Comparison of the autoregulatory mechanisms between central retinal artery and posterior ciliary arteries after thigh cuff deflation in healthy subjects.

PURPOSE: To compare dynamic autoregulation in the central retinal artery (CRA) and the posterior ciliary arteries (PCAs) after a step decrease in systemic blood pressure. METHODS: Ten healthy male young subjects were studied. Flow velocities in retrobulbar vessels and systemic blood pressure were recorded in each subject before, during, and after a step decrease in blood pressure. Continuous blood pressure recordings were made with a finger plethysmograph system and flow velocities in the CRA and the PCAs were continuously measured with color Doppler imaging. Large bilateral thigh cuffs were inflated and a pressure approximately 20 mm Hg above peak systolic blood pressure was maintained for 3 minutes. A decrease in blood pressure was induced by rapid deflation of bilateral thigh cuffs. Experiments were performed separately for the CRA and the PCAs. RESULTS: Systemic blood pressure showed a step decrease between -9% and -12% (p<0.001 each) immediately after thigh cuff release and returned to baseline 6 to 7 pulse cycles later. Peak systolic flow velocity in the CRA decreased by - 10 ± 7% (p=0.043) and returned to baseline earlier than systemic blood pressure, showing a delay of 3 pulse cycles after the blood pressure decrease. Peak systolic and end diastolic flow velocities in the PCAs decreased by - 13 ± 3% (p=0.004) and by - 10 ± 1% (p=0.0009), respectively and returned to baseline with a comparable time course to systemic blood pressure, reflecting no change in peripheral vascular resistance. There was a statistically significant difference in the time course of the velocity changes in the two selected arteries after thigh cuff release (p=0.008). CONCLUSIONS: The results of the present study indicate differences in the autoregulatory behavior of the vascular beds peripheral to the CRA and the PCAs. Our data indicate that the vascular bed distal to the CRA shows better autoregulatory properties as compared to the PCAs. Whether this is related to a myogenic mechanism remains to be investigated. The thigh cuff technique represents an interesting approach to study dynamic autoregulation in the human eye.

Diagnostic ability of retinal ganglion cell complex, retinal nerve fiber layer, and optic nerve head measurements by Fourier-domain optical coherence tomography.

PURPOSE: To evaluate the diagnostic ability of Fourier-domain optical coherence tomography (FD-OCT) measurements in glaucoma patients, patients with ocular hypertension, and normal subjects. METHODS: Ninety-three participants with open-angle glaucoma (OAG), 58 patients with ocular hypertension (OHT), and 60 healthy control subjects were included in the study. All study participants underwent FD-OCT imaging. Retinal ganglion cell complex (GCC), macular thickness, peripapillary retinal nerve fiber layer thickness (RFNL), and optic nerve head parameters (ONH) were measured in each participant. The diagnostic ability was evaluated using area under the receiver operating characteristics curves (AUROC). RESULTS: Glaucoma patients showed a significant reduction in GCC and macular retinal thickness compared to patients with OHT and normal subjects. No differences in GCC were found between the patients with OHT and normal subjects. The best diagnostic ability in the comparison between glaucoma and normal subjects after adjusting for age was found for cup-to-disc ratio (AUROC = 0.848), RNFL average thickness (AUROC = 0.828), and GCC global loss volume (AUROC = 0.805). The diagnostic power of the best GCC, RNFL, and ONH parameter did not show differences beyond random variation (p > 0.05). CONCLUSIONS: Imaging of the GCC using FD-OCT (RTVue-100) has a comparable diagnostic ability to RNFL and ONH measurements in distinguishing between glaucoma patients and healthy subjects. No differences were found between patients with OHT and normal subjects with regard to ONH, RNFL, and GCC parameters.

Reproducibility of ocular response analyzer measurements and their correlation with central corneal thickness.

