Ophthalmology
Volume 117, Issue 8 , Pages 1554-1559.e1, August 2010

Progression of Geographic Atrophy and Genotype in Age-Related Macular Degeneration

  • Michael L. Klein, MD

      Affiliations

    • Macular Degeneration Center, Casey Eye Institute, Oregon Health & Science University, and Devers Eye Institute, Portland, Oregon
    • Corresponding Author InformationCorrespondence: Michael L. Klein, MD, Casey Eye Institute, 3375 SW Terwilliger Blvd., Portland, OR 97239
    • ,
  • Frederick L. Ferris III, MD

      Affiliations

    • National Eye Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland
    • ,
  • Peter J. Francis, MD, PhD

      Affiliations

    • Macular Degeneration Center, Casey Eye Institute, Oregon Health & Science University, and Devers Eye Institute, Portland, Oregon
    • ,
  • Anne S. Lindblad, PhD

      Affiliations

    • The EMMES Corporation, Rockville, Maryland
    • ,
  • Emily Y. Chew, MD

      Affiliations

    • National Eye Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland
    • ,
  • Sara C. Hamon, PhD

      Affiliations

    • Laboratory of Statistical Genetics, Rockefeller University, New York, New York
    • ,
  • Jurg Ott, PhD

      Affiliations

    • Laboratory of Statistical Genetics, Rockefeller University, New York, New York
    • Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China

Received 6 May 2009; received in revised form 8 December 2009; accepted 8 December 2009. published online 09 April 2010.

Available online: April 9, 2010.

Purpose

We sought to determine whether genotype is associated with rate of growth of geographic atrophy (GA) in eyes with age-related macular degeneration (AMD).

Design

Prospective analysis of participants in a randomized controlled clinical trial.

Participants

We included 114 eyes of 114 participants in the Age-Related Eye Disease Study (AREDS).

Methods

Fundus photographs from AREDS participants with GA from whom a DNA specimen had been obtained and serial photographs had been taken over a minimum of 2 years were evaluated for progression as determined by change in cumulative area of GA. All fundus photographs were scanned, digitized, and centrally graded longitudinally for area of GA. The relationship of GA progression with previously identified genetic variants associated with AMD was assessed.

Main Outcome Measures

Genotype frequencies and change in cumulative area of GA.

Results

The mean growth rate of GA for the 114 eyes was 1.79 mm2/year (range, 0.17–4.76). No association between growth rate and genotype was present for variants in the CFH, C2, C3, APOE, and TLR3 genes. For the single nucleotide polymorphism rs10490924 in LOC387715/ARMS2, there was a significant association of GA growth rate, both adjusted and unadjusted for initial lesion size, with the homozygous risk genotype as compared with the homozygous nonrisk genotype (unadjusted P = 0.002; Bonferroni-corrected P = 0.014) and for allelic association (Bonferroni-corrected P value = 0.011). Analyses of other measures of GA progression (progression to central GA from extrafoveal GA and development of bilateral GA in those initially with unilateral GA) showed no statistically significant association between progression and the LOC387715/ARMS2/HTRA1 genotype.

Conclusions

Growth rates of GA calculated from digitized serial fundus photographs showed no association with variants in the CFH, C2, C3, APOE, or TLR3 genes. There was a nominally significant association with the LOC387715/ARMS2/HTRA1 genotype, although this finding was not supported by analyses of secondary measures of GA progression. Replication in other populations is needed to establish the existence of an association.

Financial Disclosure(s)

The authors have no proprietary or commercial interest in any of the materials discussed in this article.

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 Manuscript no. 2009-605.

 Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

 Supported by contracts and grants from the National Eye Institute, National Institutes of Health, Bethesda, Maryland, R01-EY12203 (MLK), China NSFC grant 30730057 (JO), grants to the Casey Eye Institute, Oregon Health & Science University from Research to Prevent Blindness, New York, New York (PJF, MLK), the Foundation Fighting Blindness, Owings Mills, Maryland (PJF), and the Casey Eye Institute Macular Degeneration Fund (MLK and PJF). The authors have no proprietary interest in any materials or products discussed herein. No authors have any financial/conflicting interests to disclose.

PII: S0161-6420(09)01416-X

doi:10.1016/j.ophtha.2009.12.012

Ophthalmology
Volume 117, Issue 8 , Pages 1554-1559.e1, August 2010

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