Are there treatments other than lowering eye pressure?

Take Home Points

We are sometimes confronted with a patient who has obeyed all the rules of treatment, taking drops religiously, coming for exams on time, and still vision seems to be slowly declining. From large studies, we know that lowering the eye pressure significantly slows the progress of glaucoma so that most patients don’t end up impaired. However, there is a limit to what lowering eye pressure can do. For one thing, in some persons when we lower it too much surgically, vision gets so blurred we have to operate to raise it back again.

It would be very important to develop treatments that add to pressure lowering, that protect ganglion cells from dying by making them less sensitive to the bad influences of glaucoma. We and many of our very bright colleagues have spent many years working on that problem. It is one of the highest priorities of the National Eye Institute and each of the non-governmental organizations that fund research into glaucoma. The word that is used for this kind of non-pressure lowering treatment is neuroprotection, meaning protecting the nerves in the eye.

The steps that have been taken so far involve several lines of work. First, we study how glaucoma affects human eyes, what seems to make it better or worse, and look for clues that can be studied in controlled laboratory research. Then, we develop models of glaucoma in individual cells in culture dishes, in pieces of the eye studied in the lab, and in animal models in animals that are as close to human glaucoma as possible. In each of these, we look for pathways that lead from some bad thing that glaucoma does, and step by step cause ganglion cells to die. We have found pathways that lead to ganglion cell death. There are also survival pathways that are activated when the injury starts and whose job it is to keep the nerve cells alive. Your glaucoma could be helped either by blocking the death pathways or by strengthening the survival pathways.

To illustrate how far we’ve come along one pathway, we’ll point out an approach that could be tried in human glaucoma patients quite soon. It’s fair to say that this is the best-studied potential new treatment, but we could list another 12 that have shown benefit all the way up to blocking glaucoma nerve cell death in animal models. In the section How did you get glaucoma?, we mentioned that the ganglion cell fiber is damaged in glaucoma as it passes out of the eye through the optic nerve head. When the fiber is injured there, its ability to carry messages from outside the eye back to the ganglion cell in the eye is blocked (obstructed axonal transport). The cell depends on receiving these messages every day to tell it what is going on up at the other end of its long fiber and to reassure it that it’s connected to the right target cells in the brain.

When the messages don’t arrive properly at the cell body, it triggers a response left over from life in the womb. When you were a fetus, fibers knew that they had gone to the right target cell in the brain by receiving the right messages or neurotrophic factors (called names like BDNF and CNTF). Baby nerve cells that didn’t receive the BDNF message thought that they were connected incorrectly, and evolution developed a mechanism for getting rid of these mistargeted nerve cells. They committed suicide by a genetic program in their DNA. This cell suicide process is called apoptosis. It sounds horrifying, but it is actually an important tool our bodies use to keep only healthy cells and to develop correctly. In glaucoma, when the message is blocked and BDNF levels fall in the cell body, this program is activated and the cell commits apoptosis. We found this pathway was active in both animals and humans with glaucoma. The logical solution would be to provide more BDNF, which we did by inserting the gene for it into the retina of rats. Presto! Fewer ganglion cells died in those rats with lots of BDNF. A similar experiment worked with the factor called CNTF. The reason that’s important is that a company has developed a way to give CNTF continuously to the eye and has already treated humans with glaucoma to see if it helps. Their ingenious system is a little capsule that can be sewn inside the eye. This is not trivial, but certainly possible for many eyes without interfering with vision. Inside the capsule are human cells that are engineered to constantly produce CNTF. The recipient eye’s defense mechanism can’t kill these cells by immune rejection, because they are inside the capsule, but the CNTF gets out to bathe the retina. Such capsules have been safely put in human eyes for a year or more without ill effects.

