Location, time and patient inclusion

The study protocol was reviewed and approved by the Institutional Review Board of the Department of Ophthalmology at the Ludwig-Maximilians-University Munich (Ethikkommission LMU München) and the tenets of the Declaration of Helsinki were followed throughout the study. All patients participated in the study voluntarily and were informed of their right to abandon it at any chosen time without having to provide a reason. Informed consent was obtained in written form.

Medical records of 26 patients (52 eyes) who underwent myopia correction with LASIK and 26 patients (52 eyes) treated with SMILE were evaluated for this study. The LASIK group was composed of 26 patients with preoperative refractive values that were comparable to those from the SMILE group. Surgeries were performed by one experienced surgeon (D.K.) based at the SMILE Eyes Eye Clinic Munich Airport, Germany. All eyes meeting the following criteria were included: age over 18 years, complete preoperative and postoperative data, stable refraction, no additional ocular diseases and corneal abnormalities such as keratoconus, no previous corneal surgery, and no active infections. Our aim was to fully correct preoperative manifest refraction in all eyes.

Preoperative and postoperative assessment

The following preoperative measurements were all performed using the Scheimpflug camera Pentacam (OCULUS Optikgeräte GmbH, Wetzlar, Germany): sphere, cylinder, partial CV of regions with 3, 5, and 7 mm diameters from the apex and total CV for which a 10 mm diameter was assumed, as well as pachymetry at the apex (central corneal thickness, CCT) and at peripheric zones of 2, 4, 6, and 8 mm diameters. The examination process was standardized and performed in a windowless clinical assessment room. The patients were instructed to blink repeatedly, then to focus and not to blink or move their eyes while the examination was in progress. Our study relied exclusively on data with the quality label “ok” and without any movement or blinking errors.

Postoperative assessment included measurements of CV and CT and was obtained at 3 and 12 months postoperatively.

Surgery and postoperative medication

Surgical techniques were the same for all patients of one group. In the LASIK group, a hinged corneal flap with a thickness of 110 μm and a diameter of 8.4 to 8.5 mm was created with the VisuMax® femtosecond laser (Carl Zeiss Meditec, Jena, Germany). The Mel 80 excimer laser (Carl Zeiss Meditec, Jena, Germany) with iris recognition software was used for photoablation within a 6.5–6.75 treatment area. In contrast to LASIK, SMILE is a flapless procedure. Before starting the surgery, the patient was asked to fixate on a blinking target. When adequate centration was achieved, the eye was fixated using a curved suction contact glass. A lenticule was produced using the VisuMax® femtosecond laser system (Carl Zeiss Meditec, Jena, Germany) that was set at an intended cap thickness of 120 μm and optical zone of 6.25–6.5 mm. The lenticule was then grasped and removed through a small incision. All surgeries were uneventful and no severe postoperative complications occurred.

Postoperatively, patients in both groups received polymyxin/ neomycin/ dexamethasone eye-drops (Isopto-Max, Alcon) 4 times daily for 5 days. For 4 weeks, artificial tear supplements were prescribed, starting hourly the first week and reduced to weekly as needed.

Evaluation

Assessment included changes in corneal volume (ΔCV) and corneal thickness (ΔCT). They were calculated as differences of 3-month postoperative minus preoperative measurements (ΔCV_3mo, ΔCT_3mo) and 12-month postoperative minus preoperative values (ΔCV_12mo, ΔCT_12mo). For each group, mean values and standard deviations of the evaluated outcomes were calculated. Differences of ΔCV and ΔCT between both groups were compared.

Statistical analysis was performed with Stata software. Normality of all data samples was checked with the Shapiro-Wilk test. Differences between the 2 groups were evaluated using independent sample t-tests for data following normal distribution. Where normal distribution criteria were not met, the Mann-Whitney U test was applied. Tests, for each group separately, were employed as follows: the Mann-Whitney U test was performed to compare differences between 3- and 12-month measurements; and the Pearson’s correlation coefficient (r) was applied to assess the correlation between the preoperative spherical equivalent (SE) and ΔCV_3mo of the 7 mm diameter region, as well as the correlation between the SE and central ΔCT_3mo. A P-value less than 0.05 was considered statistically significant.

Changes of corneal volume and thickness

Significant differences in the statistics between both groups were found at ΔCV_3mo and ΔCT_3mo. Alterations in partial CV of regions with 3, 5, and 7 mm diameters were significantly larger in the lenticule extraction group (P = .001). Changes in CT were comparatively higher in the SMILE group than in the LASIK group. This was also found to be significant for the apical pachymetry and the 2, 4, and 6 mm diameter zones (P < .01). Comparing total ΔCV_3mo and ΔCT_3mo in the 8 mm diameter area, no significant difference was found. Alterations remained stable after 12 months postoperatively.

One possibility that explains why the SMILE technique achieves greater alterations in CV and CT is the fact that the maximal depth in LASIK is ablated in the central treatment zone [11]. Due to the laser beam being oval-shaped, less tissue ablation occurs towards the periphery [12]. Another possibility may be different wound healing processes. Between the flap stroma and the ablated area keratocytes produce a lamellar corneal stromal scar [13]. The keratocyte-mediated stromal production can be stated to increase towards the periphery as this process at the margin is necessary to fixate the flap [13]. Therefore, a strong, hypercellular and fibrotic corneal stromal scar is clinically seen in the periphery at flap wound margins, whereas the primitive hypocellular scar in the center is not visible postoperatively [13, 14]. Since the corneal stroma is created postoperatively, it seems like the intraoperative ablation volume is smaller. In contrast, Luft et al. [10] found comparable levels of keratocyte apoptosis and proliferation in the ex vivo human corneas after LASIK and SMILE. Similar findings were reported by Riau et al. in a rabbit model [15].

Using the SMILE procedure, apical ΔCT_3mo was higher than in the LASIK group (64.5 μm versus 38.3 μm) in the study by Kobashi et al. [7] which was congruent with our results. Another study [16] reported central ΔCT_3mo to be larger using LASIK (89.3 μm) compared to SMILE (81.2 μm).

Furthermore, especially in correction of very low refractive errors there is a highly variability in loss of corneal thickness as seen in Fig 1. We assume that this is due to the high level of mechanical manipulation during SMILE which makes more likely that higher variations occur. Future studies need to evaluate how good the flapless technique performs due to this specifically for the correction of very low refractive errors around -1 dpt.

Impact on corneal biomechanical properties

The cornea is an anisotropic tissue with interlamellar branching collagen fibers that is stronger in the periphery than in the center [17]. Moreover, the vital collagen bundles in the anterior stroma are stiffer than in the posterior part and the interconnectivity of the lamellae in the anterior stroma provides the main biomechanical strength to the cornea [17, 18]. These strong anterior lamellae are preserved and remain intact during flapless surgery. In contrast, flap-based LASIK effects the corneal biomechanics more than flapless SMILE as it impairs the strong anterior stroma overlying the exposed stromal bed [19]. Besides lifting the flap before excimer laser ablation, the stroma is exposed to hydration changes that fracture the stability needed for exact refractive correction [7]. Overall, only considering the surgical procedure, corneal biomechanical strength is better preserved after SMILE as it causes less disruption of the corneal structural integrity [13].

Corneal hysteresis (CH) and corneal resistance factor (CRF), which can be obtained from the Ocular Response Analyzer, illustrate viscoelastic properties of the cornea and thus are a measure of stability. We did not analyze CH and CRF in our patients. However, we can draw assumptions about the biomechanical properties based on the changes of CT and CV. The more volume that is ablated with LASIK, the more CH and CRF are reduced [20]. Lower values stand for a biomechanically weaker cornea.

At short notice, LASIK is likely to show reduced CH and CRF due to wound healing processes, whereas SMILE is supposed to have larger CH and CRF as the cornea is unimpaired. We assessed our measurements at 3 months postoperatively. Hence, we expect the wound healing processes not to have any influence on our results.

In general, a higher CCT results in a stiffer appearance of the cornea [21]. We found a lower CCT after SMILE, significantly more reduced than after LASIK. Logically, we should expect greater decrement of CH and CRF in the lenticule extraction group which means that biomechanical properties have been more affected by the flapless technique. One possible explanation for this finding is that the removed lenticule volume was larger than the ablation volume with LASIK. Although less stromal collagen fibers are severed in SMILE, it does not mean that corneal rigidity is unconditionally higher after flapless surgery. It must be pointed out that, after having removed the lenticule, the length of the back of the anterior cap will be longer than the corresponding arc length of the unaffected residual stroma. Hence, differences in arc lengths contribute to a corrugated contact surface. Since a rearrangement of anterior collagen lamellae is necessary, the unimpaired cap is not as strong as expected [21]. The more volume that is removed, the greater the differences in arc lengths, and hence the corrugation. The more decreased CCT after SMILE than after LASIK causes the necessity of augmented rearrangement that may reduce corneal stability. To date, several studies have evaluated changes in CH and CRF after LASIK and SMILE. Most studies report similar reductions of CH and CRF values in both groups [19, 21, 22]. Wang et al. [19] found a greater reduction of CRF with flap-based surgery, but differences between the 2 groups were not statistically significant. It should be remarked that collagen crosslinking modifies corneal strength significantly, whereas CH and CRF might be unaffected [23]. Therefore, an absence of differences in CH and CRF between both techniques is not equivalent to an absence of biomechanical alteration. Corneal properties might be different after the two procedures even if CH and CRF remain similar.

With regard to our previous considerations, we cannot state definitively whether corneal structural integrity is more affected by LASIK or SMILE.

Long-term examination of total CV and CCT

Comparing total CV and CCT measured at 3 and 12 months postoperatively, we found no significant difference in each group which illustrates that alterations in volume and pachymetry occurred during the first 3 months. We suppose that most of the measured ΔCV_3mo correspond with intraoperative ablation volume and lenticule volume, respectively. Except for wound healing procedures, we did not expect the volume to change much postoperatively. Later on, the CV and CCT stayed approximately constant and we do not expect them to alter further. This was similar to the findings by Kobashi et al. [7] that stated CCT remain unchanged during the postoperative period.

Limitations

Our study has several limitations. The main deficiency is that the study was not a prospective and randomized controlled study. Results might have been different if we had matched the patients preoperatively and referred them to a certain group by randomization.

One aspect that may have influenced the results is the difference between LASIK flap thickness (110 μm) and SMILE cap thickness (120 μm). It is not clear whether extracting corneal material from superficial or deeper stroma obtains better results. On one hand and as mentioned before, the deeper the intervention, the less influence on anterior corneal properties. Generally, with SMILE, the excess tissue is removed from deeper corneal stroma. Since the stronger anterior stroma stays untouched, it seems reasonable to assume greater biomechanical strength after SMILE than after LASIK. On the other hand, the deeper the lenticule is removed more volume has to be extracted to result in similar changes in the shape of the anterior corneal surface. That means, removing a lenticule from deeper stroma, more material has to be extracted to achieve the same refractive correction as with a superficial lenticule [22]. For LASIK, increased flap thickness leads to decreased corneal stability owing to intensified wound healing processes at the margin and lower residual stromal bed thickness [24]. In our study, cap and flap thicknesses were intentionally not equally set in order to maintain standard parameters usually used in the clinical setting.

We measured intraocular pressure before and after intervention, but as there were no pressure spikes it was not noted in the patients’ files. Therefore, we were not able to analyse changes in intraocular pressure (IOP) before and after intervention in our study, even though this is a widely discussed issue after refractive surgery. SMILE is reported to be less sensitive to IOP changes due to higher biomechanical stability [14]. We could not take a position on this issue.