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 !