Femtosecond Laser in Ophthalmology

Surgery and Imaging

Josef F.Bille
Kirchhoff Institute of Physics
University of Heidelberg
 Contents

•Femtosecond Laser-Tissue Interaction

•Medical Laser System Considerations
•Femtosecond Laser for Lamellar Cuts
•Femtosecond Laser as Refractive Laser
•Multiphoton imaging of the human eye
 Laser-tissue Interactions

1015 Photodisruption
Irradiance [W/cm2]

1012
Photoablation
109 Plasma induced 1000 J/cm2
ablation
106 1 J/cm2

103 Thermal Interaction

100
Photochemical Interaction
10-3
1 fs 1 ps 1 ns 1 µs 1 ms 1s 103
Exposure Time [S]
 Photodisruption Photoablation
YAG Laser Capsulotomy Excimer Laser Refractive Surgery

Photothermal Interaction
Photochemical Interaction Laser Photocoagulation
Photo Dynamics Therapy
 Femtosecond ... ?

1s 1 fs
Femtosecond Laser Technology
RRegenerative Amplifier
ClinicalCC
 Femtosecond Laser/Tissue Interaction

Cornea

Ultrashort Microplasma
Infrared (intrastromal)
Laser Pulses

• „Plasma-mediated“ ablation in the very focus

• So fast that it is non-thermal (no thermal coupling)
• Precise 3-D cutting and ablation within the transparent material
by scanning the laser focus in XYZ
 Ablation Threshold with ultrashort laser
pulses

170-fs pulses 300-ps pulses

Well defined threshold Poorly defined threshold

Courtesy of Kurtz et al.

 Ablation Threshold: Cornea Tissue

Why
femtosecond
laser pulses?
 For shorter
laser pulses
FEMTO PICO a lower pulse
energy is
needed to
achieve
ablation!
 Plasma-Mediated Ablation:
Gas Bubbles


Shorter laser pulses
with low energy
generate
smaller gas bubbles

Precisely defined
ablation
 Plasma-Mediated Ablation:
Shock Waves


Shorter laser pulses
with low energy
generate
smaller shock waves

Precisely defined
ablation
 Ophthalmic Femtosecond Laser and
Excimer Laser in Comparision

Parameter Femto Excimer

Wavelength 1 µm 193 nm
infrared UV
 cornea is transparent absorbing
Pulse width several 100 fs several ns
Repetition rate multi-kHz up to 200 Hz
Fluence 1-10 J/cm2 150-250 mJ/cm2
Spot size several micron 0.65 – 6.5 mm
Interaction plasma- direct photo-
Comparision of typical systems
process mediated ablation
 Laser Microkeratome Procedure:
FEMTEC Applanation-Free Approach

A B
 Intrastromal Ablation Applications of
FEMTEC Femtosecond Laser
• Noninvasive intracorneal
intra tissue ablation
without the need to open the cornea
• For precisely correcting smaller
refractive errors (up to 2 D per session)
• For personalized touch-ups

A B
Personalized Intrastromal
Refractive Procedures
Under evaluation:

Non-invasive
intrastromal
refractive
correction
(no need to open
the cornea)
 The Intrastromal Procedurere
• Combination of new,
completely intrastromal
ablation geometry
and predictable
biomechanical response
lead to desired refractive
effect

• Taylored to the individual

patient and the FEMTEC
laser

01/23/ Hawaiian Eye

 Motivation for Developing Femtosecond
Laser Intrastromal Surgery
• A refractive laser correction performed completely
intrastromal has huge potential:
– Non-invasive
– No impact on epithelium
– Low infection risk
– Advantageous wound healing
– Maintaining the structural integrity of the cornea
as much as possible

• But, is it predictable?
Previous approaches were limited in this aspect
01/23/2008 Hawaiian Eye 2008
 Technical Requirements
• Model to predict impact of intrastromal
ablations on the biomechanical response
must be available
(e.g. FEM model)

• Cornea must be as stress-free as possible

during treatment to allow precise, 3-
dimensional positioning of the laser pulses

01/23/2008 Hawaiian Eye 2008

 Eye Fixation with Minimal
Biomechanical Impact for High
Level of Predictability

FEMTEC eye fixation

Applanating eye fixation

01/23/ Hawaiian Eye
intraCOR Procedure
Corneal Inflation Simulation by Finite Element
Modeling Method
 Apical-rise vs. IOP increase

