Sildenafil induces retinal vasodilatation in healthy subjects

BACKGROUND: The cardiovascular effects of sildenafil (Viagra), a selective inhibitor of phosphodiesterase type 5 (PDE5), have been extensively studied. However, its effect on human retinal arteries and veins has not yet been investigated. The effect of a single dose administration of sildenafil on the retinal vessel diameters of healthy subjects was evaluated. METHODS: Sildenafil 50 mg was administered to 10 healthy subjects (male:female = 4:6; mean age 31 (SD 6) years). The diameters of retinal arteries and veins were measured by means of a retinal vessel analyser (RVA) immediately before and at 30, 60, 90, and 120 minutes after sildenafil uptake. Blood pressure, heart rate, and intraocular pressure were monitored in parallel. RESULTS: A significant increase of 5.8% (p<0.001) in both retinal arterial and venous diameters was found 30 minutes after sildenafil uptake. The diameters returned to baseline after 120 minutes. A mild systemic hypotensive response was seen. Changes in heart rate and intraocular pressure were not observed. CONCLUSION: Sildenafil causes a significant dilatation of retinal arteries and veins in healthy subjects. A possible role for PDE5 in the regulation of retinal blood flow is implicated.     

Effect of noradrenaline on retinal blood flow in healthy subjects

PURPOSE: To gain insight into the role of circulating catecholamines on retinal blood flow in vivo. DESIGN: Nonrandomized, open, crossover design. PARTICIPANTS: In 10 healthy male subjects, tyramine and noradrenaline were administered in stepwise increasing doses. These doses were selected to induce comparable changes in systemic blood pressure. METHODS: During each infusion step, retinal vessel diameter and retinal venous blood speed were measured with the Zeiss retinal vessel analyzer (Zeiss, Jena, Germany) and laser Doppler velocimetry, respectively. MAIN OUTCOME MEASURES: Retinal blood flow through a major temporal vein was calculated. RESULTS: As expected, tyramine and noradrenaline induced a systemic hypertensive response. Tyramine caused a moderate increase in noradrenaline plasma levels, whereas exogenous noradrenaline increased noradrenaline plasma levels more than 10-fold. Nevertheless, neither tyramine nor noradrenaline induced any effect on retinal hemodynamic parameters. CONCLUSIONS: These data indicate that even high levels of circulating noradrenaline have little impact on retinal vascular tone and retinal blood flow. Hence, the adrenergic system appears not to play a major role in retinal blood flow regulation.     

Nimodipine plasma concentration and retinal blood flow in healthy subjects

PURPOSE: Calcium antagonists are strong vasodilators, and nimodipine is known to improve cerebral blood flow. The purpose of this study was to measure retinal blood flow and nimodipine plasma concentrations during repeated oral dosing. METHODS: In a double-blind, two-way, crossover study, 20 healthy subjects (mean age, 22.8 +/- 3.7 years) underwent examination of retinal perfusion and nimodipine plasma concentrations. In a placebo-controlled fashion, nimodipine was orally administered at a dosage of 30 mg three times a day for two periods of 5 days including a 9-day washout interval. At days 1, 5, 15, and 19, plasma concentrations of nimodipine and retinal perfusion were measured 11 times within 3 hours. Stereoselective analysis of nimodipine plasma concentrations was performed with the use of liquid chromatography-tandem mass spectrometry. Scanning laser Doppler flowmetry was used to measure the microcirculation of the juxtapapillary retina. Perfusion images were evaluated with the automatic full-field evaluation procedure (AFFPIA). RESULTS: Areas under the plasma concentration versus time curves were similar at day 1 and day 5 of nimodipine administration (t test: P = 0.64). Values of C(max) displayed a large interindividual variance and ranged from 0 ng/mL to 57.5 ng/mL. On average, maximum nimodipine plasma concentrations (C(max)) were 16.6 +/- 14.9 ng/mL and 12.0 +/- 10.3 ng/mL at day 1 and day 5, respectively (P = 0.068). They were observed at 81 +/- 50 and at 93 +/- 40 minutes (t(max)) after the administration of nimodipine at day 1 and day 5, respectively (P = 0.43). Retinal microcirculation was greater after nimodipine than after placebo, as reflected in significantly larger areas under the curves of percentage change in blood flow from baseline versus time (P < 0.01). The maximum increase of retinal blood flow from baseline was significantly more pronounced after nimodipine (28.5% +/- 14.4% and 39.6% +/- 21.4% at day 1 and day 5, respectively) than after placebo (20.5% +/- 16.8% and 31.9% +/- 14.6% at day 1 and day 5, respectively; P = 0.032). CONCLUSIONS: Oral nimodipine significantly increases retinal perfusion in healthy subjects.     

