Focal Point Episode 4: The Aniridic Cornea – An Introduction

Guest: John Freeman, MD

Dr. Freeman is currently serving on ANA’s Medical Advisory Board.  He serves as medical director of the Mid-South Eye Banks and on the board of the World Cataract Foundation and the Advancing Sight Network.  He has recently retired from private practice but continues to staff and teach residents for the VA and the University of Tennessee Ophthalmology Department and is looking forward to staying involved in the care of and research for congenital aniridia corneal conditions.

Host: Janelle Collins

Janelle serves as the 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 – An Introduction

Date: February 12, 2025

Time: 7:30 pm EST

Transcript:

Janelle Collins: Good evening, everybody. Welcome to the fourth episode of Focal Point presented by Aniridia North America. We are so glad to have you here. I am going to get us ready here to get started.

My name is Janelle Collins. I’m your host for tonight. I serve as the member-at-large on the Board of Directors of ANA, and I live in Florida in the United States with my husband and two children. My 16-year-old daughter has aniridia, so that’s how I’m connected to the community.

Our episode tonight is focused on the aniridic cornea. Our guest is Dr. John Freeman. Dr. Freeman is board-certified by the American Board of Ophthalmology and specializes in cataract surgery and corneal disease. He has quite a bio here that I’m going to read because I couldn’t memorize it all that fast. So I’m going to just read it off to you so that you know who he is.

Prior to receiving his medical degree, Dr. Freeman received his BA in English from Davidson College in North Carolina. He earned his medical degree from the University of Tennessee College of Medicine. He served as residency at the University of Tennessee Health Science Center and completed a cornea and external disease and refractive fellowship under Dr. Edward J. Holland at the University of Cincinnati College of Medicine. Many of you have heard that name before in the Aniridia world. His fellowship included training in ocular surface reconstruction and advanced anterior segment surgery.

Dr. Freeman has worked with aniridia patients for many years, first during his fellowship under Ed Holland, then in Memphis with Peter Netland. During this time, he was the first to characterize aniridic fibrosis syndrome. I just learned that a couple of years ago about you, Dr. Freeman. I thought that was really interesting. He’s currently serving on ANA’s new medical advisory board.

He also serves as a medical director of the Mid-South Eye Banks and on the board of the World Cataract Foundation and the Advancing Sight Network. He has recently retired from private practice but continues to staff and teach residents for the VA and the University of Tennessee Ophthalmology Department and is looking forward to staying involved in the care of and research for congenital aniridia corneal condition.

Now, since I have met Dr. Freeman but I’ve never had the privilege of seeing him as a patient, I asked one of his patients to tell me a little about him. This was Carrie Carlyle’s response: “I was a patient of Dr. Freeman’s from the time that I was about 10 years old. He has taken really good care of me along with all of his other patients. One thing that stuck out to me was that he’s not only concerned with my eyes, but he was also always interested in everything else going on in my life. He would ask me questions about my service dog, my family, how work was going. To me, that’s what makes a fantastic doctor—one that wants to know about all the aspects of their patient’s lives. Dr. Freeman is honest, kind, hardworking, and he will be so dearly missed as he retires from private practice.”

Dr. Freeman, I am so honored that you’ve joined us here tonight. Thank you.

Dr. Freeman: Well, thank you. It’s an honor to be here. It really is. Thank you.

Janelle Collins: I want to say thank you to everybody who submitted questions ahead of time. I got a whole bunch of them—four pages of questions here for us to go over. If you think of more questions as we talk, please feel free to ask them in the chat. We will do our best to answer as many as possible tonight. However, I do want to mention that the aniridic cornea is an extremely complex topic.

I hope you are seeing my screen with an iceberg on it. The reason I’m showing this is because what we see as patients when it comes to the cornea is really just the tip of the iceberg here. What happens to give us this clinical care really is much more deep and involved than most of us know. So tonight, Dr. Freeman and I plan to handle this tip of the iceberg. We’re going to talk about an introduction to the cornea, the anatomy—how it works, how it is supposed to work. We are not going to get in-depth into clinical research, preclinical research, or things of that nature. We are going to have multiple episodes actually related to the cornea.

Right now we’re planning at least two more. We might even do a third after that. We’re not sure yet. But in those, we will handle things like clinical research and things that are coming up in the realm of treatment. So I just wanted to set that stage ahead of time to know that we aren’t going to cover absolutely everything because there’s way too much to cover with the cornea to do that in one hour. So this is just, like I said, the first in a multi-part series.

