On Optic Nerve Head Blood Flow Research Articles

Preperimetric Glaucoma Prospective Observational Study (PPGPS): Design, baseline characteristics, and therapeutic effect of tafluprost in preperimetric glaucoma eye

PurposeThere is no consensus on the diagnosis or treatment policy for Preperimetric Glaucoma (PPG) because the pathogenesis of PPG is not clear at this time. Preperimetric Glaucoma Prospective Observational Study (PPGPS) is a first multicenter, prospective, observational study to clarify the pathogenesis of PPG. This article indicates study design, patient baseline characteristics, and analysis focused on optic nerve head (ONH) blood flow in PPG, as well as the intraocular pressure (IOP) -lowering effect and ONH blood flow-improving effects of Tafluprost.MethodIn this study, 122 eyes from 122 subjects (mean age: 53.1 ± 14.3) newly diagnosed as PPG were enrolled. The circumpapillary retinal nerve fiber layer thickness (cpRNFLT) was evaluated with optical coherence tomography (OCT). The ONH blood flow was measured with laser speckle flowgraphy. The therapeutic effect of Tafluprost was evaluated at Month 0 (ONH blood flow-improving effect) and Month 4 (IOP-lowering effect).ResultsThe untreated IOP, cpRNFLT, and baseline Mean deviation (MD) value was 16.4 ± 2.5 mmHg, 80.4 ± 8.2 μm, and -0.48 ± 1.29 dB, respectively. In the site-specific visual field evaluation using the sector map, there was no appreciable site-specific visual field defect in the eye with PPG. The inferior region of cpRNFLT in 4-quadrant OCT sector analysis and 6 o’clock region in 12-o’clock OCT sector analysis was the highest rate of abnormality in PPG eyes. Topical administration of Tafluprost significantly reduced IOP from 16.4 ± 2.5 mmHg at baseline to 14.5 ± 2.3 mmHg at Month 4 (P < 0.001, paired t-test). In the linear regression analysis, there was a significant relationship between the increase of ONH blood flow and baseline value.ConclusionPPGPS is a first prospective study focusing on the pathology of PPG. This study is expected to elucidate the pathology of PPG, with evidence useful for determining a treatment strategy for PPG.

Continuous Response of Optic Nerve Head Blood Flow to Increase of Arterial Blood Pressure in Humans

This study investigates the effect of increased ocular perfusion pressure (OPP) on optic nerve head (ONH) hemodynamics. 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). 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. 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.).

Changes in optic nerve head blood flow, visual function, and retinal histology in hypercholesterolemic rabbits

We investigated the effects of hypercholesterolemia on optic nerve head (ONH) blood flow, visual function, and retinal histology in a rabbit model. Hypercholesterolemia was induced in rabbits by feeding them a high cholesterol (1%) diet for 12 weeks. Changes in blood pressure, intraocular pressure (IOP), and ONH blood flow were monitored at 6 and 12 weeks after treatment. The autoregulation of ONH blood flow as detected by laser speckle flowgraphy was verified by an artificial elevation of IOP at 12 weeks. Visually evoked potentials (VEPs) were also recorded and analyzed at 6 and 12 weeks. Finally, a histological examination as well as immunohistochemistry to endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) was performed. In the hypercholesterolemic rabbits, blood pressure, IOP, and ONH blood flow did not alter significantly throughout this study. The autoregulation of ONH blood flow against IOP elevation was found to be impaired at 12 weeks. The amplitudes of the first negative peak of VEPs were diminished. Both the density of the retinal ganglion cells and the thickness of the inner nuclear layer and photoreceptor cell layer were reduced. Immunoreactivity to eNOS was reduced and that to iNOS was enhanced in the hypercholesterolemic rabbits compared to those in the normal control rabbits. The results of this study show that hypercholesterolemia induces impairment in the autoregulation of ONH blood flow and deterioration in visual function and histology. Downregulation of eNOS activity might be one of the causes for impairment of the autoregulation. Enhanced activity of iNOS might be involved in the impaired visual function and histology.