Effect of intravenous administration of sodium-lactate on retinal blood flow in healthy subjects

PURPOSE: The present study was designed to investigate the effect of intravenously administered sodium lactate on ocular blood flow. METHODS: Twelve healthy male volunteers received either sodium lactate (0.6 mol/L) or physiologic saline solution in a randomized, double-masked, two-way crossover study. Sodium lactate or placebo were administered at an infusion speed of 500 and 1000 mL/h for 30 minutes each. Blood flow measurements were performed in the last 10 minutes of the infusion periods. Retinal blood flow was calculated based on the measurement of maximum erythrocyte velocity, assessed with bidirectional laser Doppler velocimetry, and retinal vessel diameter obtained with a retinal vessel analyzer. Choroidal blood flow was assessed with laser Doppler flowmetry and laser interferometric measurement of fundus pulsation amplitude. RESULTS: Administration of lactate increased blood lactate concentration from 1.3 +/- 0.4 to 3.9 +/- 0.7 mmol/L (P < 0.001) and to 7.1 +/- 1.4 mmol/L (P < 0.001) at infusion speeds of 500 and 1000 mL/h, respectively. At these blood lactate concentrations, retinal blood flow increased by 15% +/- 20% and by 24% +/- 37% (ANOVA, P = 0.01). Fundus pulsation amplitude increased by 3% +/- 6% and 10% +/- 5% (ANOVA, P = 0.04) at the two plasma lactate concentrations. Subfoveal choroidal blood flow measured with laser Doppler flowmetry tended to increase by 10% +/- 15% and 13% +/- 20% (ANOVA, P = 0.19), but this effect was not significant. Infusion of sodium lactate induced alkalosis in arterial blood taken from the earlobe (7.41 +/- 0.03 at baseline; 7.50 +/- 0.03 during lactate infusion; P = 0.001). CONCLUSIONS: The data indicate that intravenously administered sodium lactate increases retinal blood flow. Whether this is related to a cytosolic redox impairment or to other hitherto unidentified mechanism remains to be clarified. Further studies are needed to determine whether lactate plays a role in regulation of choroidal blood flow.     

Hyperglycemia affects flicker-induced vasodilation in the retina of healthy subjects

Flickering light stimulation of retinal photoreceptors induces retinal vessel dilation in humans. In the present study the effect of high blood glucose levels on this neuro-vascular mechanism was investigated in 12 healthy young male subjects. Blood glucose levels were consecutively increased during 30 min to 100, 200 and 300 mg/dl and kept at the respective level for the following 30 min using hyperglycemic insulin clamps. Eight Hertz flickering light was applied to the fundus at the end of each glucose plateau during continuous retinal vessel diameter measurements with the Zeiss retinal vessel analyser (RVA). During normoglycemia (100 mg/dl) flickering light induced a significant vasodilation of retinal arteries (+2.8+/-0.4%, p<0.0001) and veins (+2.6+/-0.4%, p<0.0001). At 300 mg/dl blood glucose the flicker response in retinal veins was significantly decreased by 55% (p=0.015 versus 100 mg/dl). The modified RVA employed in the present study provides high sensitivity and is capable of studying flicker-induced retinal vasodilation. Using this technique the present study confirms that flickering light stimulation of the human retina induces vasodilation in retinal vessels in healthy subjects. In addition, our data indicate that the retinal vessel response to flickering light stimulation is significantly reduced during hyperglycemia in humans. The relevance of this finding for diabetes-related eye disease remains to be shown.     

