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Predictability of SMILE over four years in high myopes
Journal français d’ophtalmologie (2017) 40, e201—e209
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EDITOR’S CHOICE
Predictability of SMILE over four years in high myopes J. Burazovitch a,∗, D. Naguzeswski b, T. Beuste c, M. Guillard b a
Ophthalmology service, Argentan medical center, 47, rue Aristide-Briand, 61200 Argentan, France b rue Quadrant, 14123 Fleury-sur-Orne, France c Ophthalmology service, Caen university medical centre, 32, rue Desmoueux, 14000 Caen, France Received 21 April 2017; accepted 2 May 2017 Available online 7 June 2017
KEYWORDS SMILE; Small incision lenticule extraction; Myopia; High myopia; Predictability
∗
Summary Objective. — To determine whether the visual outcomes of the refractive surgery technique small incision lenticule extraction (SMILE), are stable, effective, and predictable for high myopia over a four-year period. Research design. — This is a retrospective study. The data were collected between March 2012 and July 2016. Participants. — Two hundred and forty-eight patients participated in the study; that is, 496 eyes: 140 eyes of 70 patients (52 women/18 men) were classified into the highly myopic group (refraction measured in spherical equivalent (RMSE) > −6 D), and 356 eyes of 178 patients (98 women/80 men) into the control group (RMSE < −6 D). Follow-up tests were conducted immediately following the procedure (D + 1), after three months, after one year, and after four years. Refraction, uncorrected visual acuity (UCVA), and best visual corrected acuity (BCVA) were measured. The highly myopic group (HMG) contained more women, and astigmatism was higher for this group than for the control group (CG). Primary and secondary study criteria. — These were BCVA, refractive stability, the index of safety (SI: BCVA preoperatively D + 1/BCVA postoperatively), and predictability (the percentage of eyes within ± 0.5 D of the target). Results. — In both groups, UCVA was better after the fourth year than it was immediately after the procedure (HMG: P = 0.001; CG: P = 0.001). Although it differed at one year (P = 0.01), the groups’ refractive stability tended to converge over four years (P = 0.138). The groups’ SI was found to be identical in the four follow-up tests (P = 0.734 at D + 1; P = 0.07 at M + 1; P = 0.160 at M3 and Y1; and P = 0.274 at Y4). For the HMG, SI stability was attained after three months
Corresponding author. E-mail address: burazovitch [email protected] (J. Burazovitch).
http://dx.doi.org/10.1016/j.jfo.2017.05.001 0181-5512/© 2017 Elsevier Masson SAS. All rights reserved.
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J. Burazovitch et al. (1.00 ± 0.1); whereas it was attained after one month (0.91 ± 0.11) for the CG. Four years after the surgery, we observed that 87% of the operated-upon eyes in the HMG were within 0.5 D of the target. Conclusion. — SMILE is a good refractive surgery technique for treating high myopia. It yields stable, safe, effective, and predictable results over four years. © 2017 Elsevier Masson SAS. All rights reserved.
Introduction The refractive surgery technique SMILE (SMall Incision Lenticule Extraction), for the correction of myopia and astigmatism, is a recent technique [1—3], performed with a single laser: the Visumax© femtosecond laser (Carl Zeiss Meditec, Jena, Germany). Short-term studies in moderate and high myopes have confirmed the safety of refractive surgery using SMILE [4—8]. The long-term results of the procedure appear equally encouraging [9—11]. To find out whether this procedure is a long-lasting solution, as well as to respond to the growing demands of patients, is a significant objective in the management of high myopia. The goal of this study is thus to determine, as with similar studies performed to date, if the visual outcomes over four years of the refractive surgery technique SMILE are stable, safe, effective, and predictable in a group of high myopes as compared to a group of low and moderate myopes.
Materials and methods Patient population This was a retrospective study of a cohort of patients who underwent refractive surgery at the Saint-Martin Clinic in Caen between March 2012 and July 2016. The inclusion criteria were absence of contraindications to refractive surgery or the SMILE procedure, based on the Randelman criteria [12], i.e. signs of forme fruste keratoconus on topography; a residual bed less than 250 microns in thickness; age less than 20 years; corneal thickness less than 500 microns; as well as severe dry eye syndrome, atopy, and best corrected visual acuity less than 8/10. The patient was seen for postoperative follow-up the first day, at one month, at three months, at one year, and at four years. At these visits, refraction, uncorrected visual acuity (UCVA), and best corrected visual acuity (BCVA) were measured. The study included 496 eyes of 248 myopic and astigmatic patients separated into two groups (Table 1) depending on their preoperative spherical equivalent refraction (MRSE): 70 patients or 140 eyes were classified into the high myope group (MRSE > −6 D); and 356 eyes of 178 patients into the control group (MRSE < −6 D). The control group (CG) consisted of 55% women and 45% men, with a mean age of 29 years (± 5.17); the youngest patient was 20 years and the oldest 55 years. The mean MRSE
was −3.77 ± 1.15 D, the mean sphere was −3.52 ± 1.13 D, and the mean cylinder was −0.51 ± 0.41 D. The high myope group (HMG) consisted of 74% women and 26% men, with a mean age of 30 years (± 5.95); the youngest patient was 20 years, and the oldest 49 years. The mean MRSE was −7.59 ± 1.12 D, the mean sphere was −7.23 ± 1.14 D, and the mean cylinder was −0.71 ± 0.57 D. The two groups thus presented differences preoperatively in terms of MRSE (P < 0.001), sphere (P < 0.01), gender distribution (P < 0.053; more women in the HMG), and cylinder (P = 0.001; higher astigmatism in the HMG). However, there was no notable difference in mean age.
