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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.

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.

Publisher Summary The eye fundus in higher mammals is supplied by two distinct vascular systems, namely the retinal and the uveal systems. Both systems are derived from the ophthalmic artery (OA), a branch of the internal carotid. The uveal system includes the anterior uvea, which comprises the iris and the ciliary body, and the choroid. The retina has a dual blood supply, the inner two-thirds being nourished by branches from the central retinal artery (CRA), whilst the outer third is nourished by the choroidal circulation. Quantitative information on blood velocity and flow in the normal human eye under physiological conditions has been obtained from the various ocular vascular systems using a number of different techniques. In the human eye, two vascular systems are present which differ anatomically and physiologically: the retinal vessels, which supply the neural region of the retina and the prelaminar portion of the ON and the uveal or ciliary blood vessels, which supply the rest of the eye. The rate of blood flow in the intraocular tissues is determined by the ocular perfusion pressure (OPP) and the vascular resistance (R). R depends upon the blood viscosity, length, and diameter of the blood vessels. The diameter of the resistance vessels is modulated by the interaction of multiple control mechanisms affecting the smooth muscle and vascular pericytes: myogenic, metabolic, neurogenic, humoral, and endothelium-derived factors. The determinants of ocular blood flow include systemic, local, neural, endothelial, endocrine, and paracrine factors.

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.

An ocular fundus reflectometer to measure non-invasively the light reflectance changes in response to diffuse flicker stimulation at two wavelengths (569 and 600 nm) simultaneously is presented. Image registration to minimize the effect of involuntary eye motion is described. Two-dimensional maps of reflectance changes of the optic disc and peripapillary retinal tissues in healthy volunteers are presented. These functional maps suggest increases in blood volume during stimulation, with changes in the optic disc as large as 10.7% at 569 nm and 3.5% at 600 nm.

A fundus camera-based instrument to investigate increased retinal neuronal activity effect on optic nerve blood flow is described. It incorporates (a) near infrared fundus illumination and observation, (b) near infrared laser Doppler flowmeter (LDF), (c) pupil position monitoring and (d) delivery of visual stimuli. Two types of stimulation are currently used: diffuse heterochromatic and chromatic luminance flicker generated by light emitting diodes, and contrast reversal pattern displayed on a video monitor. Recordings of the changes in the LDF parameters (blood velocity, volume and flow) from the optic nerve in response to these stimuli illustrate the potential of the technique.

A non-invasive functional imaging technique of the nervous tissue of the human eye fundus based on two wavelength light reflectance changes (DR %) is presented. The effect of 308 diffuse luminance flicker field made of two spectral components (569 and 600 nm) on DR was studied in six normal volunteers. Group averaged DR was significant and similar in all quadrants of the optic disc at 569 nm with a mean equal to 210.7% for the tissue of the optic disc and 2 3.6% for the peripapillary regions. At 600 nm, the DR were also significant but smaller, i.e. 2 3.5% for the disc tissue and 21.7% 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. q 2004 Elsevier Ireland Ltd. All rights reserved.

Background: The precise and rapid measurement ofeye length and eye shape isessential for investigating eye growth regulation andmyopia. For this purpose, we developedan optical low coherence reflectometer (OLCR) andpresent preliminary measurements.Methods: The OLCR includes a super luminescentdiode (wavelength: 845 nm,coherence length: ∼30 μm) and rotatingglass cube to produce longitudinal scansat a velocity of 0.42 m/s and a repetition rateof ∼13 scans/s. Heterodyne detection oflight reflected from the anterior cornea andthe posterior retina permits to measure axial eyelength and eye shape (off-axis eye length).Each measurement consists of five consecutivescans. Reproducibility and precision weredetermined in one volunteer by measuring axialeye length five consecutive times, each timerepositioning the eye. Eye shapes weredetermined in right eyes of four volunteers bymeasuring eye length every 3.3° from10° nasally to 10° temporally.Results: Axial eye length measured repeatedlyin one volunteer did not differ between orwithin the measurements (one-factor ANOVA). Theaverage standard deviation was11 μm. Eye shapes (a) varied substantiallyamong subjects and (b) differed considerablyfrom the corresponding shapes of sphericalmodel eyes with identical axial eye lengths.Conclusion: The newly developed OLCRpermits the precise and rapid measurement ofeye length and eye shape. Such measurements,especially in children, may provide importantinformation about mechanisms of eye growthregulation and the development of myopia.

BACKGROUND Previous studies have demonstrated, in the cat, a vasodilatation of retinal vessels in response to neuronal activity induced by diffuse luminance flicker. The aim of this study was to determine whether a similar diameter variation is detectable in humans. MATERIALS AND METHODS Nine normal subjects were exposed to 1 min of sinusoidally varying diffuse luminance flicker (10 Hz, 30 degrees around optic nerve head). Monochromatic fundus pictures before and after the stimulation were taken. The diameter of retinal arteries and veins was measured on the digitised photographs with the NIH-Image software and an own algorythm. RESULTS The diameter immediately after flicker was significantly larger than the pre-stimulus diameter by 4.2 +/- 2.2% (p < 0.014) (mean +/- SD) for the retinal arteries and 2.7 +/- 1.7% (p < 0.001) for the retinal veins. Six seconds after cessation of the flicker, arterial diameter was not significantly different from that of pre-flicker value. CONCLUSIONS Diffuse luminance flicker induces an increase in retinal vessel diameter. This suggest that retinal blood flow is coupled with neuronal activity as previously evidenced by the blue field simulation technique in the macula.

