Therapeutic use of the 193-nm excimer laser in corneal pathologies

Purpose: To analyze the results of phototherapeutic keratectomy. Patients and methods: We performed 193-nm excimer laser phototherapeutic keratectomy (PTK) in 252 eyes of 216 patients suffering from pain and/or decrease in visual acuity. One hundred and three eyes had recurrent erosions of the cornea, 86 eyes underwent excimer laser smoothing of the cornea after pterygium surgery, 29 eyes had a bandlike keratopathy (25 rough, 4 smooth) and 34 eyes had other pathologic conditions such as amyloidosis of the cornea, anterior corneal dystrophies, scars after injuries, alkali burns, superficial stromal dystrophies and infections. Recurrent erosions and epithelial dystrophies were treated with 15–20 pulses (160–200 mJ/cm², 8 mm ablation zone) after mechanical abrasion of the epithelium. Removal of corneal opacities and scars required the use of a masking fluid (methylcellulose) in different concentrations and slit-lamp control (integrated in the delivery system of the excimer laser). Results: Some 91% of the eyes with recurrent erosions were recurrence-free. Fifty-two per cent of the eyes with pterygium had recurrences if the baresclera technique was used and 33% of the eyes if a free conjunctival graft was used. The difference was not significant. All of the patients with bandlike keratopathy were pain-free. In 88% of the eyes with special indications the treatment goal was achieved. No positive effect was seen after alkali burn, in a patient with anterior membrane dystrophy (Grayson-Wilbrandt corneal dystrophy) or in a patient with a corneal protuberance. In one patient with scleroperikeratitis a late recurrence of the opacity was observed 3 years after surgery. A loss of best corrected visual acuity was found only in one patient with bullous keratopathy in whom the treatment goal was the reduction of pain. All patients with smooth bandlike keratopathy had an improvement in best corrected visual acuity of at least one line. About 70% of patients with special indications improved by at least one line, up to nine lines. A possible hyperopic shift in all groups could be minimized using a large ablation zone. Conclusion: PTK with the 193-nm excimer laser is a safe and effective treatment for many superficial diseases of the cornea.Werner Förster is the Primary Investigator for Schwind Keratom     

Human corneal ablation threshold using the 193-nm ArF excimer laser

PURPOSE: To determine the human corneal threshold ablation energy density for the 193-nm ArF excimer laser, approximating clinical conditions. METHODS: The VISX Star (Santa Clara, CA) 193-nm argon fluoride excimer laser was used to ablate the cornea in human eye bank eyes under clinical conditions. Corneas were exposed to energy densities of 10, 20, 30, 35, 40, 45, and 140 to 160 mJ/cm2. Corneas were fixed for light and transmission electron microscopy immediately after laser exposure. RESULTS: Different ablation thresholds for various corneal structural elements were observed. The ablation threshold for the collagen in the corneal stroma was determined to be 30 mJ/cm2. Keratocytes had ablation thresholds of 40 mJ/cm2. These different ablation thresholds accounted for the production of stromal peaks and valleys, with the keratocytes atop the peaks. CONCLUSIONS: Different corneal structural elements have different ablation threshold energy densities.     

An acute light and electron microscopic study of ultraviolet 193-nm excimer laser corneal incisions

The 193-nm ultraviolet beam from an argon fluoride excimer laser was focused on the corneas of rabbits to produce incisions of the type necessary for radial keratotomy. The energy densities used were in two ranges, 1.0 to 2.1 J/cm2 per pulse and 200 to 700 mJ/cm2 per pulse. The eyes were enucleated and fixed for histologic and electron microscopic examination immediately after exposure. Structural analysis of the higher energy density exposures showed ridging on the surface of the cornea, micro-pitting on the stromal surface inside the cut, and denudation of the endothelium under the ablation zone. The lower energy density incisions did not exhibit significant surface ridging or endothelial cell loss but did exhibit significant stromal swelling during the laser exposure thus making it difficult to produce incisions of a precisely controlled depth. Beam profile measurements and infrared thermal measurements of the cornea surface during laser exposure were made.     

Long-term results of phototherapeutic keratectomy with 193-nm excimer laser for macular corneal dystrophy

