Laser in situ keratomileusis (LASIK) is currently the most frequently used surgical treatment for the correction of ametropia with an excimer laser. To improve the safety and efficacy of the procedure, there is a need for a method of measuring layered anatomy of the cornea: the thickness of the epithelium, the flap, and the residual stroma under the flap. In current practice, the thickness profile of the flap is a largely unknown quantity; thickness variations within a flap and among flaps can affect the result. Variability in flap thickness can increase the risk of long-term plastic corneal changes such as ectasia in cases where the flap is significantly thicker than expected.1 Variability in flap thickness can also have a direct effect on refractive correction because the depth of keratectomy relates to the amount of intraoperative bioelastic corneal change, which in turn affects the accuracy of the desired curvature change.2 Detailed knowledge of the performance of microkeratomes can improve the safety and efficacy of LASIK.
Evaluation of the accuracy of microkeratomes and corneal flap thickness commonly relies on eye bank experiments, which our studies have shown to be inaccurate (data on file, Moria, Antony, France), or an intraoperative measurement of corneal thickness with a hand-held ultrasound pachymeter before and after lifting the flap. The accuracy of such intraoperative measurements is hampered by several factors: 1) stromal bed hydration and thickness can change due to the use of a coupling solution on the bed before thickness measurement and to drying that occurs within seconds of lifting the flap1; 2) stromal edema produced by fluid brought in by the microkeratome at the time of the keratectomy1; and 3) ultrasound probe positioning, as this technique measures only a single point at a time, which may lead to variable determination of the "thinnest point" of the residual stromal bed,3 so that thickness variations within the flap cannot be detected. This technique also introduces an unnecessary risk of infection due to the difficulty in sterilizing hand-held ultrasound probes.
In this study we used a prototype digital very highfrequency (VHF) ultrasound system developed at the Weill Medical College of Cornell University to overcome these difficulties. This system scans a series of meridians in an arc motion matched to the curvature of the cornea, allowing measurement of the thickness of individual corneal layers (including the flap) over an 8- to 10-mm diameter zone in three dimensions.3 This system has been shown to measure flap thickness with reproducibility of 1.3 µm, and epithelial and corneal reproducibility of <1 µm.3 The technology has been made into a commercially available scanner, the Artemis (Ultralink LLC, St Petersburg, Fla), which was approved by the US Food and Drug Administration in 2000.
According to Jose Barraqueras principles of lamellar refractive surgery, the anterior disc or flap created by the microkeratome is intended to be a disc with parallel faces following the surface of the anterior cornea because it is flattened by an applanation plate leading ahead of the cutting blade.1 An advantage of being able to accurately measure the flap thickness in three-dimensions is that the uniformity of the flap profile can be studied as well as the central thickness.
The purposes of this study were to 1) describe a new technique of measuring flap thickness, which takes into account postoperative edema and epithelial changes; 2) apply this technique to measure and report the characteristics of the Moria LSK-One (Moria, Antony, France) microkeratome; 3) establish standardized criteria for publishing the performance of microkeratomes; and 4) to investigate whether the flap thickness can be predicted by clinical variables.
PATIENTS AND METHODS
PATIENTS AND SURGICAL TECHNIQUE
This study conformed to the Declaration of Helsinki and patients were scanned after their informed consent.
Study participants were recruited from a high-volume refractive surgical practice by general distribution of an information sheet regarding the nature of the study. During the study period, 18 patients (9 for each surgeon) agreed to participate in the study. A complete ocular examination was performed including manifest refraction, videokeratographic mapping (TMS-I; Tomey Technologies Ine, Cambridge, Mass) and Orbscan (Bausch & Lomb, Irvine, Calif) to screen for ocular abnormalities and determine patient candidacy for LASIK. Inclusion criteria, in addition to medical candidacy for LASIK, included willingness to undergo VHF ultrasound scanning of both eyes before and at least 3 months after surgery. Keratometry was derived from the TMS-I, and central pachymetry for preoperative residual stromal thickness calculation was obtained from the Orbscan mapping. The examinations were also done at postoperative follow-up.
