Medical Applications

Femtosecond Lasers in
Ophthalmology
Precise cutting using adaptive optics is pushing the limits
Ben Matthias, Uwe Oberheide, Alexander Krger, Tammo Ripken and Holger Lubatschowski

Presbyopia is the most common visual Best of

defect of the human eye. Beginning
with the age of 45 years, most people
lose the ability to focus on near objects
due to the loss of accommodation abil-
ity of the crystalline lens. Within the
research network IKARUS, a femto-
second laser system has been realized,
which is able to generate microscopic
sliding into the crystalline lens, to re-
store the accommodative capacity of
the eye. The surgical procedure only
takes a few seconds and is non-inva-
sive. As a consequence, there is no risk
of infection for the patient and the pro-
cedure can be carried out in non-sterile
environment. In addition, other clin-
ical applications with extremely high
market potential were evaluated in
the context of ex vivo investigations. It
could be shown that, using adaptive op-
tics, it is possible to create precise cuts
even in the posterior segment of the eye
(retina) and thus open up a multitude
of new treatment options.
Femtosecond lasers in ophthal-
mology
Applications
OPTIK &
PHOTONIK
Invited Article
Fig. 1 Restoring crystalline lens flexibility by generating smooth cuts inside the crystalline
lens acting as sliding planes. Left: principle of the procedure. Right: extracted crystalline
lens with sliding planes inside
surgery. On presbyopic eyes, where ac- normalities. When applied to human au-
commodation fail, due to the age re- topsy eyes, an average increase of 100 m
lated hardening of the crystalline lens, in the antero-posterior lens thickness was
fs-laser pulses might have the chance seen, corresponding to a 2.00 to 3.00 D
to regain accommodation by creating gain in accommodative amplitude.
micro-incisions inside the lens without Moreover, ultrashort laser pulses
surgically opening the eye (Fig. 1). These may replace posterior vitrectomy for the
micro-channels could reduce the inner treatment of tractional vitreous attach-
friction of the lens tissue, acting as slid- ments in the near future. The traditional
ing planes [4]. When delivered to rabbit method for treating vitreoretinal trac-
eyes, these laser incisions did not cause tion is a posterior vitrectomy, an invasive
cataract growth or wound-healing ab- procedure in which the band of vitreous

Since the launch of the first commer-

cial femtosecond laser system for cor-
neal surgery in 2001 by IntraLase, more
than thousand systems have been sold
and more than twenty million patients
have been treated for refractive corneal
surgery. Today, femtosecond lasers have
developed from a pure Flap-maker for
LASIK surgery to a multiple tool for cor-
neal surgery [1] as well as for cataract sur-
gery [2, 3]. In cataract surgery, the laser
has extended its field of action from the
cornea to the crystalline lens where it is Fig. 2 Sketch of a vitreoretinal traction, specifically a posterior hyaloid traction exhibiting
retinoschisis. In this condition, a portion of the vitreous tissue of the eye has adhered to
used to open the capsular bag (capsulot-
the retinal tissue, causing the retinal tissue to lift away from the underlying retinal pig-
omy) and performing lens fragmentation. ment epithelium. Left: untreated, vitreoretinal traction can lead to damage to the retina as
But, there is even more potential well as retinal detachment. Middle: conventional posterior vitrectomy. Right: Cutting the
of femto-applications in ophthalmic strands with a fs-laser.

2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Optik&Photonik 2/2016 49
 www.optik-photonik.de

tissue in traction with the retina is re-

moved. The rate of post-operative mor-
bidity in this invasive procedure is signif-
icant, with a high incidence of cataract
formation due to the invasive nature of
the procedure. Using fs-pulses, the vitre-
ous tissue could be removed without any
surgical opening of the eye, avoiding the
known post-operative side effects (Fig. 2). Far 55 cm 25 cm

