Your Eyes and Chronic Graft-versus-Host Disease
Saturday, April 30, 2022
Presenter: Zhonghui Katie Luo, MD, PhD, Massachusetts Eye and Ear
Presentation is 37 minutes long with 23 minutes of Q & A.
Summary: Ocular graft-versus-host-disease occurs in 40% to 60% of allogeneic transplant patients. Early detection and treatment are important. This presentation reviews the most common symptoms and effective remedies for ocular GVHD.
- Ocular GVHD GVHD attacks the surface of the eye and tear glands causing swelling, dryness, crusting and scarring.
- Patients with ocular GVHD should not wear conventional contact lenses, rub their eyes, dig mucus out of the corner of the eye, or use redness relievers, and should wear sunglasses outdoors and reduce screen time.
- Eye surgeries, including cosmetic surgeries, should be avoided unless necessary for vision such as cataract and glaucoma surgery. Ideally these surgeries should be done by a surgeon who understands GVHD.
(05:02): Ocular GVHD typically occurs five to 24 months after transplant, although it can also occur later.
(07:26): Ocular GVHD can cause scarring on the surface of the eye
(07:56): Ocular GVHD destroys tear glands, causing very dry eyes and a sensitivity to light.
(14:07): Ocular GVHD may look like an infection, but it is not, and will not respond to antibiotics.
(14:46): Adding moisture to your environment and using preservative-free lubricant drops frequently can help dry eyes.
(18:04): Common dry eye products, such as Restasis and Xiidra may not work will not work for patients with ocular GVHD whose tear glands have been destroyed.; oral Pilocarpine or Cevimeline are better prescription choices.
(19:18): Punctal plugs help relieve dry eyes by preventing tears from draining from the eyes into the throat
(20:10): Steroids, tacrolimus, sirolimus and other drugs suppress the immune system and can help reduce inflammation in the eye.
(21:59): A very good treatment is autologous serum tears. They provide both moisture and nutrition to the eyes.
(22:52): Therapeutic scleral lenses, designed specifically to treat dry eyes, can be life-changing.
Transcript of Presentation
(00:01): [Michala O'Brien] Introduction of Speaker. Hello, my name is Michala O'Brien. Welcome to the workshop, "Your Eyes and Chronic Graft-versus-Host Disease. It is my pleasure to introduce you to our speaker, Dr. Katie Luo. Dr. Luo is a physician at Massachusetts Eye and Ear, Harvard Medical School. Her specialty is ocular surface diseases in cataract surgery. For the past eight years, she has worked closely with Dana Farber Cancer Institute to detect and treat ocular graft-versus-host disease after stem cell transplantation. Dr. Luo is the principal investigator on a recently completed phase two randomized clinical trial on a novel treatment for ocular GVHD. Her long-term goal is to form a patient centered care system to best serve the BMT population. Please join me in welcoming Dr. Luo.
(00:53): [Dr. Katie Luo] Overview of Talk. Hello everybody. Hi, this is Katie Luo. Thank you so much. Thank you, Sue for inviting me. Thank you Michala, for moderating. I'm so excited to be back here after two years. And before this, I was listening in on Dr. Alousi's wonderful talk on GVHD in general. If you haven't heard it, please go click and listen to it again after my talk. Some of you, I know you are there, and you are my patients, and I know who you are. I want to just give you a special shout out.
(01:26): Now, I'm going to start my talk. Today I wanted to talk about what is ocular graft-versus-host disease, and what do we see, and what do you feel if you have ocular GVHD; the etiology of ocular GVHD; and the management. After my talk two years ago, some patients told me, they said, "Your slides are scary." I feel bad I put up scary pictures, but then I thought about it. I still kept a lot of the scary pictures because they're real. I hope to improve awareness of what can happen with ocular GVHD, therefore promote our strong attention and our motivation to get early diagnosis and early treatment.
(02:29). What is graft-versus-host disease (GVHD)? Like Dr. Alousi explained earlier, our patients, because of varies of systemic conditions, mostly blood cancer, they don't have a good immune system. What happened is their own immune system gets wiped out, but a healthy donor's stem cells get transplanted into the donor's body. The pink, healthy cells are getting planted into the blue patient's body. And when they form a new system, alive and hard at work, they can defend you like your own immune system. However, sometimes because they recognize you as not their own, they recognize you as someone foreign, they might start to attack you, sometimes in one organ, sometimes in several different organs. That's why it is called, it's a graft-versus-host disease.
(03:37): Ocular GVHD occurs in 40-60% of patients transplanted with cells from a donor (allogeneic transplant). Ocular graft-versus-host disease is quite common. Conservatively speaking, 40 to 60% patients after the allogeneic stem cell transplant would have it, but a lot of patients are actually under-diagnosed. The real numbers can probably be higher.
(03:56): There are two types of GVHD: acute GVHD and chronic GVHD. It can come as just purely ocular graft-versus-host disease. It can come along with the involvement in many other organ systems at the same time. Briefly talking about... Dr. Alousi nicely explained the difference between acute versus chronic ocular graft-versus-host disease. The timing is not that strict, but the acute GVHD that involves the skin, the liver, the digestive system, sometimes and oftentimes, the eyes can be affected too. Because that's early on, that is usually quite readily detected by your transplant doctor. My focus of this talk, we're going to talk about the chronic ocular graft-versus-host disease, where most of you guys are already at home, already not seeing the transplant doctor that frequently.
