Optic Nerve Head Blood Velocity Research Articles

Compact Laser Doppler Flowmeter (LDF) Fundus Camera for the Assessment of Retinal Blood Perfusion in Small Animals.

PurposeNoninvasive techniques for ocular blood perfusion assessment are of crucial importance for exploring microvascular alterations related to systemic and ocular diseases. However, few techniques adapted to rodents are available and most are invasive or not specifically focused on the optic nerve head (ONH), choroid or retinal circulation. Here we present the results obtained with a new rodent-adapted compact fundus camera based on laser Doppler flowmetry (LDF).MethodsA confocal miniature flowmeter was fixed to a specially designed 3D rotating mechanical arm and adjusted on a rodent stereotaxic table in order to accurately point the laser beam at the retinal region of interest. The linearity of the LDF measurements was assessed using a rotating Teflon wheel and a flow of microspheres in a glass capillary. In vivo reproducibility was assessed in Wistar rats with repeated measurements (inter-session and inter-day) of retinal arteries and ONH blood velocity in six and ten rats, respectively. These parameters were also recorded during an acute intraocular pressure increase to 150 mmHg and after heart arrest (n = 5 rats).ResultsThe perfusion measurements showed perfect linearity between LDF velocity and Teflon wheel or microsphere speed. Intraclass correlation coefficients for retinal arteries and ONH velocity (0.82 and 0.86, respectively) indicated strong inter-session repeatability and stability. Inter-day reproducibility was good (0.79 and 0.7, respectively). Upon ocular blood flow cessation, the retinal artery velocity signal substantially decreased, whereas the ONH signal did not significantly vary, suggesting that it could mostly be attributed to tissue light scattering.ConclusionWe have demonstrated that, while not adapted for ONH blood perfusion assessment, this device allows pertinent, stable and repeatable measurements of retinal blood perfusion in rats.

Intravitreal injection of endothelin-1 caused optic nerve damage following to ocular hypoperfusion in rabbits

The purpose of this study was to investigate the time course of the ocular hypoperfusion, retinal damage, and optic nerve damage induced by intravitreal injection of endothelin-1 (ET-1) in rabbits. ET-1, at 5 pmol (20 μL, twice a week for 2 or 4 weeks), was injected from the pars plana into the posterior vitreous of the right eye. Optic nerve head (ONH) blood flow and retinal artery diameter, together with the neurofilament light chain (NF-L) content, retinal morphology, and axon density of the optic nerve, were evaluated at 2, 4, and 8 weeks after the first injection of ET-1 ( n = 7 or 8). Tissue blood velocity in ONH was measured using a laser speckle method, and the diameter of major retinal arteries on the rim of the ONH was calculated from fundus photographs by a masked observer. Histological analysis and immunoblot evaluation of NF-L in the optic nerve were performed to evaluate optic nerve damage. At 2 weeks after the first ET-1 injection, tissue blood velocity was decreased by approximately 20% (versus the contralateral eye), and the diameter of retinal arteries had decreased by approximately 40%. These changes were sustained at the same level until 8 weeks after the first ET-1 injection. At 4 and 8 weeks after the first ET-1 injection, the amount of NF-L in the optic nerve was significantly less in the ET-1 treated eyes than in the contralateral eyes. At 8 weeks after the first ET-1 injection, a loss of myelinated axons and increases in gliosis and connective tissue were noted in the optic nerve of the treated eye, and the optic nerve-axon number had decreased significantly (each, versus the untreated eye). Retinal ganglion cells in the retina were not observed any damage at 2, 4, and 8 weeks after ET-1 injection. In conclusion, intravitreal injection of ET-1 induced chronic hypoperfusion in the ONH and retina, which presumably caused decreases in NF-L content and axon number in the optic nerve noted in the later part of the observation period.

