The Dark Atrophy with Indocyanine Green Angiography in Stargardt Disease

Abstract

PURPOSE. To evaluate differences in fluorescein angiography (FA) and indocyanine green angiography (ICGA), findings between subjects affected by Stargardt disease (STGD) and atrophic AMD.METHODS. This was a consecutive, cross-sectional case series. A total of 24 eyes of 12 patients with STGD and 23 eyes of 14 patients with atrophic AMD were enrolled in the study. Patients underwent dynamic simultaneous FA and ICGA using a dual beam confocal scanning system. Images were recorded from the initial filling of choroidal and retinal vessels throughout all the phases of the angiogram. Spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence were also executed. FA and ICGA findings in the two groups were evaluated.RESULTS. In 92% (22/24) of eyes affected by STGD, ICGA showed hypocyanescence from the areas of atrophy, more evident in the late phases. This finding, defined as ICGA-imaged ''dark atrophy,'' was present in only 13% (3/23) of the eyes affected by atrophic AMD. The remaining eyes in both groups showed iso-or mild hypercyanescence from the areas of atrophy. Eyes with ICGA-imaged dark atrophy, both in STGD and in atrophic AMD groups, did not show early obscuration of the choroidal vessels by FA. SD-OCT revealed morphologically intact choroid in STGD patients with ICGA-imaged dark atrophy. In atrophic AMD eyes with ICGA-imaged dark atrophy, SD-OCT revealed a severely thinned choroid. CONCLUSIONS.Hypocyanescence by ICGA from the areas of atrophy was more frequent in STGD compared with atrophic AMD. This finding, along with SD-OCT evidence of intact choroid, suggests a possible selective damage of the choriocapillaris in STGD. (Invest Ophthalmol Vis Sci. 2012;53:3999-4004) DOI:10.1167/iovs.11-9258 R ecessive Stargardt disease (STGD) and age-related macular degeneration (AMD) lead to progressive and severe visual acuity loss. STGD is one of the most common inherited retinal dystrophies, while AMD is the most important cause of central visual acuity loss in western countries. STGD typically appears before age 20. It exhibits simple Mendelian transmission and is caused by mutations in the ABCA4 gene. A reduction in ABCA4 activity in the photoreceptors results in the increased production and accumulation of A2E and related bisretinoids within RPE cells.1,2 These compounds cannot be readily metabolized and have negative effects on RPE cell function and viability. 2 The result of these pathogenic elements is a progressive loss of RPE and photoreceptors. In contrast, AMD, which typically appears in the sixth decade, has an acquired etiology with a progressive and multifactorial pathology. RPE damage constitutes the initial event.3,4 RPE cell loss might originate from several mechanisms, including photooxidative stress, 5 vascular alterations, 6,7 and deposition of toxic lipofuscin material under RPE. 1 In the atrophic form of AMD, these alterations lead to progressive loss of RPE and photoreceptor cells.Fluorescein angiography (FA) and indocyanine green angiography (ICGA) are important tools for...

Choroidal Flow Signal in Late-Onset Stargardt Disease and Age-Related Macular Degeneration: An OCT-Angiography Study

“…30 These differences may also explain the hypofluorescence in areas of RPE atrophy during late phases of ICGA in STGD1, known as ''dark atrophy.'' 28 Previously, slower progression of RPE atrophy in STGD1 as compared to AMD was observed, implicating a relatively earlier onset of RPE atrophy in late-onset STGD1 as compared to AMD. 52 Potentially, this difference in disease duration may explain to some extent the diverging degree of vascular density within RPE atrophy between these two disease entities.…”

“…9,24,25 In this context, hypofluorescence in areas of RPE atrophy during late phases of indocyanine green angiography (ICGA), used to visualize choroidal vasculature, 26,27 was found to be more common in STGD1 compared to AMD. 28 The introduction of optical coherence tomography angiography (OCT-A) allows for noninvasive in vivo visualization of blood flow with three-dimensional resolution. Nevertheless, all reports so far describe a loss of CC within areas of RPE atrophy.…”

Multimodal Imaging in Autosomal Dominant Cone-Rod Dystrophy Caused by Novel <b><i>CRX</i></b> Variant

“…RPE, in fact, is known to produce vascular endothelial growth factor (VEGF) and VEGF receptors are expressed on the choroidal endothelium facing the RPE [16]. Conversely, choroidal vessels providing the vascular support to outer retinal layers could be primarily responsible, suggesting a possible pathogenetic role of choriocapillaris atrophy in photoreceptors degeneration [17]. CRX is known to have a role in retinal development and maintenance and expression studies reveal its presence in both cone and rod photoreceptors, possibly in the bipolar cells [18] but not in the RPE neither in any level of the choroid [19].…”

Multimodal Imaging of Nonneovascular Age-Related Macular Degeneration

“…For example, with AMD there is typically late ICG staining of the area of GA, while Stargardt disease illustrates ''dark atrophy'' without dye staining. 48 ICGA may also detect nonexudative type 1 (sub-RPE or occult) NV as a plaque of late hyperfluorescent staining in eyes that appear to have the nonneovascular form of AMD on funduscopic examination or FA. 49 Given the availability of noninvasive and superior imaging modalities, ICGA is not routinely performed in the management of nonneovascular AMD.…”