**2. Excimer laser in ophthalmology**

### **2.1. Characteristics of the excimer laser**

The *excimer* (comprising the terms *excited* and *dimer*) was named by the Russian, Nikolay Basov, in 1970, based on his work with a xenon dimer gas [1]. An *excimer* is a short-lived dimeric or heterodimeric molecule formed from two species (a noble gas and a halide), at least one of which has completely filled the valence shell by electrons. Excimers are only formed when one of the dimer components is in the excited state. When the excimer returns to the ground state, its components dissociate. The wavelength of an excimer's emission depends on the noble gas, such as ArF (193 nm), KrF (248 nm), XeCl (308 nm), or XeF (351 nm). The ultraviolet laser (193 nm) is commonly used to ablate tissue through ablative photodecomposition. The process of ablative photodecomposition involves three main components: absorption, bond breaking, and ablation. A large number of experiments have shown that the ArF excimer laser (193 nm) is the most optimal for corneal absorption and ablation because of its sufficient photon energy (6.4 eV) and precision (only penetrating the superficial layer; 0.3 μm). The tissueablation depth is positively correlated with the logarithm of laser density; 1-J/cm2 energy can ablate approximately 1-μm corneal tissue. In addition, as a cold laser, the excimer laser can ablate the tissue accurately without thermal damage.

#### **2.2. Photorefractive keratectomy (PRK)**

Professor Jose I. Barraquer described his coined technique of "keratomileusis" to correct myopia in 1949, and this could be the original form of photorefractive keratectomy (PRK). A few years later, many researchers designed similar surgical procedures. In 1983, Stephen Trokel first started using the ArF (193 nm) excimer laser as a precise and safe tool of corneal shaping in calf eyes. He found that the excimer laser not only accurately ablated central corneal tissues but also did not do excessive damage to the peripheral corneal tissues. After a large number of animal experiments, in 1989, Marguerite McDonald, who first applied the technol‐ ogy to human eyes, presented the first patency of using the excimer laser as a corneal refractive tool, and it was accepted. Since then, PRK has become the classic refractive surgery, and its safety and efficacy have been proven by abundant studies. China introduced this surgery in 1993, but the presence of postoperative complications has influenced its development [1].

Compared with the current, more popular lamellar corneal refractive surgery, PRK has shown similar postoperative visual quality but more intraoperative and postoperative complica‐ tions, such as haze. Nevertheless, Wagoner et al. [2] proposed that PRK had better visual results compared with lamellar corneal refractive surgery. O'Brart [3] also thought PRK showed better cornea curvature and excellent visual quality compared with those of lamellar corneal refractive surgery.

### **2.3. Laser epithelial keratomileusis (LASEK)**

ocular disorders, and high myopia may result in comorbidities associated with significantly increased risks of severe and irreversible loss of vision, it is always an important topic of research worldwide. Laser technology, including the excimer laser and the femtosecond laser, has brought an era of laser corneal refractive surgery. According to the location of ablation, corneal refractive surgery can be divided into two types: laser corneal surface refractive surgery and laser corneal lamellar refractive surgery. Because of the increasing numbers of applications in ophthalmology and their successful implementations, ophthalmic use of laser

The aim of this chapter is to review the evolution of laser technology in refractive and other ophthalmologic surgeries, mainly focusing on the characteristics of two types of lasers and their applications: the excimer laser applied in laser corneal surface refractive surgery and presbyopia surgery and the femtosecond laser applied in laser corneal lamellar refractive

The *excimer* (comprising the terms *excited* and *dimer*) was named by the Russian, Nikolay Basov, in 1970, based on his work with a xenon dimer gas [1]. An *excimer* is a short-lived dimeric or heterodimeric molecule formed from two species (a noble gas and a halide), at least one of which has completely filled the valence shell by electrons. Excimers are only formed when one of the dimer components is in the excited state. When the excimer returns to the ground state, its components dissociate. The wavelength of an excimer's emission depends on the noble gas, such as ArF (193 nm), KrF (248 nm), XeCl (308 nm), or XeF (351 nm). The ultraviolet laser (193 nm) is commonly used to ablate tissue through ablative photodecomposition. The process of ablative photodecomposition involves three main components: absorption, bond breaking, and ablation. A large number of experiments have shown that the ArF excimer laser (193 nm) is the most optimal for corneal absorption and ablation because of its sufficient photon energy (6.4 eV) and precision (only penetrating the superficial layer; 0.3 μm). The tissue-

ablation depth is positively correlated with the logarithm of laser density; 1-J/cm2

ablate the tissue accurately without thermal damage.