So we’re going to get started with some real practical introductory questions. I’m going to start with this because it’s almost weird to admit this now, but when my Ellie was diagnosed, you know, 16 plus years ago, almost 17, my first thought when the doctor said to me, “Well, she doesn’t have an iris,” my first thought was, “Wait. The iris is the colored part, right?” Like it had been years since I had taken a biology class or anything that talked about the eye, right? And so a lot of times I think when new parents get this diagnosis, there’s a lot of terms we don’t know.

Dr. Freeman: Sure. And I won’t necessarily share my screen, but I’ll sort of use my hands a lot. But if you imagine the eye is like a camera. So it has a lens on the front, and it has a retina or film in the back of it. The cornea is the front lens of the eye. You have an internal lens, and that is what becomes a cataract later in your life. And that’s what’s behind the pupil. The pupil is what gets bigger and larger.

Aniridia, the classic finding, is that you don’t have much of an iris at all. This can be variable. But the iris is not formed, which is largely how it’s diagnosed. But also, to go back to the iris—when you’re looking at somebody, you’re looking through your clear cornea and seeing the color of their iris. If someone has a brown eye, you’re seeing their brown iris through your cornea and through their cornea. You couldn’t see it if the cornea wasn’t clear.

Aniridia comes with a problem with the iris, and that’s where the term comes from. Then, it also has nystagmus. Nystagmus is a classic finding. This is related to the development of the visual system and probably, in large part, with what’s called foveal hypoplasia. That just means the retina, which is the film of the camera, is not fully formed.

And when the retina isn’t fully formed, it’s sort of like the brain is trying to track on something, but it doesn’t have enough data to steady itself. So it’s sort of like a camera that’s trying to focus on something, but it keeps shifting. We think that’s what nystagmus is.

So that would be the classic triad: foveal hypoplasia (which means the retina is not fully formed), aniridia (the lack of iris), and nystagmus, which is probably related to foveal hypoplasia.

Janelle Collins: Excellent. Thank you. So you talked about foveal hypoplasia and the iris. Can you talk a little bit about some of the other differences or ways that the eye anatomy itself is different?

Dr. Freeman: Well, what’s interesting is you have a series of things that kind of went wrong or went off course or were not fully finished during development. Then, you have things that happen afterward. One of the big things we’ve learned from basic science research is that PAX6, which we know is the gene involved in most aniridia cases, has adult functions as well. We think this is part of why the cornea starts to get keratopathy, which just means disease of the cornea.

The big limitation from birth is foveal hypoplasia. The fovea is not fully formed in normal human infants either. Babies don’t have their full vision at birth, but it develops over the first six to nine months of life. That’s when they gain fine vision. Initially, everything is blurry, and through this process of looking at the world and interacting, the brain develops clear vision. This happens in the first year of life.

This is why, in experiments with monkeys, if you deprive the visual system of stimulation (by, for example, covering an eye), it results in amblyopia. Similarly, if an infant is born with a cataract and we don’t remove it early, that eye won’t develop fine vision. Even something like a droopy eyelid that covers the eye can prevent it from developing normally.

So there’s an interaction between the anatomy at birth and the need for visual input to develop fine vision. In aniridia, these anatomic problems at birth prevent normal visual development.

Janelle Collins: Right. Okay. So tell us more about the cornea. I think I remember you saying once that this is literally a problem “right in front of our eyes,” because the cornea is right there. How does a typical cornea function throughout a person’s life?

Dr. Freeman: The cornea is a clear dome, like a bowl turned upside down. It has three main layers. The outermost layer is the corneal epithelium. “Epi” means outside, so this is the skin of the cornea. Then there’s the corneal stroma, which is the thickest layer, and the corneal endothelium, which is on the inside. The cornea is only about half a millimeter thick—extremely thin.

The cornea is unique because it’s a living tissue without blood vessels. Most of the body has blood vessels, but the cornea does not. That’s one of the reasons it stays clear. The outer epithelium regenerates regularly, with new cells forming at the periphery and migrating inward. This process keeps the cornea healthy.

Normally, people live their entire lives without issues. Their cornea stays clear. But in aniridia, this process starts to break down, leading to aniridic keratopathy.

