22

Comparison of Wavefront-Guided Photorefractive Keratectomy and LASEK Treatments for Myopia and Myopic Astigmatism

Zoltán Z.Nagy, MD

Semmelweis University

Budapest, Hungary

INTRODUCTION

Wavefront measurement is a new tool for determination of the visual performance of the eye and for developing a treatment plan to abolish higher-order aberrations to provide supervision for the patient. It is known that laser in situ keratomileusis (LASIK) treatment causes significant increase in higher-order aberrations because of the corneal cut (Krueger RR. Wavefront technology. 1st International LASEK Congress, March 21– 23,2002, Houston, TX); therefore, attention of the refractive surgeons focuses again to advanced surface ablation techniques such as photorefractive keratectomy (PRK) with sophisticated flying spot laser beam delivery technology and laser intraepithelial keratomileusis (LASEK) (1–5), which seems to be a viable alternative to LASIK technology.

In this study, authors compared the results with wavefront-guided refractive treatments using PRK and LASEK technology in eyes with spherical myopia and myopic astigmatism.

PATIENTS AND METHODS

Two groups were formed for the purpose of the study. Group 1 (n=40) included the PRKtreated eyes, and group 2 (n=40) included the LASEK-treated eyes. The mean age of patients in group 1 was 32.2±3.42 years (range, 23 to 48 years); in group 2, mean age was 31.4±4.02 years (range, 22 to 40 years). The preoperative mean correction to obtain the spectacle-corrected visual acuity was −4.08±1.06 diopters (D) (spherical equivalent −1.5 D to −6.0 D; spherical range and 0 to −2.5 D in the cylindrical range) in group 1 and −4.12±0.98 D spherical equivalent (−1.25 D to −6.0 D and 0 to −2.0 D in cylindrical range. Follow-up is 6 months for each patient.

During preoperative assessment, uncorrected visual acuity and spectacle-corrected visual acuity were tested and authors performed topography (Tomey-III, New York, NY), ultrasound pachymetry (Humphrey Model 850, San Leandro, CA), automated

refractometry without and with pupil dilation, retinoscopy, Goldmann applanation tonometry, and wavefront-supported customized ablation (WASCA) measurements with the Asclepion WASCA workstation. WASCA measurements were performed in a dimly lit room without and with pupil dilation, calculation was based on the result obtained with undilated pupil, and the central 5.5-mm diameter measurements were considered at the determination of higher-order aberrations of the eye, i.e., the treatment plan. Wavefront measurements (WASCA) were performed with the Asclepion-Meditec WASCA workstation (Wavefront Sciences, Albuquerque, NM). A plane infrared laser wave is emitted at the lowest possible energy with 0.45 µW, which forms a small spot on the patient’s foveola. This spot acts as a secondary light source. The distortion of wavefront emitted by this point source is then analyzed by the machine. In an ideal nonaccommodating emmetropic eye, the wavefront exiting the eye is a plane wave again. In all other cases, the exiting wavefront will deviate from the original plane. The ShackHartmann sensor analyzes the deviation of the exiting wavefront from normal. The sensor consists of an array of microlenses (1452 altogether). Each lens defines a subaperture focusing a small portion of the incident wavefront on the sensor, leading to a pattern of focal spots on the detector surface. This pattern contains the information about the spatial phase and intensity distribution of the incident wave with a resolution determined by the number of lenslets per unit area, i.e., the overall lower-order and higher-order aberrations of the eye can be described in this way. By a mathematical program, the lower-order aberration (sphero-cylindrical refractive error) can be distracted from the overall aberration, and then the higher-order (third and fourth order) aberrations can be obtained.

WASCA-guided PRK treatments were performed with the Asclepion-Meditec MEL

70 G-scan flying spot excimer laser. The laser operates with 250 mJ/cm2 fluency, with 38Hz frequency, and with a 1.8-mm diameter flying spot beam, and with an active eye

tracker.

Exclusion criteria were: blepharitis, dry eye syndrome, amblyopia worse than 20/40, connective tissue disease, keratoconus, keratoglobus, previous corneal scars, progressive myopia (more than 15% progression of refractive error during a year), pregnancy, and pacemaker.

During PRK treatment, patients received three drops of oxybucaine hydrochloride anaesthetic eye drops, and then the epithelium was removed with a blunt hockey knife (4 seconds), a 12.0-mm metal ring was placed onto the eye, and the optical center of the eye was identified with the eye tracker, which recognized the geometrical center of the metal ring. Treatment data of higher-order aberration were transported via a zip disc to the computer panel of the excimer laser. At first the lower-order aberrations were treated and then identified again in the pupillary center. The higher-order aberrations were also treated during the same session.

After WASCA-guided PRK, patients received tobramycine drops and topical fluorometholone. A soft bandage lens was applied for the first 3 postoperative days, then it was removed. The postoperative treatment protocol was the same as with traditional PRK, i.e., tobramycin drops four times daily for 5 days, then fluorometholone drops four times daily in a gradually tapering dose for 3 months. Patients were followed-up on the first postoperative day, on the fifth postoperative day, and at 1 month, 3 months, and 6 months after PRK. Postoperatively, the uncorrected visual acuity, spectacle-corrected visual acuity, Goldmann tonometry, ultrasound pachymetry, and WASCA measurements were

LASEK, PRK, and excimer laser stromal surface ablation 272

tested and recorded. Subepithelial haze was assessed by slit-lamp biomicroscopy using Hanna’s scale (6).

RESULTS

During the early postoperative period, patients in both groups had the usual mild symptoms of tearing, slight irritation, and photophobia. In group 1, the early postoperative symptoms were much milder because of the bandage contact lens than after traditional PRK. Symptoms were less pronounced in group 2 compared to group 1. Epithelial healing was normal in group 1 within 4 days. None of the patients had corneal infiltrates during the early postoperative period. Postoperative healing was normal in group 2, and no epithelial irregularity was found during the early postoperative period.

Before PRK treatment, the uncorrected visual acuity was, on average, 0.06 (20/300) in both groups; in group 1, spectacle-corrected visual acuity was 0.96 (less than 20/20) in group 2 it was 0.94 (less than 20/20).

Postoperatively in group 1, uncorrected visual acuity was 1.04±0.06 (better than 20/20); refraction was −0.12±0.02 D; spectacle-corrected visual acuity was 1.21± 0.04 (>20/15); 85% (34/40) were within ±0.25 D; 97.5% (39/40) were within ±0.5 D of intended refraction; and 100% (40/40) were within ±1.0 D. In group 2, postoperative uncorrected visual acuity was 1.02±0.04; spectacle-corrected visual acuity was 1.22± 0.06; 82.5% (33/40) were within 0.25 D of intended refraction; 95% (38/40) were within ±0.5 D, and 100% (40/40) were within ±1.0 D (Figs. 1–3).

Interestingly, best results with uncorrected visual acuity and spectacle-corrected visual acuity was reached after 3 months and occurred mainly in eyes with a preoperative refractive error less than −3.5 D of spherical equivalent.

Concerning safety, in group 1, 72.5% (29/40) of the eyes had spectacle-corrected visual acuity the same as that preoperatively; 20.0% (8/40) gained one line; 7.5% of the eyes (3/40) had spectacle-corrected visual acuity with a gain of two or more Snellen lines; none of the eyes lost any lines of spectacle-corrected visual acuity. In group 2, 70% (28/ 40) had the same spectacle-corrected visual acuity as that preoperatively; 12.5% of eyes (5/40) gained one line; 5% (2/40) gained two lines; and 12.5% (5/40) lost one line; however, none lost two or more lines (Fig. 4).

Root mean squared (RMS) values increased from a preoperative value of 0.14 to 0.21 and from 0.12 to 0.23 in group 1 and group 2, respectively.

Slit-lamp biomicroscopy revealed normal corneal wound healing in all case. None of the eyes had more than grade 1 haze according to Hanna’s scale (2). Intraocular pressure was not increased during the follow-up in any of the patients.

