Cone structure in subjects with known genetic relative risk for AMD

Optom Vis Sci. 2014 Aug;91(8):939-49. doi: 10.1097/OPX.0000000000000323.


Purpose: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cell Count
  • Complement Factor B / genetics
  • Complement Factor H / genetics
  • Female
  • Genetic Predisposition to Disease*
  • High-Temperature Requirement A Serine Peptidase 1
  • Humans
  • Lipase / genetics
  • Macular Degeneration / diagnosis*
  • Macular Degeneration / genetics
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Nerve Tissue Proteins / genetics
  • Ophthalmoscopy
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide
  • Retinal Cone Photoreceptor Cells / pathology*
  • Risk Factors
  • Serine Endopeptidases / genetics
  • Tomography, Optical Coherence
  • Visual Acuity
  • Visual Field Tests


  • CFH protein, human
  • KIDINS220 protein, human
  • LIPC protein, human
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Complement Factor H
  • Lipase
  • High-Temperature Requirement A Serine Peptidase 1
  • HTRA1 protein, human
  • Serine Endopeptidases
  • Complement Factor B