SMILE MOVES TO MAINSTREAM

  [caption id="attachment_6051" align="alignnone" width="750"] SMILE through a minimally invasive 2mm incision. Courtesy of Soosan Jacob[/caption]     Thousands of small incision lenticule extraction (SMILE) procedures have now been performed internationally, enabling surgeons to understand more about the technique’s advantages and limitations. Data has also been accumulating in the scientific literature attesting to the safety and efficacy of SMILE for myopia. As clinicians become more familiar and confident with the technology, SMILE has begun opening new frontiers into hyperopia, presbyopia and keratoconus treatments. The recently published long-term results (Br J Ophthalmol, doi:10.1136/bjophthalmol-2015-306822) for SMILE are very promising, said Jesper Hjortdal MD, PhD, Clinical Professor, Aarhus University Hospital, Denmark, who uses SMILE as his first-choice refractive procedure for suitable myopic patients. “The results showed that the refraction is stable over the long-term, and if anything the best corrected visual acuity improves and higher-order aberrations decrease from three months to three years,” he said. Dr Hjortdal’s indications for SMILE include myopia from -1.0D to -10.0D, although the majority of patients he treats are usually more than -5.0D. “In the lower range, we still find that surface ablation is a good option,” he said. With Zeiss recently expanding the indications for myopic SMILE backed by robust safety and efficacy data, interest in the procedure has gathered significant momentum in the past year or two. JUMP ON THE SMILE TRAIN “It has really taken off in a big way. Wherever I travel now I have the feeling that everyone wants to jump on the SMILE train, or feels that they're going to miss out on something if they don’t offer this treatment,” said Walter Sekundo MD, Chairman of the Department of Ophthalmology at the Philipps-University of Marburg, Germany, and one of the pioneers of intrastromal lenticule extraction. Dr Sekundo said that around 750 surgeons worldwide are now officially registered to perform SMILE procedures, but that the real figure is probably well over 1,000 and growing all the time. While SMILE’s increasing popularity is undoubtedly good news for Zeiss, the fact that the procedure can only be performed using the company’s VisuMax femtosecond laser inevitably restricts its uptake, points out Mike Holzer MD, FEBO, Vice Chairman and Director of Refractive Surgery at the University of Heidelberg, Germany. “I think it is important to emphasise that this procedure can only be performed with a specific laser, and sometimes if you read all of the articles and journals it seems like SMILE is a procedure that is available to everybody. The proviso is that first of all you need to invest in the specific femtosecond laser machine, you still should have an excimer laser available, and at the moment there is no other laser manufacturer offering anything like SMILE,” he said. As a result, the bottom line is that many physicians find it hard to justify the additional outlay on the Zeiss platform when highly predictable and consistent outcomes can already be obtained with standard femto-LASIK treatments. “At the moment, looking at the postoperative healing time and the postoperative outcomes, I think there is not really a big advantage that the patient or doctor can really feel or see. We should also bear in mind that, as more surgeons perform this procedure, so we will see an increase in complications such as incomplete lenticular removal, which can be quite challenging to deal with. On the other hand, a smaller incision is definitely better than a big LASIK flap and we are seeing an increased demand for it in Germany from patients who like the idea of a flap-free procedure. Overall, I think there is a big future for SMILE and we are still on the way to finding ways to optimise this procedure,” asserted Dr Holzer. For Dan Z Reinstein MD, MA(Cantab), FRCSC, DABO, FRCOphth, FEBO, Medical Director of the London Vision Clinic, UK, the process of optimisation is already well under way and the five-year results should not be interpreted as a definitive reflection of the procedure’s capability. “While it is important to document the longer-term outcomes for SMILE as for any procedure, I don’t think that there was any doubt that the long-term outcomes would be any different to LASIK given the similarity between the procedures. Also, these results are for the earliest populations treated, so before all the work had been carried out to optimise the laser energy and spot spacing settings. They were also performed using the 200kHz laser, whereas now we are using the 500kHz version,” he said. Surgical technique and instruments have also greatly improved with time and experience, and understanding of the SMILE nomogram has increased refractive accuracy, particularly for astigmatism, added Dr Reinstein. “With this learning curve we have seen the published results steadily improving, meaning that the results in the five-year studies will not have as good results as the more recent papers,” he said. HYPEROPIA HOPES With safety and efficacy already well established for myopia, investigators have been turning their attention to hyperopia treatments, with mixed results. An initial off-label, investigator-initiated study carried out by Osama Ibrahim MD and colleagues at Alexandria University, Egypt, delivered less impressive outcomes than those for myopia, with limited correction up to +4.5D and some regression. “Hyperopic SMILE is more challenging as the lenticule thickness at the centre is very thin and care needs to be taken not to perforate it. Also, the thick edge causes a trough that stimulates epithelial hyperplasia and hence regression. The company is testing a new software algorithm with a different edge design and a larger transition zone and the results will be released shortly by Dr Sekundo and Dr Reinstein. We also did cases with hyperopic and mixed astigmatism using a large transition zone, and our results were very encouraging in the first pilot group with less regression,” Dr Ibrahim told EuroTimes. The refinements to the optical zone, transition zone, and minimum lenticule thickness certainly appear