A Review of Pharmacologic Treatments for Presbyopia

Like death and taxes, presbyopia is inevitable—nearly everyone who lives beyond their mid-40s will experience it. Globally, presbyopia affects an estimated 1.8 billion people, including approximately 130 million Americans, or roughly one-third of the US population.^1,2 This condition is defined as the gradual, progressive loss of near vision caused by the eye’s declining ability to accommodate, as the natural lens becomes less flexible with age. Clinically, presbyopia severity is categorized based on required near add power: mild (< +1.25 D), moderate (+1.25 D to +2.00 D), and advanced (> +2.00 D).³

To manage this visual decline, individuals often rely on progressive addition lenses, bifocals, reading glasses, monovision, or multifocal contact lenses, or they simply tolerate blurred near vision.⁴ As presbyopia progresses—typically peaking in severity by 65 years of age—dependence on visual aids increases.⁵ Beyond its visual effect, presbyopia can significantly affect quality of life, with many individuals reporting anxiety, embarrassment, diminished self-esteem, and changes in social interactions as a result of their vision loss.⁶

Many patients are eager for alternatives that reduce their reliance on corrective lenses—especially as refractive and surgical options may not fully meet their expectations. As a result, several pharmacologic treatments have emerged, offering novel approaches to presbyopia management.

MECHANISM OF ACTION

The accommodative system of the eye is highly complex, involving multiple anatomical and physiological components. Accordingly, there are several theoretical approaches to treating presbyopia. These include restoring the flexibility of the natural crystalline lens, enhancing ciliary muscle function, modifying scleral biomechanics, or manipulating pupil size.⁷ While these strategies are conceptually promising, pharmacologic intervention has proven challenging in all but one domain: pupillary constriction. As such, current pharmacologic therapies primarily aim to enhance near vision by inducing miosis, thereby increasing depth of focus without significantly compromising distance visual acuity.

The Rayleigh Limit describes how pupil size influences depth of focus and visual acuity. In the context of presbyopia, this principle is used to optimize near and distance vision. As the pupil constricts, depth of focus increases, improving near visual acuity—an effect also illustrated by the Charman and Whitefoot Curve, which demonstrates how smaller pupil diameters enhance acuity up to an optimal point.⁸ For example, a pupil below 2.0 mm creates a sharp increase in depth of focus (Figure).

Historically, a pupil diameter of around 2.0 mm was considered optimal for balancing near and distance vision while avoiding issues such as dimming, field loss, and diffractive blur.⁹ However, more recent evidence indicates that a pupil size less than 2.0 mm can significantly enhance near vision by increasing depth of focus, without meaningfully reducing perceived brightness.^8,10 Concerns about diffractive blur and field loss primarily arise with very small apertures, typically at or below 1.0 mm.¹⁰ Miller and Johnson found that diffractive blur becomes a concern at a 1.0 mm pupil diameter, while both Freeman and Miller and Johnson demonstrated that a 1.5 mm aperture does not result in field loss.^9,10 As a result, modern surgical implants often target pupil apertures in the 1.6 mm to 2.0 mm range to optimize near vision while minimizing unwanted visual side effects.¹¹

PHARMACEUTICAL TREATMENT OPTIONS

To date, efforts to restore crystalline lens flexibility have proven largely unsuccessful, making pupillary constriction the primary pharmacologic strategy for managing presbyopia. Miosis can be achieved using parasympathomimetic cholinergic agents or, in some cases, sympathomimetics (Table).

Non-selective pharmacologic treatments for presbyopia stimulate both the iris sphincter and the ciliary muscle.¹² This dual action can induce a myopic shift or pseudo-myopia, potentially impairing distance vision and causing side effects such as ciliary spasm headaches.^13,14 Additionally, stimulation of the ciliary muscle may increase the risk of vitreoretinal traction, which can lead to complications such as retinal tears, detachments, or posterior synechiae.^15-17 Retinal detachments (RD) have, in fact, been associated with pilocarpine use for presbyopia.¹⁸ Therefore, selecting an optimal pilocarpine concentration is important, with lower concentrations minimizing side effects. Lower concentrations of pilocarpine and carbachol, another non-selective cholinergic agonist, has never been associated with a RD. Carbachol, in particular, has been primarily intraoperative rather than as a standalone topical medication.

