Surgical correction of refractive errors is popular and the excimer laser and the later addition of the femtosecond laser have revolutionised corneal refractive surgery. Progressive flattening of the cornea, diurnal fluctuations in vision post-operatively and the invention of laser-based techniques (PRK, LASEK and LASIK) were some of the reasons radial keratotomy (RK) is largely obsolete. Many other corneal refractive procedures have been attempted, such as thermal collagen shrinkage and epikeratoplasty, and these have largely been abandoned. Other techniques such as arcuate keratotomy and corneal inlays are still used.

More recently femtosecond lenticule extraction (FLEx) of intracorneal tissue, using only a femtosecond laser, has become possible. A stromal lenticule was created in conjunction with a lamellar flap. This was the precursor to the small incision lenticule extraction (SMILE) procedure for treating myopia and astigmatism. This article provides an introduction to SMILE.

Techniques for corneal refractive surgery

Before discussing SMILE in more detail, other available techniques for corneal refractive surgery are described briefly including the advantages and challenges of each.

PRK (photorefractive keratectomy)

PRK was the first excimer laser technique for the treatment of refractive errors. PRK involves removal of the central corneal epithelium, most commonly performed mechanically after alcohol solution application to loosen the epithelium. The anterior stroma is then reshaped by the excimer laser, with either central corneal flattening, relative steepening or a toroidal pattern when treating myopia, hyperopia or astigmatism, respectively. The introduction of a very dilute solution of a cytotoxic agent, mitomycin-C and modern surface ablation techniques has also increased the range of treatments and lowered the risk of haze and regression after PRK.

LASEK (laser sub-epithelial keratomileusis)

Of the modern methods of laser vision correction available today, it is perhaps LASEK which is the closest to the original PRK treatments of the 1990s. In LASEK, the epithelial cells are loosened with an alcohol solution and drawn to the side, after which the excimer laser reshapes the tissue beneath. The epithelium is however retained after LASEK, in contrast to PRK. Because the epithelial cells must be replaced, recovery after LASEK and PRK takes up to a week. During this time the healing cornea is protected by a bandage extended wear contact lens. LASEK treatment has also been restricted in the past due to its association with the development of haze in the post-operative period, but this again is often addressed by surgeons using mitomycin-C to prevent the aggressive healing action of the stromal fibroblasts. PRK and LASEK are associated with more marked post-operative pain in the first few days of healing, and patients are given analgesics for this.

LASIK/Femto LASIK (laser in-situ keratomileusis)

In its current form, femtosecond (FS)-LASIK requires two laser platforms (a femtosecond laser for flap creation and an excimer laser for stromal bed ablation).

Previously a microkeratome was used for flap creation. Due to the significant postoperative discomfort, relatively slow visual recovery and haze development with surface procedures, especially when treating high myopia, LASIK was introduced.1 The LASIK procedure is fast approaching the 30-year mark since its inception, and has passed the milestone of the 50 millionth treatment.2

The majority of these treatments will have been for the management of myopia. As a fundamental description, LASIK is the adjustment of the corneal morphology through laser ablation of corneal tissue with the intention of adjusting the optics of the cornea, eliminating or reducing unwanted aberrations and thereby bringing about a desirable visual outcome. From this concept derives the ‘K’ in the acronym LASIK; ‘keratomileusis’ or corneal sculpture.

The relationship between the amount of tissue ablated per dioptre of myopia corrected is given by the Munnerlyn formula3 which states the maximum ablation depth in microns is equal to the product of the spherical equivalent prescription and the square of the diameter of the optic zone in millimetres, divided by three. It follows that the higher the degree of myopia intended to be treated, the more corneal tissue will be ablated. A theoretical limit of 250 microns of untreated stromal bed soon came into being,4 as the risk of corneal ectasia in post-LASIK corneas was realised.

However, this somewhat arbitrary limit has been shown to have no firm theoretical basis. There have been reported cases of the 250 micron limit being breached without resultant ectasia, and indeed a number of documented cases of corneas with residual stromal beds in excess of 250 microns becoming diagnosed as ectatic.5 There has since been a movement toward a more conservative ethos with regard to tissue, and surgeons are likely to incline toward a minimum 300 micron residual stromal bed.6

In mathematical modelling,7 there has been a suggestion that circumventing the need for the lifting of a LASIK flap makes biomechanical sense. The anterior collagenous stromal lamellae are stronger,8 and a means of preserving them offers an attractive theoretical advantage. With the development and refinement of the femtosecond laser, intrastromal techniques including Refractive Lenticule Extraction (ReLEx) and now SMILE have arrived, the latter obviating the requirement for a formal flap. The technique was quickly shown to produce results comparable to those of longer standing methods.9

SMILE (small incision lenticule extraction)

In the 1990s developments in lasers allowed researchers to create an intrastromal lenticule which was then manually removed. The use of femtosecond lasers improved precision and around 2007 ReLEx was introduced to use one laser platform for flap creation and refractive lenticule extraction. The VisuMax FSL (figure 1) (Carl Zeiss Meditec, Jena, Germany) is used for refractive lenticule extraction without the use of an excimer laser or microkeratomes.

