Progressive Choriocapillaris Impairment in ABCA4 Maculopathy Is Secondary to Retinal Pigment Epithelium Atrophy

Abstract

Purpose: To analyze the progression of choriocapillaris (CC) impairment in recessive Stargardt disease (STGD) and compare it to the progression of retinal pigment epithelium (RPE) atrophy.

Methods: Fifty-five patients with a clinical diagnosis of STGD and genetic confirmation of pathogenic biallelic variants in ABCA4 were imaged with short-wavelength fundus autofluorescence (SW-AF) and optical coherence tomography angiography (OCTA) at a single clinic visit, whereas a subset of 12 patients were imaged with the same modalities at two different clinic visits.

Results: We observed three stages of CC impairment: an area of bright yet intact macular CC (11 patients), regions of vascular rarefaction and incomplete CC atrophy within an area of bright CC (10 patients), and areas of extensive CC atrophy (26 patients). These changes correlated to the degree of RPE atrophy observed in SW-AF imaging. Furthermore, 8 patients presented with early changes on SW-AF, but healthy CC. Quantitative analyses of the atrophic changes revealed that the area of RPE atrophy is larger (9.6 ± 1.7 mm2 vs. 6.9 ± 1.3 mm2, P < 0.001) and that it progresses at a faster rate (1.1 ± 0.1 mm2/year vs. 0.8 ± 0.2 mm2/year, P = 0.004) than the corresponding area of CC atrophy.

Conclusions: CC impairment is progressive and OCTA imaging can be used to demonstrate the stages, which culminate in extensive CC atrophy. Furthermore, CC impairment is secondary to RPE atrophy in STGD. We further advocate the use of SW-AF and OCTA imaging in monitoring the progression of STGD.

Figure 1.

Patients with early changes on SW-AF due to recessive STGD but healthy CC (group 1). Color fundus photography, SW-AF, and OCTA imaging of patients A–D. These patients present with a small area of macular hypoAF with a surrounding ring of hyperAF, both early changes associated with recessive STGD. Nevertheless, the CC appear healthy with no changes on OCTA imaging. Fundoscopy is unremarkable for patients A–C. For patient D, hyperAF flecks on SW-AF and yellow flecks on fundoscopy are observed, both characteristic of STGD.

Figure 2.

Patients with STGD exhibiting an area of bright macular CC (groups 2 and 3). Patients A–D presented with an area of bright macular yet intact CC on OCTA corresponding to the area of macular atrophy observed in SW-AF imaging. Despite the overlying RPE atrophy, the CC appear intact (group 2). Patients E–H also presented with an area of bright macular CC, but in these patients, there is obvious vascular rarefaction and CC atrophy (red arrows) (group 3). The CC changes observed in both groups of patients correspond to the overlying RPE atrophy, although damage in group 3 patients is more advanced.

Figure 3.

Patients with STGD with extensive CC atrophy in areas of retinal atrophy (group 4). Patients A–C presented with extensive atrophy of the CC, with visualization of the underlying larger choroidal vessels. These areas of atrophy corresponded to areas of extensive RPE loss on SW-AF imaging, as suggested by the dense areas of hypoAF. Furthermore, the underlying white sclera was visible on fundoscopy on these areas.

Figure 4.

Progressive atrophy detected in SW-AF and OCTA imaging of patients with STGD. SW-AF (A, C) and OCTA (B, D) of a patient with three clinical visits each 1 year apart. As observed on SW-AF, the area of hypoAF increases in size between the visits, suggesting progressive atrophy of the RPE. Similarly, progression of CC atrophy is observed on OCTA imaging as indicated by the increased area of atrophy and greater visualization of the underlying choroidal vessels. The last panel shows the areas of atrophy being outlined to analyze and compare the size of RPE versus CC atrophy quantitatively. OS, oculus sinister; OD, oculus dextrus.

Figure 5.

Accumulation of lipofuscin in the overlying RPE creates a shadow on the underlying CC. In patients A–F, SW-AF reveals variable degrees of macular RPE atrophy, with the lesion appearing bright on the underlying CC as observed on OCTA imaging. This apparent brightness of the lesion is likely created as more signal is received on this area owing to the atrophy of the overlying RPE. In addition, an apparent dark halo is appreciated on the perimeter surrounding the bright lesion on the CC. This shadow is likely created due to signal blockage from the lipofuscin that has accumulated on the overlying RPE, as appreciated from the hyperAF ring surrounding the macular atrophy on SW-AF imaging. The blockage of signal by RPE lipofuscin is further supported by analyzing the hyperAF flecks in patients D–F, as these flecks create a dark spot on the CC images (indicated by the matching color arrows on SW-AF and OCTA imaging).