Accuracy and Reproducibility of Cap Thickness in

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Oct 30, 2013 - ometry and software set-up of the SMILE lenticule, cap, and small ..... a prospective study of ReLEx((R)) flex and comparison with. TABLE 1.
ORIGINAL ARTICLE

Accuracy and Reproducibility of Cap Thickness in Small Incision Lenticule Extraction Dan Z. Reinstein, MD, MA(Cantab), FRCOphth; Timothy J. Archer, MA(Oxon), DipCompSci(Cantab); Marine Gobbe, MST(Optom), PhD

ABSTRACT PURPOSE: To evaluate the accuracy and reproducibility of cap thickness for small incision lenticule extraction (SMILE) with the VisuMax femtosecond laser (Carl Zeiss Meditec, Inc., Jena, Germany). METHODS: Artemis very high-frequency digital ultrasound (ArcScan Inc., Morrison, CO) measurements were obtained before and 3 months after SMILE in 70 eyes of 37 patients with intended cap thickness between 80 and 140 µm. True cap thickness at the time of creation was calculated as the addition of the preoperative epithelial thickness and the postoperative stromal component of the flap and mapped for the central 5-mm diameter zone. Cap thickness accuracy was calculated as the difference between the mean and intended cap thickness. Reproducibility was evaluated as the cap thickness standard deviation between eyes. Accuracy and reproducibility of cap thickness were calculated for all eyes and grouped by intended cap thickness. Within-eye variation in cap thickness was calculated as the standard deviation of all data within the central 5-mm diameter zone. RESULTS: Mean cap thickness accuracy was between -2.3 and 6.5 µm and was -0.7 µm centrally (range: -11 to +14 µm), including all eyes. Cap thickness reproducibility was 6 µm or less for the majority of the central 5-mm diameter zone and was 4.4 µm centrally. Cap thickness accuracy and reproducibility were similar for different intended cap thicknesses. Average within-eye variation in cap thickness was 4.3 µm. CONCLUSIONS: SMILE cap thickness using the VisuMax femtosecond laser was found to be accurate and reproducible across the central 5-mm diameter zone for intended cap thicknesses over the range of 80 to 140 µm. [J Refract Surg. 2013;29(12):810-815.]

S

mall incision lenticule extraction (SMILE) is a new laser refractive surgery procedure in which two interfaces are created using a femtosecond laser to isolate a lenticule of stromal tissue that can be manually removed from the cornea through a small incision.1-4 For the SMILE procedure to be refractively accurate, the accuracy of the femtosecond laser interface creation must be sufficiently high. Femtosecond lasers have been used for creating LASIK flaps since 20025 and studies have demonstrated how the accuracy and reproducibility have improved over time.6-14 Currently, SMILE has only been performed using the VisuMax femtosecond laser (Carl Zeiss Meditec, Inc., Jena, Germany), for which the flap thickness reproducibility has been reported to be between 3.8 and 14.4 µm.10-14 The aim of the current study was to evaluate the accuracy and reproducibility of cap thickness for myopic SMILE treatments with the VisuMax femtosecond laser using Artemis very high-frequency (VHF) digital ultrasound (ArcScan Inc., Morrison, CO). PATIENTS AND METHODS PATIENTS This study was a retrospective, noncomparative case series of patients who underwent a SMILE procedure at the London Vision Clinic, London, United Kingdom, between May From London Vision Clinic, London, United Kingdom (DZR, TJA, MG); the Department of Ophthalmology, Columbia University Medical Center, New York, New York (DZR); and Centre Hospitalier National d’Ophtalmologie, Paris, France (DZR). Submitted: May 17, 2013; Accepted: July 15, 2013; Posted online: October 30, 2013 Dr. Reinstein is a consultant for Carl Zeiss Meditec (Jena, Germany) and has a proprietary interest in the Artemis technology (ArcScan Inc, Morrison, Colorado) and is an author of patents related to VHF digital ultrasound administered by the Cornell Center for Technology Enterprise and Commercialization, Ithaca, New York. The remaining authors have no financial or proprietary interest in the materials presented herein. Prepared in part fulfillment of the requirements for the doctoral thesis of Dr. Reinstein for University of Cambridge. Correspondence: Dan Z. Reinstein, MD, MA(Cantab), FRCOphth, London Vision Clinic, 138 Harley Street, London W1G 7LA, United Kingdom. E-mail: [email protected] doi:10.3928/1081597X-20131023-02

810

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Accuracy and Reproducibility of Cap Thickness in SMILE/Reinstein et al

