Last September, the FDA approved the Zeiss procedure called SMILE, or SMall Incision Lenti cule Extraction, a vision-correcting surgery for myopia.
Ophthalmology Management interviewed Jon Dishler, MD, the U.S. medical monitor, to learn about the procedure. Subsequent articles will discuss how to market this new refractive surgery, as well as case studies.
Ophthalmology Management: SMILE was approved internationally in 2011, but not until last fall in the United States. What did you or Zeiss in general learn from the SMILE procedures performed internationally?
Jon Dishler, MD: We were required to have international data to support opening the study in the United States. So we had to collect data in a systematic way from two sites over a period of time. That data had to demonstrate a reasonable level of safety and effectiveness, and make the FDA comfortable with opening that clinical trial here.
OM: Did your experience overseas with SMILE influence training or protocols here?
Dr. Dishler: We looked at what doctors were doing [in the international trial] and there was a lot of variety. We crystallized that into one protocol that would allow us to collect the data in a way that would be scientifically analyzed. We looked at technical details about the laser spot and track, distance, the thickness of the cap, the size of the lenticule, the range of treatments.
We had to look at what was being done and come to a consensus. Then those data were collected. The results were good, so that led to Zeiss getting the green light to start the clinical trial here in the United States.
As part of the submission package we collected the removed small-tissue lenses from a clinical site in Denmark and sent them to a Bascom Palmer Instutute researcher. Bascom helped us to demonstrate the cut quality and architecture of this tissue. These data helped verify the precision of the process. So along with clinical data from that site all was submitted to FDA in support of the application.
OM: The FDA indication is for -1D to -8D?
Dr. Dishler: It is approved for -1D to -8D, but with a [so-called] pop-up warning, a flag warning on the screen, saying basically that there hasn’t been enough data to fully analyze the safety and effectiveness, but that actually, doctors in the U.S. can treat up to -10D. So, effectively, the treatment range is from -1D to -10D.
You had to have at least 20 eyes in each diopter bin. Although there were a lot in those two higher bins, -9 and -10, there weren’t quite 20. SMILE was very good in that range, which is why the FDA approved it.
OM: Given how popular LASIK has been, it’s got a good safety profile, and so on, why should U.S. surgeons learn another refractive procedure and how to market it?
Dr. Dishler: There are a few reasons. Although LASIK has been around for more than 20 years and is a household word, it still has certain limitations. The biggest is that it requires making a flap in the cornea, which is cutting off the front of the cornea to a certain thickness, in a circle that’s about 80%, 90% of the diameter of a flap and it’s just attached by a little hinge. When you do that you’re weakening the eye somewhat, you’re cutting some corneal nerves, and patients have to worry they might rub their eyes and move their flaps; wrinkles might develop in the flap. It probably makes people more likely to have dry eye.
So although LASIK is a good procedure, it’s certainly not a perfect procedure — and maybe nothing really is a perfect procedure.
With SMILE, one of the obvious standout benefits is that it’s a small incision, and less invasive method of correcting vision.
OM: Is there any patient for whom you maybe would not recommend SMILE, but LASIK or PRK instead?
Dr. Dishler: I think this procedure’s strongest suit is in the high diopter range, because SMILE requires no nomogram adjustment, as is many times required in LASIK. Because there are no hydration issues, or variability that occurs in long treatments during LASIK, the SMILE procedure is inherently more accurate in higher corrections than LASIK or PRK. In SMILE, an accurate pre-op refraction is likely to give an excellent result throughout the treatment range.
I don’t know exactly the reason for this, but we found very little regression in effect. In LASIK, sometimes you treat someone who’s an -8D or –9D, and the result might be great a month after surgery, but when the patient comes back six months or a year later, sometimes the eye will have regressed and the patient’s vision will go to being perhaps -1D or something like that.
This phenomenon wasn’t really examined, but in the study where we did SMILE in one eye and LASIK on the other, there were patients who at one year postop were still very close to perfect correction in their SMILE eye but had regressed slightly in their LASIK eye.
OM: Dr. John Kanellopoulos* [clinical professor of ophthalmology, New York University Medical School, New York; medical director, LaserVision Clinical and Research Institute, Athens, Greece, and president of the International Society of Refractive Surgery] has said SMILE’s learning curve is more surgeon-dependent.
Number of procedures: 750,000
Number of clinics: 600; countries: 62; surgeons: 1,000
In one U.S. study involving 360 people who ranged from low to very high myopia, each person had LASIK or PRK performed in one eye and SMILE in the other. No astigmatism was treated. 74% saw better after SMILE without glasses than with glasses before surgery; vision was uncorrected.
