Small incision lenticule extraction (SMILE) has become a widely available and increasingly popular treatment for myopia, offering results on par with LASIK with respect to safety and efficacy.1–5 However, primary refractive undercorrection and myopic regression may cause the need for re-treatment to obtain a final, satisfying result in some patients. After LASIK, regression of −1.04 diopters (D) after 10 years6 has been reported and enhancement rates currently vary from 1% to 6%.7–9 In contrast, 5-year results after myopic SMILE indicated a mean regression of −0.48 D and 21.4% of eyes not within ±1.00 D of target refraction.3 Recently published data on enhancement after SMILE provided an incidence of 2.9% at 2 years.10 However, at the moment no detailed clinical data on safety, efficacy, and speed of visual recovery are available. Therefore, this study presents the results of a multicenter retrospective analysis of 40 eyes re-treated with surface ablation after myopic SMILE. To our knowledge, this is the largest study on surface enhancement after myopic SMILE.
Patients and Methods
Databases of the SMILE Eyes Clinics in Marburg (Germany), Munich (Germany), and Linz (Austria), and the Cabinet de Chirurgie Réfractive (Luxembourg) were screened for patients who had undergone surface ablation re-treatment after myopic SMILE. Respective institutional review board approval was obtained for all centers. Prior to treatment, slitlamp biomicroscopy and funduscopy, objective, subjective, and cycloplegic refraction, and Pentacam corneal tomography (Oculus Optikgeräte GmbH, Wetzlar, Germany) were performed to rule out contraindications for corneal refractive treatment. Uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA) were assessed at all visits. Informed consent was obtained from all patients. All study-related procedures adhered to the tenets of the Declaration of Helsinki.
Details on the SMILE procedure have been provided elsewhere.1,2,11 In brief, surgery was performed under topical anesthesia with oxybuprocaine hydrochloride (Bausch & Lomb, Rochester, NY) using a 500-kHz VisuMax femtosecond laser (Carl Zeiss Meditec AG, Jena, Germany). After sterile draping, the eye of the patient was placed under the femtosecond laser's operating microscope, centered and immobilized with a suction contact glass. While the patient was asked to fixate on a target light, the posterior surface, the lateral border, and the anterior surface of the lenticule were cut by the laser, followed by one or two incisions of 40° chord length each. The lenticule planes were then manually dissected and the lenticule was removed through one of the incisions. The postoperative treatment regimen consisted of levofloxacin (Oftaquix; Santen, Osaka, Japan) eye drops four times daily for 1 week, dexamethasone (DexaSine; Alcon, Hünenburg, Switzerland) eye drops four times daily tapered to individual need, and lubricant eye drops as needed.
At each follow-up visit, individual refractive and visual outcomes were reevaluated. In cases of unsatisfying results, patients were thoroughly informed of the chances and risks of a re-treatment. All patients willing to undergo enhancement provided informed consent before treatment.
Surface ablation was performed as described previously12 with plano target in all eyes. In brief, the corneal epithelium was delaminated by application of 20% ethanol for 20 seconds, thoroughly rinsed with balanced salt solution (BSS), and then manually peeled off (LASEK technique). Ablation was performed with either the MEL 80 or MEL 90 excimer laser (Carl Zeiss Meditec AG) with plano target refraction. A total of 27 eyes (67.5%) were treated using the Triple-A advanced ablation algorithm introduced in the MEL 90 laser, combining optimized energy level correction with an aspherically optimized profile and a focus on tissue saving, which is especially useful in lower corrections up to 3.00 D. On the MEL 80 laser, the tissue-saving algorithm (TSA) (reducing ablation depth) was used in 8 (20%) eyes, the topography-guided algorithm (improving corneal surface regularity) was used in 3 (7.5%) eyes, and the aspherically optimized profile (ASA) was used in 2 (5%) eyes. To prevent haze,13 a sponge soaked with 0.02% mitomycin C solution was applied for 20 to 25 seconds immediately after excimer laser treatment, followed by thorough rinsing with BSS. At the end of surgery, the epithelium was reattached or discarded at the discretion of the surgeon. Postoperative care included application of a bandage contact lens and levofloxacin eye drops four times daily until reepithelialization, 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). Statistical comparison of manifest refraction spherical equivalent (MRSE) and visual acuity between multiple groups at different time points was performed with a repeated measures analysis of variance Bonferroni test. A P value less than .05 was considered statistically significant with a 95% confidence interval.
