Focal Point Episode 6 – The Aniridic Cornea: Research

Guest: Ali Djalilian, MD

Host: Janelle Collins

Janelle serves as a Board Member at Large for ANA. She is also the Chair of the Patient and Family Advisory Board and serves as the host for Focal Point. Janelle has been involved in the aniridia patient community via both patient advocacy groups and Facebook groups for a number of years. She enjoys reading peer-reviewed journal articles and summarizing their contents for the patient community. She also is passionate about welcoming new parents of children with aniridia to the community and assisting them as they begin their aniridia journey. 

Focus: The Aniridic Cornea – Research

Date: July 22, 2025

Time: 8:00 pm EDT

Transcript

Janelle Collins:
Welcome everybody to this, our 6th episode of Focal Point, presented by Aniridia North America. My name is Janelle Collins, and I am your host for tonight. I serve as a member at large on the Board of Directors of ANA, and I live in Florida, in the United States, with my husband and 2 children. My now 17-year-old daughter has aniridia, and so that’s how I’m connected to the community.

Our episode tonight is focused on the aniridic cornea. And our guest for tonight is Dr. Ali Djalilian. And hopefully I finally said it right. 

Ali Djalilian: (Nods and Smiles)

Janelle Collins:
All right, good.  Dr. Djalilian is a cornea specialist and a clinician scientist. He is the Searls Shank Professor of Ophthalmology at the University of Illinois. He completed fellowships with Dr. Edward Holland at Cincinnati Eye Institute, and at the National Eye Institute. He has an active clinical interest in limbal stem cell disease, ocular surface reconstruction, and high-risk corneal and limbal transplantation. So you can tell that he is a great person for us to discuss this topic with.

He also is interesting in that he leads an active laboratory and a translational research program focused on developing new therapies for limbal stem cell disease. He’s been active in researching multiple avenues for treating the cornea and aniridia. He’s the editor of The Ocular Surface, a journal dedicated to major findings related to the surface of the eye. He also serves on the Medical Advisory Board for Aniridia North America. 

Now, since I haven’t had the honor of seeing him as a clinician, I asked a few people that have. Wendy Underly and her granddaughter Gabriella said, “He is kind, caring, respectful, and very personable. He spends as much time with you as needed, no matter how long it takes, and he’s very genuine.” And Amanda Krim said, when she saw him in college, she summed it up just by saying, “He’s just really wonderful.”

So, Dr.—I’m going to say it right this time—Djalilian, I’m so honored that you have joined us here tonight. Thank you so much.

Ali Djalilian:
Thank you. Thank you, Janelle, for that very kind introduction. Really, really happy to be here. It’s my pleasure.

Janelle Collins:
And it looks like it’s beautiful weather out where you are tonight.

Ali Djalilian:
Yeah, here in the suburbs of Chicago. It’s a little bit on the warm side, but it’s… I thought this way while I’m talking, I also get my steps for the day.

Janelle Collins:
That’s always good to multitask like that—if we can, right?  Awesome. So, everybody, I am so thankful for the great questions that you all submitted ahead of time. If you think of more questions as we talk, feel free to ask them in the chat. We will do our best to answer as many as possible tonight. Sometimes we get through a ton. Sometimes we really dive deep into a few topics. So we’ll see which way it works out tonight, but we will do our best.

Now, as we’ve discussed in the previous ones about the cornea, the aniridic cornea is really an incredibly complex topic. And so we used this iceberg kind of as an idea to give people—to help understand how deep this topic really is.

With Dr. Freeman, who was our first guest for corneal episodes, we covered just the very tip of the iceberg. We talked about clinical care for patients. And just really an overview of the eye and overview of the cornea: what goes wrong, what we are doing, existing treatments. And then we had Dr. Cheung from Virginia, and we dove more deeply into the clinical care side, and then a little bit into clinical research.

And so tonight, with Dr. Djalilian, we are going to dive into really more of the research. Because he’s one of those rare people that sees patients as a clinician and also does research at all levels, I am guessing we’ll hit on multiple levels of this iceberg tonight. My guess is we’ll hit some basic science, some preclinical or translational as well as clinical research, because he has just an immense amount of knowledge in this area.

So with that said, Dr. Djalilian, I think we’re gonna get started with just a real quick overview. We went over a lot of this in our first two episodes, but in 30 seconds or less, can you remind us: What is the cornea? And what is this aniridia-related keratopathy? What goes wrong?

Ali Djalilian:
Perfect, sure. So, I mean, the cornea is obviously the clear tissue in the very front of the eye. It’s right on top of our iris and pupil. It’s so clear that we can see right through it. The only way we can actually see it is by light reflection, but it’s actually completely transparent. So it allows the light, and also refracts the light as it goes into the eye.

And in aniridic keratopathy, the issue seems to be with the surface of the cornea, and the cells that cover the surface of the cornea, called the epithelial cells. And those epithelial cells are specialized for the cornea. We have epithelial cells covering almost all of our external surfaces—our skin, our mouth, everywhere. But each has its own sort of specialization.

In the cornea, the epithelium is also highly specialized. And the issue is that over time, like all other surfaces, this epithelium has to get turned over. We’re constantly making new cells and replacing older cells as they slough off.

