Age-Related Macular Degeneration Update

Cutting-edge research, review of therapies and more.

Cutting-edge research, review of therapies, and more.

If you could cure one condition that causes blindness, age-related macular degeneration (AMD) would be a good choice. AMD is the leading cause of visual impairment and blindness in the United States and it affects as many as 1.7 million people over the age of 65, and 6 million people altogether.

As you know, AMD has "wet" forms and "dry" forms. Although the wet form is more devastating to patients, the dry form affects a significantly greater number of individuals; its impact on their quality of life is why AMD is the focus of intense efforts to find a treatment. And with the ever-growing numbers of aging baby boomers, you're likely to see more cases of AMD among your patients in the years to come.

This month, we'll present some of the newest developments in research about the causes and treatments for this serious disease.

Vitamins: They Couldn't Hurt
BY STEVEN I. BENNETT, O.D., F.A.A.O., Ann Arbor, Mich.

When it comes to recommending vitamin supplements to my AMD patients, I follow my grandmother's advice: "It couldn't hurt." We don't know what role supplements play in vision preservation, but it's important to have an open mind.

Eating well

I generally discuss proper diet with my patients, along with the use of vitamin supplements, and I recommend antioxidants. As I stress to my patients, these substances are found naturally in food and include vitamin C (ascorbic acid), vitamin E (alpha-tocopherol), carotenoids, anthocyanidins, selenium and zinc.

I think good things can come from the carotenoids, which include beta-carotene, alpha-carotene, the lycopenes, lutein and zeaxanthin. Luteins and zeaxanthin are the only carotenoids found as pigment in the macula. They're also found in leafy green vegetables, corn, kiwi and many other green, red, or yellow fruits, vegetables and nuts. Because of their yellow pigment, luteins and zeaxanthin are thought to protect against macular degeneration by helping to block harmful blue light from reaching and damaging the retina.

The pill route

Some patients prefer to take a vitamin/mineral pill. I educate them about the importance of following the recommended doses, and caution them that:

  • Large amounts of vitamin A can cause pseudotumor cerebri.
  • Zinc in higher doses can have an adverse effect on high-density lipoproteins and copper metabolism. In some people, the long-term use of zinc causes digestive problems and anemia.
  • Vitamin K in high doses can be harmful to people on blood thinners because it may act as a coagulant.
  • Alcohol may deplete the body of antioxidants.

Many patients feel that the supplements help. They believe it's important to try to take some control over their own health. I haven't found any overwhelming evidence that these supplements do indeed help, but my patients who take them, and haven't had any decrease in vision over time, are happy. Most of my colleagues do recommend vitamin supplements, just in case.

Whether we believe vitamin supplements are just placebos or that they may have some value, it's important to support and educate our patients. You never know, maybe my grandmother will be proven right.

Dr. Bennett is CEO of Dr. H. W. Bennett and Associates. He's a certified low vision specialist and has been practicing optometry for 23 years.

Treating Wet AMD
A look at current options.

While there's no cure for AMD, as you know, you might want to review the existing and upcoming treatments for the more serious wet form of the disease.


Results from the Age-Related Eye Disease Study


Some results of the ongoing Age-Related Eye Disease Study (ARED), which is supported by the National Eye Institute, were recently published. The major findings are as follow:

  • Smoking is associated with the more severe forms of AMD.

  • Hypertension is associated with large drusen or neovascular AMD.

  • Use of thyroid hormones and antacids are associated with dry AMD, though this finding requires more study.

  • Use of hydrochlorothiazide diuretics and the presence of arthritis are associated with large and intermediate drusen.

  • Hyperopic refractive error is associated with more drusen and neovascular AMD.

  • Obesity is associated with neovascular AMD.

  • Lens opacity may be associated with large drusen or neovascular disease.

  • College graduates are significantly less likely to develop AMD than are people with a high school education or less.

