Prospective Observational Study Evaluating Systemic Hormones and Corneal Crosslinking Effects in Keratoconus

PURPOSE: To evaluate associations between hormone levels and corneal parameters in patients with keratoconus (KC), before and after photooxidative corneal collagen crosslinking (CXL). DESIGN: Prospective, observational cohort study. PARTICIPANTS: Twenty-eight patients with KC who were scheduled for CXL at Aarhus University Hospital in Denmark. METHODS: Androgen (dehydroepiandrosterone sulfate [DHEA-S]) and estrogen (estrone and estriol) plasma levels were measured and clinical assessments were performed before CXL and 2 to 3 months post-CXL, comparing the CXL eye with the control eye from the same participant. MAIN OUTCOME MEASURES: Associations between hormone levels and maximum corneal curvature (K(max)) and minimum central corneal thickness (CCt(min)) before and after CXL. RESULTS: Corneal collagen crosslinking was associated with a 2% reduction in K(max) values in the CXL eye, post-CXL, from baseline (median, 56.8 diopters [D]; 95% confidence interval [CI], 50.4–60.3) to the second visit (55.7 D; 95% CI, 50.4–58.8; P < 0.001). Systemic DHEA-S levels were 5 to 6 orders of magnitude higher than estriol or estrone concentrations in plasma. Importantly, estriol levels, rather than DHEA-S or estrone levels, were more closely correlated with K(max) before CXL (Spearman’s r = 0.55, P = 0.01). Post-CXL K(max) and CCt(min) were not associated with DHEA-S, estrone, or estriol plasma levels at the same timepoint. CONCLUSIONS: This study provides supporting evidence based on a KC clinical population that systemic estrogen levels may influence corneal parameters (curvature and thickness) pre-CXL. Further studies evaluating the interplay between the therapeutic benefits of CXL and systemic hormone distributions are needed to determine if perturbation of the local corneal microenvironment influences endocrine function. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.