What is the differential diagnosis and management for a 57-year-old Asian woman with intermittent pain in her right eye, who used Benadryl (diphenhydramine) this morning?

Acute Angle-Closure Crisis Must Be Ruled Out Immediately

This 57-year-old Asian woman with intermittent eye pain following Benadryl (diphenhydramine) use requires urgent ophthalmologic evaluation to exclude acute angle-closure crisis, as this demographic and medication combination creates high risk for vision-threatening disease. 1

Critical Risk Factor Analysis

Why This Patient Is High-Risk

• Asian ethnicity is a major risk factor for primary angle-closure disease, with significantly higher prevalence than other populations 1
• Age 57 years places her in the peak risk category for angle-closure (older phakic patients with narrower anterior chamber angles) 1
• Female gender further increases risk 1
• Diphenhydramine has strong anticholinergic effects that can precipitate angle closure by causing pupillary dilation and angle narrowing 1, 2

The Benadryl Connection

The FDA label for diphenhydramine explicitly warns against use in patients with glaucoma 2. The anticholinergic properties can trigger pupillary block in anatomically predisposed individuals, potentially precipitating acute angle-closure crisis 1, 3. Similar over-the-counter medications with anticholinergic or adrenergic effects have been documented to trigger bilateral acute angle closure 4.

Differential Diagnosis Framework

Primary Consideration: Intermittent Angle Closure

Intermittent angle closure presents with episodic eye pain that resolves spontaneously but can progress to acute angle-closure crisis 5. Key features include:

• Pain episodes triggered by dim lighting, stress, or medications with anticholinergic/adrenergic effects 1
• Associated symptoms: blurred vision, halos around lights, headache, eye redness 1
• Critical pitfall: Examination between episodes may appear completely normal, requiring dark-room dynamic gonioscopy for diagnosis 5
• Untreated progression leads to permanent blindness in 18% of cases 1

Secondary Consideration: Neuropathic Ocular Pain

If structural causes are excluded, consider neuropathic ocular pain, which presents with 1, 5:

• Pain severity disproportionate to clinical findings 1, 5
• Burning, stinging, or aching quality with photophobia 5
• History of previous ocular surgery, infection, or trauma 1
• Pain persisting despite treatment of any surface abnormalities 5

Tertiary Consideration: Anterior Uveitis

Intermittent anterior uveitis can present with 5:

• Episodes of pain, photophobia, and blurred vision 5
• Minimal external signs between episodes 5
• Requires slit-lamp examination to detect anterior chamber cells 5

Immediate Management Algorithm

Step 1: Emergency Ophthalmologic Referral (Same Day)

Do not delay referral - the American Academy of Ophthalmology emphasizes that delaying diagnosis of acute angle-closure can result in permanent blindness 5. The ophthalmologist must perform 1, 5:

• Visual acuity testing as baseline measurement 5
• Pupil examination: Look for mid-dilated, asymmetric, or oval pupil; poor reactivity 1
• Slit-lamp biomicroscopy: Assess for conjunctival hyperemia, shallow anterior chamber, corneal edema, iris abnormalities 1
• Intraocular pressure measurement (may be normal between episodes) 1
• Gonioscopy (essential - standard examination may miss intermittent angle closure) 1, 5
• Fluorescein staining to identify corneal defects 5

Step 2: Immediate Actions While Awaiting Ophthalmology

• Discontinue diphenhydramine immediately 1, 2
• Avoid other anticholinergic medications, decongestants, and adrenergic agents 1
• Keep patient in well-lit environment (dim lighting can precipitate angle closure) 1
• Do not initiate empiric treatment without diagnosis, as this can mask vision-threatening conditions 5

Step 3: Treatment Based on Confirmed Diagnosis

If Intermittent Angle Closure Confirmed:

• Laser peripheral iridotomy is definitive treatment to relieve pupillary block 5
• Prophylactic iridotomy in fellow eye is indicated (untreated fellow eyes have increased risk) 1, 5
• Medical management with IOP-lowering agents as bridge to laser treatment 1

If Neuropathic Ocular Pain Diagnosed:

• Perform topical anesthetic challenge test (0.5% proparacaine) to differentiate peripheral from central sensitization 1, 5
• Peripheral component: autologous serum tears 5
• Central component: oral neuromodulators (gabapentin, pregabalin, tricyclic antidepressants) 5
• Adjunctive: transcutaneous electrical nerve stimulation or periorbital botulinum toxin A for photophobia 5

If Anterior Uveitis Confirmed:

• Topical prednisolone acetate 1% (preferred over difluprednate) 5
• Systemic immunomodulatory therapy may be required for chronic/recurrent cases 5

Critical Pitfalls to Avoid

• Never assume "just dry eye" or "allergy" in this demographic with these risk factors 5
• Do not prescribe alternative antihistamines without ophthalmologic clearance - even second-generation antihistamines may have some anticholinergic activity 1
• Recognize that severe pain with minimal signs suggests neuropathic pain, requiring completely different management than inflammatory or structural causes 5
• Do not perform pupillary dilation until angle-closure is definitively excluded 1

Patient Education Pending Evaluation

Instruct patient to return immediately or go to emergency department if she develops 1:

• Sudden severe eye pain 1
• Sudden vision loss or marked blurring 1
• Halos around lights 1
• Nausea/vomiting with eye pain 1
• Eye redness with pain 1