Eye-related headache

Headache and ocular pain often coexist. Examination of patients with eye disease will usually show visual disturbances, injection, or pupil irregularities. Patients with a normal examination may have ocular pain or symptoms caused by entities ranging from carotid dissection to primary headache disorders, such as migraine. In this update, we focus on the many causes and treatment of eye-related headache. We discuss the management of ocular emergencies, including pituitary apoplexy, and unusual diseases such as Tolosa-Hunt, Behcet disease, and optic neuritis related to West Nile virus infection and examine the causes and importance of photophobia in migraine.

Key points

• Eye pain is more likely related to ocular disease, such as glaucoma, when the eye is injected, edematous, or pupils are abnormal.
• Patients with vision loss, ophthalmoparesis, or progressive symptoms usually require urgent neuroimaging or referral.
• Pituitary apoplexy is a neurologic emergency presenting with severe headache, vision loss, ophthalmoparesis, or delirium.
• Ocular symptoms such as visual aura, blurry vision, or photophobia are common in patients with primary headache disorders such as migraine.

Overview

Because headache may be accompanied by pain in the eye or visual symptoms, it is often attributed to ocular disease. However, if the sclerae are white and noninjected, ocular disease is rarely the cause of headache. When eye disease is the cause of pain, the location and character of the pain, associated symptoms, and ocular signs are usually evident to the careful observer. Conjunctival injection, corneal edema, abnormal pupils, and decreased vision are the hallmarks of such disorders. Clinicians other than ophthalmologists should be familiar with the symptoms and signs of ocular diseases, such as infection, inflammatory disorders, and glaucoma, that cause headache.

Ocular symptoms are commonly associated with both primary and secondary headache disorders (ie, idiopathic intracranial hypertension). Patients with primary headaches, such as migraine or cluster headache, may present with complaints of photophobia, blurred vision, tearing, ptosis, or ocular pain.

Glaucoma.  Misdiagnosis (eg, corneal erosion, dental problem, cluster headache) is not uncommon. Acute closure glaucoma differs from headache in the following ways: (1) acute closure glaucoma causes a mid-dilated pupil, whereas cluster headache causes a mild Horner syndrome (a smaller pupil on the side of pain) or no pupillary abnormality; (2) acute closure glaucoma causes a cloudy (“steamy”) cornea with impaired light reflex and impaired vision, whereas cluster headache causes no such abnormality; (3) acute closure glaucoma causes marked elevation of intraocular pressure, and the globe feels hard; in cluster headache the intraocular pressure is normal, and the eyeball feels normal to palpation.

Subacute primary angle-closure glaucoma may mimic a primary headache disorder. Patients report a dull ache in or around a single eye with only mild blurring of vision. Symptoms may occur when the patient watches television or movies in a dark room, reads, or is fatigued. Intraocular pressure is normal (10 to 23 mmHg). Ophthalmologic (slit-lamp) evaluation reveals a shallow anterior chamber, iris bombe (an increase of fluid in the posterior chamber that causes a forward bulging of the peripheral iris), and an enlarged pupil. A review of 9 patients with subacute angle-closure glaucoma and headaches without ocular pain revealed that most patients in this group had episodic headaches that were worse with physical activity (Nesher 2005).

The chronic form of primary angle-closure glaucoma may be asymptomatic or have symptoms of the subacute form. An enlarged cup-to-disc ratio may suggest the diagnosis, but the pupils and intraocular pressures may be normal.

The link between glaucoma and migraine is uncertain. Although the majority of patients have elevated intraocular pressures, about 25% of patients have normal pressures. Many of these patients have migraine (Cursiefen 2000), and it may be that other factors that may be important in migraine, such as vasospasm, autoimmune diseases, or genetic factors, worsen nerve damage in glaucoma patients (Wax 2011).

Eye strain. Patients with headaches that are triggered or aggravated by close visual work should have the benefit of proper correction, but corrective measures are unlikely to have an effect on severe headaches. Uncorrected hyperopic (farsighted) patients may have eye strain causing a mild, bilateral, persistent brow ache that occurs when the patient must “strain” to clear a blurred (or possibly diplopic) image, especially with near tasks (Romano 1975). Such headaches are associated with extended and persistent close visual tasks and do not occur instantaneously with a visual challenge (Vincent et al 1989). Myopia (nearsightedness) or astigmatism is unlikely to cause significant headache. In general, severe headaches cannot be attributed to eye strain alone.