PURPOSE: To investigate functional and morphologic long-term outcome of phototherapeutic keratectomy (PTK) in macular corneal dystrophy. DESIGN: Retrospective, clinical single-center study. METHODS: Between October 1990 and February 2004, 10 eyes (five oculus dexter, five oculus sinister) of 6 patients (mean age, 23 +/- 8 years [range, 15 to 37 years]) with superficial plaque-like opacities that were caused by macular corneal dystrophy were included. After epithelial debridement and pannus removal, PTK was performed with the 193 nm MEL 60 excimer laser. Intended laser ablation depth varied from 20 to 100 microm; the repetition rate was 20/s or 25/s, and the pulse number was 1774 +/- 502 (range, 976 to 2422). Mean follow-up was 4.5 +/- 3.1 years [maximum, 8.7 years]). Main outcome measures included: uncorrected visual acuity, best corrected visual acuity (BCVA), spherical equivalent, keratometric central power, keratometric astigmatism and regularity (semiquantitative classification of Zeiss keratometry; scale 0 to 3), postoperative "haze," time interval until complete epithelial closure, recurrence rate, and necessity of subsequent penetrating keratoplasty (PK). RESULTS: BCVA increased from 0.3 +/- 0.2 before the operation to 0.6 +/- 0.1 after the operation; the mean spherical equivalent increased from -0.9 +/- 1.1 diopters to -0.4 +/- 1.8 diopters. Mean keratometric central power decreased from 44.5 +/- 0.7 diopters to 42.5 +/- 0.6 diopters. During follow-up, recurrences occurred in nine eyes (90%) after 3.4 +/- 0.4 years. In six eyes, a PK was performed after an average of 5.0 years (range, 3.7 to 6.7 years). None of the transplants had a recurrence during the follow-up period. CONCLUSION: In superficial opacities that are caused by macular corneal dystrophy, PTK can increase BCVA moderately for a limited period of time. Despite possible complications, primary PK still appears to be the definite therapeutic option for patients with macular corneal dystrophy.     

Mutagenic potential of a 193-nm excimer laser on fibroblasts in tissue culture

In response to concerns regarding possible DNA damage by far ultraviolet radiation during excimer laser corneal surgery, the mutagenic potential of an argon fluoride excimer laser (193 nm) on BALB/3T3 mouse fibroblasts grown in tissue culture was investigated. The cumulative incidence of anaplastic transformation after subablative radiant exposures from 3.5 mJ/cm2/pulse to 13.4 mJ/cm2/pulse was 3.6% of all cell cultures. The incidence of anaplastic transformation in nonirradiated controls was 4.2%. Transformation after exposure to x-ray radiation (60.9 rad) was 98.8%. The difference between the incidence of transformation of nonirradiated controls or excimer-treated cultures compared with x-ray radiation-treated cells was significant P less than 0.0001 (chi square test). In this standard cell line, 193-nm laser energy does not appear to have substantial mutagenic potential.     

Clinical follow-up of 193-nm ArF excimer laser photokeratectomy.

The excimer laser has been undergoing rapid development for clinical use since the early 1980s. The authors report 2-year follow-up results from studies in 31 eyes (15 women and 14 men) to evaluate the excimer laser in performing photokeratectomy. Patients were divided into two groups: 27 eyes (group 1) underwent phototherapeutic keratectomy, and 4 eyes (group 2) underwent photorefractive keratectomy. Visual function improved in 21 of 27 eyes in group 1 and in 2 of 4 eyes in group 2. Complications were minimal and manageable. The authors describe a procedure to minimize induced hyperopia in phototherapeutic keratectomy patients, and, although not statistically significant, less induced hyperopia was noted in these patients. Photokeratectomy may be an alternative to penetrating or lamellar keratoplasty and more invasive refractive procedures, but the long-term effects must be carefully observed.     

Microsurgery of the retina with a needle-guided 193-nm excimer laser.

This article presents a method used to guide the beam from an argon fluoride excimer laser to make it suitable for microsurgical purposes and confine it to areas that can be varied in dimension from 1 micron to tens or hundreds of microns. This approach guides the excimer laser beam with an articulated mechanical arm and confines it with variable-diameter tapered tubes, possibly allowing the use of this laser in in vitro retinal surgery with endolaser techniques. Currently, because of the lack of a delivery and focusing system for the 193-nm argon fluoride beam and its absorption by biologic liquids, this laser is used exclusively in ophthalmology for topical applications, such as corneal sculpting. This new method resolves these problems in a unique way with impressive results. Specifically, it was shown that, with this needle-guided excimer laser, it is possible to remove retinal tissue accurately without detectable damage to surrounding cells. Applications of this new technique in retinal surgery are discussed.     

准分子激光屈光性角膜切削术治疗重度近视

目的 探讨准分子激光屈光性角膜切削术（ＰＲＫ）治疗重度近视的疗效。方法 使用Ｃｈｉｒｏｎ Ｖｉｓｉｏｎ的Ｋｅｒａｃｏｒ１１６准分子激光机,采用多光区切削方法治疗重度近视４９例８９眼,屈光度范围：－１０．００～－２５．００Ｄ。术后随访１ａ,并对结果进行分析。结果 ８９眼重度近视ＰＲＫ术后１ａ时,裸眼视力≥１．０者１２眼,占３．４９％,０．５～０。８者１７眼,占１９．１０％,≤０．４者６０眼,占７６７     

