Are Intrastromal Treatments the Future of Refractive Surgery?

The trend for all surgical procedures has been to evolve toward a minimally invasive technique, such as the robotically assisted keyhole techniques that have revolutionized many types of surgery in terms of safety, postoperative recovery, and patient perception.

Unsurprisingly, the same trend has been seen in refractive surgery—although the emphasis on safety is even higher here than in other fields, as refractive surgery is performed in patients who can already see. “It’s my eyes,” is a phrase that we all hear, every day, in the clinic.

This is why early refractive surgery techniques such as keratomileusis1 and RK2 did not gain widespread use. Even refractive lens exchange could be included; this approach was rarely used in patients with a clear lens because the risks associated with intraocular surgery were deemed too high for such patients.

Refractive surgery eventually gained acceptance when the excimer laser was introduced to perform PRK, an approach that was seen as a less invasive and more accurate method than RK. LASIK, with the addition of the mechanical microkeratome, represented the next step in minimizing the invasiveness of the procedure by eliminating the epithelial wound of PRK. Replacing the microkeratome blade with a femtosecond laser continued the evolution, and the bladeless tagline was quickly taken up as a marketing differentiator to attract patients.

However, refractive surgery did not join the ranks of truly minimally invasive keyhole procedures until the introduction of small incision lenticule extraction (SMILE), which avoids the need for the corneal flap.

CONSIDER THESE PERSPECTIVES

Are intrastromal treatments the future of refractive surgery? Let us look at this question first from the perspective of our patients and then from our own perspective as surgeons.

The patient perspective. From a patient’s perspective, the answer to the question is a resounding “yes.” Patients do not need a lengthy explanation about the pros and cons of LASIK versus SMILE, as they tend to be immediately attracted to the flapless nature of the procedure. All that is needed is to say that both treatments remove a lens of tissue from inside the cornea, but one does it by lifting a flap and the other through a keyhole incision.

The surgeon perspective. While there is an initial attraction to the no-flap approach, surgeons also want scientific justification for preferring SMILE to LASIK. Since the introduction of SMILE and the results of the first prospective trials,3-5 which demonstrated safety and efficacy slightly lagging behind LASIK, SMILE has gained popularity. There are now many publications demonstrating that the safety and refractive outcomes of SMILE are similar to those of LASIK.6-17 More than 250,000 SMILE procedures have been performed worldwide, and more than 700 surgeons regularly perform it as their procedure of choice for myopia. The feasibility of the procedure has been shown by studies on the surface quality of the lenticules,18,19 wound healing and inflammation,20-22 and lack of impact on the corneal endothelium.23 The accuracy of lenticule thickness parameters has been verified using very high-frequency digital ultrasound24,25 and OCT.26-29

The safety of SMILE has also been demonstrated to be similar to that of LASIK,30 and a recent publication from my center removes doubt that SMILE does equally well as LASIK for treatment of low myopia.15 There was a question mark regarding the correction of astigmatism, as early studies reported undercorrection,31-33 but this has been resolved by the use of a nomogram for cylindrical correction.34

TWO ADVANTAGES

In terms of safety, SMILE holds two major advantages over LASIK: faster dry eye recovery and an extended range of treatment due to better spherical aberration control as a result of better biomechanics. Both of these advantages stem from the nature of the opening through which the procedure is performed—a minimally invasive pocket incision—as this results in maximal retention of anterior corneal innervation and structural integrity.

Advantage No. 1: Fewer dry eye symptoms. It was expected that there would be less postoperative dry eye after SMILE: While the trunk nerves that ascend into the epithelial layer within the diameter of the cap are still severed in SMILE, those that ascend outside the cap diameter or that are anterior to the cap interface are spared. A number of studies have demonstrated lower reduction and faster recovery of corneal sensitivity after SMILE than LASIK,35-44 with recovery to baseline in 3 to 6 months after SMILE compared with 6 to 12 months after LASIK. Some studies have also used confocal microscopy to demonstrate a lower decrease in subbasal nerve fiber density after SMILE than LASIK.38,42,44,45

Advantage No. 2: An extended range of treatment and spherical aberration control. The other major advantage of SMILE is its biomechanical profile, as the anterior stroma above the lenticule remains uncut (except in the location of the small incision), unlike in LASIK in which most anterior stromal lamellae are severed by the creation of the flap. Surgeons are accustomed to calculating the residual stromal thickness in LASIK as the amount of stromal tissue left under the flap, and, therefore, the first instinct is to apply this rule to SMILE. However, the actual residual stromal thickness in SMILE should be calculated as the total uncut stroma (ie, the stroma both above and below the lenticule).