2011 and December 2012. A complete ocular examination was performed to screen for corneal abnormalities and determine patient candidacy for refractive surgery. Eyes with ocular pathology such as keratoconus, corneal scar, corneal dystrophy, and previous ocular surgery were excluded. Our routine preoperative assessment was performed and has been described previously.15 All patients also had an Artemis VHF digital ultrasound scan as described below. Informed consent and permission to anonymously use their data for analysis and publication were obtained from all patients. SURGICAL PROCEDURE All SMILE treatments were performed using the VisuMax 500-kHz femtosecond laser by a single surgeon (DZR). The VisuMax femtosecond laser has been described in detail previously.1-4,10-14 Details of the geometry and software set-up of the SMILE lenticule, cap, and small incision have been described previously.1-4 In the current study, two incisions were created in all eyes: a 2-mm incision superonasally and a 3-mm incision superotemporally. The optical zone diameter used was between 5.75 and 7.00 mm. During the SMILE procedure, at the moment of contact between the disposable curved contact glass and the cornea, a meniscus tear film appears, at which point the patient is able to see the fixation target clearly because the vergence of the system is focused according to the patient’s refraction. In this way, the patient essentially auto-centrates the system, and hence the center of the lenticule on the corneal vertex, which closely approximates the visual axis. The femtosecond laser ablation was performed as described previously.1-4 Total suction time was approximately 35 seconds, independent of refractive error treated. The 3-mm superotemporal incision was opened and the upper and lower edges of the lenticule were delineated, so that the tissue planes were well defined. If it was not possible to delineate the edge of both interfaces, the second 2-mm superonasal incision was opened to find the edge(s) that had yet to be delineated. The upper interface was separated first using a standard lamellar corneal surgical technique of waving the instrument back and forth. The lower layer was then dissected in a similar fashion. Once both layers had been separated, the lenticule was removed from the cornea using a pair of retinal microforceps. The patient was then taken to the slit lamp and fluorescein was instilled and the full distention of the cap centrally was achieved by a dry microspear sponge to ensure that any redundant cap (due to mismatch of cap vs bed length) was not left in the central cornea, but rather redistributed to the periphery. Journal of Refractive SurgeryÊUÊ6œ°Êә]Ê œ°Ê£Ó]ÊÓä£Î

POSTOPERATIVE EVALUATION Patients were instructed to wear plastic shields for 7 nights. Tobramycin/dexamethasone (Tobradex; Alcon Laboratories, Inc., Fort Worth, TX) and ofloxacin (Exocin; Allergan Ltd., Marlow, UK) drops were prescribed four times daily for the first week. Patients were observed at 1 day, 1 month, and 3 months. Artemis VHF digital ultrasound was performed at the 3-month postoperative visit. ARTEMIS CAP THICKNESS CALCULATION The Artemis VHF digital ultrasound technology is capable of measuring individual layers within the cornea in three dimensions; the details of the Artemis system and patient set-up have been described previously.16-21 Cap thickness was measured by the Reinstein Flap Thickness Method of adding the thickness of the stromal component of the flap measured 3 months after surgery to the preoperative epithelial thickness, as we have described previously for measuring true LASIK flap thickness at the time of creation.16,17 Measuring the cap thickness at least 3 months after surgery ensures that postoperative edema has resolved, and using the preoperative epithelial thickness accounts for any postoperative epithelial changes known to occur after LASIK.19,20 Because the SMILE procedures were all centered on the corneal vertex and the Artemis scans were also centered on the corneal vertex, the central cap thickness was defined as the thickness at the Artemis coordinate (0,0). The repeatability of Reinstein Flap Thickness measurements has been shown to be 2.79 µm within the central 4-mm diameter, with a central repeatability of 1.68 µm.18 STATISTICAL ANALYSIS Accuracy of cap thickness was calculated as the difference between the intended and measured flap thickness. Reproducibility of cap thickness was evaluated as the cap thickness standard deviation between eyes. The accuracy and reproducibility were calculated for all eyes and grouped by intended cap thickness and plotted for the central 5-mm diameter zone using DeltaGraph v5.0 (SPSS, Inc., Chicago, IL). Epithelial thickness values for left eyes were reflected in the vertical axis and superimposed onto the right eye values so that nasal/temporal characteristics could be combined. A Bland–Altman plot was performed to visualize the accuracy and reproducibility of central cap thickness; a scattergram of the difference between intended and measured cap thickness were plotted against the intended cap thickness.22 A horizontal line delineating the mean difference and two further lines delineating a range of 1.96 standard deviations were also plotted, which corresponded to the range in which 95% of the error values lie. 811

Accuracy and Reproducibility of Cap Thickness in SMILE/Reinstein et al

Figure 1. Artemis very-high frequency digital ultrasound (ArcScan Inc., Morrison, CO) horizontal B-scan of a cornea 3 months after a small incision lenticule extraction procedure using the VisuMax femtosecond laser (Carl Zeiss Meditec, Inc., Jena, Germany). Digital signal processing is performed on the B-scan signal and layer thickness measurements are obtained by a computer algorithm on the I-scan, resulting in the red line image of the interfaces.