**2.2. Photorefractive keratectomy (PRK)**

ablate approximately 1-μm corneal tissue. In addition, as a cold laser, the excimer laser can

Professor Jose I. Barraquer described his coined technique of "keratomileusis" to correct myopia in 1949, and this could be the original form of photorefractive keratectomy (PRK). A few years later, many researchers designed similar surgical procedures. In 1983, Stephen Trokel first started using the ArF (193 nm) excimer laser as a precise and safe tool of corneal shaping in calf eyes. He found that the excimer laser not only accurately ablated central corneal tissues but also did not do excessive damage to the peripheral corneal tissues. After a large number of animal experiments, in 1989, Marguerite McDonald, who first applied the technol‐

energy can

technology is expected to continue flourishing.

376 378High Energy and Short Pulse Lasers

surgery and other ophthalmologic surgeries.

**2. Excimer laser in ophthalmology**

**2.1. Characteristics of the excimer laser**

Laser epithelial keratomileusis (LASEK), also called laser sub-epithelial keratectomy, was first proposed and named by Italian doctor Massimo Camellin in 1998. The first case of LASEK was performed by Azar at Massachusetts Eye and Ear Infirmary in 1996. It is a modified opera‐ tion based on the PRK, which enabled the epithelium to be preserved as a flap (about 50–70 μm) using 20% ethanol to infiltrate and release the connection between the corneal epitheli‐ um and Bowman layer and then overturn the flap. The flap is then reset after ablating the stroma using the excimer laser.

Therefore, LASEK can be considered a kind of PRK that is "wearing flap." The key to success throughout the surgical procedure is the activity and good adhesion of the flap. Owing to the viable flap, it combines the advantages of laser in situ keratomileusis (LASIK) and PRK. Because LASEK is essentially a kind of surface ablation evolved from PRK; consequently, it reserves the features of safety, validity, simplicity, and stability in low to moderate ametro‐ pia and presbyopia correction. Moreover, its flap design, which is similar to that of LASIK, has several merits: postoperative discomfort can reduce within 2–8 h after the procedure; the epithelium of the optical region in the slit lamp after surgery is as complete and clear as it is before surgery within 12–24 h; there is no edema or postoperative haze; and early complica‐ tions, such as corneal epithelium necrosis, are less common compared with PRK. These outstanding characteristics are likely to have provided the inspiration for the advent of LASIK.

Furthermore, LASEK preserves the corneal biomechanical integrity and results in good clinical outcomes. Scholars have indicated that LASEK shows better postoperative outcomes includ‐ ing postoperative corneal topography and contrast sensitivity, and faster postoperative recovery rate in low to moderate myopia correction compared with PRK. In addition, LASEK has a unique advantage for patients with retinal diseases, high myopia, or blepharophimosis. Lu Xiong conducted a study on the clinical outcomes in low to moderate myopia after LASEK treatment, and the results showed that LASEK has a good effect and better postoperative experience compared with PRK.

According to the principles of LASEK, it not only optimizes PRK but also avoids some disadvantages of laser lamellar corneal refractive surgery such as LASIK. First, it avoids the risk associated with the corneal flap (e.g., free flap, broken flap, and button flap) made by

microkeratome in LASIK. Second, it has less effect on the corneal nerve and less serious dry eye syndrome than LASIK. Third, LASEK creates less surgically induced wavefront aberra‐ tion because of its thinner flap. In addition, it saves the cost of the microkeratome or femto‐ second laser used in LASIK.

Nevertheless, LASEK has some common risks of surface ablation in high myopia correction, such as postoperative haze and side effects of corticosteroid eye drops required after sur‐ gery. What is more, LASEK is a complex surgical procedure that requires high surgical skill with a long learning curve for beginners.

### **2.4. Epipolis laser in situ keratomileusis (Epi-LASIK)**

Epipolis laser in situ keratomileusis (Epi-LASIK) was first reported by the Greek doctor Pallikaris in 2003. Different from LASEK, Epi-LASIK uses a microkeratome instead of ethyl alcohol to bluntly separate the corneal epithelial from the Bowman layer. Therefore, Epi-LASIK avoids direct stimulation of alcohol and reserves the intact epithelial basement membrane, which results in good subjective feelings in patients as well as quick recovery and haze reduction.

Epi-LASIK surgery takes the activity of the flap as the core, which is crucial to the therapy effect. Compared with PRK, Epi-LASIK has an extra flap covering the corneal stromal bed, which can effectively protect the stroma below and also promotes corneal tissue healing. Epi-LASIK has different methods of flap creation than those of LASEK. Its flap basement mem‐ brane is intact, continuous integrity segments of stratum lucidum and a longer compact layer. The postoperative healing time of Epi-LASIK is shorter without alcohol stimulation or chemical damage to the corneal epithelium. Even though the flap of Epi-LASIK is closer to corneal natural state, the postoperative biomechanical change of the corneal flap and the effect on corneal healing are yet to be determined [4].

