A once-commonly used topical ophthalmic medication, pilocarpine has recently re-emerged and gained popularity as a novel treatment for presbyopia.1,2 Although this drug has been around for several decades chiefly as a glaucoma therapy, it has not been routinely prescribed in recent years. With its newly approved use, it is time to re-explore this topical agent and its many (sometimes overlooked) ophthalmic uses as well as potential adverse side effects to be on the lookout for.

Mechanism of Action

Pilocarpine is a muscarinic acetylcholine agonist. It can be administered topically or orally. In order to understand its effects, it is important to first be aware of the muscarinic receptors in the body and their mechanisms of action. There are five different types of muscarinic acetylcholine receptors: M1 through M5. The expression and actions of each vary, and pilocarpine works primarily on the M1 through M3 subtypes, eliciting parasympathetic effects. Specifically, its action on the M3 receptor is most pertinent to its ocular uses. This receptor is expressed in salivary glands and smooth muscle cells, in addition to other areas throughout the body. The parasympathetic effects it has on these areas stimulate salivary gland function, increasing salivation and smooth muscle contraction.1

Clinical Uses

Contraction of the ciliary muscle enables Vuity’s improvement of near vision acuity in patients responsive to such action.

Contraction of the ciliary muscle enables Vuity’s improvement of near vision acuity in patients responsive to such action. Click image to enlarge.

Pilocarpine is not readily used in the clinical setting. Diagnostically, it can help with the diagnosis of Adie’s tonic pupil, which is characterized by the loss of the direct and indirect pupillary light response. Additionally, there are accommodative paresis and slit lamp findings such as segmental iris palsy. Because the underlying pathophysiologic mechanism is a result of damage to the postganglionic parasympathetic nerve of the iris sphincter, which is made up of smooth muscle, pilocarpine testing can help elicit the diagnosis. 

Administration of either 0.125% or 0.062% pilocarpine in the affected eye, in dim lighting, can help assess cholinergic supersensitivity.3 This action substantiates the amount of acetylcholine, resulting in constriction of the pupil by stimulating the sphincter. It also affects accommodation due to its action on the ciliary muscle.4

Other Considerations

Although it is no longer first-line, pilocarpine has long been used in the management of elevated intraocular pressure (IOP) in glaucoma. Its action on the smooth muscle stimulates the iris sphincter and results in the iris pulling away from the trabecular meshwork and aqueous outflow, increasing the eye’s ability to lower IOP.5,6 As such, pilocarpine is a known treatment for glaucoma secondary to acute angle closure from mydriasis or pupil block. 

A necessary consequence of this mechanism of action is pupillary miosis.5 While pilocarpine treatment normally increases the width of the angle due to reduced iris thickness, it can cause acute angle closure in rare cases. For example, a patient with spherophakia who has a highly convex lens and weak zonules will have anterior displacement of the iris-lens diaphragm into the anterior chamber. Other risks include patients with pseudoexfoliation syndrome, phacomorphic glaucoma and malignant glaucoma.5,6

Studies also indicate that oral administration of a pilocarpine 20mg daily dose can serve as treatment for Sjögren’s-related dry eye. Because of its parasympathetic activity, it can increase lacrimation and has been shown to improve both dry eye symptoms and tear film quality. One study showed improvement in Schirmer’s testing, ocular surface disease index and tear breakup time. It was also shown to be well-tolerated, with the most common side effects being sweating and increased salivation.7 Due to pilocarpine’s effect on salivation, it is also approved orally for the treatment of xerostomia (dry mouth) resulting from radiation exposure.1

On the other hand, topical administration of pilocarpine has been shown to affect the morphology and survival of meibomian gland epithelial cells. Meibomian glands are imperative in tear film stability and prevention of tear film evaporation. Topical pilocarpine has been speculated to act on the meibomian gland receptors and deter their function, exacerbating dry eye and having the opposite effect of what is seen with oral treatment.8

