LASIK has gained worldwide acceptance after two decades of development and practice.1 To prevent flap complications induced by the mechanical microkeratome, the femtosecond laser was introduced to create the corneal flap in 2003.2 Femtosecond laser-assisted LASIK (FS-LASIK) improved the symmetry and uniformity of the corneal flap and started the new era of femtosecond laser refractive surgery.3,4
Femtosecond lenticule extraction (FLEx) is an all-in-one procedure that creates the flap and refractive lenticule in one step. The visual outcomes have been good.5,6 However, the flap still needs to be lifted to remove the lenticule manually, which interrupts the integrity of the anterior stroma.7 Recently, small incision lenticule extraction (SMILE) was introduced to remove the refractive lenticule through an incision of 2 to 5 mm length without flap creation.7 Preservation of the most area of anterior stroma and epithelium is expected to provide the least disturbance to corneal biomechanics and physical functions of the ocular surface. The 6-month studies have shown promising results to correct myopia and myopic astigmatism.8,9
Due to the innovation of avoiding flap creation in SMILE, interests are focused on the morphological and biomechanical changes in corneal lamella. The new generation of Fourier-domain optical coherence tomography (FD-OCT) provides higher resolution to show the in vivo structure of the epithelium and Bowman’s layer.10 During our practice, we observed that there were microdistortions in Bowman’s layer detectable by FD-OCT on the first day postoperatively. A similar phenomenon was also noticed after FS-LASIK. To further evaluate the new forms of rearrangement of corneal lamella after the flapless lenticule extraction, we conducted this prospective study to examine the microdistortions in Bowman’s layer after SMILE and also to investigate the possible risk factors and their potential visual impact.
Patients and Methods
Patients and Design
Fifty-two eyes of 29 consecutive patients undergoing SMILE (10 male and 19 female), aged 18 to 45 years, participated in this nonrandomized, controlled, prospective study. All eyes had corrected distance visual acuity (CDVA) of 20/20 or better and no other ocular conditions except myopia. The morphology of Bowman’s layer was imaged using Fourier-domain optical coherence tomography (FD-OCT) at 1 day, 1 week, 1 month, and more than 3 months postoperatively as long-term follow-up. The corneal topography was measured using Scheimpflug imaging (Pentacam; Oculus Optikgeräte, Wetzlar, Germany) (Table 1). Wavefront aberrations were measured with the COAS analyzer (Carl Zeiss, Meditec, Jena, Germany) and analyzed at 5-mm pupil size using sixth order Zernike polynomials. The root mean square (RMS) values of total higher-order aberrations (HOAs), spherical aberrations, coma, trefoil, fifth and sixth order aberrations were calculated.
Preoperative Parameters of SMILE and FS-LASIK Eyes
As the control group, 38 eyes of another 20 contemporaneous patients who underwent FS-LASIK were examined on the first day postoperatively and at long-term follow-up. Informed consent was obtained from each patient after the nature and possible consequences of the study were explained. The research followed the tenets of the Declaration of Helsinki with ethics approval obtained from the Institutional Review Board of Fudan University.
All surgeries were performed by the same surgeon (XZ), who had experience with the SMILE procedure for more than 3 months. Target refraction in all eyes was plano. SMILE was performed using the VisuMax femtosecond laser system (Carl Zeiss Meditec) with a repetition rate of 500 kHz, pulse energy of 130 nJ, intended cap thickness of 100 μm, cap diameter of 7.5 mm, lenticule diameter of 6.3 to 6.5 mm according to the refractive errors, and a side cut with a circumferential length of 4.2 mm at the superior 12-o’clock position.
FS-LASIK was performed using the VisuMax system for flap creation followed by Mel 80 excimer laser (Carl Zeiss Meditec) for stromal ablation, with an intended flap thickness of 100 μm and pulse energy of 185 nJ. The hinge was located at the superior 12-o’clock position.
