Genetic factors for choroidal neovascularization associated with high myopia

Nonsyndromic high myopia, defined by a refractive error greater than -6 diopters (D), is associated with an increased risk of macular choroidal neovascularization (CNV), a vision-threatening complication. The aim of this study was to investigate whether genetic factors associated with age-related macular degeneration (AMD) are related to myopic CNV.

We conducted a case-control study, including 71 cases with myopic CNV and 196 myopic controls without CNV, from Creteil and Toulouse, France, and Boston, MA. Single nucleotide polymorphisms (SNPs) from 15 genes reported to be related to AMD were selected for association testing in this study.

In univariate analysis, the rs10033900 SNP located in CFI was associated with myopic CNV (P = 0.0011), and a SNP in APOE was also related (P = 0.041). After adjustment for age, sex, and degree of myopia, SNPs in three genes were significantly associated, including CFI (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.3-3.37, P = 0.0023), COL8A1 (OR 1.88, 95% CI 1.18-2.98, P = 0.0076), and CFH (OR 1.65, 95% CI 1.02-2.66, P = 0.04). After correction for multiple testing, only CFI remained significantly related to high myopic CNV (P = 0.045).

We report the first genetic associations with choroidal neovascularization (CNV) in a high myopic Caucasian population. One SNP (rs10033900) in the CFI gene, which encodes a protein involved in the inflammatory pathway, was significantly associated with myopic CNV in multivariate analysis after correction for multiple testing. This SNP is a plausible biological marker associated with CNV outgrowth among high myopic patients. Results generate hypotheses about potential loci related to CNV in high myopia, and larger studies are needed to expand on these findings.