Aceclidine: A Non-Surgical Solution for Presbyopia

ACECLIDINE (ophthalmic solution) is a newly approved prescription eye drop for the treatment of presbyopia (Fig1)-a common, age-related condition that makes it harder to see objects up close. ^[1] It is the first and only eye drop in the United States to use aceclidine, a novel type of medication developed specifically for this purpose.

ACECLIDINE works by gently reducing pupil size, creating a subtle “pinhole effect” that sharpens near vision while preserving clear distance vision. A single daily dose provides rapid improvement in near vision that can last for up to 10 hours.

The drops are preservative-free, supplied in single-use vials, and applied directly to the eye once a day. ^[2] ACECLIDINE is expected to become available in the U.S. beginning October 2025, with broader distribution anticipated by the end of the year.

ACECLIDINE is designed for individuals experiencing presbyopia, a natural part of aging in which the lens of the eye becomes less flexible, making it difficult to focus on nearby objects. This condition typically begins around age 40 and gradually progresses over time. Common symptoms include blurred near vision, eye strain, and headaches. Presbyopia can be diagnosed by an eye care professional and managed through reading glasses, bifocals, contact lenses, surgical procedures, or newer pharmacologic options such as ACECLIDINE.

FIG 01: ACECLIDINE eye drops

MECHANISM OF ACTION:

• Aceclidine is a selective muscarinic acetylcholine receptor agonist primarily used as an ophthalmic agent.^[3] It works by selectively binding to muscarinic receptors on the iris sphincter muscle, causing gentle pupillary constriction while producing minimal stimulation of the ciliary muscle.
• Unlike non-selective miotic agents such as pilocarpine, aceclidine’s receptor selectivity results in a marked reduction in pupil size without triggering significant accommodation or myopic shift. This helps minimize side effects such as lens thickening, accommodative spasm, or visual discomfort.
• In the treatment of presbyopia, aceclidine’s targeted mechanism creates a small, stable pupil that produces a “pinhole effect,” increasing the depth of focus and improving near vision while preserving distance clarity.^[4] Its limited action on the ciliary muscle provides a favourable safety profile, reducing the risk of retinal or vitreous traction and minimizing accommodative disturbances compared with other cholinergic agonists.

PHARMACOKINETICS:

• When administered ophthalmically, aceclidine is primarily absorbed through the conjunctival and corneal tissues, allowing for a rapid onset of action due to efficient local uptake. Because its therapeutic effect is largely confined to the eye, systemic metabolism is limited, resulting in minimal systemic exposure.
• Following ocular administration, aceclidine’s distribution remains localized, with a low risk of systemic accumulation. ^[5] While detailed excretion pathways have not been fully characterized, evidence suggests that-similar to other topical miotic agents-aceclidine exhibits minimal systemic bioavailability and is likely eliminated through local ocular routes and normal metabolic processes.

COMPOSITION OF DRUG:

• This ophthalmic solution contains 1.75% aceclidine hydrochloride (equivalent to 1.44% aceclidine).
• The chemical names of aceclidine hydrochloride are:

• 3-Acetoxyquinuclidine hydrochloride
• 3-Quinuclidinyl acetate hydrochloride

• Its molecular weight is 205.68 g/mol, and its molecular formula is C?H??NO?·HCl.
• Each 1 mL of ACECLIDINE contains 1.75% (17.82 mg) aceclidine hydrochloride as the active ingredient.
• The inactive ingredients in the ophthalmic solution include polysorbate 80, mannitol, Hypromellose, edetate disodium dihydrate, sodium citrate dihydrate, and water for injection.
• Hydrochloric acid and/or sodium hydroxide may be used to adjust the pH to between 4.5 and 5.5, if necessary.
• ACECLIDINE is preservative-free and contains no antimicrobial agents.

CHEMISTRY:

• Aceclidine is an organic compound structurally related to quinuclidine, and is also known by the alternative name 3-acetoxyquinuclidine. Its protonated form has a pKa of 9.3.

