THE INTRASTROMAL REVOLUTION

The excimer laser has been the reliable workhorse of corneal refractive surgery practices for the past two decades, providing excellent visual outcomes and a high degree of safety for millions of satisfied patients worldwide.

Yet while LASIK remains the undoubted gold standard for refractive correction, some surgeons are already taking the first steps into a post-LASIK era by embracing intrastromal femtosecond laser treatments for myopia, presbyopia and astigmatism.

Techniques such as FLEx (femtosecond lenticule extraction) and SMILE (small incision lenticule extraction), Intracor presbyopia correction, and intrastromal astigmatic keratotomy (AK) have already won over a small but growing band of surgeons who cite predictable refractive outcomes, fast recovery and respect for corneal biomechanical integrity as among the main reasons for their conversion.

ReLEx, FLEx and SMILE

Walter Sekundo MD, chairman of the Department of Ophthalmology at the Philipps University of Marburg, Germany, vividly remembers the American Academy of Ophthalmology meeting in Las Vegas in 2006 where he presented for the first time his vision of a refractive surgery procedure that could be performed intrastromally using a femtosecond laser and without ablating the cornea.

“People were laughing and couldn’t believe that this idea of an intrastromal treatment was ever going to work. I told the audience that it might take a decade but that this procedure was eventually going to replace laser surgery. No one took it seriously. Eight years later, over 300 surgeons worldwide are now using this approach and nobody is laughing anymore. It is simply a better procedure than LASIK, even though there are still a few drawbacks and weak points that need to be addressed,” he told EuroTimes.

Taking advantage of the properties of the VisuMax femtosecond laser (Carl Zeiss Meditec AG), Dr Sekundo’s vision was to perform refractive corrections by carving out an intrastromal lenticule that could be removed in one piece manually without having to resort to excimer laser ablation.

Known initially as ReLEx, Dr Sekundo published the first results in 2008 of the FLEx procedure in which a lenticule was manually removed after lifting a flap. Evolving from that early success, a new procedure called SMILE was developed in which the lenticule interface could be separated through one or two small incisions, thereby eliminating the need for a flap.

This ability to dispense with the corneal flap and all its associated complications is one of SMILE’s biggest selling points, said Dr Sekundo.

“The idea of not having a flap and being able to maintain a stronger cornea with an intrastromal approach is very appealing to patients. In my practice, I still perform femtosecond LASIK procedures but they are less than 10 per cent of the total volume. For patients with low myopia, it is always SMILE despite the fact that femtosecond LASIK gives a slightly faster visual recovery. But the patients tell me that they are prepared to have marginally slower visual recovery in order to have a flap-free procedure,” he said.

Not surprisingly, patients are not the only ones who are happy to see the back of the LASIK flap.

“The dream of over a decade ago was to eliminate the microkeratome and the LASIK flap – in effect to have the safety of a PRK procedure in terms of no flap-related complications, while achieving the visual recovery of LASIK,” said Steve Schallhorn MD, Professor of Ophthalmology at UCSF, and Chief Medical Director, Optical Express.

“SMILE has no flap and the visual recovery profile is much closer to LASIK, so that is a huge advantage from my perspective,” he said.

The biomechanical advantages of SMILE are also part of the procedure’s appeal, added Dr Schallhorn. “Because the procedure is intrastromal it respects the tensile strength of the cornea and reduces the risk of ectasia. This is not a smoke-and-mirrors procedure with questionable physiological advantages – SMILE offers unique, solid science-based advantages, which is why so many surgeons are interested in its potential,” he said.

By focusing the treatment exclusively on the stroma, SMILE preserves Bowman’s layer, which is inherently good for biomechanical stability, noted Tobias H Neuhann MD, Medical Director at AaM Augenklinik in Munich, Germany.

“We know that Bowman’s membrane is tough and keeps the cornea from swelling forward. Treating purely corneal stroma means preserving corneal stability. Another positive effect of intrastromal treatments is the very low grade of infections compared to surface treatments,” he said.

The ideal candidates for SMILE are patients with moderate to high myopia in the range of -5.0D to -10.0D, according to Jesper Hjortdal MD, PhD, Aarhus University Hospital, Denmark, who said it has now replaced LASIK as his treatment of choice for suitable patients.

“Compared with LASIK, we have found that a SMILE procedure does not induce spherical aberrations in the cornea. This should have implications for the overall quality of vision and especially night vision, but proper prospective randomised or contralateral studies are needed to further clarify this,” he said.

Nevertheless, evidence pertaining to the feasibility of SMILE is accumulating in the scientific literature, points out Dan Reinstein MD, FRCOphth, medical director of the London Vision Clinic.

“The feasibility of the procedure has been proved by studies on the surface quality of the lenticules, wound healing and inflammation, and the accuracy of the lenticule thickness parameters have been verified using very high-frequency digital ultrasound and optical coherence tomography (OCT),” he said.

Safety has also been demonstrated to be similar to LASIK, said Dr Reinstein. “Our recent publication has shown that there are no concerns in treating patients with SMILE for low myopia. In terms of safety, SMILE brings two advantages over LASIK, relevant to the most common complication, dry eye, and the most serious complication, ectasia,” he added.

On the debit side, SMILE demands a financial outlay, which may be dissuasive for smaller refractive practices. Furthermore, the fact that the procedure is currently limited to myopic treatments is another potential brake on its adoption. Dr Sekundo is optimistic, however, that this will be rectified in the near future.

“We have been working on this and have shown that the hyperopia treatment works as well, so it will probably be available in the next year or two. We also need better control of cyclotorsion – not necessarily an eye tracker – but an electronic device within the system that monitors the eye after suction has been applied, and allows for an adjustment of the treatment zone if there is a misalignment of the axis. Once this has been achieved, then the astigmatic results will also improve,” he said.

Dr Sekundo added that he expects FDA approval for the FLEx and SMILE procedures probably by the end of 2015.

One other possible concern with SMILE is the difficulty of enhancement procedures, as unlike LASIK there is no flap that can be lifted to facilitate access. If retreatment is needed, Dr Hjortdal advises surgeons not to attempt a repeat SMILE procedure.

“The options are to open the cap and convert the cap into a LASIK-like flap, and then use the excimer laser to ablate. Or one can also perform a surface ablation procedure. We prefer to perform the procedure transepithelially and we always use Mitomycin 0.02 per cent for 20 seconds after the procedure,” he said.

Intracor innovation

Intrastromal approaches have also been tried with some success for presbyopia. The Intracor treatment uses the Technolas femtosecond laser (Bausch & Lomb) to create intrastromal concentric rings of different depths in the cornea of the patient’s non-dominant eye. The goal of the rings is to create a slight steepening of the central cornea while sparing the epithelium, Bowman’s membrane and Descemet’s membrane. The procedure works well in emmetropic and mild hyperop presbyopes, said Dr Neuhann.

In a clinical study carried out at four German clinical centres, more than 70 per cent of patients could read J3 or better without glasses while the other 25 per cent could read with weaker reading glasses, said Dr Neuhann, who added that a new study using the latest-generation Victus femtosecond laser will be carried out for hyperopic and astigmatic eyes.

While Intracor works well in a majority of patients, there is a sizeable minority (around five per cent to 15 per cent) that do not respond so well to the treatment, and it is this unpredictability which has held back the procedure’s adoption, according to Mike Holzer MD, University of Heidelberg, Germany.

“Sometimes the effect is much higher than anticipated, and then there are other patients where the effect is minimal or non-existent,” said Dr Holzer. “The predictability certainly could be better, especially bearing in mind that we have other presbyopia-correcting procedures such as multifocal IOLs available to us that offer better predictability,” he said.

For Dr Holzer, the likely cause of this erratic predictability stems from an inability to accurately determine individual corneal stability and how each patient
will react to the intrastromal incisions.
“I think once we have better preoperative diagnostics we can much better predict the outcome of such a procedure. Enhancements also pose a problem, because you can really only do these intrastromal incisions just once in my opinion, although I know some surgeons have retreated intrastromally using the laser,” he said.

Dr Holzer said that Intracor works best in patients that are slightly hyperopic. “We have performed this in about 350 patients now with a high degree of success. When the treatment works as expected, there is minimal or no regression years after the procedure which is an advantage over LASIK. Patients also like it because we are not opening the cornea, there is no risk of infection, the healing is very quick and the patient can return to normal activities very quickly afterwards,” he said.

For Dr Neuhann, the ideal Intracor candidate is a presbyopic patient around 50 years of age with objective refraction of +1.0 to +1.75D, less than 0.75D of astigmatism, realistic expectations, no corneal scars or other corneal or ocular pathologies.

Dr Neuhann said that careful study of the Intracor underperformers has enabled him to elaborate a strategy to help such patients. “The key after a perfect treatment with no shape change is to understand individual biomechanical properties as well as the precise effect of the laser. In our group in Munich we could demonstrate that intrastromal bridges in the femtosecond laser channels could be broken after the treatment with careful manual deforming of the cornea with fingertip massage, resulting in a positive and wanted shape change,” he said.

Astigmatic keratotomy

Intrastromal astigmatic keratotomy using femtosecond lasers such as the IntraLase (AMO/Visx’s) or LenSx (Alcon Inc) also gives surgeons a less invasive option for patients with astigmatism.

There are several advantages to using the femtosecond laser for intrastromal astigmatic keratotomy with greater precision in incision length, depth and angle, said Dr Schallhorn. Moreover, because the incisions are made without breaking the epithelium or Bowman’s layer, there is less risk of infection and wound problems.

“The level of precision is unsurpassed with the femto AK and that results in improvement in the predictability of the surgery. Not breaking the epithelium minimises the chance of an infection and the discomfort that the patient experiences,” he said.

The singular disadvantage is the fact that the femtosecond laser technology is expensive, said Dr Schallhorn, who said it works best for regular corneal astigmatism below +2.0D.

“I think this technology will really come into its own as we move more towards femtosecond cataract procedures. If we are using the laser anyway for IOL procedures then it really is a no-brainer to use that to correct the patient’s 1.0D of corneal astigmatism as well. With increased use will come better outcomes as well,” he added.

Steve Schallhorn: scschallhorn@yahoo.com

Jesper Hjortdal: jesper.hjortdal@dadlnet.dk

Dan Reinstein: dzr@londonvisionclinic.com

Mike Holzer:
mike.holzer@med.uni-heidelberg.de

Tobias Neuhann: dr.neuhann@email.de

Walter Sekundo:
sekundo@med.uni-marburg.de