Optic Neuritis and OCT in Multiple Sclerosis
Transcript of Optic Neuritis and OCT in Multiple Sclerosis
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Optic Neuritis Raed Behbehani , MD FRCSC
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Eye involvement in MS
• Afferent : Optic neuritis , Intermediate Uveitis , Visual Pathway Lesions
• Efferent : INO , nystagmus , Cranial nerve palsy
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Optic Neuritis• Young, female
• Pain ( dull-aching , peri-ocular headache , worse with EOM)
• Visual acuity can be normal.
• RAPD
• Visual field defect
• Fundus : 60%-70% Normal (retrobulbar neuritis)
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Visual Field Defact
• In ONTT : Central field > peripheral
• Focal defect (42%) : Arcuate , Altitudinal , Nasal
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ONTT 15 years
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Course of optic neuritis• Vision recovery starts within 2 weeks.
• ONTT : at 3 months, visual acuity was >=20/40 in 93 %.
• 35 % recurrence in the affected or fellow eye ( 10 year ONTT)
• Recurrence twice more common in MS patients than non-MS patients.
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Atypical optic neuritis“Red Flags”
• Age <12 years or >50 years• Severe loss of vision (NLP) , Bilateral onset in an adult, no
improvement after 6 weeks , progressive course.• No pain.• Ocular findings : severe disc edema , marked hemorrhages,
uveitis, exudate, retinitis, phelbitis• Recurrences within a short interval or during steroid taper.• Pre-existing systemic diagnosis ( Cancer, CT disease,
Vasculitis, immunosuppression)
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Mimickers of Typical Optic Neuritis
• Ischemic (AION, PION).
• Neuromyelitis Optica (NMO)
• Compressive.
• Infectious/ para-infectious.
• Inflammatory and infiltrative.
• Leber’s optic neuropathy.
• Auto-immune.
• Paraneoplastic.
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Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION)
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Neuro-retinitis
http://medstat.med.utah.edu/NOVEL
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Leber Mitochondrial Optic Neuropathy
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Neuromyelitis OpticaWingerchuk et al, Neurology, 2006
• Median age : 35-44 years ; children : 4.4 years
• Less common than demyelinating (Asia , African , West Indies 50% of demyelination)
Diagnostic Criteria
1) Optic neuritis
2) Transverse Myelitis
3) At least 2 of 3
• LETM ( 3 contiguous veterbal segments)
• NMO IgG (70% sensitive , 100% specific)
• Brain lesions not compatible with MS
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International Consensus Diagnostic Criteriafor Neuromyelitis Optica Spectrum
Disorders 2015
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Neuro-imaging NMO
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Neuro-imaging NMO
Khanna et al: J Neuro-Ophthalmol 2012
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Is NMO Screening Indicated in All Optic
Neuritis Cases?
• Sensitivity issues.
• NMO-negative patients .
• Anti-MOG antibodies .
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Anti-MOG Optic Neuritis
• Younger or even pediatric onset (25%)
• MS-like Brain lesions or ADEM , positive OCB
• Antibody level show fluctuating course (need to re-test to follow up)
• Monophasic usually.
• Simultaneous/sequential optic neuritis and myelitis.
• Better visual and motor (EDSS) recovery
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Neuromyelitis Optica Spectrum Disorders With Aquaporin-4 and Myelin-Oligodendrocyte Glycoprotein Antibodies: A Comparative Study
JAMA Neurol. 2014;71(3):276-283. doi:10.1001/jamaneurol.2013.5857
MRI In MOG + vs AQP4 + ON
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Suggested Blood Work up for Atypical Optic Neuritis
Test Disease
CBC with Differntial, ESR, CRP Infections, Inflammatory
Serum CSF-VDRL, FTA-Abs Syphilis
ACE Sarcoid
ANA, Anti-DNA SLE
NMO IgG (Anti-AQP4, Anti-MOG) NMO
C-ACNA, anti-pretinase 3
PPD TB
Bartoenlla Hensellae Serology Cat Scratch
LHON genetic testing LHON
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Additional Work up• Tissue biopsy of lesions of conjunctiva ,
ocular adnexa , sinus mucosa and sometimes optic nerve sheath.
• Radiologic studies : must include MRI of the brain and orbit with fat-suppression and gadolinium enhancement of the optic nerve sheath.
• PET/CT imaging, galluim scan.
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The Use of OCT in MS
Raed Behbehani , MD FRCSC
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Optical Coherence Tomography• Non-invasive imaging technique routinely
used in ophthalmology (glaucoma , retinal diseases)
• The retina contains axons and glia but no myelin , thus ideal to monitor neurodegeneration.
• Quantitative Measurement of retinal nerve fiber layer (RNFL) , macular thickness (MT), Ganglion cell layer (GCL).
• Qualitative assessment (Ultra-high resolution).
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Why OCT ?• Axonal degeneration was recognized as an
early pathological manifestation of MS .
• The role of inflammation, acute and chronic axonal loss, and neuro-degeneration is in the core of pathophysiology of MS.
• Noninvasive methods of monitoring and treating axonal pathologic changes in MS patients.
