Secondary Logo

Journal Logo


Corneal biomechanics after laser refractive surgery: Unmasking differences between techniques

Fernández, Joaquín MD, PhD; Rodríguez-Vallejo, Manuel PhD*; Martínez, Javier OD; Tauste, Ana PhD; Piñero, David P. PhD

Author Information
Journal of Cataract & Refractive Surgery: March 2018 - Volume 44 - Issue 3 - p 390-398
doi: 10.1016/j.jcrs.2017.10.054
  • Free


Corneal biomechanics has generated great interest among researchers and clinicians in laser refractive surgery because of 2 important factors; that is, postoperative ectasia can occur without apparent preoperative risk factors using the currently available technology1 and the potential influence of biomechanics on the prediction of laser refractive surgery outcomes.2 Corneal ectasia after laser refractive surgery is the most frightening complication for any refractive surgeon. Despite the wide number of screening tools, such as corneal wavefront aberrations, anterior curvature irregularity, thin pachymetry, atypical pachymetry profiles, posterior surface elevation anomalies, and epithelial thickness mapping, none of these has shown to be totally effective in screening corneas with early changes in biomechanical properties associated with the beginning of an ectatic process.3 Moreover, new advances integrating corneal tomography and dynamic Scheimpflug tonometry have been introduced with the goal of increasing the sensitivity and specificity of the detection of suspect cases.4

The introduction of small-incision lenticule extraction (SMILE, Carl Zeiss Meditec AG) has led to an increase in controversies on the preservation of corneal biomechanics after laser refractive surgery. Bowman layer is stiffer than the anterior stroma and in turn, the anterior stroma is stiffer than the posterior stroma.5 Because small-incision lenticule extraction preserves stiffer layers better, there is a theoretical basis to hypothesize that this new technique preserves the corneal biomechanics better than laser in situ keratomileusis (LASIK) or photorefractive keratectomy (PRK).6 In fact, mathematic biomechanical models suggest that deeper corrections in the stroma might be possible with small-incision lenticule extraction without an additional risk for ectasia because the residual stromal bed supports greater stress in LASIK than in small-incision lenticule extraction.7 However, this conclusion must be interpreted with caution because the link between corneal stress and ectasia has yet to be defined,7 and a conservative approach similar to that used for LASIK and PRK is being adopted after the report of some ectasias after small-incision lenticule extraction in patients with normal8 and suspicious topographies.9–11

Despite the suggestions of mathematic6 and finite biomechanical model simulations,7 there is no clear clinical evidence that small-incision lenticule extraction has advantages over other laser refractive surgery techniques in terms of corneal biomechanics. The aims of the current review were the following: (1) to describe the current techniques in laboratory and clinical practice for measuring corneal stiffness from the macrostructural to the microstructural viewpoint and to describe the limitations of these techniques, (2) to identify changes generated in the cornea with different laser refractive surgery techniques and to understand why biomechanical variations between them are not clinically detected with current clinical devices, and (3) to propose special considerations in the design of clinical studies to enhance the capabilities of clinical devices to detect these differences by improving the research methodology to reduce the impact of confounding variables on the results.

Laboratory Versus Clinical Practice

The interpretation of results obtained from laboratory methods for assessing corneal biomechanics can be confusing to the clinician. First, studies report as results the elastic Young's modulus and shear moduli obtained from the ratio of applied stress (force) to resultant strain (deformation). However, Young's modulus quantifies the response of a perfectly elastic material, which is not the case of soft tissues such as the cornea.12 Therefore, to overcome this problem, soft biological tissues are typically assumed to behave as elastic solids if a significant linear regimen of stress-to-strain exists in the limit of a small-strain response to applied stress.12 This allows one to obtain the tangent modulus, which is defined as the instantaneous slope of the stress–strain curve at a specific stress (Figure 1).13

Figure 1.
Figure 1.:
Representation of a nonlinear stress–strain function typical of the cornea. Tangent modulus is obtained from the slope at a particular stress for which the function is almost linear (elastic behavior). A graphic of tensile stretching is included in the figure to explain the stress–strain relationship.

The resultant Young's modulus of the cornea varies widely according to the method of measurement as follows: (1) indentation (˜29 KPa), deformation maximized on the point of contact of the indenter depending on the shape of tip used to apply the indentation, and (2) tensile stretching (˜3 MPa), which induces macroscopic deformations that span the bulk of a tissue (Figure 1).12 Indentation techniques can be optimal to obtain the stiffness of a small location of the tissue from millimeters to nanometers and the tensile techniques to obtain stiffness of the bulk cornea, considering that a higher elastic modulus indicates that the material is stiffer. Furthermore, a limitation of these methods is that the manipulation of the eye for performing the measurement may result in fiber reorientation and hence, tissue stiffening. A new methodology capable of mechanically testing intact eye globes has been proposed which is based on speckle laser interferometry. The use of this technology has led to conclusions, such as the central cornea is stiffer than the peripheral cornea.14

Current techniques for assessing corneal biomechanics in clinical practice are based on the acquisition of some parameters during the corneal deformation by an air puff. These parameters include corneal hysteresis and the corneal resistance factor derived from the pressures obtained with a biomechanical waveform analyzer (Ocular Response Analyzer, Reichert Technologies). More recently, a dynamic Scheimpflug tonometer device (Corvis ST, Oculus Optikgeräte GmbH) that records the cornea movement with a high-speed camera was developed that allows the acquisition of multiple parameters, including applanation, times, velocities, and deflections. However, parameters obtained with both devices differ widely from the standard descriptors of mechanical properties used in the laboratory. A new corneal indentation device has been proposed to measure the tangent modulus of elasticity of the cornea in clinical practice.15–17 These 3 clinical methods are based on the response of the bulk cornea, and a small change in corneal biomechanics resulting from the physical composition might be not detected, mainly because confounding variables such as corneal thickness and intraocular pressure (IOP) play a major role in the resistance of the cornea.

