Unilateral Mydriasis: Causes, Implications, and More

Unequal pupil size can be alarming, especially when one pupil is noticeably larger than the other. This condition, known as unilateral mydriasis, has various causes, ranging from benign to serious neurological concerns. Identifying the reason behind this asymmetry is essential for appropriate medical evaluation and intervention.

Understanding what triggers a single dilated pupil helps determine whether it requires urgent attention or routine monitoring.

Normal Pupillary Reflex Pathways

The pupillary reflex regulates pupil size in response to light and other stimuli. This process involves the autonomic nervous system and the midbrain, ensuring the eye adapts to changing light conditions. The reflex begins when photoreceptors in the retina detect light, transmitting signals through the optic nerve (cranial nerve II) to the pretectal nucleus in the midbrain. From there, the signal reaches the Edinger-Westphal nuclei, which house parasympathetic neurons responsible for pupil constriction.

Once activated, parasympathetic fibers travel along the oculomotor nerve (cranial nerve III) to the ciliary ganglion behind the eye. Here, the signal is relayed to postganglionic fibers that innervate the sphincter pupillae muscle, causing pupil constriction. This reaction, known as the direct light reflex, occurs in the illuminated eye, while the consensual light reflex causes simultaneous constriction in the opposite pupil. Any disruption in this circuit can lead to abnormal pupillary responses, including unilateral mydriasis.

The sympathetic nervous system mediates pupil dilation through a separate pathway. This process starts in the hypothalamus, where descending sympathetic fibers travel through the brainstem and spinal cord to synapse in the ciliospinal center of Budge (C8-T2). From there, preganglionic fibers ascend to the superior cervical ganglion, synapsing with postganglionic neurons that follow the internal carotid artery into the orbit. These fibers innervate the dilator pupillae muscle, allowing the pupil to enlarge in dim lighting or during stress or pain responses.

Common Features of Unilateral Pupil Dilation

When one pupil is noticeably larger than the other, distinct characteristics help determine the cause. The degree of dilation, response to light, associated symptoms, and duration provide valuable diagnostic clues. Some cases involve persistent dilation unresponsive to light, while others fluctuate or resolve spontaneously.

A key feature of unilateral mydriasis is its response—or lack thereof—to light stimulation. If the affected pupil remains dilated despite bright light, parasympathetic dysfunction is often implicated, suggesting impairment of the oculomotor nerve or ciliary ganglion damage. If the pupil constricts sluggishly but still reacts, pharmacologic agents such as anticholinergic medications or exposure to substances like scopolamine may be involved. A thorough history, including medication use and environmental exposures, helps differentiate these causes.

Accompanying neurological symptoms refine the diagnosis. Ptosis (drooping eyelid), diplopia (double vision), or ocular pain may indicate a cranial nerve deficit or compressive lesion. A sudden onset of pupil dilation with headache, altered consciousness, or motor deficits raises concern for serious conditions like intracranial hemorrhage or impending herniation. Isolated anisocoria without additional symptoms is more likely benign, as seen in physiologic anisocoria, where slight pupil size differences are normal.

Some cases involve transient dilation, appearing intermittently before returning to normal. This occurs in episodic mydriasis, where brief episodes of unilateral pupil enlargement lack structural abnormalities. Patients with recurrent episodes may document triggers such as stress, fatigue, or specific visual tasks. The speed of pupil normalization also provides insight into the cause—rapid recovery suggests a functional or pharmacologic origin, while prolonged recovery may indicate nerve dysfunction.

Migraine-Related Phenomena

Migraines, particularly those with aura, can cause neurological disturbances, including transient changes in pupil size. Unilateral mydriasis linked to migraines often results from autonomic dysfunction, where imbalances in sympathetic and parasympathetic activity lead to abnormal pupillary responses. During a migraine, disruptions in brainstem regions involved in autonomic control, such as the locus coeruleus and periaqueductal gray, may interfere with normal pupil regulation, causing a persistently dilated pupil.

