Macular Degeneration Treatments
(Investigational)

By Marilyn Haddrill; reviewed by Charles Slonim, MD

Investigational treatments for macular degeneration are in various stages of research or FDA clinical studies.

This usually means that the drug or treatment is not generally available, unless you happen to be enrolled in a clinical trial that helps determine safety and effectiveness. [See also: More about macular degeneration and FDA-approved macular degeneration treatments.]

Investigational Treatments for Macular Degeneration

Avastin. Some eye doctors are using Avastin (bevacizumab), already an FDA-approved cancer drug, as an "off label" treatment for macular degeneration. "Off label" use means that Avastin has not been specifically FDA-approved as a macular degeneration drug. Like Macugen and Lucentis [see also: FDA-approved treatments], which is a form of Avastin, the drug is injected directly into the vitreous in the back of the eye.

A small study of Avastin reported in the March 2006 issue of Ophthalmology demonstrated early positive results. Other recent studies reported in the March 2006 issue of Retina also have shown promising positive results.

While Genentech (San Francisco) markets Avastin for treatment of colorectal cancer, the company has announced it has no plans to place the drug in clinical trials for treatment of macular degeneration. In early 2008, eye centers began announcing enrollment plans for a National Eye Institute-backed study (Comparison of Age-Related Macular Degeneration Treatments Trials or CATT) to assess effectiveness of Avastin and Genentech.

Some eye care practitioners continue to use Avastin off label for AMD treatment, because costs to patients may be significantly lower than that of Lucentis, which recently received FDA approval. Some eye doctors argue that Lucentis should be the preferred treatment, even though it is more expensive, because the drug has undergone clinical trials with verifiable results specifically as a macular degeneration treatment. For more details, read about the Lucentis vs. Avastin debate.

Vascular Endothelial Growth Factor (VEGF) Trap-Eye. Like several other FDA-approved and investigational drugs, this treatment injected into the eye is aimed at stopping action of a naturally occurring protein (VEGF) responsible for formation of abnormal blood vessel growth that causes eye damage in wet AMD.

Regeneron Pharmaceuticals Inc. (Tarrytown, N.Y.) and Bayer HealthCare (Leverkusen, Germany) initiated third phase clinical trials in August 2007 to compare effectiveness of VEGF Trap-Eye with Lucentis (Genentech). Company officials said early study results indicate VEGF Trap-Eye may be effective at lower dosing frequencies.

Retaane. In July 2008, Alcon announced termination of studies of Retaane (anecortave acetate) as a potential treatment for advanced macular degeneration because treatment objectives were not met. Retaane attacks enzymes that allow abnormal blood vessel growth by weakening the walls of retinal blood vessels.

Retaane would have offered the advantage of not being injected into the vitreous of the eye, but instead was deposited behind the eye alongside the "white of the eye" or sclera. Another advantage was that Retaane treatments were spaced about six months apart. The drug had been in clinical trials for several years. Retaane now is being investigated as a possible treatment for glaucoma.

Combretastatin. Early U.S. clinical trials also are underway for another drug, produced by OXiGENE Inc., known as Combretastatin. The anti-tumor drug is aimed at preventing development of abnormal blood vessels, which could be beneficial in slowing or halting progression of macular degeneration.

In early 2007, OXiGENE reported that preliminary results of clinical studies do appear promising. Injections of Combretastatin A4 Phosphate (CA4P) were found to stop progression of myopic macular degeneration, a form that can affect younger people with certain diseases or inherited tendencies.

Company officials announced that they were exploring further investigation of Combretastatin as a topical drug, which also might have applications for the age-related form of macular degeneration.

Encapsulated Cell Technology (ECT). This investigational treatment for the dry form of macular degeneration by Neurotech (Lincoln, R.I. and Paris) entered second phase clinical trials in early 2006. The company's plastic implant is designed to maintain sustained release of genetically engineered cells to offset eye damage in the diseased retina.

Radiation treatment. Theragenics Corporation is working on a device called the TheraSight Ocular Brachytherapy System that uses low energy x-rays for treating AMD. Early clinical studies are being conducted to test the therapy's safety and feasibility in treating the abnormal blood vessel formation associated with wet AMD.