The standard deviation of flap thickness within the central 5 mm diameter zone was determined to represent the within-eye variation of flap thickness for each eye. The average within-eye variation in the population was calculated as the square root of the mean variance. Microsoft Excel 2010 (Microsoft Corporation, Redmond, WA) was used for data entry and statistical analysis. RESULTS The study included 70 eyes of 37 patients. The contralateral eye in 3 patients underwent LASIK, and one patient had one eye treated. The mean age of the population was 34.8 ± 11.1 years (range: 21 to 61 years). The mean maximum myopic meridian treated was -7.81 ± 2.33 diopters (D) (range: -2.25 to -12.50 D). The mean cylinder treated was 0.57 ± 0.42 D (range: 0.00 to 1.50 D). The mean thinnest corneal thickness by handheld ultrasound was 532 ± 32 µm (range: 468 to 591 µm). The optical zone diameter was 5.75 mm in 6 eyes (9%), 6.00 mm in 22 eyes (31%), 6.25 mm in 12 eyes (17%), 6.50 mm in 16 eyes (23%), 6.75 mm in 3 eyes (4%), and 7.00 mm in 11 eyes (16%). The mean minimum thickness programmed at the edge of the lenticule was 9 ± 4 µm (range: 3 to 25 µm). 812

The intended cap thickness was 80 µm in 1 eye (1.4%), 100 µm in 1 eye (1.4%), 106 µm in 1 eye (1.4%), 110 µm in 15 eyes (21%), 120 µm in 13 eyes (19%), 125 µm in 5 eyes (7%), 128 µm in 1 eye (1.4%), 130 µm in 25 eyes (36%), 135 µm in 6 eyes (9%), and 140 µm in 2 eyes (3%). The mean intended cap thickness was 123 ± 11 µm (range: 80 to 140 µm). Figure 1 shows a horizontal Artemis B-scan image of the cornea of one eye 3 months after SMILE. Figure 2 shows the maps of the accuracy and reproducibility of cap thickness for all eyes and grouped by cap thickness. On average the cap was thinnest (2.3-µm thinner than intended) 0.8-mm superior to the corneal vertex and thickest (6.5-µm thicker than intended) 2.5-mm inferior to the corneal vertex. Table 1 shows the accuracy and reproducibility of central cap thickness for all eyes grouped by intended cap thickness. The central cap thickness was within 2 µm of the intended thickness in 50% of eyes (35 of 70), within 5 µm in 83% of eyes (58 of 70), and within 10 µm in 96% of eyes (67 of 70). Figure 3 shows the Bland– Altman plot comparing the intended cap thickness with the difference between the intended and measured central cap thickness. The average within-eye variation in flap thickness was 4.3 µm (range: 2.1 to 8.2 µm). Copyright © SLACK Incorporated

Accuracy and Reproducibility of Cap Thickness in SMILE/Reinstein et al

DISCUSSION In this study, cap thickness in SMILE treatments with the VisuMax femtosecond laser system was both accurate and reproducible with a mean central accuracy of -0.7 µm and reproducibility of 4.4 µm. The cap thickness was found to be uniform with only a small asymmetry of 8.8 µm in the vertical meridian. The reproducibility was found to be consistent with a reproducibility of less than 6 µm in the majority of locations. The accuracy and reproducibility were also found to be consistent and independent of intended cap thicknesses between 80 and 140 µm. In a previous study using one of the original VisuMax 200-kHz femtosecond laser systems, we reported that the accuracy of 110-µm LASIK flaps was +2.3 µm with a reproducibility of 7.9 µm measured using the Artemis VHF digital ultrasound scanner and the same method as in the current study.17 The flap thickness reproducibility with the VisuMax 200-kHz system has also been reported using other techniques to be 3.8 µm,11 5.1 µm,12 7.9 µm,13 13.9 µm,14 and in the range 7.5 to 14.4 µm (for different flap thicknesses).10 This is the first study to report the reproducibility for the 500-kHz version of the VisuMax system. Table A (available in the online version of this article) provides a summary of the accuracy and reproducibility of central flap thickness for all published studies using femtosecond lasers. However, these studies were performed with several different measurement methods, each of which has associated potential errors. We have previously discussed in detail the relative unreliability of other methods compared to the method used in the current study.17,23 To summarize, there are three main issues: 1. The repeatability of the measurement device. The Artemis has a flap thickness repeatability of 1.68 µm,18 compared with 4.2 to 7.4 µm with the RTVue OCT (Optovue Inc., Fremont, CA)24,25 and 4.8 to 8.7 µm with the Visante OCT (Carl Zeiss Meditec),6,26,27 whereas handheld ultrasound has a repeatability of residual stromal bed thickness measurements of 4.9 µm.28 2. Postoperative epithelial thickness changes. The changes in the epithelial thickness profile after a LASIK procedure can be up to approximately 20 µm for myopia20 and 24 µm for hyperopia,21 with significant epithelial changes occurring overnight and during the first month after surgery.19 Therefore, any study based on postoperative measurement of flap thickness will include errors due to epithelial thickness changes. On the other hand, the method used in the current study avoids Journal of Refractive SurgeryÊUÊ6œ°Êә]Ê œ°Ê£Ó]ÊÓä£Î