The Moria LSK-One is a microkeratome based on the principles of the instrument as originally described by Jose Barraquer.1 The one-element headpiece attaches to a gas-driven turbine and accommodates the blade, which oscillates at approximately 14,000 cycles per minute. The headpiece is translated within guiding tracks on the suction ring that is secured to the ocular surface. The translation speed of the microkeratome head is controlled manually by the surgeon to produce a flap with a nasal hinge.
Laser in situ keratomileusis was carried out as same session bilateral surgery, right eyes operated first, using the same blade for the second (left) eye. The -1 suction ring was used in all eyes (to obtain the largest possible flaps). The number 130 thickness head was used for all eyes, which the user manual states creates a flap with an average thickness of 160 µm. Satisfactory suction of the ring was obtained in all eyes and an intraocular pressure >60 mmHg was verified by the Barraquer tonometer included with the microkeratome. Surgeries were carried out between January and June 1998 by two ophthalmic surgeons experienced with LASIK and the use of the microkeratome, one of whom was left-handed (D.Z.R., surgeon 1) and the other right-handed (H.F.S.S., surgeon 2). Each surgeon attempted to remain manually consistent in translation speed of the head to reduce flap thickness variability that results from variable translation speed.
Preoperative Descriptive Statistics of 36 Eyes of 18 Patients Who Received LASIK for Myopia
Excimer laser ablation was carried out with the NIDEK EC-5000 (NIDEK Co Ltd, Gamagori, Japan). A summary of clinical parameters is shown in Table 1. Patients were evaluated postoperatively at 1 day, 1 week, 1 month, and 3 months. Very high-frequency ultrasound scanning was done at 3 months, or at a later date, with a full ocular anterior segment examination.
ULTRASOUND SCANNING AND ANALYSIS
Patient Preparation. The scanning system and patient setup has been described previously.3 Patients were placed in the supine position and scanned using a standard ophthalmic immersion technique. A plumbob aligned fixation target above the eye that was not being scanned provided vertical alignment of both visual axes as well as fixation of the eye during the scan sequence.
Scanning System and Procedure. A VHF (50 MHz) ultrasound broadband transducer (Panametrics Ine, Waltham, Mass) was controlled in a reverse-arc motion to follow the corneal contour and to acquire an 8- to 10-mm wide corneal B-scan in a single sweep.4 Details of the scanning procedure have been described elsewhere.3 Three-dimensional scan sets consisted of meridional scans at 45° intervals. Each scan sweep is performed in approximately 0.5 seconds. Scan alignment was verified for each sweep before proceeding to the next scan/set. Centration of the scan was based on localization of the corneal vertex, with the visual axis vertically oriented and parallel to the central axis of scanning as described previously.3
Ultrasound Data Analysis. The radiofrequency ultrasound data digitized and stored were subsequently processed to B-scan images for visualization and I-scan traces for biometry,5 using a speed of sound constant for the cornea of 1640 m/s.6 The thickness of each corneal layer was then derived from the distance between surfaces in the radial direction (perpendicular to the back surface of the cornea).7 Thickness maps of the flap were calculated by adding two components: 1) the epithelial thickness profile before surgery, and 2) the stromal component of the flap ≥3 months after surgery. Measuring the flap at least 3 months after surgery ensures that postoperative edema has resolved. Using the preoperative epithelial thickness accounts for any postoperative epithelial changes known to occur after LASIK.8-10 This technique is known as the Reinstein Flap Thickness Profile. Eleven other maps of individual layered corneal information before and after LASIK comprise the Reinstein C12 display, as previously described.3
Central Flap Thickness Analysis. The central Reinstein Flap Thickness was determined for all eyes. These central measurements were taken from the 0,0 (x,y) coordinate on each of the three-dimension thickness maps. Mean, standard deviation, median, and range were determined. Paired Student t test was used to determine whether significant differences existed between right and left flap thickness for all eyes as well as for right and left eyes between surgeons. Univariate and stepwise multivariate linear regression analysis was used to determine significant correlations between central flap thickness and mean keratometric power as well as eye (right eye vs left eye), preoperative corneal thickness, epithelial thickness, spherical equivalent of myopia treated, surgeon hand dominance, and patient age and sex. The central residual stromal thickness was determined directly from the postoperative VHF digital ultrasound scans and the ablation depth was calculated as the difference between the pre- and postoperative stromal thickness. The pachymetric breakdowns of flap thickness, ablation depth, and residual stromal thickness were displayed as a bar plot. Statistical analysis was performed using SPSS v. 8.0 software (SPSS Ine, Chicago, Ill).
