Visual and refractive outcomes of 100 small incision lenticule extractions (SMILE) in moderate and high myopia: a 24-month follow-up study

1 2 3 56 57 58 59 60 61 62 63 64 65 2 24 36 39 4 Visual and refractive outcomes of 100 small incision lenticule extractions (SMILE) in moderate and high myopia: a 24-month follow-up study Sánchez-González, José-Maríaa, Alonso-Aliste, Federicob a Department of Physics of Condensed Matter, Optics Area, University of Seville, Reina Mercedes St. Physic Faculty, Seville, Spain b Department of Ophthalmology, Tecnolaser Clinic Vision®, Refractive Surgery Centre, Juan Antonio Cavestany 14 Street, Seville, Spain Abstract 5 6 7 Purpose: We aimed to present the visual results obtained in 100 small incision lenticule extraction (SMILE) 8 refractive surgeries; demonstrate whether the technique is effective in the treatment of moderate and high myopia; 9 10 and observe the follow-up of these patients over 24-month period. 11 12 Methods: One hundred eyes of 50 consecutive patients were treated with SMILE. The preoperative spherical 13 14 equivalent refraction was -5.64 ± 1.23 D. During the postoperative period, patients were examined at 3, 6, 12, and 15 24 months. We analysed the efficacy, safety, predictability, and stability of the technique. 16 17 Results: The Snellen visual acuity of 99% of the patients was 20/20 or better after 24 months of follow-up. Two 18 19 eyes had a loss of two lines of visual acuity; 1% of the patients had a loss of one line of visual acuity. The 20 postoperative spherical refraction was -0.04 ± 0.35 D (-1.00 to 0.50 D). The postoperative spherical equivalent 21 22 refraction was -0.19 ± 0.38 D (-1.25 to 0.50 D). Eighty-three percent of the eyes were within ± 0.50 D, and 87% 23 obtained a residual astigmatism of 0.50 D or less. 25 26 Conclusion: The SMILE technique was demonstrated to be an effective, predictable, safe, and stable technique 27 in the treatment of moderate-to-severe myopia during the 24-month follow-up. Long-term follow-up should be 28 29 undertaken to observe possible refractive regressions. 30 31 32 33 Keywords 34 35  Small incision lenticule extraction 37  Visual outcomes 38  Femtosecond 40  Refractive surgery 41 42 43 44 1 2 3 56 57 58 59 60 61 62 63 64 65 3 45 46 47 48 49 50 51 52 53 54 55 1 2 3 56 57 58 59 60 61 62 63 64 65 4 8 11 48 51 54 4 Introduction 5 6 Small incision lenticule extraction (SMILE) is a minimally invasive procedure, in which no corneal flap is 7 performed. The first results of SMILE surgery were published in 2011 by Shah[1] and Sekundo.[2] The 9 femtosecond laser has been used In ophthalmology for corneal flaps[3], intrastromal rings or RAINDROP®, and 10 the KAMRA® pocket. In the last decade, the femtosecond laser has obtained more accuracy and several uses.[4, 12 5] 13 14 The ability to make high-precision cuts in the cornea led to the birth of intrastromal surgery, which is less 15 16 invasive[6] than femtosecond laser assisted in situ keratomileusis (LASIK). During SMILE, the femtosecond laser 17 is used to create an intrastromal lenticule with a small 2-mm incision in an arched and peripheral shape. After the 18 19 creation of the lenticule, the anterior and posterior tissue bridges of the lenticule are separated.[7] The lenticule is 20 then removed with a tweezer via the small incision. This process is performed 100% with femtosecond laser.[1] 21 22 23 SMILE is currently a surgical technique that is only performed in subjects with myopia, although it is getting 24 results in hyperopia.[8] A study has analysed the possibility of preserving the lenticule obtained from the surgery 25 26 in a myopic patient and implanting it in a hyperopic patient.