REVIEW

CURRENT
OPINION Percent tissue altered and corneal ectasia
Marcony R. Santhiago a,b

Purpose of review
This article reviews the association of a novel metric, percentage tissue altered (PTA), with the occurrence
of ectasia after laser in-situ keratomileusis in eyes with normal corneal topography, and analyses the
influence of the variables that comprise it, and its role on eyes with suspicious topography.
Recent findings
PTA is derived from [PTA ¼ (FT þ AD)/CCT] where FT ¼ flap thickness, AD ¼ ablation depth, and
CCT ¼ preoperative central corneal thickness. Our studies revealed that there is a robust relationship
between high PTA and ectasia risk in eyes with normal preoperative topography. PTA higher or equal
to 40% presented the highest odds ratio and highest predictive capabilities for ectasia risk than each of
the variables that comprise it, residual stromal bed or age. Average thicker flaps alone were insufficient
to create ectasia unless coupled with greater ablation depths, meaning a high PTA. In eyes with
suspicious topography, even low PTA value is sufficient to induce ectasia.
Summary
This new metric, PTA, should be taken into account when screening patients for refractive surgery. Patients
with normal topography or tomography, presenting a PTA higher or equal to 40% should be considered at
higher risk for post laser in-situ keratomileusis ectasia.
Keywords
ectasia, LASIK, percentage tissue altered, PTA, risk factor

INTRODUCTION reviews the PTA concept, discusses the role of

Postoperative corneal ectasia is a sight-threatening
complication, most likely associated with a reduc-
tion in the biomechanical integrity below the
threshold required to maintain corneal shape
[1,2]. This disruption of the balance in biomechan-
ical forces could theoretically occur when a cornea,
that already presents pretopographic ectatic disease,
is submitted to surgery, a preoperatively weak,
but clinically stable cornea, has surgery, or when a
relatively normal cornea is weakened below a safe
&
threshold [3 ]. Understanding, recognizing, and
accepting its risk factors are crucial steps toward a
significant reduction in the occurrence of this
PTA in ectasia after LASIK in eyes with normal
and suspicious topography, the relative contri-
bution of flap and ablation depth, its role on PRK,
and differences in measurements considering
central and thinnest corneal thickness.
CONCEPT OF PERCENTAGE TISSUE
ALTERED
There is an integrated relationship between pre-
operative corneal thickness, ablation depth, and flap
thickness in determining the relative amount of
biomechanical change that has occurred after a
&& &&

adverse event [4]. LASIK procedure. Santhiago et al. [5 –8 ] tested

Although most patients who have developed
ectasia after laser in-situ keratomileusis (LASIK)
or photorefractive keratectomy (PRK) have had
identifiable risk factors that placed them at higher
risk for this complication, ectasia cases in patients
with normal preoperative topography have still
&
been the source of extensive investigation [1,2,3 ].
&& &&
Santhiago et al. [5 –8 ] coined the term,
first proposed, investigated, and consistently deter-
mined the association of a high value of percentage
tissue altered (PTA) and ectasia risk. This article
and validated a new metric, the percentage of
a
Department of Ophthalmology at University of Sao Paulo, Sao Paulo
and bDepartment of Ophthalmology at Federal University of Rio de
Janeiro, Rio de Janeiro, Brazil
Correspondence to Marcony R. Santhiago, MD, PhD, Instituto Central,
255 Eneas de Carvalho Aguiar AV, Ophthalmology Department, Federal
University of Sao Paulo, Sao Paulo, Brazil. Tel: +55 11 26617871;
e-mail: marconysanthiago@hotmail.com
Curr Opin Ophthalmol 2016, 27:311–315
DOI:10.1097/ICU.0000000000000276

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Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

