A Prospective, Contralateral Eye Study Comparing Thin-Flap LASIK (Sub-Bowman Keratomileusis) with Photorefractive Keratectomy

A Prospective, Contralateral Eye Study Comparing Thin-Flap LASIK (Sub-Bowman Keratomileusis) with Photorefractive Keratectomy Stephen G. Slade, MD, 1 Daniel S. Durrie, MD, 2 Perry S. Binder, MD 3 Purpose: To determine the differences in the visual results, pain response, biomechanical effect, quality of vision, and higher-order aberrations, among other parameters, in eyes undergoing either photorefractive keratectomy (PRK) or thin-flap LASIK/sub-Bowman keratomileusis (SBK; intended flap thickness of 100 m and 8.5-mm diameter) at 1, 3, and 6 months after surgery. Design: A contralateral eye pilot study. Participants: Fifty patients (100 eyes) were enrolled at 2 sites. Methods: The mean preoperative spherical refraction was 3.66 diopters (D) and the mean cylinder was 0.66 D for all eyes. Eyes in the PRK group underwent 8.5-mm ethanol-assisted PRK, whereas in eyes in the SBK group, an 8.5-mm, (intended) 100- m flap was created with a 60-kHz IntraLase femtosecond laser (Advanced Medical Optics, Santa Ana, CA). All eyes underwent a customized laser ablation using an Alcon LADARVision 4000 CustomCornea excimer laser (Alcon Laboratories, Fort Worth, TX). Main Outcome Measures: Preoperative and postoperative tests included best spectacle-corrected visual acuity, uncorrected visual acuity (UCVA), corneal topography, wavefront aberrometry, retinal image quality, and contrast sensitivity. Patients completed subjective questionnaires at each visit. Results: One- and 3-month UCVA results showed a statistically significant difference: SBK, 88% 20/20 or better vs. 48% 20/20 or better for PRK. At 6 months, UCVA was 94% 20/20 or better for PRK and 92% for SBK. At 1 and 3 months, the SBK group had lower higher-order aberrations (coma and spherical aberration; P 0.05); at 1, 3, and 6 months, there was no statistically significant difference in spherical aberration and vertical and horizontal coma between the 2 groups. Conclusions: At the 1-month follow-up, the thin-flap/sbk group demonstrated clinically and statistically significant better visual acuity than the PRK group. By 3 months, the vision in the 2 groups had begun to equalize, although the SBK eyes continued to have better vision. At 6 months, there were no statistical differences between the 2 groups. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2009;116:1075 1082 2009 by the American Academy of Ophthalmology. In the 18-year history of laser refractive surgery, 2 primary approaches to refractive error correction have developed: LASIK and surface ablation (photorefractive keratectomy [PRK], epi-lasik, and laser epithelial keratomileusis [LASEK]). 1 6 Some surgeons opine that surface ablation provides better quality of vision and less dry eye and induces fewer higher-order aberrations (HOAs) than LASIK (M. McDonald, unpublished data, 2001). 1,7 9 However, the vast majority of studies comparing PRK with LASIK were conducted using mechanical microkeratomes before the introduction of the femtosecond laser for flap creation or wavefront-guided surgery. 10,11 Previously published studies show that LASIK demonstrates better visual recovery results than surface ablation procedures, both in the immediate postoperative period (to 1 month) and over the longer term. The most notable is a Cochrane collaboration methodology metaanalysis/systemic review published by Shortt et al. 12 The authors reviewed all prospective, randomized, controlled trials and the Food and Drug Administration clinical trials database. They concluded that LASIK is safer and more accurate than PRK, although the authors note that the vast majority of the literature was out of date (dating before 2001) and that clinical trials need to be performed with up-to-date techniques. Much of the more recent debate about the superiority of surface ablation over LASIK seems to stem from a growing awareness of corneal ectasia seen in post-lasik eyes. 13 21 The reasons for an increase in post-lasik ectasia are beyond the scope of the present article. It is understandable, however, that many refractive surgeons would begin to favor surface ablation to preserve corneal tissue in the hope of reducing the incidence of post-lasik ectasia. A prospective, randomized, contralateral eye pilot study, using contemporary procedures, data algorithms, and equip- 2009 by the American Academy of Ophthalmology ISSN 0161-6420/09/$ see front matter Published by Elsevier Inc. doi:10.1016/j.ophtha.2009.01.001 1075

Ophthalmology Volume 116, Number 6, June 2009 ment compared outcomes for what initially has been referred to as thin-flap LASIK, with an intended flap thickness of 100 m, against PRK. In addition, the concept of a hybrid approach to laser refractive surgery was explored, which the authors propose to call sub-bowman keratomileusis (SBK). This term describes most accurately the benefits of the type of flap used (planar and thin), the customization to the patient (myopic with a narrow refractive range), and the ablation of the excimer laser used. The authors believe there is no difference in visual results between the 3 most common advanced surface ablation techniques: PRK, epi-lasik, and LASEK. On this basis, they decided to use PRK as the advanced surface ablation technique. Results were compared using both traditional metrics (uncorrected visual acuity [UCVA], best spectaclecorrected visual acuity [BSCVA], accuracy, stability, contrast acuity), and newer measurements, including wavefront aberrometry, optical coherence tomography (OCT) flap thickness, corneal hysteresis (CH), and optical quality analysis. Additionally, tests to evaluate dry eye and corneal sensitivity were administered along with a patient satisfaction questionnaire. In this study, flap creation was performed with a femtosecond laser to achieve a more consistent, thin, planar-shaped flap. 10,11,22 29 Patients and Methods This was a prospective, contralateral, randomized, 2-center pilot study in 50 patients (100 eyes). Each patient underwent PRK in 1 eye and SBK in the contralateral eye. Each site (Kansas City and Houston) enrolled 25 patients. Randomization was based on a schedule developed to assure that each group had an equal number of dominant eyes. Informed consent was obtained from all patients. Institutional review board approval for the study was obtained through RCRC IRB. All patients underwent correction for myopia, with or without astigmatism, with the Alcon LADARVision 4000 Excimer Laser (Alcon Laboratories, Fort Worth, TX) and a customized wavefront treatment following the manufacturer s operational instructions. The pupil diameter was made equal, at 6.5 mm, on wavefront measurements by the LADARwave before and after the procedure. Neither site used nomogram adjustments in this study. The study was conducted between March and May 2006. The mean age standard deviation (SD) of the patients was 33.24 6.97 years (range, 22 48 years), with 42% (n 21) men and 58% (n 29) women enrolled. Inclusion criteria consisted of 2 to 6.00 diopters (D) of spherical myopia, with up to 3.50 D of refractive astigmatism; a stable refraction for 1 year; a best spectacle-corrected visual acuity (BSCVA) of at least 20/20 in each eye, and an average central corneal thickness of 500 m or more in each eye. Soft contact lens wearers were required to discontinue lens use for at least 3 days before surgery, whereas rigid contact lens wearers were required to discontinue use at least 3 weeks before surgery and until the refractive error was stable. The mean SD manifest spherical refraction in the SBK group was 3.64 0.97 D (range, 2.00 to 5.75 D), and the mean SD manifest cylindrical refraction was 0.63 D (range, 0 to 3.00 D). In the PRK group, the mean manifest spherical refraction was 3.68 1.06 D (range, 2.00 to 5.75 D), and the mean manifest cylindrical refraction was 0.64 D (range, 0 to 2.75 D). The mean preoperative BSCVA was 20/17 2.47 in both groups, with a range of 20/12 to 20/20. Preoperative UCVA in both groups ranged from 20/80 to counting fingers. The 2 cohorts were statistically similar in preoperative vision. In the SBK eyes, a fourth-generation IntraLase FS Laser (60 khz; Advanced Medical Optics, Santa Ana, CA) was used to create flaps. Planned flap parameters were customized to the excimer laser used and the myopic patient profile in the study. Flap diameter was 8.5 mm and the intended flap thickness was 100 m. A raster pattern was used with the hinge located in the superior position. Both centers applied the same raster energy (1.0 microjoule/spot) and spot line separation (9 9 m). The hinge angle was set at 50 and the side-cut angle was 75. The pocket software was enabled to decrease the occurrence of dense bubbles in the interface. In the PRK eyes, an 8.5-mm trephine was placed on the eye followed by the application of 20% ethanol for 25 seconds and then irrigation and chilling of the ocular surface with balanced salt solution within the trephine. All eyes received proparacaine 0.5% and tetracaine 0.5% drops during surgery. The goal of all surgeries was emmetropia. Immediately after completion of surgery, patients received Vigamox (moxifloxacin; Alcon), Econopred Plus 1% (prednisolone acetate; Alcon), and preservative-free tears. A bandage contact lens (Bausch & Lomb SofLens 66; Bausch & Lomb, Rochester, NY) was placed on each PRK eye after treatment and left in place until the cornea reepithelialized. For the first 7 postoperative days, SBK eyes received Vigamox and Econopred 4 times daily and patients were permitted to use preservative-free artificial tears as needed. The PRK eyes were administered Vigamox and prednisolone acetate 4 times daily for the first 7 days, as well as the artificial tears. The steroid was tapered to 3 times daily in the second week, twice daily in the third week, and then to once daily. These eyes also received Acular LS (ketorolac; Allergan, Irvine, CA), not to exceed thrice daily for the first 3 days, and acetaminophen/ hydrocodone 1 to 2 tablets 4 to 6 times daily for pain control. Topical anesthetic drops were not used. All patients were seen at 1 and 3 days; 1 week; and 1, 3, and 6 months after surgery. All eyes were assessed according to the Food and Drug Administration standard criteria for satisfactory LASIK and PRK outcomes for safety and effectiveness. In addition, preoperative and postoperative outcome measurements included the following: wavefront aberrometry (LADARWave; Alcon Laboratories) according to the standard custom cornea technique, residual postoperative manifest refraction, and contrast visual acuity (Vector Vision 4M ETDRS Charts; Vector Vision, Greenville, OH). Only 1 site (Kansas City) conducted additional testing: confocal microscopy (Nidek, Inc., Fremont, CA), Artemis high-frequency ultrasound imaging (Ultralink LLC, St. Petersburg, FL), Pascal contour dynamic tonometry (Ziemer, Port, Switzerland), corneal response factor (CRF) and CH (Ocular Response Analyzer; Reichert, Depew, NY), corneal sensitivity (Cochet-Bonnet aesthesiometer), Visante OCT imaging (Carl Zeiss Meditec, Jena, Germany), and optical visual acuity assessment (Optical Quality Analysis System; Visiometrics, Terrassa, Spain). 