Stargardt’s Disease

Stargardt’s disease is a rare genetic eye condition that causes progressive vision loss, usually beginning in childhood or adolescence. It affects about 1 in 10,000 people and is the most common form of inherited juvenile macular degeneration.

Table of contents

• What is Stargardt’s disease?
• Other names for the condition
• Affected parts of the eye
• Symptoms
• Causes and inheritance
• Diagnosis
• Disease stages
• Treatment and management
• Current research
• Living with Stargardt’s disease

What is Stargardt’s disease?

Stargardt’s disease is a genetic eye disorder that causes the gradual breakdown of cells in the central part of the retina called the macula (the small area of the retina responsible for sharp, central vision)^[1]. This is why healthcare providers sometimes call it juvenile macular degeneration or juvenile macular dystrophy^[2].

The disease happens when a fatty yellow substance called lipofuscin (a waste product left over from normal cell activity) builds up abnormally in the retina^[4]. Over time, this buildup damages special cells called photoreceptors (cells in the retina that convert light into signals the brain can process), particularly the cone cells that help you see fine details and colors^[2].

Stargardt’s disease typically develops during childhood or adolescence, with many people first noticing symptoms between ages 6 and 12^[3]. However, some people don’t experience vision problems until later in life. There is a late-onset form of the disease that can begin in adulthood^[3].

The condition affects about 30,000 people in the United States and approximately 1 in 10,000 individuals worldwide^[3][4]. It affects both males and females equally^[3].

Stargardt disease, Stargardt dystrophy, fundus flavimaculatus, juvenile macular degeneration, juvenile macular dystrophy

Other names for the condition

Stargardt’s disease is also known by several other names. The condition is sometimes called fundus flavimaculatus, especially when it affects the edges of the retina beyond just the central macula^[2][3].

Affected parts of the eye

• Macula
• Retina
• Retinal pigment epithelium (RPE)
• Photoreceptor cells (cone cells)

The disease primarily affects the macula, which is part of the retina responsible for central vision needed for detailed tasks such as reading, writing, and recognizing faces^[7]. The retinal pigment epithelium (a layer of cells that supports the photoreceptors) is also affected by the accumulation of lipofuscin^[3][4].

While Stargardt’s disease usually affects central vision only, some people may also experience changes to their side vision as the condition progresses^[1][2].

Symptoms

The most common symptom of Stargardt’s disease is a slow, progressive loss of central vision in both eyes^[1]. In the early stages, vision may be near normal, which can sometimes delay diagnosis^[7]. As the condition progresses, symptoms become more noticeable.

Common symptoms include^[1][2][3]:

• Gray, black, or hazy spots in the center of vision (blind spots or cloudy areas)
• Blurry or distorted vision
• Difficulty reading or seeing in dim light
• Sensitivity to light (finding bright light uncomfortable)
• Difficulty adapting when moving between bright and dark places, such as entering a darkened room or going outside at dusk
• Changes in color vision or new color blindness
• Worsened night vision

Children often first notice difficulty reading or adapting from dark to light environments^[3]. The rate at which vision is lost varies for each person. Some people lose their central vision more quickly than others^[1][7].

Eventually, most people with Stargardt’s disease have 20/200 to 20/400 vision, which cannot be corrected with prescription eyeglasses, contact lenses, or refractive surgery^[7]. However, in the vast majority of cases, people do not lose all their sight^[3]. Peripheral vision is usually preserved, allowing people to maintain some independence^[3].

Causes and inheritance

Stargardt’s disease is a genetic condition caused by changes in specific genes. Most commonly, the disease is caused by mutations in a gene called ABCA4^[1][2]. This gene provides instructions for making a protein that helps the body process vitamin A in the retina.

The body uses vitamin A to make molecules in the photoreceptor cells that enable vision. After these molecules are used, they break down into fatty waste products. The protein made by the ABCA4 gene normally helps clean up these waste materials^[1]. When the ABCA4 gene doesn’t work properly, the fatty material (lipofuscin) builds up in yellowish clumps on the macula. Over time, this buildup kills the light-sensitive cells and destroys central vision^[1].

A less common form of Stargardt’s disease is caused by changes in another gene called ELOVL4^[3].

Stargardt’s disease is most often inherited in an autosomal recessive pattern^[2][3][7]. This means that both biological parents must carry one copy of the changed gene for their child to develop the disease. Parents who are carriers (having one normal gene and one changed gene) typically do not have symptoms themselves^[3].

When two carriers have children, each child has a 25 percent (1 in 4) chance of inheriting two copies of the changed gene (one from each parent) and developing Stargardt’s disease^[3][7]. This chance is the same for each child, regardless of whether they are male or female, and regardless of birth order^[3].

The less common form caused by ELOVL4 gene changes has a dominant inheritance pattern, meaning only one changed gene from one parent is needed for the disease to develop^[3].

Diagnosis

An eye doctor can check for Stargardt’s disease through a comprehensive eye examination. The process typically begins with a dilated eye exam, which is simple and painless^[1]. The doctor gives you eye drops to dilate (widen) your pupils and then examines the back of your eye for signs of Stargardt’s disease, such as yellowish flecks on the macula^[1][7].

In many cases, your eye doctor may be able to detect Stargardt’s disease by examining your retina and macula, where characteristic yellowish flecks are often visible^[7]. These flecks are deposits of lipofuscin that accumulate abnormally in people with the condition^[4][7].

