Femtosecond laser in situ keratomileusis for consecutive hyperopia after radial keratotomy

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1 ARTICLE Femtosecond laser in situ keratomileusis for consecutive hyperopia after radial keratotomy Gonzalo Muñoz, MD, PhD, FEBO, César Albarrán-Diego, OD, Hani F. Sakla, MD, PhD, Jaime Javaloy, MD, PhD PURPOSE: To assess the use of the femtosecond laser for laser in situ keratomileusis (LASIK) in eyes with consecutive hyperopia after radial keratotomy (RK). SETTING: Private ambulatory surgical center, Valencia, Spain. METHODS: This prospective noncomparative interventional case series study included 13 eyes of 9 patients with secondary hyperopia after previous RK. The patients were operated on with the IntraLase femtosecond laser (IntraLase Corp.) and the Star S2 excimer laser (Visx, Inc.). Postoperative uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), manifest refraction, flap thickness, flap diameter, and complications were evaluated at 6 months. RESULTS: The mean spherical equivalent (SE) decreased from 2.00 diopters (D) G 0.40 (SD) to 0.41 G 0.61 D, with 8 eyes (61.5%) within G0.50 D of the targeted refraction. Twelve eyes (92.3%) had a UCVA of 20/40 or better, and 3 eyes (23.1%) lost 1 line of BSCVA. A mean change in SE of 0.10 D was observed at the 6-month follow-up. The mean flap thickness and diameter were 117 G 14 mm and 9.18 G 0.12 mm, respectively. Most complications were in eyes with more than 8 RK incisions than in eyes with 8 RK incisions. These complications were multiple intraoperative incision openings (100% versus 28.6%, respectively), interface inflammation (66.6% versus 0%, respectively), haze (83.3% versus 14.3%, respectively), and loss of BSCVA (50% versus 0%, respectively). CONCLUSIONS: The femtosecond laser provided large, thin corneal flaps for hyperopic LASIK. However, the procedure should be avoided in eyes with more than 8 RK incisions because of the increased risk for multiple intraoperative incision openings, interface inflammation, haze, and loss of BSCVA. J Cataract Refract Surg 2007; 33: Q 2007 ASCRS and ESCRS Consecutive hyperopia after radial keratotomy (RK) is a relatively common complication that may develop months to years after the primary procedure. 1,2 Several techniques have been used to treat secondary hyperopia after RK. These include laser thermal keratoplasty, 3 photorefractive keratectomy (PRK), 4 and laser in situ keratomileusis (LASIK) Laser thermal keratoplasty shows variable degrees of regression, especially for hyperopia greater than 3.00 diopters (D), 3 while PRK carries a risk for haze in eyes with radial incisions. 11 Hyperopic LASIK has provided predictable results with long-term stability However, mechanical LASIK after RK may place the eye at risk for serious complications, including intraoperative incision opening, 5,10 irregular apposition of the flap, 5 stromal opacities, 7 diffuse lamellar keratitis (DLK), 5 epithelial defects, 7 epithelial ingrowth, 5,7,10 and corneal ectasia. 9 All these complications are mainly attributable to imperfect cutting with the microkeratome and may result in permanent loss of vision. 10 Although surface ablation procedures have been fraught with the risk for scar formation, 11 many surgeons today prefer performing PRK over LASIK in RK eyes, especially with the use of mitomycin-c (MMC). 12,13 The femtosecond laser represents a revolutionary innovation in the field of refractive surgery The femtosecond laser corneal flap has advantages over the classic mechanical keratome corneal flap, including improved predictability of flap thickness and diameter, astigmatic neutrality, and reduced incidence of epithelial defects and buttonholes However, other complications such as light sensitivity, 22,23 corneal folds, 24 and increased interface inflammation 23,25 have been reported. The purpose of this study was to assess the efficacy, safety, predictability, stability, flap characteristics, and Q 2007 ASCRS and ESCRS Published by Elsevier Inc /07/$dsee front matter 1183 doi: /j.jcrs