Effects of orally administered moxaverine on ocular blood flow in healthy subjects

Background

To investigate the effect of orally administered moxaverine (Kollateral forte®) on ocular blood flow in young healthy subjects.

Methods

Sixteen healthy subjects (eight male/eight female) aged between 20 and 32 years were included in this placebo-controlled, double-masked, two-way crossover study. Volunteers received 900 mg moxaverine–hydrochloride administered orally in three equal doses or placebo identical in appearance on 2 study days. Outcome variables were measured at baseline and 5 h after first drug administration. Laser Doppler flowmetry was used to assess choroidal and optic nerve head blood flow. Blood velocities in the retrobulbar vessels were measured with color Doppler imaging.

Results

Neither moxaverine nor placebo changed mean arterial pressure or intraocular pressure. Neither moxaverine nor placebo had an effect on choroidal (moxaverine: by 9.5?±?17.2 %, placebo 3.8?±?18.8 %, p?=?0.54 between groups) or optic nerve head blood flow (moxaverine: 4.8?±?10.4 %, placebo: 1.8?±?10.9 %, p?=?0.52 between groups). Similarly, administration of moxaverine did not change blood flow velocities or calculated resistance index in the retrobulbar vessels compared to placebo.

Conclusion

The data of the present study indicate that orally administered moxaverine does not increase ocular blood flow. This is in contrast to previous findings, where parenteral administration of moxaverine lead to a significant increase in choroidal blood flow and blood flow velocities in the retrobulbar vessels. The reason for these differing results is unclear, but may be related to the low bioavailability after oral administration.     

Changes in central retinal artery blood flow after ocular warming and cooling in healthy subjects

Context:

Retinal perfusion variability impacts ocular disease and physiology.

Aim:

To evaluate the response of central retinal artery (CRA) blood flow to temperature alterations in 20 healthy volunteers.

Setting and Design:

Non-interventional experimental human study.

Materials and Methods:

Baseline data recorded: Ocular surface temperature (OST) in °C (thermo-anemometer), CRA peak systolic velocity (PSV) and end diastolic velocity (EDV) in cm/s using Color Doppler. Ocular laterality and temperature alteration (warming by electric lamp/cooling by ice-gel pack) were randomly assigned. Primary outcomes recorded were: OST and intraocular pressure (IOP) immediately after warming or cooling and ten minutes later; CRA-PSV and EDV at three, six and nine minutes warming or cooling.

Statistical Analysis:

Repeated measures ANOVA.

Results:

(n = 20; μ ± SD): Pre-warming values were; OST: 34.5 ± 1.02°C, CRA-PSV: 9.3 ± 2.33 cm/s, CRA-EDV: 4.6 ± 1.27 cm/s. OST significantly increased by 1.96°C (95% CI: 1.54 to 2.37) after warming, but returned to baseline ten minutes later. Only at three minutes, the PSV significantly rose by 1.21 cm/s (95% CI: 0.51to1.91). Pre-cooling values were: OST: 34.5 ± 0.96°C, CRA-PSV: 9.7 ± 2.45 cm/s, CRA-EDV: 4.7 ± 1.12 cm/s. OST significantly decreased by 2.81°C (95% CI: −2.30 to −3.37) after cooling, and returned to baseline at ten minutes. There was a significant drop in CRA-PSV by 1.10cm/s (95% CI: −2.05 to −0.15) and CRA-EDV by 0.81 (95% CI: −1.47 to −0.14) at three minutes. At six minutes both PSV (95% CI: −1.38 to −0.03) and EDV (95% CI: −1.26 to −0.02) were significantly lower. All values at ten minutes were comparable to baseline. The IOP showed insignificant alteration on warming (95% CI of difference: −0.17 to 1.57mmHg), but was significantly lower after cooling (95% CI: −2.95 to −4.30mmHg). After ten minutes, IOP had returned to baseline.