[9] Although, more recently, a study has pointed to 27 carving the extracted lenticule with a curvature favourable to hyperopia.[10] 28 29 30 31 32 Materials and Methods 33 34 Subjects 35 36 This retrospective, longitudinal, and descriptive study analysed the first 100 eyes (50 patients, 32 men and 18 37 38 women) subjected to refractive surgery with SMILE at the Tecnolaser Vision ® Clinic (Seville, Spain). The patients 39 received SMILE to correct their myopia between January and September 2015. The inclusion criteria were as 40 41 follows: a stable refraction, spherical equivalent between -4.00 and -10.00 D, preoperative visual acuity (VA) of 42 20/20 or higher, central corneal thickness of at least 500 µm, no previous ocular surgery, and understanding of 43 44 informed consent. The exclusion criteria were as follows: topography suggestive of keratoconus or corneal 45 degeneration, alteration of extrinsic motility, amblyopic eye, systemic medication, or active ocular disease. 46 47 Contact lens users were advised not to use them at least 15 days before surgery. The surgeries were performed by 49 two surgeon’s expert in the SMILE technique (FAA and JAC). Surgeons performed a twelve-months learning 50 curve with Femtosecond Lenticule Extraction (ReLEx Flex ®) before starting on SMILE. The pre-operative study 52 and postoperative revisions were conducted with the help of optometrists’ who are experts in refractive surgery. 53 The protocol adhered to the principles of the Helsinki declaration. Informed consent was obtained by all 55 participants after explaining the benefits and risks of the SMILE procedure. 1 2 3 60 61 62 63 64 65 5 41 6 Surgical technique 7 8 The procedures were performed with the VisuMax Femtosecond Laser System (Carl Zeiss Meditec AG, Jena, 9 10 Germany) using topical anaesthesia in drops. The patient was placed on the table under the cone. The laser was 11 focused on the patient's pupil. The patient was asked to observe a green light inside the cone. The pulses of the 12 13 laser were applied with a pulse energy of approximately 130 nJ. Focusing on a precise depth in the corneal tissue, 14 the laser created a microphotodisruption in the form of a gas bubble of carbon dioxide and water to create tissue 15 16 separation. The spot distance of each laser spot was 4.5 µm. The frequency of the laser was 500 KHz. The 17 femtosecond incisions were performed in the following order: the back surface of the lenticule, the height of 18 19 lenticule´s edge, the anterior lenticule surface, and the lateral cut incision to access the lenticule. Lenticule´s 20 diameter was fixed at 6.5 mm, and the stromal lid was terminated at the depth of 120 μm, 7.3 mm in diameter 21 22 centred on the pupil. The side cut was set to the width of 3.5 mm and was located at the 12 o'clock position. 23 24 25 26 Statistical analysis 27 28 29 Statistical analysis was performed with SPSS statistics 25.0 (IBM Corporation, Armonk, NY, USA). All VA data 30 were converted into Snellen formats. The Wilcoxon test was performed for non-parametric dependent variables. 31 32 All statistical tests were performed with a 95% confidence level (P < 0.05). 33 34 35 36 Results 37 38 Demographics 39 40 A total of 100 eyes belonging to 50 patients were included in this retrospective study. The age of the patients was 42 32.79 ± 6.71 years (20-48 y). The gender distribution was 64 men and 36 women. The results of preoperative and 43 44 postoperative examinations (i.e., spherical refraction, cylindrical refraction, refraction in spherical equivalent, 45 maximum keratometry, minimum keratometry, mean keratometry, and total central pachymetry) are described in 46 47 the Table 1. 