Figure 1. Geometrically corrected (above) and non-geometrically corrected (below) horizontal B-scan through the cornea along the visual axis. The epithelial (E), Bowman's (B), interface (I), and posterior (P) boundaries are clearly visualized from one end of the corneal scan to the other, spanning an 8-mm diameter of the cornea. The flap interface (I) can be seen to end abruptly on the nasal (left) side to form the hinge (H). The perpendicularity of the scanning mechanism to the corneal surface is evidenced by the flat profile of the anterior corneal surface (equidistant to the transducer) as seen on the non-geometrically corrected image.
Accuracy Analysis. Accuracy of flap thickness was defined as the concordance between the intended and the true value. Accuracy is calculated as the difference between the mean flap thickness and the intended flap thickness, which is 160 pm when using the Moria LSKOne with a number 130 head.
Three-dimensional Statistical and Qualitative Analysis. The mean, median, standard deviation, and range of flap thickness was determined and plotted in three-dimensions using a point-by-point topographical analysis. This was performed for all right eyes, all left eyes, and all eyes combined. Qualitative descriptive analysis of individual flap thickness profiles was also performed. All three-dimensional statistical and data manipulation was performed using Microsoft Excel 98 for Macintosh.
The median postoperative evaluation was at 3.5 months (range: 3 to 6 months). Meridional B -scans of all eyes showed the internal flap boundary as a continuous interface extending the entire length of the flap (8 to 10 mm) (Fig 1).
Preoperative characteristics of the patients recruited for the study are summarized in Table 1. Age, keratometric power, and central corneal thickness were within commonly found ranges for myopes. The mean spherical equivalent refraction was - 5.14±2.60 diopters (D).
Central Flap Thickness Accuracy. Using VHF ultrasound, the mean flap thickness was 161 µm for right eyes, 166 µm for left eyes, and 163.6 µm for all flaps together. Therefore, the Moria LSK-One cut flaps that were on average 1 µm thicker than predicted for right eyes, 6 µm thicker for left eyes, and 3.6 µm thicker for all eyes together, but with a large range. Figure 2 shows the pachymetric breakdown for all 36 eyes into flap thickness, ablation depth, and residual stromal thickness in a bar plot. The eyes are ranked by flap thickness to clearly demonstrate the range of flap thicknesses.
Figure 2. Bar graph showing thickness measurements for 36 eyes. Each eye is divided into the flap thickness (bottom), ablation depth (middle), and residual stromal thickness (RST) (top). The thickness of each layer is displayed within the bar and the preoperative corneal thickness is displayed above each bar. All flaps were created using the Moria LSK-One microkeratome (Moria, Antony, France) with the 130 head and the -1 ring, with an intended flap thickness of 160 µm (solid bold line). The eyes are sorted by the central value of the Reinstein Flap Thickness Profile. The mean thickness for all flaps was 163.6 µm with a standard deviation of 30.3 µm (dotted lines). The range of flap thickness extended from 106 µm to 228 µm. This distribution produces 11.5% of flaps with a central thickness >200 µm and 2.8% of flaps with a central thickness >220 µm.
Descriptive Statistics of Central Reinstein Flap Thickness*†
Central Flap Thickness Reproducibility. The reproducibility (standard deviation of the mean) of central flap thickness was 30.2 µm for right eyes, 30.4 µm for left eyes, and 30.3 µm for all flaps. The range observed in this group of eyes was from a thinnest flap of 106 µm to a thickest of 228 µm.
Table 2 summarizes the statistical analysis for central Reinstein Flap Thickness according to eye (right vs left), surgeon (1 vs 2), and hand-dominance (right vs left). No statistically significant differences were noted.
