Review Article
The Eye and Headache Deborah I. Friedman, MD, MPH, FAAN ABSTRACT Purpose of Review: This article highlights painful conditions involving the eyes that are encountered in practice, emphasizing those that do not have obvious findings on the neurologic examination. Recent Findings: Peripheral and central sensitization are associated with chronic neuropathic ocular pain, and hyperalgesia is associated with dry eyes. The aorta and its branches are involved in 25% of patients with giant cell arteritis. Summary: Eye pain is a common concern and one of the most difficult symptoms for the clinician to evaluate. Eye pain may be a manifestation of a primary headache disorder, as is common in migraine, the trigeminal autonomic cephalalgias, and primary stabbing headache. Secondary headache disorders, such as posterior communicating artery aneurysm, Tolosa-Hunt syndrome, and microvascular ocular motor neuropathies, frequently produce eye pain. Ophthalmic conditions producing eye pain include orbital masses, angle-closure glaucoma, intraocular inflammation, and ocular surface (corneal) disease. Of these, corneal problems are the most commonly encountered. Continuum (Minneap Minn) 2015;21(4):1109–1117.
CORNEAL NEUROPATHY AND DRY EYES The cornea receives the densest sensory innervation of the body, derived from small fiber nociceptive neurons (C and A& fibers). As most individuals have likely experienced, even a tiny foreign body contacting the cornea produces severe pain. Ocular surface disease may result from tear film deficiency or abnormality, corneal epithelial disease, contact lens use, adverse environmental conditions, or exposure to topical or systemic medications, or may be associated with rheumatologic disease. Local causes include a corneal foreign body, corneal abrasion, or infectious keratitis. Disorders associated with inadequate blinking, such as parkinsonian syndromes and thyroid eye disease, frequently produce ocular dryness. In addition to ocular pain, patients with dry eyes report ocular burning, a foreign body sensation (eg, gravel in the eyes), itching, redness, blurred vision, monocular diplopia or polyopia, Continuum (Minneap Minn) 2015;21(4):1109–1117
photosensitivity, visual distortion, or reflex tearing. The symptoms tend to be more pronounced with activities requiring visual concentration, such as reading, using the computer, watching television, and driving, as it is normal for the blink rate to decrease during these tasks. The diagnosis of dry eye is generally apparent by examining the eye using slitlamp bi-microscopy, observing the tear breakup time, and performing the Schirmer test to measure tear production. Recent research supports the role of peripheral and central sensitization in the development of chronic neuropathic ocular pain and hyperalgesia associated with dry eyes.1 In such cases, in vivo laserscanning confocal microscopy of the corneal nerve fibers reveals corneal nerve damage and aberrant regeneration.2 The initial treatment of dry eyes incorporates the frequent use of artificial tears during waking hours and an ophthalmic lubricating ointment at bedtime. Topical cyclosporine, punctal occlusion
Address correspondence to Dr Deborah I. Friedman, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, MC 9322, Dallas, TX 75390, deborah. [email protected]. Relationship Disclosure: Dr Friedman has served as a consultant and received personal compensation for the development of educational presentations from Avanir Pharmaceuticals, Inc. Dr Friedman serves on the board of directors of the American Headache Society, provides expert legal testimony regarding pseudotumor cerebri syndrome for several law firms, and receives personal compensation for speaking engagements from Allergan, Inc and Teva Pharmaceutical Industries Ltd. Dr Friedman receives research support from Autonomic Technologies, Inc; electroCore Medical, LLC; Eli Lilly and Company; and Merck & Co, Inc. Unlabeled Use of Products/Investigational Use Disclosure: Dr Friedman reports no disclosure. * 2015, American Academy of Neurology.
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The Eye and Headache KEY POINTS
h People with dry eyes may paradoxically report tearing, which is a reflex response to the dryness.
h Dry eyes are a common cause of eye pain, and the symptoms often worsen with activities requiring visual concentration.
h Uveitis usually produces eye pain, conjunctival injection, and photophobia. A slit-lamp examination and indirect ophthalmoscopy of the retina are required to make the diagnosis.
h Topiramate-induced angle-closure glaucoma is an idiosyncratic reaction that generally occurs within the first few weeks of treatment.
h The risk of precipitating angle closure from mydriatic eye drops is extremely small.
(inserting a small collagen or silicone plug into the opening of the nasolacrimal duct to prevent drainage of tears), and oral agents used to treat neuropathic pain are added in refractory cases. INTRAOCULAR INFLAMMATION Uveitis is inflammation of the uvea, which consists of the iris, choroid, and ciliary body. Inflammation of the iris, termed anterior uveitis or iritis, is the most common type of uveitis, but any layer of the uvea may be affected.3 The vitreous may also be inflamed with any type of uveitis. Typical symptoms include conjunctival injection, eye pain, tearing, photophobia, blurred or decreased vision, and floaters. Purulent material anterior to the iris (hypopyon) may be observable on routine inspection. The diagnosis is made with a slit-lamp examination and evaluation of the peripheral retina, revealing single or clumped inflammatory cells. Synechiae (adhesions) form when segments of the iris adhere to the cornea or the lens, which prevents the pupil from dilating normally and may lead to secondary glaucoma. Uveitis may be idiopathic or caused by trauma, infection, granulomatous disease (sarcoidosis), Beh0et syndrome, systemic lupus erythematosus and other immunologic disorders and spondyloarthropathies, Vogt-Koyanagi-Harada syndrome, antineutrophil cytoplasmic antibody (ANCA)Ypositive vasculitides, and multiple sclerosis. A strong association exists with the human leukocyte antigen B27 (HLA-B27). The presentation may be acute or chronic and uniocular or binocular. If visual symptoms are not prominent, the phenotype may resemble a dural arteriovenous shunt (Case 11-1). Treatment includes local or systemic immunosuppressive agents with mydriatics to prevent synechiae formation. ANGLE-CLOSURE GLAUCOMA While glaucoma is often mentioned in the differential diagnosis of eye pain or
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frontal headache, chronic open-angle glaucoma (the most common type of primary glaucoma) is not generally painful. However, angle-closure glaucoma is painful and occurs as a rare idiosyncratic reaction to medications, such as topiramate and acetazolamide, used in the treatment of headaches and other neurologic conditions.4 Topiramate-induced angleclosure glaucoma generally occurs within the first 2 weeks of treatment (ie, often at low doses) and resolves within 24 to 48 hours of discontinuation of the medication, although additional medical intervention may be needed to prevent permanent visual loss.5,6 Angle-closure glaucoma is often precipitated by pupillary dilation, which causes the iris to move anteriorly (eg, when emerging from a darkened movie theater or when experiencing pain or fright). Predisposing factors include advancing age, a strong family history of glaucoma, a history of ocular trauma, Asian ethnicity, hyperopia (farsightedness), and pseudoexfoliation.6 It may be uniocular or binocular. The dreaded fear of precipitating acute angle-closure glaucoma by using pupillarydilating drops during the patient examination is often invoked to justify not dilating the eyes, thus precluding an adequate view of the fundus. A study of nonselected white subjects over 55 years of age showed an incidence of acute open-angle glaucoma after diagnostic mydriasis of 0.03%.7 The risk increases with a shallow anterior chamber. Tropicamide appears to be the safest dilating agent in this regard. It is important to note that the attack does not occur until the drops are wearing off and the pupils are constricting, which may occur hours after the examination is complete. Prompt treatment prevents visual loss and subsequent attacks. Thus, it is safe to dilate the eyes to obtain important clinical information about the status of the optic nerve and retina. Give patients instructions to seek urgent attention if they develop eye
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Case 11-1 A 41-year-old woman followed for refractory new daily persistent headache developed new throbbing frontal pain involving her eyes. She said her eyes ‘‘always look a little bloodshot,’’ which was more noticeable when the pain was severe. There were no other autonomic symptoms. She described ‘‘foggy vision’’ in the right eye, as if a film were over it. She experienced left-sided pulsatile tinnitus, which caused anxiety. The best corrected visual acuity was 20/20 in both eyes with normal color vision, pupils, perimetry, extraocular movements, and fundi. There was mild right ptosis and temporal conjunctival injection in the right eye (Figure 11-1 and Figure 11-2). The intraocular pressures were 27 mm Hg in the right eye and 18 mm Hg in the left eye (normal is up to 20 mm Hg). Suspecting a dural arteriovenous fistula, a CT angiogram was requested and was normal. Subsequent ophthalmologic evaluation showed bilateral anterior uveitis. No etiology was found. Comment. Uveitis may simulate other secondary causes of headache. A careful slit-lamp examination is required for the diagnosis.
