Short-Term Efficacy and Safety of Pilocarpine Ophthalmic Solution for Presbyopia: A Systematic Review and Meta-Analysis.

TOPIC: This systematic review and meta-analysis (SRMA) addresses the clinical question: In patients with presbyopia, how does pilocarpine compare to a vehicle in improving near-vision acuity over a minimum follow-up of 2 weeks? Randomized clinical trials (RCTs) were included to assess the effectiveness of pilocarpine, an FDA-approved pharmacological alternative to traditional corrective measures.

CLINICAL RELEVANCE: Presbyopia is a progressive age-related condition affecting near vision, impacting approximately 1.8 billion people worldwide. Glasses and contact lenses have limitations and can cause discomfort. In 2021, the FDA approved 1.25% pilocarpine hydrochloride ophthalmic solution (VuityⓇ) as a pharmacological alternative. Pilocarpine acts on muscarinic receptors to improve accommodation and depth of focus. Its efficacy and safety, however, require further investigation.

METHODS

This SRMA followed the Cochrane Handbook and PRISMA guidelines. RCTs comparing pilocarpine to a vehicle in presbyopic patients were included. Efficacy outcomes were the gain of ≥3 lines and ≥2 lines in mesopic, high-contrast binocular distance-corrected near visual acuity (DCNVA) at 3 hours postdose after ≥14 days of treatment. Safety analyses focused on the most consistently reported reactions: headache, blurred vision, eye pain, and pupil size variation.

RESULTS

Four RCTs with 1531 participants were included. Pooled data showed 33% of pilocarpine users gained ≥3 lines in DCNVA versus 12% in the vehicle group (OR 3.69, 95% CI [2.66-5.14], P < .001) and 63% of pilocarpine users gained ≥2 lines versus 36% (OR 2.94, 95% CI [2.30-3.74], P < .001). Pilocarpine increased the risk of headache (+6.9%; OR 3.02, 95% CI 1.53-5.93), blurred vision (+3.1%; OR 4.93, 95% CI 1.92-12.65), and eye pain (+2.4%; OR 4.26, 95% CI 1.73-10.49), mostly mild and transient. A marked miotic effect was also observed, with a mean pupil size reduction of 1.38 mm versus 0.02 mm in the vehicle group. Sensitivity analysis indicated that removing the VIRGO study reduced heterogeneity, suggesting dosing frequency influence.

CONCLUSION

Pilocarpine demonstrated short-term efficacy in improving near vision in presbyopic patients, with an increased incidence of specific, mostly mild and transient adverse events and a consistent miotic effect. Further large-scale, long-term RCTs are warranted to confirm benefits, optimize dosing, and fully characterize its safety profile.