准分子激光对角膜内皮细胞影响的实验研究

目的 观察激光角膜光学切除术（ｐｈｏｔｏｒｅｆｒａｃｔｉｖｅ ｋｅｒａｔｅｃｔｏｍｙ,ＰＲＫ）对角膜内皮细胞损伤的可能性。方法 采用有血清和无血清培养正常兔角膜和ＰＲＫ切削深１５０μｍ角膜１ｗｋ后,观察内皮细胞形态和内皮细胞密度。结果 ＰＲＫ切削深１５０μｍ无血清培养１ｗｋ后,角膜内皮细胞形态、大小不一,部分细胞边界染色较宽,内皮细胞密度明显低于对照组（Ｐ〈０．０５）。ＰＲＫ切削深１５０μｍ有血清     

An ultrastructural study of corneal incisions induced by an excimer laser at 193 nm

Far ultraviolet light (193 nm) produced by an excimer laser has been used to produce a variety of incisions in the corneas of anaesthetised rabbits. Tissue was lost from the site of irradiation but the nature of the underlying molecular interactions responsible for such tissue erosion remain obscure. Ultrastructural analysis of the walls of the ablated areas show damage to the adjacent structures to be confined to a zone 60 to 200 nm in width. These dimensions could either be attributed to photochemical processes in which high energy photons directly break organic molecular bond, or to thermal reactions which result in limited heat flow and damage confined to the absorption depth at 193 nm of less than 1 micron. In non-penetrating incisions that reached within 40 micron of Descemet's membrane, endothelial cells were lost beneath the line of the irradiation. This spalling of cells seemed to be generated by shock or acoustic waves.     

Quantitative analysis of corneal excisions using argon fluoride excimer laser (193 nanometers)

Excimer lasers represent a new and distinctive class of laser-tissue interaction termed photoablation. They can ablate materials with a high degree of precision and minimal damage to surrounding structures. The argon Fluoride excimer laser, which offers the possibility of non-contact corneal cutting, has a potential for clinical application of keratorefractive surgery. Since each pulse of excimer laser etches some amounts of tissue from the cornea, the repetitive pulses focused to a narrow line can create linear excisions. In this study, a quantitative analysis of both depth and width of corneal excisions was made on cadaver eyes at a given fluence (600 mj/cm2) and a constant repetitive rate (20Hz). The amount of ablation per pulse was not constant and the excisional depth did not show a linear correlation with pulse numbers. Both the depth and width of transversal excisions were more homogenous than those of radial excisions along the entire length of ablation.     

Lamellar excimer laser keratoplasty: Reproducible photoablation of corneal tissue

We examined the depth of ablation of the recipient bed with different counts of oscillations of excimer laser beam, to determine the correlation between planned and real depth. The ablation rate per oscillation was tested preoperatively by blackened photographic paper of defined thickness and thus was calculated to be 5 m. Forty pig eyes were used for the first study. Each eight eyes were ablated in the planned depth 100 m, 200 m, 300 m, 400 m and 500 m. The corneal thickness was measured with an ultrasonic pachymeter before and after the procedure. The depth measured after the photoablation was 99.4 ± 36.4 m for 100 m planned depth, 186.7 ± 55.3 m for 200 m, 298.4 ± 68.5 m for 300 m, 373.9 ± 65.7 m for 400 m and 480.1 ± 59.3 m for 500 m. Comparing the depth measured after the photoablation to planned depth, there was a significant correlation (correlation coefficient: R = 0.93; p < 0.0001). Five other corneas trephinated from pig cadaver eyes were ablated from the endothelial side to the desired thickness (100 to 500 m) of lamellar graft. In a second step a donor mask was placed onto the cornea and a laser light spot was led until perforating on all sides. The lamellar keratoplasty was completed by suturing the corneal graft into the bed. Macroscopic and microscopic examination of sutured eyes after fixation showed a good fit of wound margins and stromal interface. These results indicate that excimer laser is useful for reproducible corneal photoablation in lamellar keratoplasty.     

提高准分子激光角膜屈光手术后角膜的安全性

自70年代至今,屈光手术经过不断的革新、改进,目前准分子激光角膜屈光手术成为矫正近视的重要方法。由于其在正常的角膜组织上通过不同方式制作各种角膜瓣后进行激光切削,因而其术后长期的安全性一直是眼科医生担心和关注的主题。本文通过比较临床应用的不同技术方法的利弊,从角膜安全性角度阐述其各自的适应证,以期为临床合理治疗提供资料。     

Superficial keratectomy with the 193 nm excimer laser: a reproducible model of corneal surface irregularities.

