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

Abstract

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 mm 2 vs. 6.9 ± 1.3 mm 2 , P < 0.001) and that it progresses at a faster rate (1.1 ± 0.1 mm 2 /year vs. 0.8 ± 0.2 mm 2 /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.

Retinal Pigment Epithelium Atrophy in Recessive Stargardt Disease as Measured by Short-Wavelength and Near-Infrared Autofluorescence

“…Furthermore, in a previous study from our group, we observed more significant atrophy of the choriocapillaris as detected by OCT angiography in patients with chorioretinal atrophy compared to patients with discrete atrophy. 32 Despite the difference in disease severity between these two phenotypes, however, we observed a similar rate of lesion enlargement between the two groups, suggesting that the process of RPE atrophy is similar amongst different STGD1 phenotypes.…”

The Role of the Choroid in Stargardt Disease

“…They also found a dark halo of the lesion perimetry, probably corresponding to a shadow cast by lipofuscin accumulation in the RPE overlying the CC. These results demonstrate the advantage of using OCTA imaging in monitoring disease, and the authors concluded that as the RPE becomes atrophic, the CC disappears as a downstream effect [ 12 ].…”

“…The near-infrared autofluorescence (NIR-AF) signal originates from melanin in the RPE and the choroid. It has been thought that NIR-AF can better delineate the degree of RPE atrophy [ 12 ] ( Figure 1 and Figure 2 ). The full-field electroretinogram is usually normal or minimally abnormal, whereas multifocal electroretinogram (mf-ERG) may show a more demonstrable reduction of central retina responses [ 6 ].…”

“…Optical coherence tomography angiography (OCTA) is a noninvasive tool that permits the study of the superficial and deep retinal vascular plexi and the CC in detail [ 3 ]. Individual CC vessels are not visualized but rather appear as homogeneous, with an area of brightness representing blood flow [ 12 ]. CC loss in STGD has been shown in many OCTA studies [ 3 , 7 , 15 , 16 , 17 , 18 ].…”

Optical coherence tomography angiography in Bietti crystalline dystrophy

“…This evidence suggests that RPE atrophy occurs first, then followed by CC atrophy, as previously described in ABCA4-related conditions. 20 The study suffers from several limitations mainly related with the "case report design" of the investigation.…”