The drug is pilocarpine, a compound derived from the leaves of the South American jaborandi plant, and it has endured in ophthalmology for a remarkably simple reason: it works. First introduced as a topical glaucoma treatment in 1875, pilocarpine holds the distinction of being the oldest anti-glaucoma medication still in clinical use. While newer drug classes have largely replaced it as a first-line therapy, pilocarpine remains a critical tool for managing angle-closure glaucoma, ocular hypertension, and certain cases of primary open-angle glaucoma — a track record that few drugs in any field of medicine can match. What makes pilocarpine’s story especially relevant today is its unexpected second act.
In December 2021, AbbVie launched VUITY, a reformulated pilocarpine eye drop that became the first FDA-approved treatment for presbyopia — the age-related loss of near vision that affects virtually everyone over 40. Suddenly, a drug that many younger ophthalmologists had never prescribed was back in the spotlight, repackaged for an entirely different condition. This article covers how pilocarpine works, why it was eventually displaced by newer glaucoma drugs, how it compares to alternatives like timolol, and what its modern comeback means for patients dealing with both vision loss and the neurological connections between eye health and brain aging. For readers of a dementia care site, the connection between glaucoma and cognitive decline is not incidental. Research has increasingly linked elevated intraocular pressure and optic nerve damage to neurodegenerative processes, making the history and future of glaucoma treatment a subject worth understanding beyond the eye clinic.
Table of Contents
- Why Has Pilocarpine Been Used for 50 Years to Treat Glaucoma?
- How Glaucoma Drugs Have Evolved Since Pilocarpine
- The Scale of Glaucoma and Why Old Drugs Still Matter
- Pilocarpine vs. Timolol — Choosing Between Two Veterans
- Pilocarpine’s Surprising New Life as a Presbyopia Treatment
- The Eye-Brain Connection and Why Glaucoma Matters for Dementia
- What Comes Next for Glaucoma Treatment
- Conclusion
Why Has Pilocarpine Been Used for 50 Years to Treat Glaucoma?
Pilocarpine is a muscarinic agonist, which means it stimulates certain receptors in the eye‘s smooth muscle tissue. When applied as a drop, it causes the pupil to constrict and opens the trabecular meshwork — the spongy tissue near the base of the iris that serves as the eye’s primary drainage channel. By physically widening this drainage pathway, pilocarpine increases the outflow of aqueous humor, the clear fluid that fills the front of the eye, thereby lowering intraocular pressure. Elevated IOP is the single most significant modifiable risk factor for glaucoma progression, and pilocarpine addressed it directly at a time when no other topical option existed. From 1875 through the late 1970s, pilocarpine was essentially the only game in town for topical glaucoma management. Carbonic anhydrase inhibitors arrived in 1954, but the real shift came in 1978 when timolol, a beta-blocker eye drop, received FDA approval and quickly became the dominant therapy worldwide.
Even then, pilocarpine did not disappear. It remained a go-to option for acute angle-closure glaucoma, where its pupil-constricting effect physically pulls the iris away from the drainage angle — a mechanical intervention that beta-blockers and later prostaglandin analogs cannot replicate. That specific utility is one reason the drug has never been fully retired. The other reason is cost and familiarity. Pilocarpine is long off-patent, widely manufactured, and well understood. In low- and middle-income countries, where glaucoma underdiagnosis exceeds 90 percent, an inexpensive and proven drug with a known safety profile remains invaluable, even if wealthier health systems have moved on to newer options.
How Glaucoma Drugs Have Evolved Since Pilocarpine
The history of glaucoma pharmacology reads like a timeline of incremental improvement, each new class addressing the limitations of the last. After pilocarpine dominated for a century, timolol’s FDA approval in 1978 offered a beta-blocker alternative that lowered IOP by reducing aqueous humor production rather than increasing outflow. Timolol worked within 20 minutes, lasted up to 24 hours, and did not cause the pupil constriction and dim vision that made pilocarpine inconvenient for many patients. For roughly two decades, timolol was the most frequently prescribed anti-glaucoma drug in the world. The next major leap came in 1996, when latanoprost (marketed as Xalatan) became the first prostaglandin analog approved for glaucoma. Prostaglandin analogs lower IOP by enhancing a secondary drainage pathway called the uveoscleral outflow, and they do so with once-daily dosing and fewer systemic side effects than beta-blockers.