(05:02): Ocular GVHD typically occurs between five and 24 months after transplant. Oftentimes the occurrence of ocular graft-versus-host disease has been reported to be between five months to 24 months, two years after the stem cell transplant. But again, timing is not strict. We did see ocular GVHD in the chronic form as soon as a few weeks after transplant. A lot of people are having other organ system involvement as well. Maybe the mild early symptoms, they don't quite pay attention to until later, it becomes quite bothersome. When I see such patients in my clinic, oftentimes my first impression is when I walk in the room, I can't really see their eyeballs because they're squinting or they wear sunglasses indoor or they put their hands over their brows. I just wouldn't know what color their eyes are because they're so uncomfortable.
(06:02): Ocular GVHD attacks the surface of the eye and the inside of the eyelids. I'm going to just talk about what you might see from outside in. Ocular graft-versus-host disease involves mostly the ocular surface, meaning the part that you can see without any instruments, without special tools. The eyelids can be red and swollen, can be crusting, hard to open in the morning. There could be the mid margin indicated by this blue arrow, you can see it's very raw and red, and there could be discharge, foam or mucus discharge in the corner of the eyes.
(00:06:40): And inside the eye lining, the conjunctival lining of the eyes, can be easily missed when things are actually happening. This is a quite a normal looking eye. The patient wasn't that uncomfortable. But when I flipped their eyelids, you can see those almost bloody blisters mixed in a patch of very raw surface. So the surface is not smooth. The surface is raw, just like when you have an ulcer inside your mouth, that looks like that. And then, these going on to form scars. So this is a fibrotic process, similarly to the process Dr. Alousi discussed in other systems.
(07:26): Ocular GVHD can cause scarring can occur on the surface of the eye. This can lead to scarring or fibrosis. When this fibrosis happens, if you look at the color pictures, they can be different extent, how much fibrosis, how much scarring there is. What we could not see at home, special tools can show you. In the black and white pictures are oil making glands. These are called the Meibomian glands. They make oil that we need in our tears. And these glands are getting destroyed by the scarring process as well.
(07:56): Ocular GVHD destroys tear glands, causing very dry eyes and a sensitivity to light. The tear glands, we can't really visualize them, but the tear glands, at the same time, are getting destroyed, and they make less tears. The eye's getting really dry. The very dry eyes would have a lot of tiny scratches. I call them tiny scratches on the surface. Our special dye and the special light can bring out all these green dots. That's what I use when I examine you in clinic. I put those drops in, to visualize these tiny, tiny thousands of scratches. That's indicating the eyes are really dry.
When the eyes is dry, and wants to heal, it wants to fix those tiny scratches. Sometimes the cells don't do what they're supposed to. They end up forming strings and clumps, and those are extremely painful. They cause you to having a lot of light sensitivity and the difficulty opening eyes.
(08:52): It’s important to get on the right treatment early once scratches on the cornea begin to form. Those were tiny scratches. Those were relatively easier to heal once we catch it, once we put you on the correct treatment. But if many, many tiny scratches, they become big scratches and become breakdowns, it's much harder to heal. For example, the previous picture showed that the little bit thinning, and now this picture shows that there's really a hole starting to form inside that purple circle. The cornea can melt and start to thin.
(09:31):. In this, I did a surgery here. I took a donor piece of cornea and sewed it onto that eye. All looks pretty good at this point, right? But then the same graft, as you can see in the first picture, that can start to melt again. This green area is showing the new melting that's adjacent to that little patch I just put on there. This was weeks after the first transplant. And then I had to take that out. I had to put a much bigger transplant there. This process actually keeps going. This patient, as we speak, actually, this nicer looking big transplant had actually melted again. And I did another procedure to try to patch it up. Once this happens, it's really not, not good. All right.
(10:22): Enough scary slides. What can we do about it? We want to understand what the problem is. We want to avoid preventable damage, and then we want you to invest. We want your commitment in management because you are the crucial part.
(10:43): Dryness, scratches and inflammation need prompt treatment. Let's talk a little bit in scientific terms of why things are happening. To simplify, I didn't put the oil glands in, but on the dryness side of the picture, basically we show that ocular graft-versus-host disease, because of the attack from the new cells living in your body, now, it destroyed the tear production in terms of making less amount of tears, in terms of not making tears, that can lead to the inability to repair. When there's no repair, we get thousands of little scratches. And those scratches are going to make the eye hurt and to make the eye want to have more inflammation. More inflammation would destroy these organs a little more and cause more scratches, so on, so forth. We start this vicious cycle. If we don't stop the vicious cycle, it's just going to keep going into the point of no return.
(11:44): The number one question I get asked in clinic is, "How long do I have to deal with this? When
(11:59): We talk about these pink cells that are getting into your body, and they do crucial, crucial stuff for you. They fight COVID, they fight flu, they fight infections and other things. But as long as they're alive, they have the potential to attack you. That's why to treat graft-versus-host disease, not only the ocular one, we have to manage them. We have to control them, don't let them burn too much, but we have to keep them alive so they do their job.
(12:33): Patients with ocular GVHD should not wear contact lenses, rub their eyes, dig for mucus or use redness relievers, and should reduce screen time. All right. Coming to the point, what are the avoidable harms that you can avoid, you can start now, start today. For example, do not wear regular contact lens. I say regular contact lens because we do have special contact lenses that I'm going to talk about later. Those are therapeutic.
