Genetic, Behavioral And Sociodemographic Risk Factors For Second Eye Progression In Age-related Macular Degeneration

Abstract

 

Purpose:

 

Patients with end-stage age-related macular degeneration (AMD) in one eye are at high risk to develop end-stage AMD in their fellow eye. 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-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, T(0) being the moment of end-stage AMD in the first eye. Multivariate cox regression survival analysis was performed for sociodemographic and behavioral risk factors (gender, age, smoking and body mass index (BMI)) and for twenty single nucleotide polymorphisms (SNPs) known to be associated with AMD.

 

Results:

 

All sociodemographic and behavioral risk factors were significantly associated with a more rapid progression towards second eye involvement. Hazard ratios (HRs) were 2.6 (95% confidence interval [CI], 1.4-5.0) for female gender, 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 to the reference groups of each category (respectively male gender, age <65, BMI 18-25 and 0-1 pack years). Heterozygous carriers of the LPL (rs12678919) risk allele were at risk for more rapid progression to end-stage AMD in the second eye compared to the homozygous carriers of the non-risk allele (HR 2.1 ; 95% CI, 1.1-3.9). For the CFI (rs10033900) SNP, the homozygous carriers of the risk allele showed a more rapid progression than the homozygous carriers of the non-risk allele (HR 2.2 ; (95% CI, 1.1-4.3). Variants in the CFH and ARMS2 genes were not significantly associated with second eye progression.

 

Conclusions:

 

Sociodemographic, behavioral and genetic risk factors are associated with the rate of second eye progression towards end-stage AMD. The findings of this study underline the importance of the complement pathway in AMD progression and provide new support for the role of HDL-metabolism in second eye progression.

 

Keywords: retina • genetics • age-related macular degeneration