Latanoprost rapidly became the new first-line standard and remains so today. More recently, netarsudil (Rhopressa), a Rho kinase inhibitor approved in 2017, introduced the first genuinely new drug class in over 20 years, and Rocklatan, a fixed combination of netarsudil and latanoprost, followed in 2019. However, if you assume that newer always means better for every patient, you will be wrong. Prostaglandin analogs can darken the iris and cause eyelash growth — cosmetic effects that some patients find unacceptable. Beta-blockers like timolol carry systemic risks including bradycardia and bronchospasm, making them dangerous for patients with asthma or certain heart conditions. Each drug class has its niche, and pilocarpine’s niche — particularly in acute angle-closure situations — has never been fully replaced by any of its successors.
The Scale of Glaucoma and Why Old Drugs Still Matter
Roughly 80 million people worldwide had glaucoma as of 2020, with about 60 million of those cases classified as open-angle glaucoma. The disease causes between 9 and 12 percent of all blindness globally, affecting approximately 5.9 million people with complete vision loss. Those numbers are expected to climb sharply: projections suggest 185 million cases by 2060 among adults aged 40 and older, with about 30 percent of new cases linked to rising rates of myopia. The geographic distribution of glaucoma is uneven in ways that matter for drug access. Prevalence of primary open-angle glaucoma is highest in Africa at 4.20 percent, while angle-closure glaucoma is most common in Asia at 1.09 percent.
In low- and middle-income countries, underdiagnosis exceeds 90 percent, compared to roughly 50 percent in high-income nations. That gap means millions of people who do eventually receive a diagnosis may have limited access to newer, more expensive medications. For those patients, pilocarpine and timolol — both affordable, both well-understood, both available in generic formulations — are not relics. They are lifelines. Consider a patient in sub-Saharan Africa presenting with acute angle-closure glaucoma. The gold standard treatment is laser iridotomy, but if the nearest laser-equipped facility is hours away, pilocarpine drops can buy critical time by mechanically opening the drainage angle. No prostaglandin analog can do that. This is not a theoretical scenario — it is a daily reality in large parts of the world, and it is one of the clearest arguments for why a 150-year-old drug remains relevant.
Pilocarpine vs. Timolol — Choosing Between Two Veterans
Both pilocarpine and timolol have been staples of glaucoma treatment for decades, but they work through fundamentally different mechanisms and suit different clinical situations. Pilocarpine increases aqueous humor outflow by opening the trabecular meshwork. Timolol decreases aqueous humor production by blocking beta-adrenergic receptors in the ciliary epithelium. The practical result is that both lower IOP effectively, but the tradeoffs differ. Pilocarpine’s main drawback is miosis — pupil constriction that can dim vision, particularly in low-light conditions. Patients often report difficulty driving at night.
It also requires dosing multiple times per day, which reduces adherence. Timolol, by contrast, is typically dosed once or twice daily and does not constrict the pupil, but it carries the risk of systemic absorption. Because beta-blockers affect the heart and lungs, timolol is contraindicated in patients with asthma, COPD, or significant bradycardia. A patient with both glaucoma and moderate asthma would be a poor candidate for timolol but could safely use pilocarpine. Today, both drugs are generally considered second-line behind prostaglandin analogs for chronic open-angle glaucoma. But in combination regimens, where one drug alone does not achieve target IOP, either or both may be added. The choice between them often comes down to the patient’s other medical conditions and their tolerance for each drug’s specific side effects — a decision that has not changed much in the 48 years since timolol was approved.
