Glaucoma Research
Chat Highlights
March 16, 2005

On Wednesday, March 16, 2005, Dr. Jeff Henderer a glaucoma specialist at Wills, and the glaucoma chat group discussed "Glaucoma Research"

Moderator:  Welcome back to chat, Dr. Henderer.  Tonight our topic is glaucoma research.

Dr. Jeff Henderer:  I have an update on new research concerning neuroprotection.  Researchers treated mice with radiation and then a bone marrow transplant.  Somehow that prevented glaucoma in the mice.  Perhaps there is some immunologic aspect that is being overcome by giving these mice a new bunch of blood cells.

[Editor's Note: In a bone marrow transplant in human beings, marrow containing healthy stem cells is infused to replace those damaged by the high dose therapy, so that the patient can produce blood cells again.  There are many different types of blood cell, but they all develop from stem cells. (www.cancerindex.org)]

P:  How did the researchers know that it prevented glaucoma?  Did they induce glaucoma in the mice?

Dr. Jeff Henderer:  The mice were of a strain that develops glaucoma spontaneously.  They didn't get glaucoma.  There are a number of animal models of glaucoma, especially in dogs.  But mice are easier to work with.  This particular lab is famous for its mouse strain, which looks a lot like pigmentary glaucoma.

Moderator:  Can you tell us more about the article you mentioned when you were here on February 23rd?  (Neuroprotection Update. http://www.willsglaucoma.org/supportgroup/20050223.php)

Dr. Jeff Henderer:  The article was published in early March.  I have not read it, but it did generate quite a buzz among the glaucoma docs on the Internet.  I don't know how we'd apply the findings to human beings, but I suppose that we might be able to infect the eye with a virus that would replace defective DNA, and thus we might be able to alter the eye.

P:  During the chat on neuroprotection, you mentioned that brimonidine (Alphagan) is being tested to see if it can protect nerve cells, as well as lower pressure.  It was being tested on patients with normal-tension glaucoma (NTG).  Does brimonidine potentially have the same neuroprotective effect on open-angle glaucoma and other types of glaucoma?

Dr. Jeff Henderer:  As far as I know, it should work in all types of glaucoma.  NTG is always a popular glaucoma to study, but the animal work was all done in models of glaucoma involving crushing the optic nerve.  That's not a great model of human glaucoma, but an excellent way to induce the apoptosis that is the mechanism for cell death in glaucoma.

P:  Although Alphagan did not lower my intraocular pressure (IOP), could it have had a neuroprotective effect?

Dr. Jeff Henderer:  Unfortunately, no one knows the answer to that.  It is certain that lowering IOP is neuroprotective.  Most docs would not leave you on a medication that does not lower your IOP, but if your back is to the wall, you might try it.

Moderator:  What is apoptosis?

Dr. Jeff Henderer:  Apoptosis is "cell suicide," that is, one of two forms of cell death.  Apoptosis is the way the body polices itself.  If a defective cell forms from radiation or something, it will kill itself so we don't get cancer. In fact, loss of apoptosis is one of the ways we get cancer.

P:  I saw an abstract reporting that glaucoma medications preserved with benzalkomium (BAK) had a pro-apoptotic effect on cultured TM (trabecular meshwork) cells.  These effects were absent in preservative-free medications.  That's pretty alarming.  Local discomfort aside, are there really any risks to the health of the TM or optic nerve from medications containing BAK?

Dr. Jeff Henderer:  That is alarming.  I did not see the study.  Since all but two glaucoma meds have this preservative and since the meds do help preserve vision, I can't say that BAK is a really bad actor, but it is something to note.

P:  Do you think that umbilical cord blood, which is sometimes saved, may have properties that might be neuroprotective?

Dr. Jeff Henderer:  It might contain stem cells, from which we might be able to regrow nerve tissue.

P:  Are you currently involved in any research?

Dr. Jeff Henderer:  My research at the moment concerns developing a new staging system for glaucoma and in glaucoma screening.  The screening is as much about getting people into care as it is about identifying disease.

P:  Once you get the new staging system, will it become universal?

Dr. Jeff Henderer:  Dr. Spaeth did a nice study not too long ago in which he looked at the genetic profile of patients who had been followed for 20 years.  Those who had a certain genetic profile seemed to do worse.  The staging scale is slowly catching on, but it is a bit harder to use, so it will take a while.  Doug Rhee at Wills is doing great work looking at why some people might respond to some drugs and not to others.

P:  Is there any research at Wills that patients can participate in, such as providing blood samples?

Dr. Jeff Henderer:  At the moment I don't know of anything at Wills.  There are some genetic projects going on around the country, but I'm not aware of any locally.

P:  How could we find out about participating in glaucoma research studies where we live?

Dr. Jeff Henderer:  The best way is to contact the ophthalmology department at your local medical school, where you can be connected to the research division or a glaucoma doctor.

P:  What about donating eyes after death?

Dr. Jeff Henderer:  That would be a wonderful gesture.  The local eye bank handles such things.

Moderator:  I know first hand about donating eyes after death.  We donated my father's eyes to the University of South Carolina.

Dr. Jeff Henderer:  I would also put in a plug for the residents who rely on cow, pig, or donated cadaver eyes to practice surgery.

P:  How would eyes from an eye bank be used in glaucoma research?

