Contributors

Dimitri T.Azar, MD Massachusetts Eye and Ear Infirmary, Schepens Eye Research Institute, Harvard Medical School, Boston, MA

Scott D.Barnes, MD Massachusetts Eye and Ear Infirmary, Schepens Eye Research Institute, Harvard Medical School, Boston, MA

Robin F.Beran, MD, FACS Columbus Laser and Cataract Center, Columbus, OH Massimo Camellin, MD Sekal Rovigo MicroSurgery, Rovigo, Italy

Jin-Hong Chang, PhD Massachusetts Eye and Ear Infirmary, Schepens Eye Research Institute, Harvard Medical School, Boston, MA

Puwat Charukamnoetkanok, MD Massachusetts Eye and Ear Infirmary, Schepens Eye Research Institute, Harvard Medical School, Boston, MA

Chun Chen Chen, MD Department of Ophthalmology, Taipei Municipal Jen-Ai Hospital, National Yang-Ming University, Taipei, Taiwan

Saira A.Choudhri, MD Pepose Vision Institute, Chesterfield, MO

Alice Z.Chuang, PhD Hermann Eye Center, Department of Ophthalmology and Visual Sciences, University of Texas Health Science Center at Houston, Houston, TX

Irwin Y.Cua, MD Pepose Vision Institute, Chesterfield, MO

Minh Hanh Duong, MD Service d’ophtalmologie, (Pr Hoang-Xuan), Hôpital Bichat, Fondation Rothschild, Université Paris VII, Paris, France

Daniel S.Durrie, MD Durrie Vision Research, Overland Park, KS

Daniel Epstein, MD, PhD Department of Ophthalmology, University Hospital, Zurich, Switzerland

Eric E.Gabison, MD Massachusetts Eye and Ear Infirmary, Schepens Eye Research Institute, Harvard Medical School, Boston, MA

Bernhard Gabler, MD University Eye Clinic, Regensburg, Germany

Damien Gatinel, MD Service d’ophtalmologie, (Pr Hoang-Xuan), Hôpital Bichat, Fondation Rothschild, Université Paris VII, Paris, France

Wolfgang Herrmann, MD University Eye Clinic, Regensburg, Germany

Joel Javier, MD Massachusetts Eye and Ear Infirmary, Schepens Eye Research Institute, Harvard Medical School, Boston, MA

James V.Jester, PhD Department of Ophthalmology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX

Maria I.Kaly vianaki, MD Vardinoyannion Eye Institute of Crete, University of Crete, Greece

Takuji Kato, MD Juntendo University, Department of Ophthalmology, Tokyo, Japan Vikentia J.Katsanevaki, MD Vardinoyannion Eye Institute of Crete, University of Crete, Greece, University Hospital of Heraklion, Department of Ophthalmology,

Crete, Greece

Stephen D.Klyce, PhD LSU Eye Center, New Orleans, LA

Ronald R.Krueger, MD Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH

Jae Bum Lee, MD, PhD Massachusetts Eye and Ear Infirmary, Schepens Eye Research Institute, Harvard Medical School, Boston, MA

Ning Lin, MD, OD Hermann Eye Center, Department of Ophthalmology and Visual Sciences, University of Texas Health Science Center at Houston, Houston, TX

Chris P.Lohmann, MD, PhD University Eye Clinic Regensburg, Germany, The Rayne Institute, Department of Ophthalmology, St. Thomas Hospital, London, England

John Marshall, PhD The Rayne Institute, Department of Ophthalmology, St. Thomas Hospital, London, England

Marguerite B.McDonald, MD Southern Vision Institute, New Orleans, LA M.Azim Mirza, MD Pepose Vision Institute, Chesterfield, MO

Zoltán Z.Nagy, MD 1st Department of Ophthalmology, Semmelweis University, Budapest, Hungary

Irini I.Naoumidi, PhD Vardinoyannion Eye Institute of Crete, University of Crete, Greece

Ahn Nguyen, MD Cornea and Refractive Surgery Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA

Loan Nguyen, MD LSU Eye Center, New Orleans, LA

David O’Brart, MD The Rayne Institute, Department of Ophthalmology, St. Thomas Hospital, London, England

Hailton B.Oliveira, MD Massachusetts Eye and Ear Infirmary, Schepens Eye Research Institute, Harvard Medical School, Boston, MA

Ioannis G.Pallikaris, MD, PhD Vardinoyannion Eye Institute of Crete, University of Crete, Greece, University Hospital of Heraklion, Department of Ophthalmology, Crete, Greece

Ann Patmore, BSC The Rayne Institute, Department of Ophthalmology, St. Thomas Hospital, London, England

Jay S.Pepose, MD, PhD Pepose Vision Institute, Chesterfield, MO; Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO

Neal J.Peterson, MD Hermann Eye Center, Department of Ophthalmology and Visual Science, University of Texas Health Science Center at Houston, Houston, TX

Mujtaba A.Qazi, MD Pepose Vision Institute, Chesterfield, MO; Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO

Richard C.Rashid, MD Clinical Associate Professor of Ophthalmology, West Virginia University School of Medicine, Charleston Division, Charleston, WV

Rajy M.Rouweyha, MD Hermann Eye Center, Department of Ophthalmology and Visual Science, University of Texas Health Science Center at Houston, Houston, TX

Amy Scally, OD Cornea and Refractive Surgery Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA

Lee Shahinian, Jr, MD Stanford University, Department of Ophthalmology, Stanford, CA

Michael K.Smolek, PhD LSU Eye Center, New Orleans, LA

Erin D.Stahl, MD Durrie Vision Research, Overland Park, KS

John P.Stokes, MD Hermann Eye Center, Department of Ophthalmology and Visual Science, University of Texas Health Science Center at Houston, Houston, TX

Suphi Taneri, MD Zentrum für Refraktive Chirurgie, Munster, Germany Paolo Vinciguerra, MD Istituto Clinico Humanitas, Milan, Italy

Corey B.Westerfield, MD Hermann Eye Center, Department of Ophthalmology and Visual Science, University of Texas Health Science Center at Houston, Houston, TX

Christoph Winkler von Mohrenfels, MD University Eye Clinic, Regensburg, Germany Richard W.Yee, MD Hermann Eye Center, Department of Ophthalmology and Visual

Science, University of Texas Health Science Center at Houston, Houston, TX Steven B.Yee, MD Hermann Eye Center, Department of Ophthalmology and Visual Science, University of Texas Health Science Center at Houston, Houston, TX Patrick C.Yeh, MD Massachusetts Eye and Ear Infirmary, Schepens Eye Research

Institute, Harvard Medical School, Boston, MA

LASEK, PRK, AND EXCIMER LASER STROMAL SURFACE ABLATION

1

Overview of LASEK and Stromal Surface

Ablation

Suphi Taneri, MD

Zentrum für Refraktive Chirurgie Munster, Germany

Dimitri T.Azar, MD

Massachusetts Eye and Ear Infirmary, Schepens Eye Research Institute,

Harvard

Medical School

Boston, MA

HISTORY

Laser subepithelial keratomileusis (LASEK) (1–8) is a relatively new laser surgical procedure for the correction of refractive error that combines certain elements of both laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK). The LASEK procedure is most commonly performed using dilute alcohol to loosen the epithelial adhesion to the corneal stroma. Laser ablation of the subepithelial stroma is performed before the hinged epithelial sheet is returned to its original position, as with the LASIK flap (Fig. 1). The flap-related LASIK complications and the slow visual recovery and haze risk of PRK may be avoided.

The first LASEK procedure was performed at the Massachusetts Eye and Ear Infirmary in 1996 by one of us (DTA) (1). Camellin popularized the procedure and coined the term LASEK for laser epithelial keratomileusis (3,9). The history of LASEK can be traced back to the use of chemical agents to replace manual epithelial debridement in PRK, which was shown to produce scratches and nicking in the Bowman’s layer and to leave variable amounts of epithelium (10,11) (Table 1). Campos used 100% ethanol for 2 minutes on rabbit corneas and noted significant decrease in stromal keratocytes (27) Agrawal used 70% isopropyl alcohol for 2 minutes for epithelium removal in rabbit eyes and observed similar damage to the keratocytes (28). Helena et al. used 50% ethanol for 1 minute and observed increased keratocyte loss (29).