  • Photodynamic therapy. A photosensitive dye, Novartis Ophthalmics' and QLT Inc.'s verteporfin (Visudyne), is given intravenously to the patient. Only the eye's abnormal blood vessels absorb it. After 15 minutes, the retina is exposed to a laser that chemically changes the verteporfin so it damages the abnormal blood vessels, preventing leakage and growth.
    The FDA has issued an approvable letter to expand the use of verteporfin (currently approved for classic subfoveal choroidal neovascularization caused by AMD) to include treatment of subfoveal choroidal neovascularization caused by other macular conditions such as pathologic myopia and ocular histoplasmosis syndrome. Final approval is expected in the next few months.
    Allergan signed an agreement with Photochemical Co., Ltd. for the right to develop and commercialize ATX-S10, a light-activated modified porphyrin compound used for photodynamic therapy. In preclinical testing, ATX-S10 has exhibited highly focused tissue selectivity capabilities that could favorably impact therapeutic results.
  • Laser photocoagulation. Thermal energy of varying wavelengths is used to coagulate tissue and reduce existing subretinal neovascularization. Frequently, studies show long-term benefits.
  • Submacular surgery. This procedure is still in the research and trial phase. It involves removing abnormal blood vessels through a vitrectomy with retinotomy, entering the subretinal space and excising the neovascular membranes. The National Eye Institute is funding studies of this approach.
  • Limited retinal translocation. Also in the research stage, this approach moves the retina so the underlying choroidal neovascularization can be treated by laser without destroying the fovea.
  • Retinal cell transplantation. Not yet viable, this treatment involves connecting 1.2 million photoreceptor nerve fibers to the optic nerve in precise order. Fetal retinal pigment epithelial cells can be transplanted to nourish and protect the photoreceptors, but this doesn't prevent or inhibit neovascularization.
  • Drugs. Efforts are underway to develop a drug that will inhibit the stimuli for blood vessel growth. A study sponsored by Nexstar is investigating the safety of vascular endothelial growth factor (VEGF) anti-sense oligonucleotides for advanced AMD. VEGF stimulates blood vessel growth.
    Alcon is sponsoring a study of the efficacy of periocular injections of angiostatic steroid to inhibit neovascularization.
    Genentech has completed enrollment for a Phase 1-A clinical trial of a humanized monoclonal antibody fragment linked to VEGF. Another anti-VEGF agent, aptamer (EyeTech), which inhibits VEGF in a different manner, has also completed enrollment for a Phase 1-A study.

Clinical Studies
More research is underway.

  • Dr. Noel Bouck and associates from Northwestern University Medical School in Chicago believe that a naturally occurring protein called PEDF can prevent the excess formation of blood vessels that cause various eye diseases, including AMD.
    The group experimented with PEDF in mice and reported that those treated with high-dose PEDF showed about one-third the abnormal new vessel formation seen in untreated mice with a disease that mimics neovascularization in oxygen-starved eyes. In some mice, neovascularization was completely blocked with high doses of PEDF. No untoward effects were noted.
  • Controversy continues about the usefulness of proton beam irradiation in AMD patients who aren't candidates for photodynamic therapy.
    Some doctors at the American Academy of Ophthalmology meeting in the fall dismissed its results as unsatisfactory and a short-term solution at best. Others, however, cited studies that provided better visual outcome at 12 and 24 months among patients who received higher doses of irradiation.
  • According to research presented at the recent meeting of the Association of Research in Vision and Ophthalmology in Fort Lauderdale, Fla., a gene that's linked with an increased risk of late-onset Alzheimer's disease seems to decrease the risk of developing AMD. Patients with the apolipoprotein E-4 gene and a family history of this form of Alzheimer's disease had half the risk of developing AMD as other patients.

Genetic Insights
Scientists are finding that genetic factors contribute to eye conditions just as they do to other diseases.

According to doctors at the Cleveland Clinic Foundation in Ohio, a 5-basepair deletion in a gene involved in synthesizing fatty acids can cause Stargardt's disease and AMD. Lead study author Dr. Kang Zhang said, "This finding will allow us to create an animal model to test potential drug therapies for both conditions."

Other researchers have focused on the ABCA4 gene, theorizing that the extent of retinal disease depends on the severity of mutations in the gene. This gene facilitates transport of the protein retinal, necessary for normal vision. It's hoped that genetic testing will soon identify patients at risk for retinal diseases.

The Macular Degeneration Center of Johns Hopkin's Wilmer Eye Institute is conducting a study on the genetics of AMD and is looking for families that have more than one living brother or sister with the problem. A small blood sample and a photograph of the back of the eye are needed from each participant. Your interested patients can contact Betsy Campochiaro at (410) 614-6209 or e-mail


Miniature Telescope Implant

Clinical trials to evaluate a miniaturized telescope that's implanted in the eyes of dry AMD patients have begun, according to VisionCare Ophthalmic Technologies, Inc. of Saratoga, Calif. The Implantable Miniaturized Telescope (IMT) is implanted in one eye to provide central vision while the other eye provides peripheral vision.

