What are the other Names for this Condition? (Also known as/Synonyms)

• Juvenile Macular Degeneration
• Stargardt Macular Dystrophy
• STGD (Stargardt Disease)

What is Stargardt Disease? (Definition/Background Information)

• Stargardt Disease (STGD) is a juvenile form of macular degeneration. Unlike age-related macular degeneration, this condition is inherited, and typically presents itself before the second decade. After its onset, progressive vision loss is inevitable, leading to severe visual impairment
• The condition is caused by mutation(s) in the ABCA4 or ELOVL4 genes. Therefore, having a family history of the condition is a major risk factor for being diagnosed with STGD
• ABCA4 and ELOVL4 genes produce proteins that localize in the light-sensing cells (photoreceptors) of the retina. Mutations cause aberrant products, which through different biochemical pathways lead to the death of the photoreceptor cells. This results in the manifestation of Stargardt Disease
• Stargardt Disease presents with signs and symptoms such as poor vision in reduced light settings, decreased color vision, and progressive loss of central vision. Severe visual impairment and blindness are potential complications of STGD
• A diagnosis of the disorder can be made through a general physical examination, symptom assessment, family history evaluation, ophthalmological examination, vision test, and electroretinography (the measurement of electrical responses in retinal cells)
• Since Stargardt Disease is caused by genetic factors, currently there is no cure for the condition. Although the loss of vision cannot be reversed, proper vision aids and adequate rehabilitation may help and support the affected individual better
• Presently, there are no guidelines available for the prevention of this disorder, since it is typically inherited. Prospective parents may benefit from genetic testing and counseling, if Stargardt Disease runs in their family
• The prognosis of Stargardt Disease depends on the age of presentation and severity of the symptoms. Disease onset in adulthood typically presents with fewer and relatively milder symptoms leading to better outcomes. If STGD manifests itself in childhood, then there is a high probability of severe and progressive visual impairment

Who gets Stargardt Disease? (Age and Sex Distribution)

• Stargardt Disease is reported worldwide, with no racial or geographical predilection being noted
• It occurs at a frequency of between 1:8,000 and 1:10,000
• Although the condition can develop at any age, it predominantly occurs in individuals aged between 6 and 20 years (children, teens, and young adults). Hence, it is also known as Juvenile Macular Degeneration
• Both male and female genders are equally affected by this condition

What are the Risk Factors for Stargardt Disease? (Predisposing Factors)

• Stargardt Disease is an inherited disorder, and therefore, having a family history of the same is a major risk factor

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Stargardt Disease? (Etiology)

Stargardt Disease (STGD) is caused by mutation(s) in either the ABCA4 gene (ATP-binding cassette subfamily A member 4 gene) or ELOVL4 gene (elongation of very long fatty acids protein 4 gene). The most frequent gene mutation found in individuals affected by STGD is that of ABCA4. The eye disorder caused by ABCA4 mutation is often termed STGD1.

Under normal circumstances, when light enters the eyes, certain specialized cells, called the photoreceptor cells, receive the signal. There are two types of photoreceptor cells in the human eyes, which are known as rod cells and cone cells. The light received by these cells is converted to electrical signal and transmitted to the brain. This process is called phototransduction.

• The ABCA4 gene codes for a protein that detoxifies the photoreceptor cells following phototransduction
  • When this gene is mutated, toxic by-products accumulate in the photosensitive and surrounding cells of the retina, forming a substance known as lipofuscin
  • Lipofuscin is a fat containing pigment granule, which is yellow to light brown in color
  • The accumulation of lipofuscin over a period results in cell death, causing progressive problems with vision
  • The ABCA4 gene mutation is inherited in an autosomal recessive pattern. The parents are carriers of the disorder and are not typically affected
• The ELOVL4 is involved in the synthesis of a type of fat called “very long chain fatty acids”; its exact function in the eyes is not clearly known
  • When this gene is mutated, the abnormal ELOVL4 protein starts accumulating in the retina
  • Over time, this accumulation of abnormal protein interferes with normal retinal cells’ function, ultimately leading to their death resulting in the disease symptoms
  • ELOVL4 gene mutations are inherited in an autosomal dominant fashion. An affected individual inherits the disorder from an affected parent

Autosomal recessive Stargardt Disease is commonly noted; autosomal dominant disease is generally rare.

