With a reported incidence of 2.2%1 to 2.9%,2 enhancement rates after myopic small incision lenticule extraction (SMILE) seem to be comparable or slightly lower than those typically reported for LASIK.3–5 Although several reasons have been discussed for this fact, the lack of a flap to re-lift and the scarcity of data on safety and efficacy of re-treatment may be the main contributors.1,2
We have previously provided data on enhancement using surface ablation.1 Although this approach has been found to be safe and efficacious, visual recovery in our study was slow. Additionally, the painful nature of the procedure might deter patients from undergoing this enhancement method.1
In contrast, a conversion of the SMILE cap into a flap using the CIRCLE option provided by the VisuMax laser (Carl Zeiss Meditec AG, Jena, Germany) followed by excimer ablation represents an alternative option for re-treatment. In one prospective study in humans and animal models, flap creation using the CIRCLE algorithm has been found safe.6,7 However, neither these nor other studies have yet provided refractive or visual outcomes of the CIRCLE technique. Hence, the rationale of the current study was to analyze clinical outcomes of patients re-treated after SMILE with the VisuMax CIRCLE option and subsequent excimer laser ablation.
Patients and Methods
The databases of the SMILE Eyes Clinics in Munich and Cologne, Germany, and Linz, Austria, were screened for patients who had undergone CIRCLE re-treatment after myopic SMILE. A standardized protocol was performed for preoperative and postoperative assessment as reported previously.1 Informed consent from all patients and the respective institutional review board approval were obtained for all centers. All study-related procedures adhered to the tenets of the Declaration of Helsinki.
The primary SMILE procedure was performed as described previously with a standard cap thickness of 130 μm and an optical zone of 5.75 to 7 mm, depending on the individual white-to-white diameter.1,8–10 At each follow-up visit, individual refractive and visual outcomes were reevaluated. In cases of unsatisfying refractive results, patients were thoroughly informed about the chances and risks of the re-treatment methods available. To be eligible for CIRCLE enhancement, the calculated residual stromal bed after re-treatment had to exceed 250 μm. In cases of doubt, corneal optical coherence tomography was performed. If residual stromal bed thickness was insufficient, surface ablation was recommended as an alternative.
Circle-Assisted Excimer Ablation
Using the CIRCLE option of the VisuMax laser, the cap of the primary SMILE was converted into a full flap. Of the four patterns (A to D), pattern D was used as recommended by Zeiss because it has been shown to produce the easiest flaps to lift.6Figure A (available in the online version of this article) provides a schematic illustration of the three consecutive laser cuts performed before. First, a lamellar ring around the original cap is cut at the same depth as the cap.6 Second, a side cut is created around the new incision plane with the exception of an area used as a hinge.6 Third, a junction cut parallel to the side cut is created to establish a connection between the planes of the primary cap and the secondary lamellar ring around it, creating one large joint plane.6
Schematic demonstration of CIRCLE pattern D (VisuMax; Carl Zeiss Meditec AG, Jena, Germany) on corneal optical coherence tomography. The small incision lenticule extraction (SMILE) interface can be seen as a hyperreflective line in the anterior part of the cornea. CIRCLE pattern D first creates (A) a lamellar ring around the SMILE cap cut at the same depth; (B) a side cut for flap lifting; and (C) a junction cut to link the SMILE plane with the newly created lamellar ring plane around it.
Care was taken to rotate the planned flap so that the new flap hinge area overlapped with the former side cut incision. After femtosecond laser application, the new flap was lifted using a blunt spatula like a regular LASIK flap.
Excimer ablation was then performed with a MEL 90 laser (Carl Zeiss Meditec AG) on the previous lenticule zone with plano target refraction in all cases. To prevent possible haze in this novel procedure,11 a sponge soaked with 0.02% mitomycin C solution was applied for 20 seconds immediately after excimer laser treatment, followed by thorough rinsing with balanced salt solution. At the end of surgery, the flap was repositioned. Postoperative care included levofloxacin eye drops four times daily for 1 week, dexamethasone eye drops four times daily tapered to individual need, and lubricant eye drops as needed.
