Pharmacological Breakthrough in Presbyopia Treatment: Pilocarpine and Aceclidine Offer New Hope

Dr. Mohd Mizanur Rahman

By Dr. Mohammad Mizanur Rahman, PhD

Presbyopia or age-related healthy eyes near reading problem, Traditionally managed through reading glasses, bifocals , multifocal contact lenses, or surgical interventions, the condition has long been considered a natural part of aging with no pharmaceutical cure. However, recent advancements in pharmacological treatments, specifically with the use of miotic agents such as pilocarpine and aceclidine, have brought renewed hope to millions seeking non-invasive solutions. Presbyopia, the age-related loss of the eye's ability to focus on near objects, affects over 1 . 8 billion people worldwide . 

Presbyopia typically begins to affect individuals after the age of 40. As a result, reading , using smartphones , or performing close up tasks becomes increasingly difficult without optical aids . It occurs due to the gradual stiffening of the eye's crystalline lens , which impairs the ability to accommodate or change shape to focus on nearby objects . Food and Drug Administration FDA approved VUITY , a pilocarpine hydrochloride 1 . 25 ophthalmic solution developed by AbbVie . While the optical industry has long dominated the management of presbyopia , pharmaceutical research is finally catching up , offering alternatives that do not require lenses or surgery . Pilocarpine and Aceclidine In 2021 , the U . S . According to a pivotal clinical trial , VUITY demonstrated a statistically significant improvement in near visual acuity in presbyopic patients aged 40 to 55 , without affecting distance vision . Pilocarpine is a cholinergic muscarinic receptor agonist that stimulates the iris sphincter muscle , causing miosis pupil constriction . This pinhole effect increases the depth of focus , thereby improving near vision without significantly compromising distance vision . A multi center Phase 3 study involving over 750 participants revealed that more than 30 of those who used VUITY could read three additional lines on a near vision eye chart without reading glasses . Minor side effects included headache , eye redness , and brow ache . The effect typically begins within 15 minutes of instillation and lasts up to six hours . Clinical trials conducted in France and Spain by Presbyopia Therapies , LLC , showed that a 2 aceclidine eye drop significantly improved near vision in over 70 of participants , with a better safety profile than pilocarpine . Researchers noted that the drug created a stable depth of focus enhancement without inducing substantial myopic shift or night vision issues . A Newcomer in the Pipeline Another promising agent is aceclidine , a miotic compound structurally related to pilocarpine but with a more targeted mechanism . Unlike pilocarpine , aceclidine does not stimulate the ciliary muscle as strongly , which minimizes accommodative spasms and reduces the risk of headaches and visual disturbances . Combination Therapy and Dual Action Eye Drops Some pharmaceutical companies are exploring combination eye drops that pair aceclidine or pilocarpine with non steroidal anti inflammatory drugs NSAIDs like diclofenac or ketorolac to improve tolerability . Others combine miotics with low dose atropine to balance pupil constriction with accommodative support . Orasis Pharmaceuticals in Israel developed a proprietary formula CSF 1 combining low dose pilocarpine with other agents to reduce side effects . Comparison with Traditional Treatments Compared to reading glasses or multifocal lenses , these pharmacological treatments offer non invasive and cosmetic advantages . They eliminate the need to carry glasses or wear contacts and appeal especially to younger presbyopic patients reluctant to adopt visible optical aids . Phase 2b clinical trials showed meaningful improvement in near vision and minimal side effects Orasis Pharmaceuticals , 2022 . Surgical options , such as corneal inlays or refractive lens exchange RLE , carry risks like infection , dry eye , or regression . Despite these breakthroughs , miotic therapy is not without limitations . In contrast , eye drops like pilocarpine and aceclidine are reversible and adjustable , allowing for a more flexible approach to vision correction . Most drops last only 4 to 8 hours , requiring daily or multiple doses . There is limited data on long term use , especially for daily use over years . Common side effects include headaches , eye irritation , reduced night vision due to miosis , and a risk of retinal detachment in predisposed individuals . Several other pharmacologic agents are under investigation , including UNR844 lipoic acid choline ester , A lens softening agent in trials by Novartis . Patients with a history of retinal disease , narrow angle glaucoma , or inflammatory eye conditions should consult an ophthalmologist or Qualified Optometrist before using these drops and check the retina and Angle condition of the eyes . These developments are reshaping how eye care professionals view and manage presbyopia . AGN 190584 An extended release pilocarpine formulation . The trial showed promising results with modified concentrations to suit smaller pupil sizes common among East Asian populations . A collaborative study between Keio University and Santen Pharmaceuticals tested pilocarpine based therapy among Japanese adults . The treatment of presbyopia using pilocarpine and aceclidine represents a paradigm shift in the field of ophthalmology and optometry . These pharmacological agents offer patients a non invasive , cost effective , and flexible alternative to glasses or surgery . Indian researchers from AIIMS , New Delhi , reported that low dose pilocarpine therapy is both effective and well tolerated in urban Indian populations , with added benefits in reducing intraocular pressure IOP , offering potential value in patients with coexisting ocular hypertension . As more research emerges and new formulations become available , optometrists and ophthalmologists worldwide will be better equipped to provide customized care tailored to the lifestyle and preferences of their patients . The journey from accepting presbyopia as a normal aging process to actively treating it pharmacologically reflects the power of modern science to transform lives and to help us all see the future a little more clearly . Although not a universal solution , and not without side effects , they mark an important milestone in personalizing vision correction for the aging population .

(By Dr. Mohammad Mizanur Rahman, PhD is an Assistant Professor & Research Fellow Management & Science University, Malaysia.)