Progression of intermediate age-related macular degeneration with proliferation and inner retinal migration of hyperreflective foci

Ophthalmology. 2013 May;120(5):1038-45. doi: 10.1016/j.ophtha.2012.10.018. Epub 2013 Jan 23.


Purpose: Drusen and migrating retinal pigment epithelium have been associated with hyperreflective foci (HF) detected by spectral-domain optical coherence tomography (SD-OCT). This study sought to quantify the change in intraretinal HF distribution and its correlation with age-related macular degeneration (AMD) disease progression.

Design: Prospective observational study from the multicenter Age-Related Eye Disease Study 2 (AREDS2) Ancillary SD-OCT Study.

Participants: Patients (n=299) with 1 enrolled eye with intermediate AMD and baseline SD-OCT, followed by SD-OCT imaging at 1-year and 2-year visits.

Methods: The number and location of HF were scored in SD-OCT scans of all 299 eyes. The change in transverse (horizontal) and axial (vertical) distribution of HF in the macula were evaluated with pairwise signed-rank tests. Two-year inner retinal HF migration was determined by the change in HF-weighted axial distribution (AxD) score calculated for each eye. The correlation of HF with SD-OCT features of AMD progression was evaluated with logistic regression analysis.

Main outcome measures: The mean change in number of HF, transverse and axial distribution of HF in the macula, and AxD per eye.

Results: In 299 study eyes, the 2-year increase in the number of HF (P<0.001) and the AxD (P<0.001) per eye represented longitudinal proliferation and shift to inner retinal layers, respectively. Eyes with geographic atrophy (GA) at 2 years were correlated with the presence of baseline HF (P<0.001; odds ratio [OR], 4.72; 95% confidence interval [CI], 2.43-9.80), greater number of baseline HF (P<0.001; OR, 1.61 per HF; 95% CI, 1.32-2.00), and greater baseline AxD (P<0.001; OR, 1.58 per AxD point; 95% CI, 1.29-1.95).

Conclusions: Proliferation and inner retinal migration of SD-OCT HF occurred during follow-up in eyes with intermediate AMD. These characteristics were associated with greater incidence of GA at year 2; therefore, SD-OCT HF proliferation and migration may serve as biomarkers for AMD progression.

Financial disclosure(s): Proprietary or commercial disclosure may be found after the references.

Trial registration: NCT00734487.

Publication types

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

MeSH terms

  • Aged
  • Cell Proliferation
  • Cohort Studies
  • Disease Progression
  • Humans
  • Logistic Models
  • Macula Lutea / pathology
  • Macular Degeneration / pathology*
  • Prospective Studies
  • Retinal Pigment Epithelium / pathology*
  • Tomography, Optical Coherence

Associated data