BACKGROUND: To evaluate the inter- and intraobserver variability of ocular response analyzer (ORA) measurements, namely corneal-compensated intraocular pressure (IOPcc), corneal resistance factor (CRF) and corneal hysteresis (CH). METHODS: One randomly chosen eye of 46 healthy volunteers was included in this study. Three clinical observers performed three consecutive measurements using ORA, with an interval of 1-2 minutes between measurements. In all subjects, central corneal thickness (CCT) was measured. The inter- and intraobserver reproducibility for IOPcc, CRF and CH was assessed by ANOVA-based intraclass correlation coefficient (ICC) and coefficient of variation (CV). RESULTS: The mean ICC for interobserver reproducibility was 0.94 for IOPcc, 0.90 for CRF, and 0.86 for CH. The corresponding CV values were 12.8%, 10.3%, and 13.6% respectively. The intraobserver ICC values for IOPcc were 0.86 for the first examiner, 0.84 for the second, and 0.89 for the third. CV was 11.7%, 11.9%, and 11.0% respectively. For CRF, the intraobserver ICC values were 0.69, 0.81, and 0.63, and corresponding CV values were 9.6%, 8.1, and 10.8%. The intraobserver ICC for CH was 0.66 for the first observer, 0.71 for the second, and 0.61 for the third examiner. The respective CV values were 12.7%, 11.8%, and 13.9%. There was a significant correlation between CCT and CRF (Rsq = 0.13, p = 0.02). The correlations of CCT with IOPcc and CH were not significant (p > 0.05). CONCLUSIONS: The interobserver reproducibility of ORA measurements was almost perfect for IOPcc, CRF, and CH. The intraobserver short-term reproducibility was almost perfect for IOPcc and substantial for CRF and CH, for all observers. The significant correlation between CCT and CRF, and no association between IOPcc and CCT, are in agreement with previous studies. There was no significant correlation between CH and CCT in our study. This device might be useful in glaucoma diagnosis and management.

Evaluation of macular abnormalities in Stargardt's disease using optical coherence tomography and scanning laser ophthalmoscope microperimetry.

BACKGROUND: The purpose of this study is to evaluate the diagnostic value of optical coherence tomography (Stratus OCT) and scanning laser ophthalmoscope (SLO) microperimetry in patients with Stargardt's disease (STGD), and the correlation between macular morphology and visual function in these patients. METHODS: Twenty-two patients with STGD (mean age 44 years, range 11 to 71 years) and 20 age-matched healthy control subjects were included in the study. OCT imaging was performed using six radial line scans manually centered on the fovea. SLO microperimetry was used to assess central scotoma and fixation behavior in patients with STGD. RESULTS: Mean best corrected Snellen visual acuity (BCVA) was 20/80, range 20/25 to 20/300 (log MAR 0.6, range 0.1 to 1.2) in the STGD group and 20/20 (log MAR 0.0) in the control group. Foveal thickness was significantly reduced in patients with STGD (119.0 +/- 19.6 microm) compared to controls (210.7 +/- 19.6 microm, P < 0.0001). A significant correlation between foveal thickness and BCVA was observed within the STGD group (R(2) = 0.62, P < 0.0001). Photoreceptor loss in the macular area and a corresponding central scotoma were observed in all STGD patients. CONCLUSIONS: OCT findings, particularly reduced foveomacular thickness and photoreceptor loss in the macular area may be useful in the diagnosis of STGD. Furthermore, a strong correlation between foveal thickness and visual function was observed in our patients. Assessment of central visual function using SLO microperimetry provides additional useful information, important in the management of STGD.

Effect of unspecific inhibition of cyclooxygenase by indomethacin on retinal and choroidal blood flow.

PURPOSE: Animal studies suggest that retinal and choroidal blood flow decrease after administration of indomethacin, a nonspecific cyclooxygenase inhibitor. Cyclooxygenase is the key enzyme involved in the arachidonic pathway and regulates the production of vasoactive substances such as prostaglandins and thromboxans. The aim of the present study was to investigate the short-term effects of indomethacin on ocular blood flow in healthy humans. METHODS: A randomized, double-masked, placebo-controlled, two-way crossover study in 12 healthy, male, nonsmoking subjects was performed. Indomethacin was administered as a bolus injection of 0.4 mg/kg followed by continuous infusion of 0.4 mg/kg/h over 120 minutes. Ocular hemodynamic parameters were measured at baseline and up to 3 hours after start of the infusion. Subfoveal choroidal blood flow and fundus pulsation amplitude were measured with laser Doppler flowmetry and laser interferometry, respectively. Retinal vessel diameters were assessed using a retinal vessel analyzer. Retinal blood flow was calculated based on retinal vessel diameters, and red blood cell velocity was measured with laser Doppler velocimetry. RESULTS: Administration of indomethacin decreased retinal arterial diameters up to -4.3% +/- 3.4% and reduced retinal blood velocity by a maximum of -29% +/- 20% (P < 0.05). Calculated retinal blood flow decreased by -27% +/- 21% (P < 0.05), reaching the maximal decrease 60 minutes after administration. Choroidal blood flow and fundus pulsation amplitude (FPA) also decreased during the infusion of indomethacin with maximum effects of -17% +/- 13% (P < 0.05, vs. placebo) and -7% +/- 4% (P < 0.05, vs. placebo), respectively. CONCLUSIONS: Results showed a marked decrease in retinal and choroidal blood flow after short-term administration of indomethacin. Whether this decrease can be attributed to a reduced production of prostaglandins or an unknown mechanism has yet to be clarified. Further studies appear to be indicated to investigate whether the long-term intake of indomethacin is associated with an increased risk for vascular eye disease.

