FDA approval of aceclidine (Vizz): a new chapter in nonsurgical presbyopia management

To the Editor,

Presbyopia is a common, age-related vision disorder characterized by a gradual decline in the ability to focus on objects at near distances. It is hypothesized to result from either weakening of the ciliary muscles or loss of elasticity of the lens, preventing the change in focal point^[1,2]. The prevalence and severity of presbyopia increase with age, with almost 85% of people aged 40 years or older developing presbyopia. In 2015, it was estimated that 1.8 billion people globally had presbyopia, and the prevalence is expected to increase to approximately 2.1 billion in 2030^[3]. Considering these statistics, while treatment options are available for presbyopia (varifocal glasses and contact lenses), patients also encounter several limitations. Individuals with presbyopia have reported experiencing difficulties with reading and using electronic devices, and felt inconvenienced by the use of varifocal glasses and contact lenses^[4]. In addition, all the treatment options currently available for presbyopia require the patient to make some compromises in the quality of vision offered at different distances^[5]. This article aligns with the TITAN Guidelines on the importance of transparency in AI use in healthcare^[6].

The FDA has recently approved Vizz (aceclidine 1.44%) as a noninvasive, nonsurgical treatment for presbyopia in adults. It is the first aceclidine-based ophthalmic solution approved for this indication. Clinical data indicate rapid improvement in near vision after instillation; however, direct randomized comparisons against pilocarpine-based drops or other pharmacological approaches have not yet been reported^[7,8]. Aceclidine acts primarily as a pupil-selective miotic, contracting the iris sphincter with minimal ciliary muscle stimulation. This pinhole effect produces a sub-2 mm pupil that increases depth of focus and improves near vision without inducing a myopic shift^[7]. Its more pupil-selective profile has been proposed to offer advantages over other miotics, though confirmatory head-to-head studies are still lacking^[8].

The approval was based on results from three randomized, double-blinded, controlled phase 3 trials. Two of these trials, CLARITY 1 and CLARITY 2, met all primary and secondary outcomes for near vision improvement. In these trials, the safety and efficacy of Vizz were evaluated in 466 participants who were given a daily dose of Vizz for a 42-day duration. Vizz demonstrated its ability to improve near vision within 30 minutes and last up to 10 hours. Specifically, a recent news release states that 71% of trial participants achieved third line or greater improvement at 30 minutes and 3 hours, and 40% continued to have these improvements at 10 hours^[7]; these outcomes were initially reported in topline announcements from the sponsor^[9,10]. Vizz was also well tolerated, with no serious treatment-related adverse effects observed over the 30 000 treatment days across all 3 CLARITY trials^[7]; these findings were also reflected in sponsor press releases^[9,10]. To date, aceclidine’s efficacy has been demonstrated in placebo-controlled CLARITY trials; direct randomized head-to-head comparisons with pilocarpine or other pharmacologic agents are not yet available^[7,8].

Although the drug was generally well tolerated, the most frequently reported side effects of Vizz eye drops include eye irritation (20%), dim vision (16%), and headache (13%). Adverse reactions reported in >5% of participants were conjunctival hyperemia (8%) and ocular hyperemia (7%). These effects are generally mild, transient, and self-limiting^[7]. Rare but serious events, such as severe allergic reactions or retinal detachment, are noted in consumer-facing drug databases^[11], and the FDA prescribing label^[7] advises immediate medical attention if they occur. Vizz is contraindicated in patients with hypersensitivity or in patients with a known history of iritis. Precautions with contact lens wear and vial handling are necessary to minimize ocular contamination. Data on Vizz use during pregnancy remain insufficient to establish safety^[7].

It is expected that LENZ Therapeutics will begin sample distribution of Vizz in October 2025, with the full commercial launch anticipated by late fourth quarter 2025^[9,10,12,13]. The approval of Vizz marks the introduction of a novel, nonsurgical treatment option for presbyopia. Currently, corneal surgical procedures such as monovision techniques, corneal inlays, or multifocal LASIK still remain in use to correct presbyopia; however, these approaches are associated with important drawbacks, including compromised intermediate and distant vision, reduced contrast sensitivity, dysphotopsia, and the potential for regression in refractive outcomes^[14]. A pharmacological approach such as Aceclidine may avoid the irreversibility and peri-procedural risks of surgery, and could be an attractive option for patients wishing to reduce reliance on spectacles or contacts. Whether it will reduce overall surgical rates or replace optical correction in routine practice remains to be determined^[15]. A comparative summary of presbyopia treatment modalities, including optical, pharmacological, and surgical approaches, is provided in Table 1.

Table 1.