The RHEO Procedure. A type of blood filtration (apheresis), the RHEO procedure was developed to treat dry AMD by removing certain substances in the blood plasma that have been associated with macular degeneration. Macro-proteins and fatty components in the blood such as LDL (bad) cholesterol, IgM (the antibody immunoglobulin M) and vWF are among these substances, which are known to thicken the blood, decrease blood flow and damage capillary vessels.

According to researchers, rheopheresis results in better blood flow through even the tiniest capillaries, and the improved circulation can better supply the eye's macular cells with oxygen and nutrients.

The RHEO procedure consists of eight filtration treatments over a 10- to 14-week period, with about 10 percent to 12 percent of the patient's blood volume circulating through the closed loop system at any given time. The RHEO device is in FDA phase III clinical trials, though it is not approved for general use in the United States.

In early 2006, announced results of late stage clinical trials were described by company officials as "anomalous" and did not meet anticipated goals. The procedure is available commercially in Canada.

Feeder Vessel Therapy. Feeder vessel therapy uses a high speed, indocyanine green ICG (dye) angiography to detect the presence and location of neovascular vessels that are "feeding" the choroidal neovascularization or abnormal blood vessel growth associated with visual loss in AMD.

The ICG dye is injected into a vein in the arm. A special, high speed camera then follows progression of the dye into the abnormal vessels in the macula. Once identified, they are photocoagulated (closed) with a special laser.

This therapy is available in the United States. Ongoing studies are comparing this treatment with other AMD current therapies.

The Implantable Miniature Telescope magnifies central images for the retina, reducing the perceived relative size of the central blind spot. An FDA panel voted against recommending it for approval in July 2006, so its future is uncertain. Photo: VisionCare Ophthalmic Technologies

Implantable telescope. A tiny, implanted device magnifies images onto the retina to improve central vision damaged by progression of AMD or Stargardt's macular dystrophy. Magnification of the overall image reduces the relative size of the central blind spot.

The Implantable Miniature Telescope (IMT) was invented during the late 1990s. In early 2006, Current Opinion in Ophthalmology reported that 89 percent of patients with vision loss from advanced macular degeneration had clinically significant gains in vision improvement and quality of life after the device was implanted. By the end of the FDA clinical trials, improved distance and near visual acuity had been experienced by 141 of 193 patients (10 patients reported a loss of either distance or near acuity).

However, in July 2006 the FDA ophthalmic devices panel voted 10-3 not to recommend approval of the IMT. Concerns included a higher than normal rate of loss of cells in the cornea after implantation, which in extreme cases could require device removal and a corneal transplant. The FDA panel felt the data presented didn't address these concerns adequately. There were also questions about efficacy.

Transpupillary Thermotherapy (TTT). An experimental method using an infrared laser combined with drug treatment for AMD, Transpupillary Thermotherapy (TTT) developed by Iridex has had mixed results — in some reports showing benefit, while in others revealing no statistically significant results.

However, Iridex officials announced at the Macula Society Meeting in Key Biscayne, Florida in February 2005 that the treatment does appear to benefit certain individuals with more severe vision loss from macular degeneration. Iridex reports that about 20 percent of patients treated with TTT had vision improvement, and about 60 percent had stable vision.

Artificial retinas. Research increasingly has become focused on developing artificial retinas or methods of stimulating the retina for those who have experienced permanent vision loss from retinal disease. As an example, Optobionics is investigating the Artificial Silicon Retina (ASR) microchip as a way of stimulating healthy retinal cells to restore vision for those who have diseases such as retinitis pigmentosa and macular degeneration.

Gene therapy. Research into gene therapy as a potential treatment for macular degeneration is in early stages. But investigators are searching for ways to introduce specially encoded genes that could alter processes causing macular degeneration.

Ophthalmology Clinics of North America (December 2003) notes that a more comprehensive understanding of how abnormal blood vessel growth occurs in AMD will be necessary before gene therapy becomes feasible.

Surgical options for macular degeneration. Surgery likely would be considered a last resort for patients who fail to respond to other, less invasive AMD therapies.

Surgical removal of damaged tissue (subretinal operation) might be one option. Injections of gas and/or a drug that dissolves blood clots also have been investigated as a way to displace unwanted blood (pneumatic displacement) accompanying abnormal blood vessel growth and leakage. Translocation operations now being studied involve moving and separating damaged tissue from healthy tissue as a way to preserve vision function.

Please click here to read about FDA-approved macular degeneration treatments.

[Page updated July 2008]