Medications

Vitamins, antioxidants, and zinc: Nutritional supplementation with vitamin C, vitamin E, and beta carotene with zinc decrease the likelihood of developing advanced age-related macular degeneration in some people. The AREDS researchers recommended that patients at risk of developing advanced age-related macular degeneration and those without contraindications, such as smoking, should consider taking antioxidant and zinc supplements. The AREDS formulation is specific and different from a regular daily multivitamin. Occuvite PreserVision (Bausch & Lomb), ICaps (Alcon), and Macular Protect Complete (Science Based Health) are products that contain the AREDS formulation. Lower amounts of vitamin A should be used in patients who also smoke. Your eye doctor should be consulted for the best recommendation for you.

Anti-VEGF therapy: Vascular endothelial growth factor (VEGF) causes new blood vessels to develop and increases leakage and inflammation of blood vessels. Most of these drugs are insoluble and therefore cannot be given as eyedrops. Thus, the ideal form of administration is directly into the eye with a very fine needle. This can be safely accomplished through the pars plana, which is an accessible part of the eye without blood vessels about 3 millimeters behind the cornea. Thousands of these intravitreal injections are given every day in the United States with an outstanding efficacy and safety record. Nevertheless, these injection procedures are a form of surgical intervention and should be performed only by an ophthalmologist familiar with the technique, indications, contraindications, possible complications, and alternative therapies. Strict sterile protocols are necessary as with any surgical procedure.

Medications: There are now several newly approved and investigational drugs for macular degeneration in the United States. Most of these medications are given directly into the eye or around the eye, and include the following:

• Anecortave acetate (Retaane) is an investigational drug aimed at inhibiting the abnormal growth of blood vessels (neovascularization) in macular degeneration. The drug has the advantage of being injected behind the eye rather than into the eye and requires less frequent administration (every six months). Alcon discontinued investigations of this medication when statistical endpoints were not met in preliminary studies. One major difficulty was determining the exact dosage to the interior of the eye since variable concentrations occur with behind-the-eye injection techniques. Reformulations with better predictability promise improved results.



• Pegaptanib (Macugen) is a drug approved by the FDA in December 2004 that blocks VEGF and helps stabilize vision. Pegaptanib was found to be beneficial in treating both classic and occult subfoveal choroidal neovascular membranes (the areas of abnormal growth of new blood vessels). The drug is administered by an ophthalmologist as an injection into the eye. This drug was the very first intravitreal injection to be approved by the FDA and opened the door for patients, their doctors, and scientists to further improve the prognosis for dry ARMD.



• Bevacizumab (Avastin) is another anti-VEGF drug that is currently approved for cancer of the colon or rectum. It is being investigated for intravitreal use (inside the eye) in the treatment of choroidal neovascularization and macular degeneration. Because it can be aliquotted or divided into numerous tiny doses for the eye, the cost is a fraction of that for Lucentis (see below). Thus, many ophthalmologists are recommending Avastin for their patients as an alternative to Lucentis, particularly since the molecule is nearly identical. There is now an NIH-sponsored trial underway to scientifically compare Avastin to Lucentis. Both drugs carry a small risk to the patients of stroke, which is already well known to cancer doctors using these medications.



• Squalamine lactate (Evizon) is an investigational drug that blocks signaling of angiogenic (blood vessel) growth factors, including vascular endothelial growth factor (VEGF). According to one study, this drug may have a role in the treatment of human choroidal neovascular membrane formation. It is administered intravenously.



• Ranibizumab (Lucentis, formerly called RhuFab) is a newly approved anti-VEGF antibody for the treatment of wet age-related macular degeneration. It is also approved for cancer when given in systemic (delivered to the entire body) form. It is administered inside the eye via the pars plana. Preliminary studies have shown improved vision in patients with many forms of wet age-related macular degeneration. The FDA approval of Lucentis in 2006 has truly changed the face of macular degeneration because rapidly detected wet macular degeneration can be effectively treated and the return of lost visual function accomplished in a high percentage of cases. Lucentis is very costly, and multiple treatments for each eye are often necessary. Thus, numerous clinical trials are now underway to study combination therapy with other agents including laser treatment, topical nonsteroidal drugs, Avastin, Macugen, photodynamic therapy, vitrectomy surgery, and steroids. Lucentis is also being investigated for treatment of other ocular diseases besides macular degeneration in which vascular overgrowth or proliferation have compromised vision. These potential new indications include diabetic maculopathy, retinal vein occlusions, and macular edema from cataract surgery or uveitis.



• Additional therapies are being evaluated and tested, including intraocular injections of corticosteroids. Specific formulations for the intravitreal injection of preservative-free triamcinolone acetonide, a well-established and effective ocular steroid, have been approved in 2008 for both Trivaris (Allergan) and Triesence (Alcon).