#### **2.5. Transepithelial photorefractive keratectomy (Trans-PRK)**

Transepithelial photorefractive keratectomy (Trans-PRK), where both the epithelium and stroma are removed in a single step, is a relatively new procedure of laser refractive error correction. It has become the focus in the refractive surgery field recently and the first choice to treat ametropia with or without an irregular cornea. The excimer laser has been devel‐ oped to the sixth-generation lasers, targeting the goal of minimally invasive laser refractive surgery during the past 30 years. The latest laser system delivers more laser spots per second so as to reduce the treatment time [5]. Tran-PRK has brought a new revolution to excimer laser techniques for its bladeless surgery process [6] and superiority in efficiency and safety. Hence, it has been considered as the representative operation of the laser corneal surface refractive surgery, and it is a step closer to the perfect refractive surgery. Trans-PRK has been indicat‐ ed in low to moderate myopia patients and a small number of high myopia patients (−8D below), but not in patients with a very low-degree myopia. Trans-PRK is currently regarded as an optimal safety choice for patients with a thin cornea. In addition, it is also the best choice for combat athletes, high-risk workers, and patients with ocular surgical history. For the second operation and patients with irregular corneas, who need synergistic or customized surgery, Trans-PRK may be the only choice.

#### *2.5.1. Advantages and disadvantages*

microkeratome in LASIK. Second, it has less effect on the corneal nerve and less serious dry eye syndrome than LASIK. Third, LASEK creates less surgically induced wavefront aberra‐ tion because of its thinner flap. In addition, it saves the cost of the microkeratome or femto‐

Nevertheless, LASEK has some common risks of surface ablation in high myopia correction, such as postoperative haze and side effects of corticosteroid eye drops required after sur‐ gery. What is more, LASEK is a complex surgical procedure that requires high surgical skill

Epipolis laser in situ keratomileusis (Epi-LASIK) was first reported by the Greek doctor Pallikaris in 2003. Different from LASEK, Epi-LASIK uses a microkeratome instead of ethyl alcohol to bluntly separate the corneal epithelial from the Bowman layer. Therefore, Epi-LASIK avoids direct stimulation of alcohol and reserves the intact epithelial basement membrane, which results in good subjective feelings in patients as well as quick recovery and haze

Epi-LASIK surgery takes the activity of the flap as the core, which is crucial to the therapy effect. Compared with PRK, Epi-LASIK has an extra flap covering the corneal stromal bed, which can effectively protect the stroma below and also promotes corneal tissue healing. Epi-LASIK has different methods of flap creation than those of LASEK. Its flap basement mem‐ brane is intact, continuous integrity segments of stratum lucidum and a longer compact layer. The postoperative healing time of Epi-LASIK is shorter without alcohol stimulation or chemical damage to the corneal epithelium. Even though the flap of Epi-LASIK is closer to corneal natural state, the postoperative biomechanical change of the corneal flap and the effect

Transepithelial photorefractive keratectomy (Trans-PRK), where both the epithelium and stroma are removed in a single step, is a relatively new procedure of laser refractive error correction. It has become the focus in the refractive surgery field recently and the first choice to treat ametropia with or without an irregular cornea. The excimer laser has been devel‐ oped to the sixth-generation lasers, targeting the goal of minimally invasive laser refractive surgery during the past 30 years. The latest laser system delivers more laser spots per second so as to reduce the treatment time [5]. Tran-PRK has brought a new revolution to excimer laser techniques for its bladeless surgery process [6] and superiority in efficiency and safety. Hence, it has been considered as the representative operation of the laser corneal surface refractive surgery, and it is a step closer to the perfect refractive surgery. Trans-PRK has been indicat‐ ed in low to moderate myopia patients and a small number of high myopia patients (−8D below), but not in patients with a very low-degree myopia. Trans-PRK is currently regarded as an optimal safety choice for patients with a thin cornea. In addition, it is also the best choice for combat athletes, high-risk workers, and patients with ocular surgical history. For the second

second laser used in LASIK.

378 380High Energy and Short Pulse Lasers

reduction.

with a long learning curve for beginners.

**2.4. Epipolis laser in situ keratomileusis (Epi-LASIK)**

on corneal healing are yet to be determined [4].

**2.5. Transepithelial photorefractive keratectomy (Trans-PRK)**

Compared with other corneal refractive surgeries, Trans-PRK has the advantages of no chemical toxicity or mechanical damage, no corneal incision, no negative pressure suction, and less risk of infection, and it avoids the potential damage caused by negative pressure suction.

