Juvenile Onset Macular Degeneration, Stargardt Disease, Fundus Flavimaculatus, Stargardt Macular Dystrophy
Historically, macular degeneration was thought to be a single disease that causes central vision loss in older people. Macular degeneration is actually a group of diseases that have one feature in common, a loss of central vision, which may affect people of any age.
Juvenile macular degeneration was first reported in 1901 by German ophthalmologist, Karl Stargardt, from whom the disease gets its name. There are several forms of early onset macular degeneration, some of which are inherited and correctly called macular dystrophies. Fundus flavimaculatus, a term used by ophthalmologist Adolphe Fransceschetti in 1963 for a degenerative loss of central vision, was identified to be of the same genetic disorder as Stargardt by Hadden and Gass in 1976. This disease affects over 25,000 (30,000-50,000) Americans and occurs in approximately one in 10,000 children.
Stargardt Macular Dystrophy begins to damage both eyes somewhere between the ages of 6 and 20, although visual impairment may not be apparent until as late as ages 30 to 40. The onset of Fundus flavimaculatus variation may begin as lat as age 20. Children first notice difficulty in reading, complaining of gray, black or hazy spots in the center of their vision. They report that a longer length of time is needed to adjust between light and dark environments.
Vision loss is usually slow until the 20/40 level, then rapidly progressing to the 20/200 (legal blindness) level. Unfortunately, in some cases, vision can degenerate to 10/200 in a period of months. Peripheral vision and night vision are not lost for most people but color vision will be affected in the later stages.
It was discovered in 1997 that this disease has a strong genetic component. A family of genes, known as ABC1 genes, was found to be involved in inherited diseases. The ABCR (one of the 21 human genes specific to the retina and so-named ABCR for the retina), recently renamed ABCA4, is believed to be responsible for Stargardt disease.
90% of cases are the Autosomal or Recessive trait type. Although there is no prior family history, a person may have the recessive gene. When both parents carry the mutated gene and a normal gene, there is a 25% chance that their offspring can inherit both mutated genes and therefore develop macular dystrophy. More than one family member may develop Stargardt. The other 75% of offspring may carry the recessive gene and would in turn affect their children if they marry someone with the recessive gene or someone who has macular dystrophy.
The defect in the ABCA4 gene produce a dysfunctional protein, which does not allow normal transport of energy to and from the photoreceptor cells in the retina, causing the photoreceptor cells to degenerate. Yellow-white fundus flecks or lipofuscin, lipid rich waste deposits accumulate in the retinal pigment epithelium (RPE). (The RPE is a layer between the rod and cone cells and the choroids, and is responsible for keeping tissue healthy.) It begins to break down as the rods just outside the macula are injured. This damage spreads to the macular cones causing atrophy in the macula and loss of central vision.
Three tests are used to establish the presence of the fundus flecks and the loss of cones to determine a diagnosis of Stargardt disease.-.fluorescein angiography, electroretinography and electro-oculography.
At present there is no cure for Stargardt disease and there is very little that can be done to slow its progression. Wearing sunglasses to protect the eyes from UVa, UVb and bright light may be of some benefit. Animal studies have shown that taking excessive amounts of vitamin A and beta carotene could promote the additional accumulation of lipofuscin, as well a toxic vitamin A derivative called A2E.
Possible Treatments to Be Tested
The Foundation for Fighting Blindness and Oxford Biomedical's gene therapy treatment, StarGen, has been given orphan drug status by the European Medicines Agency (EMEA, similar to the FDA). Clincial tials are planned for late 2010.
Advanced Cell Technology has received a patent for producing of RPE cells from human embryonic stem cells and was granted orphan drug status in March 2010 for its RPE cells. ACT announced FDA approval to begin clinical trials on November 22, 2010.
Über familiäre, progressive Degeneration in der Makulagegend des Auges. Albrecht von Graefes Archiv für Ophthalmologie, 1909, 71: 534-550.
Über tapeto-retinale Degenerationen im Kindesalter. In: Entwicklung und Fortschritt in der Augenheilkunde. Stuttgart, Enke Verlag, 1963: 107-120.
ABCA4 Gene Mutations in Japanese Patients with Stargardt Disease and Retinitis Pigmentosa. Takehiro Fukui et al, Investigative Ophthalmology and Visual Science. 2002;43:2819-2824.
Advanced Cell Technology Awarded Broad Patent for Reproduction of Retinal Pigment Epithelial Cells. Worcester, MA, June 16, 2010.
Vitamin A Warning, Stargardt Australia.