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Home , Anisocoria, Chemosis, Ocular ischemic syndrome, Oculomotor nerve palsy

11/26/17

NEURO- OPHTHALMOLOGICAL EMERGENCIES PRESENTING Disclosure Statement: IN OPTOMETRY C. Light Technologies – Clinical Research Consultant

Jacqueline Theis, OD, FAAO OptoWest

Goals/General Outline “Neuro-ophthalmological emergencies • Outline the signs, symptoms, and optometric management of constitute vision or life-threatening neuro-ophthalmological emergencies conditions if diagnosis and treatment are • Identify questions providers should add to their patient history not promptly undertaken. • Describe the epidemiology, ocular and systemic manifestations, diagnosis and optometric management of: Even with immediate therapy, these • • Horner’s Syndrome clinical entities carry a high rate of • Intracranial (Posterior-communicating artery) morbidity.” • • Intracranial Space Occupying Lesions -Lemos J, Eggenberger E. Neuro-ophthalmological emergencies. • Cavernous Sinus Lesions Neurohospitalist. 2015. 5(4): 223-233. • Pituitary Apoplexy

Symptoms of Neuro-Ophthalmological Signs of Neuro-Ophthalmological Emergencies Emergencies

• or pallor • Vision Loss • Extraocular/intraocular abnormality • • Multiple cranial nerve palsies • Eye Pain • -involving CN III Palsy • • Headache •

• PEARL for Concern: If you have more than one of the following • Pupil abnormality • abnormality • EOM abnormality

Karmel M, Eggenberger E. Deciphering Diplopia. Eye Net. Nov/Dec 2009. PP31-34

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Patient History in a Neuro-Ophthalmological Emergency Patient History in a Neuro-Ophthalmological Emergency HPI CC: Diplopia CC: Vision Loss Location Monocular or Binocular? • Pain • Vision Changes (CNII) Extent Gaze dependent? Central or peripheral visual field? • Headaches -Left vs. Right, Up vs. Down, Left vs. right visual field? • Tingling – limbs, fingers, toes Distance vs. Near Quadrant/location? • Numbness/weakness – facial (CNV/VII), extremities Onset When did it start? • Nausea/vomiting Sudden or gradual? • Imbalance/vertigo What were you doing? • Frequency Is it getting better, worse or staying the same since it started? • Hearing loss, tinnitus • Jaw claudication, neck stiffness, temporal artery pain Duration How long does it last? (seconds, minutes, hours or days) • Difficulties swallowing/breathing Intermittent or constant • Recent Weight Loss/Gain Timing Is it worse at the beginning or end of the day? • Recent Fever • Hx of (Head) Trauma What makes it Covering an eye? Blinking? • Hx of systemic disease àVasculopathy (HTN, DM, HyperChol), Cancer, better? MS, thyroid, etc • MEDICATIONS (including topical, OTC, and discontinued) Has it happened History of childhood before? , previous eye • Recent Travel? surgery? • Trouble finding your words or speaking?

Examination Monocular vs. Binocular Diplopia • Distance Visual Acuity • Pinhole Acuity • Color Vision 1) Do you see double with both eyes open? • Ishihara, AOHRR, Red Cap No Yes • • Size in light/dark • Reaction to light/dark 2) Cover the right eye, do you still see double? Yes Monocular • Near response • RAPD? No Yes • Visual Fields • Confrontation 3) Cover the left eye, do you still see double? • Amsler • Automated No • (MRD1/MRD2) • Optic Nerve Evaluation Binocular • Fundus Evaluation • Cranial Nerve Evaluation

Acute Vision Loss

Refraction/SLE 1) Does visual acuity YES • Uncorrected improve with a pinhole? • / • Vitreous abnormality Giant Cell Arteritis NO YES Dilated Fundus Exam/OCT 2) Pupils – Presence of RAPD? • Pre-optic chiasm NO

3) Visual Field Defect? Unilateral Altitudinal defect Dilated Fundus Exam/OCT • AION

Bilateral Peripheral Dilated Fundus Exam/OCT Constriction, • Enlarged blind spot MRI/MRV, Lumbar puncture

Bitemporal Homonymous quad/ Central Dilated Fundus Exam/OCT Defect hemianopia • MRI Brain/orbits + contrast

Dilated Fundus Exam/OCT Dilated Fundus Exam/OCT • pallor • Normal • Chiasm lesion – pituitary MRI Brain contrast Graves JS, Galetta SL. Acute Visual adenoma Loss and Other Neuro-Ophthalmologic MRI Brain contrast Emergencies: Management. Neurol Clin 30 (2012): 75-99

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Epidemiology Pathogenesis GCA AAION • • • Most common systemic vasculitis • Annual incidence of AAION • Infectious? immune affecting adults >50yo from GCA is 1.3 per 100,000 in trigger in a genetically • Rare in people <50yo patients >50yo predisposed subject • Average age of onset is 74-76yo • Vision loss from AAION and • T-cell mediated CRAO from GCA is severe granulomatous • For each decade after 50, of incidence increases from • 73% present with VA worse medium- and large- • 2.0 (50-60yo) than 20/200 vessels • 11.8 (61-70yo) • 15% of eyes have an • Aorta • 31.3 (71-80yo) per 100,000 persons/ improvement, likely from • External carotid year eccentric fixation artery • Women affected 2-3x more than men • Posterior ciliary • More common in whites, Nordic/ artery à AAION Northern European ancestry, and • Temporal arteries Chen JJ, Leavitt JA, Fang C, Crowson CS, Matteson EL, other northern latitudes Warrington KJ. Evaluating the incidence of arteritic ischemic optic neuropathy and other causes of vision loss from giant Ciccia F, Rizzo A, Ferrante A, Guggino G, Croci S, Cavazza A, Salvarani C, Triolo Hoffman GS. Giant Cell Arteritis. Ann Intern Med. cell arteritis. 2016: 123:1999-2003 G. New Insights into the pathogenesis of giant cell arteritis. 2016;165(9):ITC65-80 reviews. 2017 May. Epub ahead of print. Accessed May 21, 2017.

Pathogenesis Why is it an emergency?

Persistent vessel wall inflammationà vascular • Blindness • The sooner GCA is diagnosed and damage à stenosis, • Vision loss ~10% of patients treated, the lower the incidence of visual loss occlusions, and aneurysms • • However, patients presenting • Aortic or dissection with poor vision have little chance of recovery despite immediate steroid treatment • The main goal of treatment is to Ciccia F, Rizzo A, Ferrante A, Guggino G, Croci S, Cavazza A, Salvarani C, Triolo G. prevent vision loss in the fellow eye New Insights into the pathogenesis of giant cell arteritis. Autoimmunity reviews. 2017 • Usually occurs within days in May. Epub ahead of print. Accessed May 21, 2017. 50% of cases of untreated GCA

Image from: Weyand CM, Goronzy JJ. Arterial wall in giant cell Chen JJ, Leavitt JA, Fang C, Crowson CS, Matteson EL, arteritis. Arthr & Rheum. Warrington KJ. Evaluating the incidence of arteritic ischemic 1999;42(5):844-853 Hayreh SS, Podhajsky PA, Zimmerman B. Ocular manifestations optic neuropathy and other causes of vision loss from giant of giant cell arteritis. Am J Ophthalmol. 1998;125(4):509-20 cell arteritis. Ophthalmology 2016: 123:1999-2003

Ocular Manifestations Systemic Manifestations Symptoms Signs Symptoms Signs

• AAION (6.9%) – 1.3 per • Jaw Claudication (48%) • Temporal artery tortuosity, • Sudden visual loss 100,000 populuation • Neck pain (17%) prominence, and/or • Most frequent symptom ~50% of • (+) RAPD tenderness cases • Headache (57%) • Pallid ON edema • Transient visual loss ~30% • Scalp tenderness (20%) • (+/-) retinal cotton wool spots • Often followed by permanent • Accounts for 85% of cases of • Weight loss (40%) visual loss permanent vision loss • Anorexia (31%) • Diplopia ~6% • CRAO (1.6%) • Myalgias (28%) • Eye pain ~8% • CilioRAO (0.4%) • Malaise (37%) • Posterior ION 20% of cases with permanent vision • loss from GCA may present without systemic symptoms of GCA Chen JJ, Leavitt JA, Fang C, Crowson CS, Matteson EL, Chen JJ, Leavitt JA, Fang C, Crowson CS, Matteson EL, Warrington KJ. Evaluating the incidence of arteritic ischemic Warrington KJ. Evaluating the incidence of arteritic ischemic Hayreh SS, Podhajsky PA, Zimmerman B. Ocular manifestations optic neuropathy and other causes of vision loss from giant Hayreh SS, Podhajsky PA, Zimmerman B. Occult giant cell optic neuropathy and other causes of vision loss from giant cell of giant cell arteritis. Am J Ophthalmol. 1998;125(4):509-20 cell arteritis. Ophthalmology 2016: 123:1999-2003 arteritis: ocular manifestations. Am J Ophthalmol. 1998:125L4): arteritis. Ophthalmology 2016: 123:1999-2003 521-526.

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Diagnosis Differential Diagnosis • Serological Studies Temporal Artery Biopsy • Elevated ESR (85.7% sensitivity) Gold Standard BUT only 49-85% of patients with • Normal in 9.2-14.3% GCA have a (+) TAB • Common or headache • Elevated C-Reactive Protein (97.5% May need sequential if high clinical • sensitivity) suspicion of large vessels • Normal in 1.7% • NA-AION • ESR/CRP can also be elevated in and cancer • Takayasu arteritis • Abnormal CBC w/ differential (sensitivity <60%) • Other forms of vasculitis • Thrombocytosis • Polymyalgia rheumatica • Normocytic anemia • 30-50% of patients with GCA also have PMR • Leukocytosis • PMR is 2-3x more common than GCA Differentiate AAION from NAION Choroidal hypoperfusion Delayed choroidal filling

Lemos J, Eggenberger E. Neuro-Ophthalmological emergencies. Neurohospitalist. 2015;5(4):223-233. Information and image from: Hoffman GS. Giant Cell Arteritis. Ann Intern Med. 2016;165(9):ITC65-80 Hoffman GS. Giant Cell Arteritis. Ann Intern Med. 2016;165(9):ITC65-80

Treatment • Only 4% of patients Future will improve visual • Glucocorticoids are very effective at high doses • Steroids – IMMEDIATELY once AAION loss with steroids is suspected • Relapses occur in up to 50% of patients when doses are tapered • Are not ideal for chronic management • Oral (60mg po) vs. IV ASAP • 4% of patients lose • Oral taper over months to year vision within the first 5 • Adjunct immunosuppressants • Low dose Aspirin? days, even on steroid • Methotrexate treatment • Reduce risk of relapses • To reduce risk of ischemic events if • Positive effects may take >6 months to emerge no contraindications • Anti-TNFα (Infliximab, Adalimumab, Etanercept) • Consult PCP/internist Hayreh SS, Biousse V. Treatment of in giant cell arteritis: should we prescribe high-dose • No additional benefit above prednisone monoterhapy • Monitor for steroid-related intravenous steroids or just oral steroids? J • Increased risk of infection Neuroophthalmol. 2012;32(3):278-287. complications – , • Anti-IL-6 (Tocilizumab) Hayreh SS, Zimmerman B. Visual deterioration in giant , osteoporosis, infection, cell arteritis patients while on high doses of • May provide additional benefit to prednisone by inducing and maintaining remission for up etc. corticosteroid therapy. Ophthalmology. 2003;110(6): to 52 weeks. Quick onset 1204-1215 • Smoking cessation • Other targeted anti-inflammatory therapies Hayreh SS, Zimmerman B, Kardon RH. Visual • Follow up – 2-4weeks improvement with corticosteroid therapy in giant cell • Abatacept – reduced risk of relapse arteritis. Report of a large study and review of • Ustekinumab – glucocorticoid-sparing response literature. Acta Ophthalmol Scand. 2002;80(4):355-67 • Rituximab Jivraj I, Tamhankar M. The treatment of giant cell Roberts J, Clifford A. Update on the management of giant cell arteritis. Ther Adv Chronic Disease. 2017. 8(4-5):69-79 arteritis. Curr Treat Options Neurol. 2017;19(2):1-18. Jivraj I, Tamhankar M. The treatment of giant cell arteritis. Curr Treat Options Neurol. 2017;19(2):1-18.

Horner’s Syndrome Pupil Pathway Review: Sympathetic • Efferent (3 neuron chain) 1. Hypothalamusàciliospinal center of Bulge at C8-T2 (spinal cord) 2. Through sympathetic chain (adjacent lung apex)à superior cervical ganglion (located at level of carotid bifurcation) 3. Postganglionic neuron travels with the internal carotid artery until cavernous sinus, then follows CN6àCNV1à long ciliary nervesà dilator à

Abnormal: Pupil is larger in the Dark Miotic pupil is abnormal Image from: Reede DL, Garcon E, Smoker WRK, Kardon R. Horner’s syndrome: clinical and radiographic evaluation. Neuroimaging Clin N Am. 2008;18:369-385

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Pharmacologic : Prostaglandins, opioids, • CAD: Intimal wall disruption à clonidine, organo-phosphate intrusion of blood à intramural insecticides Pathophysiology hematoma

Image from: Gross JR, McClelland CM, Lee MS. An approach to Image from: Caplan LR. Dissections of brain-supplying Gross JR, McClelland CM, Lee MS. An approach to anisocoria. Curr Opin Ophthalmol. 2016;27:486-492 anisocoria. Curr Opin Ophthalmol. 2016;27:486-492 arteries. Nature Clin Pract Neurol. 2008:4(1):34-42

Ocular Manifestations of Horner’s Syndrome Epidemiology of Carotid Artery Dissection in Carotid Artery Dissection

Epidemiology Etiology • Painful third-order Horner Syndrome ~60% • Ptosis ~1-2mm • Incidence of 2.6-5 per • Traumatic • “Inverse ptosis” – when lower 100,000 population • Spontaneous lid is slightly elevated th • Miosis (anisocoria of 1-1.5mm) • Peak incidence – 5 • Underlying vasculopathy • Dilation Lag decade • Fibromuscular dysplasia • WITHOUT facial anhydrosis or • Mild male predominance • Connective tissue disorder partial • • Marfans Less common ocular signs of CAD • Responsible for 25% of • Transient monocular vision loss • Ehler’s Danlos in young adults • NAION (<45yo) • PION • CRAO • Ocular ischemic syndrome • Ocular motor nerve palsies Robertson JJ, Koyfman A. Cervical artery dissections: a Image from: Walton KA, Buono LM. Horner syndrome. Curr review. J Emerg Med 2016;52(5):508-518 Opin Ophthalmol. 2003;14:357-363

Systemic Manifestations Diagnosis Horner’s Syndrome Carotid Artery Dissection • Ipsilateral headache ~70% Pharmacologic diagnosis/localization • Ipsilateral neck pain (10-30%) • 10% • (+) = Failure of pupillary dilation after • Ipsilateral ear pain (10-30%) one hour (ie anisocoria >1mm remains) • 1% • Less common • (+) = mydriasis of affected pupil >1mm • MRI/MRA 30-45 minutes after drop instillation • Lower cranial nerves affected • 85% sensitivity • Hydroxyamphetamine • Pulsatile tinnitus • 95% specificity for dissection • Localizes between central (1st)/ • Vertigo preganglionic (2nd) and postganglionic • CTA of head/neck or carotid doppler (3rd) order lesion ultrasound • Dysgeusia (foul taste in the mouth) • If mydriasisà 1st/2nd order • CT of chest • Diseases that affect the brainstem, spinal cord, chest or • (-) mydriasis (ie anisocoria>1mm remains)à 3rd order • CBC with differential neck can present with purely ocular symptoms • Caveats • Ophthalmologic signs/symptoms can proceed ocular or cerebral • Cant perform cocaine and hydroxyamphetamine test on the same Walton KA, Buono LM. Horner syndrome. Curr Opin Ophthalmol. infarction in 33% of patients 6-14 days day (within 24-48 hours) 2003;14:357-363 Silbert PL, Mokri B, Schievink WI. Headache and neck pain in spontaneous internal carotid and vertebral artery dissections. . 1995;45(8):1517-1522 • Hydroxyamphetamine test may yield a Levy C, Laissy JP, Raveau V, et al. Carotid and vertebral artery Lemos J, Eggenberger E. Neuro-Ophthalmological Emergencies. Neurohospitalist. 2015. 5(4):223-233 false-negative, and is not commercially dissections: three-dimensional time-of-flight MR angiography and Biousse V, Touboul PJ, D’Anglejan-Chatillon J, Levy C, Schaison M, Bousser M.Ophthalmologic Manifestations of Internal Carotid available MR imaging versus conventional angiography. Radiology. Artery Dissection. Amer J Oph. 1998:9394(98):565-577 1994;190(1):97-103.

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Epidemiology Intracranial Aneurysms • 9-36% of CNIII palsies are caused by an intracranial aneurysm • Posterior communicating artery (PCA) aneurysms present with a CNIII palsy 30-60% of the time • 40% of aneurysms are located at the level of the PCA, ophthalmic

artery, and cavernous Image From: Park HK, Rha HK, Lee KJ, Chough CK, Joo W. Microsurgical anatomy sinus of the . Clin Anat. 2017;30(1):21-31.

Lemos J, Eggenberger E. Neuro-Ophthalmological Emergencies. Neurohospitalist. 2015. 5(4):223-233

Ocular Manifestations Risk factors for Aneurysmal Rupture • Pain • Increasing age (peak 6th decade) • Mid-dilated pupil • Female gender • Smoking • Poor or absent light reaction • Hypertension • Complete or partial external CNIII palsy • Heavy alcohol consumption • (+) Family history of intracranial aneurysm or subarachnoid hemorrhage • Aneurysm size>10mm • Genetic disorders– polycystic kidney disease • Aneurysm location • PCA and basilar tip have higher rupture risk at 5 years