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 20 IU/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 nerve fiber layer measurements in early-stage open-angle glaucoma.

PURPOSE: To evaluate the relationship between retinal circulatory abnormalities and retinal nerve fiber layer (RNFL) thinning in early-stage open-angle glaucoma (OAG) to help elucidate the mechanisms underlying the development of glaucomatous optic neuropathy. DESIGN: Prospective cross-sectional. METHODS: Twelve patients with early OAG and a known maximum untreated intraocular pressure less than 22 mm Hg (age, 61.4 +/- 9.7 years; Humphrey visual field mean deviation -2.7 +/- 2.1) and eight age-matched healthy control subjects (age, 58.5 +/- 8.3 years) were included in the study. Blood column diameter, centerline blood speed, and retinal blood flow were measured in the major inferior temporal retinal artery using a Canon laser Doppler blood flow instrument (CLBF 100; Canon, Tokyo, Japan). Peripapillary RNFL thickness was measured using a Stratus optical coherence tomography instrument. RESULTS: On average, there were significant reductions in retinal blood speed (P = .009) and flow (P = .010) in OAG patients compared to controls. The RNFL was significantly thinner in the OAG patients compared to controls (P = .002). There were significant inverse correlations between retinal blood flow and average RNFL thickness and RNFL thickness in the inferior quadrant within the glaucoma group (Rsq = 0.50, P = .01; Rsq = 0.62, P = .003). CONCLUSION: The results showed that a thinner RNFL was associated with a higher retinal blood flow in patients with early-stage OAG. The mechanisms underlying this phenomenon remain to be elucidated.

Retinal abnormalities in early Alzheimer's disease.

PURPOSE: There is evidence suggesting that visual disturbances in patients with Alzheimer's Disease (AD) are due to pathologic changes in the retina and optic nerve, as well as to higher cortical impairment. The purpose of this study was to evaluate retinal hemodynamic parameters and to characterize patterns of retinal nerve fiber layer (RNFL) loss in patients with early AD. METHODS: Nine patients with mild to moderate probable AD (mean Mini Mental State Examination score 24 of a possible 30 (age 74.3 +/- 3.3 years; mean +/- SD) and eight age-matched control subjects (age, 74.3 +/- 5.8 years) were included in this prospective cross-sectional study. Blood column diameter, blood velocity, and blood flow rate were measured in the major superior temporal retinal vein in each subject by using a laser Doppler instrument. Peripapillary RNFL was measured by optical coherence tomography. RESULTS: Patients with AD showed a significant narrowing of the venous blood column diameter (131.7 +/- 10.8 microm) compared with control subjects (148.3 +/- 12.7 microm, P = 0.01), and a significantly reduced venous blood flow rate (9.7 +/- 3.1 microL/min) compared with the control subjects (15.9 +/- 3.7 microL/min, P = 0.002). A significant thinning of the RNFL was found in the superior quadrant in patients with AD (92.2 +/- 21.6 microm) compared with control subjects (113.6 +/- 10.7 microm, P = 0.02). There were no significant differences in the inferior, temporal, or nasal RNFL thicknesses between the groups. CONCLUSIONS: Retinal abnormalities in early AD include a specific pattern of RNFL loss, narrow veins, and decreased retinal blood flow in these veins. The results show that AD produces quantifiable abnormalities in the retina.

Altered nitric oxide system in patients with open-angle glaucoma.