Figure 2. Topographical maps of the accuracy and reproducibility of cap thickness centered on the corneal vertex for the central 5-mm diameter zone. All left eyes were mirrored so that positive x-values represented the nasal cornea and negative x-values represented the temporal cornea. A Cartesian 1-mm grid was superimposed with the origin at the corneal vertex. All eyes were included after normalizing the cap thickness data for the intended cap thickness. For the accuracy map, the break point was set to 0 so that positive values (yellow/red) represented areas where the cap was thicker than intended and negative values (green/blue) represented areas where the cap was thinner than intended. The mean cap thickness was displayed to represent the accuracy grouped for 110, 120, and 130 µm intended cap thicknesses. The color scale represents the cap thickness in microns and the break point was set to the intended cap thickness so that yellow and red represented areas where the cap was thicker than intended and green and blue represented areas where the cap was thinner than intended. The color scale for all reproducibility maps represented the standard deviation in microns. The break point was set to 6 µm so that all areas where the reproducibility was better than 6 µm were displayed in green or blue.

these errors by combining temporally displaced measurements of the epithelial thickness preoperatively and the stromal component of the flap postoperatively (once all edema has subsided). 3. Intraoperative handheld ultrasound can also be affected by stromal hydration,29 lack of coincidence of the probe location for corneal and residual bed measurements, and compression of tissue by the application of the probe. 813

Accuracy and Reproducibility of Cap Thickness in SMILE/Reinstein et al

TABLE 1

Accuracy and Reproducibility of SMILE Cap Thickness for All Eyes and Grouped by Intended Cap Thickness Cap Thickness No. of eyes Accuracy (mean) Reproducibility (SD) Range

All

80 to 110 µm

120 µm

125 to 130 µm

135 to 140 µm

70

18

13

31

8

-0.7

+0.4

-0.6

-1.5

-0.5

4.4

4.7

5.5

3.9

3.3

-11 to +14

-9 to +11

-11 to +14

-9 to +9

-6 to +5

SMILE = small incision lenticule extraction; SD = standard deviation

Figure 3. Bland–Altman plot of the difference between the intended cap thickness and VisuMax-Artemis measured central cap thickness plotted against the intended cap thickness. The mean accuracy (intended – measured central cap thickness) of -0.7 µm was plotted as the bold green line, whereas the dotted green lines delineate the 95% limits of agreement (-9.3 to +7.9 µm, calculated as the mean difference ±1.96 3 the standard deviation of 4.4 µm). The VisuMax femtosecond laser is manufactured by Carl Zeiss Meditec, Inc., Jena, Germany, and the Artemis is manufactured by ArcScan Inc., Morrison, CO.

The cap thickness was within 2 µm of the intended thickness across the horizontal meridian, demonstrating the uniform nature of the cap. There was a slight vertical asymmetry with the cap 2.3 µm thinner than intended superiorly and 6.5 µm thicker than intended inferiorly. This small tilt has been determined to not be optically or clinically significant (personal communication, Carl Zeiss Meditec, December 19, 2007). The cap thickness was found to be highly uniform compared to microkeratome flaps, such as we have previously reported for the standard and zero compression Hansatome microkeratomes (Bausch & Lomb, Salt Lake City, UT).30 The within-eye variation of 4.3 µm for the VisuMax femtosecond laser was 60% better than the 10.7 µm for the standard Hansatome 814

microkeratome and 10.4 µm for the zero compression Hansatome microkeratome.30 This result was similar to other studies in which femtosecond laser flaps were found to be significantly more uniform than microkeratome flaps.6-9,13,14 It is difficult to compare flap thickness uniformity among studies due to the difference in which locations were measured and the method of measurement. Almost all studies that investigated flap thickness uniformity were done using postoperative myopic optical coherence tomography data. Therefore, it could be that a finding of uniform flap thickness might actually mean that the true flap thickness profile was thinner centrally than paracentrally due to lenticular epithelial thickening with thickest epithelium centrally. SMILE cap thickness using the VisuMax femtosecond laser was found to be accurate and reproducible and was independent of the intended cap thickness. These elements are critical to the refractive surgical success rates of the intralamellar femtosecond lenticule extraction technique. AUTHOR CONTRIBUTIONS Study concept and design (DZR, TJA, MG); data collection (DZR, TJA); analysis and interpretation of data (DZR, TJA, MG); drafting of the manuscript (DZR, TJA); critical revision of the manuscript (DZR, MG); statistical expertise (DZR, TJA)