Left: apical rise of the cornea with respect to the

intraocular pressure (IOP) increase. The whole
process is simulated as the cornea is subjected to an
increasing IOP from 0 kPa (stress-free state) to 4 kPa
(30mmHg). Right:corneal thickness at the apex vs.
intraocular pressure.
A. Elsheikh and D. Wang, Numerical modelling of corneal biomechanical
behaviour, Computer Methods in Biomechanics and Biomedical Engineering, Vol.
 Stress and strain analysis of the loaded
cornea under normal IOP

Finite element modeling for simulating the stress and strain

distributions throughout a loaded cornea. An intraocular
pressure of 2 kPa (15mmHg) is applied homogeneously to the
posterior surface. Only Bowman's layer is fully fixed at the
limbus. Left: Cauchy stress distribution along the radial
direction. Right: the maximum principal strain distribution.
Finite element corneal modeling simulation of
intrastromal presbyopic correction
Presbyopia correction
Intrastromal Presbyopia Correction with the FEMTEC
Workstation, Technolas Perfect Vision (TPV)
 Intrastromal Custom Corneal Surgery

Active mirror
Fs Surgical
Laser In Situ control

Intensity
Modulator

Computer Generated
Hologram
Active mirror

CCD

Wavefront Sensor
Laser Diode
eye
Second Harmonic Imaging and Two-
Photon Excited Autofluorescence
Imaging of the Human Eye
 Principle of two photon imaging

P P
2 P F

P P
 Second Harmonic Laser Scanning Microscopy

Ti:Sapphire


2

 P   (1) E   ( 2 ) EE   (3) EEE  ...

2
 E pulse 
I SHG ~   ( 2) 
  
 Second Harmonic Generation imaging
of Cornea

Bowman`s Membrane Corneal Stroma

Fs Laser Intrastromal Ablation
1 photon v.s. 2 photon excitation
 Autofluorescence from Retinal Pigment Epithelial
(RPE) Cell

16 µm 16 µm

Confocal imaging Two photon imaging

Argon laser 488 nm Ti:Sapphire laser 800 nm
 Abnormal spectrum of AF

10 µm 10 µm

AF color coded: blue (500 – 550 nm) red (575-640 nm)

80 yrs patient, 16 hrs post mortem. RPE cells in the macula of retina.
Spectrum from abnormal granules
DIC/TPEF-Imaging of GC-Apoptosis
Autofluorescent Fluorophores in the
retina-choroid complex
 Foveal Cone/Rod Mosaic

Fovea Parafovea

19 yr-old donor eye

 Bruch‘s Membrane

19 yrs 64 yrs
 Sub-choriocapillaries Layer

19 yrs 64 yrs
 Two-Photon Retina Tomography

1 photon Signal Detector 2 Photon Signal Detector

Focal plane
Pinhole

Fs Laser

Beam
splitter
Scan unit
TPFA Live Rabbit Retina
 Principle of adaptive optics

Deformable mirror

Propagation

Wavefront
regulation
Object Picture

Optical
aberrations
Wavefront
Feedback control
Regulation measurement

Hartmann-Shack unit
 Adaptive Optics
Surface of the Sun

Uncorrected Compensated
 Movie of microchip mirror

Video will start automatically

Restart with mouse click on video

Optics of customized aberration-free Imaging
Mask Structured Ion Exchange Technique

A) Thermal diffusion: exchange of Na+ by Ag+ ions.

B) Field assisted process: Ag+ ion current.
 lPrecompensation of 3rd Order Aberrations
using Phaseplatespenssae
cnm  (cn m ) 2  (cnm ) 2 Z7 1 micron
cn m
a tan( m )
cn
 nm 
m

a a
Z8 1 micron
cnm
Z9 1 micron
cnm
  2 arccos( )
2a
180
 all   nm 
m Z10 1 micron
Aberration-Free Retina Imaging
 Conclusion

• Femtosecond laser-tissue interaction provides a new

minimal-invasive surgical laser knife
• First clinical applications in laser flap cutting and cornea
transplant surgery
• Custom femtosecond laser eye surgery with adaptive
optics becomes feasible
• Second harmonic imaging provides new noninvasive
structural information of the components of the human
eye
• Two photon excited autofluorescence allows for
structural and functional information of the retina
Thank you
for your
attention !