Stargardt Disease

Stargardt disease is the most common form of inherited juvenile macular degeneration and affects the portion of the retina known as the macula. The macula is the central portion of the retina that contains photoreceptor cells known as cone cells, which are responsible for central (reading) vision and for colour vision. Stargardt disease, also known as fundus flavimaculatus, is usually diagnosed in individuals under the age of 20 when decreased central vision is first noticed; for example a person may have difficulty seeing the board in class. The progression of visual loss varies hugely between individuals, but side or peripheral vision is usually preserved. This means that patients with Stargardt disease rarely have issues with independent mobility.

What are the symptoms of Stargardt disease?

Central vision is usually the first affected, and the first symptom is often difficulty reading. Blind spots can occur, and these may increase in size over time. The condition can be slowly degenerative and progressive, but it is very uncommon for someone with Stargardt disease to become completely blind. Both eyes are usually affected in a similar manner and colour vision may be affected in the later stages of disease. The rate of progression and degree of visual loss can vary from person to person and even among affected members of the same family. It is, therefore, very difficult to predict what an individual’s vision will be like at a specific time in the future.

What is the cause of Stargardt disease and how is it inherited?

The prevalence of Stargardt disease worldwide is estimated to be one in 8,000 to one in 10,000 and in Ireland this equates to approximately 600 – 800 affected individuals. The majority of people with Stargardt disease have the recessive form of disease, involving mutations in the ABCA4 gene, which provides instructions to make the ABCA4 protein.

If there is a faulty ABCA4 gene, it leads to the build-up of a toxic waste product known as A2E in the retinal pigment epithelium (RPE), and can lead to macular degeneration and progressive loss of vision.

A very rare form of Stargardt disease may be caused by mutations in the ELOVL4 gene, which follows an autosomal dominant form of inheritance. Mutations in the ELOVL4 gene can make dysfunctional ELOVL4 protein clumps that can interfere with photoreceptor cell functions leading to cell death. Click here for more information about inheritance patterns.

If a family member is diagnosed with Stargardt disease, it is strongly advised that other members of the family also have an eye exam by an eye doctor (ophthalmologist) who is specially trained to detect retinal diseases.

What treatments are available?

At present, there are no effective treatments for Stargardt disease. There is research to suggest that UV sunlight can increase the toxicity of the waste products accumulating in the retina, therefore, it is recommended that people with Stargardt disease wear UV screening sunglasses when out in direct sunlight. Recent evidence also suggests that taking extra vitamin A, such as in a vitamin supplement, may have a negative effect on the condition and should be avoided.

Gene therapy is currently being explored for the recessive form of Stargardt disease caused by ABCA4 mutations. The idea behind gene therapy is that a “normal” copy of the ABCA4 gene can be engineered in the laboratory. This can then be injected into the eye of an affected individual, delivering the correct copy of the gene and therefore stopping the degeneration of the sight of the individual. This approach is currently in the early stages of a clinical trial in the USA and France, in order to find out if this is a safe approach. If this gene therapy is found to be safe, the trial will move on to the next stage, which will be to test how effective this experimental treatment is.

Stem cells are amazing cells that are produced in the body and have the remarkable potential to develop into many different cell types in the body during early life and growth. A number of groups worldwide are currently manipulating stem cells from various origins in order to produce retinal pigment epithelial (RPE) and these cells have been injected into a number of patients. To date, these cells have proven to be safe and well tolerated. The transplantation of these functional cells into patients may prevent the death of the remaining photoreceptors and may, therefore, help Stargardt patients avoid further sight loss. These early stage clinical trials are currently on-going. Efforts at transplanting stem cell-derived photoreceptor cells are at an even earlier stage of research, but a number of recent animal studies have shown the potential to restore function in the eye, which may pave the way for human studies in the future.

Another interesting approach that is currently being studied as a therapy involves research into a modified form of vitamin A, called deuterated vitamin A. The researchers hope that this may help slow the accumulation of A2E by blocking its formation downstream in the visual cycle. They are currently testing the safety of this approach. Please note however that recent evidence suggests that taking extra “normal” vitamin A, such as in a vitamin supplement from a health shop, may have a negative effect on the condition and should be avoided as this can increase toxic levels of A2E.

Despite the lack of current treatments for Stargardt disease, general eye check-ups are important. This is because people with Stargardt disease are still at risk for other kinds of eye problems that can affect the general population and may be treatable. Regular visits to your eye doctor can also make you aware of current advances and new treatments as we learn more about the condition.

Information about clinical trials that are currently being conducted worldwide can be found on www.clinicaltrials.gov and can be searched by condition and trial location.

Target 5000

Target 5000 is a Fighting Blindness research project which aims to provide genetic testing for the estimated 5,000 people in Ireland who have a inherited retinal condition. The purpose of this project is to provide a precise diagnosis and more detailed information about the nature and inheritance pattern of the condition. This information will be to a national patient registry which will enable patients who are eligible for clinical trials to be identified. Click here for more information about Target 5000 and how you can get involved.

Counselling Services

Being diagnosed with a condition causing sight loss can be very difficult. The Fighting Blindness Insight Counselling Service provides a range of supports for people affected by sight loss and their families. Click here for more information about the Insight Counselling Service or contact Insight on 01 674 6496 orinsight@fightingblindness.ie.

Other Useful links

Stargardt disease community on RareConnect 

RareConnect.org is an online social network for patients and families. It was created by EURORDIS (European Rare Disease Organisation) and NORD (National Organisation for Rare Disorders) to provide a safe space where individuals and families affected by rare diseases can connect with each other, share vital experiences, and find helpful information and resources. Communities for specific conditions are built in partnership with patient groups who help create, moderate and maintain the forum.