Hypoxic, Hypercapnic, and Hyperoxic Responses of the Optic Nerve Head and Subfoveal Choroid Blood Flow in Healthy Humans.

Purpose: To investigate the impact of different gas mixtures (hyperoxia, hypoxia, and hypercapnia) on the optic nerve head (ONH) and choroidal (Ch) hemodynamics. Methods: Twenty-three healthy subjects (28 ± 6 years) took part in the study. Variations in inspired oxygen and carbon dioxide fraction were produced by a gas mixing device. Arterial oxygen saturation (SpO2) was measured continuously using a transcutaneous sensor and end-tidal carbon dioxide partial pressure by capnography. The experiment comprised three successive periods: 3-minute baseline (room air breathing), 15-minute gas mixture inhalation (normocapnic hypoxia, hypercapnia, or hyperoxia), and 15-minute recovery (room air breathing). Laser Doppler flowmeter parameters-velocity (VEL), volume (VOL), and flow (BF) of red blood cells-were measured. Two-way ANOVAs were performed for statistical analysis. Results: In response to hyperoxia, ONHBF significantly decreased by -18% ± 6% (P = 0.04) from baseline, due to significant changes in VEL (-12% ± 3% P = 0.0002). During hypoxia at 85% SpO2, ONH VEL increased by +12% ± 3% (P = 0.0009), whereas VOL and BF did not change significantly. ChBF significantly increased by +7% ± 2% (P = 0.004) in response to hypoxia, due to significant changes in VEL +5% ± 2% (P = 0.03). Both Ch and ONHBFs did not vary significantly in response to hypercapnia. Conclusions: The magnitude of the blood flow response is the most significant during hyperoxia for ONH and hypoxia for ChBF. For ONHBF, a 37% difference between hyperoxia and hypoxia can be useful when vasoreactivity to O2 will be tested in patients.

Continuous response of optic nerve head blood flow to increase of arterial blood pressure in humans.

PURPOSE: This study investigates the effect of increased ocular perfusion pressure (OPP) on optic nerve head (ONH) hemodynamics. METHODS: In 21 healthy subjects, the increase in arterial blood pressure (BP), measured continuously using a pneumatic transcutaneous sensor, was produced by isometric exercise consisting of 2 minutes of hand-gripping. ONH blood flow parameters-namely the velocity (Vel), number (Vol), and flux (F) of red blood cells-were measured using the laser Doppler flowmeter (LDF). RESULTS: In those 14 healthy subjects who exhibited a similar increase in BP to handgrip superior to 30% of baseline BP, group average increases of BP and OPP amounted to 34% ± 3% (SEM) and 43% ± 3%, respectively. The increase in F of 19% ± 8%, resulting from an increase in Vel (17% ± 7%) and Vol (6% ± 7%), was significantly less than predicted for a passive autoregulatory response, as revealed also by the increase in vascular resistance (R = OPP/F). Spearman test of linear correlations between F and time during handgrip led to the identification of one group of eight subjects (with a stable F) and one group of six subjects (with an increase in F). A closed-loop gain (G) of the regulatory process, defined as G = 1 - {(F - Fbl)/Fbl}/{(OPP - OPPbl)/OPPbl}, was found to be rather independent from the OPP, with an average value 0.7 ± 0.07. G was 0.83 ± 0.06 for the group of eight subjects with stable F and 0.3 ± 0.15 for the group of six subjects with F increasing with the OPP. CONCLUSIONS: The continuous recording of both BP and LDFs represents a novel and more precise approach to the characterization of ONH hemodynamics during isometric exercise, especially useful in the future for patients with ocular diseases. The efficiency of the ONH blood flow autoregulation appears to vary significantly between healthy subjects. (ClinicalTrials.gov number, NCT00874913.).

Does pupil dilation influence subfoveal choroidal laser Doppler flowmetry?

