September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Stargardt Disease Expression on a Background of Low Lipofuscin: The Impact of the p.G1961E Mutation of ABCA4
Author Affiliations & Notes
  • Winston Lee
    Ophthalmology, Columbia University, New York , New York, United States
  • Kalev Noupuu
    Ophthalmology, Columbia University, New York , New York, United States
    Ophthalmology, Tartu University, Tartu, Estonia
  • Jana Zernant
    Ophthalmology, Columbia University, New York , New York, United States
  • Kaspar Schuerch
    Ophthalmology, Columbia University, New York , New York, United States
  • Peter Gouras
    Ophthalmology, Columbia University, New York , New York, United States
  • Stephen H. Tsang
    Ophthalmology, Columbia University, New York , New York, United States
    Pathology & Cell Biology, Columbia University, New York, New York, United States
  • Janet R Sparrow
    Ophthalmology, Columbia University, New York , New York, United States
    Pathology & Cell Biology, Columbia University, New York, New York, United States
  • Rando Allikmets
    Ophthalmology, Columbia University, New York , New York, United States
    Pathology & Cell Biology, Columbia University, New York, New York, United States
  • Footnotes
    Commercial Relationships   Winston Lee, None; Kalev Noupuu, None; Jana Zernant, None; Kaspar Schuerch, None; Peter Gouras, None; Stephen Tsang, None; Janet Sparrow, None; Rando Allikmets, None
  • Footnotes
    Support  NEI EY021163; NEI EY019861
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 2689. doi:
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      Winston Lee, Kalev Noupuu, Jana Zernant, Kaspar Schuerch, Peter Gouras, Stephen H. Tsang, Janet R Sparrow, Rando Allikmets; Stargardt Disease Expression on a Background of Low Lipofuscin: The Impact of the p.G1961E Mutation of ABCA4. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2689.

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      © 2017 Association for Research in Vision and Ophthalmology.

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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.

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