Journal of Refractive Surgery

Original Article 

Influence of Femtosecond Lenticule Extraction and Small Incision Lenticule Extraction on Corneal Nerve Density and Ocular Surface: A 1-Year Prospective, Confocal, Microscopic Study

Rie Ishii, MD, PhD; Kimiya Shimizu, MD, PhD; Akihito Igarashi, MD, PhD; Hidenaga Kobashi, MD, PhD; Kazutaka Kamiya, MD, PhD

Abstract

PURPOSE:

To compare the influence of femtosecond lenticule extraction (FLEx) and small incision lenticule extraction (SMILE) on corneal nerve density and the ocular surface for equivalent degrees of correction of myopia.

METHODS:

Sixty eyes of 30 patients (8 males and 22 females, mean age: 31.0 ± 6.0 years) were included in the study. The patients underwent FLEx in 1 eye and SMILE in the other eye by random assignment. Subbasal nerve density was measured using confocal microscopy preoperatively and at 1 week, 1 and 3 months, and 1 year postoperatively. Ocular surface parameters such as Schirmer’s test results, tear film break-up time, and corneal sensation were performed preoperatively and at 1 and 3 months postoperatively.

RESULTS:

In the FLEx group, subbasal nerve density was 18,390 ± 6,090 µm/mm2 preoperatively and 5,770 ± 3,490 µm/mm2 at 1 year postoperatively (P < .001, Dunnett’s test). In the SMILE group, subbasal nerve density was 16,810 ± 6,220 µm/mm2 preoperatively and 11,870 ± 8,200 µm/mm2 at 1 year postoperatively (P = .21). The decrease in corneal nerve density was significantly less after SMILE than after FLEx at all postoperative visits (Mann–Whitney U test, P < .05). FLEx resulted in a significant decrease in Schirmer’s test results, tear film break-up time, and corneal sensation at all postoperative visits, whereas SMILE induced no significant changes in these parameters (P > .05).

CONCLUSIONS:

There was less damage to the sub-basal nerve plexus of the cornea and less effect on the ocular surface parameters after SMILE than after FLEx.

[J Refract Surg. 2015;31(1):10–15.]

From the Department of Ophthalmology, University of Kitasato School of Medicine, Kanagawa, Japan.

The authors have no financial or proprietary interest in the materials presented herein.

AUTHOR CONTRIBUTIONS

Study concept and design (KK, KS); data collection (AI, RI, HK); analysis and interpretation of data (RI); drafting of the manuscript (RI); critical revision of the manuscript (AI, KK, HK, KS)

Correspondence: Rie Ishii, MD, PhD, Department of Ophthalmology, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa 252-0374, Japan. E-mail: x080xriex080x@yahoo.co.jp

Received: August 01, 2014
Accepted: October 28, 2014

Abstract

PURPOSE:

To compare the influence of femtosecond lenticule extraction (FLEx) and small incision lenticule extraction (SMILE) on corneal nerve density and the ocular surface for equivalent degrees of correction of myopia.

METHODS:

Sixty eyes of 30 patients (8 males and 22 females, mean age: 31.0 ± 6.0 years) were included in the study. The patients underwent FLEx in 1 eye and SMILE in the other eye by random assignment. Subbasal nerve density was measured using confocal microscopy preoperatively and at 1 week, 1 and 3 months, and 1 year postoperatively. Ocular surface parameters such as Schirmer’s test results, tear film break-up time, and corneal sensation were performed preoperatively and at 1 and 3 months postoperatively.

RESULTS:

In the FLEx group, subbasal nerve density was 18,390 ± 6,090 µm/mm2 preoperatively and 5,770 ± 3,490 µm/mm2 at 1 year postoperatively (P < .001, Dunnett’s test). In the SMILE group, subbasal nerve density was 16,810 ± 6,220 µm/mm2 preoperatively and 11,870 ± 8,200 µm/mm2 at 1 year postoperatively (P = .21). The decrease in corneal nerve density was significantly less after SMILE than after FLEx at all postoperative visits (Mann–Whitney U test, P < .05). FLEx resulted in a significant decrease in Schirmer’s test results, tear film break-up time, and corneal sensation at all postoperative visits, whereas SMILE induced no significant changes in these parameters (P > .05).

CONCLUSIONS:

There was less damage to the sub-basal nerve plexus of the cornea and less effect on the ocular surface parameters after SMILE than after FLEx.

[J Refract Surg. 2015;31(1):10–15.]

From the Department of Ophthalmology, University of Kitasato School of Medicine, Kanagawa, Japan.

The authors have no financial or proprietary interest in the materials presented herein.

AUTHOR CONTRIBUTIONS

Study concept and design (KK, KS); data collection (AI, RI, HK); analysis and interpretation of data (RI); drafting of the manuscript (RI); critical revision of the manuscript (AI, KK, HK, KS)

Correspondence: Rie Ishii, MD, PhD, Department of Ophthalmology, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa 252-0374, Japan. E-mail: x080xriex080x@yahoo.co.jp

Received: August 01, 2014
Accepted: October 28, 2014

The femtosecond laser allows precise ablation with less thermal damage to the tissues than what occurs with other lasers and it thus represents one of the most revolutionary technologies in medical care. In recent years, refractive lenticule extraction using the femtosecond laser has been introduced as a new surgical method for corneal refractive surgery.1 The refractive lenticule extraction technique involves creating a corneal flap followed by physical removal of the refractive lenticule, leading to alteration of the corneal configuration. Two refractive lenticule extraction procedures exist, including one that is used for femtosecond lenticule extraction (FLEx) by lifting the flap and one that achieves small incision lenticule extraction (SMILE) without raising the flap. Both techniques have been proposed as an alternative to conventional LASIK for the correction of refractive errors.2–7 FLEx requires an approximately 20-mm side cut from the corneal epithelium to the anterior stroma for corneal flap making, whereas SMILE requires a side cut of only approximately 3 to 4 mm for the removal of the separated lenticule. The difference in side-cut length may affect corneal subbasal nerve density and ocular surface parameters such as tear volume with Schirmer’s test, tear film break-up time, corneal sensation, and subjective symptoms after these corneal refractive procedures. The purpose of the current study was to assess the time course of the changes in corneal nerve density and ocular surface parameters in eyes that underwent FLEx and SMILE for equivalent myopic correction.

Patients and Methods

Study Population

This prospective study was approved by our institutional ethics committee of Kitasato University and followed the tenets of the Declaration of Helsinki. Informed consent was obtained from all patients after explanation of the nature and possible consequences of the study.

Sixty eyes of 30 patients (8 males and 22 females, mean age: 31.0 ± 6.0 years) were included in the study. All eyes had no ocular disease except for refractive errors. In each patient, 1 eye was randomly assigned to undergo FLEx and the other eye underwent SMILE. The patient population in part comprised those in our preceding studies.8,9 As stated in our previous studies, inclusion criteria for patients to undergo these surgical techniques at our institution were as follows: corrected distance visual acuity of 20/20 or better (logMAR acuity ≤ 0.0), unsatisfactory correction with spectacles or contact lenses, manifest refractive spherical equivalent of −1 to −9 diopters (D), manifest cylinder of 0 to 4 D, sufficient corneal thickness (estimated total postoperative corneal thickness > 400 µm and estimated residual thickness of the stromal bed > 250 µm), intraocular pressure of 21 mm Hg or less, and no history of ocular surgery, severe dry eye, progressive corneal degeneration, cataract, or uveitis. The sample size in this study offered 91% statistical power at the 5% level to detect a 5,000-µm/mm2 difference in corneal nerve density when the standard deviation of the mean difference was 8,000 µm/mm2.

Surgical Procedures

Both FLEx and SMILE were performed using the VisuMax femtosecond laser system (Carl Zeiss Meditec, Jena, Germany) with a 500-kHz repetition rate, as described previously.8,9 The main femtosecond incisions were performed in the following automated sequence: posterior surface of the lenticule (spiral-in pattern), anterior surface of the lenticule (spiral-out pattern), and side cut of the flap. The femtosecond laser parameters were as follows: 120-µm flap thickness, 7.5-mm flap diameter, 6.5-mm lenticule diameter, 140-nJ power for lenticule and flap, 310° side cut with angles of 90° for FLEx, and 50° side cut for access to the lenticule with angles of 90° for SMILE. After completion of the laser sequence during FLEx, a Seibel spatula was inserted under the flap near the hinge and the flap was lifted, and the lenticule was then grasped with forceps and extracted. The flap was then repositioned and the interface was flushed. For SMILE, the spatula was inserted through the side cut over the roof of the lenticule dissecting this plane followed by the bottom of the lenticule. The lenticule was subsequently grasped and removed. The intrastromal space was then flushed. After surgery, steroidal 0.1% betamethasone (Rinderon; Shionogi, Osaka, Japan) and antibiotic 0.3% levofloxacin (Cravit; Santen, Osaka, Japan) medications were topically administered four times daily for 2 weeks and then the frequency was steadily reduced.

Assessment of Corneal Subbasal Nerve Density

Corneal subbasal nerve densities were measured using a confocal microscope (HRT3 Rostock Cornea Module; Heidelberg Engineering GmbH, Heidelberg, Germany) preoperatively and at 1 week, 1 and 3 months, and 1 year postoperatively. Under local anesthesia of 0.4% oxybuprocaine (Benoxil; Santen), each patient was positioned in chin and forehead rests and instructed to look at a fixed light source. The center of the module contacted the corneal apex and a consecutive series of 40 photographs were taken at every 2 µm from the corneal surface. The corneal images were made anonymous and one masked observer selected the most representative images of the central corneal subbasal nerve plexus, then determined the length of corneal nerve fibers using a semi-automatic image analysis system (NeuronJ; a plug-in program to ImageJ).10,11 Nerve fiber density per area (µm/mm2) was calculated by nerve fiber length divided by area.

Assessment of Ocular Surface Parameters

Preoperatively and 1 and 3 months postoperatively, we determined the following parameters in both groups: tear volume determined with Schirmer’s I test, tear film break-up time, and corneal sensation. Natural tear volume was measured using Schirmer’s I test, in which the extent of tear flow down a piece of filter paper inserted in the lateral part of the inferior fornix of the eye during a 5-minute period without anesthetic drops. The standard tear film break-up time measurement was performed. After 1% fluorescein dye was instilled in the conjunctival sac, the interval between the last complete blink and appearance of the first corneal black spot in the stained tear film was measured three times and the mean value of the measurements was calculated. Corneal sensation was measured with a Cochet–Bonnet esthesiometer (Luneau, Paris, France). This instrument consists of a nylon monofilament that is 60 mm in length and has a diameter of 0.12 mm. The instrument was advanced perpendicular to the central surface of the cornea until contact between the instrument and cornea was made. The length of the filament was sequentially reduced from 60 mm in 5-mm steps. If the patient felt the filament, the response was defined positive. Subjective symptoms (pain, epiphora, and foreign body sensation) were also assessed 1 month postoperatively using visual analogue scale symptom intensity scores on a scale of 0 (no symptom) to 100 (maximum intensity).12

Statistical Analysis

All statistical analyses were performed using Stat-View version 5.0 (SAS Institute, Inc., Cary, NC). One-way analysis of variance (ANOVA) was used for the analysis of the time course of changes, with Dunnett’s test for multiple comparisons. The Mann–Whitney U test was used for statistical analysis to compare the data between the two groups. Unless otherwise indicated, the results are expressed as mean ± standard deviation and a P value of less than .05 was considered statistically significant.

Results

Study Population

The preoperative demographics of the study population are shown in Table 1. Time courses of corneal subbasal nerve density and ocular surface parameters after FLEx and SMILE are also shown in Tables 23.

Preoperative Patient Demographics

Table 1:

Preoperative Patient Demographics

Time Course of Corneal Nerve Density After FLEx and SMILE

Table 2:

Time Course of Corneal Nerve Density After FLEx and SMILE

Time Course of Ocular Surface Parameters After FLEx and SMILE

Table 3:

Time Course of Ocular Surface Parameters After FLEx and SMILE

Corneal Subbasal Nerve Density

In the FLEx group, the variation in corneal nerve density was statistically significant (P < .001, ANOVA). Multiple comparisons demonstrated significant differences between measurements made before surgery and at all postoperative visits (P < .001, Dunnett’s test). In the SMILE group, the variation in corneal nerve density was also statistically significant (P = .004). Multiple comparisons demonstrated significant differences between measurements made before surgery and at 1 week (P = .01) and 1 (P = .001) and 3 (P = .03) months after surgery, but no significant differences between measurements made before surgery and at 1 year after surgery (P = .21). The postoperative corneal nerve density was significantly less marked in the FLEx group than in the SMILE group at all postoperative visits (Mann–Whitney U test, P = .04 at 1 week, P < .001 at 1 month, P = .002 at 3 months, and P = .014 at 1 year postoperatively) (Figure 1).

Time courses of corneal subbasal nerve density after femtosecond lenticule extraction (FLEx) and small incision lenticule extraction (SMILE). SMILE induced significantly less damage to subbasal nerve density than FLEx at all postoperative visits. * = P < .05, Mann–Whitney U test; ** = P < .01, Mann–Whitney U test

Figure 1.

Time courses of corneal subbasal nerve density after femtosecond lenticule extraction (FLEx) and small incision lenticule extraction (SMILE). SMILE induced significantly less damage to subbasal nerve density than FLEx at all postoperative visits. * = P < .05, Mann–Whitney U test; ** = P < .01, Mann–Whitney U test

Schirmer’s Test

In the FLEx group, the variation in Schirmer’s test was statistically significant (P = .004, ANOVA). Multiple comparisons demonstrated significant differences between measurements made before surgery and at 1 (P = .02, Dunnett’s test) and 3 (P = .04) months after surgery. In the SMILE group, the variation in Schirmer’s test was not statistically significant (P = .72). Multiple comparisons demonstrated no significant differences between measurements made before surgery and at 1 (P = .56) and 3 (P = .71) months after surgery.

Break-Up Time

In the FLEx group, the variation in tear film breakup time was statistically significant (P = .03, ANOVA). Multiple comparisons demonstrated significant differences between measurements made before surgery and at 1 (P = .03, Dunnett’s test) and 3 (P = .04) months after surgery. In the SMILE group, the variation in tear film break-up time was not statistically significant (P = .12). Multiple comparisons demonstrated no significant differences between measurements made before surgery and at 1 (P = .99) and 3 (P = .82) months after surgery.

Corneal Sensation

In the FLEx group, the variation in corneal sensation was statistically significant (P < .001, ANOVA). Multiple comparisons demonstrated significant differences between measurements made before surgery and at 1 (P < .001, Dunnett’s test) and 3 (P = .001) months after surgery. In the SMILE group, the variation in corneal sensation was not statistically significant (P = .11). Multiple comparisons demonstrated no significant differences between measurements made before surgery and at 1 (P = .34) and 3 (P = .07) months after surgery.

Subjective Symptoms

The visual analog scale scores in the FLEx group were significantly higher than in the SMILE group in terms of pain, epiphora, and foreign body sensation at 1 month after surgery (Mann–Whitney U test, P < .001).

Discussion

In the current study, our results showed significantly less damage to corneal nerve density after SMILE than after FLEx up to 1 year postoperatively.

SMILE requires only a 3- to 4-mm vertical incision without flap making, whereas FLEx requires both vertical incision (approximately 20 mm) and flap making. The corneal nerve enters from the sclera into the stroma in the corneal periphery and forms a subepithelial nerve plexus beneath Bowman’s membrane, penetrates it, and forms a subbasal nerve plexus, giving rise to terminal nerves in the deep epithelium.13–19 Therefore, the vertical incision in these surgical procedures damages the subbasal nerve plexus beneath the corneal epithelium. We assumed that the difference in length of this incision in the SMILE group may cause less damage to subbasal nerve density than in the FLEX group, although even SMILE caused some degree of damage in subbasal nerve density.

There have been several studies on subbasal nerve density after corneal refractive surgery.20–29 Erie et al.20 showed that corneal subbasal nerve density does not recover to preoperative levels until 5 years after LASIK, as compared with 2 years after photorefractive keratectomy. Calvillo et al.21 demonstrated that both subbasal and stromal corneal nerves in the LASIK flap recovered slowly and did not return to preoperative levels even by 3 years postoperatively. Darwish et al.22 found that subbasal nerve density decreased significantly 1 month after LASIK and did not return to preoperative levels within 6 months, and that there was no apparent difference between LASIK and laser-assisted subepithelial keratectomy in the time required for recovery of corneal structure or function. Li et al.27 reported that the decrease in subbasal nerve density was significantly less severe in SMILE-treated eyes than in LASIK-treated eyes at 1 week and 1 and 3 months postoperatively, but no significant difference was detected at the 6-month postoperative visit. Vestergaard et al.28 stated that the total number of subbasal nerves significantly decreased more in FLEx-treated eyes than in SMILE-treated eyes at 6 months postoperatively, which was in agreement with our current findings.

With regard to ocular surface parameters, Li et al.29 reported that SMILE was followed by three changes of brief duration (an increase in dry eye symptoms, tear film instability, and loss of corneal sensitivity), but also that SMILE offers advantages over LASIK in terms of a lower risk of postoperative corneal staining and less reduction of corneal sensation. Li et al.30 also showed that the impairment of corneal sensation was less significant in the SMILE group than in the LASIK group and was independent of preoperative spherical equivalent or ablation depth. Vestergaard et al.28 demonstrated that corneal sensation 6 months postoperatively was significantly reduced in FLEx-treated eyes, but not in SMILE-treated eyes, and that no significant differences were found between FLEx- and SMILE-treated eyes in tear film evaluation tests. Their former finding was in line with our current findings of corneal sensation, but the latter finding did not match our findings in tear film evaluation tests. We assume that better preservation of the subbasal nerve plexus after SMILE may contribute to lesser involvement in the reflex tear secretion, corneal sensation, and foreign body sensation. A further long-term study with a large cohort of patients is still necessary to clarify this point.

There are two limitations to this study. One is that the amount of sample data was rather limited. However, the sample size in this study offered more than 90% statistical power at the 5% level. Another limitation is that we did not perform impression cytology of the conjunctival goblet cells. Impression cytology may provide us with more detailed information about these cells in the conjunctiva.

Our results support the view that SMILE induces significantly less damage to subbasal nerve density and less change in ocular surface parameters (eg, tear film, break-up time, corneal sensation, and subjective symptoms) than FLEx. These results indicate that SMILE offers some assurance for minimally invasive refractive surgery in the correction of myopia, especially in terms of subbasal nerve density and ocular surface parameters.

References

  1. 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]
  2. Sekundo W, Kunert KS, Blum M. Small incision corneal refractive surgery using the small incision lenticule extraction (SMILE) procedure for the correction of myopia and myopic astigmatism: results of a 6 month prospective study. Br J Ophthalmol. 2011;95:335–339. doi:10.1136/bjo.2009.174284 [CrossRef]
  3. 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]
  4. 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;248:1019–1027. doi:10.1007/s00417-009-1293-1 [CrossRef]
  5. Blum M, Kunert KS, Engelbrecht C, Dawczynski J, Sekundo W. Femtosecond lenticule extraction (FLEx): results after 12 months in myopic astigmatism [article in German]. Klin Monbl Augenheilkd. 2010;227:961–965. doi:10.1055/s-0029-1245894 [CrossRef]
  6. Shah R, Shah S. Effect of scanning patterns on the results of femtosecond laser lenticule extraction refractive surgery. J Cataract Refract Surg. 2011;37:1636–1647. doi:10.1016/j.jcrs.2011.03.056 [CrossRef]
  7. Kamiya K, Igarashi A, Ishii R, Sato N, Nishimoto H, Shimizu K. 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. doi:10.1016/j.jcrs.2012.06.052 [CrossRef]
  8. Kamiya K, Shimizu K, Igarashi A, Kobashi H. Visual and refractive outcomes of femtosecond lenticule extraction and small incision lenticule extraction for myopia. Am J Ophthalmol. 2014;157:128–134. doi:10.1016/j.ajo.2013.08.011 [CrossRef]
  9. Kamiya K, Shimizu K, Igarashi A, Kobashi H, Sato N, Ishii R. Intrain-dividual comparison of the changes in corneal biomechanical parameters following femtosecond lenticule extraction and small incision lenticule extraction. J Cataract Refract Surg. 2014;40:963–970. doi:10.1016/j.jcrs.2013.12.013 [CrossRef]
  10. Meijering E, Jacob M, Sarria JCF, Steiner P, Hirling H, Unser M. Design and validation of a tool for neurite tracing and analysis in fluorescence microscopy images. Cytometry A. 2004;58:167–176. doi:10.1002/cyto.a.20022 [CrossRef]
  11. Rasband WS. ImageJ, 1997–2009. US National Institutes of Health Web site. Available at: http://rsb.info.nih.gov/ij/
  12. Aitken RC. Measurement of feelings using visual analogue scales. Proc R Soc Med. 1969;62:989–993.
  13. Marfurt CF, Cox J, Deek S, Dvorscak L. Anatomy of the human corneal innervation. Exp Eye Res. 2010;90:478–492. doi:10.1016/j.exer.2009.12.010 [CrossRef]
  14. Müller LJ, Vrensen GF, Pels L, Cardozo BN, Willekens B. Architecture of human corneal nerves. Invest Ophthalmol Vis Sci. 1997;38:985–994.
  15. Grupcheva CN, Wong T, Riley AF, McGhee CN. Assessing the sub-basal nerve plexus of the living healthy human cornea by in vivo confocal microscopy. Clin Experiment Ophthalmol. 2002;30:187–190. doi:10.1046/j.1442-9071.2002.00507.x [CrossRef]
  16. Müller LJ, Marfurt CF, Kruse F, Tervo TM. Corneal nerves: structure, contents and function. Exp Eye Res. 2003;76:521–542. doi:10.1016/S0014-4835(03)00050-2 [CrossRef]
  17. Guthoff RF, Wienss H, Hahnel C, Wree A. Epithelial innervation of human cornea: a three-dimensional study using confocal laser scanning fluorescence microscopy. Cornea. 2005;24:608–613. doi:10.1097/01.ico.0000154384.05614.8f [CrossRef]
  18. He J, Bazan NG, Bazan HE. Mapping the entire human corneal nerve architecture. Exp Eye Res. 2010;91:513–523. doi:10.1016/j.exer.2010.07.007 [CrossRef]
  19. Patel DV, McGhee CN. Mapping of the normal human corneal sub-Basal nerve plexus by in vivo laser scanning confocal microscopy. Invest Ophthalmol Vis Sci. 2005;46:4485–4488. doi:10.1167/iovs.05-0794 [CrossRef]
  20. Erie JC, McLaren JW, Hodge DO, Bourne WM. Recovery of corneal subbasal nerve density after PRK and LASIK. Am J Ophthalmol. 2005;140:1059–1064. doi:10.1016/j.ajo.2005.07.027 [CrossRef]
  21. Calvillo MP, McLaren JW, Hodge DO, Bourne WM. Corneal re-innervation after LASIK: prospective 3-year longitudinal study. Invest Ophthalmol Vis Sci. 2004;45:3991–3996. doi:10.1167/iovs.04-0561 [CrossRef]
  22. Darwish T, Brahma A, O’Donnell C, Efron N. Subbasal nerve fiber regeneration after LASIK and LASEK assessed by noncontact esthesiometry and in vivo confocal microscopy: prospective study. J Cataract Refract Surg. 2007;33:1515–1521. doi:10.1016/j.jcrs.2007.05.023 [CrossRef]
  23. Lee SJ, Kim JK, Seo KY, Kim EK, Lee HK. Comparison of corneal nerve regeneration and sensitivity between LASIK and laser epithelial keratomileusis (LASEK). Am J Ophthalmol. 2006;141:1009–1015. doi:10.1016/j.ajo.2006.01.048 [CrossRef]
  24. Moilanen JA, Holopainen JM, Vesaluoma MH, Tervo TM. Corneal recovery after lasik for high myopia: a 2-year prospective confocal microscopic study. Br J Ophthalmol. 2008;92:1397–1402. doi:10.1136/bjo.2007.126821 [CrossRef]
  25. Patel DV, McGhee CN. In vivo confocal microscopy of human corneal nerves in health, in ocular and systemic disease, and following corneal surgery: a review. Br J Ophthalmol. 2009;93:853–860. doi:10.1136/bjo.2008.150615 [CrossRef]
  26. Patel SV, McLaren JW, Kittleson KM, Bourne WM. Subbasal nerve density and corneal sensitivity after laser in situ keratomileusis: femtosecond laser vs mechanical microkeratome. Arch Ophthalmol. 2010;128:1413–1419. doi:10.1001/archophthalmol.2010.253 [CrossRef]
  27. Li M, Niu L, Qin B, et al. Confocal comparison of corneal re-innervation after small incision lenticule extraction (SMILE) and femtosecond laser in situ keratomileusis (FS-LASIK). PLoS One. 2013;8:e81435. doi:10.1371/journal.pone.0081435 [CrossRef]
  28. Vestergaard AH, Grønbech KT, Grauslund J, Ivarsen AR, Hjortdal JO. Subbasal nerve morphology, corneal sensation, and tear film evaluation after refractive femtosecond laser lenticule extraction. Graefes Arch Clin Exp Ophthalmol. 2013;251:2591–2600. doi:10.1007/s00417-013-2400-x [CrossRef]
  29. 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. doi:10.1371/journal.pone.0077797 [CrossRef]
  30. Li M, Zhou Z, Shen Y, Knorz MC, Gong L, Zhou X. Comparison of corneal sensation between small incision lenticule extraction (SMILE) and femtosecond laser-assisted LASIK for myopia. J Refract Surg. 2014;30:94–100. doi:10.3928/1081597X-20140120-04 [CrossRef]

Preoperative Patient Demographics

VariableFLEx GroupSMILE GroupP
Age (y)31.0 ± 6.0 (20 to 41)
Gender (% female)73
Manifest refractive spherical equivalent (D)−3.5 ± 1.7 (−1.00 to −7.75)−3.9 ± 1.6 (−1.25 to −7.75).33
Manifest cylinder (D)−0.8 ± 0.9 (−0.00 to −2.75)−0.6 ± 0.7 (−0.00 to −2.25).17
UCVA (logMAR)1.06 ± 0.28 (0.30 to 1.52)1.12 ± 0.22 (0.52 to 1.52).41
UCVA (decimal)0.09 (0.03 to 0.50)0.08 (0.03 to 0.30)
CDVA (logMAR)−0.22 ± 0.07 (−0.30 to −0.08)−0.22 ± 0.07 (−0.30 to −0.08).80
CDVA (decimal)1.66 (1.20 to 2.00)1.66 (1.20 to 2.00)
Central corneal thickness (μm)547.7 ± 30.3 (492 to 626)543.3 ± 29.7 (483 to 614).53

Time Course of Corneal Nerve Density After FLEx and SMILE

Subbasal Nerve Density (µm/mm2)Preoperative1 Week Postoperative1 Month Postoperative3 Months Postoperative1 Year PostoperativeP
FLEx group (95% CI)18,390 ± 6,090 (15,280 to 21,850)3,960 ± 6,230 (700 to 7,220)1,780 ± 2,490 (760 to 7,800)2,220 ± 3,190 (750 to 3,690)5,770 ± 3,490 (4,200 to 7,340)< .001
SMILE group (95% CI)16,810 ± 6,220 (13,550 to 20,070)7,970 ± 6,290 (4,680 to 11,260)7,020 ± 5,270 (4,870 to 9,180)9,670 ± 10,750 (4,710 to 14,640)11,870 ± 8,200 (8,180 to 15,550).004

Time Course of Ocular Surface Parameters After FLEx and SMILE

TimeFLEx Group (95% Confidence Interval)SMILE Group (95% Confidence Interval)
Preoperative
  Schirmer’s test (mm)a20.3 ± 14.4 (13.0 to 27.6)16.1 ± 11.4 (10.4 to 21.9)
  Break-up time (s)b5.1 ± 2.3 (4.0 to 6.2)4.7 ± 2.3 (3.6 to 5.9)
  Corneal sensation (mm)c60 ± 060 ± 0
1 month postoperative
  Schirmer’s test (mm)a10.5 ± 9.0 (6.0 to 15.1)15.1 ± 10.5 (9.8 to 20.5)
  Break-up time (s)b3.6 ± 1.8 (2.7 to 4.5)6.3 ± 2.3 (5.1 to 7.4)
  Corneal sensation (mm)c41.7 ± 11.6 (35.8 to 47.5)50.3 ± 4.0 (48.3 to 52.4)
  Visual analog scoring
    Pain93 ± 9 (89 to 97)39 ± 34 (23 to 55)
    Epiphora87 ± 20 (77 to 96)35 ± 31 (20 to 49)
    Foreign body sensation89 ± 18 (80 to 97)44 ± 33 (28 to 59)
3 months postoperative
  Schirmer’s test (mm)a11.7 ± 9.1 (7.1 to 16.3)16.5 ± 9.8 (11.6 to 21.5)
  Break-up time (s)b3.7 ± 1.4 (2.9 to 4.4)5.1 ± 1.7 (4.2 to 5.9)
  Corneal sensation (mm)c50.3 ± 4.0 (48.3 to 52.4)58.3 ± 2.4 (57.1 to 59.6)

10.3928/1081597X-20141218-01

Sign up to receive

Journal E-contents