Evaluation and Management of Anisocoria in Patients with Mood Issues
A patient with anisocoria (unequal pupil size) and mood issues requires urgent neurological evaluation to rule out potentially life-threatening causes before attributing the finding to psychiatric medications or benign conditions. 1
Initial Assessment
Pupillary Examination
- Observe pupils in dim light to properly assess size difference
- A difference greater than 1 millimeter is clinically significant 1
- Perform swinging-light test to assess for relative afferent pupillary defect (RAPD)
- Note pupil shape, symmetry, and direct/consensual light responses
Critical Neurological Concerns
- Pupil-involving third nerve palsy requires urgent evaluation for:
- Posterior communicating artery aneurysm
- Compressive lesions (tumors, hemorrhage)
- Uncal herniation 1
Associated Symptoms to Evaluate
- Ptosis (drooping eyelid)
- Diplopia (double vision)
- Headache
- Neurological deficits (ataxia, tremor, hemiparesis)
- Visual changes 1
Diagnostic Algorithm
Step 1: Determine which pupil is abnormal
Large pupil causes:
- Pharmacologic mydriasis (anticholinergic medications, plants, eye drops)
- Third nerve palsy (if accompanied by ptosis and extraocular muscle weakness)
- Adie's tonic pupil
- Traumatic iris damage
Small pupil causes:
- Horner syndrome
- Pharmacologic miosis
- Iritis
Step 2: Evaluate for red flags requiring immediate imaging
- Pupil-involving third nerve palsy (especially with incomplete ptosis or partial extraocular muscle involvement)
- Acute onset with neurological symptoms
- Severe headache
- Altered mental status
Step 3: Consider medication and environmental exposures
- Review all medications, especially:
- Psychiatric medications with anticholinergic properties
- Nebulized medications (ipratropium) 2
- Topical agents that may have contacted the eye
- Exposure to plants with anticholinergic properties (e.g., Angel's Trumpet/Datura) 3, 4
Specific Considerations in Patients with Mood Issues
Medication-Related Anisocoria
- Many psychiatric medications have anticholinergic properties that can cause mydriasis
- Unilateral exposure (touching one eye after handling medication) can cause unilateral mydriasis
- This is typically benign and resolves within days 3
Physiologic Anisocoria
- Normal variation in pupil size (typically <0.5mm difference)
- Present in up to 20% of the population
- Difference remains relatively constant in different lighting conditions 5
- Not associated with other neurological symptoms
Diagnostic Testing
- If neurological symptoms present or cause unclear:
- MRI with gadolinium and MRA/CTA to evaluate for compressive lesions or aneurysm 1
- Consider catheter angiogram if high suspicion despite normal MRA/CTA
Management Approach
For benign causes (physiologic, medication-related):
- Reassurance
- Avoid touching eyes after handling medications
- Monitor for resolution (typically within days)
For third nerve palsy:
- Urgent neuroimaging
- Neurosurgical consultation if aneurysm or compressive lesion identified
- Monitor for progression
For Horner syndrome:
- Imaging of sympathetic pathway (head, neck, chest)
- Evaluation for underlying malignancy
Common Pitfalls to Avoid
Attributing anisocoria to psychiatric conditions without proper evaluation
- Mood disorders themselves do not cause anisocoria
- Always rule out neurological causes first
Missing pharmacologic causes
Failing to document pupil size in both bright and dim conditions
Overlooking incomplete third nerve palsies
- Even with normal pupil, partial extraocular involvement requires imaging 1
Remember that while many cases of anisocoria in patients with mood disorders may be related to medications or physiologic variation, thorough evaluation is essential to rule out serious neurological conditions that could impact morbidity and mortality.