PURPOSE: The aim of this study was to assess (i) whether pupil dilation with tropicamide influences subfoveal choroidal blood flow, as assessed by continuous laser Doppler flowmetry (LDF) and (ii) if this is the case, whether the effect is due to a haemodynamic response of the drug-induced dilation. METHODS: Following the instillation of one drop of 1% tropicamide in one eye of 18 healthy, nonsmoking volunteers (age 20-25 years), the subfoveal choroidal LDF parameters (Vel, Vol and ChBF) were recorded during 30 min, at 3-min intervals under two paradigms: through an artificial pupil (4 mm diameter) placed in front of the cornea (P1) and without this artificial pupil (P2). RESULTS: Tropicamide increased the pupil diameter from 3.3 ± 0.4 mm (mean ± SD) to 8.3 ± .4 mm. Full dilation was reached at ~24 min. During this period of time, linear regression analysis demonstrated that none of the LDF parameters varied significantly (p > 0.05), either under P1 or P2. Based on a group of 12 subjects, the smallest (%) change in the mean value of ChBF (ChBFm ) that would be detectable (sensitivity of the method, S) was found to be 2% for P1 and 6% for P2. The average coefficient of variation of ChBFm based on eight measurements during dilation was greater for P2 than for P1 by a factor of approximately 2. CONCLUSION: Tropicamide had no significant influence on the subfoveal choroidal LDF parameters measured by continuous LDF during pupil dilation. Furthermore, pupil dilation did not affect ChBFm by more than the calculated minimum percentage change of 6% detectable with our method.

Retinal blood flow evaluation.

Much of our basic knowledge of retinal blood flow regulation is based on data obtained from animal experiments through the use of invasive techniques. However, during the last decades, major developments in the field of optics and lasers have led to a variety of noninvasive techniques, which have been applied to the human eye for the investigation of retinal hemodynamics, and more specifically the regulation of retinal blood flow in response to a number of physiological and pharmacological stimuli. The Retinal Vessel Analyzer has markedly simplified the measurement of the diameter of retinal vessels, as well as the change in this diameter evoked by various physiological stimuli (dynamic measurements). Bidirectional laser Doppler velocimetry allows the measurement of absolute red blood cell centerline velocity, which, when combined with the diameter allows the calculation of retinal blood flow in the main retinal vessels. Laser Doppler flowmetry and laser speckle flowgraphy are techniques that measure the velocities of blood in discrete areas of the retinal tissue microcirculation. Adding a scanning capability, a spatial map of velocities across the retinal tissue is obtained. The blue-field simulation technique allows the quantification of the velocity, number and velocity pulsatility of leukocytes moving in the retinal capillaries of the macular region. With color Doppler imaging, the peak systolic and end-diastolic values of blood velocity in the ophthalmic and central retinal artery are measured, from which a resistivity index is obtained. These techniques may help better understand the role of altered retinal blood flow and its regulation in the pathogenesis of retinal diseases of vascular origin.

Choroidal hemodynamic in myopic patients with and without primary open-angle glaucoma.

PURPOSE: To investigate the change in subfoveal choroidal blood flow in patients with glaucoma and to assess the effect of myopia, as one of the vascular risk factors for glaucoma on this flow. METHODS: Subfoveal choroidal blood flow in groups of 12 myopic and glaucomatous eyes has been investigated by means of the laser Doppler flowmetry (LDF), comparing the results with those of 17 myopic eyes without glaucoma, 34 non-myopic glaucomatous eyes and of 50 control eyes. The subfoveal choroidal LDF parameters, that is, blood velocity (ChBVel), volume (ChBVol), and flow (ChBF), as well as the vascular resistance were studied in each group. Statistical analysis was performed by means of anova and t-test according to the Bonferroni procedure for multiple comparisons. Pearson correlation was used to establish the correlations between the hemodynamic parameters and the degree of myopia in dioptres. RESULTS: All LDF parameters (ChBVel, ChBVol and ChBF) were significantly reduced in glaucomatous patients (1.3 ± 0.4, 0.14 ± 0.06 and 4 ± 2 respectively) and myopic patients with primary open-angle glaucoma (POAG) (1.3 ± 0.4, 0.08 ± 0.04 and 2 ± 0.7 respectively) and without POAG (1.2 ± 0.3, 0.11 ± 0.08 and 2 ± 1 respectively) in comparison with age-matched controls (1.5 ± 0.4, 0.27 ± 0.1 and 8 ± 2 respectively). On the other hand, the choroidal vascular resistance (Rm) was increased in the previously described studied patients groups (16 ± 7, 26 ± 9 and 24 ± 9 respectively) compared with controls (7 ± 2). The LDF parameters did not differ significantly between myopic subjects without and with POAG (p = 0.09, p = 0.09, p = 0.2, p = 0.08 and p = 0.9 respectively). Compared to patients with emmetropic glaucomatous, significant reduction in the ChBVol and ChBF and increased Rm were recorded in patients with glaucomatous myopia (p = 0.05, p = 0.04 and p = 0.04 respectively). Pearson correlation demonstrated a significant correlation between the degree of myopia in dioptres and the ChBF (p = 0.012). CONCLUSIONS: The subfoveal choroidal LDF parameters were reduced in patients with POAG and myopia. Theses alterations are more in glaucomatous patients with myopia in comparison with age-matched glaucomatous patients without myopia. These data suggest that the impaired choroidal circulation caused by myopia might be an important additional risk factor involved in the glaucomatous damaging process.