FIGURE 11-1
Mild right eyelid ptosis and conjunctival injection in the right eye (the pupils are pharmacologically dilated) of the patient in Case 11-1.
FIGURE 11-2
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Close-up view of the conjunctival injection in the right eye (the pupil is pharmacologically dilated) of the patient in Case 11-1.
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The Eye and Headache KEY POINTS
h Intermittent attacks of angle-closure glaucoma may be mistaken for migraine.
h Trochleitis causes ocular and orbital pain with pain on eye movement.
h Tenderness to palpation of the trochlea is a key feature of trochleitis and primary trochlear headache. The landmark is just inferior and posterior to the trochlear notch in the superomedial orbital rim.
pain, redness, nausea, or blurred vision after the drops wear off. The good news is that recent technologic advances in ophthalmoscopy and fundus photography may ultimately eliminate the need for pharmacologic mydriasis to examine the eyes outside of the ophthalmology practice setting. Aqueous humor is produced by the ciliary processes in the posterior chamber of the eye. It then flows through the pupil into the anterior chamber through the trabecular meshwork and Schlemm canal (the angle), where it is ultimately absorbed into the venous system. Acute angle-closure glaucoma occurs when intraocular pressure rapidly rises as a result of closure or blockage of the drainage angle of the eye by the iris. Patients generally experience ocular pain, headache, nausea, vomiting, and conjunctival injection. The attack is often accompanied by blurred vision, and patients often report seeing halos around lights. Therefore, these attacks may be mistaken for migraine.4 The ocular examination during an attack of acute angle-closure glaucoma reveals:
&
& &
&
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Elevated intraocular pressures (typically greater than 30 mm Hg). At the bedside, the affected eye may be palpated under closed lids using the thumb pad. A hard unyielding globe indicates an elevated intraocular pressure. Conjunctival injection. Shallow anterior chamber. The iris is bowed forward toward the posterior surface of the cornea, making the anterior chamber shallower. This is best seen with gonioscopy. Mid-dilated, fixed, sluggishly reactive, or irregular pupil. The combination of pain and dilated pupil of angle closure may be mistaken for a third cranial nerve palsy but no ptosis or ocular motor palsy is present.
&
Corneal edema. The cornea may appear edematous, ‘‘steamy,’’ or cloudy. The pain associated with angle-closure glaucoma may improve using analgesics and resolves when the intraocular pressure is controlled. Agents such as pilocarpine constrict the pupil and open the angle. Topical medications, such as betablockers and "2-adrenergic agonists, as well as IV mannitol and carbonic anhydrase inhibitors may be needed to treat markedly elevated intraocular pressures (greater than 45 mm Hg). Laser peripheral iridotomy is a definitive therapy in nearly all cases.4 TROCHLEAR HEADACHE AND TROCHLEITIS As many types of primary headaches are localized around the orbital area, trochlear pain may be underrecognized. The superior oblique tendon and its surrounding fibrovascular sheath pass through the trochlea, a ringlike cartilaginous structure that is innervated by the ophthalmic branch of the trigeminal nerve.8 Trochleitis, inflammation of the superior oblique tendon within the trochlea, produces ocular or periocular (often in the area of the medial canthus or below the medial brow) swelling and tenderness that worsen with upward gaze in adduction.4 Palpation of the superomedial angle of the orbit provokes exquisite tenderness (the ocular equivalent of the ‘‘chandelier sign’’ in pelvic inflammatory disease), and localized swelling may be felt. Trochleitis is most often primary, although it may occur in patients with rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, and other inflammatory disorders. It is akin to a tendonitis and has been called ‘‘tennis elbow of the eye.’’4 It is a cause of new daily persistent headache and may simulate hemicrania continua (Case 11-2). Primary trochlear headache is not inflammatory and is commonly associated with other headache disorders,
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KEY POINT
h Headache or neck pain
Case 11-2 A 68-year-old woman developed left eye pain and pressure 9 months prior to her initial visit. The eye pain was chronic and sometimes associated with ipsilateral headaches. She described pressurelike pain in the back of her eye and forehead with pain in the upper, lower, and inner aspects of the orbital rim. The pain worsened with side gaze and caused her to have difficulty concentrating. She had no trigeminal autonomic symptoms. Her headaches were always left-sided and present every morning. They were characterized as extreme pressure with photophobia, phonophobia, and occasional nausea and were similar to migraines she had experienced in the past. The headaches sometimes awakened her from sleep between 2:00 and 4:00 AM. She took one butalbital every morning for her headache and eye pain. MRI of the orbits was normal, as was the neurologic examination. She had tenderness over the left auriculotemporal nerve, left supraorbital nerve, and left trochlea. Her pain was eliminated in the office with a left trochlear block performed by a neuro-ophthalmologist. Hemicrania continua was considered, but she did not tolerate daily indomethacin. She continued to experience relief with intermittent trochlear and zygomaticotemporal blocks. Comment. Palpation of the trochlea is helpful in the evaluation of patients with headaches and may suggest trochleitis or trochlear headache, both of which are easily treatable.
