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Original Investigation | Epidemiology

Serum Carboxymethyllysine, an Advanced Glycation End Product, and Age-Related Macular Degeneration:  The Age, Gene/Environment Susceptibility–Reykjavik Study

Richard D. Semba, MD1; Mary Frances Cotch, PhD2; Vilmundur Gudnason, MD, PhD3,4; Gudny Eiríksdottir, MSc3; Tamara B. Harris, MD5; Kai Sun, MS1; Ronald Klein, MD6; Fridbert Jonasson, MD4,7; Luigi Ferrucci, MD, PhD8; Debra A. Schaumberg, ScD, OD, MPH9
[+] Author Affiliations
1Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland
2Division of Epidemiology and Clinical Research, National Eye Institute, Bethesda, Maryland
3Icelandic Heart Association, Reykjavik, Iceland
4Department of Medicine, University of Iceland, Reykjavik, Iceland
5Laboratory of Epidemiology, Demography, and Biometry, Intramural Research Program, National Institute on Aging, Bethesda, Maryland
6Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison
7Department of Ophthalmology, Landspitali University Hospital, Reykjavik, Iceland
8Longitudinal Studies Section, National Institute on Aging, Baltimore, Maryland
9Moran Center for Translational Medicine, Department of Ophthalmology and Visual Sciences, University of Utah School of Medicine, Salt Lake City
JAMA Ophthalmol. 2014;132(4):464-470. doi:10.1001/jamaophthalmol.2013.7664.
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Importance  Advanced glycation end products have been implicated in the pathogenesis of age-related macular degeneration (AMD).

Objective  To investigate the relationship between serum carboxymethyllysine (CML), a major circulating advanced glycation end product, and AMD in older adults.

Design, Setting, and Participants  Cross-sectional study of a population-based sample of 4907 older adults (aged ≥66 years) in the Age, Gene/Environment Susceptibility–Reykjavik Study in Iceland.

Exposures  Serum CML and risk factors for AMD.

Main Outcomes and Measures  Early or late AMD, assessed through fundus images taken through dilated pupils using a 45° digital camera and grading for drusen size, type, area, increased retinal pigment, retinal pigment epithelial depigmentation, neovascular lesions, and geographic atrophy using the modified Wisconsin Age-Related Maculopathy Grading System.

Results  Of the 4907 participants, 1025 (20.9%) had early AMD and 276 (5.6%) had late AMD. Mean (SD) serum CML concentrations among adults with no AMD, early AMD, and late AMD (exudative AMD and pure geographic atrophy) were 618.8 (195.5), 634.2 (206.4), and 638.4 (192.0) ng/mL, respectively (to convert to micromoles per liter, multiply by 0.00489; P = .07). Log serum CML (per 1-SD increase) was not associated with any AMD (early and late AMD) (odds ratio = 0.97; 95% CI, 0.90-1.04; P = .44) or with late AMD (odds ratio = 0.94; 95% CI, 0.82-1.08; P = .36) in respective multivariable logistic regression models adjusting for age, sex, body mass index, smoking, and renal function.

Conclusions and Relevance  Higher serum CML concentration had no significant cross-sectional association with prevalent AMD in this large population-based cohort of older adults in Iceland.

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