Refractive surgery
KEY POINTS
 A high PTA at the time of LASIK is consistently
associated with the development of ectasia in eyes with
normal preoperative topography.
 PTA is a more robust indicator of risk than previously
recognized variables such as RSB or CCT.
 Thicker flaps alone were insufficient to create ectasia
unless coupled with greater ablation depths and thus
high PTA values.
 There remains a significant correlation between PTA
values and ectasia risk after LASIK in eyes with
suspicious corneal topography.
 There is no safe limit for PTA if topography or
tomography is abnormal.
anterior tissue depth altered, or PTA, that better
describes this interaction during excimer laser
refractive surgery, which for LASIK can be described
as: PTA ¼ (FT þ AD)/CCT [5 –8 ,9 ] where PTA is
&& && &
the percentage tissue altered, FT the flap thickness,
AD the ablation depth, and preoperative CCT is the
central corneal thickness.
&&
One of our first studies [5 ] investigated
changes in novel biomechanical descriptors after
different levels of myopic femtosecond LASIK in
normal eyes, and revealed the PTA as a much stron-
ger predictor of LASIK-induced biomechanical
change compared with ablation depth or residual
stromal bed (RSB). These findings were an important
background to specifically investigate the relation-
ship between PTA and ectasia after LASIK.
ASSOCIATION BETWEEN PERCENTAGE
TISSUE ALTERED AND ECTASIA IN EYES
WITH NORMAL TOPOGRAPHY
In order to remove bias and better understand
the potential, and specific, association between
&&
PTA and ectasia risk, Santhiago et al. [6 ] conducted
a comparative case–control study including eyes
that developed ectasia after LASIK for myopia and
myopic astigmatism with strictly normal bilateral
preoperative Placido disk-based corneal topography.
&&
The study [6 ] revealed that in eyes with normal
preoperative topography, PTA presented higher
prevalence, higher odds ratio, and higher predictive
capabilities for ectasia risk than moderate to high
ectasia risk score system (ERSS) values, RSB, CCT,
high myopia, ablation depth, or age. Through the
analysis of receiver operating characteristic (ROC)
312 www.co-ophthalmology.com
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curve we also found that PTA  40% was a more
robust indicator of risk than other variables in
patients with normal preoperative topography,
being even more sensitive than absolute cut-off
values of RSB (300 or 250 mm) itself that influenced
on the risk of ectasia the most.
The main explanation for this scientific finding
most likely lies in the relative percentage contri-
bution of the anterior stroma to the total corneal
strength, which is modified after excimer laser
refractive surgery [10,11]. As corneal tensile strength
presents an inhomogeneous distribution through-
out the central cornea, removing the anterior part of
the stromal may induce corneal weakening in
increasing proportion as the threshold of 40% is
reached and crossed. As compared to specific RSB
or CCT cut-off values, PTA likely provides a more
individualized measure of biomechanical alteration
because it considers, at the same time and in one
metric, the relationship between thickness, tissue
altered through ablation and flap creation, and
ultimate RSB thickness [10,11].
RELATIVE CONTRIBUTION OF FLAP
THICKNESS AND ABLATION DEPTH TO
PERCENTAGE TISSUE ALTERED
Despite representing a more individualized metric
than CCT or RSB, the PTA equation still has equally
weighted components, flap thickness and ablation
depth that may not have equal importance [12,13].
Because these variables affect the central cornea
similarly but have significant differences in their
relative alteration of peripheral corneal fibers, they
may have different effects on ultimate biomechan-
ical integrity, based on anatomic differences in the
anterior corneal stromal fiber interconnections.
&&
Therefore, Santhiago et al. [7 ] conducted a
specific study to investigate the relative contri-
bution of flap thickness and ablation depth to the
PTA after LASIK, and to evaluate the importance of
these differences in further differentiating between
eyes that do and do not develop ectasia with normal
preoperative topography. They found that a LASIK
flap had greater impact than ablation depth,
however average thicker flaps alone were insuffi-
cient to create ectasia unless coupled with greater
ablation depths and thus high PTA values.
It is after the combination of a relatively thick
flap cut combined with a substantial ablation depth,
leading to a high PTA value, that the biomechanical
cycle of decompensation in ectasia can occur,
with progressive thinning, redistribution of stress,
increase in curvature, more redistribution of stress
completing the cycle, and leading to progressive
&
thinning [3 ].
Volume 27  Number 4  July 2016

