Modern Refractive Lenticular Femtosecond Laser Corneal Surgery for Correction of Myopia and Myopic Astigmatism

*Maja Bohač, Mateja Jagić, Doria Gabrić, Lucija Zerjav, Smiljka Popović Suić and Iva Dekaris*

#### **Abstract**

Small-incision lenticule extraction (SMILE) is becoming the procedure of choice in treating myopia and myopic astigmatism. With great comparability in terms of visual outcome with the femtosecond laser-assisted in situ keratomileusis (FsLASIK) procedure, the method is characterized by better patient satisfaction and less postoperative dry eye induction. Moreover, it has the advantages of better eye surface stability and biomechanical strength compared to FS-LASIK. The method is now globally accepted among refractive surgeons. Patients suitable for the procedure must meet criteria for keratorefractive procedures generally. Our current clinical experience suggests that the lenticule extraction procedure delivers promising refractive results in terms of predictability, efficacy, and safety.

**Keywords:** lenticule extraction, SMILE, LASIK, femtosecond laser, myopia, refractive surgery

#### **1. Introduction**

LASIK is the most commonly used corneal refractive surgical procedure to treat ametropia worldwide [1, 2]. Compared to earlier microkeratome variant, femtosecond laser-assisted laser in situ keratomileusis (FsLASIK) provides precise flap creation achieving better morphological stability. Even so, flap related complications, induction of higher-order aberrations, as well as biomechanical corneal instability are still present [3–5]. When ablating stroma between 10 and 30% of depth, LASIK is estimated to reduce the tensile strength of the stroma by about 35% [6–8].

In recent years, the lenticle extraction method has gradually become popular as a potential alternative for traditional LASIK and PRK procedures. The femtosecond laser-assisted corneal procedure known as small-incision lenticule extraction (SMILE) was first described by Sekundo et al. in 2008 [9] and after larger series followed, the procedure became clinically available in 2011. Using an ultrashort pulse laser system, procedure delineates contour of tissue volume that needs to be excised in order to accomplish refractive correction. It is a flapless procedure where two precise intrastromal planar sections are created by femtosecond laser forming the lenticule that is manually extracted through a superiorly (nasal/temporal) placed small 2–5 mm length incision after careful dissection from the pocket. When removing intrastromal lenticule, corneal shape is altered without Bowman's membrane disruption, therefore procedure offers biomechanical stability of the cornea, especially in treatment of higher levels of myopia and astigmatism [6, 9]. Since there is no flap creation, lenticule extraction procedure rules out formerly known risks in LASIK procedures, such as flap creation complication and dislocation [6–8, 10–12].

#### **2. Small-incision lenticule extraction**

Recently, two emerging alternatives have been introduced in the market: CLEAR using Z8 by Ziemer, Switzerland [13–15] and SmartSight using ATOS by SCHWIND eye-tech-solutions, Germany [16, 17].

CLEAR (Corneal Lenticule Extraction for Advanced Refractive correction) treatment is an additional treatment program from FEMTO LDV Z8, which is a multipurpose laser (cataract surgery, corneal transplantation, flap creation for LASIK, tunnel/pocket creation for inlays, arcuate incision). In the technical aspect, it works under pulse energies below 100 nJ with a repetition rate above 20 MHz and a spiral raster laser pattern [15]. Besides eye-tracking guided centration, the laser system has intraoperative OCT, which is predominantly used for cases of corneal transplantation, tunnel creation for inlays, and cataract surgery. The ability to create two side-cuts potentially reduces the learning curve for less experienced surgeons since tunnels guide directly to the anticipated plane of the lenticule (anterior or posterior) [13, 14].

SmartSight treatment profile by SCHWIND ATOS, without using side cuts, does not have a minimal thickness (as in SMILE) and includes lenticule tapering toward the periphery, a refractive progressive transition zone, to achieve minimal refractive regression by reducing epithelial remodelling [17]. The laser works in the plasmamediated ablation regime, slightly above the threshold for laser-induced optical breakdown, and below the photodisruption regime. It works under pulse energy below 100 nJ, with spot spacing >4 μm and track spacing ~3 μm, with a repetition rate up to 4 MHz, and an asymmetric scanning pattern. The laser system has cyclotorsion control, where it incorporates a video-based eye registration from the diagnostic image along with an eye-tracker guided centration to improve the predictability of the astigmatic corrections (**Figure 1**).

When forming and extracting lenticule in SMILE procedure from anterior half of the stroma, the tensile corneal strength is reduced by 55% while this effect is less profound in the case of lenticule formed in deeper stromal layers [7]. Therefore, extent of changes in biomechanical corneal properties is depending on the lenticule volume and location (depth) in the cornea [7, 8, 18].

The differences between SMILE and FsLASIK are potential sources that could influence the final refractive and overall optical performance of the eye after surgery by inducing unwanted astigmatism. Moreover, there has been an increasing awareness and understanding of the change in higher-order optical aberrations following corneal refractive surgery over the last two decades. It is widely accepted *Modern Refractive Lenticular Femtosecond Laser Corneal Surgery for Correction of Myopia… DOI: http://dx.doi.org/10.5772/intechopen.105159*

#### **Figure 1.**

*Video-based eye registration (cyclotorsion control) from the diagnostic image along with an eye-tracker guided centration inside the Schwind ATOS.*

that higher-order aberrations should be either maintained after surgery at preoperative levels or modified to improve the overall optical and visual performances of the eye [19–22].

#### **2.1 Indications**

Indications for lenticule extraction adhere to the guidelines for all corneal refractive surgical procedures [23].

Prior to the decision if the patient meets the criteria for refractive surgery complete ophthalmologic examination is needed. The examination includes uncorrected distance visual acuity, corrected distance visual acuity, manifest and cycloplegic refraction, corneal tomography, corneal and ocular aberrometry, tonometry, slit lamp, and dilated funduscopic examination.

Patients with stable refraction, myopia up to −10.00 D, and astigmatism up to 5 D or SE up to 12.50 D with sufficient corneal thickness and normal tomography are considered eligible candidates. As the most common contraindications would be considered: abnormal corneal topography, signs of progressive preoperative corneal thickness <480 μm or calculated residual stromal bed thickness <275 μm, scotopic pupil wider than 7.5 mm, dry eye, inflammation of ocular adnexa and periocular area, active autoimmune disease or connective tissue diseases.

#### **2.2 Surgical procedure**

The surgery is performed under topical anesthesia. After standardized cleaning with 2.5% povidone-iodine and sterile draping, an eyelid speculum is used to keep the eye open. After positioning patient on the surgical bed, and connecting the surgical cone (disposable interface) to suction ports, the patient is instructed to fixate the light target when the eye is aligned with the cone. When centration coincides with the visual axis and there is visible matching of corneal vertex (from corneal tomography), suction can be applied, followed by treatment initialization and laser ablation immediately after complete suction is achieved. Caps can be 100–150 μm thick and incisions are usually positioned superotemporal with width between 2.5 and 3.2 mm. The optical zone selected depends on the scotopic pupil size and attempted correction. Automatic suction release occurs upon completion of lenticule formation. After identifying both anterior and posterior lenticular surface with thin blunt spatula, separation of the lenticule and extraction through the side cut is performed. In order to detect any residual material or tears, lenticule tissue is thoroughly inspected.

#### **2.3 Clinical results**

In two separated studies we were evaluating outcomes, safety, efficacy, and predictability of small-incision lenticule extraction procedures performed at different laser systems. For treating myopia and myopic astigmatism. In first study, ReLEx SMILE procedure was performed on VisuMax from Zeiss, with comparing refractive and visual outcomes with FsLASIK procedure performed on VisuMax for flap creation and Schwind Sirius 750s for excimer ablation at one-year period. The second study was conducted on Atos for Schwind eye-tech-solutions, performing SmartSight lenticule extraction procedure. During a three-month follow up refractive, wavefront, and topographic outcomes were evaluated. The results of both studies are presented below.

#### *2.3.1 Smile vs FS LASIK*

#### *2.3.1.1 Astigmatism*

There was a significant difference in the magnitude of astigmatism between the SMILE and the FsLASIK groups one year after the surgery [24]. Postoperatively, the amount of any astigmatism revealed by subjective refraction results from a combination of the treated astigmatism coupled with the effects of postoperative healing. In the SMILE group, we encountered more residual manifest astigmatism compared with the FsLASIK group. Vector analysis of astigmatism did not show any difference between the two groups prior to surgery. Both mean J0 and J45 values were slightly lower in the FsLASIK group in comparison with the SMILE group indicating that astigmatism is less prevalent after FsLASIK (**Figures 2**–**5**). This indication is further supported by the slightly higher surgically induced astigmatism values following SMILE compared with FsLASIK. Both techniques of vector analysis show that individual differences between the vector value pre- and postoperative were strongly correlated with the preoperative vector values. This is encouraging indicating that for individual cases the postoperative astigmatic vector values can be predicted with precision using the preoperative astigmatic value in both SMILE and FsLASIK. The Thibos' method of vector analysis [25], clearly points out that within the SMILE

*Modern Refractive Lenticular Femtosecond Laser Corneal Surgery for Correction of Myopia… DOI: http://dx.doi.org/10.5772/intechopen.105159*

#### **Figure 2.**

*Change in J0 vector value in each case treated with SMILE procedure. Significant association between the change in J0 (ΔJ0) and preop J0 value presented as linear regression. The least squares line: ΔJ0 = 1.015J0 + 0.040 (R = .861, N = 89, P < .001).*

#### **Figure 3.**

*Change in J45 vector value in each case treated with SMILE procedure. Significant association between the change in J45 (ΔJ45) and preop J45 value is presented as linear regression. The least squares line: ΔJ45 = 1.082J45 + 0.019 (R = .792, N = 89, P < .001).*

group the correlation between ΔJ45 and preoperative J45 (0.792) tended to be lower in comparison with the counterpart in the FsLASIK group (0.924). This suggests that the precision of controlling a change in astigmatism with FsLASIK is superior compared with SMILE.

Turning to the mean target and surgically induced astigmatism values, in the FsLASIK group the target and surgically induced astigmatism values were nearly identical. This can only occur when the residual astigmatism is almost totally nullified. In the SMILE group, the mean surgically induced astigmatism was significantly higher than the target induced astigmatism (−0.57 D and −0.41 D respectively). This indicates that the SMILE procedure tends to overcorrect and even induce astigmatism. The centration is different for both SMILE and FsLASIK procedures, wherein SMILE, procedure is centred on the visual axis and FsLASIK is centred on the corneal vertex. In the event that the intersection of the corneal surface and the visual axis does not coincide with corneal apex, a smaller amount of unwanted astigmatism may be predicted [26]. Given the procedure centration on corneal vertex, this should more likely occur after FsLASIK. Other factors must be responsible for the increased astigmatism after SMILE.

#### **Figure 4.**

*Change in J0 vector value in each case treated with FsLASIK procedure. Significant association between the change in J0 (ΔJ0) and preop J0 value is presented as linear regression. The least squares line: ΔJ0 = 0.952J0 − 0.005 (R = .921, N = 92, P < .001).*

#### **Figure 5.**

*Change in J45 vector value in each case treated with FsLASIK procedure. Significant association between the change in J45 (ΔJ45) and preop J45 value. Is presented as linear regression. The least squares line: ΔJ45 = 0.962J45 − 0.002 (R = .923, N = 92, P < .001).*

In **Figures 6** and **7** vector diagrams demonstrate the unwanted induced astigmatism that occurred in some cases, where surgically induced astigmatism values appear more dispersed from the central point in the SMILE group compared with the FsLASIK group. Of a total of 89 eyes treated with SMILE procedure, at one-year postop we found three cases where astigmatism increased by 0.75 D and 10 cases where astigmatism increased by 0.50 D. The results of astigmatic corrections after SMILE differ among authors. Some authors reported no significant differences in postoperative astigmatism between SMILE and FsLASIK, and no significant increases in astigmatism [27, 28]. On the other hand, others reported more favourable outcomes after FsLASIK [29]. In addition, Kunert et al. [30] and Qian et al. [31] reported up to 1.00 D overcorrection of astigmatism and an overall undercorrection of high astigmatism after the SMILE procedure. None of the available reports mentions or discusses cases where astigmatism becomes manifest during the postop period. Unexpected postoperative astigmatism following a SMILE procedure could, to some extent, be explained by insufficient intraoperative centration, decentration of refractive lenticule ablation profile relative to the visual axis, dislodged fragments from the lenticule (although we did not encounter any), and the impact of any epithelial hyperplasia

*Modern Refractive Lenticular Femtosecond Laser Corneal Surgery for Correction of Myopia… DOI: http://dx.doi.org/10.5772/intechopen.105159*

#### **Figure 6.**

*Polar diagram showing target and surgically induced astigmatic values for the SMILE group. The targeted surgically induced astigmatism data points are shown as empty circles and filled dots respectively, with semicircles from −2 DC to 0 (central point) in 0.5DC steps and from 0°to 90°and 180° (right to left) in 30° steps.*

#### **Figure 7.**

*Polar diagram showing target and surgically induced astigmatic values for the FsLASIK group. The target and surgically induced astigmatism data points are shown as empty circles and filled dots respectively, with semicircles from −2 DC to 0 (central point) in 0.5DC steps and from 0°to 90°and 180° (right to left) in 30° steps.*

during the postoperative period. The lower incidence of astigmatism in the FsLASIK group may be linked to the advanced eye-tracking devices designed to compensate for any cyclotorsional effect and eye movements during the excimer laser ablation [32]. For the SMILE procedure centration was achieved manually after instructing the patient to fixate a blinking green light and locking the laser procedure about the visual axis using suction ports [6]. Slight tilting of the lenticule, in association with any decentration, would further contribute to any unexpected postop astigmatism.

