Meta-Analysis Supports Pilocarpine Short-term Safety and Efficacy in Presbyopia Improvement

Given that presbyopia progresses with age (at a rate of about +0.1 D per year), it’s likely that the side effects of presbyopia-correcting drops will eventually outweigh the benefits when the medication is no longer sufficient to correct advancing presbyopic vision. Still, pharmacologic pupil constriction does demonstrate at least some benefit early on. Photo: Michael Trottini, OD, and Michael DelGiodice, OD. Click image to enlarge. Age-related lens changes and progressive visual decline become more noticeable around age 40. Patients seeking vision correction for presbyopia have several options, including reading glasses and contact lenses, and less commonly, surgical interventions such as presbyopic LASIK. But these all come with trade-offs. Every surgery has its risks, and patients with multifocal glasses face a doubled risk of falling due to reduced depth perception and contrast sensitivity.In 2021, a new presbyopia-correcting approach in the form of pilocarpine drops was approved. Pilocarpine causes miosis by prompting pupillary sphincter contraction, making up for some lost accommodation. Several formulations of the drug have been tested in clinical trials. However, because of this variation, the real impact and ideal dose aren’t yet clear. To gain insight, researchers reviewed the existing literature on pilocarpine’s safety and efficacy vs. vehicle and published their results in American Journal of Ophthalmology. Here’s what they found:The meta-analysis included four randomized controlled trials comparing pilocarpine to a vehicle in presbyopic patients. Of the 1,531 total participants, 763 received pilocarpine and 768 received vehicle. The proportion of patients who achieved a gain of ≥3 lines of mesopic distance-corrected near visual acuity three hours after the last drop of the day was significantly greater in the pilocarpine group than the vehicle group (33% vs. 12%). The same trend was found for the secondary outcome measure, with 63% pilocarpine group achieving ≥2 lines compared with 37% of the vehicle group.Table 1. A Summary of Four RCTs and their DosagesStudyPilocarpine DosageGEMINI I1.25% once dailyGEMINI II1.25% once dailyNEAR0.4% twice daily (3 hours apart)VIRGO1.25% twice daily (6 hours apart) Pilocarpine users experienced an average pupil size reduction of 1.38 mm three hours post-instillation, compared to 0.02 mm in the vehicle group. Other side effects identified in the study included elevated risk of headache, blurred vision and mild, transient eye pain. No cases of rhegmatogenous retinal detachment (RRD) were reported, possibly due to the short follow-up period. Long-term usage of topical pilocarpine increases the risk for RRD.A leave-out-one sensitivity analysis, which detects outliers, found that removing the VIRGO study reduced heterogeneity, suggesting dosing frequency influence.“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,” the researchers concluded. Given that this study included only four trials and had a relatively short follow-up period, the researchers advocate for further, large-scale, long-term trials to study the safety, benefits and optimal dosing of pilocarpine.Click here for the journal source. Nery Lima G, Amaral DC, Ivanov YA, et al. Short-term efficacy and safety of pilocarpine ophthalmic solution for presbyopia: a systematic review and meta-analysis. Am J Ophthalmol 2025. [Epub ahead of print]. This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.