Bruce J. Martin

Color Doppler Analysis of Ocular Vessel Blood Velocity in Normal-tension Glaucoma

The pathogenesis of normal-tension glaucoma remains unknown. Because ocular vasospasm has been proposed as a possible mechanism, we investigated ocular vessel flow velocity in normal-tension glaucoma patients at rest and under treatment with a cerebral vasodilator. Ten normal-tension glaucoma patients and nine age- and gender-matched controls had flow velocity measured in three vessels (ophthalmic artery, central retinal artery, and temporal short posterior ciliary artery) by using color Doppler imaging, under baseline conditions and during carbon dioxide supplementation sufficient to increase end-tidal PCO2 by 15%. Peak systolic and end-diastolic velocities were measured, and the resistance index (peak systolic velocity minus end-diastolic velocity, divided by peak systolic velocity) was calculated. Compared with controls, these normal-tension glaucoma patients had significantly lower end-diastolic velocities (P = .002) and higher resistance indices (P = .007) in the ophthalmic artery at baseline. When PCO2 was increased, control subjects remained unchanged, whereas it increased end-diastolic velocity in patients (P = .003) and abolished the difference in resistance index between the two groups. Patients and control subjects differed little in their baseline or carbon dioxide response velocities or in resistance in the other two vessels. These results indicate that at baseline these normal-tension glaucoma patients may have increased vascular resistance distal to the ophthalmic artery, although this increased resistance cannot be specifically ascribed to the central retinal arterial or to temporal short posterior ciliary arterial vascular beds. The responsiveness of these patients to a cerebral vasodilator (increased PCO2) indicates further that the increased resistance distal to the ophthalmic artery may be the reversible result of vasospasm.

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.

Test/retest reproducibility of color Doppler imaging assessment of blood flow velocity in orbital vessels

PurposeThe purpose of this study was to evaluate the test-retest reproducibility of measures of blood flow velocities using color Doppler imaging (CDI) in orbital arteries. Patients and MethodsMeasures of peak systolic velocity, end-diastolic velocity, and resistive index were performed in a group of 15 normal tension glaucoma patients and in 15 healthy subjects using the Siemens Quantum 2000 CDI system with a 7.5 MHz linear probe. After each velocity measure in each vessel, the probe was removed and then replaced to repeat the measurement −2 min later. ResultsFor all subjects, the coefficients of reliability for measures of peak systolic velocity were 12% in the ophthalmic artery, 25% in the central retinal artery, and 19% in a short posterior ciliary artery. For end diastolic velocity, the coefficients were 6%, 11%, and 25%, respectively. The coefficients for resistive index were 4%, 11%, and 38%. ConclusionCDI produces highly reproducible measures in the ophthalmic artery. Measures in the central retinal artery are somewhat more variable but seem reasonably reproducible. Short posterior ciliary measurements were the most variable, suggesting that current methods for assessing these vessels may not be sufficiently reliable.

Retrobulbar arterial hemodynamic effects of betaxolol and timolol in normal-tension glaucoma.

PURPOSE beta-Adrenergic blocking drugs lower intraocular pressure. The question of whether these drugs also alter, either directly or indirectly, orbital hemodynamics is potentially of great importance for patients with normal-tension glaucoma who may have some degree of reversible vasospasm. METHODS We compared the effect of selective (betaxolol) and nonselective (timolol) beta-adrenergic blocking drugs on flow velocities (as determined by color Doppler imaging) in orbital vessels in 13 patients with normal-tension glaucoma (mean age, 62 +/- 3 years; mean intraocular pressure, 15 +/- 2 mm Hg). A one-month drug treatment double-masked crossover design, with a three-week washout before each drug, was used. RESULTS Neither drug changed peak systolic velocity in any of the four vessels studied (ophthalmic, nasal and temporal posterior ciliary, and central retinal arteries). Additionally, timolol did not alter end-diastolic velocity or resistance index (defined as [peak systolic velocity minus end-diastolic velocity] divided by peak systolic velocity) in any of the vessels measured. In contrast, betaxolol tended to increase end-diastolic velocity and to decrease resistance index: the four-vessel average end-diastolic velocity increased 30% (P = .08), and the four-vessel average resistance index decreased significantly (P = .04). These reductions in resistance index occurred despite that betaxolol, in contrast to timolol, did not significantly decrease intraocular pressure. CONCLUSIONS These results suggest that, in patients with normal-tension glaucoma, selective beta-adrenergic blockade (betaxolol) may have ocular vasorelaxant effects independent of any influence on intraocular pressure, whereas nonselective blockade (timolol) lowers intraocular pressure without apparently altering orbital hemodynamics.

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 × 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 × 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.

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 × 100 × 400 μm 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 × 2560 × 400 μm), 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 intrasession 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.

Hyperoxia improves contrast sensitivity in early diabetic retinopathy.

