Objective: To investigate whether polymorphisms in the estrogen receptor alpha (ESR1) and beta (ESR2) genes were a risk factor for open-angle glaucoma (OAG).

Methods: Participants 55 years and older from the population-based Rotterdam Study underwent, at baseline and at follow-up, the same ophthalmic examination, including visual field screening and stereo optic disc photography. A diagnosis of OAG was based on an algorithm using optic disc measures and visual field loss. Haplotypes of the ESR1 and ESR2 genes were determined.

Results: We diagnosed incident OAG in 87 of 3842 participants (2.3%) at risk after a mean follow-up of 6.5 years. We could not detect any association with ESR1 haplotypes. Haplotype 1 of ESR2 showed a 3.6-fold (95% confidence interval, 1.4-9.2) higher risk of incident OAG in men. In women, no association was found between ESR2 and incident OAG.

Conclusions: Polymorphisms in the ESR1 gene are unrelated to OAG, but ESR2 polymorphisms seem to lead to increased risk of OAG in men.