Between March 2013 and June 2015, 1,963 eyes were treated with myopic SMILE. Surface ablation re-treatment was performed in 43 eyes of 31 patients (2.2%). After exclusion of 3 eyes due to follow-up shorter than 3 months, 40 eyes (22 right, 18 left) of 28 patients (17 female, 11 male) were included in this retrospective multicenter study.
At the date of SMILE, the mean age was 38.4 ± 9.4 years (range: 22 to 52 years). The mean preoperative MRSE was −6.35 ± 1.31 D (range: −9.25 to −3.75 D) (Figure 1); mean preoperative sphere and cylinder were −5.83 ± 1.43 D (range: −9.00 to −3.50 D) and −1.06 ± 0.94 D (range −3.50 to 0.00 D), respectively. Mean CDVA before SMILE was 0.01 ± 0.09 logMAR (range: −0.20 to 0.20 logMAR); 92.5% of eyes had a CDVA of 0.10 logMAR or better and 72.5% achieved 0.00 logMAR or better. The mean optical zone size of the SMILE treatment was 6.5 ± 0.1 mm (range: 6.2 to 6.7 mm).
Change of mean refractive spherical equivalent (MRSE) over time. After small incision lenticule extraction (SMILE), MRSE significantly decreased to −0.55 diopters (D). During the mean 9.8 months until enhancement, a significant mean regression of −0.31 D was noted, resulting in a spherical equivalent of −0.86 ± 0.43 D directly before re-treatment. One week after enhancement, spherical equivalent had already significantly improved and remained stable until month 3, resulting in a final spherical equivalent of 0.03 ± 0.57 D (range −1.75 to 1.75 D). SD = standard deviation
Surface ablation was performed in all 40 eyes with no intraoperative complications. Before surface ablation re-treatment, MRSE was −0.86 ± 0.43 D (range: −1.75 to 0.00 D) (Figure 1); mean sphere and cylinder were −0.64 ± 0.53 D (range: −1.50 to 0.75 D) and −0.69 ± 0.58 D (range: −3.00 to − 0.50 D), respectively. The mean optical zone of the surface ablation treatment was 6.4 ± 0.3 mm (range: 5.5 to 7 mm). The mean interval between SMILE and surface ablation re-treatment was 9.82 ± 5.27 months (range: 3 to 22.6 months).
Reepithelialization occurred in all eyes within 3 days. With respect to the postoperative complications encountered, significant haze developed in 1 eye of 1 patient (2.5%), but resolved after prolonged topical dexamethasone treatment. One week after surface ablation, mean MRSE significantly decreased to 0.07 ± 0.86 D (range: −1.50 to −0.25 D) and remained stable until month 3, finally resulting in 0.03 ± 0.57 D (range −1.75 to 1.75 D; P < .0001) (Figure 1).
The distribution of MRSE before and after re-treatment can be found in Figure 2. Before re-treatment, 22.5% and 72.5% of eyes were within ±0.50 and ±1.00 D of target refraction. After re-treatment, 80% were within ±0.50 D and 92.5% were within ±1.00 D of target refraction. The percentage of eyes greater than 1.00 D from target refraction decreased from 27.5% to 7.5%. Figure 3 lists the changes in refractive astigmatism. The number of patients within ±0.50 D of astigmatism increased from 72.5% to 90%. After re-treatment, no patients had astigmatism greater than 1.00 D (before enhancement: 10%). A comparison of attempted versus achieved manifest spherical refraction can be found in Figure 4.
Distribution of manifest spherical equivalent refraction before and after re-treatment. The number of patients within ±0.50 and ±1.00 diopters (D) from target refraction increased from 22.5% to 80% and from 72.5% to 92.5%. SA = surface ablation
Distribution of refractive astigmatism. The number of patients within ±0.50 diopters (D) of astigmatism increased from 72.5% to 90%. After re-treatment, no eyes had an astigmatism of 1.00 D or worse (before enhancement: 10%). SA = surface ablation
Attempted versus achieved spherical equivalent refraction. By definition of spherical equivalent within ±1.00 diopters (D) from target refraction, 2 eyes (5%) were overcorrected and 1 eye was undercorrected (2.5%).