AIM: The cause of vascular and visual pathology in diabetic retinopathy remains unknown. If retinal hypoxia plays a role, then early in the course of diabetes 100% oxygen breathing should normalise both contrast sensitivity and retinal blood flow. METHODS: This hypothesis was tested in 12 diabetic patients with minimal retinopathy who, none the less, exhibited reduced contrast sensitivity (p = 0.003 versus 12 age and sex-matched controls) and prolonged retinal arteriovenous dye transit (p = 0.0001 versus controls). RESULTS: Isocapnic hyperoxia failed to alter contrast sensitivity in controls, while it significantly improved contrast sensitivity in patients (at 12 cpd; p = 0.042) to levels indistinguishable from normal. Individual improvement in contrast sensitivity correlated positively with the severity of the initial defect (r = +0.84, p = 0.0008). Hyperoxia also had haemodynamic effects; it slowed retinal arteriovenous passage of fluorescein dye in controls, but did not further slow this transit time in patients. CONCLUSIONS: These results demonstrate the reversibility of early contrast sensitivity deficits in diabetes mellitus, and support the hypothesis that factors linked to tissue hypoxia initiate both visual and vascular dysfunction in diabetic retinopathy.

A comparative study of betaxolol and dorzolamide effect on ocular circulation in normal-tension glaucoma patients

OBJECTIVE To determine whether dosages of a selective beta-blocking agent (betaxolol) and a topical carbonic anhydrase inhibitor (dorzolamide), sufficient to significantly lower intraocular pressure (IOP), have similar or disparate impact on the retinal and retrobulbar circulation. DESIGN Counterbalanced crossover, with open-label use of medications. PARTICIPANTS Nine persons with normal-tension glaucoma (NTG). INTERVENTION After a 3-week drug washout, NTG patients were studied after 1 month of treatment with either dorzolamide or betaxolol, with determinations of IOP and retinal and retrobulbar hemodynamics. MAIN OUTCOME MEASURES At baseline and after treatment with each drug, retinal arteriovenous passage time was determined by scanning laser ophthalmoscopy after fluorescein dye injection, and flow velocities in the central retinal and ophthalmic arteries were measured with color Doppler ultrasonography imaging. RESULTS Betaxolol and dorzolamide each lowered IOP significantly, with these changes apparent and maximal after 2 weeks (each P < 0.05). In contrast, dorzolamide (but not betaxolol) accelerated arteriovenous passage of fluorescein dye in the inferior temporal quadrant of the retina (P < 0.05). Neither drug affected arteriovenous passage in the superotemporal retina or any aspect of central retinal or ophthalmic artery flow velocity after either 2 or 4 weeks. CONCLUSIONS Although both dorzolamide and betaxolol are effective ocular hypotensive agents and their topical instillation leaves retrobulbar hemodynamics unaltered, dorzolamide alone accelerates inferotemporal retinal dye transit.

Acute IOP elevation with scleral suction: effects on retrobulbar haemodynamics.

AIMS/BACKGROUND: Mechanical and vascular factors may both contribute to glaucoma. This study investigated the relation of mechanical to vascular factors by examining how acute IOP elevation altered flow velocities in the central retinal and ophthalmic arteries. METHODS: IOP was elevated from a baseline near 14 to approximately 45 mm Hg using suction ophthalmodynamometry. During recovery from scleral suction, IOP fell to near 8 mm Hg. At each IOP, peak systolic and end diastolic velocities (PSV and EDV) were measured in the central retinal and ophthalmic arteries using colour Doppler imaging (Siemens Quantum 2000). Eleven healthy people served as subjects. RESULTS: Acute elevation in IOP had no effect upon PSV, EDV, or the derived resistance index in the ophthalmic artery: flow velocities in this vessel were identical at IOP of 8 mm Hg or 45 mm Hg. In contrast, in the central retinal artery, PSV and EDV fell, and the resistance index rose, in steady progression as IOP was acutely elevated (each p < 0.01). At IOP of 45 mm Hg, EDV was virtually absent and the resistance index was very nearly 1.0. CONCLUSION: Ophthalmic arterial haemodynamics are unrelated to acute fluctuations of the IOP over a wide range, suggesting that ocular hypertension itself cannot induce vascular dysfunction in this artery. In contrast, flow velocities in the central retinal artery were highly IOP dependent, implying that haemodynamic and mechanical factors are closely linked in this vascular bed.

Hemodynamic and visual function effects of oral nifedipine in patients with normal-tension glaucoma.

PURPOSE To investigate ocular hemodynamic and visual function changes in patients with normal-tension glaucoma after treatment with a calcium channel blocker (nifedipine). METHODS In 21 patients with normal-tension glaucoma, color Doppler imaging of the ophthalmic, central retinal, and short posterior ciliary arteries was carried out after a 4-week washout of prior drug treatment and again after 6 months of treatment with nifedipine (30 mg per day). Visual field sensitivity, spatial contrast sensitivity, and intraocular pressure were also recorded. RESULTS Three subjects experienced intolerable side effects from the drug and were removed from the study. In two other patients, visual function was substantially reduced after 4 months of treatment; nifedipine was discontinued. In the remaining 16 subjects, mean intraocular pressure, retrobulbar hemodynamics, visual field mean sensitivity, and contrast sensitivity at 3, 12, and 18 cycles per degree (cpd), respectively, were unchanged after nifedipine treatment. Contrast sensitivity at 6 cpd, however, improved after drug treatment (P = .004). Individuals with the greatest improvements in contrast sensitivity at 6 cpd showed the largest increases in ophthalmic arterial peak systolic velocity (r = .57; P = .02) and end-diastolic velocity (r = .65; P = .001). CONCLUSION Nifedipine fails to provide uniform visual function or retrobulbar hemodynamic responses in patients with normal-tension glaucoma. Those patients who do show improved visual function also show improved indices of retrobulbar perfusion.