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Glaucoma as Manifestation of a Larger Disease

Glaucoma has long been considered a disease of the eye. For most of the 20th century, it was equated with elevated intraocular pressure. Yet, over the past two decades, an increasing number of non-pressure-dependent risk factors have been identified, suggesting that glaucoma can be broadly defined as the final common pathway of a number of different disorders that affect the eye.

Glaucoma may also be included in a larger group of neurodegenerative disorders that share aspects of nerve cell death, oxidative damage and low-grade inflammation. This group of disorders includes age-related macular degeneration and Alzheimer's disease.

In a lecture delivered today at the American Academy of Ophthalmology's Annual Meeting, Robert Ritch, MD, Professor of Clinical Ophthalmology at the New York Medical College, Chief of Glaucoma Services at the New York Eye and Ear Infirmary, and Medical Director of The Glaucoma Foundation, called upon physicians to look at glaucoma in a different light: as the ocular manifestation of a more systemic disease. Dr. Ritch examined two glaucomas with very different origins -- exfoliative glaucoma and normal-tension glaucoma, concluding that they are characterized by findings that are linked to other disorders as well.

"I would like to advocate that many of the different diseases which we categorize together as glaucoma have associated systemic manifestations," says Dr. Ritch. "We're finding a series of other risk factors that are connected to ocular disease." Dr. Ritch cites data from studies, including a recent finding linking exfoliative glaucoma with genetic variations in the formation of elastic tissue, as evidence that glaucoma is not just an isolated disease of the eye.

Exfoliative glaucoma occurs when abnormal aggregates of fibrillar material related to elastic fibers along with pigment from the iris break off and block the drainage of fluid in the eye, thus elevating interocular pressure. Exfoliative glaucoma is the most common recognizable cause of open angle glaucoma in the world and in certain countries is the cause of the majority of glaucoma cases. But the degenerated or abnormal elastic fibers whose shedding leads to exfoliative glaucoma are found in other organs as well.

"You can find exfoliative material all over the body, mostly in connective tissue, such as the walls of blood vessels and cardiac muscle," says Dr. Ritch.

Studies have found that patients with exfoliative glaucoma have a higher incidence of several other diseases, including Alzheimer's and vascular diseases. "The same genetic variation that affects the eye is probably active in all these other tissues," says Dr. Ritch. "The gene is hopefully going to explain not just exfoliation in the eye. Perhaps it's also plays a role in stroke and myocardial infarction."

By contrast, normal-tension glaucoma occurs when there is damage to the optic nerve even when pressure within the eye seems to remain normal. However, Dr. Ritch notes, patients with the disease exhibit other risk factors, particularly reduced blood flow, or ischemia.

Patients often exhibit poor circulation throughout their extremities. They are also more prone to sleep apnea and an abnormal reduction in blood pressure while sleeping.

"Normal-tension glaucoma is really a nighttime disease," says Dr. Ritch.

Other risk factors associated with ischemia directly affect the retinal ganglian cells. Cells are programmed to die when they are no longer useful or have become damaged, a process known as apoptosis. But a genetic variation affecting individuals with normal-tension glaucoma causes their retinal ganglian cells to die at a more rapid rate.

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