Subfoveal choroidal blood flow and central retinal function in early glaucoma.

PURPOSE: To assess subfoveal choroidal blood flow (ChBF) in patients with early manifest glaucoma (EMG) and to compare blood flow with functional measures of central retinal integrity, standard automated perimetry (SAP) and pattern electroretinogram (PERG). METHODS: Subfoveal ChBF was determined by confocal, real-time laser Doppler flowmetry in 24 patients with EMG [>-6 dB mean deviation (MD), age range: 29-77 years, visual acuity: 20/25-20/20] and 23 age-matched control subjects. All patients had a therapeutically (topical beta-blockers with or without prostaglandin analogues) controlled intraocular pressure (IOP < 20 mmHg). Subfoveal choroidal blood volume (ChBVol), velocity (ChBVel) and ChBF were determined as the average of three 60 second recordings. In all patients and controls, the PERG and SAP (Humphrey 30-2), following standardized protocols, were also recorded. RESULTS: In patients with EMG, reductions in average ChBVel and ChBF were roughly equal, respectively, by 30% and 33.4% (p < 0.01), when compared to control subjects, so that there was no significant difference in ChBVol between the two groups. Pattern electroretinogram amplitudes were reduced by 46% (p < 0.01) in patients compared to controls. No correlation was found between any of the ChBF parameters and PERG amplitude, or Humphrey 30-2 MD and pattern standard deviation. CONCLUSION: The results suggest a significant alteration of both ChBVel and ChBF in EMG, which does not appear to be associated with the severity of central retinal dysfunction. These findings may contribute to a better understanding of the pathophysiology of early glaucomatous damage in EMG and have implications for the treatment of this pathologic condition.

Blood flow measurements within optic nerve head during on-pump cardiovascular operations. A window to the brain?

This observational study is conducted to demonstrate optic nerve head (ONH) blood flow alterations during extracorporeal circulation (ECC) in routine on-pump cardiovascular operations in order to evaluate the perfusion status of important autoregulatory tissue vascular beds during moderate hypothermia. Twenty-one patients free from eye disease were prospectively enrolled in our database. Perioperative ONH blood flow measurements were performed using a hand-held portable ocular laser Doppler flowmeter just after administration of general anesthesia and during cardiopulmonary bypass (CPB) upon the lowest temperature point of moderate hypothermia. Important operative flow variables were correlated to optic nerve blood flow during surgical phases. Statistical analysis showed significant reduction of 32.1 ± 14.5% of mean ONH blood flow in phase 2 (P < 0.0001) compared to the reference flow values of phase 1. A negative univariate association between ECC time and ONH blood flow in phase 2 (P = 0.031) is noted. This angiokinetic approach can detect changes of flow within autoregulatory vascular tissue beds like ONH, thus creating a 'window' on cerebral microvasculature. ONH blood flow is reduced during CPB. Our data suggest that it is of paramount importance to avoid extracorporeal prolongation even in moderate hypothermic cardiovascular operations.

Subfoveal choroidal blood flow and central retinal function in retinitis pigmentosa.

PURPOSE: To determine whether subfoveal choroidal blood flow is altered in retinitis pigmentosa (RP) and whether this alteration is associated with central cone-mediated dysfunction. METHODS: In 31 RP patients (age range, 15-72 years) with preserved visual acuity (range: 20/30-20/20), subfoveal choroidal blood flow was measured by real-time, confocal laser Doppler flowmetry, and focal macular (18°) electroretinograms (FERGs) were elicited by 41 Hz flickering stimuli. Twenty normal subjects served as controls. The following average blood flow parameters were determined based on three 60-second recordings: volume (ChBVol), velocity (ChBVel), and flow (ChBF), the last being proportional to blood flow if the hematocrit remains constant. The amplitude and phase of the FERG first harmonic component were measured. RESULTS: On average, ChBF and ChBVel were reduced by 26% (P ≤ 0.02) in RP patients compared to controls, whereas ChBVol was similar in the two groups. FERG amplitudes were reduced by 60% (P < 0.01) in patients compared with controls. FERG phases of patients tended to be delayed (P < 0.08) compared with their values in the controls. In patients, FERG phase delays were correlated (r = 0.50, P < 0.01) with ChBF and ChBVel values. FERG amplitudes were correlated (r = 0.49, P < 0.01) with ChBVol values. CONCLUSIONS: These data indicate significant alterations of subfoveal choroidal hemodynamic in RP and suggest a link between the alteration of ChBF and the RP-associated central cone-mediated dysfunction as assessed by the FERG.

