 | Glaucoma: What Every Patient Should Know |  |
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| Glaucoma: What Every Patient Should Know | |
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The first type of eyedrop used by most glaucoma patients is the group called prostaglandins: bimatoprost (Lumigan), latanoprost (Xalatan), travoprost (Travatan Z), latanoprostene bunod (Vyzulta), and tafluprost (Zioptan). Through this section, we’ll use the small letter name for the chemical or generic product and Capital letter for the brand name. The first member of this group to be approved, Xalatan, has been used for over 10 years. As a group, the prostaglandins have the advantages that they only need to be put in once per day and are as effective (or more so) than any of the other drugs that most often need doses both morning and night.
The prostaglandin drugs are close in structure to a natural body chemical found throughout the body. Their discovery as the best glaucoma drug was due to the brilliance and persistence of the late Dr. Carl Camras, who endured years of being told that it wouldn’t work. Not long after Xalatan, the other products (Lumigan and Travatan Z) were approved, and it is fair to say that they are so close to Xalatan that they are essentially the same chemical once they enter the eye. In one large, masked clinical trial, the pressure lowering power of all 3 products was the same and more than 90% of patients who took all 3 drops in sequence found them to have acceptable tolerability. However, Xalatan had significantly fewer patients among the small number who complained of red eyes or some other irritation. Vyzulta is the newest of the prostaglandin analogs and works about as well as the others. Zioptan is a preservative free version of the prostaglandin medications and comes in small containers with only a few drops in them. A preservative-free version of latanoprost is being sold now, but only from certain drug stores, and has not been tested for potency against latanoprost with preservatives for eye pressure lowering ability.
The form of the chemical in Xalatan and Vyzulta breaks down more easily and becomes ineffective quicker than the other two. As a result, its bottles have only 2.5 milliliters of fluid in a 5 milliliter bottle. Patients often complain that their bottle was filled only half full and they were cheated. Sorry, but that’s done on purpose so that you won’t wind up using drops that have no good drug left in them. It’s also why the plastic in the Xalatan bottle is so soft—they found that the drug became less effective in standard hard plastic bottles. The other prostaglandin brand drugs aren’t so likely to degenerate, so they can be sold in bigger bottles. But, the trade-off is that they have a greater chance to cause side effects like redness and stinging (there’s no free lunch).
Vyzulta is a prostaglandin that is chemically linked to another molecule (bunod). When it is put on the eye and enters, the two separate components each help to lower eye pressure by different means. The bunod component may change how well aqueous leaves the eye by making the veins on the white part of the eye able to carry more fluid out. Eye pressure lowering by Vyzulta was significantly better than latanoprost alone, but the difference was fairly small.
The prostaglandin in Travatan Z has a different vehicle and preservative from latanoprost. For any drug, the vehicle has several parts: the drug, the preservative to keep bacteria from growing in the bottle, and chemicals added to prolong the drug life, keep it at the right acidity, and make it more comfortable on the eye. We’re paying more attention to the preservative issue now, since there is a lot of evidence that patients sometimes stop being able to tolerate drops because of irritation or allergy caused by the preservative, not the drug in the bottle. For many years, most eye drops used the preservative called benzalkonium chloride, which kills bacteria well, and even helps to get the drop into the eye better. But, if you became allergic to benzalkonium (BAK), you were in trouble, as most of the drops had it—so you couldn’t take any of them. More recently, every class of glaucoma drug has an alternative brand with different preservative or a preservative-free version (at significantly increased cost).
The side effects from a drug can be listed in various ways. In this section, we’ll distinguish between possible side effects and all the other things that are listed by the FDA paper that comes with drugs or the lists that are handed out by drug stores, chains, and prescription plans. The possible side effects are things that happen often enough that you might actually have them happen to you. They are side effects that are clearly associated with taking the drop type based on good evidence. These go away when the drug is stopped and come back when it is restarted. This doesn’t mean that a unique side effect couldn’t happen just to you and not to anyone else. Our approach at the Glaucoma Center of Excellence is always to stop a drop when a patient thinks something bad is due to the medicine. We like to see if the side effect comes back when the drug is restarted, too. While it is reasonable to always suspect the drug, it’s easy to test whether the drug is the cause by this type of stop trial.