Surgical technique An experienced surgeon (DN) performed all the SMILE procedures. The Visumax© (Carl Zeiss Meditec, Jena, Germany) 500 kHz femtosecond laser was used for this procedure. The energy delivered per spot was 140 nJ, and the spacing between spots was 4 to 4.5 microns. The cap thickness was 130 microns, and the optical zone diameter was 6.5 mm for all patients. The side cuts were at a 90◦ angle. The chosen target refraction was emmetropia for patients up to 35 years; and a monovision strategy for those over 35 years with an amplitude of 1 dioptre maximum as a function of the initial refraction. A correction factor of the order of 8% was programmed for high ametropia to prevent an under-correction of the myopia. The surgical procedure was performed under topical anaesthesia only, with 1% tetracaine drops (Laboratoire Théa) —– 2 to 3 drops per eye —– prior to the procedure, and was supplemented by a 10 mg tablet of Vératran (Laboratoire Amdipharm Limited) taken one hour beforehand. A standard lid speculum was used to keep the eyes open. The suction ring kept the pupil centered. To start, the posterior lenticule cut was performed in a centripetal direction, and the anterior cap cut in a centrifugal direction. Then, the 2.2 mm primary incision was placed at 12:00 in all patients. After the laser treatment, the Reinstein manipulator (Malosa Laboratory, Yorkshire, England) was used to detach stromal adhesions, and the lenticule extracted mechanically through the primary incision. No secondary incision was necessary. Medications at the conclusion of the procedure were systematically alike for all patients: Tobradex four times per day (Alcon Laboratory) for one week, and Vismed four times per day (HORUS pharma laboratory) for one month.
Predictability of SMILE over four years in high myopes Table 1
CG HMG
Table 2
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Composition of groups. Number of men, n (%)
Number of women, n (%)
80(45) 18(26)
98(55) 52(74)
Total 178 70
Mean age (years)
Cylinder (in D)
29 30
−0.51 ± 0.41 −0.71 ± 0.57
Distribution of uncorrected visual acuity between the two groups. UCVA (Monoyer’s scale)
HMG mean ± standard deviation CG mean ± standard deviation P-value between the two groups * **
D+1
M+1
M+3
Y+1
Y+4
7.57 ± 1.74 7.94 ± 1.66 0.552
8.82 ± 1.22 9.26 ± 1.11 0.002**
8.85 ± 1.22 9.07 ± 1.17 0.440
8.72 ± 1.05 9.44 ± 1.03 0.001**
8.76 ± 0.94 9.48 ± 0.85 0.027*
P < 0.05 P < 0.01
Pre- and postoperative evaluation
Results
The preoperative ophthalmologic patient examination included refraction, uncorrected visual acuity (UCVA), bestcorrected visual acuity (BCVA), refractive stability (< 0.25 D change over two consecutive exams), corneal topography (GALILEI G4; Ziemer), examination of the optical quality of the tear film (HDA), and a systematic orthoptic work-up with a cycloplegic refraction if necessary. The postoperative patient care included a systematic examination at D + 1, one week, one month, three months, one year, and four years; autorefraction, UCVA, and BCVA on the Monoyer’s scale were measured during these examinations.
Visual efficacy
Statistical analyses These were performed on the biostaTGV website (https://www.marne.u707.jussieu.fr/biostatgv). The normal sample distribution was verified by the Kolmogorov-Smirnov test. The quantitative data comparison between the two non-paired groups required use of the Student T-test. The comparison between the two paired groups respecting a normal data distribution required the Student T-test for paired data; if the data did not respect a normal distribution, the Wilcoxon signed rank test was then utilized. For nominal data, the Chi2 test was performed.
Table 3
This is defined by the change in UCVA after SMILE surgery. Table 2 and Fig. 1 show the mean UCVA between the control group (CG) and the high myope group (HMG) at the various intervals of postoperative follow-up. There was a difference between UCVA at D + 1 and that at M + 1, M + 3, Y + 1, and Y + 4 in the high myope group. The long-term results were better than the immediate postoperative results (D + 1) in the high myope group (P < 0.001, Fig. 1A), and in the control group (P < 0.001; Fig. 1B). Fig. 1C shows that there was no statistically significant difference in UCVA between the high myope group and the control group at D + 1 (P = 0.0552) and at M + 3 (P = 0.440). However, UCVA was found to be lower in the high myope group than the control group at one year (P = 0.0019) and at four years (P = 0.0277).
