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 All of Us Research Program. All patients with a KC diagnosis (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.