OBJECTIVE: To investigate the ocular blood flow response to systemic nitric oxide synthase inhibition in patients with primary open-angle glaucoma. METHODS: In 12 patients with glaucoma and 12 age-matched control subjects, subfoveal choroidal blood flow, optic nerve head blood flow, ocular fundus pulsation amplitude, intraocular pressure, and systemic hemodynamic parameters were measured at baseline and after inhibition of nitric oxide synthase by intravenous administration of NG-monomethyl-L-arginine. RESULTS: The increase in blood pressure in response to NG-monomethyl-L-arginine was comparable between the 2 study cohorts. In patients with glaucoma, the decrease of optic nerve head blood flow (P = .03) and fundus pulsation amplitude (P<.001) during nitric oxide synthase inhibition was significantly less pronounced than in healthy control subjects. A tendency toward a reduced response in choroidal blood flow was seen (P = .051 between groups) in patients with glaucoma. CONCLUSIONS: This is the first in vivo study providing evidence for an altered ocular L-arginine/nitric oxide system in patients with glaucoma. Normalization of the ocular nitric oxide production may be beneficial in terms of normalization of ocular blood flow and neuroprotection of retinal ganglion cells.

C-peptide does not affect ocular blood flow in patients with type 1 diabetes.

OBJECTIVE: The aim of the present study was to investigate the effect of intravenous C-peptide infusion on ocular blood flow in patients with type 1 diabetes under euglycemic conditions. RESEARCH DESIGN AND METHODS: The study was performed in a randomized, placebo-controlled, double-masked, two-way, crossover design in 10 type 1 diabetic patients. C-peptide was intravenously administered at two different dosages (dosage 1: 25 pmol . kg(-1) . min(-1) bolus followed by 5 pmol . kg(-1) . min(-1) continuous infusion; dosage 2: six times higher than dosage 1), each for 60 min. Physiologic saline solution was used as a control for C-peptide on a different study day. On both study days, euglycemic clamps were performed. To assess retinal blood flow, laser Doppler velocimetry (blood flow velocities) and retinal vessel analyzer (vessels diameters) measurements were performed. Laser interferometric measurements of fundus pulsation were used to assess pulsatile choroidal blood flow. Blood velocities in the ophthalmic artery were measured using color Doppler imaging. RESULTS: Eight patients (two female and six male) completed the study according to the protocol and without adverse events. One patient developed an anaphylactic reaction to C-peptide, which resolved without sequelae. The following results originate from the remaining eight subjects. Systemic hemodynamic parameters remained stable during both study days. Infusion of C-peptide did not affect any ocular hemodynamic parameter. CONCLUSIONS: The data of the present study indicate that exogenous C-peptide exerts no effect on ocular hemodynamic parameters in type 1 diabetic patients under euglycemic conditions. The maximum detectable change in these parameters was <25%.

Comparison of the autoregulatory mechanisms between middle cerebral artery and ophthalmic artery after thigh cuff deflation in healthy subjects.

PURPOSE: To compare dynamic autoregulation in the middle cerebral artery (MCA) and the ophthalmic artery (OA) after a step decrease in systemic blood pressure. METHODS: Eighteen healthy male young subjects were studied. Ultrasound parameters and systemic blood pressures were recorded in each subject before, during, and after a step decrease in blood pressure. Continuous blood pressure recordings were made with a finger plethysmograph system, and flow velocities in the MCA and the OA were continuously measured with Doppler ultrasound. Large bilateral thigh cuffs were inflated and a pressure approximately 20 mm Hg above peak systolic blood pressure was maintained for 3 minutes. A decrease in blood pressure was induced by rapid deflation of bilateral thigh cuffs. Experiments were performed separately for the OA and the MCA. RESULTS: Systemic blood pressure showed a step decrease immediately after thigh cuff release (9%-15%) and returned to baseline 7 to 10 pulse cycles later. Flow velocities in the MCA returned to baseline earlier than systemic blood pressure, indicating peripheral vasodilatation, with a maximum of five to six pulse cycles after the blood pressure decrease. By contrast, flow velocities in the OA returned to baseline later than systemic blood pressure, reflecting peripheral vasoconstriction with a maximum 10 to 15 pulse cycles after cuff release. There was a statistically significant difference in the time course of the resistance changes in the two selected arteries after thigh cuff release (P < 0.001). CONCLUSIONS: The results of the present study suggest substantial differences in the autoregulatory behavior of the vascular beds peripheral to the MCA and the OA. Results in the MCA would be compatible with either metabolic or myogenic vasodilatation, whereas the results in the OA could reflect sympathetic vasoconstriction. Further studies are needed to support this hypothesis. The thigh cuff technique may represent an interesting approach to the study of autoregulation in patients with ocular vascular disease.