Rough corneal surfaces may be smoothed by performing a superficial keratectomy with the 193 nm excimer laser. In order to smooth an irregular surface, a substance must be used during ablation to protect low corneal areas so that high spots are ablated preferentially. A simple, accurate, and reproducible method for modelling various corneal surface irregularities was developed. The technique uses the excimer laser to imprint the patterns of various metallic grids onto the stromal surface. The model was used to facilitate a comparison of three potential smoothing agents: 0.5% tetracaine, 2% hydroxypropylmethylcellulose, and a fluorescein-containing hyaluronate preparation. Preliminary results indicate that tetracaine may be the most efficacious smoothing agent.     

Complications of laser keratomileusis with the excimer laser (193 nm)]

Complications of photorefractive keratectomy (PRK) for myopia correction are presented based on 615 procedures with a follow-up of up to 2 years. Intraoperative complications with experienced surgeons are extremely rare. The used laser system worked without technical failures for the last 18 months. Gross eccentricities of the ablative zone (1.0 mm to 1.5 mm) occurred in two eyes (0.3%). Also, epithelial disorders are very rare. Recurrent erosions did not occur. Increased intraocular pressure due to the postoperative steroid medication (dexamethasone 0.1% or prednisolone 1%) was manifest in about 30% in patients with a baseline myopia of up to -9.0 D. In myopia over -9.0 D the incidence of steroid glaucoma was about 50%. Steroid responders reveal an increased risk of overcorrection. Subepithelial haze is a common symptom after PRK. Scarring interfering with vision correlates with the amount of attempted correction: up to 6.0 D the incidence of scars is about 0.5% and increases to more than 10% in corrections of more than 10 D. Also, undercorrections of more than 1 D depend strongly on the attempted correction. The most severe complication was a noninfectious corneal ulcer in a patient with systemic lupus erythematosus. Therefore, autoimmune and connective-tissue diseases represent an absolute contraindication for PRK. Corrections of more than 6.0 to 7.0 D should be considered as a relative contraindication for PRK at this time.     

Mass spectroscopic analysis of excimer laser ablated material from human corneal tissue

The clinical feasibility of photorefractive keratectomy depends on the surface structure of the ablated cornea. Two factors that influence the remodeled surface are the homogeneity of the energy distribution and the properties of the laser source (energy and wavelength). Currently, the homogeneity of the beam is difficult to control. The second factor, laser source properties, was the focus of this study. We investigated the effect of laser wavelength and energy by analyzing the reaction products of photoablation. We monitored the fragments produced by UV-laser ablation of human corneas using mass spectroscopy in the range of 0 to 100 atomic mass units. At 248 nm (KrF), average photon energy was 5 mJ/cm2, increased to 90 mJ/cm2 by intervals of 5 mJ/cm2. At 193 nm (ArF), photon energy was increased by the same interval from 5 mJ/cm2 to 80 mJ/cm2. Our experiments showed that there was a fluence threshold of approximately 40 mJ/cm2 at 193 nm (ArF) and 50 mJ/cm2 at 248 nm (KrF). Exceeding this threshold led to sudden increases in the number and relative intensity of fragment peaks in mass spectroscopy. This indicates the onset of multiple-photon processes and effective photochemical breakdown. There was a significant difference between both wavelengths in the distribution of mass peaks, indicating higher ionization power at 193 nm.     

准分子激光角膜上皮瓣下磨镶术和准分子激光屈光性角膜切削术后角膜上皮下雾状浑浊的对比观察

目的探讨准分子激光角膜上皮瓣下磨镶术（LASEK）手术和准分子激光屈光性角膜切削术（PRK）手术后角膜上皮下雾状浑浊（haze）的发生率。方法分别对120例（240眼）左右眼分别行LASEK和PRK手术,观察12个月,计算出低中度近视组（等于或低于-6.00D）和高度近视组（-6.00D以上）haze的发生率。结果低中度近视组和高度近视组LASEK手术后1,3,6,12个月haze的发生率均低于PRK手术后1,3,6,12个月haze的发生率,其中低中度近视组和高度近视组LASEK手术后1,3个月1级haze的发生率和PRK手术后1、3个月1级haze的发生率比较差异均有统计学意义（P〈0.05）,低中度近视组LASEK手术后12个月1级haze的发生率和PRK手术后12个月1级haze的发生率比较差异有统计学意义（P〈0.05）。结论 LASEK手术后haze形成情况显著好于PRK手术。     

Preliminary study of argon fluoride (193 nm) excimer laser trabeculectomy. Scanning electron microscopy at five months

There is an increasing interest in the use of the excimer laser in ophthalmology, particularly in refractive surgery. The argon fluoride (193 nm) excimer laser ablates tissue with a high degree of precision and without any mechanical or thermal damage to surrounding structures. In this study, the argon fluoride excimer laser was experimentally used in the rabbit model to perform a trabeculectomy. Clinical and scanning electron microscopic evaluations showed a successful and patent filtering procedure. At the five-month follow-up the trabeculectomy was smooth and regular and there was no evidence of inflammation or thermal damage on the surrounding structures.