Role of Corneal Layers in Corneal Biomechanics

Thin Layers of the Cornea Tensile stretching methods, either pulling a strip of the cornea18 or applying pressure behind the cornea,19 have been used to make conclusions about the contribution of the different corneal layers to biomechanics, concluding that some layers, including the epithelium19,20 and the Bowman layer,18 might be neglected in numerical simulations because of their small contribution. These experiments measured the differences in the whole cornea while maintaining or removing the epithelium and Bowman layer, but without isolating each layer. It is difficult to isolate each layer for mechanical testing because tensile testing requires a mechanical grip to hold and pull the material, which would be difficult to do with thin layers. More sophisticated indentation methods, such as atomic force microscopy nanoindentation, have been proposed to determine the local elastic modulus of each corneal layer.21

Last et al.5 reported that Bowman layer has a Young's modulus of 109.8 kPa, higher than that of the anterior stroma (33.1 kPa) and Descemet membrane (50 kPa). Furthermore, Xia et al.22 found an increase in Young's modulus for the stroma and Descemet membrane23 from MPa to GPa (109 Pa) with corneal dehydration. From these results, we can reasonably hypothesize that the small contribution of these layers to the entire corneal biomechanics is the result of their being less thick than the total thickness of the cornea. From our perspective, because all these thin layers are affected in keratoconus,24 they should not be neglected in the future research studies of corneal biomechanics.

The development of advanced imaging techniques, such as serial block face scanning electron microscopy, has provided further knowledge about some other microstructural components, such as elastic fibers, that have been overlooked in recent years and that differ between normal corneas and keratoconic corneas.25 Specifically, it has been reported that cornea contains a network of microfibrils anterior to Descemet membrane that becomes progressively less abundant anteriorly. Conversely, in the keratoconus cornea, there are few elastic fibers anterior to Descemet membrane and these fibers increase in number below the basal epithelium in thinned central regions.26

Corneal Stroma The stroma is the thicker layer of the cornea with a microstructural composition of collagen fibrils that varies with depth (Figure 2). The basic structure of collagen is the helical structure of tropocollagen (1 nm). These molecules are crosslinked to form collagen fibrils (50 to 100 nm), and these fibrils are assembled to form collagen fibers or corneal lamellae (500 to 1000 nm).27 The stromal thin collagen fibrils are embedded in a soft hydrated matrix formed by proteoglycans and interstitial fluid.28 The proteoglycans are composed of protein core and covalently linked glycosaminoglycan side chains and are important for corneal transparency by keeping the fibrils apart at a regular spacing.29 Today, it is known that the branching density of collagen fibers decreases along the corneal depth and that the collagen fibers have steep angles in the most anterior part of the cornea, with fibers inserted into the Bowman membrane forming bow spring-like structures (Figure 2).30 This collagen organization confers significantly higher stiffness31 and less elasticity32 to the anterior stroma compared with the middle and posterior stroma.

Figure 2.
Figure 2.:
Role of different variables in the clinical measurement of corneal biomechanics. From the macrostructural to the microstructural viewpoint, the role of the different variables decreases in comparison to the mechanical displacement of the bulk cornea (CCT = central corneal thickness; IOP = intraocular lens).

Furthermore, the anterior cornea is isotropically organized, whereas the middle and posterior parts have 2 preferential orientations attributed to the nasal–temporal and inferior–superior directions; the fibers are reorganized with the increase of loading inflation pressure in the middle and posterior stroma.33 The stiffness of the stroma varies with depth from 7.71 KPa to 240 KPa for the anterior stroma, from 1.99 KPa to 70 KPa for the central stroma, and from 1.31 KPa to 10 KPa for the posterior stroma.34,35

Macrostructural and Microstructural Changes After Surgery

From a theoretical perspective, small-incision lenticule extraction preserves the stiffer layers of the cornea, and for eyes with the same IOP and the same corneal thickness after surgery, the cornea should be stiffer after small-incision lenticule extraction than after PRK or LASIK. However, other microstructural changes can lead to variations in the stiffness between techniques or even for the same technique. Knox Cartwright et al.20 reported greater alteration of mechanical properties, increasing the LASIK flap depth from 90 to 160 μm, and less variation for horizontal delamination than for vertical side cuts. However, the advantages of horizontal delamination should be interpreted with caution because of the possibility of increasing the risk for epithelial ingrowth.36 Wang et al.37 reported that the creation of a thin flap of 90 to 110 μm in rabbits did not additionally compromise the elastic modulus of the cornea and that the mechanical response of the cornea after LASIK might be predominantly influenced by laser ablation. He et al.38 found a higher Young's modulus in rabbits' eyes having small-incision lenticule extraction using a lenticule thickness of 160 μm compared with the use of 100 μm. Likewise, Spiru et al.39 found that the Young's modulus after small-incision lenticule extraction treatment was significantly higher than after femtosecond lenticule extraction (FLEx, Carl Zeiss Meditec AG) in ex vivo porcine corneas, suggesting that the cap-based technique of small-incision lenticule extraction can be considered better in terms of biomechanical stability.

Santhiago et al.40 reported that the percentage of tissue altered, including flap thickness and ablation depth, is a more robust risk factor for corneal ectasia than the residual stromal bed and central corneal thickness (CCT). They suggested that for patients with the same percentage of tissue ablated, those with thicker flaps have a major risk for corneal ectasia compared with in those with a greater ablation depth. Kling et al.41 found no differences in the biomechanical properties measured with stress–strain extensometry in porcine corneas after retreatment with small-incision lenticule extraction and PRK in comparison with untreated corneas; however, a less elastic modulus was found after LASIK than in the control group. Although the highest preservation of corneal biomechanics was expected after small-incision lenticule extraction compared with PRK, no differences were found, perhaps because Bowman membrane in porcine corneas is not as highly developed as in human or primate corneas.41

The epithelium thickness increases after laser refractive surgery compared with that in unoperated eyes. In small-incision lenticule extraction, this increase is reported to be between 2.51 μm42 and 15 μm43 greater at the center, decreasing along the periphery and acquiring a lenticular shape.44 Furthermore, central epithelium hyperplasia has been reported to be less by approximately 1 μm after small-incision lenticule extraction than after LASIK.42 This epithelial remodeling in small-incision lenticule extraction is reported to be correlated with age and the corrected refractive error but not with the refractive results.45 Conversely, the difference between the achieved stromal reduction and the planned tissue removal is reported to be between 8 μm43 and 11.9 μm thicker on average for small-incision lenticule extraction but only 0.4 μm for LASIK 3 months postoperatively, and this was related to the residual refractive error.43,42 From these findings, it has been hypothesized that the stromal expands after small-incision lenticule extraction43 and that this is compensated for by a lower increase in the central epithelial thickness.42 This can lead us to hypothesize that corneas with the same thickness after surgery might be stiffer in small-incision lenticule extraction than in LASIK as a result of the expansion of the stroma instead of the epithelium, which is a less stiff layer.19,20 However, this is only a hypothesis that should be confirmed in future studies because the nature of this expansion might vary with the stiffness in the stroma in comparison to the untreated cornea.

Corneal hydration also has an important role in corneal biomechanics. As the permeability of the cornea increases, the cornea becomes thicker but the stiffness decreases from GPa to MPa.22,46 This means that 2 corneas with the same thickness might have different biomechanical behavior depending on the level of corneal hydration. It would be interesting to differentiate between the components from stromal collagen fibrils and the soft hydrated matrix.28 The combination of corneal densitometry and biomechanical analysis might be an option to characterize the impact of corneal hydration.47

Combination of Densitometry and Biomechanics

The corneal structure previously described leads to disparities in the refractive index that produce light scattering visible through densitometry maps.48 The major sources of light scattering are the anterior superficial corneal epithelial cell layer and the posterior corneal endothelium because of the higher difference in the refractive index from air and aquous.49 However, variations in light scattering are also present in the cornea as a result of disparities of the refractive index along epithelium, anterior stroma, and posterior stroma.50 Furthermore, different refractive indexes are present in the hydrated fibrils and the extrafibrillar matrix, and the refractive index of the corneal stroma is reduced as the cornea swells.51 In fact, the refractive index increase in the stroma has been associated with the dehydration after LASIK52 and is higher in older corneas; this directly correlates with the increase of densitometry53 and stiffness.54

At the baseline state, densitometry measured with the Pentacam rotating Scheimpflug camera (Oculus Optikgeräte GmbH) is highest in the anterior 120 μm of the cornea compared with that in the center and posterior layers.53 Considering that the normal epithelial thickness is approximately 53.4 μm ± 4.6 (SD)55 and that the lamellar angles relative to the stromal surface are highest in the anterior-most 83 μm of the corneal stroma, our hypothesis is that the increase in anterior densitometry is not only the result of epithelial thickness but also of the angle of the collagen lamellae30 at this part of the cornea and possibly because the anterior stroma tends to be less hydrated and more resistant to water flow than the posterior stroma.52

The densitometry increases after laser refractive surgery,56 probably as a result of the increase in the refractive index because of stromal dehydration by the laser application.52 It returns to values even below the preoperative status 12 months after PRK56 and small-incision lenticule extraction.57 Furthermore, the preoperative values are reached 3 months after LASIK and small-incision lenticule extraction without differences between techniques,58 but not after PRK.56 The decrease in densitometry over the postoperative period might be related to the recovery of corneal hydration, with a decrease in the refractive index of the stroma, even for levels of hydration higher than preoperative values. This is in an agreement with the possible expansion of the stroma and the increase in corneal thickness over time.59,60