Comparison of Laser Scanning Diagnostic Devices for Early Glaucoma Detection.

BACKGROUND: To compare the diagnostic accuracy and to evaluate the correlation of optic nerve head and retinal nerve fiber layer thickness values between Fourier-Domain optical coherence tomography (FD-OCT), confocal scanning laser ophthalmoscopy (CSLO), and scanning laser polarimetry (SLP) for early glaucoma detection. PATIENTS AND METHODS: Ninety-three patients with early open-angle glaucoma, 58 patients with ocular hypertension, and 60 healthy control subjects were included in this observational, cross-sectional study. All study participants underwent FD-OCT (RTVue-100), CSLO (HRT3), and SLP (GDx VCC) imaging of the optic nerve head and the retinal nerve fiber layer. Area under the receiver operating characteristic curves (AUROC) and Bland-Altman analysis were performed. RESULTS: The parameters with the highest diagnostic accuracy were found for FD-OCT cup-to-disc ratio (AUROC=0.841), for SLP NFI (AUROC=0.835), and for CSLO cup-to-disc ratio (AUROC=0.789). Diagnostic accuracy of the best CSLO and SLP parameter was similar (P=0.259). There was a small statistically significant difference between the best CSLO and FD-OCT parameters for differentiating between glaucoma and healthy eyes (P=0.047). CONCLUSIONS: FD-OCT and SLP have a similarly good diagnostic ability to distinguish between early glaucoma and healthy subjects. The diagnostic accuracy of CSLO was comparable with SLP and marginally lower compared with FD-OCT.

Effects of sildenafil on retinal blood flow and flicker-induced retinal vasodilatation in healthy subjects.

PURPOSE: Sildenafil is a specific inhibitor of phosphodiesterase V, which is widely used for the treatment of erectile dysfunction. Sildenafil has been shown to induce vasodilation in several vascular beds by inhibiting the cGMP breakdown. The present study was conducted to investigate whether sildenafil increases blood flow in the human retina. METHODS: In a randomized, double-masked, placebo-controlled, two-way crossover study in 12 healthy male volunteers the effects of a single dose of 100 mg sildenafil were studied. Subjects received sildenafil or placebo on two different study days. After administration, retinal hemodynamic parameters were measured every 20 minutes. Retinal vessel diameters and retinal blood velocity were assessed with the retinal vessel analyzer and bidirectional laser Doppler flowmetry, respectively. In addition, the response of retinal vessel diameters to stimulation with diffuse flicker light was studied. Blood pressure and intraocular pressure were measured with noninvasive techniques. RESULTS: Sildenafil had no effect on mean arterial pressure, pulse rate, intraocular pressure, retinal blood velocity, or retinal arterial diameter. However, a significant increase in retinal venous diameters (4.7% +/- 3.2%; P=0.0028 versus placebo) and retinal blood flow 15.7% +/- 18.0%; P=0.029 versus placebo) was observed. Sildenafil had no effect on flicker-induced vasodilation in retinal arteries or veins. CONCLUSIONS: The data indicate that sildenafil increases retinal venous diameters and retinal blood flow in healthy subjects. By contrast, it does not affect intraocular pressure and flicker-induced retinal vasodilation. Further studies are needed to elucidate whether this drug may be therapeutically used in retinal ischemic disease.

Effects of isometric exercise on subfoveal choroidal blood flow in smokers and nonsmokers.

