This article is more than 5 years old. Information may no longer be current.
Blood flow measurements: what do they mean?
The cause and effect of ocular blood flow measurements has not yet been determined.
Click Here to Manage Email Alerts
LAGUNA NIGUEL, Calif. — The cause of glaucoma has been debated since the 1850s. Despite a large volume of published studies on the subject, causation remains lacking. According to Joseph Caprioli, MD, none has been able to determine if abnormalities of blood flow lead to damage, are associated with damage or are a consequence of loss of neural tissue caused by other mechanisms.
Currently, a number of methods exist to estimate ocular blood flow. Most of these techniques, according to Dr. Caprioli, cannot provide a real measurement of blood flow as it relates to the delivery of nutrients to the ocular tissues, especially the optic nerve head.
What to consider
If blood flow is involved in glaucoma, it may be an ischemic pathway involving some excitoxins, such as glutamate, sodium and calcium entry into cells. Perhaps the pathway is nitric oxide, which can be extremely toxic to neurons and causes ganglion cell death. “[Another pathway] is a blockade of the retrograde flow of neurotrophins from the target tissue of ganglion cells back to the ganglion cell body,” Dr. Caprioli said. “This retrograde flow of neurotrophins is important for the sustenance and health of the ganglion cell.” If this flow is blocked, cell death occurs through cell mediated suicide. Therefore, it can be proposed that blood flow abnormalities are involved in either of these major possible pathways.
Clinical observations support the concept that vascular insufficiency may be at least a contributing cause to glaucomatous optic nerve damage. “Some patients with normal tension glaucoma are particularly at risk if they have a history of vasospasm and migraine headache,” Dr. Caprioli said at the Ocular Drug and Surgical Therapy Update meeting, sponsored by Ocular Surgery News under a grant from Allergan. “There is other evidence of peripheral vasospasms [such as Raynaud’s phenomenon] and there have been some reports of possible beneficial effects of the calcium channel blockers, although this issue is certainly still controversial.”
Disk hemorrhage, although it is not known whether it is related to primary vascular abnormality, has been used to argue that glaucoma is an ischemic process. Additionally, focal disk excavation that progresses independently of intraocular pressure suggests that this is a localized, stepwise process.
Quantifying blood flow
Issues to consider include whether real blood flow can be measured at the most appropriate locations, such as the capillary beds of the optic nerve head. Researchers are most interested in whether measurements reflect the delivery of nutrients in the target tissue. According to Dr. Caprioli, the superficial choroidal capillaries do not contribute as much to the blood vessels as the deeper layers of the ciliary arteries do.
A number of methods exist to estimate blood flow in and behind the living eye, including the measurement of vessel caliber, scanning laser angiography of the retina by means of fluorescein and of the choroid by means of indocyanine green, laser Doppler flowmetry, ocular pulse amplitude measurements and color Doppler imaging of retrobulbar arteries.
Laser Doppler flowmetry can estimate flow, but only from a limited area of the surface of the nerve head, Dr. Caprioli said. Reproducibility remains a problem with this technique, he added. Reductions in blood volume, flow and velocity have been seen in glaucoma, with a reduced flow in the peripapillary retina in patients with normal tension glaucoma. The measurements obtained with this technique seem to measure predominantly the flow at the surface of the optic nerve head, with little contribution being obtained from the deeper layers. The deeper layers may be important in the optic nerve head blood flow relevant to glaucoma, Dr. Caprioli explained.
Blue field entoptic imagery has been used to measure macular leukocyte velocity in glaucoma patients and is lower in these patients. That is a large presumption, according to Dr. Caprioli, and what it exactly means is currently not clear.
Blood flow has been measured in the nail bed capillaries as a surrogate measure of peripheral perfusion. Again, lower flow rates have been shown in patients with normal tension glaucoma and there was a greater response to cold, but the relevance to the optic nerve head and to the glaucoma is questionable, he added.
Ocular pulse pressure, also known as pulsatile flow, has been measured and is lower in primary open-angle glaucoma and normal tension glaucoma. Surgery for glaucoma increases ocular pulse pressure and asymmetric differences in ocular pulse pressure agree with asymmetry of damage – the lower the flow, the more damage.
“Lowering the eye pressure certainly increases the pulsatile flow,” Dr. Caprioli said. “I think we’d be surprised if it didn’t.” But cause and effect with the disease has not been established, he said.
Color Doppler
Color Doppler imaging looks at the major vessels behind the eye, such as the ciliary circulation and ophthalmic artery circulation, and reduction of blood flow velocity in glaucoma has been recorded. With the reduction of pressure there tends to be an improvement in the retrobulbar hemodynamics. According to Dr. Caprioli, there tends to be some progression in normal tension glaucoma with decreased retrobulbar blood velocity compared with stable patients. These differences were not found in higher pressure glaucoma and this has been used as an argument to apply a cause and effect relationship. But Dr. Caprioli said this is still a rather weak argument.
“Neither timolol nor latanoprost appear to alter retrobulbar hemodynamics,” Dr. Caprioli said. “It can be improved with carbonic anhydrase inhibitors, and even gingko biloba can increase retrobulbar blood velocity.” Whether the latter has any relevance to glaucoma has yet to be determined, he added.
Hypertension has long been argued that it may be a risk factor for glaucomatous damage and there has been some conflicting evidence in this regard, according to Dr. Caprioli. According to the Baltimore Eye Survey, patients with longstanding hypertension, the relationship between that and glaucoma were strongest for older patients. Dr. Caprioli said this suggests that longstanding hypertension can be associated with small vessel disease. Researchers also have proposed that nocturnal dips in blood pressure may be a risk factor in patients for glaucoma, particularly patients with progressive low tension glaucoma.
Blood flow has been visualized with the use of fluorescein angiographic techniques that have resulted in evidence of localized perfusion defects. But whether the defect is a result of damage or a cause of damage has yet to be determined, Dr. Caprioli said.
For Your Information:
- Joseph Caprioli, MD, can be reached at Jules Stein UCLA School of Medicine, 100 Stein Plaza, Box 957004, Los Angeles, CA 90095-7004; (310) 825-0146; fax: (310) 206-7773; e-mail: caprioli@ucla.edu.