The progress in the field of laser corneal refractive surgery observed during the past decade has been substantially due to the introduction of the femtosecond laser. The laser-assisted in situ keratomileusis (LASIK) procedure achieved a new level of safety once the microkeratome was replaced by the femtosecond laser. This evolutionary step made femtosecond laser–assisted LASIK (FS-LASIK) the most popular laser refractive surgery. In contrast, in 2008 Sekundo et al.1 introduced an entirely new modality of laser reshaping procedure, the small incision lenticule extraction (SMILE). SMILE offers several potential advantages, such as more postoperative comfort and patient satisfaction,2 faster epithelial healing,3 less neurotrophic keratopathy, and a presumed better preservation of biomechanical stability.3–6
Corneal biomechanical properties are determinant in the development of keratectasia. The success and long-term stability of a given corneal refractive surgery depends on not only biological, but also biomechanical factors. Hence, the understanding of the corneal biomechanical response to a given surgical procedure may help not only in predicting surgical outcomes, but also in handling possible postoperative complications. Because SMILE supposedly is superior in preserving corneal integrity when compared to flap-based procedures such as FS-LASIK, it would be reasonable to assume that SMILE might also show more biomechanical stability in comparison to surface ablation techniques. Reinstein et al.7 demonstrated this hypothesis with a mathematical model estimating the relative differences in postoperative stromal tensile strength following photorefractive keratectomy (PRK), FS-LASIK, and SMILE procedures. Following the same coherence, a finite-element analysis by Sinha Roy et al.8 suggested a higher residual stromal bed stress after FS-LASIK than after SMILE procedures. A few experimental studies analyzed differences in the in vivo corneal deformation response following an air-puff,9,10 but did not find a significant difference between FS-LASIK and SMILE procedures. The corneal deformation response following an air-puff is sensitive to changes in corneal thickness11 and intraocular pressure (IOP), which might have masked the subtle differences between FS-LASIK and SMILE in this set-up. In addition, an air-puff directed at the surface of the cornea does not truly correspond to the force of the IOP that comes from within the eye, neither in terms of the force direction nor under consideration of the cornea's shape being convex on the surface but concave toward the anterior chamber.
Several systems (eg, air-puff tonometers or Brillouin microscopy) developed to assess the corneal biomechanical properties in vivo are either inconclusive or not yet established in clinical practice. The most accurate tests are destructive and can only be performed in ex vivo tissue. One-dimensional stress-strain testing is the gold standard technique for ex vivo testing. However, the stress distribution is not representative for the natural stress situation in the eye implied by the IOP. In 2010, Kling et al.12 developed a set-up for two-dimensional stress-strain testing to overcome this issue. An indenter is used to apply the load similar to the IOP and, simultaneously, the spherical deformation of the corneal sample is recorded. This set-up allows elastic and viscoelastic soft tissue characterization and was previously applied to determine the experimental difference between flap-based and cap-based corneal refractive procedures13 in porcine and human corneas.6 In the current study, we used the same setting to experimentally determine the biomechanical differences between PRK and SMILE, to our knowledge for the first time, in human ex vivo fellow eyes.
Materials and Methods
In this experimental study, 13 pairs of human corneas (N = 26 eyes) obtained from various corneal banks and unsuitable for transplantation were equally divided into two groups (13 eyes in each): corneas from the right eye were treated with PRK and corneas from the left eye with SMILE. Ultrasound pachymetry was performed in each cornea directly before laser refractive surgery. All corneas were treated on the same day.
The corneas were mounted onto an artificial anterior chamber (Katena Products Inc., Denville, NJ) and the IOP was adjusted to approximately 20 mm Hg. For further standardization of the refractive procedure, and given that the epithelium hardly contributes to the mechanical corneal properties,14 the epithelium was scraped off from all corneas prior to the laser treatment, ensuring that differences in epithelial transparency did not interfere with the laser beam. The medium-sized contact glass (treatment pack) was used to applanate the cornea by the VisuMax 500 kHz femtosecond laser (Carl Zeiss Meditec AG, Jena, Germany) with the following energy settings: 130 nJ and 4.5 µm track/spot distance. The minimum lenticule thickness was set to 15 µm. In the PRK group, ablation was performed using the MEL 90 excimer laser (Carl Zeiss Meditec AG). All corneas were subjected to a refractive correction of −10.00 diopters (D) sphere and −0.75 D cylinder at 0° axis with a 7 mm zone using either surface ablation (PRK) or 130 µm cap (SMILE). Directly after the surgical intervention, the corneoscleral buttons were preserved in Optisol GS (Bausch & Lomb, Rochester, NY) until the biomechanical measurements were performed.
Two-dimensional biomechanical characterization was performed on entire corneoscleral buttons, as described earlier.13,15 Briefly, buttons were mounted circumferentially (10 mm diameter) and a spherical indenter was used to apply the three-dimensional test force from the posterior surface, similar to the IOP. A commercial stress-strain extensometer/indenter (Z0.5; Zwick GmbH & Co., Ulm, Germany) was used for the experiments. Each corneal specimen underwent two cycles of stress-strain preconditioning between 0.03 and 9.0 N (571 kPa stress), followed by a stress-relaxation test at 9.0 N for 120 seconds. To calculate the elastic modulus, the second cycle was used in all corneas. The vertical extension was recorded as a function of stress and converted into tensile strain according to the geometrical context (see our previous studies for detailed equations13,15). Stress was computed from the applied test force and the individual central corneal pachymetry of each cornea. Homogeneous material properties and no difference between central and peripheral corneal thickness were assumed.
Statistical analysis was performed in SPSS Statistics software (version 23.0.0; IBM Corporation, Armonk, NY). Normality was tested with the Shapiro–Wilk test. Subsequently, a two-tailed paired test was applied to analyze significant differences between treatment groups. Confidence intervals of 95% were applied.
Corneal thickness was not significantly different between the SMILE (741 ± 125 µm) and PRK (722 ± 133 µm) groups (P = .179).
According to the Shapiro–Wilk test, stress-strain data of the SMILE group were normally distributed (P > .089). Figure 1 presents the stress-strain relationship and the elastic modulus as a function of strain for the different treatment groups. The effective elastic modulus (Figure 2) was not significantly different (P = .081) between SMILE (9.58 ± 4.26 MPa) and PRK (11.9 ± 4.90 MPa). The effect size according to Cohen was medium (r = 0.58).
Stress-strain data for the small incision lenticule extraction (SMILE) and photorefractive keratectomy (PRK) groups.
Elastic modulus data for the small incision lenticule extraction (SMILE) and photorefractive keratectomy (PRK) groups.
According to the Shapiro–Wilk test, stress-relaxation data were also normally distributed in both groups (P > .218). No significant (P = .878) difference in terms of the remaining stress after relaxation was observed between SMILE (122 ± 33 kPa) and PRK (123 ± 30 kPa) (Figure 3).
Stress-relaxation data for the small incision lenticule extraction (SMILE) and photorefractive keratectomy (PRK) groups.
Our previous studies6,13,15 could demonstrate (as widely presumed in the refractive community) that the flap-based procedure weakens the cornea more than the cap-based procedure when tested on porcine corneas. In human corneas, we found even greater differences, with corneas after SMILE being 1.47 times stronger compared to corneas after FS-LASIK.6
The most plausible explanation is the presence of the membrane-like condensed structure of the anterior stroma and the presence of Bowman's layer in human corneas, which is virtually absent in porcine corneas. The creation of a flap severs both the Bowman's layer and the anterior, biomechanically stronger, stroma.16
In the current study, we compared fellow corneas after SMILE and PRK and demonstrated that both techniques can be considered equivalent in terms of biomechanical stability. We were surprised to some extent to see similar test results with both PRK and SMILE procedures, which was contradictory to Reinstein et al.'s mathematical model.7
Recently, finite element simulations17 of air-puff applanation on LASIK, SMILE, and PRK models showed that PRK eyes had the least decrease in stiffness parameters (better than LASIK or SMILE), when a cohort of eyes was measured with the Corvis ST before and after surgery. Clinical results of comparative studies between LASIK and PRK with the Corvis ST generally indicate a stiffer biomechanical response after PRK than predicted by the model.18–20 Such difference was suggested to be due to a greater degree of fibrotic scars and haze formation in PRK than in LASIK,21,22 which could have resulted in some biomechanical compensation to removal of the stiffest region of the stroma.
On the other hand, this assumption does not apply to our experimental setting because no healing response is expected in ex vivo tissues. Hypothetically, the stress distribution might also depend on the removed region of the cornea, with more anterior ablation leading to a better stress distribution over the entire corneal surface. At the same time, it is possible that the difference is too small to show up in a study limited to 13 pairs of fellow eyes.
Unfortunately, a larger experimental sample is not feasible due to the difficulties in obtaining fellow eye corneal buttons. In contrast, despite different postmortem times and donors ages in our study, a paired eye study overcame this sample bias once each treatment group had an equal number of corneas with identical characteristics of age, degree of degeneration, and possible underlying pathologies, finally reducing the source of error and increasing the statistical power.
An interesting aspect is the hydration of the ex vivo cornea. We assumed the behavior of the swollen cornea in its hydrated state is not the same after those two different approaches. Because the PRK “dries off” the swollen cornea, whereas in SMILE there is only a cutting effect, we believe that the postoperative pachymetry cannot serve as real feedback on the refractive power ablated, as in in vivo experiments. Hence, this aspect could also be the explanation for PRK performing somewhat better than SMILE in this setting and also the cause for possible mixed results (in vivo versus ex vivo).
Another limitation for the current study could be considered the assumption of homogeneous material properties and uniform corneal thickness.
Compared to excimer laser–based procedures, the SMILE procedure currently does not cover the entire range of refractive errors eligible for laser refractive correction. However, for eligible corneas and refractive errors, SMILE seems to offer no biomechanical advantage over surface ablation. The advantages are rather present on the clinical level, such as a higher degree of correction with a better refractive predictability, absence of haze, and a higher degree of postoperative comfort leading to a better patient satisfaction after SMILE.23,24
The lenticule extraction procedure (SMILE) and the surface ablation technique (PRK) may be considered equal in terms of biomechanical stability, when measured experimentally in ex vivo human fellow eye corneas. Further prospective non-inferiority clinical studies matched by refraction, treatment zone, age, and sex may be envisaged as more sensitive in vivo measurement techniques for corneal biomechanics become available.
- 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. doi:10.1136/bjo.2009.174284 [CrossRef]
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- Yan H, Gong LY, Huang W, Peng YL, Clinical outcomes of small incision lenticule extraction versus femtosecond laser-assisted LASIK for myopia: a meta-analysis. Int J Ophthalmol. 2017;10:1436–1445.
- Spiru B, Kling S, Hafezi F, Sekundo W. Biomechanical properties of human cornea tested by two-dimensional extensiometry ex vivo in fellow eyes: femtosecond laser–assisted LASIK versus SMILE. J Refract Surg. 2018;34:419–423. doi:10.3928/1081597X-20180402-05 [CrossRef]
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