Etminan N, Rinkel GJ. Unruptured intracranial aneurysms: development, rupture, and prevention. Nat Rev Neurol. 2016;12(12): 699-713, Image From: Ahmad K, Wright M, Lueck CJ. Ptosis. Practical Neurology. 2011;11:332-340

Lemos J, Eggenberger E. Neuro-Ophthalmological Emergencies. Neurohospitalist. 2015. 5(4):223-233

Rule of the Pupil Topographical localization of CNIII Palsy • Brainstem • Complete CN III • Hemiparesis • Pupil-sparingà likely • Hemisensory loss ischemic • Other cranial neuropathies • Pupil-involvingà likely Parasympathetic Pupil Fibers Aneurysm • Subarachnoid space compressive • Meningeal signs • Incomplete CN III CN3 • Stiff neck Internal vasculature • Severe headache • Pupil-sparing à??? • Other cranial neuropathies • 14% will have aneurysm, just • Cavernous sinus present to office in an early phase before the pupillary fibers are • CN – 4, 5, or 6 involvement involved • Horner syndrome • Pupil-Involvingà compressive • • Proptosis Compressive lesions: • Chemosis • Most common – aneurysm • Optic neuropathy • Less common – tumor, trauma, congenital, uncal herniation, cavernous sinus mass, pituitary apoplexy, orbital disease, varicella zoster virus, Lee AG, Hayman LA, Brazis PW. The evaluation of isolated third nerve palsy revisited. An update on the evolving role of magnetic , leukemia resonance, computed tomography, and catheter angiography. Surv Ophthalmol. 2002;47(2):137-57

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Diagnosis and Management Myasthenia Gravis Diagnosis Management

• Digital subtraction angiography • 70-100% of surviving patients (DSA) make a complete or partial • 1-2% morbidity risk recovery of the oculomotor • Gold standard deficit • MRA/CTA • Usually starting with resolution of • Noninvasive ptosis • Can detect 95% of aneurysms • Pupillary and EOM abnormalities • Aneurysm needs to be >5mm may persist • MRI/CT/LP • Sometimes aberrant • ESR/CRP/CBC w differential regeneration • Fresnel prism please J Lee AG, Hayman LA, Brazis PW. The evaluation of isolated Patel K, Guilfoyle MR, Bulters DO, Kirollos RW, Antoun NM, third nerve palsy revisited. An update on the evolving role Higgins JNP, Kirkpatrick PJ, Trivedi RA. Recovery of of magnetic resonance, computed tomography, and secondary to posterior communicating catheter angiography. Surv Ophthalmol. 2002;47(2):137-57 artery aneurysms. Brit J Neurosurg. 2014;28(4):483-487

Pathophysiology Epidemiology

• Neuromuscular junction • Incidence – 0.4-5 cases/100,000 per year dysfunction leads to painless, • Prevalence – 0.5-30 cases/100,000 per year fatigable weakness of voluntary • Age muscles • Juvenile MG • Autoantibodies • 10-15% of Caucasians (28) • Anti-AChR • 50% of Chinese cases (29) • Anti-MuSK • Early-Onset MG (EOMG) <50yo • Role of the Thymus? • Female predominance (60-70%) • Pathogenic/inflammatory • Between 50-60yo triggersà chronically inflammed • No gender difference thymusà autosensitization to • Late-Onset MG (LOMG) >60yo AChRà autoreactive T Cells • Male predominance

Vaphiades M, Bha M, Lesser R. Ocular Myasthenia Gravis: A Review. Curr Opin Ophthalmol. 2012. 23(6):537-542 Image and information from: Berrih-Aknin S, Frenkian-Cuvelier M, Eymard B. Diagnostic and clinical classification of autoimmune myasthenia gravis. J Autoimunityi. 2014;48-49:143-148

Ocular Manifestations Systemic manifestations

• 85% of MG patients • Ptosis • Skeletal Muscle Fatigue • 15% of MG patients have ocular • variable, worse with fatigue MG only • Facial muscles • Diplopia/EOM involvement/ • Majority of patients have ocular • Proximal limb muscles Ophthalmoplegia manifestations in first year of onset • Muscles for swallowing/breathing • variable, worse with fatigue • Required to have 2 years • Other autoimmune disease • Orbicularis weakness without further generalization • Thyroid disorders (Hashimoto’s or Basedow diseases) • Normal pupils of MG to be diagnosed as having purely ocular form • Thymus problems • Cogan’s Lid Twitch • Thymic follicular hyperplasia ~70% • Thymoma (thymic epithelial cell tumor) ~10-15%

Vaphiades M et al. Ocular Myasthenia Gravis. Curr Opin Oph. 2012. 23(6):537-42 Spillane E, et al. Myasthenia Gravis. BMJ. 2012. 8497:1-4.

