What causes a misshapen pupil?

Causes of Misshapen Pupil

A misshapen pupil most commonly results from direct ocular trauma (including surgical trauma), third nerve palsy with pupillary involvement, or structural iris abnormalities—each requiring distinct diagnostic and management approaches based on the underlying etiology.

Traumatic Causes

Direct Ocular and Surgical Trauma

• Iris sphincter rupture is the most common cause of pupil abnormalities following extracapsular cataract extraction (16% incidence), while iris trauma during phacoemulsification accounts for most cases in that surgical approach (5.3% incidence) 1
• Orbital trauma with direct globe injury can cause pupillary deformities through mechanical disruption of iris structures, often accompanied by other ocular injuries 2
• Traumatic brain injury with fixed, dilated pupils indicates severe neurological compromise, with approximately three-quarters of cases involving diffuse brain injury and 72% of survivors experiencing long-term ophthalmological deficits 3

Iatrogenic Surgical Complications

• Pupil abnormalities after cataract surgery result from iris sphincter rupture, iris trauma during phacoemulsification, or mechanical complications during lens implantation 1
• Refractive surgery complications including LASIK can rarely affect ocular alignment and potentially iris structure, though direct pupillary shape changes are uncommon 4

Neurological Causes

Third Nerve Palsy

• Pupil-involving third nerve palsy is a critical red flag requiring urgent evaluation, as it suggests vascular compression from an adjacent aneurysm and mandates immediate CTA or MRA 4, 2, 5
• The inferior division of the third nerve sends parasympathetic fibers to the pupillary sphincter; lesions affecting this pathway result in a dilated, poorly reactive, and often irregular pupil 4
• Compressive lesions (aneurysms, tumors including meningioma and schwannoma, metastatic lesions) must be urgently ruled out when pupillary involvement is present 4
• Even with partial pupillary involvement or incomplete ptosis, neuroimaging with MRI with gadolinium and MRA or CTA is recommended, as compressive lesions may present atypically 4

Brainstem and Central Pathology

• Demyelinating plaques, tumors, hemorrhage, and infections involving the brainstem may cause non-reactive or misshapen pupils through disruption of central pupillary pathways 2
• Dorsal midbrain syndrome impairs the light response and can affect pupillary shape through parasympathetic pathway disruption 6

Structural and Congenital Abnormalities

Iris Pathology

• Congenital or structural iris anomalies are common causes of pupillary abnormalities, particularly in infants and children, requiring careful observation of iris and pupil movements 7
• Acquired iris structural defects from inflammation, ischemia, or previous surgery can result in permanent pupillary distortion 7, 6
• Disorders of the iris including application of cholinergic agents need consideration when evaluating impaired pupillary light reaction and shape 6

Systemic and Toxic Causes

Neurotoxic Conditions

• Botulism causes abnormally reactive pupils (sluggish, poorly reactive, or fixed) in 24% of confirmed cases, with fixed pupils serving as a recognized clinical criterion for triggering diagnostic suspicion 2

Diagnostic Approach

Immediate Assessment

• Distinguish pupil-involving from pupil-sparing presentations, as this fundamentally changes the urgency and diagnostic pathway 4, 5
• Perform pupillary examination in bright and dim illumination to assess reactivity and detect anisocoria 4
• Conduct fundus examination to evaluate for papilledema or optic atrophy, which may indicate elevated intracranial pressure or compressive lesions 4

Imaging Strategy

• CT head without contrast is the initial study for acute traumatic presentations to assess for hemorrhage, mass effect, and basal cistern compression 2
• MRI brain with and without contrast is preferred for non-traumatic, subacute presentations to evaluate structural lesions, demyelination, or neoplasm 2
• CTA or MRA should be obtained urgently when pupil-involving third nerve palsy suggests aneurysmal compression 4, 2, 5
• If high suspicion for aneurysm persists despite normal MRA or CTA, catheter angiography should be considered after brain MRI with specific attention to the third nerve 4

Additional Testing

• Serologic testing for infectious diseases (syphilis, Lyme disease) if neuroimaging is normal 4
• Lumbar puncture with glucose, protein, cell count, cytology, and culture may be indicated for suspected infectious or inflammatory etiologies 4
• Pharmacological testing with cocaine eye-drops helps distinguish physiological anisocoria from Horner's syndrome when sympathetic pathway involvement is suspected 6

Critical Pitfalls

• Never assume a pupil-sparing presentation when there is any degree of pupillary involvement, even mild—this requires full neuroimaging workup 4
• Do not delay imaging in pupil-involving third nerve palsy, as aneurysmal rupture carries devastating morbidity and mortality 4, 2
• Recognize that post-surgical pupil abnormalities are often permanent and cosmetically undesirable, affecting quality of vision and fundus examination 1
• Bilateral fixed dilated pupils after traumatic brain injury carry 88% mortality, though survivors may have favorable outcomes without persistent vegetative state 3