2 1184 FEMTOSECOND LASIK FOR CONSECUTIVE HYPEROPIA AFTER RK complications after the use of the femtosecond laser for hyperopic LASIK after RK. To our knowledge, there are no previous peer-reviewed studies of the use of the femtosecond laser in creating a flap for hyperopic LASIK in eyes that had RK. PATIENTS AND METHODS Study Design A prospective noncomparative interventional case series study comprised 13 consecutive eyes of 9 patients who had femtosecond hyperopic LASIK for significant hyperopia or hyperopic astigmatism. All eyes had RK for myopia ranging from 5.00 to 8.00 D of spherical equivalent (SE) at least 10 years previously. All eyes had 3.0 mm optical zone RK. Seven eyes had 8 radial incisions, and 6 eyes had 12 or more radial incisions. The depth of the incisions, determined by slitlamp biomicroscopy, ranged from 80% to 90% of total corneal depth. Epithelial inclusion cysts and evidence of clinical wound gape were ruled out. Before the procedure was attempted, signs of progressive hyperopic instability were studied; all patients had a stable refractive history for more than 2 years, and topography ruled out signs of corneal ectasia. The tenets of the Declaration of Helsinki were followed, and informed consent was obtained. Before the LASIK procedure, patients had a complete ophthalmologic examination including manifest and cycloplegic refractions, uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), computerized videokeratography, slitlamp biomicroscopy, Goldmann applanation tonometry, binocular indirect ophthalmoscopy, and ultrasonic pachymetry. Postoperative examinations were performed at 1, 3, and 7 days and 1 and 6 months and included UCVA, BSCVA, slitlamp evaluation, applanation tonometry, and corneal topography. All patients completed a 6-month follow-up. Femtosecond Laser In Situ Keratomileusis Technique Antibiotic prophylaxis before surgery consisted of topical ciprofloxacin (Oftacilox) every 8 hours for 3 days. Antiseptic prophylaxis was performed by applying 1 drop of povidone iodine 5% solution to the conjunctiva immediately before surgery. The femtosecond laser for flap creation has been described. 17 All surgeries were performed by the same surgeon Accepted for publication March 6, From the Refractive Surgery Department (Muñoz, Albarrán-Diego), Centro Oftalmológica Marqués de Sotelo and Hospital NISA Virgen del Consuelo, Valencia, and the Refractive Surgery Department (Muñoz, Sakla, Javaloy), VISSUM Instituto Oftalmológico de Alicante, Alicante, Spain. No author has a financial or proprietary interest in any material or method mentioned. Corresponding author: Gonzalo Muñoz, Centro Oftalmológico Marqués de Sotelo, Avenida Marqués de Sotelo 5, Planta 2 a, Valencia, Spain. (G.M.) using the 15 KHz IntraLase FS laser (IntraLase Corp.). Femtosecond laser flaps were programmed with the following settings: 110 mm thickness, 9.5 mm diameter, 45-degree hinge angle, 135-degree nasal hinge position (right eyes) or 45-degree nasal hinge position (left eyes), 70-degree sidecut angle, 0.2 mm stromal pocket, 9.0 mm laser raster patterns for both spot separation and interbeam separation, and 2.0 mj raster stromal energy with 2.6 mj side-cut energy. In all eyes, the flap was centered relative to the pupil until a predicted flap of at least 9.0 mm was achieved. Intraoperative pachymetry was performed after the flap was lifted and before the excimer laser ablation. Excimer laser ablation was performed with the Star S2 laser system (Visx, Inc.) with a target of full cycloplegic correction in all eyes. After surgery, topical tobramycin dexamethasone eyedrops (TobraDex) were used every 2 hours for 3 days and then every 8 hours for 4 days. Statistical Analysis Statistical analysis was performed using SPSS for Windows (version 12.0, SPSS, Inc.). Visual acuity data were transformed into logmar notation for means computation and comparison using the t test for paired variables. Differences were considered statistically significant when P!.05. RESULTS The mean age of the 7 men and 2 women in the study was 46.4 years G 4.8 (SD) (range 41 to 53 years). In 4 patients, both eyes were treated. Efficacy The UCVA (Snellen decimal) improved in all eyes from preoperatively to 6 months postoperatively (Table 1), with an efficacy index of 0.79 in the whole group (Figure 1). The percentage of eyes with a UCVA of 20/40 or better was 92.3% (Table 1). Stratifying by number of radial incisions, the efficacy index was 0.83 for eyes with 8 RK incisions and 0.76 for eyes with more than 8 RK incisions. Safety Six months after surgery, 3 eyes (23.1%) lost 1 line of BSCVA and 10 eyes (76.9%) had no change. The safety index ratio was 0.98 in the whole group, and there were no differences in mean BSCVA before and after surgery in the whole group (P Z.50, Student t test). Stratifying by number of radial incisions, none of the 7 eyes with 8 RK incisions lost a line of BSCVA, whereas 3 of the 6 eyes (50%) with more than 8 RK incisions lost 1 line of BSCVA. The safety index ratio was 1 for eyes with 8 RK incisions and 0.94 for eyes with more than 8 RK incisions. Predictability Table 1 shows the mean preoperative and 6-month postoperative SE and astigmatism. Eight eyes (61.5%) were within G0.50 D and 10 eyes (76.9%)

3 FEMTOSECOND LASIK FOR CONSECUTIVE HYPEROPIA AFTER RK 1185 Table 1. Results of femtosecond LASIK in eyes with consecutive hyperopia after RK. Parameter Preop 6 Months Postop Sphere (D) 2.65 G G 0.64 Astigmatism (D) 1.31 G G 0.33 SE (D) 2.00 G G 0.61 G0.50 D SE (%) UCVA R 20/40 (%) Mean decimal UCVA (lines) 0.41 G G 1.21 Mean decimal BSCVA (lines) 0.86 G G 0.65 Mean logmar UCVA C0.39 G 0.11 C0.17 G 0.12 Mean logmar BSCVA C0.06 G 0.06 C0.08 G 0.07 BSCVA Z best spectacle-corrected visual acuity; SE Z spherical equivalent; UCVA Z uncorrected visual acuity within G1.00 D of the targeted refractive change. Postoperative astigmatism was within G0.50 D of the intended astigmatic correction in 8 eyes (61.5%) and within G1.00 D in 13 eyes (100%). Stability The mean SE changed from 0.51 G 0.72 D at 1 month to 0.41 G 0.61 D at 6 months. Data for the 3-month follow-up were not obtained. There was a mean change in SE of 0.10 G 0.23 D between 1 month and 6 months; in all eyes, the change was 0.25 D or less. The Flap The mean achieved flap thickness was 117 G 14 mm (range 96 to 138 mm) for a planned thickness of 110 mm. The mean flap diameter was 9.18 G 0.12 mm. As a stromal pocket of 0.2 mm was used, the maximum achieved flap diameter was 9.3 mm. A diameter of 9.3 mm was achieved in 4 of the 13 eyes; in the other 9 eyes, the achieved flap diameter was between 9.0 mm and 9.2 mm. The planned diameter had to be reduced from the attempted diameter when the applanation cone was decentered in respect to the pupil. Intraoperative Complications Lifting the flap was the most difficult part of the intervention. In all eyes, separation of at least 1 radial incision was observed intraoperatively. It was especially difficult to lift the flap in eyes with more than 8 RK incisions. Two or more incisions opened in all 6 eyes with more than 8 RK incisions and in 2 eyes (28.6%) with 8 RK incisions (Table 2). In some eyes, the opening of the RK incision was produced during the femtosecond ablation and it was detected by a sudden change in the homogeneous pattern of the intrastromal bubbles to a nonhomogeneous pattern, with vertical lines following the direction of the laser beam. In most eyes, incision opening occurred during flap lifting (Figure 2). The radial incisions closer to the hinge opened first. For instance, with a nasal hinge in the left eye, the radial incisions that opened were mainly at the 7 to 8 o clock position or the 10 to 11 o clock position. In the right eye, they gaped primarily at the 1 to 2 o clock position or at the 4 to 5 o clock position. Small epithelial irregularities were produced at the junctions between the margin of the flap and the radial incisions. There were no cases of free caps, buttonholes, or suction loss during the femtosecond ablation, and a smooth stromal bed was obtained in all cases. Postoperative Complications Four eyes (30.8%) presented with moderate DLK between 1 and 3 days postoperatively. These cases 100 Pre-surgery BCVA Post-surgery UCVA 80 Percentage of Eyes ,0 0,9 0,8 0,7 0,6 0,5 0,4 Cumulative Decimal Visual Acuity Figure 1. Efficacy: postoperative UCVA versus preoperative BSCVA. Figure 2. The opening of 2 RK incisions next to the hinge in a case of femtosecond hyperopic LASIK after RK.

