Purpose
To determine the association between the age of onset of neovascular age-related macular degeneration (AMD) and genetic, socio-demographic, behavioral and ocular risk factors.
Methods
We conducted a retrospective cohort study with 286 patients from the European Genetic Database (EUGENDA). Univariate analysis of covariance (ANCOVA) was performed for gender, body mass index (BMI), smoking, education, diabetes, hypertension, alcohol consumption, refractive error, pseudophakia, subtype of wet AMD, and 20 single nucleotide polymorphisms (SNPs) associated with AMD. Significant risk factors were then included in a multivariate model.
Results
A significant association was observed for smoking, with each pack year contributing to an earlier age of onset of 0.88 months (P=0.015). Higher educated patients (above high school level) had an average age of onset that was 44.78 months later than patients with the lowest education levels (P=0.002). Carriers of risk alleles in the Age-Related Maculopathy Susceptibility 2 (ARMS2) (rs10490924) and the Complement Factor H (CFH) (rs1410996) genes developed neovascular AMD at an earlier age compared to carriers of the wild-type genotypes. The mean age of onset was 57.74 (P=0.001) and 60.85 (P=0.041) months earlier for homozygous carriers of the ARMS2 and CFH risk alleles, respectively. For the Cholesteryl Ester Transfer Protein (CETP) (rs3764261) and the Serpin peptidase inhibitor clade G type 1 (SERPING1) (rs2511989) genes a significant association was found only for heterozygous risk allele carriers compared to the wild-type carriers (mean age of onset 30.03 (P=0.029) and 27.70 (P=0.044) months earlier, respectively).
Conclusions
Both environmental and genetic risk factors are associated with an earlier age of onset of wet AMD. The results of this study demonstrate that risk factors previously described to be associated with the development of AMD also influence the age of onset of AMD. This could provide patients with more accurate information about their prognosis, could give them more insight in their individual risk profile, and could provide them with an incentive to change their lifestyle, in order to preserve vision as long as possible.
Keywords: 412 age-related macular degeneration •
539 genetics