43.1 Features
Stargardt disease is the most commonly inherited macular dystrophy, with prevalence ranging from 1 in 8,000 to 1 in 10,000. Diagnosis can be difficult as the disease has an incredibly heterogeneous presentation, with varied age of onset and clinical findings. Patients usually present in childhood to early adulthood, but there have been cases described in patients up to the age of 50. Autosomal recessive mutations in the gene ABCA4 are the leading cause, with as many as 1 in 20 people carrying a mutation. Mutations in this gene are also linked to various other retinal dystrophies, including cone, “cone–rod,” “rod–cone,” and retinitis pigmentosa. In a small percentage of the population, other genes, including ELOVL4, PRPH2, or BEST1 are linked to Stargardt development.
The ABCA4 gene encodes for a retinal adenosine triphosphate-binding transporter, ABCR, which is located on the outer segments of cones and rods. ABCR transports the end products of the visual cycle from the photoreceptors to the retinal pigment epithelium (RPE). Without ABCR, biretinoid products accumulate in the outer segments of photoreceptors, which are ultimately digested by the RPE. In the RPE, the biretinoids react with other compounds to form a toxic by-product, N-retinylidene-N-retinylethanolamine (A2E), which leads to the accelerated formation of lipofuscin and death of the RPE with the subsequent decline of the overlying photoreceptors. Several hundred disease-causing mutations have been found in the ABCA4 gene, creating a myriad of phenotypes. More drastic variants of the genotype, including nonsense mutations, are linked to earlier and more severe expression, while missense mutations are often linked to milder phenotypes.
43.1.1 Common Symptoms
Central vision loss or paracentral scotomas are characteristic, with preservation of the full visual field. Presenting visual acuity ranges from 20/20 to light perception. Patients may have no visual symptoms and are diagnosed when incidental findings are found on routine examination.
43.1.2 Exam Findings
Variable findings such as subtle fundus manifestations (e.g., blunted foveal reflex, mild RPE changes, fine granular yellow–white accumulations in the macula) can precede perceived vision loss. The most common findings are a result of the accumulated A2E and lipofuscin, creating white, yellow, or orange flecks in the RPE. Flecks are typically oblong and often connect at oblique angles, which resemble a fishtail (“pisciform”). The distribution of flecks differs, localized to the macula in some, extending to the equator in others (▶ Fig. 43.1). The number, color, and borders of these flecks vary between patients, creating an even more complex clinical picture. In addition to flecks, pigmentary changes and bull’s-eye maculopathy (e.g., atrophy) may develop (▶ Fig. 43.2, ▶ Fig. 43.3). Subretinal fibrosis can accompany the flecks in select patients with severe disease. In some patients, the accumulation of material of A2E and lipofuscin in the RPE results in brown discoloration in the macula and choroidal vessels loss on ophthalmoscopy (▶ Fig. 43.4). The peripapillary RPE is typically spared, even with extensive disease.
Fig. 43.1 (a) Fundus photograph of the right eye with Stargardt disease with widespread pisciform flecks up to the arcades and foveal pigmentary changes. (b) Fundus autofluorescence shows the same flecks as hyperfluorescent and atrophy at the fovea.
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