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Macular Degeneration Treatments
(Investigational)

By Marilyn Haddrill; reviewed by Charles Slonim, MD

Investigational treatments for macular degeneration (AMD) 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.

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. While Genentech (South San Francisco, Calif.) 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.

When used off label to treat AMD, Avastin, like FDA-approved macular degeneration drugs Macugen (Eyetech; Palm Beach Gardens, Fla.) and Lucentis (Genentech), 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 showed promising positive results.

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 compare and assess effectiveness of Avastin and Lucentis. And in May 2011, the first-year results of CATT were announced: the two drugs showed equal effectiveness (see news item). However, safety results were not yet analyzed or compared, and the study was set to continue for a second year.

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 received FDA approval as a macular degeneration treatment in 2006).

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.

iSONEP. Currently in early stage clinical trials, this novel treatment for "wet" AMD involves injections of a therapeutic antibody into the eye. Lpath (San Diego) in October 2009 announced promising early study results showing that the treatment appears to target abnormal blood vessel growth in AMD as well as inflammation and excessive formation of fibrous tissue.

In December 2010, Lpath announced it had granted Pfizer (New York, N.Y.) a global license for commercial development and future sales of the drug pending appropriate studies and regulatory approvals.

In March 2011, Lpath company officials announced that a key patent had been awarded related to development of the technology. Clinical trials are continuing, including for conditions such as retinal pigment epithelium (RPE) detachment.

The company also is exploring therapies for conditions such as cancer, autoimmune disorders and inflammation.

MC-1101. Early study results indicate that this investigational AMD drug applied to the eye's surface appears to increase blood flow in the retina, according to developers MacuCLEAR Inc. (Plano, Tex.) and Mystic Pharmaceuticals Inc. (Austin). The VersiDoser drug delivery system used with the treatment delivers a "spray plume" in lieu of eye drops for effective penetration to the back of the eye.

"This study provides additional scientific evidence supporting our theory that restoring blood flow in the choroid will have a positive effect on preventing the progression of this terrible disease," said MacuCLEAR CEO and President Philip G. Ralston Jr.

Evizon. This investigational treatment for wet AMD has found new life, now that Ohr Pharmaceutical announced in late 2009 that it acquired the technology from Genaera. Known as squalamine, the drug has demonstrated ability to prevent development of abnormal blood vessels that damage the eye in wet AMD. Company officials say the drug's safety profile is a major advantage, and researchers are developing ways to enhance the drug's properties.

Zybrestat. In June 2010, Oxigene (South San Francisco, Calif.) announced encouraging preclinical data regarding development of its investigational Zybrestat treatment for wet AMD.

Unlike other macular degeneration drugs, Zybrestat is being designed for topical use in the form of eye drops and could eliminate the need for eye injections. The company said it believes the topical formulation could be ready for clinical development in early 2011.

Fenretinide. Based on positive study results, ReVision Therapeutics (San Diego) has announced that a late-stage (phase 3) clinical trial will be launched in 2011 for fenretinide as a treatment for dry macular degeneration. A demonstration of effectiveness and safety could lead to FDA approval.

Fenretinide, a derivative of vitamin A, has been shown to reduce growth of lesions associated with geographic atrophy — a condition associated with end-stage dry AMD. When geographic atrophy occurs, a lesion forms in the central part of the macula and causes significant central vision loss.

Study results presented at the 2010 American Academy of Ophthalmology (AAO) conference showed that fenretinide also appears to reduce the possibility of choroidal neovascularization — formation of abnormal blood vessels associated with advanced or "wet" macular degeneration.

Fenretinide is designed to be taken orally in pill form. Side effects can include delayed dark adaptation.

NT-501. In April 2011, Neurotech Pharmaceuticals (Lincoln, R.I.) announced promising results in a clinical study of its NT-501 intraocular implant for the treatment of retinitis pigmentosa.

The implant contains genetically modified human cells capable of secreting a nerve growth factor capable of rescuing and protecting dying photoreceptors in the retina. The company says the treatment might also be effective for the treatment of macular degeneration in the future.

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.

Another company, Oraya Therapeutics, announced in early 2010 that it has launched a study using radiation therapy for treating wet AMD at seven European sites. Participants will receive anti-VEGF injections in addition to radiation therapy, which will be evaluated for potential to enhance outcomes and reduce the need for costly injections.

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.

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.

Stem cells. In what could be a milestone for treatment of dry AMD, Advanced Cell Technology (Marlborough, Mass.) officials announced in late 2010 that the company had applied for FDA clearance to begin clinical studies using human embryonic stem cell (hESC) derived retinal pigment epithelium (RPE) cells.

Officials said the first phase of the small study involving about 12 participants will involve injecting stem cells to repair photoreceptors damaged by macular degeneration. The same company in November 2010 already received FDA approval to begin a clinical trial that uses the same therapy for treating another form of macular degeneration, typically affecting young people, known as Stargardt's.

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.

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[Page updated November 2011]