A Morphological Study of Corneal Flap after Thin-flap Laser-assisted In Situ Keratomileusis by Anterior Segment Optical Coherence Tomography

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1 The Journal of International Medical Research 2010; 38: A Morphological Study of Corneal Flap after Thin-flap Laser-assisted In Situ Keratomileusis by Anterior Segment Optical Coherence Tomography Y XU, X ZHOU, L WANG AND H XU Department of Ophthalmology, Eye and ENT Hospital affiliated with Fudan University, Shanghai, China This prospective study assessed corneal flap morphology in 115 patients undergoing laser-assisted in situ keratomileusis (LASIK). Flaps were created using the Moria M2 90-µm or KM-5000D 110-µm micro - keratomes. Flap thickness was measured using anterior segment optical coherence tomography at seven points in a 7-mm diameter zone 1 h, 1 day, 3 days, 1 week and 1 month after surgery. Flap accuracy, reproducibility, uniformity and changes over time were evaluated. The Moria M2 microkeratome created flaps with less accuracy in the centre than the KM-5000D microkeratome ( ± 6.46 µm vs ± 6.79 µm, respectively, at 1 week). For both microkeratomes, flap thickness varied between most of the peripheral areas and the central point. Both microkeratomes created flaps with good central predictability and reproducibility, but high variation and significant deviation from intended thickness were observed in peripheral flap thickness. KEY WORDS: LASER-ASSISTED IN SITU KERATOMILEUSIS (LASIK); CORNEAL FLAP THICKNESS; THIN FLAP; FLAP MORPHOLOGY; ANTERIOR SEGMENT OPTICAL COHERENCE TOMOGRAPHY (AS-OCT) Introduction Due to quick visual recovery and mild postoperative pain, 1 laser-assisted in situ keratomileusis (LASIK) has become the procedure of choice for correcting refractive errors, despite increasing concern over corneal ectasia and other corneal flap damage. 2 4 The ablation of an excessive amount of stromal tissue may lead to weakness in the cornea and a subsequent loss of its biomechanical properties, resulting in corneal ectasia. 5 A thinner and more predictable corneal flap allows for the correction of a larger amount of myopia while maintaining a thicker residual stroma, improving biomechanical stability and potentially reducing the risk of ectasia. 6 Flap thickness and reproducibility, therefore, play significant roles in the safety of the LASIK procedure. Historically, flap quality was evaluated exclusively by the central-flap thickness. 7 Flap morphology describes the architecture of the entire flap, which is related to the biomechanical properties of the cornea as well as visual quality, and has become a new 1952

2 and important parameter in modern LASIK surgery. 8 The latest generation of microkeratomes seem to generate more predictable flaps with achieved thicknesses closer to those intended; 9 11 however, most create meniscus-shaped flaps, which are thinner in the central cornea and thicker in the periphery. 12 The present study focused on two microkeratomes that generate a mechanical cut with applanation. First, the Moria M2 microkeratome, with a 90-µm single-use head (Moria Surgical, Antony, France), is a popular automated microkeratome with a mechanical stop designed for maximum safety that is able to create thin flaps Secondly, the KM-5000D 110-µm microkeratome (Wuxi Kangming Medical Device Corp, Jiangsu, China), is an automatic microkeratome based on the oscillating blade principle that is also able to create thin flaps. 13 Although clinical use of both microkeratomes is widespread, flap morphology and post-surgery changes have not been thoroughly studied. The present study utilized anterior segment optical coherence tomography (AS- OCT) to perform non-contact comprehensive measurements of corneal flap thickness in order to assess the accuracy, reproducibility and uniformity of flaps created by the two microkeratomes. In addition, post-operative time-dependent changes in flap thickness were evaluated. Patients and methods PATIENTS AND INCLUSION CRITERIA In this prospective, non-randomized study, patients were consecutively recruited from the Refractive Surgery Centre at the Eye and ENT Hospital, Shanghai, China, between November 2007 and January Criteria for inclusion were: spherical myopia of from 2 to 16 dioptres; refractive astigmatism of up to 3 dioptres; stable refraction for 1 year; a best-spectacle corrected vision of 20/25; and normal corneal appearance on slitlamp microscopy. Exclusion criteria were suspicion of keratectasia, active ocular disease and history of prior ocular surgery or trauma. The study was performed in accordance with the Helsinki Declaration and reviewed and approved by the Ethics Committee of the Eye and ENT Hospital affiliated with Fudan University, Shanghai, China. Written informed consent was obtained from all patients after explanation of the purpose of the study. Depending on the pre-operative spherical equivalent refraction, patients were divided into two groups: the Moria group, for patients with a spherical equivalent refraction larger than 6 dioptres; and the KM group, for patients with a spherical equivalent refraction less than 6 dioptres. Patients in both groups were assessed for age, pre-operative corneal keratometry and central corneal thickness as measured using the Pentacam Comprehensive Eye Scanner (Oculus, Wetzlar, Germany). SURGICAL TECHNIQUES All surgical procedures were performed by one of the authors (X.Z.). In the Moria group, an intended 110-µm corneal flap was created using the Moria M2 microkeratome with a 90-µm single-use head. In the KM group, an intended 130-µm corneal flap was created using the KM-5000D 110 µm microkeratome. All procedures were performed first on the right eye, then on the left eye, using the same blade. For the right eye, the incision was made from the temporal and inferior side to the nasal side and, for the left eye, the incision was made from the nasal side to the temporal side. Ablation was performed with the MEL 80 excimer laser (Carl Zeiss Meditec, Jena, 1953