PURPOSE: Little is known about potential effects of smoking on ocular blood flow regulation. In the present study, the hypothesis was that choroidal blood flow (CBF) changes during an increase in ocular perfusion pressure induced by isometric exercise are altered in chronic smokers. METHODS: The study was performed in 24 (12 smokers and 12 nonsmokers) healthy male volunteers in an observer-masked, two-cohort study design. The difference in CBF regulation between smokers and nonsmokers was tested during isometric exercise over a period of 6 minutes. CBF was assessed with laser Doppler flowery (LDF), and ocular perfusion pressure (OPP) was calculated from mean arterial pressure (MAP) and intraocular pressure (IOP). RESULTS: Six minutes of isometric exercise induced a significant increase in MAP, pulse rate (PR), OPP, and CBF in smokers and nonsmokers (each P<0.001). The increase in CBF was significantly higher in the smoking group (P<0.001) than in the healthy control group, whereas a comparable increase in MAP (P=0.18), PR (P=0.18), and OPP (P=0.43) occurred in smokers and nonsmokers. IOP remained unchanged during isometric exercise in both groups. Moreover, in smokers, CBF started to increase at OPPs more than 49% above baseline, whereas CBF in nonsmokers remained stable until an increase in OPP of 74% over baseline. This difference between the two groups was significant (P<0.001). CONCLUSIONS: These data indicate abnormal CBF regulation in chronic smokers compared with age-matched nonsmoking subjects during isometric exercise. The pathways responsible for this abnormal blood flow response remain to be elucidated.

A study comparing ocular pressure pulse and ocular fundus pulse in dependence of axial eye length and ocular volume.

PURPOSE: There is a long-standing discussion about whether myopia is associated with decreased choroidal blood flow, as suggested by pneumotonometric measurements of pulsatile ocular blood flow (POBF). However, it has been noted previously that calculations of POBF depend on intraocular volume. METHODS: In the present study we investigated this volume dependence through the comparison of ocular pressure pulse and ocular fundus pulse. Fifty-one healthy participants with different refractive errors participated in the study. Pulse amplitude (PA) and POBF were measured using pneumotonometry. Fundus pulsation amplitude (FPA) was measured with laser interferometry. Axial eye length (AEL) was measured with partial coherence interferometry. A mathematical model was used to calculate choroidal volume changes based on FPA. The ocular pressure pulse was converted into pulse volume (PV) according to the standard procedure used for pneumotonometry. RESULTS: PA and POBF were found to decrease with increasing axial length (r = -0.55, p < 0.001 and r = -0.57, p < 0.001, respectively). A similar relationship existed for PV (r = -0.57, p < 0.001) and FPA (r = -0.46, p = 0.001). In addition, there was a significant association between PV and choroidal volume change during the cardiac cycle (r = 0.61, p < 0.001). CONCLUSION: The present study confirms experimentally that PA, FPA and POBF are dependent on ocular volume and indicates that the pulsatile component of ocular blood flow is not reduced in myopic patients. Accordingly, the relationship between AEL and POBF described previously appears to be a consequence of different ocular volumes. Our findings have important implications for studies using PA or POBF.

Defective myogenic response to posture change in retinal vessels of well-controlled type 1 diabetic patients with no retinopathy.

PURPOSE: The current approach to the prevention of diabetic retinopathy relies on intensive anti-diabetes treatment and is only partially successful. A marker of retinopathy risk would enable strategies of surveillance, screening of adjunct drugs, and targeted drug interventions. The authors sought to identify early abnormalities of retinal vessels that are not prevented by the current therapeutic approach. METHODS: Retinal thickness (an informer of vascular permeability) and hemodynamic parameters at baseline and longitudinally were measured in 27 subjects (age, 32 ± 9 years [mean ± SD]) with well-controlled type 1 diabetes of 12.4 ± 6.4 years' duration and no retinopathy, and in 27 control subjects. In a subset of 17 patients and 11 controls, the hemodynamic response to reclining, a postural change that increases retinal perfusion pressure, was measured. RESULTS: Baseline foveal thickness and hemodynamic parameters were similar in the diabetic and control subjects. Foveal thickness increased over 12 months in the diabetic subjects, from 217 ± 22 µm to 222 ± 20 µm (P = 0.0036), remaining however within the normal range. Reclining uncovered in 47% of diabetic subjects (P = 0.016 compared with controls) an absent myogenic response (i.e., unchanged or increased arterial diameter instead of the normal decrease). The patterns were repeatable. Only the diabetic group with defective vasoconstriction showed widening arterial diameter over 12 months, a change presaging vascular dilatation in diabetic retinopathy. CONCLUSIONS: Defective myogenic response to pressure was the first detectable abnormality of retinal vessels in subjects with well-controlled type 1 diabetes. Because of its selective occurrence, interpretability in individual patients, and pathogenic potential, the abnormality deserves evaluation as a risk marker for retinopathy.

Influence of Ginkgo biloba on ocular blood flow.