particularly migraine. It affects women 90% of the time, producing pressurelike or dull pain in the trochlear and temporoparietal regions that worsens with supraduction of the affected eye. There may be nocturnal awakening, but autonomic features are absent.8 One series of 25 patients with trochlear headaches found a female preponderance (80%) with a median time from symptom onset to diagnosis of 6.7 months (range 2 weeks to 10 years).9 The site of pain was most focused at the medial eyebrow, orbit, or forehead, with radiation into the forehead, temple, orbit, or retro-orbital area. All patients had continuous pain that was achy, dull, pressurelike, and usually moderate to severe in intensity. Photophobia and pain with eye movement during reading were common associated symptoms. Standard migraine treatment was ineffective. The treatment of both trochleitis and trochlear headache is a single injection of corticosteroids (methylprednisolone, dexamethasone, or betamethasone) with or without lidocaine into the trochlear Continuum (Minneap Minn) 2015;21(4):1109–1117
with an ipsilateral Horner syndrome is a carotid dissection until proven otherwise.
area. Relief occurs rapidly, and the patient may be rendered pain free for months or years. The injection may also provide relief of associated migraine pain.10 CERVICAL ARTERIAL DISSECTION Headache or neck pain and an ipsilateral Horner syndrome is a carotid dissection until proven otherwise. Its symptoms may be mistaken for cluster headache at the initial presentation. Dissection of the internal carotid artery affects people of all ages and is a frequent cause of stroke in patients under 45 years of age. It is characterized by an ipsilateral frontotemporal headache that may be gradual or thunderclap in onset. There may be neck, jaw, or ear pain. Relatively minor trauma, such as hyperextension, rotation, or lateroversion of the neck; vomiting; yoga; running; and prolonged head tilt (such as when talking on the phone) have been implicated in precipitating dissection in predisposed individuals with connective tissue matrix abnormalities.11 Half of patients have orbital pain, and less than one-third have the classic triad www.ContinuumJournal.com
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The Eye and Headache KEY POINT
h Tolosa-Hunt syndrome is a diagnosis of exclusion and should not be made in a patient who is immunocompromised or has diabetes mellitus.
of headache, partial Horner syndrome (ptosis and miosis), and cerebral ischemia.12 Lower cranial nerves (XII) may be affected, and up to 25% of patients report pulsatile tinnitus. Ischemic stroke, often a delayed manifestation, results from thromboembolism or hemodynamic insufficiency. Retinal stroke may also occur. MRI reveals an intramural hematoma with an increase in the external diameter of the artery and may demonstrate an intimal flap (Figure 11-3A).11 Magnetic resonance angiography (MRA) and CT angiography are frequently employed, with CT angiography being preferred in traumatic cases to demonstrate the relationship of the dissection to bony structures (Figure 11-3B and C). No randomized trials exist to guide therapy, and treatment options include thrombolysis, antithrombotic therapy, antiplatelet therapy, endovascular therapy, and, less commonly, surgery. In the absence of dissection, other causes of headache and oculosympathetic paresis should be considered, including Raeder paratrigeminal neuralgia. TOLOSA-HUNT SYNDROME The syndrome of painful ophthalmoplegia, Tolosa-Hunt syndrome, was recently awarded the distinction of being a ‘‘big red flag’’ in neuro-ophthalmology.13
FIGURE 11-3
Tolosa-Hunt syndrome is an idiopathic granulomatous inflammatory condition affecting the cavernous sinus. Patients experience orbital and retro-orbital pain that is typically severe and associated with a cranial neuropathy affecting the oculomotor nerve, trochlear nerve, abducens nerve, and ophthalmic and maxillary divisions of the trigeminal nerves. MRI reveals focal enhancing masses expanding the ipsilateral cavernous sinus, sometimes extending beyond the cavernous sinus into the orbital apex.14 The treatment is corticosteroids, which produce a rapid improvement in the pain, with the ophthalmoparesis responding more slowly (weeks to months). Relapse may occur if the prednisone dose is tapered too rapidly. The diagnosis of Tolosa-Hunt syndrome is a diagnosis of exclusion and should be made with extreme caution in an immunocompromised individual, as fungal infections and malignancies (particularly lymphoma) are clinical mimics. Prednisone treatment in such cases could worsen the process in the case of fungal involvement or temporarily mask lymphoma (Case 11-3). GIANT CELL ARTERITIS Giant cell arteritis is a systemic disorder with wide variation in clinical manifestations. Patients with giant cell arteritis
Carotid dissection. Axial T2-weighted MRI shows narrowing of the left internal carotid artery surrounded by high signal intensity indicating dissection (A). CT angiography reveals tapering of the left carotid artery in the neck entering the skull base (B) compared to the normal diameter of the internal carotid artery on the right side (C). Courtesy of Nathan Troy Tagg, MD.
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Case 11-3 A 45-year-old woman with no prior history of headaches developed daily headaches that she treated with ibuprofen. The pain was global and aching ‘‘like a stress headache.’’ One week later, she noticed that her vision was ‘‘different,’’ and she was diagnosed with presbyopia. Examination by her primary care physician revealed problems in left gaze. Her headaches worsened and were associated with nausea. MRI, magnetic resonance angiography (MRA), and blood work were normal. The patient suddenly developed the inability to adduct the right eye, which appeared lower and exotropic in primary gaze. The headaches were localized to the right side of the head, radiating from the right eye to the back of her head. She could function by turning her head to the left and started using an eye patch to avoid diplopia. She had photophobia in her right eye. Three days prior to her evaluation in the office, her head pain was extreme, like a vise, and her right eye was abducted and elevated. There was pain with eye movement in the right eye. She went to the emergency department, had a normal CT scan, and was treated with antiemetics and pain medications and discharged home. On examination in the office, her best corrected visual acuity was 20/20 in both eyes, with normal color vision, pupils, visual fields, and fundi in both eyes. There was no ptosis or proptosis, but she experienced mild tenderness to pressure applied to the right globe. There was no intraocular inflammation. Ocular motility was normal in the left eye. She had a marked right exotropia and slight right hypertropia in primary gaze. There was full abduction, no adduction or infraduction, and 20% of normal supraduction of the right eye. Incyclotorsion (inward rotation of the eye) was present, and forced duction testing showed no restriction (Figure 11-4). MRI showed subtle enhancement of the right orbital apex. Prednisone 80 mg per day was prescribed; additional testing, including lumbar puncture with cytology and flow cytometry, antinuclear antibody (ANA), antiYdouble-stranded DNA, rheumatoid factor, antineutrophil cytoplasmic antibody (ANCA), rapid plasma reagin (RPR), and angiotensin-converting enzyme were normal or negative. Her pain resolved within days, and the prednisone was gradually decreased over months with continued improvement in her ocular motility. Comment. The Tolosa-Hunt syndrome of painful ophthalmoplegia is a diagnosis of exclusion. Resolution of symptoms with corticosteroid treatment may take months, and recurrence is possible.
FIGURE 11-4
Tolosa-Hunt syndrome affecting the right eye of the patient in Case 11-3. A, Upgaze; B, right gaze; C, primary gaze; D, left gaze; E, down gaze. Note marked exotropia in primary gaze with limited adduction, supraduction, and infraduction.
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The Eye and Headache KEY POINTS
h Failure to diagnose giant cell arteritis is the most common reason for a lawsuit in neuro-ophthalmology.
h In suspected giant cell arteritis, treat now and ask questions later. That is, do not delay treatment while waiting for the results of the laboratory tests or the temporal artery biopsy if the clinical suspicion for giant cell arteritis is high.
h The serologic markers may be normal in giant cell arteritis.
h Always obtain a temporal artery biopsy in a patient with suspected giant cell arteritis.
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may seek medical attention from an internist, family practitioner, rheumatologist, dermatologist, neurologist, dentist, ophthalmologist, or cardiologist or in the emergency department, depending on their symptoms. Age is the major risk factor for developing giant cell arteritis, as the prevalence rises from 20 in 100,000 in the sixth decade to 1110 in 100,000 in the ninth decade of life.15 The feared complication is blindness. Findings from a recent study suggest that the varicellazoster virus (VZV) may trigger the immunologic response that leads to giant cell arteritis, as the VZV antigen was found in 74% of temporal arteritis patients who tested positive for giant cell arteritis, compared to 8% of normal postmortem temporal arteries.16 Failure to diagnose and promptly treat giant cell arteritis is one of the most common reasons for a lawsuit in neuro-ophthalmology. The headache of giant cell arteritis is nonspecific, and the diagnosis should be suspected in anyone over 50 years of age who has developed new headaches or experienced a change in their previous headache pattern. Giant cell arteritis is in the differential diagnosis of new daily persistent headache in this age group. The headache may be unilateral (resembling hemicrania continua or migraine), bilateral, aching, or throbbing, and is often severe. Visual symptoms include amaurosis fugax, visual loss, diplopia, and eye pain. Blindness is usually caused by ischemic optic neuropathy, with both eyes affected simultaneously or in rapid succession. Other symptoms and signs include jaw claudication, which is highly specific for diagnosing giant cell arteritis, scalp necrosis, and scalp tenderness. Symptoms of polymyalgia rheumatica, such as fever, weight loss, myalgias, malaise, and depression may be present. Transient ischemic attack, stroke, and myocardial infarction are uncommon manifestations.
About one-third of patients have ‘‘occult’’ giant cell arteritis, experiencing visual loss without other systemic symptoms. The aorta and its major branches are involved in one-fourth of patients with giant cell arteritis.17 The author’s mantra for suspected giant cell arteritis is ‘‘treat now, ask questions later.’’ High-dose corticosteroid treatment (prednisone 80 mg to 100 mg daily or IV methylprednisolone) is initiated immediately, especially if the patient has had an episode of amaurosis fugax or visual loss. A dose of IV methylprednisolone (1 g) is recommended in the emergency department prior to discharging a patient on prednisone pending further evaluation. Elevated erythrocyte sedimentation rate, C-reactive protein, and fibrinogen levels are typically present. One large study showed that the erythrocyte sedimentation rate had a sensitivity of 84% and an elevated C-reactive protein had a sensitivity of 86% for diagnosing biopsy-confirmed giant cell arteritis, but the specificity of these two markers was only 30%.18Y20 A complete blood count with platelet count is recommended to evaluate for anemia and thrombocytosis. However, the only confirmatory laboratory test is a temporal artery biopsy, which is recommended in all suspected cases as the treatment carries significant potential morbidity in this vulnerable population (eg, osteoporosis, psychosis, fracture, diabetes mellitus, weight gain, ulcer, capillary fragility). The biopsy should be performed within 1 week of starting corticosteroids and is 95% sensitive. Treatment with prednisone is continued for at least 1 year, following the sedimentation rate and clinical symptoms. Other immunosuppressant agents are sometimes employed, but none have shown better effectiveness than prednisone alone. The headache and other systemic symptoms usually improve within days, although visual loss is generally irreversible.
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CONCLUSION Conditions causing eye pain without apparent ocular or neuro-ophthalmic signs may be challenging for nonophthalmologists to diagnose. Palpation of the trochlea is a simple and helpful addition to the examination of patients with headache and eye pain. Headaches developing in late life may indicate giant cell arteritis. Early treatment with corticosteroids may prevent blindness; the evaluation includes a temporal artery biopsy within 1 week of initiating treatment. The symptoms of dry eyes include pain, visual concerns, tearing, and conjunctival injection, which worsen with activities requiring visual concentration. When no signs are apparent to inspection, an ophthalmologic evaluation for signs of ocular surface disease, intraocular inflammation, narrow angles, and retinal abnormalities is invaluable. REFERENCES 1. Galor A, Levitt RC, Felix ER, et al. Neuropathic ocular pain: an important yet underevaluated feature of dry eye. Eye (Lond) 2015;29(3): 301Y312. doi:10.1038/eye.2014.263. 2. Rosenthal P, Borsook D. The corneal pain system. Part I: the missing piece of the dry eye puzzle. Ocul Surf 2012;10(1):2Y14. doi:10.1016/j.jtos.2012.01.002. 3. Selmi C. Diagnosis and classification of autoimmune uveitis. Autoimmun Rev 2014;13(4Y5):591Y594. doi:10.1016/ j.autrev.2014.01.006. 4. Friedman DI, Gordon LK, Quiros PA. Headache attributable to disorders of the eye. Curr Pain Headache Rep 2010;14(1): 62Y72. doi:10.1007/s11916-009-0088-8. 5. Rajjoub LZ, Chadha N, Belyea DA. Intermittent acute angle closure glaucoma and chronic angle closure following topiramate use with plateau iris configuration. Clin Ophthalmol 2014;8:1351Y1354. doi:10.2147/OPTH.S65748. 6. Fraunfelder FW, Fraunfelder FT, Keates EU. Topiramate-associated acute, bilateral secondary angle-closure glaucoma. Ophthalmology 2004;111(1):109Y111. doi:10.1016/j.ophtha.2003.04.004. 7. Lee DA, Higginbotham EJ. Glaucoma and its treatment: a review. Am J Health Syst Pharm 2005;62(7):691Y699.
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8. Friedman DI, Frishberg B. Neuro-ophthalmology and its contribution to headaches: a case-based approach. Expert Rev Neurother 2010;10(9):1467Y1478. doi:10.1586/ern.10.113. 9. Wolfs RC, Grobbee DE, Hofman A, de Jong PT. Risk of acute angle-closure glaucoma after diagnostic mydriasis in nonselected subjects: the Rotterdam Study. Invest Ophthalmol Vis Sci 1997;38(12):2683Y2687. 10. Pareja JA, Sa´nchez del R
The Eye and Headache Deborah I. Friedman, MD, MPH, FAAN ABSTRACT Purpose of Review: This article highlights painful conditions involving the eyes that are encountered in practice, emphasizing those that do not have obvious findings on the neurologic examination. Recent Findings: Peripheral and central sensitization are associated with chronic neuropathic ocular pain, and hyperalgesia is associated with dry eyes. The aorta and its branches are involved in 25% of patients with giant cell arteritis. Summary: Eye pain is a common concern and one of the most difficult symptoms for the clinician to evaluate. Eye pain may be a manifestation of a primary headache disorder, as is common in migraine, the trigeminal autonomic cephalalgias, and primary stabbing headache. Secondary headache disorders, such as posterior communicating artery aneurysm, Tolosa-Hunt syndrome, and microvascular ocular motor neuropathies, frequently produce eye pain. Ophthalmic conditions producing eye pain include orbital masses, angle-closure glaucoma, intraocular inflammation, and ocular surface (corneal) disease. Of these, corneal problems are the most commonly encountered. Continuum (Minneap Minn) 2015;21(4):1109–1117.
CORNEAL NEUROPATHY AND DRY EYES The cornea receives the densest sensory innervation of the body, derived from small fiber nociceptive neurons (C and A& fibers). As most individuals have likely experienced, even a tiny foreign body contacting the cornea produces severe pain. Ocular surface disease may result from tear film deficiency or abnormality, corneal epithelial disease, contact lens use, adverse environmental conditions, or exposure to topical or systemic medications, or may be associated with rheumatologic disease. Local causes include a corneal foreign body, corneal abrasion, or infectious keratitis. Disorders associated with inadequate blinking, such as parkinsonian syndromes and thyroid eye disease, frequently produce ocular dryness. In addition to ocular pain, patients with dry eyes report ocular burning, a foreign body sensation (eg, gravel in the eyes), itching, redness, blurred vision, monocular diplopia or polyopia, Continuum (Minneap Minn) 2015;21(4):1109–1117
photosensitivity, visual distortion, or reflex tearing. The symptoms tend to be more pronounced with activities requiring visual concentration, such as reading, using the computer, watching television, and driving, as it is normal for the blink rate to decrease during these tasks. The diagnosis of dry eye is generally apparent by examining the eye using slitlamp bi-microscopy, observing the tear breakup time, and performing the Schirmer test to measure tear production. Recent research supports the role of peripheral and central sensitization in the development of chronic neuropathic ocular pain and hyperalgesia associated with dry eyes.1 In such cases, in vivo laserscanning confocal microscopy of the corneal nerve fibers reveals corneal nerve damage and aberrant regeneration.2 The initial treatment of dry eyes incorporates the frequent use of artificial tears during waking hours and an ophthalmic lubricating ointment at bedtime. Topical cyclosporine, punctal occlusion
Address correspondence to Dr Deborah I. Friedman, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, MC 9322, Dallas, TX 75390, deborah. [email protected]. Relationship Disclosure: Dr Friedman has served as a consultant and received personal compensation for the development of educational presentations from Avanir Pharmaceuticals, Inc. Dr Friedman serves on the board of directors of the American Headache Society, provides expert legal testimony regarding pseudotumor cerebri syndrome for several law firms, and receives personal compensation for speaking engagements from Allergan, Inc and Teva Pharmaceutical Industries Ltd. Dr Friedman receives research support from Autonomic Technologies, Inc; electroCore Medical, LLC; Eli Lilly and Company; and Merck & Co, Inc. Unlabeled Use of Products/Investigational Use Disclosure: Dr Friedman reports no disclosure. * 2015, American Academy of Neurology.
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The Eye and Headache KEY POINTS
h People with dry eyes may paradoxically report tearing, which is a reflex response to the dryness.
h Dry eyes are a common cause of eye pain, and the symptoms often worsen with activities requiring visual concentration.
h Uveitis usually produces eye pain, conjunctival injection, and photophobia. A slit-lamp examination and indirect ophthalmoscopy of the retina are required to make the diagnosis.
h Topiramate-induced angle-closure glaucoma is an idiosyncratic reaction that generally occurs within the first few weeks of treatment.
h The risk of precipitating angle closure from mydriatic eye drops is extremely small.
(inserting a small collagen or silicone plug into the opening of the nasolacrimal duct to prevent drainage of tears), and oral agents used to treat neuropathic pain are added in refractory cases. INTRAOCULAR INFLAMMATION Uveitis is inflammation of the uvea, which consists of the iris, choroid, and ciliary body. Inflammation of the iris, termed anterior uveitis or iritis, is the most common type of uveitis, but any layer of the uvea may be affected.3 The vitreous may also be inflamed with any type of uveitis. Typical symptoms include conjunctival injection, eye pain, tearing, photophobia, blurred or decreased vision, and floaters. Purulent material anterior to the iris (hypopyon) may be observable on routine inspection. The diagnosis is made with a slit-lamp examination and evaluation of the peripheral retina, revealing single or clumped inflammatory cells. Synechiae (adhesions) form when segments of the iris adhere to the cornea or the lens, which prevents the pupil from dilating normally and may lead to secondary glaucoma. Uveitis may be idiopathic or caused by trauma, infection, granulomatous disease (sarcoidosis), Beh0et syndrome, systemic lupus erythematosus and other immunologic disorders and spondyloarthropathies, Vogt-Koyanagi-Harada syndrome, antineutrophil cytoplasmic antibody (ANCA)Ypositive vasculitides, and multiple sclerosis. A strong association exists with the human leukocyte antigen B27 (HLA-B27). The presentation may be acute or chronic and uniocular or binocular. If visual symptoms are not prominent, the phenotype may resemble a dural arteriovenous shunt (Case 11-1). Treatment includes local or systemic immunosuppressive agents with mydriatics to prevent synechiae formation. ANGLE-CLOSURE GLAUCOMA While glaucoma is often mentioned in the differential diagnosis of eye pain or
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frontal headache, chronic open-angle glaucoma (the most common type of primary glaucoma) is not generally painful. However, angle-closure glaucoma is painful and occurs as a rare idiosyncratic reaction to medications, such as topiramate and acetazolamide, used in the treatment of headaches and other neurologic conditions.4 Topiramate-induced angleclosure glaucoma generally occurs within the first 2 weeks of treatment (ie, often at low doses) and resolves within 24 to 48 hours of discontinuation of the medication, although additional medical intervention may be needed to prevent permanent visual loss.5,6 Angle-closure glaucoma is often precipitated by pupillary dilation, which causes the iris to move anteriorly (eg, when emerging from a darkened movie theater or when experiencing pain or fright). Predisposing factors include advancing age, a strong family history of glaucoma, a history of ocular trauma, Asian ethnicity, hyperopia (farsightedness), and pseudoexfoliation.6 It may be uniocular or binocular. The dreaded fear of precipitating acute angle-closure glaucoma by using pupillarydilating drops during the patient examination is often invoked to justify not dilating the eyes, thus precluding an adequate view of the fundus. A study of nonselected white subjects over 55 years of age showed an incidence of acute open-angle glaucoma after diagnostic mydriasis of 0.03%.7 The risk increases with a shallow anterior chamber. Tropicamide appears to be the safest dilating agent in this regard. It is important to note that the attack does not occur until the drops are wearing off and the pupils are constricting, which may occur hours after the examination is complete. Prompt treatment prevents visual loss and subsequent attacks. Thus, it is safe to dilate the eyes to obtain important clinical information about the status of the optic nerve and retina. Give patients instructions to seek urgent attention if they develop eye
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Case 11-1 A 41-year-old woman followed for refractory new daily persistent headache developed new throbbing frontal pain involving her eyes. She said her eyes ‘‘always look a little bloodshot,’’ which was more noticeable when the pain was severe. There were no other autonomic symptoms. She described ‘‘foggy vision’’ in the right eye, as if a film were over it. She experienced left-sided pulsatile tinnitus, which caused anxiety. The best corrected visual acuity was 20/20 in both eyes with normal color vision, pupils, perimetry, extraocular movements, and fundi. There was mild right ptosis and temporal conjunctival injection in the right eye (Figure 11-1 and Figure 11-2). The intraocular pressures were 27 mm Hg in the right eye and 18 mm Hg in the left eye (normal is up to 20 mm Hg). Suspecting a dural arteriovenous fistula, a CT angiogram was requested and was normal. Subsequent ophthalmologic evaluation showed bilateral anterior uveitis. No etiology was found. Comment. Uveitis may simulate other secondary causes of headache. A careful slit-lamp examination is required for the diagnosis.
FIGURE 11-1
Mild right eyelid ptosis and conjunctival injection in the right eye (the pupils are pharmacologically dilated) of the patient in Case 11-1.
FIGURE 11-2
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Close-up view of the conjunctival injection in the right eye (the pupil is pharmacologically dilated) of the patient in Case 11-1.
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The Eye and Headache KEY POINTS
h Intermittent attacks of angle-closure glaucoma may be mistaken for migraine.
h Trochleitis causes ocular and orbital pain with pain on eye movement.
h Tenderness to palpation of the trochlea is a key feature of trochleitis and primary trochlear headache. The landmark is just inferior and posterior to the trochlear notch in the superomedial orbital rim.
pain, redness, nausea, or blurred vision after the drops wear off. The good news is that recent technologic advances in ophthalmoscopy and fundus photography may ultimately eliminate the need for pharmacologic mydriasis to examine the eyes outside of the ophthalmology practice setting. Aqueous humor is produced by the ciliary processes in the posterior chamber of the eye. It then flows through the pupil into the anterior chamber through the trabecular meshwork and Schlemm canal (the angle), where it is ultimately absorbed into the venous system. Acute angle-closure glaucoma occurs when intraocular pressure rapidly rises as a result of closure or blockage of the drainage angle of the eye by the iris. Patients generally experience ocular pain, headache, nausea, vomiting, and conjunctival injection. The attack is often accompanied by blurred vision, and patients often report seeing halos around lights. Therefore, these attacks may be mistaken for migraine.4 The ocular examination during an attack of acute angle-closure glaucoma reveals:
&
& &
&
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Elevated intraocular pressures (typically greater than 30 mm Hg). At the bedside, the affected eye may be palpated under closed lids using the thumb pad. A hard unyielding globe indicates an elevated intraocular pressure. Conjunctival injection. Shallow anterior chamber. The iris is bowed forward toward the posterior surface of the cornea, making the anterior chamber shallower. This is best seen with gonioscopy. Mid-dilated, fixed, sluggishly reactive, or irregular pupil. The combination of pain and dilated pupil of angle closure may be mistaken for a third cranial nerve palsy but no ptosis or ocular motor palsy is present.
&
Corneal edema. The cornea may appear edematous, ‘‘steamy,’’ or cloudy. The pain associated with angle-closure glaucoma may improve using analgesics and resolves when the intraocular pressure is controlled. Agents such as pilocarpine constrict the pupil and open the angle. Topical medications, such as betablockers and "2-adrenergic agonists, as well as IV mannitol and carbonic anhydrase inhibitors may be needed to treat markedly elevated intraocular pressures (greater than 45 mm Hg). Laser peripheral iridotomy is a definitive therapy in nearly all cases.4 TROCHLEAR HEADACHE AND TROCHLEITIS As many types of primary headaches are localized around the orbital area, trochlear pain may be underrecognized. The superior oblique tendon and its surrounding fibrovascular sheath pass through the trochlea, a ringlike cartilaginous structure that is innervated by the ophthalmic branch of the trigeminal nerve.8 Trochleitis, inflammation of the superior oblique tendon within the trochlea, produces ocular or periocular (often in the area of the medial canthus or below the medial brow) swelling and tenderness that worsen with upward gaze in adduction.4 Palpation of the superomedial angle of the orbit provokes exquisite tenderness (the ocular equivalent of the ‘‘chandelier sign’’ in pelvic inflammatory disease), and localized swelling may be felt. Trochleitis is most often primary, although it may occur in patients with rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, and other inflammatory disorders. It is akin to a tendonitis and has been called ‘‘tennis elbow of the eye.’’4 It is a cause of new daily persistent headache and may simulate hemicrania continua (Case 11-2). Primary trochlear headache is not inflammatory and is commonly associated with other headache disorders,
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KEY POINT
h Headache or neck pain
Case 11-2 A 68-year-old woman developed left eye pain and pressure 9 months prior to her initial visit. The eye pain was chronic and sometimes associated with ipsilateral headaches. She described pressurelike pain in the back of her eye and forehead with pain in the upper, lower, and inner aspects of the orbital rim. The pain worsened with side gaze and caused her to have difficulty concentrating. She had no trigeminal autonomic symptoms. Her headaches were always left-sided and present every morning. They were characterized as extreme pressure with photophobia, phonophobia, and occasional nausea and were similar to migraines she had experienced in the past. The headaches sometimes awakened her from sleep between 2:00 and 4:00 AM. She took one butalbital every morning for her headache and eye pain. MRI of the orbits was normal, as was the neurologic examination. She had tenderness over the left auriculotemporal nerve, left supraorbital nerve, and left trochlea. Her pain was eliminated in the office with a left trochlear block performed by a neuro-ophthalmologist. Hemicrania continua was considered, but she did not tolerate daily indomethacin. She continued to experience relief with intermittent trochlear and zygomaticotemporal blocks. Comment. Palpation of the trochlea is helpful in the evaluation of patients with headaches and may suggest trochleitis or trochlear headache, both of which are easily treatable.
