On Wednesday, April 29th, 2020, Prof. Farhad Hafezi gave the presentation “High refractive corrections using transPRK” as part of the SCHWIND eye-tech-solutions online seminar “Surface Treatments in 2020”.
I will give you some insights on a project that we have been running as a directed research project with SCHWIND eye-tech-solutions over the past six years. So, the main idea is if you think about what we are doing as refractive surgeons, then many of us perform both cosmetic and therapeutic approaches. And let’s look at this anterior segment OCT image of a corneal scar at a certain depth. It goes down to 160, 170 maybe 180 microns. Is there a reason we wouldn’t address this scar with and surface ablation. Yes, there is, right? It is really, really relatively deep to be addressed by surface ablation. On the other hand, if we look at cosmetic applications, we perform transPRK to stabilize myopia, we performed transPRK case down to 4 diopters, 4 diopters, 4 six diopters. But would you perform a transPRK for high refractive corrections; -12 diopters, let’s say if you end up with a reasonable Kmax, that still allows you for good physiological vision?
No, you probably wouldn’t. And if you look back historically, there is a reason for that. If you look at the initial multicenter trials from the beginning of the 1990s, Theo certainly knows a lot about these, then there was a reason why a PRK for -22 diopters (i.e. very high refractive corrections) was stopped at the time. And the main reason was at a given moment, if you go too much into the depth of the stroma with high refractive corrections, you will inevitably end up with something like that – excessive haze. And so this, of course, is a catastrophe. Excessive haze in a cosmetic case and this haze is the reason why we limit ourselves in many instances to a certain depth. Now looking more into it, we also know that for years now, we all have been using a substance that should interfere with the wound healing process, which is mitomycin C. And none of us really liked to use this substance.
We use it with great caution. We count the seconds and we rinse extensively, and still, you might run into major issues. So the question was, is there maybe a way to perform high refractive corrections with a really deep ablation while controlling the wound healing reaction while controlling the scarring reaction? Now, let’s go back to the very basics. This is an animation that must be almost 20 years old. So what you see here, is, whenever you ablate the surface of the cornea in a myopic correction, you push the focal point towards the retina. And looking more into it, how did this all evolve? Well, it all evolved with certain formulas that had been used (and that are probably still in use today for the central ablation) formulas that describe how the tissue should be ablated. And then on the right-hand side, you see the first block beam lasers that had a number of disadvantages, and these disadvantages have been corrected by introducing flying spot lasers.
The shot profile has been adapted: top hat, Gaussian profile, and so on. All these things share one thing in common. This is mathematical/physical. So more than 20 years ago, surgeons spoke to physicists and engineers and described the problem they had and the physicists and engineers developed solutions. And these solutions are based on mathematics and physics and they should allow you like a sculptor to step by step, get closer to the original that you would like to sculpt, like the figure in the background. Now if you plot this over time let’s say you perform a PRK; left is before the PRK. So what are you doing with the patient before you perform the surface ablation? You see the patient at the center, okay, you make sure that everything is fine so far, but then it very quickly becomes very physical and mathematical, you look at refraction, you look at higher-order aberrations, you look at the depth of your profile.
The only physical consideration that we gave to the engineers for many years was do not heat up my cornea. If you heat it up too much, you will denature the proteins. That’s a fact. And this is why the flying spot lasers have to jump across the cornea in order to avoid heating. But that’s about it. So before the intervention, we think mathematically and physically. Four weeks after the intervention, the patient comes back to you with quite massive haze, what will you do? You look at the slit lamp and say, ooh, I have a lot of haze. I should have suppressed the local immune response. Now let’s give some steroids. All of a sudden you think like a biologist, you think like an MD. So the big question is why don’t we think biologically before the surgery? In other words, we should be trying to find the ablation patterns that do not only respect mathematics and physics, they should also respect the biology of the tissue.
In other words, is there a way to optimize ablation profiles – especially those in high refractive corrections – using biological parameters? And this was the basic idea that brought to SCHWIND back in 2013 and it was an exciting journey. It’s lots of work and lots and lots of ideas. And basically, we ran this study in two phases. The first phase was animal studies. So we performed the deep ablation PRK, I think it was a 6.5 millimeter zone corresponding to roughly, an ablation depth of a 100 microns and so on. It was the equivalent of 10 diopters of a myopic correction in a transPRK approach. And what you looked at, yes, we spoke to Sam Mosquera and asked him: is there a way you can give us different fluences in your ablation profile?
