On a different note, the choroidal vascularity index, a biomarker reflecting the relative ratio of vascular to stromal components in the choroid, exhibited a noteworthy decrease in BVMD irrespective of its stage. However, a more recent investigation observed no significant difference in subfoveal choroidal thickness between BVMD and control eyes. Conversely, in later stages marked by outer retinal degeneration and reduced metabolic demands, choroidal thickness would be expected to decrease. The underlying hypothesis was that the metabolic strain on the RPE and photoreceptor layers, due to the accumulation of vitelliform material, could lead to increased blood flow and the dilation of choroidal vessels, consequently resulting in greater choroidal thickness. One study examined changes in choroidal thickness across various BVMD stages, revealing that stages featuring vitelliform deposits showed a thicker choroid, while atrophic/fibrotic stages exhibited a thinner choroid compared to healthy controls. Researchers have also explored biomarkers related to choroidal angioarchitecture in BVMD. It is reasonable to assume that more researchers in the future will use OCT parameters as the primary endpoint for STGD1 trials.

In this case, the investigators evaluate the mean rate of change in the area of the EZ defect measured on en face OCT to determine disease progression. The STAR phase 2b trial (NCT03364153) evaluates the safety and efficacy of the C5 avacincaptad pegol (IVERIC bio, an Astellas company, Middlesex County, NJ, USA) as compared to sham in patients with STGD, and it is the only currently active trial that uses OCT-derived measurements as the primary endpoint ( accessed on 24 October 2023). However, the visualization of the OCT reflectance image using an en face projection (coronal view) and a subRPE slab reveals that atrophy is seen as a hyperreflective area and that there is a good correlation between areas of atrophy measured on FAF and en face OCT. Nonetheless, its adoption in other IRDs is still uncommon, particularly for i/cORA, which may not occur in all degenerative diseases.įinally, most studies of STGD1 determine disease progression by enlargement of areas of definitely decreased fundus autofluorescence (also known as DDAF), as reported in the ProgStar study. Since GA is a subset of all cRORA, the use of this terminology has also been expanded to other degenerative diseases for example, Doheny Imaging Reading Center investigators used it for defining atrophy on OCT in STGD1 in the ProgStar study. These definitions were developed for geographic atrophy (GA) secondary to AMD. Incomplete forms, with smaller regions of RPE loss and choroidal hypertransmission (iRORA), and incomplete and complete forms of photoreceptor degeneration without RPE loss (iORA and cORA, respectively), were also proposed. These findings were collectively called complete RPE and outer retina atrophy or cRORA. In 2017, the Consensus of Atrophy Meeting (CAM) study group proposed a set of criteria to define atrophy on OCT, which included the following: (i) a region of choroidal hypertransmission ≥ 250 µm (ii) a zone of attenuation or disruption of the RPE ≥ 250 µm (iii) overlying photoreceptor degeneration and (iv) the absence of an RPE tear. The hallmarks of STGD1 (and many other macular dystrophies) on OCT are areas of macular RPE, photoreceptor, and choriocapillaris loss ( Figure 3). Over 2000 confirmed or potentially disease-causing variants in the ABCA4 gene have been documented as contributors to STGD1.

The antioxidant properties of RPE melanin may modulate disease severity since studies conducted in albino Abca4 −/− rodents suggest an earlier onset and more severe course of disease than in their pigmented counterparts. Its dysfunction leads to increased accumulation of all-trans and 11-cis retinoids that build up A2E and other bisretinoids in the form of toxic lipofuscin within the RPE. The product of the ABCA4 gene is the ABCA4 protein, an ATP-binding cassette transporter located in the photoreceptor outer segments that transports N-retinyledene-phosphatidylethanolamine and phosphatidylethanolamine. No large population-based studies have been conducted to determine its frequency, but its estimated prevalence ranges between 1:8.000 and 10.000. It is the most common macular inherited retinal disease (IRD). Stargardt disease 1 (STGD1, OMIM #248200) is an autosomal recessive MD caused by homozygous or compound heterozygous variants in the ABCA4 gene (chromosome 1p22) and characterized by the atrophy of the retinal pigment epithelium (RPE) and the loss of photoreceptors.

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