Vasoprotection as neuroprotection for the optic nerve.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
L Kagemann
Publications and source records attributed to L Kagemann.
Optic nerve head blood flow measurements in non-arteritic anterior ischaemic optic neuropathy.
PURPOSE: To determine whether a decrease in blood flow, measured by the Heidelberg retiinal flowmeter, can characterise a disc at risk and predict the occurrence of non-arteritic anterior ischaemic optic neuropathy (NAION). METHODS: Blood flow, volume and velocity were measured in the optic nerve heads of 14 unaffected fellow eyes of patients with unilateral NAION, and compared with those of the affected eyes and of the eyes of 7 age-matched healthy controls. RESULTS: The affected eyes were found to differ from the unaffected eyes in all three haemodynamic parameters. Flow (measured in arbitrary units) is the most important parameter to be taken into consideration. Blood flow was significantly lower in affected than in unaffected eyes (upper rim, p < 0.05; lower rim, p < 0.025). It was also significantly lower in the unaffected eyes than in the healthy control eyes (p < 0.005, upper and lower rims), and in the affected eyes than in the control eyes (p < 0.00005, upper and lower rims). CONCLUSION: Decreased blood flow in the optic nerve head may indicate a risk for NAION and be considered a characteristic of the disc at risk.
Aged↗
Relationship between the effect of carbon dioxide inhalation or nilvadipine on orbital blood flow in normal-tension glaucoma.
PURPOSE: To investigate the relationship between the effect of carbon dioxide (CO2) inhalation or oral nilvadipine, a calcium-channel blocker, on orbital blood flow in patients with normal-tension glaucoma, as determined by color Doppler imaging. PATIENTS AND METHODS: Sixteen patients with normal-tension glaucoma (mean age, 55.6+/-9.8 years; male:female ratio, 3:13) underwent color Doppler imaging to measure the resistance index, and peak systolic and end-diastolic blood flow velocities of the ophthalmic artery, central retinal artery, and nasal and temporal short posterior ciliary arteries. Measurements were taken before and during CO2 supplementation sufficient to increase the end-tidal CO2 partial pressure by 10%. The color Doppler imaging measurements were repeated after 2 to 4 weeks of treatment with 2 mg oral nilvadipine, and comparisons were made between the effects of the two treatments. RESULTS: Both CO2 inhalation and nilvadipine treatment significantly reduced the resistance index in the central retinal artery, nasal short posterior ciliary artery, and temporal short posterior ciliary artery. There was a significant correlation between the effects of the two treatments on the difference in the resistance indexes of the ophthalmic artery and central retinal artery, but not on those of the nasal or temporal short posterior ciliary artery. CONCLUSIONS: Both CO2 inhalation and oral nilvadipine significantly reduce the resistance index measured by color Doppler imaging in orbital vessels. The effect of oral nilvadipine might be predicted by CO2 inhalation in patients with normal-tension glaucoma.
Administration, Inhalation↗
Comprehensive assessment of retinal, choroidal and retrobulbar haemodynamics during blood gas perturbation.
BACKGROUND: A study was performed to evaluate the effect of isoxic hypercapnia on ocular haemodynamics using colour Doppler imaging (CDI), scanning laser Doppler flowmetry (SLDF) and ocular blood flow (OBF) tonography. METHODS: Measurements were taken for one eye of each of 14 healthy subjects (mean age 27 +/- 6 years) during breathing of room air and then during isoxic hypercapnia (breathing CO2 and room air). Using CDI, blood flow velocities and resistance indices were determined for the ophthalmic artery (OA), central retinal artery (CRA) and short posterior ciliary arteries (SPCAs). Using SLDF a 10 x 10 pixel frame was used to measure blood flow, volume and velocity in each quadrant of the peripapillary retina. Pulsatile ocular blood flow (POBF) was measured using the OBF tonograph. RESULTS: Using CDI, peak systolic and end diastolic velocities increased and resistance index decreased significantly in the SPCAs during hypercapnia. Using SLDF, blood flow, volume and velocity increased significantly during hypercapnia in the superior temporal quadrant of the peripapillary retina. No significant difference was observed between baseline and hypercapnia for POBF. CONCLUSIONS: Isoxic hypercapnia resulted in an increase in peripapillary retinal and SPCA blood flow parameters as determined by SLDF and CDI respectively. This implies the presence of autoregulatory activity in these vasculatures. These findings may be of significance in the pathogenesis of ocular disease such as glaucoma where autoregulation is thought to be compromised.