3 Germany). The optical zone diameter ranged from 6.0 to 7.0 mm depending on the scotopic pupil size. OCT IMAGING All eyes were evaluated via AS-OCT (Visante AS-OCT Device; Carl Zeiss Meditec) at 1 h, 1 day, 3 days, 1 week and 1 month post-operatively. The AS-OCT device uses a 1310 nm superluminescent diode source and operates up to a speed of 2000 axial scans/s. Cross-sectional scans were displayed continuously on the integrated video monitor at a rate of up to 8 frames/s. Images were judged to be of adequate quality based on the following criteria: good demarcation of the anterior and posterior corneal boundaries; and absence of artifacts owing to motion or eyelid margins. The flap image was a horizontal line profile consisting of 512 axial scans. The flap interface was visualized and marked using the flap tool of the built-in software by one examiner who was blinded to the attempted flap depth. Each flap thickness was measured at seven points (0, ± 1.5, ± 2.5 and ± 3.5 mm from the vertex of the cornea; Fig 1). STATISTICAL ANALYSES Studies have suggested that corneal flap thicknesses can be significantly different between the two eyes of one patient as the microkeratome usually cuts a thicker flap in the first eye versus second eye. 9 Thus, only data obtained from measurements in the right eye of each patient, the first to undergo LASIK in the present study, were included in the statistical analyses. Accuracy was defined as the difference between measured flap thickness and the reference values of the manufacturer. The inter-individual standard deviation for flap dimension was calculated to FIGURE 1: Example of a horizontal cross-sectional optical coherence tomography flap profile scan. Callipers were located at the seven measurement points from the temporal to the nasal regions inside the central 6 7-mm diameter zone 1954

4 assess reproducibility, and flap uniformity was evaluated using the differences between each measured point. Since post-operative oedema has usually resolved by 1 week after surgery, 14 accuracy, reproducibility and uniformity were evaluated using the measurements from this time point. The results were analysed by multivariate statistical analysis and comparisons between the two groups were made using analysis of variance. Statistical analyses were performed using SAS software, version 9.0 (SAS Institute Inc., Cary, NC, USA) for Windows. A P-value 0.05 was considered to be statistically significant. Results PATIENTS This study recruited 115 patients (63 male and 52 female, mean ± SD age 24.1 ± 6.2 years). Baseline pre-operative optical characteristics of patients are shown in Table 1. The two groups were well matched in terms of age, pre-operative corneal keratometry and central corneal thickness (Table 1). All corneal flaps were created uneventfully and no intra-operative complications occurred. FLAP ACCURACY AND REPRODUCIBILITY Table 2 shows the flap-thickness variations at the seven measured points in the Moria and KM groups. The Moria M2 microkeratome created a mean ± SD central-flap thickness of ± 6.46 µm, 4.06 µm thicker than the intended 110 µm, and the KM-5000D microkeratome produced a mean ± SD central-flap thickness of ± 6.79 µm, 1.61 µm thinner than the intended 130 µm. Both groups had good central-flap accuracy, with the flap thickness in the KM group being significantly more accurate than in the Moria group (P < 0.01). Reproducibility of flap thickness was stable for the central area but showed variability in the periphery (Table 2). The variation in flap thickness was not significantly lower in the Moria group than in the KM group in all areas of the cornea. FLAP UNIFORMITY Significant differences were found in peripheral flap thickness compared with the central point in both groups (P < 0.05). For the Moria group, flaps were thinnest in the centre and thickened toward the periphery. The temporal portions were thicker than the nasal portions, with a difference of 5.98 µm in the 3-mm diameter zone, µm in the 5-mm diameter zone and µm in the 7- mm diameter zone. For the KM group, the flap became thinner from the temporal to the nasal areas, with the smallest thickness at 3.5 mm nasally. The difference between the temporal and nasal thickness was 6.29 µm in the 3-mm diameter zone, µm in TABLE 1: Baseline demographics and optical characteristics of patients before laser-assisted in situ keratomileusis surgery with the Moria M2 90-µm single-use head microkeratome or the KM-5000D 110-µm microkeratome Moria M2 KM-5000D Characteristic (n = 66) (n = 49) Age, years 24.3 ± ± 5.9 Spherical equivalent refraction, dioptres 8.48 ± ± 1.93 Corneal keratometry, dioptres ± ± 1.79 Central corneal thickness, µm ± ± Data presented as mean ± SD. 1955