Increased neuronal activity induced by diffuse flickering illumination of the ocular fundus generates increases in blood flow and decreases in tissue pO 2 in the optic nerve head (ONH). This suggests that in the ONH, as in the brain, a coupling exists between function, perfusion, and metabolism, in accordance with the hypothesis of Roy and Sherrington. Following a review of the characteristics of the activity-induced blood flow response in the cat ONH, the relationship between blood flow and metabolism is discussed. We then examine possible mediators of the neurovascular coupling, some of the factors which may interfere with it, and point out various problems which remain to be addressed in order to better understand this coupling.

Objective: To investigate capillary blood flow in the optic nerve head (ONH) of children with cerebral malaria. Methods: Malawian children with cerebral malaria admitted to a paediatric research ward were examined by direct and indirect ophthalmoscopy. ONH blood flow was measured using laser Doppler flowmetry (LDF) in suitable patients. Mean blood volume and velocity were obtained from 30 to 60 s recordings from the temporal ONH and used to calculate blood flow. These were compared with admission variables, funduscopic findings and disease outcomes. Results: 45 children with cerebral malaria had LDF recordings; 6 subsequently died and 5 survivors had neurological sequelae. 12 (27%) had papilloedema. The mean microvascular blood volume was higher in patients with papilloedema (3.28 v 2.54 arbitrary units, p = 0.002). The blood velocity correlated directly with haematocrit (r = 0.46, p = 0.001) and inversely with blood glucose (r = −0.49, p = 0.001). Conclusion: The increase in ONH microvascular blood volume in papilloedema measured by LDF is consistent with current theories of pathogenesis of papilloedema. LDF has potential as a tool to distinguish papilloedema from pseudopapilloedematous disc swellings. The relationship between blood velocity and haematocrit may relate to levels of sequestration in cerebral malaria.

• Background: Studies in animals have demonstrated that optic nerve head (ONH) blood flow (Fonh) is autoregulated, but there is a lack of evidence for such a process in humans. Therefore, we investigated the relationship between Fonh and mean ocular perfusion pressure (PPm) in normal volunteers when PPm is decreased through elevation of the intraocular pressure (IOP). • Methods: Laser Doppler flowmetry (LDF) was used to measure relative mean velocity (Velohn), volume (Volonh) and Fonh of blood at sites of the ONH away from visible vessels, while PPm was decreased in two ways: (1) rapidly, by IOP increments of 15 s duration, and (2) slowly, by IOP increments of 2 min duration, both by scleral suction cup in one eye of each of nine subjects. • Results: A rapid and large decrease of PPm of more than 100% induced a decrease of more than 80% in Fonh. With the slower decrease in PPm Fonh remained constant down to a PPm of ≃22 mm Hg (IOP=40 mm Hg) and then decreased, predominatly due to a decrease in Velohn. Immediately after removal of the suction cup, Fonh increased transiently by 44% above baseline. • Conclusions: This study demonstrates efficient blood flow autoregulation in the OHN, which is probably brought about by an increase in vascular capacitance. The magnitude of the reactive hyperaemia agrees with the compensatory decrease in ONH vascular resistance during IOP elevation. The time scale of the autoregulatory process and the dependence of the hyperaemia upon duration of IOP elevation suggest a metabolic mechanism of autoregulation.

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 ± 0.4 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.

The effect of decreased ocular mean perfusion pressure (PPm), defined as mean arterial blood pressure minus intraocular pressure (IOP), on optic nerve head blood flow (Fonh) and on the response of this flow (RFonh) to diffuse luminance flicker was investigated in 19 anesthetized cats using laser Doppler flowmetry. PPm was decreased by increasing the IOP. The flicker stimulus consisted of 20-msec flashes delivered at 10 Hz for 30-60 sec. It illuminated a 30 degrees diameter area of the fundus, centered at the optic disk. Decreasing PPm by 10-35% from its resting value resulted in a 23% increase in RFonh (supranormal RFonh). With further decreases in PPm, RFonh decreased, reaching zero at a PPm below 20 mmHg. Fonh remained constant until PPm was < 40 mmHg and then decreased thereafter. When PPm was brought back to resting value after having been decreased for approximately 45 min, Fonh first increased by approximately 380% and then returned to its value at rest within approximately 4.5 min. At low PPm, hyperoxia decreased Fonh by 23% and restored the attenuated RFonh back to the value at resting PPm and hypoxia did not increase Fonh, as it did at normal PPm. This study confirms that the optic nerve head circulation is autoregulated over a wide range of PPm and reveals, for the first time, a hyperemic response to a prolonged decrease in PPm. It suggests that hypoxia plays a role in abolishing RFonh at low PPm and that the supranormal RFonh at moderately decreased PPm is due to an increase in the flicker-induced ganglion cell activity.

