Excimer Lasers





Introduction


The possibility of using the excimer laser for the cornea was first raised in the early 1980s. Using Munnerlyn’s equation, which established a relationship between the change in refractive power and the amount of corneal tissue ablated, McDonald showed that stable correction of primate corneas could be obtained by refractive photokeratectomy without compromising corneal transparency. The US Food and Drug Administration (FDA) authorized the first clinical study of myopic refractive photokeratectomy on nine legally blind eyes in 1988; the first sighted eye was treated later in the same year. The technology has advanced since then through 6 generations ( Table 7.1 ), gradually extending refractive indications to all types of ametropia (spherical and cylindrical) with increasing reliability and safety. The technology is still evolving rapidly and advances have led to the development of customized ablation profiles, with the current goal to treat high-order optical aberrations and to avoid inducing unwanted ones.



TABLE 7.1

Various Generations of Excimer Lasers

Adapted from El Bahrawy M, Alió JL. Excimer laser 6th generation: state of the art and refractive surgical outcomes. Eye Vis (Lond) . 2015;2:6.

























Generation Feature
1st generation Preclinical
2nd generation Broad beam laser, fixed optical zone
3rd generation Broad beam laser, variable optical zone multizone treatment
4th generation Flying spot laser, built-in tracker, hyperopic treatment
5th generation Customized wavefront (guided, optimized) treatments
6th generation Faster ablation rates and tracking systems, lower biologic interaction, more variables under control, pupil size, advanced ablation profiles, cyclotorsion control, online pachymetry


The reduction of induced aberrations has become the main focus in modern laser refractive surgery. Laser platforms with a small spot size as a key factor have been designed. The treatment of high hyperopic refractive errors and presbyopia remain challenging. Today, excimer laser profiles can be classified into: topography-guided, wavefront-guided, wavefront-optimized, and aspheric or Q-factor-adjusted profiles.


In this chapter, we will describe the principles and properties of excimer lasers, along with summarizing the various conventional excimer laser treatments and custom-guided (topography- and wavefront-based) treatments.




Lasers: General Physical Principles


Principles of Laser Emission


Light emission is linked to a phenomenon known as atomic relaxation, when an excited electron in an atom returns to its initial energy level. This leads to the emission of a photon whose energy corresponds precisely to this energy differential. When photon emission is provoked by the arrival of other photons with the same energy as the photon emitted by de-excitation of the target atom, this “stimulated emission” produces coherent (in phase), monochromatic (a single wavelength) radiation. Lasers (the word is an acronym of light amplification by stimulated emission of radiation) are based on this phenomenon. It amplifies light and focuses it into a narrow unidirectional beam, allowing its energy to be delivered to a small, very precise target. The production of laser radiation requires an active medium that differs according to the type of laser, an excitation system (electrical stimulators), and a system to amplify the emitted radiation. This amplifier is known as a resonance chamber and is usually composed of two reflective surfaces. One surface is totally opaque while the other is only partially opaque, allowing laser energy to escape from the chamber. Luminescence (fluence) is responsible for the effects of laser radiation on matter. It is measured in joules per square centimeter (J/cm 2 ).


Laser–Cornea Interactions


There are four types of interaction between laser radiation and the cornea: absorption, transmission, reflection, and dispersion. Reflection and dispersion are weak phenomena on the cornea. The respective importance of absorption and transmission depends on the wavelength of the laser beam. Transmission is maximal at wavelengths between 400 and 1600 nm; this is the case of argon and yttrium-aluminum-garnet (YAG) lasers, which pass through the cornea without significant interactions. Absorption becomes predominant at wavelengths below 350 nm. This is the principal effect used for photoablative corneal surgery.


Absorption itself can be broken down into three distinct effects: photothermal, photodisruptive, and photochemical. The photothermal effect is linked to the molecular vibrations induced by photonic energy and results in a temperature increase. The photodisruptive effect follows ionization. It emerges only at very high wavelengths of the micron order (infrared). This is the mechanism of action of the YAG and femtosecond (FS) lasers. The photochemical effect usually occurs at short wavelengths.


