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New Developments in the Lenticule Extraction Procedure

European Ophthalmic Review, 2014;8(1):31–6 DOI:


For the last 20 years controlled excimer laser ablation of corneal tissue, either directly from the corneal stromal surface or from the corneal interior after creation of a superficial corneal flap, has become widely used to correct myopia, hyperopia and astigmatism. Recently, an intrastromal refractive procedure whereby a tissue lenticule is cut free in the corneal stroma by a femtosecond laser and removed through a small peripheral incision has been introduced. The procedure avoids creation of a corneal flap and the potential associated risks while avoiding the slow visual recovery of surface ablation procedures. The all-femtosecond-based flap-free intracorneal refractive procedure has been documented to be a predictable, efficient and safe procedure for correction of myopia and astigmatism. Technological developments related to further improved cutting quality, hyperopic and individualised treatments are desirable.

Keywords: Corneal refractive surgery, femtosecond laser, small incision lenticule extraction, myopia, astigmatism
Disclosure: Jesper Hjortdal, MD, PhD, has received travel support from Carl Zeiss Meditec, Jena, Germany. Anders Ivarsen, MD, PhD, has no conflicts of interest to declare.
Received: January 07, 2014 Accepted: March 01, 2014
Correspondence: Jesper Hjortdal, MD, PhD, Department of Ophthalmology, Aarhus University Hospital, 8000 Aarhus C, Denmark. E:

Over the last few years, surgical extraction of a refractive lenticule, or ReLEx®, has evolved as a new treatment in the field of keratorefractive surgery. Currently, the VisuMax® femtosecond (FS) laser (Carl Zeiss Meditec, Jena, Germany) is the only platform to offer this treatment. The 500 kHz VisuMax laser generates very fast pulses (10-15 s range) in the near-infrared spectrum. Depending on the specific laser settings, each pulse conveys approximately 150 nJ, which causes localized photodisruption at the focal point. The generated plasma expands, creating a cavitation bubble, and, as individual cavitation bubbles fuse, the stroma is cut with a minimum of collateral damage. The VisuMax FS laser uses a high numerical aperture and a concave contact glass to focus the laser pulses with very high precision. Thus, laser spots of approximately 1 μm diameter are placed with a defined distance of 2–5 μm in a spiral pattern. To ensure centration on the visual axis, the patient fixates on a blinking light, and suction is applied at the limbus to maintain stability of the eye. Initially, the posterior refractive surface of the lenticule is cut, followed by creation of the plano anterior surface, which is slightly enlarged in diameter to facilitate surgical manipulation.

This review article reviews the current state of the technique, updated clinical results,1 experimental studies, and, finally, presents some of the challenges that need to be addressed by new technologies.

Depending on the method used to access the lenticule, ReLEx can be split into FLEx, in which a laser-assisted in situ keratomileusis (LASIK)-like flap allows surgical removal of the lenticule, and small incision lenticule extraction (SMILE) in which a small incision (approximately 2–4 mm in length) is created for manual lenticule extraction. A blunt spatula is used to break any remaining tissue bridges after the laser treatment, and thelenticule is removed with a pair of forceps (see Figure 1). For further details on the surgical approach, please refer to Sekundo et al.,2 Shah et al.,3 and Vestergaard et al.4

In contrast to LASIK, ReLEx is a one-laser approach, where the critical laser treatment is performed on the intact cornea rather than on exposed corneal stroma. Consequently, the potential variability associated with the excimer laser photoablation is avoided. In addition, the minimally invasive SMILE treatment has several theoretical advantages over flap-based treatments, including little trauma to the corneal surface, less corneal denervation, and better biomechanical strength due to an almost intact anterior stroma. Since the first introduction of ReLEx, the repetition rate of the VisuMax laser has been increased from 200 to 500 kHz, and the settings for laser spot size, energy, and distance have been optimized, changes that may have had a significant impact on the clinical outcome after surgery. Furthermore, the flap-based FLEx represents an evolutionary step before SMILE and is today primarily used as an introductory step for new ReLEx surgeons. Due to these changes, this review focuses primarily on studies concerning SMILE.

Currently, the VisuMax allows myopic corrections up to –10 diopters (D) spherical equivalent (SE) correction, with an astigmatic component of up to 5 D. Hyperopic treatments are not available at the moment, although one study has reported on the outcome of hyperopic FLEx.5 The VisuMax laser is Conformité Européenne (CE) marked and is currently being evaluated in clinical studies for the approval of SMILE by the US Food and Drug Administration (FDA).

Refractive Outcome
Overall, ReLEx has been reported to have high refractive predictability in moderate and high myopia. In the largest report to date on SMILE in 670 myopic eyes 3 months after surgery (preoperative SE refraction was –7.2 D) the mean error in SE refraction was –0.25 ± 0.44 D, with 80 % of eyes within ± 0.50 D and 94 % within ± 1.0 D.6 We recently extended this evaluation to the first 1,574 eyes 3 months after SMILE and found a similar mean error of –0.15 ± 0.50 D with 77 % of eyes within ± 0.50 D and 95 % within ± 1.0 D.7 Other reports on SMILE3,4,8,9 and 500 kHz FLEx10–14 have found similar refractive outcomes in smaller numbers of patients. Most studies have included patients with moderate and high myopia, while the refractive predictability in treatment of low myopia (less than 2 D) has not been evaluated thoroughly or compared with results after FS-LASIK or photorefractive keratectomy (PRK).

The refractive stability after SMILE has not been extensively investigated. However, in one study on 279 eyes with high myopia, refraction was found to be stable from 1 to 3 months after surgery, although a minor regression of –0.15 D was observed during the first month.4 Another study on 54 eyes found no regression during the first 6 months after surgery.8 Similarly, no regression has been found during the first 3–6 months after 500 kHz FLEx10,11,13,14 or for 1 year after 200 kHz FLEx.15,16 A prospective, randomized, paired-eye study comparing SMILE and FLEx documented no significant regression between 1 week and 6 months. The procedures were similar in terms of safety, efficacy, predictability, and stability, suggesting that the presence or absence of lifting the flap does not significantly affect these visual and refractive outcomes.17

Interestingly, the refractive predictability after SMILE has been found to be unrelated to the degree of the attempted myopic correction.6 This is in contrast to excimer-based treatments, which show decreasing precision with increasing myopic correction.18 Furthermore, other parameters including preoperative corneal power, patient age, and gender have beenfound to have limited impact on the refractive outcome after SMILE.6

  1. Ivarsen A, Hjortdal J, All-femtosecond laser keratorefractive surgery, Curr Ophthalmol Rep, 2014;2:26–33.
  2. 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;34:1513–20.
  3. Shah R, Shah S, Sengupta S, Results of small incision lenticule extraction: all-in-one femtosecond laser refractive surgery, Cataract Refract Surg, 2011;37:127–37.
  4. Vestergaard A, Ivarsen AR, Asp S, Hjortdal JØ, Small-incision lenticule extraction for moderate to high myopia: predictability, safety, and patient satisfaction, J Cataract Refract Surg, 2012;38:2003–10.
  5. Blum M, Kunert KS, Voßmerbäumer U, Sekundo W, Femtosecond lenticule extraction (ReLEx) for correction of hyperopia – first results, Graefes Arch Clin Exp Ophthalmol, 2013 251:349–55
  6. Hjortdal JØ, Vestergaard AH, Ivarsen A, et al., Predictors for the outcome of small-incision lenticule extraction for myopia, J Refract Surg, 2012;28:865–71.
  7. Ivarsen A, Asp S, Hjortdal J, Safety and complications of more than 1500 small-incision lenticule extraction procedures, Ophthalmology, 2013 [Epub ahead of print).
  8. Zhao J, Yao P, Li M, et al., The morphology of corneal cap and its relation to refractive outcomes in femtosecond laser small incision lenticule extraction (SMILE) with anterior segment optical coherence tomography observation, PLoS ONE, 2013;8:e70208.
  9. Sekundo W, Kunert KS, Blum M, Small incision corneal refractive surgery using the small incision lenticule extraction (SMILE) procedure for the correction of myopia and myopic astigmatism: results of a 6 month prospective study, Br J Ophthalmol, 2011;95:335–9.
  10. Vestergaard A, Ivarsen A, Asp S, Hjortdal JØ, Femtosecond (FS) laser vision correction procedure for moderate to high myopia: a prospective study of ReLEx FLEx and comparison with a retrospective study of FS-laser in situ keratomileusis, Acta Ophthalmol, 2013;91:355–62.
  11. Kamiya K, Igarashi A, Ishii R, et al., Early clinical outcomes, including efficacy and endothelial cell loss, of refractive lenticule extraction using a 500 kHz femtosecond laser to correct myopia, J Cataract Refract Surg, 2012;38:1996–2002.
  12. Kamiya K, Shimizu K, Igarashi A, et al., Comparison of visual acuity, higher-order aberrations and corneal asphericity after refractive lenticule extraction and wavefront guided laserassisted in situ keratomileusis for myopia, Br J Ophthalmol, 2013;97:968–75.
  13. Ang M, Chaurasia SS, Angunawela RI, et al., Femtosecond lenticule extraction (FLEx): clinical results, interface evaluation, and intraocular pressure variation, Invest Ophthalmol Vis Sci, 2012;53:1414–21.
  14. Demirok A, Agca A, Ozgurhan EB, et al., Femtosecond lenticule extraction for correction of myopia: a 6 month follow-up study, Clin Ophthalmol, 2013;7:1041–7.
  15. Blum M, Kunert KS, Engelbrecht C, et al., Femtosecond lenticule extraction (FLEx)—results after 12 months in myopic astigmatism, Klin Monbl Augenheilkd, 2010;227:961–5.
  16. Gertnere J, Solomatin I, Sekundo W, Refractive lenticule extraction (ReLEx FLEx) and wavefront-optimized Femto-LASIK: comparison of contrast sensitivity and high-order aberrations at 1 year, Graefes Arch Clin Exp Ophthalmol, 2013;251:1437–42.
  17. Kamiya K, Shimizu K, Igarashi A, Kobashi H, Visual and refractive outcomes of femtosecond lenticule extraction and smallincision lenticule extraction for myopia, Am J Ophthalmol, 2014;157:128–34.
  18. Gazieva L, Beer MH, Nielsen K, Hjortdal J, A retrospective comparison of efficacy and safety of 680 consecutive lasik treatments for high myopia performed with two generations of flying-spot excimer lasers, Acta Ophthalmol, 2011;89:729–33.
  19. Blum M, Kunert K, Schröder M, Sekundo W, Femtosecond lenticule extraction for the correction of myopia: preliminary 6-month results, Graefes Arch Clin Exp Ophthalmol, 2010;248:1019–27.
  20. Shah R, Shah S, Effect of scanning patterns on the results of femtosecond laser lenticule extraction refractive surgery, J Cataract Refract Surg, 2011;37:1636–47.
  21. Riau AK, Ang HP, Lwin NC, et al., Comparison of four different VisuMax circle patterns for flap creation after small incision lenticule extraction, J Refract Surg, 2013;29:236–44.
  22. Kunert KS, Blum M, Duncker GI, et al., Surface quality of human corneal lenticules after femtosecond laser surgery for myopia comparing different laser parameters, Graefes Arch Clin Exp Ophthalmol, 2011;249:1417–24.
  23. Kamiya K, Shimizu K, Igarashi A, Kobashi H, Time course of optical quality and intraocular scattering after refractive lenticule extraction. PLoS One, 2013;8:e76738.
  24. Yao P, Zhao J, Li M, et al., Microdistortions in Bowman’s layer following femtosecond laser small incision lenticule extraction observed by Fourier-Domain OCT, J Refract Surg, 2013;29:668–74.
  25. Tomita M, Waring GO 4th, Magnago T, Watabe M, Clinical results of using a high-repetition-rate excimer laser with an optimized ablation profile for myopic correction in 10,235 eyes, J Cataract Refract Surg, 2013;39:1543–9.
  26. Farjo AA, Sugar A, Schallhorn SC, et al., Femtosecond lasers for LASIK flap creation: a report by the American Academy of Ophthalmology, Ophthalmology, 2013;120:e5–20.
  27. Dong Z, Zhou X, Irregular astigmatism after femtosecond laser refractive lenticule extraction, J Cataract Refract Surg, 2013;39:952–4.
  28. Kunert KS, Russmann C, Blum M, Sluyterman VLG, Vector analysis of myopic astigmatism corrected by femtosecond refractive lenticule extraction, J Cataract Refract Surg, 2013;39:759–69.
  29. Ivarsen A, Hjortdal J, Correction of myopic astigmatism with small incision lenticule extraction, J Refract Surg, (accepted for publication, 2014).
  30. Reinstein DZ, Carp GI, Archer TJ, Gobbe M. LASIK for presbyopia correction in emmetropic patients using aspheric ablation profiles and a micro-monovision protocol with the Carl Zeiss Meditec MEL 80 and VisuMax, J Refract Surg, 2012;28:531–41.
  31. Vestergaard AH, Grønbech KT, Grauslund J, et al., Subbasal nerve morphology, corneal sensation, and tear film evaluation after refractive femtosecond laser lenticule extraction, Graefes Arch Clin Exp Ophthalmol, 2013;251:2591–2600.
  32. Demirok A, Ozgurhan EB, Agca A, et al., Corneal sensation after corneal refractive surgery with small incision lenticule extraction, Optom Vis Sci, 2013;90:1040–7.
  33. Wei S, Wang Y, Comparison of corneal sensitivity between FS-LASIK and femtosecond lenticule extraction (ReLEx flex) or small-incision lenticule extraction (ReLEx SMILE) for myopic eyes, Graefes Arch Clin Exp Ophthalmol, 2013;251:1645–54.
  34. Li M, Niu L, Qin B, et al., Confocal comparison of corneal reinnervation after small incision lenticule extraction (SMILE) and femtosecond laser in situ keratomileusis (FS-LASIK), PLoS One, 2013;8:e81435.
  35. Li M, Zhao J, Shen Y, et al., Comparison of dry eye and corneal sensitivity between small incision lenticule extraction and femtosecond LASIK for myopia, PLoS One, 2013;8:e77797.
  36. Randleman JB, Dawson DG, Grossniklaus HE, et al., Depth-dependent cohesive tensile strength in human donor corneas: implications for refractive surgery, J Refract Surg, 2008;24;S85–9.
  37. Reinstein DZ, Archer TJ, Randleman JB, Mathematical model to compare the relative tensile strength of the cornea after PRK, LASIK, and small incision lenticule extraction, J Refract Surg, 2013;29:454–60.
  38. Agca A, Ozgurhan EB, Demirok A, et al., Comparison of corneal hysteresis and corneal resistance factor after small incision lenticule extraction and femtosecond laser-assisted LASIK: a prospective fellow eye study, Cont Lens Anterior Eye, 2014;37:77–80.
  39. Vestergaard A, Grauslund J, Ivarsen A, Hjortdal J, Central corneal sublayer pachymetry and biomechanical properties after refractive femtosecond laser lenticule extraction, J Refract Surg, (accepted for publication, 2013).
  40. Ozgurhan EB, Agca A, Bozkurt E, et al., Accuracy and precision of cap thickness in small incision lenticule extraction, Clin Ophthalmol, 2013;7:923–6.
  41. Tay E, Li X, Chan C, et al., Refractive lenticule extraction flap and stromal bed morphology assessment with anterior segment optical coherence tomography, J Cataract Refract Surg, 2012;38:1544–51.
  42. Reinstein DZ, Archer TJ, Gobbe M, Accuracy and reproducibility of cap thickness in small incision lenticule extraction, J Refract Surg, 2013;29:810–8.
  43. Ivarsen A, Fledelius W, Hjortdal JØ, Three-year changes in epithelial and stromal thickness after PRK or LASIK for high myopia, Invest Ophthalmol Vis Sci, 2009;50:2061–6.
  44. Patel SV, Erie JC, McLaren JW, Bourne WM, Confocal microscopy changes in epithelial and stromal thickness up to 7 years after LASIK and photorefractive keratectomy for myopia, J Refract Surg, 2007;23:385–92.
  45. Alio JL, Javaloy J, Corneal inflammation following corneal photoablative refractive surgery with excimer laser, Surv Ophthalmol, 2013;58:11–25.
  46. Dong Z, Zhou X, Wu J, et al., Small incision lenticule extraction (SMILE) and femtosecond laser LASIK: comparison of corneal wound healing and inflammation, Br J Ophthalmol, 2014;98:263–9.
  47. Riau AK, Angunawela RI, Chaurasia SS, et al., Early corneal wound healing and inflammatory responses after refractive lenticule extraction (ReLEx), Invest Ophthalmol Vis Sci, 2011;52:6213–21.
  48. Moller-Pedersen T, Cavanagh HD, Petroll WM, Jester JV, Stromal wound healing explains refractive instability and haze development after photorefractive keratectomy: a 1-year confocal microscopic study, Ophthalmology, 2000;107:1235–45.
  49. Ivarsen A, Laurberg T, Møller-Pedersen T, Characterisation of corneal fibrotic wound repair at the LASIK flap margin, Br J Ophthalmol, 2003;87:1272–8.
  50. Pradhan KR, Reinstein DZ, Carp GI, et al., Femtosecond laserassisted keyhole endokeratophakia: correction of hyperopia by implantation of an allogeneic lenticule obtained by SMILE from a myopic donor, J Refract Surg, 2013;29:777–82.
  51. Mohamed-Noriega K, Toh KP, Poh R, Bet al., Cornea lenticule viability and structural integrity after refractive lenticule extraction (ReLEx) and cryopreservation, Mol Vis, 2011;17:3437–49.
  52. Riau AK, Angunawela RI, Chaurasia SS, et al., Reversible femtosecond laser-assisted myopia correction: a non-human primate study of lenticule re-implantation after refractive lenticule extraction, PLoS ONE, 2013;8:e67058.
  53. Angunawela RI, Riau AK, Chaurasia SS, et al., Refractive lenticule re-implantation after myopic ReLEx: a feasibility study of stromal restoration after refractive surgery in a rabbit model, Invest Ophthalmol Vis Sci, 2012;53:4975–85.
  54. Liu H, Zhu W, Jiang AC, et al., Femtosecond laser lenticule transplantation in rabbit cornea: experimental study, J Refract Surg, 2012;28:907–11.
  55. Lim CH, Riau AK, Lwin NC, et al., LASIK following small incision lenticule extraction (smile) lenticule re-implantation: a feasibility study of a novel method for treatment of presbyopia, PLoS One. 2013;8:e83046.
  56. Reinstein DZ, Gobbe M, Archer TJ, Coaxially sighted corneal light reflex versus entrance pupil center centration of moderate to high hyperopic corneal ablations in eyes with small and large angle kappa, J Refract Surg, 2013;29:518–25.
  57. Munnerlyn CR, Koons SJ, Marshall J, Photorefractive keratectomy: a technique for laser refractive surgery, J Cataract Refract Surg, 1988;14:46–52.
  58. Maeda N, Clinical applications of wavefront aberrometry – a review, Clin Experiment Ophthalmol, 2009;37:118–29.
  59. Netto MV, Wilson SE, Flap lift for LASIK retreatment in eyes with myopia, Ophthalmology, 2004;111:1362–7.
  60. Sharma R, Vaddavalli PK, Implications and management of suction loss during refractive lenticule extraction (ReLEx): J Refract Surg, 2013;29:502–3.
Keywords: Corneal refractive surgery, femtosecond laser, small incision lenticule extraction, myopia, astigmatism