The role of nitric oxide (NO) in the regulation of optic nerve head (ONH) blood flow was investigated from direct electrochemical measurements of NO and simultaneous measurements of ONH blood flow by laser Doppler flowmetry during increased neuronal activity with diffuse luminance flickering light stimuli. For normal physiological conditions, there was a consistent increase in ONH blood flow with each flicker stimulus (n = 10 cats). Simultaneous NO measurements were made in the vitreous humor immediately in front of the ONH (n = 6 cats). During flicker, NO increased by 88 +/- 23 nM (P < 0.05) above basal NO levels. Measurements were repeated after inhibiting NO synthase by intravenous infusion of either NG-nitro-L-arginine (n = 5 cats) or NG-nitro-L-arginine methyl ester (n = 5 cats). After inhibition, NO levels were significantly reduced and both ONH blood flow and NO responses to flicker were significantly attenuated. We conclude that NO plays a key vasodilatory role in the ONH, modulating blood flow during greater neuronal activity with flicker stimuli.

Purpose. Laser Doppler interferometry (LDI) permits the measurement of intraocular distances to a precision of better than 20 microm. The signal complex from the posterior segment of the eye consists of four peaks in the chick, an animal frequently used in ocular development studies. The present study sought to identify anatomical landmarks corresponding to these LDI peaks. Methods. Distances obtained with LDI at the posterior pole were compared to axial length components measured with three independent methods: vernier calipers, tissue sections and high frequency A-scan ultrasound. Results. LDI reflections appear to originate from the retinal inner limiting membrane, Bruch's membrane and the inner and outer scleral surfaces. Conclusions. The non-invasive and highly precise nature of LDI measurements enables repetitive and accurate assessment of intraocular distances. Such measurements should prove particularly useful for the assessment of short-term cyclic variations in intraocular distances as well as post-natal eye growth.

We determined the effects of endothelin-1 on optic nerve head (ONH) blood flow in anesthetized cats. Endothelin-1 (50-2500 pmol) injected into the vitreous produced a dose-related and sustained decrease (22 +/- 6% by 500 pmol and 36 +/- 11% by 2500 pmol) in the ONH blood flow. Blood pressure (BP) and heart rate (HR) remained, however, unchanged. In contrast, intravenous (i.v.) injected endothelin-1 (0.004-0.4 nmol kg-1) produced a dose-related and short-lasting increase in the ONH blood flow; its maximum increase by 0.4 nmol kg-1 was 135 +/- 34%. Endothelin-1, at 0.4 nmol kg-1, i.v., produced a transient decrease followed by a more sustained increase in BP, but had no remarkable effect on HR. The increase in ONH blood flow by i.v. injection of endothelin-1 was abolished by N(G)-nitro-L-arginine methyl ester (L-NAME, 5 mg kg-1 min-1, i.v.). The suppression of blood flow by L-NAME was reversed by the addition of L-arginine (50 mg kg-1 min-1). Pressor responses to endothelin-1 (0.4 nmol kg-1, i.v.) were augmented in the presence of L-NAME, but reversed in combination with L-arginine. These findings suggest that i.v. injection of endothelin-1 causes NO release from endothelial cells which increases ONH blood flow, whereas intravitreal injection of endothelin-1 decreases ONH blood flow by its vasoconstrictive effect. Different populations of ET receptors on vascular smooth muscles or endothelial cells would reflect the opposing effects of endothelin-1.

The measurement of blood flow in the ocular fundus is of scientific and clinical interest. Investigating ocular blood flow in the choroid may be important to understand the pathogenesis of numerous ocular diseases, such as glaucoma or agerelated macular degeneration (AMD). Laser Doppler flowmetry (LDF) was applied to measure relative velocity, volume and flux of red blood cells in the tissues of human eye. Its main application lies in the possibility of assessing alterations in blood flow early in the course of diseases. The purpose of the present study was to investigate the effect of pupil dilatation with one drop of 1% tropicamide on blood flow in the foveal region of the choroid of the human fundus. The blood flow parameters were measured in 24 eyes during 30 minutes (one measurement in every 3 minutes) after the application of the drop. Since the Doppler parameters depend on the scattering geometry, which may change as the pupil dilates; an artificial pupil of 4mm in diameter was placed directly in front the eye. Following the administration of tropicamide the mean pupil diameter was increased from 3.29 mm to 8.25 mm (P

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.

