S1P receptor modulators are associated with an increased risk of macular edema, typically within the first 4 months of treatment, as well as lymphopenia and liver transaminase elevations.5,28-31 Due to the risk of varicella zoster virus (VZV) reactivation with S1P receptor modulators, patients who do not have immunity to VZV must be vaccinated before starting treatment.28 Finally, for siponimod, cytochrome P450 2C9 (CYP2C9) genotyping is needed prior to initiation to identify individuals in whom the medication is contraindicated or who need a reduced dose.28-31. The gene discussed is CYP2C9; the disease is macular retinal edema.