Eyelid disorders. The presence of a condition affecting the eyelids is readily apparent to the patient and physician. The most common disorders include the following:

• Hordeolum (stye)
• Chalazion
• Sebaceous carcinoma of the lid
• Blepharitis
• Dacryoadenitis
• Dacryocystitis
• Erysipelas of the face and other forms of cellulitis

Both a stye and a chalazion usually present as a small, painful lump in the eyelid. A stye is an infection of a lash follicle, and chalazia stem from chronic inflammation of oil-producing meibomian glands.

Blepharitis is an inflammatory reaction of the eyelid margin. It usually occurs as seborrheic (nonulcerative) or staphylococcal (ulcerative) blepharitis. Both types may coexist. Symptoms of staphylococcus aureus blepharitis include itching, lacrimation, burning, and photophobia. Symptoms are usually worse in the morning. Ulcerations at the base of eyelashes and broken, sparse, or misdirected eyelashes (trichiasis) may also be present.

Dacryoadenitis is an infection and inflammation of the lacrimal gland and is characterized by swelling, pain, tenderness, and redness over the upper temporal aspect of the upper eyelid. Acute dacryoadenitis must be differentiated from viral infection (mumps), sarcoidosis, Sjogren syndrome, tumors, leukemia, and lymphoma.

Acute dacryocystitis causes pain, redness, and edema about the lacrimal sac. Additional symptoms include epiphora (an overflow of tears on the cheek, due to imperfect drainage by the tear-conducting passages), conjunctivitis, blepharitis, fever, and leukocytosis. Recurrent acute inflammations may result in a red, brawny, indurated area over the sac.

Cellulitis around the eyes is a potentially dangerous periorbital and orbital infection. Symptoms of periorbital cellulitis include lid edema, rhinorrhea, orbital pain, tenderness, headache, conjunctival hyperemia, chemosis (edema of the bulbar conjunctiva), ptosis, limitation to ocular motion, increased intraocular pressure, congestion of retinal veins, chorioretinal stria, and gangrene and sloughing of the lids.

Disorders of the conjunctiva and cornea. Conjunctivitis per se does not cause severe pain but may cause orbital discomfort. Allergic conjunctivitis is commonly associated with intense itching, whereas infectious (viral, bacterial, chlamydial) and irritant conjunctivitis usually does not cause significant pruritus.

Dry eye, or aqueous tear insufficiency, is a common cause of eye pain. Symptoms include stinging, burning, or a foreign body sensation. Multiple medications, such as anticholinergic drugs or sympathomimetics, can worsen symptoms. Treatment consists of artificial tears or topical corticosteroids or cyclosporine.

In the United States, keratitis due to herpes simplex virus infection is the second most important corneal disease (after corneal trauma) leading to loss of vision. Herpes simplex type 1 is the type most closely associated with eye infection. In primary herpes infection, clusters of vesicles on the face, eyelids, and mucous membranes precede the conjunctivitis, which is follicular, occasionally membranous, and self-limited, lasting 2 to 3 weeks. Preauricular lymphadenopathy is present. Patients may require corneal transplantation and continued antiviral prophylactic treatment (Goldblum 2008). Both acyclovir and valacyclovir are effective (Miserocchi 2007). The hallmark of herpetic epithelial keratitis is the superficial dendritic or geographic ulcer (best demonstrated with fluorescein) associated with a decrease in corneal sensitivity. Herpetic stromal keratitis is a cell-mediated immune response to noninfectious herpes virus antigen. Patients with stromal keratitis have disciform stromal edema with corneal thickening, opacification, and striae in the Descemet membrane (posterior limiting membrane of cornea). Disciform keratitis may be caused by trauma, herpes varicella zoster, vaccinia, mumps, and chemical injury. Herpetic eye disease is more common and often severe in immunosuppressed patients and diabetics. In 1 cohort study, poor glycemic control was shown to correlate with increased acyclovir consumption (Kaiserman 2005). Rarely, this can lead to complete ophthalmoplegia (Delengocky and Bui 2008).