Background: The relationship between the flicker-evoked changes in optic nerve blood flow (F onh ) and neural retinal activity was investigated by laser Doppler flowmetry and electroretinogram (ERG), respectively. Material and methods: In five normal subjects F onh was continuously recorded before, during and after exposure to green flicker modulation (30° field at the posterior pole), at different levels of mean illuminance between 0.9 and 13.5 lux. During flicker stimulation, ERGs were simultaneously recorded with F onh . The flicker-evoked changes in F onh (RF onh ) and the amplitudes of the first (1F) and second (2F) harmonic component of the ERG were measured. Results: By increasing mean flicker illuminance, RF onh and ERG 2F, but not 1F amplitude first increased and then saturated beyond 10 lux. RF onh and the corresponding 2F amplitudes, recorded at the various mean illuminances, showed a significant positive correlation (r = 0.79, p < 0.01). Conclusions: Under specific experimental conditions, changes in human RF onh are quantitatively correlated with those of the flicker ERG 2F amplitudes. Since the 2F component reflects, unlike 1F, a strong contribution from inner retina, the present findings support the presence of an association between vasoactivity and inner retinal activity changes in the human eye. This finding may provide a new approach to the study of neuro-ophthalmic disorders.

Laser Doppler flowmetry (LDF) is a technique used to measure relative average velocity, number and flux (number times velocity) of red blood cells in vessels or capillaries. In this study, the effect of topical timolol on the choroidal circulation was investigated in 12 healthy subjects. Maximum velocity of red blood cells and volumetric blood flow rate in sub-foveal choroids are determined in each eye just before instillation of drops and then every 30 min upto 2 hours. Average intraocular pressure (IOP) decreased significantly in the timolol-treated eyes compared to that of placebo-treated eyes. Nevertheless no significant differences in choroidal blood hemodynamic between timolol and placebo-treated eyes were observed.

Recessed cathode O2 microelectrodes were used to measure spatially detailed oxygen tension (PO2) gradients in the vitreous humor near the cat retina. Measurement sites (n = 41 in 8 cats) included single arterioles and venules and parallel vessel pairs. Mean vitreous PO2 was 37.9 +/- 1.5 (SE) Torr. Close to the retinal surface (approximately 200 microns), PO2 was found to be both higher and lower than the vitreous PO2, depending on the proximity of the microelectrode tip to retinal vessels. Both positive (inward) and negative (outward) O2 fluxes (JO2) were measured, consistent with the anatomy and expected boundary conditions in the eye. The PO2 at the closest approach above arterioles was 55.2 +/- 2.3 Torr, significantly higher than in the vitreous (P < 0.0001). All arterioles had outward JO2 with an overall mean of -2.58.10(-6) ml O2/sec/cm2. Some of the venules were also losing O2, but at much lower rates than arterioles. Several venules were gaining O2. Countercurrent transport (A-V shunting) was also seen between vessel pairs. Our experimental results allow theoretical predictions to be made for the axial drop in blood PO2 along an arteriole as a function of blood flow.

Purpose: To determine the response of human optic nerve head (ONH) blood flow (ΔF) to heterochromatic equiluminant flicker modulation (eql-fl) and compare it to the response induced by pure luminance flicker (I-fl). Methods: In 5 normal volunteers the ONH blood flow was measured by conventional laser Doppler flowmetry. Stimuli were generated by green and red light emitting diodes and delivered to the eye through a fundus camera illumination optic. Both green and red illuminances were square wave modulated in counter phase at different frequencies between 2 and 40 Hz. ΔF was defined as the ratio between the ONH blood flow after 1 min stimulation and a baseline blood flow measured prior to the stimulation. Results: In response to a 2 Hz eql-fl, ONH blood flow increases by 36% in average. AF versus flicker frequency displayed the characteristics of a low-pass function with a cutoff frequency of 10 Hz for an eql-fl and a band-pass function with broad maximum around 10 Hz for the I-fl. Conclusions: AF in human ONH can be evoked by heterochromatic equiluminant flicker modulation. The blood flow frequency response to eql-fl and I-fl are similar to the neural activity dominated by the Parvo- and Magno-cellular activity, respectively. These findings offer a new approach to study the neurovascular coupling at the ONH in both physiological and diseased conditions involving predominantly or selectively the Magno- and Parvo-pathways.

A laser Doppler interferometer was built for the precise measurement of intraocular optical distances in humans and chicks. A technique using Purkinje images was developed to position the chick's eye reproducibly. A computer algorithm for the objective analysis of the interference signal and determination of the optical distances is presented. The precision of this noncontact interferometric method for measuring the cornea-retina distance is better than ±20 µm.

A new bidirectional laser Doppler velocimeter (LDV) is described for absolute measurement of the speed of red blood cells flowing in individual retinal vessels. The basic component of the instrument is a standard retinal camera that eliminates the need for a contact lens. The laser beam is delivered to the eye through the fundus illumination optical system of the camera. Target fixation is done with the eye under examination. The measurements are independent from the ocular refraction; only the axial length of the eye need be determined. The instrument markedly simplifies the technique of retinal blood flow measurement.

