Download Journal of Cataract and Refractive Surgery Symposium Corneal

Lisbon 2005
Journal of Cataract and Refractive Surgery Symposium
Corneal Biomechanics
Cheryl Guttman
in Lisbon
ONCE a subject of scientific curiosity,
corneal biomechanics is now the focus of
intense research in many areas of clinical
ophthalmology. A special symposium of the
Journal of Cataract and Refractive Surgery
held during the XXIII Congress of the
ESCRS spotlighted the most recent
developments.
Cynthia Roberts PhD, The Ohio State
University, chairperson of the symposium,
explained that with increased
understanding of corneal biomechanics
comes the potential to identify sources of
error in IOP measurement and therefore
to develop more accurate tonometry
techniques. A better understanding of
corneal biomechanics might also allow for
improved predictability of refractive
surgery outcomes and could improve the
preoperative identification of eyes at risk
for developing ectasia after refractive
surgery.
“Corneal biomechanics
can be exploited to
manipulate shape and
vision, and I see
biomechanical
customisation as the
next generation in
refractive surgery,”
segments that are
drivers to the
biomechanical
response and doing
that reduces the
variability associated
with variation in
biomechanical
properties,” noted Dr
Roberts.
In addition, a
contralateral eye study
performed by Dr
Roberts and
colleagues
demonstrated the
biomechanical
response after LASIK
could be manipulated
by the choice of laser
used to perform the
ablation.The effect was
measured by
differences in induced
higher order
aberrations and could
be attributed to
between-laser
differences in ablation
zone sizes.
Schematic diagram of the biomechanical response to circumferential severing of corneal lamellae.
The anterior peripheral lamellar segments are “relaxed” allowing swelling which leads to central
flattening and peripheral steepening.
Schematic diagram of the proposed influence of ablation zone size on the biomechanical response.
By ablating more of the peripheral lamellar segments, the biomechanical response is reduced, and
the variability due to individual biomechanical properties is reduced.
“Corneal biomechanics can be exploited
to manipulate shape and vision, and I see
biomechanical customisation as the next
generation in refractive surgery,” Dr
Roberts said.
She cited various studies to show that
the corneal biomechanical response can be
manipulated once it is understood. For
example, a study by John Marshall PhD,
showed refractive predictability after
LASIK could be improved by changing
from a 5.0 mm to a 6.0 mm optical zone.
The explanation for the differences lies in
corneal biomechanics.
“Adding 1.00 mm to the ablation zone
wipes out some of the peripheral lamellar
Courtesy of Cynthia Roberts PhD
Cynthia Roberts PhD
Average tangential curvature maps from a contralateral eye study indicating that the eyes with the
smaller ablation zone (right) had significantly greater paracentral steepening and also spherical
aberration induction, than the contralateral eyes.
Modelling based on
structural
characterisation
William J. Dupps MD,
PhD, first described a
biomechanical model
of corneal response to
surgery in 1995.
According to that
model, the normal
cornea is seen as a
stacked layer of
lamellae and can be
analogised to rubber
bands with sponges in
between. A refractive
surgery procedure that
circumferentially severs
the tension-bearing
lamellae can be
thought of as removing
tension from some of
the rubber bands. As a
result, they can no
longer hold water out
of the sponges, and in
the midperiphery and
periphery, the sponges
swell.
In the eye, that change is seen as
paracentral and peripheral thickening and
steepening. However, due to structural
interconnections and communication
between anterior and posterior layers
within the cornea, any procedure that
circumferentially severs tension-bearing
lamellae also leads to central biomechanical
flattening.
Biophysicist Keith Meek PhD, and
colleagues at Cardiff University have been
using X-ray diffraction to analyse the
ultrastructure of the corneal stroma in
order to shed light on how the cornea
responds as a unit to a procedure that
affects only one part of it.
“Collagen provides mechanical strength
to the cornea and it is the orientation and
distribution of the fibrils that largely govern
how the cornea responds to mechanical
stress.That is why it is important to study
the distribution and organisation of lamellae
in the cornea,” Dr Meek said.
