Anisocoria Workup in the Emergency Department
In the ED, immediately determine which pupil is abnormal by examining pupillary responses in both bright and dim lighting, then assess for pupil-involving third nerve palsy (dilated pupil with ptosis and/or ophthalmoplegia), which requires urgent neuroimaging to rule out posterior communicating artery aneurysm—a neurosurgical emergency. 1, 2
Initial Critical Assessment
The first priority is identifying life-threatening causes:
- Check pupil size in bright AND dim lighting to determine which pupil is abnormal 1, 2
- Examine for ptosis and extraocular movement limitations immediately 1, 2, 3
- Assess for associated neurological deficits including headache, altered mental status, or focal findings 2
Red Flags Requiring Urgent Neuroimaging
Obtain immediate MRI with gadolinium and MRA or CTA for: 1, 2, 3
- Pupil-involving third nerve palsy (dilated pupil with ptosis and/or ophthalmoplegia) 1, 2
- Anisocoria with headache or altered mental status 2
- Anisocoria following head trauma 2
- Any new neurological deficits accompanying anisocoria 2
Critical Nuance on Third Nerve Palsy
- Complete ptosis with complete ophthalmoplegia but NORMAL pupil (classic pupil-sparing third nerve palsy) is almost always microvascular from diabetes, hypertension, or hyperlipidemia and does NOT require emergent imaging 1, 3
- However, if there is partial extraocular muscle involvement OR incomplete ptosis, even with a normal pupil, do NOT assume microvascular etiology—obtain neuroimaging 1
Systematic Diagnostic Algorithm
Step 1: Rule Out Pharmacologic Mydriasis
Before ordering expensive imaging, consider recent medication exposure: 4, 5, 6, 7
- Nebulized ipratropium bromide can leak from face masks and cause unilateral mydriasis 4, 7
- Topical anticholinergics, antihistamines, or tropane alkaloids can cause pharmacologic mydriasis 1
- Pilocarpine 1% testing: Pharmacologically dilated pupils will NOT constrict with pilocarpine 1%, while third nerve palsy pupils will constrict 1, 4, 6
Step 2: Assess for Acute Angle-Closure Crisis
If the enlarged pupil is mid-dilated, oval, or asymmetric with associated symptoms: 1
- Perform gonioscopy and measure intraocular pressure immediately 1
- Initiate IOP-lowering therapy if angle-closure confirmed 1
- The fellow eye requires urgent prophylactic laser iridotomy 1
Step 3: Perform Slit-Lamp Examination
Essential findings to document: 1, 3
- Pupil size, shape, and reactivity 1
- Irregular pupils suggest traumatic sphincter damage, iritis, or congenital abnormality 1
- Check for relative afferent pupillary defect (RAPD), which should prompt search for compressive optic neuropathy or retinal pathology 1
Step 4: External Examination
- Ptosis and levator function 1, 3
- Eyelid retraction, proptosis, or globe retraction 1
- Head position abnormalities 1
Benign Causes (Diagnosis of Exclusion)
Physiologic anisocoria can be diagnosed when: 1, 2
- Difference is typically <1 mm 1, 2
- Pupils react normally to light 1, 2
- No ptosis or other abnormalities present 1, 2
- Anisocoria remains constant in different lighting conditions 2
Common Pitfalls to Avoid
- Do NOT assume microvascular third nerve palsy without complete ptosis, complete ophthalmoplegia, AND normal pupil—partial presentations require imaging 1
- Do NOT order MRI before checking for metallic intraocular foreign bodies—undiagnosed metallic objects can move during MRI causing serious ocular injury 8
- Do NOT skip pilocarpine testing in patients recently exposed to nebulized medications—this simple test prevents unnecessary radiation exposure 4, 7
- Do NOT attribute large RAPD to amblyopia alone—always search for compressive optic neuropathy or retinal abnormality 1
Disposition Considerations
Neurosurgical consultation required if aneurysm identified 1, 2
Neurology or neurosurgery referral for cavernous sinus lesions (multiple cranial nerve palsies including III, IV, VI, V1) 1, 2
Pathological causes require follow-up based on underlying etiology and specialist recommendations 1