Stargardt disease: clinical features, molecular genetics, animal models and therapeutic options

Abstract

Stargardt disease (STGD1; MIM 248200) is the most prevalent inherited macular dystrophy and is associated with disease-causing sequence variants in the gene ABCA4 Significant advances have been made over the last 10 years in our understanding of both the clinical and molecular features of STGD1, and also the underlying pathophysiology, which has culminated in ongoing and planned human clinical trials of novel therapies. The aims of this review are to describe the detailed phenotypic and genotypic characteristics of the disease, conventional and novel imaging findings, current knowledge of animal models and pathogenesis, and the multiple avenues of intervention being explored.

Keywords: Dystrophy; Imaging; Retina.

Figure 1

(A) Colour fundus photograph showing typical yellow–white retinal flecks with macular atrophy. (B) Corresponding fundus autofluorescence image showing flecks of both increased and decreased autofluorescence and reduced central macular autofluorescence surrounded by an increased signal.

Figure 2

Multimodal imaging of the right eye of a molecularly proven 15-year-old patient with Stargardt disease. (A) Fundus autofluorescence image. The yellow line indicates the scanning level of the optical coherence tomography (OCT) scan in (B). (B) OCT scan showing central loss of outer retinal structure. The yellow arrows indicate the location and extent of the adaptive optics scanning light ophthalmoscopy (AOSLO) montages in (C) and (D) through the transition zone. (C) Confocal AOSLO montage of the photoreceptor mosaic. (D) Split-detection AOSLO montage of the photoreceptor mosaic. The far left side of (C) and (D) is closer to the fovea and lacks cone structure, corresponding with the lack of outer hyper-reflective layers in (B). Moving towards the right of (C) and (D), away from the fovea and superiorly on the retina, (C) shows structural changes that are relatively challenging to interpret, whereas (D) clearly shows the presence of cones. Scale bars represent 100 µm.