Clinical trial NCT01216475: Randomized, Non-inferiority Trial Comparing SMILE and LASIK
Official title: Comparison of Small Incision Lenticule Extraction (SMILE) and VisuMax Femtosecond Laser In Situ Keratomileusis (FemtoLASIK): A Randomized, Non-inferiority Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Myopia
Astigmatism
Hypermetropia
Lead sponsor: Singapore National Eye Centre
Sponsor class: OTHER_GOV
First posted: 2010-10-07
Enrollment: 70
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Background: Small Incision Lenticule Extraction or SMILE is a novel form of 'flapless' corneal refractive surgery that was adapted from Refractive Lenticule Extraction (ReLEx). SMILE uses only one femtosecond laser to complete the refractive surgery, potentially reducing surgical time, side effects and cost. If successful, SMILE could potentially replace the current, widely practiced Laser In-situ Keratomileusis or LASIK. The aim of this study is to evaluate whether SMILE is non-inferior to LASIK in terms of refractive outcomes at 3-months post-operatively.

Methods/ Design: Single tertiary center, parallel group, single-blinded, paired-eye design, non-inferiority, randomized controlled trial. Participants who are eligible for LASIK will be enrolled for study after informed consent. Each participant will be randomized to receive SMILE and LASIK in each eye. Our primary hypothesis (stated as null) in this non-inferiority trial would be that SMILE differs from LASIK in adults (\>21 years old) with myopia (\> -3.00D) at a tertiary eye center in terms of refractive predictability at 3 months post-operatively. Our secondary hypothesis (stated as null) in this non-inferiority trial would be that SMILE differs from LASIK in adults (\>21 years old) with myopia (\> -3.00D) at a tertiary eye center in terms of other refractive outcomes (efficacy, safety, higher-order aberrations) at 3 months post-operatively. Our primary outcome is refractive predictability, which is one of several standard refractive outcomes, defined as the proportion of eyes achieving a postoperative spherical equivalent (SE) within ±0.50 diopter (D) of the intended target. Randomization will be performed using random allocation sequence generated by a computer with no blocks or restrictions, and implemented by concealing the number-coded surgery within sealed envelopes until just before the procedure. In this single-blinded trial, subjects and their caregivers will be blinded to the assigned treatment in each eye.

Discussion: This novel trial will provide information on whether SMILE has comparable, if not superior, refractive outcomes compared to the established LASIK for myopia, thus providing evidence for translation into clinical practice.

Detailed description: Surgical correction for refractive errors may be performed by a number of procedures. Laser correction involves procedures such as EpiLASIK, LASIK or conductive keratoplasty, while lens based corrections involve the use of phakic intra-ocular lenses. Despite the emergence of other procedures, due to its fast visual rehabilitation and painless postoperative course, LASIK is still the procedure of choice for both patients and refractive surgeons.

LASIK consists of two steps: the first step involves the formation of a corneal flap and the second one is when the excimer ablation is performed in the corneal stromal bed. Femtosecond lasers (FL) have been widely used in LASIK surgery to fashion the corneal flap. The laser will cut a lamellar followed by a vertical corneal incision. We are able to produce a vertical cut since the Femtosecond laser can deliver laser pulses of 1 micron diameter at a preselected depth in the cornea, which then expands to 2 to 3 microns with the formation of a cavitation bubble. These pulses create micro-photodisruption of the corneal tissue by the formation of an expanding bubble of carbon dioxide and water, which in turn cleaves the tissue and creates a plane of separation. The flap is then removed to expose the stroma and the refractive treatment is done by the excimer laser over the denuded stroma. The advantages of femtosecond laser over microkeratome LASIK flaps have been reduced postoperative dry eye symptoms, less chance of dislocation from trauma and reduced incidence of button holes or free caps.

Even though femto-LASIK has demonstrated good efficacy, it can still be asssociated with side effects found in standard LASIK e.g. glare, haloes, dry eye and still requires the use of two laser machines, one for the flap the other for the excimer ablation. This increases the length of time of the overall procedure and the costs.