Complex regulation of optic nerve head blood flow during combined isometric exercise and elevation of intraocular pressure

AbstractPurpose For a long time it was assumed that ocular vascular beds are characterized by one specific pressure/flow curve. Recently we have, however, shown that this behavior is much more complex in the choroid, because alterations in arterial and venous pressure lead to different regulatory behaviors. In the present study we tested the hypothesis that this is also the case in the optic nerve head.Methods Two study days were performed in 40 healthy subjects. On the 1st day the effect of isometric exercise and an elevation of IOP on optic nerve head blood flow (ONHBF) were studied separately. On the 2nd day the effect of combined IOP and mean arterial pressure (MAP) increase was investigated. IOP was increased in a stepwise way using the suction cup method. ONHBF was measured using laser Doppler flowmetry. For correlation analysis all values from all subjects were pooled according to IOP and MAP values.Results When data were grouped according to MAP values a highly significant correlation was found between ONHBF and IOP (p&lt;0.001). The regression lines at different MAP levels were almost equal. When data were pooled according to IOP levels a significant correlation was found between MAP and ONHBF for IOP values up to 25 mmHg (p&lt;0.05) and the correlation lines were almost identical. At higher IOP values, however, no correlation between ONHBF and MAP was found.Conclusion Our data are in agreement with previously published studies that ONHBF shows some autoregulatory capacity. The autoregulatory behavior appears to be complex and dependent on the site of perfusion pressure regulation (arterial vs venous). Compared to the choroid the ONH adapts its perfusion better to an increase in IOP

Effects of Repeated Administrations of Tafluprost, Latanoprost, and Travoprost on Optic Nerve Head Blood Flow in Conscious Normal Rabbits

The aim of this study was to evaluate and compare the effects of repeated administrations of three prostaglandin F(2alpha) analogs (tafluprost, latanoprost, and travoprost) on optic nerve head (ONH) blood flow in normal rabbits. Male Dutch rabbits were housed under a 12-h light-dark cycle for use in this study. A quantitative index of blood flow, the squared blur rate (SBR), was determined using laser speckle flowgraphy. Saline, 0.0015% tafluprost, 0.005% latanoprost, or 0.004% travoprost (each 50 microL) was topically administered into the left eye once daily for 28 days. ONH blood flow was measured before the start at the course of treatment (baseline), and on day 14 and/or day 28 [measurements being made at 0, 30, and/or 60 min after drugs application on day 14 and/or day 28]. Heart rate was also measured at these time points. Tafluprost, latanoprost, and travoprost each increased the ONH blood flow at all measurement points on day 14 and/or day 28. The 0 min SBR value on day 14 was greater than the baseline SBR value by 8.7% + or - 4.4% for tafluprost and by 5.8% + or - 1.7% for latanoprost. The 0 min SBR value on day 28 was greater than the baseline SBR value by 11.9% + or - 3.9% for tafluprost, by 7.2% + or - 4.3% for latanoprost, and by 6.7% + or - 3.5% for travoprost. The increasing state of the ONH blood flow continued within 60 min after a topical administration of tafluprost, latanoprost, or travoprost. Tafluprost, latanoprost, and travoprost did not change heart rate (vs. the baseline value) at any measurement points. Repeated topical administration of any of the three prostaglandin F(2alpha) analogs increased ONH blood flow in rabbits, without changing heart rate. The increase in ONH blood flow induced by tafluprost was greater than that induced by latanoprost (P = 0.086) or travoprost (P = 0.037) at 60 min on day 28.

Changes in optic nerve head blood flow induced by the combined therapy of latanoprost and beta blockers

To assess the effects of combined therapy with latanoprost and beta blockers on optic nerve head (ONH) blood flow in normal-tension glaucoma (NTG) patients. Intraocular pressure (IOP), ONH blood flow (laser speckle flowgraphy) and blood pressure were measured in 15 eyes of 15 NTG patients (41-76 years old) before treatment or after a 1-month washout period. Similar measurements were performed at 2 months after the commencement of treatment with latanoprost and at 3 months after the start of combined therapy of latanoprost with 0.5% timolol or 2% carteolol in a crossover study using the envelope method. Measurement was carried out 2-3 hr after the morning application of eyedrops. Latanoprost decreased IOP with no significant change in ONH blood flow. Concomitant use of timolol or carteolol further decreased IOP with no significant difference between these two drugs. Only the combined therapy of latanoprost with carteolol significantly (p < 0.01) increased ONH blood flow by approximately 10%, compared to initial levels. There was no significant change in mean blood pressure, ocular perfusion pressure or pulse rate as a result of these therapies. Topical latanoprost-carteolol combined therapy increased ONH blood flow in NTG patients, unlike latanoprost-timolol therapy. Because ocular perfusion pressure was unchanged, direct vasodilative effects were suspected as the mechanism.

