Pilocarpine for Presbyopia: A Meta-Analysis of Short-Term Efficacy and Safety – Implications for Vitreoretinal Practice

Pilocarpine for Presbyopia: A Meta-Analysis of Short-Term Efficacy and Safety – Implications for Vitreoretinal Practice

Introduction
As vitreoretinal surgeons, we are keenly aware of the delicate balance between therapeutic innovation and ocular safety. The recent FDA approval of 1.25% pilocarpine hydrochloride (Vuity®) for presbyopia has introduced a new pharmacological option into the refractive arena. While this may seem peripheral to our subspecialty, the potential retinal implications and the drug’s mechanism of action warrant our attention. This post summarizes key findings from a recent systematic review and meta-analysis (SRMA) on pilocarpine’s short-term use in presbyopia, with a focus on data relevant to retinal health and surgical planning.

Key Efficacy Findings
The SRMA, published in the American Journal of Ophthalmology (2025), analyzed four RCTs involving 1,531 patients. The primary efficacy outcome was the gain of ≥3 lines in mesopic, binocular distance-corrected near visual acuity (DCNVA) after at least 14 days of treatment, measured 3 hours post-dose.

• Gain of ≥3 lines: 33% of pilocarpine users achieved this versus 12% in the vehicle group (OR 3.69, 95% CI 2.66–5.14, P < .001).
• Gain of ≥2 lines: 63% of pilocarpine users achieved this versus 36% with vehicle (OR 2.94, 95% CI 2.30–3.74, P < .001).

These results confirm pilocarpine’s significant short-term efficacy in improving near vision, primarily through its miotic effect, which increases depth of focus.

Safety Profile: The Vitreoretinal Perspective
The safety analysis is particularly relevant for our practice. The meta-analysis focused on consistently reported adverse events:

1. Common Adverse Events: Pilocarpine increased the risk of mostly mild and transient side effects:
   • Headache: +6.9% absolute risk increase (ARI).
   • Blurred Vision: +3.1% ARI.
   • Eye Pain: +2.4% ARI.
2. Miotic Effect: A consistent finding was a mean pupil size reduction of 1.38 mm in the pilocarpine group versus 0.02 mm with vehicle. This sustained miosis has direct implications for our clinical examinations and surgical procedures.
3. Rhegmatogenous Retinal Detachment (RRD): Crucially, no RRD cases were reported in these short-term (14-30 day) trials. The authors note this is likely due to the brief follow-up. They cite other evidence, including a 2024 study by Elhusseiny et al., which found pilocarpine use was associated with a 3.14-fold increased risk of RRD in patients over 40, and a multicenter case series reporting detachments in patients using topical pilocarpine for presbyopia. This underscores a potential serious risk that may only manifest with longer-term use.

Clinical Implications for Vitreoretinal Surgeons

1. Pre-operative Assessment: A patient scheduled for retinal surgery (e.g., vitrectomy, pneumatic retinopexy) who uses pilocarpine for presbyopia may have a poorly dilating pupil due to potential “permanent miosis” from prolonged use, as noted in the discussion. This can complicate peripheral retinal examination and surgical access. A detailed medication history is now more important than ever.
2. Post-operative Care: The drug’s mechanism—ciliary muscle contraction and accommodative spasm—theoretically could influence vitreous dynamics or intraocular inflammation, though this was not reported in the short-term studies. Caution is advised when considering pilocarpine in eyes with compromised zonules or in the post-vitrectomy eye.
3. Patient Counseling: When patients inquire about presbyopia treatments, we must be prepared to discuss the efficacy and all risks. We should inform them that while pilocarpine is effective short-term, its long-term safety profile, particularly regarding RRD risk, is not fully characterized. The discussion should balance this against the risks of surgical presbyopia corrections (e.g., PresbyLASIK, corneal inlays), which carry their own risks of infection, retinal detachment, and visual disturbances.

Conclusions and Future Directions
Pilocarpine represents a novel, effective short-term pharmacological option for presbyopia. For the vitreoretinal community, the pronounced miotic effect and the signal of a potential increased RRD risk with longer-term use are the key takeaways. These factors necessitate heightened awareness during preoperative workups and in patient counseling.

The authors of the SRMA call for further large-scale, long-term RCTs to confirm benefits, optimize dosing, and fully characterize the safety profile. As retinal specialists, we should monitor this evolving literature closely, as the long-term ocular safety data will ultimately define this drug’s place in therapy and its implications for our surgical landscape.