Refractive stability This is defined as the change in and stability of the measured refraction over time, converted to spherical equivalent (MRSE). Table 3 and Fig. 2 compare MRSE (in D) between the HMG and the CG at the various intervals of postoperative follow-up.
Distribution of Spherical Equivalent Refraction between the two groups. Spherical Equivalent Refraction (MRSE) in Dioptres
HMG mean SE ± standard deviation CG mean SE ± standard deviation P-value between the two groups
Preoperation
D+1
M+3
Y+1
Y+4
−7.59 ± 1.12 −3.77 ± 1.15
−0.12 ± 0.33 −0.01 ± 0.25 0.0002**
−0.17 ± 0.41 −0.10 ± 0.32 0.557
−0.30 ± 0.37 −0.09 ± 0.24 0.0023**
−0.36 ± 0.28 −0.18 ± 0.34 0.138
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J. Burazovitch et al.
Figure 1. A. Change in uncorrected visual acuity in the high myope group. B. Change in uncorrected visual acuity in the control group. C. Comparison of uncorrected visual acuity between the two groups.
There is a significant difference in the high myope group between the day 1 MRSE, and that obtained at one month (P = 0.031; Fig. 2A) and at one year (P = 0.0001). The SE thus tends to shift negatively during the first year, then stabilize up to the fourth year. However, there is no significant difference observed in the control group between
the early and late postoperative period, which demonstrates good stability of the surgery from the first postoperative day for low and moderate myopes (Fig. 2B). There is no significant difference between the MRSE of the control group and the high myope group at four years (Table 3 and Fig. 2C).
Predictability of SMILE over four years in high myopes
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Figure 2. A. Change in spherical equivalent refraction in the high myope group. B. Change in spherical equivalent refraction in the control group. C. Comparison of spherical equivalent refraction between the two groups.
Safety The safety index (SI) is defined as the ratio of the postoperative best corrected visual acuity (BCVA) to the preoperative BCVA; it equates to a gaining of a line if it is greater
than 1, a recovery of initial visual acuity if it is equal to 1, or a loss of a line if it is less than 1. Table 4 and Fig. 3 show the comparisons between the SI of the HMG and the CG at the various intervals of postoperative follow-up.
e206 Table 4
J. Burazovitch et al. Distribution of safety index between the two groups. Safety Index (SI)
HMG mean CG mean P-value between the two groups
D1
M1
M3
Y1
Y4
0.80 ± 0.18 0.83 ± 0.13 0.734
0.90 ± 0.11 0.91 ± 0.11 0.077
1.00 ± 0.1 0.92 ± 0.10 0.160
1.00 ± 0.08 0.94 ± 0.13 0.160
0.90 ± 0.09 0.99 ± 0.04 0.274
As noted in Table 3, there is no significant difference between the two groups with respect to the safety indices recorded at the various intervals of postoperative follow-up. There is a difference in the high myope group between the SI on day one and that obtained at three months (P = 0.0139; Fig. 3A), as well as in the control group between the SI at day one and that obtained at one month (P < 0.001; Fig. 3B). In the high myope group, the maximum SI is recorded at the third month; it then tends to stabilize up to the fourth year. For the control group, this stability is obtained at month 1.
Figure 3.
Predictability Predictability was defined as the percentage of eyes achieving within ± 0.5 D of the target refraction. As shown in Fig. 4A, 97% of operated-upon eyes in the control group are within 0.5 D of the target SE at four years, compared to 87% of operated-upon eyes at four years in the HMG. The predictability in the control group, as demonstrated in Fig. 4B, is 96% at four years (i.e. 96% are within ± 0.5 D of the target). Fig. 5 shows the linear regression curve between the achieved correction (in D) compared to the expected, four years after the procedure, on 17 eyes (9 patients) in the HMG
A. Change in safety index in the high myope group. B. Change in safety index in the control group.
Predictability of SMILE over four years in high myopes
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Figure 4. A. Percentage of eyes at the target spherical equivalent in the high myope group at various intervals postoperatively. B. Percentage of eyes at the target spherical equivalent in the control group at various intervals postoperatively.
and 20 eyes (10 patients) in the CG. As shown in Fig. 5A, the equation in the high myope group may be expressed as: R2 = 0.9323. We note that the relationship is parallel at R2 = 1, and that there are a certain number of undercorrected eyes (6 eyes). As shown in Fig. 5B, for the control group, the relationship may be expressed as: R2 = 0.91235, with a tendency to stretch out to R2 = 1. As with the high myope group, we note that there are a certain number of under-corrected eyes (3 eyes).