Adolescent↗
Color Doppler imaging discloses reduced ocular blood flow velocities in nonexudative age-related macular degeneration.
PURPOSE: To study ocular perfusion defects in age-related macular degeneration. METHODS: Twenty-five subjects with nonexudative age-related macular degeneration were compared with 25 age-matched control subjects in studies of flow velocities in several retrobulbar vessels. Color Doppler imaging, which was performed by an examiner who was masked to the subjects' assignment to the control or age-related macular degeneration group, measured peak systolic and end diastolic velocity in the ophthalmic, central retinal, and nasal and temporal posterior ciliary arteries of one eye. A resistive index was calculated from the peak systolic and end diastolic velocity. RESULTS: Subjects with nonexudative age-related macular degeneration showed a consistent trend toward lower peak systolic and end-diastolic velocities in the posterior ciliary arteries. For example, in the nasal posterior ciliary artery, the mean end diastolic velocity measured 1.45 +/- 0.34 cm per sec in the age-related macular degeneration group compared with 1.96 +/- 0.66 cm per sec in the control group, yielding a 26% decrease in the age-related macular degeneration group, which represented the largest difference and was highly statistically significant (P = .0012). The resistive index was not significantly altered in the nasal or temporal posterior ciliary artery. Subjects with nonexudative age-related macular degeneration did not differ from control subjects in peak systolic velocity, end diastolic velocity, or resistive index in the ophthalmic artery. In the central retinal artery, the end diastolic velocity was lower (1.37 +/- 1.95 cm per sec vs 1.95 +/- 0.66 cm per sec), whereas the resistive index was higher (0.83 +/- 0.05 vs 0.76 +/- 0.06 cm per sec), in the age-related macular degeneration group; these results were highly statistically significant (P = .0007 and P < .0001, respectively). CONCLUSIONS: Retrobulbar vascular changes in nonexudative age-related macular degeneration subjects include reduced flow velocities in the nasal and temporal posterior ciliary arteries. The reduced peak systolic velocity, combined with the reduced end diastolic velocity at a constant resistive index, seen in nonexudative age-related macular degeneration, is consistent with reduced bulk flow in these vessels, suggesting that choroidal perfusion is abnormal in this form of age-related macular degeneration. The changes in the central retinal artery suggest there may be a more generalized perfusion abnormality beyond the choroid in patients with age-related macular degeneration or that the central retinal artery exhibits a secondary autoregulatory response to a primary change elsewhere.
Aged↗
Vascular aspects in the pathophysiology of glaucomatous optic neuropathy.
Glaucoma remains a major eye illness with unknown etiology. Although elevated intraocular pressure is clearly a major risk factor, vascular deficits may contribute to initiation and progression of glaucoma. When intraocular pressure is acutely elevated in healthy individuals, the resistance index (derived from the peak systolic and end-diastolic velocities and an indirect index of vascular resistance distal to the site of measurement) in the central retinal and posterior ciliary arteries increases progressively. This result implies that mechanical and vascular factors may be coupled in such a way that perfusion of the retina and optic nerve head may be influenced by changes in the intraocular pressure. Further, at night, when ophthalmic artery flow velocities fall as arterial blood pressure falls in glaucoma patients, the risk of disease progression may be increased. The constancy of these same flow velocities in age-matched healthy individuals points to a possible vascular autoregulatory defect in glaucoma. In addition, in normal-tension glaucoma, vasodilation (CO2 inhalation) normalizes retrobulbar arterial flow velocities, hinting that some vascular deficits in glaucoma may be reversible. Finally, Ca2+ channel blockade improves contrast sensitivity in patients with normal-tension glaucoma, who also show increased retrobulbar vessel flow velocities, a result suggesting that visual function loss may be linked to ocular ischemia. Emerging evidence points to a role of ischemia in the pathogenesis of glaucoma, suggesting that treatments designed to improve ocular blood flow may benefit glaucoma patients.
