ESCRS 2012 - Course IC 71 - Treatment strategy for custom ablation of visually
disturbing irregular astigmatism after refractive surgery and in keratoconus
Tomography and Biomechanical Assessment for Enhanced Planning Therapeutic
Corneal Procedures
Renato Ambrósio Jr, MD, PhD

Professor of Ophthalmology of Federal University of São Paulo and Pontific Catholic Federal
University of Rio de Janeiro

Scientific Coordinator of the Rio de Janeiro Corneal Tomography and Biomechanics Study Group

Director of Cornea and Refractive Surgery of Instituto de Olhos Renato Ambrósio, Visare Personal
Laser and Refracta-RIO
Correspondence to:
Renato Ambrósio Jr
Rua Visconde de Pirajá 595/808 – Ipanema
Rio de Janeiro, RJ – 22410-002
Dr.renatoambrosio@gmail.com
I.
Why it is critical to evolve on the diagnosis in Refractive Surgery?

Refractive surgery determined the need for understanding corneal shape
(geometry), optical (power and quality - aberrations) and biological
(healing and biomechanical) properties.

Parallel to progresses on corneal semiology, there has been an associated
increase in understanding other issues, such as corneal wound healing and
biomechanics.

Also, sphere and cylinder refraction evolved to the measurement of
wavefront optical aberrations of the whole eye.

Integration of corneal and whole eye optics measurements enables
calculations of internal optics.

Understanding the clinical relevance of these new methodologies has been
a critical part of the evolution in this field!

Ectasia is a very severe complication after keratorefractive procedures.
Risk factors have been described based on surgical parameters and
preoperative screening tools: topography (axial anterior curvature map –
typically from Placido´s reflection) and single point central pachymetry.

However, there are many cases that had ectasia without risk factors.

There are also cases with one or more risk factors with excellent and
stable long-term outcomes.

Thereby, new technologies have been needed to enhance sensitivity
and specificity for screening refractive candidates, as well as to
provide objective parameters to choose and plan the refractive procedure
(increasing efficacy and safety) and to evaluate clinical results.

However, we believe that corneal topography and central thickness
measurements do NOT provide enough clinical data for decision
making if we should ablate FFK cases.

Interestingly, there are also many reports and there is a major
concern regarding non-explained cases of ectasia after LASIK (and
also surface ablation) with normal preoperative topography and low
risk scores.

This is why we considered, 5 years ago, the need for advanced
technologies to screen refractive candidates and started working
with new diagnostic tests such as the non contact air puff
tonometer with corneal biomechanical measurements (Ocular
Response Analyzer [Reichert], Corvis ST [Oculus]) and the rotating
Scheimpflug Corneal Tomography (Pentacam [Oculus]).

Other imaging technologies such as the OCT, very high frequency
ultrasound tomography and also other biomechanical tests, such as
the electronic speckle pattern interferometry, would definitively add
to the exams that may be used for enhanced screening of refractive
candidates.

Other approaches for the evolution for the enhanced evaluation of
ectasia would include keratocyte counts, in vivo molecular biology
testing of the cornea and eventually genetic testing.
II.
Defining: Forme-fruste Keratoconus (FFK)

Forme-fruste is an incomplete or abortive form of a disease
or condition

Forme-fruste keratoconus (FFK) is defined as an incomplete or
abortive form of keratoconus. This condition was described by
Amsler in 1937.

Krachmer advocates that the term “mild” may be more appropriate
(Cornea Day, Pre AAO 2008), based on the fact that mildly
irregular mires with inferior steepening is keratoconus. “Early” is
not appropriate as well since “early” implies progression, which
cannot be anticipated.

“Sub-clinical” keratoconus may be used to describe mild disease in
asymptomatic patients with normal BSCVA.

In this scenario (FFK), there is little to no slit lamp findings
(Fleischer ring [iron line], Vogt's striae), and typically the patient has
normal BSCVA. Prominent corneal nerves are very common
among such cases but this is a non specific finding.
III.
How is the Diagnosis of FFK made? Corneal Topography and
Beyond…

This is possible to detect “mild” keratoconus cases or (FFK)
without corneal topography.
(Note that Amsler was able to describe FFK in 1937, much before
the advent of computerized topography).