Trans-PRK was considered as a kind of minimally invasive surgery for its optimal safety. Without creating a corneal flap, Trans-PRK significantly reduces the postoperative corneal biomechanical change, and it has little effect on the structure of the cornea, without corneal flap mark and flap-related complications. In addition, Tran-PRK offers faster epithelial healing, lower postoperative pain, and significantly less haze formation. Kaluzny et al. [7] used optical coherence tomography to supervise the epithelial recovery time and found that Trans-PRK (3 days) has a significantly shorter recovery time than PRK does (4 days). Aslanides et al. randomly selected 60 eyes of 30 myopic patients who had undergone conventional alcoholassisted PRK in one eye and Trans-PRK in the other eye. The postoperative follow-up showed that Trans-PRK offers faster epithelial healing and 64% lower average pain scores. The haze level was consistently lower after Trans-PRK from 1 to 6 months [8].

Trans-PRK is considered a minimal complication, maximum security single-laser surgery at present. There is no significant different between Trans-PRK and other laser surgery in final visual acuity [9, 10]. Patient satisfaction is not as high with Trans-PRK compared with the femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) and small-incision lenticule extraction (SMILE) soon after surgery because of the slightly higher incidence of haze, pain, and slower recovery of visual acuity. However, Trans-PRK has good long-term postopera‐ tive satisfaction.

#### *2.5.2. Visual outcomes and visual quality*

Many studies have shown that [8, 9, 11] Trans-PRK has high-precision visual outcomes and good stability in ametropia correction. A large retrospective comparison of transepithelial PRK with LASEK, Epi-LASIK, and LASIK detected better visual outcomes with Trans-PRK for high myopia [12]. In hyperopia correction, the effectiveness showed a substantial increase over the previous study, but there are still difficulties, such as the relatively high rate of secondary operation, residual refractive error, surgically induced negative spherical aberration, and astigmatism. In astigmatism correction, static cyclorotation component and dynamic cycloro‐ tation component techniques greatly improve the effectiveness.

With the development of refractive surgery technology, its safety is high. Increasingly, researchers have focused on improving postoperative visual quality. The assessment of the visual quality is divided into two main aspects. The subjective part includes vision acuity (near, intermediate, and distance) and contrast sensitivity, whereas the objective part in‐ cludes the objective wavefront aberration, point spread function, modulation transfer function, visual quality scale, and so on. Research shows that topography-guided Trans-PRK can

effectively correct the irregular astigmatism and improve the postoperative contrast sensitiv‐ ity in patients. On the contrary, Trans-PRK simplifies the process, which reduces the poten‐ tial higher order wavefront aberration caused by irregular ablation and decreases postoperative glare and night vision loss. Therefore, increasingly ophthalmologists choose Trans-PRK to improve postoperative visual quality.

Trans-PRK is the easiest laser refractive surgery for refractive surgeons to learn, and it is stable in techniques and cost-effective. As a result, it is considered an ideal corneal refractive operation for patients.

#### **2.6. Excimer laser in presbyopia correction**

Presbyopia is an age-related condition in which accommodation gradually decreases and the eyes are unable to focus and obtain clear near vision. There is one approach to correct presbyopia through laser refractive surgery commonly called PresbyLASIK. Synonymous with LASIK, PresbyLASIK contains the process of making a special ablation profile to either perform a multifocal cornea procedure or increase the depth of field.

PresbyLASIK has been described in three different approaches: central PresbyLASIK, peripheral PresbyLASIK, and transitional multifocality. In central PresbyLASIK, the central area is shaped for near vision and the mid-peripheral cornea is shaped for distant vision. On the contrary, in peripheral PresbyLASIK, the central area is shaped for distant vision and the mid-peripheral corneal area for near vision. Both central and peripheral techniques reported‐ ly obtained adequate spectacle independence in both myopia and hyperopia. In addition, a neuroadaptation process is needed in peripheral techniques. The third approach combines depth of field increase and micro-monovision, which induces a certain degree of spherical aberration to each eye to increase the depth of field while making the nondominant eye slightly myopic [13].

Presbyopia remains the biggest challenge to be corrected: the mechanism of accommodation and the cause of presbyopia are complex to understand fully. Therefore, the efficacy of presbyopia correction even with the latest platform is still in dispute. However, there is enough scientific evidence to consider PresbyLASIK as a useful tool in presbyopia correction [14]. Epstein and Gurgos [15] reported that 89% hyperopia (25/28) patients and 91.3% myopia (94/103) patients who underwent peripheral PresbyLASIK were completely spectacle inde‐ pendent and with distance unaided visual acuity of 20/20 in 67.9% (19/28) in hyperopia patients and 70.7% (53/75) in myopia patients.