PURPOSE: To investigate the effect of Ginkgo biloba extract (EGb761) on ocular blood flow. METHODS: This randomized, double-masked, placebo-controlled, two-way crossover study included 15 healthy male volunteers. Measurements were taken with laser Doppler flowmetry, laser Doppler velocimetry, a retinal vessel analyser, laser interferometry and applanation tonometry, before and up to 3 hours after oral intake of 240 mg EGb761. RESULTS: At baseline, no significant differences in ocular and systemic haemodynamic parameters were observed between the two study days. Ginkgo biloba significantly decreased retinal venous diameters (p < 0.05 versus baseline), but there was no significant difference between the two groups. Blood pressure, retinal arterial and venous diameters, choroidal blood flow, fundus pulsation amplitude, intraocular pressure and retinal blood flow remained unchanged in both groups and did not differ between groups. Optic nerve head blood flow significantly increased in response to Ginkgo biloba (p < 0.002 versus baseline), but this effect was not significant compared with that of placebo. CONCLUSIONS: The results of this study indicate that a single administration of Ginkgo biloba does not influence ocular blood flow to a relevant degree. Whether the drug may influence ocular blood flow in patients with ocular vascular disease after longterm treatment remains to be investigated in a randomized, placebo-controlled clinical trial.

Response of retinal blood flow to systemic hyperoxia in smokers and nonsmokers.

BACKGROUND: We investigated the influence of chronic smoking on ocular vascular reactivity during breathing of 100% oxygen. METHODS: Retinal vascular reactivity was tested during inhalation of 100% oxygen over 10 min. The observer-masked two-cohort study was performed in 24 healthy male volunteers (12 smokers and 12 nonsmokers) using the Zeiss Retinal Vessel Analyzer and laser Doppler velocimetry. From these parameters retinal blood flow was calculated. RESULTS: Hyperoxia significantly decreased arterial (smokers: p<0.001 vs baseline; nonsmokers: p=0.003 vs baseline) and venous (smokers: p<0.001 vs baseline; nonsmokers: p<0.001 vs baseline) diameters. This decrease was significantly more pronounced in smokers (arterial diameter: p<0.001, venous diameter: p=0.003). Hyperoxia decreased venous blood flow velocity (smokers: p=0.02 vs baseline; nonsmokers: p<0.001 vs baseline) to a comparable degree (p=0.51). The two groups showed a comparable decrease in retinal blood flow during hyperoxia (smokers: p<0.001 vs baseline; nonsmokers: p<0.001 vs baseline; p=0.76 between groups). The decrease of PCO(2) during inhalation of 100% oxygen was significantly more pronounced in smokers than in nonsmokers (p=0.038). CONCLUSION: The present study indicates an abnormal retinal vascular response to hyperoxia in smokers. Further studies are needed to identify possible neural or humoral factors involved in this shifted vasoconstrictory status in smokers.

LPS-induced microvascular leukocytosis can be assessed by blue-field entoptic phenomenon.

Administration of low doses of Escherichia coli endotoxin [a lipopolysaccharide (LPS)] to humans enables the study of inflammatory mechanisms. The purpose of the present study was to investigate whether the blue-field entoptic technique may be used to quantify the increase in circulating leukocytes in the ocular microvasculature after LPS infusion. In addition, combined laser Doppler velocimetry and retinal vessel size measurement were used to study red blood cell movement. Twelve healthy male volunteers received 20 IU/kg iv LPS as a bolus infusion. Outcome parameters were measured at baseline and 4 h after LPS administration. In the first protocol (n = 6 subjects), ocular hemodynamic effects were assessed with the blue-field entoptic technique, the retinal vessel analyzer, and laser Doppler velocimetry. In the second protocol (n = 6 subjects), white blood cell (WBC) counts from peripheral blood samples and blue-field entoptic technique measurements were performed. LPS caused peripheral blood leukocytosis and increased WBC density in ocular microvessels (by 49%; P = 0.036) but did not change WBC velocity. In addition, retinal venous diameter was increased (by 9%; P = 0.008), but red blood cell velocity remained unchanged. The LPS-induced changes in retinal WBC density and leukocyte counts were significantly correlated (r = 0.87). The present study indicates that the blue-field entoptic technique can be used to assess microvascular leukocyte recruitment in vivo. In addition, our data indicate retinal venous dilation in response to endotoxin.