48 49 50 51 Efficacy 52 53 The efficacy is shown in Figure 1A as percentage of preoperative corrected distance visual acuity (CDVA) and 54 55 postoperative uncorrected visual distance acuity (UDVA). The results correspond to a 24-month follow-up period. 56 Ninety-nine percent of the eyes obtained a VA of 20/20 or better in the postoperative period. In addition, 100% 57 58 obtained a VA of 20/25 or better. Both eyes with PRK enhancement have been excluded from the statistics (UDVA 59 and CDVA). The efficacy index was 0.97 at 24 months after SMILE surgery. 1 2 3 60 61 62 63 64 65 6 11 14 32 4 5 6 7 8 Safety 9 10 The safety results for the SMILE technique are presented in Figure 1B. After the 24-month follow-up visit, it was 12 observed that 97% (95 eyes) did not obtain changes in VA on the Snellen test. One eye lost one line of sight on 13 VA Snellen, and two eyes lost two lines of vision in Snellen VA. Also, there were two eyes (2%) that achieved a 15 twoline improvement in Snellen VA. 16 17 In two of the surgeries, the lenticule did not come out complete and, thus, created an irregular astigmatism; these 18 19 two cases correspond with the patients who lost two lines of Snellen VA. This residual irregular astigmatism was 20 not correctable with ophthalmic lenses or contacts lenses. Finally, the ocular surface was adjusted by topography- 21 22 guided photorefractive surgery (PRK). During the surgeries, separation of the lenticule tissue bridges was 23 achieved for a satisfactory surgery. 24 25 26 27 28 Predictability 29 30 The results of predictability are shown in Figure 1C. The mean predictability was -0.06 ± 0.01. The regression 31 line value was 0.9979x + 0.18. The spherical equivalent obtained was as follows: 83% of the eyes were within ± 33 0.50 D range, and 97% of the eyes resulted in ± 1.00 D (Figure 1D). The residual astigmatism at 24 months 34 35 postoperatively was 87% 0.50 D or less and 99% 1.00 D or less (Figure 1E). 36 37 38 39 Stability 40 41 The stability outcome is shown in figure 1F. The change in the refraction manifested before and after SMILE was 42 43 -5.64 ± 1.23 D preoperatively and -0.19 ± 0.38 D postoperatively. There were no observed statistically significant 44 differences between the results at 3 months (-0.15 ± 0.64 D) and those at 6 months (-0.13 ± 0.59 D) (P = 0.09), 45 46 nor were there statistically significant differences observed between the results at 12 months (-0.19 ± 0.44 D) and 47 those at 24 months (-0.31 ± 0.62 D) (P = 0.12). 48 49 50 51 52 Patients described a satisfactory experience in relation to the surgical process, as well as postoperative results. 53 However, patients found that the visual recovery process was slower than expected. The average visual recovery 54 55 time was 3.05 ± 1.20 (1.00 – 4.00) weeks. 56 57 58 59 1 2 3 60 61 62 63 64 65 7 8 17 58 4 Discussion 5 6 This study reports visual outcomes obtained in 100 SMILE surgeries. We have analysed the efficacy, safety, 7 predictability, and stability with a follow-up time of 24 months. 9 10 After observing the results, our study showed that the technique of refractive surgery with SMILE is effective in 11 myopia treatment, predictable in refraction results, and stable over 2 years. To our knowledge, we presented the 12 13 largest number of eyes with a follow-up of 24 months in the scientific literature regarding SMILE visual outcomes. 14 15 Efficacy is shown with a cumulative percentage of UDVA with 20/20 or better of 99% (Figure 1A); other authors 16 obtained excellent results of over 90%.