to have yielded dividends, with early results from Dr Reinstein’s hyperopia study, carried out in conjunction with Kishore Pradhan at the Tilganga Institute of Ophthalmology, Kathmandu, Nepal, deemed sufficiently robust for Dr Reinstein to offer hyperopic SMILE in his London clinic in the near future. The first phase of the study was done for amblyopic eyes in which topographic centration was demonstrated to be similar to a LASIK control group, and achieved optical zone diameter for a 6.3 programmed optical zone was demonstrated to be equal to the achieved zone for 7mm LASIK with the MEL 80. For the subgroup of 31 sighted eyes with corrected distance visual acuity of 20/40 or better, the refractive accuracy and safety at three months were similar to matched LASIK controls, with 65 per cent within ±0.50D, compared to 53 per cent within ±0.50D for the matched LASIK control group. For his part, Dr Sekundo said that the early results of the hyperopia study carried out with Marcus Blum MD were extremely promising and he hoped to present the six-month data for all patients at the XXXIV Congress of the ESCRS in Copenhagen in September. EXPERIMENTAL APPROACHES Intrastromal techniques such as SMILE have also prompted interest in the possibility of using tissue-addition procedures to treat hyperopia, presbyopia and keratoconus. The basic idea is that refractive lenticules might be stored so that reimplantation can be performed at a later date if a patient develops ectasia, for instance, or if their myopia progresses to presbyopia. But reimplanted lenticules might also potentially come from other patients. Following initial work by Pradhan et al, Sri Ganesh MD in Bangalore, India reported the results of a series of nine eyes in which cryopreserved lenticules from patients with myopia were reimplanted into patients with hyperopia. Although there was an undercorrection of the hyperopia in all eyes, the mean undercorrection of 21 per cent was less than the 50 per cent found in the first case report by Pradhan (although this case was for attempted correction of +10D), and the procedure was deemed safe with minimal risk of rejection of the implanted lenticule. For treatment of mild to moderate keratoconus, Dr Ganesh and colleagues refined the surgical technique to punch a doughnut-shaped lenticule from a central 3mm portion of tissue. This lenticule was then implanted into a pocket created in the cornea by femtosecond laser at 100-micron depth, and followed by accelerated crosslinking. Of nine eyes treated in this fashion with a mean follow-up of 12 months, the authors observed a significant improvement in visual acuity with reduction in mean keratometry, asphericity, and total higher order aberrations. Biomechanical stability was also improved postoperatively. For presbyopia, Soosan Jacob MS, FRCS, DNB, in Chennai, India, has recently described a technique in which a lenticule is marked and trephined at its centre to 1mm diameter, and implanted in the cornea under a 120-micron femtosecond cap in the non-dominant eye (S Jacob, EuroTimes, Volume 21, Issue 4, 42-43). The PEARL (PrEsbyopic Allogenic Refractive Lenticule) inlay acts by creating a small central area of hyper-prolateness on the cornea. The extremely small size of the PEARL inlay creates a small hyperprolate area surrounded by normal topography, both of which lie within the pupillary zone. This allows improved depth-of-focus while still preserving good distance vision, unlike larger implants which can degrade quality of vision. The other advantage of PEARL is that the allogenic material of the inlay ensures good biocompatibility and avoids inflammation related to insertion of synthetic material into the cornea. Although such approaches push the boundaries for SMILE, they nevertheless remain niche, experimental techniques that will take a long time to percolate into day-to-day practice, if ever, advises Dr Hjortdal. “While we have not yet corrected hyperopia at our own clinic, we have treated penetrating keratoplasty patients for high astigmatism and ametropia using SMILE with good results. For keratoconus, milder cases may be treated, but the future will show whether SMILE in combination with lenticule inlays may be a viable treatment. As for the presbyopia treatment, in Europe and the USA, this is considered a corneal transplant procedure and the transplanted tissue needs to be checked under regulations applying to normal corneal transplantation with corneal donor tissue,” he said. Quality of vision may also be a potential issue for the tissue-added approach to presbyopia, said Dr Reinstein. “This procedure aims to intentionally create a central island in order to have a central steep zone for near vision. But this will inevitably be associated with a reduction in quality of vision and reduction in safety, as we know from experience with early excimer lasers, central islands cause problems for many patients. Some patients will be extremely happy because they get distance and near vision and are able to adapt to the multifocality, but there may be a sizeable percentage who will be unhappy due to quality of vision issues,” he said. While only time will tell whether these newer techniques ever make the leap into daily clinical practice, SMILE’s place as a viable and safe alternative to LASIK for treating a broad range of refractive errors seems assured. “We are definitely not at the end of SMILE’s development, but are probably somewhere in the middle. We can now produce very good, reproducible results and have brought it to the stage where every surgeon can get good outcomes. So it is a technique that is not just for the select few. A lot of the demand is also being driven by patients, who like the sound of a flap-free, painless procedure with a more stable cornea. LASIK is a wonderful procedure and will be around for a long time to come. However, having SMILE gives us even more treatment options and that has to be a good thing for our patients,” Dr Sekundo concluded. Jesper Hjortdal: jesper.hjortdal@dadlnet.dk Walter Sekundo: sekundo@med.uni-marburg.de Mike Holzer: mike.holzer@med.uni-heidelberg.de Dan Reinstein: dzr@londonvisionclinic.com Osama Ibrahim: ibrosama@gmail.com Soosan Jacob: dr_soosanj@hotmail.com