OCT: A Tool to objectively assess MS Progression?
16th STATE OF THE ART Symposium, SMSSSaturday 11-JAN-2014, 12:05-12:30, axel petzold
Disclosures
SC: OCTiMS study (Novartis)
To be covered
• The method: OCT
• Accurate quantification of atrophy in MS• Time course of atrophy• Inner and outer retinal layers• What does it mean for the patient?
How does it work?
Petzold et al. TLN 2010
What information can be gained?
• Normal
• Too thick
• Too thin
Too thick
● Fingolimod associated macular oedema
● Microcystic macular oedema (MMO) Gelfland et al. 2012 (15 patients)
● INL thickening predicts disease activity Saidha et al. 2012 (10 patients)
Microcystic macular oedema (MMO)
Burggraaff et al. IOVS 2014
Burggraaff et al. IOVS 2014
MS ERM
RION VMT
CRION Diabetic retinopathy
NMO Vascular occlusion
LHON/DOA Optic neuropathy
Harding's disease CSR
Endemic optic neuropathy
RP
ARMD Optic nerve glioma
Retinal teleangiectasis Medication
The clinical spectrumof MMO
How accurate is OCT?
Optic disc no EBF with EBF no EBF with EBF
Global mean 0.94 0.96 0.98 1.00
Temporal 0.79 0.85 0.94 1.00
PMB 0.67 0.69 0.89 1.00
Balk and Petzold IOVS 2013
Inter-observer ICC Intra-observer ICC
Summary of time-domain data
MSON vs CTRL (n=2063): -20.38 μm
MSON vs non-MSON (n=4199): -14.57 μm
Non-MSON vs CTRL (n=3154): -7.08 μm
Petzold et al. TLN 2010
To be covered
• The method: OCT
• Accurate quantification of atrophy in MS• Time course of atrophy• Inner and outer retinal layers• What does it mean for the patient
Lesion location is relevant for the time course of atrophy
Petzold et al. TLN 2010
OCT trial power-calculations
A. Henderson et al. BRAIN 2010
Power (80%, for different models and effect size) at:3 months: 38-1024 subjects6 months: 14-358 subjects12 months: 15-292 subjects
More severe atrophy in PPMS?
RNFL:Henderson (2008) 23 PPMS: no Henderson (2010) 16 PPMS: no (longitudinal !)Siepman (2010) 29 PPMS: noAlbrecht (2012) 12 PPMS: no
Pulicken (2007) 12 PPMS: trend (p=0.08)
Gelfland (2012) 33 PPMS: yesOberwahrenbrock (2012), 41 PPMS : yes
RNFL + other layers:Balk (in press), 29 PPMS: no
20 years later: how “benign” is MS?
Balk et al. MSJ 2014
MSNON eyes
n=61 n=85 n=126
To be covered
• The method: OCT
• Accurate quantification of atrophy in MS• Time course of atrophy• Inner and outer retinal layers• What does it mean for the patient
Balk et al. JNNP (in press)
Inner and outer retinal layers
Does progression stop in the eye?
Balk et al. JNNP (in press)
Does progression stop in the brain?
Gabilondo et al. ANN (in press)
OCT 0.6 um of RNFL loss <=> MRI 1cm3 visual cortex loss
Plasticity
L. Balk et al. JNNP (in press)
To be covered
• The method: OCT
• Accurate quantification of atrophy in MS• Time course of atrophy• Inner and outer retinal layers• What does it mean for the patient
Why OCT in MS?
Visual impairment ranked 2nd for reduced QoL(Heesen 2008)
MS damages the anterior visual pathways (Oppenheim 1887) in >90% of patients (Lisch 1933, Lumsden 1970, Ikuta 1976, Mogensen 1990, Green 2010)
A tool to investigate the cascade of neurodegeneration in MS (Waxman 2007)
What does it mean for the patient ?
Conclusion
• OCT is accurate and reliable (QC !)
• Evidence for inner retinal layer atrophy• Strength: acute optic neuritis, early CIS• Weakness: PPMS, long disease duration• Trans-synaptic axonal degeneration
Thank you !
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