Distribution of UDVA before and after re-treatment is given in Figure 5. The number of eyes with a UDVA of 0.10 logMAR or better increased from 47.5% to 80%, and the proportion of eyes with a UDVA of 0.00 logMAR or better could be expanded from 12.5% to 62.5%. Concerning safety, changes in CDVA at 3 months are given in Figure 6. CDVA remained unchanged in 52.5% of re-treated eyes, 30% gained one line, and 2.5% gained two lines. A total of 6 eyes (15%) lost one line; of these, final CDVA was 0.00 logMAR in 4 eyes and 0.10 logMAR in 2 eyes. Changes in UDVA are displayed in Figure 6. A proportion of 65% of eyes gained at least one line, 15% gained two lines, and 22.5% gained more than two lines. All but 2 eyes (MRSE: −1.75 and +0.88 D) had a final UDVA of 0.30 logMAR or better. At 3 months, the safety and efficacy indices were 1.06 and 0.90, respectively.
Distribution of uncorrected distance visual acuity (UDVA) before and after re-treatment. The number of eyes with UDVA of 0.10 logMAR or better increased from 47.5% to 80% and the proportion of eyes with UDVA of 0.00 logMAR or better increased from 12.5% to 62.5%. SA = surface ablation
A total of 65% of eyes gained at least one line of uncorrected distance visual acuity (UDVA), 15% gained two lines and 22.5% gained more than two lines, 15% lost one line, and UDVA remained unchanged in 20%. Corrected distance visual acuity (CDVA) remained unchanged in 52.5% of re-treated eyes, 30% gained one line, 2.5% gained two lines, and 15% lost one line.
The time course of recovery can be found in Figure 7. UDVA significantly improved from 0.23 ± 0.15 to 0.05 ± 0.11 logMAR at 6 weeks and remained stable until month 3, finally resulting in 0.08 ± 0.15 logMAR (P < .0001). Starting at 0.01 ± 0.07 logMAR, CDVA deteriorated at week 1 but returned to baseline at week 6 and remained stable until month 3 (−0.01 ± 0.05 logMAR, P = .99).
Time course of uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA) after surface ablation (SA). UDVA significantly improved at 6 weeks and remained stable until month 3. CDVA significantly worsened at week 1 but returned to baseline at week 6 and remained stable until month 3.
At 3 months, eyes treated with the Triple A, TSA, and topography-guided algorithms were considerably closer to target refraction (−0.13 ± 0.50 vs 0.11 ± 0.34 vs 0.13 ± 0.13 D, respectively) than eyes treated with the ASA profile. The two eyes treated with the latter profile were both overcorrected (1.56 ± 0.27 D). Excluding these two eyes from analysis, the efficacy index was 0.92 at 3 months.
In contrast to LASIK, which offers flap relifting as a safe option for re-treatment,14 choosing the optimal enhancement method after SMILE remains a highly debatable topic. Currently, creating another lenticule beyond the posterior cleavage plane (re-SMILE) has only been described in a case report by Donate and Thaeron15 and is not being performed in clinical routine. Therefore, at the moment flap-based approaches or surface ablation are the only methods available.2
In thicker caps, secondary thin-flap femtosecond laser–assisted LASIK with the flap being created superficial to the original SMILE interface is possible. In thin caps, a LASIK flap located more deeply in the stroma can be created or a femtosecond laser can be used to convert the cap into a full flap.16 For the latter, the CIRCLE option in the VisuMax software is available, most popularly set to create a lamellar ring at the same depth as the original SMILE interface, a side cut with a hinge, and a junction cut.17,18 However, from a patient perspective it may seem paradoxical to be offered a flap-based re-treatment after having chosen SMILE over LASIK in the first place in light of its possible advantages as a flap-free procedure.
In this context, surface ablation offers an alternative treatment preserving possible advantages of a flap-free approach. Both SMILE and surface ablation have been shown to have less impact on corneal biochemanical19,20 and tear film stability than LASIK.21,22 Our study indicates that surface ablation with mitomycin C is a safe and effective option in patients significantly disturbed by insufficient refractive correction after SMILE. The re-treatment rate of 2.2% reported in our study correlated well with previous findings. Liu et al.10 reported an incidence of 2.9% at 2 years. Preoperative MRSE was similar to previous studies reporting enhancement after LASIK.3,6,23–26 At 3 months, the safety index was 1.06, all patients achieved a CDVA of at least 0.1, and 90% had visual acuity of at least 0.00 logMAR. Of note, Beerthuizen and Siebelt12 reported late-onset haze occurring in a patient 8 months after surface ablation enhancement after LASIK. Therefore, longer follow-up is needed for a final evaluation of safety. In our study, significant haze was only observed in one patient, which is most likely attributable to the prophylactic use of mitomycin C. Although no data on its necessity after SMILE enhancement are available, its use has been firmly established for surface ablation enhancement after LASIK, and also seemed necessary in the case of SMILE enhancement. Despite the low intended correction, removal of the lenticule in the first procedure represents significant corneal trauma, which in combination with additional surface treatment poses a high risk of exaggerated wound healing. Although 6 eyes (15%) lost one line of CDVA, in these cases final CDVA was 0.0 in 4 eyes and 0.10 logMAR in 2 eyes, and no obvious anatomical features correlating with this reduction in visual acuity (eg, haze formation) were encountered at month 3.