There are two principal types of photochemical effect: photoradiation and photoablation. The property used for refractive surgery is photoablation, which is obtained with ultraviolet radiation associated with very high energies. The action is very superficial (a few microns) at these very short wavelengths. The photonic energy exceeds that of chemical bonds, meaning that compounds are dissociated and tissue components are vaporized ( Fig. 7.1 ). The shorter the pulse, the lower the risk of a thermal effect. With flying spot excimer lasers, which have a high pulse frequency, thermal effects are limited by the small size of the spots and by the fact that consecutive pulses are delivered at regular distances, giving the target site the time to cool off between impacts. The photoablative effect causes bleeding and therefore cannot be used to treat vascularized tissues.




Fig. 7.1


Mechanism of photoablation following absorption of excimer laser energy by the cornea. The photon energy (6.4 eV) exceeds the energy of molecular bonds. Molecular fragments are ejected at high speeds. A single impact removes about 0.25 µm.




Principles of Laser Emission


Light emission is linked to a phenomenon known as atomic relaxation, when an excited electron in an atom returns to its initial energy level. This leads to the emission of a photon whose energy corresponds precisely to this energy differential. When photon emission is provoked by the arrival of other photons with the same energy as the photon emitted by de-excitation of the target atom, this “stimulated emission” produces coherent (in phase), monochromatic (a single wavelength) radiation. Lasers (the word is an acronym of light amplification by stimulated emission of radiation) are based on this phenomenon. It amplifies light and focuses it into a narrow unidirectional beam, allowing its energy to be delivered to a small, very precise target. The production of laser radiation requires an active medium that differs according to the type of laser, an excitation system (electrical stimulators), and a system to amplify the emitted radiation. This amplifier is known as a resonance chamber and is usually composed of two reflective surfaces. One surface is totally opaque while the other is only partially opaque, allowing laser energy to escape from the chamber. Luminescence (fluence) is responsible for the effects of laser radiation on matter. It is measured in joules per square centimeter (J/cm 2 ).




Laser–Cornea Interactions


There are four types of interaction between laser radiation and the cornea: absorption, transmission, reflection, and dispersion. Reflection and dispersion are weak phenomena on the cornea. The respective importance of absorption and transmission depends on the wavelength of the laser beam. Transmission is maximal at wavelengths between 400 and 1600 nm; this is the case of argon and yttrium-aluminum-garnet (YAG) lasers, which pass through the cornea without significant interactions. Absorption becomes predominant at wavelengths below 350 nm. This is the principal effect used for photoablative corneal surgery.


Absorption itself can be broken down into three distinct effects: photothermal, photodisruptive, and photochemical. The photothermal effect is linked to the molecular vibrations induced by photonic energy and results in a temperature increase. The photodisruptive effect follows ionization. It emerges only at very high wavelengths of the micron order (infrared). This is the mechanism of action of the YAG and femtosecond (FS) lasers. The photochemical effect usually occurs at short wavelengths.


There are two principal types of photochemical effect: photoradiation and photoablation. The property used for refractive surgery is photoablation, which is obtained with ultraviolet radiation associated with very high energies. The action is very superficial (a few microns) at these very short wavelengths. The photonic energy exceeds that of chemical bonds, meaning that compounds are dissociated and tissue components are vaporized ( Fig. 7.1 ). The shorter the pulse, the lower the risk of a thermal effect. With flying spot excimer lasers, which have a high pulse frequency, thermal effects are limited by the small size of the spots and by the fact that consecutive pulses are delivered at regular distances, giving the target site the time to cool off between impacts. The photoablative effect causes bleeding and therefore cannot be used to treat vascularized tissues.




Fig. 7.1


Mechanism of photoablation following absorption of excimer laser energy by the cornea. The photon energy (6.4 eV) exceeds the energy of molecular bonds. Molecular fragments are ejected at high speeds. A single impact removes about 0.25 µm.




