New findings from a study published in Clinical and Experimental Optometry assessed the impact of pilocarpine hydrochloride ophthalmic solution 1.25% (pilocarpine HCl 1.25%) on night-driving performance 1 hour after instillation.
Give me some background first.
Presbyopia is an age-related condition that results in a progressive reduction in lens accommodation, leading to near-vision impairment.
To note, the FDA approved Vuity (pilocarpine HCl 1.25%; Allergan, an AbbVie company) in October 2021 for once-daily dosing as the first eye drop indicated to treat presbyopia.
And in March 2023, it was approved for twice-daily use.
Tell me more.
Constricting the pupil with pilocarpine or other miotic agents can reduce retinal illumination and potentially affect activities performed in dim lighting—including driving at night.
While the FDA requires that the label of pilocarpine HCl 1.25% include warnings and precautions related to this, there have been limited studies measuring the impact of pilocarpine on night-driving performance.
Now, talk about the study.
In this double-masked, crossover, phase 3b study (NCT04837482), investigators evaluated the night-driving performance of 43 adults (40-55 years) with presbyopia.
Participants were randomized to bilateral treatment with pilocarpine HCl 1.25% followed by placebo or placebo followed by pilocarpine. A >7-day washout period took place between interventions.
The night-driving performance was assessed at twilight on a closed-circuit course 1 hour following intervention administration (the peak constriction time for pilocarpine HCl 1.25%).
Patient criteria?
Participants included in the study had presbyopia impacting daily activities and mesopic, high-contrast, binocular distance-corrected vision 20/40-20/100.
And the primary efficacy endpoint?
The overall composite night-driving performance Z score—a measure of distance for datum in a normally distributed sample—at the end of the 7-14 day intervention period, 1 hour post-instillation.
The pilocarpine treatment was considered non-inferior if the lower limit of the 95% confidence interval (CI) for the least squares mean difference (LSMD, pilo minus placebo) was >-0.25.
Any other efficacy endpoints?
The researchers included efficacy endpoints related to individual components of the night-driving performance test, such as:
- Hazard avoidance rate
- Road sign recognition rate and distance
- Pedestrians recognition distance
- Overall driving and lane-keeping times
They also analyzed the responses to a night-driving experience questionnaire and treatment-emergent adverse events (TEAEs).
Results?
The mean overall composite Z scores were -0.121 (pilocarpine HCl 1.25%) and 0.118 (placebo).
The LSMD (pilocarpine minus placebo) was -0.224 (95% CI -0.346, -0.103), with three of the seven individual tasks being significantly better with the placebo.
The questionnaires did not reveal significant differences between pilo and placebo.
Can you explain that in a more practical way?
According to the study authors, “The road sign and pedestrian recognition distances were well below the American National Standards Institute-defined, historic 25% cut-off within which differences are deemed acceptable.”
They added: “Had the test been conducted at Hour 3 (primary endpoint in the GEMINI 1 study), the difference between pilocarpine HCl 1.25% and placebo reported for the individual driving-related tasks and overall night-driving performance score would likely have been reduced.”
Tell me more about TEAEs.
No serious or severe TEAEs and no TEAE-related discontinuations were observed.
The most common TEAEs were headache and visual impairment with pilocarpine HCl 1.25% (both 27.9%) and dry eye (7%) with the placebo.
Take home.
The overall performance of night driving was inferior with pilocarpine HCl 1.25% in comparison to placebo.
These findings are consistent with the current class labeling of pilocarpine HCl 1.25% and provide evidence to inform regulators and guide clinicians considering prescribing it to adults seeking treatment for symptoms of presbyopia who drive at night.