#### *2.3.1.2 Higher order aberrations (HOAs)*

At one-year postop, significant differences between the two groups were found for all higher-order aberrations (HOAs). Coma, trefoil, and spherical aberration (SA) tended to be lower in the FsLASIK group compared with SMILE. In the SMILE group, a significant increase in postoperative SA was revealed while there were no differences for coma or trefoil. For the FsLASIK group, significant changes in coma and trefoil were observed but not for SA. The changes in the mean values of some HOAs were statistically significant, but their clinical relevance is open to question. **Figures 8**–**13** show there are highly significant correlations between changes in coma, trefoil, and SA in individual cases when compared with preoperative values. The results of these linear regressions can be used to predict the likely change in an HOA we can expect to encounter after surgical intervention on an individual case-by-case basis. For example, **Figures 8** and **9** show preoperative values for coma below 0.15 μm are not expected to change greatly after either SMILE or FsLASIK. The magnitude of coma is predicted to fall by approximately 0.14 μm after either procedure when the preop value is in the region of 0.30 μm. Turning to **Figures 12** and **13**, when the preoperative SA is of the order +0.10 μm the postoperative value should reduce by nearly 50% after either SMILE or FsLASIK. However, if the preoperative was −0.10 μm the predicted postoperative value after SMILE is +0.010 μm and +0.002 μm after FsLASIK. Thus, when refractive surgery is the desired option, it would be advisable to treat highly aberrated eyes with FsLASIK.

Our results conflict with other published reports. Wu et al. [33] reported the magnitude of all higher-order aberrations increased after either SMILE or FsLASIK. However, after surgery, the average values for SA and horizontal coma were lower in the SMILE group compared with the FsLASIK group. Lin et al. [34] also reported increases in all ocular higher-order aberrations after both SMILE and FsLASIK but, with significantly lower values of SA and coma after the SMILE procedure. Others report that contrast sensitivity improved after SMILE implying more favorable high order aberration profiles [6, 28]. Our experience does not support previous reports because we found SA increased after SMILE with coma and trefoil reduction after the FsLASIK. The differences between some reports may be due to several factors such as geographical factors. For example, the work of Wu et al. [33] Lin et al. [34], and Liu et al. [35] were based in Southeast Asia, and the work by Ganesh et al. [36] was based in India. Our results were obtained predominantly from Caucasian eyes. The differences in the outcomes between studies can result from a variety of reasons including genetic factors. However, results based on studies in other territories are concordant with the findings from Asia [6, 27, 37].

#### *2.3.1.3 Conclusion*

In conclusion, our experience with both procedures yields satisfactory visual acuity results. However, FsLASIK offers a marginally improved outcome as indicated by the residual high order aberrations and astigmatism.

#### **Figure 8.**

*Change in coma value in each case treated with SMILE procedure. Significant association between the change in coma (y) and preop coma (x) value presented as linear regression. The least squares line: y = 0.847x − 0.094 (R = .562, N = 89, P < .001).*

*Modern Refractive Lenticular Femtosecond Laser Corneal Surgery for Correction of Myopia… DOI: http://dx.doi.org/10.5772/intechopen.105159*

#### **Figure 9.**

*Change in coma value in each case treated with FsLASIK procedure. Significant association between the change in coma (y) and preop coma (x) value presented as linear regression. The least squares line: y = 0.688x − 0.034 (R = .743, N =92, P < .001).*

#### **Figure 10.**

*Change in trefoil value in each case treated with SMILE procedure. Significant association between the change in trefoil (y) and preop trefoil (x) value presented as linear regression. The least squares line: y = 0.793x − 0.057 (r = .515, N = 89, P < .001).*

#### **Figure 11.**

*Change in trefoil value in each case treated with FsLASIK procedure. Significant association between the change in trefoil (y) and preop trefoil (x) value presented as linear regression. The least squares line: y = 0.741x − 0.027 (R = .618, N = 92, P < .001).*

#### **Figure 12.**

*Change in spherical aberration (SA) value in each case treated with SMILE procedure. Significant association between the change in SA (y) and preop SA (x) value presented as linear regression. The least squares line: y = 0.832x − 0.027 (R = .779, N = 89, P < .001).*

#### **Figure 13.**

*Change in spherical aberration (SA) value in each case treated with FsLASIK procedure. Significant association between the change in SA (y) and preop SA (x) value presented as linear regression. The least squares line: y = 0.428x + 0.004 (R = .545, N = 92, P < .001).*

#### *2.3.2 SmartSight lenticule extraction on SCHWIND ATOS*

#### *2.3.2.1 Efficacy and safety*

The short-term changes at three-month follow-up of the efficacy and safety of lenticule extraction treatments using the SmartSight profile were analyzed.

The main difference and advantage of SCHWIND ATOS and SmartSight at this time of development is the low energy delivered to the cornea since the laser works slightly above the threshold for the laser-induced optical breakdown with energies between 80 and 100 nJ. In addition, the laser also possesses features such as cyclotorsion control and eye-tracker guided centration. Lack of the abovementioned technologies was one of the main drawbacks for the surgeons in transition from excimer laser-based procedures to lenticular extraction and was often emphasized as the main shortcoming in the treatment of a higher amount of astigmatism.

The analysis revealed promising results after the treatment. The unaided vision was expected to improve overall. Most of the outcome measures showed significant *Modern Refractive Lenticular Femtosecond Laser Corneal Surgery for Correction of Myopia… DOI: http://dx.doi.org/10.5772/intechopen.105159*

improvement compared to the preoperative status. The improvement in visual acuities was significant (**Figures 14**–**16**).

#### *2.3.2.2 Refractive outcome and keratometry*

An excellent refractive outcome was observed in terms of manifest refraction, but this was only partly confirmed by the objective refraction and the topographical changes. This suggests that manifest refraction may be more forgiving in terms of exactly determining the accuracy of the treatments, but at the same time, UDVA is the main driver for patient satisfaction. CDVA loss of two lines occurred only in a single eye (**Figure 17**).

At three months after the surgery, for the change in wavefront refraction or corneal keratometry 68% of eyes were within 0.5D from target (**Figures 18** and **19**), with 63% and 58% of eyes within 0.5D from target astigmatism for wavefront refraction and corneal keratometry, respectively (**Figures 20** and **21**). The angle of error was within 25° from the attempted astigmatism axis in 60% and 42% of the eyes for wavefront refraction and corneal keratometry, respectively (**Figure 22**).

#### **Figure 14.**

*Standard graphs for reporting outcomes in laser vision correction: Cumulative Snellen Visual acuity.*

**Figure 15.** *Difference between UDVA and CDVA.*

**Figure 16.** *Accuracy of MRSEq to intended target (D).*

**Figure 17.** *Change in Snellen lines of CDVA.*

**Figure 18.** *Wavefront refraction vs. attempted SEQ (D).*

*Modern Refractive Lenticular Femtosecond Laser Corneal Surgery for Correction of Myopia… DOI: http://dx.doi.org/10.5772/intechopen.105159*

**Figure 19.** *Accuracy of SEQ to intended target (D).*

**Figure 20.** *Scattergram of achieved change in wavefront refraction vs attempted correction of the astigmatism.*

#### **Figure 21.**

*Percentage of eyes within intended target of postoperative astigmatism.*

**Figure 22.** *Angle of error from attempted astigmatism axis.*

Previous publications, like recent studies by Sideroudi et al. [38] and Ganesh et al. [39], suggest that undercorrection in SMILE can be associated with forward shifting of posterior corneal surface that leads to posterior curvature steepening. Opposite to our findings, some works report lower changes observed in keratometries than in refraction. This could be due to using simpler models and not considering difference in refractive indices (used for keratometry) and actual refractive corneal index, the effect of central tissue removal on refraction, or effect of the vertex distance on planned refraction (spectacle plane to corneal plane). Taking this into consideration, The SmartSight profile involves tapering the lenticule toward the edge to achieve smoothing of the transition zone from treated to the untreated cornea in an attempt to reduce the biomechanical changes and epithelial remodelling on the edge of the treatment. It is determined as refractive progressive transition zone, similar to the one used in the SCHWIND AMARIS ablation profiles, ranging from 0.2 mm to 0.8 mm, determined by corneal curvature gradient and also induced by correction.

In this study at three months, the scattergram of achieved change in wavefront refraction vs. achieved change in keratometry readings of the SEQ showed a very good correlation (**Figure 23**), with 75% eyes within 0.75D (**Figure 24**).

**Figure 23.** *Scattergram of achieved change in wavefront refraction vs achieved change in keratometry readings of the SEQ.*

*Modern Refractive Lenticular Femtosecond Laser Corneal Surgery for Correction of Myopia… DOI: http://dx.doi.org/10.5772/intechopen.105159*

#### *2.3.2.3 Corneal and ocular wavefront (aberrations)*

Corneal aberrations slightly increased after the treatment, but the change of ocular aberrations was very minor and non-significant (**Figures 25** and **26**). This may confirm the relatively neutral behaviour in terms of aberrations reported from other refractive lenticule extraction techniques, as well as be indicative of adequate centration. SA was less positive when measured with ocular aberrations than for corneal aberrations. Postoperative corneal SA increased more than ocular SA, remaining stable at three months follow-up. The RMS higher-order aberrations increased, both for corneal and ocular aberrations, with corneal aberrations showing systematically higher inductions HOA than the ocular counterparts (**Figure 27**). Corneal topography and aberrometry revealed an induction of positive SA associated with an increase in the RMS higher-order aberrations.

#### *2.3.2.4 Conclusion*

A limitation of this work is that only 50 eyes of 31 consecutive patients completed the three-months follow-up and were included for analyses. Another limitation is the retrospective nature of the study. Several confounding factors may be argued in our review, we have considered both eyes of the patients.

#### **Figure 24.**

*Agreement of change in SEQ between wavefront refraction and keratometry readings.*

#### **Figure 25.**

*Preoperative and postoperative corneal wavefront aberrations.*

#### **Figure 26.**

*Preoperative and postoperative ocular wavefront aberrations.*

#### **Figure 27.**

*Change in postoperative HOAs from preoperative baseline.*

These clinical results are presented based on a three-month clinical follow-up, which is considered minimal for establishing notable clinical significance in refractive surgery. In literature, however, there are results with shorter follow-ups reported for determining the time-course of visual recovery. Studies with longer follow-ups and a greater number of clinical cases will shed light on the durability of performance and allow for further nomogram refinement to improve outcomes.

#### **3. Conclusions**

When achieving excellent clinical visual outcomes in refractive surgery, it is often difficult to demonstrate that novel procedures like lenticule extraction are superior to the standardized LASIK procedure. Up to this point, comparable outcomes in terms of refractive predictability, efficacy, and safety at minimum of three months were found, also theoretical biomechanical advantage of lenticule extraction over Fs. LASIK was described in the literature. Still, a longer learning curve for the surgeons, more frequent suction loss occurrence, prolonged visual recovery, and complicated enhancement treatment have been observed when comparing lenticule extraction to traditional Fs. LASIK. Aforementioned requires further enhancement and refinement of the procedure. Given the increasing clinical use over the last decade,

*Modern Refractive Lenticular Femtosecond Laser Corneal Surgery for Correction of Myopia… DOI: http://dx.doi.org/10.5772/intechopen.105159*

lenticule extraction treatment has continuously been optimized and improved through multiple iterations. Introduction of new laser platforms such as CLEAR and SmartSight, with different energy levels, repetition rates and spot spacing has significantly improved visual outcomes. Precisely, combining high frequency and low energy profile for smooth cutting results in lenticule surface that could provide better clinical performance and optical quality for each laser platform. SmartSight treatment includes even a refractive progressive transition zone tapering the lenticule towards the edge of the transition zone to reduce epithelial remodelling and, therefore refractive regression. Additionally, eye tracking, the centring according to pupil, vertex or defined offset by surgeon, and the video-based cyclotorsion compensation are particularly helpful in astigmatism correction. More studies involving a larger number of patients with longer follow-up will evaluate if new profiles and laser platforms can improve already achieved good visual outcomes after lenticule extraction.

#### **Conflict of interest**

The authors declare no conflict of interest.

#### **Appendices and nomenclature**


#### **Author details**

Maja Bohač\*, Mateja Jagić, Doria Gabrić, Lucija Zerjav, Smiljka Popović Suić and Iva Dekaris University Eye Hospital Svjetlost, Zagreb, Croatia

\*Address all correspondence to: maja.bohac@svjetlost.hr

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

*Modern Refractive Lenticular Femtosecond Laser Corneal Surgery for Correction of Myopia… DOI: http://dx.doi.org/10.5772/intechopen.105159*

#### **References**

[1] Schmack I, Auffarth G, Epstein D, Holzer M. Refractive surgery trends and practice style changes in Germany over a 3-year period. Journal of Refractive Surgery. 2010;**26**:202-208

[2] Lundström M, Manning S, Barry P, et al. The European Registry of Quality Outcomes for Cataract and Refractive Surgery (EUREQUO): A database study of trends in volumes, surgical techniques and outcomes of refractive surgery. Eye and Vision. 2015;**2**:8. DOI: 10.1186/ s40662-015-0019-1

[3] von Jagow B, Kohnen T. Corneal architecture of femtosecond laser and microkeratome flaps imaged by anterior segment optical coherence tomography. Journal of Cataract & Refractive Surgery. 2009;**35**:35-41

[4] Binder PS. Flap dimensions created with IntraLase FS laser. Journal of Cataract & Refractive Surgery. 2004;**30**:26-32

[5] Randleman JB, Woodward M, Lynn MJ, Stulting RD. Risk assessment for ectasia after corneal refractive surgery. Ophthalmology. 2008;**115**:37-50

[6] Reinstein DZ, Archer TJ, Gobbe M. Small incision lenticule extraction (SMILE) history, fundamentals of a new refractive surgery technique and clinical outcomes. Eye and Vision. 2014;**1**:3. DOI: 10.1186/s40662-014-0003-1

[7] 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. Journal of Refractive Surgery. 2013;**29**:454-460

[8] Randleman JB, Dawson DG, Grossniklaus HE, et al. Depth-dependent cohesive tensile strength in human donor corneas: Implications for refractive surgery. Journal of Refractive Surgery. 2008;**24**:S85-S89

[9] 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. British Journal of Ophthalmology. 2011;**95**:335-339

[10] Vestergaard AH, Grauslund J, Ivarsen AR, Hjortdal JO. Central corneal sublayer pachymetry and biomechanical properties after refractive femtosecond lenticule extraction. Journal of Refractive Surgery. 2014;**30**:102-108

[11] Agca A, Ozgurhan EB, Demirok A, et al. Comparison of corneal hysteresis and corneal resistance factor after small incision lenticule extraction and femtosecond laser-assisted LASIK: A prospective fellow eye study. Contact Lens & Anterior Eye. 2014;**37**:77-80

[12] Wu D, Wang Y, Zhang L, et al. Corneal biomechanical effects: Smallincision lenticule extraction versus femtosecond laser-assisted laser In Situ keratomileusis. Journal of Cataract & Refractive Surgery. 2014;**40**:963-970

[13] Mehta JS. CLEAR for advanced refractive correction. CRS Today Europe. February 2021

[14] Izquierdo L Jr, Sossa D, Ben-Shaul O, Henriquez MA. Corneal lenticule extraction assisted by a low-energy femtosecond laser. Journal of Cataract & Refractive Surgery. 2020;**46**(9):1217-1221

[15] Fuest M, Mehta JS. Advances in refractive corneal lenticule extraction. Taiwan Journal of Ophthalmology. 2021;**11**(2):113-121

[16] KR, Arba-Mosquera S. Three-month outcomes of myopic astigmatism correction with small incision guided human Cornea treatment. Journal of Refractive Surgery. 2021;**37**(5):304-311. DOI: 10.3928/1081597X-20210210-02. Epub 2021 May 1

[17] Tsai PS, Blinder P, Migliori BJ, et al. Plasma-mediated ablation: An optical tool for submicrometer surgery on neuronal and vascular systems. Current Opinion in Biotechnology. 2009;**20**(1):90-99

[18] Abahussin M, Hayes S, Knox Cartwright NE, et al. 3D collagen orientation study of the human cornea using X-ray diffraction and femtosecond laser technology. Investigative Ophthalmology & Visual Science. 2009;**50**:5159-5164

[19] Smadja D, Santhiago MR, Mello GR, et al. Corneal high order aberrations after myopic wavefront-optimized ablation. Journal of Refractive Surgery. 2013;**29**:42-48

[20] Schallhorn SC, Farjo AA, Huang D, et al. Wavefront-quided LASIK for the correction of primary myopia and astigmatism: A report by the american academy of ophthalmology. Ophthalmology. 2008;**115**:1249-1261

[21] Benito A, Redondo M, Artal P. Temporal evolution of ocular aberrations following laser in situ keratomileusis. Ophthalmic and Physiological Optics. 2001;**31**:421-428

[22] Kouassi FX, Blaizeau M, Buestel C, et al. Comparison of lasik with femtosecond laser versus Lasik with mechanical microkeratome: Predictability of flap depth, corneal

biomechanical effects and optical aberrations. Journal Français d'Ophtalmologie. 2012;**35**:2-8

[23] Sutton G, Lawless M, Hodge C. Laser in situ keratomileusis in 2012: A review. Clinical and Experimental Optometry. 2014;**97**:18-29

[24] Bohac M, Koncarevic M, Dukic A, Biscevic A, Cerovic V, Merlak M, et al. Unwanted astigmatism and high-order aberrations one year after excimer and femtosecond corneal surgery. Optometry and Vision Science. 2018 Nov;**95**(11):1064-1076. DOI: 10.1097/ OPX.0000000000001298

[25] Thibos LN, Horner D. Power vector analysis of the optical outcome of refractive surgery. Journal of Cataract & Refractive Surgery. 2001;**27**(1):80-85. DOI: 10.1016/s0886-3350(00)00797-5

[26] Charman WN. Unwanted astigmatism in lenses with a concentric variation in sagittal power. American Journal of Optometry and Physiological Optics. 1982;**59**:997-1001

[27] Zhang J, Wang Y, Chen X. Comparison of moderate- to highastigmatism corrections using wavefront-guided laser In Situ keratomileusis and small-incision lenticule extraction. Cornea. 2016;**35**:523-530

[28] Reinstein DZ, Carp GI, Archer TJ, Gobbe M. Outcomes of small incision lenticule extraction (SMILE) in low Myopia. Journal of Refractive Surgery. 2014;**30**:812-818

[29] Chan TC, Ng AL, Cheng GP, et al. Vector analysis of astigmatic correction after small-incision lenticule extraction and femtosecond-assisted LASIK for low to moderate myopic astigmatism. British Journal of Ophthalmology. 2016;**100**:553-559

*Modern Refractive Lenticular Femtosecond Laser Corneal Surgery for Correction of Myopia… DOI: http://dx.doi.org/10.5772/intechopen.105159*

[30] Kunert KS, Russmann C, Blum M, Sluyterman VLG. Vector analysis of myopic astigmatism corrected by femtosecond refractive lenticule extraction. Journal of Cataract & Refractive Surgery. 2013;**39**:759-769

[31] Qian Y, Huang J, Zhou X, Wang Y. Comparison of femtosecond laser smallincision lenticule extraction and laserassisted subepithelial keratectomy to correct myopic astigmatism. Journal of Cataract & Refractive Surgery. 2015;**41**:2476-2486

[32] Arba Mosquera S, Merayo-Lloves J, de Ortueta D. Clinical effects of pure cyclotorsional errors during refractive surgery. Investigative Ophthalmology & Visual Science. 2008;**49**:4828-4836

[33] Wu W, Wang Y. The correlation analysis between corneal biomechanical properties and the surgically induced higher-order aberrations after small incision lenticule extraction and the femtosecond laser in situ keratomileusis. Journal of Ophthalmology. 2015;**2015**:758196. DOI: 10.1155/2015/758196

[34] Lin F, Xu Y, Yang Y. Comparison of the visual results after SMILE and femtosecond laser-assisted LASIK for myopia. Journal of Refractive Surgery. 2014;**30**:248-254

[35] Liu M, Chen Y, Wang D, et al. Clinical outcomes after SMILE and femtosecond laser-assisted LASIK for myopia and myopic astigmatism: A prospective randomized comparative study. Cornea. 2016;**35**:210-216

[36] Ganesh S, Gupta R. Comparison of visual and refractive outcomes following femtosecond laser assisted LASIK with SMILE in patients with myopia and myopic astigmatism. Journal of Refractive Surgery. 2014;**30**:590-596

[37] Sekundo W, Gertnere J, Bertelmann T, Solomatin I. One-year refractive results, contrast sensitivity, high-order aberrations and complications after myopic small-incision lenticule extraction (ReLEx SMILE). Graefe's Archive for Clinical and Experimental Ophthalmology. 2014;**252**:837-843

[38] Sideroudi H, Lazaridis A, Messerschmidt-Roth A, Labiris G, Kozobolis V, Sekundo W. Corneal irregular astigmatism and curvature changes after small incision lenticule extraction: Three-year follow-up. Cornea. 2018;**37**(7):875-880. DOI: 10.1097/ICO.0000000000001532

[39] Ganesh S, Patel U, Brar S. Posterior corneal curvature changes following refractive small incision lenticule extraction. Clinical Ophthalmology. 2015;**9**:1359-1364. DOI: 10.2147/OPTH. S84354

## When LASIK Goes Wrong or LASIK Complications Dilemmas

*Fanka Gilevska, Maja Bohač, Smiljka Popović Suić and Mateja Jagić*

#### **Abstract**

Laser in situ keratomileusis (LASIK) is one of the most commonly performed refractive surgical procedures. During the last two decades, surgical procedure has evolved, but still, there are several intraoperative and postoperative complications possible. Every young LASIK surgeon spends most of the reading time on LASIK complications. They are not frequent, but you have to know precisely what to do when they happen. This chapter should be a guide, based on literature and experience, on how to deal with intraoperative, early postoperative, and late postoperative complications. This chapter will include managing irregular flaps, buttonholes, and free flaps. The treatment scheme for DLK, epithelial ingrowth, and PISK, and when is the time for flap re-lifting. How frequent should be patients' visits not to miss the complication on time? When is the right time for LASIK reoperation? Post LASIK corneal ectasia and how to perform cross-linking over LASIK. Young surgeons need precise guidelines, not just theoretical treatment options to achieve optimal visual outcomes after LASIK procedure.

**Keywords:** LASIK, complication, DLK, PISK, epithelial ingrowth, ectasia

#### **1. Introduction**

Refractive surgery has made great strides over the last two decades. Technological advances have not only been made at the level of keratorefractive surgery, but also in cataract surgery-the introduction of femtosecond lasers, small incision surgery, and presbyopia-correcting IOLs. LASIK is currently the most commonly performed surgical procedure in refractive surgery. Nowadays, postoperative visual acuity less than 20/20 after refractive surgery has become unacceptable given the growing patients' demands for perfect vision and the fact that the vast majority of patients have 20/20 vision achieved with spectacle or contact lens correction preoperatively. Complications in keratorefractive surgery are extremely rare, and serious side effects occur in less than 0.4% of cases. This chapter will present an overview of all known complications of the LASIK keratorefractive procedure with a recommendation for their management.