Surveying the crystalline lens

during accommodation
During accommodation, there is a
change in the shape of the crystalline
lens leading to an increase in refractive
power. In order to understand the effects
of the laser generated sliding planes in-
side the lens, it is helpful to record shape
of the lens at different refractive states as
well as the correlating optical power and
the resulting aberrations. At the start of
IKARUS several diagnosis systems ex-
isted to monitor either the shape of the
crystalline lens or its optical properties
[5, 6]. However, so far there was no
method for the direct correlation of op-
tical with the anatomical changes. To al-
low such a simultaneous measurement,
a combination of an optical coherence
tomography (OCT) and an aberrometer
was realized.
For this, the beam paths of a com-
mercially available time-domain OCT
for clinical measurements of the ante-
rior segment of the eye (SL-OCT, Hei-
delberg Engineering, Germany) and
clinical aberrometer using raytracing
(iTrace,Tracey Technologies, USA) were
combined collinearly with a dichroic
beam splitter due to the wavelengths of
785 nm and 1300 nm used by the aber-
rometer and the OCT, respectively. Fig.3
shows OCT images of the shape of the
lens at three different accommodative
states and the simultaneously measured
spherical aberrations as an example. On
average, the lens thickness increased by
82 3 microns per diopter of accommo-
Fig. 3 OCT images (top) of the shape of the lens at three different accommodative states
(far, intermediate, near) and the simultaneously measured spherical aberrations (bottom)
Integrating OCT-Technology
Since inter-individual anatomical dif-
ferences lead to variations in the lens
position and geometry, the integration
of an intraoperative depth-resolved
imaging is vital to the safety and suc-
cess of fs-laser lens surgery. Internal
structures must be reliably addressed
in adherence to safety zones to the lens
capsule. Optical coherence tomography
has been originally introduced as such a
measurement technique for intraocular
distances and has evolved into a versatile
diagnostic imaging tool used in numer-
ous medical disciplines.
The realized clinical prototype for
fs-laser lens surgery utilizes a custom-
ized spectrometer-based Fourier-do-
main OCT (FD-OCT) system to guide
laser beam positioning in the anterior
SLD
attenuation
eye (Fig. 4). A detailed system descrip-
tion is given in [7].
Compared to time domain OCT
(TD-OCT), FD-OCT has considerable
advantages regarding signal-to-noise
ratio and imaging speed. But it has two
drawbacks that restrict the measuring
depth. First, there is a sensitivity roll-
off with increasing measuring depth in
FD-OCT. The most sensitive measuring
range is close to the zero delay position,
where the OCT interferometer arms
are matched in length. Second, conven-
tional FD-OCT images suffer from dis-
turbing mirror artifacts due to a complex
ambiguity in the Fourier analysis of the
real-valued measured spectral signals.
Different full range OCT methods
exist to eliminate mirror artifacts and
effectively double the usable imaging
range. Most of them use phase shifting
reference arm
scanning focusing

dative power. x-y z

During the accommodation pro- spectrometer fs-laser dichr.
mirror
cess, the spherical aberrations of the en-
tire eye change toward negative spheri- sample arm
sample

cal aberrations, for the measured group

0.038 0.005 m per diopter accom-
modative power. With these measure-
ments, the changes of the wavefront
are correlated with changes in the lens
thickness and shape for the first time.
Fig. 4 Schematic setup of the OCT-guided fs-laser surgery system for cutting the crystal-
line lens. The customized FD-OCT system (840nm central wavelength) and the fs-laser
(1040nm) are in common path configuration sharing the scanning unit and the focusing
optics. The coupling interface is a dichroic mirror. Dispersion compensation glasses are
deliberately omitted in the OCT reference arm to create a dispersion imbalance in the OCT
interferometer required for dispersion encoded full range (DEFR) processing [7].

50 Optik&Photonik 2/2016 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
 Medical Applications

techniques which can roughly be classi-

fied into alternating phase shifts between
stationary A-scans (Inter-A-Phaseshift)
and continuous phase shifts during lat-
erally scanning the sample (BM-Mode-
Scan). These techniques try to generate
or reconstruct a complex-valued an-
alytical signal which is unambiguous
under Fourier transform. Phase shifting
methods usually make use of additional
hardware and thereby increase the sys-
tem complexity.
Within IKARUS, a version of the
dispersion encoded full-range (DEFR)
technique [8] was implemented. Mov-
ing and error-prone elements for artifact
Fig. 5 OCT B-mode images of the anterior segment of a porcine eye ex vivo after conven-
suppression are unnecessary and system tional processing (left) and DEFR processing (right). Disturbing mirror artifacts symmetrical
complexity is not increased. The DEFR to the zero delay position (dashed horizontal line) are suppressed and image interpreta-
algorithm removes mirror artifacts by tion is facilitated. The shown A-scan signals are generated along the blue vertical lines.
exploiting a dispersion mismatch be- Imaging is performed by composing two B-scans with two different z-focus positions; one
B-scan is acquired in the front and one in the rear part of the anterior segment while the
tween the OCT interferometer arms.
zero delay position remains unchanged (modified from [7]).
True structure and mirror terms get dis-
tinguishable after numerical dispersion
compensation and mirror artifacts can means of the full range OCT images a laser cutting. Furthermore, the eye pupil
be removed iteratively. Despite a high surgeon is capable to define the follow- limits the usable numerical aperture
computational effort, OCT B-mode ing surgical procedure more reliably. down to about 0.2, increasing the focal
frames are displayed in real time by spot and threshold energy as well. Thus,
highly parallelized image processing on the risk of retinal damage is increased.
Adaptive optics
a graphics processing unit. Because target structures may be in the
The full range imaging capability of Extending the field of application even direct vicinity of the retina, cutting pre-
the clinical prototype is demonstrated deeper into the posterior eye segment, cision and retinal safety are even more
in Fig 5. The OCT B-mode images show individual eye aberrations have a no- critical than in the established applica-
the whole anterior eye segment of a por- ticeable impact and fs-laser surgery is tions in the anterior eye.
cine eye ex vivo including the cornea and impaired by focus degradation. The in- In prior studies, it could be shown that
the rear lens surface. DEFR-processing duced aberrations considerably increase the threshold energy for laser induced
clearly reduces the mirror artifacts and the focal volume and lead to higher optical breakdown (LIOB) in water can
the true sample structure is retained. By threshold energies that are required for be reduced and cutting precision can be

IKARUS
fs-laser

/2 Innovative cataract, presbyopia and retinal

Hartmann-Shack treatment using ultrashort laser pulses
sensor
ip mirror PBS
The German joint research project IKARUS has
deformable
y-scanner
realized an ultrashort pulse laser scalpel, which
mirror
enables minimally invasive laser cuts with high
beam expander precision in order to induce microscopic sliding
planes within the aged lens. Due to the gain in
SLD lens flexibility, the accommodation ability will
be restored by up to three diopters. The system
spectrometer attenuator will be controlled by the surgeon via a simple
interface and enables online monitoring of the
target lens dispersion therapy due to OCT (optical coherence tomo-
wheel compensation graphy) imaging.
photodiode x-scanner Project partners are ROWIAK GmbH, Hannover
(coordinator), ARGES GmbH, Wackersdorf,
eye model QIOPTIQ Photonics GmbH & Co. KG, Gttingen,
photodiode
Laserforum Kln e.V., Cologne, and Laser
Zentrum Hannover e.V., Hannover.
Fig. 6 Schematic overview of an AO-assisted fs-laser system extended by a spectrometer
based FD-OCT system for image-guided cutting in an eye model (modified from [9]). www.ukp-laser.de

2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Optik&Photonik 2/2016 51
 www.optik-photonik.de

Zernike polynomial decomposition Point spread function of the human eye. Different targets can
0.12
aberrated
1.0 aberrated be dipped into the chamber from above.
0.08 corrected
0.8
corrected By means of AO aberration correc-
0.04 tion wavefront errors are reduced, the
Value in m

Irradiance
0.6
0.00 fs-laser focus is improved and the LIOB
-0.04 0.4 threshold energy is lowered (Fig.7).
-0.08 The waveform errors are reduced from
0.2
-0.12 270nm rms (root mean square) down
-0.16 0.0 to 64 nm rms, ignoring tilts and defo-
4 6 8 10 12 14 16 18 20 22 24 26 -15 -10 -5 0 5 10 15
Modal coefcient Distance from center in m
cus aberrations. The point spread func-
tion narrows down to a sharp peak; the
Pulse transmission measurement
0.85 Strehl ratio is improved from 0.11 to
photo- fs-laser
diode 0.78. The LIOB threshold energy in wa-
water 0.80
ter is decreased from about 3.0 J pulse
photo- /2 Transmission
diode 0.75 energy, measured at the entrance of the
0.70
eye model, down to about 1.3 J. LIOB
PBS
thresholds were determined by trans-
0.65 aberrated mission measurements comparing the
collecting LIOB focusing lens
corrected
lens (EFL 17.0 mm) 0.60 energy values at two energy calibrated
0 1 2 3 4 5
Incident pulse energy in J
photodiodes before and behind the eye
model. The onset of a reduced transmis-
Fig. 7 Waveform errors are reduced by closed loop AO correction from 270nmrms down
sion through the eye model is used as
to 64nmrms, ignoring tilts and defocus aberrations. The Zernike polynomial decom- LIOB threshold.
position of the waveform (top left) clearly shows the improvement. The focus quality is A proof of concept for epiretinal cut-
enhanced after AO correction demonstrated by the point spread functions calculated from ting at animal tissue is demonstrated in
the wavefront maps (top right). The Strehl ratio is improved from 0.11 up to 0.78. The LIOB Fig. 8. Targeted cutting of a membrane
threshold energy in water measured at the entrance of the eye model is reduced from
like phantom in front of retinal tissue is
about 3.0J pulse energy in the aberrated case down to about 1.3J in the corrected
case (bottom right). The LIOB thresholds were determined by transmission measurements performed with the corrected system.
comparing the energy values at two energy calibrated photodiodes (bottom left). The The tissue sample was excised carefully
onset of a reduced transmission through the eye model is used as LIOB threshold. from a porcine eye ex vivo. The OCT
images were used to target the fs-laser
enhanced using adaptive optics (AO) for their inner sides. The entrance lens is onto the membrane prior cutting and to
aberration correction. an uncoated aspheric condenser lens inspect the cutting afterwards. The used
The presented functional prototype with effective focus length of 17.0mm pulse energy for cutting of about 1.3 J
for image-guided vitreo-retinal fs-laser in air and models the refractive power at the entrance lens of the eye model was
surgery combines AO for spatial beam
shaping and OCT for focus positioning
(Fig. 6). A detailed description of the lab-
oratory setup is given in [9].
The AO-assisted fs-laser system
at 800 nm is extended by a spectro
meter-based FD-OCT system with
890nm central wavelength and 150nm
spectrum width. The path of the OCT
sample beam is mostly identical to the
fs-laser sharing the deformable mirror,
the scanners and the focusing optics.
The coupling interface is a flip mirror. A
Hartmann-Shack sensor (HASO3-first,
Imagine Eyes, France) is used for ab-
erration measurement and a deform-
able mirror (mirao 52-e, Imagine Eyes,
France) for aberration correction. A Fig. 8 Targeted fs-laser line cutting of a membrane like phantom (synthetic foil) in front
point source for performing wavefront of excised retinal pigment epithelium (RPE) on choroid of a porcine eye ex vivo. The AO
aberration correction is produced by system was operated in open loop configuration with the deformable mirror held in the
corrected shape. The line cut was programmed along the x-axis with 550m length. To
focusing fs-laser pulses at low energy
cut reliably through the foil the laser focus was shifted 10m around the middle position
levels on a diffuse reflecting target
in twenty steps along the z-axis using the deformable mirror. The laser pulse energy was
within the eye model. The eye model near the LIOB threshold of 1.3J at the entrance of the eye model. The foil is separated
consists of a water filled chamber with well about 300m in length as indicated in the B-scans along and perpendicular to the
two lenses in water contact towards line cut. A laser lesion or modification of the RPE is not visible in the OCT images [9].

52 Optik&Photonik 2/2016 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

near the LIOB threshold. The foil is sep-
arated well about 300 m in length. At
each edge, 125 m in length are par-
tially cut. A laser lesion or modification
in the retinal tissue is not visible in the
OCT images. Detailed risk analyses, like
neurophysiological studies in an animal
model, could provide greater insights
concerning retinal safety.
Acknowledgements
The work was part of the research proj-
ect IKARUS (innovative cataract, age
related presbyopia and retina treat-
ment with ultrashort pulsed lasers;
NOs. 13N11847, 13N11848, 13N11850,
13N11851, 19AP9HIz) and was spon-
sored by the German Federal Ministry
of Education and Research (BMBF). The
authors thank Dorothee Brockmann for
Authors
Ben Matthias
was born in Hannover
in 1986, graduated
in technical physics
at Leibniz Universitt
Hannover in 2013.
Since 2010, He is
working at the Laser
Zentrum Hannover
e.V. in the Biomedical Optics Department.
His research is focused on image-guided
fs-laser surgery in the field of ophthalmic
technologies taking advantage of optical
coherence tomography and adaptive optics.
Uwe Oberheide
studied physics at the
University of Hannover
and finished his PhD
at the Laser Zentrum
Hannover in 2002.
He worked in med-
ical research at the
Laserforum Kln and
the Augenklinik am
Neumarkt, in Cologne. Since 2014, he is full
professor at the TH Kln, focusing on opti-
cal technologies and biomedical optics.
Holger Lubatschowski, ROWIAK GmbH, Garbsener Landstr. 10, D-30419 Hannover, E-mail: h.lubatschowski@rowiak.de, Phone: +49 511 277 2950
Ben Matthias, Tammo Ripken, Alexander Krger, Laser Zentrum Hannover e.V., Hollerithallee 8, 30419 Hannover, E-mail: b.matthias@lzh.de, Phone: +49 511 2788 369
Uwe Oberheide, Institut fr Angewandte Optik und Elektronik, Technische Hochschule Kln, Campus Deutz, Betzdorfer Strae 2, 50679 Kln; E-mail: uwe.oberheide@
th-koeln.de, Phone: +49 221-8275-2437
2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
helpful discussions and assistance re-
garding the preparation of the ocular
tissue.
DOI: 10.1002/opph.201600007
[1] G. D. Kymionis et al.: Femtosecond Laser
Technology in Corneal Refractive Surgery:
A Review, J Refract Surg 28 (2012) 12
[2] R. G. Abell et al.: Femtosecond laseras-
sisted cataract surgery versus standard
phacoemulsification cataract surgery: Out-
comes and safety in more than 4000 cases
at a single center, Journal of Cataract & Re-
fractive Surgery 41 (2015) 1
[3] D. V. Palanker et al.: Femtosecond La-
ser-Assisted Cataract Surgery with Inte-
grated Optical Coherence Tomography, Sci
Transl Med 2(58):58ra85 (2010)
[4] H. Lubatschowski et al.: Femtosecond len-
totomy: generating gliding planes inside
the crystalline lens to regain accommoda-
tion ability, J. Biophoton. 3 (2012) 5-6
Alexander Krger
(ne Popp), born
1970, graduated in
physics in 1998 and
finished his disser-
tation about optical
parametric oscillators
in January 2003 at the
University of Bonn.
Optical coherence tomography became one
of his mayor interests in the years 2003
2007 at the Medical Faculty of Technical
University Dresden. Since 2008, he has
worked at the Laser Zentrum Hannover e.V.,
and is now Head of the Image-guided Laser
Surgery Group in the Biomedical Optics
Department.
Tammo Ripken
was born in Hannover
in 1974. Study of
Physics with diploma,
PhD obtained from
the Leibniz Universitt
Hannover in 2007.
Since 2001, he is
working at the Laser
Zentrum Hannover e.V.
(LZH), from 2005 to 2008 as project leader
for fs-laser in ophthalmology, and from 2008
to 2010, as Head of the Laser Medicine
Group. Since 2011 Ripken acts as Head of
Medical Applications
[5] M. Dubbelman et al.: Change in shape of the
aging human crystalline lens with accom-
modation, Vision Research (2005) 117132
[6] D. M. Win-Hall, A. Glasser: Objective
accommodation measurements in pseu-
dophakic subjects using an autorefractor
and an aberrometer, Journal of Cataract
and Refractive Surgery (35) (2009)
[7] B. Matthias, T. Ripken, A. Krger: Disper-
sion Encoded Full Range Fourier Domain
Optical Coherence Tomography for Im-
age-Guidance of Fs-Laser Lens Surgery,
Biomed. Tech. 59 (2014) s1
[8] B. Hofer et al.: Fast dispersion encoded full
range optical coherence tomography for
retinal imaging at 800 nm and 1060 nm,
Opt. Express 18 (2010) 5, 4898-4919
[9] B. Matthias et al.: Concept for image-guided
vitreo-retinal fs-laser surgery adaptive
optics and optical coherence tomography
for laser beam shaping and positioning,
Proc. SPIE 9307, Ophthalmic Technologies
XXV, 93070Z (2015)
the Biomedical Optics Department. His main
research areas are laser-assisted medicine,
laser-tissue interaction and laser-based
medical imaging.
Holger Lubatschowski
studied physics at the
University of Bonn,
Germany. After his
PhD he moved to
Hannover and became
Head of Medical Laser
Group at the Laser
Zentrum Hannover
e.V. (LZH). In 2001, he
completed his postdoctoral lecture qualifica-
tion for physics at the physics faculty of the
University of Hannover and became assis-
tant professor. Since then, Lubatschowski
has headed the department of Biomedical
Optics at the LZH. Here, he acquired
expertise in laser processing of biological
tissue which is demonstrated by more than
200 scientific publications in the area of
laser medicine and laser-tissue interaction
in leading scientific journals. Since 2010,
Lubatschowski concentrates his work on his
own company ROWIAK GmbH, a spin-off
from the LZH. ROWIAK develops and pro-
duces ultrafast laser systems for ophthalmic
surgery.
Optik&Photonik 2/2016 53