Why, Despite Everything Do Some Glaucoma Patients Get Worse?

One reason why patients believed to have glaucoma get worse is because in fact they do not really have glaucoma. Diagnoses cannot always be made with 100% accuracy, and sometimes a condition can look like glaucoma but not be glaucoma.

Sometimes a person can have glaucoma and develop another condition which causes glaucoma-like damage and is not considered because attention is being paid by the physician and the patient to the glaucoma that both know the patient has. Because it is not yet possible to determine just what is the right level of intraocular pressure that will prevent further damage in a specific patient, sometimes treatment is too vigorous, and the treatment itself causes problems. Sometimes the treatment is not vigorous enough, and the glaucoma gets worse, until it is noted that it is getting worse, and more vigorous treatment is initiated.

It is also likely that there are some types of glaucoma in which the optic nerve becomes so damaged that damage continues even when the intraocular pressure is very low, even as low as 8 mm Hg.

Isn't There Some More Effective Way to Keep Glaucoma Patients from Getting Worse?

For all of these reasons and surely for others as well some patients with glaucoma get worse. This is discouraging for everybody. Consequently, other methods than just lowering intraocular pressure have been studied to see if it is possible to prevent people with glaucoma from getting worse.

Neuroprotection

Since the usual reason why people with glaucoma lose vision is because of damage to the nerve cells (the ganglion cells) that send electrical impulses from the retina back to the brain it would make sense to try to protect these cells from becoming damaged. That is what lowering intraocular pressure tries to do. But perhaps there are other ways of protecting the cell. This idea of protecting nerve cells, neuroprotection, is an old one and was attempted by physicians in the past such as Bernard Becker at Washington University in St Louis. Recently the idea has surfaced again, at least partially as a consequence of many new discoveries in the fields of genetics, neurobiology, and pharmacology.

But before proceeding further, the reader should know that, to date, there is no proof that there is any way to protect the nerves of patients with glaucoma other than lowering the pressure within the eye. Every other approach, so far, is something that is appropriate to do in addition to lowering intraocular pressure the appropriate amount, and not in place of lowering the intraocular pressure the proper amount.

Why Do Nerve Cells Die?

Cells are factories. They need fuel, they make wastes, they need instruments to utilize the fuel and dispose of the wastes, and they must have structural integrity in order to survive. The ganglion cells of the retina need sugar and oxygen, but they also need nerve growth factors to sustain them. They can be killed by their own waste products, such as the acids that result from burning sugars and fats, the ammonias that result from using protein.

A toxin of special interest in glaucoma is glutamate, a substance which is essential for cell functioning, but which in excess can cause the death of the cell. The wall of the cell must be intact, but must function to let in those things it wants and keep out those things it does not want. Calcium is needed for the heart to beat properly, for the bones to develop, but when the cell membrane breaks down and allows the calcium outside to get inside, the cell quickly dies. Some substances cause cells to become excited, and when present in excess, can literally excite the cells to death. Many different genes control the way these processes occur, normally or abnormally, and how they are changed and modified depending upon the environment in which the cell finds itself.

Using Drugs to Block the Mechanisms that Cause Nerve Cells to Die

Blocking the way these mechanisms cause the cell to die or can enhance the life of the cell. For example, some of the agents used to treat high blood pressure, such as "Procardia" (nifedipine) or nimodipine stabilize the cell membrane and prevent excess calcium from entering the cell. These "calcium channel blockers" have been studied extensively in the field of glaucoma. Kitazawa, in Japan, is convinced that they can help prevent damage in some patients with glaucoma, especially those in whom damage occurs with low pressures. Others, including those of us at Wills Eye Hospital, are less certain that this is a wise approach. The calcium channel-blockers have a variety of side effects, including low blood pressure, which could result in less blood flowing to the eye, making the glaucoma worse. Additionally, we have not been able to confirm a beneficial effect.

Protection of nerves would be beneficial in many conditions other than just glaucoma. However, in general, little benefit has been demonstrated in these other areas either. Lou Gehrig's disease (amyotrophic lateral sclerosis) is a rare condition in which there is gradually loss of function of the nerves that move the muscles; some individuals with Lou Gehrig's disease have been helped by being treated with a neuroprotective agent. Other than for this one condition, however, neuroprotection is more of a promise than an actuality.

It is quite interesting that two drugs already used in the treatment of patients with glaucoma have been shown to have a neuroprotective effect. That is not to say that they have been shown to have a neuroprotective benefit in glaucoma. But betaxolol (Betoptic) and brimonidine (Alphagan) in certain experimental cases have been shown to limit damage to neurons. Additionally, three studies have suggested that patients with glaucoma who are treated with betaxolol have more preservation of their visual field than would be expected on the basis of lowering intraocular pressure alone. These studies, however, are preliminary and not conclusive.

The Neuroprotection Provided by a Healthy Life-Style

There are a variety of other approaches to the whole field of neuroprotection, some of which were hinted at in our earliest discussion of the relationship between life-style and glaucoma. It is prudent to live in a way that keeps one's general health as thriving as possible. Certainly, good general health is neuroprotective.

For example, alcohol is highly toxic to living cells. That is why alcohol is used as an antiseptic agent to kill bacteria. Sensitivity to alcohol toxicity varies from person to person. In many individuals small amounts of alcohol appear to be tolerated without any harmful biological effect. But for some people, especially those of Asiatic descent, even minimal amounts of alcohol are damaging; for everybody large amounts of alcohol are devastating to the well-being of the body.

Also, for example, marked malnutrition, especially lack of the B vitamins, causes severe neurologic disease. It does not follow that taking large amounts of certain nutrients, such as "megadoses" or vitamin B, is a healthy thing to do. Indeed, excess amounts of almost all nutrients cause diseases themselves, including large amounts of some of the B vitamins.

The Take-Home Message

• There is a great deal of interest in the field of medicine and in the field of glaucoma in finding ways to protect nerves from becoming damaged.
• The only proven way to prevent progression of glaucoma damage is to lower intraocular pressure an appropriate amount in the individual with glaucoma.
• Avoiding known toxic agents and caring for one's body and spirit are good for one's heart and soul and probably help with glaucoma also.
• Every drug and every treatment has side effects, some of which are serious or even fatal, and this includes "neuroprotective agents" as well.

Therefore, any treatment should be approached with careful consideration of the known and potential risks and the known and potential benefits. Neuroprotection may be an important part of treatment for glaucoma in the future. At the present time, however, treatments alleged to be "neuroprotective" are mostly "mirrors," reflecting the hope of the investigator or the desperation of the patient, and they should be used with full recognition that they are still investigational and not without problems themselves.

In contrast, being fit physically, emotionally, and spiritually is probably more likely to be specifically beneficial to nerves, and, of course, has no negative side effects at all.