particularly migraine. It affects women 90% of the time, producing pressurelike or dull pain in the trochlear and temporoparietal regions that worsens with supraduction of the affected eye. There may be nocturnal awakening, but autonomic features are absent.8 One series of 25 patients with trochlear headaches found a female preponderance (80%) with a median time from symptom onset to diagnosis of 6.7 months (range 2 weeks to 10 years).9 The site of pain was most focused at the medial eyebrow, orbit, or forehead, with radiation into the forehead, temple, orbit, or retro-orbital area. All patients had continuous pain that was achy, dull, pressurelike, and usually moderate to severe in intensity. Photophobia and pain with eye movement during reading were common associated symptoms. Standard migraine treatment was ineffective. The treatment of both trochleitis and trochlear headache is a single injection of corticosteroids (methylprednisolone, dexamethasone, or betamethasone) with or without lidocaine into the trochlear Continuum (Minneap Minn) 2015;21(4):1109–1117
with an ipsilateral Horner syndrome is a carotid dissection until proven otherwise.
area. Relief occurs rapidly, and the patient may be rendered pain free for months or years. The injection may also provide relief of associated migraine pain.10 CERVICAL ARTERIAL DISSECTION Headache or neck pain and an ipsilateral Horner syndrome is a carotid dissection until proven otherwise. Its symptoms may be mistaken for cluster headache at the initial presentation. Dissection of the internal carotid artery affects people of all ages and is a frequent cause of stroke in patients under 45 years of age. It is characterized by an ipsilateral frontotemporal headache that may be gradual or thunderclap in onset. There may be neck, jaw, or ear pain. Relatively minor trauma, such as hyperextension, rotation, or lateroversion of the neck; vomiting; yoga; running; and prolonged head tilt (such as when talking on the phone) have been implicated in precipitating dissection in predisposed individuals with connective tissue matrix abnormalities.11 Half of patients have orbital pain, and less than one-third have the classic triad www.ContinuumJournal.com
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The Eye and Headache KEY POINT
h Tolosa-Hunt syndrome is a diagnosis of exclusion and should not be made in a patient who is immunocompromised or has diabetes mellitus.
of headache, partial Horner syndrome (ptosis and miosis), and cerebral ischemia.12 Lower cranial nerves (XII) may be affected, and up to 25% of patients report pulsatile tinnitus. Ischemic stroke, often a delayed manifestation, results from thromboembolism or hemodynamic insufficiency. Retinal stroke may also occur. MRI reveals an intramural hematoma with an increase in the external diameter of the artery and may demonstrate an intimal flap (Figure 11-3A).11 Magnetic resonance angiography (MRA) and CT angiography are frequently employed, with CT angiography being preferred in traumatic cases to demonstrate the relationship of the dissection to bony structures (Figure 11-3B and C). No randomized trials exist to guide therapy, and treatment options include thrombolysis, antithrombotic therapy, antiplatelet therapy, endovascular therapy, and, less commonly, surgery. In the absence of dissection, other causes of headache and oculosympathetic paresis should be considered, including Raeder paratrigeminal neuralgia. TOLOSA-HUNT SYNDROME The syndrome of painful ophthalmoplegia, Tolosa-Hunt syndrome, was recently awarded the distinction of being a ‘‘big red flag’’ in neuro-ophthalmology.13
FIGURE 11-3
Tolosa-Hunt syndrome is an idiopathic granulomatous inflammatory condition affecting the cavernous sinus. Patients experience orbital and retro-orbital pain that is typically severe and associated with a cranial neuropathy affecting the oculomotor nerve, trochlear nerve, abducens nerve, and ophthalmic and maxillary divisions of the trigeminal nerves. MRI reveals focal enhancing masses expanding the ipsilateral cavernous sinus, sometimes extending beyond the cavernous sinus into the orbital apex.14 The treatment is corticosteroids, which produce a rapid improvement in the pain, with the ophthalmoparesis responding more slowly (weeks to months). Relapse may occur if the prednisone dose is tapered too rapidly. The diagnosis of Tolosa-Hunt syndrome is a diagnosis of exclusion and should be made with extreme caution in an immunocompromised individual, as fungal infections and malignancies (particularly lymphoma) are clinical mimics. Prednisone treatment in such cases could worsen the process in the case of fungal involvement or temporarily mask lymphoma (Case 11-3). GIANT CELL ARTERITIS Giant cell arteritis is a systemic disorder with wide variation in clinical manifestations. Patients with giant cell arteritis
Carotid dissection. Axial T2-weighted MRI shows narrowing of the left internal carotid artery surrounded by high signal intensity indicating dissection (A). CT angiography reveals tapering of the left carotid artery in the neck entering the skull base (B) compared to the normal diameter of the internal carotid artery on the right side (C). Courtesy of Nathan Troy Tagg, MD.
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Case 11-3 A 45-year-old woman with no prior history of headaches developed daily headaches that she treated with ibuprofen. The pain was global and aching ‘‘like a stress headache.’’ One week later, she noticed that her vision was ‘‘different,’’ and she was diagnosed with presbyopia. Examination by her primary care physician revealed problems in left gaze. Her headaches worsened and were associated with nausea. MRI, magnetic resonance angiography (MRA), and blood work were normal. The patient suddenly developed the inability to adduct the right eye, which appeared lower and exotropic in primary gaze. The headaches were localized to the right side of the head, radiating from the right eye to the back of her head. She could function by turning her head to the left and started using an eye patch to avoid diplopia. She had photophobia in her right eye. Three days prior to her evaluation in the office, her head pain was extreme, like a vise, and her right eye was abducted and elevated. There was pain with eye movement in the right eye. She went to the emergency department, had a normal CT scan, and was treated with antiemetics and pain medications and discharged home. On examination in the office, her best corrected visual acuity was 20/20 in both eyes, with normal color vision, pupils, visual fields, and fundi in both eyes. There was no ptosis or proptosis, but she experienced mild tenderness to pressure applied to the right globe. There was no intraocular inflammation. Ocular motility was normal in the left eye. She had a marked right exotropia and slight right hypertropia in primary gaze. There was full abduction, no adduction or infraduction, and 20% of normal supraduction of the right eye. Incyclotorsion (inward rotation of the eye) was present, and forced duction testing showed no restriction (Figure 11-4). MRI showed subtle enhancement of the right orbital apex. Prednisone 80 mg per day was prescribed; additional testing, including lumbar puncture with cytology and flow cytometry, antinuclear antibody (ANA), antiYdouble-stranded DNA, rheumatoid factor, antineutrophil cytoplasmic antibody (ANCA), rapid plasma reagin (RPR), and angiotensin-converting enzyme were normal or negative. Her pain resolved within days, and the prednisone was gradually decreased over months with continued improvement in her ocular motility. Comment. The Tolosa-Hunt syndrome of painful ophthalmoplegia is a diagnosis of exclusion. Resolution of symptoms with corticosteroid treatment may take months, and recurrence is possible.