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Why is it life threatening? • Myasthenic crisis Diagnostic Management • Respiratory failure due to muscle weakness • Severe weakness of respiratory muscles, upper airway muscles, or both • Usually due to poor control of generalized disease • OD Diagnosc Tests – In Office Other triggers for crisis • Ptosis à Fague, Rest, Ice Tests • Concomitant use of certain antibiotic (aminoglycosides, quinolones, antimalarials), muscle relaxants, anti-convulsants antipsychotics, botox, Beta- • OD/MD Diagnosc Tests (Neurologist/Neuro-Ophthalmologist) blockers (including topicals), and iodinated radiocontrast agents • Tensilon Test (Edrophonium Chloride), 95% sensivity • Systemic infection involving respiratory tract, aspiration, and surgery • Side Effects: Bradycardia, arrhythmia, hypotension • Emotional stress, hot environment, sudden elevation of body temperature (9) • Hyperthyroidism • Serologic Tesng for Autoanbodies, Thyroid funcon • Require immediate ventilatory assistance • 5% of paents with myasthenia gravis also have dysthyroidism • Pre-immunotherapy era • CT/MRI of Thorax (rule/out Thymic abnormalies) • Myasthenic crisis had significant mortality rate (up to 75%), but has fallen to <5% in recent years • Neurophysiological Specific Tests • 20-30% life-time prevalence of myasthenic crisis in patients with MG • RNS – Repeve Nerve Smulaon • Usually occurs during the course of first symptomatic presentation in the young and later in the course of disease in the elderly • SFEMG – Single Fiber Electromyography • White patients more likely to respond poorly to treatment then black patients • Pregnancy is known to aggravate MG Benetar M, Kaminski H. Evidence report: the medical treatment of ocular myasthenia (an evidence-based review). Neurology 2007. Chaudhuri A, Behan PO. Myasthenic Crisis. Q J Med. 2009;102:97-107 68(24):2144-2149 Juel VC. Myasthenia gravis: management of myasthenic crisis and perioperative care. Semin Neurol. 2004;24:75-81. Benatar M. A systematic review of diagnostic studies in myasthenia gravis. Neuromusc Disord. 2006. 16(7):459-467

Serological Testing Medical Treatment

• Generalized Myasthenia – 96% sensivity, high PPV Long-Acng Acetylcholinesterase • 87% have autoanbodies inhibitor (Pyridosgmine) Immunomodulatory Therapy • 85% - AChR • 40-70% MuSK • Improves ptosis, less • Oral corcosteroids • Ocular Myasthenia – 44% sensivity, low NPV effecve in resoluon of • Effecvely controls diplopia AND ptosis symptoms • 50-80% have autoanbodies EOM involvement/diplopia • Lowers risk of progression from • (+)Autoanbody assay highly suggests MG • Does not affect the course OMGà GMG • BUT (-) Autoanbody assay = inconclusive of the disease • Other: Azathioprine, • Seronegave – (-)AChR, (-)MuSK Mycophenolate Mofel, • High prevalence of cranial and bulbar muscle involvement Controversial Methotrexate, Tacrolimus, • Repeated serological tests • (-) Potenal long term side effects Cyclosporine, Rituximab • 15% seroconversion rate over 1 year period • (-) Disease is not life-threatening • Thymectomy • (+) Ocular symptoms could decrease • Paents with OMG may persistently test seronegave • IV Ig quality of life • Plasma Exchange Benetar M, Kaminski H. Evidence report: the medical treatment of ocular myasthenia (an evidence-based review). Neurology 2007. 68(24):2144-2149 Benatar M. A systematic review of diagnostic studies in myasthenia gravis. Neuromusc Disord. 2006. 16(7):459-467

Intracranial Space Occupying Lesions Swollen Optic Nerve(s)

• Tumor Papilledema Differential Diagnosis • Inflammation • Infection • “Disc swelling from • Congenital Anomaly • Ischemic infarct elevated intracranial • pressure” • Increased intracranial pressure • Infection • Mass • Inflammation • Pseudotumor/IIH • Ischemia

Until lumbar puncture – better to diagnose “optic nerve head edema”

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Blurred Disc Margins Optic Nerve Edema – EVALUATION Unilateral Bilateral 1) SLOW YOURSELF DOWN AND BREATHE (+)APD (-)APD Asymptomac Headache

Opc Ischemic Opc Drusen Increased ICP Infecon Infiltrave Neuris Neuropathy (Papilledema) Central or Altudinal Enlarged blind Visual Field Enlarged blind spot Variable Variable cecocentral Variable spot Peripheral scotoma Peripheral constricon constricon Inferior-nasal Reduced Variable Normal Visual Acuity Normal Variable Variable

Reduced Variable Normal Color Vision Normal Variable Variable

Pain on EOMs Hx of transient Hyaline bodies Other Ocular Disc hyperemia +/- exudates Disc pallor vision loss Absent cup Finding CWS, +/- exudates, Macular star +/-exudates hemorrhages, +cup Hemorrhages Visual obscuraons 20-40yo, Hx of >50yo,Hx of HTN, Other Tinnitus Fever Hx of MS or other DM, or Systemic Nausea , inflammatory hypotensive Findings sarcoid, or disorder episode infiltrave dis MRI brain, Serological CT or orbital MRI/MRV head, lumbar puncture, CSF, Image From: Graves JS, Galetta SL. Acute Visual Loss and Other Neuro-Ophthalmologic Emergencies: Management. Neurol Clin 30 CSF studies (2012): 75-99 studies ultrasound serological studies

Papilledema Papilledema

Symptoms Signs Diagnosis Etiology • Bilateral disc edema • Headache • Initially superior-inferior swelling • Immediate Neuroimaging • Mass lesion • Disc Hyperemia (its pink!) • Nausea • (+) Obscuration of retinal vessels • Lumbar puncture • Severe cerebral edema • Tinnitus over disc margin • Elevated intracranial (CSF) • Venous • Cup is preserved pressure • Transient visual • Hydrocephalus • (+) CWS/hemorrhages over time obscurations • (-) Spontaneous Venous Pulsation • Pseudo-tumor Cerebri • Double vision • Normal VA • Other neurological deficits • Normal Color Vision • (+) Visual field defect • Enlarged blindspot

Graves JS, Galetta SL. Acute Visual Loss and Other Neuro- • Peripheral field constriction Ophthalmologic Emergencies: Management. Neurol Clin 30 (2012): 75-99 Graves JS, Galetta SL. Acute Visual Loss and Other Neuro-Ophthalmologic Emergencies: Management. Neurol Clin 30 (2012): 75-99

Pseudo-Tumor Cerebri IIH - Management Idiopathic Intracranial Hypertension • Acetazolamide Associations/Risk Factors • May improve papilledema, visual complaints, headache • Normal neuroimaging • Obesity • OR other diuretics/CAIs • MRI/MRV brain • Recent weight gain • Weight loss • Obstructive sleep apnea • Normal CSF examination • Baseline automated VFs after treatment initiated • Anemia • Elevated opening CSF • Progressive or severe vision loss may need more aggressive therapy • h/o medication use: pressure • Ventriculoperitoneal shunt • Glucocorticoids • Optic nerve fenestration • Vitamin A products • Tetrocycline derivatives • Synthetic growth hormones • Female predilection

Banta JT, Farris BK. Pseudotumor cerebri and optic nerve sheath decompression. Ophthalmology 2000;107:1907–12. Graves JS, Galetta SL. Acute Visual Loss and Other Neuro-Ophthalmologic Emergencies: Management. Neurol Clin 30 (2012): Liu GT, Glaser JS, Schatz NJ. High-dose methylprednisolone and acetazolamide for visual loss in pseudotumor cerebri. Am J 75-99 Ophthalmol 1994;118:88–96

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Optic Disc Pallor If its progressing… IMAGE Cavernous Sinus Lesions Longstanding compression of optic nerve, chiasm or tract by a tumor or aneurysm can cause progressive optic disc pallor

Image fro: Nadarajah J, Madhusudhan KS, Yadav AK, Chandrashekhara SH, Kumar A, Gupta AK. MR imaging of cavernous sinus lesions: pictorial review. J Neuroradiol. 2015;42(6):305-319.

Cavernous Sinus Syndromes Etiology

Complete Partial • Chronic Causes • Meningiomas • Ophthalmoplegia • Depends on the location • Metastases of head and neck cancers (Diplopia) of the lesion • Slow-growing carotid aneurysm • Ptosis • Acute Causes • Cavernous sinus thrombosis • Mydriasis • Extension of facial/sinus infection • Hypesthesia of V1/V2 • Carotid cavernous fistula (facial numbness) • Painful + chemosis + pulsatile • Orbital Pain • Inflammatory reaction (Tolosa-Hunt syndrome) • Pituitary apoplexy

Cavernous Sinus Thrombosis Differential Diagnosis Ocular Manifestations Systemic Manifetations Direct High-Flow Carotid • Most common 80-100% presentation • Most common 80-100% presentation Cavernous Fistula • Proptosis • Acute onset fever • Chemosis • Less common 50-80% presentation • Painful ophthalmoplegia • Periorbital edema • Ptosis • Headache • Proptosis • Ophthalmoplegia • CN III, IV, and/or VI palsies • Lethargy • Chemosis • Increased IOP • Less common 50-80% presentation • Altered sensorium • Fever • Decreased vision • Periorbital edema • Least common <50% • Decreased vision • (+) supraorbital bruit • Optic disc edema • Meningismus • Venous engorgement • Seizures • UNILATERAL • Arterialized conjunctival • Least common <50% • Hemiparesis vessels • Decreased visual acuity (due to ION, CRAO, CRVO, or corneal ulceration) • Sluggish/dilated pupils • Periorbital and corneal sensory loss (CNV)

Lemos J, Eggenberger E. Neuro-ophthalmological emergencies. Neurohospitalist. 2015. 5(4): 223-233. Lemos J, Eggenberger E. Neuro-ophthalmological emergencies. Neurohospitalist. 2015. 5(4): 223-233.

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Pituitary Apoplexy Epidemiology

• Between 2-12% of patients with adenoma experience apoplexy • Diagnosis of pituitary tumor unknown at time of apoplexy in ¾ of cases • Presentation for 0.6-9.0% of surgically managed pituitary adenomas • Male predominance ~60% • Peak incidence in 5th decade

Briet C, Salenave S, Bonneville JF, Laws ER, Chanson P. Pituitary Apoplexy. Endocrine Reviews. 2015;36(6):622-645 Glezer A, Bronstein MD. Pituitary apoplexy: pathophysiology, diagnosis, and management. Arch Endocrinol Metab. 2015;59(3):259-64.

Pathophysiology Ocular Manifestations

• Hemorrhage or infarction of a pituitary tumor causes a • Visual Field Loss sudden enlargement of the gland due to ischemia and/or • Bitemporal necrosis • Junctional scotoma • 2/3 are spontaneous • 1/3 precipitating factor: • Unilateral and/or bilateral Bitemporal Loss • Hypotension ophthalmolplegia ~50% • Surgery • CNIII>CNVI>CNIV • Malignant hypertension • Anticoagulant treatment • Dopaminergic agonist treatment Junctional Scotoma

Biousse V, Newman NJ, Oyesiku NM. Precipitating factors in pituitary apoplexy. J Neurol Neurosurg Psychiatry. 2001; 71(4):542-545 Glezer A, Bronstein MD. Pituitary apoplexy: pathophysiology, diagnosis, and management. Arch Endocrinol Metab. 2015;59(3): 259-64. Semple PL, Webb MK, de Villiers JC, Laws ER. Pituitary apoplexy. . 2005;56(1):65-72. discussion 3.

Systemic manifestations Diagnosis • CT scan ~46% sensitivity • MRI – modality of choice • Sudden severe headache • Pituitary dysfunction ~80% • Thyrotropic deficiency • Retroorbital • Hypothyroidism • Bifrontal • Corticotropic deficiency • Diffuse • Hyponatremia • Hypotension • Assoc with vomiting/nausea • Hypercortisolism • Neck stiffness • Brain stem/hypothalamus compression • Reduced consciousness Symptoms evolve from hours to 2 days after onset • Thermoregulatory dysfunction of apoplexy • Cardiorespiratory dysfunction

Briet C, Salenave S, Bonneville JF, Laws ER, Chanson P. Pituitary Apoplexy. Endocrine Reviews. 2015;36(6):622-645 Image From: Mukhi SV, Lincoln CM. MRI in the evaluation of acute visual syndrome. Top Magn Reson Imaging. 2015;24:309-324 Glezer A, Bronstein MD. Pituitary apoplexy: pathophysiology, diagnosis, and management. Arch Endocrinol Metab. 2015;59(3): 259-64. Briet C, Salenave S, Bonneville JF, Laws ER, Chanson P. Pituitary Apoplexy. Endocrine Reviews. 2015;36(6):622-645

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Treatment Summary

• Acute Management - controversial • Neuro-ophthalmological emergencies can present to • High-dose corticosteroid replacement – IV primary care optometry • Transphenoidal surgical decompression of the sella (ideally within 1 week) • The best way to prepare is to have a systematic process • 76% visual acuity improves for examination and workflow • 79% visual fields improve • Sometimes as an optometrist you get to save a life

Thank You!

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Glezer A, Bronstein MD. Pituitary apoplexy: pathophysiology, diagnosis, and management. Arch Endocrinol Metab. 2015;59(3):259-64. Semple PL, Webb MK, de Villiers JC, Laws ER. Pituitary apoplexy. Neurosurgery. 2005;56(1):65-72. discussion 3.

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