What does pain around the eyes indicate?

Pain Around the Eyes: Differential Diagnosis and Clinical Approach

Pain around the eyes indicates a broad spectrum of conditions ranging from benign ocular surface disorders to vision-threatening emergencies and systemic diseases, requiring systematic evaluation to distinguish nociceptive ocular pain from neuropathic ocular pain, and to identify red flags for urgent conditions. 1

Primary Diagnostic Categories

Neuropathic Ocular Pain (NOP)

Neuropathic ocular pain should be suspected when symptoms significantly outweigh observable signs of disease. 1

• NOP results from dysfunction of the trigeminal nerve (cranial nerve V1) pathways, either peripherally at the ocular surface or centrally in the thalamus and higher cortical areas 1
• Pain is characteristically described as burning, stinging, or aching, often accompanied by photophobia and wind hyperalgesia 1
• Common triggers include ocular surgeries (refractive surgery, cataract extraction), post-herpetic neuralgia, chronic ocular surface inflammation, or idiopathic causes 1
• NOP frequently coexists with migraine, fibromyalgia, or traumatic brain injury 1

Nociceptive Ocular Pain

Nociceptive pain typically presents with visible ocular surface abnormalities including aqueous tear deficiency, tear film instability, inflammation, and epithelial erosions. 1

• Environmental stimuli and tear film abnormalities trigger corneal nociceptors directly 1
• Associated conditions include dry eye syndrome, meibomian gland dysfunction, and corneal abrasions 1, 2

Vision-Threatening Emergencies

Acute angle-closure glaucoma requires immediate ophthalmology referral and represents a true ophthalmologic emergency. 3, 2

• Other urgent conditions requiring immediate consultation include orbital cellulitis, scleritis, anterior uveitis, infectious keratitis, and optic neuritis 2
• Giant cell (temporal) arteritis requires urgent corticosteroid treatment to prevent vision loss 3

Systemic and Referred Pain

Pain around the eyes without obvious ocular pathology should prompt evaluation for systemic vascular, neurologic, and inflammatory conditions. 3, 4

• Vascular causes include carotid artery disease, cavernous sinus thrombosis, and transient ischemic attack 3, 4
• Neurologic causes include trigeminal neuralgia, migraine, cluster headaches, and increased intracranial pressure 3, 4
• Sinus disease can refer pain to the periorbital region 3
• Erdheim-Chester disease characteristically presents with retroorbital pain and orbital infiltration in 25-30% of cases 5

Diagnostic Algorithm

Step 1: Initial Assessment

Perform thorough ocular surface and tear parameter examination to evaluate for nociceptive sources of pain. 1

• Assess visual acuity systematically 2
• Examine conjunctiva, eyelids, sclera, cornea, pupil, anterior chamber, and anterior uvea 2
• Perform fluorescein staining to identify epithelial defects and tear film instability 1
• Measure tear break-up time and consider Schirmer testing 1

Step 2: Symptom Characterization

Use validated questionnaires to distinguish neuropathic from nociceptive pain qualities. 1

• The Neuropathic Pain Symptom Inventory (NPSI)-Eye or Ocular Pain Assessment Survey (OPAS) assess burning pain, wind sensitivity, and light sensitivity 1
• Key red flag: symptoms that persist despite appropriate treatment and resolution of ocular surface abnormalities suggest NOP 1

Step 3: Anesthetic Challenge Test

If NOP is suspected, perform the anesthetic challenge test to localize the pain source. 1

• Pain must be present before anesthetic instillation for the test to be informative 1
• If pain improves after topical anesthetic: suggests nociceptive or peripheral neuropathic component 1
• If pain does not improve: suggests central or non-ocular cause of pain 1

Step 4: Screen for Associated Conditions

Evaluate for systemic pain conditions and psychological comorbidities, particularly in patients with severe pain. 1, 6

• Higher pain intensity correlates with fibromyalgia, depression, anxiety, and migraine 6
• Younger age, history of refractive surgery, and absence of corneal staining suggest neuropathic component 6
• NOP patients frequently experience concomitant anxiety, depression, and mood disorders due to corneal nerve connections to emotional processing centers 1

Management Approach Based on Pain Type

For Peripheral Neuropathic Ocular Pain

Initiate topical nerve regenerative therapies as first-line treatment. 1

• Autologous serum tears (20% concentration) for peripheral corneal neuropathic pain 1
• Topical anti-inflammatory agents 1

For Central Neuropathic Ocular Pain

Prescribe oral neuromodulators, setting expectations for 3-4 months at therapeutic dose before pain reduction. 1

• First-line: pregabalin, gabapentin, duloxetine, amitriptyline, nortriptyline, or low-dose naltrexone 1
• Use alone or in combination based on response 1
• For patients with systemic comorbidities (fibromyalgia), systemic neuromodulators are essential 1

For Light Sensitivity and Headache

Consider adjuvant migraine strategies. 1

• Transcutaneous electrical nerve stimulation devices 1
• Periorbital botulinum toxin A injections 1

For Cutaneous Allodynia or Post-Surgical Pain

Administer periocular nerve blocks with corticosteroid and long-acting sodium channel blocker. 1

Complementary Therapies

Incorporate multidisciplinary approaches including acupuncture, cognitive behavioral therapy, or hypnosis to address the emotional component of chronic pain. 1

Critical Pitfalls to Avoid

• Do not dismiss pain in the absence of visible ocular signs - this is the hallmark of NOP and requires different management than nociceptive pain 1
• Do not expect immediate pain relief with neuromodulators - counsel patients that 3-4 months at therapeutic dose is required before assessing efficacy 1
• Do not overlook vision-threatening emergencies - acute angle-closure glaucoma and giant cell arteritis require immediate intervention 3, 2
• Do not treat in isolation - NOP warrants multidisciplinary involvement of ophthalmologists, pain specialists, neurologists, and mental health professionals 1
• Do not ignore treatment resistance patterns - patients with severe ocular pain show significantly lower response rates to standard dry eye treatments (artificial tears, cyclosporine, autologous serum tears, punctal occlusion) 6