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Cone structure in subjects with known genetic relative risk for AMD. Optom Vis Sci 2014 Aug;91(8):939-49 PMID: 25014365 PMCID: PMC4111779

Pubmed ID



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.

Author List

Land ME, Cooper RF, Young J, Berg E, Kitchner T, Xiang Q, Szabo A, Ivacic LC, Stepien KE, Page CD, Carroll J, Connor T Jr, Brilliant M


Joseph J. Carroll PhD Director, Professor in the Ophthalmology and Visual Sciences department at Medical College of Wisconsin
Megan E. Land MD Staff Physician in the Multi-Specialty department at Medical College of Wisconsin
Aniko Szabo PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin


2-s2.0-84905121542   6 Citations

MESH terms used to index this publication - Major topics in bold

Cell Count
Complement Factor B
Complement Factor H
Genetic Predisposition to Disease
High-Temperature Requirement A Serine Peptidase 1
Macular Degeneration
Membrane Proteins
Middle Aged
Nerve Tissue Proteins
Polymerase Chain Reaction
Polymorphism, Single Nucleotide
Retinal Cone Photoreceptor Cells
Risk Factors
Serine Endopeptidases
Tomography, Optical Coherence
Visual Acuity
Visual Field Tests
jenkins-FCD Prod-299 9ef562391eceb2b8f95265c767fbba1ce5a52fd6