as measured with laser Doppler flowmetry tended to increase during pentoxifylline and PGE(1) infusion by 8.9% +/- 2.9% (P = 0.062) and 4.5% +/- 6.2% (P = 0.29), respectively, but none of these effects was significant. The drugs under study had no effect on mean red blood cell velocity in retinal veins, on retinal vessel diameters, intraocular pressure, blood pressure, or pulse rate. PGE(1) did not alter the parameters of retinal or choroidal circulation in healthy subjects. Pentoxifylline increased FPA, but did not change choroidal blood flow as measured with laser Doppler flowmetry and did not affect retinal blood flow parameters. Accordingly, neither pentoxifylline nor PGE(1) appears to be suitable to improve ocular blood flow in healthy subjects. Whether long-term treatment with alprostadil would improve choroidal blood flow in patients with vascular disease remains to be established.

Inhaled Carbon Monoxide Increases Retinal and Choroidal Blood Flow in Healthy Humans

It has been hypothesized that carbon monoxide (CO) acts as an important vascular paracrine factor and plays a role in blood flow regulation in several tissues. The present study investigated the effect of inhaled CO on retinal and choroidal blood flow. Fifteen healthy male volunteers were studied in a randomized, double-masked, placebo-controlled design with washout periods of at least 1 week between study days. CO in a dose of 500 ppm or placebo (synthetic air without CO) was inhaled for 60 minutes. Ocular hemodynamics were measured at baseline and at 30 and 60 minutes after start of inhalation. Retinal vessel diameters were measured with a retinal vessel analyzer. RBC velocity was assessed using bidirectional laser Doppler velocimetry. Retinal blood flow was calculated based on retinal vessel diameters and RBC velocity. Fundus pulsation amplitude (FPA) was measured using laser interferometry, and submacular choroidal blood flow using laser Doppler flowmetry. Breathing of CO significantly increased carboxyhemoglobine, from 1.2 +/- 0.5% to 8.5 +/- 0.9% and 9.4 +/- 0.6% at the two time points, respectively (P < 0.01). The diameter of retinal arteries increased by +3.5 +/- 3.8% and +4.2 +/- 3.9% (P < 0.01) in response to CO inhalation. In retinal veins, CO also induced an increase in diameter of +4.3 +/- 3.0% and +4.8 +/- 5.0%, respectively (P < 0.01). By contrast, placebo did not influence retinal vessel diameter. RBC velocity tended to increase during CO inhalation (+8 +/- 22%), but this effect did not reach the level of significance (P = 0.1). Calculated retinal blood flow increased significantly by +12 +/- 5% (P < 0.02). FPA increased after breathing CO by +20 +/- 20% and +26 +/- 21% at the two time points, respectively (P < 0.01). Subfoveal choroidal blood flow increased by +14 +/- 9% and +15 +/- 9% during breathing of CO (P < 0.01). This experiment demonstrated that retinal and choroidal blood flow increase during inhalation of CO. Whether this increase is caused by tissue hypoxia or a yet unknown mechanism has to be clarified.

Effect of histamine and cimetidine on retinal and choroidal blood flow in humans

Intravenous administration of histamine causes an increase in choroidal blood flow and retinal vessel diameter in healthy subjects. The mechanism underlying this effect remains to be elucidated. In the present study, we hypothesized that H2 receptor blockade alters hemodynamic effects of histamine in the choroid and retina. Eighteen healthy male nonsmoking volunteers were included in this randomized, double-masked, placebo-controlled two-way crossover study. Histamine (0.32 microg.kg(-1).min(-1) over 30 min) was infused intravenously in the absence (NaCl as placebo) or presence of the H2 blocker cimetidine (2.3 mg/min over 50 min). Ocular hemodynamic parameters, blood pressure, and intraocular pressure were measured before drug administration, after infusion of cimetidine or placebo, and after coinfusion of histamine. Subfoveal choroidal blood flow and fundus pulsation amplitude were measured with laser-Doppler flowmetry and laser interferometry, respectively. Retinal arterial and venous diameters were measured with a retinal vessel analyzer. Retinal blood velocity was assessed with bidirectional laser-Doppler velocimetry. Histamine increased subfoveal choroidal blood flow (+14 +/- 15%, P < 0.001), fundus pulsation amplitude (+11 +/- 5%, P < 0.001), retinal venous diameter (+3.0 +/- 3.6%, P = 0.002), and retinal arterial diameter (+2.8 +/- 4.2%, P < 0.01) but did not change retinal blood velocity. The H2 antagonist cimetidine had no significant effect on ocular hemodynamic parameters. In addition, cimetidine did not modify effects of histamine on choroidal blood flow, fundus pulsation amplitude, retinal venous diameter, and retinal arterial diameter compared with placebo. The present data confirm that histamine increases choroidal blood flow and retinal vessel diameters in healthy subjects. This ocular vasodilator effect of histamine is, however, not altered by administration of an H2 blocker. Whether the increase in blood flow is mediated via H1 receptors or other hitherto unidentified mechanisms remains to be elucidated.

