This article originally appeared on our sister site, Ophthalmology Times.

The US FDA has approved the combination of carbachol and brimonidine tartrate (YUVEZZI; Tenpoint Therapeutics) for presbyopia in adults.¹ This marks the first approved pharmacological combination drop aimed at pupil-based near-vision improvement and provides a second noninvasive treatment option for patients seeking alternatives to spectacles, contact lenses, or surgical correction.

The FDA action was supported by 2 pivotal phase 3 studies—BRIO-I and BRIO-II—enrolling more than 800 participants overall, including a 12-month safety cohort described by the sponsor as the longest safety follow-up reported for a presbyopia eye drop. Although detailed trial reports have not yet been published in peer-reviewed journals, topline efficacy and safety outcomes were summarised in the press release and the product’s US Prescribing Information.^2,3,7

Trial and regulatory overview

BRIO-I was designed to satisfy FDA requirements for fixed-dose combinations by demonstrating superiority of the combination over its individual active components. According to the sponsor, the combination showed greater benefit than either carbachol or brimonidine alone for near-vision outcomes.² However, numerical efficacy data and full statistical methods have not been publicly reported, limiting independent appraisal.

BRIO-II was a randomised, vehicle-controlled phase 3 trial that evaluated binocular uncorrected near visual acuity (BUNVA) over an 8-hour period following once-daily dosing. The primary endpoints were achievement of a 3-line or greater improvement in BUNVA without loss of 1 line or more in binocular uncorrected distance visual acuity (BUDVA). The sponsor reported that all primary endpoints were met with statistical significance and that miosis was observed from approximately 30 minutes through up to 10 hours post-dose.³

Across more than 72 000 treatment-days in BRIO-II, no treatment-related serious adverse events were reported.³ The most commonly reported adverse events included headache, impaired vision, and transient ocular discomfort or irritation, consistent with the miotic mechanism of action.⁷ Rates of ocular hyperemia were low in both pivotal trials and were reported to be lower with the combination than with carbachol alone in BRIO-II (2.8% vs 10.7%).³

Clinical context

Presbyopia is a universal, age-related decline in near focusing ability that typically becomes symptomatic after age 45 and affects an estimated 128 million people in the US and approximately 2 billion globally.^4-6 Loss of accommodative amplitude results from biomechanical and optical changes in the crystalline lens and ciliary apparatus, leading to functional limitations in near tasks and reduced quality of life.^11,12

Standard management remains optical correction with reading glasses, multifocal spectacles, or contact lenses. Surgical approaches—including corneal inlays, refractive surgery, and lens-based procedures—may be appropriate for selected patients but are not universally acceptable. Until recently, no pharmacologic treatments were available; pilocarpine hydrochloride ophthalmic solution was approved in 2021 as the first miotic eye drop for presbyopia, establishing pupil modulation as a therapeutic strategy.

Drug and drug-class background

The newly approved combination pairs carbachol, a cholinergic agonist with miotic effects mediated primarily through iris sphincter contraction, and brimonidine tartrate, an α₂-adrenergic agonist that inhibits iris dilator muscle activity.⁷ The proposed rationale is that dual modulation enhances pupil constriction while potentially limiting ciliary muscle spasm and reducing hyperemia, thereby prolonging effect and improving tolerability compared with single-agent miotics.^6,7

Both components have long regulatory histories in ophthalmology for other indications, including glaucoma and intraocular pressure control, although their combined use for presbyopia represents a novel application.

From a clinical standpoint, the approval expands the pharmacologic toolkit for presbyopia and underscores growing interest in pupil-based approaches. Head-to-head comparisons with existing pharmacologic options and real-world adherence data are not yet available.

Early response to news of the approval

The Eye Care Network reached out to Eric D. Donnenfeld, MD, cornea, laser cataract and refractive surgeon in practice at OCLI Vision in New York, New York, US, for his perspective on what the approval would mean for ophthalmologists and patients with presbyopia.

Note: Transcript edited for clarity and length

The Eye Care Network: What is the potential clinical significance of the fixed-dose ophthalmic combination of carbachol and brimonidine tartrate (YUVEZZI; Tenpoint Therapeutics) in the presbyopia treatment landscape?

