title: VISUALIZING RETINAL PIGMENT EPITHELIUM PHENOTYPES IN THE TRANSITION TO GEOGRAPHIC ATROPHY IN AGE-RELATED MACULAR DEGENERATION.
abstract: OBJECTIVE
  To inform the interpretation of clinical optical coherence tomography and fundus autofluorescence imaging in geographic atrophy (GA) of age-related macular degeneration by determining the distribution of retinal pigment epithelium (RPE) phenotypes in the transition from health to atrophy in donor eyes.
  
  
  METHODS
  In RPE-Bruch membrane flat mounts of two GA eyes, the terminations of organized RPE cytoskeleton and autofluorescent material were compared. In high-resolution histological sections of 13 GA eyes, RPE phenotypes were assessed at ±500 and ±100 μm from the descent of the external limiting membrane (ELM) toward Bruch membrane. The ELM descent was defined as curved, reflected, or oblique in shape. Thicknesses of RPE, basal laminar deposit (BLamD), and RPE plus BLamD were measured.
  
  
  RESULTS
  A border of atrophy that can be precisely delimited is the ELM descent, as opposed to the termination of the RPE layer itself, because of dissociated RPE in the atrophic area. Approaching the ELM descent, the percentage of abnormal RPE morphologies increases, the percentage of age-normal cells decreases, overall RPE thickens, and BLamD does not thin. The combination of RPE plus BLamD is 19.7% thicker at -100 μm from the ELM descent than that at -500 μm (23.1 ± 10.7 μm vs. 19.3 ± 8.2 μm; P = 0.05).
  
  
  CONCLUSIONS
  The distribution of RPE phenotypes at the GA transition supports the idea that these morphologies represent defined stages of a degeneration sequence. The idea that RPE dysmorphia including rounding and stacking helps explain variable autofluorescence patterns in GA is supported. The ELM descent and RPE plus BLamD thickness profile may have utility as spectral domain optical coherence tomography metrics in clinical trials.
authors.affiliation: *Department of Ophthalmology, University of Alabama School of Medicine, Birmingham, Alabama; †Eye Clinic, Department of Clinical Science "Luigi Sacco," Sacco Hospital, University of Milan, Milan, Italy; ‡Department of Ophthalmology, University Hospital Würzburg, Würzburg, Germany; §Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama; and ¶Vitreous Retina Macula Consultants of New York.
authors.forename: Emma C
authors.initials: EC
authors.lastname: Zanzottera
authors.forename: Thomas
authors.initials: T
authors.lastname: Ach
authors.forename: Carrie
authors.initials: C
authors.lastname: Huisingh
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Messinger
authors.forename: Richard F
authors.initials: RF
authors.lastname: Spaide
authors.forename: Christine A
authors.initials: CA
authors.lastname: Curcio
mesh_terms: D000369:Aged, 80 and over; D016570:Bruch Membrane / Q000000981:diagnostic imaging; D002102:Cadaver; D005260:Female; D005451:Fluorescein Angiography / Q000379:methods; D057092:Geographic Atrophy / Q000000981:diagnostic imaging*; D006801:Humans; D008268:Macular Degeneration / Q000000981:diagnostic imaging; D008297:Male; D064847:Multimodal Imaging / Q000379:methods; D010641:Phenotype; D055213:Retinal Pigment Epithelium / Q000000981:diagnostic imaging*; D041623:Tomography, Optical Coherence / Q000379:methods