(12:53): Do not rub your eyes. Your eyes are very delicate, particularly when they're vulnerable. Do not rub your eyes. I give out paper to say, do not rub your eyes with your fingers, not your knuckles, not your thumb, not your wrist, not with a towel. You get what I mean. That is number one thing you want to take home today. And you do not dig for mucus. If there's some crusting, you use a warm compress to take off, but don't dig in the corner to get that crust out.
(13:30): Do not use redness relievers like Visine, Opcon-A, Naphcon-A because those actually makes the eyes more dry, and they don't solve the problem. Do not use allergy eye drops like Alaway, Zatidor. Your itching is from those surface damages. Early on, they're not painful. They could be itchy. They could be irritating, but those drops do not help the problem.
(13:53): And do decrease screen time and take tons of breaks if you are on a screen or if you're reading a book. And again, be very careful with makeup and makeup removal so you don't introduce any chemical to your eyes.
(14:07): Ocular GVHD may look like an infection, but it is not. It will not respond to antibiotics. Another common thing is that when the eyes are in the vicious cycle, like I described earlier, the eye could look red, in pain. It's not because they're infected. Oftentimes, there's a misunderstanding about this. "I got conjunctivitis," or even a provider' who is' not familiar with GVHD says, "Hey, you've got conjunctivitis, give you antibiotics." No, antibiotics don't treat it. This is not infectious conjunctivitis. This is because your surface is in pain. Erythromycin doesn't really work. And again, do not use Visine.
(14:46): Adding moisture to your environment and using lubricant drops frequently can help dry eyes. What you can do is, when the eyes are dry, you want to make your environment less dry. You want the environment to suck less moisture out of your eyes. In cold areas like in Boston, you want to definitely use a humidifier almost all the time as long as your heat is on. And you do want to wear sunglasses or sports goggles when you're outside. And you want to point the air vents in the car away from your face to decrease evaporation. And you can always do warm compress, which is very comforting, but try not to do the brisk scrubs with a Q-tip or with your hands because your lid's delicate, your eyelids are more delicate than the normal population.
(15:39): All right, so we definitely want to keep the eyes wet because you are not making enough tears at this point, because your lens are being targeted by GVHD. So you want to put the lubricant drops in very frequently. And if possible, we want you to make more tears, but it's very hard to do. I'll explain the drugs in later slides. And we want to control the environment's humidity. This is how we keep the eyes as wet as possible. Then we could also put in a plug, I'll show you in the following slides, to let you drain less, let the air suck less out, also let your own tear drainage system drain less so that you don't drink it. You keep the moisture in your eyes.
(16:28): It’s important to use preservative free lubricants and apply them frequently, and apply them one drop at a time. Before I talk about the frequency, I want to emphasize it is so important to use preservative-free lubricant. What's preservative? If you have a big bottle of tears, and you put that several times in your eyes and there's preservative in it, that can cause toxicity in and of itself. I want you to use frequently. That's why you have to buy those preservative free ones. They look like little tiny plastic tubes. They're called single use, but sometimes you can squeeze many drops out of that one tube. There are also multi-dose possible, multi-dose meaning they're in a special package, but they look like a bottle. This has to be preservative free. You want to look for those phrases on the packaging before you buy it.
(17:13): And then frequency. When I say use it frequently, I mean one drop every time, and you can use one drop every hour. You can use one drop every two hours. You can use one drop every 15 minutes, but each time our eyes can only hold one drop. So if you put eight drops in at the same time, you're basically washing your face. You are not helping your eyes. Frequency, frequency, frequency is important.
(17:41): With a recap on that, if you can keep it clean, I would say, use one tube, at least use it up in half a day. Don't carry it everywhere and let it go bad. At night, you can use ointment, but again, same thing. You want to look for preservative free. The ointment is a little thicker. If you put some in your eyes before go to bed, it might keep you more comfortable overnight.
(18:04): Common dry eye treatment, such as Restasis and Xiidra may not work will not work for patients with ocular GVHD whose tear glands have been destroyed. Oral Pilocarpine or Cevimeline are better prescription choices. Okay, make more tears. Restasis and Xiidra are very famous for the general dry eye population. They're supposed to have you make more tears. It may or may not work in our GVHD population because if the tear glands are really not working, no matter how much you beat a dead horse, you're not going to get much out of it. However, the oral Pilocarpine or Cevimeline, these are two medications frequently prescribed by your transplant doctor or by your oral medicine doctor to treat dry mouth. They actually can improve the tear secretion. The mechanism is a little different. And most of my patients, if they have ocular GVHD, they also have mouth GVHD in that sense, vaginal too, for female patients.
(18:58): The Pilocarpine and Cevimeline, they are really very good drugs.I would highly encourage you to use one of them, even though it does have side effects of night sweats and other things. But if you use it consistently for a few weeks, you might have a happy surprise.
(19:18): Punctal plugs help by preventing tears from draining from the eyes into the throat. What are punctal plugs? If you look at the middle picture, and we have these tubes connecting from the lids, from our eyelids all the way to the back of our throat. These take the excessive moisture to the back of our throat to drain . If you were to put a bitter drop in your eye and you taste it, that's why. The plug is that little sink stopper we can put in those tiny holes to decrease the amount that drains into the throat, therefore, to keep it wetter. There are different types of punctal plugs. If your provider mentioned it, don't get scared. It is really very benign and very effective.