Ocular fundus reflectometry is a technique aimed at the in-vivo measurement of the reflectance of the tissues of the ocular fundus. Studies have demonstrated a correlation between optical and physiological properties of such tissues in humans and the existence of a control mechanism, called neuro-vascular coupling (NC), which adjusts local blood perfusion to support vision-induced neural activity. We developed an instrument for functional imaging of the neural tissues of the ocular fundus based on reflectance measurements to study the NC. The images acquired with the instrument needed processing to work out reflectance time-courses. The algorithm exploited previously requires long computational time, provides poor discrimination of objects and need manual intervention. We have developed a fully automatic algorithm based on differential multiscale framework for the processing of the images of the ocular fundus with reduced computational time. This algorithm is reasonably efficient to determine relative translational displacement (translation and rotation) between the images and also to remove the geometric distortion. Simulation results performed on the fundus images show that differential multiscale framework based image registration reduces computational times up-to one fourth of the time required by the general purpose algorithm, and provides better alignment precision.

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.

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.

Purpose: To assess subfoveal choroidal blood flow in patients with early manifest glaucoma (EMG) and to compare blood flow with functional measures of retinal ganglion cell (RGC) integrity. Methods: Subfoveal choroidal blood flow was determined by confocal, real-time laser Doppler flowmetry1,2 in 25 patients with EMG (< -6 dB Humphrey mean deviation, age range: 42-64 years, visual acuity: 0.8-1.0) and in 20 age-matched control subjects. All patients had a therapeutically (topical beta-blockers with or without a prostaglandin) controlled intraocular pressure (IOP < 20 mm Hg). Subfoveal choroidal blood volume (ChBVol), velocity (ChBVel) and flow (ChBF) were determined as the average of three 60 sec recordings with changes in the DC < 10% between the recordings (the DC measures the intensity of the light scattered by the tissue and red blood cells in the illuminated volume). In all patients and controls, pattern electroretinograms (PERGs) were also recorded according to a standardized protocol.3 Results: In EMG patients, average ChBVel and ChBF were reduced by 31 and 35%, respectively (p < 0.01) compared to control values. No significant difference in ChBVol was found between the two groups. PERG amplitudes were reduced by 40% (p < 0.01) in EMG patients compared to controls. No correlation was found between anyone of the choroidal flow parameters and PERG data or IOP values. Conclusions: The results suggest a significant alteration of subfoveal choroidal hemodynamics in EMG patients, involving both ChBVel and ChBF. These changes do not appear to be associated with the severity of functional retinal ganglion cell loss. Our findings may have implications for the pathophysiology of early glaucomatous damage in EMG and its treatment. 1Riva CE, Cranstoun SD, Grunwald JE, Petrig BL. Invest Ophthalmol Vis Sci, 1994 2Geiser MH, Diermann U, Riva CE. J Biomed Opt, 1999 3Falsini B, Marangoni D, Salgarello T, et al. Graefes Arch Clin Exp Ophthalmol, 2008

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).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.During SFS, FERG 2F showed a modest increase in amplitude (about 25%, p0.05). 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.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.Our findings may have implications for diagnosis and/or pathophysiology of retinal disorders involving the inner retina.

UNLABELLED A new instrument for the measurement of choroidal blood flow in the fovea is presented. It is based on the laser Doppler method and a confocal optical system with an indirect detection of the Doppler shifted light. METHOD The intensity of the laser beam (785 nm) at the cornea is 90 microW. Measurements were obtained from a normal population of 21 subjects under resting conditions without dilating the pupil. RESULTS The reproducibility of the choroidal blood flow, based on 5 measurements of 10 s each in 5 randomly selected subjects, is 9%. The minimum detectable change for a statistical significance of p < or = 0.05, based on a population of 21 subjects and 10 s measurements, is 9%. CONCLUSION This new compact instrument appears to be suitable for the investigation of the physiology and pharmacology of choroidal blood flow and the effect of age-related macular degeneration.

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.

Using laser Doppler flowmetry, slow variations in velocity, volume, and flux of red blood cells in the optic nerve head (ONH), choroid, and retina of the anesthetized minipig have been demonstrated. The variations of velocity and volume were highly regular and vigorous in the ONH and had frequencies ranging from 2.5 to 4.5 cycles/min. The flux variations were smaller or absent due to a phase shift of approximately 180 degrees between the volume and velocity changes. The volume fluctuations were synchronized to those of the PO2 measured in the vitreous, at approximately 50 microns from the surface of the ONH tissue. The fluctuations were less regular in the choroidal and the retinal vessels and their frequencies were higher than those in the ONH. The lack of correlation between the fluctuations in the ONH and those in the retinal and choroidal vessels points toward a local mechanism. The changes in blood volume in the ONH, the phase shift between volume and velocity changes, and the predominance of venules at the surface of the ONH are three factors suggesting that this mechanism involves a change in the diameter of the venules rather than in the arterioles.

Neurovascular coupling in the optic nerve is the physiological mechanism that adjusts the blood perfusion in the microcirculation of the optic nerve to support the neural activity induced by vision. The resulting variations in blood flow and thus in neural tissue oxygenation induce changes in the optical properties of the tissues. These variations can be detected optically as reflectivity changes in the neural tissues, i.e. the retina and optic nerve disk. To achieve a better understanding of the mechanisms underlying the neurovascular coupling, our study is aimed at the evaluation of reflectance changes of the optic nerve induced by visual stimulation. For this purpose, an ocular fundus reflectometer has been developed.

