Researchers have found that immediately treating people who have early stage glaucoma can delay progression of the disease. This finding supports the medical community's emerging consensus that treatment to lower pressure inside the eye can slow glaucoma damage and subsequent vision loss. These results are reported in the October 2002 issue of Archives of Ophthalmology.
Scientists found that immediate treatment of newly-discovered primary open-angle glaucoma, the most common form of glaucoma and one of the nation's leading causes of vision loss, led to a slower rate of disease progression. The findings from this study reinforce accumulating medical evidence that lowering eye pressure in glaucoma's early stages slows progression of the disease.
"These results strongly support the body of evidence suggesting that immediate treatment of early stage, open-angle glaucoma will slow the disease progression," said Paul Sieving, M.D., Ph.D., director of the National Eye Institute (NEI), one of the Federal government's National Institutes of Health and co-sponsor of the study. "Unfortunately, glaucoma has no early warning signs, and many affected patients are unaware they have the disease until it has advanced. Once people have lost vision from glaucoma, it cannot be regained. However, early detection and timely treatment would help to save the vision of thousands of people each year."
Dr. Sieving also notes that the study results provide important new medical knowledge on the course of the disease, both among treated and untreated patients. "Because most people are treated for glaucoma as soon as they are diagnosed, little is known about the natural history of the disease," he said. "Future reports from the study will add further important information on glaucoma progression and its risk factors."
The study -- called the Early Manifest Glaucoma Trial -- followed 255 patients, aged 50-80 years, with early stage glaucoma in at least one eye. Most patients were identified in a population screening. The average age of the patients at the beginning of the study was 68 years. One group (129 patients) was treated immediately with medicines and laser to lower eye pressure, and the other group (126 patients) -- the control group -- was left untreated. Both groups were followed carefully and monitored every three months for early signs of advancing disease, using indicators that are extremely sensitive for detecting glaucoma progression. Any patient in the control group whose glaucoma progressed was immediately offered treatment.
After six years of followup, scientists found that progression was less frequent in the treated group (45 percent) than in the control group (62 percent), and occurred significantly later in treated patients. Treatment effects were also evident in patients with different characteristics, such as age, initial eye pressure levels, and degree of glaucoma damage. In the treated group, eye pressure was lowered by an average of 25 percent.
The study was a collaborative effort involving the University of Lund, Sweden, with centers in Malmö, Helsingborg, and Lund, Sweden, as well as Stony Brook University, Stony Brook, New York.
These results should be put into perspective, according to Anders Heijl, M.D., Ph.D., chairman of the Department of Ophthalmology at Sweden's Malmö University Hospital and first author of the report. "Although the study closely checked for possible glaucoma progression, many of the patients remained stable over time, even those in the control group," Dr. Heijl said. "On the other hand, despite the clear effect of treatment, glaucoma progressed in as many as 30 percent of treated patients after four years."
Dr. Heijl said that the time it took for glaucoma to progress varied greatly among patients and was sometimes rather short, even in treated patients. "This shows that in many patients with rapidly progressing glaucoma, the treatment used in this study was insufficient to halt progression of the disease," Dr. Heijl said.
Dr. Heijl emphasized that treatment for early, newly diagnosed glaucoma should be individualized and carefully balanced. Before deciding on the best treatment option, eye care professionals should consider several unique patient factors, such as age, eye pressure levels, and disease severity. "The study findings support the medical community's growing contention that glaucoma treatment should be tailored to the individual needs of the patient," Dr. Heijl said. "One option could include no initial treatment, but subsequent treatment if the disease progresses. Many glaucoma medicines have side effects, so the decision not to treat the disease in its early stage -- but closely monitor patients -- can postpone or obviate the need for medications."
Although the study results confirm the belief that reducing eye pressure is beneficial, "they do not prove that elevated eye pressure in itself is the primary cause of glaucoma," said M. Cristina Leske, M.D., chair of the Department of Preventive Medicine at Stony Brook University and a study co-author. "However, because reducing eye pressure slows the progression of glaucoma, eye pressure levels are important in the course of the disease."
Dr. Leske said that the study treatment had few side effects. The most important was an increase in nuclear opacities, a type of cataract, but the number of related cataract surgeries in the treated group was small.
Open-angle glaucoma affects about 2.2 million Americans age 40 and over; another two million may have the disease and don't know it. Glaucoma occurs when the optic nerve is damaged. In most cases, increased pressure in the eye is a risk factor for this damage. The damage to the optic nerve causes loss of peripheral (side) vision, although people are often unaware that they have glaucoma. As the disease worsens, the field of vision gradually narrows and blindness can result. However, if detected early through a comprehensive eye exam, glaucoma can usually be controlled and serious vision loss prevented.