[11–17] These authors have shown results like those obtained in our work. 18 In our case, a 100% of the eyes obtained a UDVA of 20/25 or better. There have been, however, critical studies 19 20 in which the efficacy of the SMILE technique was below 90% of VA in 20/20 or better[18–21], and even below 21 60%.[22, 23] It is important to note that the follow-up period of the studies with the worst efficacy results[22, 22 23 23] was 3 months; thus, the VA of the patients included in the study was not yet stable. 24 25 26 27 In terms of safety, 1% of the eyes in our study lost one line of VA (figure 1B). In this case, other authors[11, 13, 28 29 16, 18, 19, 21, 23] had dismissed a loss of similar VA. In contrast, other studies described worse results (between 30 12% and 23%).[12, 14, 15, 20, 24, 25]In our work, we obtained 2 eyes with a loss of two lines, which is the same 31 32 as was found by other authors who described the SMILE technique. The eyes that had a loss of two lines had an 33 incomplete extraction of the lenticule. Fragments of the lenticule were inside the interface and were impossible to 34 35 extract. These complications have been critical in a recent study published by Hamed et al.[26] and Han et al.[27] 36 Other prevalent complications have been described by Ramirez-Miranda et al. [28] as epithelial defect, cap rupture 37 38 or opaque bubble layer. It was necessary to re-treat these two eyes with topography-guided photorefractive 39 keratectomy (PRK)[29] to regulate the unequal surface caused by the lenticule´s fragments. Six months of after 40 41 re-treatment, the two eyes recovered a VA of 20/20. Other authors such as Breyer et al. [30] reported safety of 42 SMILE even with a percent of tissue altered (PTA) more than 40%. They found 97.7% eyes (in < 40% PTA group) 43 44 and 96.4% eyes (in ≥ 40% PTA group) remained unchanged or gain lines. 45 46 47 48 SMILE's predictability was also studied; after performing the linear regression, the following line was obtained: 49 50 y = 0.9977x + 0.1858 (Figure 1C). Thus, for a calculated correction refractive of - 1.00 D, the final correction 51 obtained was - 1.18 D. This implies a mean hypercorrection of - 0.18 D. The predictability obtained by the other 52 53 authors are shown in Table 2. The results of the spherical equivalent obtained (83% ≤ ± 0.50 D and 97% ≤ ± 1.00 54 D) (Figure 1D) are in line with those obtained by a large number of studies.[11–16, 18, 19, 21–23] Authors such 55 56 as Blum et al.[24] and Pedersen et al.[20] obtained greater variability in their results. As for the refractive 57 astigmatism, excellent results were obtained: 87% ≤ ± 0.50 D and 99% ≤ ± 1.00 D (Figure 1E). In this case, few 59 authors studied the refractive astigmatism obtained in SMILE. 1 2 3 61 62 63 64 65 8 18 21 24 42 54 4 As for stability, 3% of the eyes obtained a change ≥ ± 0.50 D on comparing the spherical equivalent refraction 5 between the 12-month and 24-month visits. In contrast, in terms of refractive change, patients obtained an average 6 7 refractive regression of -0.24 D on between the 3-month and 24-month visits. Other authors with follow-up periods 8 of 5 years[24] and 4 years[11] obtained a regression of - 0.48 D in the case of Blum et al.; and, 10.6% of the eyes 9 10 obtained a myopic regression ≥ ± 0.50 D in the case of Han et al. 5-years data reported by Blum et al. a 200kHz 11 laser was used, not the VisuMax System used in this study. Burazovitch et al. [31] reported that four years after 12 13 the surgery, 87% high myopic group eyes were within 0.50 D target. Other studies with a short follow-up 14 period[12, 13, 15, 16, 19, 21, 23] (from 3 months to 12 months) obtained excellent stability results. Zhao et al. 15 16 [32] reported that posterior corneal surface changes were stable after SMILE in long-term follow-up. The 17 agreement of our results with those of the other authors suggests that the SMILE technique remains stable until 19 12 months, after which there is a slight regression up to 24 months. Although, in our study, this did not seem to 20 impact in terms visual efficacy. In this sense, patients included in this study have shown their commitment to 22 follow up after 10 years from SMILE surgery. The data obtained will provide us with conclusive values of myopic 23 regression in SMILE. 