title: Cone and rod loss in Stargardt disease revealed by adaptive optics scanning light ophthalmoscopy.
abstract: OBJECTIVE
  Stargardt disease (STGD1) is characterized by macular atrophy and flecks in the retinal pigment epithelium. The causative ABCA4 gene encodes a protein localizing to photoreceptor outer segments. The pathologic steps by which ABCA4 mutations lead to clinically detectable retinal pigment epithelium changes remain unclear. We investigated early STGD1 using adaptive optics scanning light ophthalmoscopy.
  
  
  METHODS
  Adaptive optics scanning light ophthalmoscopy imaging of 2 brothers with early STGD1 and their unaffected parents was compared with conventional imaging. Cone and rod spacing were increased in both patients (P < .001) with a dark cone appearance. No foveal cones were detected in the older brother. In the younger brother, foveal cones were enlarged with low density (peak cone density, 48.3 × 103 cones/mm2). The ratio of cone to rod spacing was increased in both patients, with greater divergence from normal approaching the foveal center, indicating that cone loss predominates centrally and rod loss increases peripherally. Both parents had normal photoreceptor mosaics. Genetic testing revealed 3 disease-causing mutations.
  
  
  CONCLUSIONS
  This study provides in vivo images of rods and cones in STGD1. Although the primary clinical features of STGD1 are retinal pigment epithelial lesions, adaptive optics scanning light ophthalmoscopy reveals increased cone and rod spacing in areas that appear normal in conventional images, suggesting that photoreceptor loss precedes clinically detectable retinal pigment epithelial disease in STGD1.
authors.affiliation: Center for Visual Science, University of Rochester, Rochester, New York.
authors.forename: Hongxin
authors.initials: H
authors.lastname: Song
authors.affiliation: Center for Visual Science, University of Rochester, Rochester, New York.
authors.forename: Ethan A
authors.initials: EA
authors.lastname: Rossi
authors.affiliation: Flaum Eye Institute, University of Rochester, Rochester, New York.
authors.forename: Lisa
authors.initials: L
authors.lastname: Latchney
authors.affiliation: Flaum Eye Institute, University of Rochester, Rochester, New York.
authors.forename: Angela
authors.initials: A
authors.lastname: Bessette
authors.affiliation: Department of Ophthalmology and Visual Sciences, Carver College of Medicine, Iowa City, Iowa4Stephen A. Wynn Institute for Vision Research, University of Iowa, Iowa City5Howard Hughes Medical Institute, University of Iowa, Iowa City.
authors.forename: Edwin
authors.initials: E
authors.lastname: Stone
authors.affiliation: Center for Visual Science, University of Rochester, Rochester, New York6The Institute of Optics, University of Rochester, Rochester, New York.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Hunter
authors.affiliation: Center for Visual Science, University of Rochester, Rochester, New York6The Institute of Optics, University of Rochester, Rochester, New York.
authors.forename: David R
authors.initials: DR
authors.lastname: Williams
authors.affiliation: Center for Visual Science, University of Rochester, Rochester, New York2Flaum Eye Institute, University of Rochester, Rochester, New York.
authors.forename: Mina
authors.initials: M
authors.lastname: Chung
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D005260:Female; D006801:Humans; D008268:Macular Degeneration / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics; D008297:Male; D009154:Mutation; D009887:Ophthalmoscopy / Q000379:methods; D010375:Pedigree; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology*; D000080362:Stargardt Disease; D041623:Tomography, Optical Coherence; D014792:Visual Acuity
chemical_list: C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters