What is the appropriate evaluation and management for a teenager presenting with anisocoria (uneven pupils)?

Evaluation and Management of Anisocoria in a Teenager

Begin by determining which pupil is abnormal through the swinging-light test in a darkened room, checking pupillary responses in both bright and dim illumination, then immediately assess for red flags including ptosis, extraocular movement limitations, headache, or neurological deficits that would require urgent neuroimaging. 1

Initial Clinical Assessment

Critical Red Flags Requiring Urgent Evaluation

• New-onset pupil-involving third nerve palsy (anisocoria with ptosis and extraocular muscle weakness) requires immediate neuroimaging with MRI with gadolinium and MRA or CTA to rule out posterior communicating artery aneurysm 1
• Anisocoria with headache, altered mental status, or other neurological deficits requires urgent evaluation 1
• Anisocoria following head trauma requires urgent evaluation 1
• Even with partial extraocular muscle involvement or incomplete ptosis, if the pupil is involved, do not assume microvascular etiology—perform neuroimaging 1

Systematic Pupillary Examination

Determine which pupil is abnormal:

• If anisocoria is greater in bright light, the larger pupil is abnormal (parasympathetic dysfunction) 1, 2
• If anisocoria is greater in dim light, the smaller pupil is abnormal (sympathetic dysfunction/Horner syndrome) 1, 2
• Anisocoria greater than 1 millimeter may indicate pathological processes including Horner syndrome, Adie tonic pupil, or pupil-involving third-cranial-nerve palsy 3

Perform the swinging-light test:

• Conduct in a darkened room with patient fixing on a distant target 1, 4
• Shine bright penlight directly into each eye for less than 5 seconds and observe pupillary constriction 1, 4
• A relative afferent pupillary defect (RAPD) of 0.3 or more log units is not typical in amblyopia and should prompt investigation for compressive optic neuropathy, optic neuritis, or severe retinal disease 4

Differential Diagnosis Algorithm

Large Pupil (Anisocoria Greater in Light)

Third nerve palsy with pupillary involvement:

• Look for associated ptosis and extraocular movement limitations (inability to move eye up, down, or medially) 1
• Requires immediate MRI with gadolinium and MRA or CTA, plus neurosurgical consultation if aneurysm identified 1

Pharmacologic mydriasis:

• History of exposure to anticholinergics, antihistamines, or tropane alkaloids 1
• Diagnose with pilocarpine 1% testing—pharmacologically dilated pupil will not constrict 1

Acute angle-closure crisis:

• Mid-dilated, oval, or asymmetric pupil with associated eye pain, blurred vision, halos around lights 1
• Requires immediate gonioscopy, intraocular pressure measurement, and IOP-lowering therapy 1

Adie tonic pupil:

• Dilated pupil with poor or absent light reaction but preserved (though slow) near response 1, 5
• Typically idiopathic in young adults and does not require neuroimaging 5

Small Pupil (Anisocoria Greater in Dark)

Horner syndrome:

• Triad of miosis, ptosis (mild, 1-2mm), and anhidrosis (variable distribution depending on lesion location) 1, 2
• Assess for associated symptoms suggesting cavernous sinus lesion (multiple cranial nerve palsies) requiring MRI with contrast of brain/orbits 1

Physiologic anisocoria:

• Difference typically less than 1mm, pupils react normally to light, no ptosis or other abnormalities 3, 5
• Benign condition requiring no further workup 5

Essential Physical Examination Components

Slit-lamp biomicroscopy or direct ophthalmoscope examination:

• Assess pupil size, shape, and reactivity 1
• Examine for irregular pupils suggesting traumatic sphincter damage, iritis, or congenital abnormality (coloboma) 3
• Evaluate anterior chamber, iris, and lens 3

External examination:

• Assess for ptosis, levator function, eyelid retraction 3
• Check for proptosis or globe retraction 3
• Note head position (tilt, turn, chin-up/down posture) 3

Gonioscopy:

• Perform if acute angle-closure crisis suspected 1
• Evaluate fellow eye for prophylactic laser iridotomy if angle closure confirmed 1

Common Pitfalls to Avoid

• Do not confuse anisocoria (difference in pupil size) with RAPD (difference in pupillary response to light)—these represent entirely different pathophysiologic processes 4, 6
• Do not assume microvascular etiology in third nerve palsy if there is partial extraocular muscle involvement, incomplete ptosis, or any pupillary involvement—these require neuroimaging 1
• Be aware that pupillary evaluation in teenagers may be challenging due to hippus (physiologic oscillations), poorly maintained fixation, and rapid accommodative changes 3, 4
• A large RAPD should always prompt search for compressive optic neuropathy or retinal abnormality, not just amblyopia 3, 4