Dr. Freeman: And what happens in the normal cornea is if you look at the top picture, you have a ring of what are called limbal stem cells around the normal cornea. These provide the epithelial corneal cells, which function like the skin of the cornea. As you know, our skin is always reproducing new skin cells. If you rub your hands together, some of your skin cells fall off.

Well, your cornea is always desquamating corneal epithelial cells. A new one is made in the periphery where the limbal stem cells are, then it moves to the center and is lost on average 21 days later. So every time you blink, you probably lose a few corneal cells. Throughout your whole life, your corneal limbus—the ring around the cornea—provides epithelial cells that grow over the cornea and help keep it clear.

What’s interesting is the presence of blood vessels. Blood vessels grow up to that limbus. In fact, there are a lot of blood vessels there, forming a network of blood vessels right at the periphery. Your cornea gets part of its oxygen from those blood vessels and also from the air itself.

Janelle Collins: Oh, fascinating. I did not realize that. That’s cool. Now, how do our tears typically help our cornea?

Dr. Freeman: Tears are very important. If you don’t have tears, these are living cells. Think about how you grow cells in a petri dish—you’re always having to add nutrients to keep them alive. Similarly, living cells inside your body are bathed in fluids that keep them alive.

The skin is made up of a particular type of cells that become different as they move outward, protecting you while constantly shedding. The cornea is unique because it isn’t as tough as skin. It’s not keratinized. The skin contains keratin, a waxy substance that protects it, but the cornea does not. In fact, if you don’t have enough vitamin A, the cornea starts to become keratinized, making it similar to regular skin, which leads to scarring and vision loss.

Tears, produced by the lacrimal gland, contain essential molecules that nourish the cornea. The conjunctiva (the white of the eye) has goblet cells that secrete chemicals necessary for corneal health. The edges of the eyelids also secrete oils. So, if you look at tears, they contain a complex mix of molecules that maintain the cornea. Losing the tear film can lead to vision impairment. This is likely part of the problem in aniridia—tear production and composition are not optimal.

Janelle Collins: Okay, so that’s a great transition. How is aniridia different from a typical cornea? One person, Hannah from Hungary, asked: What causes corneal epithelial cell deficiency?

Dr. Freeman: We’re still figuring that out. It’s a classic “chicken or the egg” scenario. We believe the primary issue is the maintenance of the corneal epithelium.

Remember, the outer layer of the cornea regenerates every 21 days. In aniridia, something goes wrong with this process. If you experience a chemical burn on the cornea, for example, it damages the limbal stem cells. Even if only the surface is affected, the cornea can become scarred and opaque because the epithelial cells aren’t functioning properly.

Some conditions, like prolonged use of old-fashioned contact lenses, can damage the limbal stem cell region, leading to corneal scarring. Stevens-Johnson Syndrome is another condition that damages the limbal stem cells and ocular surface. If you don’t maintain a proper limbal region, the cornea loses clarity.

Janelle Collins: Why can’t we just do a corneal transplant in these cases?

Dr. Freeman: This is probably one of the most important concepts to understand. Corneal transplants have been performed for over 100 years. They are typically successful because the cornea lacks blood vessels, meaning the immune system does not aggressively reject the new tissue.

However, in aniridia or chemical burns, the limbal stem cells are compromised. If a corneal transplant is performed on a patient with healthy limbal stem cells, the host’s own stem cells will migrate to the new cornea and keep it clear. But in aniridia, those limbal stem cells are defective. The cornea transplant may appear clear for a short period, but over time, the limbal stem cell deficiency causes scarring and clouding.

Janelle Collins: So, why not transplant the limbal stem cells as well?

Dr. Freeman: You can, but here’s the problem—limbal stem cells are surrounded by blood vessels. If you transplant limbal stem cells from another person, the immune system recognizes them as foreign and rejects them, just like it would with a kidney or liver transplant. To prevent rejection, patients need systemic immunosuppression—medications similar to what is used for organ transplants.

Dr. Holland, one of the leading experts in the U.S., pioneered this approach. He used systemic immunosuppression, similar to what is used for kidney transplants. While it can work, these drugs are rough on the body. They help prevent rejection but have significant side effects, making this an imperfect solution.

To summarize, corneal transplants work well in normal cases because the cornea lacks blood vessels. If the limbal stem cells are healthy, the host’s own stem cells can maintain the clarity of the transplanted tissue. But in aniridia, the limbal stem cells are defective. Even if a cornea is transplanted, it will eventually become opaque again. That’s why traditional corneal transplants are not the best solution for aniridia patients.

In aniridia, it’s a problem primarily with the stem cells. We’re still figuring this out. There is some debate, but we know that stem cells are part of the issue. Dr. Holland made it clear to me that performing cornea transplants for aniridic keratopathy is not indicated because you’re not replacing the defective limbal stem cells. Sometimes they will work for a short time, but they slowly become scarred over.

Janelle Collins: You’ve mentioned the term keratopathy, and we’ve discussed it as a disease state. You’ve also brought up limbal stem cells. Are there other contributing factors besides the limbal stem cells, or is that still an area of research?

Dr. Freeman: We’re still researching this, but we know it’s part of the problem. One interesting aspect is that PAX6 is a gene conserved throughout evolution. Biologically, if a gene is conserved across different species—like worms, fruit flies, mice, and humans—it serves an important function. I believe God used it during evolution, but it also plays a role in adult maintenance throughout a person’s lifetime.

Because PAX6 is such a useful molecule, nature has applied it in various biological functions. This gives us hope that if we can replace it in individuals with aniridia, we may be able to slow down, halt, or even reverse some of the degradation that occurs over a lifetime.

Janelle Collins: Let’s discuss the progression of aniridic keratopathy. Can you describe how the cornea changes over time?

Dr. Freeman: Sure. Initially, individuals with aniridia start with a clear cornea. Over time, the condition progresses from the edges inward. We often talk about foveal hypoplasia setting the baseline for vision. This baseline may be close to 20/50 or, in some cases, as poor as 20/200. When aniridic keratopathy sets in, vision drops below that baseline.

If we could just fix the cornea, we could restore patients to their baseline vision. Other factors like glaucoma and cataracts also affect vision, but those have more conventional treatments. Corneal issues, however, lack established solutions.

Janelle Collins: That leads into my next question—what is the rate of occurrence?

Dr. Freeman: Good question. If we look at young children, say six or eight years old, aniridic keratopathy isn’t typically present. However, identifying it in babies is challenging. There’s a diagnostic method called late staining, but it may not always be clear.

A general estimate is that around age five, only about 10% of individuals with aniridia exhibit keratopathy. By age 25, that number rises to approximately 50%. There is variability, so this assessment doesn’t apply to everyone, but the condition tends to become more apparent after the teenage years, significantly impacting vision.

Janelle Collins: Is there any correlation between different genetic mutations causing aniridia and the severity of corneal disease?

Dr. Freeman: That’s a great question. I’m not entirely sure. There are some non-PAC6 genes that can cause aniridia, and there are papers exploring genotype-phenotype correlations. However, I’m not aware of strong conclusions yet.

One point I’d emphasize is the importance of knowing one’s specific genetic mutation. Targeted therapies are emerging, and certain mutations may respond to different treatments. For example, Ataluren therapy is being explored for premature termination codons (PTC), which make up about 50% of PAX6 mutations. As research progresses, individuals with specific genetic profiles may benefit from these emerging treatments.

Janelle Collins: Let’s discuss prevention. Many parents of infants with aniridia want to know—are there any treatments or preventative procedures for a three-month-old baby?

Dr. Freeman: We don’t have definitive preventive measures yet. We are trying to extrapolate from conventional therapies, but in many ways, we’re still in the early stages of treatment.

We believe that the corneal epithelium in aniridia is more fragile and delicate. Because of that, we encourage protective measures. For example, someone asked if swimming in a chlorinated pool would be a bad idea.

As a teenager, I used to swim with my eyes open in heavily chlorinated pools. I remember seeing halos around lights afterward. I think that exposure would be particularly bad for individuals with aniridia. It’s an additional insult to an already vulnerable cornea.

Individuals with aniridia likely have reduced limbal stem cell reserves, meaning their ability to maintain corneal health is compromised. We recommend minimizing potential insults to the cornea. Avoid direct exposure to strong fans or wind, as that can cause tearing and irritation. Just like when you cut an onion and your eyes water in response to irritation, your eyes react to protect themselves.

Using preservative-free artificial tears is another good measure. We know that preservatives in standard eye drops can cause long-term corneal damage. Even some preservative-free solutions contain additives that may not be ideal for aniridic eyes. It’s all about minimizing unnecessary exposure to irritants.

They add different components to preservative-free tears, and we know that some people are sensitive to these additives. If a certain brand causes red eyes, it might be due to sensitivity to thickening agents or other substances. Typically, we recommend protecting the eyes and being as gentle as possible. For instance, if using glaucoma drops, try to use preservative-free options.

Use goggles when swimming in a pool. When outside in the wind and sun, wear a hat and sunglasses to protect the eyes. Many individuals with aniridia are already sensitive to wind and sunlight, in part because they lack an iris.

Janelle Collins: Are there any tried-and-true treatments you recommend?

Dr. Freeman: I have always used autologous serum, which consists of eye drops made from the patient’s own blood. While research is still at a preliminary stage, some data suggests that autologous serum helps individuals with aniridia. It does not reverse the disease but can improve symptoms. Autologous serum contains growth factors and vitamins from the patient’s own blood, mixed with preservative-free tears. While not universally recommended, I would likely use it if my child had aniridia.

Janelle Collins: That leads me to a question I wanted to ask—if you had a child with aniridia, what would you do?

Dr. Freeman: Autologous serum would be one option. Additionally, I would take precautions such as using protective eyewear and preservative-free eye drops.

Janelle Collins: Should we be more concerned about pink eye in children with aniridia compared to other children?

Dr. Freeman: Not necessarily. Pink eye usually resolves on its own. Many cases are viral and associated with colds. Some people assume they need antibiotics for pink eye, but if it clears up in a few days, antibiotics are not required. However, if the condition does not improve or worsens, seeking medical attention is advisable. If an eye becomes excessively gooey, sticky, or has pus, visiting an eye care professional is recommended.

Janelle Collins: What about scratches on the cornea—should we be more concerned than we would for a typical patient?

Dr. Freeman: Yes. A scratch is another form of insult to the eye, depleting its reserves. Superficial keratectomy, which involves scraping off part of the corneal epithelium, is sometimes used to treat corneal scars. However, most experts believe this approach is unlikely to be effective in aniridic keratopathy. If we could scrape off diseased epithelium and apply a special solution that encourages healthy regrowth, that might be a solution. Avoid scratches whenever possible, as they can lead to infections. Using antibiotic drops after a scratch is generally recommended until healing occurs.

Janelle Collins: David from Michigan asked: What early signs should we look for in younger children or teens to detect corneal issues?

Dr. Freeman: Worsening light sensitivity, increased redness, excessive tearing, and general discomfort are indicators. Photophobia (light sensitivity) tends to be a baseline issue in aniridia, but if it worsens, that may signal a developing problem.

Recurrent corneal erosions can also occur. These are like scratches that appear without an external cause. One way to think about it is that the eyelid may stick to the cornea during sleep, and when the child opens their eyes, part of the cornea peels off.

Janelle Collins: How does environmental control help with recurrent erosions?

Dr. Freeman: Environmental factors play a role. For instance, in colder climates where heaters run frequently, indoor humidity levels drop. This increases the likelihood of dry eyes and recurrent erosions.

A classic scenario is a person catching a cold, taking Benadryl (which dries out secretions), sleeping in a room with low humidity due to heating, and then waking up with a recurrent erosion. Keeping indoor humidity levels between 40-50% can help. A humidifier may be beneficial, especially in winter. Measuring indoor humidity with a hygrometer allows for better regulation.

When humidity gets really low, typically below 35%, using a humidifier can help. In the summer, air conditioners work to keep humidity below 50%, which means protecting yourself from air movement is essential.

Janelle Collins: Oh.

Dr. Freeman: This may sound odd, but wearing a baseball cap indoors can help by reducing air movement over your face. Many dry eye patients find relief this way.

Janelle Collins: That’s a simple yet brilliant tip for managing dry eye. I had several people ask—what is the recommended treatment when keratopathy becomes severe?

Dr. Freeman: There isn’t a single recommended treatment, and this makes things challenging. If it were my child, I would struggle with the decision as well. A standard cornea transplant won’t work long-term—it may help for a short time but ultimately fails.

A limbal stem cell transplant is an option, though it comes with challenges, primarily systemic immunosuppression. While it can work, studies show that aniridic patients do not respond as well as others. We suspect this is due to ongoing maintenance issues related to the PAC6 gene. Some success has been observed, but the procedure comes with risks. If you have access to a sophisticated healthcare system that closely monitors immunosuppression, it may be a viable path. However, these transplants don’t last forever—if you get 10 years, that’s considered good. Additionally, each transplant primes the immune system, making future transplants more difficult.

Janelle Collins: If only we could grow our own corneas!

Dr. Freeman: Exactly. That would eliminate so many complications. Another potential solution is an artificial cornea. There are artificial corneas in development that could improve outcomes. A major advantage of an artificial cornea is that vision can return almost immediately. I’ve implanted the Boston keratoprosthesis (KPro) in patients with fully opacified corneas, and in some cases, they were seeing 20/20 the next day.

Janelle Collins: Wow.

Dr. Freeman: The downside of artificial corneas is that they create a connection between the sterile interior of the eye and the outside world, which increases the risk of infection. I have some aniridic patients with KPro implants who are doing well—but next month, they might not be. The risk of sudden, catastrophic vision loss due to infection is a major concern. However, a diligent patient who follows care protocols, takes medications as prescribed, and has regular check-ups can do well with artificial corneas.

Both of these treatment pathways—limbal stem cell transplantation and artificial corneas—come with risks and require active management by both the patient and clinician. Neither option is perfect, but they are currently the best we have.

Janelle Collins: Sometimes, we see babies with aniridia born with completely clouded corneas. In rare cases, a corneal transplant is necessary. But we don’t do stem cell transplants at that age, correct?

Dr. Freeman: Correct. If a baby is born with a severely cloudy cornea, they may need a corneal transplant so that their brain can develop proper vision. Otherwise, the visual system won’t develop correctly. However, pediatric corneal transplants are particularly challenging.

I recall a case involving a patient with Peter’s anomaly, a congenital condition affecting the cornea. This child had multiple complications—glaucoma, cataracts, and opacified corneas. Working with Dr. Peter Netland, we performed corneal transplants and implanted Ahmed valves for glaucoma treatment. Unfortunately, the corneal transplants failed within a year due to pediatric corneal rejection, even with steroids.

After discussing options with the family, we proceeded with Boston keratoprosthesis implants in both eyes before the child was 18 months old. Managing this case required intensive follow-up and care, but it was critical in providing the child with functional vision.

She did well for years, but about eight years later, one of her eyes developed a retinal detachment. Despite multiple attempts to repair it, the detachment became inoperable, and she lost vision in that eye. Fortunately, her other eye remained stable, and she is now starting college, studying astrophysics. It’s an inspiring story because, had we not intervened, she wouldn’t have had the vision she does today. However, she still requires monitoring by glaucoma and cornea specialists, and there is always a risk of further complications.

Janelle Collins: That is incredible. It really speaks to the complexity of these decisions.

Dr. Freeman: Exactly. If we had done nothing, she wouldn’t have had these years of vision. However, we also don’t have a perfect solution—surgery always carries risks. Maybe in the future, we’ll have a better artificial cornea, but for now, even replacing her current artificial cornea would be a risky procedure.

Janelle Collins: Joe in the chat mentioned that this balancing act of “do no harm” while trying to improve vision is incredibly tough, especially with corneal issues in aniridia.

Dr. Freeman: Absolutely. Another case that stands out was a patient from St. Louis who had undergone a keratoprosthesis (KPro) procedure due to anterior segment dysgenesis. One of his eyes had never developed, and the other had already undergone a KPro, but complications arose. The KPro was failing, and since no one locally could manage it, he came to Memphis for treatment. We attempted another KPro, but that one also started to deteriorate. Eventually, we had to remove the KPro and perform a regular corneal transplant just to save the eye. Despite our best efforts, the eye ultimately became blind.

Janelle Collins: That’s heartbreaking.

Dr. Freeman: It is. The reality is that KPros can work beautifully when they succeed, but when they fail, it’s often catastrophic. That unpredictability makes them such a difficult option to manage.

Janelle Collins: Kelly from Texas asks: “My doctor prescribed short-term steroid drops for corneal swelling. Is this safe?”

Dr. Freeman: Steroids can be helpful, but ophthalmologists are always cautious because long-term use can cause glaucoma. If corneal swelling is occurring, it could indicate an issue beyond aniridic keratopathy—possibly endothelial cell failure. Other factors, such as prior surgeries or high intraocular pressure, could contribute to endothelial cell damage. Patients using steroid drops should be monitored regularly to ensure they are not developing complications like elevated eye pressure.

Janelle Collins: Adrienne from Maryland wants to know: “For a newly diagnosed infant, what type of examination is needed to check the cornea? Can a standard ophthalmology exam detect issues?”