Cogan syndrome may present with hearing loss or ocular or systemic symptoms. The most common ocular disease is nonsyphilitic interstitial keratitis, which is bilateral in 80% of cases. Patients may present with ophthalmologic signs or symptoms alone, and headache is the most common systemic symptom (Gluth 2006).

Disorders of the iris, sclera, and globe. Hyphema is hemorrhage within the anterior chamber of the eye and is characterized by sudden decrease in visual acuity. If the intraocular pressure is elevated, there may be pain in the eye, with or without headache. The whole anterior chamber may be filled with blood, or a blood level may be seen. The conjunctiva is hyperemic with perilimbal injection.

IInflammation of the uveal tract (iris, ciliary body, and choroid) is called uveitis. Uveitis takes 3 forms: (1) anterior uveitis refers to ocular inflammation limited to the iris alone (iritis) or the iris and ciliary body (iridocyclitis); (2) intermediate uveitis refers to inflammation of the structures just posterior to the lens (pars planitis or peripheral uveitis); (3) posterior uveitis refers to inflammation of the choroid (choroiditis), retina (retinitis), or vitreous near the optic nerve and macula. When the affected eye is covered, the patient with iridocyclitis will experience pain in the affected eye when a bright light is shined into the normal eye (consensual photophobia). Intermediate and posterior uveitis can cause minimal pain unless associated with an iritis. Major features of anterior uveitis include decreased visual acuity that is generally acute in onset, deep eye pain, consensual photophobia, conjunctival vessel dilation, perilimbal (circumcorneal) dilation of episcleral and scleral vessels (ciliary flush), and small pupillary size of the affected eye. Anterior uveitis is usually unilateral (95% of HLA-B27-associated cases). Bilateral involvement and systemic symptoms (fever, fatigue, and abdominal pain) may be associated with interstitial nephritis. Systemic disease is most likely to be associated with anterior uveitis. The most common etiologies are infection and immune-mediated (especially rheumatologic) disease, but about 25% of cases are idiopathic. Anterior uveitis may be misdiagnosed as conjunctivitis, episcleritis, scleritis, keratitis, and acute angle-closure glaucoma. Close inspection of the conjunctiva, cornea, iris, pupil, and intraocular tension can minimize misdiagnosis. Ophthalmologic evaluation of the anterior chamber should be performed as soon as possible.

Multiple autoimmune disorders can cause uveitis. Systemic diseases with extra-organ involvement are seen in over one-third of cases followed by infectious diseases. Non-infectious systemic diseases, such as Behcet disease, multiple sclerosis, and sarcoidosis, are uncommon but not rare. Strictly anterior uveitis is most common, occurring in about 60% of cases. Systemic diseases are responsible for over one-third. Ocular toxoplasmosis is especially important in isolated posterior uveitis (Barisani-Asenbauer et al 2012).

Behcet disease often presents with uveitis and causes visual loss, and it is one of the most common causes of uveitis in adults (Kazokoglu et al 2008). A recent survey demonstrated a prevalence of 80% of recurrent headache in patients with Behcet disease, with most patients experiencing moderate to severe disability (Kidd 2006).

Scleritis is an inflammation of the scleral outer coat of the eye. Usual symptoms include redness and inflammation of the sclera and pain ranging from mild discomfort to extreme localized tenderness. However, posterior scleritis is an exception to the rule that a “white” eye without visual symptoms is not the cause of pain. Posterior scleritis can present with monosymptomatic eye pain that requires ultrasound for diagnosis (Daroff 1995). The eye should be exquisitely tender, however.

Inflammation of the episclera, or episcleritis, is a benign and frequently recurrent disorder that primarily affects young adults. Edema and congestion of the episclera are often sectoral but may be diffuse or nodular. Ocular pain, redness, photophobia, tenderness, tearing, and mild uveitis (15% of patients) are common. The cause is usually unknown, but hypersensitivity reactions may play a role. Episcleritis may be associated with rheumatoid arthritis, collagen vascular diseases, herpes zoster, gout, coccidiomycosis, tuberculosis, and syphilis.

Endophthalmitis is an acute microbial infection confined within the globe. Infection involving the sclera as well as other intraocular structures is called panophthalmitis. Infections of the globe can be exogenous or endogenous. Exogenous infection results from a penetrating injury or it may follow intraocular surgery or a ruptured corneal ulcer. Endogenous infection by the hematogenous route is less common and may be accompanied by fever and chills. The patient complains of pain, blurred vision, and photophobia. Examination discloses redness of the eye, chemosis of the conjunctiva, swelling of the eyelid, hypopyon (pus in the anterior chamber), and cloudy media (fundus hazily seen or absent red reflex).

Infectious and inflammatory eye diseases. The differential diagnosis of eye pain and headache also includes many infectious and inflammatory causes.

Idiopathic inflammatory orbital pseudotumor refers to a noninfectious, inflammatory, space-occupying lesion of the orbit that simulates a neoplasm. Signs and symptoms develop acutely and consist of orbital pain, lid swelling, conjunctival chemosis and injection, proptosis, iritis, optic disc edema, and extraocular muscle disturbances. Proptosis and pain are the predominant features. Approximately one-half of patients eventually develop bilateral orbital involvement. Half of all patients develop systemic manifestations, including headache, fever, vomiting, pharyngitis, anorexia, abdominal pain, and lethargy. Trauma, infection, foreign body, and malignancy must be excluded by examination and laboratory testing.

Orbital cellulitis, orbital abscess, and subperiosteal abscess may cause lid swelling, erythema, proptosis, and ophthalmoplegia. Vision is often impaired with orbital abscess and subperiosteal abscess.

Mucormycosis (zygomycosis or phycomycosis) is a fungal infection that is typically seen in immunocompromised or debilitated patients. Predisposing conditions include diabetic ketoacidosis, chronic renal failure, and treatment with steroids or cytotoxic drugs. The diagnosis should be considered in diabetic patients with black, necrotic lesions (eschars) of the nose or sinuses or with new cranial nerve abnormalities. Without treatment, cerebral invasion may ensue. Bacterial cavernous sinus thrombosis may result from spread from the contiguous sphenoidal or ethmoidal air sinuses, either directly or via the emissary veins. Exophthalmos, papilledema, severe cerebral symptoms (headache, decreased level of consciousness, convulsions), cranial nerve palsies, and high fever are present. The prognosis is grave; the mortality rate remains about 30%, despite antibiotic therapy.

Dysthyroid ophthalmopathy is probably the leading cause of unilateral exophthalmos and is the leading cause of bilateral exophthalmos in adults. Ocular ache is more common than severe eye pain. Inflammatory cells and a mucilaginous ground substance infiltrate the extraocular muscles and other orbital contents. This is followed by fibrosis of orbital tissues. Patients often have diplopia caused by restriction of the extraocular muscles, most commonly the inferior rectus. Forced ductions, wherein the examiner attempts to manually rotate the eye, show that the passive movement of the eye is limited by the involved muscle. Other findings include proptosis, vascular congestion over the insertion of the lateral or medial rectus muscle on the globe, lid retraction or lid lag, and edema of the eyelids. Dysthyroid ophthalmopathy can occur in a patient who is hyperthyroid, but it can also occur in patients who have been treated for hyperthyroidism and are euthyroid or even hypothyroid. It may even occur in patients who have not yet developed other evidence of thyroid disease. Therefore, it is a clinical diagnosis based on the eye findings rather than on laboratory evidence of thyroid dysfunction.

Orbital hematoma is most often due to zygomatic fracture. Diplopia may be present as a result of orbital hematoma. Facial paresthesias or hypesthesias of the upper lip and cheek occur if the infraorbital nerve is damaged at the infraorbital foramen or more posteriorly in the orbital floor, where the infraorbital canal constitutes an area of weakness.

Pituitary apoplexy. Pituitary apoplexy occurs almost exclusively in patients with pituitary tumors and is due to hemorrhagic infarction of the tumor or the pituitary gland itself. Chronic hemorrhage into the pituitary gland or gradual infarction of it may occur without symptoms. Sudden hemorrhage or infarction is a medical emergency. Neurologic symptoms are most prominent, and transient neurologic symptoms frequently precede the acute event over several days. The usual symptoms and signs include the following: increasing headache, diplopia, blurred vision, visual loss, and visual field defects (especially bitemporal hemianopia); extraocular motor palsies are common; altered mental status with lethargy, confusion, and delirium that may progress to coma; nausea and vomiting; less commonly, paresthesias, ataxia, seizures, and focal hemispheric symptoms; symptoms of the preexisting pituitary adenoma, eg, previous headache, visual defects, and hypopituitarism; meningeal irritation may be prominent; fever is common and may result from subarachnoid bleeding, acute hypoadrenalism, or hypothalamic compression; hypotension is present in those with acute adrenal insufficiency; and respiratory failure may occur because of hypothalamic compression or increased intracranial pressure. Early treatment with surgical decompression can improve visual outcomes (Muthukumar 2008).

Carotid artery dissection. Spontaneous carotid artery dissection sometimes mimics migraine headache and is in the differential diagnosis of sudden-onset “thunderclap” headaches. Carotid artery dissection may also be associated with visual symptoms that resemble migrainous visual aura. Most patients with carotid artery dissection present with unilateral headache and facial or neck pain, followed by focal cerebral ischemic symptoms, retinal ischemia, or oculosympathetic palsy. However, pain as the only symptom of cervical artery dissection is rare and only sporadically reported. In a series of 44 patients with cervical artery dissection, only 2 presented with pain alone (Sturzenegger 1995). Headache or neck pain typically is ipsilateral to the side of dissection. In patients with an internal carotid artery dissection, pain is limited to the anterior head in 60%. Pain is limited to the anterior head in 60% of patients with an internal carotid artery dissection. A recent meta-analysis did not show differences between anticoagulation or antiplatelet treatment for stroke prevention after dissection (Kennedy et al 2012).

Parasellar syndromes. The parasellar syndrome consists of dysfunction of the third, fourth, and sixth cranial nerves. Involvement of the ophthalmic division of the trigeminal nerve may be added. Primary neoplasms sometimes occur in this region, but metastatic lesions are more common. Other processes that produce the parasellar syndrome include cavernous sinus thrombosis, carotid-cavernous sinus fistula, and aneurysm of the intracavernous carotid artery. If a specific cause cannot be found, the diagnosis of Tolosa-Hunt syndrome may be considered. A dramatic response to steroids is characteristic of, but not diagnostic for, Tolosa-Hunt syndrome. Diagnosis requires thorough investigation before empiric corticosteroid therapy. Granulomatous inflammatory diseases such as seen with rheumatoid arthritis, Wegener granulomatosis, sarcoidosis, lupus, and eosinophilic granulomas should be considered (Johnston 2002). A prompt response to steroids has been observed repeatedly in neoplasms, and exacerbations and remissions are not uncommon with aneurysms, neoplasms, or infectious granulomas.

Orbital causes of painful ophthalmoplegia include the orbital diseases mentioned above (eg, orbital cellulitis, abscess) and neoplasms at the orbital apex (primary, contiguous, or metastatic). Nonorbital causes of painful ophthalmoplegia include intracranial, cranial, pericranial, and metastatic neoplasms. Common primary intracranial neoplasms causing painful ophthalmoplegia would include pituitary adenoma, meningioma, and craniopharyngioma. Cranial tumors include chondroma, multiple myeloma, and lymphoma. Nasopharyngeal carcinoma is a relatively common cause, and biopsy should be obtained if another cause cannot be easily identified. Intracranial hypertension can cause a sixth nerve palsy as a false localizing sign.

Eye pain and vision loss. Giant cell, or temporal, arteritis should be considered in any individual over the age of 50 who has unexplained headache of recent onset. Elevation of the Westergren erythrocyte sedimentation rate and C-reactive protein level has a strong correlation with positive temporal artery biopsy. However, biopsy-proven giant cell arteritis can occur with either normal sedimentation rate or normal C-reactive protein levels (Parikh 2006). Jaw claudication and polymyalgia rheumatica may heighten the suspicion, but their absence does not exclude the diagnosis. If giant cell arteritis is likely, presenting with markedly elevated erythrocyte sedimentation rate and typical symptoms, steroids should be started and the patient should have a long segment temporal artery biopsy.

