Stargardt macular degeneration, or Stargardt disease, or fundus flavimaculatus, is a rare, inherited eye condition that usually causes progressive vision loss. People with Stargardt macular degeneration will develop progressive vision loss primarily due to a fatty yellow pigment, called lipofuscin that forms in the macula, the area in the retina used for sharp straight ahead vision specifically utilized for reading, driving, and distinguishing faces. 

Stargardt disease is the most common form of juvenile macular degeneration, and it can start presenting as early as childhood or adolescence although some patients report little to no symptoms until adulthood. Agerelated macular degeneration (AMD), also includes progressive vision loss, however this commonly affects older adults. Stargardt disease is hereditary and is most commonly found in younger people, so this results in progressive central vision loss over time, but generally retains peripheral vision. The rate and degree of visual loss occurs at varying rates and based upon the individual. 

In a person diagnosed with Stargardt disease, photoreceptors (specialized light-sensing cells) in the macula deteriorate and die off. The nerve cell death and deterioration, generally impacts the visual function and regular daily activities such as reading, identifying faces and distinguishing details become increasingly more difficult.

Stargardt disease arises when specific genes responsible for normal retinal function are mutated. ABCA4 is the most commonly affected gene (The Human Gene Mutation Database; 2014). ABCA4 provides instructions for making a protein that is integral to the visual cycle and plays an intricate role in eliminating toxic metabolic by-products that are produced in the retina when it processes light. If the ABCA4 gene is mutated, it alters the body’s use of vitamin A and results in the elimination of metabolic by-products being improperly accomplished. When this occurs, the photo receptor cells, and more specifically the macula, can become dysfunctional leading to the accrual of a fatty yellow-brown pigment called lipofuscin. Over time the lipofuscin is toxic to the retinal cells, killing the photoreceptors (aka rods and cones) and leading to progressive vision loss.

There are also rare cases of other gene mutations considered to be linked to Stargardt-like disease such as ELOVL4, PROM1, and RDS/PRPH2. These mutations lead to Stargardt-like diseases that are similar in some aspects to Stargardt disease, but differ in disease progression and inheritance patterns.

Stargardt disease is most often passed down to offspring through an autosomal recessive inheritance pattern. In terms of inheritance, this means an individual must inherit two copies of the mutated ABCA4 gene from both parents in order to develop Stargardt disease. If an individual only has one faulty copy of the gene, that individual is simply a carrier, meaning they would not have any symptoms but could potentially pass on the mutation to their offspring. If both parents are carriers for the ABCA4 mutation, a child has following chances of inheritance: 

1. A 25% chance of inheriting two normal genes; completely unaffected.
2. A 50% chance of inheriting one faulty copy of the gene, and becoming a carrier; completely unaffected.
3. A 25% chance of inheriting two faulty copies of the genes, and developing Stargardt disease. 

In rare cases, a few other genes, ELOVL4 and PROM1, have been shown to be inherited in an autosomal dominant pattern. This means just one copy of the mutated gene inherited from one parent can cause the disease. 

It is possible to obtain genetic testing to confirm the diagnosis of Stargardt disease, to identify the exact mutation in the ABCA4 gene or in other related genes. Genetic testing is also useful for families that have a history of Stargardt disease in the family, or if symptoms of the condition appeared at an early age and are very concerning. Genetic testing may provide useful information about family planning.

The signs and symptoms of Stargardt macular degeneration are variable based on the age of onset, the specific genetic mutation that underlies the condition, and how quickly the condition progresses. Despite this variability, there are several common symptoms that many people see.

• Central Vision Loss: One of the primary symptoms of Stargardt disease is a central vision loss (which can be a sudden or chunklike gradation) that can no longer be corrected with glasses or contacts. This will impact one’s ability to complete tasks that require central vision (eg. reading, identifying people, driving, etc.). Typically both eyes are impacted, although one may be worse than the other in the early stage.
• Blurriness and Distortion: Blurriness or visual distortion is often reported. For example, a patient may report seeing a straight line that appears to be wavy or bendy (metamorphopsia). When engaging with smaller print, it often becomes impossible to see any fine details or small, even though a patient does have their vision corrected.
• Trouble in dim lighting: A common complaint among patients is difficulty seeing in dim lighting, also referred to as nocturnal blindness (nyctalopia). In addition to the central vision loss experienced by cone cells, rod cells (related to low-light vision) are also affected.
• Changes in Color Vision: Some individuals report a reduced capacity to perceive colors accurately, and while this is not always a symptom toward the beginning of the disease, color vision can begin to change as Stargardt disease progresses, and as more photoreceptor cells are lost.
• Dark or Empty Spots in the Visual Field: Individuals with Stargardt disease often develop scotomas, dark, blurry, or empty spots in the central visual field. These blind spots can disrupt activities that require focused sight, for example reading and recognizing faces.
• Sensitivity to Bright Light: Also known as photophobia, sensitivity to bright light is another common symptom of Stargardt disease. The sensitivity can be triggered by sunlight, headlights, fluorescent light, and may cause suffering, thus individuals with Stargardt disease may prefer dim or shaded environments.

Typically, the progression of Stargardt disease is slow and gradually worsens, but in some cases, vision loss is more rapid or severe. Most individuals will continue to have peripheral vision (with some exceptions) in the later stages of the disease, but by middle age, vision loss in the central visual field may be significantly impaired.

