Prof. Michael Mrochen presentation at the 2014 Total Keratoconus Solution user meeting organized by Mediphacos London, 2014 ESCRS

1. Clinical results with UV-X
K-max comparison at 6 and 12 months
Safety aspects

2. Optimized beam profile
Peripheral intensity 30% higher than ENERGY DOSE (not intensity)
=
Increased biomechanical strengthening of the cornea
=
improved corneal flattening

3. K-max value

4. Change of Kmax @ 6 months
UV-X1000 (n=273); UV-X2000 (n=38)
Clinical data form Cummings, Seiler, Raiskup

5. Evaluation criteria
• Kmax > +1 D; continuation of progression (Failure)
• -1D < Kmax <+1D; no change
• Kmax < -1 D; improvement
No progression
(Success)

6. Change of K-max @ 6 months
No-progression
(success)
Failure
UV-X™ 2000 91% 9%
UV-X™ 1000 79% 21%
The difference between the proportions are statistically significant.
Clinical data form Cumming, Seiler, Raiskup

7. Change of Kmax @ 12 months
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
≥1D ≥2D
UV-X™ 1000
UV-X™ 2000
Latest results presented by Prof. Theo Seiler
September 2013

8. Safety aspects
• No difference in terms of safety between the
two devices.
– Loss of CDVA of more then 2 lines < 1%
– Loss of endothelium cells (not significant)

9. Adverse events for both devices
• Transient pain
• Corneal haze
• Corneal scars
• Delayed epithelium closure
• Sterile infiltrates
• Corneal edema
• Corneal erosion (recidive)
• Corneal infections after CXL

10. Evidence based benefit / risk ratio
• Benefits
– Stabilization of the cornea
– Stops the progression of KC
– Improvement of subjective visual performance
– Improved contact lens tolerance
– Avoid keratoplasty surgery
• Risk
– Low risk of visual loss
– Low risk for adverse events
– Transient visual disturbances
– Tolerable pain
Corneal cross linking can be considered to be effective and safe with a high
benefit and low risk ratio.

11. Evidence based data in KC
(peer reviewed) Aug. 2013
Cross-linking device No. of eyes
IROC Innocross UV-X 2269
CBM X-Linker (Sooft) 677
OptoGlobal 24
Avedro ??
Peschke ??

12. VISION - OPTICS - LIGHT
Unmeet medical need
• Biomechanics of the ocular tissue structures
• Clinical applications
– Pre-Op Screening of Refractive Patients
– Early Diagnosis of Ectasia / Keratoconus
– Measure Effect of Cross Linking
– More Accurate IOP Measurement
– Assessment of Other Tissues
• Lens, Lamina, Retina…?
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13. VISION - OPTICS - LIGHT
Missing technology
In-vivo mapping of
biomechanical parameter
of the cornea
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2
1
0
crosslinked
untreated
?
0 2 4 6 8 10 12
Strain in %
Stress in 10 5 Pa
porcine corneas
Kmax
In-vitro stress-strain measurements

14. VISION - OPTICS - LIGHT
Current technical developments
• Air puff tonometry
• Optical coherence elastography
• Dynamic ultra high speed Scheimpflug imaging
• Dynamic OCT imaging
• Quantitative ultrasound spectroscopy
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Disadvantage: Applying a mechanical force to achieve measurement

15. VISION - OPTICS - LIGHT
Brillouin Spectroscopy
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16. VISION - OPTICS - LIGHT
Brillouin Spectroscopy
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Spectrometer
Brillouin scattering arises when light
is scattered by periodic fluctuations
in density that occur as a results
of thermally exited hyperfrequency
sound waves.

17. VISION - OPTICS - LIGHT
Brillouin Spectroscopy
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Laser beam
Spectrometer
Sound waves with
wave lenght Ʌ
the light rays reflected by the
consecutive planes of sound
waves -> Bragg relation
Frequency shift by
Doppler's principle

18. Spectral shift is related to the elastic modulus (M′) of the material where,
ρ = mass density, λ = wavelength, n= the refractive index.
VISION - OPTICS - LIGHT
Brillouin Scattering
Scarcelli G, Kim P, Yun SH.
Biophys J. 2011;101:1539–1545.
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M′ = ρλ2Ω2/4n2
Comparison of Brillouin
longitudinal and Young’s
moduli of a porcine Lens.
Randall J, Vaughan JM. Proc R Soc Lond B Biol Sci.
1982;214:449–470.
Scarcelli G, Kim P, Yun SH. Biophys J. 2011;101:1539–1545.
Scarcelli G, Kling S, Quijano E, Pineda R, Marcos S,and Yun SH.
Invest Ophthalmol Vis Sci. 2013;54:1418–1425)

19. Control Porcine Cornea
Brillouin Peaks
Avedro Laboratory Data, 7/2014
VISION - OPTICS - LIGHT
7.91 GHZ
Rayleigh
Peak
Cross-Linked Porcine Cornea
8.06 GHZ
8.34 GHZ
8.53 GHZ
Low
Dose
1.8
J/cm2
Medium
Dose
10.8
J/cm2
High
Dose
18
J/cm2

20. Brillouin Spectroscopy in Cross-Linking
Scarcelli et al measured differences in treated and
untreated porcine corneas that are in agreement
with Avedro laboratory findings for the same dose
Scarcelli G, Kling S, Quijano E, Pineda R, Marcos S,and Yun SH. Invest Ophthalmol Vis Sci. 2013;54:1418–1425)
VISION - OPTICS - LIGHT
They also demonstrated that Brillouin Spectroscopy could
show effect as a function of depth, and was sensitive enough
to detect differences between cross-linking protocols
5.4 J/cm2

21. Corneal Tomography Biomechanical Properties
VISION - OPTICS - LIGHT
Customized
Treatment Plan
Customized Treatment Design

22. VISION - OPTICS - LIGHT
Summary
• Brillouin spectroscopy has be shown to quantify
biomechanical properties of the eye (in-vitro).
• Initial measurement in-vivo are reported.
• Brillouin spectroscopy has the potential to provide
clinical relevant measurements to address the unmeet
medical need of quantifying the biomechanics of the
ocular tissue structures.
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