title: Cone structure in subjects with known genetic relative risk for AMD.
abstract: OBJECTIVE
  Utilize high-resolution imaging to examine retinal anatomy in patients with known genetic relative risk (RR) for developing age-related macular degeneration (AMD).
  
  
  METHODS
  Forty asymptomatic subjects were recruited (9 men, 31 women; age range, 51 to 69 years; mean age, 61.4 years). Comprehensive eye examination, fundus photography, and high-resolution retinal imaging using spectral domain optical coherence tomography and adaptive optics were performed on each patient. Genetic RR scores were developed using an age-independent algorithm. Adaptive optics scanning light ophthalmoscope images were acquired in the macula extending to 10 degrees temporal and superior from fixation and were used to calculate cone density in up to 35 locations for each subject.
  
  
  RESULTS
  Relative risk was not significantly predictive of fundus grade (p = 0.98). Only patients with a high RR displayed drusen on Cirrus or Bioptigen OCT. Compared to an eye with a grade of 0, an eye with a fundus grade equal to or greater than 1 had a 12% decrease in density (p < 0.0001) and a 5% increase in spacing (p = 0.0014). No association between genetic RR and either cone density (p = 0.435) or spacing (p = 0.538) was found. Three distinct adaptive optics scanning light ophthalmoscope phenotypical variations of photoreceptor appearance were noted in patients with grade 1 to 3 fundi. These included variable reflectivity of photoreceptors, decreased waveguiding, and altered photoreceptor mosaic overlying drusen.
  
  
  CONCLUSIONS
  Our data demonstrate the potential of multimodal assessment in the understanding of early anatomical changes associated with AMD. Adaptive optics scanning light ophthalmoscope imaging reveals a decrease in photoreceptor density and increased spacing in patients with grade 1 to 3 fundi, as well as a spectrum of photoreceptor changes, ranging from variability in reflectivity to decreased density. Future longitudinal studies are needed in genetically characterized subjects to assess the significance of these findings with respect to the development and progression of AMD.
authors.affiliation: *MD †BS ‡PhD §MS Department of Ophthalmology (MEL, JY, KES, JC, TC), Division of Biostatistics, Institute for Health and Society (QX, AS, CDP), Medical College of Wisconsin, Milwaukee, Wisconsin; Department of Biomedical Engineering, Marquette University, Milwaukee, Wisconsin (RFC); Department of Computer Sciences, University of Wisconsin-Madison, Madison, Wisconsin (EB); and Center for Human Genetics (TK, MB), Core Laboratory (LCI), Marshfield Clinic Research Foundation, Marshfield, Wisconsin.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Land
authors.forename: Robert F
authors.initials: RF
authors.lastname: Cooper
authors.forename: Jonathon
authors.initials: J
authors.lastname: Young
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Berg
authors.forename: Terrie
authors.initials: T
authors.lastname: Kitchner
authors.forename: Qun
authors.initials: Q
authors.lastname: Xiang
authors.forename: Aniko
authors.initials: A
authors.lastname: Szabo
authors.forename: Lynn C
authors.initials: LC
authors.lastname: Ivacic
authors.forename: Kimberly E
authors.initials: KE
authors.lastname: Stepien
authors.forename: C David
authors.initials: CD
authors.lastname: Page
authors.forename: Joseph
authors.initials: J
authors.lastname: Carroll
authors.forename: Thomas
authors.initials: T
authors.lastname: Connor
authors.forename: Murray
authors.initials: M
authors.lastname: Brilliant
mesh_terms: D000368:Aged; D002452:Cell Count; D011415:Complement Factor B / Q000235:genetics; D017242:Complement Factor H / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D008049:Lipase / Q000235:genetics; D008268:Macular Degeneration / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D009887:Ophthalmoscopy; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology*; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000235:genetics; D041623:Tomography, Optical Coherence; D014792:Visual Acuity; D058609:Visual Field Tests
chemical_list: C493495:CFH protein, human; C482591:KIDINS220 protein, human; C504173:LIPC protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D017242:Complement Factor H; D008049:Lipase; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases; D011415:Complement Factor B