title: Centrifugal expansion of fundus autofluorescence patterns in Stargardt disease over time.
abstract: OBJECTIVE
  To study the longitudinal changes in autofluorescence in Stargardt disease to reveal aspects of disease progression not previously evident. Changes in autofluorescence reflect changing fluorophore compositions of lipofuscin and melanin in retinal pigment epithelial cells, which has been hypothesized to contribute to Stargardt disease pathogenesis.
  
  
  METHODS
  We examined the temporospatial patterns of fundus autofluorescence with excitation at both 488 nm (standard fundus autofluorescence) and 795 nm (near-infrared autofluorescence) in a longitudinal case series involving 8 eyes of 4 patients (range of follow-up, 11-57 months; mean, 39 months). Image processing was performed to analyze spatial and temporal cross-modality associations.
  
  
  RESULTS
  Longitudinal fundus autofluorescence imaging of fleck lesions revealed hyperautofluorescent lesions that extended in a centrifugal direction from the fovea with time. Patterns of spread were nonrandom and followed a radial path that left behind a trail of diminishing autofluorescence. Longitudinal near-infrared autofluorescence imaging also demonstrated centrifugal lesion spread but with fewer hyperautofluorescent lesions, suggestive of more transient hyperautofluorescence and more rapid decay at longer wavelengths. Fundus autofluorescence and near-infrared autofluorescence abnormalities were spatially correlated with each other, and together they reflect systematic progressions in fleck distribution and fluorophore composition occurring during the natural history of the disease.
  
  
  CONCLUSIONS
  Stargardt disease fleck lesions do not evolve randomly in location but instead follow consistent patterns of radial expansion and a systematic decay of autofluorescence that reflect changing lipofuscin and melanin compositions in retinal pigment epithelial cells. These progressive foveal-to-peripheral changes are helpful in elucidating molecular and cellular mechanisms underlying Stargardt disease and may constitute potential outcome measures in clinical trials.
authors: Division of Epidemiology and Clinical Research, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA. cukrasc@nei.nih.gov
authors: Catherine A
authors: CA
authors: Cukras
authors: Wai T
authors: WT
authors: Wong
authors: Rafael
authors: R
authors: Caruso
authors: Denise
authors: D
authors: Cunningham
authors: Wadih
authors: W
authors: Zein
authors: Paul A
authors: PA
authors: Sieving
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000328:Adult; D001284:Atrophy; D002648:Child; D018450:Disease Progression; D005260:Female; D005451:Fluorescein Angiography; D005500:Follow-Up Studies; D005654:Fundus Oculi; D006801:Humans; D008062:Lipofuscin / Q000378:metabolism; D008268:Macular Degeneration / Q000151:congenital / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D008543:Melanins / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000378:metabolism / Q000473:pathology*; D012189:Retrospective Studies; D000080362:Stargardt Disease; D013997:Time Factors
chemical_list: C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters; D008062:Lipofuscin; D008543:Melanins