Facing the AMD Epidemic
Results of a recent survey emphasize the grave nature of the situation, but there's much that can be done.
BY MICHAEL L. KLEIN, M.D.

In February 2004, Eyetech Pharmaceuticals, Inc. and Pfizer Inc., in consultation with Lighthouse International, surveyed 100 leading U.S. retina specialists on their attitudes about age-related macular degeneration (AMD) and existing treatment options. The survey's goal was to bring into focus a series of forces that will significantly impact the way we look at the disease, as well as its diagnosis and management. Those forces include the wellness and life expectancies of the elderly population, the aging of baby boomers, and the scientific advances in treatments for wet (neovascular) AMD.

The survey found that retina specialists are concerned about the increasing number of cases of wet AMD; they believe the disease will have a serious impact on public health unless new approaches to managing the disease are created. The respondents rank AMD among the top eye disease concerns, saying it seriously impacts a patient's quality of life, including the ability to drive, live independently and perform daily activities. They expressed concern about consequences such as emotional distress and clinical depression, as well as AMD's potential to increase costs within the healthcare system and society. (For more details, see "Highlights of the Survey Results" on page 50.)

This spring, I participated in a roundtable discussion of Macula Society members to review the results of that poll as they relate to the emerging public health threat of wet AMD and the advent of new treatments, as well as the clinical and societal implications of the findings. Here, I'd like to review some of the observations and conclusions that emerged from that discussion, including thoughts on the current status of AMD treatment, some of the options that may be available soon, and specific steps each of us can take right now to help minimize the damage being caused by AMD.

Currently Available Treatments

Unfortunately, most cases of wet AMD can't be prevented. However two recent treatment approaches do improve outcomes in many cases:

Reducing the risk of development. Recent studies have shown that a high-dose combination of vitamin C, vitamin E, beta-carotene and zinc reduces the risk of developing advanced AMD (including wet AMD) by about 25% in patients with certain high-risk features. Results of the Age-Related Eye Disease Study (AREDS) define these high-risk patients as those with intermediate AMD in one or both eyes (i.e., at least one large druse [125 microns or greater] or several intermediate drusen, or geographic atrophy not involving the center of the macula), as well as those with advanced AMD in one eye but not the other eye. (The results of AREDS were published in Archives of Ophthal-mology, October 2001; additional information about the use of nutrients can be obtained from the National Eye Institute Web site, www.nei.nih.gov.) If individuals at risk took these nutritional supplements, about 60,000 people each year would reduce their chances of developing wet AMD.

Treating existing disease. Currently, we only have two approved treatment options for those patients who do develop wet AMD: laser photocoagulation and ocular photodynamic therapy (PDT). Patients who are likely to be good candidates for laser photocoagulation include those with well-demarcated extrafoveal or juxtafoveal choroidal neovascularization (CNV). Those who should be considered for photodynamic therapy include patients with predominantly classic subfoveal CNV, and certain cases of subfoveal minimally classic CNV and subfoveal occult lesions with no classic CNV.

Recently, the Centers for Medicare and Medicaid Services announced treatment guidelines that expand its coverage of PDT to include cases involving subfoveal occult with no classic CNV, and subfoveal minimally classic CNV when the lesions are small (four disc areas or less in size) and show evidence of progression within the previous 3 months (decrease of visual acuity, lesion growth, or appearance of blood associated with the lesion).

This change increases the number of eyes we can treat, but many patients still have no treatment options. And even when a patient can be treated, visual improvement is unlikely to occur. Continued visual decline is common.

Ideally, future therapies will actually improve AMD-damaged vision. For now, the goal is simply to stabilize the disease. According to the survey, most retina specialists would agree that stabilizing vision loss across all subtypes would be an improvement over current therapies.

On the Horizon

Fortunately, new treatments on the horizon promise to help slow and/or stabilize vision loss resulting from CNV. These include anti-angiogenic drugs such as Eyetech Phar-maceuticals' Macugen (designated for fast-track approval by the FDA), Genentech's Lucentis (currently in Phase III trials) and Alcon's Retaane (Phase III trial completed).

Because these pharmacological therapies are not limited by lesion subtype or size, they should further expand the number of treatment-eligible patients, and enhance opportunities for combination therapies.

What Can We Do Right Now?

Despite current treatment limitations, there are several important steps we can take to improve patient outcomes:

Timely care. In order to preserve and maintain the highest level of functioning possible, it's most advantageous to see patients and begin treatment when the least amount of damage has been done. For example, patients with recent onset of visual symptoms are most likely to have extrafoveal and juxtafoveal lesions that can be treated with laser photocoagulation. Likewise, PDT yields better visual acuity results when we're treating smaller subfoveal lesions.

For that reason, one of the best things a general ophthalmologist can do is to make sure patients are seen by a retina specialist soon after the initial diagnosis of a neovascular AMD lesion. Early treatment maximizes the amount of vision that's preserved.

Public education. To change the paradigm of care, we need to share the responsibility for increasing public awareness of AMD and its symptoms and risk factors. We must educate health authorities and older people (who are at the greatest risk) about the need for early diagnosis.

The public needs to know that:

• AMD is the leading cause of severe vision loss and blindness in people over age 50 in the Western world.
• Currently, more than 9 million people in the United States suffer from some form of the disease.
• Of these individuals, more than 1.2 million are experiencing the active blood vessel growth and leakage associated with wet AMD, the more serious form of the disease.
• The National Eye Institute estimates that 200,000 new cases of wet AMD are diagnosed annually.
• The number of people with AMD is expected to increase 50% by 2020 as a result of the baby-boomer generation aging and overall life expectancy increasing.

Clearly, AMD needs to be recognized as a top medical and social priority.

Keeping patients informed. We must take steps to educate our patients about AMD, including fostering realistic treatment expectations and providing information about vision rehabilitation and community support services.

Staying up-to-date. It is our personal obligation to stay fully apprised of the rapidly developing advances in this area so that our patients can take full advantage of them.

Moving in the Right Direction

Certainly, the sentiments expressed by the specialists re-sponding to the survey reflect the serious nature of the situation. However, there is reason for hope; current treatments do help many patients and new options are on the horizon.

In the meantime, if we all take the concrete steps listed above -- treating patients as early as possible, educating the public and our patients, and staying on top of the latest information and options -- we can do a lot to help minimize the damage being caused by this disease.

Dr. Klein is a professor of ophthalmology and director of the Macular Degeneration Center at the Casey Eye Institute at Oregon Health and Science University.