"The IMT may offer significant potential in meeting unmet needs of individuals suffering severe central vision loss due to AMD," says Allen W. Hill, president and CEO of VisionCare Ophthalmics Technologies.

The IMT was invented in Israel. Only 3 mm in diameter and 4.6 mm long, it comprises an assembly of miniature lenses that are integrated within the eye to create an enlarged image that the patient can see from both distance and near. It's inserted under local anesthetic in only a few minutes. Patients in the static phase of AMD and whose eyes are able to naturally follow an object will be eligible candidates for this device.

FDA approval is expected to take a few years.


AMD Patients Beware


AMD patients who are treated with anticoagulant drugs are at significant risk of developing a massive intraocular hemorrhage according to a Dutch study, though antiplatelet medications pose a less significant risk.

Researchers designed a study to determine the role of anticoagulant therapy, when prescribed for vascular or cardiac indications, in the development of a massive hemorrhage. Fifty patients in the study had AMD complicated by massive subretinal and vitreous hemorrhage. The control group had 50 cases of AMD with only small subretinal hemorrhages.

There was a considerable difference in the use of anticoagluant medication (warfarin sodium) between the groups, but use of antiplatelet medication (aspirin) wasn't significant.

The researchers concluded that doctors prescribing anticoagulant therapy should be informed of the patient's macular status and prescribe anticoagulants only for absolute systemic indications in cases of AMD patients with neovascularization.













Products to Help Patients Cope
You might want to look into the following products for your AMD patients.

The VisAble VideoTelescope. Optikos Corporation has completed key lens components for Betacom Corporation's VisAble VideoTelescope. This technology, developed in partnership with the University of Waterloo, is the first product for visually impaired people that delivers digital video magnification and extensive contrast enhancement in a portable, handheld unit.

The MagnaGrid. A convenient and reliable way for dry AMD patients to monitor their vision and report deterioration early, this device was developed by a retinal specialist at the request of his patients and has been tested by them for over 2 years. It's being used daily by many AMD patients. It doesn't replace your care, but augments it.

The MagnaGrid

Unlike paper Amsler grids that can tear or fade, MagnaGrid is made of virtually indestructible heavy-gauge vinyl and is magnetic so that patients can mount it on the refrigerator. It also comes with materials to allow mounting on a mirror. It features a high-contrast grid pattern with easily located cross-hair fixation. A wet-erase pen is included for documenting vision changes.

Plans are underway to create a program by which a doctor's name and other information can be printed on the MagnaGrid before he gives it to his patients.

Call (888) 673-8462 or visit for a free sample of the MagnaGrid to use for in-office demonstrations.

The Eger Macular Stressometer

The Eger Macular Stressometer. Gulden Ophthalmics' Eger Macular Stressometer is a handheld diagnostic instrument that stresses the macula with a controlled, repeatable light burst and measures the time it takes the eye to recover central vision.

The Eger Macular Stressometer is the first handheld device with this capability and therefore helps you identify patients at risk for AMD and other macula-related diseases.

The SmartView Video Magnifier. This electronic tool from PulseData International, Inc., allows people with partial vision to read and write by magnifying objects and presenting the images on a computer screen or T.V. monitor. Users select the size and color of text and the level of contrast.

The Diagnostic Galilean Telescope Kit

New Eschenbach products. The company has introduced a smaller, lightweight version of its Bright Field Stand Magnifier and pendant magnifiers that include 28-inch chains. Also new are light emitting diode (LED) magnifiers that provide a different spectrum of light from incandescent or halogen light and have longer lasting batteries. Finally, the company has partnered with Designs for Vision, Inc., to offer a Diagnostic Galilean Telescope Kit that snaps in and out of customized trial frames to demonstrate telescopes to patients.

NuVision. Keeler Instruments' NuVision is a small, lightweight, head-mounted visor that conceals a miniature video camera and optical system. The camera projects an image onto two small screens on the inside of the visor, equivalent to watching a 62" wide-screen T.V. from 6 feet away. Many patients who can read only the largest print without handheld magnifiers can use this for reading or watching T.V. 

