What is the approach to a patient presenting with headache and right eye pain, including history, physical examination, laboratory tests, and differential diagnoses?

Headache with Right Eye Pain: Clinical Approach

Focused History

Prioritize identifying red flags immediately to distinguish between benign primary headache disorders and sight-threatening or life-threatening emergencies 1, 2.

Critical Red Flags to Assess

• Thunderclap onset ("worst headache of life") suggesting subarachnoid hemorrhage 1
• Age >50 years with new-onset headache raising concern for giant cell arteritis 1, 2
• Progressive worsening indicating possible space-occupying lesion 1
• Headache awakening from sleep or worsened by Valsalva/cough suggesting increased intracranial pressure 1, 2
• Focal neurological symptoms (weakness, numbness, speech changes) 1, 2
• Fever with neck stiffness indicating meningitis 1
• Recent head/neck trauma 1

Pain Characteristics

• Onset and duration: Sudden (minutes) vs gradual (hours/days); episodic attacks lasting 15-180 minutes suggest cluster headache, 4-72 hours suggest migraine 1, 3
• Location: Strictly unilateral retro-orbital/supraorbital pain with ipsilateral autonomic symptoms (lacrimation, conjunctival injection, nasal congestion, ptosis) is pathognomonic for cluster headache 3
• Quality: Severe, boring pain with restlessness (cluster) vs pulsating (migraine) vs pressing/tightening (tension-type) 1, 3
• Frequency: 1-8 attacks daily occurring in clusters vs episodic vs chronic (≥15 days/month) 1, 3

Associated Ocular Symptoms

• Vision changes: Acute vision loss, blurred vision, or visual field defects require urgent ophthalmologic evaluation 4, 5
• Foreign body sensation suggesting corneal pathology 4
• Photophobia: Present in migraine, corneal abrasion, uveitis, and angle-closure glaucoma 4, 5
• Eye redness: Conjunctivitis, scleritis, uveitis, or acute angle-closure glaucoma 4, 5
• Halos around lights: Acute angle-closure glaucoma 4

Medication History

• Acute medication overuse: Non-opioid analgesics ≥15 days/month or other acute medications ≥10 days/month for >3 months indicates medication-overuse headache 1, 2

Focused Physical Examination

Visual acuity testing is mandatory as the first step in any patient with eye pain to identify vision-threatening conditions 4.

Systematic Ocular Examination

• Visual acuity: Document for each eye separately; acute vision loss requires emergency ophthalmology consultation 4, 5
• Pupillary examination:
  • Relative afferent pupillary defect suggests optic neuritis 4
  • Mid-dilated, non-reactive pupil suggests acute angle-closure glaucoma 4
  • Miosis with ptosis (Horner syndrome) can occur with cluster headache 3
• Conjunctival injection: Ipsilateral injection with lacrimation supports cluster headache; diffuse injection suggests conjunctivitis or acute glaucoma 3, 4
• Corneal examination with fluorescein staining: Identifies corneal abrasion, herpetic keratitis, or foreign body 4
• Anterior chamber depth: Shallow chamber suggests angle-closure risk 4
• Tonometry: Elevated intraocular pressure (>21 mmHg, often >40 mmHg in acute angle-closure glaucoma) 4

Neurological Examination

• Cranial nerve testing: Focal deficits suggest secondary causes 1, 2
• Temporal artery palpation: Tenderness, decreased pulse, or nodularity in patients >50 years suggests giant cell arteritis 1
• Neck examination: Stiffness or limited flexion suggests meningitis 1
• Occipital nerve palpation: Tenderness reproducing eye pain suggests cervicogenic headache 6

Laboratory Investigations

Laboratory testing is selective, not routine, based on clinical suspicion from history and examination 1, 2.