4 1186 FEMTOSECOND LASIK FOR CONSECUTIVE HYPEROPIA AFTER RK Table 2. Complications based on number of RK incisions. Number Eye RK Incisions Intraoperative RK Incision Openings Loss of 1 Line of BSCVA Interface Inflammation Postoperative Haze Yes C C Yes C C Yes C C No C C No C No No C No No No No No No BSCVA Z best spectacle-corrected visual acuity; Pt Z patient; RK Z radial keratotomy responded well to topical TobraDex every 2 hours for 7 days. This complication did not require lifting of the flap. All eyes that developed DLK had more than 8 RK incisions. Postoperatively, all RK incisions looked well aligned with no signs of progressive fibrosis or epithelial ingrowth despite the opening of the incision. The flap margin showed a degree of fibrosis typical of femtosecond flaps that was no different from that in non- RK eyes. There was no epithelial ingrowth despite the small epithelial irregularities produced intraoperatively at the junctions between the margin of the flap and the radial incisions. Diffuse interface haze and small particles at the interface were present in 6 eyes (46.2%) at final follow-up. Haze was present in 5 eyes (83.3%) with more than 8 RK incisions and 1 eye (14.3%) with 8 RK incisions. In these cases, confocal microscopy showed keratocyte activation and highly reflective particles at the level of the interface with normal epithelium, posterior stroma, and endothelium. Many oval cells (keratocytes) with diameters of approximately 10 to 12 mm were detected; they were diffusely distributed or arranged in lines (Figure 3, A). Also, clusters and lines of small, highly reflective particles were seen (Figure 3, B). There were no cases of epithelial ingrowth at the margin of the flap despite the epithelial irregularities produced when the flap was lifted. There were no cases of decentered ablations or transient light sensitivity in any eye. DISCUSSION Our study found that the efficacy, safety, predictability, and stability of the femtosecond hyperopic LASIK procedure were comparable to those of hyperopic LASIK using mechanical microkeratomes after RK, 5 10 with 92.3% of eyes having a UCVA of 20/40 or better and nearly two thirds within G0.50 D of the targeted refraction. The stability index at 6 months was excellent, with a mean change in SE of 0.10 D. These results should be viewed within the context of eyes previously operated on using radial incisions. The main finding in the present study was the increased risk for developing complications in eyes with more than 8 RK incisions. Complications mainly affected eyes with more than 8 RK incisions versus eyes with 8 RK incisions and included difficulty lifting the flap with multiple incision openings (100% versus 28.6%), interface inflammation (66.6% versus 0%), haze (83.3% versus 14.3%), and loss of BSCVA (50% versus 0%). A main difficulty when performing LASIK in eyes with previous RK is the creation of a large enough corneal flap A eye that has had RK has a flat cornea resulting from the incisional procedure; when mechanical microkeratomes are used, the incidence of small and free caps is higher in the presence of low keratometric values. 26 Because stromal ablation in hyperopic LASIK is mainly peripheral, a large flap is needed to prevent peripheral haze and regression. In fact, hyperopic LASIK in the presence of a small flap has been related to a higher incidence of undercorrection, regression, epithelial ingrowth, and peripheral haze. 5,8 In the present study, the mean preoperative K-value was low (mean G 1.50 D) for a group of eyes that had previous RK for myopia ranging from 5.00 to 8.00 D. The femtosecond laser uses an applanation glass contact lens cone to create

5 FEMTOSECOND LASIK FOR CONSECUTIVE HYPEROPIA AFTER RK 1187 Figure 3. Confocal microscopy of interface showing activated keratocytes (A) and highly reflective particles (B). a 0.00 D K-cornea, thus avoiding the K-factor. A recent study by Binder 18 of his first 1000 consecutive femtosecond laser LASIK cases found preoperative corneal curvature had no impact on flap dimensions. In our study, we were able to consistently create at least a 9.0 mm diameter flap and a small, predictable hinge in all the eyes. This is important in maximizing stromal exposure for the excimer laser ablation. There were no cases of suction loss during the procedure. Another advantage of the femtosecond laser is that in the event of suction loss, the focal plane shifts to the epithelial surface, avoiding vertical lacerations and irregular or buttonholed flaps. Regarding predictability of flap thickness, intraoperative pachymetry showed a mean flap thickness of 117 mm for a planned thickness of 110 mm with a low standard deviation of G14 mm. Binder 