Eye pain and vision loss are commonly seen with processes affecting the optic nerve. The most common cause of acute optic neuropathy in young patients is demyelinating disease, such as multiple sclerosis or neuromyelitis optica. The pain of optic neuritis is believed to be caused by traction of the inflamed optic nerve sheath at the orbital apex (Lepore 1991). Eye pain and pain on eye movement precede visual symptoms in about 40% of patients with demyelinating optic neuritis (Optic Neuritis Study Group 1991).

Ocular pain is less common in anterior ischemic optic neuropathy. Other causes of optic neuritis include infections, such as measles, mumps, or syphilis, and inflammatory disorders, including systemic lupus erythematosus, Sjogren syndrome, or sarcoidosis. West Nile virus infection has also been described as a cause of bilateral optic neuritis and chorioretinitis (Anninger 2003).

Idiopathic intracranial hypertension (pseudotumor cerebri) may present with headache, diplopia, pulsatile tinnitus, visual field loss, and visual obscurations. Most patients have papilledema, but some patients may present without papilledema despite similar clinical symptoms (Digre et al 2009).

Primary headache disorders and ocular pain. Eye pain and periorbital pain may be symptoms of primary headache disorders. Migraine, the trigeminal autonomic cephalgias (eg, cluster, paroxysmal hemicrania, hemicrania continua, sudden unilateral neuralgiform pain with conjunctival infection and tearing [or SUNCT syndrome], and idiopathic stabbing headache) may all have eye pain as a major symptom. The pain is episodic or nonprogressive and usually associated with other symptoms. Without obvious ocular pathology, the eye itself is rarely responsible for the pain and discomfort (Behrens 1978). Pain with eye movement is an uncommon symptom of migraine; however, significant bilateral pain with eye movement could be a symptom of meningeal irritation or idiopathic intracranial hypertension. Orbital cellulitis, orbital myositis (eg, trichinosis), orbital periostitis, and optic neuritis can also cause pain with eye movement, but additional signs and symptoms should suggest the diagnosis.

Primary headaches may be associated with oculosympathetic paresis, conjunctival injection, and lid edema, but not with proptosis, limitation of ocular motion, erythema, an eschar, fever, congestion of retinal veins, consensual photophobia, halos around lights, an enlarged cup-to-disc ratio, or cloudy media.

Many migraine patients will endorse the symptom of “double vision” off a checklist. The examiner must determine whether the patient is referring to “blurred vision” (the vast majority of cases) or true diplopia, with separation of images with binocular vision and resolution of diplopia with 1 eye covered. Momentary diplopia is sometimes related to a heterophoria brought on by medication, fatigue, and distress.

Photophobia commonly accompanies, but is not specific for, migraine. Photophobia is of 2 types: (1) peripheral and (2) central. “Peripheral” photophobia occurs with inflammation of the anterior segment of the eye. Pupillary constriction pulls or displaces the pain-sensitive iris and ciliary muscles; immobilization of the iris and ciliary muscles with cycloplegic eye drops reduces the photophobia despite increasing the amount of light to the retina. “Central” photophobia occurs in any condition associated with pain in the distribution of the ophthalmic nerve (ie, any headache). In general, photophobia is more prevalent with severe migraine (Daroff 1995). Unilateral photophobia is more common in patients with trigeminal autonomic cephalgias than in patients with migraine (Goadsby 2010).

Photosensitive retinal ganglion cells containing melanopsin, a photopigment, allow regulation of circadian rhythms via the suprachiasmatic nucleus and are an important part of the photophobia pathway. Noseda and colleagues studied blind individuals with migraine and found that blind persons with intact sleep patterns and pupillary light reflex had worsening pain intensity in migraine with light exposure (Noseda et al 2010). Blind persons with migraine with no light perception, such as those with severe optic nerve damage or bilateral enucleation, are not photophobic. This suggests these melanopsin-containing cells, and not rods or cones, are important in photophobia. Anterograde tracing demonstrates that these retinal images project to the posterior thalamus, which then project widely to multiple cortical regions. These cortical projections may explain other common migraine symptoms that can worsen with photophobia such as weakness, incoordination, or visual disturbances (Gooley 2003).