(20:10): Steroids, tacrolimus, sirolimus and other drugs suppress the immune system and can help reduce inflammation in the eye. Okay, next thing, what can we do? We can control the inflammation. We talk about the vicious cycle, inflammation causes more damage, damage causes more inflammation. We want to break that cycle. Systemic immunosuppression is so important. The steroids, the tacrolimus, sirolimus and the new drugs, like the Jakafi and the Rezurock, those are all great agents. They give your total body a suppression of your super active immune system. And it will work for your eyes in some capacity. They wouldn't target your eyes, but they would help with your eyes.
(20:54): When you are being tapered off of systemic steroids, you may need topical steroids for your eyes. When you are getting tapered off, particularly at lower dose or getting off those dose, and you notice some change in your eyes, you want to think about it. You want to think about it. When the strong hands put on that activity get lift up or removed, then the activity can start burning again. You want to tell your provider something that is happening. In your eyes. Your eye provider can use steroids directly in your eyes, but it is not safe to just get a bottle just to start using it. The steroids have to be monitored because you cannot go up and down as you like. It can cause severe trouble if you are doing, say four times a day, and you stop altogether, or if you just keep using four times a day for two months, and your eye pressure might get high. When you are on steroids, you have to see your provider on a regular basis to monitor possible side effects.
(21:59): Autologous serum tears - tears made from your own blood serum - provide both moisture and nutrition to the eyes. One very, very good treatment of the eyes is serum tears. What is it? We talked about the preservative for artificial tears. That's man-made lubricant. If you put a drop on your finger, it's kind of slippery, but it doesn't have any nutrition from your own body. It's basically just chemical. But serum tears are, when your blood is drawn from your arm, and the blood cells gets spun down, and the red cells gets thrown away, but the straw colored serum is put back in your eyes as lubricant tears. These are called serum tears. They not only give you moisture, but give a lot of nutrition back to your eyes. That is a very, very helpful treatment for your dry eyes.
(22:52): Therapeutic scleral lenses, specifically designed to treat dry eyes, can be life-changing. The therapeutic scleral lenses. These are not the regular soft or hard contact lens that I told you not to wear at the beginning of the talk. These are fitted by specially trained optometrists who understand what they are and who needs them. Your transplant doctor or your eye doctor should refer you to one of their trusted places to get those lenses because they can help with your discomfort. They can improve your vision. They can do a lot of wonders. It's a life changing experience for a lot of people. Of course, it's quite a process. It's high cost. Insurance coverage is not that great. There's a training that you need to learn, learn pretty hard. It's hard for you to do. However, it's something I think everybody should at least be aware of, so you were told about it, you're not like, what is that? This is a great treatment.
(23:52): There are different sites. If you download my slides, and you can click onto each places to look at what they can do for you. For example, I work a lot with the BostonSight. They have wonderful doctors, wonderful optometrists. They give you this custom made lens to put in front of your eye so that your cornea is bathed in that fluid all day long. If you look at the picture on the right side of the slide, the first line, the thin white line with a bright reflection on it, that is actually the lens. You can see the shape of the lens. And there is another thicker wider line inside that is actually the cornea of that patient. That black space between the first line and the second line, that is the pool of fluid. the cornea is bathing in all the time. That's why it is so comforting. And it does correct your vision. This is a treatment I actually started to get my patients in them much sooner than before, because why do you have to suffer if there's something that can really, that can make your life much better?
(25:00): Surgeries, including cosmetic surgeries, should be avoided because they are not curative. All right. Surgical treatment, surgical treatments, I'm going to advocate for no surgical treatments. The goal is to avoid having any surgery if you can. Why? Because it's not curative. Like I showed you those pictures, if there's a hole, I put a patch on the hole, but then the patch can melt again or the nearby tissue can melt again. Then I cut bigger. I put on bigger. This is just not going to deal with the problem. It is better not to get to the point that you would have to have a surgery, and then we can make your quality of life, maintain that quality of life, much better than if we have do those big surgeries.
(25:51): Other surgeries. Some people tells me, "My lids are drooping. Can I go get my lids lifted?" I always tell them, "Please don't, unless your lids are drooping so much, you cannot see out of the pupil. Then maybe lift up a little bit, but I would highly recommend against cosmetic eyelid surgeries, lip tattoo, lash extensions, laser vision correction, all those things, try to stay away from those cosmetic procedures because you want your tissue not to be touched if you can. Any surgery is going to damage your tissue. It might actually cause a flare up that is really hard to control.
(26:32): Cataract surgery and glaucoma surgery may be necessary but should be done by a surgeon who understands GVHD. Cataract surgery is an exception because people, after transplant, oftentimes you can't avoid having steroids somewhere in treatment. And patients tend to have earlier onset of cataracts or more rapid progression of cataracts than the general population, but you won't be able to see well if you have cataracts. That's why cataract surgery is an exception. You have to have it done, but you do have to find a surgeon who understands what GVHD is because although the surgery might be very similar, your post-op or healing process is very, very different compared to the general population.
(27:15): And then, of course, in some rare occasions, patients would need glaucoma surgery if the eye pressure's too high, can't be really treated with laser or drops. Those [kind of surgeries are] medically necessary to prevent you from going blind. Those kind of surgeries, yes. If you have to have it done, you have to have it done, but better find someone who knows what they're doing with GVHD patients.
(27:38): There still is not an FDA approved special treatment for ocular GVHD but clinical trials may help. All right. The next point is, this is a very poorly understood area. A lot of doctors are working on it. A lot of scientists are working on it. We still don't know a lot. To this day, we still don't have a FDA approved special treatment for ocular graft-versus-host disease. What you can do by participating any sort of research, you are doing you or our future patients a favor.