Eric D. Donnenfeld, MD: Presbyopia is a universal age-related condition that affects approximately 2 billion people worldwide, including an estimated 128 million in the United States. Nearly 90% of Americans older than 45 years of age have presbyopia, and globally, 45% of presbyopic individuals have impaired near vision because they lack adequate (or any) correction. A presbyopia treatment that is reversable, and is designed to deliver tolerability, safety, and durable efficacy will be greatly adopted. This newest medication to be approved by the FDA [YUVEZZI, previously known at Brimochol PF] offers significant advantages over previous topical medications for presbyopia.

What factors might influence its adoption in clinical practice (eg, efficacy, tolerability, patient acceptance, or convenience)?

Donnenfeld: In clinical practice, three basic parameters determine the success of a new pharmaceutical: safety, efficacy, and tolerability. In the treatment of presbyopia, the duration of action is also very important. [This fixed-dose ophthalmic combination of carbachol and brimonidine tartrate] provides a full workday of sharp near vision. Another major advantage [is] the addition of brimonidine which has many important effects on the tolerability of the medication. Eye redness was not a commonly reported side effect in clinical trials of [this fixed-dose ophthalmic combination of carbachol and brimonidine tartrate]. In BRIO-II, the rate of reported adverse events of ocular hyperemia (redness) was lower in subjects receiving YUVEZZI (2.8%) than carbochol alone (10.7%).

The last thing a presbyopic patient wants is to abandon their reading glasses and walk around with cosmetically red eyes. The use of brimonidine is also felt to reduce the ciliary spasm which could be why in the BRIO-II trial vitreous detachment was reported in a similar proportion of patients taking [this fixed-dose ophthalmic combination of carbachol and brimonidine tartrate] and vehicle (0.8% vs 0.6%) and there were no retinal detachments reported over 12 months.

What are the long-term implications for patients, including how this may change the role of pharmacologic therapy vs glasses or surgical options?

Donnenfeld: [This fixed-dose ophthalmic combination of carbachol and brimonidine tartrate] offers optimal safety, efficacy, tolerability, and duration of action. One of my concerns is that some medications need to be refrigerated [not needed for YUVEZZI], making compliance more difficult. When a patient wants a presbyopic correction, they expect to read but they don’t want to sacrifice their distance vision. The optimal pupil size for quality of distance and near vision is 2 mm. A medication that makes pupils too small will result in dimming of vision and loss of quality of vision. [This fixed-dose ophthalmic combination of carbachol and brimonidine tartrate] results in pupils that are great for reading without compromise to distance vision.

References

1. Tenpoint Therapeutics Ltd. announces FDA approval of YUVEZZI, the first and only combination eye drop approved to treat presbyopia. News release. January 28, 2026. Accessed January 29, 2029.

2. Tenpoint Therapeutics Ltd. BRIO-I study data on file.

3. Tenpoint Therapeutics Ltd. BRIO-II study data on file.

4. American Optometric Association Health Policy Institute. New Approaches to Presbyopia. 2023.

5. National Eye Institute. Presbyopia. Updated December 4, 2024.

6. Fricke TR, Tahhan N, Resnikoff S, et al. Global prevalence of presbyopia and vision impairment from uncorrected presbyopia: systematic review, meta-analysis, and modelling. Ophthalmology. 2018;125(10):1492-1499. doi:10.1016/j.ophtha.2018.04.013

7. YUVEZZI (carbachol and brimonidine tartrate ophthalmic solution) US Prescribing Information.

8. Ishikawa H, DeSantis L, Patil PN. Selectivity of muscarinic agonists including (+/-)-aceclidine and antimuscarinics on the human intraocular muscles. J Ocul Pharmacol Ther. 1998;14(4):363-373. doi:10.1089/jop.1998.14.363

9. Mancil GL, Baily IL, Brookman KE, et al. Care of the Patient With Presbyopia. American Optometric Association; 2011.

10. Wolffsohn JS, Leteneux-Pantais C, Chiva-Razavi S, et al. Social media listening to understand the lived experience of presbyopia: systematic search and content analysis study. J Med Internet Res. 2020;22(9):e18306. doi:10.2196/18306

11. Glasser A, Campbell MC. Biometric, optical and physical changes in the isolated human crystalline lens with age in relation to presbyopia. Vision Res. 1999;39(11):1991-2015. doi:10.1016/s0042-6989(98)00283-1

12. Kandel H, Khadka J, Goggin M, Pesudovs K. Impact of refractive error on quality of life: a qualitative study. Clin Exp Ophthalmol. 2017;45(7):677-688. doi:10.1111/ceo.12954