Title: Stargardt disease
Author (s): Jamie Odden, MS4 MPH
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Keywords/Main Subjects: Stargardt Disease; Central macular atrophy; Inherited macular dystrophy
Diagnosis: Stargardt Disease
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Epidemiology: Stargardt disease is the most common inherited macular dystrophy, with a prevalence of approximately 1 in 8,000-10,000 individuals. It is a common cause of central vision loss in individuals under 50 years old, with typical onset between 10-20 years old.
Genetics: The underlying etiology is due to accumulation of lipofuscin in the retinal pigment epithelium (RPE). Most cases are autosomal recessive due to mutations in the ABCA4 gene, which encodes for a transporter protein expressed by rod outer segments. ABCA4 mutations can cause toxins to accumulate in the photoreceptors, leading to formation of lipofuscin. Fewer cases are autosomal dominant due to a mutation in ELOVL4, which encodes a component of the fatty acid elongation system in photoreceptors.
Clinical exam: Classic fundoscopic findings include “beaten bronze” central macular atrophy surrounded by yellow round or pisciform flecks (Figure 1). The condition is referred to as “fundus flavimaculatus” if the discrete yellow flecks are widespread throughout the fundus retinal pigment epithelium (RPE). “Fundus flavimaculatus” is a milder condition rendering better visual function due to less macula involvement.
Diagnosis/testing: Fundus autofluorescence (FAF) and optical coherence tomography (OCT) can confirm diagnosis and help stage the disease. FAF and OCT often detect RPE changes before they are found on clinical fundoscopic exam. Commonly, FAF shows a hypofluorescent macula, corresponding to atrophy, and surrounding hyperfluorescent spots, corresponding to lipofuscin deposits in the RPE (Figure 2).
OCT demonstrates thinning and disorganization of the inner segment-outer segment (IS-OS) junction of the photoreceptors in the macula (Figure 3). Total loss of the IS-OS is possible over time. Choroidal hyper-reflectivity often occurs due to overlying retinal atrophy.
Historically, the “dark choroid sign” on fluorescein angiography (FA) was used to confirm clinical diagnosis, though FA has been largely replaced by FAF and OCT. The sign is present in over 80% of patients. Evidence suggests that the sign is caused by accumulation of lipofuscin throughout the RPE which masks background choroidal fluorescence.
Clinical course: In most cases, central vision loss is slow and progressive. Later-onset disease is associated with a better prognosis. Visual acuity ranges from 20/50 to 20/200, with most individuals maintaining fair acuity in one eye.
Management: Stargardt disease is incurable. No treatments are available to slow progression, though pharmacologic and genetic therapies are under investigation. Individuals should avoid vitamin A supplementation and minimize exposure to bright sunlight. Additionally, low vision therapy should be considered.
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Faculty Approval by: Paul Bernstein, MD PhD; Griffin Jardine, MD
Disclosure (Financial or other): None