Optic nerve blood flow is diminished in eyes of primary open-angle glaucoma suspects

PURPOSE: The purpose of this study was to evaluate optic nerve blood flow in primary open-angle glaucoma suspect eyes with normal automated visual fields, in an attempt to elucidate how early in the glaucomatous disease process changes in optic nerve blood flow become apparent. METHODS: Twenty-one eyes (21 patients) suspected of having primary open-angle glaucoma were studied prospectively and compared with a previously reported cohort of 22 eyes (22 patients) with primary open-angle glaucoma and 15 eyes (15 subjects) of age-matched controls. Primary open-angle glaucoma suspect eyes had untreated intraocular pressure greater than 21 mm Hg and normal visual fields using Humphrey program 24-2 or 30-2 with a full threshold strategy. Laser Doppler flowmetry was used to measure optic nerve head blood velocity, volume, and flow at four quadrants in the optic nerve, in the cup, and in the foveola of one eye of each patient. The mean flow from the superotemporal rim, inferotemporal rim, and cup was calculated (Flow 3) and identified as the main outcome measure. Measurements from primary open-angle glaucoma suspect eyes were compared with corresponding measurements from controls and eyes with primary open-angle glaucoma; a Student t test was employed with a Bonferroni corrected P value of .025 to account for comparisons of primary open-angle glaucoma suspects both to controls and to eyes with primary open-angle glaucoma. RESULTS: Compared with controls, Flow 3 was 24% lower in primary open-angle glaucoma suspect eyes ( P < .0003). In primary open-angle glaucoma suspect eyes, flow was 16% lower in the superotemporal rim ( P < .007), 35% lower in the cup ( P < .007), and 22% lower in the inferotemporal neuroretinal rim ( P < .029) compared with controls. No significant difference between primary open-angle glaucoma suspect and control eyes was seen in the inferonasal rim, superonasal rim, or foveola. No significant difference was detected at any location between primary open-angle glaucoma suspect eyes and eyes with primary open-angle glaucoma. CONCLUSIONS: Laser Doppler flowmetry detected circulatory abnormalities in primary open-angle glaucoma suspects who did not have any manifest visual field defect. Decreases in flow in glaucoma suspects were similar in magnitude to those of subjects with primary open-angle glaucoma. These data suggest that impaired optic nerve blood flow develops early in the glaucomatous process and does not develop solely as a result of glaucoma damage.

Optic nerve blood flow in glaucoma: effect of systemic hypertension

PURPOSE: To investigate optic nerve head blood flow in patients with glaucoma and to assess the effect of systemic hypertension. METHODS: This study included 24 eyes of 24 patients with primary open-angle glaucoma. Eleven of these patients had a history of systemic hypertension. Results in patients with glaucoma were compared with those of 13 eyes of 13 age-matched normal controls. Determinations of relative optic nerve head blood velocity, volume, and flow were obtained with laser Doppler flowmetry in the superotemporal and inferotemporal neuroretinal rim and also in the cup. Means of the velocity, volume, and flow of these three measurement sites were calculated for each subject. RESULTS: Mean overall optic nerve head blood flow was 29% lower in glaucoma patients than in normal controls ( t test, P < .001). This decrease in flow was mainly caused by a decrease of 23% in mean blood velocity ( P < .001). Mean flow in glaucoma patients without systemic hypertension was 26% lower than that of glaucoma patients with hypertension (Tukey honest significant difference test, P = .05). A significant direct correlation was observed between mean flow and mean blood pressure (R = 0.51, P < .02). CONCLUSIONS: Optic nerve blood flow is reduced in glaucoma patients. Glaucoma patients without systemic hypertension have lower optic nerve blood flow than those with hypertension. Our results raise concerns that treatment of systemic hypertension may further decrease optic nerve blood flow in glaucoma patients.

Effects of Topical Adrenergic Agents on Tissue Circulation in Rabbit and Human Optic Nerve Head Evaluated With Laser Speckle Tissue Circulation Analyzer