(28:21): For example, Dr. Brock, from the BostonSight, and myself, we actually did a survey study right here at the BMT InfoNet last year. And we sent questionnaires out, and kindly a lot of patients participated, answered the questionnaires. We summarized it. We wrote a paper. There are two papers, actually, just getting published right now. And it helps our understanding. It doesn't mean you have to participate in clinical trial. You should, if you can, but even in other ways, participating in research really is going to help this field going forward.
(29:01): Patients are often overwhelmed with persisting ocular GVHD. Now, about yourself. What can you do, and what should you do for yourself? I know you are very, very overwhelmed. You are very tired. You are hurt. You're fed up. I have a huge patient population, so at any given moment, I have several of them actually in the hospital from all sorts of complications, sometimes recurrence and sometimes GVHD needed treatment. It's very debilitating.
(29:34): And even those ones who are not in the hospital, you have lots and lots of clinic visits to go. You have to see the skin doctor. You have to see the mouth doctor. You have to see the lung doctor, and you might live two hours away from the hospital, so each time it's a whole day, and you're exhausted coming home. And your loved ones, the ones who are taking care of you, it is so tiring. We know. We do know that. However, nobody else knows how you feel. So you are the one who can report your symptoms. You are the one, with all this education, with all these symposium lectures, you know this is what I need to watch out. But before the transplantation, I never felt itchy or hurting in my eyes, but now what's going on? Every morning, I open up my eyes, there's so much crust, I can barely see anything if I don't put a hot towel, remove those crusts. These are the things you do want to mention it to your transplant doctor immediately. And then, you can be sent to the specialist to take care of you.
(30:49): Early diagnosis can be crucial in limiting the problem before nothing more can be done. Sometimes early diagnosis is crucial. Unfortunately, I have seen patients who, let's say things already happened, a few years later to the point, when I look at them, it's like, "Sorry, at this point, there's nothing that can be done at this point. I feel really, really bad." I really hope from this symposium, from the advocacy, we're going to make everybody aware, and then we can get everybody [treated] as early as possible. It doesn't matter if you come in and I say, "You're fine. Don't worry about it. I'll see you in six months." But I would hate you come in, and you say, "oh, it started six months ago". Well, where were you six months ago? Why didn't you tell me anything? Let's try to work together to avoid getting to the point of no return. That is sincere my hope.
(31:46): Caregivers can be crucial in urging patients to seek help, accompanying them to visits, and reminding them of important tips. What can your family do? Your family is already doing this extraordinary work to take care of you. At the same time, they might still have to do their day job and manage. If your kids are helping, if your wife, your husband, they're helping, they're already doing so much to help you get to where you are. And they can also further help advocate for diagnosis and treatment.
(32:13): For example, you might be uncomfortable. You might tell your loved ones. And then your loved ones could be the one that tells the transplant doctor say, "Hey, Susan was really not looking like who she usually was. And her eyes were beefy red for three mornings in a row." Report the information and try to get you to the right doctor who knows about a GVHD to take care of you. It's not one trip. It cannot be done in one trip. It has to be a very diligent follow up, home treatment, follow up. And with emergencies, you got to probably drive in right away, so on, so forth.
Dr. Katie Luo (33:00): Also, the family member will be best to stay in the room when there's a treatment or procedure discussion going on. An extra pair of ears always helps. Sometimes you feel like you heard everything, but two hours later, you might forget a lot. But with the [extra] pair of ears there, you might remember more or one might go home and tell you, "Okay, don't rub your eyes. Dr. Luo said, 'Don't rub your eyes.'" All those little things would help.
(33:34): Your local eye doctor should coordinate your care with an ocular GVDH specialist. What is the job of your eye doctor? Let's say, not every eye doctor is trained for ocular graft-versus-host disease. They might not have enough experience. However, they are trained eye doctors. They know what's normal, what's not normal f you tell them' this is how you feel, this is how the eye looks'., So if you have a local doctor who is only 40 minutes away from you, and your GVHD ocular doctor is two hours away from you, go to that first doctor. Get a good relationship with your local doctor, because you want to be with someone you can go to in times of emergency when you don't know if it's okay or this is not okay. And then, they can all be on your side. They can be on your team. And then they can collaborate with your GVHD doctor to maybe decrease the number of trips you have to make far away and have some care done locally. It is good for you to promote the communication and a working relationship between different doctors. You don't want to ditch your local doctor and say "You don't know anything about GVHD." That is very hurting. A.
(34:51): Conclusion. All right. In the end, I would say, I've known so many doctors in other services, the transplant service, dermatology, oral medicine, oncologists, everybody I know really wants the best for their patients. They want to work with you. And if you can be, let's say one thing you can be is say, is that, "I just saw my dermatologist two hours ago. The dermatologist didn't write a note yet, but she said, blah, blah, blah. And she wanted me to increase my steroids from 20 to 25 milligrams." That information you bring to your next doctor is crucial. If you just say, "Oh, I just saw my skin doctor, yeah, I don't know." "What's going on?" "I don't know." "Any change, your medicine?" "I don't know, send it to the pharmacy." That would be less likely to help you to have the teamwork around you.
(35:49): All right. I want to go back to the beginning of the talk to see our purpose today. First, I hope my talk has helped you understand the problems, the etiology of ocular graft-versus-host disease. And the second, remember there' are things you can do at home starting today to avoid preventable damages. And third, I want you to get on the team. The team is for you. It's we and us all working together for you to make your life better. Thank you very much. This is my talk. I'm happy to answer questions.