The morphological features of Bowman’s layer were observed using anterior segment FD-OCT (RTVue, software version 6.2; Optovue, Inc., Fremont, CA). Each measurement consisted of four line scans along the 0°, 45°, 90°, and 135° meridians (Figure 1). The twisted segments of Bowman’s layer were defined as microdistortions and the number of peaks were counted in each 1-mm segment in the whole 8-mm scan range. Thus, the peripheral 4-mm segment covered the edge of the lenticule. The total number of microdistortions on the four meridians was calculated. All imaging was performed by the same examiner (JZ) and analyzed by another masked investigator (PY).
The illustration of counting of micro-distortions in Bowman’s layer in optical coherence tomography image. The upper panel shows the eight segments on horizontal meridian. The lower left panel shows the real-time image of eyes from optical coherence tomography monitor. The lower right panel shows the total distribution of the counting segments on four meridians. The star shows the area of temporal 3 mm segment used in counting micro-distortions.
The independent t test was used to compare the groups. The paired t test or repeated measures analysis of variance was conducted to evaluate the distribution and the stability of microdistortions.
A multivariate linear regression analysis was applied to investigate the possible sources of micro-distortions such as preoperative astigmatism, preoperative corneal astigmatism, preoperative central corneal thickness, preoperative mean simulated keratometry reading of corneal anterior surface, refractive lenticule thickness (ablation depth), and surgery order.
Pearson correlation tests were conducted to investigate the correlation between the microdistortions and uncorrected distance visual acuity (UDVA), CDVA, and the induced wavefront aberrations. All statistical analysis was performed using SAS software (version 9.1.3; SAS Institute, Inc., Cary, NC).
The refraction and topography for both groups are shown in Table 1. There was no difference in preoperative parameters between the two groups except that the myopia and myopic astigmatism were higher in the FS-LASIK group. All surgeries were uneventful. On the first day postoperatively, microdistortions in Bowman’s layer were detected in 46 eyes (88.5%) after SMILE and in 16 eyes (42.1%) after FS-LASIK. In OCT images, the Bowman’s layer appeared as the double line structure wrinkled. Yet sometimes the interfaces between the cap and stroma bed seemed vague and smooth (Figure 2). The epithelial surfaces seemed smooth. All affected eyes had no detectable cap striae under slit-lamp microscopy. The total number of microdistortions was 4.1 ± 3.1 in SMILE eyes, which was significantly more than 1.2 ± 2.0 in FS-LASIK eyes (P < .001).
The optical coherence tomography images of two eyes on the first day after small incision lenticule extraction (SMILE). The arrows show the microdistortions in Bowman’s layer that were taken into account.
Forty-three SMILE eyes and 32 FS-LASIK eyes completed an average 11.1 ± 5.0 months of follow-up (range: 4 to 14 months). The total number of microdistortions was greater in SMILE eyes than in FS-LASIK eyes (3.0 ± 2.3 vs 0.8 ± 1.1, P < .001). There was a trend of decreasing total microdistortions over time in SMILE eyes (P = .001) (Figure 3). Number of microdistortions on the first postoperative day was significantly different from later visits (P < .001). However, no difference was found after 1 week postoperatively. There was no change in total microdistortions between the first day postoperatively and long-term follow-up in FS-LASIK eyes.
The total counting of micro-distortions of each eye at different postoperative times. The error bar represents the standard deviation of the mean value of the group. The star shows the significant difference in counting of microdistortions between the 1 day and later time points. SMILE = small incision lenticule extraction; FS-LASIK = femtosecond laser-assisted LASIK
In terms of distribution, the total number of microdistortions in the central 1-mm segments was 2.62 ± 2.33 on the first postoperative day and 1.98 ± 1.61 on long-term follow-up after SMILE. Both showed a decreasing trend from center to periphery (P < .001). The same trend was noted in FS-LASIK eyes (P < .001). There were fewer microdistortions in the superior than the inferior area on the first day postoperatively in SMILE eyes (1.33 ± 1.38 vs 1.77 ± 1.59, P = .022), but no difference was found after 1 week. There were more microdistortions in vertical than in horizontal meridians on long-term follow-up (1.05 ± 1.00 vs 0.60 ± 0.73, P = .007). There was no difference in microdistortions between the nasal and temporal segments at each visit. There was no difference in microdistortions between superior–inferior, horizontal–vertical, or nasal–temporal areas in FS-LASIK eyes at each visit.
