Stargardt Disease Expression on a Background of Low Lipofuscin: The Impact of the p.G1961E Mutation of ABCA4

Abstract

Purpose : 488nm autofluorescence images and spectral domain-optical coherence tomography scans were analyzed in 195 patients harboring two disease-causing ABCA4 mutations. The cohort was divided into two groups: those with at least one p.G1961E allele (G, n=61) and those with all other ABCA4 mutation combinations (N, n=134).

Methods : A longitudinal and cross-sectional analysis of autofluorescence images and spectral domain-optical coherence tomography scans was conducted in 195 patients harboring two disease-causing ABCA4 mutations. The cohort was divided into two groups: those with at least one p.G1961E allele (G, n=61) and those with all other ABCA4 mutation combinations (N, n=134).

Results : Groups were age-matched (G, mean=37.4, range=5-79; N, mean=37.9, range=8-83). Fleck distributions were different between groups. A proportion of group G patients exhibited no flecks (28%) or flecks that were distributed and morphologically “lesion-centric” (confined to/and along the contour of the central lesion). Flecks in group N were present in almost all patients (96%), were comparatively more advanced and evenly distributed across the posterior pole. Fleck severity and distribution in group G, but not N, increased with age. Incidence of geographic atrophy (GA) was lower in group G (26%) but measured area increased with fleck severity and age, while GA was evident in a majority of group N (71%) to a more varying extent. GA area never extended beyond the macula in group G while 37% of group N exhibited extensive atrophy across the posterior pole. Group N lesions were often multifocal or contained small “satellite” lesions peripherally that expanded and coalesced at differing rates (mean=1.84 mm²/yr, SD=1.84). Single, well-defined lesions were observed in all group G patients which expanded at a more consistent rate (mean=0.74 mm²/yr, SD=0.55).

Conclusions : STGD1 expression in patients with the p.G1961E allele is characterized by a focal lesion that progresses to a single, steadily expanding area of GA with lesion-centric flecks. Significant lipofuscin accumulation in all other ABCA4 mutation combinations results in the earlier widespread development of flecks which resorb and progress as GA lesions. Over time, these non-central or “satellite” lesions expand and coalesce across the posterior pole.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.