Understanding Anisocoria: What Drugs Cause Unequal Pupils?

October 10, 2025 •

4 min read

Affecting up to 20% of the population, a slight difference in pupil size, or physiologic anisocoria, is common and benign [1.5.3]. However, for others, the answer to what drugs cause unequal pupils is a critical diagnostic question when the change is sudden or significant.

Quick Summary

A detailed examination of medications that induce anisocoria (unequal pupils). The content covers specific drug classes, mechanisms of action, diagnostic considerations, and how to differentiate benign versus emergent causes.

Key Points

Anticholinergics: Drugs like scopolamine (patches) and ipratropium (inhalers) are common causes of a dilated pupil in one eye due to accidental contact [1.7.1, 1.8.1].
Mechanism: Unequal pupils are caused by drugs that either block pupil constriction (anticholinergics) or stimulate dilation (sympathomimetics) [1.5.3, 1.7.1].
Accidental Exposure: The most frequent cause of pharmacologic anisocoria is the inadvertent transfer of medication from hands to the eye [1.7.4, 1.8.3].
Diagnostic Test: A pharmacologically dilated pupil will not constrict when 1% pilocarpine drops are applied, helping differentiate it from a neurologic issue [1.6.5, 1.8.2].
Miotics: Medications like pilocarpine, used for glaucoma, will cause the pupil of the treated eye to become smaller (miosis) [1.2.3].
Red Flags: Anisocoria with a droopy eyelid (ptosis), double vision, or severe headache signals a potential medical emergency that requires immediate attention [1.2.6].
Benign but Alarming: While often harmless and temporary, medication-induced anisocoria can mimic signs of a serious neurological condition [1.8.4].

Introduction to Pharmacologic Anisocoria

Anisocoria, or unequal pupil size, can be a startling discovery. While many people have a naturally occurring and harmless difference in the size of their pupils (physiologic anisocoria), a new onset of this condition often warrants investigation [1.5.1]. When medication is the cause, it's known as pharmacologic anisocoria [1.2.3]. This occurs when a drug or chemical substance affects the muscles of the iris in one eye more than the other, leading to a visible size discrepancy [1.2.3]. The effect can be either dilation (mydriasis) of one pupil or constriction (miosis) of one pupil [1.5.3]. Understanding the mechanism is key: pupillary function is controlled by the autonomic nervous system. The sympathetic pathway triggers dilation (widening), while the parasympathetic pathway controls constriction (narrowing) [1.5.3]. Drugs that interfere with these pathways can alter pupil size.

Drugs That Cause a Dilated Pupil (Mydriasis) in One Eye

The most common cause of pharmacologic anisocoria is unilateral mydriasis [1.3.4]. This typically happens due to accidental, direct contact of a substance with the eye [1.3.1].

Anticholinergic Agents

Anticholinergics work by blocking the parasympathetic nerve signals that tell the iris sphincter muscle to constrict [1.7.1, 1.7.4]. When this signal is blocked in one eye, that pupil remains dilated and does not react well to bright light [1.2.1].

Scopolamine Patches: Used for motion sickness, these patches are a frequent culprit. If a person touches the patch and then rubs their eye, the scopolamine can be transferred, causing significant dilation that can last for days [1.7.2, 1.7.3].
Ipratropium Inhalers: Used for asthma and COPD, aerosolized ipratropium from a poorly fitting nebulizer mask can spray into one eye, causing pupil dilation [1.8.1, 1.8.3]. This is a well-documented phenomenon in hospital and emergency settings [1.3.1, 1.8.4].
Certain Plants: Plants from the belladonna alkaloid family, like Jimson Weed and Angel's Trumpet, contain naturally occurring atropine and scopolamine. Gardeners or children who handle these plants and touch their eyes can experience unilateral mydriasis [1.3.4, 1.3.5].
Eye Drops: Mydriatic eye drops used for eye exams, such as atropine, tropicamide, and cyclopentolate, are designed to dilate the pupils. Accidental instillation in only one eye will cause anisocoria [1.2.2].

Sympathomimetic Agents

These drugs mimic the sympathetic nervous system, stimulating the iris dilator muscle to contract, thus widening the pupil [1.7.1]. Examples include phenylephrine (found in some decongestant eye drops) and brimonidine [1.2.2, 1.2.3]. Recreational drugs like cocaine and amphetamines also have this effect, though they typically cause bilateral dilation [1.3.3].

Drugs That Cause a Constricted Pupil (Miosis) in One Eye

Less commonly, a drug can cause one pupil to become smaller than the other. This happens when a substance overstimulates the parasympathetic system or blocks the sympathetic system.

Cholinergic/Miotic Agents

These drugs stimulate the iris sphincter muscle to contract, resulting in miosis.

Pilocarpine: This is the classic example. As a glaucoma medication, it is used to constrict the pupil and improve fluid drainage from the eye [1.2.3, 1.4.2]. If used in only one eye, it will cause significant anisocoria.
Organophosphates: Found in some pesticides and flea collars, exposure to these chemicals can cause miosis [1.2.4, 1.4.6].
Opioids: While drugs like morphine, heroin, and fentanyl typically cause bilateral pinpoint pupils, asymmetric exposure is theoretically possible [1.4.2, 1.4.7].

