Nutrition, medication, surgery hold hope for AMD treatment

Issue: November 2001

Management of age-related macular degeneration (AMD) can be approached through several different modalities: nutritional, surgical and pharmaceutical. As research continues to unearth new information about AMD, clinicians are hopeful that this sight-compromising disease can be prevented and treated.

One of the most promising treatments to date is Visudyne (verteporfin for injection, Novartis Ophthalmics and QLT Therapeutics), which has recently been shown to have a significant benefit in AMD patients presenting with occult choroidal neovascularization (CNV) without classic components, as well as predominantly classic wet AMD.

Visudyne: reducing risk of vision loss

Novartis Ophthalmics, the eye health unit of Novartis AG, and QLT Inc. announced in May that the American Journal of Ophthalmology published favorable 2-year results from a phase 3 clinical trial, showing Visudyne to have a benefit for AMD patients with occult CNV. “Occult” and “classic” are terms used to describe different patterns of CNV leakage as seen on fluorescein angiography.

“Based on these results, ocular photodynamic therapy with Visudyne should be considered as a treatment for AMD patients with lesions composed of occult without classic CNV with presumed recent disease progression,” said Neil Bressler, MD, chair of the Visudyne study advisory group and a retinal specialist at the Wilmer Eye Institute of the Johns Hopkins University School of Medicine in Baltimore.

“The results clearly show that, for these patients, Visudyne therapy reduces the risk of moderate and severe vision loss, particularly in cases presenting with either smaller lesions or lower levels of visual acuity,” he said.

Luzi von Bidder, head of Novartis Ophthalmics, discussed the importance of the study results. “Visudyne has already gained wide acceptance around the world as an effective treatment for AMD, and through the continued publication of strong clinical results such as these, its importance will continue to grow.”

The following 2-year results are based on 258 AMD patients (76% of the study population) with occult CNV without a classic component:

55% of the Visudyne-treated group compared with 68% of the placebo-treated group lost at least 15 letters or 3 lines of vision on a standard eye chart, while 29% of the Visudyne-treated group and 47% of the placebo-treated group lost at least 30 letters or 6 lines of vision.
All secondary outcomes including visual acuity letter score less than 34 (20/200 or worse), mean change in visual acuity letter score, development of classic CNV, progression of classic CNV and size of lesion favored Visudyne-treated patients.

Further prospectively defined analysis showed that the treatment benefit was greater for patients with either smaller lesions or lower levels of visual acuity at baseline.

The trial also confirmed Visudyne’s favorable safety profile, as no new safety concerns were identified during the second year of treatment.

During the first year of treatment, 4% of patients experienced severe vision decrease — sometimes transient, sometimes without recovery — within 7 days of initial treatment. The most common adverse effects attributed to the treatment were injection site events and visual disturbances. Photosensitivity reactions were rare, occurring in less than 1% of patients. The patients received an average of five treatments during the 24-month period.

The role of lutein

Researchers have also been engaging in long-term studies that are expected to further solidify the carotenoid lutein’s place as a key nutrient in preventing and managing AMD.

According to Robert Abel Jr., MD, clinical professor of ophthalmology at Thomas Jefferson University in Philadelphia, the case for lutein continues to grow. “There is truly more information on lutein, regarding both its preventive and therapeutic effects for AMD,” he said.

Recent studies have shown that lutein is effective not only for treating AMD, but for therapy and improved contrast sensitivity; that it can help seniors attain contrast sensitivity similar to healthy adults aged 24 to 36; and that lutein and zeaxanthin levels inversely correlate with the risk for macular degeneration.

Lutein, Dr. Abel added, has been shown to be effective in the 445-nm wavelength, which is where the most sensitive and least numerous blue cones reside. “This is exactly where the lutein is deposited,” he said. “There is a strong indication that this is an important carotenoid, especially because beta-carotene does not have a great presence in the retina.”

Edward Paul, OD, PhD, clinical director at Atlantic Eye Associates, Hampstead, N.C., recommends patients take a minimum of 12 mg of lutein per day “for it to be clinically effective.” In terms of diet, he added that is equivalent to eating four large salad bowls of spinach each day.

Dr. Abel recommends that patients with wet or dry AMD take 6 mg of lutein for several months and then 2 mg daily after that. “You can actually intervene with the dry form,” he said. Dr. Abel added that the problem with eating large amounts of spinach is that oxylates can increase the risk of kidney stones, and vitamin K may interfere with anti-coagulation medications.

DHA: another key nutrient

Another nutrient that has become increasingly significant to eye health, Dr. Paul said, is the omega-3 fatty acid DHA, which is found mainly in oily fish such as tuna, mackerel and salmon. These fish are good for the heart, Dr. Abel added, because they eat algae.