Scissoring of the retinoscopic reflex, careful slit lamp
biomicroscopy, central and peripheral corneal thickness
measurements, regional keratometry and keratoscopy are clinical
tests that enable the identification of very subtle clinical signs of
keratoconus, thereby identifying FFK. However, sensitivity and
specificity is far from optimal and complementary tests are needed.

The diagnosis of FFK is critical when screening refractive surgery
candidates, because such conditions are the most important risk
factors for progressive “iatrogenic” ectasia that may occur after
LASIK and Surface Ablation.

About 1% of refractive candidates have ectasia detected during
screening (keratoconus and pellucid marginal degeneration). The
majority of such cases may present with normal BSCVA and
unremarkable slit lamp biomicroscopy (Examples 1 and 2).
Example 1: Forme-Fruste or Early (or better “mild”) Pellucid Marginal
Corneal Degeneration (PMCD)

57 years old male, presented as a candidate for LASIK

Stable refraction for 8 years; no family history of keratoconus

UCVA was 20/400 in OD and counting fingers in OS

Manifest refraction in O: −8.50 +2.50 × 013, giving 20/20;
and in OS: −9.00 +2.00 × 173, giving 20/20.

Ultrasonic corneal pachymetry measurements: 550 and 541
micron in OD and OS respectively.

Regional inferior peripheral thickness were 518 and 522
micron in OD and OS respectively.

Cornea examination by slit lamp demonstrated superficial
punctuate keratitis in both eyes but no evidence of corneal
thinning, iron lines, or protrusion.

The patient was advised not to undergo LASIK or PRK and to
return for a new exam within 6 months. If stability is
documented, Custom Surface Ablation may be advocated with
a detailed informed consent.
(Ambrósio R Jr, Wilson SE. Cornea. 2002 Jan;21(1):114-7.)
Figure 1 – Example 1: Corneal topography revealed inferior steepening
with the pattern of a “lazy C” or lobster claw shape and an area of central
corneal flattening. Age presentation and localized inferior thinning are
favorable for the diagnosis of early pellucid corneal marginal degeneration.
It has been suggested the term forme-fruste pellucid for describing such
cases.
However, this may be debatable if this is a variant of keratoconus. We
believe that the complete differentiation between keratoconus and PMCD
may be done only with elevation 3D cornel tomography and a
comprehensive pachymetric evaluation over the entire cornea.

Computerized corneal topography provided more sensitivity to
detect keratoconus patterns in asymptomatic patients.

The advent of progressive “iatrogenic” ectasia after LASIK and
Surface Ablation despite of normal topography and without other
identifiable risk factors lead to the understanding of the need for
more sensitive diagnosis.
Example 2: Asymmetric Forme-fruste Keratoconus (not unilateral)
with normal curvature maps in the contra-lateral eye

23 years old male, presented as a candidate for LASIK

No contact lens history; no family history of keratoconus

Mild allergy; Positive for eye rubbing

UCVA was 20/200 in OD and 20/80 in OS and BSCVA to
20/20 in OD and 20/15 in OS

MRx: -2.75 -1.25 x 27 – OD and -1.00 -0.50 x 126 – OS

Corneal Hysteresis (CH) and Corneal Resistance Factor (CRF)
were 8.4 and 9.1 mmHg and 6.1 and 7.2 mmHg in OD and
OS respectively with a low amplitude ORA signal in OU.

CCT (US): 519 and 531 micron in OD and OS

Slit Lamp is Normal in OU
Figure 2 – Example 1: Placido’s axial curvature map revealing
keratoconus pattern in OD and a normal pattern OS.
Considering the patient is asymptomatic unless for myopic
astigmatism, but with normal BSCVA, the right eye would be
considered as a forme-fruste or mild keratoconus.
Interestingly, the left eye has a remarkably normal topography.
Cases like the left eye represent the best model to test if the
enhanced screening tests are sensitive to detect any
abnormality (see enhanced test results).