Diagnosing Stargardt disease involves a thorough eye exam, multimodal imaging, and genetic testing. Given that symptoms can appear similar to other retinal disorders, proper diagnosis is required for appropriate management and planning. 

Here are the most common diagnostic methods: 

1. Visual acuity test: The standard eye test for distance vision. Stargradt Disease patients will show decreased central vision with normal peripheral vision. 
2. Fundus examination: Usually performed by an ophthalmologist or optometrist with specialty retinal training. The ophthalmoscope or fundus camera is used to examine the back of the eye, where Stargardt Disease is often associated with yellowish-white flecks (lipofuscin) found around the macula. These flecks are a characteristic feature of Stargardt disease. 
3. Fundus autofluorescence (FAF): This test can be performed using a fundus camera or scanned laser. FAF is a beautiful non-invasive technique to visualize the accumulation of lipofuscin in retinal cells. Increased and decreased FAF will identify areas of retinal damage and help to identify areas of the retina that have been affected which may correlate with a patient’s vision, but often quite early on before the vision symptoms become severe.
4. Optical Coherence Tomography (OCT): OCT provides high resolution, cross-sectional images of the retina. It can reveal thinning, atrophy or disruption of retinal layers – especially in the macula. OCT is useful for assessing disease progression, if applicable, and monitoring response to treatment, where relevant.
5. Electroretinography (ERG): An ERG assesses the electrical activity of the retina in response to light stimuli. In Stargardt disease, the cone cell response (related to central vision) is often more severely impaired in the ERG than the rod cell response (which is important for night and peripheral vision). The ERG quantitively evaluates the functional effect of the disease on photoreceptor cells.
6. Genetic Testing: Genetic testing provides the most conclusive diagnosis. Genetic testing can identify mutations in the ABCA4 gene and related genes in Stargardt-like diseases. Confirming the genetic cause is very important in making a diagnosis, but could also be useful for family planning, carrier testing, and clinical trial eligibility. This is currently the best way to ascertain the genetic basis of the condition.

Currently, there is no treatment for Stargardt macular degeneration, however, there are some strategies aimed at slowing progression, maintaining useful vision, and allowing for the best possible quality of life.

Research is also ongoing into potential treatments.

1. Visual Aids and Rehabilitation: Low vision specialists can help patients with daily living, as well as cope with their impairment by offering devices such as:
   • Magnifiers (both glass and electronic) 
   • Reading materials with high contrast
   • Screen readers and text to speech software
   • Mobility training 
2. Sun and Light Protection: Eye protection such as UV and blue light protection may help to minimize retinal damage.
   • Recommend wearing sunglasses that block UV light and wide-brimmed hats.
   • Recommend using filters for blue light exposure when using screens. 
3. Nutrition Recommendations: In contrast to AMD, recent studies have shown that high-dose vitamin A is harmful and exacerbates Stargardt disease by increasing lipofuscin deposits. As such, the recommendation is to:
   • Avoid vitamin A supplements, large quantities of foods high in vitamin A.
   • Maintain a healthy diet with input from medical professionals.
4. Innovative Interventions and Clinical Trials: Investigational, promising treatments comprise:
   • Gene therapy: Giving the body a healthy ABCA4 gene,
   • Stem cell therapy: Replacing dysfunctional retinal cells,
   • Drugs such as emixustat and ALK-001: to reduce toxic pigment build-up, 
   • Retinal implants: such as the Argus II;
   • CRISPR gene editing: also currently experimental;
   • Some studies offer participation in clinical trials as a potentially earlier access to these treatments.
5. Emotional and Psychological Support: Loss of vision that progresses can be difficult emotionally and you have several choices for support:
   • Counseling and therapy,
   • Peer groups and low vision training,
   • Education and materials for developing adjustment strategies.
6. Exercise Strategies:
   • Don’t smoke, and avoid second hand smoke – it could exacerbate vision loss.
   • Keep abreast of the latest developments in research.
   • Attend eye exams consistently for detecting progression.

Stargardt macular degeneration is a rare genetic eye disease that can result in significant loss of central vision. There are some patients who will develop symptoms from Stargardt’s early in childhood or early adulthood. Almost all cases of Stargardt macular degeneration are caused by mutations in the ABCA4 gene. If the ABCA4 gene is mutated, the ability for the retina to metabolize light and process it appropriately is affected. This results in an accumulation of toxic debris (lipofuscin) and damage to the retina’s light-sensing cells. Although there is no cure for Stargardt macular degeneration today, the prospect of the development of gene therapy, stem cell research, and targeted therapy is very exciting and inspiring and hopeful. Although the interventions vary from patient-to-patient, the goal of an early diagnosis and supportive approaches (vision aids, lighting, social-emotional support, etc.) is to help patients with Stargardt macular degeneration retain their independence and quality of life (in other words, their “best lives”). 

This requires an ongoing and open partnership between families, patients, and eye care providers to monitor and understand the progression of the condition, adapt to changes in vision, and find and participate in clinical trials whenever possible. Raising awareness, supporting genetic counseling access, education, and tools for low vision rehabilitation are all ways to help provide the strength and optimism in living well with a lifelong condition.

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2. Genetics Home Reference. (2020). Stargardt macular degeneration. MedlinePlus Genetics
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