#### **2. LASIK complications**

#### **2.1 Preoperative complications**

#### *2.1.1 Anesthesia*

Corneal refractive procedures are performed with topical anesthetic drops (0.5% propacaine, 0.5% tetracaine, and 0.4% oxybuprocaine). Preoperative cleaning of the operative region consists of application of Iodine 5% in the conjunctival fornices for 15 seconds. Both the anesthetic and the iodine may cause epithelial weakening, punctate erosions, or irregular corneal surface. (238) Care about the amount of anesthetic and Iodine used prior to the procedure is essential for the protection of the epithelium. Use of viscous artificial tears during the procedure may interfere with the work of microkeratome and should be avoided [1].

#### *2.1.2 Eyelashes, foil, speculum*

Securing the operative surface with transparent adhesive foil over the eyelashes, selection of the appropriate speculum providing enough space for the microkeratome, and choice of the proper microkeratome for the given eye anatomy is very important in creating regular flaps [1].

#### *2.1.3 Conjunctiva*

Adequate examination of the whole anterior segment, conjunctiva, limbal region, and fornices is very important precondition for successful surgery. Irregularities in the limbal region, scleral elevations, nevus, and tumor prominence in the region of conjunctiva, limbus, or fornices may cause irregular vacuum suction, pseudosuction, and potential vacuum loss which may result in irregular flap due to improper lamellar incision [1].

#### **2.2 Intraoperative complications**

#### *2.2.1 Microkeratome-related complications*

Automated microkeratome creates a precise cut on the cornea which represents the flap. It consists of an oscillation blade attached to a head and both work with independent motors (one for the oscillation of the blade, other for the movement forward and backward). The surgeon chooses adequate rings for the different diameters and steepness of the cornea, the thickness of the flap (from 90 to 120 microns), hinge position, and its diameter [2].

#### *2.2.1.1 Incomplete or irregular corneal flap*

The incidence of incomplete flap is 0.3−1.2% [3]. Incomplete flap occurs when the microkeratome is stopped before the planned hinge position. Stopping of microkeratome most often occurs due to collisions with eyelids and eyelashes, speculum and/ or foil, and due to suction (vacuum) loss during passage. The cause can also be of a mechanical nature-a defect in the dissection head (knife) or in the motor unit of the microkeratome [1, 4, 5]. Irregular flaps often result in lack of enough space for laser

*When LASIK Goes Wrong or LASIK Complications Dilemmas DOI: http://dx.doi.org/10.5772/intechopen.107924*

ablation, also they carry the risk of profound epithelial ingrowth which can result in corneal scarring in the visual axis or even flap melting.

*What shall we do?*

Every irregular flap has its own irregular bed underneath. If we leave the flap untouched, smooth healing will result and best corrected visual acuity achieved. If we ablate the bed under the irregular flap, then we create an inadequate match for the flap, and it can result in higher order aberrations and loss of best corrected visual acuity. Flap which has only peripheral irregularities, with a diameter larger than intended ablation area (OZ), procedure can be continued with careful flap reposition, and BSCL is case with epithelial defects.

In a highly irregular and thin flap (usually created by a lamellar cut at or above the Bowman's layer) with an inadequate stromal bed, Bowman membrane remains in the central zone or larger in diameter, the procedure is aborted, and re-treatment is postponed for 3–6 months with setting larger and deeper flap cut then initial [1, 4]. When Bowman membrane remains out of the central zone and is small in diameter, treatment can be continued with additional antimetabolite application (Mytomycine C) for 15 s to prevent the epithelial ingrowth. Surface procedures (PRK) after LASIK can increase the risk for corneal haze formation, but in cases where irregular flap is small, and hinge is positioned in ablation area (OZ), LASIK procedure needs to be aborted and surface ablation is preferred retreatment procedure within 3 months [3].

#### *2.2.1.2 Perforated (buttonhole) flap*

The incidence of perforated flap (buttonhole) is 0.1−0.6%, and for too thin flap 0.1−0.4% [6]. Flap perforation occurs when the blade of the microkeratome enters the corneal surface-Bowman membrane and epithelium during the passage, usually in the central part of the flap (**Figure 1**). Too thin flaps occur when the blade of the dissection head does not penetrate deep enough into the cornea but stays close to the surface. Perforated flaps are more common in steep corneas (>46.0 D), and inadequately

#### **Figure 1.**

*Intraoperative finding in case of buttonhole flap. Visible central area of Bowmann membrane remains after the flap lift.*

#### **Figure 2.**

*Post operative finding after reponed flap. In this case procedure was aborted - flap was reposition.*

achieved vacuum that causes poor adhesion of the cornea and microkeratome blade, also in flat and small corneas where corneal suction puts cutting plane below the blade [7, 8]. It can also be mechanical in nature due to uneven cutting speed in manual microkeratome, blunt blades, weak blade oscillations, and due to mechanical damage to the blade of the microkeratome dissection head. Perforated flaps are one with the worst visual outcome compared to other intraoperative complications, usually resulting in irregular astigmatism and epithelial ingrowth [1, 7, 8].

*What shall we do?*

When procedure results in a perforated flap, procedure is aborted, and retreatment is planned after minimum of 3 months, preferably surface ablation (**Figure 2**). In case of LASIK retreatment, a flap with larger diameter and greater thickness should be set [3, 6, 9].

#### *2.2.1.3 Free flap (free cap)*

The incidence of free flaps is 0.1−1.0%. The size of the flap depends on the volume of the cornea protruding above the vacuum ring. In the case of protrusion of a small amount of tissue, a free flap is formed. Free flaps are more common in flat corneas with keratometric values <41.0 D, in an insufficient vacuum, when selecting a too small vacuum ring, or in inadequately adjusted microkeratome stoppers [1].

*What shall we do?*

Adequate cap repositioning on the stromal bed, air dried for at least 3−4 minutes and bandage contact lens placed over for the next few days is crucial for the best visual outcomes. The patient should stay in hospital and be rechecked within 1−2 hours for flap position and its adherence to stromal bed. Dislodging or flap folds that may result from strong eyelid pressure should be treated immediately [1]. In case of excessively edematous flap that tends to dislocate, 10-0 nylon sutures should be used [4]. In case of intraoperative flap loss, procedure is aborted, and after epithelization, refractive error (usually hyperopic shift) can be managed with contact lens or flap reconstruction [10].

#### *2.2.1.4 Corneal perforation*

Penetration into the anterior chamber, that is, entry into the anterior chamber with full corneal thickness, may occur during lamellar dissection or even excimer laser photoablation. Perforations can range from simple corneal perforations to perforations with iris and lens damage with or without loss of vitreous. Perforation can occur on extremely thin corneas, in old corneal scars, ulcers, or after previous refractive surgery [1, 11]. Cases with corneal perforation usually have poor visual outcomes due to scar formation and recurrent epithelial ingrowth in perforated plane [12].

*What shall we do?*

If corneal perforation occurs during flap creation, suction should be immediately stopped. Larger perforation requires surgical repair with suturing under sterile conditions, while small perforations can be managed by flap repositioning and BSCL.

#### *2.2.1.5 Decentered flap*

Thin and irregularly decentered flaps can occur during flap formation with both microkeratome or femtosecond laser. The causes are multifactorial and include poor positioning (centering) of the vacuum ring, too low achieved vacuum on the cornea, poor corneal lubrication, poor quality of the blade, pre-existing corneal pathology or microkeratome malfunction [13].

#### *What shall we do?*

Since there is likely an unexpected visual outcome after performing centered ablation in a case of decentered flap, it is advised to abort the procedure.

#### *2.2.2 Femtosecond-related complications*

The femtosecond laser is a solid-state Nd: Glass laser that works near the infrared spectrum at a wavelength of 1053 nm and produces ultrashort pulses lasting 10−15 s. The laser is based on the principle of nonlinear absorption (corneal tissue is transparent to infrared laser radiation of moderate intensity and without absorption) and the principle of photoionization (laser-induced optical break), which leads to photodisruption. Small tissue volumes are vaporized with the formation of cavitation gas bubbles that gradually disperse into the surrounding tissue and consist of carbon dioxide and water [14–16]. Flap formation is today the most common application of femtosecond lasers, where during clinical practice the superiority of femtosecond lasers over mechanical microkeratomes is slowly indicated in terms of reducing the incidence of intraoperative complications and the ability to personalize switch parameters (diameter, thickness, lateral incision, and hinge) [15, 16].

#### *2.2.2.1 Opaque bubble layer (OBL)*

The formation of cavitation bubbles in the lamella between the flap and the stroma, which are directed to the peripheral specially designed pockets, is a standard process of flap formation. In the case of their passage into the deeper stromal layers, or even into the anterior chamber, their confluence occurs, and an opaque layer is formed which interferes with the excimer laser eye tracking system and takes up to several hours to resorb. The penetration of the bubbles into the anterior chamber

occurs due to the migration of cavitation bubbles through the 14 piscleral, schlemm canal, and trabecular meshwork into the anterior chamber [17]. Risk factors are thick cornea, small flap diameter, hard docking technique, and low laser frequency or energy [18, 19]. This complication has become very rare since the reduced vacuum pressure on the eye, reduced energy, and increased speed of femtosecond lasers [17, 20–22]. Higher order aberration (HOA) induction, especially trefoil, was reported in cases with OBL [23, 24].

*What shall we do?*

The presence of OBL suggests flap adhesion so it is advised to perform flap dissection carefully. In case of OBL persistence after flap lift, it will temporarily preclude pupillary tracking for excimer laser ablation. Therefore, waiting for a few minutes and allowing it to disappear is advised. When smaller cavitation bubbles appear in AC, excimer laser treatment can be performed by disabling automatic pupil tracking and proceeding the treatment with manual tracking. Prophylaxis: Setting a larger flap diameter flap and preferring the soft docking technique can reduce the risk of OBL occurrence [18, 19].

#### *2.2.2.2 Vertical gas breakthrough (VBG)*

Vertical gas breakthrough (VGB) occurs in the presence of corneal scar or abnormality in the Bowman's layer when the gas dissects vertically towards the stroma or epithelium [25]. When cavitation bubbles penetrate the corneal subepithelial space incomplete flaps or even buttonhole flaps may form while breaching the epithelial layer results in epithelial defect. Bubbles can also penetrate the space between the cornea and the *applanation* lens, preventing laser-treating the cornea. This leads to the formation of tissue bridges and makes it difficult or sometimes impossible to separate the flap from the adjacent stroma. Incidence of VBG is 0.03−0.13% according to the literature [25, 26].

#### *What shall we do?*

When the VGB appears, the femtosecond laser treatment should be continued to avoid a partial flap. After assessing the position of the VGB within the flap, further actions are considered: *when* VGB is affecting the visual axis or ahead of the advancing edge of the flap, the flap should not be lifted, and surgery should be aborted [26].

#### *2.2.3 Photoablation-related (excimer laser ablation related) complications*

#### *2.2.3.1 Decentered ablation*

Centered (over the pupil zone) ablation is crucial for optimal visual outcome, so every deviation in ablation position compromises the visual outcome [4]. Decentration of the ablation zone can occur due to the movement of the laser beam before the excimer laser ablation itself and due to the eye movement during the excimer laser ablation [27].

Decentration is more common in the correction of larger refractive errors (longer excimer laser ablation allows more eye movements), and in patients with poor uncorrected visual acuity who fix the target point even worse due to additional image blur due to corneal dehydration.

During surgery, the decentralized ablation zone may go unnoticed and result in irregular astigmatism and consequent poor visual acuity, dysphotopsia (glare, halo),

#### **Figure 3.**

*Decentered ablation after myopic excimer profile.*

and monocular diplopia. Usually, it can be presented as asymmetric corneal contour in topography (one side steepening, other side flattening) (**Figure 3**). Decentration can be graded as mild (0−0.5 mm), moderate (0.5−1.0 mm) and severe (>1.0 mm). The magnitude of symptomatic decentration and consequent vision problems varies from patient to patient [1, 27, 28].

*What shall we do?*

When highly decentered ablation is noticed, with large amount of HOA induction, temporarily miotics can reduce dysphotopsia. After 3 months, customized ablation profiles should be used for retreatment: wavefront- or topo-guided PRK or LASIK procedure [29].