Use of laser speckle flowgraphy in ocular blood flow research.

Laser speckle flowgraphy (LSFG) allows for the quantitative estimation of blood flow in the optic nerve head, choroid, retina and iris in vivo. It was developed to facilitate the non-contact analysis of ocular blood flow in living eyes, utilizing the laser speckle phenomenon. The technique uses a fundus camera, a diode laser, an image sensor, an infrared charge-coupled device (CCD) camera and a high-resolution digital CCD camera. Normalized blur (NB), an approximate reciprocal of speckle contrast, represents an index of blood velocity, and shows a good correlation with tissue blood flow rates determined with the microsphere method in the retina, choroid or iris, as well as blood flow rates determined with the hydrogen gas clearance method in the optic nerve head. The square blur ratio (SBR), another index for quantitative estimation of blood velocity, is proportional to the square of the NB. The SBR is theoretically a more exact measurement which is proportional to velocity, whereas the NB is an approximation. Normalized blur was calculated in earlier versions of LSFG because of technical limitations; the SBR is used in current versions of the LSFG instrument. As these values are in arbitrary units, they should not be used to make comparisons between different eyes or different sites in an eye. Clinical protocols, calibration, evaluation procedures and possible limitations of the LSFG technique are described and the results of ocular blood flow studies using LSFG are briefly summarized. The LSFG method is suitable for monitoring the time-course of change in the tissue circulation at the same site in the same eye at various intervals, ranging from seconds to months. Unresolved issues concern the effect of pupil size on measurement results, the effects of various stimulations, and how to measure choroidal and retinal blood flow velocity separately without using the blue-component of argon laser.

Ocular blood flow assessment using continuous laser Doppler flowmetry.

This article describes the technique of continuous laser Doppler flowmetry (LDF) as applied to the measurement of the flux of red blood cells in the optic nerve head, iris and subfoveal choroid. Starting with the exposition of the physical principles underlying LDF, we first describe the various devices developed to perform LDF in these vascular beds. We then discuss the clinical protocols, blood flow parameters, calibration procedures, reproducibility and limitations of the LDF technique. Various problems still need to be solved in order to bring to light the full potential of LDF in the assessment of microcirculatory haemodynamics.

Lack of habituation in the light adapted flicker electroretinogram of normal subjects: a comparison with pattern electroretinogram.

OBJECTIVE: Sustained pattern stimulation (SPS) induces habituation in the normal pattern electroretinogram (PERG). In this study, the authors evaluated whether sustained flicker stimulation (SFS) induces habituation in the normal flicker ERG (FERG). METHODS: FERGs were elicited in normal volunteers by an 8Hz flicker stimulus, presented continuously over 3 min after 20 min of light adaptation. One stimulus temporal period was sampled and averaged in packets (n=20) of 60 events, each of 8s duration. Amplitudes and phases of the response 1st and 2nd harmonics (1F and 2F, respectively) were measured. FERG results were compared with those obtained by recording PERGs with a similar SPS paradigm. RESULTS: During SFS, FERG 2F showed a modest increase in amplitude (about 25%, p<0.05). No changes were observed for the 1F amplitude and for the phase of both components. In contrast, PERG amplitude showed SPS-induced habituation, described by an exponential decay with a time constant of approximately 20s. CONCLUSIONS: The normal FERG, unlike PERG, does not show habituation, suggesting that the adaptive changes of retinal neurons underlying FERG are different from those of PERG generators. SIGNIFICANCE: Our findings may have implications for diagnosis and/or pathophysiology of retinal disorders involving the inner retina.

Functional laser Doppler flowmetry of the optic nerve: physiological aspects and clinical applications.