Dr. Abel explained that DHA helps support cell membranes. The eye’s receptors consist of at least 30% DHA, and light stresses them, causing them to break down and build up. Dr. Abel recommended that, in addition to eating and sleeping well, patients should be cautious with antacids, which stop acid production and “decrease your metabolism of food right from the beginning of the cycle.”

Dr. Paul tells his AMD patients that not only should they take an antioxidant and a separate lutein supplement, but also a daily dosage of 500 mg of DHA. “We’ve known for years that DHA was good for neural health and eye health,” he said.

Surgical approaches

Before laser treatment: drusen are evident.

Post-treatment: drusen have been reduced.

Researchers also continue to pursue surgeries that have the potential to effectively treat AMD. One of these possible treatments, subfoveal surgery with retinal pigment epithelial cell transplant may hold promise for patients with choroidal neovascularization, clinicians claim.

“Because 90% of age-related macular degeneration patients have choroidal neovascular membrane (CNVM) at the subfoveal level, a potential future option is a CNVM excision combined with a retinal pigment epithelial (RPE) cell transplant,” said Lucian V. Del Priore, MD, PhD, in a presentation at a seminar held at the Glaser Murphy Retina Treatment Center.

RPE transplant surgery begins with a pars plana vitrectomy on the recipient eye. RPE cells can be derived from one of a number of potential sources: stem cells, human adult donor eyes from an eye bank or the iris pigment epithelium. The RPE cells are inserted into the subretinal space before the choriocapillaris undergoes atrophy. If the RPE cells migrate and proliferate, a successful RPE transplant has occurred.

Another possibility being explored is laser treatment of drusen, which was the subject of several clinical trials in the United States and abroad. The studies showed that drusen in eyes with AMD can resolve by more than half following laser photocoagulation.

Allen C. Ho, MD, reported on the status of laser treatment of drusen for AMD at Retina 2001 in Koloa, Hawaii.

“There are several pilot clinical trials in the United States, Spain, Sweden, England and elsewhere investigating the potential beneficial effects of light laser photocoagulation in eyes with high-risk drusen and early AMD,” Dr. Ho said. “Many patients resolve their drusen, with significant reduction characterized by greater than 50%. So laser does work, but the reduction of drusen is not our object — it is really improving the long-term outlook and visual function.”

For Your Information:

Neil Bressler, MD, is a retinal specialist at the Wilmer Eye Institute of Johns Hopkins University. He can be reached at Wilmer Eye Institute, Maumenee 207, Johns Hopkins University Hospital, 600 N. Wolfe St., Baltimore, MD 21287; (410) 955-8342; fax: (410) 955-0845. Dr. Bressler has no direct financial interest in the products mentioned in this article. He has been paid as a consultant to QLT Inc. and Novartis Ophthalmics. The terms of this agreement are managed by the Johns Hopkins University in accordance with its conflict of interest policies.

Luzi von Bidder is head of Novartis Ophthalmics and can be reached at 11695 Johns Creek Parkway, Duluth, GA 30097; (800) 656-5660; fax: (770) 905-1883.

Robert Abel Jr., MD, is clinical professor of ophthalmology at Thomas Jefferson University in Philadelphia. He can be reached at Delaware Ophthalmology Consultants, Concord Plaza, 3501 Silverside Rd., Naamans Bldg., Wilmington, DE 19810; (302) 477-2600; fax: (302) 477-2650. Dr. Abel has no direct financial interest in the products mentioned in this article. He is a paid consultant for Kemin Foods, as chairman of the Lutein Information Bureau Advisory Board, and for Martek Biosciences, which distributes DHA.

Edward Paul, OD, PhD, is clinical director at Atlantic Eye Associates. He can be reached at PO Box 1200, Hwy. 17 North, Hampstead, NC 28443; (910) 270-2700; fax: (910) 270-9100. Dr. Paul has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any of the companies mentioned.

Lucian V. Del Priore, MD, PhD, can be reached at Columbia University, Edward S. Harkness Eye Institute, 635 W. 165^th Street, New York, NY 10032; (212) 305-2923; fax: (973) 450-3044. Dr. Del Priore has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.

Allen Ho, MD, can be reached at Wills Eye Hospital, Retina Services, 900 Walnut St., Philadelphia, PA 19107; (215) 928-3300; fax: (215) 238-0804. Primary Care Optometry News could not determine if Dr. Ho has a direct financial interest in the products mentioned in this article, or if he is a paid consultant for any companies mentioned.

Suggested Reading:

“Researchers continue to find nutrition’s value in preventing – and even treating – AMD,” Primary Care Optometry News, August 2001.

“Subretinal surgery and RPE cell transplantation holds promise for AMD,” Ocular Surgery News, Aug. 15, 2001.

“Visudyne clinical results show benefit in AMD patients with occult,” OSN SuperSite, May 11, 2001.

“Laser treatment of drusen aims for improved visual function,” Ocular Surgery News, Aug. 15, 2001.