Transcript Corneal Biomechanical Properties in Keratoconic, Forme Fruste

Multiple studies have shown ex vivo
that keratoconic (KCN) corneas are
more elastic and less rigid than
normal eyes. Recently, by use of the
Ocular Response Analyzer, these
properties are able to be measured in
vivo. Keratoconus, however, is a
disease that often can be easily
diagnosed clinically at the slit lamp.
It is the more subtle cases of forme-fruste keratoconus that at times can be
more difficult to accurately diagnose, which, in a laser refractive center, can
have devastating consequences (see picture). It was the goal of this study to
evaluate the biomechanical differences between normal and keratoconic
corneas through the entire range of disease states: from the earliest stage
(‘pre’ forme-fruste keratoconus) all the way through fulminant clinical
disease.
It is our hypothesis that there is a
continuum of impaired
biomechanics that is significantly
different from normal corneas. It is
our hope that through evaluating,
understanding, and exploiting these
differences, we can more easily
diagnose even the earliest forms of
forme-fruste keratoconus. By so
doing, we hopefully can augment
our refractive screening techniques
and avoid the disasterous
consequences of operating on such
a cornea.
Statement of Commercial Interest:
RDJ: None
DRH: honoraria from Reichert for educational lectures on corneal biomechanics
•Retrospective case-review study.
•230 eyes of 201 patients were divided into
groups according to their keratoconic severity
score (KSS) as defined by the Collaborative
Longitudinal Evaluation of Keratoconus
(CLEK) study group1
•KCN group (KSS=3): 73 eyes of 54 patients
(see example figure below).
•FFKCN group (KSS=1 to 2, or 0 if it is the
fellow eye of a KCN): 42 eyes of 32 patients.
•Controls (KSS=0): 115 healthy eyes of 115
age/sex matched patients
For each eye Orbscan was used for topographical
and pachymetry measurements. The ocular
response analyzer (OR) was used to obtain a
biomechanical waveform from which the corneal
hysteresis (CH) and corneal resistance factor
(CRF) are obtained. During the measurement
procedure, a rapid air impulse is used to applanate
the cornea. Utilizing an electro-optical system,
two applanation pressures are recorded (see figure
above). The first pressure occurs when the cornea
is flattened and moving inward towards concavity
and the other as the cornea flattens and is moving
outward back to the normal convex shape. This
applanation process takes about 20 milliseconds.
Due to its viscoelastic properties, the
cornea resists the dynamic air puff
differentially on the inward and outward
applanation events, resulting in the inward
and outward flat phase of the cornea
occurring at two different pressure values.
Corneal hysteresis (CH) is defined as the
difference between these two pressure
values. CH is thought to correlate with the
amount of viscous dampening inherent to
the cornea. The CH measurement also
provides the basis for an additional
parameter, the corneal resistance factor
(CRF). This measure appears to be an
indicator of the overall mechanical
resistance of the corneal tissue, including
both viscous and elastic components, and
is derived from specific combinations of
the inward and outward applanation values
using proprietary algorithms2.
1. McMahon TT, Szczotka-Flynn L, Barr JT, et al. A new
method for grading the severity of keratoconus: the
Keratoconus Severity Score (KSS). Cornea
2006;25:794-800
2. Luce DA. Determining in vivo biomechanical
properties of the cornea with an ocular response
analyzer. J Cataract Refract Surg 2005;31(1):156-62
The table to the right summarizes
comparisons between groups. On
intergroup analysis, there was a
statistically significant difference in
mean CH and CRF in the normal group
compared to all other groups, including
both FFKCN sub-groups (p<0.0001).
There was also a statistically significant
difference in the mean CH and CRF
between the FFKCN and KCN groups
(p=0.012 and p=0.001, respectively).
However, there was a significant difference
in mean CCT between the 3 groups as well
(ANOVA p<0.0001).