REFERENCES 1. Sekundo W, Kunert KS, Blum M. Small incision corneal refractive surgery using the small incision lenticule extraction (SMILE) procedure for the correction of myopia and myopic astigmatism: results of a 6 month prospective study. Br J Ophthalmol. 2011;95:335-339. 2. Shah R, Shah S, Sengupta S. Results of small incision lenticule extraction: all-in-one femtosecond laser refractive surgery. J Cataract Refract Surg. 2011;37:127-137. 3. Hjortdal JØ, Vestergaard AH, Ivarsen A, Ragunathan S, Asp S. Predictors for the outcome of small-incision lenticule extraction for myopia. J Refract Surg. 2012;28:865-871. 4. Vestergaard A, Ivarsen A, Asp S, Hjortdal JØ. Femtosecond (FS) laser vision correction procedure for moderate to high myopia: a prospective study of ReLEx((R)) flex and comparison with

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Accuracy and Reproducibility of Cap Thickness in SMILE/Reinstein et al

a retrospective study of FS-laser in situ keratomileusis. Acta Ophthalmol. 2013;91:355-362. 5. Binder PS. Flap dimensions created with the IntraLase FS laser. J Cataract Refract Surg. 2004;30:26-32. 6. von Jagow B, Kohnen T. Corneal architecture of femtosecond laser and microkeratome flaps imaged by anterior segment optical coherence tomography. J Cataract Refract Surg. 2009;35:35-41. 7. Zhou Y, Zhang J, Tian L, Zhai C. Comparison of the Ziemer FEMTO LDV femtosecond laser and Moria M2 mechanical microkeratome. J Refract Surg. 2012;28:189-194. 8. Kanellopoulos AJ, Asimellis G. Three-dimensional LASIK flap thickness variability: topographic central, paracentral and peripheral assessment, in flaps created by a mechanical microkeratome (M2) and two different femtosecond lasers (FS60 and FS200). Clin Ophthalmol. 2013;7:675-683. 9. Zhou Y, Tian L, Wang N, Dougherty PJ. Anterior segment optical coherence tomography measurement of LASIK flaps: femtosecond laser vs microkeratome. J Refract Surg. 2011;27:408-416.

18. Reinstein DZ, Archer TJ, Gobbe M, Silverman RH, Coleman DJ. Repeatability of layered corneal pachymetry with the artemis very high-frequency digital ultrasound arc-scanner. J Refract Surg. 2010;26:646-659. 19. Reinstein DZ, Archer TJ, Gobbe M. Change in epithelial thickness profile 24 hours and longitudinally for 1 year after myopic LASIK: three-dimensional display with Artemis very high-frequency digital ultrasound. J Refract Surg. 2012;28:195-201. 20. Reinstein DZ, Srivannaboon S, Gobbe M, et al. Epithelial thickness profile changes induced by myopic LASIK as measured by Artemis very high-frequency digital ultrasound. J Refract Surg. 2009;25:444-450. 21. Reinstein DZ, Archer TJ, Gobbe M, Silverman RH, Coleman DJ. Epithelial thickness after hyperopic LASIK: three-dimensional display with artemis very high-frequency digital ultrasound. J Refract Surg. 2010;26:555-564. 22. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet. 1986;1:307-310.

10. Issa A, Al Hassany U. Femtosecond laser flap parameters and visual outcomes in laser in situ keratomileusis. J Cataract Refract Surg. 2011;37:665-674.

23. Reinstein DZ, Gobbe M, Archer TJ. Inaccuracies in reporting the accuracy of flap creating devices. J Refract Surg. 2011;27:784-785.

11. Ju WK, Lee JH, Chung TY, Chung ES. Reproducibility of LASIK flap thickness using the zeiss femtosecond laser measured postoperatively by optical coherence tomography. J Refract Surg. 2011;27:106-110.

24. Hall RC, Mohamed FK, Htoon HM, Tan DT, Mehta JS. Laser in situ keratomileusis flap measurements: comparison between observers and between spectral-domain and time-domain anterior segment optical coherence tomography. J Cataract Refract Surg. 2011;37:544-551.

12. Yu ZQ, Xu Y, Yao PJ, Qin B, Zhou XT, Chu RY. Analysis of flap thickness by anterior segment optical coherence tomography in different flap preparation styles of excimer laser surgery [article in Chinese]. Zhonghua Yan Ke Za Zhi. 2010;46:203-208. 13. Yao P, Xu Y, Zhou X. Comparison of the predictability, uniformity and stability of a laser in situ keratomileusis corneal flap created with a VisuMax femtosecond laser or a Moria microkeratome. J Int Med Res. 2011;39:748-758. 14. Ahn H, Kim JK, Kim CK, et al. Comparison of laser in situ keratomileusis flaps created by 3 femtosecond lasers and a microkeratome. J Cataract Refract Surg. 2011;37:349-357.

25. Rosas Salaroli CH, Li Y, Zhang X, et al. Repeatability of laser in situ keratomileusis flap thickness measurement by Fourierdomain optical coherence tomography. J Cataract Refract Surg. 2011;37:649-654. 26. Carl Zeiss Meditec. Visante OCT User’s Manual. Jena, Germany: Author; 2006. 27. Li Y, Netto MV, Shekhar R, Krueger RR, Huang D. A longitudinal study of LASIK flap and stromal thickness with high-speed optical coherence tomography. Ophthalmology. 2007;114:11241132.

15. Reinstein DZ, Archer TJ, Gobbe M. LASIK for myopic astigmatism and presbyopia using non-linear aspheric micro-monovision with the Carl Zeiss Meditec MEL 80 platform. J Refract Surg. 2011;27:23-37.

28. Reinstein DZ, Archer TJ, Gobbe M. Repeatability of intraoperative central corneal and residual stromal thickness measurement using a handheld ultrasound pachymeter. J Cataract Refract Surg. 2012;38:278-282.

16. Reinstein DZ, Sutton HF, Srivannaboon S, Silverman RH, Archer TJ, Coleman DJ. Evaluating microkeratome efficacy by 3D corneal lamellar flap thickness accuracy and reproducibility using Artemis VHF digital ultrasound arc-scanning. J Refract Surg. 2006;22:431-440.

29. Rosa AM, Neto Murta J, Quadrado MJ, et al. Femtosecond laser versus mechanical microkeratomes for flap creation in laser in situ keratomileusis and effect of postoperative measurement interval on estimated femtosecond flap thickness. J Cataract Refract Surg. 2009;35:833-838.

17. Reinstein DZ, Archer TJ, Gobbe M, Johnson N. Accuracy and reproducibility of Artemis central flap thickness and visual outcomes of LASIK with the Carl Zeiss Meditec VisuMax femtosecond laser and MEL 80 excimer laser platforms. J Refract Surg. 2010;26:107-119.

30. Reinstein DZ, Archer TJ, Gobbe M. LASIK flap thickness profile and reproducibility of the standard vs zero compression Hansatome microkeratomes: three-dimensional display with Artemis VHF digital ultrasound. J Refract Surg. 2011;27:417-426.

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TABLE A

Flap Thickness Studies Reporting Thickness Statistics for Femtosecond Laser Systemsa Corneal Thickness Method

Author (Year) Mai et al.1 (2012) Shetty et al.2 (2012)

Corneal Thickness Instrument

Femtosecond Laser

Eyes

Intended Flap Thickness (µm)

Mean Flap Thickness (µm)

Accuracy (µm)

SD (µm)

Minimum (µm)

Maximum (µm)

Range (µm)

(Not in abstract, no access to paper)



Femto LDV

208

110

104.8

-5.2

3.1







Intraoperative OCT

Bioptigen

Alcon WaveLight FS200

30

100

102.8

+2.8

3.2

99

105

6 21

Zhou et al.3 (2011)

1 Month Postoperative OCT

Visante

IntraLase FS60

72

100

110.7

+10.7

3.8

99

120

Ju et al.4 (2011)

1 Month Postoperative OCT

Visante

VisuMax 200 KHz

40

110

112.3

+2.3

3.8

110

115

5

Ju et al.4 (2011)

1 Month Postoperative OCT

Visante

VisuMax 200 KHz

47

120

122.2

+2.2

3.9

116

129

13

Preoperative and 3 Months Postoperative VHFUb

Artemis-1

VisuMax 500 KHz

70

80 to 140

N/A

-0.7

4.4

N/A

N/A

N/A

Reinstein et al. (current study) (2013) Murakami and Manche5 (2011)

1 Year Postoperative OCT

Visante

IntraLase FS15

18

120

108.7

-11.3

4.5

103

124

21

Pietila et al.6 (2010)

Intraoperative US

SP3000

Femto LDV

391

110

90

-20

4.6

77

106

29

Khoramnia et al.7 (2012)

Micrometer gauge



Alcon WaveLight FS200

12c

130

134.7

+4.7

5.0







Stahl et al. (2007)

1 Month Postoperative OCT

Visante

IntraLase FS60

25

100

112.0

+12.0

5.0

87

118

31

Yu et al.9 (2010)

3 Months Postoperative OCT



VisuMax 200 KHz

82

100

112.7

+12.7

5.1







Rosas Salaroli et al.10 (2011)

1 Week Postoperative OCTd

RTVue

IntraLase (Pulsion)

21

110

126

+16

5.5







11

Kanellopoulos and Asimellis (2013)

2 Year Postoperative VHF digital ultrasound

Artemis-2

Alcon WaveLight FS200

20

120

122.0

+2.0

5.6

94

135

41

Kanellopoulos and Asimellis11 (2013)

4 Year Postoperative VHF digital ultrasound

Artemis-2

IntraLase FS60

14

120

128.5

+8.5

5.7

119

137

18

8

Zhou et al.12 (2012)

1 Week Postoperative OCT

RTVue

Femto LDV

360

110

103.9

-6.1

6.1







Alió and Piñero13 (2008)

1 Month Postoperative VHFU

Artemis-2

IntraLase FS30

22

110

116.0

+6.0

6.2

101

126

25

Hu et al.14 (2007)

3 Months Postoperative CMTF

NR

IntraLase FS30

15

115 to 120

N/A

+13.9

7.1

N/A

N/A

N/A

7

c

100

96.3

-3.7

7.5







110

112.7

+2.7

7.5

100

127

27

Khoramnia et al. (2012)

Micrometer gauge



Alcon WaveLight FS200

12

Issa and Al Hassany15 (2011)

Intraoperative US

SP3000

VisuMax 200 KHz

23

Mai et al.1 (2012)

(Not in abstract, no access to paper)



Femto LDV

52

90

95.1

+5.1

7.7







Yao et al.16 (2011)

6 Months Postoperative OCT

Visante

VisuMax 200 KHz

25

100

100.2

+0.2

7.9

80

110

30

Preoperative and 3 Months Postoperative VHFUb

Artemis-1

VisuMax 200 KHz

24

110

112.3

+2.3

7.9

103

133

30

2 Months Postoperative OCT

RTVue

Femto LDV

64

110

105.8

-4.2

8.2

NR

NR

NR

1 Week Postoperative OCT

CAS-OCT (Visante prototype)

IntraLase (Pulsion)

7

110

145.0

+35.0

9.0

132

154

22

Micrometer

Digimatic

Femtec

10c

180

179.6

-0.4

9.1

167

194

27

Reinstein et al.17 (2010) Ahn et al.18 (2011) 19

Li et al.

(2007)

Holzer et al.20 (2006) Khoramnia et al.7 (2012)

Micrometer gauge



Alcon WaveLight FS200

12c

180

174.6

-5.4

9.4







Issa and Al Hassany15 (2011)

Intraoperative US

SP3000

VisuMax 200 KHz

55

120

123.8

+3.8

9.6

106

144

38

Sutton and Hodge21 (2008)

Intraoperative US

Corneo-Gage Plus

IntraLase FS30

141

115

114.0

-1.0

9.8

93

163

70

Binder22 (2006)

Intraoperative US

Cornea Scan II 50 MHz

IntraLase FS10

13

80

115.8

+35.8

10.1

96

136

40

Binder22 (2006)

Intraoperative US

Cornea Scan II 50 MHz

IntraLase FS15

21

110

131.1

+21.1

10.2

110

148

38

Micrometer

Digimatic

Femtec

10c

140

143.7

+3.7

10.7

131

159

28

Binder22 (2006)

Intraoperative US

Cornea Scan II 50 MHz

IntraLase FS15

249

90

115.8

+25.8

10.8

84

140

56

Sutton and Hodge21 (2008)

Intraoperative US

Corneo-Gage Plus

IntraLase FS15

119

105

116.8

+11.8

10.8

95

148

53

Li et al.19 (2007)

Intraoperative US

Corneo-Gage 2 50 MHz

IntraLase (Pulsion)

7

110

140.0

+30.0

11.0

122

158

36

Li et al.19 (2007)

1 Week Postoperative OCT

CAS-OCT (Visante prototype)

IntraLase (Pulsion)

8

120

156.0

+36.0

11.0

136

167

31

Micrometer

Digimatic

Femtec

10*

120

112.1

-7.9

11.1

96

135

39

Holzer et al.20 (2006)

20

Holzer et al.

(2006)

TABLE A (cont’d)

Flap Thickness Studies Reporting Thickness Statistics for Femtosecond Laser Systemsa Hu et al.14 (2007)

3 Months Postoperative CMTF

NR

IntraLase FS15

Corneal Thickness Method

Corneal Thickness Instrument

Femtosecond Laser

Binder22 (2006)

Intraoperative US

Cornea Scan II 50 MHz

IntraLase FS15

82

Binder23 (2004)

Intraoperative US

NR

IntraLase FS

22

Binder23 (2004)

Intraoperative US

NR

IntraLase FS

34

Talamo et al.24 (2006)

Intraoperative US

Pachette II

IntraLase FS

99

Issa and Al Hassany15 (2011)

Intraoperative US

SP3000

VisuMax 200 KHz

Binder22 (2006)

Intraoperative US

Cornea Scan II 50 MHz

IntraLase FS10

Rosa et al.25 (2009)

Intraoperative US (flap lifted after 20 minutes)

Corneo-Gage Plus

IntraLase FS60

20

120

115.5

+5.5

Hall et al.26 (2011)

1 Month Postoperative OCT

RTVue

VisuMax 200 KHz

40

120

133.0

+13.0

von Jagow and Kohnen27 (2009)

1 Week Postoperative OCTd

Visante

IntraLase FS60

20

100

112.0

+12.0

13.0

NR

NR

NR

Ahn et al.18 (2011)

2 Months Postoperative OCT

RTVue

IntraLase FS60

50

110

130.3

+20.3

13.2

NR

NR

NR

Intraoperative US

SP3000

VisuMax 200 KHz

53

100

109.9

+9.9

13.4

80

140

60

3 Months Postoperative OCT

Visante

IntraLase FS60

23

110

118.9

+8.9

13.6

98

142

44

Author (Year)

