by Janet S. Sunness, M.D.
March 2006
Stargardt disease is the most common cause of macular degeneration and central visual loss in young people. Stargardt disease often develops in the teens or twenties, but may develop in younger children (the youngest child I have seen with it is 5) or may develop somewhat later in life. It affects both eyes at the same time, though one may be somewhat worse than the other. In most people it affects only the central vision (reading, recognizing faces, and other fine tasks), but in certain more rare types the peripheral vision may be affected as well. Vision loss tends to progress rapidly at first, but for most people, it tends to stabilize at about 20/200.
Diagnosing Stargardt disease
Patients with Stargardt disease have findings that are different from patients with age-related macular degeneration, and some terminology is worth knowing. Many patients with Stargardt disease have yellow flecks in their retina. In these patients, the disease is also known as fundus flavimaculatus (the retina with the yellow spots). The macula, the center of the retina, often has a shiny appearance, which is called a beaten bronze appearance, and unlike age-related macular degeneration, it is often hard just by looking to tell how much of a blind spot the patient may have. The fluorescein angiogram (when dye is injected into the arm, and pictures of the retina are taken) often shows an unusual appearance called a dark choroid, meaning that the initial flush of dye which goes through the blood vessel system beneath the retina cannot be seen. Some patients with Stargardt disease start out with a bullseye appearance to the macula, in which there is a small island of spared vision surrounded by a donut-shaped blind spot. In other patients, or later in the course of the disease, there is a solid area of blind spot, which does not spare the very center.
Dealing with blind spots in the central vision
It is critical for any patient with blind spots in or near the center of vision to learn how to move the eye so that the object of interest is imaged onto a seeing part of the retina. Most Stargardt patients do this quite well, and they tend to look slightly above what they want to see. This has the effect of moving the blind spot up and out of the way. The difficulty is that as one uses retina farther from the center of the macula, larger letters are needed in order to see, so that magnification using a variety of low vision devices can be very helpful.
I have a special device called a scanning laser ophthalmoscope (SLO), which can let us plot out the exact location of the blind spot directly on a video image of the macula. This information helps us to advise the patients on strategies for using the remaining seeing retina in the most effective way. The SLO also allows us to do special imaging of the macula to determine the stage and progression of the condition. It also allows us to do autofluorescence imaging, which helps to identify areas that have had a loss of cells underlying the retina.
Living with Stargardt disease
Most patients whom I see with Stargardt disease have adapted quite well, and have busy and active lifestyles. One patient is a geologist, one a radio announcer, and one a tandem bike racing competitor. Improved low vision interventions in the future will help patients to adapt even better to this condition. It is important to remember though, that a loss of vision is a real loss to the individual, and some people may react to this with anger and depression. While these are normal stages to go through, they interfere with the person’s ability to adapt and see around the blind spot, and if there is difficulty in working through these emotions, support groups and counseling may be beneficial. Support groups are very helpful in general, for understanding the symptoms of central visual loss and for learning different ways of coping.
Some patients with Stargardt disease are able to drive. Each state has different rules in terms of the minimum visual acuity required to get a restricted license. Patients who meet this vision requirement can learn how to use a bioptic telescope to read street signs if needed, and can work with special driving instructors who can instruct them and determine whether they can drive safely.
The Genetics of Stargardt disease
Stargardt disease is an inherited, or genetic, disease; that is, it is caused by a mutation of a gene. Most patients I see with Stargardt are the only ones in their family to have the condition, and they are likely to have the autosomal recessive form, meaning that both copies of the gene (one from the mother and one from the father) are abnormal. The children of these patients in all likelihood will be carriers of the disease (have one abnormal gene) but will not be affected, since the gene they get from the other parent will presumably be normal. Patients may have siblings who are affected, but their parents and children are not likely to be affected. (There is also a rarer autosomal dominant form, meaning that only one copy of the gene has to be abnormal. In the dominant form, one parent of the patient also has the disease and other siblings or family members may have it as well.)
Researchers have found that mutations in a gene called ABCA4 are responsible for about 75% of Stargardt disease. Researchers do not yet understand why a change in the ABCA4 gene causes Stargardt disease, but it is thought that this gene abnormality leads to an accumulation of a material called lipofuscin that may be toxic to the retinal pigment epithelium, the cells needed to sustain vision.
Advances in Looking for Treatments for Stargardt disease
Scientists have been able to develop mice that are missing the ABCA4 gene (so-called knockout mice), and are studying whether various drugs or other interventions can slow or stop the accumulation of the abnormal material in these mice. They have found that if you do not expose the mice to light, the degeneration proceeds more slowly. It is difficult to know how this applies to people, but some investigatos recommend that patients should try to wear sunglasses when they are outdoors. They also found that giving the mice Accutane (a vitamin A derivative used for severe acne that has serious side effects such as birth defects and psychiatric side effects; do not use for yourself!) slowed down the accumulation of the abnormal material. Research is ongoing to find safe therapies that may help in this condition.
Researchers are also studying ways to slow down cell death in general. They are beginning a study, in patients with a severe type of retinal degeneration, whether cell death can be slowed by growth factors. They have made a small reservoir containing cells that have been genetically engineered to make a growth factor. They will implant this reservoir in the eye, and, like an internal factory, the growth factor that is made will be able to diffuse out of the reservoir and into the eye.
Much research is ongoing to try to find ways to replace the products of the abnormal genes, either by giving animals certain chemicals that can se rve in place of the gene product, or by actually trying to introduce a normal copy of the gene into the animal’s retinal cells. A naturally occurring species of dog has nightblindness and loss of side vision, similar to a retinal degeneration called retinitis pigmentosa in people. Scientists have learned which gene is abnormal in the dog; it is the same abnormality as in a type of retinal degeneration that is present in children at birth. They have taken copies of the normal gene and attached them to virus particles. They have then injected the virus-gene complex underneath the retina of the eye in these dogs. The virus allows the gene to get into the dog’s retinal cells and function there. They have found that while the untreated eye degenerates, the treated eye does not have the degeneration and the dogs can see at night and to the side with the treated eye. Investigators are working on doing a similar treatment using a different virus vector to attach to the ABCA4 gene.
Investigators here and elsewhere are working on different types of ‘artificial retinas’ that could take advantage of the fact that the nerve connection system from the retina to the brain is still normal in patients with Stargardt disease. What is diseased are the retinal pigment epithelium and the photoreceptors, the cells that ‘catch’ the light and send a signal to the other nerve cells in the retina. If one could replace the photoreceptors with an electrical or other type of light sensor and could get the signal to the nerve network in the retina, the patient would be able to see. The development of artificial retinas is still at an early stage, but progress continues to be made.
There is much interest in stem cell research, because it holds the promise of replacing defective cells with new ones. However, scientists are just beginning to learn how to make such cells develop into specific tissue, and making them replace several different layers in a very complex structure like the retina is a challenge that will take many years. So in the foreseeable future this is not a realistic option for retinal diseases.
Frequently one hears about alternative therapies, such as eye drops, nutritional supplements, microcurrent stimulation, acupuncture, and hyperbaric oxygen therapies, that are claimed to postpone the progression of retinal diseases, or even cure them. It is possible that some of these treatments, especially balanced nutrition and supplements, can help the retinal cells function a little longer, but the research to show this has not been done, and the claims made so far are only supported by anecdotal evidence (one case here and there). Before you decide to spend money on such treatments, you should collect information from independent sources, such as the National Eye Institute and respected medical information websites. It is always wise to discuss your plans with your eye doctor, and with your primary care physician.
(copyright 2006 Janet Sunness)