Dr. Jeff Henderer:  A variety of ways.  One would be getting tissue samples so that people like Doug Rhee can test the effects of drugs.  Another way would be developing new ways to check IOP.

P:  Is there little data about antioxidants because no funding is available for substantial studies?  From what sources could such funding come?

Dr. Jeff Henderer:  I suppose people are interested in other items.  That, and there is little funding to support such work.  The NIH (National Institutes of Health) wouldn't fund it.  Companies might, but in my experience the ones that make such things aren't really interested in any science, because it might negate their advertising.

P:  Is there an average number of years before any data are derived from research projects?  I mean, when is a decision made to continue or abandon the research?

Dr. Jeff Henderer:  The short answer is that there is no set time; it varies depending on the outcome you are studying.  If you are measuring the effect of a medication, you might only need two months.  If you are measuring the effect on your visual field, you might need seven years or more.  In general, the data safety and monitoring committee will be reviewing the data regularly and will make the call.

P:  I've read about work being done in Israel on Copaxone, which the FDA approved here for multiple sclerosis.  Have any human trials been done or started investigating the neuroprotective effect of Copaxone in vivo, either here or in Israel?

Dr. Jeff Henderer:  I have heard about Copaxone, too, but I'm not very familiar with it so I can't really say for sure.

P:  Most academic areas, and some medical areas, that are interested in change now use new statistical techniques that allow them to model individual trajectories over time.  Instead of just information on group means in glaucoma over time, I'd like to see visual field scores, IOPs, etc.  Do you have any idea why that informative technique isn't showing up in glaucoma research?

Dr. Jeff Henderer:  I have no idea why the researchers don't report the individual treatment effects.  I guess it's a matter of space in the journal.  And, of course, the mean is the mean and that counts for something.  But I really can't answer that question. If the study is small enough, I like to see the treatment effect for each patient, or at least some summary to indicate how many eyes got what level of effect.

P:  Does the focus on research change as knowledge about glaucoma increases?  When it was believed that high IOP caused glaucoma, was the research only centered on IOP and not on the optic nerve?

Dr. Jeff Henderer:  Yes and no. It turns out that for a long time people couldn't decide if IOP was really the culprit.  That meant simple things had to be proved first.  Now that that is done, we can move on.  People are now doing other things, like those we talked about.

P:  I would like to know more about optic nerve regeneration.  I thought that once the optic nerve was compromised, all bets were off, so to speak.  Does regeneration of the optic nerve hold promise for people blinded by glaucoma?

Dr. Jeff Henderer:  Yes, it does.  The question is, if the nerve regrows, does useful vision result? No one knows.

P:  If a robust blood flow to the optic nerve is good for the optic nerve, why is it not measured in exams?  Is there a way we patients can find out if blood flow to our nerves is adequate?

Dr. Jeff Henderer:  There is no real way to measure blood flow.  The HRF (Heidelberg Retinal Flowmeter) can do for research, but it's very tough.  Some other gizmos were developed, too.  But really, there's not much we can do about it anyway, so why measure it?

P:  Aren't there indirect ways to infer the effect of inadequate blood flow?  For example, don't glaucoma patients with Raynaud's syndrome have a poorer prognosis than those without such circulatory disorders?

Dr. Jeff Henderer:  Those sorts of correlations have been noted in large studies.  The same would apply to people with low blood pressure.  The problem is, you can't modify someone's blood pressure to raise it.

P:  Is there research about drugs to activate ailing ganglion cells to obtain better reaction to light and get sharper vision?

Dr. Jeff Henderer:  I'd have to say yes, but I'm not sure I've seen much about that yet.  I think it's still on the horizon.

P:  Are you familiar with a few recent studies reporting improvement of VEP (visual evoked potential) amplitude and latency after regimens of oral and/or intramuscular citicoline (CDP-choline)?  The authors speculate about a mechanism for neuroprotection.  I think, off the top of my head, that citicoline is otherwise used in stroke patients.

[Editor's note:  Citicoline has been shown to produce beneficial effects in both animal models and non-US clinical stroke trials.]

Dr. Jeff Henderer:  The citicoline stuff from a group in Italy was published back in 1999.  I was very interested in it, not so much for the drug effect, but because of the outcome measurement, and that the outcome could be measured in six months instead of six years.

P:  How much research is being done on contact lenses with glaucoma medications imbedded in them?

Dr. Jeff Henderer:  I'm not aware of anything, now that Ocuserts are off the market.

P:  Why were Ocuserts taken off the market?

Dr. Jeff Henderer:  They didn't sell.

P:  Is there any effort to culture real meshwork cells or develop some kind of functioning, artificial meshwork implant?

Dr. Jeff Henderer:  I'm not sure that people are much beyond infecting the meshwork with new copies of defective genes (assuming we know what they are).

P:  This may be off the subject, but could you explain what drusen are and do drusen cause blindness?

Dr. Jeff Henderer:  Drusen come in two forms.  One is associated with macular degeneration, and one is little rock-candy nuggets in the optic nerve that can cause vision loss.  The mechanism by which the nerve drusen cause blindness is unclear, but seems to be related to crimping axons.

On March 23, Dr. Wilson discussed "Lasers Used for Glaucoma Treatments" in the Chat room. Click here for highlights of that meeting.

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