18,19 The Visante OCT imaging system enables a precise view of the anterior segment, as well as providing full-thickness pachymetry measurements. Because it is noncontact, it is able to provide an accurate measurement of corneal flap thickness, as well as the residual stromal bed. The Pascal dynamic contour tonometer is designed to provide intraocular pressure and ocular pulse amplitude measurements without the corneal compression necessary with conventional applanation tonometers. A tip that matches the corneal curvature captures 100 readings per second. 1076

Slade et al Thin-Flap LASIK vs. PRK The Artemis 2 (ArcScan, Morrison, CO) technique uses very high frequency ultrasound to provide 3-dimensional corneal thickness measurements to image the anterior segment. The Ocular Response Analyzer system measures the cornea s ability to absorb energy or the viscous damping in cornea tissue. It works by using rapid air pulses to record 2 applanation pressure measurements: one while the cornea is moving inward and the second as the cornea moves outward again. The difference between these 2 measurements is termed corneal hysteresis (CH). A low CH value may suggest the cornea has weakened and is less able to absorb energy. 30 The Optical Quality Analysis System was developed to estimate retinal image quality and contrast sensitivity. The system uses a double-pass technology that shines a low-power beam of diode laser light (wavelength, 780 nm) into the eye, producing a punctual circular image on the retina. During the second pass, the reflection of this spot on the retina is measured by a highly sensitive low-light camera that directly measures the point spread function of the optical system. Fourier analysis is used to translate the point spread function to a modulation transfer function (MTF) value. The MTF value correlates to the loss of contrast in the retinal image for each spatial frequency. A higher MTF value suggests better optical quality. 31 All tests were carried out before surgery and at the 1-, 3-, and 6-month visits. Patients were also required to complete a subjective questionnaire, developed by the study sponsor (AMO) and the investigators and used at both sites, on comfort and vision at all postoperative visits. As part of this comparative study, patients responses to pain after surgery were recorded and compared. Patients were asked to record which eye had more pain at 1 day, 3 days, 1 week, and then at 1 and 3 months. They also were asked to assess eye dryness with the following question: Which eye has more feeling of dryness? Possible responses were: right eye has more feelings of dryness, left eye has more feelings of dryness, they both have about the same feelings of dryness, and not sure or don t know. Statistical analysis was performed using the Student paired t test. For the subject questionnaires, the McNemar chi-square test was used. A P value of 0.05 or less was considered to be statistically significant for all analyses. Results Snellen Visual Acuity and Spherical Equivalent Eyes were compared by the logarithm of the minimum angle of resolution. The UCVA at the 1-month postoperative visit showed 88% of the SBK eyes at 20/20 or better compared with 48% of the PRK eyes (P 0.0001; Table 1). At 3 months, the UCVA in the PRK group improved (92% SBK vs. 90% PRK 20/20 or better; P 0.5). All PRK eyes were 20/32 or better compared with 98% of SBK eyes at 3 months (1 SBK eye had an undercorrection of 0.75 D). Seventy percent of SBK eyes were 20/16 or better compared Table 1. Uncorrected Visual Acuity Results at 1 Month after Surgery 20/12.5 or 20/16 or 20/20 or 20/25 or 20/40 or SBK 18 46 88 90 100 PRK 2 16 48 48 98 PRK photorefractive keratectomy; SBK sub-bowman keratomileusis. Table 2. Uncorrected Visual Acuity Results at 6 Months after Surgery 20/12.5 or with 64% of PRK eyes at 3 months. At 6 months after surgery, there was a further equalization with 94% of the PRK eyes and 92% of the SBK eyes achieving a UCVA of 20/20 or better (P 0.63; Table 2). All SBK eyes obtained 20/40 UCVA (legal driving vision) from the first postoperative day, whereas in the PRK group, 42% were 20/40 on day 1, 39% at day 3, and 68% at 1 week. The BSCVA results showed a similar trend at 1 and 3 months, with 42% of the SBK group gaining 1 line or more of vision compared with 16% in the PRK group at 1 month (P 0.0001). Forty-two percent of the PRK group lost 1 line or more of vision, compared with 22% losing 1 line in the SBK group (P 0.0001). No eyes in the SBK group lost 2 lines or more of BSCVA, whereas in the PRK group, 6% lost 2 lines or more. The difference in BSCVA between the 2 groups was statistically similar at the 3-month visit, with 57% of the SBK eyes showing an improvement of 1 line or more of BSCVA compared with 53% in the PRK group (P 0.33). Ten percent of the PRK group lost 1 line of vision, whereas no eyes in either group lost 2 lines or more. In the SBK group, 4% lost 1 line, with no eyes losing 2 lines or more of BSCVA at 3 months (P 0.33). At 6 months, 62% of the SBK