Aceclidine is a selective muscarinic agonist that targets the iris sphincter with minimal ciliary muscle stimulation.^19,20 As a result, it reduces potential complications such as myopic shift, ciliary spasm, and retinal traction. According to Steven Dell, MD, “While this drug has never been used in the United States before, it has a historical pattern of use in Europe, where it’s been used in more than 400 million doses beginning in the 1970s for glaucoma,” where it was “even used at a QID dosage.”²¹ Despite this widespread use, aceclidine has never been linked to an RD, although the risk is theoretically possible and remains on the product's FDA label.²²

When selecting a miotic drop for presbyopia treatment, key considerations include the ability to achieve the primary endpoint (≥ 3 lines of near vision improvement at specific time points without negatively impacting distance vision), onset and duration of action, whether clinical trials assessed binocular or monocular vision, need for repeat dosing, characteristics of the study population, preservative status, degree of ciliary muscle activation (which may increase the risk of myopic shift or retinal traction), and the overall side effect profile.

PRESBYOPIA PRESCRIPTION DROPS COMPARED

The newest presbyopia-correcting eye drop on the market, aceclidine ophthalmic solution 1.44% (Vizz, Lenz Therapeutics) was approved by the FDA in July of this year. In the clinical trials, more than 70% of patients using aceclidine gained ≥ 3 lines of near vision within 30 minutes and achieved sustained improvement lasting 10 hours after a single daily dose (consisting of two drops administered 2 minutes apart). The FDA clinical trials for Vizz also included post-LASIK patients, supporting its broad applicability.²³

Pilocarpine-based drops—such as pilocarpine HCl ophthalmic solution 1.25% (Vuity, AbbVie) and pilocarpine HCl ophthalmic solution 0.4% (Qlosi, Orasis Pharmaceuticals)—generally show lower or shorter-lived response rates and often require a second dose to maintain efficacy throughout the day.^24,25

Carbachol in combination with brimonidine tartrate (Brimochol PF, Tenpoint Therapeutics) is currently under investigation, with a Prescription Drug User Fee Act date of January 28, 2026. Like pilocarpine, carbachol stimulates the iris sphincter and the ciliary muscle, while brimonidine reduces iris dilator muscle activity and allowing unopposed iris sphincter constriction.¹⁷ In the BRIO-II trial Brimochol PF met its primary endpoints in near vision improvement over 8 hours with once-daily dosing, but specific data has not yet been made publicly available. The study population included a broad age range, phakia and pseudophakia, but only emmetropes.²⁶

Pupil size likely contributes to these differences: Vizz achieves sub-2.0 mm pupil diameters (closer to the optimal range identified by the Charman and Whitefoot Curve) while carbachol/brimonidine tartrate produces intermediate pupil sizes (typically 2.0 mm to 2.5 mm), and Vuity and Qlosi tend to produce slightly larger pupils (approximately 2.3 mm to 2.5 mm).^27-30

Aceclidine minimizes ciliary muscle stimulation,²⁹ potentially avoiding myopic shift and lessening the risk of RD, whereas all other drops stimulate the ciliary muscle. Of note, pilocarpine 0.4% and carbachol have never been associated with a RD. Qlosi, Vizz, and Brimochol PF are preservative-free. Vuity and VIZZ have relatively higher rates of side effects as compared with Qlosi and Brimochol PF. Qlosi had a better side effect profile than Vuity due to having a lower concentration of pilocarpine. Vizz had the highest rate of visual dimming, which is likely explained by the greater miotic effect. Headaches associated with pilocarpine and carbachol are likely due to ciliary muscle involvement. The reason for headaches with Vizz remains unclear. Information about the most common side effects for each medication can be found in the Table.^20,28,30-34

Interestingly, Vizz also slightly improves distance vision, with 41% of participants achieving at least 1 line of improvement in distance corrected distance visual acuity at 5 hours.³⁵ This is likely due to the pinhole effect combined with the absence of a myopic shift, as aceclidine minimally stimulates the ciliary muscle.

CHOOSE CAREFULLY

In recent years, presbyopia has finally seen the emergence of effective pharmacologic treatments. Given the varying mechanisms, side effect profiles, and clinical performances, it is essential for eye care professionals to understand these differences and tailor treatment to individual patient needs. This is an exciting time in eye care, as presbyopia—a long unmet need for millions—now has safe and effective pharmaceutical options emerging to improve patients’ quality of life.