Conclusion:

This study confirms that CRA flow significantly increases on warming and decreases on cooling, the latter despite a significant lowering of IOP.     

Reactivity of retinal blood flow to 100% oxygen breathing after lipopolysaccharide administration in healthy subjects

Administration of low doses of Escherichia coli endotoxin (LPS) to humans enables the study of inflammatory mechanisms. The purpose of the present study was to investigate the retinal vascular reactivity after LPS infusion. In a randomized placebo-controlled cross-over study, 18 healthy male volunteers received 20IU/kg LPS or placebo as an intravenous bolus infusion. Outcome parameters were measured at baseline and 4h after LPS/placebo administration. At baseline and at 4h after administration a short period of 100% oxygen inhalation was used to assess retinal vasoreactivity to this stimulus. Perimacular white blood cell velocity, density and flux were assessed with the blue-field entoptic technique, retinal branch arterial and venous diameters were measured with a retinal vessel analyzer and red blood cell velocity in retinal branch veins was measured with laser Doppler velocimetry. LPS is associated with peripheral blood leukocytosis and increased white blood cell density in ocular microvessels (p<0.001). In addition, retinal arterial (p=0.02) and venous (p<0.01) diameters were increased. All retinal hemodynamic parameters showed a decrease during 100% oxygen breathing. This decrease was significantly blunted by LPS for all retinal outcome parameters except venous diameter (p=0.04 for white blood cell velocity, p=0.0002 for white blood cell density, p<0.0001 for white blood cell flux, p=0.01 for arterial diameter, p=0.02 for red blood cell velocity and p=0.006 for red blood cell flux). These data indicate that LPS-induced inflammation induces vascular dysregulation in the retina. This may provide a link between inflammation and vascular dysregulation. Further studies are warranted to investigate whether this model may be suitable to study inflammation induced vascular dysregulation in the eye.     

Retinal blood flow and systemic blood pressure in healthy young subjects

BACKGROUND: The aim of the present study was to investigate the association between systemic blood pressure and retinal blood flow in healthy young subjects. METHODS: Three independent study cohorts were included. A cross-sectional study was performed in 420 young male subjects with systolic blood pressure < 160 mmHg and diastolic blood pressure <100 mmHg. Retinal white blood cell flux (n=210) and blood velocity in the central retinal artery (n=210) were measured. In addition, a longitudinal study was performed in 40 young male subjects in whom retinal and systemic haemodynamic parameters were measured thrice within 6 weeks. Retinal white blood cell flux was measured with the blue-field entoptic technique. Blood flow velocity in the central retinal artery was measured by means of colour Doppler imaging. RESULTS: Retinal white blood cell flux (r=0.262; P<0.001) and mean flow velocity in the central retinal artery (r=0.174, P=0.010) were significantly associated with mean arterial pressure in the cross-sectional study. In the longitudinal study retinal white blood cell flux and mean flow velocity in the central retinal artery were also correlated with systemic blood pressure. CONCLUSIONS: Our data indicate a slight but significant increase in retinal blood flow with blood pressure. Whether this is of clinical relevance in eye diseases with altered retinal perfusion, such as diabetic retinopathy, remains to be established.     

Effects of systemic NO synthase inhibition on choroidal and optic nerve head blood flow in healthy subjects

