This study demonstrated in the impact of hormones on keratoconus. Photo: Mitch Ibach, OD.

The multiple factors that can contribute to the onset and progression of keratoconus, including environment, genetics and hormonal imbalances, have been well established. However, questions remain regarding the pathobiology of the condition. In a recent study, researchers sought to establish the relationship between sex hormones and their receptors and the disease process of keratoconus. They will present their in vitro and in vivo findings this Wednesday during the 2022 ARVO annual meeting in Denver.

To determine the interaction between major androgens/estrogens and sex hormone receptors in healthy and keratoconus corneal stromal cells, the study authors used a 3D in vitro self-assembled extracellular matrix model. The in vivo analysis measured androgen/estrogen ELISA expression before and after corneal crosslinking (CXL) among a small cohort of patients with keratoconus.

The study authors observed significant changes between healthy corneas and those with keratoconus, as well as between males and females in the tested sex hormone receptors. Estrone and estriol stimulation among healthy women revealed significant up-regulation of the androgen receptor, progesterone receptor and estrogen receptor beta compared with healthy men. The data also showed higher expression of estrogen receptor alpha and estrogen receptor beta in women with keratoconus vs. their male counterparts.

The research demonstrated that, following CXL, DHEA sulfate levels were lower while estrone and estriol levels were higher. These in vivo findings indicate this treatment affects the corneal tissue and modulates hormonal levels in the bloodstream, according to the researchers.

“Our data suggests that the human cornea is a sex-dependent and a hormone-responsive tissue. We posit that keratoconus is a systemic disease, at least initially, and is heavily dependent on systemic and local hormone alterations,” the study authors concluded in their abstract.

Original abstract content © Association for Research in Vision and Ophthalmology 2022.

Karamichos D, Escandon P, Nicholas S, et al. The surprising impact of hormones on keratoconus. ARVO 2022 annual meeting.