5 TABLE 2: Flap thickness variations at seven measured points from the vertex of the cornea at 1 week after laser-assisted in situ keratomileusis using the Moria M2 90-µm single-use head microkeratome or the KM-5000D 110-µm microkeratome Moria M2 KM-5000D Measurement point Flap thickness Statistical Flap thickness Statistical (distance to vertex) (µm) significance a,b (µm) significance a,b 3.5 mm (temporal) ± P < ± P < mm (temporal) ± P < ± P < mm (temporal) ± 8.39 P = ± 8.61 NS 0 mm ± ± mm (nasal) ± 6.48 NS ± 8.31 P = mm (nasal) ± 6.63 NS ± 9.66 P < mm (nasal) ± 8.40 P = ± P < Data presented as mean ± SD. a Statistical significance compared with data from central point of cornea (0 mm); b multivariate analysis of variance. NS, not statistically significant (P > 0.05). the 5-mm diameter zone and µm in the 7-mm diameter zone (Table 2). POST-OPERATIVE CHANGES IN CENTRAL-FLAP THICKNESS Central-flap thickness decreased significantly in both groups between 1 h and 1 day after surgery (P < 0.001). Subsequent to this, flap thickness increased significantly between 1 and 3 days after surgery (Moria group, P < 0.001; KM group, P = 0.04), and between 3 days and 1 week in the Moria group (P < 0.01). There were no significant changes in flap thickness between 1 week and 1 month after surgery in either group (Table 3). Discussion Both of the microkeratomes used in the present study achieved thinner corneal flaps compared with traditional mechanical microkeratomes. 15 A thin flap is generally desirable in LASIK because it retains a thicker stromal bed for ablation. Traditional LASIK, with thick flaps of approximately 160 µm, severs a significant number of collagen fibres and the subsequent loss of lamellar integrity results in compromised corneal biomechanical integrity. 5,6 Theoretically, a thin flap alleviates the effect of flap creation on corneal biomechanical integrity, thereby decreasing the risk of corneal ectasia. 16,17 The present study demonstrated good accuracy and reproducibility in central flap thickness with both microkeratomes. The Moria M2 microkeratome yielded flaps that were 4.06 µm thicker than intended, a similar finding to other studies. Aslanides et al. 9 created flaps of 106 µm with a variability of 17 µm with the Moria M2 90-µm singleuse head microkeratome measured by ultrasound pachymetry. Zhao et al. 10 found a mean central flap thickness of ± µm, and Huhtala et al. 11 found it to be ± 12.5 µm. The level of reproducibility in the present study was higher than that reported in other studies, showing a smaller SD of 6.46 µm. This may be due to a difference in measuring methods: ultrasonic pachymetry is known to have a coefficient of 1956