We reported for the first time the potential usefulness of dynamic densitometry in refractive surgery.47 It is defined as the increase in densitometry during the course of the air puff generated with the Corvis ST dynamic Scheimpflug tonometer. It is important to differentiate between static densitometry measured with any rotating Scheimpflug camera and the dynamic densitometry measured with the Corvis ST system. The first one represents the natural state of the corneal fibrils and corneal hydration, whereas the latter hypothetically would represent the modification of collagen fiber order and fluidics movement along the cornea during the course of the air puff. We found that densitometry increased during the inward stage, reaching the maximum value close to the highest concavity, whereas during the outward stage the densitometry at the second applanation status was higher than that obtained at first applanation. Our explanation of the course of dynamic densitometry is that the stromal fluid goes from the anterior to the posterior stroma with the air-puff pressure while the anterior fibers are compressed or reordered. Furthermore, we reported that the densitometry sign described as a bright, inclined fringe that appears in the peripheral corneal peaks at the highest concavity stage and moves to the corneal periphery until it disappears has a higher prevalence after small-incision lenticule extraction. Specifically, the prevalence was 48.8% preoperatively and 72.1% postoperatively. This sign might be related to greater fluid movement caused by the alteration in collagen fibers during surgery.47 However, this is only a hypothesis that suggests the possible advantages of including corneal densitometry in the algorithms to compute corneal stiffness.

Evidence of Corneal Biomechanical Changes in Comparing Refractive Surgery Techniques

Table 161–82 is a summary with the main conclusions obtained of studies that have measured corneal biomechanics in different laser refractive surgery techniques using either with the Ocular Response Analyzer (Reichert Technologies), which assesses biomechanical waveforms, or the Corvis ST system. Three of 4 studies agreed that LASIK and/or femtosecond LASIK affect the biomechanical parameters provided by those devices more than PRK and/or laser-assisted subepithelial keratectomy (LASEK). The differences between small-incision lenticule extraction and femtosecond LASIK were more controversial, with no study supporting the hypothesis that femtosecond LASIK leads to fewer changes in biomechanical parameters than small-incision lenticule extraction. The controversy increases in the comparison of small-incision lenticule extraction and PRK and/or LASEK, without any tendency to favor of 1 technique over the other. Other particularities with to regard studies of variants of the same technique are described in Table 1.

Table 1
Table 1:
Studies analyzing corneal biomechanics after laser refractive surgery techniques.

Minimizing Confounding Variables with Clinical Devices

The response of the cornea to an indentation load, similar to the air puff of dynamic Scheimpflug tonometry, depends on the physical composition of the cornea, the IOP, and the corneal thickness.83 To enhance the ability of clinical devices to detect differences between laser refractive surgery techniques, it is essential to minimize the possible effect of corneal thickness and IOP on the biomechanical measurements provided. However, despite the performance of good and well-designed studies in minimizing the impact of confounding variables, such as IOP and corneal thickness, it is still unclear whether differences in the biomechanical properties after small-incision lenticule extraction measured by dynamic Scheimpflug tonometry are biased because the anterior collagen fibers during the loading of the air puff are submitted to compression instead of tension stress.83

Moreover, for continue advancing in the clinical research with the currently available devices, some basic considerations should be considered if biomechanical changes are intended to be evaluated after laser refractive surgery with different techniques. They are as follows:

1. Patients should be measured preoperatively and postoperatively at approximately the same time of day. Although Hon et al.13 found no differences in the tangent modulus with the corneal indentation device as a result if the variation of IOP and CCT during waking hours, Ariza-Gracia et al.84 suggested that with air-puff devices, corneal displacement variations can reach 5% during the day depending on the level of stiffness of the cornea evaluated, with less variability from 10:00 am to 13:00 pm. We reported that the biomechanically corrected IOP of the Corvis ST system better predicted the preoperative IOP in patients having small-incision lenticule extraction when the analysis was applied only to patients measured at approximately the same time of day preoperatively and postoperatively.47

2. Biomechanical parameters should be compared considering their relative change as a function of the removed corneal thickness, especially when using parameters that have been shown to be significantly correlated with corneal thickness.82 Tissue removal in LASIK might be approximately determined with the Munnerlyn formula85; however, in small-incision lenticule extraction, a thickness of 10 to 15 μm should be added, corresponding to the edge thickness. Therefore, there is a slightly greater tissue removal in small-incision lenticule extraction because of this and the quadratic dependency on the diameter of the optical zone.86 The actual amount of removed thickness should be then considered instead of the refractive error treated. We reported that the new stiffness parameter described by Roberts et al.87 and biomechanically corrected IOP of dynamic Corvis ST system were the only 2 parameters for which this correlation with removed corneal thickness was not present.47

3. Exclusion criteria should include any patient under treatment that might have an influence on corneal thickness or IOP because of the possible impact on corneal composition and then on corneal biomechanics.88


We performed an exhaustive analysis of the corneal structure and methods for measuring corneal stiffness to understand the role of corneal composition on biomechanics. The stiffness highly depends on the measurement method used in the laboratory, with great variation between studies that could make the incorporation of this information in biomechanical models difficult.

The role of the corneal layers should be considered as the stiffness relative to the thickness or, in other words, how stiff the layer is considering its thickness in comparison to the total cornea. Under this scenario, Bowman and Descemet layers are stiffer than the anterior stroma, and this greater stiffness is masked when we use methods that evaluate the stiffness of the bulk cornea.

Currently available clinical methods to characterize corneal biomechanics are not able to assess the stiffness of each of the layers of the cornea, and the only option is to measure the bulk cornea. This might be considered as a limitation because of the impact of confounding variables, such as corneal thickness and IOP. According to the peer-reviewed literature, we have defined considerations to minimize the influence of these confounding variables on the results. Even if future studies apply this consideration, we cannot ensure that it will allow clinicians to clarify whether small-incision lenticule extraction is better in terms of corneal biomechanics than other laser refractive surgery techniques. With the currently available clinical devices, there are microstructural changes, such as corneal hydration alterations, stromal expansion, or anterior stromal compression, during the loading stage of the air puff; these changes might also act as confounding variables.