Indicated Laboratory Tests

• ESR and CRP: For patients >50 years with new-onset headache and suspected giant cell arteritis; note that ESR can be normal in 10-36% of cases 1
• Morning TSH and free T4: If cold intolerance or lightheadedness present 1
• Thyroid peroxidase antibodies: If biochemical hypothyroidism confirmed 1

Neuroimaging Indications

• Non-contrast CT head immediately (<6 hours from onset): Thunderclap headache with sensitivity 95% on day 0 for subarachnoid hemorrhage 1
• MRI brain with and without contrast (preferred modality): Progressive headache, new-onset after age 50, focal neurological signs, atypical features, or suspected tumor/inflammatory process 1, 2
• CT head: Acute trauma or abrupt-onset headache 1

Ophthalmologic Investigations

• Urgent ophthalmology consultation required for: Acute angle-closure glaucoma, optic neuritis, orbital cellulitis, scleritis, anterior uveitis, infectious keratitis 4, 5

Differential Diagnoses

Primary Headache Disorders with Eye Pain

Cluster headache is the most likely primary headache disorder when strictly unilateral severe retro-orbital pain occurs with ipsilateral autonomic symptoms 3.

• Cluster headache: Severe unilateral supraorbital/retro-orbital pain lasting 15-180 minutes, frequency 1-8 attacks daily, with ipsilateral lacrimation, conjunctival injection, nasal congestion, ptosis, or miosis; patients are restless and pace during attacks 3
• Migraine without aura: Moderate-to-severe unilateral pulsating headache lasting 4-72 hours with nausea/vomiting, photophobia, and phonophobia; worsens with activity; patients prefer to lie still 1, 3
• Migraine with aura: Above features plus visual/hemisensory disturbances developing gradually over ≥5 minutes, lasting 5-60 minutes, followed by headache within 60 minutes 1, 2

Sight-Threatening Ocular Emergencies

Acute angle-closure glaucoma must be ruled out urgently in any patient with severe eye pain, as delay causes irreversible vision loss 4, 5.

• Acute angle-closure glaucoma: Severe unilateral eye pain, blurred vision, halos around lights, mid-dilated non-reactive pupil, conjunctival injection, corneal edema, elevated intraocular pressure (often >40 mmHg); requires immediate ophthalmology consultation 4, 5
• Optic neuritis: Subacute vision loss, pain with eye movement, relative afferent pupillary defect; requires urgent ophthalmology and neurology consultation 4, 5
• Anterior uveitis: Eye pain, photophobia, blurred vision, conjunctival injection, small irregular pupil; requires ophthalmology consultation 4, 5
• Infectious keratitis (including herpetic): Eye pain, foreign body sensation, photophobia, conjunctival injection, corneal infiltrate on fluorescein staining; requires ophthalmology consultation 4, 5
• Scleritis: Deep, boring eye pain worse at night, scleral injection, may have associated systemic autoimmune disease; requires ophthalmology consultation 4, 5

Life-Threatening Secondary Causes

• Subarachnoid hemorrhage: Thunderclap headache, may have altered taste sensation; requires immediate non-contrast CT head 1
• Meningitis: Headache with neck stiffness, unexplained fever; requires immediate evaluation and lumbar puncture if imaging negative 1
• Giant cell arteritis: New-onset headache in patients >50 years with scalp tenderness, jaw claudication, elevated ESR/CRP; requires urgent rheumatology referral and consideration of empiric corticosteroids 1
• Brain tumor/space-occupying lesion: Progressive headache, awakens from sleep, worsens with Valsalva/cough; requires MRI brain 1
• Stroke/TIA: Atypical aura with focal neurological symptoms; requires emergency evaluation 1

Other Causes of Eye Pain with Headache

• Corneal abrasion: Acute onset, foreign body sensation, photophobia, positive fluorescein staining 4
• Conjunctivitis: Eye redness, discharge, foreign body sensation; typically benign 4
• Hordeolum: Localized eyelid swelling and tenderness 4
• Cervicogenic headache: Occipital nerve tenderness reproducing eye pain; responds to nerve blockade 6
• Orbital cellulitis: Fever, proptosis, ophthalmoplegia, periorbital swelling; requires emergency admission 4

Common Pitfall

Do not assume eye pain is always ocular in origin—many primary headache disorders (especially cluster headache) present with severe retro-orbital pain in a structurally normal eye 7, 6, 8. Conversely, intermittent angle-closure glaucoma can present with episodic headache and normal examination between attacks, requiring high index of suspicion 5.