Following Through on Your AMD Diagnosis

New and emerging therapies offer hope to AMD patients. Here’s advice from retina specialists on how to manage these patients.

We have entered an era when age-related macular degeneration (AMD) no longer means almost certain blindness. Rapidly advancing treatments for wet AMD — most recently, the anti-VEGF agents — offer patients more hope than ever. Ongoing research and clinical experience provide important evidence that these agents, sometimes in combination with one another or with other therapies, help optimize the results achieved. Because pa-tients must be treated as quickly as possible, early detection and patient education are key. We asked several retina specialists for their perspectives on the current state of AMD therapy and for advice on how general ophthalmologists can help them optimize patient care.

1. Use the Right Diagnostic Tools.
Making an accurate diagnosis requires a thorough examination with the right equipment.
“Everyone over the age of 50 or 55 should have a yearly exam, including a dilated retina exam, by an ophthalmologist,” says Nancy M. Holekamp, M.D., partner, Barnes Retina Institute, and associate professor of clinical ophthalmology, Washington University School of Medicine, St. Louis.
If blood, lipid or subretinal fluid is present or if the patient complains of reduced vision with metamorphopsia or scotoma, he or she needs a contact lens exam at the slit lamp and a fluorescein angiogram.
“In my opinion, OCT is not a substitute for fluorescein angiography to determine the presence of a choroidal neovascular membrane in your initial diagnosis,” says Jennifer I. Lim, M.D., professor of ophthalmology and medical director of clinical trials, Doheny Eye Institute, University of Southern California, Los Angeles. “You really need the fluorescein, at least to start.”
Dry AMD can progress to wet AMD early and without warning, so it’s important to see patients with dry AMD at least once a year. You may want to see high-risk patients more frequently, says Robert Bhisitkul, M.D., Ph.D., associate professor of clinical ophthalmology, University of Califor-nia, San Francisco. He notes the AREDS classification system correlates ophthalmoscopic findings with the risk of developing wet AMD within 5 years.1 According to this scale, patients with no risk factors have a 0.5% risk; one factor, 3% risk; two factors, 12% risk; three factors, 25% risk; and four factors, 50% risk.

2. Know the Treatment Options.
Two anti-VEGF therapies are FDA-approved for AMD: rani-bizumab (Lucentis) and pegaptanib sodium (Macugen). Although both drugs may halt disease progression, two pivotal clinical studies showed that ranibizumab can improve visual outcomes. In the MARINA and ANCHOR trials, approximately 95% of patients treated with monthly intravitreal injections of ranibizumab maintained or improved vision at 1 year. As many as 40% of patients in both trials had improved vision at 1 year, which was maintained at year 2 in the MARINA trial. Up to 40% of patients treated with the drug in both trials had 20/40 vision or better at 1 year, and 42% of those in the MARINA trial who received the drug had 20/40 vision or better at 2 years.
These results are being borne out in practice. “The drugs are behaving in a pattern that exactly mirrors the clinical trial results,” Dr. Holekamp says. “About 30% to 40% of people will actually have significant vision improvement, and with these new treatments, we are preventing severe vision loss. These drugs really do work.”
Alternatively, retina specialists are using intravitreal injections of bevacizumab (Avastin) as an off-label treatment for wet AMD because it’s less expensive than some approved drugs. Bevacizu-mab is approved to treat colorectal cancer and lung cancer, but it’s not approved for use in the eye.
“There are some misperceptions that Lucentis is the ‘daughter’ of Avastin,” Dr. Lim says. “That’s not correct. Both drugs were de-signed from a common monoclonal antibody, but they were subsequently specifically designed and developed to be different molecules.”
Opinions differ over which anti-VEGF treatment is best.
“Avastin never has been studied in a prospective randomized clinical trial of the magnitude that Lucentis has,” Dr. Holekamp says. “However, numerous case series and retrospective studies show that it appears to be efficacious and safe. A hotly debated controversy continues over which treatment should be given, Lucentis or Avastin, mostly because of cost.”
Keep in mind that although anti-VEGF agents are injected intravitreally, they can cause systemic side effects, such as thromboembolic events. “It’s not likely that the doses we deliver to the eye will induce hypertension,” Dr. Lim says. “In fact, none of the clini-
cal trials for either Lucentis or Macugen has shown any resultant hypertension.” In addition, she says, when you inject one eye, you may also get an effect in the fellow eye. This has been seen with bevacizumab in AMD and diabetic retinopathy.