• “In-vivo” optical biopsy.
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Optic Atrophy in MS• MS and ON and
non-ON eyes each year of follow-up was associated with an average 2-μm decrease in RNFL (P < .001) (Talman LS et al.2010)
• Post-mortem analysis show that most MS have changes in the optic nerve and RNFL. (Ikuta and Zimmerman, 1976; Toussaint et al., 1983 , Green et al. 2010)
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Spectral Domain OCT
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Optic Neuritis
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Follow Up RNFL After Optic Neuritis
• Costello et al (2006) followed 38 patients with optic neuritis using TD OCT.
• Most of RNFL loss occurred between 3-6 months (85%).
• Visual recovery is correlated with remaining RNFL at 6 months. (Henderson et al. 2010)
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Follow Up RNFL in Optic Neuritis
• RNFL thinning starts at 2-3 months , progressed till 6 months and then stabilized up to 2 years (Costello et al. 2009)
• A meta-analysis (14 studies) showed that RNFL values are reduced from 5 to 40 μm (averaging 10 to 20 μm) in eyes with MS and ON. (Petzold et al. 2010)
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RNFL Loss Following ON
Klistorner A, Arvind H, Garrick R, et al. Interrelationship of optical coherence tomography and multifocal visual-evoked potentials after optic
neuritis. Invest Ophthalmol Vis Sci. 2010;51:2770–2777
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RNFL of the Contralateral Eye in Optic Neuritis
• Many studies showed that RNFL loss occurs also in the asymptomatic affected eye in optic neuritis. (Fisher et al., 2006; Henderson et al., 2008; Jeanjean et al., 2008; Pueyo et al., 2009; Pueyo et al., 2008; Pulicken et al., 2007; Sepulcre et al., 2007).
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GCL loss in Optic Neuritis
At 3 weeks post-optic neuritis
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GCL loss in ON
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Changes in Outer Retinal Layers in ON
• Decrease GC layer in first 4 months.
• Concomitant thickening of the ONL+PS,and less markedly the INL+OPL. (Al-Louzi et al. Multi Scler 2015)
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RNFL and Visual Field
75 microns is a threshold value for visual recovery
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OCT and Disability
Costello F, Hodge W, Pan YI, Eggenberger E, Freedman MS. Using retinal architecture to characterize multiple sclerosis patients. Can J Ophthalmol.2010;45:520–526
RNFL correlates with EDSS for mild-mod
neurological impairment
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OCT vs VEPOCT VEP p-value OCT +
VEP
Prior ON 68% 86% 0.12 98%
No ON 19% 40% 0.01 44%
OCT is more likely to be abnormal in eyes with history of ONDi Maggio G et al. MSJ 2014
Sensitivity of VEP and OCT
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OCT in NMO• RNFL thickness was significantly worse in
NMO and CRION than in RRMS (Bichuetti et al, 2013)
• RNFL 41 um thickness is 100% specific for NMO and CRION. (Bichuetti et al, 2013)
• Another study found no difference in amount of pRNFL loss if adjusted for optic neuritis episodes (Outteryck et al , Multi Scler 2015)
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OCT in NMO• RNFL is generally not reduced in NMOSD non-ON eyes . (RNFL Loss
is attack-related). (Lange AP et al. JNO 2013).
• significant macular atrophy and lower average pRNFL thickness2 have already been reported in NMOSD-NON eyes. (Sortichos et al. Neurology 2013)
• NMO non-ON has reduced GCL+IPL compared to controls (?ongoing disease activity even in NMO)
• Delayed VEP P100 latency in NMOSD . (Ringelstein et al. Muti Scler )
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OCT in NMO
JL Benett et al . MSJ 2015
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Beyond RNFL
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Beyond RNFL- Inner and Outer Nuclear Loss
• Predominantly macular thinning and near normal RNFL, had thinner inner and outer nuclear layers compared to other subsets and normal ganglion cell layer.
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Use of OCT in Clinical Trials
• Retina ( Glial cells and no myelin)
• Can detect axonal loss before MRI
• The “clinical radiological paradox”
• OCT correlates with other visual functions (contrast, colour , visual fields , VEP etc).
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OCT in Neuroprotection
Raftopoulos R et al Lancet Neurology 2016• Randomised, placebo-controlled, double-blind
phase 2 trial.
• Oral phenytoin (4-6 mg/kd/day) for 3 months vs Placebo
• 42 assigned to phenytoin and 44 to placebo.
• 30% reduction in the extent of RNFL loss with phenytoin vs placebo (81 u vs 74 u ) at 6 months.
• There is a role for Neuroprotection with phenytoin in patients with acute optic neuritis at concentrations.
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Summary • Typical demyelinating Optic neuritis is a clinical
diagnosis . • NMO Optic neuritis should suspected in cases of
ON with poor recovery and some neuro-radiologic and OCT findings .
• Our understanding of the mechanisms of diseases is evolving thanks to new ultra-high resolution OCT.
• The non-invasiveness and the reporducibility of OCT makes it ideal to assess neuroprotective effects of drugs in trials.