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.

BACKGROUND The effect of changes in ocular perfusion pressure (PPm) on the choroidal blood flow (ChBF) in man was studied with the laser Doppler flowmetry (LDF) technique. MATERIALS AND METHODS We changed the PPm by increasing the intraocular pressure (IOP) or by increasing the blood pressure (BP) with isometric exercises. RESULTS We observed that a) ChBF was not significantly different from baseline up to an IOP of 27 mm Hg and b) ChBF remained constant even if PPm increased by as much as 72%. CONCLUSION Our results suggest that ChBF is autoregulated in response to an increase in IOP up to about 27 mm Hg. ChBF remains also constant in spite of an increase in systemic BP, probably due to a vasoconstriction induced by increased sympathetic activity.

BACKGROUND In this paper we present a miniaturized blue field simulator (BFS) which allows the measurement of the velocity (V) pulsatility (P) and number (D) of leukocytes in the macular retinal capillaries. A study on the effect of the aperture size of the blue light source at the subject's pupil on the measured flow parameters was performed. METHODS A blue field entoptoscope with a small halogen lamp was used to induce the perception of the "flying corpuscles" and a flat color screen was selected to display a computer simulation of this entoptic phenomenon. The aperture of the blue light source at the pupil was varied by a diaphragm placed at a conjugate pupil plane while the size and retinal irradiance of the blue field stimulus at the fundus was held constant. RESULTS The results show significant correlations between log pupil area and both V (-18% per log unit) and D (+42% per log unit). When the retinal illuminance is expressed in Log Trolands, V shows no dependency, but D is strongly correlated (+40% per log Troland). CONCLUSIONS When applying the BFS technique, the size of the blue light stimulus at the pupil, if undilated, must be well controlled to minimize instrument-related variations of the blood flow measurements.

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.

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.

Blood flow studies in the brain, heart, and other organs suggest that there could be interaction between nitric oxide (NO) and adenosine. This possibility was investigated in the optic nerve head (ONH) during photic stimulation of the dark-adapted cat eye. Functional activation of ONH blood flow was measured by laser Doppler flowmetry, simultaneously with NO and PO 2 using double-barrel recessed electrochemical sensors. Photic stimulation (diffuse luminance flickering light at 30 Hz) increased ONH blood flow to 127.4 ± 4.7% (mean ± SEM) of baseline with a transient increase in NO by 79.8 ± 12.8 nM, while P O 2 decreased from 24.5 ± 2.7 to 22.7 ± 2.4 Torr (control responses, 15 trials, 10 cats). Adenosine (3 mg/kg iv) increased baseline ONH blood flow to 113.8 ± 8.4% of control within 5 min. Functional activation of ONH blood flow was enhanced during photic stimulation, reaching a maximum of 155.8 ± 8.1% within 5 min, and remained enhanced for 30 to 45 min. NO responses during photic stimulation were not different from control responses. Treatment with a nonspecific NO synthase inhibitor ( N G -nitro- l -arginine methyl ester, 40 mg/kg iv, 5 cats) did not alter the increase in resting ONH blood flow or the enhanced functional activation after adenosine. We conclude that there is no interaction between NO and adenosine during functional activation of cat ONH blood flow by photic stimulation.

Background: In healthy subjects, choroidal blood flow is regulated when the mean ocular perfusion pressure increases. Since capillary vascular beds are altered in diabetic patients, the regulation of choroidal blood flow could be affected by this pathology. Patients and methods: 10 type I diabetic patients without retinopathy (DNR group) and 7 type I diabetic patients with retinopathy (DR group) participated in the study. In NDR and DR groups, choroidal blood flow was measured while patients raised their mean arterial blood pressure by squatting. The results were compared to those of a previous study in normals. Pupillometry was performed at rest on the two diabetic groups and on seven normals during a modification of illumination (white/black screen transition). Results: In the NDR and DR groups, mean ocular perfusion pressure raised by 61 and 50% during squatting, respectively. Consecutively, choroidal blood flow did not change in NDR as in normals, but increased linearly in DR patients. The white/black screen transition produced an increase of the pupil diameter of 52 and 49% in normals and NDR patients, respectively, while it increased by only 16% in the DR patients. Conclusions: As already shown in healthy subjects, choroidal blood flow is regulated in NDR patients when the ocular perfusion pressure increases. In DR patients, the absence of this control could be due to a failure of the autonomic nervous system, as suggested by pupillometry results.