Figure 3. Reinstein Flap Thickness Profiles for four left eye flaps. Right/left pairs represent the same flap plotted on either an absolute or normalized color scale in microns. All four plots in the left-hand column are plotted on an absolute color scale running from 80 to 245 µm to enable eye-to-eye and patient-to- patient comparison of flap thickness profiles. The plots in the right-hand column are plotted on normalized color scales based on the maximum and minimum thickness within the flap, demonstrating the marked variability in flap thickness profile from eye to eye and from patient to patient.
Central Flap Thickness Correlations. The results of univariate correlation analysis showed no statistically significant correlation between central flap thickness and mean keratometry, eye (right vs left), preoperative epithelial thickness, spherical equivalent refraction treated, surgeon's hand dominance, and patient age and sex. A statistically significant correlation was noted between central flap thickness and preoperative corneal thickness by VHF digital ultrasound (R=0.354, P=. 016), but not preoperative central corneal thickness by Orbscan (P=.208).
Stepwise linear regression was performed using central flap thickness as the dependent variable with mean keratometry, eye (right vs left), preoperative corneal thickness (Orbscan and VHF ultrasonic), preoperative epithelial thickness, spherical equivalent refraction treated, patient age and sex, and surgeon's hand dominance. Preoperative VHF ultrasonic central corneal thickness was included in the model in the first step. After inclusion of corneal thickness, preoperative keratometry was found to contribute significantly to the model and was included as well. No other variables made a significant contribution. The model provided a correlation coefficient of 0.344 (P=. 016). The equation for prediction of flap thickness was:
Central flap thickness = 0.403 × (central VHF ultrasound corneal thickness) + 5.239 × (keratometric power) - 270.74
Generating predicted flap thickness values from this model and comparing them to the actual values measured showed a mean difference of 0.0 µm, but the standard deviation of the differences was 26.7 µm. This is only slightly less than the standard deviation of 30.3 µm observed for the population of flaps as a whole, showing that the model would not be valuable in predicting flap thickness to a level that would be clinically useful, because only approximately two thirds of flaps would be within 30 µm of the predicted value.
Three-dimensional Flap Thickness Maps. Plotting of Reinstein Flap Thickness Profiles on an absolute scale allows comparison of microkeratome performance from eye to eye and from patient to patient. Figure 3 shows maps of Reinstein Flap Thickness for four left eyes of study patients, by a single surgeon (H.F.S.S.). Figure 3 contains the four maps on an absolute/identical scale for eye-to-eye comparison and with individually normalized scales to better appreciate thickness variation. A wide range in flap thickness was noted between flaps; the thinnest point of the flap for patient 3 was 75 µm compared with 190 µm for patient 2. In some cases, the flap thickness varied considerably within the flap itself; the flap thickness ranged from 75 µm to 155 µm within the central 2 mm of the flap for patient 3. Flaps could be either thicker in the center than the periphery such as in patient 2, or thinner in the center than the periphery such as in patient 1. Most commonly flaps were thinner centrally. Central thickness was generally similar between the two eyes of the same patient. Overall flap profile pattern was similar between right and left eyes in approximately half of the patients; in others, the right and left eyes were considerably different. For example, in one patient, flap thickness in the central region of the left eye varied between 80 and 100 µm, but in the right eye, flap thickness varied between 160 and 220 µm.
Figure 4. Reinstein 3D Flap Profile Statistic Display demonstrates distribution of flap thickness mean (column 1), median (column 2), reproducibility (standard deviation [SD]) (column 3), and range (column 4) for right eyes (row 1), left eyes (row 2), and all eyes combined (row 3). The most characteristic profile is one of thinner centrally and thicker peripherally. Reproducibility is generally worse centrally than peripherally. The extremes in range are greater in the periphery.
Three-dimensional Statistical Analysis. Figure 4 represents the Reinstein Flap Profile 3D Statistical Display, which we propose as a component of the standard for analysis of microkeratome performance. The structure of this display demonstrates a three-dimensional descriptive statistical analysis for right flaps (first row), left flaps (second row), and all flaps together (third row). For each of these sets, the thickness mean (first column), median (second column), reproducibility (standard deviation of the mean) (third column), and range (fourth column) are displayed topographically. For the Moria LSK-One 130 microkeratome, the mean and median maps demonstrate that flaps were most likely to be thinner centrally than peripherally. Reproducibility of flap thickness was generally less good centrally than peripherally. The thickness range, examined topographically (see Fig 4, fourth column) demonstrated greater absolute range of thickness superiorly (160 µm) than inferiorly (100 µm).
