Glaucoma, What's New?
Chat Highlights
February 20, 2008

On Wednesday, February 20, 2008, Dr. Michael Pro, a glaucoma specialist at Wills, and the glaucoma chat group discussed "Glaucoma, What's New".

Dr. Pro:  This is a great time for working on glaucoma. There are developments in many fields: studies are increasing our understanding of the disease; new drugs, new surgical techniques, and new instruments to diagnose glaucoma are being developed.

P:  There is a completed (Phase III) study for Memantine in patients with chronic glaucoma; in relation to the optic nerve. Question: Are you aware of any results (published or otherwise) that may show a positive outcome from this study and if so, is there a timetable for FDA approval?

Dr. Pro:  For those who may not know, Memantine (Namenda is the brand name) is a drug (pill) used for persons with Alzheimer's disease. But it had shown benefit in preventing progressive glaucoma in animal studies. So a large trial was sponsored for this neuro-protective agent. The study was finished about 2 years ago and we have no word yet. Unfortunately there are no published reports from this study and the company (Allergan) has not given out a timetable to publish the results that I am aware of.

P:  What new drugs are in development, and what is the time frame for their approval and clinical use?

Dr. Pro:  I prepared a list of some items.

Drops and drugs in the future:

• More fixed combination drugs—Combigan, Brimonidine 0.2% and timolol 0.5% is now available in the U.S.
• Extravan - Travaprost and timolol 0.5% is available in other countries. Approval pending in the U.S.
• New Agents are under investigation: Drops: Serotonin 5-HT(2) receptor agonists may hold promise. Agents that inhibit the activity of Rho-kinase (ROCK) are in early trials. Injections: Injection of anti-VEGF agents like Avastin and Lucentis are being used in neovascular glaucoma. Anecortave Acetate is a type of steroid. Injections have also shown benefit in case studies of patients with neovascular glaucoma and may be useful in other forms of glaucoma.

Moderator:  Do you want to say anything specific about any of them, Dr. Pro?

Dr. Pro:  There are more drugs than listed above, but I guess the most relevant right now for patients in the U.S. is Combigan. This drop combines two existing drops (Alphagan and Timolol). I think these fixed combination drops can improve compliance.

The Anti-VEGF drugs are getting the most attention for their dramatic benefit in patients with retinal disease. They have totally changed the outcome for patients with wet macular degeneration, but there is a lot of activity on the glaucoma front. We wonder if these drugs could be beneficial in glaucoma.

Already patients with neovascular glaucoma are benefiting. These patients used to almost always need surgery and typically had a very high pressure when they come into an office or clinic; but now a few of them can have an injection and avoid surgery.

P:  That's interesting about Anacortave Acetate. How would a steroid be beneficial to glaucoma? Wouldn't it raise IOP in susceptible persons?

Dr. Pro:  This is a particular agent. It actually acts as a sort of "anti-steroid". We don't have very much data about this agent right now, so we'll see what role it may play in the future.

P:  Are there any new developments to facilitate the success of implants (i.e. Baerveldt implant)? For example, preventing scar tissue from growing over the implant tubes (especially in younger patients).

Dr. Pro:  Well there have been studies published (from specialists at Wills) that suggests that using mitomycin C in tube shunts may help prevent the "hypertensive phase" where the pressure goes back up at two or three months post-op.

P:  Are there any new alternatives to trabeculectomies coming on the horizon?

Dr. Pro:  Yes, that is sort of the "holy grail" of glaucoma. We all want to develop a blebless surgery, which works a long time and keeps the pressure down. There are a few promising procedures.
First, more surgeons are using endocyclophotocoagulation (ECP). This is usually done at the time of cataract surgery. A laser treats the gland in the eye that make the aqueous fluid. This can get some patients off their glaucoma drops.

Another device is the trabectome. This can also be done during cataract surgery. It opens up the "drain"- the trabecular meshwork and can be effective to get the pressure down.

There is also "buzz" about canaloplasty. This is like a trabeculectomy, but with no bleb. It also opens up the drain with a suture that is passed along the Schlemm's canal.

P:  Is Combigan less likely to cause problems for people with asthma than just an ordinary beta-blocker by itself?

Dr. Pro:  No it would have the same effect profile as beta-blocker drops (like timolol) alone.

P:  I heard that ECP is only used by a small number of glaucoma docs. Why is that?

Dr. Pro:  Well it initially took off with surgeons doing lots of cataracts. Glaucoma specialists were late to adopt it because they often were dealing with complex disease and were not sure if the ECP would benefit. But I think it is now finding a place with glaucoma doctors, as are some of the other new devices and techniques.

And there are always new devices in the works. I mentioned some in an earlier chat, such as the gold shunt, which is a new kind of drain.

P:  Any news on neuroprotective medications, besides the Memantine?

Dr. Pro:  Well some specialists recommend ginkgo biloba. It is thought to improve optic nerve blood flow. But even though it is over the counter I tell my patients to talk to their Primary Medical Doctor because is has some side effects and can interact with prescription drugs.

P:  Is there anything new that might help patients with hypotony (low eye pressure)?

Dr. Pro:  Some of the new surgical techniques may prevent it.

P:  How are new studies furthering our understanding of glaucoma and what are the implications for treatment?

Dr. Pro:  Risk factors for glaucoma are better understood. The Ocular Hypertension Treatment Study (OHTS) has found that age, corneal thickness, IOP, appearance of the optic nerve, and performance on the visual field are risk factors for developing glaucoma.

Other studies have demonstrated risk in individuals who have a family history of glaucoma, and new genetic discoveries are constantly happening. New genes, which confer risk for glaucoma, are being found. A gene responsible for pseudoexfoliation glaucoma has been found. This means that someday individuals who are at risk for glaucoma could be tested for specific genes. We could have targeted glaucoma screening.

P:  Are any of these new surgical techniques as useful for advanced POAG?

Dr. Pro:  Some advocate the canaloplasty for all stages of glaucoma. I think most glaucoma specialists would still perform a trabeculectomy or tube shunt at this time, but who knows what will happen in 5 years or so.

P:  In the last year has there been any research progress with stem cells that might help glaucoma patients?

Dr. Pro:  The most dramatic stem cell research has been in lab animals. Human benefit in glaucoma may be some years in the future. Benefit in Retina and Cornea disease may come earlier due to the complexity of optic nerve regeneration.

P:  Are there any medications in research that would treat closed/narrow angle non-invasively?

Dr. Pro:  Pilocarpine has been used. It is a very old medicine. It has a lot of side effects, although some people do well with it. It is usually less effective than a laser iridotomy. There are no new medicines for narrow angle patients that I am aware of.

Moderator:  It's half past the hour, Dr. Pro. Thank you for your time and informative answers.

Dr. Pro:  OK, well I enjoyed it.

Moderator:  As did we. Thank you.

Dr. Pro:  Thanks for the great work.

[Editor's note: Dr. Pro added the following comment during the chat on March 5th: “I'd like to add some follow-up information to our last chat two weeks ago. There was a question about the clinical trials of Memantine as a neuroprotective agent for glaucoma patients. It seems there was no significant benefit compared to patients receiving placebo. Therefore, the study failed to meet its primary endpoint and to sufficiently replicate the results of the first Phase Three trial.”]

On March 5, Dr. Wilson discussed "Glaucoma Around the World" in the Chat room. Click here for highlights of that meeting.

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