Intravenous Administration of L-Arginine Increases Retinal and Choroidal Blood Flow

Nitric oxide (NO) is among the most important regulators of ocular perfusion. L-arginine, an amino acid, is the precursor of NO synthesis. The aim of the present study was to determine whether administration of L-arginine affects ocular blood flow. L-arginine (1 g/min) or placebo was administered intravenously for 30 minutes in 12 healthy volunteers in a randomized, double-masked, two-way cross-over design. Ocular hemodynamics were measured before, in the last 10 minutes of the infusion period, as well as 30 minutes after cessation of the administration. Retinal vessel diameters were measured with a retinal vessel analyzer, red blood cell velocities with bidirectional laser Doppler velocimetry, and pulsatile choroidal blood flow was measured using laser interferometry. L-arginine significantly decreased mean arterial pressure by -8 +/- 5% and -6 +/- 7% at the two time points (P < .01), respectively. Intravenous administration of L-arginine increased choroidal blood flow by +10 +/- 6% and +12 +/- 7%, respectively. Retinal venous diameters decreased by -2.5 +/- 2.1% and -1.4 +/- 2.7%, respectively, whereas red blood cell velocity significantly increased after administration of L-arginine by +22 +/- 23% and +20 +/- 19% at the two time points. Thus, calculated blood flow in retinal veins, increased by +21 +/- 18% and +21 +/- 19% before and after the end of L-arginine infusion. Intravenous administration of L-arginine increases retinal and choroidal blood flow in healthy volunteers. Whether this effect is related to an increased NO-production or an unidentified mechanism remains to be clarified. However, administration of L-arginine might be an interesting new approach to therapeutically increase ocular blood flow in ocular vascular disease.

Diffuse luminance flicker increases blood flow in major retinal arteries and veins

It has been shown that diffuse luminance flicker increases optic nerve head blood flow. The current study has been performed to quantify changes in retinal blood flow during flicker stimulation. In a group of 11 healthy volunteers, red blood cell velocity and retinal vessel diameters were assessed with bi-directional laser Doppler velocimetry and the Zeiss retinal vessel analyzer before, during and after stimulation with diffuse luminance flicker. Retinal blood flow was calculated for each condition. Flicker stimulation increased retinal blood flow by +59 +/- 20% (p<0.01) in arteries and by +53 +/- 25% (p<0.01) in retinal veins. These results demonstrate that diffuse luminance flicker increases retinal blood flow in the human retina.

Influence of exercise induced hyperlactatemia on retinal blood flow during normo- and hyperglycemia

Purpose. Short term hyperglycemia has previously been shown to induce a blood flow increase in the retina. The mechanism behind this effect is poorly understood. We set out to investigate whether exercise-induced hyperlactatemia may alter the response of retinal blood flow to hyperglycemia. Methods. We performed a randomized, controlled two-way cross over study comprising 12 healthy subjects, performed a 6-minutes period of dynamic exercise during an euglcaemic or hyperglycaemic insulin clamp. Retinal blood flow was assessed by combined vessel size measurement with the Zeiss retinal vessel analyzer and measurement of red blood cell velocities using bi-directional laser Doppler velocimetry. Retinal and systemic hemodynamic parameters were measured before, immediately after and 10 and 20 minutes after isometric exercise. Results. On the euglycemic study day retinal blood flow increased after dynamic exercise. The maximum increase in retinal blood flow was observed 10 minutes after the end of exercise when lactate plasma concentration peaked. Hyperglycemia increased retinal blood flow under basal conditions, but had no incremental effect during exercise induced hyperlactatemia. Conclusions. Our results indicate that both lactate and glucose induce an increase in retinal blood flow in healthy humans. This may indicate a common pathway between glucose and lactate induced blood flow changes in the human retina.

Regulation of human retinal blood flow by endothelin-1

There is evidence from in vitro and animal studies that endothelin is a major regulator of retinal blood flow. We set out to characterize the role of the endothelin-system in the blood flow control of the human retina. Two studies in healthy subjects were performed. The study design was randomized, placebo-controlled, double-masked, balanced, two-way crossover in protocol A and three way-way crossover in protocol B. In protocol A 18 healthy male subjects received intravenous endothelin-1 (ET-1) in a dose of 2.5 ng kg (-1)min(-1) for 30 min or placebo on two different study days and retinal vessel diameters were measured. In protocol B 12 healthy male subjects received ET-1 in stepwise increasing doses of 0, 1.25, 2.5 and 5 ng kg (-1)min(-1) (each infusion step over 20 min) in co-infusion with the specific ET(A)-receptor antagonist BQ123 (60 microg min (-1)) or placebo or BQ123 alone investigating retinal vessel diameters, retinal blood velocity and retinal blood flow. Measurements of retinal vessel size were done with the Zeiss retinal vessel analyzer. Measurements of blood velocities were done with bi-directional laser Doppler velocimetry. From these measurements retinal blood flow was calculated. In protocol A exogenous ET-1 tended to decrease retinal arterial diameter, but this effect was not significant versus placebo. No effect on retinal venous diameter was seen. In protocol B retinal venous blood velocity and retinal blood flow was significantly reduced after administration of exogenous ET-1. These effects were significantly blunted when BQ-123 was co-administered. By contrast, BQ-123 alone had no effect on retinal hemodynamic parameters. Concluding, BQ123 antagonizes the effects of exogenously administered ET-1 on retinal blood flow in healthy subjects. In addition, the results of the present study are compatible with the hypothesis that ET-1 exerts its vasoconstrictor effects in the retina mainly on the microvessels.