There are also cases with topographic signs of keratoconus, such as
inferior steepening which are stable with no progression over time.
This may represent 0.5% of normal population (Example 3).
Example 3: Asymmetric bow tie, stable for over 10 years

33 years old male; UCVA 20/15 OU

MRx: +0.25 = -0.25 x 21 - OD and plano OS

Corneal Hysteresis (CH) and Corneal Resistance Factor (CRF)
were 11.8 and 10.6 mmHg and 11.2 and 10.1 mmHg in OD
and OS respectively with a normal ORA signal in OU.

CCT (US) is 502 and 505 micron in OD and OS

Slit Lamp is Normal in OU

Placido’s Topography is remarkably similar to the Pentacam’s
Sagittal Anterior Map in OU with inferior steepening and
asymmetric bow tie.

Conclusion: Normal thin cornea (this case illustrates enhanced
specificity).
Figure 3: Axial curvature maps with IS /ABT, a keratoconic suspect pattern
OD.
USVA is 20/15 and there is also documented topographic stability over 10
years.

Conreal surface disorders may also lead to an abnormal corneal
topography similar to keratoconus.
Example 4: False Positive Topography for Keratoconus due to irregular
surface
Figure 4: Placido’s Reflection and Corneal Topography Maps from a case
with Anterior Basal Membrane Dystrophy.
Figure 5: Biomicroscopy from a case with ABMD demonstrationg marked
surface irregularity which leads to a keratoconic pattern on surface
topogrpahy.
This patient had custom surface ablation for treating hyperopic
astigmatismo with excellent visual results and resolution of recurrent
erosion.

Other case of a false positive for FFK in corneal topography is
contact lens corneal warpage, which is reversible, weeks to months
after discontinuation of the contact lens.

Some of these cases have documented successful LASIK with
stable results.

For example, Jampaulo and Maloney (J Refract Surg. 2008
Sep;24(7):707-9.) reported a patient with clinically evident
topographic keratoconus with a preoperative spherical equivalent
refraction of more than -10.00 diopters (D) who underwent
successful LASIK with no evidence of progression of ectasia 7 years
after surgery.

We have done LASIK and now preferably Surface Ablation in
similar cases based on the enhanced screening findings from
Corneal Tomography (CTm) and biomechanical measurements
(Example 5).
Example 5: False Positive Topography for Keratoconus Suspect based on
Corneal Tomography and Biomechanics. Patient had LASIK with stable
results in both eyes for over 3 years. (This case would be considered as very
high risk for ectasia based on corneal topography, age, thickness and high
correction).

23 yo LASIK candidate, mild asymmetry on the axial topo

MRx: - 9.50 -1.75 x 3º OD, giving 20/60

- 7.25 -1.25 x 179º OS, giving 20/20

No contact lens use

US-CCT: 565 / 545 µm (OD / OS)

Corneal Hysteresis (CH) and CRF were 12.1 and 12.0 mmHg
and 13.1 and 12.2 mmHg in OD and OS respectively with a
normal ORA signal in OU.

Corneal Tomography revealed normal posterior elevation float
and a normal thickness profile in OU.

Patient had uneventful LASIK (Hansatome with intended flap
thickness of 160 and VISX S4).

1 year Post Op UVCA: 20/50 (gain of 1 line from pre op
BSCVA) in OD and 20/20 in OS. Results remain stable for
over 3 years.
Figure 6: Placido’s derived (Vista, iTrace) Curvature topography with ABT
and IS in both eyes, which is a false postive for FFK based on enhanced
screening methodology used. Highest K was 46.3 and 47.2 in OD and OS
respectively; I/S difference at 6mm in diameter was 1.1 in OD and 1.5 in
OS.
Figure 7: Recent exam from OS by Scheimpflug Tomography by Oculyzer,
demonstrating oblate cornea with stable architecture over 3 years after
LASIK; UCVA: 20/20.