Dr. Freeman: At some point, an exam under anesthesia (EUA) is usually needed. Ideally, a pediatric ophthalmologist should collaborate with a cornea specialist. However, coordinating such care can be challenging. Centers with specialists familiar with aniridia provide the best chance for accurate diagnosis and management.

The biggest risk for irreversible damage in infants is glaucoma. High intraocular pressure can damage the optic nerve, which, like brain tissue, is very difficult to regenerate. Regular pressure monitoring is essential. Checking eye pressure in babies can be tricky—it often requires an EUA. Some handheld devices, like the iCare tonometer, can check pressure without anesthesia, but obtaining accurate readings in infants remains a challenge.

Janelle Collins: So in most cases, corneal issues are not an immediate concern for newborns with aniridia?

Dr. Freeman: Correct. If corneal problems exist at birth, they are usually obvious. The bigger risk early on is glaucoma, which requires close monitoring. Managing aniridia requires balancing necessary exams with minimizing stress on the child. It’s a long-term process of ongoing assessments and interventions.

Janelle Collins: Okay. That’s fascinating. Just a couple more questions since we only have three minutes left. If you have a nine-year-old patient whose cornea has been damaged from glaucoma treatment, what options are available? Would scleral lenses be an option?

Dr. Freeman: It depends. Glaucoma treatment can sometimes damage the endothelium, and in those cases, we have transplant options such as DMEX, which involve endothelial cell transplants. However, in a nine-year-old, these procedures are more difficult.

Whenever we discuss transplants, scarring is a major concern. Even in normal patients, repeated corneal transplants are not ideal. Each surgery introduces scar tissue, and in aniridic fibrosis syndrome, scarring can be even more pronounced. The glaucoma procedure itself could have damaged the epithelium, the stem cells, or the endothelium.

Janelle Collins: Okay. Two more quick questions. Patty from Florida asks: “What doctors would you recommend for extreme keratopathy? Do you know of anyone doing cutting-edge work?”

Dr. Freeman: Dr. Djalilian and Dr. Holland are the main experts I know of. Peter Netland in Virginia also works with a cornea specialist, Dr. Cheung. If there were groundbreaking treatments available, these doctors would be at the forefront and eager to share their findings. I hope to contribute to improving treatments for aniridic keratopathy, but as of now, we still don’t have a perfect solution.

At a recent meeting in Virginia with Peter Netland, there was discussion about the role of steroids. Once glaucoma is controlled, chronic steroid use may help prevent some of the corneal scarring that develops over time.

Janelle Collins: Final question: If your child were in their 20s with extreme aniridic keratopathy, would you lean towards treatment now, even with imperfect options? Or would you focus on maintaining eye health while waiting for future advancements?

Dr. Freeman: If they were in their 20s, I would have a serious conversation with them about their personal preferences and long-term goals. I would also advise that any surgical decision be approached cautiously—once you undergo surgery, you can’t undo it. Medical treatments can often be stopped, but surgeries are permanent.

I would recommend addressing one eye first, keeping the other as a reserve. This way, they could assess their level of function and make an informed decision about their quality of life. One of my patients from Arkansas chose to proceed with surgery, and while she understands the risks, she is grateful for the vision she has.

If it were me, I would opt for an artificial cornea in one eye while ensuring that my doctor monitored me extremely closely—perhaps even monthly. I would be proactive in addressing any issues immediately and hope for the emergence of better treatments in the near future.

Janelle Collins: Right. That makes sense. Thank you so much. That’s all the time we have for questions tonight. Before we close, I want to remind everyone that we will continue this conversation in part two of our corneal series, scheduled for April 3rd. We will be joined by Dr. Albert Cheung from EVMS, who will discuss both current treatments and exciting developments on the horizon.

Additionally, in May, we will host Dr. Djalilian, who will focus on ongoing research. There are currently many different research approaches being explored, and he will shed light on the most promising ones. Our goal is to bring hope by showcasing what’s ahead in the field of corneal treatment.

A recording of this episode will be available on the ANA website and YouTube channel soon. Be sure to sign up for ANA newsletters to receive updates on when the recording is ready.

Before we go, I’d love for everyone to turn on their cameras so we can say hello. I’ll remove the spotlights so we can see everyone.

Thank you all for joining us. Dr. Freeman, we truly appreciate your time and expertise. We look forward to continuing this conversation in future sessions!

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(The transcript continues with audience interaction and closing remarks.)