Disclosures: Bauer and Skorin report no relevant financial disclosures.
October 26, 2020
5 min read

Young man presents with ocular foreign body complaint, anisocoria

Disclosures: Bauer and Skorin report no relevant financial disclosures.
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A 24-year-old white man presented with a chief complaint of a suspected metallic foreign body in his right eye. The patient stated he was cutting a metal band earlier that day.

The metal band was holding a bundle of wires together when a piece of the wire flew off and hit his unprotected right eye. He reported irritation and epiphora in his right eye that gradually decreased after he irrigated his eye with multipurpose soft contact lens solution and water before arriving at the eye clinic.

His uncorrected entering visual acuity was 20/15 in his right eye and 20/20 in his left eye. Extraocular muscle movements were full in both eyes. Confrontation visual fields were full to finger counting in both eyes.

Asymmetric pupils

In dark room illumination, his pupil diameter was 3 mm in the right eye and 6 mm in the left eye. In bright room illumination, his pupil diameter was 2 mm in the right and 3 mm in the left. Pupil constriction was brisk in the left eye and somewhat sluggish in the right. Each pupil constricted when presented with an accommodative target. There was no afferent pupillary defect present in either eye. Anterior segment examination revealed no retained foreign bodies in either eye.

Anisocoria in bright room illumination showing smaller right pupil. Source: Scott Bauer, OD, and Leonid Skorin Jr., OD, DO, MS, FAAO, FAOCO
Anisocoria in bright room illumination showing smaller right pupil.
Source: Scott Bauer, OD, and Leonid Skorin Jr., OD, DO, MS, FAAO, FAOCO

As the rest of the eye examination progressed, the right pupil continued to constrict further. There was mild superficial punctate keratopathy present inferiorly on his right cornea. The conjunctiva on the right eye was exceptionally white, with no signs of redness, while the left eye had trace conjunctival injection. The anterior chamber of each eye was deep and quiet with no cells or flare present. There was no hyphema in either eye. Seidel test was negative in each eye. His irises were normal with no holes or tears. IOP was 14 mm Hg in each eye. He appeared to be in good health overall.

After the presence of foreign bodies had been ruled out, the patient was questioned about his different sized pupils. The patient had not previously noticed and had never been told he had asymmetric pupil sizes. The patient was quite surprised at the varied size of his pupils when he looked in a mirror and remarked that he had never seen his eyes look that way before.

After further questioning, the patient reported no nausea, headaches, double vision, head trauma or changes in mentation. He was taking no prescription medications and denied the use of illicit substances.

Differential diagnoses

New onset anisocoria is a condition that always warrants further investigation. Differential diagnoses for anisocoria include Horner syndrome, acute anisocoria, physiologic anisocoria, Argyll Robertson pupil and pharmacologically constricted pupils.

Horner syndrome classically presents with the triad of miosis, ptosis and ipsilateral facial anhidrosis. Horner syndrome may result from compression or damage to an extensive system of sympathetic and parasympathetic nerves that travel through the brain, spinal cord, neck, chest and face. This patient had neither ptosis nor facial anhidrosis. Pharmacological pupil testing with apraclonidine and phenylephrine was not performed at that time due to the highly unusual, dynamic nature of the anisocoria.

Acute anisocoria may result from more sinister conditions such as carotid artery dissection, stroke or aneurysm in the brainstem or a space-occupying lesion occurring in the brainstem, neck, upper chest, spinal cord or eye. Without appropriate imaging these conditions cannot be ruled out with full certainty.

Physiologic anisocoria is a common cause of different-sized pupils and is present in up to 20% of the population. The size of anisocoria may fluctuate, be intermittent and even switch eyes (Lam et al., Thompson et al.). Pupil testing with apraclonidine and phenylephrine can differentiate between physiologic anisocoria and a Horner syndrome affected pupil.

In an Argyll Robertson pupil, the affected pupil is smaller in diameter, and the anisocoria is more apparent in the dim lighting conditions. The pupil is responsive to accommodation but not to light stimulus. This condition occurs in neurosyphilis, an infection of the brain and spinal cord caused by the Treponema pallidum bacteria. Neurosyphilis can occur if the infection is left untreated for 10 to 20 years, unlikely in this 24-year-old patient who showed no signs of congenital syphilis (Friedman et al.).

Pharmacologically constricted pupils are known to occur in the presence of certain medications and drugs, including topical eye drops. Pilocarpine, brimonidine and apraclonidine are three commonly used topical eye drops that can cause constriction of the iris sphincter muscle leading to pupil miosis. These medications can also cause vasoconstriction of blood vessels in the eye, including those of the conjunctiva. In December 2017, the FDA approved an over-the-counter eye whitening eye drop called Lumify containing the active ingredient brimonidine 0.025% (Bausch + Lomb).

Pharmacological constriction

As we were preparing to dilate his eyes, the patient remembered that his mother had put an over-the-counter eye drop in only his right eye after the injury. We tracked down the patient’s mother, who confirmed that she did instill multiple Lumify eye drops into her son’s right eye. These were the only eye drops they had at their home, and they assumed the drops would help reduce the redness in his eye.

Alpha-2 adrenergic agonists, such as brimonidine and apraclonidine, are typically used to decrease production of aqueous humor in the eye for IOP control in glaucoma but are also used to control pupil size. Brimonidine has been used in post-refractive surgery and orthokeratology patients with night vision complaints. A smaller pupil diameter may decrease optical aberrations from the peripheral cornea.

Brimonidine readily penetrates the eye and is selective for alpha-2 adrenergic receptor sites inside the eye. Brimonidine inhibits adenylate cyclase activity that in turn reduces the production of aqueous humor by the ciliary body. The reduced production of aqueous contributes to the lowering of IOP. Alpha-2 adrenergic receptor sites on the iris are also stimulated, causing a reduced release of synaptic norepinephrine and subsequent reduction in pupil dilation response to dim lighting conditions (Acheampong et al., Canovetti et al., Shemesh et al.).

Constricted pupils are listed as a potential side effect of Lumify (Lumify side effects). Our patient’s disrupted corneal epithelium from the superficial punctate keratopathy may have led to increased corneal permeability and additional medicine absorption producing an accentuated miotic effect in the patient’s right eye.

Further probing into his case history saved our patient from an immediate emergency department referral, extensive workup and medical transport to the nearest available medical facility capable of treating a possible intracranial aneurysm.

Acute anisocoria can be an early sign of life-threatening neurologic conditions and warrants hospitalization if a benign etiology cannot be established. Anisocoria testing involves costly and extensive testing including neuroimaging, lumbar puncture and consultation with appropriate neurological specialists.

To verify our diagnosis of pharmacologic anisocoria, we contacted the patient the following day. The patient confirmed that his pupils had returned to equal size, and he was experiencing no untoward effects.

Ongoing and thorough case history gathering is a vital component to appropriate patient care and management. In this case, it saved the patient and his family undue financial burdens and the anxiety of navigating a potentially life-threatening medical situation.


For more information:

Scott Bauer, OD, is a recent graduate from Pacific University in Forest Grove, Ore. He can be reached at:

Leonid Skorin Jr., OD, DO, MS, FAAO, FAOCO, practices at the Mayo Clinic Health System in Albert Lea, Minn., and is a member of the Primary Care Optometry News Editorial Board. He can be reached at: