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Educational Objectives

The goal of this program is to improve the diagnosis and management of optic neuropathy, giant cell arteritis, and pi­tuitary apoplexy. After hearing and assimilating this program, the participant will be better able to:

1.   Recognize the signs and symptoms of typical and atypical optic neuritis (ON) and sarcoidosis.

2.   State the predictors of increased risk of developing multiple sclerosis in a patient with typical ON.

3.   Select appropriate treatment strategies for patients with typical or atypical ON.

4.   Diagnose and treat giant cell arteritis.

5.   Describe the diagnostic criteria that identify patients with pituitary apoplexy.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any per­sonal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, Dr. Arnold reported serving as a consultant for Pfizer. Dr. Lee and the planning committee reported nothing to disclose.

Acknowledgements

Dr. Arnold’s lecture was recorded at the Annual Clinical Conference, held January 9-10, 2009, in Kansas City, MO, and presented and sponsored by the Kansas City Society of Ophthalmology and Otolaryngology. Dr. Lee spoke at the Table Rock Regional Roundup-2008 Regional Ophthalmology Conference, held September 18-20, 2008, in Ridge­dale MO, and sponsored by the Arkansas Ophthalmological Society, the Kansas Society of Eye Physicians and Sur­geons, the Missouri Society of Eye Physicians and Surgeons, and the Oklahoma Academy of Ophthalmology, and jointly sponsored by the University of Arkansas for Medical Sciences College of Medicine. The Audio-Digest Foun­dation thanks the speakers and the sponsors for their cooperation in the production of this program.

Optic Neuritis: The Last Word?

Anthony C. Arnold, MD, Professor and Chief, Neuro-Ophthalmology Division, Jules Stein Eye Institute, the David Geffen School of Medicine of the University of California, Los Angeles

Typical Optic Neuritis (ON)

Presentation: usually idiopathic or related to multiple sclerosis (MS); noninfectious; patients usually young, female, and 92% experience pain with eye movement; central unilateral visual loss occurs over days; afferent pupillary de­fect present, but optic nerve appears normal in 67%, with disc edema present in remaining 33%; optic nerve abnor­mality appears in 95% of magnetic resonance imaging (MRI); neuritis usually improves over several weeks

Visual field patterns: Optic Neuritis Treatment Trial (ONTT) found classic central scotoma visual field pattern in 8% of patients; 15% had altitudinal loss; generalized depression in 30° central field occurred most often

Outcome: pain diminishes and visual recovery begins within 2 to 3 wk; end visual outcome usually good for both vi­sual acuity (VA) and field; ONTT found 74% had VA of ³20/20 at 10 yr, with very small percentage £20/200; 57% of patients who lost light perception recovered to ³20/40

Recurrence: 36% overall rate of recurrence over 15 yr; rate rises to 46% in patients with MS, and higher if oral pred­nisone taken; multiple recurrences appear to worsen visual prognosis

Risk for MS (ONTT)

Predictors of increased risk: MRI T2 images help assess risk for progression to MS; 5-yr data at 5 yr, patients with ON have 30% overall risk of developing clinical MS; ON patients with no lesions on MRI had risk of 16%; those with 1 to 2 lesions had 37% risk, and those with >2 lesions had 51% risk; 10-yr data  —  overall risk 38%; patients with no lesions had risk of 22%, and those with ³1 lesion had risk of 56%; 15-yr data  —  overall risk, 50%; those with no lesions had risk of 25%; those with ³1 lesion had risk of 72%; results from outside ONTT  —similar risks observed in Germany (54% overall risk after 8 yr), Sweden (50% after 1 yr for patients with abnormal MRI), and Italy; additional predictors of risk  —  appearance of retinal periphlebitis in absence of sarcoidosis increases risk 3-fold

Predictors of decreased risk: recently preceding viral illness, bilateral simultaneous onset, and presence of disc edema; normal MRI with severe disc edema and hemorrhages, lack of pain, and absence of light perception; edema of optic disc at onset and macular exudate (neuroretinitis)

Value of MRI: useful for confirming diagnosis; determination of location (eg, intracanalicular-intracranial portion) and extent (eg, wide area of nerve from globe to chiasm) of optic nerve involvement poor prognosis; can rule out other causes in patients whose visual fields are atypical for ON

Treatment with steroids: oral prednisone  —  ONTT showed that 1 mg/kg per day not effective (ie, had no visual ben­efit and doubled rate of recurrence); higher oral dose possibly acceptable; intravenous (IV) methylprednisolone  —  at 1 g/day (currently given as outpatient single dose) for 3 days (with or without oral taper), increased rate of recov­ery but conferred no long-term (>6 mo) visual benefit; for patients with abnormal MRI, IV bolus decreased rate of progression to MS at 2 yr but not after 2-yr point; similar results reported in Japan and Denmark

