Glaucoma is a complex multi-factorial disease. In plain English, that means it is not one disease and not caused by one factor only. Recent knowledge has made us acutely aware that eye pressure is not the determining factor in the diagnosis of glaucoma. When the pressure inside the eye was above 21 in the past glaucoma was thought to be present. Today we know that some individuals will never develop glaucoma even though their eye pressure readings may stay in the 30′s while other patients cannot tolerate normal pressures without sustaining sight loss. Glaucoma is more of a vascular disease of the optic nerve of the eye. When the auto-regulation of the blood supply starts to fail, vision begins degrading. High eye pressures do cause compression of the blood vessels supplying the nerve, but healthy blood vessels with good autoregulatory mechanisms can sustain very high pressures. Eye pressure is not static and can vary throughout the day. When we read it once when we are at the optometrists office it is only a thin slice of what your pressure range could be over a 24 hour period.
The Human Genome Project mapped the human gene structure and was an enormous undertaking completed in 2003 taking 13 years and sequencing over 3 billion codes of base pair information. This has opened the doors to tremendous future strides in treating all diseases. There is a chromosome with a gene that codes for the production of a protein called myocilin-a protein that makes up part of the structure of the trabecular meshwork. This meshwork is responsible for keeping the fluid balance in check by allowing continual drainage. When something goes awry with the drainage the pressure goes up increasing your risk for developing glaucoma. Ocugene is a company that has developed a test for defects in the myocilin/TIGR gene(GLC1A). Unfortunately, this gene is only responsible for about 4% of the cases of glaucoma. It can be useful when there is a suspected family history since patients with this genetic marker tend to have rapidly developing glaucoma and should be treated more aggressively. It also tends to be more commonly associated with glaucoma under the age of 40.The WDR36 (GLC1G) gene has also had mutations that appear to be associated with glaucoma. The optieurin gene(GLC1E) has reportedly been associated with an increased incidence of glaucoma in patients with normal pressures. One uncommon form of glaucoma know as exfoliation has also has seen the development of a genetic marker test, but due to the rarity of this condition it is not widely used .
All together, probably less than 10% of glaucoma has a direct genetic cause, and due to the expense of genetic testing it is rarely utilized. The complexity of testing is compounded by the fact that numerous defects at each gene can ocurr, and sometimes it may take two or more genes with flaws to create glaucoma. Even the most accepted genetic factor, the myocilin gene, may cause glaucoma from defects in areas other than the trabecular meshwork. It is very early in the age of genomics. Perhaps the greatest benefits will not be in diagnosing glaucoma but in tailoring treatment and actually curing some forms of glaucoma in the future.
General health issues are the most important risk factors, and some you can control. Smoking and cardiovascular diseases are high risk factors for developing glaucoma. Make sure you stay fit and have well controlled blood pressure. Keep preventative appointment and regular eye exams to monitor the eye pressure. Age is a risk factor but consider it a good one. A longer life is usually better all things considered! Most vision insurance plans like Vision Service Plan, Medicare, and many others cover preventative annual eye examinations.
The Ocular Hypertension Study was the first well documented research to justify treatment of patients with high pressures in the eyes. After years of unvalidated therapy the results were conclusive, early treatment was preventative. Ironically, today intraocular pressure has become less definitive measure for glaucoma as blood flow disruptions to the optic nerve appear to be more important. The ocular hypertension treatment study is still groundbreaking research that means patients with high pressures should be treated sooner to prevent the development of glaucoma. Furthermore, early treatment has been shown in some cases to reverse early damage that can be detected by analyzing the nerve fibers inside the eye.
Results–Ocular Hypertension Treatment Study (OHTS)
Background
Glaucoma is a group of diseases that can lead to damage to the eye’s optic nerve and result in blindness. Open-angle glaucoma, the most common form of glaucoma, is one of the leading causes of blindness in the United States and the number one cause of blindness among African Americans. Glaucoma usually has no early symptoms, and by the time people experience problems with their vision, they usually have lost a significant amount of their sight.
