New topical prescription therapies are expanding treatment options for presbyopia and dry eye disease, according to Damon Dierker, OD, FAAO, who presented "What’s in the Bottle? New Rx Therapies" at SECO. Dr. Dierker outlined respective dosing frequencies, clinical trial data, and more.

Miotic Therapy

Pilocarpine 0.4%: Clinical Trial Outcomes

Recommended dosing for pilocarpine 0.4% (Qlosi; Orasis Pharmaceuticals) is 1 drop in each eye, with an optional second dose 2 to 3 hours later. Reported adverse events occur in approximately 5% to 8% of patients and include headache and instillation site pain.¹

On day 8 of the NEAR-1 and NEAR-2 phase 3 trials, significantly more treated patients achieved more than a 3-line improvement in distance-corrected near visual acuity (DCNVA) without loss of distance acuity compared with vehicle (P<.0001 at all measured time points). On day 15, 20 minutes after the first dose, 52.9% of patients achieved 20/40 DCNVA or better in the study eye and 76.2% achieved 20/40 DCNVA or better OU. At 4 hours after the second dose, 65.5% of patients achieved 20/40 DCNVA in the study eye and 86.4% achieved 20/40 DCNVA OU.²

Aceclidine 1.44%: Pupil-Selective Miotic

The dosing regimen for aceclidine 1.44% ophthalmic solution (Vizz; Lenz Therapeutics) consists of 2 drops per eye once daily, separated by 2 minutes. In clinical use, reported adverse events included instillation site irritation (20%), dim vision (16%), and headache (13%).³

Aceclidine is a cholinergic muscarinic agonist with predominant iris sphincter activity and minimal ciliary muscle stimulation that produces a pinhole effect to increase depth of focus. Comparative data show an iris-to-ciliary muscle selectivity ratio greater than 20:1 for aceclidine, compared with less than 2:1 for pilocarpine.³

In the CLARITY-2 trial, 71% to 73% of treated participants achieved more than 3 lines of improvement in near vision within 0.5 to 1 hour on day 1, compared with 7% to 12% of vehicle-treated participants. A rapid onset of effect (within 0.5 hours) was observed in 71% of participants, and 40% maintained improvement at 10 hours. All time points showed statistically significant differences vs vehicle (P<.0001).⁴

Safety Considerations for Miotic Therapy

Classwide warnings across miotic therapies include blurred vision, caution with night driving, and risk of retinal detachment. Miotic therapies should not be used in patients with iritis, and examination of the retina prior to initiation is advised. Contact lenses should be removed before instillation, but they can be reinserted after 10 minutes.

Neuromodulation and TRPM8 Agonists for Dry Eye

Acoltremon 0.003% ophthalmic solution (Tryptyr; Alcon) is a neuromodulator that targets TRPM8 receptors on trigeminal afferent neurons. Activation of these receptors stimulates basal tear production through coordinated signaling to the lacrimal gland, goblet cells, and meibomian glands.

In the COMET-2 and COMET-3 phase 3 trials, adults aged 30 years and older with dry eye disease were treated with acoltremon twice daily. The primary endpoint was the proportion of patients who achieved more than 10 mm improvement in unanesthetized Schirmer test score at day 14. Secondary endpoints included changes in symptom scores and ocular surface staining. Reported adverse events included instillation site pain in 50% of participants, but less than 1% of patients discontinued treatment due to pain.⁵

The primary endpoint was met in both trials with statistically significant improvement vs vehicle. Secondary endpoints also demonstrated significant improvements in Symptom Assessment In Dry Eye (SANDE) scores at day 28, tear production at days 1 and 90, and reductions in both corneal and conjunctival staining compared with vehicle.⁵

Qualified autologous serum eye drops (qASED) and reproxalap are also being investigated as treatments for ocular surface disease. Dr. Dierker noted that Ocubio’s qASED was launched in April 2025 and reproxalap received a PDUFA extension on its New Drug Application in December 2025.

Clinical Applications

According to the presentation, topical miotics are approved for use in all adults with presbyopia, including post-LASIK patients and pseudophakes. Acoltremon is presented as a treatment option for multiple dry eye subtypes, either as primary therapy or adjunctive treatment, including in patients with inadequate response to immunomodulators.

References

1. Qlosi (pilocarpine hydrochloride ophthalmic solution) 0.4%. Prescribing information. Orasis Pharmaceuticals; 2023. Accessed February 18, 2026. https://47301616.fs1.hubspotusercontent-na1.net/hubfs/47301616/Prescribing%20Information%2005-2025.pdf?hsLang=en&__hstc=30800608.6bdf6bf8ce4d467bbbcc8d9878c8f149.1771425385247.1771425385247.1771425385247.1&__hssc=30800608.2.1771425385247&__hsfp=c104ac02b83bb4e8c3c0e977c02e69ca
2. Holland E, Karpecki P, Fingeret M, et al. Efficacy and safety of CSF-1 (0.4% pilocarpine hydrochloride) in presbyopia: pooled results of the NEAR phase 3 randomized, clinical trials. Clin Ther. 2024;46(2):104-113. doi:10.1016/j.clinthera.2023.12.005
3. 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
4. LENZ Therapeutics announces positive topline data from phase 3 CLARITY presbyopia trials. News release. LENZ Therapeutics. April 03, 2024. Accessed February 18, 2026. https://ir.lenz-tx.com/news-events/press-releases/detail/11/lenz-therapeutics-announces-positive-topline-data-from-phase-3-clarity-presbyopia-trials
5. Pattar GR, Wirta D, Jerkins G, et al; COMET-2 and COMET-3 Study Groups. Acoltremon ophthalmic solution 0.003% for signs and symptoms of dry eye disease: results of phase 3 pivotal COMET-2 and COMET-3 studies. Ophthalmology. 2025;
   S0161-6420(25)00605-0. doi:10.1016/j.ophtha.2025.09.018