The present paper reviews the methodology and clinical results of recording, by laser Doppler flowmetry, the hemodynamic response of the optic nerve head elicited by visual stimulation. The basic mechanism underlying this novel technique (which is called here functional laser Doppler flowmetry (FLDF)) is the coupling between visually evoked neural activity and vascular activity within the neural tissue of the optic nerve (neurovascular coupling). The blood flow responses elicited by various visual stimuli (luminance and chromatic flicker, focal and pattern stimulation) have been characterized in humans by FLDF. These responses are similar to those assessed by electrophysiological methods (flicker and pattern electroretinography) evoked by the same stimuli. In addition, a significant correlation has been demonstrated between the hemodynamic responses and the neural activity induced electrical signals arising from the inner retina, providing evidence in support of the presence of a neurovascular coupling in humans. The application of FLDF in patients with ocular hypertension and early glaucoma demonstrates that the visually evoked hyperemic responses are significantly depressed even when neural retinal activity may be still relatively preserved, suggesting that abnormal optic nerve head autoregulation in response to visual stimuli may be altered early in the disease process. FLDF may open new avenues of investigation in the field of glaucoma and other neuro-ophthalmic disorders, providing new pathophysiological data and outcome measures for potential neuro-protective treatments.

Regulation of retinal blood flow in health and disease.

Optimal retinal neuronal cell function requires an appropriate, tightly regulated environment, provided by cellular barriers, which separate functional compartments, maintain their homeostasis, and control metabolic substrate transport. Correctly regulated hemodynamics and delivery of oxygen and metabolic substrates, as well as intact blood-retinal barriers are necessary requirements for the maintenance of retinal structure and function. Retinal blood flow is autoregulated by the interaction of myogenic and metabolic mechanisms through the release of vasoactive substances by the vascular endothelium and retinal tissue surrounding the arteriolar wall. Autoregulation is achieved by adaptation of the vascular tone of the resistance vessels (arterioles, capillaries) to changes in the perfusion pressure or metabolic needs of the tissue. This adaptation occurs through the interaction of multiple mechanisms affecting the arteriolar smooth muscle cells and capillary pericytes. Mechanical stretch and increases in arteriolar transmural pressure induce the endothelial cells to release contracting factors affecting the tone of arteriolar smooth muscle cells and pericytes. Close interaction between nitric oxide (NO), lactate, arachidonic acid metabolites, released by the neuronal and glial cells during neural activity and energy-generating reactions of the retina strive to optimize blood flow according to the metabolic needs of the tissue. NO, which plays a central role in neurovascular coupling, may exert its effect, by modulating glial cell function involved in such vasomotor responses. During the evolution of ischemic microangiopathies, impairment of structure and function of the retinal neural tissue and endothelium affect the interaction of these metabolic pathways, leading to a disturbed blood flow regulation. The resulting ischemia, tissue hypoxia and alterations in the blood barrier trigger the formation of macular edema and neovascularization. Hypoxia-related VEGF expression correlates with the formation of neovessels. The relief from hypoxia results in arteriolar constriction, decreases the hydrostatic pressure in the capillaries and venules, and relieves endothelial stretching. The reestablished oxygenation of the inner retina downregulates VEGF expression and thus inhibits neovascularization and macular edema. Correct control of the multiple pathways, such as retinal blood flow, tissue oxygenation and metabolic substrate support, aiming at restoring retinal cell metabolic interactions, may be effective in preventing damage occurring during the evolution of ischemic microangiopathies.

Regulation of subfoveal choroidal blood flow in age-related macular degeneration.

PURPOSE: To assess the capability of the subfoveal choroidal circulation to regulate its blood flow in response to an acute increase in ocular perfusion pressure in the eyes of healthy elderly persons or of subjects with neovascular age-related macular degeneration (AMD). METHODS: Changes of subfoveal choroidal blood velocity (ChBVel), volume (ChBVol), and flow (ChBF) induced by isometric exercise were determined using laser Doppler flowmetry (LDF) in 19 young healthy volunteers (group 1), 24 elderly healthy volunteers with mild macular pigment distribution changes (group 2), and 23 subjects with subfoveal classic neovascularization caused by AMD (group 3). RESULTS: Isometric exercise induced significant increases in mean ocular perfusion pressure (PPm) of 19.5% +/- 4.9%, 20.2% +/- 3.8%, and 23.2% +/- 4.2%, for groups 1, 2, and 3, respectively (mean +/- 95% confidence interval). In groups 1 and 2, the increase in PPm did not induce significant changes in the mean values of the different LDF parameters. In group 3, however, ChBF increased significantly by 12.4% +/- 5.0%. No significant correlations were found between age and the changes of each of the LDF parameters and of PPm at the end of squatting for the young and elderly healthy groups. CONCLUSIONS: In response to an acute, moderate increase in PPm induced by isometric exercise, subfoveal choroidal blood flow behaves similarly in young and elderly healthy persons and is not significantly different from its value at rest. In contrast, in patients with neovascular AMD, this flow increases, indicating altered regulation in response to the increase in PPm.

