Description

Stargardt Disease, also known as fundus flavimaculatus, is an inherited retinal degeneration which causes progressive loss of vision as a result of damage to the central region of the retina known as the macula. The macula contains photoreceptor cells known as cone cells, which are responsible for fine, detailed, central (reading) vision and for colour vision. This condition in turn leads to a loss of central and colour vision, but peripheral (side vision) is usually preserved. Stargardt Disease can be variable in that the age at onset and rate of progression of vision loss can differ between individuals.

It is the most common form of inherited juvenile macular degeneration, with a prevalence estimated between one in 8,000 and one in 10,000 people. The carrier rate has been quoted as high as 1 in 20 to 1 in 50 people.

Symptoms

Stargardt Disease is usually identified in individuals under the age of 20 when decreased or impaired central vision is first noticed, although some individuals are not diagnosed until much later in life. Initial symptoms can include having difficulty seeing the board in class or having difficulty reading. Individuals may also experience difficulty in recognising faces, driving or identifying colours, more commonly in the latter stages. Seeing at night may also become more challenging. Central blind spots can develop and these may increase in size over time, potentially impacting vision. Both eyes are usually affected in a similar manner.

The condition can be slowly degenerative and progressive, but it is very uncommon for someone with Stargardt Disease to become completely blind. 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.

Causes

Stargardt Disease is a genetic condition. It is caused by mutations in genes including ABCA4 and ELOVL4 which are associated with vision. These genes are essential for making proteins which are found in the light sensitive cone photoreceptor cells. Damage to these genes can affect the function of these cells.

The majority of people with Stargardt Disease have the recessive form of disease involving mutations in the ABCA4 gene. This means that both copies of the gene don’t work properly giving rise to the condition. In this case, the individual’s mother and father have both passed on a mutation in the ABCA4 gene. This gene provides instructions to make the ABCA4 protein which has an important role in transporting toxic substances out of cone photoreceptor cells.

These toxic substances include A2E, a by-product of Vitamin A recycling. Mutations in this gene lead to the accumulation of metabolic waste, forming a substance called liopfuscin which gathers in the photoreceptor cells and supporting retinal pigment epithelium (RPE) cells. This substance causes the RPE and subsequently the photoreceptor cells to die, leading to vision loss. This accumulation of liopfuscin and consequent atrophy is most pronounced at the macula, which is the area of highest metabolic activity within the retina.

A very rare form of Stargardt-like Disease may be caused by mutations in the ELOVL4 gene, which follows an autosomal dominant form of inheritance. This means that one copy of the gene doesn’t work properly giving rise to the condition. In this case, the individual will have received a mutated copy of the gene from an affected parent. 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.

Diagnosis

Stargardt Disease is diagnosed through a number of assessments which help with providing the correct diagnosis.

The eye doctor will ask about a person’s medical history, including any family history of eye conditions. Individuals will receive a clinical eye examination where they may be asked to read letters off a chart (Snellen chart). They may also check intraocular pressure and examine visual acuity and the visual field.

An individual may receive a number of imaging tests. Information about the condition may be identified using colour or wide-field fundus photography (which essentially takes photos of the back of the eye). Fundus autofluorescence may be used to identify stress or damage to the retinal pigment epithelium. Optical coherence tomography (OCT) can also be used to assess the various layers at the back of the eye.

An individual may also have an electroretinogram (known as an ERG), which is used to evaluate the functioning of the different types of photoreceptor cells (rods and cones).

A genetic test is also an important component of testing, to ensure the correct condition is diagnosed. For people living in Ireland, genetic testing for Stargardt Disease can be performed through the Target 5000 programme.

For further information, please contact the Research Department on 01 6789004.

Genetic Diagnosis

It’s often impossible to tell which type of retinal disease a person has just by looking into the eye. As such, a genetic test may be necessary to confirm the diagnosis.

The Target 5000 programme provides free genetic and clinical testing to all individuals living in Ireland with a genetic retinal degeneration, including Stargardt Disease. Through genetic screening of the person awaiting diagnosis and their family members, the Target 5000 programme will provide more detailed information about the nature and inheritance pattern of the condition.

As gene-specific clinical trials and treatments become available, knowing the genetic mutation associated with a genetic retinal degeneration will become even more important. Taking part in this programme ensures participants are included on a national registry from which participants can be identified for clinical trials and treatments and from which further information about each of the genetic retinal degenerations can be defined. For further information on the Target 5000 programme, please contact the Research Department on 01 6789004 or email research@fightingblindness.ie.

Treatment

There are no proven treatments for Stargardt Disease as of yet, although recent years have demonstrated advances in clinical research and development. To find out more about advances made in this area, please visit the ‘Latest Research’ section.

Maximising an individual’s remaining vision is a crucial step to take and there are many low vision aids including telescopic and magnifying lenses which may offer benefit. 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. Furthermore, researchers have identified that taking extra vitamin A, such as in a vitamin supplement (or some acne medications) may have a negative effect on the condition and should be avoided.

General eye check-ups are important for people living with Stargardt Disease, as these individuals may still be at risk of developing other kinds of eye problems that can affect the general population, some of which may be treatable.

