Treating AMD

Introduction

While great progress has been booked over the past several years, there is currently no cure for either the wet or dry form of AMD. There are therapies available that can slow the disease or even restore vision.

Dry AMD therapies

Aside from cessation of smoking and a healthy diet of dark green leafy vegetables and fruits, supplemented by zinc and anti-oxidant vitamins (Vitamins E, C, and beta carotene), very little is currently available to help patients with dry AMD to prevent progression to more serious stages of debilitating disease.

Nutritional Supplementation

The National Eye Institute (NEI) recommends the combination of antioxidants plus zinc for those who are at high risk for developing advanced AMD. These people are defined as having either Intermediate AMD in one or both eyes or Advanced AMD in one eye, but not the other eye.

The doses recommended are based on the Age-Related Eye Disease Study (AREDS)  that demonstrated a significant reduction in progression. These are:

• Vitamin C 500 mg
• Vitamin E 400 IU
• Beta-carotene 15 mg (approximately 25,000 IU)
• Zinc 80 mg, as zinc oxide
• Copper 2 mg, as cupric oxide (copper should be taken with zinc because highdose zinc is associated with copper deficiency)

While most patients in the study experienced no serious side effects from the doses of zinc and antioxidants used, a few taking zinc alone had urinary tract problems requiring hospitalization.
Some patients taking large doses of antioxidants experienced some yellowing of the skin. Some supplements may interfere with each other or other medications. Smokers and former smokers should not take beta-carotene, as studies have shown a link between beta-carotene use and lung cancer among smokers. The long-term effects of taking large doses of these supplements are still unknown.

In a follow on study, underway currently, AREDS2, patients with bilateral large drusen or large drusen in 1 eye and advanced AMD in the other are given combinations of lutein, zeaxanthin, omega-3 fatty acids and the original AREDS formulation for a total of 6 years. Lutein and zeaxanthin are found in the diet and are normally deposited as beneficial retinal pigment. Subjects in the original AREDS trial were less likely to progress to advanced AMD when they had high dietary levels of these 2 carotenoids.
 Omega-3 fatty acids (DHA and EPA) are found in fish oils. Individuals who consumed at least 2 servings of fish a week are less likely to develop advanced AMD.

Genetic risk for AMD may predict the therapeutic benefit of vitamins and nutritional supplements. A longitudinal Dutch study has determined that individuals with adverse genetics respond best to dietary supplements. Those with the CFH and ARMS2 risk alleles benefit from diets rich in nutrients known to slow the progression of AMD, while progression in those without genetic risk factors appears to be independent of diet.

Wet AMD therapies

For people with the wet form of macular degeneration, there are treatment options available to help slow or stop the progression of the disease and in some cases, even restore vision.

Anti-VEGF Treatments (Lucentis, Avastin, Macugen)

Treatments targeting the fragile new macular blood vessels reduce the risk of catastrophic vision loss related to the cycle of bleeding and scarring. In the CNV cascade, hyperpermeable blood vessels grow out through Bruch’s membrane into layers of the retina. These abnormal blood vessels can lead to retinal hemorrhaging, scarring, retinal pigment epithelial (RPE) detachments, and RPE tears.

A naturally occurring protein, Vascular Endothelial Growth Factor (VEGF), inappropriately induces eye vessel formation. Anti-VEGF drugs inhibit this. The first anti-VEGF treatment, pegaptanib sodium (Macugen) has a complex 3-dimensional structure that binds to VEGF, preventing receptor binding. This inhibits VEGF and slows the progression of neovascular disease.

Two monoclonal antibodies, bevacizumab (Avastin) and ranibizumab (Lucentis) bind to VEGF molecules, inhibiting their activity much like pegaptanib. While the two monoclonal antibodies derive from the same murine monoclonal antibody, ranibizumab is cleaved to a smaller molecule which is further affinity purified. Both monoclonal antibodies represent a therapeutic breakthrough. A recent study (2011) conducted by the National Eye Institute, the Comparison of Age Related Macular Degeneration Treatment Trial (CATT), suggests that both are equally effective.

In randomized clinical trials 95% of ranibizumab-treated wet AMD patients maintain vision and 40% experience enough visual improvement to permit driving. In general, ranibizumab is administered by monthly intra-vitreal injections.

More information on Macugen

More information on Avastin

More information on Lucentis

Laser Treatment

Photodynamic Therapy (PDT) is a laser treatment that is still occasionally used to treat wet AMD, although not as often now that anti-VEGF drugs are available. PDT (known as Visudyne (verteporfin)) involves injecting the patient with a special dye that becomes active when exposed to a certain type of laser light. The drug flows into the abnormal vessels in the macula and the doctor uses a special cold laser to destroy the abnormal blood vessels.

Good safety and efficacy data to combine PDT and Lucentis were observed in recent clinical trials known as the FOCUS and PROTECT trials. A large set of clinical trials (SUMMIT) are now underway to validate and expand on these findings. Perhaps one day, by combining these treatments, clinicians can improve visual results even further and allow for a more individualized treatment regimen for patients.

More information on Visudyne