Regarding the more recent advances in corneal biomechanics, the new parameters of the Corvis ST dynamic Scheimpflug tonometer are not correlated with corneal thickness and dynamic corneal densitometry and might be an additional tool in algorithms characterizing corneal biomechanics with the currently available devices.


1.Klein SR, Epstein RJ, Randleman JB, Stulting RD. Corneal ectasia after laser in situ keratomileusis in patients without apparent preoperative risk factors. Cornea. 2006;25:388-403.
2.Roy AS, Dupps WJ Jr. Effects of altered corneal stiffness on native and postoperative LASIK corneal biomechanical behavior: a whole-eye finite element analysis. J Refract Surg. 2009;25:875-887.
3.Roberts CJ, Dupps WJ Jr. Biomechanics of corneal ectasia and biomechanical treatments. J Cataract Refract Surg. 2014;40:991-998.
4.Vinciguerra R, Ambrósio R Jr, Elsheikh A, Roberts CJ, Lopes B, Morenghi E, Azzolini C, Vinciguerra P. (2016). Detection of keratoconus with a new biomechanical index. J Refract Surg, 32, 803-810, Available at:
5.Last JA, Thomasy SM, Croasdale CR, Russell P, Murphy CJ. (2012). Compliance profile of the human cornea as measured by atomic force microscopy. Micron, 43, 1293-1298, Available at:
6.Reinstein DZ, Archer TJ, Randleman JB. (2013). Mathematical model to compare the relative tensile strength of the cornea after PRK, LASIK, and small incision lenticule extraction. J Refract Surg, 29, 454-460, Available at:
7.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.
8.Sachdev G, Sachdev MS, Sachdev R, Gupta H. Unilateral corneal ectasia following small-incision lenticule extraction. J Cataract Refract Surg. 2015;41:2014-2018.
9.Wang Y, Cui C, Li Z, Tao X, Zhang C, Zhang X, Mu G. Corneal ectasia 6.5 months after small-incision lenticule extraction. J Cataract Refract Surg. 2015;41:1100-1106.
10.El-Naggar MT. Bilateral ectasia after femtosecond laser–assisted small-incision lenticule extraction. J Cataract Refract Surg. 2015;41:884-888.
11.Mattila JS, Holopainen JM. Bilateral ectasia after femtosecond laser-assisted small incision lenticule extraction (SMILE). J Refract Surg. 2016;32:497-500.
12.McKee CT, Last JA, Russell P, Murphy CJ. (2011). Indentation versus tensile measurements of Young's modulus for soft biological tissues. Tissue Eng Part B Rev, 17, 155-164, Available at:
13.Hon Y, Wan K, Chen G-Z, Lu S-H, Lam DCC, Lam AKC. Diurnal variation of corneal tangent modulus in normal Chinese. Cornea. 2016;35:1600-1604.
14.De la Torre IM, del Socorro Hernández Montes M, Flores-Moreno JM, Mendoza-Santoyo F. Laser speckle based digital optical methods in structural mechanics: a review. Opt Lasers Eng. 2016;87:32-58.
15.Hon Y, Chen G-Z, Lu S-H, Lam DCC, Lam AKC. High myopes have lower normalised corneal tangent moduli (less “stiff” corneas) than low myopes. Ophthalmic Physiol Opt. 2017;37:42-50.
16.Lam AKC, Hon Y, Leung LKK, Lam DCC. Repeatability of a novel corneal indentation device for corneal biomechanical measurement. Ophthalmic Physiol Opt. 2015;35:455-461.
17.Ko MWL, Leung LKK, Lam DCC, Leung CKS. (2013). Characterization of corneal tangent modulus in vivo. Acta Ophthalmol, 91, e263-e269, Available at:
18.Seiler T, Matallana M, Sendler S, Bende T. Does Bowman's layer determine the biomechanical properties of the cornea? Refract Corneal Surg. 1992;8:139-142.
19.Elsheikh A, Alhasso D, Rama P. Assessment of the epithelium's contribution to corneal biomechanics. Exp Eye Res. 2008;86:445-451.
20.Knox Cartwright NE, Tyrer JR, Jaycock PD, Marshall J. Effects of variation in depth and side cut angulations in LASIK and thin-flap LASIK using a femtosecond laser: a Biomechanical Study. J Refract Surg. 2012;28:419-425.
21.Lombardo M, Lombardo G, Carbone G, de Santo MP, Barberi R, Serrao S. (2012). Biomechanics of the anterior human corneal tissue investigated with atomic force microscopy. Invest Ophthalmol Vis Sci, 53, 1050-1057, Available at:
22.Xia D, Zhang S, Hjortdal J.ϕ, Li Q, Thomsen K, Chevallier J, Besenbacher F, Dong M. Hydrated human corneal stroma revealed by quantitative dynamic atomic force microscopy at nanoscale. ACS Nano. 2014;8:6873-6882.
23.Xia D, Zhang S, Nielsen E, Ivarsen AR, Liang C, Li Q, Thomsen K, Hjortdal J.ϕ, Dong M. The ultrastructures and mechanical properties of the Descement's membrane in Fuchs endothelial corneal dystrophy. Sci Rep. 6. 2016. 23096. Available at:
24.Khaled ML, Helwa I, Drewry M, Seremwe M, Estes A, Liu Y. Molecular and histopathological changes associated with keratoconus. Biomed Res Int 2017. article ID:7803029. Available at:
25.Lewis PN, White TL, Young RD, Bell JS, Winlove CP, Meek KM. (2016). Three-dimensional arrangement of elastic fibers in the human corneal stroma. Exp Eye Res, 146, 43-53, Available at:
26.White TL, Lewis PN, Young RD, Kitazawa K, Inatomi T, Kinoshita S, Meek KM. (2017). Elastic microfibril distribution in the cornea: differences between normal and keratoconic stroma. Exp Eye Res, 159, 40-48, Available at:
27.Bueno JM, Ávila FJ, Artal P. (2016). Second harmonic generation microscopy: a tool for quantitative analysis of tissues. In Stanciu SG, editor., Microscopy and Analysis (pp. 99-119 (Rijeka, Coratia: In Tech). Available at:
28.Hatami-Marbini H, Etebu E. An experimental and theoretical analysis of unconfined compression of corneal stroma. J Biomech. 2013;46:1752-1758.
29.Jastrzebska M, Tarnawska D, Wrzalik R, Chrobak A, Grelowski M, Wylegala E, Zygadlo D, Ratuszna A. New insight into the shortening of the collagen fibril D-period in human cornea. J Biomol Struct Dyn. 2017;35:551-563.
30.Abass A, Hayes S, White N, Sorensen T, Meek KM. Transverse depth-dependent changes in corneal collagen lamellar orientation and distribution. J R Soc Interface. 12. 2015. 20140717. Available at:
31.Quantock AJ, Winkler M, Parfitt GJ, Young RD, Brown DJ, Boote C, Jester JV. (2015). From nano to macro: studying the hierarchical structure of the corneal extracellular matrix. Exp Eye Res, 133, 81-99, Available at:
32.Dias Janice, Ziebarth NM. (2013). Anterior and posterior corneal stroma elasticity assessed using nanoindentation. Exp Eye Res, 115, 41-46, Available at:
33.Benoit A, Latour G, Schanne-Klein M-C, Allain J-M. Simultaneous microstructural and mechanical characterization of human corneas at increasing pressure. J Mech Behav Biomed Mater. 2016;60:93-105.
34.Sloan SR Jr, Khalifa YM, Buckley MR. (2014). The location- and depth-dependent mechanical response of the human cornea under shear loading. Invest Ophthalmol Vis Sci, 55, 7919-7924, Available at:
35.Petsche SJ, Chernyak D, Martiz J, Levenston ME, Pinsky PM. (2012). Depth-dependent transverse shear properties of the human corneal stroma. Invest Ophthalmol Vis Sci, 53, 873-880, Available at:
36.Jhanji V, Chan TCY, Li WY, Lim RR, Yu MCY, Law K, Yi P, Yip YWY, Wang Y, Ng TK, Chaurasia SS, Mohan RR. Conventional versus inverted side-cut flaps for femtosecond laser-assisted LASIK: laboratory and clinical evaluation. J Refract Surg. 2017;33:96-103.
37.Wang X, Li X, Chen W, He R, Gao Z, Feng P. Effects of ablation depth and repair time on the corneal elastic modulus after laser in situ keratomileusis. Biomed Eng Online. 16. 2017. 20. Available at:
38.He M, Wang W, Ding H, Zhong X. Comparison of two cap thickness in small incision lenticule extraction: 100μm versus 160μm. PLoS One. 11. 9. 2016. e0163259. Available at:
39.Spiru B, Kling S, Hafezi F, Sekundo W. (2017). 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, 58, 2591-2595, Available at:
40.Santhiago MR, Smajda D, Wilson SE, Randleman JB. Relative contribution of flap thickness and ablation depth to the percentage of tissue altered in ectasia after laser in situ keratomileusis. J Cataract Refract Surg. 2015;41:2493-2500.
41.Kling S, Spiru B, Hafezi F, Sekundo W. Biomechanical weakening of different re-treatment options after small incision lenticule extraction (SMILE). J Refract Surg. 2017;33:193-198.
42.Ryu I-H, Kim BJ, Lee J-H, Kim SW. Comparison of corneal epithelial remodeling after femtosecond laser–assisted LASIK and small incision lenticule extraction (SMILE). J Refract Surg. 2017;33:250-256.
43.Reinstein DZ, Archer TJ, Gobbe M. Lenticule thickness readout for small incision lenticule extraction compared to Artemis three-dimensional very high-frequency digital ultrasound stromal measurements. J Refract Surg. 2014;30:304-309.
44.Luft N, Ring MH, Dirisamer M, Mursch-Edlmayr AS, Pretzl J, Bolz M, Priglinger SG. Semiautomated SD-OCT measurements of corneal sublayer thickness in normal and post-SMILE eyes. Cornea. 2016;35:972-979.
45.Luft N, Ring MH, Dirisamer M, Mursch-Edlmayr AS, Kreutzer TC, Pretzl J, Bolz M, Priglinger SG. (2016). Corneal epithelial remodeling induced by small incision lenticule extraction (SMILE). Invest Ophthalmol Vis Sci, 57, OCT176-OCT183, Available at:
46.Hatami-Marbini H, Etebu E. Hydration dependent biomechanical properties of the corneal stroma. Exp Eye Res. 2013;116:47-54.