#### *2.2.3.2 Central island*

Central islands are diagnosed by corneal topography and are defined as central steep areas of unablated cornea within the treatment zone, defined by their size and keratometric power (>2 mm and > 3D) (**Figure 4**). According to the literature, central island can be considered in every steep corneal zone that affects visual acuity and induces visual disturbances [4, 30]. Central islands are extremely rare in flying spot lasers and can be caused by excimer laser factors (gas dynamics, acoustic corneal shock waves made by laser beams, temporal degradation of laser optics), factors affecting uniform excimer laser delivery like fluid accumulation in the central corneal zone (uneven corneal hydration), and by corneal healing [31]. Central islands cause irregular astigmatism, dysphotopsia (halo, glare, ghost images), loss of best corrected visual acuity, decrease in contrast sensitivity, and monocular diplopia [1, 32].

#### *What shall we do?*

It is advised to wait for at least 6 months for stabilization of corneal topography and refractive status since vast majority of central island cases regress spontaneously (up to 80%). If there is a retreatment procedure required, wavefront- or topo-guided ablation profile needs to be planned, since irregular and complex corneal topography [33]. In cases of extremely irregular topography and risk of ending with questionable results of retreatment, rigid-gas permeable lenses can be used for correction.

#### **Figure 4.** *Central island in patient with buttonhole flap.*

#### *2.2.4 General introperative complications*

#### *2.2.4.1 Epithelial defect*

Epithelial defects are usually caused by the passage of microkeratome over the dry corneal surface or over the epithelium loosened by excessive use of anesthetic drops prior to surgery. Also, a higher risk occurs in patients with history of recurrent erosions, epithelial basement membrane dystrophy (EBDM), drying of the flap, and iatrogenic trauma with surgical instruments [34, 35]. Epithelial defect can be accompanied by stromal oedema and inadequate flap adherence, which increases the risk of inflammatory response as DLK, even epithelial ingrowth [36].

#### *What shall we do?*

In case of smaller epithelial defects, frequent use of artificial tears, preferably conservative-free postoperatively is recommended with higher dose of topical corticosteroids in the next few postoperative days, primarily to prevent development of DLK. For larger defects (3 or more mm) bandage soft contact lens needs to be applied to ensure smooth epithelial healing.

#### *2.2.4.2 Interface debris*

Interlamellar contamination (debris) may consist of connective and skin epithelial cells, Meibomian gland secretions, talc from the gloves, sponge fibers, metallic particles from microkeratome, and eyelash [4] (**Figure 5**). Interface debris should be carefully differentiated from an infectious or inflammatory reaction. However, impurities can support infectious or sterile inflammation of the cornea and cause mechanical disturbances in vision when placed on the visual axis [1, 37].

#### *What should we do?*

In most cases, debris does not induce inflammation since it is biodegradable, but it should be observed. However, if there is any suspicion of an inflammatory reaction or large amount of debris covering the visual axis, causing significant visual disturbances, it should be managed with flap lift and thorough irrigation [38].

**Figure 5.** *Interface debris visible at 1st postoperative day.*

#### **2.3 Postoperative complications**

#### *2.3.1 Early postoperative complications*

#### *2.3.1.1 Flap striae*

Flap striae occur in 0.03−3.5%, according to the literature [39] and are usually observed the next day after the surgery at the slit-lamp examination, best in retroillumination or with fluorescein staining at cobalt-blue light (**Figure 6**). In cases where flap is edematous, epithelial microstriae can present within 7 days postoperatively. Striae can be classified as micro- and macrostriae. Microstriae are irregularities in epithelial layer, where macrostriae result as full-thickness flap-folds. AT higher risk are cases with high refractive error ("tenting" effect due to the flap and stromal bed

**Figure 6.** *Vertical flap striae at 1st postoperative day without flap dislocation.*

contour mismatch), misalignment during repositioning, excessive manipulation of the flap during surgery, and flap contracture [3, 4, 40].

*What shall we do?*

Flap striae involving visual axis (inducing irregular astigmatism and optical aberrations) should be treated. When microstriae are presented early after the surgery, gentle stroking in a perpendicular way (flap sliding technique) with wet surgical sponge is sufficient [41]. Macrostriae must be managed with flap re-lift, stroking with surgical sponge on both stromal and epithelial side of the flap, and then careful flap repositioning. Fixed striae and flap-folds often present with epithelial hyperplasia, therefore epithelium and stromal bed debridement are necessary along with flap lift, repositioning, and stroking.

#### *2.3.1.2 Flap dislocation*

Dislocation of the flap most commonly occurs in the first 24 hours after surgery before epithelial healing of the lamellar incision occurs (**Figure 7**). However, dislocations are possible several months after the procedure, usually after ocular trauma (**Figure 8**). Flap dislocation is considered an emergency and should be treated immediately to prevent folds and epithelial ingrowth. Patients present with sudden onset blurred vision, often associated with pain in the early postoperative period, the most common cause is mechanical due to lid squeezing, forceful blinking, and rubbing of eyes. Larger diameter flaps, thinner, and those with a small hinge are more susceptible to movement. In some cases, after repositioning the flap, DLK, interface haze, or epithelial ingrowth can occur [1, 42, 43].

#### *What shall we do?*

Dislodged flap needs to be managed with flap lift, debridement of stromal bed and stromal side of the flap for possible epithelium (preventing ingrowth), interface irrigation, and flap repositioning. Careful flap handling, soft stroking, and meticulous edge drying are of great importance. BSCL is often applied, and patient is rechecked after half an hour to confirm the flap position and edge adherence [35, 44].

#### **Figure 7.** *Dislodged flap due with associated vertical striae due to eye rubbing at 1st postoperative day.*

#### **Figure 8.**

*Late flap dislocation 3 months after LASIK procedure due to blunt eye trauma. Patient presented 2 hours after the trauma occurred.*

#### *2.3.1.3 Residual refractive error (under- or overcorrection)*

Residual refractive error has been reported in up to 50% of LASIK cases [45]. Hypocorrection is the most common complication after primary LASIK and is usually diagnosed within the first few weeks after surgery. Hypercorrections are more common after repeated procedures and in elderly patients due to slightly dehydrated cornea (>50 years). Hypo- and hypercorrections are associated with excimer laser ablation algorithm, inaccurate nomograms, age, height of refractive error [45–48], and even environmental factors can affect the amount of tissue ablation depth (temperature, humidity, and atmospheric pressure) [49]. Additionally, cyclotorsion from erect to supine position and poor centration of eye during laser ablation can cause postoperative astigmatism [50].

#### *What shall we do?*

After confirmed refractive and topography stabilization, re-lift with LASIK or PRK enhancement can be done. There is a slight risk of epithelial defects postoperatively and epithelial ingrowth in case of flap re-lift [45, 51].

#### *2.3.1.4 Diffuse lamellar keratitis (DLK)*

Diffuse lamellar keratitis (DLK) is a diffuse sterile inflammation of the lamella between the flap and the stroma (interface). It has been reported in 0.13% to 18.9% of cases [52, 53]. Inflammation may occur within 24 hours or be delayed for several days after the procedure. The course of inflammation is variable, it is possible to gradually reduce, increase or persist the inflammation. Etiological DLK is an allergic or toxic reaction caused by debris left in the lamellae—tears, mucus, corneal epithelial cells, connective tissue or skin, Meibomian gland secretion, glove powder, metal particles or wax from knives, leukocytes or blood from the pannus. An immune response to a temperature-resistant toxin from a sterilizer is also possible [36, 54–59].

Another etiology of DLK is related to the use of femtosecond lasers and photodisruption caused by microscopic tissue injury enhanced by inflammatory mediators from the surface of the eye. DLK was much more common in older models of

femtosecond high-energy lasers. Today, only mild transient lamellar keratitis is seen on the periphery of the flap associated with slightly higher energies required for the formation of lateral incisions [36, 58, 59].

Symptoms include discomfort, mild to moderate pain, foreign body sensation, tearing, and light-scattering, A typical lamellar infiltrate is composed of white granular opacities limited to the lamella, without epithelial defects and reactions in the anterior chamber, while conjunctival injection can be present. DLK is divided into four stages or degrees by Linebarger et al. (I degree mild, IV degree melting of the flap) for the purpose of appropriate treatment in a timely manner and prognosis (**Figures 9** and **10**) [1, 60].

#### *What shall we do?*

When presented at grade 1 or 2, an intensive topical steroid is necessary and recheck within next 24−48 hours is crucial for early identification of cases progressing to grade 3. Early flap lift and irrigation of interface with intensive topical steroids in grade 3 should reduce the risk of progression to stage 4. There are some recommendations for introducing peroral Doxycycline in addition to standard treatment regime for advanced grades. Even though, usually there is no major benefit of any intervention after progression to grade 4 [60].

#### *2.3.1.5 Central toxic keratopathy (CTK)*

CTK is a rare acute, non-inflammatory central corneal opacification that occurs within days of uncomplicated LASIK or PRK. Incidence is reported in 0.02%−0.016% of cases [61, 62], and the etiology is unknown, but enzymatic degradation of keratocytes is suspected. Activated keratocytes without inflammatory cells with initial loss of stromal keratocytes and subsequent gradual repopulation were found by confocal microscopy. CTK causes central corneal haze, (**Figure 11**), thinning of corneal stroma, and flattening of the anterior corneal surface, mostly without affecting the posterior surface. It is important to differentiate it diagnostically from stage IV DLK. Unlike DLK, CTK develops acute within 3−9 days postoperatively as central opacification, rarely associated with conjunctival hyperemia, or ciliary flush.

#### **Figure 9.** *DLK at grade II, inflammatory reaction visible throughout complete interface, without signs of melting.*

#### **Figure 10.**

*DLK in advanced grade, visible inflammatory reaction forming characteristic shifting sands phenomenon "sands of Sahara".*

#### **Figure 11.**

*Central toxic keratopathy in patient presented 5 days after LASIK procedure. Visible centralized opacification that extends anteriorly or posteriorly from the interface.*

#### *What shall we do?*

Since CTK is a non-inflammatory condition, steroids are not indicated, thus they may hamper the healing process. Usually, there is spontaneous recovery without specific therapy needed. Recovery phase takes up to 18 months, where slight central opacification can remain, but corneal thickness increases and hyperopic shift decreases [61, 63–66].

#### *2.3.1.6 Pressure-induced stromal keratitis*

PISK, also known as interface fluid syndrome [67] is a relatively rapid response to corticosteroids that presents with elevated intraocular pressure and fluid accumulation in the lamella between the flap and the adjacent corneal stroma. The amount of

fluid varies and can be very small and clinically present as diffuse stroma opacity or large, clinically clearly separating the flap from the adjacent stroma. PISK is often misdiagnosed with DLK, bud the main difference is occurrence at least 5−7 days postoperatively, with high IOP and poor response to corticosteroids, au contraire. Hence, it is extremely important to differentiate it diagnostically from DLK in order to discontinue corticosteroid therapy. The values of intraocular pressure due to fluid are centrally falsely low, while peripheral measurements show somewhat more accurate results [63, 68].

*What shall we do?*

Management includes cessation of corticosteroid therapy and introduction of antiglaucoma therapy for avoiding glaucomatous optic nerve damage [69, 70].

#### *2.3.1.7 Infectious keratitis*

Infectious keratitis is a rare but potentially devastating and sight-threatening complication after LASIK. It is rare, with 0.034−0.2% cases with decreased incidence over the years [71, 72]. It can be caused by viruses (Adenoviruses, Herpes simplex virus), bacteria (Staphylococcus, Pseudomonas), atypical mycobacteria, fungi, and parasites (Acanthamoeba). Infectious keratitis is divided into early (within the first two postoperative weeks) and late (occurs 2–3 months after surgery). Early infectious keratitis is caused by staphylococci and streptococci (most often methicillin-resistant staphylococci), and late atypical mycobacteria and fungi. The risk of infection is blepharitis, dry eye, intraoperative epithelial defects, intraoperative contamination, prolonged epithelialization after surgery, and certain professions (medical professionals). Symptoms may include pain, lightheadedness, tearing, decreased visual acuity, image duplication, shadows, and haloes. Examination on a biomicroscope may show ciliary injection, epithelial defects, anterior chamber reaction, and hypopion. Fungal keratitis, although significantly rarer than bacterial, should be considered in the differential diagnosis [1, 73–76].

#### *What shall we do?*

When it comes to infectious keratitis, prophylaxis is preferred over treatment. Proper use of sterile gloves, caps, instruments, and betadine wash of eyelids prior to the surgery will reduce the risk of infection. In observed infectious keratitis, management includes flap lift, scraping of bed, and irrigation of bed with antibiotics. In early onset, the best choice is vancomycin and amikacin in late-onset. Cessation of corticosteroids is obligatory, and topical fourth-generation fluoroquinolone and vancomycin (early onset) or amikacin with vancomycin 5% or topical clarithromycin and 4th generation fluoroquinolone for late-onset [72]. After culture isolation and the accompanying sensitivity antibiogram, local antibiotic therapy is revised. Sometimes, in case of severe infection, flap amputation is needed, both for therapeutic and diagnostic reasons [73].