LASEK, PRK, and excimer laser stromal surface ablation 274

Figure 4 Change of spectaclecorrected visual acuity (safety) after WASCA-guided PRK and LASEK.

DISCUSSION

Wavefront analysis provides a new and comprehensive information about the overall visual performance of the eye. Frits Zernicke, the Dutch Nobel Prize holder, developed a method in the 1940s to express wavefront function as a series of polynomials in such a way that each of these polynomials describes a characteristic aberration of the human optical system. This is achievable by software developed for WASCA Analyzer, which is able to examine higher-order aberration up to the fourth order. The first-order and second-order aberrations describe the lowest-order aberration of the eye, i.e., the spherocylindrical refractive error, which can be corrected with glasses, and was the basis of traditional refractive surgery (PRK, LASIK, LASEK) until today. With a mathematical tool, it is possible to separate the lower-order and higher-order aberrations from the overall distortion of wavefront to obtain the third-order and fourth-order Zernicke polynomials. We think that by abolishing the higher-order aberrations, it is possible to obtain supervision in some of the patients.

In the literature there is still a debate regarding which refractive surgical procedure gives the best result and which is the most suitable for the purpose of wavefront-guided refractive treatments. Today, most authors agree that LASEK provides better results than LASIK (1–3), and LASEK results are comparable with results of traditional PRK (5). We can also support this finding, because in our results there was no significant difference between PRK and LASEK. Using wavefront-guided algorithms, both methods could increase spectacle-corrected visual acuity. We also know from the work of Krueger that LASIK creates more higher-order aberrations than LASEK or PRK (Krueger RR. Wavefront technology. 1st International LASEK Congress, March 21–23, 2002, Houston, TX).

Based on our results, we can conclude that WASCA-guided PRK and LASEK treatments are safe, efficient, and predictable, and that both methods provided similar

results. Despite a slight increase in RMS values, it was possible to improve spectaclecorrected visual acuity using the WASCA method in both treatment groups. The increase of spectacle-corrected visual acuity occurred at approximately the third postoperative month after surgery. WASCA-guided treatments gave better results in the lower diopter range (less than −3.5 D of spherical equivalent). Still, longer follow-up and a higher number of treated eyes are needed to judge the real value of the method.

REFERENCES

1.Azar DT, Ang RT, Lee JB, Kato T, Chen CC, Jain S, Gabison E, Abad JC. Laser subepithelial keratomileusis: electron microscopy and visual outcomes of flap photorefractive keratectomy. Curr Opin Ophthalmol; 2001; 12:323–328.

2.Scerrati E. Laser in situ keratomileusis vs. laser epithelial keratomileusis (LASIK vs LASEK). J Refract Surg; 2001; 17(S):219–221.

3.Kornilovsky IM. Clinical results after subepithelial photorefractive keratectomy (LASEK). J Refract Surg; 2001; 17(S):222–223.

4.Claringbold TV. Laser-assisted subepithelial keratectomy for the correction of myopia. J Cataract Refract Surg; 2002; 28:18–22.

5.Lee JB, Seong GJ, Lee JH, Seo KY, Lee YG, Kim EK. Comparison of laser epithelial keratomileusis and photorefractive keratectomy for low to moderate myopia. J Cataract Refract Surg; 2001; 27:565–570.

6.Hanna KD, Pouliquen YM, Waring GO, Savoldelli M, Fantes K, Keith P, Thompson KP. Corneal wound healing in monkeys after repeated excimer laser photorefractive keratectomy. Arch Ophthalmol; 1992; 110:1286–1291.

