Optic Neuritis: Current Diagnosis and Management Age 20 to 50 - - PowerPoint PPT Presentation

2/12/2014 1

Optic Neuritis: Current Diagnosis and Management

Acute Optic Neuritis: Typical History

• Age 20 to 50 years
• Unilateral
• Visual loss does not progress beyond

14 days

• Pain is present, particularly on eye

movements

• Visual recovery begins by one month

Acute Optic Neuritis: Typical Findings

• Reduced acuity in one eye
• Vision better than no light perception
• Impaired color vision
• Afferent pupil defect
• Field loss- diffuse, central, arcuate,

altitudinal

• Mild or no disc swelling
• No hemorrhages or retinal exudates

Optic Disc Appearance

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Optic Neuritis-Clinical Course

• 95% recover to 20/40 or better over

several weeks

• 50% have some permanent vision loss

(contrast sensitivity, color vision, or visual field), particularly with baseline acuity of 20/50 or less

Optic Neuritis: Treatment

• Current treatment is IV steroids
• Vision recovers faster (stops inflammation)
• BUT, final vision no better than without steroids
• Reduces short term risk of developing MS
• No known treatment prevents permanent

vision loss, unmet therapeutic need

• Most high risk patients are placed on

immunomodulatory therapy

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Optic Neuritis: Risk of Multiple Sclerosis (MS) With Normal MRI

Arch Neurol, 2008. NLP = no light perception

• No pain

0%

• Severe disk edema

0%

• Disc hemorrhage

0%

• Macular exudate

0%

• NLP vision 0%

Differential Diagnosis (Step 2)

• Ischemic optic neuropathy
• Systemic disease
• Neuro-retinitis
• Hereditary disorders
• NMO

NEURITIS VS ISCHEMIA

NEURITIS ISCHEMIA

Age 30’s 60’s Pain 90% 10% Field central altitudinal Fundus retrobulbar – 2/3 swollen

Ischemic Optic Neuropathy

2/12/2014 4 DIFFERENTIAL DIAGNOSIS (Step 2) INFLAMMATORY (Bilateral, vitreous cells, hemorrhages)

Syphilis Sarcoid Lyme Viral

Neuroretinitis

DIFFERENTIAL DIAGNOSIS(Step 2) HEREDITARY - Nutritional (Bilateral central-cecal scotomas)

Leber’s B1, B12 Toxic

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Optic Discs, VF and OCT NMO Prognosis: (5 to 10 yrs) Reasons to Distinguish It

• 62% have legal blindness in one eye
• 50% will need an assistive device

Neurology 53:1107,1999

NMO: The Chances

♦ Bilateral- 50% present of NMO present

with ON, 20% are bilateral vs 0.4% in ON with MS

♦ Severe acuity loss- < 20/200, about

33%

♦ Recurrent ON- about 20%

JNO: 32:154;2012

NMO Tidbits

• Average RNFL thickness

NMO- 63 microns, typical- 88 microns Controls- 102 microns

• About 5% of optic neuritis patients are

NMO positive

• Chronic relapsing idiopathic optic

neuropathy (CRION). Tend to have progression between episodes

Neurology 73:302, 2009

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Copper Deficiency Optic Neuropathy

Step 3- Tests

♦ MRI head with gad (typical or atypical ON) ♦ LP: IgG index, OCB, cells, protein (atypical ON) ♦ NMO IgG (recurrent, bilateral or severe ON) ♦ Leber’s mutations (severe or bilateral ON) ♦ Serological studies-Atypical ON or systemic

symptoms-ESR, ANA, ACE, RPR, Lyme, SSA, SSB, ANCA

♦ Retinal Tests-ERG, Fluorescein angiogram,

CAR antibodies, OCT

♦ VER: Subclinical ON, can use low contrast

Vision and ON as Ideal Models

RNFL = ganglion cell axons (non-myelinated)

• Axonal and neuronal

loss common

• Sensitive visual

function tests

• Structure-function

correlation can be captured by OCT

• Unique opportunity

to investigate non- myelinated axons

1.0 1.5 2.0 2.5 High Contrast Acuity ~100% Low Contrast Acuity 1.25% Contrast Sensitivity Pelli- Robson Color Vision D15-DS

Comparison of Vision Tests

Odds ratio in favor of MS

• vs. control

status (95% CI) for worse vision scores

* Low contrast acuity charts best distinguish MS patients vs. controls, accounting for age

* (1.9, 3.1) P<0.001 (1.3, 1.9) P<0.001 (1.5, 2.2) P<0.001 (1.2, 1.8) P<0.001

MS Patients: n=130 Disease Free Controls: n=90 Balcer LJ, Baier ML, Cohen JA, et al. Neurology 2003;61:1367-1373.

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• 2 lines (10 letters) = clinically

meaningful change?

• 5-letter change more sensitive for

high-contrast visual acuity

• Change by ≥7 letters is beyond test-

retest variability for low-contrast acuity, correlates w/ QOL

Defining Visual Change

Balcer, Pelak et al. Mult Scler 2000. Beck et al. Ophthalmology 2007. Rosser et al. Invest Ophthalmol Vis Sci 2003. Balcer, et al. Neurology 2007.

Worsening Vision by EDSS Progression Status

Galetta et al. Ectrims, 2010

Importance of OCT in Optic Neuritis

• Allows structure-function

correlations

• Significant RNFL loss,

acute, 99% by 6 months

• Optic neuritis as a model

for testing new therapies

Petzold A et al. Lancet Neurology 2010. Henderson et al. Brain, 2010

RNFL

Figure from Frohman, et al. Nat Clin Pract Neurol 2008;4:664-675.