A prospective study performed at the Massachusetts Eye and Ear Infirmary by Abad et al. showed that alcohol-assisted epithelial removal was a simple and safe alternative to mechanical epithelial removal before PRK (2). Other investigators using alcohol for epithelial removal included Stein et al., who were able to grasp, lift, pull apart, and split the corneal epithelium using two McPherson forceps (30), and Shah et al., who peeled the epithelium using a dry sponge (31). Carones et al. found significantly better results in terms of haze and corneal regularity in epithelial debridement using a 20% alcohol

LASEK, PRK, and excimer laser stromal surface ablation 2

solution compared to mechanical debridement (32). Other investigators focused on the formulation of ethanol (38.)

Figure 1 Schematic representation of conventional LASEK surgery showing the application of an epithelial trephine to delineate the edge of the epithelial flap (top left), alcohol application (top right), creation of an epithelial flap before laser ablation (bottom left), and replacement of the epithelial sheet over the ablated stroma (bottom right).

Table 1. Milestones in LASEK History.

1982 Technique for obtaining sheets of intact rabbit corneal epithelium (Gipson) 1983 Excimer laser application on cadaver bovine corneas (Trokel and Srinivasan) 1984 Photorefractive experiments on animals (McDonald)

1985 PRK on a blind human eye (Seiler)

1987 PRK on a human sighted eye slated for exenteration 11 days after PRK (Seiler) 1988 PRK on a normal sighted eye (McDonald)

1989 Photoablation of fully sighted eyes and treatment on the underside of a free cap (Buratto)

Overview of LASEK and stromal surface ablation 3

1990 LASIK (Pallikaris)

1994 Hartmann-Shack wavefront sensing of human eye (Liang and Williams) 1996 Alcohol-assisted epithelial flap reattached over PRK (Azar)

1998 “LASEK” term coined, specialized equipment, and procedure popularized (Camellin) 1999 Customized corneal ablation (Seiler)

1999 Butterfly LASEK (Vinciguerra)

2000 Mitomycin C treatment of corneal haze after PRK in humans (Majmudar and Epstein) 2001 Hydrodissection and viscodissection (Rachid and Langerman)

2001 Gel-assisted LASEK (McDonald)

2002 Human epithelial cell viability in LASEK (Chen and Azar) 2002 Epi-LASIK (Pallikaris)

Camellin advocated the importance of a hypotonic solution obtained by diluting alcohol in distilled water for facilitating epithelial detachment (3), whereas Vinciguerra preferred balanced salt solution for dilution (8).

Our group has investigated the mechanisms of epithelial reattachment in LASEK and the functional alterations of the cell membrane integrity and cell metabolism using livecell assays in vitro. Our studies suggested a doseand time-dependent effect of alcohol on epithelial cells. The 25% concentration of alcohol was the inflection point of epithelial survival. Significant increase in cellular death occurred after 35 seconds of alcohol exposure. Forty seconds of exposure further induced apoptosis after 8 hours of incubation.

Our studies on specimens obtained after conventional alcohol-assisted PRK showed that the epithelial cell layer is intact and the epithelial cells are still viable immediately after exposure to alcohol and surgical peeling. The presence of the basement membrane attached to the basal epithelial cell layer in many of our specimens indicates that the point of separation was between the basement membrane and Bowman’s layer (33,34).

TECHNIQUES AND TERMINOLOGY

Several techniques of LASEK are described in this book, including the Camellin technique, the Vinciguerra butterfly technique, the McDonald technique, the Pallikaris Epi LASEK technique, and the Azar flap technique (Fig. 2). Additionally, several expressions have been used, including laser subepithelial keratomileusis (1,35,36), subepithelial photorefractive keratectomy (31,37), epithelial flap photorefractive keratectomy (7), laser-assisted subepithelial keratectomy (5,38), excimer laser subepithelial ablation (39), laser epithelial keratomileusis (39–41), and Epi-LASEK (42).