23

Wound Healing After PRK, LASIK, and

LASEK

Takuji Kato, MD

Juntendo University

Tokyo, Japan

In recent years, excimer laser has provided safe and effective approaches for the correction of refractive errors. Among the various refractive surgery procedures, photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK) have been the most frequently performed for the treatment of myopia and astigmatism. Although PRK offers satisfactory refractive results for low myopia, subepithelial haze and refractive regression still remain significant concerns, especially when higher correction is attempted (1,2). LASIK is currently gaining acceptance as a more sophisticated procedure (3). Despite the fact that it leads to minimal haze and rapid recovery of vision, LASIK has its own drawbacks (4–6). More recently, laser epithelial keratomileusis (LASEK) has been introduced as a new surgical technique (7,8), which may combine the advantages and reduce the disadvantages of PRK and LASIK. The characteristics of corneal wound-healing response after refractive surgery are variable with each surgical procedure. Furthermore, the corneal wound-healing response can directly affect the surgical correction of refractive errors and is closely associated with complications after refractive surgery. It is therefore clear that scientific understanding of corneal woundhealing process will lead us to the therapeutic successes after the surgery.

This chapter describes the characteristics of the corneal wound healing after PRK and LASIK, and the limitation of each procedure, then further discusses the possible advantage of LASEK.

PRK

Epithelial Wound Healing

The corneal wound-healing response to PRK is basically similar to that after mechanical debridement. A deposition of fibronectin and fibrinogen is observed on the ablated surface 24 hours after PRK. These components provide a temporary scaffold for corneal epithelial migration and adhesion (9). The epithelial covering of the ablated area takes 2 to 3 days after the surgery (Fig. 1A). The completion of the epithelial coverage, however, does not mean complete recovery in terms of barrier function. It takes several more weeks until

LASEK, PRK, and excimer laser stromal surface ablation 278

Activation and transformation of keratocyte. (4) Extracellular matrix deposition. (B) LASIK. (1) Necrosis and apoptosis of keratocyte around the lamellar incision. (2) Epithelial plug formation. (3) Activated keratocytes at the wound edge.

the corneal epithelium regains its functional barrier (10). A number of growth factors, including epidermal growth factor (EGF), transforming growth factor-beta (TGF-β), hepatocyte growth factor (HGF), and platelet-derived growth factor (PDGF), play an important role in completing re-epithelialization of the excimer wound (11). Because the epithelial basement membrane is absent at the laser-ablated area, the newly covered epithelial cells produce basement membrane components, including collagens (types IV and VII) and laminins (types 1 and 5). Adhesion complexes (hemidesmosomes) are then formed 4 to 6 weeks after PRK in the rabbit cornea (11,12). Until the epithelial barrier is reestablished, the greater risk of bacterial infection should be remembered.

Epithelium-Keratocyte Interaction and Extracellular Matrix

The regression of the correction and subepithelial haze have been reported as problems after PRK. These undesirable phenomena are caused by an excessive expression of extracellular matrix from both keratocyte and epithelial cells in the ablated zone. The interaction between corneal epithelial cells and keratocytes is a key concept in understanding of the corneal wound-healing after PRK. Nakayasu described that the anterior corneal stroma became acellular after an atraumatic removal of the corneal epithelium (13). More recently, the disappearance of anterior stromal keratocytes in response to epithelial scrape has been shown to be the result of programmed cell death (apoptosis), which is mediated by cytokines released from the injured epithelium (14– 16). The other factors, including inflammatory cell infiltration (17–19) and oxygen free radicals (20), have been proposed as mechanisms responsible for the disappearance of stromal keratocyte after PRK. The death of the keratocytes may trigger proliferation and migration of remaining peripheral and posterior keratocytes (13,21). During the repopulation of the area of cell death, a change in keratocyte phenotype to a myofibroblastlike cell (22) and overexpression of extracellular matrix components are observed. Biochemical and histochemical studies have revealed that the composition of the subepithelial haze includes collagens (type III, type IV) and glycosaminoglycans (hyaluronan, condroitin sulfate) (9,23–27). Among these extracellular components, type III collagen is one of the key molecules that relates to a persistent corneal haze (9,23) (Fig. 2A). An increase of type III collagen is a prominent phenomenon common to various forms of wound healing (28). It has been reported that the deposition of type III collagen increases near the incision of the cornea (29,30). The content of type III collagen in the normal cornea is only approximately 10% of its dry weight (31). However, type III collagen begins to increase at the site of the wound relatively early after injury. In a study in which fibroblast were cultured in various three-dimensional collagen gels, type III

collagen gel showed the highest contraction rate (32,33). Therefore, type III collagen is presumed to play an important role in the contraction and closure of the wound. In PRK, the excessive expression of such extracellular matrix components may be a significant factor in limiting visual correction, especially in the treatment of patient with high myopia.

LASIK

Currently, LASIK is the most commonly performed refractive surgical procedure. The rapid recovery of vision, minimal risk of corneal haze, and refractive predictability are the main advantage of LASIK. Because of the minimum activation of corneal epithelial cells and keratocytes (Fig. 2B), subepithelial haze is not observed, and refractive changes are stable after the surgery. However, we still do not know whether the structural strength of the cornea is completely restored after LASIK. There are two different kinds of wounds after LASIK. One is an incision wound at the flap margin and the other is an intrastromal lamellar wound in the central stroma (34). The characteristics of woundhealing response are completely different from each other.

The wound-healing response at the flap margin is quite similar to that after incisional keratotomy. Immediately after the microkeratome incision, the corneal epithelium covers the wound margin, followed by the formation of an epithelial plug (35). Keratocytes migrate into the wound (the cutting edge) and transform into myofibroblastlike cells. These cells then produce extracellular matrix, such as collagens and proteoglycans. In contrast with the healing process at the flap margin, the healing reaction of the intrastromal lamellar wound in the central cornea is much weaker. After LASIK, one initial response at the stroma is the disappearance of keratocyte on both sides of the lamellar cut (34,36). Helena et al. reported that keratocyte apoptosis was noted within a zone approximately 50-µm anterior and posterior to the lamellar cut (37). Because such a keratocyte death does not induce strong activation of remaining keratocyte, the healing reaction around the intrastromal lamellar wound is relatively weak. Based on the results from an animal experiment, the healing process of intralamellar wound is not complete even 9 month after the surgery (Fig. 2), indicating that a much longer time than expected is required for corneal wound healing after LASIK (35). The data obtained from animal experiments are in agreement with the clinical experience. It is relatively easy to lift a corneal flap during retreatment even months after the initial LASIK surgery. Moreover, the cases of late-onset traumatic dislocation of the flap have been reported (38–40). These cases indicate that the paucity of wound-healing response after LASIK surgery may render the flap susceptible to late dislocation with trauma. As for the adhesion of LASIK flap, various mechanisms, including endothelial pumping, capillarity, and fiber interlacing, have been proposed (40,43). However, the exact mechanism by which lamellar flap adheres to the stromal bed is not known.

One more potential problem of LASIK is considerable damage to corneal innervation. During this procedure, microkeratome cuts the anterior stromal nerves at the flap margin. Perez-Santonja et al. (44) showed that corneal sensitivity was more decreased after LASIK than after PRK during the first 3 months after surgery, and only after 6 months did it return to its preoperative value. The recovery of superficial stromal nerves took more than 5 months in a rabbit experiment (45). Because the corneal epithelium is known to derive neurotrophic factors from the corneal nerves, corneal surface abnormalities that develop after LASIK may be attributable to LASIK-induced neurotrophic epitheliopathy (46). Impaired innervation may also affect the keratocyte population (34) and the stromal wound-healing response.

LASEK

LASEK has been introduced as a new surgical technique that seeks to minimize the drawbacks of both PRK and LASIK by making an epithelial flap. This procedure involves using alcohol to create an epithelial flap, followed by excimer laser ablation and repositioning of the epithelial flap. The preserved integrity of the corneal stroma and the minimal activation of both epithelial cells and keratocytes are the main advantages of LASEK. In theory, LASEK can avoid the haze and regression, which result from the excessive interaction between the corneal epithelial cells and activated keratocytes after excimer laser ablation. This procedure also offers the advantage of avoiding the flap complication of LASIK (7). In LASEK, whether the corneal epithelial cells are still vital after the exposure to alcohol is a very important point, but this fundamental question has not been definitely answered.

Initial Trials of Alcohol-Assisted Epithelial Removal

The corneal epithelium is frequently removed before PRK to obtain a smooth surface for laser ablation. Corneal epithelial debridement has been performed with a variety of techniques, including mechanical debridement (47), a rotating brush (48), transepithelial laser ablation (49,50) and chemical de-epithelialization (51,52). Among them, chemical de-epithelialization with alcohol is one of the most effective techniques. Several alcohol concentrations were initially tried in rabbits. Campos et al. showed that chemical deepithelialization with 100% ethanol caused more keratocyte loss when compared with mechanical techniques in a rabbit model (53). Helena et al. reported the same phenomena using a 50% solution. They selected 50% ethanol because more diluted solutions did not prove to be reproducibly effective in rabbit (54). Other authors reported favorable clinical results using lower concentrations and shorter durations (55–57). They indicated that chemical de-epithelialization with alcohol was more effective in performance than was mechanical scraping. However, almost all of the previous studies on chemical deepithelialization focused on the stromal changes after the epithelial debridement, and little is known about the epithelial changes after the alcohol exposure.

LASEK, PRK, and excimer laser stromal surface ablation 282

Epithelial Viability After Alcohol Exposure

Alcohol has been known to have direct toxic effects on cells. It is likely that alcohol produces its cytotoxicity through more than one mechanism. Postulated mechanisms include cell membrane damage (58,59), the suppression of membrane-associated enzymes (60), the inhibition of cell-cell communication (60), the disruption of cytoskeleton (61), and apoptosis (62). Presumably the cell membrane disorganizing effect of alcohol is more significant than another effect. The cell membrane consists of lipid molecules, which are arranged as a continuous double layer. It has been suggested that alcohol interacts with the bilayer to distort and expand the membrane, thereby increasing its fluidity (59). Although various cells have been used for toxicity studies, little information is available on the cytotoxicity of alcohol to corneal cells.

To investigate the viability of corneal epithelial cells after LASEK, Gabler et al. stained the epithelial flap of human cadaver eyes with 0.1% trypan. They found that vital epithelial cells were seen with up to 45 seconds of exposure to 20% alcohol, and longer exposure killed the most epithelial cells (63).

Electron Microscopic Study in Human

We recently conducted electron microscopic analysis on an epithelial flap obtained from alcohol-assisted epithelial removal before PRK. Transmission electron micrographs showed a regular arrangement of epithelial cell layers after exposure of 18% alcohol for 30 seconds. The normal junctional complexes were seen between each cell, indicating alcohol solution at that condition did not affect junctional complexes. Although some of the nucleus showed irregular clumping of chromatin, all of the cells seem to be vital. At the posterior surface of the flap, irregular fragments of basement membrane were still attached to the basal cells. Bowman’s layer was completely absent in this flap. Both the number and the morphology of the hemidesmosomes were normal. These results indicate that the plane of alcohol separation might be within the basement membrane or between the basement membrane and the Bowman’s layer.

Electron Microscopic Study in Rabbit

To investigate the effects of alcohol exposure on the corneal epithelial cells, we further performed LASEK on rabbit eyes and conducted transmission electron microscopy. Previous studies indicated that 18% to 20% alcohol solution for 20 to 40 seconds is the optimal condition for the human cornea (55–57). We were, however, not able to make a LASEK flap on rabbit cornea in these conditions. However, when we use 40% alcohol for 3 minutes, an epithelial flap could be created easily. Electron microscopic examination revealed distention of intracellular spaces, particularly at the level of the middle or basal cell layer. Epithelial cells demonstrated swelling of mitcondria and degeneration of their cytoplasmic structure. The clumping of chromatin was noted in the nucleus. The overall configuration of the cell is maintained despite the disorganization of the plasma membrane. These findings are compatible with the characteristics of necrosis.

The results indicate that a higher concentration of alcohol has a cytotoxic effect and induces necrosis of the epithelial cells.