Background: The precise and rapid measurement of eye length and eye shape is essential for investigating eye growth regulation and myopia. For this purpose, we developed an optical low coherence reflectometer (OLCR) and present preliminary measurements. Methods: The OLCR includes a super luminescent diode (wavelength: 845 nm, coherence length: ~30 µm) and rotating glass cube to produce longitudinal scans at a velocity of 0.42 m/s and a repetition rate of ~13 scans/s. Heterodyne detection of light reflected from the anterior cornea and the posterior retina permits to measure axial eye length and eye shape (off-axis eye length). Each measurement consists of five consecutive scans. Reproducibility and precision were determined in one volunteer by measuring axial eye length five consecutive times, each time repositioning the eye. Eye shapes were determined in right eyes of four volunteers by measuring eye length every 3.3° from 10° nasally to 10° temporally. Results: Axial eye length measured repeatedly in one volunteer did not differ between or within the measurements (one-factor ANOVA). The average standard deviation was 11 µm. Eye shapes (a) varied substantially among subjects and (b) differed considerably from the corresponding shapes of spherical model eyes with identical axial eye lengths. Conclusion: The newly developed OLCR permits the precise and rapid measurement of eye length and eye shape. Such measurements, especially in children, may provide important information about mechanisms of eye growth regulation and the development of myopia.

Laser Doppler flowmetry (LDF) has been applied to investigate the effect of increased retinal neural activity induced by diffuse luminance flicker stimulation and dark/light transition on blood flow in the optic nerve head (ONH). We describe the theoretical basis, instrumentation and software for LDF measurements of the blood flow response. The characteristics of this response strongly suggest a coupling between blood flow and neural activity at the ONH. Some of the mechanisms underlying the neurovascular coupling are discussed and problems that remain to be studied to better understand this coupling in normal and pathological conditions are mentioned.

The optic nerve head (ONH) is supplied by two main sources of blood flow: the superficial layers by the central retinal artery (CRA) and the deeper layers by the posterior ciliary arteries (PCAs). Using a fundus camera-based laser-Doppler flowmetry (LDF) technique to measure blood flow in the ONH tissue, we conducted a study in rhesus monkey eyes to obtain a better understanding of which part of the ONH circulation is measured by LDF. LDF measurements were taken at baseline, then after experimental occlusion of CRA (12 eyes), all the PCAs (9 eyes) and combined occlusion of CRA and all the PCAs (9 eyes). ONH, choroidal and retinal circulations following the various arterial occlusions were investigated by fluorescein fundus angiography. Average LDF flow during CRA occlusion alone was highly significantly decreased (p 0.20). After PCA occlusion alone, however, measurements showed a non-significant increase in LDF flow of 17±37%. Thus, the findings of this study suggest that the LDF technique is predominantly sensitive to flow changes in the surface layer of the ONH and less sensitive to those in the deeper layers of the ONH.

Choroidal thickness and axial eye length in the chick undergo day/night fluctuations that can also be modulated by visual experience. In the present study, we tested the effect of parasympathetic and sympathetic denervations on both day/night and image dependent changes in ocular dimensions. We also correlated such changes with fluctuations in intraocular pressure. Parasympathectomy influenced choroidal thickness and its day/night fluctuation, but had no effect on vision dependent choroidal thickness modulation. Parasympathectomy also influenced-to a lesser extent-axial length and reduced the axial growth response to form vision deprivation. Sympathectomy had little effect on ocular dimensions, but reduced the day/night differences in intraocular pressure. We conclude that (a) the parasympathetic nervous system influences both choroidal thickness and axial length and participates in the neural control mechanism leading to form deprivation myopia and, (b) the day/night fluctuations of choroidal thickness and axial length are unlikely to be explained by fluctuations in intraocular pressure. For the regulation of choroidal thickness, we hypothesize the existence of two independent mechanisms. One involves the parasympathetic nervous system; it influences the day/night choroidal thickness fluctuation. The other uses a separate pathway and is driven by visual input.

Low coherence laser Doppler interferometry (LDI) allows high precision measurements of the axial length of the eye and of the thickness of the individual layers of the ocular fundus. Here, we used LDI to monitor diurnal changes in these dimensions in eyes of newly hatched chicks and one-year-old chickens with normal or altered visual input. In chicks and chickens with normal visual experience, axial eye length displays diurnal fluctuations increasing during the light phase. Choroidal thickness also exhibits a diurnal pattern, shrinking during the day and expanding during the night. Retinal thickness does not vary. Based on the pressure compliance of the enucleated chick eye, the diurnal intraocular pressure (IOP) fluctuation could contribute both to the increase in axial length and to daytime choroidal shrinkage. Following deprivation of form vision by unilateral goggle wear, occluded chick eyes demonstrate enhanced axial elongation. Diurnal fluctuations in axial length but not in choroidal thickness are temporarily disrupted. The retina of form deprived eyes thins approximately 10% in five days. In contralateral eyes, the diurnal patterns of both axial length and choroidal thickness fluctuations are also disrupted. Following occluder removal in chicks, choroidal thickness increases for several days during both the light and dark phase, leading to its overall expansion. Retinal thickness returns to baseline. When deprived of form vision for five days, the eyes of year-old chickens do not exhibit measurable axial elongation. Diurnal patterns of fluctuation in axial length and choroidal thickness are however disrupted. After goggle removal, axial length fluctuation is restored to normal, but the diurnal choroidal thickness pattern is inverted. In contralateral eyes, choroidal thickness exhibits normal diurnal fluctuations both during and after form vision deprivation. In conclusion, axial length and choroidal thickness fluctuations are influenced by visual experience in both newborn chicks and one-year-old chickens. In selected instances a binocular interaction regarding axial length and choroidal thickness changes is suggested, the effect weakening with age.