PURPOSE: There is evidence from animal studies that nitric oxide (NO) is a major determinant of ocular blood flow. In humans NO synthase inhibition reduces pulsatile choroidal blood flow, but no data on optic nerve head (ONH) vasculature are available yet. The goal of this study was to investigate the effects of NO synthase inhibition on human choroidal and ONH blood flow using laser Doppler flowmetry. METHODS: The study design was a randomized, placebo-controlled, double-masked, balanced three-way crossover. On separate study days 12 healthy male subjects received infusions of N:(G)-nitro-L-arginine (L-NMMA; either 3 mg/kg over 5 minutes followed by 30 microg/kg per minute over 55 minutes or 6 mg/kg over 5 minutes followed by 60 microg/kg per minute over 55 minutes) or placebo. The effects of L-NMMA or placebo on choroidal and ONH blood flow were measured with laser Doppler flowmetry. In addition, laser interferometric measurement of fundus pulsation was performed in the macula to assess pulsatile choroidal blood flow. RESULTS: L-NMMA reduced all outcome parameters in the choroid and the ONH. The higher dose of L-NMMA caused a significant decrease in blood flow in the choroid (-26% +/- 9%; P: < 0.001) and the ONH (-20% +/- 16%; P: < 0.001) as evidenced from laser Doppler flowmetry and a significant decrease in fundus pulsation amplitude (-26% +/- 5%; P: < 0.001). CONCLUSIONS: These results indicate that NO is continuously released in human choroidal and ONH vessels.     

Twelve hour reproducibility of choroidal blood flow parameters in healthy subjects

Aims/background: To investigate the reproducibility and potential diurnal variation of choroidal blood flow parameters in healthy subjects over a period of 12 hours. METHODS: The choroidal blood flow parameters of 16 healthy non-smoking subjects were measured at five time points during the day (8:00, 11:00, 14:00, 17:00, and 20:00). Outcome parameters were pulsatile ocular blood flow as assessed by pneumotonometry, fundus pulsation amplitude as assessed by laser interferometry, blood velocities in the opthalmic and posterior ciliary arteries as assessed by colour Doppler imaging, and choroidal blood flow, volume, and velocity as assessed by fundus camera based laser Doppler flowmetry. The coefficient of variation and the maximum change from baseline in an individual were calculated for each outcome parameter. RESULTS: None of the techniques used found a diurnal variation in choroidal blood flow. Coefficients of variation were within 2.9% and 13.6% for all outcome parameters. The maximum change from baseline in an individual was much higher, ranging from 11.2% to 58.8%. CONCLUSIONS: These data indicate that in healthy subjects the selected techniques provide adequate reproducibility to be used in clinical studies. Variability may, however, be considerably higher in older subjects or subjects with ocular disease. The higher individual differences in flow parameter readings limit the use of the techniques in clinical practice. To overcome problems with measurement validity, a clinical trial should include as many choroidal blood flow outcome parameters as possible to check for consistency.     

Inhaled carbon monoxide increases retinal and choroidal blood flow in healthy humans

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.     

The effect of sildenafil on ocular blood flow

Sildenafil is a potent phosphodiesterase (PDE) 5 inhibitor that is used for patients with erectile dysfunction. Sildenafil induces vasodilation in selected smooth muscle via increased levels of guanosine 3', 5' cyclic monophosphate and increase in nitric oxide. The vasodilatory effects of the PDE 5 inhibitors led us to review its effect on the ocular vasculature. Sildenafil appears to increase blood flow velocity significantly in the retrobulbar and choroidal circulation. Most studies suggest an increase in choroidal blood flow, with a lesser effect on the retinal vasculature.     

The effects of sildenafil on ocular blood flow

PURPOSE: To investigate the effects of sildenafil, a popular new drug in the treatment of erectile dysfunction, on ocular blood flow. METHODS: This study was designed as a prospective, double-blind, placebo-controlled study. Twenty participants with erectile dysfunction were given a single oral dose of 100 mg sildenafil, while 10 participants with erectile dysfunction were given placebo. All the participants underwent routine systemic and ophthalmological examinations. Intraocular pressure, systolic and diastolic blood pressure and ocular blood flow (ophthalmic, central retinal, short posterior ciliary arteries) were measured in both eyes before and 1 hour after the dose of sildenafil or placebo. Ocular blood flow measurements were performed using colour Doppler ultrasonography. RESULTS: None of the parameters were significantly different between the groups before study drug intake. Although central retinal artery velocities were not changed, ophthalmic artery and short posterior ciliary artery peak systolic velocity, end-diastolic velocity, and mean velocity values were significantly increased 1 hour after drug intake in the sildenafil group compared to the placebo group (p < 0.05). CONCLUSION: Sildenafil causes a significant increase in blood flow in these arteries. A possible role of inhibition of phosphodiesterase-5 in vascular smooth muscles by sildenafil is implicated. Further studies are needed to investigate the effects of sildenafil on ocular blood flow in patients with senile macular degeneration, diabetic retinopathy and glaucoma.     