Animals↗
Progress in measurement of ocular blood flow and relevance to our understanding of glaucoma and age-related macular degeneration.
New technologies have facilitated the study of the ocular circulation. These modalities and analysis techniques facilitate very precise and comprehensive study of retinal, choroidal, and retrobulbar circulations. These techniques include: 1. Vessel caliber assessment; 2. Scanning laser ophthalmoscopic fluorescein angiography and indocyanine green angiography to image and evaluate the retinal circulation and choroidal circulation respectively; 3. Laser Doppler flowmetry and confocal scanning laser Doppler flowmetry to measure blood flow in the optic nerve head and retinal capillary beds; 4. Ocular pulse measurement; and 5. color Doppler imaging to measure blood flow velocities in the central retinal artery, the ciliary arteries and the ophthalmic artery. These technique have greatly enhanced the ability to quantify ocular perfusion defects in many disorders, including glaucoma and age-related macular degeneration, two of the most prevalent causes of blindness in the industrialized world. Recently it has become clear, in animal models of glaucoma, that retinal ganglion cells die via apoptosis. The factors that initiate apoptosis in these cells remain obscure, but ischemia may play a central role. Patients with either primary open-angle glaucoma or normal-tension glaucoma experience various ocular blood flow deficits. With regard to age-related macular degeneration, the etiology remains unknown although some theories include primary retinal pigment epithelial senescence, genetic defects such as those found in the ABCR gene which is also defective in Stargardt's disease and ocular perfusion abnormalities. As the choriocapillaris supplies the metabolic needs of the retinal pigment epithelium and the outer retina, perfusion defect in the choriocapillaris could account for some of the physiologic and pathologic changes in AMD. Vascular defects have been identified in both nonexudative and exudative AMD patients using new technologies. This paper is a comprehensive update describing modalities available for the measurement of all new ocular blood flow in human and the clinical use.
Animals↗
Dorzolamide, visual function and ocular hemodynamics in normal-tension glaucoma.
The purpose of this study was to determine how a topical carbonic anhydrase inhibitor, dorzolamide, alters visual function and ocular blood flow in persons with normal-tension glaucoma. Eighteen normal tension glaucoma patients, after washout of other ocular medications, were treated for four weeks with 2% dorzolamide, three times daily. A control group of eleven other normal-tension glaucoma patients received placebo eye drops. Patients were studied before treatment, and after two and four weeks of treatment. Each study included assessment of central visual function (contrast sensitivity), intraocular pressure (IOP), and several aspects of ocular hemodynamics, including measures of retinal arteriovenous passage time, retinal arterial and venous diameters, and flow velocities in the ophthalmic, central retinal, and posterior ciliary arteries. Dorzolamide significantly reduced IOP at two and four weeks (each p<0.01), and at the same time increased contrast sensitivity at both three and six cycles per degree (each p<0.05). Neither of these variables changed significantly in the control group. Dorzolamide also accelerated retinal arteriovenous passage time of fluorescein dye, at constant retinal arterial and venous diameters (p<0.05), but failed to change flow velocities in any retrobulbar vessel. The ability of dorzolamide to improve contrast sensitivity in persons with normal-tension glaucoma may be related to either IOP reduction or altered ocular perfusion.
Blood Pressure↗
Peripapillary retinal blood flow in normal tension glaucoma.
