Refractive surgery affects the cornea's biomechanical properties by reducing the biomechanical strength as a result of irreversible corneal lamellar changes. Theoretically, the small incision in small-incision lenticule extraction (SMILE) should have biomechanical advantages over flap-based techniques such as the femtosecond lenticule extraction (FLEx) and femtosecond laser–assisted laser in situ keratomileusis (LASIK) because it better preserves the stronger anterior stroma. This has been shown in a mathematic model by Reinstein et al.,1 a contralateral computational analysis by Seven et al,2 and a finite-element analysis by Sinha Roy et al.3 and in ex vivo porcine eye studies by Spiru et al.4 However, measuring the strength and stability of the cornea in vivo remains a challenge; therefore, our knowledge in this area is limited.
At present, 2 commercially available devices measure the biomechanical proportions of the cornea in vivo—the Ocular Response Analyzer biomechanical waveform analyzer (Reichert Technologies) and the Corvis ST dynamic Scheimpflug analyzer (Oculus Optikgeräte GmbH). Both systems use noncontact air puff–based tonometry. The biomechanical waveform analyzer estimates several parameters, among which corneal hysteresis (CH) and the corneal resistance factor (CRF) are the most reported when describing corneal viscoelastic properties.5 The devices are most often used for screening for glaucoma, keratoconus, and before refractive surgery.
In 2014, we published a prospective single-masked paired-eye study in which 35 patients were randomized to have FLEx in 1 eye and SMILE in the other eye to treat moderate to high myopia.6,A Among other parameters, CH and the CRF were determined before and 6 months after surgery in an attempt to detect changes in corneal biomechanical properties related to the different incision sizes. No statistically significant difference was found between the 2 techniques in that study. However, at the time we were not in possession of the latest Ocular Response Analyzer software. Thus, we could not access the 37 relatively new parameters that describe the waveform of the Ocular Response Analyzer curve or the derived keratoconus score.
The purpose of the present study was to analyze the 37 new waveform parameters and to compare FLEx and SMILE in an attempt to further quantify changes in corneal biomechanical properties. Our original article6 describes the surgical techniques and study protocol in detail.
Patients were randomized to receive FLEx in 1 eye and SMILE in the other eye for treatment of moderate to high myopia. All patients had stable myopia and no other ocular disease. A ReLEx VisuMax femtosecond laser femtosecond laser (Carl Zeiss Meditec AG) was used to make the refractive cut. Lenticule diameters were the same in both eyes and ranged from 6.00 to 6.50 mm. Flap thickness was 110 to 120 μm, and the flap or cap diameter ranged from 7.3 to 8.0 mm. All eyes were left with at least 250 μm of residual stromal bed.
Ocular Response Analyzer corneal waveform parameters were assessed. This biomechanical waveform analyzer uses bidirectional applanation through brief air pulses that rapidly deform the cornea inward and outward, providing 2 independent measurements of intraocular pressure. An electro-optical system monitors the central 3.0 mm curvature of the cornea throughout the deformation and generates a response curve. The 37 new parameters describe different characteristics of the response curve, such as areas, heights, widths, slopes, and irregularities. In this study, the original raw data were anonymized and sent to the manufacturer of the biomechanical waveform analyzer. The newer software (version 3.01) was applied, and the new waveform parameters were derived, including the keratoconus score.
Of the 35 patients included in the study, 34 completed the 6-month follow-up. There were no significant difference in any of the 37 waveform parameters, including the keratoconus score, between FLEx eyes and SMILE eyes at baseline or after 6 months (P > .05). There was a borderline significant between-group difference in the w11 parameter (width of peak 1 at the base of the peak 1 region) from preoperatively to 6 months postoperatively (P = .045); the difference was in favor of FLEx. However, in both groups there was a significant difference in the change in the majority of the 37 parameters, including the keratoconus score, from preoperatively to 6 months postoperatively (Table 1).
All previous published contralateral randomized controlled trial studies comparing SMILE with FLEx or femtosecond-assisted LASIK,6–8 found no significant differences in CH or the CRF between the cap-based SMILE technique and the flap-based techniques, although some nonrandomized studies (eg, Wu et al.9) found a difference in favor of the SMILE technique.
