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Preroll: The University of Florida College of Medicine is accredited by the Accreditation Council for Continuing Medical Education, ACCME, to provide continuing medical education for physicians. The University of Florida College of Medicine designates this enduring material for a maximum of 0.25 AMA PRA Category 1 credit. Physicians should claim only the credit commensurate with the extent of their participation in this activity.

Melanie Cole (Host): Welcome to UF Health MedEd Cast with UF Health Shands Hospital. I'm Melanie Cole. And today, we're discussing corneal transplant surgery for improved vision. Joining me is Dr. Sonal Tuli. She's a professor and the Chair of Ophthalmology for the University of Florida College of Medicine.

Dr. Tuli, it's a pleasure to have you with us today. So I'd like you to start by giving us a little bit of a history lesson here. How long have corneal transplants been around and how commonly are they done now?

Dr Sonal Tuli: Thank you for having me here today, Melanie. Corneal transplantation has actually got a fascinating history. And corneas, I don't know if you know this, were actually the first solid human tissue to be transplanted nearly 120 years ago for the first time. Corneas are also the most frequently transplanted solid organ in the United States, in fact, the entire world. So nearly 200,000 corneal transplants are performed globally every year. And over 50,000 of those are done in the US alone. But unfortunately, because corneal problems are one of the leading causes of blindness in the world. There are still about 13 million people worldwide who are blind awaiting corneal transplant.

Melanie Cole (Host): That's fascinating. I am sure that myself and other providers did not know the history of corneal transplants. That's so interesting. Tell us some of the major differences between corneal transplants and other organ transplants as far as outcomes are concerned.

Dr Sonal Tuli: So corneas are unique in the sense that, unlike other solid organs, they don't have a blood supply and they get all their nutrition from the aqueous fluid in the eye and the tears on the surface of the eye, which means there's a significantly lower risk of rejection of corneal transplants compared to other organs, since they're usually not recognized as foreign by the body's immune system.

It also means that corneal transplants don't have to be matched unlike other transplants, other kidney or heart transplants, before implantation. So patients can actually receive transplants from virtually any donor. You don't have to match that or wait for a donor. And additionally, even in high-risk cases where there's vascularization of the cornea, there are blood vessels in the cornea due to some pathology, we can prevent rejection just by using topical steroids or immunomodulatory eye drops and don't need systemic immunosuppression. So it's much safer for patients in the long run because they don't have to take medications orally or IV to prevent rejections. At the University of Florida, we have an over 95% success rate of corneal transplants.

So one of the things that makes corneas different is that they're viable for two weeks in storage. What that means is that corneal transplant surgeries can be planned well in advance and thorough testing can be performed to rule out infectious diseases, such as hepatitis or HIV. And in fact, another cool bit of information is that one of the first storage media was actually invented at the University of Florida called the MK Media. And that is one of the reasons that corneal transplantation became widely available to people.

Melanie Cole (Host): What an interesting episode we're doing here today. So please identify for us conditions that would benefit from or result in cornea transplant.

Dr Sonal Tuli: So we broadly divide the indications for corneal transplants into three major categories. So there's some overlap there. So the most common is optical, so where the transplant is done to create an optically clear cornea to improve vision. This can happen in cases where you have corneal scars from trauma or corneal infections that can lead to scarring. It can also be done to treat some of the inherited corneal conditions and these are pretty common, such as Fuchs dystrophy where you have these guttae on the cornea that acts like frosting on the cornea and they can scatter light or decrease vision or other conditions like keratoconus where the cornea, because it's irregularly protruded, can cause irregular astigmatism and poor vision that's not correctable with glasses or contact lenses. And this indication has decreased recently due to the advent of corneal cross-linking that can stabilize these corneas. But in advanced cases, you do have to do transplants.

The other very common indication for transplants is what's called therapeutics where the procedure is done to treat conditions that cause corneal damage resulting in corneal decompensation and thereby you can get corneal edema and bullae, which are like blisters on the cornea. They can get painful, but also affect the vision significantly. And this can happen in patients who've had multiple eye surgeries or complications during their eye surgery and also for corneal infections that are not responding to medical management.

And then finally, transplant can be done for what are called tectonic reasons. And those are in order to maintain the structural integrity of the eye. So these are in cases of very severe infections or injuries or certain autoimmune conditions or viral infections that can cause melting and perforation of the cornea. And in Florida, we see much higher numbers of corneal ulcers and infections than other parts of the country because of a warm and humid environment that causes infectious organisms to flourish.

So one of the very common reasons we see really severe ulcers or corneal infections is from improper contact lens use. And often these require urgent or emergent corneal transplants.