17 reports a standard deviation of G12 mm when a 110 mm thick flap was attempted using the femtosecond laser in normal eyes, which is similar to the results in the present study. The smaller range in the achieved flap thickness and the smaller standard deviation are superior results in comparison with current microkeratomes Stromal bed thickness before excimer ablation ranged from 382 to 500 mm, well above 350 mm in all cases. The preservation of a stromal bed that is as thick as possible may reduce the incidence of postoperative regression and keratectasia. The incidence of post- LASIK keratectasia in eyes with previous RK represents more than 3 times the expected incidence for non-rk eyes according to previous studies. 30,31 We had significant problems creating the flap in some eyes, especially those with more than 8 RK incisions. We previously reported the intraoperative opening of a radial incision during femtosecond laser LASIK ablation in eyes with myopic regression after previous RK. 32 That every eye in the present study had an opening of at least 1 radial incision during flap separation and lifting suggests that this procedure may pose a significant risk for epithelial ingrowth and other complications. However, the LASIK procedure using the femtosecond was still safe, effective, and predictable in the 13 eyes in our study. There were no cases of epithelial ingrowth, buttonhole, or a free cap; however, our series was small. The number of eyes with more than 8 RK incisions was low (n Z 6); thus, that none of these complications occurred does not mean they would not in a series with a larger number of eyes. It seems that more than 8 radial incisions increases the risk for complications. In all 6 eyes with more than 8 radial incisions, 2 or more incisions opened, while this occurred in only 2 of the 7 eyes with 8 radial incisions. The relative importance of the number of incisions that open during the procedure must be determined with a larger series; however, difficulty lifting the flap was definitely proportional to the number of radial incisions. The efficacy index and the safety index were better in eyes with 8 RK incisions than in eyes with more than 8 RK incisions. It is well documented that the radial incisions never heal completely. 1,2 A mechanical keratome completely separates the flap from the stromal bed; conversely, with the femtosecond laser, the surgeon dissects the flap by breaking the intrastromal adhesion remaining after the femtosecond ablation. The greater amount of strength that must be applied to the flap may increase the risk for intraoperative RK incision opening during femtosecond LASIK compared with mechanical LASIK. This issue should be clarified in future studies that compare the 2 techniques. In our experience, in most eyes, the RK incisions open during flap lifting

6 1188 FEMTOSECOND LASIK FOR CONSECUTIVE HYPEROPIA AFTER RK and the radial incisions closer to the hinge are more likely to open first. For instance, when a nasal hinge was used in the left eye, the radial incisions that opened were mainly at the 7 to 8 o clock position or the 10 to 11 o clock position. If the surgeon had chosen a superior hinge, the RK incisions at the 10 o clock and 1 o clock positions would likely separate first. Difficulties in flap-lifting techniques for experienced femtosecond laser users are related to instrumentation used to lift the flap and how femtosecond laser energy is delivered. Strategies to improve flap lifting could include decreasing the distance between spots of the same line or raster spot separation, decreasing the distance between lines of spots or raster interbeam separation, or increasing the raster energy. One could also use a double-pass technique, which consists of performing the femtosecond ablation twice in the same plane. However, all these approaches would use higher levels of energy, which may increase the postoperative inflammatory reaction as well as other complications such as transient light-sensitivity syndrome (TLSS). 22,23 We believe that increasing the flap thickness would also decrease the risk for wound separation; now we use a 160 to 180 mm flap instead of a 110 mm flap in selected cases. This does not contradict our original statement on the issue of ectasia with thicker flaps in patients with RK after mechanical LASIK. 9 Increasing the depth of the femtosecond ablation may affect the biomechanical properties of the cornea and increase the risk for future ectasia; thus, the depth of the femtosecond ablation should be considered on a case-by-case basis taking into account corneal thickness, the depth of excimer laser ablation, and the number of RK incisions. One advantage of the femtosecond laser is the better predictability of the corneal flap thickness compared with that with mechanical keratomes; this avoids creating a corneal flap that is too thick. 