Peripheral Retinal Changes Associated with Age-Related Macular Degeneration in the Age-Related Eye Disease Study 2: Age-Related Eye Disease Study 2 Report Number 12 by the Age-Related Eye Disease Study 2 Optos PEripheral RetinA (OPERA) Study Research Group

Ophthalmology. 2017 Apr;124(4):479-487. doi: 10.1016/j.ophtha.2016.12.004. Epub 2017 Jan 12.


Purpose: To compare rates of peripheral retinal changes in Age-Related Eye Disease Study 2 (AREDS2) participants with at least intermediate age-related macular degeneration (AMD) with control subjects without intermediate age-related changes (large drusen).

Design: Cross-sectional evaluation of clinic-based patients enrolled in AREDS2 and a prospective study.

Participants: Participants from prospective studies.

Methods: The 200° pseudocolor and fundus autofluorescence (FAF) images were captured on the Optos 200 Tx Ultrawide-field device (Optos, Dunfermline, Scotland) by centering on the fovea and then steering superiorly and inferiorly. The montaged images were graded at a reading center with the images divided into 3 zones (zone 1 [posterior pole], zone 2 [midperiphery], and zone 3 [far periphery]) to document the presence of peripheral lesions.

Main outcome measures: Peripheral retinal lesions: drusen, hypopigmentary/hyperpigmentary changes, reticular pseudodrusen, senile reticular pigmentary changes, cobblestone degeneration, and FAF abnormalities.

Results: A total of 484 (951 eyes) AREDS2 participants with AMD (cases) and 89 (163 eyes) controls without AMD had gradable color and FAF images. In zones 2 and 3, neovascularization and geographic atrophy (GA) were present, ranging from 0.4% to 6% in eyes of cases, respectively, and GA was present in 1% of eyes of controls. Drusen were detected in 97%, 78%, and 64% of eyes of cases and 48%, 21%, and 9% of eyes of controls in zones 2 and 3 superior and 3 inferior, respectively (P < 0.001 for all). Peripheral reticular pseudodrusen were seen in 15%. Senile reticular pigmentary change was the predominant peripheral change seen in 48% of cases and 16% of controls in zone 2 (P < 0.001). Nonreticular pigment changes were less frequent in the periphery than in the posterior pole (46% vs. 76%) and negligible in controls.

Conclusions: Peripheral retinal changes are more prevalent in eyes with AMD than in control eyes. Drusen are seen in a majority of eyes with AMD in both the mid and far periphery, whereas pigment changes and features of advanced AMD are less frequent. Age-related macular degeneration may be more than a "macular" condition but one that involves the entire retina. Future longitudinal studies of peripheral changes in AMD and their impact on visual function may contribute to understanding AMD pathogenesis.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cross-Sectional Studies
  • Docosahexaenoic Acids / administration & dosage
  • Eicosapentaenoic Acid / administration & dosage
  • Female
  • Fluorescein Angiography
  • Geographic Atrophy / diagnosis*
  • Geographic Atrophy / drug therapy
  • Humans
  • Lutein / administration & dosage
  • Male
  • Middle Aged
  • Optical Imaging
  • Prospective Studies
  • Retina / pathology
  • Retinal Drusen / diagnosis*
  • Retinal Drusen / drug therapy
  • Retinal Pigment Epithelium / pathology*
  • Tomography, Optical Coherence
  • Wet Macular Degeneration / diagnosis*
  • Wet Macular Degeneration / drug therapy
  • Zeaxanthins / administration & dosage


  • Zeaxanthins
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid
  • Lutein