BASICS
DESCRIPTION
• The most common form of juvenile macular degeneration
• Causes vision loss in the first or second decade of life
• “Fundus flavimaculatus” is the descriptive term given to the retinal appearance often found with this condition. The term is usually synonymous with Stargardt disease, although some authors reserve this term for only those patients with the classic retinal appearance or patients with later onset disease.
EPIDEMIOLOGY
Prevalence
1/8,000–1/10,000
RISK FACTORS
• Usually autosomal recessive
• Classic disease linked to mutations in ABCR (also called ABCA4) on chromosome 1p13–p21.
• More than 400 sequence variations have been described.
• Mutations in this gene are also linked to autosomal recessive cone-rod dystrophy and retinitis pigmentosa.
• Autosomal dominant Stargardt-like diseases caused by mutations on chromosomes 13q, 6q, and 4p.
GENERAL PREVENTION
Genetic counseling may be of value to some families, but there are no strategies for prevention.
PATHOPHYSIOLOGY
• The ABCR gene codes for an ATP-binding cassette known as Rim protein (RmP) involved in vitamin A metabolism.
• Vitamin A is used by rod and cone photoreceptors in the outer retina.
• It is thought that ABCR mutations interfere with transport of vitamin A between the photoreceptors and underlying retinal pigment epithelium (RPE).
• Leads to a build-up of lipofuscin in RPE cells.
• The disease affects the macula and fovea preferentially due to the high concentration of photoreceptors in the area of central fixation.
DIAGNOSIS
HISTORY
Patients describe slowly progressive vision loss. There may be affected siblings, although strong family history is uncommon given autosomal recessive inheritance.
PHYSICAL EXAM
• The fundus exam may appear completely normal. For this reason, some patients are suspected of malingering.
• Typical retinal changes are usually bilateral and include the following:
– Nonspecific foveal RPE mottling, which may take on a “beaten bronze” appearance.
– Ill-defined, yellow-white deep retinal “flecks” at the level of the RPE, referred to as “pisciform” for their fish-like shape.
– More advanced disease may have an atrophic macula with a “bull’s eye” or geographic atrophy appearance.
DIAGNOSTIC TESTS & INTERPRETATION
Lab
Genetic testing is generally not performed for this condition given the large size of the ABCR gene and the diversity of known mutations.
Diagnostic Procedures/Other
• Intravenous fluorescein angiography (IVFA) often reveals a “dark choroid,” in which retinal blood vessels are highlighted against a hypofluorescent background due to the accumulation of lipofuscin the RPE cells. This sign is highly specific for this condition, but the absence of this sign does not exclude the diagnosis.
• Fundus autofluorescence photography often reveals hypoautofluorescence at the level of fovea corresponding to RPE atrophy. This is usually surrounded by small flecks of hyperautofluorescence, which may outnumber those flecks seen clinically.
• IVFA may also reveal hyperfluorescent flecks corresponding to RPE atrophy, which may become confluent in advanced disease.
• Full-field ERG (electroretinogram) is usually normal but the photopic (bright-adapted) ERG may be slightly abnormal. Multifocal ERG may show decreased amplitudes corresponding to central vision.
• EOG (electrooculogram) may be slightly abnormal in advanced cases.
Pathological Findings
• Light microscopy reveals a loss of photoreceptors and RPE cells.
• RPE cells in the posterior pole are also irregular in size and shape with intracytoplasmic PAS-positive granules of lipofuscin.
DIFFERENTIAL DIAGNOSIS
• Fundus albipunctatus: flecks in the midperipheral retina, nonprogressive congenital night blindness
• Retinitis punctata albescens: similar appearance to fundus albipunctatus with severe, progressive vision loss
• Drusen: Small yellow-white spots in macula. Usually develop later in life. Hyperfluorescent on IVFA.
• Cone or cone-rod dystrophy: Can present with “bull’s eye” maculopathy. Significant color vision loss, abnormal ERG.
• Chloroquine/hydroxychloroquine toxicity: Can present with “bull’s eye” maculopathy
• Batten disease and Spielmeyer–Vogt syndrome: Autosomal recessive lysosomal storage disease. Can produce “bull’s eye” maculopathy.
• Functional vision loss: Normal exam and testing. Special techniques can unmask better vision than claimed.
TREATMENT
MEDICATION
• There are no treatments for this disease. Low vision referral may be of great value. UV protection is generally recommended.
• As the genetics are further understood, this disease may be amenable to gene therapy.
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
• Ophthalmologic exams
• Low vision
• Services for the blind
• Fundus autofluorescence photography may be of value in assessing disease activity.
PATIENT EDUCATION
• http://www.macular.org/stargardts.html
• http://www.lowvision.org/stargardts.htm
PROGNOSIS
• Stargardt disease is a chronic disease with poor visual prognosis.
• Once visual acuity drops below 20/40 it tends to decrease rapidly, then stabilize near 20/200.
COMPLICATIONS
Central vision loss
REFERENCES
1. Boon CJ, Jeroen Klevering B, Keunen JE, et al. Fundus autofluorescence imaging of retinal dystrophies. Vision Res 2008;48:2569–2577.
2. Koenekoop RK. The gene for Stargardt disease, ABCA4, is a major retinal gene: a mini-review. Ophthalmic Genet 2003;24:75–80.
3. Walia S, Fishman GA. Natural history of phenotypic changes in Stargardt macular dystrophy. Ophthalmic Genet 2009;30:63–68.
4. Westerfeld C, Mukai S. Stargardt’s disease and the ABCR gene. Semin Ophthalmol 2008;23:59–65.
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