Comprehensive study on late-onset Stargardt: disease characteristics, genetics and progression

Abstract

Purpose : Late-onset Stargardt disease (STGD1) is a subtype of STGD1, defined by an age of onset ≥ 45 years. Knowledge of the natural history of STGD1 subtypes is essential for the design of upcoming clinical trials. This study aims to describe disease characteristics, the genetic background and disease progression of late-onset STGD1 patients and highlights the differences from geographic atrophy (GA) as part of age-related macular degeneration (AMD).

Methods : Retrospective study in 71 patients with late-onset Stargardt. Medical files were reviewed for clinical data including age of onset, initial symptoms, best corrected visual acuity (BCVA). In addition, a quantitative and qualitative assessment of autofluorescence (FAF) images and optical-coherence tomography (OCT) scans was performed.

Results : Median age of onset was 55.0 years (IQR 50.0-61.0). Median age at diagnosis was 59.0 (IQR 53.0-64.5). A combination of one mild and one severe variant in ABCA4 was the most common found genotype (n=46; 64.8%). No combination of two severe variants was found. All patients presented with flecks on fundus autofluorescence imaging at first presentation. 33.3% of the eyes had foveal sparing with atrophy encircling the fovea by ≥180 degrees at baseline. No atrophy was present in 6 eyes (6.7%). 21.1% had atrophy with foveal involvement. A total of 19 eyes progressed from foveal sparing to foveal involvement. This development took a median time of 3.9 years (IQR 2.5-6.1). Time-to-event analysis show a median time of 15.4 years (95% CI 11.1-19.6) since onset for foveal involvement in patients with foveal sparing. The median visual acuity decline was -0.03 Snellen decimals per year (IQR -0.07-0.00). Median atrophy radius growth was 0.097 mm/year (IQR 0.042-0.156) for definitely decreased autofluorescence (DDAF) and 0.098 mm/year (IQR 0.054-0.141) for total decreased atrophy.

Conclusions : Late-onset STGD1 is a subtype of STGD1 characterized by a milder genotype and a milder phenotype with preserved central vision owing to the typical foveal sparing atrophy present in almost all late-onset STGD1 patients. Misdiagnosis with AMD should be avoided to prevent potential complications of futile invasive treatments. In addition, correct diagnosis lends late-onset STGD1 patients the opportunity to participate in potential beneficial therapeutic trials for STGD1.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.