How Open-Angle Glaucoma Develops
Increased pressure inside the eye is an important cause of open-angle glaucoma. In the front of the eye is a space called the anterior chamber. A clear fluid flows continuously in and out of this space and nourishes nearby tissues. The fluid leaves the anterior chamber at the angle where the cornea and iris meet. When the fluid reaches the angle, it flows through a spongy meshwork, like a drain, and leaves the eye.
Open-angle glaucoma gets its name because the angle that allows fluid to drain out of the anterior chamber is open. However, for unknown reasons, the fluid passes too slowly through the meshwork drain. As the fluid builds up, the pressure inside the eye rises. Elevated eye pressure can damage the optic nerve; a healthy optic nerve is necessary for good vision. When the optic nerve is damaged from increased pressure, glaucoma — and vision loss — are the result.
At first, open-angle glaucoma has no symptoms. People are not aware that glaucoma is affecting their vision, and there is no pain. When glaucoma remains untreated, people may notice that although they see things clearly in front of them, they miss objects to the side and out of the corner of their eye. Without treatment, people with glaucoma may find that they have no side vision. Over time, the remaining vision may decrease until there is no vision left.
The Ocular Hypertension Treatment Study
Prior to the Ocular Hypertension Treatment Study, there was no clear evidence as to whether reducing elevated pressure in the eye would delay or prevent the onset of glaucoma. Elevated pressure in the eye, a common condition affecting three to six million people in the United States, is thought to be the leading risk factor for development of open-angle glaucoma. For the purposes of this study, ocular hypertension — which can be diagnosed by an eye care professional — was defined as pressure of 24 mm Hg or greater in at least one eye.
Despite the lack of convincing evidence, approximately 1.5 million people in the U.S. with elevated eye pressure and no glaucoma damage are being treated with medications that lower this pressure. There was a need for a well-controlled clinical trial to determine whether medical reduction of elevated intraocular pressure could delay or prevent the onset of glaucoma. The resulting data would enable clinicians and patients to make rational choices and health care planners ensure that medical resources were being allocated in a safe and cost-effective manner.
The primary goal of the Ocular Hypertension Treatment Study was to determine whether reducing elevated eye pressure delayed or prevented the onset of glaucoma and subsequent vision loss in people at risk of developing the disease. Patient recruitment took place between February 28, 1994 and October 31, 1996. A total of 1636 individuals were selected to participate; 817 were assigned to receive topical ocular medication (eye drops), and 819 were assigned to observation. All of the medications used in the study were commercially available.
Scientists found that eye drops used to reduce pressure inside the eye were effective in delaying the onset of primary open-angle glaucoma. After five years, researchers found that treatment reduced the onset of primary open angle glaucoma by more than 50 percent.
The Ocular Hypertension Treatment Study is the first large-scale study to demonstrate that lowering eye pressure — a risk factor for the development of primary open-angle glaucoma — can safely and effectively delay and possibly prevent the disease.
High Risk Factors for Glaucoma
In a companion paper, also published in the June 2002 issue of Archives of Ophthalmology, the authors report finding several factors predictive of those who developed primary open angle glaucoma. These included personal risk factors, such as older age and African descent, as well as ocular risk factors, such as higher eye pressure, certain characteristics in the anatomy of the optic nerve, and thinness of the cornea. The authors note that “corneal thickness provides new information about the risk of developing primary open-angle glaucoma and we recommend its measurement in the clinical evaluation of patients with ocular hypertension.”
The authors also point out that the predictive factors for glaucoma, as identified in the Ocular Hypertension Treatment Study, “are most likely to be helpful for assessing the risk of patients who resemble the study participants, i.e. ocular hypertensive individuals with eye pressure between 24 and 32 mm Hg and no evidence of glaucoma damage.” Only about two percent of Americans have these high levels of pressure in at least one eye.
The authors conclude by saying that the study results “suggest that a clinician caring for an ocular hypertensive patient can assess that individual’s risk” for developing glaucoma by considering age, race, eye pressure, optic nerve anatomy, and central corneal thickness. By considering these factors, “the clinician can identify patients who are at moderate to high risk for developing [glaucoma] and who are more likely to benefit from early medical treatment,” the authors state.
