Stargardt disease

Stargardt disease (also known as Stargardt macular dystrophy or fundus flavimaculatus) is the most common inherited macular dystrophy, primarily affecting the central area of the retina (the macula) responsible for sharp, detailed vision. The disease is caused most frequently by biallelic mutations in the ABCA4 gene, which encodes a retinal-specific ATP-binding cassette transporter involved in the visual cycle. Dysfunction of this protein leads to the accumulation of toxic lipofuscin byproducts, particularly A2E, in the retinal pigment epithelium (RPE), resulting in progressive RPE and photoreceptor cell death. Patients typically present in childhood or adolescence with progressive bilateral central vision loss, difficulty reading, and problems with color discrimination. Fundoscopic examination characteristically reveals yellowish-white flecks (lipofuscin deposits) at the level of the RPE surrounding the macula, along with macular atrophy that may appear as a beaten-bronze or bull's-eye pattern. Fluorescein angiography often demonstrates a characteristic 'dark choroid' or 'silent choroid' sign due to blockage of background choroidal fluorescence by lipofuscin-laden RPE. Visual acuity typically declines to 20/200 or worse over time, though peripheral vision is usually preserved. There is currently no approved cure or treatment that halts or reverses the progression of Stargardt disease. Management focuses on low-vision aids, sun protection (UV-blocking sunglasses), and avoidance of excessive vitamin A supplementation, which may accelerate lipofuscin accumulation. Several promising therapeutic approaches are under active investigation, including gene therapy (delivery of functional ABCA4), pharmacological agents aimed at reducing toxic bisretinoid accumulation (such as visual cycle modulators), complement inhibition, and stem cell-based therapies to replace damaged RPE cells. Rare autosomal dominant forms of Stargardt-like macular dystrophy have been associated with mutations in the ELOVL4 gene (Stargardt disease type 3) and PROM1 gene (Stargardt disease type 4).

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Stargardt disease