The technique being used involves passing
an intense beam of x-rays, generated by a
synchrotron, through the cornea and
measuring how the x-rays are scattered.
This provides unique quantitative
information about fibril orientation and
distribution and allows these parameters to
be mapped across the cornea.
At present, only two-dimensional maps
are produced.Whilst these can help to
explain some of the gross biomechanical
properties of the cornea, Dr Meek noted
that a three-dimensional model would be
needed to determine potential implications
for refractive surgery.
Studies comparing normal eyes and those
with keratoconus show that the gross
organisation of the stromal lamellae is
dramatically disturbed in the keratoconic
eyes compared with the normal eyes,
particularly in the cone position. In addition,
there is variation in the distribution of the
collagen fibrillar mass in the keratoconic
eyes as compared with the relatively
uniform distribution seen in the normal
cornea.
“These findings lend further support to
the concept that collagen organisation in
the cornea is pivotal to the shape of this
tissue,” Dr Meek said.
New measurement tools
Researching corneal biomechanics and the
ability to effectively manipulate those
properties in clinical practice will depend
on the availability of tools that allow noninvasive, in vivo measurement.
EuroTimes December 2005
Courtesy of William J. Dupps MD, PhD
Jay Pepose
different regions of the cornea, yields
results that are not confounded by the
epithelium, and has a sampling depth range
that lies somewhere between 250 and 750
microns. It also performed as predicted in
showing an increase in wave velocity
following corneal cross-linking and
decreases in velocity after relaxing
incisions.
“Issues that need to be addressed in the
clinical setting include sensitivity to surface
hydration, IOP and indentation artefacts,”
he added.
A second instrument that Dr Dupps is
creating with collaborators Matthew Ford
and Andrew Rollins PhD from Case
Western Reserve University is a noncontact system that uses high-speed OCT
and sophisticated software to measure and
map both the magnitude and direction of
strain within different layers of the cornea.
Currently, the information is depicted in
two formats: 1) as a two-dimensional,
cross-sectional map using different colours
to represent different levels of strain
intensity, and 2) as a vector map that
provides information
on strain direction
and magnitude. The
researchers are
currently developing
software that will
provide a threedimensional
reconstruction of
strain within the
cornea.
Among the
potential applications
for this technology,
early detection of
keratoconus may be
most important. The
long list of other
possible uses includes
characterisation of
wound healing
responses in postkeratoplasty eyes and
the prediction of
biomechanical
responses to
refractive surgery.
“Ultimately,
however, our toolbox
for investigating
corneal biomechanical
properties will need
to contain a variety of
different instruments,
each providing a
different view of these
complex phenomena.
In addition, translation
Map based on X-ray diffraction findings showing the orientation of preferentially aligned lamellae at
different points across the cornea superimposed on a picture of an eye. The cornea’s collagen is
of this information
arranged predominantly vertically and horizontally in the central cornea whereas it is essentially
into clinical use will
tangential at the edge of the cornea. As one moves from the centre of the cornea, there is more
require
collagen so the plots get larger. The map allows you to see at a glance if a given penetrating
multidisciplinary
incision would sever the fibrils or cut parallel to most of them.
“For years, no one but scientists in the
field cared about optical aberrations.
However, with the development of
wavefront sensors and the ability to
measure wavefront errors came new
interest and research that led to
understanding of how to control that
outcome,” Dr Roberts said.
William J. Dupps MD, PhD, Cole Eye
Institute, described two investigational
modalities for measuring corneal
biomechanical properties.
The first is a handheld ultrasound
prototype device dubbed the Sonic Eye,
which is being developed by PriaVision, Inc.
It measures the “time of flight” or velocity
of a wave propagated between two points
along a tissue sample.
“This instrument provides one modality
for characterising corneal stiffness. The
propagation speed of a sonic wave is faster
in a stiffer cornea,” Dr Dupps explained.
In testing a prototype device in porcine
and human donor eyes, Dr Dupps and
colleagues found that the technology offers
good measurement repeatability across
Courtesy of Keith M. Meek PhD
Kieth Meek
EuroTimes December 2005
Jesper Hjortdal
collaboration to translate complex
biomechanical tissue data into improved
diagnostic criteria for ectasia and enhanced
surgical outcomes,” said Dr Dupps.
“Issues that need to be
addressed in the
clinical setting include
sensitivity to surface
hydration, IOP and
indentation artefacts,”
William J. Dupps MD, PhD
Characterising biomechanical
responses to corneal procedures
Several speakers presented studies
investigating the effects of different
refractive surgery procedures on the
cornea’s biomechanical response. Sunil
Shah MD, The Midland Eye Institute,
Birmingham, UK, used the currently
marketed Ocular Response Analyzer
(ORA, Reichert) to measure changes in
corneal hysteresis, which is a reflection of
corneal viscoelasticity.
The study followed
a consecutive series
of 80 eyes that
underwent LASIK or
LASEK. Betweengroup differences
were expected since
LASIK places the
ablation deeper in the
cornea where the
layers are structurally
distinct from the
more superficial
layers.
The amount of
hysteresis was
reduced significantly
from 11.5 mm Hg
(range 7.9 mmHg to
16.7 mmHg) at
baseline to 9.3 mm
Hg (range 2.5 mmHg
to 13.1 mmHg) for
the overall cohort.
However, the mean
change in hysteresis
was not significantly
different between the
LASIK and LASEK
groups.
“We were
surprised by that
finding as we had
expected cutting a
lamellar flap for
Michael Knorz
Ioannis Pallikaris
LASIK would affect the biomechanical
properties of the cornea differently than a
LASEK surface ablation,” Dr Shah said.
There were other important findings in
the study. For example, Dr Shah noted that
the mean postoperative hysteresis value of
9.3 mmHg is lower than the mean for the
keratoconus population at his clinic.
“This observation suggests that
refractive surgeons probably do need to
be concerned about the biomechanical
effects of their procedures on the cornea,”
he commented.
In addition, a regression analysis of the
relationship between change in corneal
hysteresis and change in corneal thickness
showed only a moderate correlation at
best due to very wide spread of the data.
“This finding indicates hysteresis does
not change by a predictable amount per
unit change in corneal thickness, and so
refractive surgeons cannot use corneal
thickness change to predict which patients
will have a huge postoperative reduction in
hysteresis and therefore biomechanical
property problems. However, it may be
prudent to not offer refractive surgery to
a patient with a low hysteresis or at least
to counsel that individual about potential
risk,” Dr Shah said.
Courtesy of Sunil Shah MD
Cynthia Roberts
assessment tests, including laser polarimetry
and tonometry, are filtered through the
biomechanical properties of the cornea.
Research in the area of IOP
measurement has revealed that
biomechanical properties, rather than
corneal thickness or curvature, are likely
the largest source of error in IOP
measured with Goldmann applanation
tonometry (GAT).The Ocular response
Analyzer (ORA, Reichert) and the Pascal
Dynamic Contour Tonometer (PDCT, SMT
Swiss Microtechnology) are two new
commercially available tonometry
instruments that may reduce errors due to
the biomechanical property changes
induced by laser ablation refractive surgery.
Tangential and axial difference maps (Orbscan II) after laser ablation.
Note the peripheral steepening.
Jesper Hjortdal MD and colleagues at
Aarhus University are also comparing
outcomes after surface ablation and
intrastromal procedures to determine
whether the two surgeries are
biomechanically distinct.Their long-term
study originally randomised 45 eyes with
myopia between -6.0 and -8.0 D to PRK or
LASIK. Corneal rigidity was assessed by the
apparent IOP value measured with
pneumotonometry (Reichert).