It has been shown that the vertical sidecut of the flap is responsible for almost all of the change in strain due to LASIK flap creation.46 It has also been shown that the anterior corneal stroma is the strongest part of the stroma,47-50 due to the greater interconnectivity of collagen fibers in the anterior stroma compared with the posterior stroma, where the collagen fibers lie in parallel with each other.51 Therefore, SMILE must leave the cornea with greater biomechanical strength than LASIK for the same amount of vision-correcting tissue removal.52 Differences between SMILE and LASIK have also been demonstrated using finite element modeling.53

The first benefit of this difference is that it opens the possibility of safely treating higher degrees of myopia and thinner corneas. This is, of course, once keratoconus has been excluded, as tissue-subtraction procedures are contraindicated in eyes with asymmetric corneal biomechanics with a focal weak spot at the cone.54 The two case reports of ectasia after SMILE have been in eyes with keratoconus on topography.55,56

The second benefit of the corneal biomechanical difference is that there is less induction of spherical aberration after SMILE compared with LASIK. In a recent study, colleagues and I found that SMILE, although minimally aspheric, produced similar spherical aberration induction to the highly aspherically optimized Presbyond Laser Blended Vision profile.57 However, as the ablation depth was less for SMILE, the optical zone could be increased, meaning that less spherical aberration was induced for equivalent tissue removal, thus improving the optical quality for the patient. Our results were similar to other published studies: Three studies have shown that less aberration is induced by SMILE than LASIK,11,12,58 and two studies showed that induction of aberrations was similar.10,59

The Three Phases of SMILE

By Mahipal Sachdev, MD

Phase 1: Initial docking with precise centration. During this phase, proper head position is achieved by tilting the patient’s head medially to avoid nasal contact with the cone of the contact glass interface. Precise centration should be verified before the initiation of suction.

Phase 2: Femtosecond laser delivery. Femtosecond laser pulses are fired in a spiral pattern with a pulse energy of 120 to 170 nJ and a repetition rate of 500 kHz.

Phase 3: Tissue dissection and lenticule removal. The tissue disruption planes created by the laser include the posterior lenticule surface, vertical edge cut, anterior lenticule surface, and corneal sidecut (Figures 1 and 2).

Figure 1. Cross-section of the cleavage planes created during SMILE: (1) posterior lenticule surface, (2) vertical edge cut, (3) anterior lenticule surface, and (4) corneal sidecut.

Figure 2. Surgical steps of the SMILE procedure, including laser-assisted and manual steps. Laser-assisted: posterior tissue disruption plane, or lenticule cut (A); anterior tissue disruption plane, or flap cut (B); superior flap and sidecut incision (C). Manual steps: delineation of planes (D), dissection of planes (E), and lenticule removal (F).

ADDRESSING CONCERNS

The main disadvantage of SMILE currently is the slightly slower visual recovery experienced by some patients compared with LASIK; the day 1 postoperative visual acuity is, on average, slightly lower than on day 1 after LASIK.6 Significant improvements have been made in this area by using different energy and spot-spacing settings,60 although further changes to energy settings have not resulted in further improvements.61 The difference is now approximately 1 or 2 lines of UCVA on postoperative day 1, equalizing with LASIK by 2 to 3 weeks postoperatively.

One group has described microdistortions in the Bowman layer after SMILE identified on OCT but with no clinically significant corneal striae at the slit-lamp.62,63 These microdistortions did not have an impact on visual acuity or quality and were found to decrease over time. We have studied these central microdistortions and found that they can be minimized by appropriate centrifugal cap distension immediately at the end of the procedure to distribute redundant cap to the periphery.

Some practitioners have expressed a concern with the absence of eye tracking in the SMILE procedure. However, studies have shown this concern to be misplaced: The centration of SMILE is straightforward, and the patient essentially autocentrates the lenticule to the visual axis. Once suction has been applied, there is no need for eye tracking, as the eye is locked in place. The centration of SMILE has been shown to be similar to that achieved with LASIK using a modern eye tracker.64,65

SMILE FOR HYPEROPIA

Progress is also being made on extending the SMILE technique to treatment of hyperopia. Prospective studies are currently using the ReLEx femtosecond lenticule extraction66 and SMILE67 procedures.