Comparison of Common Drug-Induced Anisocoria Causes


Drug Class	Mechanism of Action	Effect on Pupil	Common Examples	Common Route of Exposure
Anticholinergics	Blocks parasympathetic signals to the iris sphincter muscle [1.7.1]	Dilation (Mydriasis)	Scopolamine, Ipratropium, Atropine [1.2.1, 1.2.4]	Accidental hand-to-eye contact from patches, inhalers, plants [1.7.4, 1.8.3]
Sympathomimetics	Stimulates the sympathetic iris dilator muscle [1.7.1]	Dilation (Mydriasis)	Phenylephrine, Brimonidine, Cocaine [1.2.2, 1.3.3]	Eye drops, nasal sprays, systemic use [1.3.4]
Cholinergics (Miotics)	Stimulates the parasympathetic iris sphincter muscle [1.4.6]	Constriction (Miosis)	Pilocarpine, Carbachol [1.2.4, 1.4.2]	Glaucoma eye drops [1.2.3]
Opioids	Central nervous system effect on parasympathetic pathways [1.4.6]	Constriction (Miosis)	Morphine, Fentanyl, Heroin [1.4.7]	Systemic use [1.4.2]

Differentiating Benign vs. Emergent Causes

While pharmacologic anisocoria is typically benign, unequal pupils can also be a sign of a neurological emergency. A key diagnostic step for a dilated pupil is the pilocarpine test [1.6.2]. A pupil dilated by an anticholinergic agent (pharmacologic blockade) will fail to constrict even when a strong (1%) pilocarpine drop is administered [1.6.5, 1.8.2]. In contrast, a pupil dilated from a third nerve palsy (a potential emergency) will still constrict with pilocarpine because the muscle itself is healthy [1.6.5].

Seek immediate medical attention if unequal pupils are accompanied by:

A droopy eyelid (ptosis) [1.2.6]
Double vision or changes in vision [1.2.6]
A severe headache or neck pain [1.2.6]
Recent head or eye trauma [1.2.6]
Numbness or weakness on one side of the body

These can be signs of serious conditions like a brain aneurysm, tumor, or carotid artery dissection [1.2.6, 1.2.7].

Conclusion

Numerous medications and chemicals can cause unequal pupils, a condition known as pharmacologic anisocoria. The most common scenario involves accidental exposure of one eye to an anticholinergic substance like a scopolamine patch or ipratropium inhaler, leading to a fixed, dilated pupil. While often harmless and temporary, it is crucial to obtain an accurate medical history and evaluation to distinguish this benign cause from a life-threatening neurological emergency. Careful handwashing after handling certain medications and being aware of potential side effects are key preventative measures [1.7.2]. If there is any doubt about the cause, a medical evaluation is essential.

Disclaimer: This article is for informational purposes only and does not constitute medical advice. Consult a healthcare professional for diagnosis and treatment of any medical condition.

For more in-depth clinical information, consider this resource from the American Academy of Ophthalmology's EyeWiki: https://eyewiki.org/Anisocoria

Frequently Asked Questions

Many drugs can cause unequal pupils (anisocoria), most commonly anticholinergics like scopolamine patches and ipratropium inhalers which cause dilation. Other causes include sympathomimetic eye drops (phenylephrine), miotic eye drops for glaucoma (pilocarpine), and some plants like Jimson weed [1.2.1, 1.2.2, 1.2.4].

Yes, if your inhaler contains ipratropium bromide, aerosolized medication can leak from a poorly fitting face mask and get into one eye, causing that pupil to dilate. This is a known cause of temporary anisocoria [1.3.1, 1.8.3].

The pupil dilation from accidental scopolamine exposure is temporary but can be long-lasting. It typically resolves on its own within 24 to 72 hours as the medication's effect wears off [1.7.2].

The pilocarpine test helps determine the cause of a dilated pupil. A drop of 1% pilocarpine will not constrict a pupil that is dilated from a drug like atropine or scopolamine (pharmacologic blockade). However, it will constrict a pupil dilated due to nerve damage, like a third nerve palsy [1.6.2, 1.6.5].

Yes, certain antidepressants, particularly tricyclic antidepressants and SSRIs, have anticholinergic properties and have been identified as potential causes of pharmacologic anisocoria, though this is less common than topical exposure [1.2.3, 1.2.5].

It can be. While often caused by a benign medication exposure, you should seek immediate medical attention if unequal pupils are accompanied by a droopy eyelid, double vision, a new severe headache, or followed a head injury, as these can be signs of a stroke or aneurysm [1.2.6].

Other causes include physiologic anisocoria (a normal variation in about 20% of people), Adie's tonic pupil, Horner syndrome, third nerve palsy from an aneurysm or tumor, eye trauma, and inflammation within the eye (uveitis) [1.2.6, 1.5.3].