6 TABLE 3: Post-operative changes in central-flap thickness after laser-assisted in situ keratomileusis using the Moria M2 90-µm single-use head microkeratome or the KM-5000D 110-µm microkeratome Moria M2 KM-5000D Central-flap Statistical Central-flap Statistical Post-operative time thickness (µm) significance a thickness (µm) significance a 1 h ± ± day ± 8.55 P < b ± 7.94 P < b 3 days ± 7.73 P < c ± 8.43 P = 0.04 c 1 week ± 6.46 P < 0.01 d ± 6.79 NS d 1 month ± 6.48 NS e ± 6.24 NS e Data presented as mean ± SD. a Repeated-measures multivariate analysis of variance. Statistical significance compared with data from: b 1 h post-operatively; c 1 day post-operatively; d 3 days post-operatively; and e 1 week post-operatively. variation of ± 5% on the same cornea, whereas the accuracy of OCT is 1 5 µm. 18 In addition, it is possible that differences in surgical procedures may contribute to the level of reproducibility. There are few clinical reports regarding the KM-5000D microkeratome. In the present study, this technique was found to create a thinner flap than that intended, with a more accurate central-flap thickness than the Moria M2 microkeratome. The reproducibility of central-flap thickness with the KM-5000D microkeratome was comparable with that obtained with the Moria M2 microkeratome. In addition to central-flap thickness, peripheral flap morphology remains an important issue with regard to the safety and optical properties of LASIK. The present study showed that the general morphology of the flap in each group was significantly asymmetric and that the two micro keratomes possessed distinct morphological characteristics. The Moria M2 microkeratome produced a flap that was thinnest in the centre and thickened toward the periphery, in a meniscus shape. Studies on other microkeratomes, such as Zyoptix XP 19 and Hansatome microkeratomes, 14 (both Bausch & Lomb) showed similar meniscusshaped flaps. In contrast, the KM-5000D microkeratome flap was thinner from the temporal to the nasal areas. These differences can be explained by the different interactions of the devices with the cornea. In general, the course of the cut depends on the opening gap of the blade, oscillation speed and constancy of compression during forward movement of the blade at the side of the device, and the steepness and stiffness of the cornea at the other side. 20,21 As the steepness of the cornea between the two groups was consistent, the differences may result primarily from variable microkeratome performances. The thinner flap at the nasal area may be due to a faster velocity nasally 22 and, presumably, a duller blade by cutting the temporal area prior to the nasal cornea. 9,15,23 Besides the significant deviation between central-flap thickness and peripheral flap thickness, there were variations in the 7-mm diameter zone (SD ±13.11 µm in the Moria group and ±13.32 µm in the KM group). These results differ from those found with femtosecond lasers, which form a more uniform, planar and symmetrical flap by laser 1957

7 photodisruption in a surface-parallel direction, 24,25 resulting in only a slight increase in flap thickness toward the periphery. 19 Some types of microkeratomes, such as the Moria One Use-Plus microkeratome and the Schwind Carriazo-Pendular microkeratome, also demonstrate almost planar and homogeneous flap thickness comparable with the femtosecond laser. 8,26 Uniformity of flap morphology may play a role in two aspects of LASIK. First, it affects the biomechanical properties of the cornea and, secondly, it influences clinical outcome, a more recently discussed topic. Cohesive tensile strength studies have demonstrated that Bowman s layer is the strongest structural component of the cornea, followed by the anterior third of the corneal stroma. 31 In fact, the peripheral anterior third of the corneal stroma is even stronger than the paracentral and central anterior thirds. 32,33 Thus, thin corneal flap creation and increased anterior stroma reservation in the periphery have crucial significance. The larger peripheral flap thickness produced by the Moria M2 and KM-5000D microkeratomes may result in reduced corneal biomechanical strength. The morphology of the corneal flap also impacts upon optical outcome. A flap with homogeneous thickness and a planar configuration is necessary to avoid optical side-effects: such a flap is optically neutral and theoretically does not induce any refractive change. 34 Several studies evaluating the changes in optical characteristics caused by the creation of the microkeratome flap found that higher-order aberrations were introduced, especially spherical aberrations and astigmatism, but the femtosecond laser flap was reported to induce less visual disturbance than the microkeratome flap. 27,34,35 In contrast, several studies have found no difference in the induction of higher-order aberrations and visual outcome between these two methods Further controlled studies are required to reveal the clinical relevance of the optical properties of the flaps. The flap thickness during healing was monitored in the present study and similar results were found in both groups. Flap thickness was largest in the immediate postoperative period due to flap oedema and decreased after 1 day as the oedema subsided. The thickness changes between 1 day and 1 month after surgery were consistent with other studies. 14,36 Thickening may also result from epithelial hyperplasia after LASIK. Although epithelial thickness was not directly observed in the present study, previous studies using methods such as confocal microscopy, 37 high-frequency ultrasound 38 and OCT 36 have confirmed that epithelial hyperplasia can occur up to 3 months after LASIK. The mechanism of this process remains unknown, but it may be part of the wound-healing process or a response to biomechanical changes. In the present study, flap morphology was monitored via AS-OCT, which is a highresolution, non-contact optical technology allowing both central and regional pachymetry. With AS-OCT, the thickness of different layers of the cornea, such as the epithelium and corneal flap, as well as total corneal thickness, can be measured. 18,39 Moreover, AS-OCT has the overwhelming advantages over ultrasonic pachymetry and confocal microscopy of being non-contact and non-invasive. A limitation of AS-OCT is that the boundaries between the flap and stroma become ambiguous with time, increasing the examiner s subjectivity. 14 Thus, flap thickness measurements at 1 week after LASIK were recommended for evaluating the performance of the microkeratomes. The Moria M2 microkeratome and the 1958