Using a 6.3-mm optical zone and a 2-mm transition zone in a population of 36 eyes, our group has found that the achieved optical zone on topography was actually larger than that for LASIK using the MEL 80 (Carl Zeiss Meditec) with a 7-mm optical zone and that centration was not different from that with LASIK.67 This difference might be due to the elimination in SMILE of two types of errors: fluence projection68 (given that the majority of ablation is performed peripherally, these errors are increased for hyperopic LASIK compared with myopic LASIK) and truncation (ie, part of the excimer laser ablation might be applied outside the flap diameter, leading to truncation).

Analysis of a larger cohort of sighted eyes will allow investigation of refractive stability and visual outcomes in hyperopic SMILE. However, the improved optical zone observed suggests that refractive stability will be comparable to and possibly better than LASIK.

OTHER INTRASTROMAL APPLICATIONS

The ability to surgically extract an intact refractive lenticule of stromal tissue using the SMILE procedure has opened the possibility of a number of further applications. It has been demonstrated that refractive lenticules can be cryopreserved successfully for 1 month in rabbits,69,70 and as long as 5 to 6 months in humans.71 It has been suggested that these lenticules could be reimplanted as a method for restoring tissue in ectatic corneas or provide an opportunity for reversing the myopic correction in a patient progressing to presbyopia.69,70 Successful reimplantation has thus far been demonstrated in rabbits.70

There is also the potential for implanting an allogenic lenticule obtained from a myopic donor patient into a hyperopic patient to correct hyperopia, as originally proposed by Jose I. Barraquer, MD, in 1980.72 The first such endokeratophakia procedure was performed in 2012,73 and larger series have since been reported.71,74 The feasibility of the procedure has been demonstrated, as corneal clarity has been maintained; however, unintended posterior surface changes have resulted in undercorrection of the effect in attempted very high corrections.

Allogenic lenticules have also been used in patients with advanced keratoconus in whom the cornea was too thin for CXL.75 In this procedure, termed tailored stromal expansion, a myopic SMILE lenticule is placed onto the stroma after epithelial debridement so that the thickest part of the lenticule lies over the thinnest part of the stroma, and the CXL procedure is carried out.

Another area where intrastromal laser treatment is being used is in the creation of astigmatic keratotomy (AK) incisions.76 Use of the femtosecond laser enables the dimensions of the AK incision to be precisely controlled, and it introduces the potential for creating different incision shapes (Editor’s Note: See The Art and Science of Titrating Incisions).

Most important, the incision can be performed either completely within the stroma or to include the Bowman layer, but without perforating the epithelium. As with all minimally invasive procedures, the main benefit is to greatly minimize risk, particularly in this case, as there is no wound whatsoever.

CONCLUSION

The development of SMILE, a flapless intrastromal keyhole keratomileusis procedure, has introduced a minimally invasive method for corneal refractive surgery. The visual and refractive outcomes of the procedure have been shown to be similar to those of LASIK, and there is increasing evidence for benefits of SMILE over LASIK because the anterior stroma is left intact. This leads to faster resolution of dry eye symptoms, faster recovery of corneal innervation, better spherical aberration control, and the potential for extending the treatable range of refractive error. Femtosecond lasers have also enabled new intrastromal procedures to be developed, including lenticule implantation, arcuate incision creation, and intrastromal implantation of corneal inlays (Editor’s Note: See Pocket or Flap Delivery of Corneal Inlays: Does It Really Matter?).n

Dan Z. Reinstein, MD, MA(Cantab), FRCSC, DABO, FRCOphth, FEBO
• Medical Director, London Vision Clinic, London
• Adjunct Professor of Ophthalmology, Columbia University Medical Center, New York
• Associate Professor, Centre Hospitalier National d’Ophtalmologie, Paris
• Visiting Professor, School of Biomedical Sciences, University of Ulster, Coleraine, United Kingdom
• dzr@londonvisionclinic.com
• Financial disclosure: Consultant (Carl Zeiss Meditec); Proprietary interest (Artemis technology; ArcScan); author of patents related to VHF digital ultrasound administered by the Cornell Center for Technology Enterprise and Commercialization, Ithaca, New York