Melanie Cole (Host): Wow. So obviously, the type of transplant a patient receives depends on which part of the cornea is damaged and why. Can you tell us some of the options available, Dr. Tuli, and the reasons for performing the different types of cornea transplant, why you might choose one over the other?

Dr Sonal Tuli: I don't know if you know this, but for nearly a hundred years, the predominant type of transplant was what's called a penetrating keratoplasty. And this is still most commonly done in many countries in the world. In this procedure, you punch out a central corneal button of about seven to eight millimeters using what's called a trephine and then it's replaced with a similar size with a slightly larger button, which is punched out from the donor tissue. It's sutured to the patient's eye using 10-0 or 11-0 non-absorbable sutures. These are sutures that are thinner than the human hair, so very, very tiny sutures. They're left in the eye for several months to allow the cornea to heal. And then we remove them strategically a few at a time to reduce the astigmatism or the irregularity of the cornea over the next few months. What this means is that it takes about a year for the patient to recover vision enough to be able to use the eyes for activities such as reading or driving. Also the eyeglass prescription following the transplantation can be unpredictable and patients often need rigid gas permeable or scleral contact lenses for best vision correction because they might have a clear cornea, but it could be irregular.

Also the other thing that patients need to be aware of is that the eye does not achieve full structural integrity lifelong, and the patients have to be careful about trauma to the eye, even years down the road. So we still do these frequently for tectonic reasons or where the entire cornea is involved in the pathology or if the eye is perforated or has a severe infection or injury.

But about 20 years ago, this ophthalmologist from Netherlands, Gerrit Melles, introduced what's called a posterior lamellar keratoplasty. And this has completely revolutionized the management of disorders that only affect the endothelium and that's the back layer of the cornea. And that's one of the most common reasons why corneal transplants are done currently. And this has undergone several iterations, but to result in the what's the most commonly performed procedure, at least in the United States, called a Descemet's stripping endothelial keratoplasty or DSEK. And now, what we do is called Descemet membrane endothelial keratoplasty or DMEK. So you'll hear me talk about DSEKs and DMEKs, and that's what these are. And currently in the US, nearly twice as many endothelial transplants, DSEKs and DMEKs, are performed now as penetrating keratoplasty.

What's different in these procedures is that instead of removing the entire cornea in patients where the rest of the cornea is completely normal, and it's just the endothelium that's abnormal, you make a very tiny incision at the corneal limbus and go in and strip out or peel off the Descemet's membrane and the endothelium that's underlying the center of the cornea. And then you replace it with a layer that contains either the posterior corneal stroma, the Descemet's membrane, the endothelium, as in the case of DSEK or just the Descemet's membrane and endothelium in case of DMEK. So in the DMEK, you're basically replacing what you've removed. And what's nice is that because these tissues are really thin, they can be folded or rolled and then inserted into the eye where they're unfolded or unrolled and approximated to the cornea using an air or gas bubble. So you basically float them up on this gas bubble and it sticks to the patient's own cornea.

And the cool thing is that these grafts then adhere to the cornea by the suction that's created by these now healthy endothelial cells pumping fluid out of the cornea and you don't need any sutures. Also once you start pumping normally, the vision starts clearing up very rapidly.

So given that there are several advantages of these lamellar grafts, since incision is very small, the eye is structurally intact and there's low risk even down the road if there's any future trauma. Because there's a much smaller amount of donor tissue transplanted, the risk of rejection is also much lower because there's less tissue for the body to recognize as foreign. And because the majority of the cornea is not replaced, the refractive power of the cornea does not change significantly. So you don't have these very interesting changes in the eyeglass prescription or need contact lenses.

And most importantly, for the patient, the recovery of vision is much quicker, usually within one to two months. So at UF, patients with endothelial pathology basically get DSEK and DMEK, and that is the most commonly done procedure here, though we do quite a few penetrating keratoplasties too because of the infections that we see.

Another procedure that's done a lot less frequently is what's called a deep anterior lamellar keratoplasty or DALK. And this is done for conditions where the endothelium is healthy, but the superficial corneal layers are scarred. It's technically much harder. And there are very few patients that actually meet the criteria for this procedure. So it's rarely done in the US and we do it in a select few cases of keratoconus or scarring, but not very commonly.

So basically to summarize, if the entire cornea is affected or there's a perforation, you do a penetrating keratoplasty only. If just the endothelium is damaged, then a DSEK or DMEK are done. And if the anterior cornea is affected with an intact endothelium, then you do a deep lamellar anterior keratoplasty.