Comparative summary of presbyopia treatment modalities

Feature	Varifocal glasses	Contact lenses	Aceclidine (Vizz) eye drops	Other pharmacological options (e.g., pilocarpine, lens softening agents)	Corneal surgical options (monovision LASIK, corneal inlays, multifocal LASIK)
Efficacy	Effective for near/intermediate vision; compromises distance clarity at times[4,5]	Effective near correction; requires adaptation, may reduce comfort[4,5]	Rapid near vision improvement within 30 min, lasting up to 10 h; superior depth of focus via pupil modulation[7]	Pilocarpine is effective but shorter duration and more side effects[8,15]; lens softening agents are under investigation[8]	Improves near vision but is associated with reduced contrast sensitivity, dysphotopsia, and regression[14]
Onset and duration	Immediate, dependent on wearing	Immediate	Fast (30 min), lasts up to 10 h[7]	Pilocarpine onset is fast but shorter lasting than aceclidine[8,15]; lens-softening experimental[8]	Permanent correction but may regress over time[14]
Reversibility	Fully reversible (remove glasses)	Fully reversible (remove lenses)	Fully reversible, effect wears off the same day[7]	Reversible with discontinuation; long-term durability not established[8]	Irreversible surgical alteration[14]
Side effects/limitations	Inconvenience, reduced quality at some distances, cosmetic concerns[4,5]	Dryness, discomfort, inconvenience, infection risk[4,5]	Mild: irritation (20%), dim vision (16%), headache (13%); rare serious: allergy, retinal detachment[7]	Pilocarpine: headache, brow ache, myopic shift; long-term safety unclear[8,15]	Surgical risks: dysphotopsia, loss of contrast, regression, complications[14]
Cost	Moderate; recurrent replacement[4]	Moderate to high; ongoing cost of lenses and solutions[4,5]	TBD – FDA approved but not yet launched; expected commercial availability late 2025[9,13]	Variable; investigational, not yet widely available[8]	High one-time surgical cost[14]
Accessibility	Widely available[4]	Widely available[4,5]	Not yet commercially available; launch expected late 2025[9,13]	Limited; investigational[8]	Limited to specialized centers; less accessible in LMICs[14]
Patient preference	Common but associated with inconvenience[4,5]	Preferred by some younger patients but not widely tolerated long term[4,5]	Attractive to younger presbyopes avoiding glasses/surgery; noninvasive[8,15]	Mixed acceptance; still experimental[8]	Preferred by those seeking permanence but requires risk trade offs[14]

The introduction of Aceclidine eye drops as a treatment for presbyopia opens new paths for research and clinical practice. However, its long-term safety, adherence patterns, and comparative effectiveness against other nonsurgical options such as pilocarpine and emerging lens-softening agents should be investigated^[8]. Compared with pilocarpine, Aceclidine’s more pupil-selective action may lessen the risk of accommodative myopic shift, though no head-to-head RCTs exist to confirm differences in efficacy or tolerability^[7,8]. In addition, evaluating Vizz in diverse populations, including younger presbyopes, individuals with co-existing ocular conditions, and those with high digital screen use, could provide valuable real-world insights. Cost-effectiveness analyses and accessibility of this drug are also essential, especially in low- and middle-income countries where presbyopia is highly prevalent but corrective options are limited^[3]. Integrating Vizz into clinical guidelines as a first-line option will require continuous monitoring of post-marketing data to ensure sustained safety and patient satisfaction. As of now, approval is limited to the United States; regulatory submissions and access pathways in other regions remain pending, and global availability will likely vary according to local health systems and cost considerations.

In conclusion, Aceclidine (Vizz) is a promising, pharmacological option for presbyopia that produced rapid, reversible near-vision gains in Phase 3 trials. However, enthusiasm should be tempered: long-term safety, durability of effect, adherence with chronic use, comparative effectiveness versus pilocarpine and emerging lens-softening approaches, and cost-effectiveness remain uncertain. Peer-reviewed publication of the CLARITY trials, careful post-marketing surveillance, and randomized comparative studies will be essential to define Aceclidine’s place in clinical practice. If further data confirm the current findings, aceclidine may reduce the need for invasive procedures in selected patients. Until then, it should be regarded as a promising option whose wider adoption should be guided by continued evidence generation and post-marketing surveillance^[7,8].

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Sources of funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Author contributions

Conceptualization: HGA, MF. Writing – original draft preparation: HGA, MF, HS, NUNI, SBI. Writing – review and editing: HGA, MF, HS, NUNI, SBI. All authors have reviewed the final version of the manuscript.

Conflicts of interest disclosure

The authors declare that they have no conflict of interest.

Guarantor

Sakan Binte Imran.

Research registration unique identifying number (UIN)

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Provenance and peer review

Not commissioned; externally peer-reviewed.

Data availability statement

Not applicable.