AIMS: To determine if normal tension glaucoma (NTG) patients differ from age matched controls in blood flow to the peripapillary retina, as measured with confocal scanning laser Doppler flowmetry (cSLDF; "Heidelberg retinal flowmetry"). METHODS: 12 NTG patients and 12 age matched controls were compared using (a) 10 x 10 pixel boxes (the instrument default sample size), taken from the nasal and temporal peripapillary retina, (b) the average from two of these boxes, and (c) every qualifying pixel within the peripapillary retina. RESULTS: Patients and controls did not differ in blood flow measured using the default sample from a single 10 x 10 pixel box, placed in either the temporal or nasal peripapillary retina, or expressed as the average from these two boxes. However, in histograms using every pixel from the peripapillary retina, NTG patients displayed significantly higher percentages of minimal flow pixels (defined as less than one arbitrary unit of flow: 30% v 19%, p < 0.01), and significantly lower flow in the 25th, 50th, and 75th percentile flow pixel (each p < 0.05) than did age matched controls. CONCLUSION: NTG is characterised by reduced blood flow in the peripapillary retina, a result suggesting that blood flow deficits accompany, and perhaps may contribute to, disease development in these patients.
Blood Flow Velocity↗
Glaucoma patients demonstrate faulty autoregulation of ocular blood flow during posture change.
BACKGROUND/AIMS: Autoregulation of blood flow during posture change is important to ensure consistent organ circulation. The purpose of this study was to compare the change in retrobulbar ocular blood flow in glaucoma patients with normal subjects during supine and upright posture. METHODS: 20 open angle glaucoma patients and 20 normal subjects, similar in age and sex distribution, were evaluated. Blood pressure, intraocular pressure, and retrobulbar blood velocity were tested after 30 minutes of sitting and again after 30 minutes of lying. Retrobulbar haemodynamic measures of peak systolic velocity (PSV), end diastolic velocity (EDV), and resistance index (RI) were obtained in the ophthalmic and central retinal arteries using colour Doppler imaging (CDI). RESULTS: When changing from the upright to supine posture, normal subjects demonstrated a significant increase in OA EDV (p = 0.016) and significant decrease in OA RI (p = 0.0006) and CRA RI (p = 0.016). Glaucoma patients demonstrated similar changes in OA measures of EDV (p = 0.02) and RI (p = 0.04), but no change in CRA measures. CONCLUSION: Glaucoma patients exhibit faulty autoregulation of central retinal artery blood flow during posture change.
Blood Flow Velocity↗
Brightness alters Heidelberg retinal flowmeter measurements in an in vitro model.
PURPOSE: The Heidelberg Retinal Flowmeter (HRF), a laser Doppler flowmetry device, has captured interest as a research and clinical tool for measurement of ocular blood flow. Concerns remain about the range and accuracy of the values that it reports. METHODS: An in vitro blood-flow model was constructed to provide well-controlled laminar flow through a glass capillary for assessment by HRF. A change in material behind the glass capillary was used to simulate changing brightness conditions between eyes. RESULTS: Velocities reported by the HRF correlated linearly to true velocities below 8.8 mm/sec. Beyond 8.8 mm/sec, HRF readings fluctuated randomly. True velocity and HRF reported velocities were highly correlated, with r = 0.967 (P < 0.001) from 0.0 mm/sec to 2.7 mm/sec mean velocity using a light background, and r = 0.900 (P < 0.001) from 2.7 mm/sec to 8.8 mm/sec using a darker background. However, a large change in the y-intercept occurred in the calibration curve with the background change. CONCLUSIONS: The HRF may report velocities inaccurately because of varying brightness in the fundus. In the present experiment, a darker background produced an overreporting of velocities. An offset, possibly introduced by a noise correction routine, apparently contributed to the inaccuracies of the HRF measurements. Such offsets vary with local and global brightness. Therefore, HRF measurements may be error prone when comparing eyes. When used to track perfusion in a single eye over time, meaningful comparison may be possible if meticulous care is taken to align vessels and intensity controls to achieve a similar level of noise correction between measurements.
Blood Flow Velocity↗
Regional differences in retinal vascular reactivity.