47.Fernández J, Rodríguez-Vallejo M, Martínez J, Tauste A, Salvestrini P, Piñero DP. New parameters for evaluating corneal biomechanics and intraocular pressure after SMILE by Scheimpflug-based dynamic tonometry. J Cataract Refract Surg. 2017;43:803-811.
48.Cook CA, Koretz JF. Methods to obtain quantitative parametric descriptions of the optical surfaces of the human crystalline lens from Scheimpflug slit-lamp images. I. Image processing methods. J Opt Soc Am A Opt Image Sci Vis. 1998;15:1473-1485.
49.Otri AM, Fares U, Al-Aqaba MA, Dua HS. Corneal densitometry as an indicator of corneal health. Ophthalmology. 2012;119:501-508.
50.Patel S, Marshall J, Fitzke FW III. Refractive index of the human corneal epithelium and stroma. J Refract Surg. 1995;11:100-105.
51.Meek KM, Dennis S, Khan S. (2003). Changes in the refractive index of the stroma and its extrafibrillar matrix when the cornea swells. Biophys J, 85, 2205-2212, Available at:
52.Patel S, Alió JL, Pérez-Santonja JJ. (2004). Refractive index change in bovine and human corneal stroma before and after LASIK: a study of untreated and re-treated corneas implicating stromal hydration. Invest Ophthalmol Vis Sci, 45, 3523-3530, Available at:
53.Ní Dhubhghaill S, Rozema JJ, Jongenelen S, Ruiz Hidalgo I, Zakaria N, Tassignon MJ. (2014). Normative values for corneal densitometry analysis by Scheimpflug optical assessment. Invest Ophthalmol Vis Sci, 55, 162-168, Available at:
54.Elsheikh A, Wang D, Brown M, Rama P, Campanelli M, Pye D. Assessment of corneal biomechanical properties and their variation with age. Curr Eye Res. 2007;32:11-19.
55.Reinstein DZ, Archer TJ, Gobbe M, Silverman RH, Coleman DJ. (2008). Epithelial thickness in the normal cornea: three-dimensional display with Artemis very high-frequency digital ultrasound. J Refract Surg, 24, 571-581, Available at:
56.Cennamo G, Forte R, Aufiero B, La Rana A. Computerized Scheimpflug densitometry as a measure of corneal optical density after excimer laser refractive surgery in myopic eyes. J Cataract Refract Surg. 2011;37:1502-1506.
57.Pedersen IB, Ivarsen A, Hjortdal J. (2017). Changes in astigmatism, densitometry, and aberrations after SMILE for low to high myopic astigmatism: a 12-month prospective study. J Refract Surg, 33, 11-17, Available at:˜/media/journals/jrs/2017/1_january/10_3928_1081597x_20161006_04/10_3928_1081597x_20161006_04.pdf.
58.Lazaridis A, Droutsas K, Sekundo W, Petrak M, Schulze S. Corneal clarity and visual outcomes after small-incision lenticule extraction and comparison to femtosecond laser-assisted in situ keratomileusis. J Ophthalmol 2017. article ID:5646390. Available at:
59.Ivarsen A, Fledelius W, Hjortdal J.ϕ. (2009). Three-year changes in epithelial and stromal thickness after PRK or LASIK for high myopia. Invest Ophthalmol Vis Sci, 50, 2061-2066, Available at:
60.Ivarsen A, Hjortdal J. (2012). Seven-year changes in corneal power and aberrations after PRK or LASIK. Invest Ophthalmol Vis Sci, 53, 6011-6016, Available at:
61.Kirwan C, O'Keefe M. (2008). Corneal hysteresis using the Reichert ocular response analyser: findings pre- and post-LASIK and LASEK. Acta Ophthalmol, 86, 215-218, Available at:
62.Kamiya K, Shimizu K, Ohmoto F. Comparison of the changes in corneal biomechanical properties after photorefractive keratectomy and laser in situ keratomileusis. Cornea. 2009;28:765-769.
63.Hassan Z, Modis L Jr, Szalai E, Berta A, Nemeth G. Examination of ocular biomechanics with a new Scheimpflug technology after corneal refractive surgery. Cont Lens Anterior Eye. 2014;37:337-341.
64.Shen Y, Chen Z, Knorz MC, Li M, Zhao J, Zhou X. Comparison of corneal deformation parameters after SMILE, LASEK, and femtosecond laser-assisted LASIK. J Refract Surg. 2014;30:310-318.
65.Pedersen IB, Bak-Nielsen S, Vestergaard AH, Ivarsen A, Hjortdal J. Corneal biomechanical properties after LASIK, ReLEx flex, and ReLEx smile by Scheimpflug-based dynamic tonometry. Graefes Arch Clin Exp Ophthalmol. 2014;252:1329-1335.
66.Wang D, Liu M, Chen Y, Zhang X, Xu Y, Wang J, To C-h Liu Q. Differences in the corneal biomechanical changes after SMILE and LASIK. J Refract Surg. 2014;30:702-707.
67.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.
68.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.
69.Sefat SMM, Wiltfang R, Bechmann M, Mayer WJ, Kampik A, Kook D. Evaluation of changes in human corneas after femtosecond laser-assisted LASIK and small-incision lenticule extraction (SMILE) using non-contact tonometry and ultra-high-speed camera (Corvis ST). Curr Eye Res. 2016;41:917-922.