#### *2.3.1.8 Stromal melting or flap melting*

Stromal melting is mostly unilateral and occurs 2−5 weeks after LASIK. It most commonly occurs after epithelial defects, thin and/or irregular flaps, perforated flaps, epithelial ingrowth, and deep lamellar keratitis. It may also be associated with systemic immune diseases such as thyroiditis, systemic lupus, Sjögren's disease, rheumatoid arthritis, eczema, and erythema. The disease is usually self-limiting for 21–45 days and results in variable intensity of opacification (leukemia) and regular or incorrect astigmatism. Melting of the flap is very likely caused by apoptosis induced by an implanted layer of epithelial cells caused by epithelial ingrowth. Epithelial ingrowth, as well as possible melting of the flap edge, is more common in reoperations, especially in hyperopic eyes, than in primary operations [77–79].

#### *2.3.1.9 Transient photosensitivity*

It is characterized by light-headedness and mild pain with normal visual acuity but without inflammation. It occurs a few days after the procedure and can last for several weeks. The complication is related to the high energy and low frequency of mostly older generations of femtosecond lasers, and the hypothetical cause is the stimulation of keratocytes and corneal nerves by the shock waves of the femtosecond laser [80].

#### *2.3.2 Late postoperative complications*

#### *2.3.2.1 Refractive regression*

Regression is the return of diopters in the direction of primary refractive error documented in several arrivals 3–6 months after LASIK. Regression is more common after hyperopic LASIK, observed in nearly 30% of hyperopes and 5.5–27.7% of myopes [81]. Regression after LASIK is associated with an increase in corneal thickness and curvature. Potential mechanisms involved in regression include nucleus sclerosis, stromal synthesis and remodeling (wound healing), compensatory epithelial hyperplasia, decreased flap thickness, an anterior shift of cornea, and iatrogenic keratectasia [82].

*What shall we do?*

After confirmed refractive stability, within 3–4 months, enhancement with LASIK re-lift, PRK, or even LASEK can be advised.

#### *2.3.2.2 Epithelial ingrowth*

Epithelial ingrowth at the terminal periphery of the flap is normal flap healing. Clinically significant epithelial ingrowth occurs when a fistula develops under the flap, which allows epithelial cells to migrate in the lamella between the flap and the stroma and causes opacification. It occurs in 0−3.9% of cases undergoing primary treatment and 10−20% in re-treatment cases [83]. In primary uncomplicated LASIK, a higher incidence of epithelial ingrowth was observed in the treatment of hyperopia, in microkeratome compared to femtosecond lasers, LASIK after radial keratotomy, intraoperative epithelial defects, and in the elderly. After repeated procedures and application of therapeutic soft contact lenses, an increased incidence of epithelial ingrowth was observed, as well as in operations performed three or more years after primary LASIK. Isolated epithelial islets rarely cause problems (**Figure 12**). However, if the ingrowth is connected to the superficial epithelium and continues to grow and reach the visual axis, it can cause distortion of the flap surface and the development of irregular astigmatism (**Figure 13**). Symptoms of epithelial ingrowth include lightheadedness, glare, decreased visual acuity, and foreign body sensation. Theoretically, there are several ways in which epithelial cells can get into the lamella: by mechanical indentation on the microkeratome blade or with water during irrigation after photoablation, and by ingrowth of cells derived from peripheral epithelium.

Biomicroscopically, epithelial ingrowth is shown with epithelial beads in the lamella formed by dividing epithelial cells, fluorescein accumulation at the edges of

**Figure 12.** *Epithelial cell collection under the flap.*

**Figure 13.**

*Epithelial ingrowth from flap margin advancing to the central part of the interface.*

the flap or even below the flap, fibrotic demarcation line at the leading edge of epithelial ingrowth, keratolysis, or melting of the flap edge [63, 84–87]. Patients usually present with foreign body sensation and dysphotopsia (glare) in the early stages and decreased visual acuity in later stages.

#### *What shall we do?*

In the initial stages (grade 1) observation is recommended, but for advanced stages, flap lift, thorough mechanical debridement of epithelial cells with profound wash of stromal bed, and Mitomycine C 0.02% application for preventing ingrowth recurrence (observed in one-third of cases) [83]. Some literature advise low energy (0.6 mJ) Nd-YAG laser for treating ingrowth [83, 88].

#### *2.3.2.3 Induced and iatrogenic keratectasia*

Iatrogenic keratectasia is a serious complication seen in 0.033−0.6% cases [4, 89] associated with a weakening of the mechanical strength of the cornea. It is clinically presented by progressive weakening of uncorrected visual acuity and increase in myopia, and by progressive increase in corneal curvature visible on corneal topography (**Figure 14**). Iatrogenic keratectasia occurs several weeks to several years after the procedure. The flap does not contribute to the biomechanical strength of the cornea, and all biomechanical stress is tolerated by untreated deeper parts of the cornea. Risk factors include irregular corneal topography, thin central corneal thickness (<450 μm), low residual corneal thickness (<250 μm), young age, and high spherical refractive error equivalent [90–92].

#### *What shall we do?*

In the case of keratectasia, prophylaxis as careful and detailed screening of corneal topography is of most importance. When progressive ectasia is observed, collagen Cross-linking is performed. Additionally, rigid gas-permeable CL or intracorneal ring segments can restore vision. For advanced cases, anterior lamellar keratoplasty or event perforative keratoplasty is required [89, 93].

#### *2.3.2.4 Dry eye*

Corneal refractive surgery can induce or even worsen dry eye symptoms (**Figure 15**). Dry eye syndrome causes discomfort, fluctuations in vision quality, delayed healing and epithelial damage, and can lead to regression of refractive error and reduced vision quality. In most patients, the symptoms are mild and do not cause interference, and pass within 6 months when the healing period ends. According to the literature and clinical practice, dry eye is observed in more than 90% of cases [94]. The main risk factors for chronic dry eye after surgery are preoperative dry eye and female sex [95–98]. Symptoms of dry eye are thought to be caused by denervation and cutting of nerve fibers during flap formation,

#### **Figure 14.**

*Iatrogenic corneal ectasia 1 year after LASIK procedure.*

#### **Figure 15.**

*Severe dry eye 1 month after LASIK procedure.*

excimer laser removal of corneal tissue, and corneal reshaping. Denervation causes a decrease in corneal sensitivity and interrupts the flow of information from the cornea to the lacrimal system. Lack of corneal sensitivity can lead to a decrease in the number of blinks, and to a lack of information about the need to produce a larger amount and/or a specific tear component. Improvement in corneal sensation and DED by 3−6 months occur in most cases, but corneal innervation can be delayed by 2−3 years [99].

#### *What shall we do?*

The choice of patients and the treatment of dry eye symptoms before the procedure are extremely important. Standard therapy includes artificial tears for prolonged period of 6 months or longer, and topical corticosteroids (currently most commonly used is low dose hydrocortisone) [100]. In severe cases of DED, topical cyclosporine drops and Punctal Plug instillation for occluding tear punctum.

#### *2.3.2.5 Night vision disturbances*

The main cause of decreased vision quality and glare symptoms is an increase in spherical aberration in the centrally flattened cornea. Symptoms worsen at night due to the physiological dilation of the pupil and the entry of light rays through the untreated periphery. Glare can also cause decentralized ablations, too small optical zones, newly formed lens blurring, and induced astigmatism. Patients with scotopic pupils larger than 7.5 mm and high myopic corrections are most often affected. Fortunately, most symptoms resolve over time without treatment due to cortical adaptation [101–104].

#### **3. Conclusions**

It is of the greatest interest for every refractive surgeon to perform safe surgery and successfully treat possible complications. Therefore, meticulous knowledge of intraoperative and postoperative complications will ensure timely and appropriate preventive measures to reduce the occurrence of complications, their early detection, and appropriate management in order to achieve optimal results.

#### **Conflict of interest**

The authors declare no conflict of interest.

### **Author details**

Fanka Gilevska1 , Maja Bohač2 , Smiljka Popović Suić2 and Mateja Jagić2 \*

1 Eye Clinic Sistina Oftalmologija, North Macedonia

2 University Eye Clinic Svjetlost, Croatia

\*Address all correspondence to: mateja.jagic@svjetlost.hr

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

#### **References**

[1] Farah SG, Ghanem RC, Azar DT. LASIK complications and their management. In: Azar DT, editor. Refractive Surgery. 2nd ed. Philadelphia: Elsevier Inc; 2007. pp. 195-221. DOI:10.1016/B978-0-323-03599- 6.50076-6

[2] Vayr F, Chastang P, Hoang-Xuan T. Laser and mechanical microkeratomes. In: Azar DT, editor. Refractive Surgery. 2nd. ed. Philadelphia: Elsevier Inc; 2007. pp. 147-155. DOI: 10.1016/ B978-0-323-03599-6.50072-9

[3] Moshirfar M, Gardiner JP, Schliesser JA, et al. Laser in situ keratomileusis flap complications using mechanical microkeratome versus femtosecond laser: Retrospective comparison. Journal of Cataract and Refractive Surgery. 2010;**36**(11):1925- 1933. DOI: 10.1016/j.jcrs.2010.05.027

[4] Melki SA, Azar DT. LASIK complications: Etiology, management, and prevention. Survey of Ophthalmology. 2001;**46**(2):95-116. DOI: 10.1016/s0039-6257(01)00254-5

[5] Rao SK, Padmanabhan P, Sitalakshmi G, Rajagopal R. Partial flap during laser in-situ keratomileusis: Pathogenesis and timing of retreatment. Indian Journal of Ophthalmology. 2000;**48**(3):209-212

[6] Jain V, Mhatre K, Shome D. Flap buttonhole in thin-flap laser in situ keratomileusis: Case series and review. Cornea. 2010;**29**(6):655-658. DOI: 10.1097/ICO.0b013e3181c377d5

[7] Leung AT, Rao SK, Cheng AC, Yu EW, Fan DS, Lam DS. Pathogenesis and management of laser in situ keratomileusis flap buttonhole. Journal of Cataract and Refractive Surgery. 2000;**26**(3):358-362. DOI: 10.1016/ s0886-3350(99)00414-9

[8] Tham VM, Maloney RK. Microkeratome complications of laser in situ keratomileusis. Ophthalmology. 2000;**107**(5):920-924. DOI: 10.1016/ s0161-6420(00)00004-x

[9] Al-Mezaine HS, Al-Amro SA, Al-Obeidan S. Incidence, management, and visual outcomes of buttonholed laser in situ keratomileusis flaps. Journal of Cataract and Refractive Surgery. 2009;**35**(5):839-845. DOI: 10.1016/j. jcrs.2009.01.013

[10] Geggel HS. Treatment of lost flaps and slipped flaps. International Ophthalmology Clinics. 2008;**48**(1):65-71. DOI: 10.1097/IIO.0b013e31815eb96d244

[11] Joo CK, Kim TG. Corneal perforation during laser in situ keratomileusis. Journal of Cataract and Refractive Surgery. 1999;**25**(8):1165-1167. DOI: 10.1016/s0886-3350(99)00117-0

[12] Liu Q, Gong XM, Chen JQ, Yang B, Ge J, To CH. Laser in situ keratomileusis induced corneal perforation and recurrent corneal epithelial ingrowth. Journal of Cataract and Refractive Surgery. 2005;**31**(4):857-859. DOI: 10.1016/j.jcrs.2004.09.027 251

[13] Walton OB, Slade SG. Thin, irregular, buttoonhole flaps. In: Jl A, Azar DT, editors. Management of Complications in Refractive Surgery. Springer Inc.; 2018. pp. 23-26. DOI: 10.1007/978-3-319-60561-6\_3

[14] Chung SH, Mazur E. Surgical applications of femtosecond lasers. Journal of Biophotonics.