The Early Manifest Glaucoma Trial was co-sponsored by the Swedish Research Council. A list of EMGT study centers and principal investigators is attached.
The National Eye Institute is part of the National Institutes of Health (NIH) and is the Federal government's lead agency for vision research that leads to sight-saving treatments and plays a key role in reducing visual impairment and blindness. The NIH is an agency of the U.S. Department of Health and Human Services.
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.
The Early Manifest Glaucoma Trial
Prior to this study, the natural history of glaucoma was not well defined. Researchers did not know how rapidly, if at all, early stage glaucoma would progress if it were not treated initially. Because most eye care professionals immediately treat newly-diagnosed glaucoma by reducing intraocular pressure, the natural progression of the disease (in its untreated state) was not clear. Researchers were also unclear as to how effective treatment was for early stage glaucoma, because they did not know how rapidly the disease would progress without treatment.
This raised a key question: What price, in terms of side effects, inconvenience, and cost, can be considered acceptable when treatment effects are uncertain? To begin answering this question, a randomized study was designed with a control arm in which participants were followed without treatment as long as progression did not occur, thus not exposing study participants to unacceptable risks.
The Early Manifest Glaucoma Trial is the first large, controlled, randomized clinical trial to evaluate the effects of treatment versus no treatment on early stage glaucoma. More specifically, the study compared glaucoma progression in treated (lowering intraocular pressure) versus control patients. The study also determined how much treatment reduced eye pressure, and helped researchers chart the natural history of the disease.
Patient screening began in October 1992 and ended in April 1997. Study participants came from the Swedish cities of Malmö and Helsingborg. The study followed 255 patients, of which 66 percent were women. All patients were between 50-80 years of age, inclusive (average age: 68), and all had early stage glaucoma (open angle glaucoma or normal tension glaucoma) in at least one eye. One group (129 patients) was treated immediately with medicines and laser to lower eye pressure. A second, control group had 126 patients who were left untreated. Both groups were followed carefully and monitored every three months for early signs of advancing disease, using indicators that are extremely sensitive for detecting glaucoma progression. Any patient in the control group whose glaucoma progressed was immediately offered treatment.
After six years of followup, scientists found that in the control group, it took an average of 48 months to detect early signs of advancing disease. However, in the treated group, it took an average of 66 months -- 18 months longer -- to detect these early changes. In the treated group, eye pressure was lowered by an average of 25 percent. All the study participants will continue to be followed and regularly monitored.
The information from this clinical trial adds to the scientific knowledge gained from several other glaucoma-related studies supported by the National Eye Institute, including the Ocular Hypertension Treatment Study (www.nei.nih.gov/news/pressreleases/061302.htm ), the Advanced Glaucoma Intervention Study (www.nei.nih.gov/news/pressreleases/pr798.htm), and the Collaborative Initial Glaucoma Treatment Study (www.nei.nih.gov/news/statements/cigts.htm).
The study is an example of international collaboration between Swedish and U.S. researchers. The National Eye Institute's co-sponsorship, along with the Swedish Research Council, of this clinical trial allowed for a sufficiently large study to evaluate the research question of whether lower pressure inside the eye can slow glaucoma damage and subsequent vision loss.
The Early Manifest Glaucoma Trial is a collaborative effort that involves a clinical center at the Department of Ophthalmology of Malmö University Hospital at the University of Lund, Sweden, and its Satellite Center in Helsingborg, Sweden; an independent Data Center at the Department of Preventive Medicine, Stony Brook University, Stony Brook, New York; and a Disc Photography Reading Center at the Department of Ophthalmology in Lund at the University of Lund.
Early Manifest Glaucoma Trial Study Centers & Investigators
Anders Heijl, M.D., Ph.D., Chairman
Bo Bengtsson, M.D., Ph.D.
Boel Bengtsson, Ph.D.
Department of Ophthalmology
Malmö University Hospital
University of Lund
M. Cristina Leske, M.D., M.P.H., Chair
Leslie Hyman, Ph.D.
Mohamed Hussein, Ph.D.
Department of Preventive Medicine
Stony Brook University
Stony Brook, NY
Satellite Clinical Center
Kerstin Sjöström, M.D.
Department of Ophthalmology
Disc Photography Reading Center
Anders Bergström, M.D.
Department of Ophthalmology
University Hospital of Lund
Donald Everett, M.A.
National Eye Institute
National Institutes of Health