One would have hoped that a century and a half of intense study would have produced at least a general consensus as to the pathogenesis of glaucoma. Unfortunately the roots of the disease remain grimly elusive, and widespread prevention efforts have failed to preclude tens of thousands from spending their golden years blind because of it. Tracking intraocular pressure is still the mainstay of diagnosis, but many patients with high pressure never develop the condition, while many patients with low or normal pressure do.
The possibility of variations in ocular blood flow (OBF) serving as an alternative early indictor of the disease has undergone a great deal of study. That the connection exists is beyond dispute.1 Glaucoma patients display reduced blood flow. Lowering IOP leads to enhanced blood flow, and raising pressure restricts blood flow, studies have shown.
This Paradigm system measures the ocular pulse via fluctuations in IOP.
Does that mean you should routinely monitor the ocular blow flow of your borderline patients? As with all things glaucomatous, there are no easy answers. Its not a silver bullet, says Elliot Kirstein, O.D., who uses Paradigms Ocular Blood Flow Analyzer to keep track of pulsatile ocular blood flow (POBF) in a large number of his patients. But for me it is a valuable piece of the glaucoma pie. My analogy is blood flow is IOPs fraternal twin.
What Causes Glaucoma?
The end result of glaucoma is the death of retinal ganglion cells. What causes the cell death is at issue. Two theories lie at the heart of this debate. The mechanical theory states that increased IOP results in stretching of the laminar beams and damage to the cells. On the other hand, the vascular theory states the damage is the result of insufficient ocular blood supply, possibly but not necessarily caused by elevated IOP. Both theories acknowledge that elevated pressure plays a role in a large percentage of glaucoma cases, especially congenital glaucoma, angle-closure glaucoma and secondary glaucomas. However, in normal-tension glaucoma, many experts believe there must be another factor at work because pressures appear so normal. Some have blamed variations in corneal thickness, but accounting for these changes does not explain all cases of normal tension glaucoma, says Iselin, N.J., optometrist Christopher J. Quinn. Also, most studies have found reduced ocular perfusion in glaucoma patients compared to healthy patients.2
Researchers believe the reduced blood flow seen in some glaucoma patients is caused by some sort of vascular dysregulation, leading to low perfusion pressure and insufficient autoregulation. Autoregula-tion is the bodys method of modulating the intratubal pressure of the capillary bed in response to variations in systemic blood pressure and IOP. When systemic blood pressure is at its lowest during sleep, the autoregulatory mechanism induces decreased microvascular resistance, which enhances choroidal perfusion. Researchers believe endothelin 1 and nitric oxide, which are derived from the microvascular endothelium, may cause the necessary contraction and relaxation of this process. Research-ers understanding of autoregulation is somewhat murky, but many postulate that defects or limitations in this process could be responsible for some glaucomas, says Dr. Kirstein. However, this is only a theory, he adds.
Measuring Blood Flow Medications and POBF
The technology used to measure POBF was developed by Maurice Langham in the 1970s. Since then there have been several improvements, but the basic concept is still used in Paradigms BFA. The Paradigm system is a pneumo-tonometer that measures the ocular pulse via fluctuations in IOP, during which the globe expands and contracts as the erectile choroidal vasculature fills and empties, and as IOP rises and falls.
The BFA records intraocular pressure at a frequency of 200Hz and the data is transformed into a volume profile. This is converted into a value of pulsatile blood flow, measured in microliters per second (ml/sec.). Normal values are considered from 12 to 22ml/sec. Values below 12 ml/sec are considered either to have sustained glaucomatous field loss or are highly suspect of being at risk for loss.
One practical benefit of the BFA is the ability to monitor ocular and systemic drugs that have the potential to modify OBF. This is especially true of beta- and calcium-level blockers, particularly when they are administered at bedtime, says Dr. Kirstein. There is a theory that the blood pressure lowering effects of non-selective beta-blockers combined with the bodys proclivity toward reduced systemic blood pressure during sleep might increase ischemic axonal damage.5
In addition to pulsatile ocular blood flow, the instrument produces an IOP and pulse amplitude (mm Hg) reading. According to the manufacturer, the BFAs IOP values are more accurate than Goldmann tonometry because the probe is smaller in diameter and the device is less influenced by variations in the patients corneal thickness. The company makes the corneal thickness claim in part because the pneumatonometer allows for the elastic deflections of the cornea and the opposing intraocular pressures via differential equations. The results have been borne out in studies.3
The most tangible data provided by POBF is in regard to normal tension glaucoma patients. Untreated NTG patients tend to have lower BFA values and lower ocular pulse amplitudes than their normal counterparts. In a large percentage of glaucoma patients, the disease continues to progress even at target pressures. The Collaborative Normal Tension Trial found that about 12% of treated glaucoma patients experience this. Many O.D.s believe some kind of vascular etiology is at work, and blood flow measurements could serve as a means of identifying these patients.
Additional Views
Not everyone is an advocate of measuring ocular blood flow. A dissenting conclusion was published this September in the American Journal of Ophthalmology. The study concluded that there was a wide range of normal values and a low discriminating power of POBF between normal and glaucomatous eyes. Given these results, the usefulness of the POBF in the clinical setting is questionable, the trials investigators stated; however, The device might be useful for evaluating the individual vascular response to treatment, a possibility the researchers did not evaluate.4
Though the relationship among glaucoma, pressure, and OBF remains enigmatic, many swear by OBF as a determining factor in borderline patients, and many more are closely watching the debate. Says New Jersey optometrist Robert M. Cole III: There is a tremendous amount of potential.
1. Geyer G, et al. Acute Effect of Latanoprost on pulsatile ocular blood flow in normal eyes. Am J Ophthalmol 2001;131:198-202.
2. Flammer J, Orgul S, Costa VP, et al. The impact of ocular blood flow in glaucoma. Prog Retin Eye Res 2002 Jul;21(4):359-93.
3. Silver DM, Farrell RA. Validity of pulsatile ocular blood flow measurements. Surv Ophthalmol 1994 May;38 Suppl:S72-80.
4. Aydin A, Wollstein G, Lyn Price L, Schuman JS. Evaluating pulsatile ocular blood flow analysis in normal and treated glaucomatous eyes. Am J Ophthalmol 2003;136:448-453.
5. Hayreh SS. Inter-individual variation in blood supply of the optic nerve head: its importance in various ischemic disorders of the nerve head and glaucoma, low-tension glaucoma, and allied disorders. Doc Ophthalmol 1985;59:217.