Patient management: all patients with ON undergo MRI to determine risk for progression to MS; because MS exac­erbations produce early axonal damage, many clinicians treat early; some administer bolus of steroids intermit­tently in patients with lesions to reduce brain damage and long-term disability (effectiveness of intermittent treatment still unproven)

Immunomodulatory agents: Controlled High Risk Subjects Avonex Multiple Sclerosis Prevention Study (CHAMPS)  —sponsored by makers of interferon beta-1a (Avonex); enrolled 383 patients at first demyelinating event (ON accounted for 50% of events) with ³2 lesions on MRI; all patients received IV and oral steroids within 14 days of onset; patients then randomized to intramuscular interferon beta-1a vs placebo within 4 wk of onset; study terminated after first interim analysis (£3 yr) because of definite beneficial effect of treatment (»50% reduc­tion in rate of development of MS); controversial questions  —  whether treatment appropriate for 25% to 50% of patients who do not progress; whether to wait for appearance of new lesions before initiating therapy

Atypical Optic Neuritis

Features: presence of systemic illness or vasculitis; atypical demographics; immunocompromise or autoimmune dis­ease; absence of pain; clinical course atypical (eg, progresses slowly or dependent on steroids); persistence of pain and edema over 1 to 2 mo; severe vision loss; bilateral simultaneous onset; severe disc edema; neuroretinitis; asso­ciated uveitis; simultaneous bilateral papillitis; macular star; imaging optic nerve important to rule out typical de­myelinating optic neuritis (contrast-intense lesion with more of sheath involved than parenchyma and involvement of adjacent orbit or brain tissue suggest atypical form); sarcoidosis and orbital inflammatory disease can mimic atypical ON

Infectious optic neuritis: likely infections include Bartonella henselae (cat scratch fever), viral infection, syphilis, tuberculosis (TB), and Lyme disease; neuroretinitis  —  if patient has bilateral swelling of optic nerve and macular star, rule out hypertensive crisis

Bartonella: ask about cat scratches; systemic illness may or may not occur; patients typically have greater than ex­pected loss of VA because of maculopathy; fluorescein angiography shows no leakage; serologic testing avail­able; visual prognosis good (90% recover VA to 20/50); rarely associated with MS; treatment  —  optional in absence of systemic illness; specific antibiotic therapy unknown, and steroids not effective

Viral or postviral ON: infection and autoimmune response to virus present similarly; typical presentation bilateral simultaneous optic nerve involvement with disc edema; common presentation in children; infectious agent often unknown (presumptive diagnosis based on accompanying systemic illness); spontaneous recovery common; role of steroids unclear, but often used in children

Other infections: ON due to syphilis, TB, or Lyme disease difficult to diagnose because of variable presentation; ask about systemic symptoms; look for skin lesions and associated intraocular inflammation; perform standard serologic testing, ie, VDRL, fluorescent treponemal antibody (FTA), Lyme titers, tuberculin skin test, chest x-ray; treatment  —patients require aggressive antibiotic therapy under care of internist

Sarcoidosis

Presentation: eye problem possibly first sign; gradually progresses over 3 wk to 2 mo; possibly retrobulbar, with papillitis, or infiltrative; no specific visual field pattern; suspect if acute optic neuropathy accompanied by uve­itis, iris nodules, retinal periphlebitis, lacrimal gland enlargement, or choroidal granuloma; MRI atypical, with extensive eye and adjacent brain involvement

Screening: tests include angiotensin-converting enzyme (ACE) assay and chest x-ray; refer to rheumatologist; bi­opsy conjunctival lesion if present; lumbar puncture needed to determine extent of central nervous system (CNS) involvement

Treatment: initially responds to oral steroids; often recurs on tapering, and immunosuppressive agents possibly in­dicated

Other Conditions

Systemic lupus erythematosus (SLE): presentation may be similar to typical ON; usually seen in patients with diag­nosed SLE; ON most often retrobulbar; rarely shows other CNS involvement (eg, overt CNS vasculitis); treatment  —  responds well to oral steroids

Nonspecific autoimmune optic neuropathy: usually found in older women; usually bilateral; treatment  —  response to oral steroids variable

Giant Cell Arteritis and Pituitary Apoplexy: Two Neuro-ophthalmologic Diagnoses that you Cannot Afford to Miss

Andrew G. Lee, MD, Professor of Ophthalmology, Neurology, and Neurosurgery, University of Iowa Hospitals and Clinics, Iowa City

Giant Cell Arteritis

Presentation and diagnosis: acute loss of vision in elderly patients accompanied by headache or other pain (eg, jaw pain); afferent pupillary defect; diagnosis of ON unlikely in elderly patient; order erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP tests) immediately; signs of giant cell arteritis  —  unexplained cotton wool patch, transient diplopia, temporal pain, scalp tenderness, jaw claudication, or retrobulbar posterior ischemic optic neuropathy (PION) in elderly patient; optic nerve and retina typically normal