Complications Over the four years, the complications were: one case of epithelial ingrowth treated successfully with YAG laser; no severe case of dry eye, a few cases of suction loss with recommencement of the procedure without sequelae; several cases of ‘‘black spots,’’ one of which was particularly difficult but with improvement in visual acuity at six months; and some rare incisional tears without sequelae and lenticular tears, in the low myopes. However, no cases of DLK
(Diffuse Lamellar Keratitis) or TLSC (Transient Light Sensitivity Syndrome), infection, or secondary ectasia have been reported; likewise, no decentration of the treatment has been reported to date.
Discussion By way of the criteria analyzed, this study has allowed us to determine the long-term predictability, stability, safety, and efficacy of the SMILE procedure for high myopia. By comparing high myopes to a control group of moderate and low myopes, the procedure has demonstrated reliable results. The visual acuity in high myopes improves over time and stabilizes from the third month, when compared to the control group. This is consistent with published data on SMILE and the long-term cohort study, which showed long-term improvement in UCVA. However, there are to date several published cases of ectasia post-SMILE [13—16], leading to the same contraindications for this procedure with at-risk corneas.
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Figure 5.
J. Burazovitch et al.
A. Linear regression curve for the high myope group. B. Linear regression curve for the control group.
There was a significant regression (P = 0.0001) in the high myope group over the first year, which did not appear in the control group. Various explanations for this exist, and are reported in the literature [8], for instance: a more significant healing phenomenon in high myopes with more significant activation of keratocytes in high myopes [17] with the SMILE procedure [18], leading to more rapid myofibroblastic transformation and a change in corneal rigidity [18,19]. Another reason may be corneal epithelial hyperplasia with greater thickness in certain corneal zones [20]. A thin pachymetry and residual stromal bed may also predict regression in high myopes [21,22]. In Blum’s study [10], the five-year regression was −0.48 D at five years. Predictability for the control group is comparable with studies by: Sekundo [4], which obtained 92% within 0.5 D of the target SE at one year; A˘ gca [23], obtaining a result of 95% at one year; and Wu [8], with 95% at one year. Our results are consistent with the published data in the literature and demonstrate high long-term predictability for both groups.
The limitations of this study centre around the fact that it is a retrospective cohort study, and that the two groups are not comparable: the high myope group contained more women, and the astigmatism was greater amongst them. The study results will need to be verified by a randomized study of a larger cohort. In conclusion, the long-term results of the SMILE procedure with regard to visual acuity and safety index are reassuring. There is a regression over the first year in the high myope group, which tends to stabilize at four years, with the predictability at the fourth year remaining slightly less than that of the control group. A correction factor of the order of 8% of the initial total SE value was used for the high myopes, but despite this, there were still some eyes with a final under-correction. Finally, no severe complications were reported during the study period.
Disclosure of interest The authors declare that they have no competing interest.
Predictability of SMILE over four years in high myopes
References [1] 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—9. [2] 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—37. [3] Hjortdal JØ, Vestergaard AH, Ivarsen A, Ragunathan S, Asp S. Predictors for the outcome of small-incision lenticule extraction for Myopia. J Refract Surg 2012;28:865—71. [4] 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). Graefes Arch Clin Exp Ophthalmol 2014;252:837—43. [5] Albou-Ganem C, Lavaud A, Amar R. [SMILE: refractive lenticule extraction for myopic correction]. J Fr Ophtalmol 2015;38:229—37. [6] Kim JR, Kim BK, Mun SJ, Chung YT, Kim HS. One-year outcomes of small-incision lenticule extraction (SMILE): mild to moderate myopia vs. high myopia. BMC Ophthalmol 2015; 15:59. [7] Fernández J, Valero A, Martínez J, Pi˜ nero DP, Rodríguez-Vallejo M. Short-term outcomes of small-incision lenticule extraction (SMILE) for low, medium, and high myopia. Eur J Ophthalmol 2016:0. [8] Wu W, Wang Y, Zhang H, Zhang J, Li H, Dou R. One-year visual outcome of small incision lenticule extraction (SMILE) surgery in high myopic eyes: retrospective cohort study. BMJ Open 2016;6:e010993. [9] Han T, Zheng K, Chen Y, Gao Y, He L, Zhou X. Four-year observation of predictability and stability of small incision lenticule extraction. BMC Ophthalmol 2016;16:149. [10] Blum M, Täubig K, Gruhn C, Sekundo W, Kunert KS. Five-year results of Small Incision Lenticule Extraction (ReLEx SMILE). Br J Ophthalmol 2016;100:1192—5. [11] Messerschmidt-Roth A, Sekundo W, Lazaridis A, Schulze S. [Three years follow-up study after refractive small incision lenticule extraction (SMILE) using 500kHz femtosecond laser in ‘‘Fast Mode’’]. Klin Monatsbl Augenheilkd 2016.