LASEK, PRK, and excimer laser stromal surface ablation 4

ADVANTAGES OF LASEK OVER PRK AND LASIK: EVIDENCE-

BASED COMPARISONS

We have performed a meta-analysis to determine the advantages of LASEK over PRK and LASIK(14) (Table 2). LASEK may avoid several of the inherent complications including free caps, incomplete pass of the microkeratome, flap wrinkles, epithelial ingrowth, flap melt, interface debris, and diffuse lamellar keratitis after LASIK (22,46– 63), and postoperative pain, subepithelial haze, and slow visual rehabilitation after PRK (64–73). Our meta-analysis aimed at evaluating potential benefits and risks of LASEK and investigates the visual outcome in a semi-quantitative fashion showing distinct advantages (14):

Safety

One eye out of 907 (0.11%) lost two lines of Best Spectacle Corrected Visual Acuity (BSCVA). This was a loss observed in one of our patients on his final visit at 1 month from 20/20 to 20/30.

Efficacy

Uncorrected Visual Acuity (UCVA) of 20/20 or better at that time was achieved in 76% and of 20/40 or better in 99% (5,14,36,40).

Predictability (Spherical Equivalent)

The mean spherical equivalent of 152 eyes at 6-month follow-up was calculated to be −0.32 diopter (D)A (7,8,40). At 6-month follow-up, 83% of eyes (5,14,36,40) were within plusmn; 0.50 D and 98.35% of eyes were within ±1.00 D of desired postoperative refractive error (5,14,36).

Stability

Rouweyha et al. (40) reported a regression of approximately 2 D in 4 eyes of 2 patients (8% of their eyes) with visually significant haze at 6 months, whereas several other authors point out the absence of regression (3).

The remarkable aspects of our review are the long-term stable results in complete absence of serious complications, like infections, recurrent erosions, scar, or late-onset corneal haze formation. Second, epithelial closure with recovery of functional vision could

LASEK, PRK, and excimer laser stromal surface ablation 6

Figure 2 (CONT) (G) Laser ablation is applied to the exposed Bowman’s layer and stroma. (H, I) A 30-gauge Rycroft irrigating cannula is used to hydrate and reposition the epithelial flap. (J) Care is taken to realign the wound edges using the preplaced marks as a guide. (K) Flap edges are aligned, and no epithelial defects are noted after flap repositioning and during the 5-minute waiting period. (L) A bandage soft contact lens is applied at the end of the procedure.

Overview of LASEK and stromal surface ablation 7

be shown to happen at day 4 to day 7 in most cases. Third, we found a tendency toward overcorrection with PRK nomograms. Fourth, we may hypothesize that this tendency may be caused by the decreased wound healing response, which may lead to myopic regression in PRK. Last, postoperative pain and prolonged visual recovery until the epithelium closes remain the biggest disadvantages of LASEK compared to LASIK (14). (See Table 2.)

A potential superiority of LASEK to LASIK in wavefront-guided ablations still remains speculative (Fig. 3). LASEK surgery is especially valuable in patients with thin corneas who would not qualify for LASIK surgery. Additionally, LASEK has become a viable option in patients with professions or lifestyles that predispose to flap trauma (contact sports athletes and military personnel) and in patients with low myopia who are at a lower risk for subepithelial haze.

Table 2. Widely Accepted Relative Differences

Among PRK, LASIK, and LASEK.

LASEK, PRK, and excimer laser stromal surface ablation 8

Keratoconus suspects (irregular astigmatism) Glaucoma suspects Recurrent erosion syndrome

Dry eye syndrome Basement membrane disease (18)

Additional factors such as surgeon experience, type of laser, age of patient, amount of correction, and administrative regulations of various countries may influence these comparisons.

LASEK, PRK, and excimer laser stromal surface ablation 10

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Overview of LASEK and stromal surface ablation 11

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Overview of LASEK and stromal surface ablation 13

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