Small-Incision Lenticule Extraction (ReLEx SMILE)

Refractive lenticule extraction (ReLEx) small-incision lenticule extraction (SMILE) is used to treat myopia, with or without astigmatism.

Laser in situ keratomileusis (LASIK) and its variant, femtosecond LASIK (FS-LASIK), despite their success in providing independence from corrective eyeglasses (spectacles) and contact lenses, has continued to be associated with rare complications, including flap-related complications, postoperative dry eye, denervation of corneal nerves, and biomechanical instability leading to corneal ectasia. Engineers, scientists, and surgeons have continued to study alternatives to LASIK because of these uncommon but potentially serious complications.

Refractive lenticule extraction (ReLEx) was the byproduct of existing applications—automated lamellar keratoplasty, automated in situ keratomileusis, and femtosecond lasers. In 2007, an intrastromal femtosecond lenticule extraction (FLEx) was revisited for patients with extreme myopia. In 2011, a small-incision lenticule extraction (SMILE) procedure was introduced as a third-generation laser refractive surgery procedure. The flap creation was eliminated and replaced with creation of a corneal pocket, in which a lenticule is gently removed from a small keyhole incision, usually 2-4 mm in width. Fewer corneal nerves are severed during creation of the pocket and removal of the lenticule, so dry-eye symptoms and loss of corneal sensitivity may occur less frequently after SMILE.

The VisuMax® Femtosecond Laser System is the only laser approved to perform the SMILE procedure.

The image below shows a comparison of the different treatment steps of SMILE, LASIK, and photorefractive keratectomy (PRK).

SMILE treatment steps in comparison to LASIK and PRK. Courtesy of ZEISS (http://www.zeiss.com/corporate/en_us/home.html).

VisuMax® ReLEx SMILE (Carl Zeiss, Inc., [Carl-Zeiss-Straße 2273447, Oberkochen, Germany] is indicated for myopia and astigmatism with the following ranges:

• Sphere: -0.50 to -10.00 diopters (D)
• Cylinder: 0 to 5.00 D

The US FDA–approved indications are as follows:[1]

• Sphere: -1.00 D to -8.00 D
• Cylinder: ≤ -0.50 D
• Manifest refraction spherical equivalent (MRSE): -8.25 D

Absolute contraindications to ReLEx SMILE include the following:

• Unstable refraction over a 12-month period
• Age younger than 18 years
• Insufficient corneal thickness
• Visually significant cataract
• Uncontrolled glaucoma or external disease
• Unrealistic patient expectations
• Hyperopia (current studies are underway)

Relative contraindications to ReLEx SMILE are as follows:

• Prior history of diseases that lead to neurotrophic keratopathy (herpes zoster ophthalmicus [HZO], herpes simplex virus [HSV] keratitis, uncontrolled diabetes mellitus)
• Uncontrolled systemic immune-mediated diseases (Sjögren syndrome, rheumatoid arthritis, systemic lupus erythematous, ankylosing spondylitis, psoriatic arthritis, inflammatory bowel disease (IBD) with arthritis, Behçet disease)
• Abnormal tear film with dry eye disease
• Patients with AIDS, patients who have ocular complications related to HIV or AIDS, or patients who are noncompliant with their HIV/AIDS medications

VisuMax® femtosecond laser system

System components are as follows:

• Patient supporting system, including platform
• Integrated uninterruptible power supply (UPS)
• Surgical microscope with additional slit illumination
• Video camera with integrated digital recording

Laser parameters are as follows:

• Wavelength: 1043 nm
• Pulse duration: 220-580 fs
• Laser pulse rate: 500 kHz

Installation and setup conditions

The weight of the system is 870 kg (including patient support system, platform, UPS).

The recommended space requirement is 3.8 x 4.4 meters (standalone) or 3.8 x 6 meters in combination with the MEL 80 excimer laser.

The electrical connection is 100-240 V, 50/60 Hz, 16 amp max. The system has a separately fused circuit.

Operating conditions

Room temperature: 18-25°C

Atmospheric humidity: 30%-70%

Accessories include the following:

• Single-use contact glasses treatment pack (sizes small/medium/large, type KP)
• Keratoplasty adapter for patient support system

At 6 months following SMILE, the LogMAR uncorrected and corrected distance visual acuity was -0.15 ± 0.10 and -0.19 ± 0.07, respectively. All eyes were within 0.5 D of the targeted spherical equivalent correction. Changes of 0.00 ± 0.30 D occurred in manifest refraction from 1 week to 6 months postprocedure among patients who underwent SMILE.[2]

Potential complications of ReLEx SMILE include the following:

1. Epithelial defect due to vigorous application of dissecting spatula and lenticule forceps, leading to damage of the epithelium at the corneal pocket (< 1%)
2. Suction loss due to patient movement, eyelash or foreign body at the edge of the curved cornea glass cone, redundant conjunctiva, too much liquid interface, or poor suction application (< 1%)
3. Opaque bubble layer due to delayed application of the curved cornea glass cone, leading to the corneal epithelium drying up prior to docking and suction (< 1%)
4. Cap rupture due to overly vigorous windshield wiper movement that does not respect the fulcrum at the pocket (< 1%)
5. Lenticule rupture due to incomplete windshield wiper dissection of the lenticule (< 1%)
6. Foreign body inside the pocket: Loose epithelium, lint, or other foreign body may inadvertently enter the corneal pocket during dissection or removal of the lenticule (< 1%)
7. Diffuse lamellar keratitis ^[3]
8. Ectasia ^[4]

Potential complications #1-6 may occur during the initial learning curve. As the skill of the surgeon improves, these potential complications become rare.

Numerous studies are underway for future applications of ReLEx SMILE, as follows:

• Higher myopia (ie, >10.00 D SE)
• Higher astigmatism (ie, >5.00 D)
• Hyperopia
• Enhancement of prior SMILE
• Lenticule cryopreservation and reimplantation

The Carl Zeiss VisuMax® SMILE procedure, like LASIK, is a safe, effective, and predictable surgical option for treating myopia. Dry-eye symptoms and loss of corneal sensitivity may occur less frequently after SMILE than after LASIK.[5]

A standard ReLEx SMILE patient education pamphlet is given to and reviewed with the patient.

The video below depicts animation of ReLEx SMILE.

SMILE animation. Courtesy of ZEISS (http://www.zeiss.com/corporate/en_us/home.html).

The video below shows the key steps during the surgical procedure.

A standard refractive surgery consent form is given to, reviewed with, and signed by the patient.

Refractive surgery suitability screening should address the following:

• Baseline systemic evaluation to rule out any contraindications and/or relative contraindications (see Contraindications)
• Refraction (automated, manifest, cycloplegic)
• Lid margin and meibomian gland function
• Ocular pressure
• Tear film and ocular surface evaluation, including tear film inspection, tear breakup time (TBUT), and ocular surface staining
• Lens, vitreous, retina, and optic nerve status
• Lensometry
• Optical biometry
• Specular microscopy
• Corneal topography
• Aberrometry
• Tomography
• Pupillometry
• Color fundus photos
• OCT macula
• OCT optic nerve
• Color vision testing
• Contrast sensitivity testing

The ReLEx SMILE procedure, as with other refractive surgery procedures, is elective. The author includes color fundus photography, OCT macula, and OCT optic nerve documentation in all refractive surgery suitability screenings.

The refractive surgery planning sheet information is transferred to the VisuMax® planning software.

The following parameters can be selected by the surgeon when planning the ReLEx SMILE treatment:

• Cap thickness (the current trend is to make this thicker, 120-140 microns)
• Cap diameter (usually 1 mm larger than the optical zone)
• Cap side-cut angle
• Refractive correction
• Lenticule diameter (optical zone, ideally minimum of 6.5 mm)
• Lenticule side-cut angle (the author of this article preferentially has it both at 120°, allowing dominant right hand to dissect the lenticule)
• Minimum lenticule thickness (it is easier to identify the anterior and posterior lenticule plane if it is thicker)

Equipment used for ReLEx SMILE treatment is depicted in the images below.

Carl Zeiss VisuMax Femtosecond Laser. Published with permission from St Luke's Medical Center Global City Tan Eng Gee Eye Institute.

The VisuMax Femtosecond Laser, used in performing ReLEx SMILE, is part of the Carl Zeiss VisuMax MEL80 (or MEL90) Refractive Laser Surgery Suite. Published with permission from St Luke's Medical Center Global City Tan Eng Gee Eye Institute.

Topical ocular anesthetic is administered to the patient, who is placed on a slit-lamp biomicroscope, and the corneal limbus is marked with a surgical marker at 0° and 180°. It is important that the head of the patient be aligned properly to avoid tilt and erroneous marking. The patient is then seated and given a facial povidone iodine facial and eyelid scrub and is given perioperative antibiotic ophthalmic solutions.

