Glaucoma Medications
Chat Highlights
May 21, 2008

On Wednesday, May 21, 2008, Dr. Michael Pro, a glaucoma specialist at Wills, and the glaucoma chat group discussed "Glaucoma Medications".

Moderator: Welcome back to chat Dr Pro and chatters. This evening our topic is Glaucoma Medications.

First we have a question that was emailed in:

Alcon has a new medication that is injected. I read it was presented at the annual meeting of the American Glaucoma Society in Washington DC. This new medication is a juxtascleral injection of Anecortave Acetate that appears to produce lasting reductions in intraocular pressure in patients with open angle glaucoma. Could you please comment on this?”

Dr. Pro:  Anecortave Acetate is an angiostatic steroid that has shown some promise as a treatment for open angle glaucoma in the form of an injection. I am fortunate that I hope to be working with this medication in trials soon. But with many new drugs, some of the initial great results occur with small patient samples. The real test will be to try the medication on greater numbers of patients.

P:  Will this next injection (Anecortave Acetate) possibly replace other medications? Or, will it prevent either laser or cutting surgery?

Dr. Pro:  It's too soon to know. For now we will probably be looking for individuals on very few medications who have not had surgery.

P:  Is it injected in the eye and how often is it given?

Dr. Pro:  It would be injected under the "skin" of the eye, over the sclera. There is no dosing schedule yet because it is so new.

Moderator: Thank you doctor. Now, would you tell us something about the different classes of glaucoma drugs?

Dr. Pro:  Sure. There are several:

1. Cholinergics, the most famous of which is Pilocarpine, have been used for over 100 years The drawbacks of Pilocarpine are QID dosing [latin—quater in die; four times a day—Ed.], reduced scotopic vision, ciliary muscle stimulation, brow ache, and myopia.

2. Epinephrine is a non-selective alpha agonist. Its side effects include allergy and adenochrome deposits. Dipivifren (Propine) was introduced in 1989. It is a pro-drug of epinephrine [Note: A pro-drug (also prodrug) is a drug that is administered in an inactive (or significantly less active) form and then becomes active—Ed.].

3. Carbonic Anhydrase Inhibitors (CAIs) have been used systemically for over 50 years. Dorzolamide hydrochloride (Trusopt) and brinzolamide hydrocloride (Azopt) were FDA approved in 1998.

4. Timolol, a beta-adrenergic antagonist (beta blocker), was introduced in 1978. Its systemic side effects include difficulty breathing, impotence, mood changes, and inhibition of cardiac function.

5. Selective Alpha 2 Adrenergic Agonists, which include apraclonidine (Iopidine) and brimonidine (Alphagan), came to market in the mid-1990s. They effect aqueous production and uveoscleral outflow. Brimonidine has a dual mechanism of lowering IOP. It enhances uveoscleral outflow and suppresses aqueous humor production (inflow).

6. Prostaglandin Analogues (anti-hypertensive lipids) are now the first-line anti-glaucoma drugs. They affect uveoscleral and trabecular outflow. Latanoprost (Xalatan) was the first successful product, launched in 1996. Bimatoprost (Lumigan) and travaprost (Travatan) followed. Side effects include conjunctival hyperemia and darkening of the peripheral iris stroma.

P:  Do drops loose their ability to work over a long period of time?

Dr. Pro:  There are two theories on that. The first says, yes, the target receptor of that drug gets saturated so the eye compensates with other modes of producing aqueous. The second theory says that the reduced effect of the drop is simply the progression of the disease process so the drain (outflow) gets progressively deficient and more drugs are needed to keep the pressure down.

P:  Do you know why glaucoma medication as Alphagan P, which comes in different strengths, does not differentiate the different strengths of the drops by bottle or cap color? Why is medication for the visually impaired often identical in color, with only small print showing the strength of the solution? Shouldn't the user of the medication be the last checkpoint for the correctness of the prescription?

Dr. Pro:  I agree entirely. Sometimes the colors of the caps are standardized across manufacturers, but I don't think there are any guidelines about your line of reasoning from the FDA.

P:  Can any of the drops cause systemic allergic reactions like itching and hives?

Dr. Pro:  Certainly. Any drop has the potential to cause allergy. It would be rare, though. I guess the most likely candidate for hives would be carbonic anhydrase inhibitors.

P:  What is the effect on the body being on glaucoma medication for twenty or more years?

Dr. Pro:  We don't really know. Certainly beta-blockers have been around that long and cholinergics much longer.

P:  If one drop is not working, do you add another or try a different class of drops altogether?

Dr. Pro:  The European Glaucoma Society has more rigorous guidelines about new drops, recommending replacing one drop with another if the first drop isn't working. In real life it is not always so simple and I will sometimes add drops to individuals with glaucoma if I am worried.

P:  Do any drops need refrigeration? Does it hurt to refrigerate? I recall one chatter saying it helped her to know the drop landed in the eye, as she could feel the cool drop.

Dr. Pro:  I agree that chilled drops are easier to feel go in the eye and sometimes chilling the drop can lessen the sting. Currently there are no drops that must be refrigerated.

P:  My specialist is only prescribing Alphagan P 0.1% and not the 0.15%. Allergan now shows only the 0.1% on their website. Did something happen with the 0.15% solution?