Multivariate linear regression analysis showed that the total number of microdistortions in SMILE eyes on the first postoperative day was first associated with the surgery order, second with refractive lenticule thickness, and then with preoperative corneal curvature. However, at long-term follow-up, the total number of microdistortions was first associated with the refractive lenticule thickness, then with surgery order (Table 2).
Multivariate Linear Regression Analysis Shows Potential Factors of Microdistortions in Bowman’s Layer After SMILE
As for the visual outcomes, 93.1% of SMILE eyes and 78.1% of FS-LASIK eyes obtained UDVA of 20/20 or better at long-term follow-up. UDVA after SMILE continued to improve with time (P = .003). UDVA was better in SMILE eyes than in FS-LASIK eyes (−0.05 ± 0.10 vs 0.03 ± 0.19 logMAR, P = .046). Two lines of visual acuity were gained in 18.6% of SMILE eyes and 9.4% of FS-LASIK eyes. None of the eyes lost any lines in either group (Figure 4). CDVA in logMAR was not significantly different between the two groups. The total number of microdistortions was not correlated with UDVA or CDVA in either group.
Percentage of eyes achieving the postoperative corrected visual acuity levels at long-term follow-up after small incision lenticule extraction (SMILE) and femtosecond laser-assisted LASIK procedures.
Cylinder of −0.50 diopters (D) or less was present in 79.1% of SMILE eyes and 81.2% of FS-LASIK eyes. Spherical equivalent (SE) was within ±0.50 D in 67.6% and 65.6% of eyes and the mean value of SE was −0.15 ± 0.57 and −0.61 ± 0.85 D (P = .011) in the SMILE and FS-LASIK groups, respectively.
Among the components of wavefront aberrations, HOA and coma significantly increased after both procedures. Spherical aberrations and fifth order aberrations increased after FS-LASIK. SMILE eyes obtained more coma and FS-LASIK eyes obtained more spherical aberrations (Table 3). Total number of microdistortions was weakly correlated with the induction of sixth order aberrations after SMILE (r = −0.31, P = .042) and with the induced fifth and sixth order aberrations after FS-LASIK (r = 0.38, P = .033 and r = 0.39, P = .029, respectively).
Wavefront Aberrations at Long-Term Follow-up in SMILE and FS-LASIK Eyes
The current study is the first to report microdistortions in Bowman’s layer detected by high-resolution FD-OCT after SMILE. A similar but much less pronounced phenomenon was also noticed after FS-LASIK. Corneal striae under slit-lamp examination or linear distortion under confocal microscopy was previously reported after LASIK.11–15 They could reduce the visual acuity by two to three lines or cause non-specific blur and require early treatments such as flap irrigation, readjustment, or soft contact lens.16 As flap irrigation skills during the surgery improved, fewer flap folds were reported.