So in the cornea, this regenerative potential comes from the stem cells, which are located at the edge of the cornea near the sclera—the area that we call the limbus. And those stem cells have to regenerate this epithelium. Usually, we have enough stem cells to last our whole life. But in aniridia, it seems like we run out. The stem cells give out after—it’s variable—after one, two, three, four… I’ve seen it as late as the fifth or even sixth decade of life where it becomes an issue. So anywhere in that range, the stem cells could start to give out and we don’t have enough.

So then conjunctival epithelial tissue—immediately next to the cornea—starts to grow over the cornea, and that leads to more opacification and loss of the transparency of the cornea.

Janelle Collins:
Okay, thank you. All right.

Ali Djalilian:
Oh, that was longer than you wanted?

Janelle Collins:
No, no, that was great though! That was still a really nice summary of a pretty complex thing. So that was great. We’ll get to the research questions in a minute, but I do like to ask a couple. People gave some good questions about prevention, and we hit that pretty hard in some of the others, but I still like to get your opinion—because each doctor looks at some of this a little differently.

So first of all, Lauren from New York wondered: How is the progression of keratopathy monitored? Like, how can you tell that as a doctor?

Ali Djalilian:
Yeah, so that’s—on exam, when we look behind the microscope, the slit lamp—we can distinguish the corneal epithelium from conjunctival epithelium by how they look, but also by their staining.

And that’s why almost always we’ll use some little strip of fluorescein in the eye, and with a blue light, that helps us see the properties of the epithelium. That helps us distinguish the two types of epithelium. So really, that’s the only way to see it on exam.

And you know, the progression is not… that is not so fast that we can see it from—like over the course of a few months. Usually, this is over the course of years. We’ll start to see, oh, now we can start to see more conjunctival versus cornea. So it’s a very slow progression.

So basically by exam.

Janelle Collins:
Okay, okay, that’s helpful. And again, this is a question we did hit, but I’m going to ask it again because it got asked again. Kanayla in Oregon asked: Do moisturizing or lubricant eye drops, or artificial tears help with the health of the cornea in aniridia in any way?

Ali Djalilian:
Uh, yes. I mean, we know that the aniridic cornea probably is more prone to—or the surface of the eye is more prone to—dryness. So using artificial tears helps to alleviate part of the dryness.

Because, you know—and we’ll get to this in more detail—but bottom line is, we want to do anything that can… anything we can do to make the surface of the eye a hospitable and healthy environment is quite likely to help prolong the health of those stem cells that are there.

And so anything we can do to minimize trauma, toxicity, or anything that disrupts the healthy environment on the surface of the eye—avoiding those is likely to be beneficial.

Janelle Collins:
Okay, okay. Great.

Ali Djalilian:
The bottom line is yes. But however, one little caveat here. I mean, if someone is using artificial tears that have preservative—particularly this particular kind of preservative that is now becoming less and less common in artificial tears but still some of the generic brands may still contain it—this benzalkonium chloride, that’s actually the one that definitely should be avoided.

So that does create toxicity. So I would say artificial tears that have a very gentle preservative—I mean, a lot of these big name brands like Refresh, Systane, all of them—they use a very gentle preservative, or ideally no preservative.

Janelle Collins:
Okay. And can you repeat that name—the one that we should definitely avoid?

Ali Djalilian:
Yeah. Benzalkonium chloride.

Janelle Collins:
Okay, excellent. Thank you. That’s helpful.

So speaking of maintaining the health of the eye, and that environment—we had multiple people ask: What are the best ways to slow the progression or the top three things we can do to preserve that health?

Ali Djalilian:
Yeah, so—perfect. So, I mean, I would say, if I can think of the most important things… So many of these factors are beyond our control. But let’s say there are factors that we could control.

One is dryness, like you just brought up.

Another one—I mean, frequently or it’s not uncommon that patients also have concomitant glaucoma. They have to be on multiple—one or more—eye drops for the glaucoma.

Janelle Collins:
Right.

Ali Djalilian:
So I think there’s an opportunity there—being on drops that have no preservative or a gentle preservative, not benzalkonium chloride. Unfortunately, many of the generic, or even some non-generic, still contain this. Even some of the new glaucoma medications that are approved—still, they use this preservative. I mean, not just in aniridia, but even in other glaucoma patients, I’ve seen… it’s not uncommon that we’ll see limbal stem cell deficiency in patients who use these drops for a number of years.

Eliminating preservatives from their drops—that’ll be another factor they could control.

Janelle Collins:
Okay.

Ali Djalilian:
Let me think about a third one… yeah. I mean, this one’s a little bit tricky—and that’s the contact lens wear.

Janelle Collins:
Right.

Ali Djalilian:
Because, I mean, soft contact lenses in general can cause trauma to the surface—low-level trauma. But at the same time, I know for many patients it helps them see better.

But I would say, if you are going to be wearing contact lenses, be under the care of someone who regularly can check their cornea. And if at all possible, let’s say instead of soft lenses, wearing gas permeable lenses, which are probably gentler on the epithelium—the surface of the eye—and create less trauma.

They allow more oxygen to get to them. They don’t block oxygen like soft lenses do. So yeah, I mean, contact lens wear is probably the third thing that people could control that could prolong the health of those stem cells.

Janelle Collins:
Okay, okay, that’s helpful. Somebody in the chat—Vasil in the chat—said if the artificial tears say that it’s preservative-free, does this mean that it does not contain that preservative that you mentioned? It should, right?

Ali Djalilian:
Absolutely correct. That’s correct—definitely.

Janelle Collins:
Okay. Okay. Excellent.
So you talked a little bit about glaucoma, and we had a couple of questions related to that and the cornea. One person asked: What is the minimum eye pressure we need for a cornea to stay healthy? Suzanne from Florida asked that.

Ali Djalilian:
Oh, that’s a very good question. Yeah.

I would say around 10. Ten or above should be good. I mean, I’ve seen patients with corneas even below 10 that have done well for many years as well, but I would say in general, I like to see them 10 or higher. And in that case, I’m sure that pressure will be good—the cornea will be okay with that pressure.

Janelle Collins:
Okay. That’s helpful. Now, how do glaucoma shunts or tubes—especially if you have multiple—affect the cornea? And what are the best options to minimize that limbal stem cell failure? Nicole from the U.S. asked that.

Ali Djalilian:
So again, another very critical question. The issue is that, on the one hand, tubes are great in that they reduce the need for using drops—so, less toxicity from the drops to the surface.

But in some patients—and this is not always predictable—the tube and the cornea don’t get along with each other. Especially if the tube is placed close to the cornea—that’s not good. But I think most experienced glaucoma surgeons, like Dr. Netland who you’ve had on the program, follow a technique of placing the tube away from the cornea.

He places them in what we call the sulcus area, which is nice and far from the cornea. That significantly reduces the likelihood of the cornea becoming unhappy from the tube.

But still, there are some eyes that—just having a tube in the eye—somehow makes the cornea unhappy. Those are challenging cases. That’s not the typical scenario, but it definitely does happen. There are some corneas where the tubes interfere with corneal function.

Janelle Collins:
Okay. And then Patti in the chat just asked: All right, we were told what pressure was too low—what pressure is too high?

Ali Djalilian:
Yeah, so perfect. That’s something a glaucoma specialist could probably answer better than me. But I would say for the purpose of the cornea—for the health of the cornea—pressures of 30 and higher usually can have a detrimental effect on the cornea over time.

Into the mid-twenties is okay for the cornea. Again, it may not be okay for the optic nerve.

Janelle Collins:
Right. Right. Different perspectives here.

Ali Djalilian:
Yeah, yeah.

Janelle Collins:
Yeah, for sure. Okay, thank you. And then, before we get into the treatments and the research, one last question that came in today from Geraldine here in the U.S. was: Why are cornea transplants alone not very successful for aniridia patients?

Ali Djalilian:
Yeah, fantastic question. Really. And this, I think, is something that everybody who’s going to require some kind of corneal surgery should be aware of.

The regular cornea transplant does not contain those stem cells. And if someone has a problem in the cornea—we know the fundamental issue in aniridia is the lack of stem cells or insufficient stem cells.

So if you’re trying to fix that problem, a regular cornea transplant is not going to solve it. And if anything, doing that before you do something about the stem cells is going to set you back even further—make things even more challenging to fix the stem cell issue later on.

So really, if a patient reaches a point where they do need surgical intervention, then the proper first step is a stem cell replacement or transplantation—before a cornea transplantation, if corneal transplantation even becomes necessary.

Janelle Collins:
Right. Okay. So talking more then about treatments like that—Michael from New York asked: What is the key to finding the right balance for treatment using steroids, serum tears, and other eye lubricants?

Ali Djalilian:
Great, great question. There are studies now, and most of us are in the practice of seeing that  those early stages—or early to not-so-advanced stages—of limbal stem cell deficiency, with some steroid drops, we see improvement in the surface. Which likely indicates that there is probably some inflammation on the surface, but also, steroids block many pathways. So somehow they improve the health of those remaining stem cells.

But, as you know, steroids have complex side effects if you’re going to be on them long term—most importantly, the pressure.

Janelle Collins:
Steroids are one of those necessary evils sometimes, aren’t they?

Ali Djalilian:
Exactly, exactly right. We can save a lot of things, but they can also damage a lot of them.

Janelle Collins:
They sure can. That’s for sure.

Ali Djalilian:
But then another treatment that you just mentioned—that Michael had mentioned—is autologous serum. And this is basically where we take the patient’s own blood and separate the blood cells, and just the serum component.

A compounding pharmacy can—or some physicians even in their office—mix it up with some artificial tears and make it into an eye drop. It’s a little bit cumbersome, let’s say, because it has to be refrigerated, has to be kept sterile… but still, it provides a lot of nutrients and growth factors, which again can help the surface of the eye, especially in those early to moderate stages of limbal stem cell deficiency. But not much, probably, in the very advanced cases.

Janelle Collins:
Okay. And that relates to a question that Lindsay just asked in the chat: Are serum tears beneficial for older users, or does it matter depending on what the state of the keratopathy is?

