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S610 Journal of Refractive Surgery Volume 18 September/October 2002
ABSTRACT
PURPOSE: The purpose of this article is to dis-
cuss missing information on the basic physical and
biological processes of ultraviolet corneal photo-
ablation and to evaluate its potential clinical impli-
cations.
METHODS: A physical description of ultraviolet
laser corneal ablation that includes photothermal,
photochemical, and radiative processes is pro-
posed.
RESULTS: Unresolved issues include the nature
of the primary ablation process, the tissue and bio-
logical effects of the photothermal and photochem-
ical components of the interaction, and the static
and dynamic absorption process.
CONCLUSIONS: A better understanding of the
basic physics and biology of ultraviolet corneal
photoablation may help us better understand, pre-
dict, and perhaps minimize the effect of tissue
hydration, plume formation, and other factors that
affect the predictability of ablation and the induced
tissue damage. [J Refract Surg 2002;18:S610-S614]
In 1983, Trokel, Srinivasan, and Braren1demon-
strated that an argon fluoride (ArF) excimer
laser emitting nanosecond pulses at 193 nm can
create controlled corneal incisions with submicron
precision and minimal collateral damage adjacent to
the ablation zone. The initial description for the
basic physical mechanism leading to ultraviolet
(UV) laser ablation of the cornea was adapted from
Srinivasan’s earlier investigations of UV photoabla-
tion of organic polymers, such as polymethyl-
methacrylate (PMMA) and polyimide.2According to
this model, UV photoablation invokes a photochem-
ical process whereby the photon energy is high
enough to break molecular bonds (photodissocia-
tion). Photodissociation is followed by an explosive
expansion and ejection of the dissociated fragments
at supersonic speeds (Fig 1). Srinivasan named this
process “ablative photodecomposition.” The term
photoablation is often used as an abbreviation for
ablative photodecomposition, even though the
expression UV photoablation may be more appropri-
ate in order to distinguish ablative photodecomposi-
tion from other photoablation processes, such as
photovaporization (photothermal process) or plas-
ma-mediated ablation (photoionization process).
The assumption that UV photoablation of the
cornea is a purely photochemical interaction where
heat plays a negligible role also led some investiga-
tors to name this process “cold ablation.” As dis-
cussed in the next section, the term cold ablation is
misleading, since the corneal surface temperature
locally reaches at least several hundreds if not thou-
sands of degrees during UV photoablation.
A number of experimental studies on the basic
processes and biological effects of UV corneal pho-
toablation followed the initial experimental obser-
vations of Trokel, Srinivasan, and Braren. Excellent
reviews of these studies and discussions of factors
affecting the ablation process have been
published.3-8 Ultimately, the goal of these investiga-
tions is to provide understanding that will help
maximize the safety of the procedure, as well as the
predictability and stability of the refractive out-
come. The rationale for conducting basic laser-tissue
interaction studies is to gain a better understanding
of the ablation process and how laser parameters
and biological factors affect the ablation, so that one
can maximize the precision and smoothness of abla-
tion, and minimize undesired side effects and
wound healing.
When the first experimental systems for photore-
fractive keratectomy (PRK) became available for
clinical use, research focus rapidly shifted from fun-
damental laboratory studies to clinical outcome
studies. Even though there are still many
Ultraviolet Corneal Photoablation
Fabrice Manns, PhD; Peter Milne, PhD; Jean-Marie Parel, PhD
From the Biomedical Optics and Laser Laboratory, Department of
Biomedical Engineering, University of Miami College of Engineering,
Coral Gables, FL and the Ophthalmic Biophysics Center, Bascom Palmer
Eye Institute, University of Miami School of Medicine, Miami, FL.
This work was supported in part by Quantel Medical, SA; The Henri
and Flore Lesieur Foundation; The Florida Lions' Eye Bank; Research to
Prevent Blindness, New York, NY.
The authors have no financial interest in the research or instruments
described herein.