Role of Basement Membrane and Adhesion Complex

During the PRK operation, both epithelial cell layers and basement membrane are removed, which distinguishes PRK from LASEK. One of the theoretical advantages of LASEK, compared with PRK, is the preservation of adhesion complex and basement membrane fragments at the epithelial flap. These components may play an important role in the wound-healing process after LASEK.

Basement membrane influences the biological behavior of epithelial cells and vice versa. Until recently, basement membrane was simply thought to be a scaffold for epithelial cells. It has recently become apparent that the basement membrane plays a far more active and complex role in regulating the behavior of cells. Basement membrane can affect the shape, adhesion, and migration of cells by transmitting extracellular positional information to the intracellular cytoskeletal system via transmembrane receptor molecules (64). In an unwounded stable state, the epithelial cells are joined to neighboring cells by cell-cell junctions called desmosomes and to basement membrane by hemidesmosomes. Even in wound-healing process, desmosomes are retained as the cell-cell adhesion junction, thus enabling cells to move as a sheet rather than as individual cells (65). However, hemidesmosomes disappear from the basal cell when epithelial cells begin to migrate to cover a wound (66). The adhesion to basement membrane via hemidesmosome is essential to the stability of epithelial cells. The loss of this adhesion induces a different signal transduction, then triggers a cascade of cell activation. It is known that activated cells produce a variety of chemokine and extracellular matrix, which subsequently results in corneal haze and regression in the case of PRK. As mentioned, transmission electron micrographs showed that LASEK flap has a regular arrangement of hemidesmosomes and fragments of basement membrane after exposure to 18% alcohol for 30 seconds. These adhesion complexes enable epithelial cells to avoid an excessive activation after the surgery. Therefore, LASEK ensures quick wound healing with minimal tissue proliferation, which is in contrast to the excessive cellular activity after PRK.

Inflammation and Role of Epithelial Flap

It has been shown that neutrophils from the tear film are more prominent than those migrating from the limbus in early inflammation of the central cornea cells (67), and basement membranes are a physical barrier against such an influx of inflammatoty cells. Because, in PRK, the central cornea does not have epithelial basement membrane just after laser ablation, one of the early histologic findings after PRK is an influx of inflammatory cells into stroma (19). Infiltrating neutrophil generates oxygen radicals and matrix metalloproteinases, which may partially be responsible for initial stromal degradation. Therefore, as has previously been pointed out (68), it is likely the LASEK flap may act as a physical barrier to the infiltration of inflammatory cells from tears and consequently protects the corneal stroma from the inflammatory damage.

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CONCLUSIONS AND PERSPECTIVES

LASEK can offer faster epithelial healing, stromal integrity, and avoidance of excessive cellular activation. This procedure can be a feasible alternative to conventional refractive surgery. However, our understanding of cellular and molecular mechanisms associated with LASEK is still incomplete. We are just beginning to understand some of the biological mechanisms responsible for wound healing after LASEK. At the molecular level, the identification of precise mechanisms by which alcohol facilitates the epithelial flap separation is an important challenge for the future. At the cellular level, a clear goal of future studies will be to further define cell kinetics, cell adhesion, and cell viability after this technique. We also need to understand the toxicity of alcohol and long-term effects after the surgery. Clinical progress over the past several years sets the stage for exploring a number of key unresolved issues. Further research in this area is bound to be exiting.

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4.Davis EA, Hardten DR, Lindstrom RL. LASIK complications. Int Ophthalmol Clin; 2000; 40: 67–75.

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6.Holland SP, Srivannaboon S, Reinstein DZ. Avoiding serious corneal complications of laser assisted in situ keratomileusis and photorefractive keratectomy. Ophthalmology; 2000; 107: 640–652.

7.Azar DT, Ang RT, Lee JB, Kato T, Chen CC, Jain S, Gabison E, Abad JC. Laser epithelial keratomileusis: electron microscopy and visual outcomes of flap photorefractive keratectomy. Curr Opin Ophthalmol; 2001; 12:242–249.

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