Genetic, behavioral, and sociodemographic risk factors for second eye progression in age-related macular degeneration.

PURPOSE This study was conducted to investigate the correlation of genetic, sociodemographic, and behavioral risk factors with second eye progression to end-stage AMD. METHODS One hundred and eight patients with end-stage AMD in one or both eyes were included in a retrospective time-to-event analysis of the onset of end-stage AMD in the second eye. Multivariate Cox regression survival analysis was performed for sex, age, smoking, body mass index (BMI), education, and 16 single nucleotide polymorphisms (SNPs) associated with AMD. RESULTS Except for education, all sociodemographic and behavioral risk factors analyzed were significantly associated with a more rapid progression toward second eye involvement. Hazard ratios (HRs) were 2.6 (95% confidence interval [CI], 1.4-5.0) for female sex; 5.0 (95% CI, 2.0-12.5) for age >80; 2.2 (95% CI, 1.1-4.1) for BMI >30; and 4.4 (95% CI, 1.4-14.3) for >40 pack years, compared with the referent groups. Carriers of the lipoprotein lipase (LPL; rs12678919) risk alleles were at risk for more rapid progression to end-stage AMD in the second eye compared with the referent wild-type genotype (HR 2.0; 95% CI, 1.0-3.6). For complement factor I (CFI; rs10033900), homozygous carriers of the risk allele progressed faster than wild-type individuals (HR 2.2; 95% CI, 1.1-4.3). CONCLUSIONS Sociodemographic, behavioral, and genetic risk factors are associated with the rate of second eye progression toward end-stage AMD. The findings of this study underline the importance of lifestyle factors and the complement pathway in AMD progression and suggest a role of the high-density-lipoprotein metabolism in second eye progression.