PURPOSE: Although glaucomatous visual field defects are more common in the superior field than in the inferior field, microaneurysms are more frequent in the superior than in the inferior retina in diabetic retinopathy. The authors hypothesized that differences in vascular hemodynamics in the two areas might contribute to these phenomena. METHODS: The blood flow response to hyperoxia and hypercapnia was evaluated in peripapillary retinal tissue superior and inferior to the optic nerve head using confocal scanning laser Doppler flowmetry. In 14 young, healthy persons, blood flow was measured while breathing room air and during isocapnic hyperoxia (100% O2 breathing) and isoxic hypercapnia (PCO2 increased 15% above baseline). Histograms were generated from pixel-by-pixel analysis of retinal portions of superior and inferior temporal quadrants of the entire image. RESULTS: Baseline blood flow in the inferior temporal quadrant was significantly greater than in the superior temporal quadrant (P < 0.05). However, the inferior region failed to increase in perfusion during hypercapnia and experienced significant mean blood flow reduction; flow reduction in the pixels at the 25th, 50th, 75th, and 90th percentile of flow; and an increased percentage of pixels without measurable flow, during hyperoxia (each P < 0.05). In contrast, in the superior temporal region, hyperoxia failed to reduce blood volume, velocity, or flow, whereas hypercapnia significantly increased mean flow; increased flow in the pixels at the 25th, 50th, 75th, and 90th percentile of flow; and reduced the percentage of pixels without measurable flow (each P < 0.05). CONCLUSIONS: The inferior temporal quadrant of the peripapillary retina is, in comparison with the superior temporas region, less responsive to vasodilation and more responsive to vasoconstriction. These differences could contribute to different susceptibility to visual field defect or vascular dysfunction in the superior and inferior retina.
Adolescent↗
Heidelberg retinal flowmetry: factors affecting blood flow measurement.
AIMS: To evaluate factors affecting Heidelberg retinal flowmeter (HRF) measurements of retinal and optic nerve head blood flow in human subjects. METHODS: The angle of incidence between laser beam and fundus, and camera distance from the eye, were evaluated for their effect upon measures of blood volume, velocity, and flow in a single 100 x 100 x 400 microns volume of temporal peripapillary retinal tissue in normal volunteers. Both intra and intersession reproducibility of these measures were studied. Intersession data were obtained by taking one image per week for 4 weeks. Finally, the intersession haemodynamic data were examined in the entire image (640 x 2560 x 400 microns), using histograms of pixel by pixel blood flow. RESULTS: Measures of blood volume, velocity, and flow from a single anatomical site were unaffected by laser beam to fundus angle of incidence (n = 12). As camera distance from the eye was increased (from 2 to 5 to 7 cm), flow measurements showed increasing individual changes, despite unaltered measured vessel lengths and constant overall mean flow (n = 14). The coefficient of variation for two intersession images of optic nerve head blood flow averaged 7% (n = 20); in contrast, the 4 week intersession coefficient of variation averaged 30% (n = 15). Intersession reproducibility was increased by using flow histograms from the entire image: the coefficients of variation averaged 16% for total flow and 17% for flow in the pixel of median flow. CONCLUSION: HRF measures of flow are independent of the laser beam to fundus angle of the incidence and dependent upon camera distance from the eye. Intersession reproducibility is best using pixel by pixel analysis of the entire image.
Blood Flow Velocity↗
Laser Doppler flowmetry measurement of changes in human optic nerve head blood flow in response to blood gas perturbations.
PURPOSE: The objective of this study was to establish the ability of laser Doppler flowmetry to detect relative changes in human optic nerve head hemodynamics caused by physiologic blood gas perturbations. METHODS: Laser Doppler flowmetry permits the noninvasive assessment of relative blood velocity, volume, and flow (flux) in a sample volume of the nerve head. Such measurements were performed in two groups of healthy subjects. The first group (n = 11) was tested during normal room air breathing and then while breathing 100% oxygen (isocapnic hyperoxia). The second group (n = 10) was also tested under normal conditions as well as during isoxic hypercapnia (+ 15% end-tidal carbon dioxide). Results were analyzed by paired t tests. RESULTS: Hyperoxia created a significant 25% (p = 0.002) decrease in optic nerve head blood flow, with blood volume decreased by 9% (p = 0.095) and blood velocity reduced by 13% (p = 0.154) compared to the room air condition. During hypercapnia, optic nerve head blood flow was increased by 28% (p = 0.012), with blood volume increased by 22% (p = 0.017) and blood velocity increased by 9% (p = 0.218) as compared to the normal room air condition. CONCLUSION: Blood flow in the optic nerve head capillaries changes in response to hyperoxia and hypercapnia as demonstrated in the brain and retina. Laser Doppler flowmetry permits the noninvasive assessment of these responses in humans under conditions within the physiologic range.
