What is the differential diagnosis and initial management for a patient presenting with eye pain?

Eye Pain Differential Diagnosis and Initial Management

The differential diagnosis for eye pain requires immediate identification of vision-threatening emergencies—particularly acute angle-closure glaucoma, infectious keratitis, and orbital cellulitis—followed by systematic evaluation for inflammatory conditions, neuropathic pain, and referred pain syndromes. 1

Immediate Vision-Threatening Emergencies

Acute Angle-Closure Glaucoma

• Presents with severe eye pain, blurred vision, halos around lights, mid-dilated poorly reactive pupil, and markedly elevated intraocular pressure (IOP). 2, 1
• Bilateral transient episodes with halos and opaque vision are pathognomonic for intermittent angle closure, carrying a 50% risk of acute crisis within 5 years if untreated. 1, 3
• Untreated eyes have an 18% risk of blindness and 48% develop glaucomatous optic neuropathy within 4-10 years. 2, 1
• Requires urgent ophthalmology referral for gonioscopy to confirm iridotrabecular contact and immediate IOP-lowering treatment. 1

Infectious Keratitis

• Presents with severe pain, photophobia, blurred vision, and corneal infiltrate on examination. 1
• Demands immediate ophthalmologic consultation before initiating any treatment. 1

Orbital Cellulitis

• Characterized by periorbital soft tissue swelling, pain, restricted eye movement, and proptosis. 1
• Requires immediate imaging and treatment due to risk of vision loss and intracranial extension. 1

Optic Neuritis

• Presents with eye pain worsened by eye movement, vision loss, and relative afferent pupillary defect. 4
• Requires urgent ophthalmology consultation. 4

Non-Emergent Inflammatory Conditions

Inflammatory Eye Disease (Most Common Overall)

• Accounts for 69.1% of all eye pain presentations, including conjunctivitis, blepharitis, keratitis, uveitis, dry eye, chalazion, and scleritis. 5

Anterior Uveitis

• Presents with eye pain, photophobia, blurred vision, and ciliary flush on examination. 4
• Bilateral, insidious onset uveitis may indicate systemic inflammatory disease association. 2
• Requires ophthalmology referral for slit-lamp confirmation and treatment with topical and potentially systemic steroids. 2

Episcleritis

• May present with burning sensation, hyperemic sclera, but typically less severe pain than scleritis. 2
• Usually responds to topical steroids or NSAIDs without systemic treatment. 2

Scleritis

• Presents with severe, boring eye pain that may radiate to the face and awaken patients from sleep. 4
• Requires ophthalmology consultation due to association with systemic inflammatory diseases. 4

Neuropathic Corneal Pain

Clinical Presentation

• Characterized by symptoms disproportionate to clinical signs—patients report severe burning, stinging, or foreign body sensation with minimal findings on examination. 2, 6, 1
• Associated with photophobia, wind hyperalgesia, and sensitivity to light. 6
• Commonly follows ocular surgery, infections, or chronic surface abnormalities. 6

Diagnostic Approach

• Proparacaine challenge test differentiates peripheral from central neuropathic pain: complete relief suggests peripheral origin, no relief indicates central sensitization, partial relief suggests mixed pathology. 2
• In vivo confocal microscopy can confirm corneal nerve damage showing decreased nerve density, increased tortuosity, and beading. 2
• Fluorescein staining evaluates corneal epithelial integrity and tear break-up time. 6

Management

• Peripheral neuropathic pain responds to topical nerve regenerative therapies; central pain requires oral neuromodulators. 6, 1
• Combination therapy addressing multiple factors is essential. 1

Dry Eye Syndrome

• Presents with burning, stinging, foreign body sensation, photophobia, and symptoms worsening later in the day. 2
• Exacerbated by wind, air travel, low humidity, and prolonged visual tasks. 2
• Managed with ocular lubricants and treatment of underlying inflammation. 6, 1
• Patients with severe pain may have coexisting neuropathic component. 7

Conditions in the "White and Quiet Eye"

Intermittent Angle Closure

• Transient episodes of blurred vision, halos, and eye pain that resolve spontaneously. 3, 8
• Requires gonioscopy for diagnosis and laser peripheral iridotomy for definitive treatment. 3

Recurrent Corneal Erosion

• Sharp pain upon awakening, often with history of previous corneal trauma. 8
• Diagnosed with fluorescein staining showing epithelial defect. 8

Trochleitis/Trochleodynia

• Localized pain at superior medial orbit, worsened by eye movement. 8

Posterior Scleritis

• Deep eye pain with minimal external signs, requires B-scan ultrasonography for diagnosis. 8

Neurologic Causes

Migraine

• Accounts for 51% of eye pain presentations in neurology clinics, but only 3% in ophthalmology clinics. 5
• Associated with photophobia, nausea, and headache patterns. 5

Trigeminal Neuralgia

• Sharp, lancinating pain in trigeminal distribution. 5

Critical Examination Components

Every patient with eye pain requires: 6, 1

• Visual acuity testing as baseline
• Pupil examination for reactivity, size, shape, and afferent defects
• Slit-lamp biomicroscopy of anterior segment
• IOP measurement, especially if angle closure suspected
• Fluorescein staining for corneal integrity

Management Algorithm

1. Immediate ophthalmology referral if: 1

   • Vision changes present
   • Mid-dilated, poorly reactive, or oval pupil
   • Severe photophobia
   • Elevated IOP
   • Suspected infectious keratitis

2. Urgent referral (same day) if: 1, 4

   • Transient symptoms suggesting intermittent angle closure
   • Signs of anterior uveitis or scleritis
   • Suspected optic neuritis

3. Non-urgent management for: 6, 1

   • Dry eye syndrome with ocular lubricants and anti-inflammatory treatment
   • Neuropathic pain with appropriate topical or systemic neuromodulators
   • Inflammatory conditions after excluding emergencies

Critical Pitfalls to Avoid

• Never dismiss transient symptoms as benign—they represent warning episodes before potentially blinding acute attacks. 1, 3
• Do not delay fellow eye prophylaxis after treating one eye for angle closure. 1, 3
• Avoid fluorescein-anesthetic combination drops for tear break-up time assessment as anesthetic affects results. 6, 1
• Do not initiate treatment before establishing diagnosis in patients with blurred vision, pain, and photophobia. 1
• Neuropathic ocular pain is frequently misdiagnosed because symptoms outweigh clinical signs. 6, 1
• Patients with severe ocular pain often have associated psychological conditions (fibromyalgia, depression, anxiety, migraine) and respond poorly to standard dry eye treatments. 7