Chemical structure of aceclidine

3D structure of aceclidine

CHEMICAL AND PHYSICAL DATA:

• Chemical formula: C?H??NO?
• Molar mass: 169.22 g/mol
• IUPAC name: 1-Azabicyclo [2.2.2] oct-3-yl acetate (also known as 3-Quinuclidinyl acetate)

DIAGNOSIS AND TREATMENT: -

DIAGNOSIS:

• Presbyopia can be diagnosed by an eye care professional through a comprehensive and painless eye examination that evaluates how well your eyes focus at different distances.

CORRECTIVE LENS:

• Reading Glasses: Designed to bend light and compensate for the eye’s reduced focusing ability, improving near vision.
• Bifocal or Varifocal Lenses: Provide multiple focusing powers within one lens to aid both near and distance vision.
• Contact Lenses: ^[6] Modern multifocal contact lenses allow the eyes to naturally focus at varying distances for clear vision up close and far away.

SURGICAL OPTIONS:

• Surgical treatments such as LASIK, refractive lens exchange, or conductive keratoplasty may be considered to correct presbyopia and reduce dependence on glasses or contact lenses.

LIFESTYLE ADJUSTMENTS:

• Symptoms can also be managed by making simple changes, such as using larger print materials, increasing font sizes on digital devices, and improving lighting for reading and close-up tasks.

ADVERSE REACTIONS:

• The most commonly reported side effects were instillation site irritation (20%), dim vision (16%), and headache (13%).
• Additional adverse reactions occurring in more than 5% of participants included conjunctival hyperaemia (8%) and ocular hyperaemia (7%).
• Most adverse reactions were mild, temporary, and resolved without treatment.

SIDE EFFECTS:

• Eye redness or irritation.
• Headache.
• Slight dimming of vision in low light (because the pupil becomes smaller.
• Mild burning or stinging right after putting the drops in eye.
• Temporary blurry vision.

Less common but serious side effects(rare):

• Retinal detachment or tears-more likely if have existing retinal problems.
• Severe allergic reactions-such as swelling, rash or difficulty breathing.

If you experience sudden flashes of light, a curtain-like shadow in your vision or severe eye pain, stop using the drops and seek immediate medical help.

CLINICAL TRIALS:

The CLARITY ^[7] clinical trial program consisted of three randomized, double-masked, controlled Phase 3 studies designed to evaluate the safety and efficacy of aceclidine for the treatment of presbyopia.

CLARITY-1 and CLARITY-2 ^[8] assessed the efficacy and safety of aceclidine 1.44% in 466 participants who received once-daily dosing for 42 days, while CLARITY-3 examined the long-term safety of the formulation over six months in 217 patients.^[9] Across CLARITY-1 and CLARITY-2, all primary and secondary endpoints were met, showing consistent improvement in near vision. ^[10] The formulation was well tolerated, and no serious treatment-related adverse events were reported in any of the studies.

Regulatory approval was primarily supported by two pivotal Phase 3 trials:

• CLARITY-1 (ClinicalTrials.gov Identifier: NCT05656027)
• CLARITY-2 (ClinicalTrials.gov Identifier: NCT06045299)

These studies enrolled 466 adults aged 45–75 years with a refractive range of –4.00 to +1.00 D sphere, astigmatism up to 2.00 D, and a spherical equivalent no more myopic than –4.00 D. Participants who had undergone refractive surgery and/or were pseudophakic were also included.

In CLARITY-1 (N=366), participants were randomly assigned to receive aceclidine or brimonidine once daily for 42 days, while in CLARITY-2 (N=153), they received either aceclidine or vehicle control.

The primary endpoint was the proportion of participants who gained three or more lines of distance-corrected near visual acuity (DCNVA) at 40 cm, without losing one or more lines (≥5 letters) of distance-corrected distance visual acuity (DCDVA) at 4 meters, measured at Day 1, Hour 3.

