title: REFRACTILE DRUSEN: Clinical Imaging and Candidate Histology.
abstract: OBJECTIVE
  To evaluate eyes with refractile drusen using clinical imaging and to identify candidate histologic correlates of refractile drusen.
  
  
  METHODS
  Refractile drusen were defined as drusenoid material containing small refractile spherules. Retrospective analysis of color, autofluorescence, and spectral domain optical coherence tomography images of eyes with refractile drusen was performed to characterize the morphology and topography of these lesions. Macular sections from donor eyes were processed with a von Kossa stain for calcium phosphate and viewed by light microscopy. Punches of retinal pigment epithelium-choroid from donors with geographic atrophy were prepared for transmission electron microscopy.
  
  
  RESULTS
  Fundus findings of 14 eyes of 10 patients with age-related macular degeneration (age, 82.9 ± 5.6 years) were evaluated. A generalized loss of autofluorescence signal over refractile drusen appeared to spread over a larger area than each druse, for drusen located centrally. By color fundus photography, refractile drusen showed corresponding depigmentation around drusen that were located in the center of the macula. Optical coherence tomography imaging of refractile drusen showed hyperreflective dots. In the histologic specimens, drusen contained many small spherules rich in calcium phosphate. Ultrastructural examination of the spherules showed complex assemblies consisting of concentric shells containing thin layers of calcium.
  
  
  CONCLUSIONS
  Refractile drusen appear to be a stage of drusen regression marked by loss of retinal pigment epithelium, thus contributing to the development of geographic atrophy. Calcium-containing spherules appear to account for the glistening appearance.
authors.affiliation: *Vitreous Retina Macula Consultants of New York and LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear, and Throat Hospital, New York, New York; †Department of Ophthalmology, University of Alabama, Birmingham, Alabama; and ‡Department of Ophthalmology and Visual Sciences, Wynn Institute for Vision Research, University of Iowa, Iowa City, Iowa.
authors.forename: Mihoko
authors.initials: M
authors.lastname: Suzuki
authors.forename: Christine A
authors.initials: CA
authors.lastname: Curcio
authors.forename: Robert F
authors.initials: RF
authors.lastname: Mullins
authors.forename: Richard F
authors.initials: RF
authors.lastname: Spaide
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002114:Calcinosis / Q000378:metabolism / Q000473:pathology*; D002130:Calcium Phosphates / Q000378:metabolism; D002829:Choroid / Q000473:pathology; D005260:Female; D057092:Geographic Atrophy / Q000473:pathology*; D006801:Humans; D008297:Male; D046529:Microscopy, Electron, Transmission; D061848:Optical Imaging; D015593:Retinal Drusen / Q000378:metabolism / Q000473:pathology*; D055213:Retinal Pigment Epithelium / Q000473:pathology; D012189:Retrospective Studies; D018874:Spheroids, Cellular / Q000378:metabolism / Q000648:ultrastructure*; D014019:Tissue Donors; D041623:Tomography, Optical Coherence
chemical_list: D002130:Calcium Phosphates