Retinal blood flow autoregulation after dynamic exercise in healthy young subjects

PURPOSE: To evaluate the retinal blood flow before and after the increase in systemic blood pressure to assess the autoregulation in healthy young subjects. METHODS: Twenty eyes of 20 healthy volunteers were examined. The retinal blood flow was assessed by a Heidelberg retina flowmeter (HRF), while the systemic pressure was assessed by a portable electronic sphygmomanometer. Furthermore intraocular pressure (IOP) was always measured by a Goldmann tonometer immediately after HRF assessments. All measurements of physiological and flow parameters were performed with the subjects seated at rest and then immediately after stair climbing. RESULTS: The IOP decreased significantly after dynamic exercise, while the heart rate and the systemic artery pressure increased significantly. At the baseline, the mean retinal blood flow was 276.8 +/- 80.7 arbitrary units (AU) in the superotemporal area, 243.4 +/- 63.68 AU in the superonasal area, 258.2 +/- 67.37 AU in the inferotemporal area and 243.9 +/- 72.24 AU in the inferonasal area. After dynamic exercise the mean retinal blood flow was 249.8 +/- 86.78 AU in the superotemporal area, 248.7 +/- 63.87 AU in the superonasal area, 245.4 +/- 83.85 AU in the inferotemporal area and 228.8 +/- 62.53 AU in the inferonasal area. No significant change in retinal blood flow was found. CONCLUSION: Our data support the hypothesis that in normal subjects autoregulation is sufficient to compensate the increase in blood pressure and maintain a stable retinal blood flow after exercise.     

Interaction between flicker-induced vasodilatation and pressure autoregulation in early retinopathy of Type 2 diabetes

BACKGROUND: Diabetic retinopathy is accompanied with changes in the autoregulation of retinal blood flow secondary to changes in the systemic blood pressure and the retinal metabolism. In the present study we tested the working hypothesis that there is an interaction between these mechanisms that might be relevant for understanding and treating flow disturbances in diabetic retinopathy. METHODS: Fifty-four persons divided into three age and sex matched groups were studied: Group 1: twenty normal persons. Group 2: fourteen patients with type 2 diabetes mellitus and no diabetic retinopathy. Group 3: twenty type 2 diabetic patients with minimal diabetic retinopathy and a diabetes duration similar to that of the patients in group 2. Using the Retinal Vessel Analyzer (RVA) the diameter response of retinal arterioles was studied in all groups after an increase in the blood pressure by isometric exercise, during exposition to 8 Hz flickering light, and during simultaneous exposition to both stimulus conditions. RESULTS: The increased blood pressure induced by isometric exercise induced a non-significant vasoconstriction in the normal persons and in the diabetic patients without retinopathy (p=0.10 and p=0.84 respectively), and a non-significant vasodilatation in the diabetic patients with mild retinopathy (p=0.10). The flicker stimulus elicited a significant vasodilatation of retinal arterioles that decreased significantly from the normal persons to the diabetic patients without and with retinopathy (linear regression, p<0.01). The flicker-induced vasodilatation was not significantly affected by a simultaneous increase in the arterial blood pressure in normal persons (p=0.85). Conversely, in the diabetic patients the reduced diameter response during flicker was counteracted by a simultaneous increase in the blood pressure, to a level not differing significantly from the response of normal persons (p=0.75). CONCLUSIONS: Intervention studies aimed at modifying perfusion in retinal disease should consider the interaction between different mechanisms for autoregulating retinal blood flow. New treatment modalities for retinal vascular disease might need to target several mechanisms of tone control in retinal arterioles simultaneously.