*When LASIK Goes Wrong or LASIK Complications Dilemmas DOI: http://dx.doi.org/10.5772/intechopen.107924*

2009;**2**(10):557-572. DOI: 10.1002/ jbio.200910053

[15] Salomão MQ, Wilson SE. Femtosecond laser in laser in situ keratomileusis. Journal of Cataract and Refractive Surgery. 2010;**36**(6):1024- 1032. DOI: 10.1016/j.jcrs.2010.03.025

[16] Kymionis GD, Kankariya VP, Plaka AD, Reinstein DZ. Femtosecond laser technology in corneal refractive surgery: A review. Journal of Refractive Surgery. 2012;**28**(12):912-920. DOI: 10.3928/1081597X-20121116-01

[17] Srinivasan S, Rootman DS. Anterior chamber gas bubble formation during femtosecond laser flap creation for LASIK. Journal of Refractive Surgery. 2007;**23**(8):828-830. DOI: 10.3928/1081-597X-20071001-14

[18] Jung HG, Kim J, Lim TH. Possible risk factors and clinical effects of an opaque bubble layer created with femtosecond laser-assisted laser in situ keratomileusis. Journal of Cataract and Refractive Surgery. 2015;**41**(7):1393-1399. DOI: 10.1016/j.jcrs.2014.10.039

[19] Lim DH, Hyun J, Shin E, Ko BW, Chung ES, Chung TY. Incidence and risk factors of opaque bubble layer formation according to flap thickness during 500-kHz FS-LASIK. Journal of Refractive Surgery. 2019;**35**(9):583-589. DOI: 10.3928/1081597X-20190814-01

[20] Hurmeric V, Yoo SH, Fishler J, Chang VS, Wang J, Culbertson WW. In vivo structural characteristics of the femtosecond LASIK-induced opaque bubble layers with ultrahigh-resolution SD-OCT. Ophthalmic Surgery, Lasers & Imaging. 2010;**41**(Suppl.):S109-S113. DOI: 10.3928/15428877-20101031-08

[21] Kanellopoulos AJ, Asimellis G. Digital analysis of flap parameter

accuracy and objective assessment of opaque bubble layer in femtosecond laser-assisted LASIK: A novel technique. Clinical Ophthalmology. 2013;**7**:343-351. DOI: 10.2147/OPTH.S39644

[22] Soong HK, de Melo Franco R. Anterior chamber gas bubbles during femtosecond laser flap creation in LASIK: Video evidence of entry via trabecular meshwork. Journal of Cataract & Refractive Surgery. Dec 2012;**38**(12):2184-2185. DOI: 10.1016/j. jcrs.2012.09.012. Epub 2012 Oct 13. PMID: 23073481

[23] dos Santos AM, Torricelli AA, Marino GK, et al. Femtosecond laserassisted LASIK flap complications. Journal of Refractive Surgery. 2016;**32**(1):52-59. DOI: 10.3928/1081597X-20151119-01

[24] Tse SM, Farley ND, Tomasko KR, Amin SR. Intraoperative LASIK complications. International Ophthalmology Clinics. 2016;**56**(2):47-57. DOI: 10.1097/IIO.0000000000000110

[25] Srinivasan S, Herzig S. Sub-epithelial gas breakthrough during femtosecond laser flap creation for LASIK. The British Journal of Ophthalmology. 2007;**91**(10):1373. DOI: 10.1136/ bjo.2007.129213

[26] Wei CH, Mei LX, Ge Y, Zhang PF. Managements of vertical gas breakthrough in femtosecond laser assisted LASIK. International Journal of Ophthalmology. 2020;**13**(9):1503-1504. DOI: 10.18240/ijo.2020.09.25

[27] Vinciguerra P, Camesasca FI. Decentration after refractive surgery. Journal of Refractive Surgery. 2001;**17**(Suppl. 2):S190-S191. DOI: 10.3928/1081-597X-20010302-07

[28] Melki SA, Azar DT. Eight pearls in prevention and management of LASIK complications. In: Melki SA, Azar DT, editors. 101 Pearls in Refractive, Cataract and Corneal Surgery. Thorofare, NJ: Slack; 2001. pp. 23-32

[29] Manche E, Roe J. Recent advances in wavefront-guided LASIK. Current Opinion in Ophthalmology. 2018;**29**(4):286-291. DOI: 10.1097/ ICU.0000000000000488

[30] Duffey RJ. Central islands and decentered ablations after LASIK. International Ophthalmology Clinics. 2000;**40**(3):93-101. DOI: 10.1097/ 00004397-200007000-00012

[31] Kang SW, Chung ES, Kim WJ. Clinical analysis of central islands after laser in situ keratomileusis. Journal of Cataract and Refractive Surgery. 2000;**26**(4):536-542. DOI: 10.1016/ s0886-3350(99)00458-7

[32] Tsai YY, Lin JM. Natural history of central islands after laser in situ keratomileusis. Journal of Cataract and Refractive Surgery. 2000;**26**(6):853-858. DOI: 10.1016/s0886-3350(00)00375-8

[33] Johnson JD, Azar DT. Surgically induced topographical abnormalities after LASIK: Management of central islands, corneal ectasia, decentration, and irregular astigmatism. Current Opinion in Ophthalmology. 2001;**12**(4):309-317. DOI: 10.1097/00055735-200108000- 00012

[34] Randleman JB, Lynn MJ, Banning CS, Stulting RD. Risk factors for epithelial defect formation during laser in situ keratomileusis. Journal of Cataract and Refractive Surgery. 2007;**33**(10):1738-1743. DOI: 10.1016/j.jcrs.2007.05.038

[35] Smirennaia E, Sheludchenko V, Kourenkova N, Kashnikova O. Management of corneal epithelial defects following laser in situ keratomileusis.

Journal of Refractive Surgery. 2001;**17**(Suppl. 2):S196-S199. DOI: 10.3928/1081-597X-20010302-09

[36] Shah MN, Misra M, Wihelmus KR, Koch DD. Diffuse lamellar keratitis associated with epithelial defects after laser in situ keratomileusis. Journal of Cataract and Refractive Surgery. 2000;**26**(9):1312-1318. DOI: 10.1016/ s0886-3350(00)00570-8

[37] Hirst LW, Vandeleur KW Jr. Laser in situ keratomileusis interface deposits. Journal of Refractive Surgery. 1998;**14**(6):653-654. DOI: 10.3928/1081-597X-19981101-15

[38] Mimouni M, Vainer I, Assad N, et al. Incidence, indications, and outcomes of eyes needing early flap lifting after LASIK. Cornea. 2018;**37**(9):1118-1123. DOI: 10.1097/ICO.0000000000001617

[39] Wallerstein A, Gauvin M, Adiguzel E, et al. Clinically significant laser in situ keratomileusis flap striae. Journal of Cataract and Refractive Surgery. 2017;**43**(12):1523-1533. DOI: 10.1016/j.jcrs.2017.09.023

[40] Shah DN, Melki S. Complications of femtosecond-assisted laser in-situ keratomileusis flaps. Seminars in Ophthalmology. 2014;**29**(5-6):363-375. DOI: 10.3109/08820538.2014.959194

[41] Abdelazeem K, Nassr MA, Abdelmotaal H, Wasfi E, El-Sebaity DM. Flap sliding technique for managing flap striae following laser in situ keratomileusis. Journal of Ophthalmology. 2020;**2020**:5614327. [Accessed: February 24, 2020]. DOI: 10.1155/2020/5614327

[42] Hardten DR, Hardten AG, Hardten SA. Management of the distorted Flap. In: Alio J, Azar D, editors. Management of Complications *When LASIK Goes Wrong or LASIK Complications Dilemmas DOI: http://dx.doi.org/10.5772/intechopen.107924*

in Refractive Surgery. Cham: Springer; 2018. pp. 33-36. DOI: 10.1007/978-3-319-60561-6\_5

[43] Iskander NG, Peters NT, Anderson Penno E, Gimbel HV. Late traumatic flap dislocation after laser in situ keratomileusis. Journal of Cataract and Refractive Surgery. 2001;**27**(7):1111-1114. DOI: 10.1016/s0886-3350(01)00752-0

[44] Clare G, Moore TC, Grills C, Leccisotti A, Moore JE, Schallhorn S. Early flap displacement after LASIK. Ophthalmology. 2011;**118**(9):1760-1765. DOI: 10.1016/j.ophtha.2011.01.053

[45] Netto MV, Wilson SE. Flap lift for LASIK retreatment in eyes with myopia. Ophthalmology. 2004;**111**(7):1362-1367. DOI: 10.1016/j.ophtha.2003.11.009

[46] Yuen LH, Chan WK, Koh J, Mehta JS, Tan DT. SingLasik research group. A 10-year prospective audit of LASIK outcomes for myopia in 37,932 eyes at a single institution in Asia. Ophthalmology. 2010;**117**(6):1236-1244. e1. DOI: 10.1016/j.ophtha.2009.10.042

[47] Alió JL, Muftuoglu O, Ortiz D, et al. Ten-year follow-up of laser in situ keratomileusis for myopia of up to −10 diopters. American Journal of Ophthalmology. 2008;**145**(1):46-54. DOI: 10.1016/j.ajo.2007.09.010

[48] Randleman JB, White AJ Jr, Lynn MJ, Hu MH, Stulting RD. Incidence, outcomes, and risk factors for retreatment after wavefront-optimized ablations with PRK and LASIK. Journal of Refractive Surgery. 2009;**25**(3):273-276. DOI: 10.3928/1081597X-20090301-06 62

[49] Hood CT, Shtein RM, Veldheer D, et al. The effect of humidity and temperature on visual outcomes after myopic corneal laser refractive surgery. Clinical Ophthalmology.

2016;**10**:2231-2236. [Accessed: November 4, 2016]. DOI: 10.2147/OPTH.S118503

[50] Shen EP, Chen WL, Hu FR. Manual limbal markings versus irisregistration software for correction of myopic astigmatism by laser in situ keratomileusis. Journal of Cataract and Refractive Surgery. 2010;**36**(3):431-436. DOI: 10.1016/j.jcrs.2009.10.030

[51] Schallhorn SC, Venter JA, Hannan SJ, Hettinger KA, Teenan D. Flap lift and photorefractive keratectomy enhancements after primary laser in situ keratomileusis using a wavefrontguided ablation profile: Refractive and visual outcomes. Journal of Cataract and Refractive Surgery. 2015;**41**(11):2501- 2512. DOI: 10.1016/j.jcrs.2015.05.031

[52] Gritz DC. LASIK interface keratitis: Epidemiology, diagnosis and care. Current Opinion in Ophthalmology. 2011;**22**(4):251-255. DOI: 10.1097/ ICU.0b013e3283477b52

[53] Smith RJ, Maloney RK. Diffuse lamellar keratitis. A new syndrome in lamellar refractive surgery. Ophthalmology. 1998;**105**(9):1721-1726. DOI: 10.1016/S0161-6420(98)99044-3

[54] MacRae S, Macaluso DC, Rich LF. Sterile interface keratitis associated with micropannus hemorrhage after laser in situ keratomileusis. Journal of Cataract and Refractive Surgery. 1999;**25**(12):1679-1681. DOI: 10.1016/ s0886-3350(99)00248-5

[55] Holland SP, Mathias RG, Morck DW, Chiu J, Slade SG. Diffuse lamellar keratitis related to endotoxins released from sterilizer reservoir biofilms. Ophthalmology. 2000;**107**(7):1227-1234. DOI: 10.1016/s0161-6420(00)00246-3

[56] Kaufman SC. Post-LASIK interface keratitis, Sands of the Sahara syndrome, and microkeratome blades. Journal of Cataract and Refractive Surgery. 1999;**25**(5):603-604

[57] Fogla R, Rao SK, Padmanabhan P. Diffuse lamellar keratitis: Are meibomian secretions responsible? Journal of Cataract and Refractive Surgery. 2001;**27**(4):493-495. DOI: 10.1016/ s0886-3350(01)00819-7

[58] Gil-Cazorla R, Teus MA, de Benito-Llopis L, Fuentes I. Incidence of diffuse lamellar keratitis after laser in situ keratomileusis associated with the IntraLase 15 kHz femtosecond laser and Moria M2 microkeratome. Journal of Cataract and Refractive Surgery. 2008;**34**(1):28-31. DOI: 10.1016/j. jcrs.2007.08.025

[59] Choe CH, Guss C, Musch DC, Niziol LM, Shtein RM. Incidence of diffuse lamellar keratitis after LASIK with 15 KHz, 30 KHz, and 60 KHz femtosecond laser flap creation. Journal of Cataract and Refractive Surgery. 2010;**36**(11):1912-1918. DOI: 10.1016/j. jcrs.2010.09.003