Ophthalmoplegic migraine, a rare subtype, involves headache followed by cranial nerve III palsy, leading to pupil asymmetry, ptosis, and impaired eye movement. Now classified as recurrent painful ophthalmoplegic neuropathy, this condition involves inflammation and possible demyelination of the oculomotor nerve. Unlike typical migraine-related pupillary changes, ophthalmoplegic migraine can cause prolonged mydriasis lasting days to weeks, requiring further neurological evaluation.

Neurotransmitter fluctuations during migraine attacks may also contribute to episodic anisocoria. Changes in serotonin and dopamine levels, which modulate autonomic function, have been implicated in migraine pathogenesis. Serotonergic pathways influence vascular tone and pain signaling, potentially affecting parasympathetic fibers responsible for pupil constriction. Dopamine dysregulation has been linked to premonitory migraine symptoms, including photophobia and autonomic instability. These neurochemical shifts may temporarily impair pupillary responsiveness, leading to dilation without permanent structural damage.

Other Neurological Factors

Unilateral mydriasis can result from various neurological conditions affecting pupillary control. Oculomotor nerve (cranial nerve III) lesions are particularly concerning, as this nerve provides parasympathetic input to the sphincter pupillae muscle. Compression from an aneurysm, especially at the junction of the posterior communicating artery and the internal carotid artery, can cause a dilated, nonreactive pupil with ptosis and impaired eye movement. This presentation warrants immediate neuroimaging, as expanding aneurysms pose a high risk of rupture and subarachnoid hemorrhage.

Structural brain lesions such as tumors, strokes, or demyelinating diseases may also disrupt pupillary regulation. A midbrain mass effect can cause asymmetric pupillary responses by compressing parasympathetic fibers. In multiple sclerosis, inflammatory demyelination can lead to episodic or progressive pupillary dysfunction. Similarly, ischemic strokes affecting the midbrain tegmentum have been documented to cause pupillary asymmetry, often alongside other neurological deficits such as hemiparesis or altered consciousness.

Distinguishing from Other Ocular Anomalies

Unilateral mydriasis may resemble other ocular abnormalities, making differentiation essential. Conditions such as Adie’s tonic pupil, Horner’s syndrome, and physiologic anisocoria can all present with asymmetry in pupil size, but their mechanisms and clinical features vary. Evaluating pupillary response to light, accommodation, and pharmacologic testing helps establish the correct diagnosis.

Adie’s tonic pupil results from damage to the ciliary ganglion or postganglionic parasympathetic fibers, leading to a dilated pupil that reacts sluggishly to light but constricts better with near accommodation. This condition is often unilateral and typically affects young adults, with associations to viral or autoimmune processes. Unlike oculomotor nerve palsy, Adie’s pupil does not present with ptosis or extraocular muscle dysfunction. Pharmacologic testing with dilute pilocarpine confirms the diagnosis, as denervated iris sphincter muscles exhibit hypersensitivity and constrict abnormally in response.

Horner’s syndrome, by contrast, presents with a smaller pupil (miosis) rather than dilation, accompanied by ptosis and anhidrosis due to disrupted sympathetic innervation. Lesions anywhere along the sympathetic pathway, from the hypothalamus to the superior cervical ganglion, can cause this syndrome. Pharmacologic agents such as apraclonidine or cocaine drops help differentiate Horner’s syndrome by assessing the affected pupil’s responsiveness. Physiologic anisocoria, a benign variation in pupil size that remains consistent under different lighting conditions, must also be considered when no other pathological signs are present.

Clinical Assessment Procedures

A structured evaluation is essential for determining the cause of unilateral mydriasis. Clinicians begin with a comprehensive medical history and detailed neurological examination, assessing symptom onset, duration, and progression. Associated findings such as headache, visual changes, or systemic illness are noted. Medication use, toxic substance exposure, and recent ocular trauma are also documented to rule out pharmacologic or mechanical causes.

Pupillary light reflex testing is a cornerstone of assessment, with both direct and consensual responses evaluated under different lighting conditions. The swinging flashlight test helps identify afferent defects, while near response testing assesses accommodation. If the affected pupil reacts sluggishly or not at all, pharmacologic testing with agents like pilocarpine or apraclonidine may differentiate parasympathetic from sympathetic dysfunction. Imaging, including MRI or CT scans, is warranted when structural or compressive lesions are suspected, particularly if neurological deficits accompany anisocoria.