Reproducibility Analysis by Surgeon and Hand Dominance. Figure 5 shows three-dimensional mean flap thickness for right and left eyes of surgeon 1 (lefthanded) and surgeon 2 (right-handed). The Moria LSKOne produced a nasal hinge by horizontal temporalto-nasal manual trajectory of the microkeratome head. Non-dominant hands were on average less likely to produce a homogeneous thickness along the horizontal. Figure 6 shows three-dimensional flap reproducibility for right and left eyes of surgeon 1 (left-handed) and surgeon 2 (right-handed). Three of the four categories demonstrated worse reproducibility centrally and inferonasally than elsewhere. The exception was for the dominant hand of surgeon 1, which showed better reproducibility centrally and inferiorly.
We have demonstrated a comprehensive method of measuring the accuracy and reproducibility of microkeratome-created corneal flap thickness in three dimension by using digital VHF ultrasound. By adding the thickness of the preoperative epithelium to the thickness of the postoperative stroma of the flap, we were able to determine the thickness of the flap at the time it was created. This technique accounts for postoperative edema and epithelial changes that are known to occur after LASIK.8-10 We have also demonstrated that by using VHF digital ultrasound scanning, the uniformity of the flap thickness profile can be studied for the first time.
Figure 5. Mean Reinstein Flap Thickness Profile for right and left eyes of two patients shown on an absolute scale running from 145 to 185 µm. The patient and surgeon are indicated in the rows and hand dominance and patient eye in the columns. The flaps created by the dominant hands demonstrated more homogenous mean thickness along the horizontal direction compared to flaps created by non-dominant hands, indicating that manual passage of the microkeratome head was more consistent when the dominant hand was used.
The Moria LSK-One head is stamped as 130 and the manual states that this will produce a mean central flap thickness of 160 µm, but the standard deviation is not reported. We found that the mean flap thickness was 163.6 µm, 3.6 µm thicker than expected, with a standard deviation of 30.3 µm. Assuming that flap thickness is normally distributed, this means that approximately 55% of all flaps will be thicker than 160 µm, 11.5% will be thicker than 200 µm, and 3.1% will be thicker than 220 µm. In this study, 1 (2.8%) of the 36 flaps measured was found to be 228-µm thick (see Fig 2). The Moria LSK-One was thus found to have a mean central flap thickness close to the reported thickness, but it has a high standard deviation of >30 µm, which can be seen in Figure 2.
Reports of iatrogenic keratectasia in the literature11 are not confined to patients with preoperative high myopia.12,13 It is likely that some of these cases of ectasia might have occurred due to a residual stromal thickness that was excessively low. Barraquer recommended surgical anatomical limits for the prevention of ectasia in keratomileusis; his protocol stated that the corneal cap created by the microkeratome should not be thicker than 300 µm.1 Assuming the average cornea, measured at that time by slit-lamp optical pachymetry, had a central thickness of approximately 550 µm,14 Barraqueras statement would translate to leaving a residual stromal thickness of at least 250 µm (300 to 550 µm). Today, 250 µm remains the generally accepted standard minimum target residual stromal thickness for an eye to be suitable for LASIK.11,15 The large variability of flap thickness and sizeable risk of getting a flap >60 µm thicker than expected (3.1% in this study) provides a possible explanation for cases of ectasia in low or moderate myopia. Figure 2 demonstrates the effect that a high flap thickness standard deviation has on safety. Eye #19 received a 159-µm flap, exactly as predicted, and ended up with a residual stromal thickness of 280 µm, which is within the safety limit of 250 µm. However, had this eye received the 228 µm flap of eye #36, then it would have ended up with a residual stromal thickness of 211 µm. Reducing the standard deviation of the mean flap thickness is one of the major keys in improving the safety of LASIK.
