What is the differential diagnosis of bilateral eye pain?

Differential Diagnosis of Bilateral Eye Pain

Bilateral eye pain requires immediate consideration of life-threatening causes first, followed by systematic evaluation of infectious, inflammatory, and structural etiologies based on associated symptoms and examination findings.

Life-Threatening Causes Requiring Urgent Evaluation

Acute Angle-Closure Glaucoma

• Presents with severe bilateral eye pain, headache, significantly elevated intraocular pressures (>60 mmHg), corneal edema, and vision loss 1
• Triggered by medications containing decongestants (phenylephrine), anticholinergics, or topiramate 1
• Requires immediate treatment with intravenous acetazolamide, pilocarpine, and IOP-lowering drops to prevent permanent vision loss 1
• Can occur even in patients with previous peripheral iridotomies 1

Bilateral Optic Neuritis

• Presents with painful visual loss (though can be painless), often bilateral in neuromyelitis optica spectrum disorders 2
• Pain typically worsens with eye movements 2
• Requires urgent MRI of orbits and brain with contrast to evaluate for demyelinating lesions and assess risk of multiple sclerosis 2
• Associated with abnormal optic nerve enhancement and signal changes on MRI 2

Infectious Causes

Viral Conjunctivitis

• Bilateral presentation (often sequentially bilateral) with watery discharge, follicular reaction, chemosis, and preauricular lymphadenopathy 2, 3
• Self-limited with improvement within 5-14 days, though severe cases (epidemic keratoconjunctivitis) can cause subepithelial infiltrates and corneal scarring 2
• Highly contagious through contact with infected individuals, especially in school settings 2

Bacterial Conjunctivitis

• Gonococcal: Marked eyelid edema, significant purulent discharge, rapid progression to severe hyperpurulent conjunctivitis with risk of corneal perforation 2
• Chlamydial: Follicular conjunctivitis with chemosis, papillary hypertrophy, and potential for chronic inflammation leading to scarring 2
• Both require urgent treatment to prevent corneal complications 2

Herpes Simplex/Varicella Zoster

• Can be bilateral in atopic or immunocompromised patients 2
• Associated with vesicles on eyelid margins, watery discharge, and follicular reaction 2
• Risk of serious sequelae including keratitis, stromal scarring, and perforation 2

Inflammatory/Autoimmune Causes

Anterior Uveitis

• Bilateral presentation with eye pain, photophobia, blurred vision, and conjunctival injection 4
• Associated with inflammatory bowel disease (ulcerative colitis), where it may be bilateral, insidious in onset, and long-lasting 2
• Requires both topical and systemic steroids; urgent ophthalmology referral needed due to risk of vision loss 2

Episcleritis

• Bilateral hyperemic sclera and conjunctiva with burning sensation or itching 2
• Associated with inflammatory bowel disease 2
• Usually responds to topical steroids or NSAIDs 2

Scleritis

• Deep, severe boring pain that worsens with eye movement 4
• Posterior scleritis presents with deep pain, hyperemia, painful eye movements, and serous retinal detachment 2
• Requires systemic corticosteroids and immunosuppressive therapy 2

Vogt-Koyanagi-Harada Disease

• Rapid onset bilateral presentation (95% of cases) with vitritis, optic disc edema, and numerous central leakage points on fluorescein angiography 2
• Requires systemic corticosteroids and immunosuppressive medication 2

Medication-Induced Causes

Drug-Induced Keratoconjunctivitis

• Bilateral conjunctival injection, punctal edema, and inferior fornix follicles 2
• Most common with glaucoma medications (especially those with preservatives), topical NSAIDs, antibiotics, and antivirals 2
• Gradual worsening with continued use; may cause corneal epithelial erosion 2

Latanoprost and Other Prostaglandin Analogs

• Burning, stinging, conjunctival hyperemia, foreign body sensation, and blurred vision in 5-15% of patients 5
• Can cause intraocular inflammation (iritis/uveitis) and corneal edema 5
• Less than 1% require discontinuation due to conjunctival hyperemia 5

Allergic Causes

Allergic Conjunctivitis

• Bilateral chemosis with itching, watery discharge, and mucoid discharge 3
• Follicular or papillary conjunctival reaction 3
• Typically resolves within days to weeks 3

Giant Papillary Conjunctivitis

• Bilateral (pattern associated with contact lens wear), papillary hypertrophy of superior tarsal conjunctiva, mucoid discharge 2
• Chronic gradual increase in symptoms with contact lens wear 2
• May require months to resolve even after contact lens withdrawal 2

Orbital/Structural Causes

Orbital Cellulitis/Infection

• Bilateral presentation rare but possible in severe cases or immunocompromised patients 2
• Requires CT orbits with contrast initially, with MRI for detailed assessment of intra-orbital spread 2
• High index of suspicion needed for invasive fungal infection in immunocompromised patients due to high morbidity 2

Thyroid Eye Disease

• Bilateral chemosis, upper-eyelid laxity, and eyelid imbrication 3
• Associated with proptosis and restrictive extraocular motility 3

Diagnostic Approach Algorithm

Step 1: Assess for emergent causes requiring immediate intervention

• Check intraocular pressure bilaterally (>21 mmHg concerning, >40 mmHg emergent) 1
• Assess visual acuity and pupillary responses 2
• Examine for corneal edema, which suggests acute angle closure 1

Step 2: Characterize pain quality and associated symptoms

• Severe, acute onset with nausea/vomiting → acute angle closure glaucoma 1, 4
• Pain with eye movements → optic neuritis or posterior scleritis 2
• Deep, boring pain → scleritis 4
• Burning, foreign body sensation → conjunctivitis or keratitis 2

Step 3: Examine discharge characteristics

• Watery discharge → viral or allergic etiology 2, 3
• Purulent discharge → bacterial infection 2, 3
• Mucoid discharge → allergic conjunctivitis 3

Step 4: Look for specific examination findings

• Follicular reaction → viral, chlamydial, or allergic 2
• Preauricular lymphadenopathy → viral etiology 2, 3
• Chemosis → viral, allergic, thyroid eye disease, or GVHD 3
• Corneal findings → keratitis, HSV, or medication-induced 2

Step 5: Obtain targeted imaging when indicated

• MRI orbits and brain with contrast for suspected optic neuritis 2
• CT orbits with contrast for suspected orbital cellulitis 2
• Neuroimaging essential when eye appears "quiet" but pain persists, as delayed diagnosis can cause significant morbidity 6

Critical Pitfalls to Avoid

• Never dismiss bilateral eye pain as "just conjunctivitis" without checking intraocular pressure, as acute angle closure can be triggered by common over-the-counter medications 1
• Do not delay ophthalmology referral for suspected uveitis, as progression to vision loss can occur rapidly 2
• Consider medication-induced causes in patients on multiple topical eye medications, especially glaucoma drops with preservatives 2
• In immunocompromised patients, maintain high suspicion for invasive fungal infection requiring urgent MRI 2
• Bilateral optic neuritis requires urgent MRI to assess for demyelinating disease and prevent permanent vision loss 2