Question and Answer Session
(36:34): [Michala O'Brien] Thank you, Dr. Luo. This is an excellent presentation. We are now going to move into the question and answer part of this presentation. As a reminder, if you have a question for Dr. Luo, please type it in the chat box on the lower left-hand corner of your screen.
(36:53): The first question is I'm on Jakafi five milligrams a day. My eyes have gotten worse when I went from 10 milligrams to five milligrams. The corneas look good, but they're dry and painful. I'm afraid that my eyes are going to get worse. I'm four years post-transplant. My physician wants to wean me off Jakafi and manage my eyes topically. Your thoughts please.
(37:21): [Dr. Katie Luo] Okay. This is a frequent condition. When any immunosuppression gets weaned off, one might see a flare up of local organ involvement, including the eyes. In this case, I think ,if I were to handle this condition, I would communicate it directly with your transplant doctor who's managing tapering you off Jakafi. Let them talk. Bring your eye doctor and the transplant doctor together to talk about what is the reason to ween you off at this moment. Can we delay a little bit because of the eye or there's a reason to we you off? Then we have to really increase the local treatment for the eyes to assist the weaning of Jakafi, so on and so forth. This is not something that can be done just by one person. The communication is key in this case.
(38:19): [Michala O'Brien] Thank you. Do you think PRGF is superior to autologous serum drops?
(38:27): [Dr. Katie Luo] PJ... Is that Prograf? What does that stand for? If you can, whoever asked this question, can you please type in? I don't know what that stands for. I don't want to misunderstand it, but I would say, if that is not a biological product, I don't believe it is, the serum tears, the best thing is, there's no rejection. There's no reaction to serum tears because it is your own blood. It is basically your own blood, your own factors. So the eye definitely likes that drop more than the tears. It is time consuming to go get your blood drawn all the time to get it made, but when you can have it, I would say serum tears is probably the best natural occurring. This is a natural occurring fluid you can put in your eyes.
(39:22): [Michala O'Brien] Another patient asked, I frequently often have strands of mucus that cross my pupils affecting my vision. What's the safest way to remove them?
(39:32): [Dr. Katie Luo] Very good question. Yes. Mucus formation. When the eyes are not comfortable, the defensive mechanism of the eye is to make a lot of mucus. It wants to make the sticky stuff cover the surface to ease the pain. The sticky stuff forms those strings and they can block your vision. They can accumulate in corner and nobody likes them. A lot of people, they use the finger or tissue or towel to go dig. When you dig, you can pull out that long string. And that's very satisfying at the moment, but before you know it, half an hour later, another one's coming in. This behavior is actually called mucus fishing. It's a very bad behavior because the very fact that you are picking, that is stimulating the tissue inside to make more so you'll never get to the end of it, never.
(40:25): What I tell my patients is to sit on your hands. You do not touch the mucus. If it's blocking your view, you put the preservative free artificial tears in to wash them from the middle to the corner. And they're going to accumulate in the corner. I say, once a day, when you do your warm compress with the towel, you put it near the corner without digging, you just touch it. And the mucus, if there's enough, it'll come all off with the towel. But you are only allowed to do that once a day. And nobody cares how you look with a mucus in there. You have to stop digging. Stop digging is only way to stop it from forming. And I've done this so many times with so many of my patients. I know it works. But if, say, you're good for a week, you start digging on the eighth day, sorry, it'll come back.
(41:19): Okay. Let me just answer the previous question. That says it's a plasma rich growth factor. Yes. That is a synthetic sort of nutrition-containing drop. It is very good. It is very good in the sense there's a recombinant growth factor put in there. However, I don't know if there's a head-to-head study of that growth factor tears compared to own serum tears, which one is better. And I don't know the insurance, how much insurance is going to pay for that. This probably, the best way is to try both, and then use whichever one you like more.
(42:03): [Michala O'Brien] Okay. This is a question about pain management. Do you advise any prescription medications taken by the mouth to alleviate pain?
(42:14): [Dr. Katie Luo] This is a tough question. First of all, you have to know why there is so much pain. Dryness itself can cause pain. If you've got a corneal abrasion, it causes pain. If somewhere the conjunctiva is melting, it certainly causes pain. At the same time when you have pain, yes, I think it is very fair to take oral medication to help with the pain. It is really important to understand the pain so you do not mask the pain and delay the treatment for the source of the pain.
(42:50): [Michala O'Brien] Okay. Why does ocular GVHD make it impossible to cry?
(42:56): [Dr. Katie Luo] Very good question. Earlier in my slide, I showed that. The inflammation causes scarring on the tissue that we can see when you pull down the lid. When you can see the scar, you can see the scar forming. Our tear gland is hiding on top of our eyeballs under the bone, so you can't really see the tear gland, but the same scarring process is happening there too. When the outside is scared, inside is scarring too. Those scars just choke those little ducts that allow the tears to come out from the gland or probably just strangle the tear producing units themselves. After a while, it's so constricted, there's no more tears coming out. That's why, when you cut an onion or when you're sad, you cannot cry. But that is a sign. I definitely know you already lost the tear producing capability, so you really need aggressive treatment at this point before it gets too far.
(44:05): [Michala O'Brien] What do you think of Refresh a non-preservative tears post-transplant?