“There appears to be
some interlamellar
healing during the first
year after LASIK while
over the long-term,
some re-stiffening
appears to occur in eyes
that undergo PRK,”
Jesper Hjortdal MD
The results showed the apparent IOP
readings were significantly affected after both
surgeries, mainly due to the reductions in
corneal thickness. For both groups, apparent
IOP was approximately 6.0 to 7.0 mmHg
lower after the procedure, and that change
could be partly explained by the 70 to 80
micron reductions in central corneal
thickness (CCT) associated with the
procedures.
When the results were analysed with the
data divided by follow-up interval, timedependent differences were noted. Between
one and 12 months after surgery, there was
a large increase in CCT in the PRK eyes but
little change in the LASIK group. However,
apparent IOP increased significantly in the
LASIK eyes. Between one and three years
after surgery CCT increased slightly and to a
similar extent in both groups, while apparent
IOP increased slightly in the PRK eyes and
decreased slightly in the LASIK eyes.
“These data indicate corneal rigidity is
permanently decreased after both LASIK and
PRK. However, there appears to be some
interlamellar healing during the first year
after LASIK while over the long-term, some
re-stiffening appears to occur in eyes that
undergo PRK,” Dr Hjortdal said.
Michael C. Knorz MD, FreeVis LASIK
Centre, Mannheim, Germany, evaluated the
topographic and wavefront changes
occurring when LASIK was performed in a
two-step procedure in order to separately
characterise the cornea’s biomechanical
responses to flap creation and ablation. He
obtained measurements from 48 eyes of 24
patients after the flap was cut, lifted, and
replaced.Then, patients returned three
months later for the ablation, and the
topographic and aberrometry measurements
were repeated.
The topographic evaluations showed the
flap creation caused no change in central
curvature, although cutting the cornea was
associated with a significant increase in
paracentral curvature and an even greater
increase in peripheral curvature. Consistent
with the biomechanical response model
introduced by Dr Dupps, the ablation caused
a significant decrease in central curvature
and was also accompanied by a significant
increase in paracentral and peripheral
curvature.
“These findings
underline the
importance of
understanding corneal
biomechanics in order
to refine ablation
pattern algorithms,”
Michael Knorz MD
Results from wavefront evaluation showed
the flap creation caused a significant increase
in spherical aberration that was consistent
with the increase in peripheral steepening.
Spherical aberration was also increased
significantly by the ablation, despite the fact
that the procedures were customised.
“The results of this study show that both
cutting the flap and the laser ablation
independently cause an increase in peripheral
corneal curvature and thereby spherical
aberration, and these findings underline the
importance of understanding corneal
biomechanics in order to refine ablation
pattern algorithms,” Dr Knorz said.
Implications for IOP measurement
Understanding of corneal biomechanics and
the effects of refractive surgery on those
properties is also important for determining
glaucoma risk because some of the standard
“More accurate
measures of IOP
will require
instrumentation that
performs dynamic
rather than static
applanation
measurements and
therefore assesses and
compensates for
corneal biomechanics,”
Jay Pepose MD PhD
Jay Pepose MD PhD, Pepose Vision
Institute and Washington University School
of Medicine, reported the results of a
prospective study comparing pre- to postLASIK IOP changes measured using GAT,
the ORA, and the PDCT in a cohort of 66
eyes with an average MRSE of -5.0 D.Two
values were generated with the ORA: the
ORA-G, which has been shown to correlate
with the GAT value, and an IOP-CC, which
is a corneal compensated measure,
generated using a new third-generation
nomogram.
There was a greater mean reduction in
post-LASIK IOP when it was measured with
the GAT and ORA-G than with PDCT.The
IOP reduction measured with the ORA was
minimised by the IOP-CC.The GAT and
ORA-G values were correlated to
pachymetry, while the IOP measurement
derived with the PDCT was not.
“While there have been proposals to
create linear algorithms to modify the GAT
data in eyes after laser ablation refractive
surgery, there is no scientific basis to
support that approach because there is only
a weak positive correlation between the
GAT IOP and central pachymetry.We know
Goldmann IOP generally drops after radial
keratotomy and hyperopic LASIK.Those
procedures induce little change in central
pachymetry but do have a profound effect
on corneal rigidity.Therefore, more
accurate measures of IOP will require
instrumentation that performs dynamic
rather than static applanation
measurements and therefore assesses and
compensates for corneal biomechanics,” Dr
Pepose said.