RESULTS:

• In CLARITY-1, 65% of patients treated with aceclidine achieved the primary endpoint, compared with 12% of those receiving brimonidine (P < .01).
• In CLARITY-2, 71% of the aceclidine group met the endpoint versus 8% of the vehicle control group (P < .01).
  Both studies demonstrated that aceclidine improved near vision within 30 minutes, with effects lasting up to 10 hours after dosing.

PATHOPHYSIOLOGY OF ACECLIDINE:

• ACECLIDINE (Aceclidine ophthalmic solution 1.44%) acts as a direct-acting muscarinic receptor agonist, primarily stimulating M3 receptors located on the iris sphincter and ciliary muscles of the eye.^[11] Activation of these receptors leads to contraction of the iris sphincter muscle (miosis), resulting in a pinhole effect that increases the depth of focus and reduces the size of the pupil, thereby improving near vision in patients with presbyopia (age-related blurry near vision).
• Additionally, aceclidine induces moderate contraction of the ciliary muscle, which enhances the accommodative ability of the lens, allowing the eye to better focus on near objects. ^[12] Unlike stronger miotic agents such as pilocarpine, aceclidine achieves this effect with minimal impact on distance vision and fewer adverse effects such as headaches or dim vision in low light.
• The pharmacological action of ^[13] Aceclidine results in a temporary pseudo-accommodation, improving near visual acuity without permanently altering the ocular anatomy or refractive state. ^[14] This mechanism allows ACECLIDINE to restore functional near vision by improving depth of field and enhancing accommodative performance, offering patients a non-surgical, reversible solution to manage presbyopia.

PRESBYOPIA:

Presbyopia is ^[15] an age-related physiological condition characterized by the gradual loss of the eye’s ability to focus on near objects (Fig 2). ^[16] It is an almost universal aspect of the aging process, typically becoming noticeable between the ages of 40 and 50, and affecting nearly all individuals by their mid-50s.

The underlying pathophysiology involves the progressive loss of elasticity of the crystalline lens and reduced contractility of the ciliary muscle.^[17] As people age, the crystalline lens becomes more compact and rigid due to protein cross-linking, lens sclerosis, and reduced water content, making it less capable of changing shape (accommodating) to focus on near objects. Additionally, structural and biomechanical changes in the ciliary body and zonular fibres contribute to the decline in accommodative function.

 Consequently, ^[18] light rays from near objects are focused behind the retina, leading to blurry near vision, while distance vision typically remains unaffected. Adults over age 50 lose, on average, 1.5 lines of near vision every six years. ^[19] Symptoms progress gradually, though many individuals experience a noticeable and sudden difficulty with near tasks in their mid-40s-such as reading fine print, using digital devices, or performing close-up work.

Traditionally, ^[20] presbyopia has been managed with optical corrections, including over-the-counter reading glasses, prescription bifocals, trifocals, or multifocal contact lenses. However, these solutions only compensate for the loss of accommodation rather than addressing the underlying physiological changes.^[21] Recent pharmacological advancements, such as miotic agents like Aceclidine (ACECLIDINE Eye Drops), provide a novel, non-invasive approach to temporarily improve near vision through pupillary modulation.

FIG 02:  Presbyopia

ACECLIDINE INDICATION AND IMPORTANT SAFETY INFORMATION INDICATION:

ACECLIDINE is a prescription ^[22] ophthalmic solution containing Aceclidine 1.44%, indicated for the treatment of age-related blurry near vision (presbyopia) in adults. By inducing controlled pupillary constriction (miosis), ACECLIDINE enhances the depth of focus and improves near visual acuity without significantly affecting distance vision.