17,28,29 In some cases, a semi-sharp or sharp corneal dissector could be used when separation is difficult because of incomplete cuts; this would also decrease the difficulties with both flap lifting and wound separation. A dissector used for lamellar keratoplasty could be adequate and should be available when dealing with these eyes. Radial keratotomy wound integrity should be examined clinically before surgery. Epithelial inclusion cysts or evidence of clinical wound gape should be ruled out at the slitlamp. Before the LASIK procedure, any sign of progressive hyperopic instability should be ruled out. If in doubt, any attempt at improvement should be done with a procedure that has a minimal biomechanical impact such as surface ablation with MMC. 12,13 Surgeons performing femtosecond laser or microkeratome LASIK surgery in RK eyes must evaluate these clinical findings and determine whether they will perform LASIK or surface ablation. It is noteworthy that 4 eyes (30.8%) developed moderate postoperative DLK and 6 eyes (46.2%), diffuse haze and small particles in the interface. Confocal microscopy showed activated keratocytes and highly reflective particles, suggesting there is more interface reaction in eyes that have had radial incisions before femtosecond laser application. Postoperative interface inflammation after femtosecond LASIK in eyes with previous RK incisions may represent a relative disadvantage compared with mechanical LASIK, especially in the presence of more than 8 radial incisions. This issue should be studied further by comparing femtosecond LASIK and mechanical LASIK. The femtosecond laser has been associated with a higher post-lasik inflammatory reaction and fibrosis. 23,25,33 We used the 15 khz femtosecond laser; however, new lasers that work at 30 or 60 khz would deliver much less energy to the eyes, causing fewer inflammatory side effects. In our study, DLK after femtosecond laser LASIK responded well to topical steroids and did not require flap lifting. At the final follow-up, diffuse haze and small particles in the interface were present in a significant number of eyes, causing a subtle loss of transparency that may explain the loss of 1 line of BSCVA in some eyes. These particles have been described as cell-degradation products. 25 Causes other than the femtosecond ablation may be related to the high incidence of postoperative DLK and small particles in the interface. Difficult flap lifting may cause more reflux of tears into the interface, and oil from the tear film could explain the biomicroscopic and confocal findings. Thus, it could be a technique-related complication rather than something unique to the femtosecond laser. Despite the association between DLK and TLSS, 23 no patient reported increased photophobia during the followup period. In conclusion, the femtosecond laser provided large and thin flaps for hyperopic LASIK with a range of flap thickness smaller than that reported with conventional microkeratomes. The procedure proved to be safe, effective, predictable, and stable for the treatment of consecutive hyperopia after RK, especially in eyes with 8 or less RK incisions. Femtosecond laser ablation for LASIK should be avoided in eyes with more than 8 RK incisions as there is an increased risk for complications such as multiple intraoperative incision openings, DLK, haze, and loss of BSCVA. REFERENCES 1. Deitz MR, Sanders DR, Raanan MG, DeLuca M. Long-term (5- to 12-year) follow-up of metal-blade radial keratotomy procedures. Arch Ophthalmol 1994; 112:

7 FEMTOSECOND LASIK FOR CONSECUTIVE HYPEROPIA AFTER RK Waring GO III, Lynn MJ, McDonnell PJ. Results of the Prospective Evaluation of Radial Keratotomy (PERK) Study 10 years after surgery; the PERK Study Group. Arch Ophthalmol 1994; 112: Nano HD, Muzzin S. Noncontact holmium:yag laser thermal keratoplasty for hyperopia. J Cataract Refract Surg 1998; 24: Joyal H, Grégoire J, Faucher A. Photorefractive keratectomy to correct hyperopic shift after radial keratotomy. J Cataract Refract Surg 2003; 29: Francesconi CM, Nosé RA, Nosé W. Hyperopic laser-assisted in situ keratomileusis for radial keratotomy-induced hyperopia. Ophthalmology 2002; 109: Lipshitz I, Man O, Shemesh G, et al. Laser in situ keratomileusis to correct hyperopic shift after radial keratotomy. J Cataract Refract Surg 2001; 27: Clausse MA, Boutros G, Khanjian G, et al. A retrospective study of laser in situ keratomileusis after radial keratotomy. J Refract Surg 2001; 17:S200 S Attia WH, Alió JL, Artola A, et al. Laser in situ keratomileusis for