Stargardt disease (also known as fundus flavimaculatus and Stargardt macular dystrophy) is the most common form of inherited juvenile macular degeneration. Inherited as an autosomal recessive trait, it is a severe form of MD that begins in late childhood, leading to legal blindness. Stargardt disease is symptomatically similar to age-related macular degeneration, and it affects approximately one in 10,000 children.
Stargardt disease is usually diagnosed in individuals under the age of twenty, when decreased central vision is first noticed. It causes a progressive loss of central vision and, in the early stages, patients may have good visual acuity, but they may experience difficulty with reading and seeing in dim lighting. Other common symptoms of Stargardt disease include blurriness and distortion. On examination, the ophthalmological findings vary significantly with the progression of the disease. In fundus photos, patients with early Stargardt disease appear to have simple macular degeneration. Children with the disease typically begin experiencing dark adaptation problems and central vision loss between six and twelve years of age, but symptoms may also first appear in adulthood.
As the disease progresses, lipid rich deposits accumulate in the retinal pigment epithelium (RPE) layer beneath the macula. This "lipofuscin" appears as yellowish-tinted flecks. The RPE is a layer of cells that lies between the retina and the choroid, where it serves the purpose of nourishing the photoreceptor cells. In advanced Stargardt disease, the buildup of lipofuscin causes atrophy of the macula and the underlying RPE. The progression of vision loss is variable and can start with a visual acuity of 20/40 and decrease rapidly (especially in children) to 20/200 (legal blindness). By age 50, approximately 50% of all of those studied in clinical trials had visual acuities of 20/200 to 20/400. In late stages of this disease, there may also be color vision impairment.
Stargardt disease is almost always inherited as an autosomal recessive disorder, with only ten percent of cases resulting from a dominant mode of inheritance. Autosomal recessive means that both parents are carriers, having one gene for the disease paired with one normal gene. As a consequence, each of their children has a 25 percent chance of inheriting the two copies of the Stargardt gene (one from each parent) needed to cause the disease. Carriers are unaffected because they have only one copy. At this time, it is impossible to determine who is a carrier for Stargardt disease until after an affected child is diagnosed.
Stargardt disease is thought to be caused by the accumulation of lipofuscins (waste deposits) in the retina, due to the cells' inability to transport vitamin A from the retinal pigment epithelium (RPE) to the photoreceptor cells. This is a result of a buildup of A2E, a toxic by-product of Vitamin A that is normally released after light exposure during the visual cycle. Dark adaptation, therefore is delayed.
Rhodopsins are disc-shaped molecular structures present in the rod and cone photoreceptor cells. They contain a pigment called retinal (made from vitamin A), which is converted to retinol when a rhodopsin structure is exposed to light. This process causes the rhodopsin to break down, and the resulting waste material is supposed to then be transported to the RPE for recycling.
The gene responsible for the transport of retinol to the RPE is the ABCA4 (formerly ABCR) gene, discovered in 1997. If this gene is defective, transport cannot take place, and the waste remains in the photoreceptor tissue, where the toxic A2E poisons the healthy cells.
A recent study ("Light exposure stimulates formation of A2E oxiranes in a mouse model of Stargardt macular degeneration" by Roxana A. Radu, Nathan L. Mata, Aarti Bagla, and Gabriel H. Travis. Jules Stein Eye Institute and Department of Biological Chemistry, School of Medicine, University of California, Los Angeles) showed that the formation of A2E is strongly suppressed by treating the ABCR mice with Accutane (isotretinoin), an inhibitor of rhodopsin regeneration. And now, fenretinide is showing promising results as another type of A2E suppressor.
Current research also shows that patients with Stargardt disease could slow its progression by wearing UV-protective sunglasses and avoiding exposure to bright light. Researchers have observed that mice which had a mutation of the ABCA4 gene, and which were reared in dark environments had virtually no lipofuscin deposits.
The disease is often misdiagnosed, or not diagnosed in the first few years of onset, and this could be the result of little evidence being found during eye examinations. The discovery of the Stargardt gene could help in a test for the direct diagnosis of the disease. It is possible that the effect of this newly discovered gene may not be limited only to juvenile MD, in that it could also aid in the search for causes for age-related macular degeneration, the leading cause of vision loss in people over age 65.
Currently, there is no effective treatment for Stargardt disease, but having the genetic "instruction manual" may assist in developing new strategies for therapy. It is also important that the learning and working environment be adapted for people with Stargardt disease. Appropriate low vision aids and lighting are two important considerations for helping both children and adults to function as normally as possible.
For further information, visit the following pages on the MD Support web site:
Eye Diseases & Conditions
Stargardt Disease--Information for Patients and Their Families
Future Gene Therapy Possible For
Inherited MD Patterns
Stargardt Patients Need Special Light Protection
Glossary
Types of Juvenile Macular
Degeneration
To meet others who are affected by Stargardt disease, see The Stargardt Team on this site.