Retinal Precursors and the Development of Geographic Atrophy in Age-Related Macular Degeneration
Received 13 April 2007; received in revised form 15 August 2007; accepted 15 August 2007. published online 05 November 2007.
Purpose
To determine specific retinal precursor lesions and sequence of events preceding the onset of geographic atrophy (GA) in eyes with age-related macular degeneration (AMD).
Design
Retrospective review.
Participants
All participants in the Age-Related Eye Disease Study (AREDS) at 2 clinical centers (Devers Eye Institute, Portland, Oregon, and University of Wisconsin, Madison, Wisconsin) in whom GA initially appeared in at least one eye a minimum of 4 years after the baseline study visit.
Methods
All stereoscopic fundus photographs taken before the appearance of GA in the involved (study) eye were reviewed. Fundus features at the site of future GA were graded and recorded. Three graders reviewed photographs, with independent grading and adjudication by mutual agreement. Features graded included drusen (classified by size and confluence), focal hyperpigmentation, hypopigmentation, and refractile deposits. The time between first appearance of these features and initial appearance of GA was recorded.
Main Outcome Measure
Appearance of GA.
Results
Of all AREDS participants at the 2 sites, 95 eyes of 77 developed GA at least 4 years after entrance into the study. Average time from baseline to initial appearance of GA was 6.6 years (range, 4–11). Drusen were found in 100% of eyes at the site of later developing GA, drusen >125 μm in diameter in 96% of eyes, confluent drusen in 94%, hyperpigmentation in 96%, drusen > 250 μm in 83%, hypopigmentation in 82%, and refractile deposits in 23%. Time from lesion appearance to onset of GA varied by lesion type, ranging from 5.9 years for drusen confluence to 2.5 years for hypopigmentation or refractile deposits. Lesions generally followed a uniform sequence of appearance.
Conclusions
By focusing on the location of initial GA appearance and then retrospectively analyzing prior photographs, we were able to identify specific precursor lesions and the most common sequence of events leading to GA formation in eyes with AMD. The progression was usually characterized by large drusen formation and development of hyperpigmentation, followed by regression of drusen, appearance of hypopigmentation, and ultimately development of GA, sometimes preceded by the appearance of refractile deposits.
Available online: November 5, 2007.
1Devers Eye Institute, Legacy Good Samaritan Hospital and Medical Center, Portland, Oregon.
2Macular Degeneration Center, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon.
3National Eye Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland.
4Fundus Photograph Reading Center, Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine, Madison, Wisconsin.
5Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
6Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine, Madison, Wisconsin.
Correspondence to Michael L. Klein, MD, Casey Eye Institute, 3375 SW Terwilliger Boulevard, Portland, OR 97239.
Manuscript no. 2007-505.
Supported by contracts from the National Eye Institute and in part by an unrestricted grant to Casey Eye Institute from Research to Prevent Blindness, New York, New York.
The authors have no proprietary interest in any materials or products discussed herein.
ABSTRACT