After adjustment for CCT the
difference in mean CH and CRF
remained statistically significant
when comparing normal controls
with all other groups, including the
2 FFKCN sub-groups (p<0.0001
in all comparisons). After
adjustment for CCT, the difference
in mean CH between FFKCN and
KCN groups was no longer
significant (p=0.13), while the difference in mean CRF remained significant (p=0.015). In further
analysis of the FFKCN subgroups, mean CRF between FFKCN-A (fellow eye of the keratoconic)
and KCN groups remained significant (p=0.027) but was no longer significant between FFKCNA and FFKCN-B or FFKCN-B and KCN groups. The table above shows the comparison
between each subgroup for both CH and CRF.
Correlations between the keratoconic
severity score (KSS) and CH, CRF and
CCT are shown in the table to the left.
There was a strong Spearman correlation
coefficient between all three parameters and
severity of disease (CH: r=-0.73; CRF: r=0.78; CCT=-0.73; ANOVA p<0.001 in all).
Student T-test showed a significant
difference in all parameters between KSS 2
and 3 (CH: p=0.014; CRF: p=0.003; CCT:
p=0.023). Comparison between KSS 1 and
2 showed a significant difference for CCT
(p=0.013), but not for CH or CRF (p=0.769
and 0.136, respectively). Linear regression
analysis showed a significant correlation
between KSS and CH as well as CRF
2
(p<0.001) with the R value strongest in the
CRF (R2=0.57, figure to left) compared to
CH (R2 =0.48).
Our study found that the CH and CRF measurements in eyes
with KCN and FFKCN are significantly lower than eyes with
normal corneas. This study suggests that the CH and CRF values
may be useful additional parameters, in conjunction with
topography, to aid the clinician in the difficult task of identifying
subtle forms of FFKCN. In particular, when faced with normal
topographic findings (KSS<1), the CH and CRF parameters hold
significant value in identifying abnormal corneal biomechanics.
An important finding in our study is the
statistically significant differences in CH and
CRF between the topographically normal
fellow eyes in patients with manifest KCN in
the other eye compared to age and CCT
matched normal controls. In our study, there
were 10 patients with KSS scores of 0 (n=4) or
1 (n=6) whose fellow eye had manifest
keratoconus, (FFKCN-A subgroup). We did not
label these eyes as fellow eyes of patients with
“unilateral” keratoconus because the authors
believe keratoconus to be a bilateral,
asymmetric disease. An example Orbscan of an
eye with manifest keratoconus (above) and its
topographically normal fellow eye (below) is
shown.
Normal fellow
eye (n=10)
Mean CCT (µm)
499 ± 34.9
Mean CH (mm Hg) 8.6 ±1.4
Mean CRF (mm Hg) 8.7 ±1.4
Controls
(n=20)
500 ±14.8
10.4 ±1.7
10.4 ±1.7
P value
0.891
0.006
0.010
Indeed, our findings support this hypothesis: the mean CH and CRF of these
eyes (8.6 ±1.4 and 8.7 ±1.4 mm Hg respectively) were statistically
significantly different from the mean CH and CRF of eyes from age and CCT
matched normal controls (n=20 eyes of 20 patients, 10.4 ±1.7 and 10.4 ±
1.7 mm Hg respectively). Interestingly, there was not a statistically significant
difference between the manifest keratoconic eye and the fellow,
topographically normal eye with regard to CCT, CH, or CRF. This further
supports the hypothesis that the fellow eye is not “normal” but, in fact, has
more biomechanical similarity to the pathologic eye.
Forme fruste keratoconus can be a subtle ectatic condition often
missed by topographic/tomographic analysis. The long term success
of refractive surgery, particularly LASIK, depends on our ability to
identify corneas at risk for keratectasia. This study suggests that the
corneal biomechanical parameters CH and CRF may be useful tools
in further refining our ability to identify subtle forme fruste
keratoconus. New ORA software will allow detailed assessment of
the biomechanical waveform obtained, analysis which may further
enhance our diagnostic capabilities. Ultimately, combining ORA
metrics with tomographic data should lead us to improved exclusion
criteria and, consequently, to a further reduction in the incidence of
keratectasia following refractive surgery.