8 KM-5000D microkeratome created flaps with good predictability and reproducibility in the central cornea; however, the periphery showed high variation and significant deviations from intended flap thickness. This difference, compared with the femtosecond laser and other newer microkeratomes that create more homogeneous flaps, may influence both biomechanical and optical properties. Further study on the clinical impact of flap morphology is warranted. Acknowledgements We extend sincere thanks to the patients for their willingness to participate in this study. We also thank the staff of the Refractive Surgery Centre of the Eye and ENT Hospital for supporting this study. The study was supported by a grant from the Committee on Science and Technology of Pudong, Shanghai, China (grant No. PKJ2009-Y01). Conflicts of interest The authors had no conflicts of interest to declare in relation to this article. Received for publication 14 July 2010 Accepted subject to revision 23 July 2010 Revised accepted 3 November 2010 Copyright 2010 Field House Publishing LLP References 1 Sugar A, Rapuano CJ, Culbertson WW, et al: Laser in situ keratomileusis for myopia and astigmatism: safety and efficacy: a report by the American Academy of Ophthalmology. Ophthalmology 2002; 109: Rabinowitz YS: Ectasia after laser in situ keratomileusis. Curr Opin Ophthalmol 2006; 17: Ciolino JB, Belin MW: Changes in the posterior cornea after laser in situ keratomileusis and photorefractive keratectomy. J Cataract Refract Surg 2006; 32: Kerautret J, Colin J, Touboul D, et al: Bio - mechanical characteristics of the ecstatic cornea. J Cataract Refract Surg 2008; 34: Tham VM, Maloney RK: Microkeratome complications of laser in keratomileusis. Ophthalmology 2000; 107: Slade SG: Thin-flap laser-assisted in situ keratomileusis. Curr Opin Ophthalmol 2008; 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: Alió JL, Piñero DP: Very high-frequency digital ultrasound measurement of the LASIK flap thickness profile using the IntraLase femtosecond laser and M2 and Carriazo- Pendular microkeratomes. J Refract Surg 2008; 24: Aslanides IM, Tsiklis NS, Astyrakakis NI, et al: LASIK flap characteristics using the Moria M2 microkeratome with the 90-µm single use head. J Refract Surg 2007; 23: Zhao MH, Zou J, Cheng QY, et al: Evaluating corneal flap thickness following laser in situ keratomileusis with the Moria M2 90-µm single-use-head microkeratome. Jpn J Ophthalmol 2008; 52: Huhtala A, Pietila J, Makinen P, et al: Corneal flap thickness with the Moria M2 single-use head 90 microkeratome. Acta Ophthalmol Scand 2007; 85: Stonecipher K, Ignacio TS, Stonecipher M: Advances in refractive surgery: microkeratome and femtosecond laser flap creation in relation to safety, efficacy, predictability, and bio - mechanical stability. Curr Opin Ophthalmol 2006; 17: Wu LC, Zhou XT, Ouyang CH, et al: Clinical research of KM-5000D automatic micro - keratome for making corneal flap in LASIK. Rec Adv Ophthalmol 2006; 26: [in Chinese]. 14 Li Y, Netto MV, Shekhar R, et al: A longitudinal study of LASIK flap and stromal thickness with high-speed optical coherence tomography. Ophthalmology 2007; 114: Shemesh G, Dotan G, Lipshitz I: Predictability of corneal flap thickness in laser in situ keratomileusis using three different microkeratomes. J Refract Surg 2002; 18(3 suppl): S347 S Qazi MA, Roberts CJ, Mahmoud AM, et al: Topographic and biomechanical differences between hyperopic and myopic laser in situ keratomileusis. J Cataract Refract Surg 2005; 31: Jaycock PD, Lobo L, Ibrahim J, et al: Interferometric technique to measure biomechanical changes in the cornea induced by refractive surgery. J Cataract Refract Surg 2005; 31:

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