Making Your Practice Low Vision-Friendly
Low vision services can enhance lives.
BY LOUIS L. LIPSCHULTZ, O.D., Lithia Springs, Ga.

With the number of AMD patients rapidly growing, there's an urgent need for low vision services. According to the American Foundation for the Blind, more than 10 million people have severe vision impairment, and 5.5 million individuals over 65 can be certified as blind or visually impaired.

The number of individuals with vision loss from AMD and other disorders will double in the next 10 years. Incorporating basic low vision services in a primary-care practice can enhance the lives of many patients and increase revenue, too.

Going about it

I recommend an "educational approach" to evaluating patients with newly developed low vision. Reviewing magnification options will help them understand the problem well enough to relieve their anxiety. After working through the following steps, the patient's capabilities will be more evident to both you and him.


Rheophoresis for Dry AMD


Investigators are using this experimental, controversial patented process, which is similar to kidney dialysis, to flush toxins from the bloodstream in the belief that removing the substances that begin the cascade of effects that lead to the problem can benefit some of their patients who have dry AMD.

This blood filtration system depletes circulating macromolecules from the blood, which lowers blood viscosity, fibrinogen and choroidal blood flow while increasing blood flow to the choroid.

With the patient in a standard reclining chair, blood is pumped from the body (250 cc at a time), separated, filtered and replaced into the body. The complete process takes about 3 hours, and the patient is awake and unanesthetized throughout.

Although two German studies have shown improvement in visual acuity following this procedure, it re mains controversial because some experts feel that the investigators haven't offered a plausible explanation about the mechanisms of the procedure's success. Skeptics note that there's no evidence that AMD is reversible; that AMD has a more complex cause than blood toxins; and that because toxins build in a patient's system in a week, continual retreatment would be needed, indefinitely.

  • Refract. Refract and assess visual acuity with a Lighthouse or EDTRS chart. Documenting vision with "finger-counting" is imprecise and may not reflect changes in future acuity.
  • Start with a high add. Begin the magnification evaluation with high plus lenses for reading. This is best done with trial clips or a trial frame. When adding plus, modify the working distance to coincide with the focal length. Be prepared to try adds over +10D.
  • Try handheld magnifiers. Evaluate the functionality of 3, 5, 7, 10 and 12.5x stand-magnifiers with bright illumination. Remember: The higher the magnification, the closer to the eye the patient should hold the page-magnifier combination.
  • Evaluate telescopes. Evaluate 3x and 7x handheld or spectacle-mounted telescopes. Many practitioners prefer spectacle-mounted scopes to minimize the blurring effects of hand movements or tremors. Evaluate the benefit of a 3x or 4x near spectacle-mounted telescope.
  • Demonstrate video magnification. Video magnifiers, also known as CCTVs, are essential when visual acuity is worse than 20/200. Providing magnification from 3x to over 60x, these devices are often the only option for reading. I recommend that a demonstration unit be available so patients can realize the potential benefits of this device. If a demonstration unit isn't available, provide your patients with one or two referral sources of local manufacturers' representatives who will visit them.
  • Make non-magnification options available. Have technicians demonstrate talking watches and large-print phone books, bibles and household items for the patient. Other commonly requested items include tactile tools for drawing insulin, talking thermometers and blood glucose gauges, as well as glare-control products. Provide a letter of certification to patients who meet the "legally blind" status.
  • Identify local resources. Coping with advanced vision loss requires specialized orientation and mobility training, computer technology or other rehabilitative services. Research and identify local resources, and be prepared to supply the patient with a list of the state and federal programs available.
  • Understand billing policies. Consult your Medicare carrier for billing policies for professional services. A generally accepted policy is to bill a low-vision refraction fee for the magnification evaluation along with the appropriate E&M code for the associated medical services. In some cases, you may bill for consultative fees.

An essential service

By offering basic low vision services, you can give patients an understanding of possible solutions to their vision problems. This educational approach to low vision will differentiate your practice from the competition, and provide an essential service.

Dr. Lipschultz is founder of Sight Systems Rentals, Inc., a low vision device rental company, and Vision Rehab, Inc., which owns and operates low vision centers and provides management, marketing and consultative services for low vision practitioners. Dr. Lipschultz is president of Pulse Data International, Inc. in Atlanta Ga..