eyes had gained 1 line or more compared with 56% of the PRK group (P 0.56). Table 3 shows the mean refractive spherical equivalent and cylinder before surgery and at 1, 3, and 6 months after surgery. Flap Thickness Results One of the goals of this study was to create a femtosecond-laser flap with an intended thickness of 100 m. The OCT analysis showed that the SBK flaps had a mean thickness of 112 5 m (range, 87 118 m; Fig 1). The OCT measurements obtained at 16 spots across the entire surface of each flap demonstrated that the flaps were planar with no statistical difference in thickness. The SD for each individual flap was 4 m. 32 Subjective Results 20/16 or 20/20 or 20/25 or 20/40 or SBK 24 72 92 98 100 PRK 26 70 94 98 100 PRK photorefractive keratectomy; SBK sub-bowman keratomileusis. Pain Response Results. Eyes that underwent PRK were significantly more painful, particularly during reepithelization in the first Table 3. Mean Refractive Spherical Equivalent and Cylinder at Baseline and 1, 3, and 6 Months after Surgery Before Surgery 1 Month 3 Months 6 Months MRSE SBK 3.95 0.10 0.11 0.17* (P 0.05) PRK 3.99 0.02 0.08 0.08* (P 0.05) Cylinder SBK 0.63 0.38 0.24 0.29 PRK 0.64 0.25 0.32 0.26 MRSE mean refractive spherical equivalent; PRK photorefractive keratectomy; SBK sub-bowman keratomileusis. *Statistically significant. 1077

Ophthalmology Volume 116, Number 6, June 2009 Figure 1. Bar graph showing average flap thickness as measured by optical coherence tomography demonstrating a standard deviation of 5 m. The arrows at the top indicate the direction and placement of the measurement. The x-axis represents the thickness of the corneal flap, whereas the y-axis indicates the range of deviation for each of the four measurements. The shaded bars show the spread of the measurements. SD standard deviation. 3 days after surgery. At day 3, 88% reported the PRK eye to be more painful, with 10% indicating that both eyes felt the same, and 2% finding their SBK eye to be more painful. By 1 week, this difference had decreased, with patients reporting that the PRK eye had more pain (49%) or that both eyes felt the same or that they were unsure (49%; 2% reported that the SBK eye was more painful). At 1 month, 74% reported that both eyes felt the same, with 22% indicating the PRK eye and 4% finding the SBK eye to be more painful (P 0.01). At 3 months, 88% of patients (P 0.69) said that both eyes felt the same, which improved to 94% at 6 months (P 1.00). Patients also reported through their subjective questionnaire responses that their PRK eyes were drier throughout every postoperative visit to 6 months, although this symptom also equalized over time. At 1 day, 43% believed the PRK eye was drier, with 47% saying both eyes felt the same and 11% reporting the SBK eye to be drier (P 0.0001). By 1 month, 68% of patients believed that both eyes were equal, with 24% saying the PRK was drier and 8% saying the SBK eye was drier (P 0.05). At 6 months, 84% indicated that both eyes felt the same, although a higher percentage of patients believed the PRK eye was drier than the SBK eye (12% vs. 4%; P 0.29). Satisfaction with Vision. At the 1- and 3-day and 1-week visits, patients showed a preference for their SBK eye by a factor of 20:1 (P 0.0001). At the 1-month visit, the ratio was 10:1, and then the ratio was approximately 2:1 at 3 months after surgery (P 0.15). The greatest difference between the 2 eyes was seen in the early recovery period (days 1 and 3 and 1 week), with a trend of equalization seen at 1 and 3 months. At 6 months, 65% said that both eyes had the same vision, with 15% indicating the SBK eye and 20% favoring the PRK eye (P 0.63). Figure 2 shows patient response when asked which eye has better vision overall to 6 months. In ranking their distance vision under various lighting conditions on a scale of 1 (poor vision) to 10 (excellent vision), patients favored the SBK eye at all postoperative visits through 3 months. At 1 week, under sunlit conditions, patients gave their SBK eye a rating of 8.37 compared with 6.14 for the PRK eye; at 3 months, this improved to 9.43 for the SBK eye and 9.37 for the PRK eye (P 0.05). In dim lighting conditions, patients gave their SBK eye a rating of 8.37 versus 6.24 for the PRK eye at 1 week. At 3 months, the SBK and PRK ratings were equal at 9.06 (P 0.05). Figures 3 and 4 show the breakdown of subjective distance vision under the 3 lighting conditions. For near vision, the results were similar, with patients preferring their SBK eye, particularly up to the 1-month visit. At 1 week, under normal lighting conditions, patients gave the SBK eye a ranking of 8.76 compared with 6.98 for the PRK eye (P 0.05). At 3 months, patients still preferred the SBK eye to the PRK eye (9.22 vs. 9.14; P 0.05). In dim lighting conditions, the SBK eye was given a rating of 8.55 at 1 week versus 6.57 for the PRK eye (P 0.05). At 3 months, there was no significant difference between eyes, with a ranking of 9.10 for the SBK eye and 9 for the PRK eye (P 0.05). Figures 5 and 6 show the subjective near vision results for 3 different lighting conditions. At no time did any patients report dissatisfaction with the SBK eye, whereas 1 patient reported being dissatisfied with the PRK eye Figure 2. Bar graph showing patient questionnaire results: Which eye has better vision overall? PRK photorefractive keratectomy; SBK sub- Bowman keratomileusis. 1078

Slade et al Thin-Flap LASIK vs. PRK Figure 3. Bar graph showing self-reported satisfaction with distance vision under bright light (sunshine) conditions. PRK photorefractive keratectomy; SBK sub-bowman keratomileusis. through 3 months but was satisfied with that eye at the 6-month visit. Patient-Reported Symptoms. Through the first postoperative week, patients reported that the SBK eye was less painful than the PRK eye at a ratio of 25:1 (87% vs. 8%; P 0.0001). At 1 month, this ratio improved to 5:1 (P 0.01) and then 2:1; at 3 months after surgery, there was no difference (P 0.65). Patients reported that the SBK eye had less pain and visual fluctuation through 1 month after surgery than the PRK eye (28% vs. 38%; P 0.09). They also reported fewer difficulties with night driving (12% SBK eye vs. 18% PRK eye; P 0.08). Through the 3-month assessment, patients reported less double or ghost vision (2% SBK vs. 6% PRK; P 0.1) and glare and halos (8% SBK vs. 12% PRK; P 0.08). At 6 months, the most frequently reported symptom was fluctuating vision, experienced in 20% of PRK eyes and 18% of the SBK eyes (P 1.00). The second most frequently reported symptom was difficulty with night driving, with 10% of PRK eyes and 8% of SBK eyes experiencing difficulties. Retinal Image Quality. The Optical Quality Analysis System was used to assess retinal image quality by measuring the MTF and contrast values for each group before surgery and at 1, 3, and 6 months after surgery. The average MTF value before surgery Figure 5. Bar graph showing self-reported satisfaction with near vision under bright light (sunshine) conditions. PRK photorefractive keratectomy; SBK sub-bowman keratomileusis. was 30.09 8 for the SBK eyes and 29.39 10 for the PRK eyes. At 1 month, the average MTF value increased by 6% in the SBK eyes and decreased by 13% in the PRK eyes (P 0.05). At 3 months, the average MTF value was 30.88 8 for the SBK eyes and 29.49 8 for the PRK eyes (P 0.05). This represented a gain in quality of vision of 3% in the SBK eyes compared with no change in the PRK eyes. At 6 months, the average MTF value for the SBK eyes was 29.93 and 27.81 for the PRK eyes (P 0.05). Table 4 demonstrates the changes from baseline to 6 months for the MTF and contrast values. Contrast Visual Acuity. At 1 month, the SBK eyes had statistically better high (90%) uncorrected contrast visual acuity (0.01 SBK vs. 0.12 PRK; P 0.0001) and BSCVA ( 0.04 SBK vs. 0.03 PRK; P 0.0001). Low (10%) contrast acuity results also were better in the SBK group: for UCVA, 0.18 in the SBK eye versus 0.29 in the PRK eye (P 0.0001), and for BSCVA, 0.13 in the SBK eye versus 0.18 in the PRK eye (P 0.002). Results for 3 and 6 months also showed superiority with SBK, with no change from the 1-month results. Wavefront Aberrometry. The 1-month results compared with baseline indicated that the SBK eyes had the same or lower HOA compared with the PRK eyes (50% SBK vs. 28% PRK; P 0.05). The total change in HOA root mean square (RMS) from baseline Figure 4. Bar graph showing self-reported satisfaction with distance vision under dim light conditions. PRK photorefractive keratectomy; SBK sub-bowman keratomileusis. Figure 6. Bar graph showing self-reported satisfaction with near vision under dim light conditions. PRK photorefractive keratectomy; SBK sub-bowman keratomileusis. 1079

Ophthalmology Volume 116, Number 6, June 2009 Table 4. Optical Quality Analysis System (Visiometrics, Terrassa, Spain) Results: Change from Baseline to 6 Months after Surgery to 1 month was 0.04 m in the SBK group and 0.11 m inthe PRK group (P 0.61). There was no statistical difference between groups for vertical and horizontal coma or spherical aberration. At the 3-month follow-up, 41% of the PRK eyes showed improved HOA RMS results with the same or lower HOA RMS compared with baseline HOA. Forty-nine percent of the SBK eyes had the same or lower HOA RMS at 3 months. The difference in the total HOA RMS from baseline was 0.05 m in the SBK group and 0.04 m in the PRK group (P 0.49). There was no statistical difference between the 2 groups for vertical and horizontal coma or spherical aberration. At 6 months, there was a change in the total HOAs present in the 2 groups ( 0.18 m SBK vs. 0.29 PRK m; P 0.23). There was no statistical difference between the SBK eyes and the PRK eyes for horizontal (P 0.49) and vertical (P 0.05) coma or spherical aberration (P 0.01). Biomechanical Results Before Surgery 1 Month* 3 Months 6 Months Change in Modulation Transfer Function Value from before Surgery SBK 6% 3% 1% PRK 13% 0% 5% Change in Contrast Value from before Surgery SBK 8% 2% 1% PRK 13% 1% 7% PRK photorefractive keratectomy; SBK sub-bowman keratomileusis. *P 0.05. Ocular Response Analyzer Results. Lower CH and CRF values theoretically are suggestive of a biomechanically weaker cornea. 