Recently, a new "one laser" refractive surgery has been proposed: Femtosecond Lenticule Ex-traction (FLEx). It consists of performing the entire refractive procedure without an excimer laser. The Femtosecond laser creates four stromal incisions to create a corneal lenticule and a corneal flap. The size and shape of the lenticule is calculated based on the patient refractive error. The lenticule is separated from the flap above and the rest of the cornea below using a small spatula. Following this, the lenticule is grasped with a forceps and extracted from the eye. Finally, the flap is repositioned and the interface washed. At this time the refractive error is already corrected without the use of a second laser.

The advantages of FLEx treatment are shortened length of the refractive procedure, reduced patient inconvenience from moving from one laser to another, reduced risk of intraoperative infections and more accurate ablation since the patient need to fixate only once.

Currently there are no publications comparing FLEx to LASIK, hence this study will be unique in the fact that the paired eye approach will act as an internal patient control to assess the objective and subjective outcomes in patients following both these procedures.

The study will be a prospective randomized trial of patients comparing SMILE (a variation of FLEx) with LASIK to treat their myopic refractive error. One eye will be randomized for SMILE and other eye for LASIK. Each procedure will be performed sequentially. Randomization will be performed by a random number generator, and assignment concealed in envelopes.

Eligibility criteria: Inclusion Criteria:

1. 21 years of age or older.
2. Cycloplegic spherical equivalent of \>-2.00D
3. Refractive cylinder -4.00 D or less, Anisometropia of \>1D
4. Best spectacle corrected visual acuity (BSCVA) of 6/12 or better in BOTH eyes.
5. Spherical or cylindrical error has progressed at -0.50D or less per year from date of baseline measurement.
6. Contact lens wearers must have removed contact lenses at least two (2) weeks before the baseline measurement.
7. No evidence of irregular astigmatism on corneal topography.
8. Available to attend post-operative examinations for a 3 month period.

Exclusion Criteria:

1. Progressive or unstable myopia and/or astigmatism.
2. Clinical or corneal topographic evidence of keratoconus.
3. Residual, recurrent or active ocular disease such as uveitis, severe dry eyes, severe allergic eye disease, glaucoma, visually significant cataract and retinal disease.
4. Previous corneal surgery or trauma within the corneal flap zone.
5. Patent corneal vascularization within 1mm of the corneal flap zone.
6. Taking systemic medications likely to affect wound healing, such as corticosteroids and antimetabolites.
7. Systemically immunocompromised.
8. Systemic disease likely to affect wound healing, such as diabetes, connective tissue disease and severe atopy.
9. Pregnant or nursing.

Primary outcomes:
measure: Refractive predictability
timeFrame: 3 months Post-operative
Secondary outcomes:
measure: Efficacy
timeFrame: 3 months Post-operative
measure: Safety
timeFrame: 3 months Post-operative
measure: Contrast sensitivity
timeFrame: 3 months Post-operative
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: Singapore National Eye Centre
Study officials:
affiliation: Singapore National Eye Centre
name: Donald T Tan, FRCS(Ed),
role: STUDY_DIRECTOR
affiliation: SNEC
name: Jodhbir S Mehta, FRCS (ed)
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sekundo W, Kunert K, Russmann C, Gille A, Bissmann W, Stobrawa G, Sticker M, Bischoff M, Blum M. First efficacy and safety study of femtosecond lenticule extraction for the correction of myopia: six-month results. J Cataract Refract Surg. 2008 Sep;34(9):1513-20. doi: 10.1016/j.jcrs.2008.05.033.
citation: Ang M, Tan D, Mehta JS. Small incision lenticule extraction (SMILE) versus laser in-situ keratomileusis (LASIK): study protocol for a randomized, non-inferiority trial. Trials. 2012 May 31;13:75. doi: 10.1186/1745-6215-13-75.