19.4.4  Angiography

The passage of fluorescent dye in angiography is an effective way to topographically assess choroidal and retinal blood flow, as well as anatomical structures. The introduction of indocyanine green (ICG) in the last decade, in addition to fluorescein dye, has provided valuable information on the pathological conditions of the choroid and retina [75]. Due to the use of a near infrared wavelength of light that penetrates well into the choroid, ICG has a better ability than fluorescein to examine choroidal vascular abnormalities and can be used to quantify flow in large choroidal vessels. ICG binds to plasma proteins, which prevents its leakage from choroidal vessels into surrounding tissues.

Most angiography-based approaches utilize the measurement of retinal arteriovenous passage time (time between first appearance of the dye in an artery and in the corresponding vein) [9] or mean retinal circulation time (the difference between venous and arterial time) as measures of retinal blood velocity. These methods use video angiography and scanning laser ophthalmoscopy [76, 77]. One limitation of these methods is their assumption that all the blood in an area is supplied by one artery and drained by a specific vein, a fact that is not true [67]. These methods require excellent image quality to assess hyper and hypo-fluorescent areas.

19.4.5  Canon Laser Blood Flowmeter

(CLBF)

The quantitative measurement of blood flow, rather than just blood velocity, is technologically challenging. The Canon laser blood flowmeter is the only device currently available that can simultaneously measure centerline blood velocity (mm/s) using Doppler and vessel diameter (mm) using densitometry, in order to derive retinal blood flow (mL/min) in absolute units.

With the average velocity (Vmean) over a pulse cycle and diameter (D), flow through the vessel can be calculated

as (Vmean) × (60cp ) × (D/2) [2].)

The Canon laser blood flowmeter is a quantitative, noninvasive laser Doppler flowmeter that utilizes bidirectional laser Doppler velocimetry (BLDV), which provides an absolute measurement of blood velocity in the target vessel, irrespective of the angle between the

vessel and incident laser beam. The Canon laser blood flowsmeter also incorporates a vessel tracking system that employs a linear sensor to monitor the target vessel and maintain centration of the laser beam during the 2-second measurement window (velocity is continuously measured over this time). It subsequently calculates retinal blood flow assuming a circular vessel profile and Poiseuille flow with high reproducibility [78]. However, the technique can only be used to measure blood flow within the major retinal arterioles and venules (i.e. those with lumen diameter > 60 mm), and it is not suitable for the measurement of optic nerve head blood flow. We have used the Canon laser blood flowmeter to measure retinal blood flow in normal patients [78] as well as patients with glaucoma [79] and diabetes [80–83].

Summary for the Clinician

››There are many different instruments that measure various parameters related to blood flow.

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Core Messages

››Recent population-based studies have found low ocular perfusion pressure to be a risk factor for open-angle glaucoma (OAG).

››During the last two decades, ocular hemodynamic assessment has evolved from a subjective description of visible vessels to direct quantitative measurement of blood-flow parameters.

››No single examination technique can be used to study all the optic nerve vascular beds simultaneously or separately.

››A majority of the techniques for examining optic nerve hemodynamics are currently available only for research.

››Patients with both normal and high tension OAG have been found to manifest ocular vascular abnormalities within different vascular beds of the optic nerve.

20.1  What Evidence Is There that Vascular Alterations Play a Role in Open-Angle Glaucoma (OAG)?

One-third of patients with primary OAG have normal intraocular pressures (IOPs) at the time of glaucoma diagnosis. This suggests that other risk factors, such

A. Harris ( )

Department of Ophthalmology, Indiana University, 702 Rotary Circle, Indianapolis, IN 46202-5175, USA e-mail: alharris@indiana.edu

as vascular changes, contribute to the pathogenesis of glaucomatous optic neuropathy [1, 2]. Recent popula- tion-based studies, including the Barbados Eye Study, Proyecto VER (vision evaluation and research), Baltimore Eye Survey, and Egna-Neumarkt Glaucoma Study, have shown that reduced ocular perfusion pressure, and most often diastolic perfusion pressure, is a significant risk factor for the prevalence and incidence of OAG [3–6]. The Early Manifest Glaucoma Trial (EMGT) recently found that lower systolic perfusion pressure, lower systolic blood pressure, and cardiovascular disease history are new predictors for glaucoma progression, strengthening the evidence for the role of vasculopathy in glaucoma [7]. Nevertheless, the role of ocular blood flow in glaucoma is controversial. A debate remains regarding whether blood flow abnormalities can lead to OAG primarily, if elevated IOP can secondarily damage the vasculature, or if the combination of vascular dysregulation and increased IOP causes OAG.

Summary for the Clinician

››Up to one-third of cases of OAG have normal IOPs at diagnosis.

››Low ocular perfusion pressure has been found to be a risk factor for the development of OAG.

››The EMGT found low systolic perfusion pressure to be a risk factor for OAG progression.

››These findings support the role of optic nerve ischemia in the pathogenesis of OAG.