The end result should be exactly the same as we usually have in our ablation profile, but the path from the beginning of the laser ablation to the end, to be a different one with a modified fluence. And in the midst of these experiments, SCHWIND also introduced the Smartsurface module that was developed with Paolo Vinciguerra. So we had yet another factor. So we looked at standard ablation is our control. We looked at low fluence ablation that would basically cost you less than a second per diopter more time but would be more gentle to the tissue. And we looked at the effect of Smartsurface by performing in the first stage, performing this in animals. Then, later on, sacrificing the animals, excising the cornea solid, homogenizing the corneas, extracting the mRNAs, and looking for target genes in the inflammatory pathway that would be differentially regulated.
In other words, do we see more inflammation on the genetic level as opposed to the standard ablation profile? So identifying activated inflammatory genes. Phase one was from 2013 to 2015. Phase two in the rabbits went from 2015 to 2018 and then the third phase, from 2018 into 2019, and to cut a long story short, yes indeed, we found differentially upregulated inflammatory genes that showed major differences between the different profiles. In other words, we found profiles that will give you the same end result out, but on a side note will elicit much less inflammation. So you start with a cornea that is less inflamed, to begin with, which is really, really interesting. So what we found in our laboratory study was a distinct reduction of post-op inflammation. And most interestingly, this was not due to different fluence. It was more the smooth surface that made the main difference.
So Smartsurface had more impact than reducing the overall fluence when performing high reactive corrections. And theoretically, this should mean if you have a Smartsurface module, you should be able to do a deeper ablation with less inflammation. And if you can go deep enough to rival anterior lamellar surgery, then this would be something really nice to have both on the therapeutic end, but also, of course, have on the cosmetic end. So in phase two, we took these results and transitioned from animal to human in a clinical prospective study on at the ELZA Institute in Zurich. And we assessed the post-op haze after transPRK in highly myopic eyes without any mitomycin C. So we took the results that we had from the animals and we went into humans without any further consequence because we were using an ablation profile that had already been freshly introduced clinically.
And what we have seen with the total number of 23 eyes and the six months follow up. We have seen that we completely avoid mitomycin C in stromal ablations between 80 and 140 microns. So with the mean of more than 100 microns, then we looked at the haze reaction, we looked at it clinically with the classical haze grading and we also took the densitometry module off the Pentacam and looked at haze in the anterior and posterior cornea in the center versus the periphery. And the main message was that clinically we have never exceeded a haze more of more than grade one. And the densitometry showed a certain decrease in the more anterior central cornea, a certain statistically significant increase, but still, clinically, this was absolutely manageable. Well, just the usual postop schemes I use fluorometholone. And when my haze gets too strong, I used dexamethasone, and all these cases where very deeps stromal ablations using the normal arsenal of postop medication with no major surprises.
So in conclusion, a transPRK of more than 100 microns on without the use of any mitomycin and in the absence of clinically relevant haze is possible in middle European settings. Now let’s put this into perspective. We have now performed in Switzerland, on Swiss patients, transPRK cases up to minus 12 D in a 6.5 millimeter zone. And that’s more than 140 microns of ablation without mitomycin. Now if I, if I look at our friends in Oman, they start using mitomycin starting at corrections of one diopter of myopic sphere. I started using mitomycin before roughly 60 to 70 microns of stromal ablation. So -5, -6 diopters. And now I’m doubling my, my ablation without using mitomycin. And I think this is also relevant to other parts of the world.
But you should, if you decide on using this new approach, start slowly and just gently push the limits of where you’re comfortable with not using mitomycin. If you had started using mitomycin at minus three in certain areas of the world, you might want to try going up to minus four, four and a half or five without mitomycin, then push it forward. But in our hands and in the middle of Europe setting, we are way beyond minus 10 right now. This work on high refractive corrections has been awarded, the poster prize in both the main ESCRS in 2019 and the winter ESCRS in 2020. This is our current research group at the University of Zurich.