In an attempt to enhance our knowledge about corneal biomechanical properties, we further evaluated Ocular Response Analyzer waveforms. In theory, the derived waveforms provide a unique fingerprint for each cornea that might be helpful in differentiating between healthy corneas and diseased corneas, although little is known about the clinical significance of the various waveform parameters.10
In this study, the 37 relative new waveform parameters from the Ocular Response Analyzer and the resulting keratoconus score were not able to detect major differences between the FLEx and the SMILE procedures. The single parameter with a borderline statistically significant value in favor of FLEx could not be related to any clinically relevant change and is speculated to be a result of the multiple significance tests performed. When 37 statistical tests are performed, 1 to 2 parameters will, by chance, be statistically different with a standard α level of 0.05. After correction of multiple comparisons (Bonferroni), the parameter was no longer statistically significant. The majority of the waveform parameters were significantly reduced after both procedures, indicating weakening of corneal strength, and the changes were highly related to the changes in central corneal thickness, as previously shown by other biomechanical parameters (CH and CRF).6 However, the presumed corneal biomechanical advantage of SMILE over the flap-based procedure (FLEx) was not found.
Because of the paired-eye design, most sources of variability could be ignored when comparing FLEx and SMILE. However, potential limitations include variability in patient alignment and corneal centration during the air-pulse measurements and the ocular pulse amplitude.
To our knowledge, this is the first paired-eye study to directly compare Ocular Response Analyzer–derived waveform parameters after 2 all-femtosecond laser refractive techniques (FLEx and SMILE). Future studies should include a longer follow-up to assess the risk for corneal ectasia development over time and an evaluation of new in vivo and ex vivo techniques for quantifying corneal biomechanical properties and stability.
Dr. Hjortdal received travel reimbursement from Carl Zeiss Medite cAG. None of the other authors has a financial or proprietary interest in any material or method mentioned.
Reinstein DZ, Archer TJ, Randleman JB. Mathematical model to compare the relative tensile strength of the cornea after PRK, LASIK, and small incision lenticule extraction. J Refract Surg 2013; 29:454-460
Seven I, Vahdati A, Pedersen IB, Vestergaard A, Hjortdal J, Roberts CJ, Dupps WJ Jr. Contralateral eye comparison of SMILE and flap-based corneal refractive surgery: computational analysis of biomechanical impact. J Refract Surg 2017; 33:444-453
Sinha Roy A, Dupps WJ Jr, Roberts CJ. Comparison of biomechanical effects of small-incision lenticule extraction and laser in situ keratomileusis: Finite-element analysis. J Cataract Refract Surg 2014; 40:971-980
Spiru B, Kling S, Hafezi F, Sekundo W. Biomechanical differences between femtosecond lenticule extraction (FLEx) and small incision lenticule extraction (SmILE) tested by 2D-extensometry in ex vivo porcine eyes. Invest Ophthalmol Vis Sci 2017; 58:2591-2595
Luce DA. Determining in vivo biomechanical properties of the cornea with an ocular response analyzer. J Cataract Refract Surg 2005; 31:156-162
Vestergaard AH, Grauslund J, Ivarsen AR, Hjortdal JØ. Central corneal sublayer pachymetry and biomechanical properties after refractive femtosecond lenticule extraction. J Refract Surg 2014; 30:102-108
Agca A, Ozgurhan EB, Demirok A, Bozkurt E, Celik U, Ozkaya A, Cankaya I, Yilmaz OF. Comparison of corneal hysteresis and corneal resistance factor after small incision lenticule extraction and femtosecond laser-assisted LASIK: a prospective fellow eye study. Cont Lens Anterior Eye 2014; 37:77-80
Kamiya K, Shimizu K, Igarashi A, Kobashi H, Sato N, Ishii R. Intraindividual comparison of changes in corneal biomechanical parameters after femtosecond lenticule extraction and small-incision lenticule extraction. J Cataract Refract Surg 2014; 40:963-970
Wu D, Wang Y, Zhang L, Wei S, Tang X. Corneal biomechanical effects: small-incision lenticule extraction versus femtosecond laser-assisted laser in situ keratomileusis. J Cataract Refract Surg 2014; 40:954-962
Zarei-Ghanavati S, Ramirez-Miranda A, Yu F, Hamilton DR. Corneal deformation signal waveform analysis in keratoconic versus post-femtosecond laser in situ keratomileusis eyes after statistical correction for potentially confounding factors. J Cataract Refract Surg 2012; 38:607-614
OTHER CITED MATERIAL
U.S. National Institutes of Health Clinical Trials. A prospective study of femtosecond laser intracorneal lensectomy. NCT01673503. Available at: http://www.clinicaltrials.gov/ct2/show/NCT01673503?term=NCT01673503&rank=1
. Accessed November 15, 2018