Stargardt Disease is a genetically inherited disease that affects the eye. It is due to a build-up of a fatty material known as ‘Lipofuscin’ in the macular region of the retina. This part of the eye is responsible for sharp central vision, and this build-up of lipofuscin causes loss of central vision over time. It is the most common genetically inherited form of macular dystrophy (degeneration of a region over time).¹

Genetics and Inheritance

Stargardt disease is caused by a mutation on a specific gene (the ABCA4 gene on chromosome 1). This results in a recessive allele for the disease meaning that you need both parents to have the disease before it can be passed along to the child in an ‘active’ form (if only one parent has the disease and it is passed onto the child, then the child will be a carrier of the disease but will not suffer from it themselves). This is the most common form of the disease to be inherited. The ABCA4 gene normally creates a protein in the body that is responsible for cleaning up excess lipofuscin. But variations on this gene can make it faulty and prevent it from creating the protein, which in turn, allows a build up of lipofuscin that damages the cells in the macular and that causes a loss in central vision.

However, there is another form of the disease that is caused by a variation on a different gene. A variation on the ELOVL4 gene results in a dominant allele (this means only one parent has to pass this gene on for the child to be born with Stargardt disease). But this form of the disease is less common. Some other variations of genes that can cause Stargardt disease include the BEST1 and PRPH2 genes. 

Symptoms and Onset

Common symptoms (central vision loss, blurriness, light sensitivity)

The first symptoms that can be noticed in children at the onset of the disease include a difficulty adapting when moving from a dark environment to a well-lit environment (or vice versa).  They may also experience some blurry vision or distortion of vision. Additionally, they may even find it hard to read or see in well-lit surroundings. 

Age of onset (typically in childhood or adolescence)

Most people with Stargardt disease will receive a diagnosis before the age of 20 as the symptoms typically begin between the ages of six and twelve. However, there are instances of late onset where individuals do not experience any symptoms until after the age of 50. 

Pathophysiology

Explanation of how Stargardt Disease affects the retina

The main region of the retina affected by Stargardt disease is the macular region which is the central part of the retina. This part of the retina is what gives you your central vision and the build up on lipofuscin will mostly affect your central vision. An interesting point to note is that your peripheral vision will remain unaffected, and it is unlikely for Stargardt disease to cause full blindness. Instead, you will have a gap in the centre of your vision.   

Accumulation of lipofuscin in retinal cells

Lipofuscin is a fatty material that accumulates on the macular region as a yellow pigment. As the ABCA4 gene is not able to produce the protein that breaks down the built-up lipofuscin, it will continue to build up and damage the cells in the macular region. 

Impact on photoreceptor function

The macular region is what gives you your central vision and this is achieved by light sensing cells known as photoreceptors. The build up of lipofuscin on the macular causes these cells to become damaged and to eventually die. Without these cells, your clear central vision will decline. The vision loss caused by the disease is irreversible.²

Diagnosis and Evaluation

Methods for diagnosing Stargardt Disease (fundus autofluorescence, genetic testing)

There are a few different ways to test for Stargardt disease. This can include:

• Fundus photography- taking a picture of the retina and observing if there any yellow flecks which can indicate the build-up lipofuscin
• Electroretinography- this is a test to see how well your retina is able to respond to light (the build up of lipofuscin destroys the photoreceptors and prevents the macula from being able to respond to the light)
• Colour vision testing- in some people, Stargardt disease can cause colour blindness
• Optical coherence tomography- this involves using light rays to take a detailed picture of the retina
• Genetic testing- if there is a family history or suspected case of Stargardt disease then it is a good idea to confirm the presence of Stargardt disease through genetic testing.

Importance of early diagnosis and vision assessment

Early testing and diagnosis can allow you to receive the help you need to adjust to the changes in your vision. 

Types and Stages

Overview of different stages of the disease (early, intermediate, advanced)

On average, the onset of the disease is between the ages of six and twelve but can also be later in life. Most people will receive their diagnosis before the age of twenty. The rate of progress for the disease is different for everyone. At first, your vision may deteriorate slowly from normal vision (20/20 or 6/6) to around 20/40 or 6/12. After that point, the vision loss is a lot more rapid till the individual reaches a visual acuity of 6/60. Most people with Stargardt disease have a visual acuity of between 6/60 to 6/120. Visual acuity refers to the ability to distinguish between details and shapes. 

Subtypes and variations in presentation

The gene is normally inherited in the recessive form (variations with the ABCA4 gene) but can also be inherited in the dominant form, but this is not very common. 

There is also a late onset form of the disease which first starts to show symptoms after the age of 50. In some cases, with a later onset than average (above 20), the individuals tend to have a longer time maintaining a visual acuity of 20/200 compared to those who first displayed symptoms under the age of 20 suggesting a link between age and progression of the disease.³ However, more research is needed in this area to fully understand the link between age and progression of the disease.

Treatment and Management

Current treatment options

Currently, there are no treatment options for Stargardt disease and the vision loss cannot be corrected with glasses, contact lenses or surgery. However, there are some options to help with the vision loss such as low vision aids and rehabilitation. Some people may find it helpful to try navigating with a guide dog. 

Ongoing research and potential therapies

Since there are no treatments for Stargardt disease at the moment, you may wish to take part in a clinical trial for potential treatments. There is interest in developing treatments as it is a genetically inherited disease. One potential treatment is the use of CRISPR tools to modify the gene sequences that cause the disease.⁴ There is also some potential with stem cell therapies, but further research is needed before these therapies can be implemented. 

Progression and Prognosis

There is no way, at the moment, to prevent the disease as it is genetically inherited from your parents. Instead, there are some ways to manage the symptoms of the disease. This can include wearing sunglasses or a hat to shield your eyes from UV rays while you are outside, and this can also help with managing sensitivity to light. It may also be helpful to seek support from your healthcare provider to quit smoking.

Living with Stargardt Disease

Coping strategies for individuals with Stargardt Disease

As the disease affects your central vision, it can cause significant difficulties with your daily life. You may find it difficult to adjust as your vision deteriorates. Speak to your healthcare provider to find support and resources to help you make the most of your independence. 

Support systems and resources for affected individuals and their families

It is important to note that a diagnosis for Stargardt disease can be a particularly distressing time for an individual. Check in with your loved one during this time and encourage them to seek support if they feel like they are struggling to cope with the symptoms. 

Awareness and Advocacy

Depending on where you live, there will be different organisations that offer support for individuals that suffer with Stargardt disease. In the UK you can seek support from the Macular Society or from Guide Dogs (registered charity). 

Summary

Stargardt disease is a genetically inherited disease that cannot be prevented. The disease causes a loss of central vision but does not cause complete blindness, though it can lead to colour blindness. It is also not currently treatable, nor can it be corrected with glasses, contact lenses or corrective surgery. There are some potential treatments, but they still require further research. This includes CRISPR tools and Stem cell therapies.