title: Flecks in Recessive Stargardt Disease: Short-Wavelength Autofluorescence, Near-Infrared Autofluorescence, and Optical Coherence Tomography.
abstract: OBJECTIVE
  We evaluated the incongruous observation whereby flecks in recessive Stargardt disease (STGD1) can exhibit increased short-wavelength autofluorescence (SW-AF) that originates from retinal pigment epithelium (RPE) lipofuscin, while near-infrared AF (NIR-AF), emitted primarily from RPE melanin, is usually reduced or absent at fleck positions.
  
  
  METHODS
  Flecks in SW- and NIR-AF images and spectral-domain optical coherence tomography (SD-OCT) scans were studied in 19 STGD1 patients carrying disease-causing ABCA4 mutations. Fleck spatial distribution and progression were recorded in serial AF images.
  
  
  RESULTS
  Flecks observed in SW-AF images typically colocalized with darkened foci in NIR-AF images; the NIR-AF profiles were larger. The decreased NIR-AF signal from flecks preceded apparent changes in SW-AF. Spatiotemporal changes in fleck distribution usually progressed centrifugally, but in one case centripetal expansion was observed. Flecks in SW-AF images corresponded to hyperreflective deposits that progressively traversed photoreceptor-attributable bands in SD-OCT images. Outer nuclear layer (ONL) thickness negatively correlated with expansion of flecks from outer to inner retina.
  
  
  CONCLUSIONS
  In the healthy retina, RPE lipofuscin fluorophores form in photoreceptor cells but are transferred to RPE; thus the SW-AF signal from photoreceptor cells is negligible. In STGD1, NIR-AF imaging reveals that flecks are predominantly hypofluorescent and larger and that NIR-AF darkening occurs prior to heightened SW-AF signal. These observations indicate that RPE cells associated with flecks in STGD1 are considerably changed or lost. Spectral-domain OCT findings are indicative of ongoing photoreceptor cell degeneration. The bright SW-AF signal of flecks likely originates from augmented lipofuscin formation in degenerating photoreceptor cells impaired by the failure of RPE.
authors.affiliation: Department of Ophthalmology Columbia University, New York, New York, United States 2Department of Pathology and Cell Biology, Columbia University, New York, New York, United States.
authors.forename: Janet R
authors.initials: JR
authors.lastname: Sparrow
authors.affiliation: Department of Ophthalmology Columbia University, New York, New York, United States.
authors.forename: Marcela
authors.initials: M
authors.lastname: Marsiglia
authors.affiliation: Department of Ophthalmology Columbia University, New York, New York, United States 2Department of Pathology and Cell Biology, Columbia University, New York, New York, United States.
authors.forename: Rando
authors.initials: R
authors.lastname: Allikmets
authors.affiliation: Department of Ophthalmology Columbia University, New York, New York, United States 2Department of Pathology and Cell Biology, Columbia University, New York, New York, United States.
authors.forename: Stephen
authors.initials: S
authors.lastname: Tsang
authors.affiliation: Department of Ophthalmology Columbia University, New York, New York, United States.
authors.forename: Winston
authors.initials: W
authors.lastname: Lee
authors.affiliation: Department of Ophthalmology Columbia University, New York, New York, United States.
authors.forename: Tobias
authors.initials: T
authors.lastname: Duncker
authors.affiliation: Department of Ophthalmology Columbia University, New York, New York, United States.
authors.forename: Jana
authors.initials: J
authors.lastname: Zernant
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D004596:Electroretinography; D005260:Female; D005451:Fluorescein Angiography / Q000379:methods*; D005654:Fundus Oculi; D006801:Humans; D008268:Macular Degeneration / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D000080362:Stargardt Disease; D041623:Tomography, Optical Coherence / Q000379:methods*; D055815:Young Adult