Effects of high-dose prednisolone on optic nerve head blood flow in patients with acute optic neuritis

In this study, patients with optic neuritis were treated with high-dose prednisolone. Little information is available about the effects of this treatment on ocular blood flow. We set out to investigate the effects of high-dose prednisolone on optic nerve head (ONH) blood flow in patients with acute optic neuritis. Thirteen patients with acute optic neuritis were included in the study. 1000 mg of prednisolone was infused intravenously over 30 minutes on 3 consecutive days. On each study day, ONH blood flow was measured using laser Doppler flowmetry. The ocular hemodynamic measurements were performed on the unaffected eye of the patients with unilateral acute optic neuritis before and immediately after cessation of the infusion. Intraocular pressure (IOP) and systemic blood pressure was measured before and after the infusion on each study day. Data was analyzed using a repeated measures ANOVA model. Prednisolone increased ONH blood flow in the patients under study (p = 0.04), although the effects were in generally small. No significant change in mean arterial pressure (p = 0.70) or IOP (p = 0.20) could be detected in the patients treated with high-dose prednisolone. A small but significant increase in ONH blood flow resulted from infusion of high-dose prednisolone. Further studies are required to investigate whether this effect contributes to the therapeutic efficacy of cortisone in patients with optic neuritis.

CS-088, an Angiotensin Type 1 Receptor Antagonist, Ameliorated the Impaired Blood Flow in the Optic Nerve Head of Rabbits

The effect of CS-088, an angiotensin type 1 receptor antagonist, on optic nerve head (ONH) circulation was investigated in anesthetized rabbits. ONH blood flow was measured for 3 h using laser Doppler flowmetry. ONH blood flow disturbance was induced by intravenous injection of endothelin-1. Blood flow was decreased by 30%; this decrease was reversed by the injection of CS-088. A single injection of CS-088, however, did not alter the baseline ONH blood flow. It is concluded that CS-088 can have a beneficial effect on disturbed ONH blood flow.

Liposomal prostaglandin E1 enhances optic nerve head blood flow in cats.

We investigated the effects of intravenous administration of prostaglandin E1 (PGE1) and lipo-prostaglandin E1 (lipo-PGE1), on optic nerve head blood flow (ONHBF) using ten anesthetized cats. Changes in relative ONHBF were noninvasively and continuously measured with fundus camera-based laser Doppler flowmetry. The blood pressure (BP) decreased significantly by 6 +/- 5 (mean +/- SD)% and 8 +/- 4%, respectively, after PGE1 (30, 100 ng/kg/min) administration, but at either of these concentrations there were no significant changes in ONHBF. On the other hand, with lipo-PGE1 (10 ng/kg/min), the BP remained unchanged, but ONHBF increased significantly by 61 +/- 49%. A larger dose of lipo-PGE1 (30 ng/kg/min) had opposite effects because the BP decreased significantly by 14 +/- 4% after administration, and the ONHBF remained unchanged (i.e., 67 +/- 102%). In all cases, there were no changes in IOP. With 10 ng lipo-PGE1, the large increase in ONHBF can be accounted for by vasodilation since perfusion pressure was unchanged. The inability of 30 ng lipo-PGE1 to affect ONHBF could be ascribed to the decrease in BP resulting in decreased ocular circulation. These results suggest that, in humans, lipo-PGE1 may also increase ONHBF provided that it is used at doses that do not produce large decreases in BP.

Effects of 0.005% Latanoprost on Optic Nerve Head and Peripapillary Retinal Blood Flow

Fifty-two eyes of 26 healthy volunteers were recruited for evaluating the effects of 0.005% latanoprost on optic nerve head (ONH) and peripapillary retinal blood flow. In a randomized double-blind design, one eye received one drop of 0.005% latanoprost and its fellow eye received one drop of a placebo eyedrop. Intraocular pressure (IOP), ONH and peripapillary retinal blood flow were measured with Heidelberg retinal flowmetry (HRF) before, 2 and 24 h after administration of eyedrops. IOP was decreased significantly in latanoprost-treated eyes at 2 and 24 h after administration (p < 0.05). In the volume, flow or velocity of ONH and peripapillary retina, there were no significant changes from the baseline values at 2 and 24 h after latanoprost administration in either latanoprost-treated eyes or their fellow eyes (p > 0.05). No significant differences were found in the measured quantities between latanoprost-treated eyes and their fellow eyes at each time point (p > 0.05). This result may suggest that 0.005% latanoprost in healthy subjects does not have any adverse effect on ONH and peripapillary retinal blood flow.

Effects of 0.5% apraclonidine on optic nerve head and peripapillary retinal blood flow

AIMSTo examine the effects of 0.5% apraclonidine on optic nerve head (ONH) and peripapillary retinal blood flow by scanning laser Doppler flowmetry (SLDF).METHODSONH and peripapillary retinal blood flow of 17...

Effects of endothelin-1 on optic nerve head blood flow in cats.

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.