Dr. Pro:  Allergan brought out the 0.1% solution after studies showed equal effect as the 0.15% solution. Both are still available.

P:  Are there drops that shouldn't get hot, such as from being left in a vehicle, or a window in the sun?

Dr. Pro:  Any drop could lose efficacy if overheated. There are directions on the package insert on proper storage. Generally room temp is OK.

P:  Does refrigerating the drop alter its effectiveness in any way?

Dr. Pro:  Not that I have heard. I have asked the pharmaceutical representatives who visit my office about this, and none have warned against refrigeration.

P:  Can we talk about the importance of punctal occlusion (closing the tear duct)? What is the best method to occlude and why should one occlude after inserting eye drops?

Dr. Pro:  Occlusion helps promote drop absorption through the cornea and helps prevent systemic absorption. The best way is to press against the side of the nose at the lower corner of the eye with the index finger. Hold it there for a minute with the eye closed. Wait at least five minutes between different drops.

P:  I have had three doctors say that occlusion does not make any difference and have never recommended it. Why are there such differing opinions?

Dr. Pro:  I disagree. There may be is a lack of contolled studies, but I would have to check again. Really I am for any procedure that gives patients control over their condition. I think occlusion makes sense physiologically and I recall some old data that showed an improvement in effect.

P:  About occlusion, can one use knickles instead of the index fingers? I have long fingernails and they get in the way.

Dr. Pro:  I think using the knuckle would be OK, but be careful not to press into your eye. That is the one problem I often find. Patients frequently press on the eye rather than on the tear duct on the corner of the eye.

P:  What is considered overheating in relation to drops? I put my afternoon medicine in my jeans pocket if I am not going to be home. Is body heat too hot?

Dr. Pro:  Probably not, but the inside of a parked car gets really hot in the summer, so don't leave your drops in the car.

P:  Dr. Pro, is there anything that is known to increase aqueous production, and if so, increase it beyond a level that the trabecular meshwork can handle for increased outflow?

Dr. Pro:  We think part of the effect of steroids on IOP is increasing aqueous production along with decreased outflow.

P:  What new glaucoma medications are being developed?

Dr. Pro:  I'm glad you asked, as there are many in the pipeline. Here's a list of some of the new drugs in development or recently developed (credit to Gary Novack, PhD for much of the content of this review from the AAO Glaucoma subspecialty day 2007):

1. Prostaglandins
Travatan Z uses non-BAK preservative. Less toxic to corneal epithelium.

2. Fixed Combination Medications
Cosopt puts Trusopt and Timolol 0.5% into one drop;
Combigan;
Brimonidine (Alphagan 0.2% and Timolol 0.5% in one drop);
Awaiting approval—Xalcom (Xalatan and timolol) and DuoTrav (Travatan and timolol).

3. Rho-kinase (ROCK) inhibitors work on a novel pathway to increase aqueous outflow.

4. Steroids
Anecortave Acetate is an angiostatic steroid that has shown some promise as a treatment for open angle glaucoma in the form of an injection;
Kenalog (triamcinolone) is sometimes used in glaucoma filtering surgery.

There are many others just in the early trials. Some have new mechanisms of actions; others are new versions of existing classes.

P:  What new mechanisms of action are there?

Dr. Pro:  Santen is working on an angiotensin II antagonist. Pfizer is working with another company on a prostaglandin with nitric oxide donating properties. Biovitrum (Swedish Company) is working on a serotonin receptor anatagonist.

Many drugs show promise in animal models, but only a small fraction wind up in human trials. Often the clinical dose is toxic or irritating, or there is no vehicle to deliver the drug to the target (can't get through the cornea). Then those drugs that do get tried on humans may fail to show a large effect. The bar has been raised pretty high by the prostaglandins like Xalatan. They are very effective and since then the FDA and the pharmaceutical companies are looking for a similar effect in new agents.

P:  Once a bottle of drops has been opened, for how long can it be used?

Dr. Pro:  Once the bottle is opened it should be used up within a month or two.

P:  If we forget to take a drop, what is the best way to minimize the consequences?

Dr. Pro:  Take it when you remember and then take the next dose when you are supposed to.

P:  What is the best way to take artificial tears with glaucoma drops?

Dr. Pro:  Wait five minutes until using the tears. Otherwise, there is no problem with using tears in glaucoma patients. If you use tears very frequently you should use a non-preserved artificial tear.

P:  What are the classes of artificial tears?

Dr. Pro:  I don't know all, but the main lubricants used are polyvinyl alcohol or methycellulose. Beyond that the differences are in the concentration of the lubricant, the preservatives used, and marketing.

P:  Can I administer too little medicine in my eye?

Dr. Pro:  If you get one drop in then it is not too little. Sometimes at the end of the bottle, the medicine comes out as a bubble. In that case the dose may be too small.

P:  Is there any problem if we forget that we already instilled a drop a few minutes ago and take the same drop again, besides losing money?

Dr. Pro:  No, just the cost.

Moderator: Dr. Pro, that's all for this evening. We thank you for your time!

Dr. Pro:  A pleasure, goodnight!

On June 4, Dr. Pro discussed "Ocular Hypertension Treatment Study" in the Chat room. Click here for highlights of that meeting.

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