The drugs are behaving in a pattern that exactly mirrors the clinical trial results.

3. Educate Patients.
Patients with wet AMD are important partners in their care. Keep them informed about how they can help themselves.
“It’s clearly established with any form of AMD therapy that early disease responds better to treatment,” Dr. Holekamp says. “So it’s very important that patients who have high-risk characteristics for AMD or who already have wet macular degeneration in one eye be taught to use an Amsler grid and to notify their ophthalmologist or retina specialist right away if they have problems.”
Remind patients to check vision in each eye independently. “They should close one eye and look at something with a straight edge like window blinds, a doorjamb or a telephone pole, and then cover the other eye and do the same thing,” Dr. Holekamp says. “It’s a simple 2-second test, but we rely on educated patients to notify us of problems because it’s unlikely we’ll detect significant disease during a routine visit.”
Ophthalmologists can be part of an overall AMD public health awareness program for their pa-tients, Dr. Holekamp says. “We’re seeing more and more about AMD in publications like Reader’s Digest and AARP Magazine, and this is all good because the public needs to be made aware of the signs and symptoms of age-related macular degeneration,” she says. “I’d encourage general ophthalmologists to order handouts on age-related macular degeneration from the American Academy of Ophthalmology. In addition, Genentech and Eyetech have pamphlets on anti-VEGF therapy for patients, and it’s very helpful to give patients written information to take home.”
Patients who are anxious about their condition may look to the Internet for additional information on AMD and treatment, so be prepared to recommend some reliable Web sites, cautioning patients to avoid sites that may be questionable. A good source is the National Eye Institute’s section on AMD (nei.nih.gov/amd).
Talk to patients about preventive measures, such as the AREDS formula of vitamins for high-risk patients. “I tell my patients that taking these supplements can decrease their risk by 25% to 27%,” Dr. Lim says. For more on risk factors, see “Who’s at Risk for AMD?”
Also urge patients to maintain a healthy lifestyle. Large population studies have shown that eating plenty of fruits, green leafy vegetables and certain fish, and reducing the intake of fried foods are associated with less severe macular degeneration, Dr. Lim says. And patients also should stop smoking. “Smoking has the second highest association with AMD, and it is associated with the more severe form of AMD,” she says.
In addition, suggest that high-risk patients enroll in the AREDS II study, which is examining if lutein, zeaxanthin and omega-3 fatty
acids given prospectively and prophylactically can decrease the risk of neovascularization in high-risk patients, Dr. Lim says.

4. Prepare Your Staff.
Conversion to wet macular degeneration is an urgent situation, so it’s important for your staff to know how to respond to patients who complain of vision loss or distorted vision, Dr. Bhisitkul says, and most doctors agree that timing is critical.
“If I have a patient with known macular degeneration who notes a sudden loss of vision or sudden onset of distortion in either eye, we have to see the patient that day or the next day so we can initiate anti-VEGF therapy right away,” Dr. Holekamp says. “Early disease responds better.”

5. Prepare Patients for Therapy.
Your patients will have questions. Answer them thoroughly, and remember that it’s OK to be hopeful.
“With Lucentis, you can tell patients they’ll avoid severe vision loss 90% to 95% of the time,” Dr. Holekamp says. “They can avoid any vision loss about 70% of the time, and they can expect significant improvement about 30% to 40% of the time.”
However, Dr. Bhisitkul says un-resolved questions remain as to how frequently patients will need to be treated with anti-VEGF therapies and how long therapy will need to be maintained. Some evidence from the uncontrolled, un-masked PrONTO study showed good efficacy when ranibizumab was injected as needed based on OCT findings and other clinical features, he explains. He says many retina specialists have adopted this approach because it may reduce the number of injections given as well as associated risks and cost. “However, this approach has not yet been tested to the same level of medical evidence that we have obtained from the MARINA and the ANCHOR trials,” he says.
It’s important to be prepared to explain to patients what their treatment may entail.
“Ophthalmologists need to tell patients this is a course of therapy and they can expect to be injected every month, perhaps up to 2 years,” Dr. Lim says. “Now realistically, what we are doing is injecting three injections, 1 month apart and then reassessing. If there’s still evidence of fluid or retinal swelling, then we’ll inject again, but otherwise we might wait a month.”