Incidence: increases dramatically after 50 to 55 yr of age

Testing: ESR with upper limit corrected for age and sex (ie, [age + 10]/2 for women, age/2 for men); CRP uncor­rected; platelet count useful adjunctive test, but ESR and CRP more rapid; perform fluorescein angiography in pa­tients with PION to identify areas of choroidal perfusion deficit and blocking from cotton wool patches; choroidal perfusion deficit in peripapillary region or watershed zone between lateral and medial choroid indicates giant cell arteritis; nonarteritic form of anterior ischemic optic neuropathy (AION) not associated with transient diplopia and vision loss (amaurosis fugax); involvement of 2 circulations (systemic vasculitis), retinal artery occlusion and AION indicate giant cell arteritis; MRI and neuroimaging often normal in patients with giant cell arteritis

Treatment: begin prednisone immediately

Pituitary Apoplexy

Presentation and diagnosis: severe headache and blurred vision (ie, bitemporal hemianopsia); imaging  —  if directed at sella, computed tomography (CT) show suprasellar mass with rim of hemorrage; MRI shows bright signal on TI precontrast; diagnosis  —  perform visual field test if possible (or confrontation field test) on any patient with acute painful loss of vision; if bitemporal or homonymous hemianopsia present, emergent neuroimaging required

Study: 62 patients (average 51 yr of age) with pituitary apoplexy; average time of presentation, 14 days after ictus; 81% had no history of pituitary tumor; 56% of patients came to ophthalmologist because of loss of VA; only 34% had classic bitemporal hemianopsia; 73% hypopituitary, and 8% had diabetes insipidus, either of which possibly fa­tal without therapy

Presentation of chiasmal lesion: location of tumor determines presenting signs; bitemporal hemianopsia indicates lesion at chiasm; if tumor grows slightly anteriorly, it affects single optic nerve (not chiasm) and presents as acute unilateral optic neuropathy; if tumor grows in middle, disease presents as acute bilateral optic neuropathy; if tumor strikes tract, disease presents as acute homonymous hemianopsia; if tumor grows laterally into cavernous sinus, disease presents as ophthalmoplegia and diplopia; any patient with acute painful unilateral insert neuro-ophthalmo­logic complaint could have apoplexy

Neuroimaging: MRI procedure of choice in neuro-ophthalmology for everything except bone, blood, and calcifica­tion; CT not sufficient; imaging may not detect level of hemorrhage in apoplexy; apoplexy diagnosed clinically, not radiographically; in some cases, hemorrhage not present (only necrosis of preexisting tumor and edema)

Suggested Reading

Biousse V et al: Management of optic neuritis and impact of clinical trials: an international survey. J Neurol Sci 276:69, 2009; Bonhomme GR et al: Pediatric optic neuritis: brain MRI abnormalities and risk of multiple sclerosis. Neurology 72:881, 2009; Braswell RA, Kline LB: Neuro-ophthalmologic manifestations of sarcoidosis. Int Ophthal­mol Clin 47:67, 2007; Chang KK, Rizzo JF 3^rd: Recent advances in the immunopathology of giant cell arteritis. Int Ophthalmol Clin 49:99, 2009; Hall JK: Giant-cell arteritis. Curr Opin Ophthalmol 19:454, 2008; Hayreh SS: Isch­emic optic neuropathy. Prog Retin Eye Res 28:34, 2009; Kawasaki A, Purvin VA: Idiopathic chiasmal neuritis: clin­ical features and prognosis. Arch Ophthalmol 127:76, 2009; Kolappman M et al: Assessing structure and function of the afferent visual pathway in multiple sclerosis and associated optic neuritis. J Neurol Mar 18, 2009 [Epub ahead of print]; Kolbe S et al: Optic nerve diffusion changes and atrophy jointly predict visual dysfunction after optic neuritis. Neuroimage 45:679, 2009; Luneau K et al: Ischemic optic neuropathies. Neurologist 14:341, 2008; Mowry EM et al: Multiple sclerosis and the ophthalmologist. Compr Ophthalmol Update 8:37, 2007; Optic Neuritis Study Group: Multiple sclerosis risk after optic neuritis: final optic neuritis treatment trial follow-up. Arch Neurol 65:727, 2008; Osborne BJ, Volpe NJ: Optic neuritis and risk of MS: differential diagnosis and management. Cleve Clin J Med 76:181, 2009; Plant GT: Optic neuritis and multiple sclerosis. Curr Opin Neurol 21:26, 2008; Schofield TM, Leff AP: Rehabilitation of hemianopia. Curr Opin Neurol 22:36, 2009; Swanton JK et al: Early MRI in optic neuri­tis: the risk for disability. Neurology 72:542, 2009; Tumani H: Corticosteroids and plasma exchange in multiple scle­rosis. J Neurol 255 (Suppl 6):36, 2008.