Adult↗
A new system to supply carbon dioxide safely to glaucoma patients.
PURPOSE: To develop a new system for safely supplying carbon dioxide (CO2) to open-angle glaucoma patients. METHODS: The orbital hemodynamics of 7 glaucoma patients were determined by color Doppler imaging under baseline conditions and during CO2 supplementation sufficient to increase the end-tidal CO2 partial pressure by 10%. Systemic conditions, including oxygen saturation and blood pressure, were monitored throughout the CO2 inhalation. RESULTS: Our results demonstrate that this new system enables us to supply CO2 in a safe, controlled manner to glaucoma patients. CONCLUSIONS: This new system will be useful for investigating the effects of vasodilation by CO2 on orbital blood flow.
Administration, Inhalation↗
Assessment of human ocular hemodynamics.
Vascular abnormality and altered hemodynamics play important roles in many ophthalmic pathologies. Much of our knowledge of ocular hemodynamics was gained from invasive animal research, although a number of noninvasive methods suitable for in vivo use in humans have been developed. Data from these methods now produce a significant literature of their own. Understanding the origins of the data and appreciating their limitations can be difficult. Modern hemodynamic assessment techniques each examine a unique facet of the ocular circulation. No single facet provides a complete description of the hemodynamic state of the eye. These methods have contributed a great deal to our understanding of normal hemodynamics. More importantly, they continue to add to our understanding of altered hemodynamics found in disease. Some have found their way into limited clinical practice. The predominant ocular hemodynamic assessment techniques are reviewed with the aims of introducing the fundamental principles behind each, highlighting their inherent advantages and limitations, highlighting their contributions to understanding ocular physiology, and considering their potential to provide signs for diagnosis.
Animals↗
Effect of intravenous droperidol on intraocular pressure and retrobulbar hemodynamics.
PURPOSE: Topically-applied dopamine antagonists reduce intraocular pressure (IOP) and inrease retinal blood flow in animal models. We examined the acute effects of intravenous infusion of a dopamine blocker (droperidol) on these parameters in healthy humans. METHODS: Sixteen subjects free from ocular or systemic disease (mean age 33 +/- 10 yrs) received either 5 mg i.v. droperidol over 5 minutes, or i.v. saline placebo in double-masked fashion. IOP was determined 30 and 60 minutes later, while color Doppler imaging was used to determine flow velocities in the ophthalmic, central retinal, and nasal and temporal posterior ciliary arteries 60 minutes after drug infusion. RESULTS: 30 minutes after drug infusion, IOP was reduced 6.0 mmHg as compared with baseline (p<0.001); after 60 minutes, IOP remained reduced by 3.7 mmHg (p<0.001). Placebo had no effect on IOP. While droperidol slightly elevated blood pressure and increased the calculated ocular perfusion pressure, the drug reduced visual acuity and contrast sensitivity (p<0.05). Droperidol elevated peak systolic velocity in the central retinal and nasal posterior ciliary arteries, without changing end-diastolic velocity or the resistance index in either of these vessels. Droperidol had no effect on flow velocities in the ophthalmic artery or the temporal posterior ciliary artery. CONCLUSIONS: The rapid and marked ocular hypotension resulting from intravenous droperidol suggests that this agent may prove useful in the management of acute ocular hypertension. The retrobulbar changes consequent to the ocular tension reduction likely represent autoregulatory responses to altered ocular perfusion pressure.
Adult↗