At one year, about 95% had 20/25 vision. Stability was achieved within six months and confirmed within nine. Low incidences of halos and glare were reported. As for patient satisfaction, at month six 93% said they were very satisfied with their vision.
Source: Zeiss media event held during ASCRS conference, with Vance Thompson, MD, a SMILE clinical trial investigator and director, Refractive Surgery, Vance Thompson Vision, Sioux Falls, SD, May 6, 2017.
Dr. Dishler: This is a real surgery and it does take some degree of surgical skill, more so I would say than LASIK does. However, I wouldn’t say it’s extremely difficult. Experienced corneal refractive surgeons or cataract surgeons, after they’ve done perhaps half a dozen to one dozen of these, start to feel comfortable with the process. The first few take some significant concentration.
The reason that it’s a little difficult is that there are two parts to the procedure. The first part uses the VisuMax (Zeiss) femtosecond laser to cut the lenticule, and that part isn’t really much more difficult, if at all more difficult, than making a flap. It takes a few seconds longer.
In the second part, you remove the lenticule through the small incision. You have to follow certain steps to separate the lenticule and then remove it. But virtually everyone who has taken this on has learned to do this procedure without much problem.
Teaching the SMILE technique does require a little more hand-holding at first. I think the company is spending two or three surgery days at each site with the surgeon to be sure that they don’t run into problems.
You have to be able to look through a microscope and somewhat by sight and somewhat by feel identify the two different planes of tissue you dissect.
First, the surgeon dissects the more superficial plane, then the deeper plane and finally the internal side cut before removing the lenticule with a forceps. The removed lenticule can be placed on the corneal surface to be certain it is intact and completely removed.
After you get the feel for how to find and identify those planes, it becomes relatively routine.
Initially physicians are most concerned about removing the lenticule, but after some experience, they are more concerned about patient selection. That’s because while the laser is cutting the lenticule in that first step, there are certain critical phases for about 15 seconds where if the patient moves violently, or squeezes an eye, or does something that makes the suction come off and the process stop, you can’t go back and just restart it the way you could if you were making a LASIK flap.
So, patients who are extremely nervous, or have extremely strong blink reflexes, or who are uncooperative — which is a small percentage — those patients are not great candidates for this refractive procedure.
But as for everybody else, the patients in our study who had SMILE in one eye and LASIK in their other eye, almost all said they thought the SMILE procedure was easier, the recovery was easier. All the patients I treated said they felt virtually no pain or discomfort postoperatively.
OM: About how long does the procedure take?
Dr. Dishler: The actual cutting of the lenticule takes about 38 seconds and then the removal of the lenticule usually takes maybe two minutes, something like that.
The overall procedure time is similar to that of LASIK.
OM: I understand also there’s an ongoing clinical trial for myopic astigmatism.
Dr. Dishler: Yes. I’m also part of that trial. There were more than 300 eyes at five clinical sites. We’re waiting now for the last follow-up exams. Patients have to be followed for a year, so all the exams have been done except for a few to be completed over the next couple of months.
After that, it will be a matter of analyzing and submitting the data to FDA. Then the FDA has six months to either approve the application or ask additional questions. So we’re hopeful that will be approved about one year from now.
Five-year data show a stable SMILE
Five-year results for 56 out of the first 91 eyes treated with SMall Incision Lenticule Extraction (in 2008/2009) for myopia and myopic astigmatism showed no significant change from the six-month follow-up data, according to researchers in Germany.1 Spherical equivalent was -0.375 D (close to emmetropia). Thirty-two of the 56 eyes had gained 1–2 Snellen lines, and there was no loss of two or more lines over the 5-year period. Regression in the long term was 0.48D.
The investigators examined those of the original treatment group who volunteered for re-examination. They documented uncorrected and corrected distance visual acuity; objective and manifest refractions; and evaluation of the interface and corneal surface by slit lamp examination.
Researchers also documented late side effects such as corneal ectasia, corneal scars and persistent dry eye symptoms.
Their conclusion: “This first long-term study demonstrates SMILE to be an effective, stable and safe procedure for treatment of myopia and myopic astigmatism.”
- Blum M, Täubig K, Gruhn C, Sekundo W, Kunert KS. Five-year results of Small Incision Lenticule Extraction (ReLEx SMILE). BJO. 2016.100;9:1192. http://bjo.bmj.com/content/100/9/1192 .
OM: And what about hyperopes? Does Zeiss have any plans right now for an FDA clinical trial for that group?
Dr. Dishler: There’s been some limited work on hyperopes internationally and the initial results have been good. So there is a planned international trial on hyperopia that should be under way in the not-too-distant future.
After this trial is completed and the results are analyzed, Zeiss will have to decide whether to pursue a clinical trial for hyperopia, mixed astigmatism, or both here in the United States. OM