e209 [12] Chan CCK, Hodge C, Sutton G. External analysis of the Randleman Ectasia Risk Factor Score System: a review of 36 cases of post-LASIK ectasia. Clin Experiment Ophthalmol 2010;38:335—40. [13] Mattila JS, Holopainen JM. Bilateral ectasia after femtosecond laser-assisted small incision lenticule extraction (SMILE). J Refract Surg 2016;32:497—500. [14] El-Naggar MT. Bilateral ectasia after femtosecond laserassisted small-incision lenticule extraction. J Cataract Refract Surg 2015;41:884—8. [15] Wang Y, Cui C, Li Z, Tao X, Zhang C, Zhang X, et al. Corneal ectasia 6.5 months after small-incision lenticule extraction. J Cataract Refract Surg 2015;41:1100—6. [16] Sachdev G, Sachdev MS, Sachdev R, Gupta H. Unilateral corneal ectasia following small-incision lenticule extraction. J Cataract Refract Surg 2015;41:2014—8. [17] Wilson SE. Analysis of the keratocyte apoptosis, keratocyte proliferation, and myofibroblast transformation responses after photorefractive keratectomy and laser in situ keratomileusis. Trans Am Ophthalmol Soc 2002;100:411—33. [18] Liu Y-C, Teo EPW, Lwin NC, Yam GHF, Mehta JS. Early corneal wound healing and inflammatory responses after SMILE: comparison of the effects of different refractive corrections and surgical experiences. J Refract Surg 2016;32:346—53. [19] Moshirfar M, Anderson E, Hsu M, Armenia JM, Mifflin MD. Comparing the rate of regression after conductive keratoplasty with or without prior laser-assisted in situ keratomileusis or photorefractive keratectomy. Middle East Afr J Ophthalmol 2012;19:377. [20] Ganesh S, Patel U, Brar S. Posterior corneal curvature changes following Refractive Small Incision Lenticule Extraction. Clin Ophthalmol Auckl NZ 2015;9:1359—64. [21] Alió JL, Soria F, Abbouda A, Pe˜ na-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. [22] Shojaei A, Mohammad-Rabei H, Eslani M, Elahi B, Noorizadeh F. Long-term evaluation of complications & results of photo refractive keratectomy in myopia: an 8-year follow-up. ResearchGate 2009;28:304—10. [23] A˘ gca A, Demirok A, Cankaya K˙I, Yas¸a D, Demircan A, Yildirim Y, et al. Comparison of visual acuity and higher-order aberrations after femtosecond lenticule extraction and small-incision lenticule extraction. Cont Lens Anterior Eye 2014;37:292—6.
Disponible en ligne sur
ScienceDirect www.sciencedirect.com
EDITOR’S CHOICE
Predictability of SMILE over four years in high myopes J. Burazovitch a,∗, D. Naguzeswski b, T. Beuste c, M. Guillard b a
Ophthalmology service, Argentan medical center, 47, rue Aristide-Briand, 61200 Argentan, France b rue Quadrant, 14123 Fleury-sur-Orne, France c Ophthalmology service, Caen university medical centre, 32, rue Desmoueux, 14000 Caen, France Received 21 April 2017; accepted 2 May 2017 Available online 7 June 2017
KEYWORDS SMILE; Small incision lenticule extraction; Myopia; High myopia; Predictability
∗
Summary Objective. — To determine whether the visual outcomes of the refractive surgery technique small incision lenticule extraction (SMILE), are stable, effective, and predictable for high myopia over a four-year period. Research design. — This is a retrospective study. The data were collected between March 2012 and July 2016. Participants. — Two hundred and forty-eight patients participated in the study; that is, 496 eyes: 140 eyes of 70 patients (52 women/18 men) were classified into the highly myopic group (refraction measured in spherical equivalent (RMSE) > −6 D), and 356 eyes of 178 patients (98 women/80 men) into the control group (RMSE < −6 D). Follow-up tests were conducted immediately following the procedure (D + 1), after three months, after one year, and after four years. Refraction, uncorrected visual acuity (UCVA), and best visual corrected acuity (BCVA) were measured. The highly myopic group (HMG) contained more women, and astigmatism was higher for this group than for the control group (CG). Primary and secondary study criteria. — These were BCVA, refractive stability, the index of safety (SI: BCVA preoperatively D + 1/BCVA postoperatively), and predictability (the percentage of eyes within ± 0.5 D of the target). Results. — In both groups, UCVA was better after the fourth year than it was immediately after the procedure (HMG: P = 0.001; CG: P = 0.001). Although it differed at one year (P = 0.01), the groups’ refractive stability tended to converge over four years (P = 0.138). The groups’ SI was found to be identical in the four follow-up tests (P = 0.734 at D + 1; P = 0.07 at M + 1; P = 0.160 at M3 and Y1; and P = 0.274 at Y4). For the HMG, SI stability was attained after three months
Corresponding author. E-mail address: burazovitch [email protected] (J. Burazovitch).
http://dx.doi.org/10.1016/j.jfo.2017.05.001 0181-5512/© 2017 Elsevier Masson SAS. All rights reserved.
e202
J. Burazovitch et al. (1.00 ± 0.1); whereas it was attained after one month (0.91 ± 0.11) for the CG. Four years after the surgery, we observed that 87% of the operated-upon eyes in the HMG were within 0.5 D of the target. Conclusion. — SMILE is a good refractive surgery technique for treating high myopia. It yields stable, safe, effective, and predictable results over four years. © 2017 Elsevier Masson SAS. All rights reserved.