THE CORRECT MANNER TO USE
PERCENTAGE TISSUE ALTERED IN
PRACTICE
The integrated analysis of the studies conducted
&& &&
by Santhiago et al. [5 –8 ] provided evidence that
a high value of PTA, especially greater than 40%, is a
relevant factor in the development of post-LASIK
ectasia in eyes with normal preoperative Placido
disk-based topography and, therefore, PTA should
be taken into account as a screening parameter
for refractive surgery candidates. This metric more
accurately represents the risk of ectasia than the
individual components that comprise it [6 –8 ].
&&
According to the studies conducted by San-
&&
thiago et al. [6 ] the risk of ectasia rapidly increases
with a PTA higher than 35% (with 100% sensitivity)
and peaks its maximum combination of sensitivity
and specificity when equal to or higher than 40%.
It should be clear though, that PTA is not a
screening method, but actually a robust risk factor,
and as such, there will still occur ectasia cases in eyes
with low PTA values, especially those with, even
if subtle, preoperative abnormal topography, as well
as there will be eyes with high PTA that will never
develop ectasia. However, considering the elective
nature and the young population associated with
refractive surgery, it is advisable to lean towards
a safer procedure. If topography is really normal
and a high PTA is the only identifiable risk factor,
the surgeon could change the surgery to surface
ablation, and the value would fall again within
a safer range.
ROLE OF PERCENTAGE TISSUE ALTERED
IN EYES WITH SUSPICIOUS
TOPOGRAPHY
Previous studies have arguably demonstrated
that abnormal corneal topographic patterns are
the most significant risk factor for postoperative
ectasia [1,2]. In a study specifically conducted on
eyes with suspicious topography, Santhiago et al.
&&
[8 ] revealed that there remains a significant corre-
lation between PTA values and ectasia risk after
LASIK, even in eyes with suspicious corneal topog-
raphy. Less tissue alteration, or a lower PTA value,
was necessary to induce ectasia in eyes with more
remarkable signs of topographic abnormality. PTA
again provided better discriminative capabilities
&&
than RSB for all study populations [8 ].
It should also be clear that these results do
not indicate that is safe to perform LASIK in eyes
with suspicious topographic patterns simply by
respecting a low PTA limit. In fact, these findings
do corroborate that even subtle signs of abnormal
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PTA and ectasia Santhiago
topography are associated with ectasia after
minimal tissue removal and therefore there is no
safe limit under this setting.
PERCENTAGE TISSUE ALTERED AND
PHOTOREFRACTIVE KERATECTOMY
The ideal scientific context to specifically investi-
gate the role of PTA on ectasia after PRK would be
having eyes that developed ectasia after PRK with
strictly preoperatively bilateral normal topography.
However, the vast majority of these specific cases of
&&
ectasia after surface ablation [14] occurred in eyes
with preoperative suspicious, or clearly abnormal,
topography or tomography.
For PRK, PTA can be described as: PTA ¼
(Epithelium Thickness þ AD)/CCT. Although we
should not easily transpose the findings obtained
investigating eyes submitted to LASIK to eyes sub-
mitted to PRK, if preoperative topography is really
normal, the limits may be potentially higher in PRK,
because of its surgical structural differences, as there
is no flap cut and peripheral impairment of corneal
fibers. Considering the knowledge obtained so far,
we would still advise against any surgery in any
surgical setting with high PTA.
PERCENTAGE TISSUE ALTERED AND
SMALL-INCISION LENTICULE EXTRACTION
Although the flapless lenticule would theoretically
spare the corneal stronger component, the anterior
cornea may not be completely neutral, and the
combination of a high PTA, even for small-incision
lenticule extraction (SMILE), could still be associ-
ated with disruption of biomechanical balance
and higher ectasia risk. For SMILE, PTA can be
described as: PTA ¼ (Lenticule Thickness þ Cap
Thickness)/CCT.
Analysing a recent report of ectasia after SMILE
&
[15 ] in eyes with bilateral normal topography, and
subtracting the informed RSB (305 mm) by CCT
(513 mm), the patient would have a combination
of lenticule and cap thickness of 208 mm, leading
to a PTA of 40.5%, which may be an explanation
for this case. It should also be noted that, even
for SMILE, this threshold could be lower if topog-
&
raphy is abnormal [16 ].
Unfortunately, although this case can be used
to indirectly illustrate the theoretical concept,
we have not yet acquired enough data to make
any conclusions about the relationship between
high PTA, SMILE, and ectasia. We still need more
specific biomechanical knowledge and ectasia
cases with measured, rather than estimated,
www.co-ophthalmology.com 313
Refractive surgery
lenticule and cap thickness to make any
conclusions. Apart from this, we should not trans-
pose the findings and limits obtained for LASIK
to SMILE, and we still need to better elucidate
and understand the biomechanical differences
and potential neutrality of the anterior stroma
and actual tissue alteration for this surgery. Further
knowledge could even conclude that PTA calcu-
lation for SMILE should only include Lenticule
Thickness/CCT.
MEASURES OF PERCENTAGE TISSUE
ALTERED AT THINNEST POINT AND
CENTRAL CORNEAL
There is a wide range of corneal thickness values