EuroTimes December 2005
Courtesy of Jay Pepose MD PhD
Courtesy of Jesper Hjortdal MD
Courtesy of Michael C. Knorz MD
Tangential and axial difference maps (Orbscan II) after LASIK cut without ablation.
Note the peripheral steepening.
The
the
Courtesy of Jay Pepose MD PhD
18
globe and how they
may modulate
characteristics of
corneal stress. Dr
Pallikaris is
investigating
relationships
between ocular
rigidity, which
expresses the
elastic properties of
the entire globe,
blood flow, and the
The Ocular Response Analyzer (Reichert) (left) is a non-contact device that utilizes a collimated air pulse to
applanate the cornea, along with an infrared electro-optical detection system (right).
cornea.
He explained that
the cornea is a living
structure that exists
under a
continuously
fluctuating pressure
load as a result of
the pulsatile blood
flow in the choroid.
When the cornea
is ablated in
refractive surgery,
the stress localised
at the cornea may
be increased, despite
the fact that the
system is continuing
to work under the
same pressure. That
change may cause
the cornea to bend
outwards, affecting
The Pascal Dynamic Contour Tonometer (Zeimer) (left) utilises the “principle of Pascal” that when the contours of
its final curvature.
the cornea and tonometer match, then the pressure measured at the surface of the eye equals the pressure inside
The risk of ectasia
the eye (right).
may be associated to
Adding another dimension
the temporal characteristics and
Ioannis G. Pallikaris MD PhD, Institute of
fluctuation amplitude of the pressure load
Vision and Optics, Crete, approaches the
on the cornea.
subject of the consequences of refractive
However, responses elsewhere in the
surgery on corneal biomechanics with a
globe must also be taken into account, and
broader view. Recognising that the cornea
in that regard, it is important to consider
is just one part of a larger organ, he is
the fact that highly myopic eyes may have
considering responses elsewhere in the
relatively thin scleras. Therefore, it seems
EuroTimes December 2005
reasonable that tissue relaxation
posteriorly, away from the cornea, may
result to reduced corneal stress in those
eyes after the cornea is ablated.
“According to this model, the localised
stress on the cornea may be relatively
reduced in highly myopic eyes with thin
walls and low rigidity. Perhaps that explains
why ectasia is more of a problem in eyes
that have been treated for between -6 and
-10 D of spherical error than it is for
higher myopes. Studies we have performed
indicate ocular rigidity is not strongly
related to corneal biomechanics. However,
ocular rigidity can modulate the
characteristics of corneal stress. Its role in
keratectasia needs to be investigated,” Dr
Pallikaris said.
Cynthia Roberts PhD
Torrence A. Makley Research Professor
Department of Ophthalmology
Associate Director, Biomedical Engineering
The Ohio State University
[email protected]
Kieth Meek PhD
Structural Biophysics Group
School of Optometry and Vision Sciences,
Cardiff University, UK
[email protected]
William J. Dupps MD PhD
Cole Eye Institute, Cleveland, Ohio, USA
[email protected]
“According to this
model, the localised
stress on the cornea
may be relatively
reduced in highly
myopic eyes with thin
walls and low rigidity.”
Sunil Shah MD
The Midland Eye Institute, Birmingham, UK
[email protected]
Jay Pepose MD
Professor of Clinical Ophthalmology and
Visual Sciences
Washington University School of Medicine
St. Louis, Missouri, USA
[email protected]
Jesper Hjortdal MD
Department of Ophthalmology
Århus University Hospital, Denmark
[email protected]
Ioannis Pallikaris MD PhD
Michael C. Knorz MD,
FreeVis LASIK Center,
University Medical Center
Mannheim, Germany
[email protected]
Ioannis G. Pallikaris MD PhD
Institute of Vision and Optics
University of Crete, Greece
[email protected]