The latest FD-OCT provides the distinct image of Bowman’s layer, which is better than the previous generations of OCT.10 This enables the early detection of more subtle details in the corneal structure, such as the microdistortions in the current study. We found significantly more microdistortions on the first day after SMILE than after FS-LASIK. During SMILE, the cap containing the Bowman’s layer was not lifted in the whole procedure. Thus, the causes of flap folds after LASIK such as insufficient lubrication prior to microkeratome pass, decenter flap creation, flap dehydration during laser ablation, overhydration of reflected flap, and unsmooth flap reposition might not be the cause after SMILE.11
We hypothesize that one of the possible causes for Bowman’s layer microdistortions might be due to the new condition of matching between the cap and the interface stroma after the extraction of refractive lenticule. After myopia correction, the curvature of the residual stroma bed is flatter than the posterior surface of the corneal cap, which follows the anterior surface of the cornea. According to Charman’s theoretical model,17 the area of the posterior surface of the LASIK flap will be larger than that of ablated stroma bed. To achieve the intimate adhesion at the interface, the flap either overlaps the edge of the stroma or compresses radially to reach an exact match between the two surfaces. In SMILE, fractional compression of the corneal cap might be the only way to match the larger area of the posterior surface of the cap to the smaller area of the residual stroma bed. This may explain the larger number of microdistortions after SMILE than after FS-LASIK in this study. The distribution of the microdistortions provided further evidence. The center area presented more microdistortions than the periphery, perhaps because the center had the largest change of curvature. In addition, the only asymmetric distribution was fewer microdistortions in the superior quadrant than in the inferior quadrant, probably because the superior small incision allows the local extension of the cap, resulting in less compression in Bowman’s layer. The flaps were capable of extending in three quadrants in FS-LASIK eyes, which may explain why there was no difference in microdistortions between the superior and inferior areas despite the superior 12-o’clock hinge.
We also found that the number of microdistortions increased with refractive lenticule thickness. This is consistent with the result of Charman’s model that the mismatch of the interface increases with the magnitude of myopia correction in LASIK.17 Although Charman did not isolate the effect of the radius of initial corneal surface, we found that steeper corneal surface was correlated with more microdistortions in the early stage. This finding suggests the inevitable changes in the biomechanics determined by the SMILE design, especially in high myopia and eyes with steep corneal surface. However, there were other factors that might induce the microdistortions in Bowman’s layer.
The fact that microdistortions were much more prevalent on the first day after SMILE, significantly decreased at 1 week, and then remained stable suggested that severe corneal cap edema on the first day might contribute to the form of microdistortions. Multivariate linear regression analysis showed that among all potential factors, the total number of microdistortions on the first day was first associated with the surgery order. Although the surgeon had finished the learning stage of the SMILE procedure, the surgical experience is still accumulating. The manual lenticule extraction might induce mechanical disturbance to the overlying corneal cap and leave subtle bending in the Bowman’s layer. The slight reduction of the microdistortions in later cases indicated that gentle surgical techniques can contribute to reducing the microdistortions. Previous scanning electron microscopy study of FLEx,6 showing a rougher posterior surface of lenticule, also suggested the trauma from manual removal of the lenticule. However, the mechanical disturbance should be more in the periphery because of the difficulty in separating the tissue bridge at the edge of the lenticule in a smaller space, which could not explain the fact that more microdistortions were found in the center area. In addition, we found that surgery order became less effective than the lenticule thickness in long-term follow-up.
Other possible factors may include the uneven laser pulse energy causing the bubbles within the disrupted interface. Bubbles may raise the adjacent Bowman’s layer and result in the microdistortions. This might result from the high laser energy and lack of venting pocket. However, the low energy used in this study produced mild bubbles that could eliminate in several minutes and mildly affected the visualization during the dissection of posterior lenticule surface.
Refractive lenticule extraction, including FLEx and SMILE procedures, has been proved to achieve promising efficacy and safety in 6-month results to correct myopia and myopic astigmatism up to −10 D SE with maximum −5 D of astigmatism, even for the hyperopia.5–8,18–22 Our results were consistent with the previous reports in good predictability and little secondary astigmatism. We also found that UDVA was not influenced by the presence of the Bowman’s layer microdistortions. This indicates that the microdistortions discussed here are different from the flap folds after LASIK that affect the visual outcomes.11 The microdistortions became stable after 1 week postoperatively and the CDVA was not affected by microdistortions at long-term follow-up. Both added to the safety of the procedure.
Our results showed the increased HOA after both procedures and SMILE induced less spherical aberrations but more coma. This is consistent with the former studies,6,8,23 but it seems that microdistortions were not primarily responsible for the changes in certain forms of wavefront aberrations. This might be because of the random distribution of the microdistortions. In addition, we noticed that the surface of epithelium was smooth and epithelium thickness varied in the OCT image. It seems that the epithelium growth covered the irregular surface of Bowman’s layer. This might explain why the microdistortions in Bowman’s layer had almost no effect on HOA.
Considering the biomechanics of the cornea after SMILE, our observation of microdistortions in Bowman’s layer raised an interesting question. The twisting of Bowman’s layer indicates the possible microfolds in the cornea cap. Although no interface fluid or space was observed in the current study or in previous articles, would the distortion of interface cause instability of the interface adhesion, especially in those high myopic eyes with steep corneal surface? In this case, the rough surface of the interface might induce more intense inflammatory responses that could help to form a solid adhesion between the surfaces. Back to the original expectations of SMILE design, the reserved integrity of epithelium and anterior stroma is supposed to strengthen the whole corneal tension and to overcome the fundamental weakness of flap-based corneal refractive surgery. Yet it requires further elucidation whether the presence of the microdistortions in Bowman’s layer would compromise the overall corneal strength or enhance the biomechanical propriety of the cornea through promoting inflammation and scar formation.
Microdistortions in Bowman’s layer are detectable on FD-OCT after SMILE. The severity is related to refractive lenticule thickness and surgical experience. The microdistortions became stable after 1 week postoperatively and had no influence on the long-term safety of the SMILE procedure. Further investigations are necessary to elucidate the long-term influence on the corneal biomechanics.
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Preoperative Parameters of SMILE and FS-LASIK Eyes
|Mean ± SD||Range||Mean ± SD||Range|
|Spherical equivalent (D)||−6.63 ± 1.48a||−3.50 to −10.39||−8.59 ± 2.57||−4.25 to −14.63|
|Cylinder (D)||−0.74 ± 0.63b||0 to −3.00||−1.02 ± 0.58||0 to −3.25|
|Central corneal thickness (μm)||542.5 ± 29.9||499 to 614||530.8 ± 21.7||514 to 577|
|Mean simulated K reading (D)||43.0 ± 1.5||39.3 to 46.1||43.9 ± 1.1||44.8 to 46.0|
|Corneal astigmatism (D)||1.10 ± 0.51||0.40 to 2.50||1.22 ± 0.63||0.25 to 3.25|
Multivariate Linear Regression Analysis Shows Potential Factors of Microdistortions in Bowman’s Layer After SMILE
|Time||Priority||Potential Factor||Standardized Coefficient||Pa|
|Postoperative 1 day||1st||Surgery order||−0.66||< .0001|
|2nd||Refractive lenticule thickness||0.59||< .0001|
|3rd||Preoperative corneal curvatureb||0.30||.009|
|Long-term follow-up||1st||Refractive lenticule thickness||0.41||.0046|
Wavefront Aberrations at Long-Term Follow-up in SMILE and FS-LASIK Eyes
|Time||HOA||Sphericala||Comab||Trefoil||5th Order||6th Order|
| Preoperative||0.21 ± 0.09||0.08 ± 0.07||0.12 ± 0.08||0.12 ± 0.05||0.04 ± 0.02||0.04 ± 0.02|
| Postoperative||0.34 ± 0.11b||0.10 ± 0.07||0.24 ± 0.12b||0.13 ± 0.07||0.05 ± 0.02||0.04 ± 0.02|
| Increment||0.13 ± 0.11||0.02 ± 0.07||0.12 ± 0.13||0.01 ± 0.07||0.01 ± 0.03||0.00 ± 0.02|
| Preoperative||0.20 ± 0.06||0.07 ± 0.04||0.10 ± 0.06||0.10 ± 0.07||0.04 ± 0.02||0.04 ± 0.02|
| Postoperative||0.32 ± 0.12b||0.19 ± 0.13b||0.17 ± 0.11b||0.12 ± 0.07||0.05 ± 0.02b||0.04 ± 0.02|
| Increment||0.13 ± 0.13||0.12 ± 0.14||0.07 ± 0.14||0.02 ± 0.05||0.01 ± 0.03||0.01 ± 0.02|