Presented at the 3rd International Congress of Wavefront Sensing and
Aberration-free Refractive Correction, February 15-17, 2002, Interlaken,
Switzerland.
Correspondence: Fabrice Manns, PhD, Bascom Palmer Eye Institute,
1638 NW 10th Avenue Miami, FL 33136. Tel: 305.326 6137; Fax: 305.326
6139; E-mail: fmanns@miami.edu
unresolved issues, few basic studies on UV corneal
photoablation have been published since the United
States Food and Drug Administration approved
lasers for photorefractive keratectomy (PRK) in
1996. At first sight, given the current success of
PRK and especially its successor, laser in situ ker-
atomileusis (LASIK), the clinical relevance of our
incomplete understanding of the basic ablation
processes may be moot. However, with the promised
development of customized wavefront-guided treat-
ments, laser corneal reshaping is entering a new
era. Customized wavefront-guided surgery may
require ablation with submicron precision, and mod-
ified (eg, flying-spot) delivery systems that use high-
er repetition rates and radiant exposures. Our pho-
tophysical and clinical understanding of the opti-
mum implementation of these alternative laser
corneal reshaping procedures may be inadequate.
Answering the remaining questions about the abla-
tion process may prove to be a critical issue in the
development and optimization of delivery systems
for customized aberration-guided corneal reshaping.
We review some of the remaining questions and
issues concerning UV corneal photoablation, and
discuss how they may affect the quality of ablation.
We also propose a qualitative physical description of
UV corneal photoablation, which goes beyond the
simple photochemical model.
MODELS AND METHODS
UV Corneal Photoablation is Not Just Bond Breaking
Experimental observations indicate that UV pho-
toablation of organic polymers and of the cornea is
not just bond breaking. Early studies already
demonstrated that corneal irradiation with the ArF
excimer laser produces a measurable corneal tem-
perature increase, both below and above the abla-
tion threshold.9,10 In a recent study using thermal
radiometry with nanosecond resolution, Ishihara
and colleagues11 found that the corneal surface tem-
perature reaches between 100°C and 300°C during
ablation at 193 nm with radiant exposures ranging
from 80 to 300 mJ/cm2. Also, the cornea luminesces
during ArF excimer laser irradiation, both below
and above the ablation threshold.12,13 UV corneal
photoablation produces a photomechanical
effect.14-19 Siano and colleagues14,15 demonstrated
that irradiation at radiant exposures above the
ablation threshold induces a pressure wave with a
peak amplitude of 90 bars in the anterior chamber.
This pressure wave, which includes compression
and rarefaction phases, propagates through the eye
and produces a measurable transient pressure
increase as far as 20 mm away from the corneal sur-
face. The above experimental observations demon-
strate that UV corneal photoablation is not solely a
photochemical process, but that it also involves pho-
tothermal, photomechanical, and radiative interac-
tions.
Photophysical Description of UV Laser Corneal Ablation
In recent years, several photophysical20-22, ther-
modynamic23-27, and hydrodynamic28 models of UV
photoablation of organic polymers have been pro-
posed. Photophysical models generally describe the
interaction of UV photons with polymers as a com-
bination of different competing radiative and non-
radiative excitation and relaxation processes that
lead to ablation if the irradiance exceeds a threshold
value. These models can be modified to provide a
qualitative description of the interaction of UV pho-
tons with the cornea above and below the ablation
threshold (Fig 2). The following description does not
Journal of Refractive Surgery Volume 18 September/October 2002 S611
UV Corneal Photoablation/Manns et al
Figure 1. Simplified photochemical ablation
model (adapted from Srinivasan and
Braren2).
include plasma formation and multiphoton effects,
which may occur at higher irradiances or shorter
pulse durations, outside the clinical range.
