Genotype-Phenotype Correlations for Exudative AMD Associated With Homozygous HTRA1 and CFH Genotypes

Purpose:Major genetic factors for age-related macular degeneration (AMD) have recently been identified. Our purpose was to analyze the angiographic features of patients homozygous for at-risk genotypes at HTRA1 and CFH genes, in a French exudative AMD population.Patients and Methods:200 patients affected with exudative AMD were genotyped for the polymorphisms rs11200638 of HTRA1 and Y402H of CFH genes. Based on the genotype, 4 homozygous groups were extracted from the entire cohort: double homozygous for wild alleles of both HTRA1 and CFH genes (group 1), homozygous for the at-risk allele of the HTRA1 gene only (group 2), homozygous for at-risk allele of CFH gene only (group 3), and double homozygous carriers for both at-risk alleles (group 4). Based on fluorescein angiography, infracyanin green angiography and optical coherence tomography. exsudative AMD was graded as classic CNV, predominantly classic CNV, occult CNV, minimally classic CNV, retinal angiomatosis proliferation or polypoidal choroidal vasculopathy. Results:Group 1 (n=9; mean age=72.8) presented 44.4% classic and predominantly classic CNV, 33.3% occult CNV and 11.1% minimally classic CNV. Group 2 (n=12; mean age=71.7) presented 50.0% classic and predominantly classic CNV, 33.3% occult CNV and no minimally classic CNV. Group 3 (n=30; mean age=71.1) presented 10% classic and predominantly classic CNV, 63.3% occult CNV and 13.3% of minimally classic CNV. Group 4 (n=17; mean age= 69.2) presented 29.4 % of classic and predominantly classic CNV, 52.9% of occult CNV and 11.8% of minimally classic CNV. Comparison between group 2 versus group 3 demonstrated that occult CNV and MC CNV were more frequently observed in group 3 than in group 2 (p<0.02). Occult plus minimally classic CNV were mainly associated with the Y402H CFH polymorphism (OR5.1 [IC95:1.5-17.5], p=0.01). Classic and predominantly classic CNV were more prevalent, but not significantly associated with the HTRA1 at-risk alleles (OR 2.5 [IC95:0.8-8.4], p=0.14). Conclusions:This attempt for a genotypic-angiographic correlation in a French population of exudative AMD suggests an association between occult CNV and CFH gene and an association between classic CNV and the HTRA1 gene.