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children, born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected). 

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Stargardt Disease?

The signs and symptoms of Stargardt Disease may vary among the affected individuals. Typically, the symptoms are reported to be more severe in early-onset disease when compared to adult-onset disease, which can even be asymptomatic in some cases.

• Problems with central vision which may deteriorate over time - this may be the initial sign noticed by the individual
• Spots in the center of vision, which may be gray/hazy/blurred/cloudy
• Vision deterioration may be rapid in many individuals; the decreased vision may then stabilize after a certain period
• Eyes taking longer than normal to adjust when moving from brightly-lit to dimly-lit conditions
• Difficulty with night vision
• Sensitivity to bright light
• Decreased color vision
• Side vision generally remains unaffected, although in some individuals even side vision may be lost

The signs and symptoms are progressive in nature i.e., their severity worsens over time.

How is Stargardt Disease Diagnosed?

The diagnosis of Stargardt Disease is made based on the following tests and exams:

• A general physical examination and an assessment of symptoms
• Evaluation of personal and family medical history
• Vision acuity tests
• Testing for color vision
• Fundus examination and fundus autofluorescence photography, which may show:
  • Pigment changes of the macula
  • Classic “beaten-bronze” appearance of the macula
  • Yellow fleck-like lesions scattered throughout the retina
• Fundus fluorescein angiography (FFA): In this technique, the eye blood vessels are examined using a fluorescein dye. This technique is an important tool to establish a diagnosis of Stargardt Disease
• Electroretinography (ERG): It helps measure the electrical responses of retinal cells to light
• Optical coherence tomography (OCT): An imaging test to assess damage to the retina
• Genetic testing to check for or confirm mutation(s) in the causative genes

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Stargardt Disease?

The potentials complications due to Stargardt Disease may include:

• Emotional stress
• Severe visual impairment
• Blindness
• Decreased quality of life

How is Stargardt Disease Treated?

At the present time, there are no treatments available for Stargardt Disease. The signs and symptoms of the condition may be managed through the following measures:

• Use of low vision aids and vision rehabilitation, in order to help maximize one’s remaining vision
• Gene replacement therapy
• Occupational therapy
• Counseling for depression owing to deteriorating vision
• Clinical trials

Generally, proper follow-up care with regular eye screening and check-ups are important.

How can Stargardt Disease be Prevented?

• Currently, there are no specific methods or guidelines to prevent Stargardt Disease, since it is a genetic condition. However, the formation and accumulation of lipofuscin may be slowed by considering the following steps:
  • Reducing exposure to bright lights by wearing dark glasses
  • Avoiding high doses of vitamin A supplements: Some animal studies have shown that high doses of vitamin A supplements can cause increased accumulation of lipofuscin and faster deterioration of eyesight
  • Smoking cessation
  • Reducing exposure to second-hand smoke
• Genetic testing of expectant parents (and related family members, if needed) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as Stargardt Disease

Regular medical screening at periodic intervals with tests and physical examinations are highly recommended.

What is the Prognosis of Stargardt Disease? (Outcomes/Resolutions)

The prognosis of Stargardt Disease is determined by the age of onset and severity of disorder.

• Early-onset disease has poorer outcomes with severe and progressive vision impairment
• However, if the condition presents during adulthood (typically in the 4th or 5th decade), the prognosis is much better, with fewer and less severe symptoms being reported

Additional and Relevant Useful Information for Stargardt Disease:

• Fundus Flavimaculatus and Stargardt Disease are considered variants of the same genetic condition, but Fundus Flavimaculatus is usually the diagnosis for the adult-onset condition
• With Fundus Flavimaculatus, if the yellow fleck-like lesions in the retina do not involve the macula, prognosis for maintaining 20/40 vision, or better, becomes much greater
• Studies involving stem cells and genetic therapy remain promising for future treatment options