obtained with different technologies that are able to
measure not only CCT but also the thinnest point
&
[17 ]. When available, we would recommend that
PTA should be calculated considering the thinnest
point, because it represents a more conservative
measure. However, in a recent study with normal
eyes, the differences between central and thinnest
corneal thickness measurements varied from 3.1 mm
obtained with Scheimpflug to 8.6 mm with
&
Scanning-slit technology [17 ], which would mean
a variation in PTA of approximately 0.5%. Eyes with
a thin cornea are at higher risk for ectasia not only
because they are the source of theoretically low PTA
values but also because it could be an early sign
of keratoconus and should always be considered
&
with caution [18 ].
CURRENT STUDIES
Even with efficacious methods to halt ectasia
& &
progression [19 ,20 ], novel screening strategies
have been the source of extensive discussion and
& 2. Randleman JB, Woodward M, Lynn MJ, Stulting RD. Risk assessment for
investigation [21 ,22]. We are currently working on
a point system and a new algorithm taking into
account PTA and other risk factors in a weighted
fashion. Our studies have shown promising results
with this new screening method, with a combi-
nation of a very high sensitivity and specificity [23].
Any scientific study analysing or calculating
the role of PTA should only be seriously considered,
cited or validated, if all the flap thicknesses were
measured, rather than only estimated. As a premise
of scientific study it is very important to have data
acquired as accurately as possible, especially when
investigating possible cut-offs and comparing to
studies that have used this correct method. Along
with this, any author doing research in this field
should make sure they are investigating eyes with
bilateral normal Placido disk based topography, and
not normal fellow eyes of contralateral eyes with
314 www.co-ophthalmology.com
Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
suspicious or clearly abnormal topography, to be
able to draw any scientific evidence.
CONCLUSION
Our studies provide evidence that PTA obtained
from LASIK is a more significant risk factor and
provide better discriminative capabilities than the
variables that comprise it or nonindividualized
metrics, such as cut-offs for corneal thickness or
RSB thickness. High PTA values are consistently
associated with ectasia risk in eyes with normal
preoperative topography, whereas a lower PTA value
may be enough to induce ectasia in eyes with more
remarkable signs of topographic abnormality. This
compilation of findings, from which the reader is
able to draw useful conclusions, is reasonably rep-
resentative of the relationship between PTA and
ectasia risk.
Acknowledgements
None.
Financial support and sponsorship
M.R.S. is a consultant for Alcon (Fort Worth, Texas,
USA) and Ziemer (Port, Switzerland).
Conflicts of interest
There are no conflicts of interest.
REFERENCES AND RECOMMENDED
READING
Papers of particular interest, published within the annual period of review, have
been highlighted as:
& of special interest
&& of outstanding interest
1. Randleman JB, Russell B, Ward MA, et al. Risk factors and prognosis for
corneal ectasia after LASIK. Ophthalmology 2003; 110:267–275.
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3. Roberts CJ, Dupps WJ Jr. Biomechanics of corneal ectasia and biomecha-
& nical treatments. J Cataract Refract Surg 2014; 40:991–998.
This review highlights the focal reduction in elastic modulus precipitates cycle of
biomechanical decompensation.
4. Randleman JB. Evaluating risk factors for ectasia: what is the goal of asses-
sing risk? J Refract Surg 2010; 26:236–237.
5. Santhiago MR, Wilson SE, Hallahan KM, et al. Changes in custom biome-
&& chanical variables after femtosecond laser in situ keratomileusis and photo-
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928.
This study revealed the PTA as a much stronger predictor of LASIK-induced
biomechanical change compared with ablation depth or RSB.
6. Santhiago MR, Smadja D, Gomes BF, et al. Association between the
&& percentage tissue altered and post-laser in situ keratomileusis ectasia in
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95.
This study provides the first scientific evidence of the relationship between high
PTA and ectasia in eyes with normal preoperative topography.
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&& contribution of flap thickness and ablation depth to the percentage tissue
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This study found that LASIK flap had greater impact than ablation depth, however;
average thicker flaps alone were insufficient to create ectasia unless coupled with
greater ablation depths and thus high PTA values.
Volume 27  Number 4  July 2016

8. Santhiago MR, Smadja D, Wilson SE, et al. Role of percentage tissue altered
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1040-8738 Copyright ß 2016 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
PTA and ectasia Santhiago
17. Randleman JB, Lynn MJ, Perez-Straziota CE, et al. Comparison of central and
& peripheral corneal thickness measurements with scanning-slit, Scheimpflug
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This article reveals the long-term efficacy and safety of corneal cross-linking for
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& corneal collagen cross-linking. J Refract Surg 2015; 31:419–422.
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