Visually evoked hemodynamical response and assessment of neurovascular coupling in the optic nerve and retina.

The retina and optic nerve are both optically accessible parts of the central nervous system. They represent, therefore, highly valuable tissues for studies of the intrinsic physiological mechanism postulated more than 100 years ago by Roy and Sherrington, by which neural activity is coupled to blood flow and metabolism. This article describes a series of animal and human studies that explored the changes in hemodynamics and oxygenation in the retina and optic nerve in response to increased neural activity, as well as the mechanisms underlying these changes. It starts with a brief review of techniques used to assess changes in neural activity, hemodynamics, metabolism and tissue concentration of various potential mediators and modulators of the coupling. We then review: (a) the characteristics of the flicker-induced hemodynamical response in different regions of the eye, starting with the optic nerve, the region predominantly studied; (b) the effect of varying the stimulus parameters, such as modulation depth, frequency, luminance, color ratio, area of stimulation, site of measurement and others, on this response; (c) data on activity-induced intrinsic reflectance and functional magnetic resonance imaging signals from the optic nerve and retina. The data undeniably demonstrate that visual stimulation is a powerful modulator of retinal and optic nerve blood flow. Exploring the relationship between vasoactivity and metabolic changes on one side and corresponding neural activity changes on the other confirms the existence of a neurovascular/neurometabolic coupling in the neural tissue of the eye fundus and reveals that the mechanism underlying this coupling is complex and multi-factorial. The importance of fully exploiting the potential of the activity-induced vascular changes in the assessment of the pathophysiology of ocular diseases motivated studies aimed at identifying potential mediators and modulators of the functional hyperemia, as well as conditions susceptible to alter this physiological response. Altered hemodynamical responses to flicker were indeed observed during a number of physiological and pharmacological interventions and in a number of clinical conditions, such as essential systemic hypertension, diabetes, ocular hypertension and early open-angle glaucoma. The article concludes with a discussion of key questions that remain to be elucidated to increase our understanding of the physiology of ocular functional hyperemia and establish the importance of assessing the neurovascular coupling in the diagnosis and management of optic nerve and retinal diseases.

Flicker-evoked response measured at the optic disc rim is reduced in ocular hypertension and early glaucoma.

PURPOSE: To determine in patients with ocular hypertension (OHT) or early glaucoma (EOAG) the change in blood flow measured at the neuroretinal rim of the optic disc in response to a 15-Hz diffuse green luminance flicker, a stimulus that activates predominantly the ganglion cell magnocellular pathway. METHODS: Thirteen patients with EOAG, 29 with OHT, and 16 age-matched control subjects, all with excellent fixation, were examined. Blood flow (F(onh)) at the neuroretinal rim of the optic disc was continuously monitored by laser Doppler flowmetry before and during exposure to a 15-Hz, 30 degrees field green luminance flicker. The response of F(onh) to this stimulus (RF(onh)) was expressed as percentage change in F(onh) between baseline and the last 20 seconds of flicker. Two to three temporal sites of the disc were tested, and the highest RF(onh) was considered for further analysis. RF(onh) results in patients were correlated with morphologic (cup-to-disc area ratio, cup shape neuroretinal rim area) and functional (perimetric mean deviation and pattern electroretinogram amplitude) clinical parameters. RESULTS: In the patients with OHT or EOAG, F(onh) and RF(onh) were both reduced compared with their respective values in the control group. Both quantities decreased significantly with neuroretinal rim area when the patients' data were pooled. No significant correlation was found between F(onh) or RF(onh) and the other morphometric and functional parameters. The group-averaged time course of RF(onh) was not significantly different from that in the normal subjects. CONCLUSIONS: Luminance flicker-evoked RF(onh) is abnormally reduced in patients with OHT or EOAG, indicating an impairment of neurally mediated vasoactivity. The data suggest that PERG-derived neural activity and flicker-evoked RF(onh) can be independently altered early in the disease process.