Pilocarpine’s Surprising New Life as a Presbyopia Treatment
The most unexpected chapter in pilocarpine’s long history began in December 2021, when AbbVie launched VUITY, a 1.25 percent pilocarpine hydrochloride formulation approved as the first eye drop for presbyopia. Presbyopia is the gradual, age-related stiffening of the lens that makes it difficult to focus on near objects — the reason most people over 40 need reading glasses. VUITY exploits pilocarpine’s pupil-constricting effect to create a pinhole-camera effect that extends depth of focus, allowing patients to read without glasses for several hours after instillation. The concept is elegant, but the limitations are real. VUITY’s effect typically lasts four to six hours, and it does not work equally well for everyone. Patients with advanced presbyopia or large pupils may see less benefit.
The miosis that helps near vision can also reduce peripheral vision and make dim environments harder to navigate — the same tradeoff that made pilocarpine inconvenient for glaucoma patients decades earlier. AbbVie’s commercial results with VUITY were underwhelming, and uptake was slower than projected. Competing products have attempted to address these drawbacks. In early 2025, Orasis Pharmaceuticals launched Qlosi, a lower-concentration pilocarpine formula at 0.4 percent, designed to reduce the vision-dimming side effects while still improving near focus. And in July 2025, the FDA approved VIZZ, an aceclidine-based drop from LENZ Therapeutics that works through a similar miotic mechanism but with a different pharmacological profile. These newer entries suggest that pilocarpine did not just return to relevance — it opened an entirely new therapeutic category that other companies are now racing to refine.
The Eye-Brain Connection and Why Glaucoma Matters for Dementia
For anyone following dementia research, glaucoma is more than an eye disease. The optic nerve is an extension of the central nervous system, and the retinal ganglion cells that glaucoma destroys share structural and biochemical similarities with neurons lost in Alzheimer’s disease. Several large population studies have found statistical associations between glaucoma and increased dementia risk, though the relationship remains complex and likely involves shared mechanisms such as vascular dysfunction, neuroinflammation, and impaired cerebrospinal fluid dynamics rather than a direct causal pathway.
What this means practically is that managing intraocular pressure — whether with pilocarpine, timolol, prostaglandin analogs, or surgical intervention — may have implications beyond preserving sight. It also means that caregivers and family members of people with cognitive decline should pay attention to eye health as part of comprehensive neurological care. Vision loss compounds the disorientation and confusion associated with dementia, and treating reversible or manageable causes of visual impairment is one of the more straightforward interventions available.
What Comes Next for Glaucoma Treatment
The glaucoma drug pipeline is more active now than at any point since the prostaglandin era. Rho kinase inhibitors like netarsudil have introduced new mechanisms, and combination formulations are reducing the pill — or rather, drop — burden for patients on multiple medications. Gene therapies and sustained-release implants that could eliminate daily dosing altogether are in various stages of clinical development.
But the projected surge to 185 million glaucoma cases by 2060, driven in part by population aging and rising myopia rates, means that access will remain as important as innovation. The drugs that will matter most in the next 50 years are not necessarily the newest or most sophisticated — they are the ones that reach patients who need them, in formulations they can afford and use consistently. Pilocarpine has survived for 150 years not because it is the best drug, but because it is good enough, cheap enough, and versatile enough to remain useful even as the field transforms around it. That is a harder standard to meet than most people realize.
Conclusion
Pilocarpine’s longevity is not a curiosity of medical history — it is a case study in what makes a drug genuinely durable. It addressed a fundamental mechanism of disease, remained useful as a second-line and acute-care option even after superior alternatives arrived, and then found an entirely new application in presbyopia treatment more than a century after its introduction. Its story also illustrates how the global burden of glaucoma, with 80 million cases today and projections nearly doubling by 2060, demands both innovation and continued access to proven, affordable therapies.
For those navigating dementia care or concerned about cognitive decline, the takeaway is that eye health and brain health are more connected than most clinical conversations acknowledge. Ensuring that glaucoma is diagnosed and treated — whether with a drug first used in 1875 or one approved last year — is part of a broader strategy for preserving neurological function and quality of life. Talk to an ophthalmologist about screening, especially after age 40, and do not assume that an old drug is an obsolete one.