33 The average preoperative CH measurement for the SBK eyes was 9.3 (SD, 1.3) and was 9.5 (SD, 1.4) for the PRK eyes. The preoperative CRF measurements were 10.0 ( 1.5) and 10.3 ( 1.8), respectively. At 1 month after surgery, Ocular Response Analyzer testing showed a CH of 8.0 (SD, 1.0) for the SBK eyes and 7.1 (SD, 1.3) for the PRK eyes (P 0.0002) and a CRF of 7.3 ( 1.2) for SBK eyes and 6.6 ( 1.7) for PRK eyes (P 0.08). At 3 and 6 months, this trend continued. The CH measurement at 3 months for the SBK eyes was 8.0 ( 1.0) and 7.8 ( 1.0) for PRK eyes (P 0.03). The CRF values at 3 months were 7.2 ( 1.1) and 7.3 ( 1.5), respectively (P 0.12). At 6 months, the CH was 8.1 ( 1.2) for SBK eyes and 7.8 ( 1.2) for PRK eyes (P 0.004), and the CRF was 7.3 ( 1.2) and 7.1 ( 1.4; P 0.12), respectively. The CH decreased after both SBK and PRK, which may suggest that there was no biomechanical advantage to the surface ablation technique. The same was true with the CRF results, with a theoretic equal biomechanical weakening seen in both the SBK and PRK eyes. Pascal Tonometer. The preoperative ocular pulse amplitude in both groups was 1.8. At the 1-month follow-up, this measurement was 1.71 for the SBK group and 2.00 for the PRK group (P 0.001). At 3 months, the ocular pulse amplitude was 1.69 and 1.83 (P 0.05), respectively, and at 6 months it was 1.80 and 1.81 (P 0.89). There was only a small change between the preoperative and postoperative measurements, but more data are needed to understand fully the significance of these results. Dry Eye Testing Schirmer I Testing. Before surgery, the 2 groups were essentially equal (17 mm SBK vs. 16 mm PRK; P 0.12). At 1 month, there was a slight reduction in wetting in both groups: 14 mm in the SBK eyes versus 13 mm in the PRK eyes (P 0.41). At 3 months, the groups were equal: 16 mm (P 0.79); and at 6 months, the 2 groups were essentially equal as well, with the PRK eyes at 19 mm and the SBK eyes at 20 mm (P 0.09). Lissamine Green Test. At 1 month, 98% of the SBK eyes and 92% of the PRK eyes had no corneal staining, with 8% of the PRK eyes and 2% of the SBK eyes having grade 1 mild staining. At 3 months, 90% of the SBK eyes had no staining, with the remaining 10% having grade 1 staining. Ninety-two percent of the PRK eyes had no staining, with the remaining 9% having grade 1. By 6 months, the groups were equal, with 98% having no staining and 2% having grade 1 staining. Conjunctival staining was not performed in this study. Corneal Sensitivity Results At 1 month, there was an average reduction in corneal sensitivity of 15% in the SBK eyes compared with preoperative values. In the PRK eyes, there was an average reduction in corneal sensitivity of 5%. At the 3-month follow-up, the average reduction in corneal sensitivity in the SBK eyes remained at 15%, but increased to 7% in the PRK eyes. At 6 months, the corneal sensitivity in the SBK eyes had improved to an average reduction of 13%, whereas it remained unchanged in the PRK eyes at 7%. Complications There were no intraoperative or postoperative complications encountered in the femtosecond laser flap group. Discussion Recent studies have focused on the biomechanical strength of the cornea to determine an optimal refractive laser procedure. 34 Work performed by Ortiz et al 35 demonstrated that when the LASIK flap was created with the use of a femtosecond laser, the corneas had greater stability than when a mechanical microkeratome was used to create the flap and were equivalent to eyes treated with a surface ablation. Cadaver eye studies conducted by Marshall et al demonstrated similar results (J. Marshall et al, unpublished data, 2007). A long-term follow-up on visual results and stability of LASIK flaps of less than 100 m showed good visual results and stability. 35 On the basis of preliminary evidence that thinner flaps are biomechanically more stable than thicker LASIK flaps, the present study explored an alternative procedure with the potential to bridge surface techniques and LASIK to preserve corneal integrity, while providing faster visual rehabilitation. The authors propose to call this procedure sub- Bowman keratomileusis because it most accurately reflects what they believe needs to be achieved: a customized flap 1080

Slade et al Thin-Flap LASIK vs. PRK designed to match the patient s needs and with a diameter and shape that is based on the type of excimer laser ablation being performed. In this study, the parameters of an intended thickness of 100 m and a 8.5-mm diameter corneal flap were based on the excimer laser used and the patient profile: myopic patients with a narrow range of refractive error. There are a number of flap-creation instruments capable of making a corneal flap of between 90 and 100 m, including the Moria M2 mechanical microkeratome (Moria, Antony, France), the Schwind Carriazo Pendular mechanical microkeratome (Schwind-Eye-Tech-Solutions, Kleinostheim, Germany), and the IntraLase Femtosecond laser keratome. The femtosecond laser was chosen for this study because of its ability to create an almost planar flap, as well as evidence that it reduces the incidence of flap-related complications in previously reported studies. 22 24 Further, the IntraLase laser allows the surgeon to customize the diameter on the basis of the ablation size and to center precisely on the cornea for maximum stromal exposure. At every postoperative visit through 3 months and with most measurements used in this study, the SBK eyes demonstrated better results than the PRK eyes, although at 6 months, UCVA was similar in the 2 groups (94% of PRK eyes had 20/20 vision vs. 92% of SBK eyes). In particular, the earlier visual results and subjective patient responses favor SBK. When comparing the biomechanical changes to the cornea caused by PRK and SBK, the evidence suggests that there are similar effects on the cornea. There was a greater loss of corneal sensitivity in the SBK flaps than in the PRK eyes through 6 months. The clinical results in this series of eyes demonstrate the quicker visual recovery of SBK versus PRK in the early postoperative period, particularly in the first week after surgery. The SBK eyes were able to recover visual acuity and to return to functioning vision more quickly than the PRK patients, with 100% of the SBK eyes at legal driving vision (20/40) at day 1. As seen in other published comparisons, by the third postoperative month, the difference between the 2 patient groups had begun to close. 