Ophthalmoplegic migraine is a rare condition (Daroff 1995) that almost always begins in childhood with repeated episodes of headaches that usually last several days and gradually resolve, whereas a third (rarely fourth or sixth) nerve palsy slowly evolves, leaving the patient with a painless unilateral third nerve palsy that recovers over the course of weeks (Daroff 2001). Lance and Zagami propose that ophthalmoplegic migraine is a recurrent demyelinating or inflammatory cranial neuropathy (Lance and Zagami 2001). The cause and mechanism for ophthalmoplegic migraine remain elusive. Case reports suggest an inflammatory etiology with MRI evidence of cranial nerve enhancement and elevated IgG index in the CSF of the affected patient (van der Dussen 2004). The most recent International Classification of Headache Disorders characterize this as a rare entity with “recurrent attacks of headache with migrainous characteristics associated with paresis of 1 or more ocular cranial nerves (commonly the third nerve) in the absence of any demonstrable intracranial lesion other than MRI changes within the affected nerve.”

Monocular visual loss may be seen with retinal migraine. For the diagnosis of retinal migraine to be secure, the patient should have experienced multiple stereotyped episodes of monocular visual loss associated with migraine headaches. However, the vast majority of reported cases of retinal migraine do not conform to this pattern (Daroff 1995). Binocular visual disturbances are a hallmark of migraine with aura. Diplopia can be seen as an isolated neurologic symptom with ophthalmoplegic migraine or associated with other brainstem symptoms in basilar migraine.

Conjunctival injection, periorbital edema, ptosis, or lacrimation can be seen with cluster headache, the autonomic hemicranias, and SUNCT syndrome. Cluster headache typically presents with severe episodes of pain that last 15 to 180 minutes and often localize to the eye. The pain may be described as burning, stabbing, or as if “the eye is being pushed out.” Up to 25% of patients develop a permanent Horner syndrome (Brazis 2002). The pain of hemicrania continua is usually unilateral with constant pain with a variable degree of autonomic symptoms ipsilateral to the side of pain. Hemicrania continua is a syndrome that responds dramatically to treatment with indomethacin (Klein 2006). SUNCT syndrome often causes ocular pain lasting from 5 to 250 seconds, usually with conjunctival injection and tearing, with attacks occurring up to 200 times per day. Trigeminal neuralgia is a distinctive lancinating, unilateral pain in the distribution of the trigeminal nerve. This can involve the ophthalmic division and cause eye pain, but is more commonly seen in the maxillary or mandibular divisions of the nerve.

Differential diagnosis

Eyelid disorders

• Vision: normal
• Proptosis: absent
• Ptosis: edema may mimic
• Pupils: normal
• Photophobia: absent
• Local signs of inflammation: present
• Intraocular pressure: normal

Dacryoadenitis

• Vision: normal
• Proptosis: absent
• Ptosis: absent
• Pupils: normal
• Photophobia: absent
• Local signs of inflammation: present
• Intraocular pressure: normal
• Other: localized swelling, pain, and tenderness

Periorbital cellulitis

• Vision: may have irritated eye movement
• Proptosis: absent
• Ptosis: edema may mimic
• Pupils: normal
• Photophobia: absent
• Local signs of inflammation: present
• Intraocular pressure: may be elevated
• Other: untreated can cause septic cavernous thrombosis

Conjunctivitis

• Vision: normal
• Proptosis: absent
• Ptosis: absent
• Pupils: normal
• Photophobia: mild
• Local signs of inflammation: present
• Intraocular pressure: normal

Hyphema

• Vision: abrupt decrease in vision
• Proptosis: absent
• Ptosis: absent
• Pupils: normal
• Photophobia: absent
• Local signs of inflammation: present
• Intraocular pressure: can be elevated

Anterior uveitis - iritis

• Vision: decreased
• Proptosis: absent
• Ptosis: absent
• Pupils: miosis, irregular
• Photophobia: present
• Local signs of inflammation: present
• Intraocular pressure: normal
• Other: mydriatics relieve symptoms

Anterior uveitis - iridocyclitis

• Vision: decreased
• Proptosis: absent
• Ptosis: absent
• Pupils: miosis
• Photophobia: consensual photophobia
• Local signs of inflammation: present
• Intraocular pressure: normal