Introduction The refractive surgery technique SMILE (SMall Incision Lenticule Extraction), for the correction of myopia and astigmatism, is a recent technique [1—3], performed with a single laser: the Visumax© femtosecond laser (Carl Zeiss Meditec, Jena, Germany). Short-term studies in moderate and high myopes have confirmed the safety of refractive surgery using SMILE [4—8]. The long-term results of the procedure appear equally encouraging [9—11]. To find out whether this procedure is a long-lasting solution, as well as to respond to the growing demands of patients, is a significant objective in the management of high myopia. The goal of this study is thus to determine, as with similar studies performed to date, if the visual outcomes over four years of the refractive surgery technique SMILE are stable, safe, effective, and predictable in a group of high myopes as compared to a group of low and moderate myopes.
Materials and methods Patient population This was a retrospective study of a cohort of patients who underwent refractive surgery at the Saint-Martin Clinic in Caen between March 2012 and July 2016. The inclusion criteria were absence of contraindications to refractive surgery or the SMILE procedure, based on the Randelman criteria [12], i.e. signs of forme fruste keratoconus on topography; a residual bed less than 250 microns in thickness; age less than 20 years; corneal thickness less than 500 microns; as well as severe dry eye syndrome, atopy, and best corrected visual acuity less than 8/10. The patient was seen for postoperative follow-up the first day, at one month, at three months, at one year, and at four years. At these visits, refraction, uncorrected visual acuity (UCVA), and best corrected visual acuity (BCVA) were measured. The study included 496 eyes of 248 myopic and astigmatic patients separated into two groups (Table 1) depending on their preoperative spherical equivalent refraction (MRSE): 70 patients or 140 eyes were classified into the high myope group (MRSE > −6 D); and 356 eyes of 178 patients into the control group (MRSE < −6 D). The control group (CG) consisted of 55% women and 45% men, with a mean age of 29 years (± 5.17); the youngest patient was 20 years and the oldest 55 years. The mean MRSE
was −3.77 ± 1.15 D, the mean sphere was −3.52 ± 1.13 D, and the mean cylinder was −0.51 ± 0.41 D. The high myope group (HMG) consisted of 74% women and 26% men, with a mean age of 30 years (± 5.95); the youngest patient was 20 years, and the oldest 49 years. The mean MRSE was −7.59 ± 1.12 D, the mean sphere was −7.23 ± 1.14 D, and the mean cylinder was −0.71 ± 0.57 D. The two groups thus presented differences preoperatively in terms of MRSE (P < 0.001), sphere (P < 0.01), gender distribution (P < 0.053; more women in the HMG), and cylinder (P = 0.001; higher astigmatism in the HMG). However, there was no notable difference in mean age.
Surgical technique An experienced surgeon (DN) performed all the SMILE procedures. The Visumax© (Carl Zeiss Meditec, Jena, Germany) 500 kHz femtosecond laser was used for this procedure. The energy delivered per spot was 140 nJ, and the spacing between spots was 4 to 4.5 microns. The cap thickness was 130 microns, and the optical zone diameter was 6.5 mm for all patients. The side cuts were at a 90◦ angle. The chosen target refraction was emmetropia for patients up to 35 years; and a monovision strategy for those over 35 years with an amplitude of 1 dioptre maximum as a function of the initial refraction. A correction factor of the order of 8% was programmed for high ametropia to prevent an under-correction of the myopia. The surgical procedure was performed under topical anaesthesia only, with 1% tetracaine drops (Laboratoire Théa) —– 2 to 3 drops per eye —– prior to the procedure, and was supplemented by a 10 mg tablet of Vératran (Laboratoire Amdipharm Limited) taken one hour beforehand. A standard lid speculum was used to keep the eyes open. The suction ring kept the pupil centered. To start, the posterior lenticule cut was performed in a centripetal direction, and the anterior cap cut in a centrifugal direction. Then, the 2.2 mm primary incision was placed at 12:00 in all patients. After the laser treatment, the Reinstein manipulator (Malosa Laboratory, Yorkshire, England) was used to detach stromal adhesions, and the lenticule extracted mechanically through the primary incision. No secondary incision was necessary. Medications at the conclusion of the procedure were systematically alike for all patients: Tobradex four times per day (Alcon Laboratory) for one week, and Vismed four times per day (HORUS pharma laboratory) for one month.