Issa and Al Hassany15 (2011) Kim et al.28 (2008)

15

115 to 125

N/A

+16.8

11.1

N/A

N/A

N/A

Eyes

Intended Flap Thickness (µm)

Mean Flap Thickness (µm)

Accuracy (µm)

SD (µm)

Minimum (µm)

Maximum (µm)

Range (µm)

100

120.1

+20.1

11.8

94

150

56

120

122.4

+2.4

11.9

103

148

45

110

125.0

+15.0

12.0

94

154

60

110

119.0

+9.0

12.0

82

149

67

52

80

91.4

+11.4

12.3

63

118

55

320

90

119.2

+29.2

12.4

78

152

74

12.5

92

148

56

12.1

NR

NR

NR

Pfaeffl et al.29 (2008)

Intraoperative OCP

Online OCP

IntraLase FS30

287

100

100.4

+0.4

13.6

57

138

81

Cummings et al.30 (2013)

Intraoperative OCT

EX500 built-in optical pachymeter

Alcon WaveLight FS200

431

120

120.2

+2.2

13.9

73

176

103

2 Months Postoperative OCT

RTVue

VisuMax 200 KHz

40

110

133.9

+23.9

13.9

NR

NR

NR

Intraoperative US

Pachette 50/60 KHz pachymeter

IntraLase FS

106

130

114.0

-16.0

14.0

78

155

77

Binder22 (2006)

Intraoperative US

Cornea Scan II 50 MHz

IntraLase FS10

140

100

129.7

+29.7

14.3

89

165

76

Issa and Al Hassany15 (2011)

Intraoperative US

SP3000

VisuMax 200 KHz

8

90

98.5

+8.5

14.4

65

107

42

Binder22 (2006)

Intraoperative US

Cornea Scan II 50 MHz

IntraLase FS10

49

110

127.4

+17.4

15.2

86

158

72

Ahn et al.18 (2011) 31

Kezirian and Stonecipher

(2004)

Binder23 (2004)

Intraoperative US

NR

IntraLase FS

21

130

128.7

-1.3

16.6

90

157

67

Binder22 (2006)

Intraoperative US

Cornea Scan II 50 MHz

IntraLase FS10

25

130

129.6

-0.4

17.1

90

156

66

28

Kim et al.

3 Months Postoperative OCT

Visante

IntraLase FS60

36

100

104.8

+4.8

17.6

75

128

53

Binder23 (2004)

Intraoperative US

NR

IntraLase FS

26

140

132.5

-7.5

18.5

80

158

78

Binder22 (2006)

Intraoperative US

Cornea Scan II 50 MHz

IntraLase FS10

38

140

130.6

-9.4

19.0

80

158

78

Li et al.19 (2007)

Intraoperative US

Corneo-Gage 2 50 MHz

IntraLase (Pulsion)

8

120

160.0

+40.0

19.0

136

190

54

Intraoperative US

Cornea Scan II 50 MHz

IntraLase FS10

31

120

133.4

+13.4

22.1

103

187

84

22

Binder

(2008)

(2006)

SD = standard deviation; OCT = optical coherence tomography; VHFU = very high-frequency digital ultrasound; N/A = not applicable; US = handheld ultrasound; CMTF = confocal microscopy through focusing; NR = not reported; CAS-OCT = cornea and anterior segment optical coherence tomography; OCP = optical coherence pachymetry a Table sorted in ascending order of flap thickness standard deviation. b Stromal component of the flap plus preoperative epithelium. c Porcine eyes. d Measured at ±0.5 mm from the center, horizontal +0.5 location used for table. The IntraLase FS60, IntraLase FS30, IntraLase FS15, IntraLase FS10, IntraLase FS, and IntraLase (Pulsion) are manufactured by Abbott Medical Optics, Inc., Abbott Park, IL; the Femto LDV is manufactured by Ziemer Ophthalmic Systems AG, Port, Switzerland; the Femtec is manufactured by 20/10 Perfect Vision, Heidelberg, Germany; the VisuMax 200 KHz, VisuMax 500 KHz, CAS-OCT, and Visante are manufactured by Carl Zeiss Meditec, Jena, Germany; the Alcon WaveLight FS200 is manufactured by Alcon WaveLight, Fort Worth, TX; the Artemis-1 and Artemis-2 are manufactured by ArcScan Inc, Morrison, CO; the Cornea Scan II 50 MHz, Corneo-Gage Plus, and Corneo-Gage 2 50 MHz are manufactured by Sonogage Inc, Cleveland, OH; the Pachette II and Pachette 50/60 KHz pachymeter are manufactured by DGH, Exton, PA; the Digimatic is manufactured by Mitutoyo Inc, Kangawa, Japan; the Online OCP is manufactured by Heidelberg Engineering GmbH, Heidelberg, Germany; the SP3000 is manufactured by Tomey Corp, Nagoya, Japan; and the RTVue is manufactured by Optovue Inc, Fremont, CA.

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