The chosen mean flap thickness is also a source of risk; surgeons using a microkeratome with a high mean flap thickness will have more patients with a predicted residual stromal thickness near the safety limit, usually 250 µm. The variability of the flap thickness is less relevant in cases where the predicted residual stromal thickness is considerably more than 250 µm. For example, the thickest flap found in this study (228 µm in eye #36) happened to be in a patient with a thick cornea (574 µm) and with low myopia (only 36 µm ablation). The residual stromal thickness was 310 µm, which is within the safety limit of 250 µm despite the fact that the flap was 68 µm thicker than expected. Microkeratomes with a lower mean flap thickness will inherently decrease the risk of ectasia16; however, the mean flap thickness cannot be too low because of the risk of buttonholes occurring.
Figure 6. Reproducibility (standard deviation of the local thickness mean) of Reinstein Flap Thickness Profile for right and left eyes of two patients shown on an absolute scale running from 10 to 50 µm, accordingly. The patient and surgeon are indicated in the rows and hand dominance and patient eye in the columns. No clear relationship between hand dominance and thickness reproducibility is seen. Three of the four maps (all except top right) demonstrate decreased reproducibility inferonasally. Possibly, this could be related to manually induced instability of the inferior track if the surgeon was causing torsional rotation with the superior track acting as a fulcrum.
Microkeratome labeling is applied inconsistently by manufacturers. The label stamp on one of the heads of the Moria LSK-One microkeratome is 130, which refers to the physical gap width in the head. The manual states that the flap thickness produced when using this 130 head is 160 µm. In terms of a risk analysis, it is conceivable that a surgeon could incorrectly base the predicted residual stromal thickness calculation using 130 as the flap thickness. Other manufacturers label the microkeratome head with the mean flap thickness, such as the Amadeus (AMO, Irvine, Calif),17 and some label the microkeratome head with a value above the mean flap thickness, such as the Hansatome (Bausch & Lomb).18 By way of risk analysis, a surgeon may use the labeled mean flap thickness to calculate residual stromal thickness, despite the fact that 50% of flaps would be expected to be thicker than the mean. Labeling the flap thickness one standard deviation above the mean may be a more sensible convention to adopt because it would increase the safety of the procedure. Using this convention, 84% of flaps would be thinner than the value of flap thickness used for residual stromal thickness calculations. For example, the Moria LSK-One 130 head would be labeled as 190 µm (mean 160 µm + standard deviation 30 µm). Given a predicted residual stromal thickness of 250 µm, the flap would have to be a further 50 µm thicker (total 80 µm ~ 2.67 standard deviation) for the residual stromal thickness to end up less than 200 µm. Approximately 99.6% of values in a normal distribution lie within a range of 2.67 standard deviations, and so the risk of leaving a residual stromal thickness <200 µm would be greatly reduced if this convention were to be used.
Microkeratome safety would be improved further if flap thickness were found to be correlated to preoperative variables such as corneal thickness and keratometry. In this study, stepwise multivariate regression analysis found that preoperative corneal thickness (by VHF digital ultrasound, not Orbscan) and mean preoperative keratometry were statistically significant. However, this model did not provide sufficient predictive power to significantly improve safety. Jacobs et al19 published the mean and standard deviation of flap thickness for the Moria LSK-One (also using the nominal 130 head) using hand-held subtraction pachymetry and found similar mean thickness (159 µm) and standard deviation (28 µm), but they also found no correlation between keratometry and flap thickness. The statistical power of the regression analysis in this study is inherently low due to the relatively small numbers. Larger studies, albeit using hand-held subtraction pachymetry techniques, have managed to demonstrate correlations between central flap thickness and corneal thickness as well as keratometry.20
In this study, we demonstrated a method for evaluating microkeratome efficacy by using digital VHF ultrasound. We have described the Reinstein Flap Profile 3D Statistical Display, which we propose could be used as a standard for analysis of microkeratome performance. This includes three-dimensional maps of topographical flap thickness mean, median, reproducibility (standard deviation of the mean), and range. Importantly, this technique not only analyzes the central flap thickness mean and reproducibility, but it also highlights the regional variation in flap thickness. Standardized, detailed documentation of flap thickness characteristics for microkeratomes (ideally provided by the manufacturer) could significantly benefit the accuracy and safety of LASIK.