Ali Djalilian:
Yeah, I mean, I would say either way, serum tears—the great majority of patients will find that serum helps them, to some degree. Some more than others.

I mean, one issue is that each person’s serum is also different, and really, we don’t always know what we’re actually doing. We’re applying the serum, but it seems to be a good replacement—substitute—for our own natural tears, which there’s no other way to make.

But I would say it probably is more likely to be beneficial in the earlier stages than the later stages.

Janelle Collins:
Okay. Okay.

Ali Djalilian:
And of course, it has other issues—it’s not covered by insurance, it’s not available everywhere. So it’s really something that we cannot always rely on.

Janelle Collins:
Right. That’s super helpful. So Natalie from Texas asked: What is the best way to treat corneal swelling in a young adult?

Ali Djalilian:
Yeah. So corneal swelling, I mean, obviously that indicates there are issues with the back layer of the cornea—not the epithelium, but the endothelium, what we call the endothelium. That’s what controls the swelling or hydration of the cornea.

So when those cells are not functioning well, or we’ve lost those cells for one reason or another, then the cornea starts to swell up.

Really, at this time, we don’t have any effective non-surgical solutions for that. In very, very mild stages, topical 5% sodium chloride—which is available over the counter—may be beneficial. But really, once you get a little past that very mild stage, they’re not so effective.

The only treatment option is surgical—to replace that back layer of the cornea surgically with a partial cornea transplant.

Janelle Collins:
Okay. Oh, so a partial corneal transplant is a possibility, then?

Ali Djalilian:
Mhm, mhm.

Janelle Collins:
Okay, interesting.
 

Rita, I saw your question in the chat, and it looks like maybe we’re missing part of the question. So if you could go in and clarify what it is that you want to know that they should wear, that would be helpful.

Patti in the chat just asked: What do you think of using Prolensa—for corneal pain and discomfort?

Ali Djalilian:
Yeah. So I’d have to check what the preservative is in Prolensa.

My first quick answer would be no—I’m not in favor of it as a long-term option. I think long-term it’s going to have detrimental effects on the surface if you’re using it chronically.

It’s not meant to be a chronic, long-term medication. But for short-term, I think it’s fine. Or occasional—if it’s once a week or once every two or three weeks, that’s fine.

But if it’s daily use, likely with time, it’s going to have negative effects on the surface.

Janelle Collins:
Okay, excellent. And I see Vasil and Rebecca—I saw that you both asked good questions. We’re going to get to those topics here in a little bit, so I’m going to hold off on that. But I wanted you to know I did see them.

All right, so Rex from Tennessee asked: Is it possible to wait too long to seek treatment for a cornea?

Ali Djalilian:
Good question. Yeah. So the issue is, if the cornea has lost stem cells and there’s conjunctiva that grows over the cornea, then over time—not short time, let’s say over a period of years—scarring starts to develop in the cornea.

If you wait too long, that scarring becomes deeper. Then, to help that eye, it would definitely require more than just stem cells. It would likely require a corneal transplantation—at least to replace that front part of the cornea, where the scar is.

So it does add more complexity if you wait too long and develop more scarring.

Janelle Collins:
Galina from Spain asked: Blood vessels growing into the cornea are a big challenge for patients and doctors. What could you recommend in this regard?

Ali Djalilian:
Yeah, that’s another good question—and also a really challenging problem.

There again, we don’t really have very effective treatments for blood vessels in the cornea.
The issue is, those blood vessels are growing because it’s the conjunctival epithelium that’s starting to grow over the cornea. The corneal epithelium, like we said, is highly specialized for the cornea, and one of its very special properties is that it stops blood vessels from growing into the cornea.

A conjunctival epithelium cannot do that. So when conjunctival epithelium starts to grow, then blood vessels start to grow also. So really, the ultimate fix is to bring in new stem cells for the cornea—so you have a healthy corneal epithelium.

But if that’s not an option—or for one reason the patient’s not ready for that treatment—then some treatments are focused on trying to control inflammation on the surface. If there is inflammation, then topical anti-inflammatory drops can help.

And again, I don’t want to go into this too much because we still don’t have a lot of data on this, but there are techniques—not for aniridia specifically—where people try to ablate those blood vessels. But they’re not straightforward, and they’re not always effective.

So, anyway—bottom line, unfortunately we don’t have very good treatment for those blood vessels—short of just bringing in healthy stem cells that will then prevent those blood vessels.

Janelle Collins:
Right.  All right, so here’s the kind of one million dollar treatment question—before we get into the one million dollar research questions, right?

The one million dollar treatment question came from Neil Lagali in Sweden—who I know you probably know—but also from Mary in Wisconsin, and Wendy, and a bunch of other people:

What is the best available treatment today for advanced keratopathy, and what vision gain can be expected?

Ali Djalilian:
Yeah, great, great question.

So I would say, really, still—if you put all the treatments that are available—I would still say the best treatment is, like we said, transplanting and bringing new stem cells to the surface of the eye. That’s likely to be the best for sure, because it’s addressing the underlying problem.

Janelle Collins:
Right.

Ali Djalilian:
Everything else that you do is not addressing the underlying problem. And I’m sure—I mean, when you had Albert on the program, he must—I’m sure he went into this. What makes that treatment more challenging is that it requires medications to prevent rejection, because that’s the most challenging problem you have to overcome for that treatment.

