OCT: A Tool to objectively assess MS Progression? Speaker: Axel Petzold VUmc MS Centrum Amsterdam

1. OCT: A Tool to objectively
assess MS Progression?
16th
STATE OF THE ART Symposium, SMSS
Saturday 11-JAN-2014, 12:05-12:30, axel petzold

2. Disclosures
SC: OCTiMS study (Novartis)

3. 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?

4. How does it work?
Petzold et al. TLN 2010

5. What information can be gained?
• Normal
• Too thick
• Too thin

6. 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)

7. Microcystic macular oedema (MMO)
Burggraaff et al. IOVS 2014

8. 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 spectrum
of MMO

9. 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

10. 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

11. 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

12. Lesion location is relevant
for the time course of atrophy
Petzold et al.
TLN 2010

13. OCT trial power-calculations
A. Henderson et al. BRAIN 2010
Power (80%, for different models and effect size) at:
3 months: 38-1024 subjects
6 months: 14-358 subjects
12 months: 15-292 subjects

14. More severe atrophy in PPMS?
RNFL:
Henderson (2008) 23 PPMS: no
Henderson (2010) 16 PPMS: no (longitudinal !)
Siepman (2010) 29 PPMS: no
Albrecht (2012) 12 PPMS: no
Pulicken (2007) 12 PPMS: trend (p=0.08)
Gelfland (2012) 33 PPMS: yes
Oberwahrenbrock (2012), 41 PPMS : yes
RNFL + other layers:
Balk (in press), 29 PPMS: no

15. 20 years later: how “benign” is MS?
Balk et al. MSJ 2014
MSNON eyes
n=61 n=85 n=126

16. 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

17. Balk et al. JNNP (in press)
Inner and outer retinal layers

18. Does progression stop in the eye?
Balk et al. JNNP (in press)

19. Does progression stop in the brain?
Gabilondo et al. ANN (in press)
OCT 0.6 um of RNFL loss <=> MRI 1cm3
visual cortex loss

20. Plasticity
L. Balk et al. JNNP (in press)

21. 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

22. 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)

23. What does it mean for the patient ?

24. 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

25. Thank you !