[60] Linebarger EJ, Hardten DR, Lindstrom RL. Diffuse lamellar keratitis: Diagnosis and management. Journal of Cataract and Refractive Surgery. 2000;**26**(7):1072-1077. DOI: 10.1016/ s0886-3350(00)00468-5

[61] Moshirfar M, Hazin R, Khalifa YM. Central toxic keratopathy. Current Opinion in Ophthalmology. 2010;**21**(4):274-279. DOI: 10.1097/ ICU.0b013e32833a8cb2

[62] Jutley G, Aiello F, Robaei D, Maurino V. Central toxic keratopathy after laser in situ keratomileusis. Journal of Cataract and Refractive Surgery. 2014;**40**(12):1985-1993. DOI: 10.1016/j. jcrs.2014.03.030

[63] Randleman JB, Shah RD. LASIK interface complications: Etiology, management, and outcomes. Journal of Refractive Surgery. 2012;**28**(8):575-586. DOI: 10.3928/1081597X-20120722-01

[64] Hazin R, Daoud YJ, Khalifa YM. What is central toxic keratopathy syndrome if it is not diffuse lamellar keratitis grade IV? Middle East African Journal of Ophthalmology. 2010;**17**(1):60-62. DOI: 10.4103/0974-9233.61218

[65] Thornton IL, Foulks GN, Eiferman RA. Confocal microscopy of central toxic keratopathy. Cornea. 2012;**31**(8):934-936. DOI: 10.1097/ ICO.0b013e3181f7f109

[66] Sikder S, Khalifa YM, Neuffer MC, Moshirfar M. Tomographic corneal profile analysis of central toxic keratopathy after LASIK. Cornea. 2012;**31**(1):48-51. DOI: 10.1097/ICO.0b013e31821de341

[67] Tourtas T, Kopsachilis N, Meiller R, Kruse FE, Cursiefen C. Pressure-induced interlamellar stromal keratitis after laser in situ keratomileusis. Cornea. 2011;**30**(8):920-923. DOI: 10.1097/ ICO.0b013e3182032002

[68] Belin MW, Hannush SB, Yau CW, Schultze RL. Elevated intraocular pressureinduced interlamellar stromal keratitis. Ophthalmology. 2002;**109**(10):1929-1933. DOI: 10.1016/s0161-6420(02)01163-6

[69] Kurian M, Shetty R, Shetty BK, Devi SA. In vivo confocal microscopic findings of interlamellar stromal keratopathy induced by elevated intraocular pressure. Journal of Cataract and Refractive Surgery. 2006;**32**(9):1563- 1566. DOI: 10.1016/j.jcrs.2006.03.041

[70] Cabral-Macias J, García-De la Rosa G, Rodríguez-Matilde DF, et al. Pressure-induced stromal keratopathy *When LASIK Goes Wrong or LASIK Complications Dilemmas DOI: http://dx.doi.org/10.5772/intechopen.107924*

after laser in situ keratomileusis: Acute and late-onset presentations. Journal of Cataract and Refractive Surgery. 2018;**44**(10):1284-1290. DOI: 10.1016/j. jcrs.2018.06.053

[71] Ortega-Usobiaga J, Llovet-Osuna F, Djodeyre MR, Llovet-Rausell A, Beltran J, Baviera J. Incidence of corneal infections after laser in situ keratomileusis and surface ablation when moxifloxacin and tobramycin are used as postoperative treatment. Journal of Cataract and Refractive Surgery. 2015;**41**(6):1210-1216

[72] Donnenfeld ED, Kim T, Holland EJ, et al. ASCRS White Paper: Management of infectious keratitis following laser in situ keratomileusis. Journal of Cataract and Refractive Surgery. 2005;**31**(10):2008-2011. DOI: 10.1016/j. jcrs.2005.10.030

[73] Moshirfar M, Welling JD, Feiz V, Holz H, Clinch TE. Infectious and noninfectious keratitis after laser in situ keratomileusis Occurrence, management, and visual outcomes. Journal of Cataract and Refractive Surgery. 2007;**33**(3):474-483. DOI: 10.1016/j.jcrs.2006.11.005

[74] Solomon R, Donnenfeld ED, Azar DT, et al. Infectious keratitis after laser in situ keratomileusis: results of an ASCRS survey. Journal of Cataract and Refractive Surgery. 2003;**29**(10):2001-2006. DOI: 10.1016/ s0886-3350(03)00512-1

[75] Solomon R, Donnenfeld ED, Perry HD, et al. Methicillin-resistant Staphylococcus aureus infectious keratitis following refractive surgery. American Journal of Ophthalmology. 2007;**143**(4):629-634. DOI: 10.1016/j. ajo.2006.12.029

[76] Garg P, Chaurasia S, Vaddavalli PK, Muralidhar R, Mittal V, Gopinathan U.

Microbial keratitis after LASIK. Journal of Refractive Surgery. 2010;**26**(3):209- 216. DOI: 10.3928/1081597X-20100224-07

[77] Güell JL, Morral M, Elies D, Gris O, Gaytan J, Manero F. Melting. In: Alio JL, Azar DT, editors. Management of Complications in Refractive Surgery. 2nd ed. Springer; 2018. pp. 91-98

[78] Castillo A, Diaz-Valle D, Gutierrez AR, Toledano N, Romero F. Peripheral melt of flap after laser in situ keratomileusis. Journal of Refractive Surgery. 1998;**14**(1):61-63. DOI: 10.3928/1081-597X-19980101-12

[79] Smith RJ, Maloney RK. Laser in situ keratomileusis in patients with autoimmune diseases. Journal of Cataract and Refractive Surgery. 2006;**32**(8):1292- 1295. DOI: 10.1016/j.jcrs.2006.02.059

[80] Stonecipher KG, Dishler JG, Ignacio TS, Binder PS. Transient light sensitivity after femtosecond laser flap creation: Clinical findings and management. Journal of Cataract and Refractive Surgery. 2006;**32**(1):91-94. DOI: 10.1016/j.jcrs.2005.11.015

[81] Yan MK, Chang JS, Chan TC. Refractive regression after laser in situ keratomileusis. Clinical & Experimental Ophthalmology. 2018;**46**(8):934-944. DOI: 10.1111/ceo.13315

[82] Alió JL, Soria F, Abbouda A, Peña-García P. Laser in situ keratomileusis for −6.00 to −18.00 diopters of myopia and up to −5.00 diopters of astigmatism: 15-year follow-up. Journal of Cataract and Refractive Surgery. 2015;**41**(1):33-40. DOI: 10.1016/j.jcrs.2014.08.029

[83] Ting DSJ, Srinivasan S, Danjoux JP. Epithelial ingrowth following laser in situ keratomileusis (LASIK): Prevalence, risk factors, management and visual

outcomes. BMJ Open Ophthalmology. 2018;**3**(1):e000133. [Accessed: March 29, 2018]. DOI: 10.1136/ bmjophth-2017-000133

[84] Chen S, Feng Y, Stojanovic A, Jankov MR 2nd, Wang Q. IntraLase femtosecond laser vs mechanical microkeratomes in LASIK for myopia: A systematic review and meta-analysis. Journal of Refractive Surgery. 2012;**28**(1):15-24. DOI: 10.3928/1081597X-20111228-02

[85] Friehmann A, Mimouni M, Nemet AY, Sela T, Munzer G, Kaiserman I. Risk factors for epithelial ingrowth following microkeratomeassisted LASIK. Journal of Refractive Surgery. 2018;**34**(2):100-105. DOI: 10.3928/1081597X-20180105-01

[86] Asano-Kato N, Toda I, Hori-Komai Y, Takano Y, Tsubota K. Epithelial ingrowth after laser in situ keratomileusis: Clinical features and possible mechanisms. American Journal of Ophthalmology. 2002;**134**(6):801-807. DOI: 10.1016/ s0002-9394(02)01757-9

[87] Caster AI, Friess DW, Schwendeman FJ. Incidence of epithelial ingrowth in primary and retreatment laser in situ keratomileusis. Journal of Cataract and Refractive Surgery. 2010;**36**(1):97- 101. DOI: 10.1016/j.jcrs.2009.07.039

[88] Mohammed OA, Mounir A, Hassan AA, Alsmman AH, Mostafa EM. Nd:YAG laser for epithelial ingrowth after laser in situ keratomileusis. International Ophthalmology. 2019;**39**(6):1225-1230. DOI: 10.1007/ s10792-018-0923-1

[89] Bohac M, Koncarevic M, Pasalic A, et al. Incidence and clinical characteristics of post LASIK Ectasia: A review of over 30,000 LASIK cases. Seminars in Ophthalmology. 2018;**33**(7-8):869-877. DOI: 10.1080/08820538.2018.1539183

[90] Randleman JB, Woodward M, Lynn MJ, Stulting RD. Risk assessment for ectasia after corneal refractive surgery. Ophthalmology. 2008;**115**(1):37- 50. DOI: 10.1016/j.ophtha.2007.03.073

[91] 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**(4):388-403. DOI: 10.1097/01. ico.0000222479.68242.77

[92] Seiler T, Quurke AW. Iatrogenic keratectasia after LASIK in a case of forme fruste keratoconus. Journal of Cataract and Refractive Surgery. 1998;**24**(7):1007-1009. DOI: 10.1016/ s0886-3350(98)80057-6

[93] Santhiago MR, Wilson SE, Smadja D, Chamon W, Krueger RE, Randleman JB. Validation of the percent tissue altered as a risk factor for ectasia after LASIK. Ophthalmology. 2019;**126**(6):908-909. DOI: 10.1016/j. ophtha.2019.01.018

[94] Cohen E, Spierer O. Dry eye postlaser-assisted in situ keratomileusis: Major review and latest updates. Journal of Ophthalmology. 2018;**2018**:4903831. [Accessed: January 28, 2018]. DOI: 10.1155/2018/4903831

[95] Albietz JM, Lenton LM, McLennan SG. Chronic dry eye and regression after laser in situ keratomileusis for myopia. Journal of Cataract and Refractive Surgery. 2004;**30**(3):675-684. DOI: 10.1016/j. jcrs.2003.07.003

[96] Albietz JM, Lenton LM. Management of the ocular surface and tear film before, during, and after laser in situ keratomileusis. Journal of Refractive Surgery. 2004;**20**(1):62-71. DOI: 10.3928/1081-597X-20040101-11

*When LASIK Goes Wrong or LASIK Complications Dilemmas DOI: http://dx.doi.org/10.5772/intechopen.107924*

[97] Raoof D, Pineda R. Dry eye after laser in-situ keratomileusis. Seminars in Ophthalmology. 2014;**29**(5-6):358-362. DOI: 10.3109/08820538.2014.962663

[98] Shtein RM. Post-LASIK dry eye. Expert Review of Ophthalmology. 2011;**6**(5):575-582. DOI: 10.1586/ eop.11.56

[99] Darwish T, Brahma A, O'Donnell C, Efron N. Subbasal nerve fiber regeneration after LASIK and LASEK assessed by noncontact esthesiometry and in vivo confocal microscopy: Prospective study. Journal of Cataract and Refractive Surgery. 2007;**33**(9):1515-1521. DOI: 10.1016/j. jcrs.2007.05.023

[100] Salib GM, McDonald MB, Smolek M. Safety and efficacy of cyclosporine 0.05% drops versus unpreserved artificial tears in dryeye patients having laser in situ keratomileusis. Journal of Cataract and Refractive Surgery. 2006;**32**(5):772-778. DOI: 10.1016/j.jcrs.2005.10.034

[101] Myung D, Schallhorn S, Manche EE. Pupil size and LASIK: A review. Journal of Refractive Surgery. 2013;**29**(11):734- 741. DOI: 10.3928/1081597X-20131021-02

[102] Miraftab M, Fotouhi A, Hashemi H, Jafari F, Shahnazi A, Asgari S. A modified risk assessment scoring system for post laser in situ keratomileusis ectasia in topographically normal patients. Journal of Ophthalmic and Vision Research. 2014;**9**(4):434-438. DOI: 10.4103/2008-322X.150806

[103] Pop M, Payette Y. Risk factors for night vision complaints after LASIK for myopia. Ophthalmology. 2004;**111**(1):3- 10. DOI: 10.1016/j.ophtha.2003.09.022

[104] Schallhorn SC, Tanzer DJ, Kaupp SE, Brown M, Malady SE. Comparison of night driving

performance after wavefrontguided and conventional LASIK for moderate myopia. Ophthalmology. 2009;**116**(4):702-709. DOI: 10.1016/j. ophtha.2008.12.038

Section 4