Predictability of SMILE over four years in high myopes Table 1
CG HMG
Table 2
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Composition of groups. Number of men, n (%)
Number of women, n (%)
80(45) 18(26)
98(55) 52(74)
Total 178 70
Mean age (years)
Cylinder (in D)
29 30
−0.51 ± 0.41 −0.71 ± 0.57
Distribution of uncorrected visual acuity between the two groups. UCVA (Monoyer’s scale)
HMG mean ± standard deviation CG mean ± standard deviation P-value between the two groups * **
D+1
M+1
M+3
Y+1
Y+4
7.57 ± 1.74 7.94 ± 1.66 0.552
8.82 ± 1.22 9.26 ± 1.11 0.002**
8.85 ± 1.22 9.07 ± 1.17 0.440
8.72 ± 1.05 9.44 ± 1.03 0.001**
8.76 ± 0.94 9.48 ± 0.85 0.027*
P < 0.05 P < 0.01
Pre- and postoperative evaluation
Results
The preoperative ophthalmologic patient examination included refraction, uncorrected visual acuity (UCVA), bestcorrected visual acuity (BCVA), refractive stability (< 0.25 D change over two consecutive exams), corneal topography (GALILEI G4; Ziemer), examination of the optical quality of the tear film (HDA), and a systematic orthoptic work-up with a cycloplegic refraction if necessary. The postoperative patient care included a systematic examination at D + 1, one week, one month, three months, one year, and four years; autorefraction, UCVA, and BCVA on the Monoyer’s scale were measured during these examinations.
Visual efficacy
Statistical analyses These were performed on the biostaTGV website (https://www.marne.u707.jussieu.fr/biostatgv). The normal sample distribution was verified by the Kolmogorov-Smirnov test. The quantitative data comparison between the two non-paired groups required use of the Student T-test. The comparison between the two paired groups respecting a normal data distribution required the Student T-test for paired data; if the data did not respect a normal distribution, the Wilcoxon signed rank test was then utilized. For nominal data, the Chi2 test was performed.
Table 3
This is defined by the change in UCVA after SMILE surgery. Table 2 and Fig. 1 show the mean UCVA between the control group (CG) and the high myope group (HMG) at the various intervals of postoperative follow-up. There was a difference between UCVA at D + 1 and that at M + 1, M + 3, Y + 1, and Y + 4 in the high myope group. The long-term results were better than the immediate postoperative results (D + 1) in the high myope group (P < 0.001, Fig. 1A), and in the control group (P < 0.001; Fig. 1B). Fig. 1C shows that there was no statistically significant difference in UCVA between the high myope group and the control group at D + 1 (P = 0.0552) and at M + 3 (P = 0.440). However, UCVA was found to be lower in the high myope group than the control group at one year (P = 0.0019) and at four years (P = 0.0277).
Refractive stability This is defined as the change in and stability of the measured refraction over time, converted to spherical equivalent (MRSE). Table 3 and Fig. 2 compare MRSE (in D) between the HMG and the CG at the various intervals of postoperative follow-up.
Distribution of Spherical Equivalent Refraction between the two groups. Spherical Equivalent Refraction (MRSE) in Dioptres
HMG mean SE ± standard deviation CG mean SE ± standard deviation P-value between the two groups
Preoperation
D+1
M+3
Y+1
Y+4
−7.59 ± 1.12 −3.77 ± 1.15
−0.12 ± 0.33 −0.01 ± 0.25 0.0002**
−0.17 ± 0.41 −0.10 ± 0.32 0.557
−0.30 ± 0.37 −0.09 ± 0.24 0.0023**
−0.36 ± 0.28 −0.18 ± 0.34 0.138
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Figure 1. A. Change in uncorrected visual acuity in the high myope group. B. Change in uncorrected visual acuity in the control group. C. Comparison of uncorrected visual acuity between the two groups.
There is a significant difference in the high myope group between the day 1 MRSE, and that obtained at one month (P = 0.031; Fig. 2A) and at one year (P = 0.0001). The SE thus tends to shift negatively during the first year, then stabilize up to the fourth year. However, there is no significant difference observed in the control group between
the early and late postoperative period, which demonstrates good stability of the surgery from the first postoperative day for low and moderate myopes (Fig. 2B). There is no significant difference between the MRSE of the control group and the high myope group at four years (Table 3 and Fig. 2C).
Predictability of SMILE over four years in high myopes
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Figure 2. A. Change in spherical equivalent refraction in the high myope group. B. Change in spherical equivalent refraction in the control group. C. Comparison of spherical equivalent refraction between the two groups.
Safety The safety index (SI) is defined as the ratio of the postoperative best corrected visual acuity (BCVA) to the preoperative BCVA; it equates to a gaining of a line if it is greater
than 1, a recovery of initial visual acuity if it is equal to 1, or a loss of a line if it is less than 1. Table 4 and Fig. 3 show the comparisons between the SI of the HMG and the CG at the various intervals of postoperative follow-up.
e206 Table 4
J. Burazovitch et al. Distribution of safety index between the two groups. Safety Index (SI)
HMG mean CG mean P-value between the two groups
D1
M1
M3
Y1
Y4
0.80 ± 0.18 0.83 ± 0.13 0.734
0.90 ± 0.11 0.91 ± 0.11 0.077
1.00 ± 0.1 0.92 ± 0.10 0.160
1.00 ± 0.08 0.94 ± 0.13 0.160
0.90 ± 0.09 0.99 ± 0.04 0.274
As noted in Table 3, there is no significant difference between the two groups with respect to the safety indices recorded at the various intervals of postoperative follow-up. There is a difference in the high myope group between the SI on day one and that obtained at three months (P = 0.0139; Fig. 3A), as well as in the control group between the SI at day one and that obtained at one month (P < 0.001; Fig. 3B). In the high myope group, the maximum SI is recorded at the third month; it then tends to stabilize up to the fourth year. For the control group, this stability is obtained at month 1.
Figure 3.
Predictability Predictability was defined as the percentage of eyes achieving within ± 0.5 D of the target refraction. As shown in Fig. 4A, 97% of operated-upon eyes in the control group are within 0.5 D of the target SE at four years, compared to 87% of operated-upon eyes at four years in the HMG. The predictability in the control group, as demonstrated in Fig. 4B, is 96% at four years (i.e. 96% are within ± 0.5 D of the target). Fig. 5 shows the linear regression curve between the achieved correction (in D) compared to the expected, four years after the procedure, on 17 eyes (9 patients) in the HMG
A. Change in safety index in the high myope group. B. Change in safety index in the control group.
Predictability of SMILE over four years in high myopes
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Figure 4. A. Percentage of eyes at the target spherical equivalent in the high myope group at various intervals postoperatively. B. Percentage of eyes at the target spherical equivalent in the control group at various intervals postoperatively.
and 20 eyes (10 patients) in the CG. As shown in Fig. 5A, the equation in the high myope group may be expressed as: R2 = 0.9323. We note that the relationship is parallel at R2 = 1, and that there are a certain number of undercorrected eyes (6 eyes). As shown in Fig. 5B, for the control group, the relationship may be expressed as: R2 = 0.91235, with a tendency to stretch out to R2 = 1. As with the high myope group, we note that there are a certain number of under-corrected eyes (3 eyes).
Complications Over the four years, the complications were: one case of epithelial ingrowth treated successfully with YAG laser; no severe case of dry eye, a few cases of suction loss with recommencement of the procedure without sequelae; several cases of ‘‘black spots,’’ one of which was particularly difficult but with improvement in visual acuity at six months; and some rare incisional tears without sequelae and lenticular tears, in the low myopes. However, no cases of DLK
(Diffuse Lamellar Keratitis) or TLSC (Transient Light Sensitivity Syndrome), infection, or secondary ectasia have been reported; likewise, no decentration of the treatment has been reported to date.
Discussion By way of the criteria analyzed, this study has allowed us to determine the long-term predictability, stability, safety, and efficacy of the SMILE procedure for high myopia. By comparing high myopes to a control group of moderate and low myopes, the procedure has demonstrated reliable results. The visual acuity in high myopes improves over time and stabilizes from the third month, when compared to the control group. This is consistent with published data on SMILE and the long-term cohort study, which showed long-term improvement in UCVA. However, there are to date several published cases of ectasia post-SMILE [13—16], leading to the same contraindications for this procedure with at-risk corneas.
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Figure 5.
J. Burazovitch et al.
A. Linear regression curve for the high myope group. B. Linear regression curve for the control group.
There was a significant regression (P = 0.0001) in the high myope group over the first year, which did not appear in the control group. Various explanations for this exist, and are reported in the literature [8], for instance: a more significant healing phenomenon in high myopes with more significant activation of keratocytes in high myopes [17] with the SMILE procedure [18], leading to more rapid myofibroblastic transformation and a change in corneal rigidity [18,19]. Another reason may be corneal epithelial hyperplasia with greater thickness in certain corneal zones [20]. A thin pachymetry and residual stromal bed may also predict regression in high myopes [21,22]. In Blum’s study [10], the five-year regression was −0.48 D at five years. Predictability for the control group is comparable with studies by: Sekundo [4], which obtained 92% within 0.5 D of the target SE at one year; A˘ gca [23], obtaining a result of 95% at one year; and Wu [8], with 95% at one year. Our results are consistent with the published data in the literature and demonstrate high long-term predictability for both groups.
The limitations of this study centre around the fact that it is a retrospective cohort study, and that the two groups are not comparable: the high myope group contained more women, and the astigmatism was greater amongst them. The study results will need to be verified by a randomized study of a larger cohort. In conclusion, the long-term results of the SMILE procedure with regard to visual acuity and safety index are reassuring. There is a regression over the first year in the high myope group, which tends to stabilize at four years, with the predictability at the fourth year remaining slightly less than that of the control group. A correction factor of the order of 8% of the initial total SE value was used for the high myopes, but despite this, there were still some eyes with a final under-correction. Finally, no severe complications were reported during the study period.
Disclosure of interest The authors declare that they have no competing interest.
Predictability of SMILE over four years in high myopes
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