The initiating step of the interaction is the
absorption of UV photons by the cornea. Photon
absorption produces transitions between electronic
or molecular energy levels, leading to formation of
“excited states.” The primary effect of UV irradia-
tion is determined by the relaxation process from
the excited state or by photodissociation (ie, bond
breaking). This effect is a combination of lumines-
cence, heating, and photochemical reactions, lead-
ing to ablation if the irradiance is above a threshold
value. Radiative (luminescence), photothermal, and
photochemical interactions are present both below
and above the ablation threshold. Heating and abla-
tion produce secondary physical effects, including
the formation and propagation of a thermoelastic
pressure wave in the tissue, of a shock wave both in
air and in tissue, and of a plume formed by the eject-
ed tissue fragments.29,30 In addition, a secondary
luminescence is produced in the plume. These asso-
ciated primary and secondary physical processes
produce a range of biological and tissue responses
that eventually determine the extent of acute and
long-term tissue damage and the magnitude of the
wound healing response. Potential biological and
tissue effects include cytotoxicity and mutagenicity,
photothermal, and photomechanical tissue and cell
damage. Most studies indicate that the risk of cyto-
toxicity and mutagenicity induced by UV corneal
photoablation at 193 nm is minimal.4
DISCUSSION
What Is the Contribution of Each of the Primary
Processes?
The first unresolved question is the respective
contribution of each of the primary physical process-
es (photochemical, photothermal, photolumines-
cence) to the ablation mechanism and to the final
tissue response. The fluorescence spectrum overlaps
with the action spectrum for cytotoxicity and
cataractogenesis. Seiler31 demonstrated that
excimer laser-induced corneal fluorescence could
damage cell lines, but other experimental studies
indicate that the cytotoxic or mutagenic risk is min-
imal and that the total radiation dose produced by
fluorescence during ablation is well below the cur-
rently accepted threshold for UV-induced cataract
formation.4On the other hand, the fluorescence
spectrum was found to vary with the ablation
depth13, probably because of differences in structure
and composition between anterior and posterior
stromal tissue. Cohen and colleagues13 suggested
that corneal fluorescence measurements could
therefore be used as a feedback system for online
ablation control.
The cytotoxic or mutagenic risk of the primary
photochemical interaction is minimal during UV
corneal photoablation at 193 nm.4However, some
experiments have shown that excimer laser irradia-
tion induces phototoxic effects due to free radical
formation and that photogenerated free radicals
may contribute to the loss of keratocytes during
wound healing following in vivo excimer laser abla-
tion.32-34
Heating is generally believed to be responsible for
the small region of tissue damage produced around
the ablation site during UV corneal photoablation.
The clinical importance of thermal damage and its
role in wound healing are still unknown. It is possi-
ble that thermal damage and its effects might
become more important with flying spot delivery
systems that use high repetition rates10 (>100Hz).
At high repetition rates, the heat produced during
the laser pulse may not be able to dissipate before
the next pulse is applied.
One of the most debated issues is the primary
physical process leading to ablation. Is it a pho-
tothermal mechanism or is it a photochemical mech-
anism? If it is a combination of the two, can the rel-
ative extent be controlled? Would this affect the clin-
ical outcome? The photochemical theory was
S612 Journal of Refractive Surgery Volume 18 September/October 2002
UV Corneal Photoablation/Manns et al
Figure 2. Photophysical description of UV
corneal photoablation.
described in the introduction (Fig 1). According to
the photothermal theory, absorption of UV photons
by corneal collagen leads to a temperature increase
that is high enough to induce water vaporization,
leading to ablation.9,11 There is experimental evi-
dence, and counter-evidence, for both theories,
which seems to indicate that UV photoablation is
probably a combination of photodissociation (bond
breaking) and thermal vaporization.20
What Are the Static and Dynamic Absorption Properties?
The initiating step of the photophysical descrip-
tion of UV photoablation of the cornea is the absorp-
tion of UV photons. An accurate knowledge of the
absorption properties of the cornea could help
resolve the question of the UV photoablation mech-
anism. For instance, one of the arguments that is
often used to support the bond breaking theory, is
that the curve of the ablation rate as a function of
fluence has a logarithmic behavior at low fluences.
