Stargardt Disease

Overview

Stargardt disease (STGD1) is the most common inherited macular dystrophy, affecting approximately 1 in 8,000–10,000 individuals. Caused primarily by mutations in the ABCA4 gene, it is characterized by progressive central vision loss, macular atrophy, and accumulation of lipofuscin in the retinal pigment epithelium (RPE). Onset typically occurs in the first two decades of life, with visual acuity declining to 20/200 or worse in most patients.

Genetics

STGD1 is autosomal recessive, caused by biallelic mutations in ABCA4. STGD3 (ELOVL4) and STGD4 (PROM1) are rare autosomal dominant forms. ABCA4 has over 1,000 pathogenic variants identified.

Clinical Presentation

Diagnosis

• Fundus examination: Beaten-bronze macular appearance, flecks at RPE level
• Fundus autofluorescence (FAF): Hypoautofluorescent macular atrophy with hyperautofluorescent flecks
• Fluorescein angiography: Dark choroid sign (pathognomonic in ~80%)
• OCT: Photoreceptor layer and RPE loss in macula
• ERG: May be normal early; cone-rod pattern in advanced disease
• Genetic testing: ABCA4 sequencing and deletion/duplication analysis

Current Research & Treatment

Multiple therapeutic strategies are in clinical trials for Stargardt disease. Gene augmentation therapy using AAV5-ABCA4 (AGTC-402) and lentiviral vectors (StarGen) have completed Phase 1/2 trials. Stem cell-based therapies (RPE replacement) are in early trials. Emixustat and other visual cycle modulators aim to reduce lipofuscin accumulation. Gene editing approaches for ABCA4 are in preclinical development.

Active Clinical Trials

The following active clinical trials are investigating treatments for Stargardt Disease. Trial status and enrollment may change; always verify directly on ClinicalTrials.gov.

Supporting Organizations

The following nonprofit organizations fund research, support patients, and advocate for advances in the treatment and cure of Stargardt Disease.