CYP3A4 Poor and Intermediate Metabolizers Have a Higher Rate of Steroid-Induced Intraocular Pressure Response

Purpose: Evaluate the relationship between CYP3A4 phenotype, the gene encoding the enzyme that metabolizes exogenous steroids, and the rate of steroid-induced intraocular pressure (IOP) response. Materials and Methods: Lymphocyte-derived DNA sequencing of CYP3A4 from 10073 patients was completed using the PGRN-Seq assay. Subjects with CYP3A4 intermediate metabolizer or slower phenotypes were identified and compared with controls matched by age, race, and sex. All subjects had at least 3 eye exams with at least an exam while on topical/systemic/local steroid in any body location except the eye. Patients with pre-existing glaucoma or glaucoma suspects were excluded. Results: Of the 10,073 patients, there were 63 patients who had CYP3A4 poor or intermediate metabolizer phenotype. Of the 63 patients, 22 had documented steroid use. Fifty-nine percent (13/22) of patients with CYP3A4 poor/intermediate metabolizer had a steroid-induced IOP response of 3 mm Hg or more, significantly higher compared with 23% (5/22) of matched controls ( P =0.031). Although more poor/intermediate metabolizers were steroid responders, the average IOP elevation in steroid responders in both groups was similar (5.0±2.5 mm Hg in CYP3A4 poor/intermediate metabolizers compared with 4.1±2.1 mm Hg in controls, P =0.327). Family history of glaucoma was similar in both groups (7/22 vs. 8/22, P =1.0). Conclusion: Reduced CYP3A4 phenotypes may help identify patients at a higher risk of steroid-induced IOP elevation.