Transcript Optic Neuritis - University of Louisville Ophthalmology

Grand Rounds
Mark Mugavin M.D., MPH
University of Louisville School of Medicine
Department of Ophthalmology & Visual Sciences
10/2/2015
Subjective
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CC: Painless Central Vision Loss OS
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HPI: 38 year old AAF with history of hypertension, obesity, prior
pulmonary embolism presents to ED with CC of persistent,
painless central vision loss in her left eye for the last four days.
Patient noticed black dots in her field of vision in her left eye
which became most obvious while watching TV. Also described
dull, bi-lateral headaches surrounding her frontal sinuses and felt
“funny”. No flashes of light, floaters, curtains. Right Eye
unaffected.
Subjective
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Medical HX: Hypertension, Obesity, Prior pulmonary embolism
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Surgical HX: Prior tubal ligation
Ocular HX: Myopia
Medications: Lisinopril 10 mg q Day, Atorvastatin 20 mg q day
Review of Systems: Positive for paresthesias in her left hand
noticed approximately one to two episodes a week for the last 3
months, no dysarthria, no overt clumsiness
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Exam
OD
OS
VA(cc, near):
20/20
20/25-2
Pupils:
4
4
2
3
+APD OS
IOP:
EOM
15
17
0
0
0
0
0
Ishihara Plates
16/16
0
0
0
12/16
Exam: Anterior Segment
OD
Eyelids/Eyelashes
Conjunctiva/Sclera
Cornea
Anterior Chamber
Iris
Lens
Vitreous
OS
wnl ou
clear ou
Racial Melanosis OU
Formed
Formed
Dark. Round
Dark. Round
Clear
Clear
Clear
Clear
Posterior Segment
Differential Diagnosis
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Optic Neuritis
Non-Arteritic Anterior Ischemic Optic Neuropathy
MRI Axial Cut T2 Flair Sequence
MRI T2 Flair
Hospital Course
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VEP Obtained by Neurology
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Increased latency of the P-100
waveforms for both eyes (OD 117
and OS 116)
Slowing of electrical conduction
suggestive of demyelination
Assessment and Plan
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38 yr old Female presenting with:
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4 day hx of painless, new onset
central scotoma
dyschromatopsia
endorsing paresthesias
relatively unremarkable fundus
MRI suggestive of demyelinating
plaques.
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Retrobulbar Optic Neuritis
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Neurology Consult initiated.
Pt started on Solumedrol 1 gm IV for
5 days
Lumbar Puncture to eval CSF
Visual Evoked Potentials
Visual Field in 2 weeks
Hospital Course
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Pt received 5 days of IV
Solumedrol
Day 5 of hospitalization reported
significant improvement in vision
deficit
Objectively improved to 16 of 16
Ishihara Plates OU
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Lumbar Puncture
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Oligoclonal Bands – Negative
Albumin 9.2 low (13.9 to 24.6)
IgG Synthesis low
Serology
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ANA negative
Lyme negative
VRDL Negative
ACE Negative
Thyroid Peroxidase 312 (nml <30)
Epidemiology
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Annual incidence in U.S. of 6.4 per 100,000
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Presenting feature in M.S for 15-20% of patients, develops in 50% of
M.S. patients at some point during course of their illness
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Approximately 77% of patients are female, mean age of 32
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Incidence is highest in populations of higher latitudes, particularly in
United States and Western Europe while lower in regions close to the
equator
Classic Clinical Features
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92% Periorbital Pain many times
associated with movement
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+RAPD
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Visual defect classically central
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Loss of color vision out of
proportion to the loss of visual acuity
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Visual Acuity can range from 20/25
to 20/190 median of 20/60
Optic Neuritis
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Pathophysiology
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Inflammatory demyelination of the
Optic Nerve
Complex Immune mediated process
Know that Activated Dendrites cross
the Blood Brain Barrier where naïve
CD4 Cells differentiate into:
Th1 helper Cells secreting
Inteferon Gamma
-Typically defend against
intracellular pathogens
30% of SNP’s linked to M.S. are
near regions where immune system
genes are coding for cytokine
pathways
TH 17 cells secrete granulocyte
macrophage colony stimulating
factor
-Typically involved in fungal
defense
Optic Neuritis Clinical Treatment Trial
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Initiated in 1988, enrolled 457 patients,
utilizing 15 clinical centers throughout
U.S.