FIGURE 11-4
Tolosa-Hunt syndrome affecting the right eye of the patient in Case 11-3. A, Upgaze; B, right gaze; C, primary gaze; D, left gaze; E, down gaze. Note marked exotropia in primary gaze with limited adduction, supraduction, and infraduction.
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The Eye and Headache KEY POINTS
h Failure to diagnose giant cell arteritis is the most common reason for a lawsuit in neuro-ophthalmology.
h In suspected giant cell arteritis, treat now and ask questions later. That is, do not delay treatment while waiting for the results of the laboratory tests or the temporal artery biopsy if the clinical suspicion for giant cell arteritis is high.
h The serologic markers may be normal in giant cell arteritis.
h Always obtain a temporal artery biopsy in a patient with suspected giant cell arteritis.
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may seek medical attention from an internist, family practitioner, rheumatologist, dermatologist, neurologist, dentist, ophthalmologist, or cardiologist or in the emergency department, depending on their symptoms. Age is the major risk factor for developing giant cell arteritis, as the prevalence rises from 20 in 100,000 in the sixth decade to 1110 in 100,000 in the ninth decade of life.15 The feared complication is blindness. Findings from a recent study suggest that the varicellazoster virus (VZV) may trigger the immunologic response that leads to giant cell arteritis, as the VZV antigen was found in 74% of temporal arteritis patients who tested positive for giant cell arteritis, compared to 8% of normal postmortem temporal arteries.16 Failure to diagnose and promptly treat giant cell arteritis is one of the most common reasons for a lawsuit in neuro-ophthalmology. The headache of giant cell arteritis is nonspecific, and the diagnosis should be suspected in anyone over 50 years of age who has developed new headaches or experienced a change in their previous headache pattern. Giant cell arteritis is in the differential diagnosis of new daily persistent headache in this age group. The headache may be unilateral (resembling hemicrania continua or migraine), bilateral, aching, or throbbing, and is often severe. Visual symptoms include amaurosis fugax, visual loss, diplopia, and eye pain. Blindness is usually caused by ischemic optic neuropathy, with both eyes affected simultaneously or in rapid succession. Other symptoms and signs include jaw claudication, which is highly specific for diagnosing giant cell arteritis, scalp necrosis, and scalp tenderness. Symptoms of polymyalgia rheumatica, such as fever, weight loss, myalgias, malaise, and depression may be present. Transient ischemic attack, stroke, and myocardial infarction are uncommon manifestations.
About one-third of patients have ‘‘occult’’ giant cell arteritis, experiencing visual loss without other systemic symptoms. The aorta and its major branches are involved in one-fourth of patients with giant cell arteritis.17 The author’s mantra for suspected giant cell arteritis is ‘‘treat now, ask questions later.’’ High-dose corticosteroid treatment (prednisone 80 mg to 100 mg daily or IV methylprednisolone) is initiated immediately, especially if the patient has had an episode of amaurosis fugax or visual loss. A dose of IV methylprednisolone (1 g) is recommended in the emergency department prior to discharging a patient on prednisone pending further evaluation. Elevated erythrocyte sedimentation rate, C-reactive protein, and fibrinogen levels are typically present. One large study showed that the erythrocyte sedimentation rate had a sensitivity of 84% and an elevated C-reactive protein had a sensitivity of 86% for diagnosing biopsy-confirmed giant cell arteritis, but the specificity of these two markers was only 30%.18Y20 A complete blood count with platelet count is recommended to evaluate for anemia and thrombocytosis. However, the only confirmatory laboratory test is a temporal artery biopsy, which is recommended in all suspected cases as the treatment carries significant potential morbidity in this vulnerable population (eg, osteoporosis, psychosis, fracture, diabetes mellitus, weight gain, ulcer, capillary fragility). The biopsy should be performed within 1 week of starting corticosteroids and is 95% sensitive. Treatment with prednisone is continued for at least 1 year, following the sedimentation rate and clinical symptoms. Other immunosuppressant agents are sometimes employed, but none have shown better effectiveness than prednisone alone. The headache and other systemic symptoms usually improve within days, although visual loss is generally irreversible.
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CONCLUSION Conditions causing eye pain without apparent ocular or neuro-ophthalmic signs may be challenging for nonophthalmologists to diagnose. Palpation of the trochlea is a simple and helpful addition to the examination of patients with headache and eye pain. Headaches developing in late life may indicate giant cell arteritis. Early treatment with corticosteroids may prevent blindness; the evaluation includes a temporal artery biopsy within 1 week of initiating treatment. The symptoms of dry eyes include pain, visual concerns, tearing, and conjunctival injection, which worsen with activities requiring visual concentration. When no signs are apparent to inspection, an ophthalmologic evaluation for signs of ocular surface disease, intraocular inflammation, narrow angles, and retinal abnormalities is invaluable. REFERENCES 1. Galor A, Levitt RC, Felix ER, et al. Neuropathic ocular pain: an important yet underevaluated feature of dry eye. Eye (Lond) 2015;29(3): 301Y312. doi:10.1038/eye.2014.263. 2. Rosenthal P, Borsook D. The corneal pain system. Part I: the missing piece of the dry eye puzzle. Ocul Surf 2012;10(1):2Y14. doi:10.1016/j.jtos.2012.01.002. 3. Selmi C. Diagnosis and classification of autoimmune uveitis. Autoimmun Rev 2014;13(4Y5):591Y594. doi:10.1016/ j.autrev.2014.01.006. 4. Friedman DI, Gordon LK, Quiros PA. Headache attributable to disorders of the eye. Curr Pain Headache Rep 2010;14(1): 62Y72. doi:10.1007/s11916-009-0088-8. 5. Rajjoub LZ, Chadha N, Belyea DA. Intermittent acute angle closure glaucoma and chronic angle closure following topiramate use with plateau iris configuration. Clin Ophthalmol 2014;8:1351Y1354. doi:10.2147/OPTH.S65748. 6. Fraunfelder FW, Fraunfelder FT, Keates EU. Topiramate-associated acute, bilateral secondary angle-closure glaucoma. Ophthalmology 2004;111(1):109Y111. doi:10.1016/j.ophtha.2003.04.004. 7. Lee DA, Higginbotham EJ. Glaucoma and its treatment: a review. Am J Health Syst Pharm 2005;62(7):691Y699.
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8. Friedman DI, Frishberg B. Neuro-ophthalmology and its contribution to headaches: a case-based approach. Expert Rev Neurother 2010;10(9):1467Y1478. doi:10.1586/ern.10.113. 9. Wolfs RC, Grobbee DE, Hofman A, de Jong PT. Risk of acute angle-closure glaucoma after diagnostic mydriasis in nonselected subjects: the Rotterdam Study. Invest Ophthalmol Vis Sci 1997;38(12):2683Y2687. 10. Pareja JA, Sa´nchez del R