undercorrection and overcorrection after radial keratotomy. J Cataract Refract Surg 2001; 27: Lyle WA, Jin GJC. Laser in situ keratomileusis for consecutive hyperopia after myopic LASIK and radial keratotomy. J Cataract Refract Surg 2003; 29: Afshari NA, Schirra F, Rapoza PA, et al. Laser in situ keratomileusis outcomes following radial keratotomy, astigmatic keratotomy, photorefractive keratectomy, and penetrating keratoplasty. J Cataract Refract Surg 2005; 31: Probst LE, Machat JJ. Conservative photorefractive keratectomy for residual myopia following radial keratotomy. Can J Ophthalmol 1998; 33: Lee DH, Chung HS, Jeon YC, et al. Photorefractive keratectomy with intraoperative mitomycin-c application. J Cataract Refract Surg 2005; 31: Taneri S, Koch JM, Melki SA, Azar DT. Mitomycin-C assisted photorefractive keratectomy in the treatment of buttonholed laser in situ keratomileusis flaps associated with epithelial ingrowth. J Cataract Refract Surg 2005; 31: Vogel A, Günther T, Asiyo-Vogel M, Birngruber R. Factors determining the refractive effects of intrastromal photorefractive keratectomy with the picosecond laser. J Cataract Refract Surg 1997; 23: Kurtz RM, Horvath C, Liu H-H, et al. Lamellar refractive surgery with scanned intrastromal picosecond and femtosecond laser pulses in animal eyes. J Refract Surg 1998; 14: Nordan LT, Slade SG, Baker RN, et al. Femtosecond laser flap creation for laser in situ keratomileusis: six-month follow-up of initial U.S. clinical series. J Refract Surg 2003; 19: Binder PS. Flap dimensions created with the IntraLase FS laser. J Cataract Refract Surg 2004; 30: Binder PS. One thousand consecutive IntraLase laser in situ keratomileusis flaps. J Cataract Refract Surg 2006; 32: Kezirian GM, Stonecipher KG. Comparison of the IntraLase femtosecond laser and mechanical keratomes for laser in situ keratomileusis. J Cataract Refract Surg 2004; 30: Durrie DS, Kezirian GM. Femtosecond laser versus mechanical keratome flaps in wavefront-guided laser in situ keratomileusis; prospective contralateral eye study. J Cataract Refract Surg 2005; 31: Tran DB, Sarayba MA, Bor Z, et al. Randomized prospective clinical study comparing induced aberrations with IntraLase and Hansatome flap creation in fellow eyes; potential impact on wavefront-guided laser in situ keratomileusis. J Cataract Refract Surg 2005; 31: Stonecipher KG, Dishler J, Ignacio TS, Binder PS. Transient light sensitivity alter femtosecond laser flap creation: clinical findings and management. J Cataract Refract Surg 2006; 32: Muñoz G, Albarrán-Diego C, Sakla HF, et al. Transient light-sensitivity syndrome after laser in situ keratomileusis with the femtosecond laser; incidence and prevention. J Cataract Refract Surg 2006; 32: Biser SA, Bloom AH, Donnenfeld ED, et al. Flap folds after femtosecond LASIK. Eye Contact Lens 2003; 29: Sonigo B, Chong Sit D, Ancel J-M, et al. Évaluation en microscopie confocale des modifications morphologiques cornéennes induites après LASIK et découpe du volet stromal par laser femtoseconde IntraLaseÒ. [In vivo confocal microscopy evaluation of corneal changes induced after LASIK using the IntraLase femtosecond laser technique.]. J Fr Ophtalmol 2005; 28: Mahler O, Sofinski SJ, Gimbel HV, et al. Retrospective analysis of actual LASIK flap diameter compared with microkeratome ring size performed by different surgeons. J Cataract Refract Surg 2004; 30: Arbelaez MC. Nidek MK 2000 microkeratome clinical evaluation. J Refract Surg 2002; 18:S357 S Shemesh G, Dotan G, Lipshitz I. Predictability of corneal flap thickness in laser in situ keratomileusis using three different microkeratomes. J Refract Surg 2002; 18:S347 S Yildirim R, Aras C, Ozdamar A, et al. Reproducibility of corneal flap thickness in laser in situ keratomileusis using the Hansatome microkeratome. J Cataract Refract Surg 2000; 26: Muñoz G, Montés-Micó R, Albarrán-Diego C, Alió JL. Keratectasia after bilateral laser in situ keratomileusis in a patient with previous radial and astigmatic keratotomy. J Cataract Refract Surg 2005; 31: Pallikaris IG, Kymionis GD, Astyrakakis NI. Corneal ectasia induced by laser in situ keratomileusis. J Cataract Refract Surg 2001; 27: Muñoz G, Albarrán-Diego C, Sakla HF, et al. Femtosecond laser in situ keratomileusis after radial keratotomy. J Cataract Refract Surg 2006; 32: Javaloy J, Artola A, Vidal MT, et al. Severe DLK after femtosecond lamellar keratectomy. In press, Br J Ophthalmol 2007 First author: Gonzalo Muñoz, MD, PhD, FEBO Refractive Surgery Departments, Centro Oftalmológica Marqués de Sotelo and Hospital NISA Virgen del Consuelo, Valencia, and VISSUM Instituto Oftalmológico de Alicante, Alicante, Spain

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