Other alternative approaches have been described to provide more
specificity to detect “real” ectasia, such as the evaluation of the
epithelial profile using the very high frequency ultrasound
tomography (Reinstein, Refractive Surgery SubDay 2007 and 2008).
This is based on the previous study of the epithelial profile among
normal corneas and on the observation that the epithelium thins
over the protruded cone area as an attempt to mask the
irregularities. Thereby a case with ABT and IS with a THICK
epithelium over the cone would be considered as a FALSE
POSITIVE on corneal topography, thereby a candidate for corneal
refractive ablation.
IV - The Concept of Ectasia Susceptibility

Corneal thinning is a hallmark of these ectatic diseases. The area of
maximal thinning, relative to the location of maximal corneal
protrusion differentiates keratoconus, pellucid marginal
degeneration, and keratoconus.

Ectasia is a process of biomechanical failure, which is the biological
equivalent of a well-known composite science process described in
biomechanical engineering by Puk and Knops: interfiber fracture.

Significant evidence supports that thinning does occur prior to
steepening.

A genetic predisposition, combined with behavioral (eye rubbing)
and environmental stress factors influence the biomechanical
susceptibility to develop ectasia.

Thereby, a concept of a balance between corneal resistance
(individual genetic-driven corneal biomechanical and biochemical
properties) and stress factors (individual phenotype) would lead to a
net result which we refer as ECTASIA SUSCEPTIBILITY.

More sensitive analyses reveal a continuum of findings from normal
cornea towards ectatic disease, even in its earliest presentations. For
example, this is well documented that some family members of
keratoconus patients have mild topography abnormalities.

Studies from asymmetric keratoconus and examples indicate that
novel tests based on corneal tomography and biomechanical
measurements are sensitive to detect abnormalities in the contralateral eyes with normal topography (Salomão, ASCRS 2008).

We believe that any cornea may undergo ectasia IF enough stress is
applied to overpass its resistance limit, leading to biomechanical
failure.

For example, some corneas may undergo spontaneous ectasia
(keratoconus) even without eye rubbing history. Others cases may
undergo ectasia IF there is enough stress, such as eye rubbing and
corneal surgery to overcome corneal resistance limit.
V - Enhanced Screening Corneal Tomography

Along with anterior curvature data, CTm provides detailed
architecture information so that elevation maps from the front and
back surfaces are calculated, along with the paquimetric map.

Much attention has been devoted to the posterior corneal elevation
map. The BFS (best fit sphere) for the 9mm corneal area is one of
the most accepted parameters for referencing the elevation map.

The thickness map provide detailed information regarding the
thinnest point (value and location in relation to the apex [0;0]) nad
pachymetric distribution.

Corneal Thickness Spatial Profile (CTSP): average of the thickness
values along twenty-two imaginary circles centered on the thinnest
point (TP).

Percentage Thickness Increase (PTI): percentage of increase of
each of these circles from the TP.

CTSP and PRI Graphs displays 95%CI limits of normals.

Thinned corneas (likely ectatic) have profiles out of the 95% CI more abrupt (going down) increase.
Normal Thin Cornea
CCT = 493 µm
Figure 8: CTSP and PTI Graphs for the thickness profiles. Example
from a normal thin cornea.

Anterior and Posterior Enhanced Elevation: standard BFS
“subtracted” from the enhanced BFS (best fits to peripheral cornea
excluding 4mm in diameter centered on the thinnest).
Figure 9: Belin’s Concept for Enhanced Elevation. Peripheral fit
highlights the cone area.
Figure 10: Normal Enhanced Elevation in a thin cornea.

Enhanced Elevation Map (Three colors Format):
Anterior: Green < 6,
Yellow: 6 – 12, Red > 12 µm
Posterior: Green < 8, Yellow: 8 – 20, Red > 20 µm

Corneas with higher elevation around the TP (likely ectatic) have
pronounced differences between the standard and enhanced BFS
(YELLOW and RED).

