BRIO I was designed to satisfy fixed-dose combination regulatory requirements by demonstrating that the combined therapy provided superior near vision benefit compared with its individual components. In the vehicle-controlled BRIO II study, carbachol and brimonidine tartrate ophthalmic solution 2.75%/0.1% met all primary efficacy endpoints. According to sponsor data, the formulation produced statistically significant ≥3-line improvement in binocular uncorrected near visual acuity (BUNVA) over an 8-hour period without inducing a loss of ≥1 line in binocular uncorrected distance visual acuity (BUDVA). Rates of ocular hyperemia (eye redness) were reportedly low and appeared lower in the carbachol and brimonidine tartrate ophthalmic solution 2.75%/0.1% arm (2.8%) versus carbachol monotherapy (10.7%) in BRIO II. In October 2021, the FDA approved pilocarpine hydrochloride 1.25% ophthalmic solution (Vuity) as the first topical pharmacologic therapy for presbyopia, using a pupil-constricting or “pinhole” mechanism to improve near vision while preserving distance acuity.