1. Barraquer JI. Queratomileusis y Queratofakia. Bogota, Columbia: Instituto Barraquer de America; 1980:342.
2. Reinstein DZ, Srivannaboon S, Silverman RH, Coleman DJ. The accuracy of routine LASIK: isolation of biomechanical and epithelial factors. Invest Ophthalmol Vis Sci. 2000;41:S318.
3. Reinstein DZ, Silverman RH, Raevsky T, Simoni GJ, Lloyd HO, Najafi DJ, Rondeau MJ, Coleman DJ. Arc -scanning very highfrequency digital ultrasound for 3D pac hy metric mapping of the corneal epithelium and stroma in laser in situ keratomileusis. J Refract Surg. 2000;16:414-430.
4. Silverman RH, Reinstein DZ, Raevsky T, Coleman DJ. Improved system for sonographic imaging and biometry of the cornea. J Ultrasound Med. 1997;16:117-124.
5. Reinstein DZ, Silverman RH, Rondeau MJ, Coleman DJ. Epithelial and corneal thickness measurements by high-frequency ultrasound digital signal processing. Ophthalmology. 1994;101:140-146.
6. Coleman DJ, Silverman RH, Lizzi FL, Rondeau MJ, Lloyd HO, Daly SW, Reinstein DZ. Ultrasonography of the Eye and Orbit 2nd ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2005.
7. Segali M, Reinstein DZ, Johnson NF. Computer aided analysis and visualization of high-frequency ultrasound scanning of the human cornea. IEEE Computer Graphics Applications. 1999;19:74-82.
8. Srivannaboon S, Reinstein DZ, Sutton HFS, Silverman RH, Coleman DJ. Effect of epithelial changes on refractive outcome in LASIK. Invest Ophthalmol Vis Sci. 1999;40:S896.
9. Reinstein DZ, Silverman RH, Sutton HF, Coleman DJ. Very high-frequency ultrasound corneal analysis identifies anatomic correlates of optical complications of lamellar refractive surgery: anatomic diagnosis in lamellar surgery. Ophthalmology. 1999;106:474-482.
10. Lohmann CP, Guell JL. Regression after LASIK for the treatment of myopia: the role of the corneal epithelium. Semin Ophthalmol. 1998;13:79-82.
11. Seiler T, Koufala K, Richter G. Iatrogenic keratectasia after laser in situ keratomileusis. J Refract Surg. 1998;14:312-317.
12. Geggel HS, Talley AR. Delayed onset keratectasia following laser in situ keratomileusis. J Cataract Refract Surg. 1999; 25:582-586.
13. Speicher L, Gottinger W. Progressive corneal ectasia after laser in situ keratomileusis (LASIK) [German]. Klin Monatsbl Augenheilkd. 1998;213:247-251.
14. Giasson C, Forthomme D. Comparison of central corneal thickness measurements between optical and ultrasound pachometers. Optom Vis Sci. 1992;69:236-241.
15. Probst LE, Machat JJ. Mathematics of laser in situ keratomileusis for high myopia. J Cataract Refract Surg. 1998;24:190-195.
16. Reinstein DZ, Cremonesi E. Ectasia in routine LASIK: occurrence rate is reduced by one third when consistently using a thinner flap. Invest Ophthalmol Vis Sci. 2001;42:S725.
17. Jackson DW, Wang L, Koch DD. Accuracy and precision of the Amadeus microkeratome in producing LASIK flaps. Cornea. 2003;22:504-507.
18. Gailitis RP, Lagzdins M. Factors that affect corneal flap thickness with the Hansatome microkeratome. J Refract Surg. 2002;18:439-443.
19. Jacobs BJ, Deutsch TA, Rubenstein JB. Reproducibility of corneal flap thickness in LASIK. Ophthalmic Surg Lasers. 1999;30:350-353.
20. Price FW Jr, Koller DL, Price MO. Central corneal pachymetry in patients undergoing laser in situ keratomileusis. Ophthalmology. 1999;106:2216-2220.
Preoperative Descriptive Statistics of 36 Eyes of 18 Patients Who Received LASIK for Myopia