This is only one of a number of ways that an implanted device, or a drug taken as a pill, or a viral carrier containing a new gene could be used to attempt neuroprotection in glaucoma. There has already been one trial of 1,000 patients with a pill that might have worked. Unfortunately, it didn’t work with the drug called Memantine. We and other researchers are working very hard to try other approaches that could work. For example, the same carrier particle that put the CNTF into rats in our lab experiments has been used to put another gene into the eyes of human patients with a disease called Leber’s Congenital Amaurosis, with great benefit to their vision. This is called gene therapy, and some form of it will surely be used in the future. With the millions of glaucoma patients, there should be plenty of reason for drug companies to help us to develop new treatments.

The problem is that we are impatient (and we’re at least as impatient as our patients are) for a breakthrough in neuroprotection. However, this leads to behavior that doesn’t make sense. For example, well before we found out that Memantine, the failed neuroprotection drug, didn’t work, lots of eye doctors decided to start prescribing it for their patients. This was possible because the drug was FDA approved to treat dementia, so it was legal to write prescriptions in what is called off-label use. This means that using it for glaucoma is not approved by the FDA, because there is no evidence it will help. This kind of prescribing is frequently done, as long as the patient knows that the drug hasn’t been shown to help their problem. However, if we don’t know it will help, how do we know it won’t hurt? Giving someone a drug without knowing the side effects on their eye and on their glaucoma is taking a risk without proven benefit.

But, at least using Memantine off label was using a drug that we know what is in each pill and whose general body bad effects have been studied scientifically. Use of other nutraceuticals, herbal remedies, and alternative treatments is another realm altogether. There is not a single one of the so-called treatments in these areas that has ever been shown scientifically to benefit glaucoma. Vitamins were shown not to help anything about glaucoma in a large, controlled research study. And, when you buy such a product, neither you nor I have any idea what is in it. I have heard from patients taking Gingko biloba, Echinacea, St Johns’ Wort, and fish oil that they do it because they are “natural products, and after all, it can’t hurt, can they?” Companies or web sites that sell these products have no external regulation system for what is in the product. Many of you read about the addition of melamine, a plastic molecule and poison to the kidneys, to milk products in China, killing many children. We have regulations on things that we take as medicine for a reason. Someone could cut their lawn today, put the clippings in a capsule and sell it to you at a health store or web site as an herbal medicine. Dr. Quigley once had a patient who said he was taking a pill called “MK 801." Because a lab experiment in rats had shown benefit to rat glaucoma by dosing them with MK801, some enterprising Internet site was selling a white pill labeled as MK801 to gullible (and desperate) patients. The truth is that if the patient were actually taking MK801 in the dose it said, he would have died from it. MK801 is highly toxic, and the dose needed to help rats nearly killed them. Some of these herbals have bad effects that are unpredictable, like blocking the effects of birth control pills and causing strokes. It’s not true that “it can’t hurt.”

If you were taking insulin for diabetes, would you take 10 times more one day and none the next, without knowing which you were doing? The FDA web site lists a similar study, titled: Tainted Products Marketed as Dietary Supplements.

One book written by a glaucoma patient for other glaucoma patients has actively advocated the benefit of holistic and alternative treatments. Anecdotal testimonials by individuals who claim to have been helped are not reasons to do something. If you wish to be a supporter of the development of truly acceptable new treatments for glaucoma, don’t waste money on things that have no evidence to help you. Donate the money to a research group studying future neuroprotection for glaucoma in legitimate research laboratories.

One of the most frequently asked questions about unapproved treatments for glaucoma is whether marijuana really helps. After all, many states now permit use of medical marijuana. The bottom line is that you don’t want to smoke or swallow pot to treat your glaucoma. It is true that marijuana has some power to lower eye pressure. However, there are several good reasons why it’s not useful. First, no one can standardize how much potency it has—the chemicals in pot are a very complex mixture of things called cannabinoids, and no one can figure out which single one of them alone might be approved as an official FDA drug. Second, you can’t separate the pressure-lowering from being stoned, and you would have to be high all day, every day to get the effect on glaucoma. Third, if you smoke it, you ruin your lungs and increase your lung cancer risk. Fourth, you’re at risk for ingesting whatever insecticide someone put on it. Finally, you’d be supporting some drug cartel if you get it off the street.

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