All data were gathered and analyzed in Microsoft Excel spreadsheets (Microsoft Corporation, Redmond, WA). Statistical analysis was performed in SPSS software (version 23; SPSS, Inc., Chicago, IL). A P value of less than .05 was considered statistically significant. Statistical comparison of manifest refraction spherical equivalent and visual acuity between multiple groups at different time points was performed with a repeated measures analyses of variance Bonferroni correction applied for multiple comparisons.
Demographic data and refractive results are summarized in Table 1. Flap-lifting after CIRCLE was possible in all cases without any intraoperative complications. The mean optical zone of the CIRCLE enhancement was 6.5 ± 0.4 mm (range: 6 to 7 mm).
Demographic Data and Refractive Results
Change of manifest refraction spherical equivalent (MRSE) over time is shown in Figure 1. MRSE remained significantly improved and stable until the end of follow-up at 3 months, resulting in a final +0.18 ± 0.31 D (range: −0.25 to 0.88 D) (P = .008). The distribution of MRSE before and after re-treatment can be found in Figure 2. The number of eyes within 0.50 and 1.00 D from target refraction increased from 31.8% to 90.9% and from 77.3% to 100%, respectively. The percentage of eyes greater than 1.00 D from target refraction decreased from 22.7% to 0%. Changes in astigmatism can be found in Figure B (available in the online version of this article). The number of eyes with astigmatism of 0.50 D or less increased from 40.9% to 95.4%. After re-treatment, no eye had astigmatism greater than 0.75 D (before enhancement: 31.8%). A comparison of attempted versus achieved manifest spherical refraction can be found in Figure 3.
Change of manifest refraction spherical equivalent (MRSE) over time. After small incision lenticule extraction (SMILE), MRSE significantly decreased to +0.29 diopters (D). During the mean 10 months until enhancement, a significant mean regression to −0.51 ± 1.08 D directly before re-treatment was noted. One week after enhancement, spherical equivalent had already significantly improved and remained stable until month 3, resulting in a final spherical equivalent of 0.18 ± 0.31 D (range: −0.25 to 0.88 D).
Distribution of manifest refraction spherical equivalent before and after re-treatment. The number of eyes within 0.50 and 1.00 diopters (D) from target refraction increased from 31.8% to 90.9% and from 77.3% to 100.0%, respectively.
Distribution of refractive astigmatism. The number of eyes within 0.50 diopters (D) of astigmatism increased from 40.9% to 95.4%. After re-treatment, no eyes had an astigmatism of greater than 0.75 D (before enhancement: 31.8%).
Attempted vs achieved spherical equivalent refraction. By definition of spherical equivalent beyond 1.00 diopter (D) from target refraction, no eye was undercorrected or overcorrected.
At 3 months, there was a significant improvement in UDVA (0.37 ± 0.16 to 0.03 ± 0.07 logMAR; range: 0.2 to 0.0 logMAR; P < .0001). CDVA remained unchanged at all time points (0.01 ± 0.07 logMAR preoperatively vs 0.02 ± 0.04 logMAR [range: 0.1 to 0.0 logMAR] after re-treatment; P = .40). A comparison of CDVA before and UDVA after re-treatment is given in Figure 4. After re-treatment, 77.3% of eyes achieved a UDVA of 0.0 logMAR or better, 86.4% achieved 0.1 logMAR or better, and all eyes achieved at least 0.2 logMAR.
Distribution of preoperative corrected distance visual acuity (CDVA) and postoperative uncorrected distance visual acuity (UDVA). A total of 86% of eyes with a preoperative corrected distance visual acuity (CDVA) of 20/25 also had 20/25 uncorrected distance visual acuity (UDVA) postoperatively (89% for 20/20).
Changes in lines of UDVA and CDVA from preoperative to 3 months postoperatively are given in Figure 5. Although there was no loss of lines of UDVA, two eyes (9.1%) lost one line of CDVA without any explaining correlate but ending up with 0.0 and 0.1 logMAR. In 72.7% of re-treated eyes, CDVA remained unchanged, whereas 18.2% gained one line. The safety index was 1.03. Concerning efficacy (ie, UDVA), all eyes gained at least one line. In 40.9% of eyes each, two or more lines were gained. The efficacy index was 0.97.
Change in lines of corrected distance visual acuity (CDVA) and uncorrected distance visual acuity (UDVA). Two eyes lost one line of CDVA (9.1 %). UDVA improved by at least one line in 100% of eyes.
The time course of visual recovery can be found in Figure 6. There was already significant improvement in UDVA at 1 week (0.37 ± 0.16 to 0.08 ± 0.16 logMAR; P < .0001). From week 1 to month 3, a further slight improvement was noted (0.08 ± 0.16 to 0.03 ± 0.07 logMAR; P = .03). During the complete follow-up, there was no worsening of CDVA as compared to preoperatively. No eye developed haze.
Time course of uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA) after CIRCLE enhancement (VisuMax; Carl Zeiss Meditec AG, Jena, Germany). There was no loss of UDVA at any time point during the study. UDVA already improved significantly at 1 week and remained stable until the end of follow-up at 3 months.
In contrast to LASIK, the absence of a flap to re-lift makes the choice of enhancement after myopic SMILE less obvious. Because femtosecond lasers used for myopic SMILE are currently unable to routinely relocate the primary treatment plane, enhancement creating a second lenticule anteriorly or posteriorly has only been described as a case report12 and is not available in today's clinical practice.2,13 Thus, surface ablation or flap-creating approaches (CIRCLE re-treatment, thin-flap LASIK) are the only commonly available options of refractive corneal re-treatment.1,13 We have previously published evidence on the safety and efficacy of surface re-treatment, but with the expected slow visual recovery.1 In contrast, the CIRCLE option of secondary flap creation for re-treatment after SMILE seems to offer minimal discomfort, quick visual recovery and is performed in clinical practice. However, there still is no evidence on the effect of CIRCLE flap creation on refractive outcome.
In this context, our study provides to our knowledge the first proof of safety and refractive efficacy of CIRCLE re-treatment after SMILE. Additionally, confirming previous results,7 our data add to the body of evidence that CIRCLE enhancement allows for a safe and effective conversion of a SMILE cap cut into a full flap. In every eye in our study, the flap could be manipulated without any intraoperative (eg, flap tear or flap dislocation) or postoperative (eg, haze) complications. Because the CIRCLE procedure represents a primary flap creation and not a re-lift, epithelial ingrowth was not observed in any case as expected.14
Concerning efficacy, final MRSE was comparable to surface ablation reported at a similar interval after SMILE (CIRCLE: +0.18 ± 0.31 D, re-treated after 10 months, vs surface ablation: 0.03 ± 0.57 D after 9.8 months). A total of 91% and 100% of CIRCLE treated eyes were within 0.50 and 1.00 D of emmetropia, which is slightly better than our results after surface ablation (73% and 93%).1 This translates into a higher percentage of eyes gaining at least one line (all eyes after CIRCLE vs 65% after surface ablation) and the percentage of eyes gaining two lines and more (82% vs 38%).
Compared to surface ablation, CIRCLE provided an improved safety index (1.03 vs 0.90). Although surface ablation re-treatment led to loss of one line of CDVA and UDVA in 15% of eyes each,1 only two eyes (9.1%) in our CIRCLE study lost one line of CDVA and no eye lost any line of UDVA.
In addition to the hypothesized improved safety and efficacy profile demonstrated herein, the prospect of a painless and fast visual recovery might be one of the main reasons for choosing CIRCLE over surface ablation. In our previous study on the latter, UDVA had not yet improved at 1 week after surface ablation despite a highly significant improvement in MRSE, and CDVA had worsened from 0.01 to 0.12 logMAR. In contrast, CIRCLE enhancement in the current study allowed for significant improvement of UDVA already at 1 week. Additionally, no decrease of CDVA at any time point after enhancement was seen.
When comparing results between both of our studies, possible confounders have to be considered. First, the refractive error in the current study was slightly lower than before surface ablation re-treatment (−0.51 ± 1.08 vs −0.86 ± 0.43 D). Second, CIRCLE was also performed for hypermetropic overcorrection in 46% of cases, as compared to myopic correction only in our previous surface ablation study. Third, this study includes fewer eyes (22 vs 40). Because enhancement rates after SMILE are low in general1,2 and CIRCLE still represents a fairly new procedure, larger sample sizes were not possible despite it being a multicenter study.
The advantages of CIRCLE re-treatment reported herein might to a certain extent be attributable to the impact of refractive (re)treatment on the corneal epithelium. Several studies have demonstrated the induction of epithelial remodeling after SMILE,15–17 leading to a maximum thickening by 9.3% at 3 months.16 Although this change seems to stabilize earlier after SMILE than LASIK (ie, after 3 months), its effect on refractive predictability remains unclear.15,16 Although Luft et al.16 found no significant correlation of epithelial thickening and refractive predictability, Ganesh et al.17 reported increased thickening in higher degrees of myopia capable of causing refractive regression. In this context, CIRCLE re-treatment might allow for better reproducibility because the remodeled epithelium is not as directly exposed to another treatment as in the case of surface ablation.
Another option for re-treatment after SMILE is thin-flap LASIK. Reinstein et al. recently reported 12-month outcomes in 100 patients.18 Their study found a final MRSE of +0.19 ± 0.46 D, which is close to the +0.18 ± 0.31 D after CIRCLE reported in our study. Although 81% of eyes were within ±0.50 D of target refraction (CIRCLE: 91%), there was a slightly better percentage of eyes achieving at least 20/20 of UDVA (83% vs 77% after CIRCLE in our study).
Comparing the surgical technique of CIRCLE with thin-flap LASIK, using a thin flap on top of the previous cap surface has been argued to be advantageous because it obviates the creation of lamellar ring, rendering the flap smaller, does not require a junction cut, and, most importantly, spares the stromal lamellae in the middle between the cap and the new LASIK treatment plane above. In contrast, in CIRCLE all anterior stromal fibers above the cap are cut and thus cannot contribute to corneal stability after re-treatment. Because the anterior stroma mainly contributes to corneal biomechanical stability (the anterior fibers have been shown to be the most robust due to dense packing,19 interlacing,20 and insertion into Bowman's membrane21), the reduced amount of stromal fibers cut in thin-flap LASIK might hypothetically preserve biomechanical stability better than CIRCLE re-treatment (as suggested by Reinstein et al.). However, it is unclear whether this consideration significantly translates into clinical practice.22 Experimental studies comparing surface ablation, re-SMILE and CIRCLE enhancement have been published, yet there are no laboratory data available at the moment comparing biomechanical stability after CIRCLE versus thin-flap LASIK re-treatment. In contrast to CIRCLE, widespread use of thin-flap LASIK might be limited by the fact that it simply is more challenging, because any cross-talk between both treatment planes could lead to complications.
Although firmly established for surface ablation retreatments,1,23 the necessity of mitomycin C for CIRCLE re-treatments remains questionable. To ensure maximum safety in this novel procedure, we decided to use mitomycin C in the first cases to prevent possible haze and limit excessive interface remodeling. However, because CIRCLE represents a primary flap procedure, some surgeons have meanwhile also adopted a mitomycin C–free approach with good results. Further studies are needed to evaluate its importance for haze prevention and refractive outcomes.
CIRCLE conversion of a SMILE cap into a flap with subsequent excimer laser ablation offers a safe and effective treatment option for residual ametropia after myopic SMILE. This initial report on clinical outcomes hints at comparable, if not superior, results compared to surface ablation re-treatment. In particular, the improved safety profile and accelerated visual recovery may represent significant advantages for patients willing to sacrifice the concept of flaplessness. Retrospective matched-pair analyses and prospective trials with longer follow-up will add valuable evidence in the future.
- Siedlecki J, Luft N, Kook D, et al. Enhancement after myopic small incision lenticule extraction (SMILE) using surface ablation. J Refract Surg. 2017;33:513–518. doi:10.3928/1081597X-20170602-01 [CrossRef]
- Liu YC, Rosman M, Mehta JS. Enhancement after small-incision lenticule extraction: incidence, risk factors, and outcomes. Ophthalmology. 2017;124:813–821. doi:10.1016/j.ophtha.2017.01.053 [CrossRef]
- 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. J Refract Surg. 2009;25:273–276.
- Mimouni M, Vainer I, Shapira Y, et al. Factors predicting the need for retreatment after laser refractive surgery. Cornea. 2016;35:607–612. doi:10.1097/ICO.0000000000000795 [CrossRef]
- Pokroy R, Mimouni M, Sela T, Munzer G, Kaiserman I. Myopic laser in situ keratomileusis retreatment: Incidence and associations. J Cataract Refract Surg. 2016;42:1408–1414. doi:10.1016/j.jcrs.2016.07.032 [CrossRef]
- Riau AK, Ang HP, Lwin NC, Chaurasia SS, Tan DT, Mehta JS. Comparison of four different VisuMax circle patterns for flap creation after small incision lenticule extraction. J Refract Surg. 2013;29:236–244. doi:10.3928/1081597X-20130318-02 [CrossRef]
- Chansue E, Tanehsakdi M, Swasdibutra S, McAlinden C. Safety and efficacy of VisuMax(R) circle patterns for flap creation and enhancement following small incision lenticule extraction. Eye Vis. 2015;2:21. doi:10.1186/s40662-015-0031-5 [CrossRef]
- Sekundo W, Kunert K, Russmann C, et al. First efficacy and safety study of femtosecond lenticule extraction for the correction of myopia: six-month results. J Cataract Refract Surg. 2008;34:1513–1520. doi:10.1016/j.jcrs.2008.05.033 [CrossRef]
- Sekundo W, Kunert KS, Blum M. Small incision corneal refractive surgery using the small incision lenticule extraction (SMILE) procedure for the correction of myopia and myopic astigmatism: results of a 6 month prospective study. Br J Ophthalmol. 2011;95:335–339. doi:10.1136/bjo.2009.174284 [CrossRef]
- Ivarsen A, Asp S, Hjortdal J. Safety and complications of more than 1500 small-incision lenticule extraction procedures. Ophthalmology. 2014;121:822–828. doi:10.1016/j.ophtha.2013.11.006 [CrossRef]
- Majmudar PA, Forstot SL, Dennis RF, et al. Topical mitomycin-C for subepithelial fibrosis after refractive corneal surgery. Ophthalmology. 2000;107:89–94. doi:10.1016/S0161-6420(99)00019-6 [CrossRef]
- Donate D, Thaeron R. Preliminary evidence of successful enhancement after a primary SMILE procedure with the sub-caplenticule-extraction technique. J Refract Surg. 2015;31:708–710. doi:10.3928/1081597X-20150928-04 [CrossRef]
- Riau AK, Liu YC, Lim CHL, et al. Retreatment strategies following small incision lenticule extraction (SMILE): in vivo tissue responses. PloS One. 2017;12:e0180941. doi:10.1371/journal.pone.0180941 [CrossRef]
- Wang MY, Maloney RK. Epithelial ingrowth after laser in situ keratomileusis. Am J Ophthalmol. 2000;129:746–751. doi:10.1016/S0002-9394(00)00357-3 [CrossRef]
- Ryu IH, Kim BJ, Lee JH, Kim SW. Comparison of corneal epithelial remodeling after femtosecond laser-assisted LASIK and small incision lenticule extraction (SMILE). J Refract Surg. 2017;33:250–256. doi:10.3928/1081597X-20170111-01 [CrossRef]
- Luft N, Ring MH, Dirisamer M, et al. Corneal epithelial remodeling induced by small incision lenticule extraction (SMILE). Invest Ophthalmol Vis Sci. 2016;57:176–183. doi:10.1167/iovs.15-18879 [CrossRef]
- Ganesh S, Brar S, Relekar KJ. Epithelial thickness profile changes following small incision refractive lenticule extraction (SMILE) for myopia and myopic astigmatism. J Refract Surg. 2016;32:473–482. doi:10.3928/1081597X-20160512-01 [CrossRef]
- Reinstein DZ. Small-incision lenticule extraction retreatments by thin flap LASIK. Presented at: the American Academy of Ophthalmology annual meeting. ; October 27–30, 2017. ; New Orleans, LA. .