Emergent Treatment

Vuity (pilocarpine 1.25%, Allergan) was approved in late 2021 as a treatment for adults with presbyopia. It is the first of its kind and gives patients an option for a non-surgical management strategy for visual correction.9 Treatment outcomes can be explained by pilocarpine’s parasympathetic activity on the ciliary muscle. By causing contraction of this muscle, the lens increases in thickness and depth of focus, allowing for clear near vision in affected patients with presbyopia. Since the lens does not readily change its shape, one study suggested the addition of topical nonsteroidal anti-inflammatory drugs to decrease the intensity of the pupil and ciliary muscle contraction. This allows the lens to more easily change its shape and position, allowing for clear vision at distance as well.2

Side Effects

In addition to the aforementioned effects, pilocarpine also has a unique side effect when administered topically: it induces the presence of flare in the anterior chamber. Flare is characterized by an increase in protein content and can affect vision due to light scattering. This phenomenon is commonly documented and termed “miotic iridocyclitis.” The precise mechanism is not fully understood but presumed to arise from a breakdown in the blood-aqueous barrier. Furthermore, studies have concluded that there is a reservoir of plasma-derived proteins in the iris stroma that originate from the fenestrated blood vessels of the ciliary body. As such, it is speculated that thinning of the iris in miosis causes these proteins to permeate through the anterior chamber and appear as flare.10

Additional side effects, particularly with oral administration of pilocarpine, include those that pertain to an increase in parasympathetic activity. Since pilocarpine acts on muscarinic receptors, which are located throughout the body, systemic side effects are not uncommon. These include vasodilation, sweating, diaphoresis, increased salivation, vomiting, bradycardia, bronchospasm and increased urination and diarrhea. As such, contraindications for treatment are chronic obstructive pulmonary disease, peptic ulcer disease, arrhythmia, coronary vascular disease, hyperthyroidism and urinary obstruction, to name a few.1


Although pilocarpine has been around for a very long time, it previously had limited ocular uses. However, the drug’s recent re-emergence has earned increasing attention for its treatment of adults with presbyopia. Given this new use, it is important to revisit and understand the mechanisms and many effects of the drug. 

Dr. Labib graduated from Pennsylvania College of Optometry, where she now works as an associate professor. She completed her residency in primary care/ocular disease and is a fellow of the American Academy of Optometry and a diplomate in the Comprehensive Eye Care section. She has no financial interests to disclose.

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2. Benozzi G, Perez C, Leiro J, et al. Presbyopia treatment with eye drops: an eight year retrospective study. Transl Vis Sci Technol. 2020;9(7):25.

3. Yoo YJ, Hwang JM, Yang HK. Dilute pilocarpine test for diagnosis of Adie’s tonic pupil. Sci Rep. 2021;11(1):10089.

4. Senthilkumaran S, Balamurugan N, Menezes RG, Thirumalaikolundusubramanian P. Bedside test for anisocoria: not a small matter. Indian J Crit Care Med. 2014;18(7):480-1.

5. Yang MC, Lin KY. Drug-induced acute angle-closure glaucoma: a review. J Curr Glaucoma Pract. 2019;13(3):104-9.

6. Day AC, Nolan W, Malik AN, et al. Pilocarpine induced acute angle closure. BMJ Case Rep. 2012;2012:bcr0120125694.

7. Felberg S, Dantas PEC, Sato EH. Oral pilocarpine for the treatment of dry eye in patients with Sjögren’s syndrome. Arq Bras Oftalmol. 2021:S0004-27492021005009201.

8. Zhang Y, Kam WR, Liu Y, et al. Influence of pilocarpine and timolol on human meibomian gland epithelial cells. Cornea. 2017;36(6):719-24.

9. Jackson MA, Giyanani J, Shabaik Y, et al. In vitro and in-eye comparison of commercial pilocarpine ophthalmic solution and an optimized, reformulated pilocarpine for presbyopia treatment. Ophthalmol Ther. 2022;11(2):869-79.

10. Freddo TF, Neville N, Gong H. Pilocarpine-induced flare is physiological rather than pathological. Exp Eye Res. 2013;107:37-43.