The effects of topical adrenergic agents on the tissue circulation of the optic nerve head (ONH) were studied in animal and human eyes with use of a laser speckle tissue circulation analyzer. Drugs studied were nipradilol, a β1–2-blocker with weak α-blocking and nitroglycerinlike activities; bunazosin, a selective α1-blocker; carteolol, β1–2-blocker with intrinsic sympathomimetic activity; and betaxolol, a selective β1-blocker. In the animal experiment, one eye each of nine albino rabbits received 0.25% nipradilol (N = 9) twice daily for 15 days or 0.01% bunazosin (N = 10) twice daily for 20 days; the fellow eye received the vehicle of each drug in a randomized masked design. Normalized blur (NB) in an area of ONH free of visible surface vessels, a quantitative index of peripheral blood velocity in ONH, was measured under general anesthesia before treatment and 2 hours after the last instillation on the 15th or 20th day. At 15 days, intraocular pressure and NB in the nipradilol-treated eyes decreased by 4.3 mm Hg (P < 0.01) and increased by 15.9% (P < 0.01), respectively, while those in the vehicletreated eyes showed little change. At 20 days NB in both bunazosin- and vehicle-treated eyes showed little change, while intraocular pressure decreased only in the bunazosin-treated eyes (P < 0.01). In the human volunteer experiment NB was averaged over five pulses (mean NB) in both eyes before and 1.5, 3.0 and 4.5 hours after a 30 μL instillation of the vehicle of carteolol or betaxolol to serve as a control. Intraocular pressure, blood pressure and pulse rate were also measured. One week later a 30 μL drop of 2.0% carteolol (N = 6) or 0.5% betaxolol (N = 10) was instilled in one randomly chosen eye and the vehicle for each drug in the other eye, and those parameters were measured as above in a doublemasked manner. In the carteolol experiment, mean NB in both eyes was significantly higher at 3 hours than it was in the control experiment (P < 0.05), while intraocular pressure was significantly lower in both eyes and blood pressure and pulse rate showed little change. In the betaxolol experiment, intraocular pressure at 1.5 hours and blood pressure at 4.5 hours were significantly lower than those in the control experiment (P < 0.05), while mean NB and pulse rate showed little change. In summary, using the laser speckle method we found that topical nipradilol and carteolol increase ONH blood velocity in rabbits and humans, respectively. This finding suggests that some topical P-blockkes used clinically may influence the ONH tissue circulation in patients and that this method may be used in clinical situations to assess the effect of various drugs on ONH circulation.

Perspectives on aqueous humor formation

The effects of topical adrenergic agents on the tissue circulation of the optic nerve head (ONH) were studied in animal and human eyes with use of a laser speckle tissue circulation analyzer. Drugs studied were nipradilol, a β1–2-blocker with weak α-blocking and nitroglycerinlike activities; bunazosin, a selective α1-blocker; carteolol, β1–2-blocker with intrinsic sympathomimetic activity; and betaxolol, a selective β1-blocker. In the animal experiment, one eye each of nine albino rabbits received 0.25% nipradilol (N = 9) twice daily for 15 days or 0.01% bunazosin (N = 10) twice daily for 20 days; the fellow eye received the vehicle of each drug in a randomized masked design. Normalized blur (NB) in an area of ONH free of visible surface vessels, a quantitative index of peripheral blood velocity in ONH, was measured under general anesthesia before treatment and 2 hours after the last instillation on the 15th or 20th day. At 15 days, intraocular pressure and NB in the nipradilol-treated eyes decreased by 4.3 mm Hg (P < 0.01) and increased by 15.9% (P < 0.01), respectively, while those in the vehicletreated eyes showed little change. At 20 days NB in both bunazosin- and vehicle-treated eyes showed little change, while intraocular pressure decreased only in the bunazosin-treated eyes (P < 0.01). In the human volunteer experiment NB was averaged over five pulses (mean NB) in both eyes before and 1.5, 3.0 and 4.5 hours after a 30 μL instillation of the vehicle of carteolol or betaxolol to serve as a control. Intraocular pressure, blood pressure and pulse rate were also measured. One week later a 30 μL drop of 2.0% carteolol (N = 6) or 0.5% betaxolol (N = 10) was instilled in one randomly chosen eye and the vehicle for each drug in the other eye, and those parameters were measured as above in a doublemasked manner. In the carteolol experiment, mean NB in both eyes was significantly higher at 3 hours than it was in the control experiment (P < 0.05), while intraocular pressure was significantly lower in both eyes and blood pressure and pulse rate showed little change. In the betaxolol experiment, intraocular pressure at 1.5 hours and blood pressure at 4.5 hours were significantly lower than those in the control experiment (P < 0.05), while mean NB and pulse rate showed little change. In summary, using the laser speckle method we found that topical nipradilol and carteolol increase ONH blood velocity in rabbits and humans, respectively. This finding suggests that some topical P-blockkes used clinically may influence the ONH tissue circulation in patients and that this method may be used in clinical situations to assess the effect of various drugs on ONH circulation.