Functional imaging of the human papilla and peripapillary region based on flicker-induced reflectance changes.

A non-invasive functional imaging technique of the nervous tissue of the human eye fundus based on two wavelength light reflectance changes (DeltaR %) is presented. The effect of 30 degrees diffuse luminance flicker field made of two spectral components (569 and 600 nm) on DeltaR was studied in six normal volunteers. Group averaged DeltaR was significant and similar in all quadrants of the optic disc at 569 nm with a mean equal to -10.7% for the tissue of the optic disc and -3.6% for the peripapillary regions. At 600 nm, the DeltaR were also significant but smaller, i.e. -3.5% for the disc tissue and -1.7% for the peripapillary region. The changes at 569 and 600 nm represent most probably blood volume changes. The 600 nm reflectance did not show evident features suggesting the presence of flicker-induced oxygenation changes.

Posture changes and subfoveal choroidal blood flow.

PURPOSE: To evaluate the effect of posture change on subfoveal choroidal blood flow (ChBF) in normal volunteers. METHODS: The pulsatile, nonpulsatile, and mean ChBF were measured with laser Doppler flowmetry in 11 healthy volunteers with a mean age of 32 +/- 13 (SD) years. The posture of the subjects was changed from standing (90 degrees ), to supine (-8 degrees ), and back to standing, with a mechanically driven table. During the whole experimental procedure, ChBF and heart rate (HR) were continuously recorded. After 30 seconds in standing position, the subjects were tilted to supine during approximately 30 seconds. They remained in this position for approximately 2 minutes, after which they were tilted back to the standing position (recovery), where they remained for another approximately 2 minutes. Systemic brachial artery blood pressure (BP) was measured in the baseline, supine, and recovery positions. This procedure was repeated to measure the intraocular pressure (IOP) at the different postures. RESULTS: Mean BP did not change significantly throughout the experimental procedure. As the body was tilted from standing to supine, HR decreased by 16% (P < 0.0004), IOP increased by 29% (P < 0.001), and mean ChBF increased by 11% (P < 0.01). The increase in ChBF was primarily due to an increase in the nonpulsatile component of the blood velocity. CONCLUSIONS: Based on previously reported experimental data that indicate that the ocular perfusion pressure increases less than predicted by purely hydrostatic considerations when the body is tilted from the standing to the supine position, the observed increase in ChBF suggests a passive response of the choroidal circulation to the posture change.

Temporal dynamics and magnitude of the blood flow response at the optic disk in normal subjects during functional retinal flicker-stimulation.

Near-infrared laser Doppler flowmetry was applied in 15 normal volunteers to record the time course and magnitude of changes in the velocity (Vel), volume (Vol) and flow (F) of blood and tissue reflectance (R) at the optic disk in response to 40 and 50 s of increased retinal neural activity. This activity was evoked by diffuse luminance flicker of the retinal posterior pole. After 20 s of flicker, the group averages of Vel, Vol, and F were significantly higher than at baseline (pre-flicker) by 12, 24 and 38%. Time constants of the increases in Vel, Vol, and F were 3.4, 12.7 and 9.1 s, respectively. The group average change in R of 1% was not significant. However, in one subject, 15 recordings from the same site of the optic disk showed a significant increase in R of 8%, with a time course similar to that of Vol. Our findings show that, in the human optic nerve, a white matter tissue, the temporal dynamics and magnitude of the response of blood flow to an increase in retinal neural activity are similar to those reported for brain gray matter. Furthermore, although the R-response could be due, in part, to changes in blood volume, other factors, such as activity-evoked tissue scattering changes, may also affect this response.

Investigating the role of nitric oxide in regulating blood flow and oxygen delivery from in vivo electrochemical measurements in eye and brain.

We have previously shown from direct, in vivo measurements of NO in cats with recessed electrochemical microsensors that NO mediates increases in ONH blood flow during functional activation of the eye by flickering light. We have also reported that there are low frequency (< 15 cycles/min) spontaneous oscillations in NO that appear to be passively coupled to oscillations in blood flow at similar frequencies in the cat ONH. In this paper, we describe similarities between in vivo measurements of NO in the ONH of the cat eye and in the cortex of the rat brain. These data are consistent with a role for NO in the coupling of blood flow with increases in neuronal activity, autoregulation of blood flow, hyperemia, and vasodilation during hypoxia and hypercapnia.