The long lists of side effects that are listed for each drug by the FDA, and sometimes handed out by drug stores, contain side effects that are rare and even ones that actually aren’t related to the drug. Drugs are tested for effectiveness by comparing the response of people treated with the drug to people who took drops that haven't got any drug in them. These dummy drops are called placebos, and we use them to show that the drug has a real effect that wouldn't be seen by chance. The FDA listing includes as a side effect anything that happened to 1 in 100 (1%) or more persons in the year-long studies done to get the drug approved. However, they include things that happened 1% of the time whether they happened in the drug-treated group or the placebo group. So, prostaglandin eye drops are said to be more likely to cause upper respiratory infections, probably because there were a lot of colds in everyone in the final study trial. Prostaglandin eye drops have a tiny amount of chemical per drop. The amount is measured in micrograms, or millionths of a gram. Most of it winds up staying in the eye, or it is broken down before it gets into the blood stream. In fact, you can’t measure any prostaglandin drug in the blood after standard doses even with the most sensitive tests. So how could it cause systemic things like a cold? Some of the things on drug store side effect lists have never happened during our many years’ experience seeing glaucoma patients every week. The best approach is to ask your doctor about side effects you are worried about.
The possible side effects of prostaglandins are all in the eye. Most common is growing longer and thicker eyelashes. This led to development of a commercial product in mascara brushes that is marketed to grow lashes. In general, it’s not so vigorous a growth that the lashes become a problem, and many consider it a nice side effect. Rarely, fine hair can grow on the eyelid skin, or lashes grow in the corner of the eye. In some persons, lashes grow so big that they turn in and rub on the eye. Also, the amount of a pigment called melanin increases with this drop. This is the same pigment that leads to tanning from the sun. That means that the iris and the skin around the eyes can turn a darker color after treatment. For those who tell me that their wife married them “because of my beautiful hazel eyes,” having the iris turn browner is sometimes not acceptable. It happens to only a minority of those treated, but it is permanent when it happens to the iris, even when drug is stopped. It is not noticeable if you have brown eyes to start with. Most often, patients tell me that they care if they see with their eyes, not what color their eyes are. The darkening of eyelid skin is reversible if the drug is stopped. These side effects happen to a similar extent with all prostaglandins.
Other possible effects of prostaglandins are the eyes becoming red, irritated, puffy, or definitely allergic. Allergy shows itself by itching that goes on all day and redness and swelling that often include the eyelid skin. While it does happen with prostaglandins, allergy is infrequent. Finally, there are events that happen in a few unlucky patients, but one can’t say for sure that they are actually due to the drug. With the following conditions, it is said that prostaglandins can make the disease occur or reoccur if it was present before: inflammation (uveitis), reactivation of a previous herpes infections of the cornea, and swelling of the retina (macular edema). Interestingly, in each of these cases, a report was published showing a small group of patients who got the problem, stopped the prostaglandin, and had the condition go way, then got the condition again when given the drug a second time. We’ve treated hundreds of persons with these conditions who got the benefit of the drug and didn’t have these disorders occur. We discuss this with each patient when there is no other alternative drug.
How do the prostaglandins lower the eye pressure? It’s an interesting story, but to make it short, they work to allow aqueous out of the eye by two ways. Early after their discovery, it was found, in animal eyes, that they change the makeup of the ciliary body and the sclera to speed aqueous outflow through the uveoscleral pathway, a path that allows aqueous to exit through the space between the choroid and the sclera. There wasn’t much attention paid after that to effects of prostaglandins on the more standard trabecular meshwork pathway. But, the mechanism of changing the chemical content of these eye tissues would take days to weeks to happen, and the drug is well-known to lower eye pressure the same day it starts. So, later work has shown that at least one and probably all of the prostaglandins lower pressure also by improving outflow of aqueous through the standard meshwork outflow path.
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