25 26 In conclusion, SMILE has proved to be effective, safe, predictable, and stable in the treatment of moderate myopia 27 with a 24-month follow-up. 28 29 30 31 32 Compliance with Ethical Standards 33 34 Funding: No funding was received for this research 35 36 Conflict of interest: Sánchez-González, José-María declares that he has no conflict of interest. Alonso-Aliste, 37 38 Federico declares that he has no conflict of interest. 39 40 Ethical approval: All procedures performed in studies involving human participants were in accordance with the 41 ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration 43 and its later amendments or comparable ethical standards. 44 45 Informed consent: Informed consent was obtained from all individual participants included in the study. 46 47 48 49 50 References 51 52 1. Shah R, Shah S, Sengupta S (2011) Results of small incision lenticule extraction: All-in-one 53 femtosecond laser refractive surgery. J Cataract Refract Surg 37:127–137 . doi: 55 10.1016/j.jcrs.2010.07.033 56 57 2. Sekundo W, Kunert KS, Blum M (2011) Small incision corneal refractive surgery using the small 58 59 incision lenticule extraction (SMILE) procedure for the correction of myopia and myopic astigmatism: 60 results of a 6 month prospective study. Br J Ophthalmol 95:335–339 . doi: 10.1136/bjo.2009.174284 1 2 3 61 62 63 64 65 9 8 11 54 4 3. Kim P, Sutton GL, Rootman DS (2011) Applications of the femtosecond laser in corneal refractive 5 surgery. Curr Opin Ophthalmol 22:238–244 . doi: 10.1097/ICU.0b013e3283477c9c 6 7 4. Sekundo W, Kunert K, Russmann C, et al (2008) First efficacy and safety study of femtosecond 9 lenticule extraction for the correction of myopia. Six-month results. J Cataract Refract Surg 34:1513– 10 1520 . doi: 10.1016/j.jcrs.2008.05.033 12 13 5. Ang M, Chaurasia SS, Angunawela RI, et al (2012) Femtosecond lenticule extraction (FLEx): Clinical 14 results, interface evaluation, and intraocular pressure variation. Investig Ophthalmol Vis Sci 53:1414– 15 16 1421 . doi: 10.1167/iovs.11-8808 17 18 6. Moshirfar M, McCaughey M V., Reinstein DZ, et al (2015) Small-incision lenticule extraction. J 19 20 Cataract Refract Surg 41:652–665 . doi: 10.1016/j.jcrs.2015.02.006 21 22 7. Park JH, Koo HJ (2017) Comparison of immediate small-incision lenticule extraction after suction loss 23 with uneventful small-incision lenticule extraction. J Cataract Refract Surg 43:466–472 . doi: 24 25 10.1016/j.jcrs.2016.12.034 26 27 8. Blum M, Kunert KS, Vobmerbäumer U, Sekundo W (2013) Femtosecond lenticule extraction 28 29 (ReLEx®) for correction of hyperopia-first results. Graefe’s Arch Clin Exp Ophthalmol 251:349–355 . 