Exploring New Links Among Keratoconus, Hormonal Factors, and Medications: Insights From a Case–Control Study Utilizing the All of Us Database

Purpose: We aimed to identify clinical factors associated with keratoconus (KC) risk in the All of Us database. Methods: This retrospective matched case–control study utilized patient data from the AllofUsResearchProgram.AllpatientswithaKCdiagnosis(n=572) were enrolled in the study and matched with three controls (n = 1716) based on age ± 1 year, race, ethnicity, and sex. The patients’ medical histories, including diabetes, sleep apnea, obesity, smoking, ocular surface disease (encompassing dry eye, eczema, and allergic or atopic conjunctivitis), allergic rhinitis, pregnancy, estrogen-containing medications, tetracyclines, and vitamin C supplementation, were collected using electronic health records. Multivariable odds ratios (ORs) between KC and health history were calculated using the R programming language. Results: The study included 2288 participants with an average age of 58.7 years. All included variables showed a significant positive correlation with KC except smoking history, which showed a negative correlation. The most significant correlations were ocular surface disease (OR = 6.04) and obesity (OR = 1.82). Significant positive associations were also identified for tetracyclines and estrogen-containing medications with KC. Smoking was negatively correlated. Conclusions: In addition to previously known risk factors, patients with a history of increased estrogen exposure and tetracycline usage were more likely to have a KC diagnosis whereas those with a smoking history were less likely. Translational Relevance: Understanding the risk factors for KC, including estrogen exposure and tetracycline medications, enhances our ability to identify at-risk patients and implement earlier screening, diagnosis, and interventions.