Janelle Collins:
Yes. Right, right. And that brings up a question that—

Ali Djalilian:
Yeah. Still, I think—go ahead! Go ahead! Go to the next question.

Janelle Collins:
I was just gonna say that brings up the question—and we’ll talk about this in research—are there any corneal surgical procedures or treatments being developed where anti-rejection meds don’t have to be taken? I think we’ll get to that here in some of our research stuff.

Ali Djalilian:
Yeah, sure. Sure. Mhm, definitely.

Janelle Collins:
So then Ryan from Iowa asked: Can you give the pros—and I guess you’ve already talked about the pros—we have the potential for it actually fixing the corneal issues, right? But can you give the cons of having or not having the stem cell surgery? Or are there any alternatives to that?

Ali Djalilian:
Yeah. So again, I’m sure Albert probably went through this. Really, the main challenge is the need for immune suppression. But again, for an otherwise healthy patient—or generally healthy patient—that’s not a problem.

As most people know, Dr. Holland has done the most number of these procedures of anyone in the world, and he has published his outcomes and results. It’s extremely uncommon for patients to have an irreversible toxicity from the medications, as long as they’re under the care of someone who is highly familiar with those medications. That’s really a key to the success of the procedure.

Janelle Collins:
Yeah, that’s super important.

Ali Djalilian:
Other cons, I guess… I mean, of course, after that surgery, steroids are necessary long-term. So if a patient has glaucoma and they’re already on—like prior to surgery—two or more drops, chances are quite likely they will need surgical intervention for their glaucoma.

Because with steroids afterward, their pressure will rise even more. So they will likely need some type of tube shunt surgery for their glaucoma if they already have existing glaucoma and they’re on drops.

Janelle Collins:
Right. That’s that whole steroid thing again we were talking about.

Ali Djalilian:
Yeah, exactly. Steroids—again, necessary evil here. Besides those two, I can’t really think of any other negatives associated with the procedure. But really, a lot to be gained if it’s done properly and medications are managed properly.

But still—I mean, yeah—it’s still… one cannot say this is a 100%—

Janelle Collins:
We can’t say it’s perfect, right?

Ali Djalilian:
Exactly. We can’t say it’s perfect.

Janelle Collins:
Exactly.

So related to that immunosuppressant—Wendy asked: What is your opinion of using something like umbilical stem cells? Would you not need as many suppressant meds for something like that?

Ali Djalilian:
Yeah, that’s a good question to take us into the research now, I think.

Janelle Collins:
Right—let’s pivot a little bit.

Ali Djalilian:
So really, the stem cells for the surface of the eye—for the cornea—are highly specialized. They’re what we call limbal epithelial stem cells.

Other stem cells may have a beneficial role, potentially. Our group is also studying a particular type of stem cells called mesenchymal stem cells that help support the limbal stem cells.

The idea is that if there are some limbal stem cells left on the surface, we help support them so they function better or survive longer. That’s our hypothesis.

Those umbilical cord stem cells would work by a similar mechanism—potentially supporting stem cells that may still be there.

But in a more advanced case, where most of the stem cells are gone and the cornea is covered by conjunctival epithelium, at that point it’s unlikely that they’re going to do much—or not enough to change the epithelium back to a corneal type.

So here’s really the question: How can we help the corneal epithelium?

Janelle Collins:
Well, I was gonna say—my next question was really to hit that research. I know Dr. Cheung mentioned you’re working on some exciting stuff. I’ve heard you talk about it. I’d love to hear the stuff you’re working on, and then the other types of approaches being studied. Go ahead and hit us with it.

Ali Djalilian:
Sure, sure. So basically, the idea is that we know the fundamental genetic defect is in the gene PAX6. And in almost every patient, we know for sure they already have one healthy copy of the PAX6 gene. It’s the other copy that’s not working well.

In many genes, that may be okay—as long as you have one healthy copy, it’s sufficient. But PAX6 is a bit more dose-sensitive, so having both healthy copies seems to be important.

So the idea is: can we improve or promote the expression of the healthy PAX6 gene—can we increase that healthy copy’s activity?

There are some medications designed not specifically for PAX6, but for genetic diseases where there’s one healthy copy, and the drugs work by depressing the mutant copy so you get more of the healthy one. Or, they help the cells make more of the good copy of PAX6.

Some medications that are approved for other conditions have been tested in the lab and found to increase PAX6 expression.

That’s one general approach—try to increase PAX6 expression.

This is likely to be most helpful the earlier you start such treatment. In very advanced disease, it’s probably not going to make a big difference, because the cells you want to act on are already gone.

Still, it may help by improving the health of the remaining cells.

<<Video above begins here>>

Ali Djalilian:
So that’s one approach—playing with the PAX6 gene.

We and others have published studies on different drugs that, at least in animal models, seem to help increase PAX6 and improve or prolong the health of the epithelium.

Then another general approach is to try to improve the function of those stem cells by supporting them. And that’s where we’re talking about those mesenchymal stem cells we’re working on—or those umbilical cord stem cells—which are basically supporting cells, helping the stem cells on the surface function better.

Janelle Collins:
Okay.

Ali Djalilian:
Yeah, so that’s a lot of what we’re focusing on. We have started a clinical trial to look at that question—whether topical, or in a drop form, these supportive factors can help improve the function of the remaining stem cells on the surface of the eye and improve corneal health.

That remains to be seen. We’ve completed a safety study, so we know it’s safe. Now we need to test efficacy, and hopefully in a year or so, when that study is done, we’ll know more.

Another way to think about helping the surface of the eye is: how can we bring back stem cells once they’ve been lost? How can we restore stem cell function?

That’s probably the more challenging issue.

But there are studies looking into manipulating certain genes—PAX6 being one of them—that could help bring back some of those lost stem cells.

I should also mention another approach. When someone has lost all their limbal stem cells, we try to use their own cells from elsewhere and turn them into corneal stem cells or limbal stem cells to help restore the surface of the eye.

Janelle Collins:
Oh, interesting. Okay.

Ali Djalilian:
Those are active areas of research.

Ryuji’s group in Japan has done the most work in this area. They’ve already tested that approach in some patients—not in aniridia yet, but in other types of limbal stem cell deficiency. So there’s still more to come. That looks promising too.

Janelle Collins:
Okay, interesting. So there’s really a lot of different things being looked into—some better for early disease, some possibly better for later stages.

I think you kind of already answered this, but Diana had asked: Are there any gene therapies being tried?

Ali Djalilian:
Perfect, yes—correcting the genetic defect, then putting those corrected cells back into the eye.
A lot of those are still at the cell culture level, but we have seen some promising work.

Dr. Simpson from Canada has published studies showing that this approach is viable, and you can get long-term expression of a gene using gene therapy when introduced into the cornea.

Janelle Collins:
Yeah, and I think she’s the one who said before, “You’ve got to cure the mouse before you can cure the human.”

Ali Djalilian:
Exactly.

Janelle Collins:
They haven’t quite cured the mouse yet, but they’re making progress.

Ali Djalilian:
Yes, yes. Her work looks very exciting and promising.

Janelle Collins:
That is exciting.

Somebody had sent me an article a while ago about nanoparticles from Northwestern—some new development involving limbal stem cells.

I have to admit, when I hear “nanoparticles” I start thinking Avengers or something. But people were wondering: could this help aniridia patients down the road?

Ali Djalilian:
Yeah—perfect. Great.

Yes, I know that study and the investigators quite well. Very nice work. That was tested in an injury model, not a genetic model, but it seems like their nanoparticles have mostly anti-inflammatory and regenerative effects for the surface of the eye. So yes, those could potentially be beneficial in an aniridic cornea as well.

It’ll be interesting to study those.

That reminds me—nanoparticles are also another way to deliver genes or proteins to the surface of the eye.

One approach we’re looking at involves extracellular vesicles—or exosomes. These are small particles secreted by cells. They contain a lot of “goodies”—they’re packed with proteins, RNA, and other types of factors.

It’s a way that cells can communicate with each other. People are becoming very interested in exosomes as a way to deliver therapeutic factors and manipulate cell function.

We’re looking at how to use these tiny packets—about 100 nanometers in size—to deliver factors to the surface of the eye.

If you know all the right factors to package in, you can potentially help support the remaining stem cells—or even bring back stem cells to the surface.

Janelle Collins:
Interesting. Okay.

Rachel asked: Is there any risk to the funding or the research for the studies that you’re working on?

Ali Djalilian:
Yeah, good question.

There’s risk for all of us dependent on NIH funding. 

Already, based on the latest budget that passed, we know the NIH budget was cut significantly.
So it’s quite likely all investigators will need to take a cut to continue their research programs.

It’s going to be challenging times for the next few years, at least.

Janelle Collins:
Yeah, for researchers, for sure. Thank you for addressing that.

Ali Djalilian:
Yeah.

Janelle Collins:
Vasil had asked (and I think it was already on our list): Are there any current preclinical trials about to enter clinical trials—or any clinical trials coming up for people with aniridia?

Ali Djalilian:
Besides our own trial—with the mesenchymal stem cell–derived factors—I’m trying to think if there are others. I haven’t looked recently to see if anything new is about to start. I probably should have looked on ClinicalTrials.gov. I could’ve given a better answer.

But in terms of what I know right now—there’s nothing I would specifically refer a patient to and say, “Go travel to this place and get into that trial.”

Most things are probably still a few years away.

Janelle Collins:
That’s kind of what I had heard, too. But I wasn’t sure if you had some secret knowledge I hadn’t heard yet.

Ali Djalilian:
No, nothing that I’ve heard—nothing I’d refer someone to yet.

Janelle Collins:
Now Miguel from Nebraska asked a great question: What are the biggest challenges in making some of these advanced keratopathy treatments accessible in lower-resource or rural areas?

Ali Djalilian:
Yeah, that’s a great question…As you know, this is not a common disease, and so not as many physicians or ophthalmologists are familiar with it and manage it. So really, you’re limited to mostly major academic centers in big cities.

And those who are hopefully close enough to these academic centers could potentially get access to it. But if they’re far from an academic center, that does limit what they’ll have access to—no question.

Of course, any of these treatments, if they do become available, they likely won’t be cheap. Even for simple things like dry eyes, treatments that get approved are not cheap—let alone for a genetic disease or any kind of severe disease of the cornea, unfortunately.

There are problems in our healthcare system for sure.

Janelle Collins:
Right, there is for sure. There’s no doubt about that.

Before we go—we only have, believe it or not, about 5 minutes left. I can’t believe this hour has gone that quickly!

But before we wrap up, Rita had a question: With aniridia, is it true that you should wear sunglasses most of your life? Does that help the retina? Does it help the cornea?

Ali Djalilian:
Great question! Yeah, I actually neglected to mention that.

I think if someone is going to be spending a decent amount of time outdoors, it’s definitely a good idea to wear sunglasses.

We know that UV light promotes aging of the cells. Just look at our skin, which is exposed to UV light—it’s the number one factor that accelerates aging. Or one of the most important factors. 

So yes, definitely, wearing sunglasses—especially for someone outdoors a lot—is likely beneficial. If you’re closer to the equator or in more southern regions of the northern hemisphere (or further north in the southern hemisphere), the exposure is even more intense.

It helps not just with corneal aging, but we also know UV exposure promotes cataracts. And likely, it plays a role in issues at the back of the eye, too—though it’s harder to say exactly how much.

Janelle Collins:
Okay, that’s very helpful.

So to wrap up, I’ve got two questions.

One of them is kind of complex—it’s a combo from several people: Susan from Illinois, Rebecca from Michigan, Sherry from Maryland…

They all asked: Do you think we’re going to see cures or improvements in treatment in the next 3 to 5 years? And if so, which of those do you think hold the most promise?

Ali Djalilian:
Great. Oh, you’re really putting me on the spot now!
So I’ll answer that in two ways.

First: preventive therapies—those that can slow down the loss of limbal stem cells on the surface of the eye—That’s probably quite likely. Already, there are drugs out there that can do that—even among FDA-approved drugs (though not yet approved for the eye).

If we can formulate those into eye drops, the drugs are there—we just have to figure out which one is right, test it in models, and then take it to a clinical trial. That’ll likely take two to three years to show an effect.

So maybe three years is ambitious, but within five years we could have something like that—if we put energy into it and push through.

Now, the second part—more advanced limbal stem cell deficiency—where we try to bring back lost stem cell function…
That’s more complicated, but with tools we already have, like gene therapy or delivering factors to the eye, or manipulating stem cells—we already have most of the pieces.

We don’t necessarily need a major technological breakthrough. But we do need to figure out which factors to deliver, how to deliver them, and how to do it safely.

That’s going to take more work.
<laughing> I’ve been saying “3 to 5 years” for the last 10 years!

Janelle Collins:
Right.

Ali Djalilian:
Still, I think it’s conceivable that in 3 to 5 years we could put the pieces together to bring back lost stem cells to the surface of the eye.

That timeline is ambitious—especially given the funding environment we’re facing—but it’s not out of reach.

So I’d say:
Therapies that restore stem cell function on the surface of the eye through gene or factor delivery are probably the most promising.
But to get to a clinical trial, we’re still at least a few years away.

Janelle Collins:
Okay, that’s really helpful.

So really, there is hope on the horizon for all of this stuff.

Ali Djalilian:
For sure, for sure. Yeah, mhm.

Janelle Collins:
It’s just not the horizon—tomorrow.

Ali Djalilian:
Right.

Janelle Collins:
So the key is—I often say that, you know, my daughter’s 17. But we get new babies born every day with aniridia, and those new babies are going to have a whole different set of treatments available for them when they’re in their twenties and thirties than what we have today.

Ali Djalilian:
Absolutely. That I can say pretty confidently as well. I agree.

Janelle Collins:
Yeah, yeah. So that’s an exciting thing to think about—what’s coming.

And then my last question—and this is related to what Rebecca asked earlier—

She said she was born and lives with aniridia. She’s in her early thirties. She’s asking what the best recommended procedure would be for her. And I’m going to change that question slightly to be a little more generic.

If you had a child who had aniridia, and they hit their twenties or thirties right now—and they needed something done with their cornea—what would you do?

And if, for some reason, they weren’t a good candidate for stem cell procedures, then what would you do?

Ali Djalilian:
Yeah, that’s tough—really tough.

If they’re not a candidate for stem cell transplantation, then…

There are options out there. I mean, as you all know, the artificial cornea—the keratoprosthesis, particularly the Boston KPro—is an option.

Janelle Collins:
Right.

Ali Djalilian:
For someone young, though, it really is a last resort.
Just because, for someone young to have that in their eye for the rest of their life—it really is…

The risk of problems accumulates over time.

They’re likely to have other problems. Glaucoma is a common one—probably one of the more common issues—but there are other things too.

With time, the risk of complications increases.

So yeah, I mean, I would say: if they were going to do that, I would only consider it for one eye, and leave the other eye alone.

Because chances are, for that young person, in the foreseeable future, we’re going to have—hopefully—safer and more effective treatment options.

