New findings from a study published in Ophthalmology sought to characterize the genotype and phenotype of patients with late-onset Stargardt’s disease (STGD1).
Talk about the study.
In this retrospective case series, investigators included 21 STGD1 patients with an age at onset of >45 years and >1 rare variant in the ABCA4 gene.
How were the primary outcomes measured?
The primary outcome measures were evaluated using:
- Age at onset
- Best-corrected visual acuity (BCVA)
- Fundus photography
- Fluorescein angiography (FA)
- Spectral-domain optical coherence tomography (OCT)
- Fundus autofluorescence (FAF) imaging
- ABCA4 mutations
- Genotype-phenotype correlation
What about genetic analyses?
The study also included analysis of the ABCA4 gene using microarray analysis, sequencing, and multiplex ligation-dependent probe amplification. The PRPH2 and CFH genes were also sequenced.
Tell me more about the participants.
The mean age at onset was 55 years (range: 45-72 years) and seven patients were diagnosed without visual symptoms.
The VA was >20/40 in 24 eyes of 14 patients (59%) due to foveal sparing.
The research team discovered on fundoscopic exam that:
- 15 patients had flavimaculatus flecks
- 3 patients had small flecks surrounding mottled foveal changes
- 2 patients had extensive chorioretinal atrophy
- 1 patient had small yellowish spots in the macula
On FAF, the fundus flecks demonstrated increased autofluorescence, and on FA the choroidal background fluorescence was obscured in 16 patients (80%).
After performing genetic analyses, investigators found:
- 11 patients had a single heterozygous ABCA4 variant (52%)
- 8 patients had two compound heterozygous variants (38%)
- 2 patients had a homozygous variant (10%)
No PRPH2 or CFH mutations were detected.
According to the study authors, “Atrophic lesions in the late-onset disease subtype grow more outwards than centrally, leaving the fovea intact longer.”
“While the majority of the late-onset patients have well-demarcated retinal pigment epithelium (RPE) atrophy, a third present with mottled atrophy, i.e., poorly demarcated questionably decreased autofluorescent atrophy,” they stated.
Late-onset STGD1 is on the milder end of the spectrum of retinal dystrophies caused by ABCA4 mutations; as a result, this phenotype may be caused by one or two ABCA4 variants.
Additionally, visual acuity is often preserved in these patients due to foveal sparing.
What about differential diagnoses?
The study authors noted that while the differential diagnosis between late-onset STGD1 and age-related macular degeneration (AMD) may be difficult, using multimodal imaging—such as color fundus photography, FAF, and OCT—is sufficient to make a distinction between them.
If imaging is not enough to distinguish the two, ABCA4 genetic analyses will ultimately tell the difference.