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Secondary Causes of Eye A localization approach and good clinical history and examination can help diagnose the 45% of eye pain not caused by or trigeminal neuralgias. By Neena R. Cherayil, MD

Eye pain is frequently encountered in neurol- Behavioral coping strategies include frequent blinking and ogy clinics, and primary syndromes minimizing windy or low-humidity environments. People are an especially common cause (given the with dry eye who spend prolonged periods reading or using rich innervation of the by the trigeminal nerve). In a published series, 51% of people presenting with eye pain to a neurologist’s THE FLAG LIST office had migraine with an additional 4.1% diagnosed with or other cranial nerve disorder.1 This Expedite evaluation of eye pain with: review focuses on the pertinent clinical features of second- ary etiologies of eye pain that may present to an outpatient Any vision loss practice; see the Red Flag list for eye pain red • Pay special attention to darkening of vision in flags that may signify true emergencies. Taking a localiza- some or all areas not fixable by any means tion approach while highlighting salient historical and exam features, we begin with ocular surface causes of eye pain and New-onset binocular double vision move posteriorly through the structures of the eye to the and orbit. New focal neurologic deficits

Ocular Surface New Dry Eye is a result of insufficient lubrication of Sudden thunderclap or headaches the eye and a common cause of ocular discomfort, compris- suggestive of increased intracranial pressure ing 3.1% of eye pain presenting to a neurologist.1 A healthy aqueous and lipid-mucous tear film is required for lubrication and nourishment of the ocular surface as well as flushing of foreign bodies.2 Patients with dry eye may complain of mild- “Can’t miss” diagnoses include: to-moderate, typically bilateral ocular discomfort that is vague or burning. Many also endorse a gritty, foreign body sensation Hydrocephalus in the eye.3 Discomfort can be accompanied by redness and paradoxical watering caused by reflex tearing secondary to Cerebral aneurysm irritation from dryness. Resolution of discomfort with topical anesthetic eye drops supports the diagnosis. Carotid dissection Individuals with fascicular or peripheral facial nerve pal- sies or parkinsonian syndromes are particularly susceptible Giant cell arteritis to dry eye because of inadequate blinking. Anyone under age 65 with accompanying dry mouth and other systemic Mass lesion symptoms should be evaluated for Sjögren syndrome. Use of • especially a mass impinging cavernous sinus, selective serotonin reuptake inhibitors (SSRIs), anticholiner- which houses oculomotor, ophthalmic, and gics, and antihistamines can also contribute to dry eye.4 trigeminal (1st and 2nd division) nerves Treatment is aimed at increasing tear production, decreas- ing tear loss, and reducing ocular surface .

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digital screens should adhere to the 20-20-20 rule (see Clinical with debilitating and unrelenting Gem). Frequent application of over-the-counter artificial tears pain in and around the eye.6 (4 times a day) can improve symptoms within days to weeks.5 People with dry eye should be followed by a comprehensive Elevated Intraocular Pressure ophthalmologist, and those with abnormal function or Elevated intraocular pressure (IOP) above 40 mm Hg (nor- anatomy should be referred to an oculoplastic surgeon. mal <22 mm Hg) or a sudden, dramatic rise in IOP can cause eye pain, headache, and nausea/vomiting, as well as vision and 7 CLINICALGEMS pupillary changes. Untreated narrow angle or acute angle clo- sure is a common cause. People with chronic insidi- The 20-20-20 rule can help minimize dry ous elevations in IOP typically do not develop pain. eye and during extended periods of screen time: focus on a target 20 feet away for 20 seconds every 20 minutes CLINICALGEMS Intermittent angle-closure glaucoma can Eye Infections mimic migraine with frontal pain ipsilateral Stabbing eye pain with purulent discharge from the eye to the affected eye; head pain of elevated is associated with infectious or and intraocular pressure (IOP) has symptom onset more often presents to ophthalmologists.1 An important later in life than typical for migraine infectious cause of eye pain that may present to neurology is herpes zoster ophthalmicus (HZO), which is a reactivation With elevated IOP, there may be a hard, or blurry of the varicella zoster virus involving the ophthalmic division vision with glare/haloes around lights because of conjuncti- of the trigeminal nerve (cranial nerve V-1 [CN V-1]). Patients val hyperemia and corneal edema.8 Head pain accompany- with HZO may complain of prodromal ocular or periocular ing elevated IOP is characteristically described as frontal or pain or dysesthesia in the CN V-1 dermatome before erup- cranial pain ipsilateral to the affected eye and may be more tion of the classic vesicular rash. The presence of severe than the eye pain itself. A study of 11 people with nar- skin lesions near the tip of the nose (Hutchinson sign) is a row angle glaucoma found initial misdiagnosis of migraine strong predictor for ocular involvement (Figure).6 Treatment for an average of 2.7 years before proper diagnosis.8 Those includes oral antiviral therapy as well as eye drops. HZO can with elevated IOP have average age 54 at onset, much later cause severe sight-threatening inflammation of the eye, and than is typical of migraine, and none formally fulfilled the people with HZO must be urgently referred to an ophthal- International Classification of Headache Disorders criteria mologist. Unfortunately, even when treated appropriately, for migraine.9 Importantly, topiramate, a first-line agent for over a third of patients over age 60 with HZO can develop migraine preventive treatment, can worsen angle closure.7,10

Figure. Herpes zoster opthalmicus. Note classic grouped vesicular shingles rash in the left V-1 distribution including the forehead and eyelid (left) that 1 week later have blistered with involvement of the nose, which is a strong predictor for ocular involvement (right).

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Acute angle closure must be treated promptly by an ophthal- Treatment Trial reported eye pain.16 Eye pain or pain with mologist with pressure-lowering drops and medications as eye movements is more common when longer or intracana- well as procedures to alleviate anatomic angle closure.7 licular segments of the optic nerve are involved.16 Pain often improves with vision; high-dose steroids accelerates the Intraocular Inflammation rate of visual recovery but is not thought to improve visual outcome because most people begin having spontaneous Inflammation of the anterior chamber of the eye can cause recovery within a month of onset. eye pain and is termed anterior uveitis, iritis, or iridocyclitis. People with anterior uveitis will often complain of red eye, Ischemic blurry vision, , and moderate-to-severe pain con- Temporal arteritis or giant cell arteritis (GCA) can centrated within the eye with occasional radiation to the face. occasionally cause eye pain but is better known to cause Individuals with vitreous inflammation, termed vitritis, inter- new-onset headache related to ischemia from the inflam- mediate uveitis, or pars planitis, or chorioretinal inflammation, matory narrowing or occlusion of superficial extradural termed posterior uveitis, are more likely to complain of pain- blood vessels.17,18 GCA is the most common systemic vas- less vision loss or . The presence of abnormal culitis in adults over age 50 and can rapidly progress to cells and protein within the affected eye chamber is evident blindness, if not diagnosed and treated early, often from on slit lamp examination. Uveitis has a vast etiologic differ- arteritic ischemic optic neuropathy, and other complica- ential diagnosis including infectious and systemic immune- tions.14 Nonthrobbing headache anywhere over the head19 mediated diseases, many with neurologic manifestations (eg, or scalp tenderness when brushing or shampooing hair are [MS],11 , and Behcet disease). commonly described. On exam, patients may demonstrate Ocular B-cell lymphoma with or without central nervous sys- point tenderness, palpable cords, or absent pulses over the tem (CNS) involvement is an important mimic. temporal arteries and rarely, scalp or tongue ulcers.14 A care- ful history should be taken with attention to these signs and constitutional symptoms including fever, malaise, weight Scleritis or inflammation of the opaque fibrous white loss, proximal myalgias, and jaw claudication with chewing outer coat of the eye causes increasingly severe, boring eye or talking. Prompt initiation of high-dose steroids is critical pain, often with tenderness to palpation of the affected to prevent further irreversible vascular complications. eye.12,13 Scleritis can be anterior and visible by examina- tion or posterior with an externally “quiet,” white eye but notable inflammation on orbital ultrasound or CT/MRI CLINICALGEMS imaging. Pain caused by scleritis is often exacerbated by eye movement because the insert into Temporal headache is common in giant cell the . The sclera will be edematous with or without arteritis (GCA) which must be diagnosed and vessel dilation on slit lamp examination with abnormal dis- treated early with high-dose steroids to avoid coloration. Posterior scleritis can cause optic nerve edema vasculitic complications, including vision loss and vision loss because of the sclera’s fusion with the optic nerve sheath posteriorly. Less than half of cases have adja- cent anterior uveitis; scleritis is frequently idiopathic or Orbit associated with systemic rheumatologic disorder.12,13 Orbital disease is characterized by space-occupying hyper- trophy or mass lesion and is hallmarked by proptosis or Optic Nerve bulging of the eyes as result of forward displacement of the Optic . Thyroid-related (TED) is a frequent cause Demyelinating is the most common cause of of orbital dysfunction in adults with Graves thyroiditis and inflammatory optic neuropathy14 and is often the first mani- frequently presents with dry eye symptoms. Ocular or peri- festation of MS. Classic optic neuritis presents as acute vision ocular discomfort can also occur independently of dry eye loss—blurred or missing vision with dyschromatopsia— in TED and a pressure sensation or feeling of ocular fullness progressing over days to weeks and associated with orbital and strain may be described, especially if there is extraocular pain or pain on eye movement in women age 20 to 40. Eye muscle enlargement. A series of 120 people with TED noted pain can precede vision loss by several days and is thought that 30% had eye pain and 15.8% had photophobia.19 Severe to result from dural contact with an inflamed optic nerve, eye pain or pain on eye movements is uncommon in TED. which is often exacerbated by pulling eye movements.14,15 Idiopathic orbital inflammatory syndrome (IOIS), also Up to 92% of participants enrolled in the Optic Neuritis known as orbital myositis or orbital pseudotumor, repre-

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sents 0.5% of people with eye pain presenting to ophthal- mology clinics.1 IOIS involves noninfectious inflamma- tion and lymphocytic infiltration of the orbit, often with irregular thickening of the extraocular muscles. Symptoms include periorbital swelling, unilateral proptosis, double vision, and significant eye pain that worsens with move- ment in the direction of the inflamed muscle.20,21 MRI of the orbit, along with accompanying clinical picture, confirms the diagnosis, although other inflammatory and infiltrative disorders should be ruled out. Nonsteroidal anti-inflammatory drugs (NSAIDs) can be used to manage eye pain, but IOIS patients respond most briskly and effec- tively to oral steroids. n

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Neena R. Cherayil, MD Assistant Professor Division of Neuro-Ophthalmology Department of Neurology Northwestern University Feinberg School of Medicine Chicago, IL

Disclosures NRC reports no disclosures

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