Glaucoma reconsidered


High intraocular pressure has long been viewed as a crucial element in a dangerous continuum that can take as long as 25 years to progress: Fluid buildup presses on the optic nerve in the back of the eye; after years of prolonged pressure, it causes changes in the visual field and, inevitably, loss of vision. Why the fluid buildup occurs is unknown. Until recent years, it was not unusual for people to be given a diagnosis of glaucoma when their only symptom was minimal elevation in intraocular pressure. This resulted in the overtreatment of a large number of people who would never have progressed to blindness. Lifelong drug therapy wasand still isthought to be essential early in the continuum because damage to the optic nerve occurs well before the individual experiences any vision loss. (See Glaucoma Drugs article on facing page.)

Now, elevated intraocular pressure is considered to be a factor that places a person at high risk for developing glaucoma, but it is no longer part of the disease definition. The most common form of the disease is called primary open-angle glaucoma; it usually affects both eyes. The average person with open-angle glaucoma is actually at relatively low risk for blindness, according to a December 1997 editorial in the journal Ophthalmology. (This will probably come as news to anyone who pays attention to glaucoma public education campaigns.) The editorial went on to state that only a minority with this common form of glaucoma will demonstrate measurable signs of worsening, and though an even smaller percentage will ever go blind, they are large in number since glaucoma afflicts about 40 million Americans.

Nerve Toxin Implicated
The possibility that a nerve toxin called glutamate may be the cause of glaucoma-related blindness has become a major area of research interest. In 1957, two investigators found that glutamate is toxic to the inner retinait is toxic to the same cells killed by glaucoma, said Evan Dreyer, M.D., associate professor of ophthalmology at University of Pennsylvanias Scheie Institute, Philadelphia. This finding could explain why glaucoma can occur in people with normal eye pressure. It might also explain why lifelong drug therapy does not prevent vision loss in about 10% of people with glaucoma.

In a telephone interview, Dr. Dreyer said that there are many ongoing studies exploring the effect of glutamate. In rat studies, he continued, researchers can replicate the optic nerve damage seen in glaucoma by putting glutamate in the animals eyes. Similar studies in humans would be unethical, and theres no way to sample someones glutamate levels without surgery. In a study of monkeys and humans, Dr. Dreyer and his colleagues found that the level of glutamate in the eye fluid was much higher in those with glaucoma than those without the disease (Archives of Ophthalmology, March 1996). Sampling of human participants eye fluid came from specimens extracted during cataract surgery.

Glutamate could be a more significant factor in glaucoma, but that is not the same as saying it is a greater risk factor, explained Dr. Dreyer. By his definition, a risk factor can be modulated, but there might not be anything a person can do to lower glutamate levels.Oral ingestion of glutamate, for example, seems to have nothing to do with systemic or ocular levels. Glutamate is a non-essential amino acid, found in all tissues, according to Dr. Dreyer, and it is the number one neurotransmitter in the eye. As with high intraocular pressure, the source of elevated glutamate is unknown. Drugs that block glutamate are about to be tested. Asked to speculate whether positive findings would mean that glutamate antagonists might one day be prescribed instead of pressure-lowering drugs, Dr. Dreyer replied, At first pass, doctors will probably give both drugs.

Although some doctors think that theres too much attention given to intraocular pressure alone, interest in glutamates role in glaucoma tends to be divided along specialty lines. Its a hot topic in neurology where physicians specialize in the treatment of stroke, HIV-related dementia, and trauma, observed Dr. Dreyer, but not in ophthalmology where physicians are more concerned with lowering intraocular pressure. Researchers have found that high levels of glutamate can also be fatal to nerve cells in neurological disorders like stroke, Lou Gehrigs disease and Huntingtons disease.


By Maryann Napoli

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