11,22 24,26 28 Although visual results remain of great importance, another critical aspect to the success of a laser refractive procedure is the patient experience. Because this was a contralateral eye study, the opportunity to have patients assess the pain and healing process after surgery was taken. Contralateral study results are particularly powerful for a survey, because the only variable is the type of surgery performed on each eye. The close correlation in preoperative measures also demonstrates the power of a contralateral eye study. In the dry eye testing with lissamine green, only corneal staining was used. Conjunctival staining was not included, which might have helped to improve the sensitivity of the test. The results show that even with modern pharmaceutical therapy to manage pain and discomfort, patients in this study overwhelmingly found their PRK eye to be more painful, particularly in the first week, but even past the 1-month mark. On the basis of findings from previous comparative studies, it is reasonable to conclude that there will be an equalization of results between the SBK and PRK groups between the 3- and 6-month follow-up visits. To the best of the authors knowledge, this was the first prospective, contralateral clinical study to compare the stateof-the-art techniques for PRK and SBK using wavefrontguided excimer laser technology and the femtosecond laser for flap creation in the SBK cases. The initial results seen in this contralateral study would seem to suggest the potential benefit of matching the size of the flap to the ablation of the excimer laser used. Additional evaluation of wavefront results, biomechanical response, and longer-term follow-up will be needed to support these conclusions. There is also a need for further independent, contralateral studies to verify these results, particularly to compare results obtained with the femtosecond laser versus mechanical microkeratomes that are capable of creating thin, planar (SBK) flaps. From this first study to compare SBK with PRK, the authors conclude that this new procedure offers refractive surgeons and patients many of the advantages of both LASIK and PRK, with the quicker visual recovery and comfort associated with LASIK and the theoretical biomechanical changes and tear function of PRK. There was an equalization of the results between the 3- and 6-month postoperative visits. However, this should not come as a surprise given the general acknowledgment that PRK patients begin to achieve their best visual results starting at approximately the third postoperative month. Proponents of surface procedures argue that it is unfair to compare the results between a flap-based and surface ablation procedure before the 3-month visit. However, they may be missing what is important from the patient s perspective. Sub-Bowman keratomileusis would seem to be more practical for the patient with less pain, quicker visual recovery, fewer medications, and an overall superior experience. For all 3 authors, PRK remains the preferred procedure in eyes where LASIK is contraindicated. Although further clinical studies on SBK are needed, as well as a better understanding of these new biomechanical tests, all 3 authors (SGS, DSD, PB) currently use SBK as their primary procedure. In the future, we can expect to have greater flexibility in how the femtosecond laser flap is customized with the ability to design the flap dimensions on the basis of epithelial thickness, corneal diameter, planned ablation zone, corneal curvature, or laser algorithms. This will provide the potential to improve visual outcomes even further. References 1. Hersh PS, Brint SF, Maloney RK, et al. Photorefractive keratectomy versus laser in situ keratomileusis for moderate to high myopia: a randomized, prospective study. Ophthalmology 1998;105:1512 22. 2. Yang XJ, Yan HT, Nakahori Y. Evaluation of the effectiveness of laser in situ keratomileusis and photorefractive keratectomy for myopia: a meta-analysis. J Med Invest 2003;50:180 6. 3. Neeracher B, Senn P, Schipper I. Glare sensitivity and optical side effects 1 year after photorefractive keratectomy and laser in situ keratomileusis. J Cataract Refract Surg 2004;30:1696 701. 4. Pirouzian A, Thornton J, Ngo S. One-year outcomes of a bilateral randomized prospective clinical trial comparing laser subepithelial keratomileusis and photorefractive keratectomy. J Refract Surg 2006;22:575 9. 1081