Patients randomized to one of three
regiments
A)
B)
C)
Oral Prednisone (1mg/kg/day for 14
days
IV Methylprednisolone (250mg every 6
hours for 3 days, followed by Oral
Prednisone 1 mg/kg for 11 days
Oral Placebo for 14 days
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Eligible Patients
a)
b)
c)
d)
e)
f)
18 to 46 years of age
Acute unilateral optic neuritis with
visual symptoms 8 days or less
+RAPD and Field Defect in
affected eye
No previous episodes of Optic
Neuritis in affected eye
No previous corticosteroid
treatment for optic neuritis or M.S.
No systemic dx other than M.S. that
could cause Optic Neuritis
Key Findings of ONTT
1.
2.
3.
4.
Corticosteroid Therapy for Optic Neuritis has no long term
beneficial effect on vision
Methylprednisolone regiment sped recovery by 1-2 weeks
Patients receiving Oral Prednisone regiment didn’t experience
any benefit, in fact there was a recurrence rate double of the other
groups
Patients with MRI scans demonstrating 2 or more white matter
lesions, treated with IV steroids experience a 2 year protective
effect (36% untreated vs 16%) that disappeared after year 3
Key Findings of ONTT
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Periventricular white matter lesions demonstrating demyelination
most critical for assessing risk of developing M.S.
Zero Lesions: 25% chance of developing M.S. within 5 years
 One Lesion or more: 72% chance of developing M.S. in 15 year period
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Lower risk of developing M.S. associated:
a)
b)
c)
male sex
optic disc swelling
atypical features of optic neuritis (absence of pain, NLP vision,
peripapillary hemorrhages, retinal exudates)
Literature Review
Control
All M.S. Eyes
M.S. without Optic
Neuritis
M.S. with hx of
Optic Neuritis
Low Contrast (2.5%)
# of letters correct
25 +/- 7 (61 eyes)
16 +/- 10 (239 eyes)
18 +/- 10 (150 eyes)
11 +/- 11 (87 eyes)
Spectralis Domain
OCT (peripapillary
RNFL thickness μm)
92.9 +/- 10 (61 eyes)
84.3 +/- 12.8 (239
eyes)
87.6 +/-11.1 (150
eyes)
78.4 +/- 13.6 (87
eyes)
• Study found significant relationship between well validated National Eye Institute: Vision Related
Quality of Life Survey Score and the following:
• Low Contrast Visual Acuity Score
• RNFL
• Clinical Trials utilizing OCT to evaluate the effectiveness of immunomodulatory therapy
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Activated Microglia can be a source for:
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Nitric Oxide
Glutamate
Proteases
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All of which can damage the axonal
mitochondria
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Damaged mitochondria produce an energy
imbalance. Voltage gated Na fast channels
become more prominent in demyelinated
areas
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Na+/Ca2+ exchanger expression increases
in response. Higher levels of intracelluar
Ca2+ lead to axon cell death
References
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Trapp et al “Virtual Hypoxia and Chronic Necrosis of Demyelinated Axons in Multiple Sclerosis”
Neurology Vol 8 Issue 3 March 2009, Pages 280-291
Petzold et al “Optical Coherence Tomography in multiple sclerosis: a systematic review and metaanalysis” Neurology Vol 10 March 2010 Pages 921-932
Winges et al “Baseline Retinal Nerve Fiber Layer Thickness and Macular Volume Quantified by OCT in
the North American Phase 3 Fingolimod Trial for Relapsing-Remitting Multiple Sclerosis Journal of
NeuroOphthalmology. December 2013; 33 (4) Pages 322-329
Galetta, K and Balcer, L “Measures of Visual Pathway Structure and Function in M.S.: Clinical Usefulness
and role for M.S. Trials Multiple Sclerosis and Related Disorders 2013 2, 172-182
“Optic Neuritis” Neuro-ophthalmology Section 5 Basic and Clinical Science Course Chapter 4 pages 131132 Publisher American Academy of Ophthalmology