Retinal Nerve Fiber Layer Imaging by Optical Coherence Tomography (OCT)

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Quantifying Axonal Loss After Optic Neuritis with OCT

• Patients with acute ON (n=54)
• Followed for a mean of 13 months
• 74% developed significant RNFL thinning

(20%) in the affected eye

• RNFL values significantly thinner in

affected eyes (78 µm) vs. fellow eyes (100 µm, P< 0.0001)

Costello F et al. Ann Neurol 2006.

OCT in Optic Neuritis

• Patients (n=54) with ON, 74% had 20% RNFL loss
• Thickness at ≥3 months = 78±30 µm in affected eyes
• RNFL <75 µm vs. ≥75 µm predicted visual outcome

Costello F et al. Ann Neurol 2006

Visual Field Mean Deviation (dB)

• 35
• 30
• 25
• 20
• 15
• 10
• 5

5 40 50 60 70 80 90 100 110

50 70 90 110 130 150 170 Overall average Temporal Superior Nasal Inferior

R N F L th ic k n e s s (m ic r o n s ) MS ON eyes MS non-ON eyes Disease-free control eyes

P < 0.001 for ON vs. non ON eyes, P = 0.03 for MS non ON vs. controls

Relation to Low-Contrast Acuity, Optic Neuritis History

Fisher J et al. Ophthalmology 2006.

2 lines low-contrast letter acuity = 7.6 µm RNFL, P< 0.001

MS Eyes: n=180 Disease Free Control Eyes: n=72 n=201 n=242, p=0.06 n=109, p<0.001 * n=41, p<0.001 *

• 8
• 6
• 4
• 2

RNFL change from baseline (microns) 0.5 - 1 year >1 - 2 years >2 - 3 years >3 years Follow-up interval, all MS eyes

Longitudinal Data: RNFL Thinning for All MS Eyes (n=593)

* Degree of RNFL thinning significantly greater compared to 0 – 1-year interval

Talman et al., Ann Neurol 2010.

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Low-Contrast Acuity Reflects Axonal Loss Over Time

n = 493

n = 67, p<0.001 vs. no visual loss n = 560

• 6
• 4
• 2

No visual loss Loss of 7 or more letters All MS eyes

RNFL thinning from baseline (microns)

Low-contrast letter acuity, 2.5%

Talman L et al. Ann Neurol 2010.

Retinal Neuronal Atrophy in MS Eyes

79% of MS patient eyeballs (N=80) had GCL dropout and 40% had INL (amacrine and bipolar cell) atrophy

Ganglion cell dropout Inner nuclear layer Neuron dropout

Green A et al. Brain 2010. Above courtesy of James Fujimoto, Ph.D.

Ganglion Cell Layer RNFL

• High resolution

(4-6 µm)

• Segmentation of

retinal layers

Spectral-Domain OCT

Tan O, …Schuman JS..., et al. Ophthalmology 2009.

MS vs. Controls

P values are from GEE models accounting for age and inter-eye correlations

Thickness in microns

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r = 0.49, P<0.0001 r = 0.31, P=0.0006

20 40 60 80 100 60 70 80 90 100 Thickness of GCL+IPL (microns)

NEI-VFQ-25 Composite (best QOL = 100 points) 95% Confidence Interval on Fitted Line Low-Contrast 2.5% (number of letters identified correctly)

Implications

• Subclinical injury is common in MS
• OCT and LCA are important outcome

measures for clinical trials in MS

• In practice, used to detect subtle atrophy,

longitudinal changes and macular changes

• Correlates with QOL and MRI measures
• Unmet therapeutic need for

neuroprotective therapy in MS

24 Y.O. WOMAN

♦Decreased vision over 7 days ♦No pain upon eye movement

EXAMINATION

Acuity: NLP O.D 20/20 O.S. Pupil: Right amaurotic Motility: Full

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EXAMINATION -MW

♦Slit lamp exam showed 1+

vitreous cells OD

♦Tension applanations were 16 OU ♦Fundus exam revealed the

following:

LABORATORY

♦nl lytes, CBC, LFTs ♦RPR (-), ESR 40, PPD (-), anergy (+) ♦ANA 1:320, nl complements ♦(-) anti- dsDNA, -smith, -RNA, -Ro, -La ♦ACE 53.18 (10-50) ♦LP:2W 0R protein:29 glucose:59 ♦nl CXR

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COURSE -MW

♦Conjunctival and lacrimal biopsies

showed non-specific chronic inflammation without granulomas

♦Gallium scan was normal ♦She was started on steroids and had

no improvement

♦She underwent biopsy of right optic

nerve

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OPTIC NERVE IN SARCOID

♦Occurs in 1-5% of pts with systemic

disease

♦Five categories – Primary granuloma of the optic nerve – Papillitis – Retrobulbar optic neuritis – Papilledema secondary to increased ICP – Optic atrophy

20 Y.O. MAN

♦Decreased vision O.U. ♦Visual acuity 20/200 O.U. ♦Fields: centrocecal scotomas

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30 Y.O. MAN

♦Sudden visual loss O.D. ♦No pain on eye movement

Central Serous Chorio- retinopathy

• OD

OS

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72 Y.O. WOMAN

(August 1996)

♦Progressive visual loss right eye ♦Right periorbital ache ♦No neurologic or constitutional

symptoms

EXAMINATION

(August 1996)

♦Acuities: 20/100+ OD, 20/50+

OS

♦Pupils: sluggish, no APD ♦Color: no control OU

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Summary

♦

There are typical history and examination features of idiopathic optic neuritis

♦

The decision to use corticosteroids for visual impairment in optic neuritis should be individualized.

♦

Natural history suggests that CIS patients with positive MRIs will progress to CD-MS

♦

Corticosteroids followed by immunomodulatory therapy should be strongly considered for such patients

♦

Functional and structural visual correlates permit the testing of novel neuro-repair therapies.