In recent years, increased attention has been directed to the circadian effects of glaucoma medications. While prostaglandin analogues (PGA) and, to a lesser degree, carbonic anhydrase inhibitors (CAI) have been shown to have a sustained IOP-lowering effect at nighttime, beta-blockers and alpha-sympathomimetics do not. Pilocarpine is one of the oldest glaucoma medications, but has been largely abandoned for glaucoma therapy due to its unfavorable safety profile, the necessity of four times daily applications, and modest efficacy. Scarce data were available on its 24-h efficacy.
In this interesting and potentially impactful paper, Seibold et al. studied the 24-h IOP effects of four times daily pilocarpine 2% as an add-on to PGA therapy. Twenty-seven patients with ocular hypertension and open-angle glaucoma were housed in a sleep laboratory for 24 hours. IOP and ocular perfusion pressure (OPP) were measured in the habitual body positions. The investigators found that pilocarpine could lower IOP significantly in patients on PGA monotherapy throughout the 24-h cycle, while there was no effect on OPP. Important questions remain unanswered: Which would be the optimal sequence of pilocarpine instillation, before or after PGA? What would be the effect of pilocarpine in patients on more than PGA monotherapy? What would be the effect of previous SLT on pilocarpine (this study is probably underpowered to answer this)?
More intense medical therapy leads to lower IOP
These findings may potentially herald a new era for pilocarpine in glaucoma treatment. As we move towards better monitoring of IOP over the full circadian cycle, treatments to lower nighttime IOP will be sought. It can be argued that a once-daily dose of pilocarpine (bedtime) would eliminate most of this drugs' unpleasant side effects.