prof. mrochen "clinical results with uv-x" (2014)

Clinical results with UV-XK-max comparison at 6 and 12 monthsSafety aspects

Optimized beam profile

Peripheral intensity 30% higher than ENERGY DOSE (not intensity)

=Increased biomechanical strengthening of the cornea

=improved corneal flattening

K-max value

Change of Kmax @ 6 months

UV-X1000 (n=273); UV-X2000 (n=38)

Clinical data form Cummings, Seiler, Raiskup

Evaluation criteria

• Kmax > +1 D; continuation of progression (Failure)

• -1D < Kmax <+1D; no change• Kmax < -1 D; improvement

No progression(Success)

Change of K-max @ 6 months

No-progression(success)

Failure

UV-X™ 2000 91% 9%

UV-X™ 1000 79% 21%

Clinical data form Cumming, Seiler, Raiskup

The difference between the proportions are statistically significant.

Change of Kmax @ 12 months

≥1D ≥2D0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

UV-X™ 1000

UV-X™ 2000

Latest results presented by Prof. Theo SeilerSeptember 2013

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)

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

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.

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 ??

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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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Missing technology

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0

1

2

0 2 4 6 8 10 12

Strain in %

Stre

ss in

10

5 Pa

porcine corneas

crosslinked

untreated

Kmax

In-vitro stress-strain measurements

?In-vivo mapping of biomechanical parameterof the cornea

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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

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Brillouin Spectroscopy

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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 hyperfrequencysound waves.

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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

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Brillouin Scattering

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Scarcelli G, Kim P, Yun SH. Biophys J. 2011;101:1539–1545.

Comparison of Brillouin longitudinal and Young’s moduli of a porcine Lens.

Spectral shift is related to the elastic modulus (M′) of the material where, ρ = mass density, λ = wavelength, n= the refractive index.

M′ = ρλ2Ω2/4n2

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)

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Avedro Laboratory Data, 7/2014

Control Porcine Cornea

7.91 GHZBrillouin Peaks

Rayleigh Peak

Cross-Linked Porcine Cornea

8.06 GHZ

8.34 GHZ

8.53 GHZ

Low Dose1.8

J/cm2

Medium

Dose10.8

J/cm2

High Dose

18 J/cm2

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Scarcelli G, Kling S, Quijano E, Pineda R, Marcos S,and Yun SH. Invest Ophthalmol Vis Sci. 2013;54:1418–1425)

Scarcelli et al measured differences in treated and untreated porcine corneas that are in agreement with Avedro laboratory findings for the same dose

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

Brillouin Spectroscopy in Cross-Linking

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Corneal Tomography Biomechanical Properties

Customized Treatment Plan

Customized Treatment Design

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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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