No matter what level of vision a person may have, it is important to look after the eyes. To find out more about what can be done to take care of the eyes on a daily basis, please visit our Tips for Good Eye Health.

For further information, please contact the Research Department on 01 6789004.

Research

Advances in research have yielded a greater understanding of the condition, with much progress made to develop therapies for it.

Researchers are actively gathering as much information (such as the information from clinical tests and genetic testing) as possible in an effort to fully understand this condition. The aim is that this information will bring benefits such as yielding new treatments and ways to improve quality of life.

Gene therapy has become an area of investigation for conditions including Stargardt Disease. With this technique, researchers use small, safe viruses to deliver the correct version of the gene of interest to the retina. As the ABCA4 gene is most commonly affected in individuals living with Stargardt Disease, it has become a gene therapy target for researchers. An early-phase clinical trial is now underway to determine the safety and tolerability of this gene therapy, with follow-up being performed to examine the intervention over time. If it is found to be safe, further investigations will be carried out to determine how effective it is.

Stem cell technology holds great potential to replace retinal cells that have already died due to degeneration. Stem cells are like precursor cells which have the potential to self-renew and generate many other different cell types. This has become an area of interest for Stargardt Disease, with a number of groups worldwide seeking to identify a new treatment. Previous clinical trials have examined the transplantation of human retinal pigment epithelial stem cells, with results demonstrating no major safety concerns and follow-up underway.

There are a small number of clinical trials currently underway, involving the transplantation of human retinal pigment epithelial stem cells and bone marrow-derived stem cells. These clinical trials are in the early-phase of investigation, with further study required.

Another interesting approach takes the form of therapeutic agents which aim to target the formation of toxic by-products and the resulting cell death associated with Stargardt Disease. At present, there are two interventions being examined in clinical trials which aim to tackle the formation of toxic by-products. The first is an oral drug which aims to inhibit the function of an enzyme needed for the formation of toxic A2E. This agent is advancing rapidly though clinical trials, with a phase 3 clinical trial now underway to determine the effectiveness of the intervention.

Another drug, also administered orally aims to slow down the generation of the toxic by-products, with a phase 2 clinical trial investigating this intervention due to get underway soon. Another early phase 2 clinical trial is underway to examine the safety and efficacy of an intervention which aims to inhibit the function of a protein, known as complement component 5 (Complement C5) involved in cellular inflammation and death.

Researchers have investigated numerous supplements in previous clinical trials, however, no significant positive findings have yet been found.

Information about clinical trials can be found on their website by clicking the following link: Clinical Trials Website and can be searched by condition and trial location.

Fighting Blindness currently support a number of research initiatives which aim to improve the diagnosis, care and quality of life of individuals living with Stargardt Disease.

Target 5000 research, largely funded by Fighting Blindness aims to determine the genetic cause and understand the nature of the condition over time. Through Target 5000, a national registry will also be developed which will greatly improve access to suitable clinical trials and treatments for people living in Ireland with Stargardt Disease. For further information, please click here for more information on Target 5000.

A study by Professor Kennedy and Ms Rebecca Ward at University College Dublin is currently examining an animal model (zebrafish) of Stargardt Disease in an effort to further understand the genetic basis of the condition. This study also aims to examine neuroprotectant drugs which may slow the rate of photoreceptor cell loss and hence identify new therapeutic targets. To find out more about this study, please click here.

StarT is an European Training Network which aims to understand the regulation of the ABCA4 gene, to elucidate its hidden genetic variation, and to develop novel treatments. A total of 14 early stage researchers will receive training opportunities in outstanding vision research groups across UK and Europe. To find out more about this study, please click here.

Support

Receiving a diagnosis can be overwhelming for anyone, but this is not a journey that you have to make alone. There are many groups and resources available to provide support for people living with Stargardt Disease.

Fighting Blindness offers a free and confidential counselling service (Insight Counselling). For further information please contact insight@fightingblindness.ie or call 01 6746496.

A mindfulness group is also available on every Wednesday at the Fighting Blindness office at 11am.

For technology support and guidance, the Dublin-based Technology Exchange Club meets every Monday at the Fighting Blindness office at 11am. Another Technology Exchange Club, based in Cork, meet every Saturday in the Cork City Library, Grand Parade, Cork City at 11am. The Cork-based club do not meet on Bank Holiday weekends or on the second Saturday of the month. For further information please contact insight@fightingblindness.ie or call 01 6746496.

Resources

Féach provides support for parents of children living with sight loss in Ireland.
Click the following link to view their website: Feach Website

ChildVision is the national education centre for children with sight loss in Ireland.
Click the following link to view their website: ChildVision Website

NCBI (National Council for the Blind in Ireland) provides support and services for people living with sight loss in Ireland.
Click the following link to view their website: NCBI Website

Retina International provides useful information on Stargardt Disease.
Click the following link to view their website:Retina International Website

Stargardt Disease community on RareConnect 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.
Click the following link to view their website: RareConnect Website

Stargardt’s Connected is a resource which provides information and support for people living with Stargardt Disease. In addition, this website includes regular updates on research.
Click the following link to view their website: Stargardts Connected Website

Last Updated: 4th February 2019