30 doi: 10.1007/s00417-012-2064-y 31 32 9. Ganesh S, Brar S, Rao PA (2014) Cryopreservation of extracted corneal lenticules after small incision 33 34 lenticule extraction for potential use in human subjects. Cornea 33:1355–62 . doi: 35 10.1097/ICO.0000000000000276 36 37 38 10. Reinstein DZ, Pradhan KR, Carp GI, et al (2017) Small Incision Lenticule Extraction (SMILE) for 39 Hyperopia: Optical Zone Centration. J Refract Surg 33:150–156 . doi: 10.3928/1081597X-20161220-01 40 41 11. Han T, Zheng K, Chen Y, et al (2016) Four-year observation of predictability and stability of small 42 43 incision lenticule extraction. BMC Ophthalmol 16:149 . doi: 10.1186/s12886-016-0331-0 44 45 12. Kamiya K, Shimizu K, Igarashi A, Kobashi H (2014) Visual and Refractive Outcomes of Femtosecond 46 47 Lenticule Extraction and Small-Incision Lenticule Extraction for Myopia. Am J Ophthalmol 157:128– 48 134.e2 . doi: 10.1016/j.ajo.2013.08.011 49 50 13. Kim JR, Kim BK, Mun SJ, et al (2015) One-year outcomes of small-incision lenticule extraction 51 52 (SMILE): mild to moderate myopia vs. high myopia. BMC Ophthalmol 15:59 . doi: 10.1186/s12886- 53 015-0051-x 55 56 14. Kobashi H, Kamiya K, Igarashi A, et al (2018) Two-years results of small-incision lenticule extraction 57 and wavefront-guided laser in situ keratomileusis for Myopia. Acta Ophthalmol 96:e119–e126 . doi: 58 59 10.1111/aos.13470 60 1 2 3 61 62 63 64 65 1 0 11 39 48 54 57 4 15. Liu M, Chen Y, Wang D, et al (2016) Clinical Outcomes After SMILE and Femtosecond Laser-Assisted 5 LASIK for Myopia and Myopic Astigmatism: A Prospective Randomized Comparative Study. Cornea 6 7 35:210–6 . doi: 10.1097/ICO.0000000000000707 8 9 16. Yildirim Y, Olcucu O, Alagoz C, et al (2016) Visual and Refractive Outcomes of Photorefractive 10 Keratectomy and Small Incision Lenticule Extraction (SMILE) for Myopia. J Refract Surg 32:604–610 . 12 doi: 10.3928/1081597X-20160602-02 13 14 17. Miao H, Tian M, Xu Y, et al (2015) Visual Outcomes and Optical Quality After Femtosecond Laser 15 16 Small Incision Lenticule Extraction: An 18-Month Prospective Study. J Refract Surg 31:726–731 . doi: 17 10.3928/1081597X-20151021-01 18 19 20 18. Fernández J, Valero A, Martínez J, et al (2017) Short-term outcomes of small-incision lenticule 21 extraction (SMILE) for low, medium, and high myopia. Eur J Ophthalmol 27:153–159 . doi: 22 23 10.5301/ejo.5000849 24 25 19. Kim JR, Hwang H Bin, Mun SJ, et al (2014) Efficacy, predictability, and safety of small incision 26 lenticule extraction: 6-months prospective cohort study. BMC Ophthalmol 14:117 . doi: 10.1186/1471- 27 28 2415-14-117 29 30 20. Pedersen IB, Ivarsen A, Hjortdal J (2015) Three-Year Results of Small Incision Lenticule Extraction for 31 32 High Myopia: Refractive Outcomes and Aberrations. J Refract Surg 31:719–24 . doi: 33 10.3928/1081597X-20150923-11 34 35 21. Torky MA, Alzafiri YA (2017) Visual and refractive outcomes of small-incision lenticule extraction in 36 37 mild, moderate, and high myopia: Six-month results. J Cataract Refract Surg 43:459–465 . doi: 38 10.1016/j.jcrs.2017.01.015 40 41 22. Hansen RS, Lyhne N, Grauslund J, Vestergaard AH (2016) Small-incision lenticule extraction 42 (SMILE): outcomes of 722 eyes treated for myopia and myopic astigmatism. Graefe’s Arch Clin Exp 43 44 Ophthalmol 254:399–405 . doi: 10.1007/s00417-015-3226-5 45 46 23. Lin F, Xu Y, Yang Y (2014) Comparison of the visual results after SMILE and femtosecond laser- 47 assisted LASIK for myopia. J Refract Surg 30:248–54 . doi: 10.3928/1081597X-20140320-03 49 50 24. Blum M, Täubig K, Gruhn C, et al (2016) Five-year results of Small Incision Lenticule Extraction 51 (ReLEx SMILE). Br J Ophthalmol 100:1192–5 . doi: 10.1136/bjophthalmol-2015-306822 52 53 25. Messerschmidt-Roth A, Sekundo W, Lazaridis A, Schulze S (2016) Drei Jahre Nachbeobachtung nach 55 refraktiver Small Incision Lenticule Extraction (SMILE) mit einem 500-kHz-Femtosekundenlaser im 56 „Fast Mode“. Klin Monbl Augenheilkd 234:102–108 . doi: 10.1055/s-0042-117281 58 59 26. Hamed AM, Abdelwahab SM, Soliman TT (2018) Intraoperative complications of refractive small 60 incision lenticule extraction in the early learning curve. Clin Ophthalmol 12:665–668 . doi: