**Purpose**:
To quantitatively evaluate microdistortions in Bowman's layer and change in corneal stiffness after small incision lenticule extraction (SMILE).

**Methods**:
This was a prospective, longitudinal, and interventional study. Thirty eyes of 30 patients were screened preoperatively and underwent SMILE for treatment of myopia with astigmatism. Visual acuity, refraction, optical coherence tomography (OCT; Bioptigen, Inc., Morrisville, NC) imaging of the layer and air-puff applanation (Corvis-ST, OCULUS Optikgeräte Gmbh, Germany) was performed before and after surgery (1 day, 1 week, and 1 month). The Bowman's Roughness Index (BRI) was defined as the enclosed area between the actual and an ideal smooth layer to quantify the microdistortions. A viscoelastic model was used to quantify the change in corneal stiffness using applanation.

**Results**:
Uncorrected distance visual acuity improved (*P* < 0.001) and refractive error decreased (*P* < 0.0001) after SMILE. BRI increased from preoperative levels (1.81 × 10^{−3} mm^{2}) to 1 week (3.14 × 10^{−3} mm^{2}) after SMILE (*P* < 0.05) and then decreased up to a month (2.43 × 10^{−3} mm^{2}; *P* < 0.05). Increase in the magnitude of the index correlated positively with refractive error (*P* = 0.02). However, corneal stiffness reduced after SMILE (105.86 ± 1.4 N/m versus 97.97 ± 1.21 N/m at 1 month, *P* = 0.001). The decrease in corneal stiffness did not correlate with refractive error (*P* = 0.61).

**Conclusions**:
BRI correlated positively the magnitude of refractive error. However, decrease in corneal stiffness, assessed by air-puff applanation, may not be related to microdistortions after SMILE.

**Translational Relevance**:
An objective method of quantification of Bowman's layer microdistortions using OCT was developed to monitor corneal wound healing and improve lenticule extraction methods.

^{1}In 2011, a new method called small incision lenticule extraction (SMILE) was reported.

^{2}Since then several studies have demonstrated comparable refractive outcomes between SMILE and LASIK, with significantly less dryness and inflammation.

^{3–5}Theoretical biomechanical advantage of SMILE over LASIK was analyzed in recent studies.

^{6,7}Clinical significance and utility of this biomechanical advantage is yet to be proven (e.g., assessment of ectasia risk).

^{8–10}There are several factors related to the induction of microdistortions (e.g., ease of separation and extraction of lenticule from the stroma, corneal biomechanics, refractive error).

^{11}In this study, a new index, named Bowman's Roughness Index (BRI), was defined to quantify the microdistortions in the central cornea following SMILE. It was hypothesized that change in BRI would be greater in eyes with greater refractive error. Therefore, correlation between change in BRI and change in refractive error was assessed. BRI quantified the smoothness of the anterior edge of the Bowman's layer and was used for location-specific analyses, without the need for peripheral corneal imaging.

^{12}A mathematical method using a linear spring-dashpot model to estimate corneal stiffness from air-puff applanation was used for biomechanical analyses.

^{8}The same examiner performed the OCT imaging of all the eyes and at all time points. At each time point, the scan was performed along the nasal-temporal direction. The location of the 2-D scan was set at each follow-up such that it subdivided visually the en face projection image of the cornea in to nearly two equal halves. Further, at least three 2-D scans were acquired in quick succession at each follow-up time point.

^{13}After segmentation, a third order polynomial was curve fit to the segmented pixels of the edge (green line in Fig. 1, top). A third order polynomial was chosen since a paraxial second order equation can be used to represent a meridian of most normal corneas.

^{13}With a third order polynomial, the second order gradient necessary for curvature calculations can be captured better. Since the same order of the polynomial was used before and after SMILE, the spatial resolution of curve fitting method was also the same before and after SMILE. A schematic overlay of the segmented edge of Bowman's layer and third order polynomial curve fit is shown in Figure 1 bottom. The shaded areas represent the areas enclosed between the microdistortions and curve fit. If

*A*

_{1},

*A*

_{2}, …,

*A*were n enclosed areas, BRI was defined as the summation:

_{n}^{14}to quantify the corneal deformation independent of the extra-ocular tissue deformation. The spring and dashpot model was used to describe the deformation amplitude (reported by Corvis-ST), which was a sum of the cornea and extra-ocular tissue deformation in response to the force applied by the air-puff (

*F*

_{air-puff}).

^{14}The previous study was not able to assess the stiffness of the cornea independently.

^{14}In this study, the model was improved further by using a combination of a spring, having stiffness Kc (in N/m), and a parallel network, having stiffness Kg (in N/m) and viscosity μg (in Pa.sec). This improved model is shown in Figure 2. The mathematical description that linked

*F*

_{air-puff}and the corneal deformation was as follows:

*u*

_{1}was the deformation amplitude waveform reported by Corvis-ST.

*u*

_{2}was the deformation of the extra-ocular tissues only. The term

*du*

_{2 }/

*dt*accounted for the viscous delay in the deformation of the extra-ocular tissues. Thus, corneal deformation was given by

*u*

_{1}−

*u*

_{2}. By using equation (2), the effect of SMILE on the change in deformation of both the cornea and extra-ocular tissues could be assessed. By measuring the deformation of the segmented anterior edge of the cornea near its endpoints,

*u*

_{2}was calculated.

^{15}The stiffness of the cornea varies nonlinearly with applied stress or force.

^{16}Therefore, Kc was represented as a function of applied air-puff pressure (

*P*

_{air-puff}):

*F*

_{IOP}) of the intraocular pressure (IOP) in vivo. During applanation, there was a net force being applied, which can be mathematically represented as

*F*

_{IOP}+

*F*

_{air-puff}. By treating the in situ configuration of the cornea as the baseline, the corneal deformation during applanation was simply due to

*F*

_{air-puff}(i.e.,

*F*

_{IOP}+

*F*

_{air-puff}minus

*F*

_{IOP}). By combining equations (2) and (3) into equation (4), a unique quantification of the nonlinear corneal stiffness and extra-ocular stiffness plus viscosity was achieved.

*F*

_{air-puff}=

*P*

_{air-puff}× Applanation Area and

*t*was the current applanation time. Applanation area was approximated as a circle of diameter 2.5 mm.

^{16}Equation (2) was solved for all time points of the applanation period simultaneously. Least squares technique and finite difference method was used to obtain Kc, Kg, and μg. In Corvis-ST,

*P*

_{air-puff}varied from 0 to 180 mmHg. Since

*P*

_{air-puff}varied during applanation, Kc also varied. After

*β*and

*α*were computed from equation (4), Kc was computed at all

*P*

_{air-puff}ranging from 0 to 180 mmHg in steps of 10 mmHg. Mean corneal stiffness (

*P*

_{air-puff}. In equation (4), mass inertia of the cornea was neglected as it had negligible impact on the computed values of Kc and

^{14,16}Both Kc and

^{17}area under the corneal deformation curve,

^{17}and area under the extra-ocular tissue deformation curve.

*t*-test and repeated measures analysis of variance with Bonferroni adjustment. Correlation between the ratio of post- to preoperative BRI and change in spherical equivalent was assessed. Similarly, the ratio of post- to preoperative BRI and change in UDVA was assessed. The ratio of post to preoperative BRI would be greater than 1, if microdistortions increased after SMILE and vice versa. The above correlations were also assessed for the ratio of post- to preoperative

^{18}Coefficient of variation, expressed as percentage, was calculated as the ratio of standard deviation to mean value of BRI from the three images. All variables were presented as mean ± SEM, where SEM was the standard error of the mean. A two-sided

*P*-value < 0.05 was considered statistically significant. Statistical analyses were performed with MedCalc v16.4.3 (MedCalc Software bvba, Ostend, Belgium).

*P*< 0.0001). Mean programmed lenticule thickness was 90.68 ± 22.99 μm. Mean CCT was 507.5 ± 4.4 μm and 436.4 ± 7.14 μm before and 1 month after SMILE, respectively (

*P*< 0.0001). Mean IOP was 16.7 ± 0.26 and 15.9 ± 0.27 before and 1 month after SMILE, respectively (

*P*= 0.32). Mean UDVA (in LogMAR) was 1.06 ± 0.11 and 0.05 ± 0.01 before and 1 month after SMILE, respectively (

*P*< 0.0001). Mean CDVA (in LogMAR) was 0.03 ± 0.01 and 0.07 ± 0.02 before and 1 month after SMILE, respectively (

*P*= 0.34). All eyes had unchanged CDVA at 1 month (

*P*> 0.05).

^{−3}± 6.9 × 10

^{−5}mm

^{2}, 2.56 × 10

^{−3}± 3.7 × 10

^{−5}mm

^{2}, 3.14 × 10

^{−3}± 8.5 × 10

^{−5}mm

^{2}, and 2.43 × 10

^{−3}± 8.5 × 10

^{−5}mm

^{2}before, 1 day after, 1 week after, and 1 month after SMILE, respectively (Fig. 3). The mean ratio of post- to preoperative BRI at 1 day, 1 week, and 1 month after SMILE was 1.40 ± 0.04, 1.64 ± 0.07 and 1.34 ± 0.05, respectively. Mean BRI before surgery was significantly different from mean BRI at day 1 (

*P*< 0.0001), week 1 (

*P*< 0.0001), and month 1 (

*P*< 0.0001). Mean BRI at week 1 was significantly different from mean BRI at day 1 (

*P*< 0.0001) and month 1 (

*P*< 0.0001) . The coefficient of variation of BRI was 0.1%. The mean coefficient of regression of the third order polynomial curve fit on segmented Bowman's layer edge was 0.99 ± 1 × 10

^{−3}. The ratio of post- to preoperative BRI correlated positively with postoperative decrease in spherical equivalent refractive error (

*r*= +0.51,

*P*= 0.02) and with postoperative improvement in UDVA (

*r*= +0.38,

*P*= 0.03).

*du*

_{2}/

*dt*to model the viscous deformation of the extra-ocular tissues. Figure 5 (top) shows a comparison of Kc versus applanation pressure (symbols) before and 1 month after surgery. The two continuous lines (solid and dashed) in Figure 5 (top) are regressions using equation (3) applied to before and after SMILE data. From Figure 5 (bottom), it is evident that Kc reduced after surgery at all applanation pressures.

*P*= 0.001). However, the ratio of post- to preoperative

*r*= +0.13,

*P*= 0.61) and with postoperative improvement in UDVA (

*r*= +0.02,

*P*= 0.72) 1 month after SMILE. In these correlations, the same eyes were evaluated before and after surgery. Thus, age and IOP were not potential confounders and change in corneal thickness was highly correlated to attempted refractive correction by design.

*P*= 0.001), time of first applanation (7.53 ± 0.03 msec versus 7.23 ± 0.06 msec,

*P*= 0.001), time of second applanation (21.27 ± 0.06 msec versus 21.60 ± 0.08 msec,

*P*= 0.001), and time at which highest concavity (14.98 ± 0.08 msec versus 15.20 ± 0.07 msec,

*P*= 0.001) was attained. The area under the deformation amplitude curve (13.33 ± 0.22 mm.msec versus 14.73 ± 0.32 mm.msec,

*P*= 0.001) and area under the corneal deformation curve (9.94 ± 0.25 mm.msec versus 11.28 ± 0.33 mm.msec,

*P*= 0.001) were significantly higher after SMILE indicating increased compliance of the cornea. However, area under extra-ocular tissue deformation curve, Kg and μg were similar before and 1 month after SMILE (

*P*= 0.73, 1.0, and 0.73, respectively) indicating that SMILE did not alter extra-ocular tissue deformation.

^{12}Both LASIK and SMILE were designed to preserve the Bowman's layer. In SMILE, microdistortions may be a cause of potential biomechanical instability after the surgery.

^{8}The earlier study on microdistortions after SMILE used visual examination of the Bowman's layer only to quantify the microdistortions as local peaks.

^{8}An OCT device was used that had a digital resolution of 5 μm over a scan area of 6 mm.

^{8}This study improved on the earlier study by using a fully automated image segmentation method to define BRI as a quantifier of microdistortions using high resolution OCT images over a 3-mm scan area. BRI increased and then decreased after SMILE similar to index M.

^{8}However, an interesting finding was that BRI had a nonzero magnitude before SMILE, which contradicts the assumption of a smooth Bowman's layer preoperatively in the earlier study.

^{8}Thus, the relative impact of the microdistortions in Bowman's layer on visual quality needs to be assessed with respect to preoperative visual quality in future studies.

^{8,10}This study showed that BRI increased up to 1 week and then decreased contrary to the earlier reports.

^{8,10}The index may serve as a useful metric to quantitatively analyze corneal healing in an individual eye after SMILE. It may also serve as a metric for the surgeons to improve the surgical technique of lenticule separation and extraction to minimize the microdistortions. Surgeons may also modify the femtosecond laser parameters to deliver optimum energy, which may further reduce the magnitude of the index. Further in eyes where the index does not decrease longitudinally after week 1, there may be unwanted optical complications, which need to be evaluated further.

^{11}and extraction; (b) corneal biomechanics

^{11}; (c) mismatch between the surface area of the anterior and posterior surface of the lenticule

^{19}; and (d) relaxation of the anterior lamellae due to severance of the transverse fibers in the anterior stroma.

^{20}This would cause the anterior lamella to distort acutely and lead to a temporary increase in BRI. It is not clear how these phenomena can be dissociated from each other. Therefore, these phenomena require further study. In this study, a new method of quantification of corneal stiffness (Kc) was also introduced.

^{21}A study with Ocular response analyzer (ORA) reported decrease in corneal hysteresis (CH) and corneal resistance factor (CRF) after SMILE, but the decrease in magnitude was similar to measurements obtained after LASIK.

^{22}When the myopic refractive error was > −6 D, the decrease in CH, CRF, and other ORA waveform variables in SMILE eyes were lower than the decrease measured in LASIK eyes.

^{23}Another study reported that time of first applanation and deformation amplitude were similar after SMILE and LASIK.

^{24}None of these studies actually reported corneal stiffness nor was the magnitude of any variable delineated from the extra-ocular tissue deformation. Further studies are needed to evaluate

^{16,25}Advanced biomechanical models have shown that high air-puff pressure induced high mechanical stresses in the cornea, which can cause the collagen fibers to be recruited.

^{16,25}Under such a scenario, it becomes complex to segregate the linear (matrix modulus) and nonlinear (collagen modulus) contribution to corneal stiffness by the model used in this study (equation 3).

^{16,25}Though corneal stiffness was assumed to be a nonlinear function of applanation pressure, better mathematical representation may be needed to capture the nonlinearity of corneal stiffness in future studies. This may enable better biomechanical characterization of the tissue in proportion to the amount of tissue removed and emphasize some biomechanical contribution to the acute increase in BRI.

^{12}However, the low coefficient of variation of BRI and concordance with past studies supported the conclusions from this study. Improved methods

^{26}and devices

^{27}for extraction of the lenticule may also reduce the magnitude of BRI after SMILE. This needs to be evaluated further.

**R. Shroff**, None;

**M. Francis**, None;

**N. Pahuja**, None;

**L. Veeboy**, None;

**R. Shetty**, None;

**A. Sinha Roy**, None

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