70.Osman IM, Helaly HA, Abdalla M, Shousha MA. Corneal biomechanical changes in eyes with small incision lenticule extraction and laser assisted in situ keratomileusis. BMC Ophthalmol. 16. 2016. 123. Available at:
71.Wang B, Zhang Z, Naidu RK, Chu R, Dai J, Qu X, Yu Z, Zhou H. (2016). Comparison of the change in posterior corneal elevation and corneal biomechanical parameters after small incision lenticule extraction and femtosecond laser-assisted LASIK for high myopia correction. Cont Lens Anterior Eye, 39, 191-196, Available at:
72.Zhang J, Zheng L, Zhao X, Xu Y, Chen S. (2016). Corneal biomechanics after small-incision lenticule extraction versus Q-value–guided femtosecond laser-assisted in situ keratomileusis. J Curr Ophthalmol, 28, 181-187, Available at:
73.Dou R, Wang Y, Xu L, Wu D, Wu W, Li X. Comparison of corneal biomechanical characteristics after surface ablation refractive surgery and novel lamellar refractive surgery. Cornea. 2015;34:1441-1446.
74.Yıldırım Y, Ölçücü O, Başcı A, Ağca A, Özgürhan EB, Alagöz C, Demircan A, Demirok A. (2016). Comparison of changes in corneal biomechanical properties after photorefractive keratectomy and small incision lenticule extraction. Turk J Ophthalmol, 46, 47-51, Available at:
75.Chen M, Yu M, Dai J. (2016). Comparison of biomechanical effects of small incision lenticule extraction and laser-assisted subepithelial keratomileusis. Acta Ophthalmol, 94, e586-e591, Available at:
76.Al-Nashar HY, Awad AMB. (2017). Comparison of corneal hysteresis and corneal resistance factor after small-incision lenticule extraction and photorefractive keratectomy. Delta J Ophthalmol, 18, 1-6, Available at:
77.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.
78.Shen Y, Zhao J, Yao P, Miao H, Niu L, Wang X, Zhou X. Changes in corneal deformation parameters after lenticule creation and extraction during small incision lenticule extraction (SMILE) procedure. PLoS One. 9. 8. 2014. e103893. Available at:
79.Mastropasqua L, Calienno R, Lanzini M, Colasante M, Mastropasqua A, Mattei PA, Nubile M. Evaluation of corneal biomechanical properties modification after small incision lenticule extraction using Scheimpflug-based noncontact tonometer. Biomed Res Int 2014. article ID:290619. Available at:
80.El-Massry A.A.E.-K, Goweida MBB, Shama A.E.-S, Elkhawaga MHE, Abdalla MF. Contralateral eye comparison between femtosecond small incision intrastromal lenticule extraction at depths of 100 and 160 μm. Cornea. 2015;34:1272-1275.
81.Leccisotti A, Fields SV, Moore J, Shah S, Moore TCB. Changes in ocular biomechanics after femtosecond laser creation of a laser in situ keratomileusis flap. J Cataract Refract Surg. 2016;42:127-131.
82.Fernández J, Rodríguez-Vallejo M, Martínez J, Tauste A, Piñero DP. Corneal thickness after SMILE affects Scheimpflug-based dynamic tonometry. J Refract Surg. 2016;32:821-828.
83.Ariza-Gracia M.Á, Zurita JF, Piñero DP, Rodriguez-Matas JF, Calvo B. Coupled biomechanical response of the cornea assessed by non-contact tonometry. A simulation study. PLoS One. 10. 3. 2015. e0121486. Available at:
84.Ariza-Gracia MA, Piñero DP, Rodriguez JF, Pérez-Cambrodí RJ, Calvo B. (2015). Interaction between diurnal variations of intraocular pressure, pachymetry, and corneal response to an air puff: Preliminary evidence. JCRS Online Case Reports, 3, 12-15, Available at:
85.Chang AW, Tsang AC, Contreras JE, Huynh PD, Calvano CJ, Crnic-Rein TC, Thall EH. Corneal tissue ablation depth and the Munnerlyn formula. J Cataract Refract Surg. 2003;29:1204-1210.
86.Bischoff M, Strobrawa G., 2015. Femtosecond laser keratomes for small incision lenticule extraction (SMILE). In: Sekundo W, editor., Small Incision Lenticule Extraction (SMILE); Principles, Techniques, Complication Management, and Future Concepts. Springer, London, UK, pp. 3-11.
87.Roberts CJ, Mahmoud AM, Bons JP, Hossain A, Elsheikh A, Vinciguerra R, Vinciguerra P, Ambrósio R Jr. Introduction of two novel stiffness parameters and interpretation of air puff induced biomechanical deformation parameters with a dynamic Scheimpflug analyzer. J Refract Surg. 2017;33:266-273.
88.Alnawaiseh M, Zumhagen L, Zumhagen S, Schulte L, Rosentreter A, Schubert F, Eter N, Mönnig G. Corneal densitometry as a novel technique for monitoring amiodarone therapy. Ophthalmology. 2016;123:2294-2299.

Disclosures:None of the authors has a financial or proprietary interest in any material or method mentioned.

© 2018 by Lippincott Williams & Wilkins, Inc.