- Bergmanson JP, Horne J, Doughty MJ, Garcia M, Gondo M. Assessment of the number of lamellae in the central region of the normal human corneal stroma at the resolution of the transmission electron microscope. Eye Cont Lens. 2005;31:281–287. doi:10.1097/01.ICL.0000165280.94927.0D [CrossRef]
- Radner W, Zehetmayer M, Aufreiter R, Mallinger R. Interlacing and cross-angle distribution of collagen lamellae in the human cornea. Cornea. 1998;17:537–543. doi:10.1097/00003226-199809000-00012 [CrossRef]
- Morishige N, Petroll WM, Nishida T, Kenney MC, Jester JV. Noninvasive corneal stromal collagen imaging using two-photon-generated second-harmonic signals. J Cataract Refract Surg. 2006;32:1784–1791. doi:10.1016/j.jcrs.2006.08.027 [CrossRef]
- Sefat SM, Wiltfang R, Bechmann M, Mayer WJ, Kampik A, Kook D. Evaluation of changes in human corneas after femtosecond laser-assisted LASIK and small-incision lenticule extraction (SMILE) using non-contact tonometry and ultra-high-speed camera (Corvis ST). Curr Eye Res. 2016;41:917–922. doi:10.3109/02713683.2015.1082185 [CrossRef]
- Beerthuizen JJ, Siebelt E. Surface ablation after laser in situ keratomileusis: retreatment on the flap. J Cataract Refract Surg. 2007;33:1376–1380. doi:10.1016/j.jcrs.2007.04.024 [CrossRef]
Demographic Data and Refractive Resultsa
|Eyes||22 (10 left, 12 right)|
|Patients||17 (8 male, 9 female)|
|Follow-up (mo)||3 ± 0 (3 to 3)|
|Age at SMILE (y)||37.5 ± 10.6 (22 to 53)|
| Mean MRSE (D)||−5.56 ± 2.22 (−9.25 to −2.50)|
| Mean astigmatism (D)||−1.74 ± 1.07 (−4.00 to −0.50)|
| Mean CDVA (logMAR)||0.01 ± 0.07 (0.2 to 0.0)|
|Time between SMILE and CIRCLE (mo)||10.0 ± 7.9 (3 to 29)|
| Mean MRSE (D)||−0.51 ± 1.08 (−2.75 to 1.00)|
| Mean astigmatism (D)||−0.68 ± 0.36 (−1.25 to 0.00)|
| Mean UDVA (logMAR)||0.37 ± 0.16 (0.6 to 0.2)|
| Mean CDVA (logMAR)||0.01 ± 0.07 (0.2 to −0.1)|
|3 months after CIRCLE|
| Mean MRSE (D)||+0.18 ± 0.31 (−0.25 to 0.88)|
| Mean astigmatism (D)||−0.20 ± 0.24 (−0.50 to 0.00)|
| Mean UDVA (logMAR)||0.03 ± 0.07 (0.2 to 0.0)|
| Mean CDVA (logMAR)||0.02 ± 0.04 (0.1 to 0.0)|