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

Lyly Van; Sashia Bennett; Sarah E Nicholas; Jesper Hjortdal; Tina B McKay; Dimitrios Karamichos

doi:10.1016/j.xops.2023.100364

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

Ophthalmol Sci. 2023 Jul 11;4(2):100364. doi: 10.1016/j.xops.2023.100364. eCollection 2024 Mar-Apr.

Authors

Lyly Van¹, Sashia Bennett², Sarah E Nicholas^{3

4}, Jesper Hjortdal², Tina B McKay⁵, Dimitrios Karamichos^{3

4

6}

Affiliations

¹ Department of Ophthalmology, Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
² Department of Ophthalmology, Aarhus University Hospital, 8200 Aarhus N, Denmark.
³ North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, Texas.
⁴ Department of Pharmaceutical Sciences, University of North Texas Health Science Center, Fort Worth, Texas.
⁵ Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
⁶ Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, Texas.

Abstract

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 disclosures: The authors have no proprietary or commercial interest in any materials discussed in this article.

Keywords: Cornea; Corneal crosslinking; Estrogen; Hormones; Keratoconus.

Grants and funding

R01 EY028888/EY/NEI NIH HHS/United States