Alon Harris, Ph.D.
Director, Glaucoma Research & Diagnostic Laboratory
Indiana University School of Medicine
Dr. Harris completed his undergraduate training in Israel and his masters and Ph.D. at Indiana University. Currently, Dr. Harris has a dual appointment in the departments of ophthalmology and physiology where he is an Associate Professor of both. Dr. Harris focuses his research and laboratory work at the basic and applied level on ocular vascular physiology. He studied physiochemical factors involved in the regulation of blood flow to the optic nerve head in healthy individuals as well as in disease states such as glaucoma and diabetic retinopathy. Dr. Harris' research possesses all the cutting edge technologies that are designed to image both optic nerve head topography and hemodynamics as well. Dr. Harris has published extensively in his field and has applied his background as a vascular physiologist to glaucoma. Dr. Harris was named the Mary Greve International scholar for his outstanding work in glaucoma research, given by Research to Prevent Blindness. In addition to his interest in glaucoma research, Dr. Harris participates and performs work that relates to medical ethics in research. He is an author and co-author of many abstracts and papers on glaucoma, specifically the vascular etiology as well as the effects of various ophthalmic preparation on optic nerve head circulation.
Source The Glaucoma Foundation
Interview Glaucoma : Ocular Blood Flow, Therapeutics & Technologies
Question 1: Which technologies do you use and would you recommend to explore ocular bloodflow in patients with glaucoma ?
We use a variety of technologies. We do not believe that there is one single method that is good for evaluating ocular blood flow. It depends on the question that you are asking. For instance are you expecting to see the changes in the retina, or in the choroid or in the optic nerve heads ?
Because we do not know exactly where to look yet, the pathophysiology indicates that there is abnormalities of blood flow in all of these areas, we do a comprehensive test these days. The comprehensive test includes the following methods :
Choroid - Mainly 3 Methods
- On the choroid currently in our clinic we use mainly three technicals which can be listed as scanning laser ophthalmoscopy (SLO), ICG dye angiography with Heidelberg retinal angiography (HRA) and pulsatile ocular blood flow (POBF) measurements although there are different technicals like Flare cell meter. In SLO and HRA technicals we record the angiogram on a video and we digitize the videotape. From the digitized videotape, we have established a new image analysis system that enables us to look at different areas in the choroid between the macula and the peripapillary area, including in the fovea.
Retina - 2 Different Technicals
- For the retina we use two different technicals,
- One is the Heidelberg retina flowmeter. But we use it in a different way that is available commercially. Instead of analysing with a ten by ten pixel window, we analyse the entire image pixel by pixel, and we build flow distribution curves with a pixel count against flow. That gives us the possibility to have much higher reproducible data on the HRF than the manufacturer suggests, and also we can look at different areas in the retina because we do not know where the damage will be.
- We also use on the retina a Rodenstock system with a fluorescein angiography, again looking at intensity curves or hemi-dilution curves at the different quadrants supplying the optic nerve. We also look with a fluorescein angiography at the superficial layer of the optic nerve nerve head.
A Comprehensive Analysis
In addition to those technicals, we use color doppler imaging, which is a B-scan grey scale technical superimposed on color dupplex sonography that enables us the evaluation at the retrobulbar vessels : the ophthalmic artery, the central retina artery and the posterior ciliary arteries. Of course the posterior ciliary arteries are very important and we put it in conjunction with ICG for the choroid, because they supply blood to the optic nerve and to the choroid itself. In addition to that, in some cases, we will use the OBF, the ocular pulsatility, when we want to just get an idea of whole eye pulsatility on top of it.
So the answer to the question « what technicals do you use ? » is : we use a comprehensive analysis, we have all technicals and we do not recommend to stick to one method.
Question 2: Which are the medications that can modify ocular blood flow today ?
I think we need to divide this question to two kinds of medications. One is to understand what the available medications for lowering intraocular pressure in glaucoma can do, and the other one is to see what non conventionally can be available.
Calcium Channel Blockers
Last year we published a paper in American Journal of Ophthalmology, where we looked at patients on calcium channel blockers, on nifedipin 30 mg. We found that, as a group, the patients did not benefit from that, but individuals did. Those same individuals that showed an increase in ocular blood flow, also showed an increase or improvement in visual field in mean sensitivity and improvement in contrast sensitivity. We also found it useful that patients who are treated on different kinds of calcium channel blockers like nimodipin, which is essentially activating calcium channel blocker, also benefited.
Carbonic Anhydrase Inhibitors
From the topical available medications, I think the only medication that has a rationale to improving blood flow when applied topically is the carbonic anhydrase inhibitors. This is taken from a study we did in the brain and the eye and published in Journal of Glaucoma in 1993 or 1994. Basically acetazolamide in the brain is being used by neurologists and is a known vasodilator. It has similar effects on brain vessels as does CO2. In the retina, we find that CO2 and acetazolamide both increase blood flow. When we look at topical carbonic anhydrase inhibitors, we find similar effects to acetazolamide taken orally, that is it effects retinal vessels and optic nerve heads but does not effect the retrobulbar vessels. These papers are published in Acta Ophthalmologica and in Ocular Pharmacology.
A far as other medications the question is what that you apply topically can get to the back of the eye?. It has been shown that carbonic anhydrase inhibitors (CI) do penetrate to the back of the eye ; betablockers are questionable. In most peoples hands, applied topically they do not get there in enough concentrations. There is of course a few papers to show that selective betablockers are better for blood flow in the back of the eye than non-selective betablockers, but I would question the availability of the back of the eye, that is something that is also interesting. There is a paper that shows that topically applied CIs get to the back of the eye but topically applied betablockers do not get to the back of the eye.
The prostaglandins can go either way in the body. In some places they are vasoconstrictors in other places; they dilate vessels. I think we have to look at them closely, there is a few reports on latanoprost, that does not show much of an effect in humans, and there is a few animal reports on rescula, which is a prostaglandin F2 alpha metabolite that shows increases in blood flow in animal models, but not in humans yet.
So, from all of these drugs that are available for the treatment of glaucoma, I think that one that shows the most promise for blood flow because of its physiological rationale and similarity to CO2 are the carbonic anhydrase inhibitors. That means dorzolamide, brinzolamide and timolol-dorzolamide association.
Alon Harris, PhD (20/05/99)
By Henri Gracies, Glaucoma Institute, fondation hôpital Saint-Joseph, Paris
Thanks Faruk H. Orge, M.D.
The Glaucoma Foundation http://www.glaucoma-foundation.org/
OSN International - Edition HomePage Treatment of low-tension glaucoma with oral nifedipine http://www.slackinc.com/eye/osni/199607/harris.htm
AJO Hemodynamic and Visual Function Effects of Oral Nifedipine in Patients With Normal-tension Glaucoma
Wills Eye Hospital Glaucoma Service Foundation Understanding the Role of Blood Flow in Glaucoma http://wills-glaucoma.org/blood.htm
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