The post-SMILE follow-up schedule at the authors’ center is as follows:

• Day 0: Evaluate for any residual foreign body (eg, lint, epithelium) in the pocket
• Day 1: Side-cut epithelialization, uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), topography, slit lamp examination (SLE), tonometry
• Day 7: UCVA, BCVA, topography, tomography, SLE, tonometry
• Month 1: UCVA, BCVA, topography, tomography, SLE, tonometry
• Month 3: UCVA, BCVA, topography, tomography, SLE, tonometry
• Month 6: UCVA, BCVA, topography, tomography, SLE, tonometry
• Month 9: UCVA, BCVA, topography, tomography, SLE, tonometry
• Month 12: UCVA, BCVA, topography, tomography, SLE, tonometry

The refractive surgery planning sheet information is transferred to the VisuMax® planning software.

Topical ocular anesthetic is given to the patient, who is placed on a slit lamp biomicroscope, and the corneal limbus is marked with a surgical marker at 0° and 180°. It is important that the head of the patient be aligned properly to avoid tilt and erroneous marking. The patient is then seated and given a facial povidone iodine facial and eyelid scrub, followed by perioperative antibiotic ophthalmic solutions.

A sterile Carl Zeiss curved contact glass is opened and attached to the VisuMax® at two points. The distal end (curved contact glass) is attached to a suction device, with the proximal end attached to the laser head, and will be in contact with the corneal surface. Centration is achieved with the patient looking at the center of the cone and focusing at a blinking green light. Once 90% contact between the curved cornea glass cone and the corneal surface is achieved, suction is initiated.

The centration is tested with an infrared light. Once centration is acceptable, it is possible to proceed with firing of the femtosecond laser.

Femtosecond laser shots create bubbles applied side by side, creating a cleavage plane, initially creating a posterior surface of the lenticule, followed by the lenticule border, then the anterior surface of the lenticule, and, finally, the side-cut incision, which creates an entrance to the pocket to access the lenticule. A thin spatula is inserted via the side-cut incision to bluntly dissect the intrastromal lenticule using windshield wiper–like side-to-side motion based on a fulcrum (the pocket entrance).

This lenticule is then extracted from the cornea using a pair of thin reverse-action forceps. The corneal pocket is lightly hydrated with balanced salt solution. The corneal epithelial surface is squeegeed with a moistened microsponge toward the direction of the side-cut incision. Topical antibiotic steroids and lubricants are applied. An eye patch is applied. The fellow eye undergoes the same procedure.

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Class Summary

Corticosteroids have anti-inflammatory properties and cause profound and varied metabolic effects. In addition, these agents modify the body's immune response to diverse stimuli.

Prednisolone ophthalmic (Omnipred, Pred Forte, Pred MIld)

Prednisolone is used to treat acute inflammation following eye surgery or other insults to the eye. It decreases inflammation and corneal neovascularization, suppresses migration of polymorphonuclear leukocytes, and reverses increased capillary permeability.

Dexamethasone ophthalmic (Maridex)

Dexamethasone is used for various allergic and inflammatory diseases. It decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reducing capillary permeability.

Class Summary

Antimicrobial therapy must be comprehensive and cover all likely pathogens in the context of this clinical setting.

Moxifloxacin ophthalmic (Moxeza, Vigamox)

Moxifloxacin is indicated for treating bacterial conjunctivitis. It inhibits topoisomerase II (DNA gyrase) and IV enzymes. DNA gyrase is essential in bacterial DNA replication, transcription, and repair. Topoisomerase IV plays a key role in chromosomal DNA portioning during bacterial cell division.

Ofloxacin ophthalmic (Ocuflox)

Ofloxacin is a pyridine carboxylic acid derivative with broad-spectrum bactericidal effect. It inhibits bacterial growth by inhibiting DNA gyrase. It is indicated for superficial ocular infections of conjunctiva or cornea due to susceptible microorganisms.

Trimethoprim/polymyxin B ophthalmic (Polytrim Ophthalmic Solution)

This combination is used for ocular infection of the cornea or conjunctiva caused by susceptible microorganisms.

Ciprofloxacin ophthalmic (Ciloxan)

Ciprofloxacin has activity against Pseudomonas and Streptococcus species, methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis, and most gram-negative organisms; it has no activity against anaerobes.

Class Summary

Sodium hyaluronate

Hypromellose