Melanie Cole (Host): Dr. Tuli, cool is hardly the word for this. Amazing is more the word for what you just described as the different procedures and the different ways of doing cornea transplant and the history as well. Now, do you have any patient selection criteria you'd like other providers to know about?

Dr Sonal Tuli: So, fortunately, there are very few patients with corneal problems that are not candidates for corneal transplantation of some sorts, so that could be some one of these procedures. Rarely, we might have patients whose general health is too poor to go through surgery, but that's very unusual because we can do this procedure under local anesthesia, which is a lot less risky than general anesthesia. So most patients are candidates for this procedure even health-wise, unless they cannot lie flat for some reason or have enough risk that even local anesthesia would be problematic.

But in some cases, along with corneal problems, patient may have retinal or glaucomatous damage that limits their vision. So even if you do a corneal transplant, their vision would not improve. And in those cases, we don't do corneal transplants given the limited amount of corneas available.

At the University of Florida, actually, we do see many patients that have very, very complex eye pathology or chemical burns that may not be amenable to routine transplantations, any of the types that I mentioned earlier. Some of these patients have also had repeated rejections of their transplants because their corneas have vascularized or their lack limbal stem cells. Or they get recurrent infections, viral infections, for example, herpes or shingles in their eye. And for these patients, we perform what's called a keratoprosthesis or an artificial cornea.

So this keratoprosthesis is made of an anterior plate and stem that's made out of a PMMA plastic. And it looks somewhat like a transparent mushroom and then there's a titanium back locking plate. And what we do is sandwich the donor cornea between these two plates and snap it into place. And then this entire apparatus is sutured to the eye similar to a penetrating keratoplasty. This are complex procedures and it requires very complex post-operative management and coordinated care with several subspecialists in ophthalmology. So it's done by very few cornea specialists and UF is one of those centers that does several of these every year.

But what's great about this procedure is that the recovery of vision is almost immediate and it's often superior to regular corneal transplants. And also, these can be life-changing for patients because these patients have often been told that nothing can be done for them because their eyes have such complex eye problems. And so we've had a lot of patients that had been sort of written off by other physicians and we were able to provide keratoprosthesis surgeries for them and got them to see again.

Melanie Cole (Host): doctor since we're discussing transplantation, what role can our listeners play in the donation process?

Dr Sonal Tuli: corneal transplantation is life-altering and a miraculous surgery. It's only possible because caring individuals donated their corneas after they died. I would encourage everyone to register to be an organ donor and not only transform a life, but also leave a legacy and let someone see life through your eyes.

Melanie Cole (Host): Well, Dr. Tuli, before we wrap up this absolutely fascinating episode, tell us about any innovative or future technology in corneal transplant, current emerging therapies for these kinds of issues, any game changers, any of the latest or most exciting advances that you would like other providers to know about and why it's so important that they refer to the incredible specialists at the University of Florida College of Medicine and UF Health Shands Hospital.

Dr Sonal Tuli: So some of the exciting procedures that we're doing at UF are called DWEK, we love these acronyms, so that's called Descemet stripping without endothelial keratoplasty. In some select patients with endothelial dysfunction, we strip just the central four to five millimeters off the Descimet membrane. And then we use medications called Rho-kinase inhibitors and steroids to let the patient's own endothelial cells migrate across the defect without needing a transplant in several of these patients. We just completed a clinical trial on this procedure and now offering it to patients who meet the criteria for this procedure.

There's work being done on 3D printing corneas and expanding patient's own endothelial cells ex vivo or outside the eye, and then re-injecting them back in the eye. But those are not ready for prime time yet, but coming down the pike. And we're also doing research on ways to prevent corneal scarring and preventing some of the viral infections that cause corneal scars from causing infections and thereby trying to reduce the need for transplants altogether.

So the University of Florida offers the entire spectrum of corneal transplant procedures for patients. So any patient with a corneal problem can usually undergo one of these procedures that we offer and recover their vision. So if you're not sure if the patient can be helped, we are happy to see them and see if they would be candidates for any of these new, innovative, or even traditional transplants that are being done at the University of Florida.

Melanie Cole (Host): Well, thank you so much, Dr. Tuli, for joining us today and sharing your incredible expertise for other providers today. And to refer your patient to Dr. Tuli, you can call (352) 265-2020 or visit ufhealth.org/eyecenter for more information. And to listen to more podcasts from our experts, you can visit ufhealth.org/medmatters.

That concludes today's episode of UF Health MedEd Cast with UF Health Shands Hospital. And please remember to subscribe, rate and review this podcast and all the other UF Health Shands Hospital podcasts. I'm Melanie Cole.