In terms of efficacy, refraction significantly improved at 1 week and remained stable until the end of follow-up at 3 months. Mean UDVA significantly increased from 0.20 to 0.00 logMAR and the percentage of eyes within ±0.50 D of target refraction increased from 27.5% to 80%. A proportion of 65% of eyes gained at least one line of UDVA. These data are similar to results of surface ablation on virgin eyes, but with a greater standard deviation and rate of overcorrection.12,25 In this context, the effects of mitomycin C on overcorrection (+0.47 D as reported by Leccisotti27) have to be considered. However, efficacy in our study was similar to enhancement after LASIK. Beerthuizen and Siebelt12 reported an efficacy index of 0.87 at 3 months after surface ablation for LASIK re-treatment, corresponding well with our finding of 0.90. It is known that efficacy can drop after month 3 due to secondary regression.7 Therefore, longer follow-up is needed for final evidence.
At 3 months after surface ablation re-treatment, two eyes had a UDVA of 0.30 logMAR or worse. One of these eyes had a final spherical equivalent of −1.75 D. We believe that early regression might have developed in this case because two risk factors were present (early re-treatment after 4.4 months and highest MRSE before SMILE) and because MRSE was +0.63 at 1 week after SMILE.14,25 As Liu et al.10 have shown, risk of re-treatment is increased with higher MRSE before SMILE. The second patient was overcorrected and had a final spherical equivalent of +0.88 D. Nevertheless, in both eyes final CDVA was 0.00 logMAR.
Four surface ablation algorithms were used, including the TSA, ASA, and topography-guided profiles on the Zeiss MEL 80 laser and the newly introduced Triple-A mode on the MEL 90 laser. Although there was no evident difference in accuracy between the TSA, Triple-A, and topography-guided profile, in our hands the two eyes treated with the ASA profile were the ones with the highest overcorrection (+1.75 and +1.38 D). This can be explained by the fixed amount of induced asphericity in the ASA profile independent of the degree of myopia to be corrected, thus leading to an increased ablation depth in low myopia.28 Because the amount of MRSE is generally low in secondary enhancement, the authors do not recommend the use of the ASA profile in these cases.
In our study, 7 eyes underwent enhancement before 6 months, with overall good refractive results (MRSE within ±0.50 D from target refraction) in 5 of these (71.4%). Nevertheless, it must be noted that we only present a 3-month follow-up period and longer clinical observation is needed to determine whether early retreatment is advisable concerning refractive stability and patient satisfaction.
Surface ablation augmented with mitomycin C seems to be a safe and effective enhancement method after myopic SMILE. There is a need for larger scale studies and longer follow-ups beyond 3 months to provide conclusive evidence, especially in the light of future developments in SMILE-based enhancement methods.
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- Shah R, Shah S, Sengupta S. Results of small incision lenticule extraction: all-in-one femtosecond laser refractive surgery. J Cataract Refract Surg. 2011;37:127–137. doi:10.1016/j.jcrs.2010.07.033 [CrossRef]
- Vestergaard A, Ivarsen A, Asp S, Hjortdal JO. Femtosecond (FS) laser vision correction procedure for moderate to high myopia: a prospective study of ReLEx((R)) flex and comparison with a retrospective study of FS-laser in situ keratomileusis. Acta Ophthalmol. 2013;91:355–362. doi:10.1111/j.1755-3768.2012.02406.x [CrossRef]
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- Randleman JB, White AJ, Hu MH, Stulting RD. Incidence, outcomes, and risk factors for enhancement after wavefront-optimized advanced surface ablation and laser in situ keratomileusis. 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]
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- 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]
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- Donate D, Thaeron R. Preliminary evidence of successful enhancement after a primary SMILE procedure with the sub-cap-lenticule-extraction technique. J Refract Surg. 2015;31:708–710. doi:10.3928/1081597X-20150928-04 [CrossRef]
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