Understanding the pathophysiology of the optic nerve head (ONH) requires precise knowledge of the oxygenation of this tissue. Previous investigations used methods based on oxygen sensitive microelectrodes to measure the partial pressure of oxygen in the ONH tissue. These microelectrodes are inserted into the eye through the pars plana. New methods are now being developed to measure the intravascular PO2 in the ONH. They are based on the quenching of phosphorescence of a porphyrin dye by oxygen. Although these methods require an intravenous injection of this dye, the eye is left untouched. This article reviews these noninvasive methods.

Mechanisms coupling blood flow with changes in neuronal activity (functional hyperemia) in the brain, eye, and other organs are not completely understood. Nitric oxide (NO) has been suspected to play an important role, especially in the brain (Iadecola, 1993). We have shown that optic nerve head (ONH) blood flow increases during stimulation of the cat eye by flickering light, depending on the frequency and luminance of the stimulus, using a microscope-mounted infrared laser Doppler system to measure relative changes in ONH blood flow simultaneously with changes in extracellular K+ measured with ion-selective microelectrodes in the vitreous humor immediately above the ONH (Buerk et al., 1995). We have also measured changes in ONH blood flow simultaneously with NO near the ONH using recessed electrochemical microsensors (Buerk et al., 1996). We found that NO increased during neuronal activation by flickering light, and that the functional hyperemia in ONH blood flow and NO increases were significantly attenuated after inhibiting NO synthase. In this report, we describe simultaneous ONH blood flow, NO and PO2 measurements during increased neuronal activity with flickering light. Preliminary results are consistent with coupling of functional hyperemia with increased O2 consumption, but multiple interactions with NO need to be taken into account.

We evaluated in ocular hypertension (OHT) and early glaucoma (EOAG) patients the optic nerve head (ONH) blood flow response (RFonh) to chromatic equiluminant flicker. This stimulus generates neural activity dominated by the parvo-cellular system. Eleven EOAG, 20 OHT patients, and 8 age-matched control subjects were examined. The blood flow (Fonh) at the neuroretinal rim was continuously monitored by laser Doppler flow- metry before, during, and after a 60-s exposure to a 4 Hz, red-green equiluminant flicker stimulus (30 deg field). RFonh was expressed as percentage Fonh-change during the last 20 s of flicker relative to baseline Fonh. Responses were collected at a number of temporal sites. The highest RFonh value was used for subsequent analysis. As compared to controls, both OHT and EOAG patients showed a decrease (p < 0.01) in mean RFonh. We conclude that RFonh elicited by chromatic equiluminant flicker is abnormally reduced in OHT and EOAG patients indicating an impairment of the parvo-cellular-mediated vasoactivity. This decrease of vascular response may occur independently of neural activity loss early in the disease process. © 2014 Society of Photo

AIMS--The purpose of this study was to investigate the effect of instituting strict diabetic glycaemic control on the retinal macular microcirculation and to compare this effect with that observed in the main retinal veins. METHODS--In 28 insulin dependent diabetic patients with poor glycaemic control a regimen of strict diabetic control, consisting of four daily insulin injections was instituted and maintained for 6 months. Retinal haemodynamics were investigated in the macular microcirculation by the blue field simulation technique and in the major retinal veins by a combination of bidirectional laser Doppler velocimetry and monochromatic fundus photography. Progression of diabetic retinopathy was assessed from fundus photographs taken at baseline and at the end of the study. RESULTS--Institution of strict diabetic control resulted in a significant increase in leucocyte velocity in the macular circulation (p = 0.013). No significant difference in this increase was observed between eyes that showed progression (n = 8) and no progression (n = 20) of retinopathy during the study. Significant correlations were found between relative changes over time of blood flow measured in the main retinal veins and relative changes of leucocyte velocity determined in the macular microcirculation at 2 months (p = 0.008) and 6 months (p = 0.001) but not at 5 days (p = 0.49). In the eight eyes that showed progression of retinopathy, the product of leucocyte velocity and density at baseline was significantly higher than normal (p < 0.05). During the length of this study, this product was also significantly higher in the eight eyes that showed retinopathy progression than in the 20 eyes that did not show progression (p = 0.005). CONCLUSION--Our results suggest that increased flow in the macular microcirculation may be associated with progression of retinopathy, thus supporting the hypothesis that increased blood flow may play a role in the development of diabetic microangiopathy. Although there are correlations between the changes detected in the macular microcirculation and those measured in the main retinal vessels, there are also differences which need to be further investigated in order to better understand pathogenetic mechanisms.