Recent research published in the American Journal of Ophthalmology offered an in-depth look at the the safety and efficacy of pilocarpine hydrochloride 1.25% when dosed twice daily (BID) in patients diagnosed with presbyopia.
Give me some background first.
Standard treatment for presbyopia has historically included non-surgical methods—such as spectacles and contact lenses—and surgical methods like monovision photorefractive keratectomy (PRK), presbyopia-correcting intraocular lenses (PCIOLs), small incision lenticule extraction (SMILE) monovision, or laser-assisted in situ keratomileusis (LASIK), to name a few.
However, such methods may cause reduced visual quality or potential risks and complications.
Now talk about pilocarpine.
Pilocarpine is a muscarinic receptor agonist in topical ophthalmic formulations used to treat elevated intraocular pressure (IOP) associated with various types of glaucoma and to induce miosis (pupil constriction).
It is also available as an oral treatment to manage dry mouth (xerostomia) and glaucoma.
Isn’t it already FDA approved?
Yes it is! The FDA approved Vuity (pilocarpine HCI 1.25%; Allergan, an AbbVie company) in October 2021 as the first and only eye drop indicated to specifically treat presbyopia.
The approval was based on data from two phase 3 trials, GEMINI 1 and GEMINI 2 (NCT03857542), which confirmed the formulation’s short-term safety and efficacy when dosed bilaterally, once a day, for 30 days.
To note, Vuity dosed once daily demonstrated a duration of effect of approximately 6 hours.
So why pilocarpine HCl 1.25%?
Investigators sought to determine if this concentration may benefit presbyopia patients in achieving longer coverage of their respective near-vision needs when dosed twice daily (BID).
Gotcha. Now talk about this study.
The randomized, multicenter, vehicle-controlled, double-masked, parallel-group, phase 3 VIRGO study (NCT04983589) evaluated pilocarpine HCI 1.25% (referred to then as AGN-190584) in 230 patients (ages 40 to 55 years) diagnosed with presbyopia.
What were the dosings?
Patients were randomized 1:1 into two groups, stratified by age (≤50 vs >50 years) to receive either:
- Pilocarpine HCI 1.25%, BID, for 14 days (n = 114)
- Vehicle, BID, for 14 days (n = 116)
Each participant received one drop of their respective dosage, bilaterally, with a gap of 6 hours between both doses.
How was treatment efficacy measured?
Both primary and secondary outcomes were measured 3 hours after the second dosage on Day 14.
The primary included:
- Percentage of patients gaining 3 lines or more in photopic, high-contrast, binocular distance-corrected near visual acuity (DCNVA) with no less than a 5-letter loss in photopic corrected distance vision acuity (CDVA) with the same refractive correction.
Secondary included:
- Percentage of participants gaining 2 lines or more in mesopic, high-contrast, binocular DCNVA with no less than a 5-letter loss in mesopic CDVA with the same refractive correction.
Treat-emergent adverse events (TEAEs) were also monitored.
Findings?
Out of the 230 participants, 97.4% completed the study in each group (total: 57.4% female; 54.8% >50 years of age).
Overall, a significantly higher proportion of participants in the pilocarpine group achieved both primary and secondary outcomes vs the vehicle group.
Give me specifics.
The treatment difference between the two was 27.3% (P < .01) (primary endpoint) and 26.4% (P < .01) (secondary endpoint).
- Primary endpoint
- Pilocarpine (35.1%)
- Vehicle (7.8%)
- Secondary endpoint
- Pilocarpine (32.5%)
- Vehicle (6%)
Any adverse effects?
TEAEs were reported in 24.6% (pilocarpine group) and 11.2% (vehicle group) of participants, with 20.2% and 4.3% of those being ocular TEAEs, respectively.
The most common TEAE was headache (8.8% of all participants), while the most common ocular TEAEs among the pilocarpine group included:
- Eye irritation (6.1%)
- Visual impairment (4.4%)
- Punctate keratitis (3.5%)
- Eye pain (2.6%)
The vehicle group reported punctate keratitis in 2.6% of patients.
Limitations?
The study authors noted the following:
- Evaluations of the second daily dose were not conducted at any other time point other than Hour 6.
- Efficacy of the second dose was not evaluated beyond 3 hours (Hour 9).
See here for the complete list, under “Findings.”
Expert opinion?
According to the authors, these findings indicate that pilocarpine HCI 1.25% demonstrates statistically greater improvements in near vision without compromising distance acuity.
And compared to pilocarpine HCI 1.25% once daily?
They concluded that the safety profile of pilocarpine HCI 1.25% BID was consistent with that of a once-daily administration.
Which means …
This data led to the FDA approval of pilocarpine HCI 1.25% (VUITY) to be administered BID in March 2023 (see our coverage here).
And for the future?
The authors also recommended that additional studies are needed to, “assess the effects of pilocarpine HCl 1.25% in individuals performing daily tasks involving distance, intermediate, and near vision (corrected and uncorrected).”