Properties of the Excimer Laser


Laser Beam Generation


Gaseous Medium


All excimer (combination of “excited dimer”) lasers are based on the same light-emitting mechanism: the reaction between a rare gas and a halogen. Excimer lasers employed in refractive corneal surgery use a gaseous mixture of argon and fluorine. An inert gas, helium, serves for energy transfer. Under the effect of strong electrical discharges (pulsed mode), electrons of the argon–fluoride (ArF) atoms move to a higher energy level; the excited atoms form an unstable molecule known as a dimer. The latter then returns to its stable state, emitting high-energy photons with a wavelength of 193 nm. Pulsed emission offers more power than continuous emission does.


The ArF combination is chosen because it has the following properties: highly energetic photons, weak penetration into adjacent tissues, minimal thermal effects, a very regular impact surface, strong absorption by water, and lack of mutagenicity. Latest resonance chambers used to amplify photon emission are in ceramic. They generate highly fluent emissions, between 180 and 200 mJ/cm 2 .


Beam Homogenization


Homogenization consists of narrowing the beam that emerges from the resonance chamber and maximizing cross-sectional power uniformity. The beam is passed through an optical system consisting of mirrors, lenses, and prisms. Masks are used to select the central part of the beam, which has the highest and most constant energy. This beam homogenization process entails a certain loss of power. The smaller the number of optical interfaces, the lower the energy loss. Each manufacturer has a proprietary homogenization system.


Beam Delivery System


Once homogenized, the laser beam must be formatted to the desired photoablative effect. There are three main types of beam delivery system: full beam, scanning slit, and flying spot.


Full-Beam Systems ( Fig. 7.2 )


These were used in first-generation lasers. Full beams offer more rapid treatment (for a given frequency) and are less sensitive to decentering. However, they are more difficult to homogenize and, therefore yield less regular ablation surfaces. Bystander thermal effects are also a problem. In addition, the shock wave generated by these lasers has been implicated in the higher frequency of central islands. A diaphragm or ablative mask must be used for refractive treatment. Customized treatment of complex shapes is impossible.




Fig. 7.2


Broad-beam delivery systems. Ablative diaphragms or masks are placed between the full beam and the cornea in order to obtain the desired refractive profile.


Scanning Slit Delivery


A diaphragm is placed between the eye and a full beam, creating a rectangular beam with a smaller width (10 mm × 1 mm) and improving homogeneity. The ablation masks have a rotary motion, allowing the beam to scan in different directions ( Fig. 7.3 ). These modifications overcome some of the disadvantages of full-beam systems while preserving their principal advantages (rapid treatment and low sensitivity to decentering). All types of ametropia can be corrected with scanning slit systems. It is now possible to divide each slit into several small rectangles. Such systems resemble flying spot systems and, theoretically, offer the possibility to treat complex, irregular shapes.




Fig. 7.3


Rotary slit delivery system. This system combines corneal scanning by a fine rectangular slit (10 × 1 mm) with 120 degrees of rotation of the slit every n pulses and gradual opening of a motorized diaphragm. The schemas show an example of spherical myopic treatment: (A) passages 1 and 2; (B) passage 3.


Flying Spot


In this case, the beam is small and circular (between 0.6 and 2.0 mm in diameter). Only the most central, homogeneous part of the beam is used. The beam direction is controlled by pivoting mirrors ( Fig. 7.4A ). The target is ablated by repeated delivery of a large number of pulses, each pulse removing only a very small area of tissue. A very high pulse frequency is necessary to reduce overall treatment time, particularly when the spots are very small. The spots must be precisely dispersed in order to avoid thermal effects. An active eye tracker is crucial, as this type of system is very sensitive to decentering. The cross-sectional energy profile of each spot is generally Gaussian, to obtain smooth ablation surfaces. An interval of half a spot diameter between adjacent spots offers a regular depth of ablation between the two peaks. The main advantage of flying spot lasers is that they can provide asymmetric ablation profiles when coupled with corneal topography or wavefront analyzers. The capacity of these systems to correct complex irregularities increases as spot size decreases.




Fig. 7.4


Flying spot delivery system. (A) (1) Small laser beam; (2) mirror in X axis; (3) mirror in Y axis. A small laser spot sweeps the cornea. The pulse frequency must be high because of the small spot size (0.6-mm to 2-mm diameter). Spot mobility is ensured by a set of pivoting mirrors. No diaphragm or ablative mask is necessary for refractive ablation profiles. (B) Adjacent impacts must be offset by half a beam diameter so that the spatial sum of the energy profiles yields a constant ablation rate and a regular ablation substrate.


Computer


A computer controls the laser’s key parameters. In particular, fluence must remain constant throughout the procedure, which is achieved by modifying the power of the electrical discharges in the resonance chamber to compensate for the gradual degradation of the gaseous mixture. The computer is also used to choose the refractive or therapeutic mode, the ablation profiles (according to the refraction), and the diameters of the optical and transition zones.


For customized ablation profiles, the computer integrates the corneal topography or wavefront data and calculates the optimal ablation profile accordingly.


Work Area


The operating table, microscope, and consoles differ with each system. The operating table must allow the patient’s head to be positioned correctly. The microscope must offer an adequate focal range and magnification, especially for laser in situ keratomileusis (LASIK) surgery. The focal length varies for each laser and must be sufficient to allow the flap to be cut with a mechanical microkeratome in good condition.


Parameters of the Laser Beam


The 193-nm photon beam has a number of characteristic physical parameters. Variations in these parameters can modify both the photoablative effects on the target site and the bystander effects on adjacent corneal tissue.


Pulse Duration


The pulses last from 4 to 25 ns, the excited dimer being highly unstable (half-life, 9–23 ns). Shorter pulses have lower thermal effects, limiting the consequences for adjacent tissue.


Pulse Frequency


Pulse frequency (number of pulses emitted per second) varies from 10 to 1000 Hz, depending on the model. In theory, high frequencies are to be avoided, as thermal effects on the cornea start to emerge at 1 Hz. A compromise must be reached, however, as the treatment will take too long if the pulse frequency is too low. With full-beam lasers, the ideal frequency is between 10 and 50 Hz. The use of high frequencies with flying spot lasers is limited by the heat generated by each impact, which must be allowed to dissipate before hitting the same spot again.


Pulse Energy


The energy delivered per broad beam pulse ranges between 10 and 250 mJ according to the laser. The energy difference between impacts can reach 10%. During a typical refractive procedure using a broad beam laser involving about 50 impacts, the total depth variation is ±0.1% (corresponding to about 0.1 D) and is negligible in clinical practice.


Fluence


The photoablation threshold at the surface of the cornea is about 50 mJ/cm 2 at a wavelength of 193 nm. Below this threshold, the photoablative action is irregular and incomplete. Each pulse with a fluence above this threshold ablates a precise amount of corneal tissue. The amount of tissue ablated per pulse increases in nonlinear fashion relative to fluence, up to a value of about 600 mJ/cm 2 , beyond which an increase in fluence no longer increases the amount of tissue photoablated by each pulse. Different lasers have fluences between 100 and 360 mJ/cm 2 , the optimal range.


Rate of Ablation


Each laser possesses its own mean ablation rate per impact, ranging from 0.25 µm to 0.6 µm. A number of factors can influence the ablation rate. Each histologic layer of the cornea responds differently to laser radiation. Thus the epithelium ablates more rapidly than the stroma, which ablates about 30% more rapidly than the Bowman layer. Corneal scars ablate less rapidly than healthy tissue. The ablation rate per impact also increases with corneal dehydration, which can lead to under- or overcorrection of 10% to 15%.


Effects of the Excimer Laser on Corneal Tissue


Absorption of excimer laser radiation by the cornea mainly produces a photochemical effect (ablative photodecomposition), together with a small photothermal effect. A challenge of using excimer lasers in the human cornea is the biologic interaction. Wound healing responses may limit predictability of laser ablation and may contribute to the development of complications, such as haze formation.


Molecular Effects


The 193-nm excimer laser emits very-high-energy photons (6.4 eV) that can break chemical bonds (ablative photodecomposition). These ruptured bonds cannot reform if the photon density exceeds a critical threshold. The formation of high-energy molecular fragments is accompanied by marked expansion and the creation of a hot gas (about 500°C). The molecular fragments are ejected at supersonic speeds (1000–3000 m/s) in a plume. This plume evacuates excess energy, thereby avoiding thermal damage to the residual tissue. The recoil generated by the ejection of photoablated matter creates a wave on the corneal surface. This wave, together with the shock waves created by the laser impacts, accounts for the noise associated with each impact (acoustic shock). The amplitude of the shock wave decreases gradually as it moves away from the center of the impact. When these two mechanical waves cross, they create fluid movement (clearly visible during photoablation for strong ametropia).


Secondary ultraviolet radiation (fluorescence), with a wavelength above 193 nm, is produced when the pulse impacts the cornea. Only 0.001% of the primary radiation is converted into secondary radiation. It has a wavelength of 460 nm at the epithelium and 310 nm at the stroma and is visible as a discreet bluish light, particularly on the epithelium. During transepithelial photoablation, the change in color (disappearance of blue fluorescence) signals the end of the phase of epithelial ablation. The corneal penetration of this secondary irradiation is negligible, as its fluence is low (< 5 mJ/cm 2 ).


Mutagenicity


Ultraviolet light with a wavelength between 248 and 358 nm is absorbed by DNA and can cause mutations. Therefore the 193-nm laser beam should not be mutagenic, which has been confirmed by experimental studies. The secondary ultraviolet radiation emitted by fluorescence at the stromal level (310 nm) could theoretically be mutagenic, but its fluence (5 mJ/cm 2 ) is below the mutagenic threshold (10 mJ/cm 2 ).


Tissular Effects


These effects, secondary to the photothermal effect, lead to structural modifications of corneal collagen, which can be affected by temperatures above 40°C. These modifications are reversible as long as the temperature remains below a threshold. In clinical practice, temperature increase in the stroma adjacent to the treatment field is no more than 1°C to 10° C. The collagen denaturation induced by this minimal temperature increase leads to the formation of a pseudomembrane, visible under the electron microscope as an electron-dense layer about 0.02 to 0.05 µm thick. Studies based on electron microscopy confirm that the residual tissue is not disrupted.




Laser Beam Generation


Gaseous Medium


All excimer (combination of “excited dimer”) lasers are based on the same light-emitting mechanism: the reaction between a rare gas and a halogen. Excimer lasers employed in refractive corneal surgery use a gaseous mixture of argon and fluorine. An inert gas, helium, serves for energy transfer. Under the effect of strong electrical discharges (pulsed mode), electrons of the argon–fluoride (ArF) atoms move to a higher energy level; the excited atoms form an unstable molecule known as a dimer. The latter then returns to its stable state, emitting high-energy photons with a wavelength of 193 nm. Pulsed emission offers more power than continuous emission does.


The ArF combination is chosen because it has the following properties: highly energetic photons, weak penetration into adjacent tissues, minimal thermal effects, a very regular impact surface, strong absorption by water, and lack of mutagenicity. Latest resonance chambers used to amplify photon emission are in ceramic. They generate highly fluent emissions, between 180 and 200 mJ/cm 2 .


Beam Homogenization


Homogenization consists of narrowing the beam that emerges from the resonance chamber and maximizing cross-sectional power uniformity. The beam is passed through an optical system consisting of mirrors, lenses, and prisms. Masks are used to select the central part of the beam, which has the highest and most constant energy. This beam homogenization process entails a certain loss of power. The smaller the number of optical interfaces, the lower the energy loss. Each manufacturer has a proprietary homogenization system.


Beam Delivery System


Once homogenized, the laser beam must be formatted to the desired photoablative effect. There are three main types of beam delivery system: full beam, scanning slit, and flying spot.