Also, I just thought of something else that maybe Albert may have touched on—and again, it’s something that Josh Huo, one of our former trainees who’s now at the University of Minnesota, has developed.

He developed this technique of using the back layer of the cornea—without cells—putting it on the surface of the cornea. I know he’s doing a trial with that. So, if somebody wanted to be in an interventional trial, that trial is available at the University of Minnesota.

It’s not something that will permanently fix the cornea…

Janelle Collins:
Right. That’s the Bright-Mem procedure, right?

Ali Djalilian:
…Or fix the stem cell issue. Bright-Mem—perfect. Exactly. So it’s not going to permanently fix things, but it may—let’s say—buy some time.

Because from the time that that procedure is done until the conjunctiva grows back, this Descemet’s membrane—or this tissue that’s placed on the front surface of the cornea—likely does help preserve the function or health of the epithelium for some time before the disease recurs.

That’s still under study—we don’t know exactly—but Josh is specifically studying this very question. That may buy us some time, basically. That’s the bottom line.

Janelle Collins:
Right, and given that we have other things on the horizon, buying some time might be really helpful.

Ali Djalilian:
Exactly. Perfect. That’s exactly right.

Janelle Collins:
Okay, that’s great.

One quick question, just because I think this is important—Lindsay asked: What is the rejection rate of an artificial cornea for aniridic eyes?

Ali Djalilian:
Artificial cornea? Not low.

We still need to be on some drops, or depending on how much inflammation they have, maybe a little more. Because that central piece is plastic, there’s no immune rejection—but if you think of “rejection” more generally, meaning the body didn’t quite like this tissue, yeah—that could be a problem.

There could be membrane formation, especially in eyes that have had multiple surgeries—they’re prone to fibrosis.

So, if the question is: long term, how many eyes with those artificial corneas develop some kind of problem—It’s not low. I’d say maybe one third of the eyes long term will probably get into some kind of problem because of the artificial cornea.

Which is why, like I said, we really keep it as a last resort.

Janelle Collins:
Okay. That makes sense—particularly because if they develop a complication with that, it can be catastrophic to the eye, correct?

Ali Djalilian:
Perfect. That’s exactly right. That’s the issue, unfortunately.

Janelle Collins:
Whereas with the stem cells, if for some reason we reject it, it can be done again—or at least it’s not catastrophic to the eye, correct?

Ali Djalilian:
Exactly. If it’s rejected, you basically go back to where you started.

Janelle Collins:
And then still related to the same thing—without the stem cell transplant, how long will the Brightman last? Or is that going to depend on each person?

Ali Djalilian:
Yeah, perfect. It’s going to depend on how much reserve they have, how much stem cell function they still have.

Hopefully, that’s one of the questions that Josh will be able to answer for us.

Janelle Collins:
Hopefully—that would be great.

Alright, I have kept you 10 minutes over what I promised—and everybody else!

But this has been really a delightful discussion, Dr. Djalilian. I really appreciate it.

Ali Djalilian:
Oh!

Janelle Collins:
Stay tuned—because we may have a Part 4 of the Cornea series after we have the ANA Symposium coming up this fall.

We might do one focused on more of that basic science. Not quite in mice yet—we’re still in… I’m going to call it Petri dishes, because that’s what we as patients tend to say.

Ali Djalilian:
Right.

Janelle Collins:
And if we do that, we’ll round it out with Dr. Jim Lauderdale, probably, to discuss more of the basic research—if he has something new to share with us.

A recording of this will be available on the ANA website and on our YouTube channel, as well as a transcript. That way, if anyone wants it translated, we do have translation abilities on the website.

Before we leave, it’s always nice if everybody can—if you’re willing—turn on your camera.
We’ll turn off the focus mode here. It always takes me a second to do all that. I’ll un-spotlight us so we can kind of see everyone.

But it’s nice to see everyone who’s here—so many friends! And again, I’m having a hard—there we go—now I can remove my spotlight.

Would love to see everyone if you’re willing to show us who’s here. So many friends have joined us. Thank you all for being here tonight.

It’s always encouraging to remember that alone, we in the aniridia community might be rare—but together, we’re strong.

And with researchers like Dr. Djalilian and others we’ve heard from—Dr. Cheung, Dr. Freeman—we really do have a lot of hope on the horizon for new treatments and exciting developments.

So if you have feedback about tonight’s episode or suggestions for future topics—I won’t lie—I have like a 3-page list of things I want to do in Focal Point eventually. But I’m always taking new suggestions too. You can email them to: focalpoint@aniridiana.org

I’ll leave this active for a few more seconds in case anyone has anything to say in the chat.

Otherwise, we’ll look forward to seeing you at the next episode.
And Dr. Djalilian—thank you again so much for joining us tonight. I really appreciate everything you contributed.

Ali Djalilian:
Thank you. Thanks to you and everyone who sent in those great questions. It was fun. It was fun to chat with you.

Janelle Collins:
Thank you! It was delightful. I really appreciate it.

Ali Djalilian:
Alright! My pleasure.

Janelle Collins:
Alright! Have a great evening, everybody—and hopefully we’ll see you again soon.

Ali Djalilian:
Great.

Janelle Collins:
Alright. Good night!