Stargardt disease (STGD) is an autosomal recessive disease with a prevalence of approximately 1:10,000.
1,2 It is the most common form of hereditary, recessive macular dystrophy and is characterized by reduced visual acuity and central vision loss with onset in childhood or early adulthood.
3,4 The clinical appearance is characterized by yellow flecks at the level of the RPE distributed around the macula and the midperiphery of the posterior pole.
2 Additionally, in later stages of disease, there is progressive bilateral atrophy of the RPE resembling geographic atrophy in age-related macular degeneration. In the majority of patients (80%), the disease is caused by a mutation in the ATP-binding cassette transporter (ABCA4) gene, located within chromosome 1p13.
5–8 ABCA4 encodes for the ABCA4 receptor (ABCR), which is a photoreceptor-specific adenosine triphosphate–binding cassette transporter. ABCR acts as a phospholipid flippase within the rims and incisures of cone and rod outer segments, enabling vitamin A derivatives to be transported through the outer segment disc membranes.
9 Dysfunctional ABCR leads to abnormal lipofuscin accumulation within the RPE.
10–12 Lipofuscin is a byproduct of the visual cycle degradation and consists of various fluorophores including
N-retinylidene-
N-retinylethanolamine (A2E).
13 Fundus autofluorescence (FAF) has been established as a tool to visualize lipofuscin components in vivo
10,14 and has significantly promoted our understanding of the pathophysiology of retinal dystrophies.
15,16 However, it is still disputed which specific components of the visual cycle lead to an increase in FAF. A recent study using mass spectrometry has shown that A2E is predominantly distributed toward the periphery of the retina and does not correlate with lipofuscin distribution and thereby may not contribute to the increase in FAF levels within the macular center in physiologic aging conditions.
17 Furthermore, increased FAF observed in the border zone of geographic atrophy in age-related macular degeneration has been attributed to formation of stacked RPE cells and not primarily to lipofuscin accumulation within individual cells.
18,19 The FAF in STGD is characterized by a general increase of autofluorescence intensity, particularly in the short wavelengths, at early stages of the disease.
11 With advanced disease, well-demarcated hyperautofluorescent lesions corresponding to the visible yellowish flecks appear.
20–22 Furthermore, in the later stages of STGD, there is marked hypoautofluorescence in the area of atrophic changes, usually located at the posterior pole.
23,24