The Pentacam Belin-Ambrósio Enhanced Ectasia Display (BAD)
combines thickness profile with enhanced elevation from front and
back.
VI - Enhanced Screening and Corneal Biomechanics: ORA (Ocular
Response Analyzer)
A
ORA Signal
2
1
B
4
3
Figure 11: A - ORA Measurement and B – ORA Normal Signal

Corneal response to a collimetric air pulse is monitored by the
infrared light reflection (applanation => peak)

Detects two applanation events correlated with the air pulse
pressure (INWARD - p1 and OUTWARD - p2)

The delay of p2 caused by corneal viscous damping

[CH = p1 – p2] and [CRF = p1 - (K * p2)]

Normal Values: CH: 10.17 ± 1.82 mmHg (3.23 to 14.58)
CRF: 10.14 ± 1.8 mmHg (range 5.45 to 15.1)

Ectasia leads to lower CH and CRF and altered signals

CH or CRF < 8.8mmHg is considered a relative contra indication
for LASIK based on normal population values

Advanced Bio-corneagram Analysis provides 38 waveform
morphology parameter.

Combination these new parameters can provide new information
regarding corneal behavior, allowing a better biomechanical study.
VII - Corneal Biomechanics with the Corvis ST (Oculus, Germany)

Ultra High-Speed (UHS ST) Scheimpflug Technology: 4,330
frames/sec that monitors 8mm horizontal Scheimpflug image in
response to a symmetrically metered air pulse with fixed peak
pressure.

The metered collimated air pulse or puff has a symmetrical
configuration and fixed maximal internal pump pressure of 25 kPa. The
bidirectional movement of the cornea in response to the air puff is
monitored. Measurement time is 30ms, with 140 frames acquired.
Advanced algorithms for edge detection of the front and back corneal
contours are applied for every frame.

IOP is calculated based on the first applanation momentum.

Deformation amplitude is determined as the highest displacement of
the apex in the highest concavity momentum. Applanation length and
corneal velocity are recorded during ingoing and outgoing phases.

Such parameters provide clinical in vivo characterization of corneal
biomechanical properties, which are relevant for different applications
in Ophthalmology.
Figure 12: Corvis ST and corneal Scheimpflug imaging in response to a
symmetrically metered air pulse with fixed peak pressure
VIII - Integration of tomographic and biomechanical evaluation in clinical
practice
Enhanced Screening Findings from Asymmetric Forme-fruste Keratoconus
(not unilateral) with normal curvature maps in the contra-lateral eye
Sagittal Anterior Curvature Map from Pentacam Scheimplfug CTm with
similar findings as in Placido’s Topography
Abnormal profile in both eyes. Note the escape from the superior limit
(lower dot line) in the PTI in both eyes.
ORA Signal with relatively low amplitudes and waveform scores in both
eyes. The findings in OS are abnormal and, despite the normal anterior
curvature map, this case is considered as a high risk for ectasia (Ectasia
Susceptible).
Conclusions
A. Curvature -based Corneal Topography is a more traditional and intuitive language for
Ophthalmologists and will always be critical since it reflects refractive power of the cornea
and optical regularity. It is (and will always be) a critical step for the evaluation of refractive
properties of the cornea and quality of the ocular surface tear film.
B. However, curvature maps does not represent all the picture for screening candidates for
Refractive Surgery.
C. Central Corneal Thickness (CCT) of Pachymetry does not represent the thinnest value.
D. Corneal Tomography is defined as a 3D representation of the corneal architecture, with
detailed and reliable data from the front and back surface of the cornea and a pachymetric
map.
E. Elevation subtraction maps is the preferred method for describing the front and back
surfaces of the cornea. However, this is a more complex way and less intuitive for the
general Ophthalmologist. In addition, there are many possible options to calculate the
reference surface for the subtraction with the corneal surface (front or back).
F. Corneal Thickness Distribution enables the identification of ectasia and the differentiation
of a normal thin cornea from ectasia.
G. The Belin-Ambrósio Enhaced Ectasia Display (BAD) combines tomographic elevation
from anterior and posterior corneal data, along with a more comprehensive thickness
evaluation, which provide complementary critical additional information for screening
refractive candidates.
H. Corneal Biomechanical measurements represent a complementary method for the
enhanced screening for ectasia
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