Posterior uveitis

• Vision: decreased
• Proptosis: absent
• Ptosis: absent
• Pupils: absent
• Photophobia: absent
• Local signs of inflammation: absent
• Intraocular pressure: normal

Corneal disorders

• Vision: decreased
• Proptosis: absent
• Ptosis: absent
• Pupils: absent
• Photophobia: present
• Local signs of inflammation: present
• Intraocular pressure: normal

Acute angle-closure glaucoma

• Vision: decreased
• Proptosis: absent
• Ptosis: absent
• Pupils: fixed mid-dilated, oval
• Photophobia: present
• Local signs of inflammation: present
• Intraocular pressure: high
• Other: mydriatic = disaster

Subacute angle-closure glaucoma

• Vision: absent or mild blurring
• Proptosis: absent
• Ptosis: absent
• Pupils: enlarged
• Photophobia: present during episode
• Local signs of inflammation: usually absent
• Intraocular pressure: usually normal
• Other: elevated cup-to-disc ratio

Chronic angle-closure glaucoma

• Vision: usually normal
• Proptosis: absent
• Ptosis: absent
• Pupils: normal
• Photophobia: absent
• Local signs of inflammation: absent
• Intraocular pressure: usually normal
• Other: elevated disc-to-cup ratio

Scleritis

• Vision: normal
• Proptosis: absent
• Ptosis: absent
• Pupils: normal
• Photophobia: present
• Local signs of inflammation: usually present, globe tender
• Intraocular pressure: normal
• Other: posterior scleritis may cause eye pain with "white" eye

Episcleritis

• Vision: normal
• Proptosis: absent
• Ptosis: absent
• Pupils: normal
• Photophobia: present
• Local signs of inflammation: present
• Intraocular pressure: normal
• Other: minimal pain; often idiopathic, whereas scleritis is often associated with immune-related diseases

Endophthalmitis

• Vision: blurred
• Proptosis: normal
• Ptosis: normal
• Pupils: normal
• Photophobia: present
• Local signs of inflammation: present
• Intraocular pressure: normal

Orbital disease

• Vision: may be decreased; diplopia
• Proptosis: present
• Ptosis: may be present
• Pupils: normal
• Photophobia: absent
• Local signs of inflammation: present
• Intraocular pressure: may be elevated
• Other: systemic symptoms and fever common

Cavernous sinus thrombosis

• Vision: may be decreased; diplopia
• Proptosis: present
• Ptosis: may be present
• Pupils: oculomotor or Horner syndrome may be present
• Photophobia: minimal
• Local signs of inflammation: present
• Intraocular pressure: may be elevated

Dysthyroid ophthalmopathy

• Vision: usually normal; diplopia
• Proptosis: present; may be unilateral or bilateral
• Ptosis: uncommon
• Pupils: normal
• Photophobia: absent
• Local signs of inflammation: may be present
• Intraocular pressure: may be elevated
• Other: thyroid studies may be normal

Parasellar syndrome

• Vision: diplopia due to third, fourth, or sixth nerve palsy
• Proptosis: absent
• Ptosis: may be present
• Pupils: third nerve mydriasis
• Photophobia: absent
• Local signs of inflammation: absent
• Intraocular pressure: normal

Pituitary apoplexy

• Vision: blurred vision and diplopia often present
• Proptosis: absent
• Ptosis: may be present
• Pupils: third nerve mydriasis
• Photophobia: absent
• Local signs of inflammation: absent
• Intraocular pressure: normal
• Other: cerebral symptoms and cranial neuropathy common

Optic neuritis

• Vision: present, but eye pain may precede visual loss in 40% of patients
• Proptosis: absent
• Ptosis: absent
• Pupils: relative afferent pupillary defect
• Photophobia: present
• Local signs of inflammation: absent
• Intraocular pressure: normal

Referred pain (eg, sinusitis)

• Vision: normal
• Proptosis: absent
• Ptosis: absent
• Pupils: normal
• Photophobia: absent
• Local signs of inflammation: pericranial inflammation
• Intraocular pressure: normal
• Other: purulent discharge; postural exacerbation