The absorption coefficient can be calculated from a
logarithmic curve fit of the ablation rate curve.
Using this approach, Bor and colleagues6found a
value of approximately 20000 cm-1 for the corneal
absorption coefficient at 193 nm. On the other hand,
the fact that the temperature increases approxi-
mately linearly with fluence during UV photoabla-
tion11 supports the photothermal theory. In this
case, the absorption coefficient can be calculated
from the slope of the temperature increase as a
function of fluence. Using this technique and a lin-
ear regression of Ishihara's data11, a value of
approximately 4200 cm-1 is obtained for the corneal
absorption coefficient at 193 nm.
Because the cornea is strongly absorbing at wave-
lengths around 200 nm, it is difficult to accurately
measure the corneal absorption coefficient using
traditional techniques, such as transmission mea-
surements. Accepted values of the corneal absorp-
tion coefficient at 193 nm differ by more than one
order of magnitude. Early experiments using trans-
mission measurements of thin corneal sections35
produced a value of 2700 cm-1. More recently, using
reflectance measurements, Pettit and Ediger36
obtained a value of 39900 cm-1.
Another parameter that is still not clearly under-
stood is how the ablation rate is affected by dynam-
ic variations of the absorption properties of the
cornea during UV irradiation.4The accepted values
of the absorption coefficient are static values mea-
sured at ambient temperatures and pressures.
During ablation, the amount of UV radiation
absorbed by the cornea is affected by dynamic
changes in the absorption coefficient caused by the
dramatic increase in temperature and pressure dur-
ing ablation, but also by hydration changes and by
absorption and scattering of radiation in the plume.
There is also some evidence that photochemical
changes in the tissue induced by subthreshold irra-
diation or tissue damage induced by previous pulses
affect the absorption behavior of the cornea.4
How Do the New Laser Parameters Affect Laser-Cornea
Interaction?
Other factors that may affect the predictability of
the ablation rate and smoothness of the corneal sur-
face include the effect of hydration37, the attenua-
tion effect of the plume, the effect of variability of
the ablation rate in depth3,38 and across the ablation
zone, and the effect of redeposited debris.39 Some of
these effects have been studied to various extents
using broadbeam delivery systems with uniform
intensity distribution, at low repetition rates (10 to
50 Hz), and moderate radiant exposures (100 to
300 mJ/cm2). One of the remaining issues is to know
if and how these factors, and the primary laser-
tissue interaction, are changed when the cornea is
ablated with a flying spot with Gaussian intensity
distribution, at a higher repetition rate and a high-
er fluence. For instance, the experiments of Siano
and colleagues14,15 and Krueger and colleagues19
clearly demonstrate that the propagation of the
acoustic pressure wave induced by UV photoabla-
tion strongly depends on the diameter of the abla-
tion spot.
Many aspects of the primary process and sec-
ondary effects of UV corneal photoablation are still
poorly understood. At first sight, the success of PRK
and LASIK indicates that the missing information
is not a critical issue with current delivery systems
that aim at correcting mainly spherical refraction
with an accuracy of approximately ±0.50 diopters.
However, a better understanding of the ablation
process could help predict some of the factors affect-
ing ablation, help optimize the treatment parame-
ters of the new flying spot delivery systems and help
produce the ablation precision required for cus-
tomized aberration-guided corneal reshaping.
However, maximizing the control of the ablation
depth and minimizing side effects are only the first
steps in controlling the precision of corneal reshap-
ing. Biomechanical effects and wound healing also
play an important role in determining the final
refractive outcome: “The cornea is not a piece of
plastic.”40
Journal of Refractive Surgery Volume 18 September/October 2002 S613
UV Corneal Photoablation/Manns et al
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UV Corneal Photoablation/Manns et al
