Study of Late-Onset Stargardt Type 1 Disease

PurposeLate-onset Stargardt disease (STGD1) is a subtype of STGD1, defined by an age of onset ≥ 45 years. We describe the disease characteristics, underlying genetics and disease progression of late-onset STGD1 patients and highlight the differences from geographic atrophy.DesignRetrospective cohort studySubjects71 patients with late-onset STGD1MethodsMedical files were reviewed for clinical data including age of onset, initial symptoms, and best corrected visual acuity (BCVA). A quantitative and qualitative assessment of retinal pigment epithelium atrophy (RPE) was performed on fundus autofluorescence (FAF) images and optical-coherence tomography (OCT) scans.Main Outcome MeasuresAge of onset, genotype, BCVA, RPE atrophy growth rates on FAF images, and loss of external limiting membrane, ellipsoid zone, and RPE on OCT.ResultsMedian age of onset was 55.0 years (range 45–82). A combination of a mild and severe variant in ABCA4 was the most commonly found genotype (n = 49; 69.0%). The most frequent allele c.5603A>T (p.Asn1868Ile) was present in 43 of 71 patients (60.6%). No combination of two severe variants was found. All patients presented with flecks on FAF imaging at first presentation. Foveal sparing atrophy was present in 33.3% of the eyes, while atrophy with foveal involvement was found in 21.1%. Extrafoveal atrophy was present in 38.9% of the eyes, and no atrophy in 6.7%. Time-to-event curves showed a median duration of 15.4 years (95% CI 11.1–19.6) from onset to foveal involvement. The median visual acuity decline was -0.03 Snellen decimals per year (IQR -0.07–0.00; 0.03 logMAR). Median atrophy growth was 0.590 mm2/year (IQR 0.046–1.641) for definitely decreased autofluorescence and 0.650 mm2/year (IQR 0.299–1.729) for total decreased autofluorescence.ConclusionsLate-onset STGD1 is a subtype of STGD1 with most commonly one severe and one mild ABCA4 variant. The general patient presents with typical fundus flecks and develops retinal atrophy in a foveal sparing pattern, resulting in a preserved central vision. Misdiagnosis with age-related macular degeneration should be avoided to prevent futile invasive treatments with potential complications. In addition, correct diagnosis lends late-onset STGD1 patients the opportunity to participate in potentially beneficial therapeutic trials for STGD1.

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