Ophthalmology Volume 116, Number 6, June 2009 5. Durrie DS, Kezirian GM. Femtosecond laser versus mechanical microkeratome flaps in wavefront-guided laser in situ keratomileusis: prospective contralateral eye study. J Cataract Refract Surg 2005;31:120 6. 6. Tobaigy FM, Ghanem RC, Sayegh RR, et al. A controlmatched comparison of laser epithelial keratomileusis and laser in situ keratomileusis for low to moderate myopia. Am J Ophthalmol 2006;142:901 8. 7. Rajan MS, Jaycock P, O Brart D, et al. A long-term study of photorefractive keratectomy: 12-year follow-up. Ophthalmology 2004;111:1813 24. 8. Randleman JB, Loft ES, Banning CS, et al. Outcomes of wavefront-optimized surface ablation. Ophthalmology 2007; 114:983 8. 9. Chung SH, Lee IS, Lee YG, et al. Comparison of higher-order aberrations after wavefront-guided laser in situ keratomileusis and laser-assisted subepithelial keratectomy. J Cataract Refract Surg 2006;32:779 84. 10. 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;19:8 14. 11. Binder PS. One thousand consecutive IntraLase laser in situ keratomileusis flaps. J Cataract Refract Surg 2006;32:962 9. 12. Shortt AJ, Bunce C, Allan BD. Evidence for superior efficacy and safety of LASIK over photorefractive keratectomy for correction of myopia. Ophthalmology 2006;113:1897 908. 13. Binder PS. Analysis of ectasia after laser in situ keratomileusis: risk factors. J Cataract Refract Surg 2007;33:1530 8. 14. Randleman JB, Caster AI, Banning CS, Stulting RD. Corneal ectasia after photorefractive keratectomy. J Cataract Refract Surg 2006;32:1395 8. 15. Condon PI. 2005 ESCRS Ridley Medal Lecture: will keratectasia be a major complication for LASIK in the long term? J Cataract Refract Surg 2006;32:2124 32. 16. Binder PS. Ectasia after laser in situ keratomileusis. J Cataract Refract Surg 2003;29:2419 29. 17. Randleman JB. Post-laser in-situ keratomileusis ectasia: current understanding and future directions. Curr Opin Ophthalmol 2006;17:406 12. 18. Reinstein DZ, Srivannaboon S, Archer TJ, et al. Probability model of the inaccuracy of residual stromal thickness prediction to reduce the risk of ectasia after LASIK. Part I: quantifying individual risk. J Refract Surg 2006;22:851 60. 19. Reinstein DZ, Srivannaboon S, Archer TJ, et al. Probability model of the inaccuracy of residual stromal thickness prediction to reduce the risk of ectasia after LASIK. Part II: quantifying population risk. J Refract Surg 2006;22:861 70. 20. Rabinowitz YS. Ectasia after laser in situ keratomileusis. Curr Opin Ophthalmol 2006;17:421 6. 21. Ciolino JB, Belin MW. Changes in the posterior cornea after laser in situ keratomileusis and photorefractive keratectomy. J Cataract Refract Surg 2006;32:1426 31. 22. Flanagan GW, Binder PS. Precision of flap creation for laser in situ keratomileusis in 4428 eyes. J Refract Surg 2003;19: 113 23. 23. Talamo JH, Meltzer J, Gardner J. Reproducibility of flap thickness with IntraLase FS and Moria LSK-1 and M2 microkeratomes. J Refract Surg 2006;22:556 61. 24. Solomon KD, Donnenfeld E, Sandoval HP, et al. Flap Thickness Study Group. Flap thickness accuracy: comparison of 6 microkeratome models. J Cataract Refract Surg 2004;30:964 77. 25. 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;31:97 105. 26. Stonecipher K, Ignacio TS, Stonecipher M. Advances in refractive surgery: microkeratome and femtosecond laser flap creation in relation to safety, efficacy, predictability and biomechanical stability. Curr Opin Ophthalmol 2006;17:368 72. 27. Kezirian GM, Stonecipher KG. Comparison of the IntraLase femtosecond laser and mechanical microkeratomes for laser in situ keratomileusis. J Cataract Refract Surg 2004;30:804 11. 28. Munoz G, Albarran-Diego C, Sakla HF, et al. Femtosecond laser in situ keratomileusis after radial keratotomy. J Cataract Refract Surg 2006;32:1270 5. 29. Montes-Mico R, Rodriguez-Galietero A, Alio JL. Femtosecond laser versus mechanical keratome LASIK for myopia. Ophthalmology 2007;114:62 8. 30. Kirwan C, O Keefe M. Corneal hysteresis using the Reichert ocular response analyzer: findings pre- and post-lasik and LASEK. Acta Ophthalmol 2008;86:215 8. 31. Güell JL, Pujol J, Arjona M, et al. Optical Quality Analysis System: instrument for objective clinical evaluation of ocular optical quality [letter]. J Cataract Refract Surg 2004;30:1598 9. 32. Stahl JE, Durrie DS, Schwendeman FJ, Boghossian AJ. Anterior segment OCT analysis of thin IntraLase femtosecond flaps. J Refract Surg 2007;23:555 8. 33. Rajan MS, O Brart D, Jaycock P, Marshall J. Effects of ablation diameter on long-term refractive stability and corneal transparency after photorefractive keratectomy. Ophthalmology 2006;113:1798 806. 34. Ortiz D, Pinero D, Shabayek M, et al. Corneal biomechanical properties in normal, post-laser in situ keratomileusis, and keratoconic eyes. J Cataract Refract Surg 2007;33:1371 5. 35. Ortiz D, Alió JL, Piñero D. Measurement of corneal curvature change after mechanical laser in situ keratomileusis flap creation and femtosecond laser flap creation. J Cataract Refract Surg 2008;34:238 42. Footnotes and Financial Disclosures Originally received: January 31, 2008. Final revision: January 5, 2009. Accepted: January 6, 2009. Manuscript no. 2008-158. 1 The Slade & Baker Vision Institute, Houston, Texas. 2 Durrie Vision, Overland Park, Kansas. 3 The Gordon, Binder & Weiss Vision Institute, San Diego, California. Presented in part at: American Society of Cataract and Refractive Surgery Annual Meetings, 2006 in San Francisco, and 2007 in San Diego, California. Financial Disclosure(s): The author(s) have made the following disclosure(s): Stephen G. Slade - Consultant - Advanced Medical Optics (AMO), Alcon Laboratories. Daniel S. Durrie - Consultant - Advanced Medical Optics (AMO), Alcon Laboratories. Perry S. Binder - Consultant - Alcon Laboratories. Supported by Advanced Medical Optics (AMO), Irvine, California. Correspondence: Stephen G. Slade, MD, Slade & Baker Vision, 3900 Essex Lane, Suite 101, Houston, TX 77027. E-mail: sgs@visiontexas.com. 1082