(44:10): [Dr. Katie Luo] Yeah, there are many, actually many good companies. Refresh is one of them. There's Systane, Theratears. There are actually many, many good companies making high quality preservative free tears. And they even come in different flavors, like this is more cloudy. The other one might be more clear. The cloudy one may contain some oil or lipid components, so on and so forth. I wouldn't say I know one brand is definitely better than the other because my patients are all telling me different things. One might like Refresh Mega-3 better. The other one might like Theratears better. You might want to buy smaller packages. These are little small boxes, the preservative free anyway. And whichever one makes you feel most comfortable, go with that one.
(45:05): [Michala O'Brien] This person says I use gamma globulin and serum drops. Will I have to use these for the rest of my life?
(45:24): [Dr. Katie Luo] I can't really hear very [crosstalk 00:45:28]. But it doesn't matter whatever drop that is. This is a similar question. Am I ever going to get through with this? Am I ever going to be done with this? I would say, let's try to look from a different perspective. It is not how long you have to do the drops. The key is to make your eyes comfortable and functional, right? You want to see. You will not be in pain all the time. Turn the thoughts a little bit to a different perspective. Are there other ways, for example, scleral lenses, for example, punctal plugs? Other things can make my eyes less miserable. If your eyes are less miserable, probably we can go down a little bit on the treatment frequency and the treatment choices. Yeah, don't give yourself a deadline. Think about comfort and vision.
(46:25): [Michala O'Brien] All right. This question, they're asking about a slide in your presentation that you had mentioned the goggles with moisture chambers. How does it work? Can you wear them while you sleep?
(46:37): [Dr. Katie Luo] Yes. Yes, you can. That's a great question. There are goggles called moisture chambers, but my patients gave me this really practical choice. If you go to some glasses store or online, like a store where, they make these goggles for motorcyclists because they ride at high speed. These goggles are designed to have a pretty wide rim, and they seal pretty well. They're not water-tight. If they're water-tight it's too foggy, you can't see, but they are fairly wide and the sealed fairly well. If you wear these, the moisture that's coming out from your eyes actually forms a little mini moisture chamber. And I do have patients sleep in them, and they think it works pretty well. Just go on to Google and search for rider sunglasses or rider glasses. You'll see.
(47:42): [Michala O'Brien] This person says I have chemosis in my left eye. Is this caused by GVHD? I do have very dry eyes.
(47:51): [Dr. Katie Luo] Depends. A common thing I see with chemosis is if someone's on a pretty high dose of oral steroids for awhile, say you've been on 30, 40 milligrams for awhile, and the chemosis can definitely happen. This is water retention, just like other puffiness in the rest of your body. It's the same thing. If it's not that reason, why do you have chemosis? I think that this is a really good question to study. Some people have abnormal lens vessels that make it look like chemosis. So without knowing why you have this in that particular eye, it's hard to answer this question, but you should work with your eye doctor to look at it.
(48:39): [Michala O'Brien] You mentioned the three eye centers that you're aware of and that you work with. I live in another part of the country. How could I get a list of ocular GVHD doctors?
(48:53): [Dr. Katie Luo] I think actually, Michala, I think your BMT InfoNet that has a resources to tell your patients about the subspecialty providers around the country. Am I right?
(49:10): [Michala O'Brien] Yes. We do have a GVHD directory. I just thought this person was looking for some, maybe you knew of some resource that we didn't have.
(49:22): [Dr. Katie Luo] Ah, I think if anything, your resource is probably more complete than mine. Yeah.
(49:29): [Michala O'Brien] What's your opinion of using saline flushes?
(49:34): [Dr. Katie Luo] Saline flushes. If, let's say, you got a piece of hair stuck in there, or you got a mucus strand you want to flush out, I applaud you if you use saline instead of using your hand to dig. But other than that, there's really no utilization of saline. Saline cannot be used as lubricant. Okay? If you already wear the specialty scleral lenses, you put the saline in there to fill the reservoir. But if you don't wear scleral lens, or if the scleral lens is already in your eyes, your lubrication has to be the lubricant, has to be the preservative free lubricant. It cannot be saline. It's not a lubricant.
(50:19): [Michala O'Brien] Would consuming foods rich and high in omega-3 fats be beneficial, such as salmon, avocado, those kind of things?
(50:29): [Dr. Katie Luo] In dry eyes, there are some previous studies show that omega-3 could help with dry eyes and probably by improving the quality of the oil glands that we showed that oGVHD could destroy. So those Meibomian glands supposedly could benefit from omega-3 oil. I don't think there's any study done in the oGVHD population specifically. That said, omega-3 oil is pretty good for the cardiovascular health. I tell my patients to go ahead and take it anyway. The worst case is, it wouldn't harm you, but I'm sorry. The worst case is, it wouldn't benefit your eyes, but at least it wouldn't do any harm. I'm supportive of taking omega-3 supplements.
(51:17): [Michala O'Brien] What's your opinion of medical marijuana for pain management?
(51:23): [Dr. Katie Luo] That I got asked, I think only one of my patients, only told me she did marijuana. I don't have a direct experience on this. I don't have a patient population on marijuana and who report to me about their eyes for GVHD. So with the legalization of marijuana now, not only medical, but it's actually legal in many states in the United States, I guess it wouldn't hurt to try. But I don't have any experience with that.
(51:58): [Michala O'Brien] This patient asked, they said they've had an increased dryness after the second Moderna shot, and it's not decreased a year later. Will GVHD get better over time? They're 8 1/2 years post donor transplant.
