The Future

New Therapies for Retinal Diseases

This is an exciting and hopeful time for patients with many retinal diseases which have been difficult to treat. Many productive research programs promise new and better treatment for diabetic retinopathy, macular degeneration, retinitis pigmentosa and other retinal diseases. Several of these new therapies are in clinical trials and will probably approved by the FDA for patients’ use within the next few years. Many others are being tested in animals for safety and efficacy (preclinical studies) prior to their use in patients. These treatments may require years of research before they are proven safe and effective. None of these medications is presently available outside of strictly controlled clinical trials, but their potential for the future is great. Information on these new treatments often appears in the news and is sometimes misleading. It is very important that patients understand where these experimental treatments fit into the “big picture” of their retinal disease.

Anti-Angiogenesis Medications

Angiogenesis is the process by which the body creates new blood vessels. Under normal circumstances, angiogenesis is important in wound healing and tissue growth. However, angiogenesis is harmful to vision when it causes the growth of abnormal tissues in diabetic retinopathy and macular degeneration. Retane (anacortave acetate) (http://www.blindness.org/anacortave-acetate-for-macular-degeneration.asp), and Lucentis are two anti-angiogenic drugs which are being tested for efficacy in patients with macular degeneration. Retina Associates of New Jersey is a participating center in these national clinical trials. Squalamine is another investigational anti-angiogenic drug given by repeated intravenous infusions for macular degeneration; this drug is being evaluated in phase III clinical trials. Additional studies are testing the possible usefulness of these and other anti-angiogenic medications in treating diabetic retinopathy. Used separately or in combination with each other or with laser treatment, these medications hold the promise of significant reduction of the retinal damage caused by macular degeneration and diabetic retinopathy.

Several anti-angiogenic drugs must be given by relatively frequent intraocular injections (every 4 to 6 weeks). Researchers are developing methods for delivering these medications into the eye without frequent injections. There is also great interest in designing a drug which would be effective (and also more convenient) for patients over a much longer period of time. One such novel treatment (not yet used in humans) uses a medication (Cand5: a small, double-stranded RNA molecule designed to interfere with VEGF production) to permanently block angiogenesis within the eye after just one intraocular injection. Retane is another anti-angiogenic drug which requires injection only once every six months. (See Research page.)

Retane is the only anti-angiogenic drug that is being evaluated for the prevention rather than the treatment of severe macular degeneration. It is one of a new class of compounds known as angiostatic cortizines which work by slowing or stopping the growth of new blood vessels. Retane is injected adjacent to the better seeing eye of patients with severe macular degeneration in the fellow eye. The goal of the study is to determine whether Retane can reduce the incidence of neovascularization and vision loss in these eyes with high risk characteristics for the development of choroidal neovascularization..

Gene Based Therapy

Another novel treatment (also not yet used in humans) is the intraocular injection of genes which cause the retinal cells themselves to produce anti-angiogenic drugs. Thus, the cells of the eye become tiny factories which constantly produce anti-angiogenic agents to limit the retinal damage caused by macular degeneration or diabetic retinopathy. This method of delivering a therapeutic gene into the eye is not just a scientist’s fantasy; it has already been successfully and repeatedly carried out to cure a form of retinitis pigmentosa in dogs. If the defective genes responsible for macular degeneration can be determined, the replacement of such defective genes could be carried out in a similar fashion.

Rheophoresis

Membrane differential filtration (MDF) is a form of therapeutic blood filtration that has been used for the treatment of vascular diseases for over a decade. The MDF system under study for age related macular degeneration (AMD) in the US is the Rheopheresis® MDF system. Rheopheresis removes substances termed "vascular risk factors" that accumulate in the blood of some patients. These include substances like LDL cholesterol, fibrinogen and lipoprotein A. Recent studies have shown that AMD progression may be related to the presence of elevated blood levels of certain vascular risk factors. Rheopheresis reduces these substances in the blood to promote an improvement in blood flow and vascular function in the retina and elsewhere. Rheopheresis is similar to blood donation. An IV line is placed in each forearm and connected to the apheresis blood pump with a sterile tube. As the patient’s whole blood is withdrawn, it is directed to the cell separator, which divides the whole blood into its cellular and plasma components. A plasma separator collects the high molecular weight compounds (“vascular risk factors”) as the plasma flows through the filter. The filtered plasma is then reunited with the warmed cells and the reconstituted whole blood is returned into the patient. The procedure takes approximately 2 to 3 hours. Other than a drug to prevent clotting, no medications are required. The company cites previous research to support the clinical trial. German ophthalmologists at the University of Cologne accidentally discovered the use of Rheopheresis for the treatment of AMD nearly a decade ago. Since then, numerous studies have been conducted; all of which have demonstrated the potential utility of the treatment for select patients with the disease. In 1999 the results of the German study "MAC-1" were reported (Retina Vol. 20 No. 5-2000; 483-91). Currently, the Rheopheresis MDF system for the treatment of Dry AMD is now undergoing Phase III clinical trial in the United States and is authorized to enroll up to 200 patients. Qualifying patients will have at least one eye with Dry AMD characterized by more than 10 large soft drusen, vision between 20/32 and 20/125, elevated levels of 2 of 3 blood components (fibrinogen, IgA and cholesterol) and other criteria. See www.vascularsciences.net . Early reports from the current clinical trial are positive. We await the final results.

Retinal Cell Transplants and Stem Cell Transplants

An important theoretical advantage of retinal cell transplantation is that a retina that has been badly damaged could be made functional again. Transplantation of retinal cells can be either “endogenous” (cells transplanted from a normal area to an abnormal area of the same patient’s retina), or “exogenous” (healthy retinal cells from outside the body transplanted into a diseased retina). The cells which are transplanted can be either the neural (nerve) cells of the retina or the RPE (pigmented or nourishing) cells of the retina. Research all types of retinal cell transplants is being carried out in several research centers. Most of the research is being carried out in animals. However, a few patients with severe retinitis pigmentosa have received transplants of fetal retinal cells and the results have been encouraging.

Stem cells are those cells that have not gone through the process which turns them into specialized cells, like bone cells, muscle cells, or retina cells. This means that stem cells have the possibility of turning into many different kinds of specialized cells, including retina cells and retinal blood vessel cells. Stem cells from bone marrow or fetal tissue are being investigated as a means of treating macular degeneration and other retinal diseases.

Want To Learn More?

To learn more about any of the above topics, click on the links within the text. Or go to www.blindness.org and simply register as a user by clicking the appropriate link. Once you are registered, you will have free access to all of their articles on retinal research, and they will send you timely updates on new retinal research. If you have a scientific background, you may find that searching PubMed (www.ncbi.nlm.nih.gov/PubMed), a service of the National Library of Medicine, is a bountiful source of primary information.

2/12/2005