Important Safety Information:

• Allergy Warning: Do not use ACECLIDINE if you are allergic to Aceclidine or any of the ingredients in the formulation.
• Avoid Contamination: To help prevent eye injury or contamination, do not allow the vial tip to touch the eye, fingers, or any other surface. Discard the vial immediately after single use (Fig 3).
• Contact Lens Use: Remove contact lenses before applying ACECLIDINE. Contact lenses may be reinserted 10 minutes after administration.
• Use with Other Eye Medications: If using more than one topical ophthalmic medication, administer each at least 5 minutes apart to ensure proper absorption.
• Vision Precautions: Temporary dimness, reduced night vision, or blurred vision may occur after using ACECLIDINE. Do not drive, operate machinery, or perform hazardous tasks until your vision has fully cleared.
• Seek Immediate Medical Attention: If you experience sudden onset of flashing lights, floaters, partial loss of vision, or severe eye pain, discontinue use and contact your healthcare provider immediately.

FIG 03: ACECLIDINE eye drop vials

VIZZ AN ACECLIDINE BASED EYE DROPS:

VIZZ-It is the first and ACECLIDINE based eye drops approved by U.S (FDA) in the treatment of presbyopia. It is a NON-surgical solution to treat the presbyopia which includes ACECLIDINE as a major component that makes it clear to see near objects.

FDA APPROVAL:

SAN DIEGO, July 31, 2025 (GLOBE NEWSWIRE) — LENZ Therapeutics, Inc. (Nasdaq: LENZ), ^[23] announced that the U.S. Food and Drug Administration (FDA) has approved VIZZ (aceclidine ophthalmic solution) 1.44%, marking it as the first and only FDA-approved aceclidine-based eye drop for the treatment of presbyopia in adults.

Product samples are expected to reach the U.S. market by October 2025, with broad commercial availability anticipated by mid–Q4 2025. LENZ will begin direct sales and marketing activities to eye care professionals immediately.

“The FDA approval of VIZZ (Fig 04) is a defining moment for ^[24] LENZ and represents a major advancement in treatment options for the 128 million adults in the United States affected by blurry near vision,” said Eef Schimmelpennink, President and Chief Executive Officer of LENZ Therapeutics. “We are excited to launch the first and only once-daily eye drop that provides proven near-vision improvement lasting up to 10 hours. This achievement reflects the dedication of our team, our clinical partners, and the many participants who made this milestone possible.”

VIZZ is powered by aceclidine, a pupil-selective miotic with a unique mechanism of action that primarily targets the iris sphincter muscle while minimizing stimulation of the ciliary muscle. By gently constricting the pupil, VIZZ produces a “pinhole effect”, enhancing near vision and depth of focus without inducing a myopic shift

FIG 04: FDA approval

Aceclidine, the active ingredient in VIZZ, is a new chemical entity in the United States, and this approval marks a global first for aceclidine-based therapy in the treatment of presbyopia.

The FDA approval of VIZZ, developed by California-based LENZ Therapeutics, introduces a once-daily prescription eye drop that can temporarily improve age-related blurry near vision for up to 10 hours—offering a convenient, non-invasive alternative for individuals with presbyopia.

 “This FDA approval ^[25] represents a paradigm shift in how we manage presbyopia,” said Dr. Marc Bloomenstein, OD, FAAO, of Schwartz Laser Eye Care Centre in Scottsdale, Arizona. “VIZZ provides optometrists and ophthalmologists with an exciting new option—an effective, once-daily treatment that could quickly become a standard of care for patients seeking clear near vision without compromising distance clarity.”

Benefits and Key Information of ACECLIDINE (Ophthalmic Solution):

Aceclidine is a fast-acting,^[26] long-lasting, and non-invasive treatment for age-related blurry near vision (presbyopia). Within 20–30 minutes of application, it enhances near vision by gently constricting the pupil through a selective muscarinic receptor agonist mechanism, creating a natural “pinhole effect” that improves focus without compromising distance vision.

The effects typically last for 8–10 hours, providing sustained visual clarity throughout the day. ACECLIDINE is supplied in preservative-free, single-use vials for once-daily topical administration offering a convenient alternative to reading glasses or surgical interventions.

TABLE 1: Benefits of ACECLIDINE