Your doctor may perform additional tests to diagnose Stargardt’s disease or track your symptoms^[1][2][7]:

• Color vision testing: Stargardt’s disease can cause color blindness, so your eye doctor may test your ability to see colors
• Fundus photography or fundus autofluorescent photography: Your doctor takes detailed photos of your retina to check for yellowish flecks on your macula and assess the extent of changes
• Optical coherence tomography (OCT): This test uses light waves to create a detailed picture of your retina, showing its structure and any damage
• Fluorescein angiography: A test that may be recommended to obtain more detailed images of your retina
• Electroretinography (ERG) or multifocal ERG: These tests measure how well your retina responds to light
• Genetic testing: Your doctor may suggest a genetic test using a blood sample or saliva sample to confirm the diagnosis of Stargardt’s disease and identify the specific gene mutation

Tell your doctor when you first noticed changes in your vision or other symptoms, as this information helps with diagnosis^[2].

Disease stages

Eye care specialists may classify Stargardt’s disease into stages as it progresses^[2]:

Stage 1: Flecks of excess lipofuscin begin to form in your macula. You might have mild symptoms during this stage.

Stage 2: The flecks have built up enough to spread beyond your macula to other areas of your retina around it. Symptoms will become more noticeable at this stage.

Stage 3: The flecks have been absorbed back into your macula and caused damage (a process called atrophy, which means the tissue has wasted away). This causes worsening symptoms.

Stage 4: The atrophy in your macula is severe enough to erase some or all of your central vision.

Understanding these stages helps doctors monitor disease progression and plan appropriate support and management strategies.

Treatment and management

Currently, there is no treatment available that can reverse Stargardt’s disease or repair the damage it causes^[1][2][7]. However, there are steps you can take to slow vision loss and ways to make the most of your remaining vision.

Protecting your vision

You can take several protective steps^[1]:

• Wear a hat and sunglasses to protect your eyes from sunlight when you go outside. Ultraviolet light exposure may accelerate vision loss
• Don’t take dietary supplements that contain more than the daily recommended amount of vitamin A. Excess vitamin A may contribute to the buildup of harmful fatty deposits
• Don’t smoke cigarettes, and try to avoid secondhand smoke. Some research suggests that avoiding smoking may help slow down vision loss for people with Stargardt’s disease

Vision aids and support

While there is no cure, vision rehabilitation and supportive care can help people perform everyday tasks^[1][7]. Your eye care specialist will suggest ways to manage symptoms and adapt to vision changes^[2].

Vision aids and technology are invaluable tools that enable people with Stargardt’s disease to live as normally as possible. Without them, many daily activities like working, reading, using a phone, or reading cooking instructions would be much more difficult^[19].

Low-vision services, mobility training, and other supportive care can help you adapt to vision changes and maintain independence^[7].

Current research

Although no FDA-approved treatments are currently available for Stargardt’s disease, researchers are actively working to develop therapies. Several companies are conducting clinical trials for potential treatments^[10][15].

Emerging therapies being studied

Six companies are actively developing therapies for Stargardt’s disease using various approaches^[15]:

• Vitamin A modification therapies: One promising approach involves using a modified form of vitamin A that produces less waste when processed in the retina. A drug called gildeuretinol (ALK-001) has received special recognition from the US Food and Drug Administration. This daily tablet treatment showed in clinical trials that it could slow retinal damage by more than 20 percent over two years^[12][16]. Early-stage patients taking the drug appeared to maintain stable vision for up to seven years. The treatment was safe and well-tolerated with no serious side effects^[12]
• Gene therapy approaches: Several companies are developing gene therapies that aim to correct or compensate for the faulty ABCA4 gene^[10][15]
• Protein splicing therapy: SpliceBio has dosed the first person in a Phase 1/2 clinical trial for a protein splicing therapy, marking the first FDA-authorized clinical trial for this type of treatment for Stargardt’s disease^[10]
• mRNA trans-splicing gene therapy: VeonGen has received FDA authorization to launch a clinical trial for an emerging therapy^[10]
• Stem cell therapy: Research is exploring whether stem cells could replace damaged retinal cells^[11]

Interested patients may be able to receive experimental treatments by joining a clinical trial^[7]. Talk to your eye doctor about whether participating in research might be appropriate for you.

Initial funding from organizations like BrightFocus Foundation has been crucial in supporting the development of these novel treatments^[16].

Living with Stargardt’s disease

Being diagnosed with Stargardt’s disease can be distressing, but with the right information and support, people can cope very well and lead fulfilling lives^[3]. Many people find that being diagnosed at a young age has enabled them to adapt, and their condition has never stood in the way of achieving their goals.

Finding a supportive work environment is important. Some employers are understanding and accommodating, making it possible for people with Stargardt’s disease to have successful careers^[19].

People with Stargardt’s disease and their families often adapt over time. Family members and friends automatically make small adjustments, such as reading menus aloud or reading subtitles^[19]. The people you surround yourself with may not even notice the disease after a while.

Many people with Stargardt’s disease report that their life is none the worse for having the condition. While certain things like not being able to drive may cause initial disappointment, not dwelling on these limitations helps people maintain a positive outlook^[19].

Vision loss can present challenges in dating and relationships. Being open about your condition upfront can help, although it may take time to find understanding partners^[19].

For children and teenagers with the condition, using assistive devices at school is important, even though young people may initially resist because they don’t want to appear different from their peers^[18].

Support services, counseling, and connecting with others who have the condition can help people adjust emotionally and practically to living with Stargardt’s disease^[17].