Full-Beam Systems ( Fig. 7.2 )


These were used in first-generation lasers. Full beams offer more rapid treatment (for a given frequency) and are less sensitive to decentering. However, they are more difficult to homogenize and, therefore yield less regular ablation surfaces. Bystander thermal effects are also a problem. In addition, the shock wave generated by these lasers has been implicated in the higher frequency of central islands. A diaphragm or ablative mask must be used for refractive treatment. Customized treatment of complex shapes is impossible.




Fig. 7.2


Broad-beam delivery systems. Ablative diaphragms or masks are placed between the full beam and the cornea in order to obtain the desired refractive profile.


Scanning Slit Delivery


A diaphragm is placed between the eye and a full beam, creating a rectangular beam with a smaller width (10 mm × 1 mm) and improving homogeneity. The ablation masks have a rotary motion, allowing the beam to scan in different directions ( Fig. 7.3 ). These modifications overcome some of the disadvantages of full-beam systems while preserving their principal advantages (rapid treatment and low sensitivity to decentering). All types of ametropia can be corrected with scanning slit systems. It is now possible to divide each slit into several small rectangles. Such systems resemble flying spot systems and, theoretically, offer the possibility to treat complex, irregular shapes.




Fig. 7.3


Rotary slit delivery system. This system combines corneal scanning by a fine rectangular slit (10 × 1 mm) with 120 degrees of rotation of the slit every n pulses and gradual opening of a motorized diaphragm. The schemas show an example of spherical myopic treatment: (A) passages 1 and 2; (B) passage 3.


Flying Spot


In this case, the beam is small and circular (between 0.6 and 2.0 mm in diameter). Only the most central, homogeneous part of the beam is used. The beam direction is controlled by pivoting mirrors ( Fig. 7.4A ). The target is ablated by repeated delivery of a large number of pulses, each pulse removing only a very small area of tissue. A very high pulse frequency is necessary to reduce overall treatment time, particularly when the spots are very small. The spots must be precisely dispersed in order to avoid thermal effects. An active eye tracker is crucial, as this type of system is very sensitive to decentering. The cross-sectional energy profile of each spot is generally Gaussian, to obtain smooth ablation surfaces. An interval of half a spot diameter between adjacent spots offers a regular depth of ablation between the two peaks. The main advantage of flying spot lasers is that they can provide asymmetric ablation profiles when coupled with corneal topography or wavefront analyzers. The capacity of these systems to correct complex irregularities increases as spot size decreases.




Fig. 7.4


Flying spot delivery system. (A) (1) Small laser beam; (2) mirror in X axis; (3) mirror in Y axis. A small laser spot sweeps the cornea. The pulse frequency must be high because of the small spot size (0.6-mm to 2-mm diameter). Spot mobility is ensured by a set of pivoting mirrors. No diaphragm or ablative mask is necessary for refractive ablation profiles. (B) Adjacent impacts must be offset by half a beam diameter so that the spatial sum of the energy profiles yields a constant ablation rate and a regular ablation substrate.


Computer


A computer controls the laser’s key parameters. In particular, fluence must remain constant throughout the procedure, which is achieved by modifying the power of the electrical discharges in the resonance chamber to compensate for the gradual degradation of the gaseous mixture. The computer is also used to choose the refractive or therapeutic mode, the ablation profiles (according to the refraction), and the diameters of the optical and transition zones.


For customized ablation profiles, the computer integrates the corneal topography or wavefront data and calculates the optimal ablation profile accordingly.


Work Area


The operating table, microscope, and consoles differ with each system. The operating table must allow the patient’s head to be positioned correctly. The microscope must offer an adequate focal range and magnification, especially for laser in situ keratomileusis (LASIK) surgery. The focal length varies for each laser and must be sufficient to allow the flap to be cut with a mechanical microkeratome in good condition.

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Oct 10, 2019 | Posted by in OPHTHALMOLOGY | Comments Off on Excimer Lasers

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