Figure 1: VisuMax laser. Image courtesy Carl Zeiss Meditec AG

A stromal lenticule is created in the case of FLEx with a flap, which allowed its removal. This approach was the precursor to the SMILE technique. In SMILE, only one or two small incisions are made, minimising the disruption to the corneal surface but allowing removal of the lenticule (figures 2 to 4).10-18 Theoretically, this approach should reduce the effects on corneal denervation, dry eye and epithelial ingrowth, and preserve biomechanical stability when compared to flap-related procedures.

Clinical outcomes

Various studies have assessed the outcomes of SMILE for the treatment of myopia. In a recent publication visual and refractive data one year after treatment was analysed and the authors found a mean uncorrected distance visual acuity of -0.16 ±0.11 logMAR and a mean corrected distance visual acuity of -0.22 ±0.07 logMAR in 52 eyes of 39 patients.

All eyes in the study cohort were within ±0.50 D of predicted post-operative refraction one year after surgery and the mean change of refraction between one week and one year was -0.05 ± 0.32 D. The endothelial cell density did not change significantly between pre-operative and post-operative measurements.19 Zhang et al20 also measured changes over one year and found similar results.

Lin et al21 compared the results of SMILE and FS-LASIK at one and three months after surgery. They did not find a statistically significant difference between the two procedures in terms of mean spherical equivalent refraction and percentage of eyes with an uncorrected visual acuity of 6/6 or better at either visit.

One month after treatment four eyes of the SMILE cohort had lost one or more lines. In the FS-LASIK group one eye lost one or more lines. However, this difference was not statistically significant. At both visits a significant difference was found for higher order aberrations with eyes undergoing SMILE having reduced levels of higher-order aberrations. In contrast, Yildrim et al22 compared SMILE with PRK using an aberration-free ablation profile and found that higher order aberrations were significantly higher after SMILE.

Figure 2: Lenticule is created within the cornea under topical anaesthesia. Patient is centred under the operating microscope and the surgeon orientates the docking mechanism. The interface consists of a cone and curved contact interface. The laser creates the posterior lenticule surface, the anterior lenticule surface, and the edge incisions. Finally the peripheral corneal incisions are created to allow for the lenticule extraction.27

The first study cohort that underwent SMILE was seen again for follow up 12 months after treatment by Kunert et al23 Refraction was measured one month, three months, six months and 12 months after treatment and was found to be stable over the period. Complications at the 12 month follow-up visit were minimal; in one eye two microstriae were found, in another eye a mild corneal opacity was observed, with visual acuity 6/7.5, and in another case epithelial ingrowth was observed.

Shen et al24 performed a review and a meta-analysis comparing SMILE with FS-LASIK. Their database comprised 12 studies and 1,076 eyes and they concluded that both surgical techniques are safe, predictable and effective in treating myopia. Dry eye symptoms and loss of corneal sensitivity occurred less frequently after SMILE than after FS-LASIK.

Figure 3: The lenticule is removed through a small incision. A flap separator is moved over the anterior and then the posterior lenticule surface. Once the lenticule has been separated, forceps are used to gently extract the lenticule

Several other studies confirmed similar results in terms of visual and refractive outcomes.14,25,26 However, long-term data will be required to conclusively demonstrate the safety and efficacy. As the SMILE technique is relatively new, it is envisaged that longitudinal data will continue to appear in the literature.

In summary, early data suggests the SMILE procedure is safe. Intraoperative complications may occur, although these are unlikely to be sight-threatening. Suction loss may require the procedure to be abandoned in favour of a later surface ablation. Epithelial disturbance due to the docking procedure or removal of the lenticule can also occur. The difficulty of extracting the lenticule may vary depending on laser energy settings and it is important to ensure any remaining remnants are removed in the case of a partially torn lenticule.27 The SMILE procedure has a similar post-operative risk profile to other laser refractive surgical procedures, although the risk of flap displacement or striae is obviated. Reported post-operative complications include infection, epithelial ingrowth, diffuse lamellar keratitis, corneal haze, irregular astigmatism, increased aberrations, ectasia, punctate corneal staining and mild dry eye.16,18,26,27

Figure 4: Lenticule removal changes the shape of the cornea correcting the refractive error. Images courtesy of Carl Zeiss Meditec AG

Advantages and disadvantages of SMILE

Some of the empirical and theoretical advantages of SMILE as compared to an excimer-based treatment, include;

Potential advantages

  • No smell of burned corneal tissue
  • Potentially less variation in corneal hydration and tissue removal, because the refractive cut is performed before the stroma is exposed to ambient change
  • Minimally invasive stromal tissue removal
  • Since fewer corneal nerves are disturbed in an intrastromal procedure, post-operative dry eye may be less frequent and reduced in severity compared to LASIK
  • Offers an alternative to LASEK in patients deemed by the surgeon to be at risk of marked dry eye
  • Maintenance of biomechanical properties due to preservation of more of the stronger anterior stroma leading to minimal impact on corneal strength
  • Possibility to cryopreserve the refractive lenticule, which could in future be used for lamellar surgery

Potential disadvantages

  • Treatment of hyperopia is not yet commercially available
  • SMILE is more surgically demanding than flap-based procedures
  • Lenticule tissue remnants and corneal irregularities can occur in cases involving difficulties with lenticule removal
  • The optimal approach to performing enhancement procedures is yet to be determined. Currently, retreatments are more easily performed in FS-LASIK by lifting the flap. In SMILE, a new SMILE procedure, Circle technique, or laser-based opening of the ‘cap’ with subsequent photoablation are possible options
  • Slightly delayed visual recovery in early postoperative period

Suitability and patient selection

The Zeiss VisuMax laser can therefore be used to perform all-in-one femtosecond laser refractive surgery by the creation and extraction of a precise refractive lenticule to alter the curvature of the cornea to correct myopia and/ or astigmatism.

The criteria for SMILE surgery broadly reflect the standard parameters for other laser refractive surgery techniques including ocular health, age and refractive error. The available range for treatment currently is for myopes between;

  • Sphere -0.50 to -10.00D
  • Cyl 0.00 to -5.00 DC
  • Or combined up to -10.00D

The surgeon will naturally make the final decision regarding suitability for treatment. Emerging data on hyperopic treatment studies are being presented, although SMILE is not commercially available for this application at present.

In order to determine suitability for SMILE, a full examination is carried out pre-operatively. The relative and absolute contraindications for SMILE are similar to those for LASIK.

Relative contraindications:

  • Moderate dry eye disease
  • Recurrent corneal erosions
  • History of herpes simplex or zoster ophthalmicus
  • Atopic disease
  • Autoimmune disorders
  • Thin corneas (dependant on pre-operative refraction)
  • Glaucoma
  • Mild irregular or abnormal corneal topography

Absolute contraindications:

  • Unstable refraction
  • Residual stromal bed ≤250 microns
  • Keratoconus
  • Corneal scarring
  • Visually significant cataract
  • Uncontrolled systemic or ocular disease
  • Unrealistic patient expectations

Pre-surgical assessment

The pre-assessment for SMILE includes refraction (checking stability), eye dominance, mesopic or scotopic pupil size measured with pupilometer, keratometry, topography, central corneal thickness, slit lamp tear film assessment and fundus examination. A cyclopegic refraction in young myopes may also be required. Contact lens wearers are advised to leave their contact lenses out prior to the pre-operative assessment in order to give the most accurate topography and keratometry measurements.

Post-operative dry eye can occur with any corneal refractive surgery procedure, so it is important to identify patients who have habitual dry eyes pre-operatively. However, as stated above, studies have shown that dry eye symptoms are less common post-operatively with SMILE compared to LASIK.24

Follow-up

As with LASIK, patients are examined one day after their treatment. At this point, most patients will notice their vision is better than without their contact lenses/spectacles although still not at the point that most LASIK treatments would be at day one. The difference is, on average, one to two lines of unaided distance vision. The visual outcomes are typically similar for the two procedures by two to three weeks post-operatively. The patient is required to return at intervals of around one week, one month, three months and six months post operatively.

Future

SMILE appears to represent a safe and efficacious refractive option for the correction of myopia. Refractive outcomes in patients with high myopia approach if not exceed patients undergoing LASIK. The possible biomechanical benefits of SMILE in these high refractive error ranges will be determined in longer-term studies. The incidence of complications appears minimal and although some reports suggest visual recovery may be somewhat slower when compared to LASIK, optimisation of settings has improved this.27

The use of donor lenticules to treat hyperopia, presbyopia or even ectasia in the future poses an exciting possibility. It has been suggested SMILE used in combination with collagen cross-linking procedures may further stabilise the refractive change in certain cases and further reduce the possibility of ectasia. As with any new technology, further studies need to be performed to fully understand SMILE. However, the emerging data do seem to suggest all femtosecond laser-based refractive surgery, using refractive lenticule extraction without a flap, is a complementary technique that may offer certain advantages for some patients, when compared to excimer laser-based LASIK and surface ablation techniques.

References

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