6. Respond to Problems.
Generally, retina specialists who are actively treating AMD patients will monitor them. However, you need to be aware of treatment-related problems that could arise in case a patient calls your office first.
Patients complaining of discomfort, which could signal endophthalmitis, should be seen immediately. Another potential cause for discomfort is corneal irritation resulting from Betadine cleansing before the procedure. “Betadine can cause corneal irritation, tiny corneal abrasions or punctate epitheliopathy and discomfort,” Dr. Lim says.
If a patient has vision loss or distortion after an injection but no pain, examine the back of the eye for vitreous hemorrhage, a retinal tear or detachment or lens damage. “These are extremely rare complications,” Dr. Lim says, “but they are in the differential for decreased vision after an intravitreal injection. The most severe, of course, is endophthalmitis. That’s what you need to watch out for.”

7. Follow Research Progress.
The Complications of AMD Treatment Trials (CATT) will evaluate ranibizumab and bevacizu-
mab head to head. Other trials are
comparing anti-VEGF drug treat-
ments alone versus an anti-VEGF drug combined with photodynamic therapy (PDT) with verteporfin (Visudyne). Researchers also are studying a three-pronged approach using PDT with verteporfin to treat existing blood vessels, anti-VEGF therapy to block formation of new blood vessels and a steroid to treat inflammation.
“The theory is to treat AMD as you would cancer, to hit it hard with everything you’ve got and then treat the recurrences or put patients on maintenance therapy,” Dr. Holekamp says. “Retina specialists are reporting that triple therapy can knock out the disease.” She says the investigators are claiming a much lower recurrence rate with triple therapy compared with monthly anti-VEGF injections. However, triple therapy is still in the earliest stages of investigation.
“AMD treatment has been a rapidly evolving field over the past 5 years,” Dr. Bhisitkul says. “First, we had just argon laser treatment. We went on to Visudyne PDT, then the anti-VEGF aptamer Macugen, and now the antibody-based treatments Lucentis and Avastin. Re-search continues with trials of combination therapies and novel new drugs, so it’s evolving almost every 6 months to a year.
“What’s more, researchers are exploring a whole host of alternative drug delivery systems that could help us avoid some of the problems with monthly injections into the eye,” Dr. Bhisitkul says.

8. Instill Hope.
With ongoing development of new therapies, combinations and drug-delivery systems to treat wet AMD, you can continue to encourage your patients.
“We can inform patients diagnosed with wet AMD that we have much more effective treatments than we did even a year ago,” Dr. Lim says. “We also can let them know of the new research developments leading to new drugs to target the cause of the neovascularization. There are novel targeted treatments in the pipeline.”
Adds Dr. Holekamp, “These anti-VEGF therapies are an incredible advance in treating this disease. They truly work, and we’re
preventing severe blindness. There are so many resources devoted to research in this area, I have no doubt we’ll continue to make progress.”

Who’s at Risk for AMD?
The greatest risk factor for age-related macular degeneration (AMD) is age. Although AMD may occur during middle age, studies show that people over age 60 are clearly at greater risk than younger people. Other risk factors include:
• Smoking. Smoking may increase the risk of AMD.
• Obesity. Research studies suggest a link between obesity and the progression of early and intermediate stage AMD to advanced AMD.
• Race. Whites are much more likely to lose vision from AMD than blacks.
• Family history. Anyone with immediate family members who have AMD is at a higher risk of developing the disease.
• Sex. Women appear to be at greater risk than men.

Lifestyle can play a role in reducing the risk of developing AMD. Advise your patients to:
• Eat a healthy diet high in green leafy vegetables and fish.
• Quit smoking.
• Maintain normal blood pressure.
• Maintain a healthy weight.
• Exercise.

Source: The National Eye Institute, www.nei.nih.gov