(52:13): [Dr. Katie Luo ] I would say some events could definitely trigger a GVHD activity, not only in eyes, but in other places too. It's almost like, for example, if someone's got a pretty bad cold, and after that cold, they could have a GVHD flare up in many places. This is similar. I, personally, think any vaccination that could induce a strong reaction could potentially just stir up the immune system a little bit. That said, vaccination is so important. Probably, still have to do it. Sometimes I do have my patients, if they say, "Next month, I'm going to have five shots altogether on this day," I do bring them back in two or three weeks, just to take a look in case anything flared up out of control.
(53:12): [Michala O'Brien] I was recently diagnosed with early macular degeneration in my left eye. I'm 57 years old, five years post an allo stem cell transplant. Is this from GVHD? What do you recommend?
(53:26): [Dr. Katie Luo] So far, I have not seen any correlation between macular degeneration and ocular GVHD. Although some of the review papers basically said, OGVHD can do anything, give you retinal detachment. I really haven't been seeing that. I would say it'll be extremely rare if the manifest of ocular GVHD goes beyond the front part of your eyes. I would think you should see a retina specialist just to treat the macular degeneration as a general population, and deal with that separately.
(54:11): [Michala O'Brien] Would scleral lenses help if the corneas look healthy? I produce no tears, and my eyes hurt a lot.
(54:32): [Dr. Katie Luo] Depending on if you're symptomatic. If the eye looks fine, and you don't have any pain, you're seeing well, I don't think there's any reason to get scleral lenses. But if you don't make any tears, and even though you can still see pretty well, but getting more and more irritated, maybe you could benefit from scleral lenses. But those places, you can have an evaluation first. Talk to your eye doctor first, then have an evaluation. Then you'll see, the moment they put a scleral lens in your eyes, if you are like, "oh my goodness, this is wonderful", then you will benefit from them. But you have to try.
(55:14): [Michala O'Brien] Can symptoms be in one eye only with GVHD and cataracts, or would that be a separate problem?
(55:22): [Dr. Katie Luo] If I understand the question correctly, I think the GVHD can definitely affect both sides. Sometimes it's asymmetric. One eye can be affected more than the other. And then, cataracts, the same. Cataracts usually is a bilateral process, but certainly one can be more affected than the other or earlier than the other. And the cataracts and oGVHD, these two are sort of two unrelated. One can have no oGVHD still with cataract, and vice versa.
(55:53): [Michala O'Brien] This person is 29 years old. She's two years post-transplant, and she just found out she has cataracts from chemo. Is this normal?
(56:04): [Dr. Katie Luo] Yes. In this population, I would say, yes. That's actually, yeah, not unusual from a history of steroid treatment or chemo, radiation, all those treatments can definitely predispose someone to cataracts. And this is not just in the transplant patients. Any other patients with severe systemic disease, one can have cataracts earlier. I'm very sorry to hear that you're 29, and you have to deal with this, but the good thing is cataracts are actually relatively easy to deal with. Get rid of it, put a new lens in, and you're done.
(56:42): [Michala O'Brien] What frequency do you recommend for artificial tears?
(56:48): [Dr. Katie Luo] This is a great question. I would say, right now, I don't know how you're feeling. I don't know who you are, so I would just give a blanket answer. If you are uncomfortable, I would recommend start with one drop every hour when you are awake. If between the one drop and the next drop, that one hour, you are completely comfortable, you increase that to one drop every two hours, so on, so forth. Then you will work out a frequency that works for you. You might only need six times a day. You might need four times a day. You might need 12 times a day, but you are the only one to find it out. But you go from more frequent to less frequent to find your comfort zone.
(57:35): [Michala O'Brien] Can you get GVHD in the eyes from the sun? If so, what are suggestions to protect your eyes from the sun?
(57:45): [Dr. Katie Luo] I would say, I'm not aware of the sun causing GVHD, but I know if one has GVHD, one can be very light sensitive, more so than other people. Certainly, in other ocular health perspective, just like anybody, if they're in the sun, you should wear sunglasses. Particularly, if you are light sensitive, certainly you want to wear sunglasses. And then if you are more sensitive than your friends and your family, you probably should be seen by an eye doctor to figure out why. Is this from oGVHD?
(58:21): [Michala O'Brien] If someone has a preexisting mild, dry eye prior to the BMT, would you be aggressive in starting Restasis or [inaudible 00:58:31] in the history of contact lens wear for 20 plus years?
(58:40): [Dr. Katie Luo] All right, so we're running out of time, but I would say that there was a paper showing that pretreated with Restasis for the population before the transplant, actually made their incidence of oGVHD smaller afterwards. Starting treatment early, if you already have GVHD, that is a great idea. At that time, Restasis probably would still work.
(59:08): [Michala O'Brien] What are the side effects of Salagen? It's a medication for dry mouth and eyes.
(59:14): [Dr. Katie Luo] Yeah. It's pilocarpine. Salagen's pilocarpine. It will give you night sweats or cold sweats. That's the biggest side effect. People tell me they're drenched in their sweat if the pills work, but on the other hand, if it makes you sweat, it might make your mouth watery. It might make you make more tears. Adjust the dosing and the frequency and when in the day to take it, and maybe stage a shower an hour after you've taken the pills, so on and so forth, try to manage it. I think it's a great medication. Thank you.
(59:50): [Michala O'Brien] Closing. On behalf of BMT InfoNet and our partners, thank you, Dr. Luo, in your very helpful remarks. And thank you, the audience, for your excellent questions. Please feel free to contact BMT InfoNet if we can help you in any way and enjoy the rest of the symposium. Thank you.
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