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Graft-versus-Host Disease: What to Do When it Affects your Eyes

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Graft-versus-Host Disease: What to Do When it Affects Your Eyes

Sunday, May 4, 2025

Many thanks to Incyte Corporation and Sanofi whose support, in part, made this presentation possible.

Presenter: Dr. Zhonghui Katie Luo, MD, PhD Massachusetts Eye and Ear, Harvard Medical School  

Presentation is 42 minutes with 19 minutes of Q & A

Summary: This presentation describes what ocular graft-versus-host disease (oGVHD) is, its causes, signs and symptoms, and current management and treatment options.

Key Points:  

  • Ocular graft-versus-host disease (oGVHD) occurs when the donor’s immune system attacks and damages some of the tissue in the eyes. This decreases tear and oil production and causes scarring. As a result, the patient develops very dry eyes.
  • Symptoms include increased discharge and tearing, followed by significant dryness and damage to the eyes. Patients aren’t usually aware of these early symptoms of oGVHD, which often causes a delay in treatment and increases the damage to the eyes.
  • There are many interventions that patients can utilize to help improve and manage their oGVHD, including lifestyle modifications, over-the-counter and pharmacological eye drops and oral medications, medical procedures, and surgeries. 
Highlights:

(06:15): Patients who undergo a bone marrow/stem cell transplant with donor cells (allogeneic transplant) have a 50% chance of getting graft-versus-host disease in the eyes, regardless of whether other organs are affected by GVHD.

(08:35): A common sign for spotting a patient with ocular GVHD is that they're typically squinting, and they often wear sunglasses indoors because their eyes are very dry.

(13:37): Ocular GVHD often occurs after an immunogenic event – an event that triggers an immune system response, such as receiving a vaccine.

(14:57): If eye lesions caused by oGVHD are treated early and aggressively, there is less scarring.  

(19:40): When the surface of the eye is that dry, and the oil and tear production are deficient, the surface can break down because healing is severely compromised. Erosion can occur, and in just days, the cornea can actually melt.

(24:19): There are things we can be mindful of to avoid exacerbation of oGVHD, including not touching your eyes, using only preservative-free eye medications, limiting time spent staring at screens, and being careful when putting on and removing makeup.

(30:32): Punctal plugs and punctal cautery can help maintain eye lubrication.

(33:04): Steroids and serum tears are two other treatment options.

(34:25): The therapeutic scleral lens is another lifesaver for many patients.  

(35:41): Any cosmetic surgery of the lids or the eyes, and LASIK surgery should be avoided. 

Transcript of Presentation.  

(00:01): [Susan Stewart]: Welcome to the workshop Graft-versus-Host Disease, What to Do When it Affects Your Eyes.

(00:12): Before we begin, I would like to thank Incyte Corporation and Sanofi, whose support helped make this workshop possible.  

(00:21): Speaker Introduction. It's now my pleasure to introduce you to our speaker, Dr. Katie Luo. Dr. Luo is a Physician-Scientist at Massachusetts Eye and Ear and Harvard Medical School. Her specialty is ocular surface diseases and cataract surgery. Dr. Luo collaborates closely with Dana-Farber Cancer Institute to diagnose and treat patients who have developed ocular graft-versus-host disease following a stem cell transplant. Please join me in welcoming Dr. Luo.

(01:02): [Dr. Zhonghui Katie Luo]: Good afternoon, everybody. I am so happy to be back here. Sue has invited me a few times to this symposium before, and I love the format. I love the opportunity to spread awareness and get patient engagement through this platform, even without being together in person.

(01:28): I have worked for over 10 years with the Dana-Farber bone marrow transplant unit and have taken care of the majority, if not all, of the patients with graft-versus-host disease in their eyes. I have learned so much from studying the process and from the interaction with you, the patients, the family, and other physicians taking care of you.

(02:27): Overview of Talk. I'm going to talk about these four points: What is ocular graft-versus-host disease? How does it happen? What are the early signs of ocular graft-versus-host disease, and what can we do to manage it?

(02:48): I will mostly use the phrase 'ocular graft-versus-host disease' (oGVHD) throughout the talk, but sometimes I might just slip and say GVHD. Most likely, I mean ocular GVHD.

(03:05): I want to warn you that some patients have told me that some of the images I will be showing are pretty graphic. They’re a little scary. I decided to keep them because sometimes reality needs to be displayed so that we understand the importance of prevention.

(03:29): Let’s start by discussing what graft-versus-host disease is. When we have a person who's got something wrong with their bone marrow, such as leukemia, lymphoma, or some kind of malignancy that's taken over their immune system, if all treatments such as chemo and radiation fail, fortunately, there is another treatment available. By wiping out their own immune system, including their bone marrow, and giving them new stem cells from a healthy donor, we are able to hopefully eradicate and cure the disease.

(04:17): This graphic shows a visual depiction of what a bone marrow transplant is. The pink person is a healthy donor who donated some pink stem cells to the blue recipient. This pink system will populate within the recipient's body and take over the immune defense system. This will enable the recipient – or host – to protect itself from attacks by pathogens and other diseases. This is the goal and intent of a bone marrow transplant.  

(04:51): However, this is the donor's immune system, not the patient’s, so it can also recognize the recipient – or host – as an enemy. The donor’s immune system may start to attack and destroy an organ or tissue in the recipient. That's how graft-versus-host disease starts, and it can affect a single organ or multiple organs. Because so many systems can be targeted, patients are all put on immunosuppression medication to control the newly transplanted immune system from going too wild.

(05:50): However, at some point, the immunosuppression medication needs to be tapered to allow the new immune system to get to work. We cannot continue to suppress it indefinitely. That's when graft-versus-host disease (GVHD) typically occurs – after the acute transplant process has been completed.

(06:15): Unfortunately, ocular graft-versus-host disease affects at least half of all patients – meaning you have a 50% chance of getting graft-versus-host disease in the eyes, regardless of other organ involvement. It is often underdiagnosed and not always easily recognizable.

(06:41): There can be acute or chronic graft-versus-host disease (GVHD). Acute GVHD is a devastating condition that occurs when the host or patient suddenly becomes exposed to a burst of activity from the newly transplanted immune system. It can affect the skin, liver, digestive system, and eyes. This can be lethal, but it can also be almost completely healed. It only affects that person for a short period of time, which is why it is called ‘acute’ GVHD.  

(07:42): Chronic graft-versus-host disease in the eye – or any organ – can happen much later. It can happen a few months later or a few years later. Once it happens, it typically lingers.

(07:58): It is more common to experience chronic graft ocular GVHD than acute. Typically, we talk more about the chronic condition because it affects more patients. Therefore, whenever I do not specify acute or chronic, I will be referring to chronic ocular graft-versus-host disease by default.

(08:35): A common sign for spotting a patient with ocular GVHD is that they're typically squinting, and they often wear sunglasses indoors. Sometimes they put their hands over their brows, and while their eye exam numbers might be pretty good, their functional vision – such as driving, watching TV, or enjoying some reading on the iPad – is not good.

(09:04): This is because their eyes are typically very dry. Oftentimes, we equate chronic ocular graft-versus-host disease with dry eyes. That's not completely wrong, but I want to make everyone aware that while dry eyes are the most common symptom, dry eyes are actually a late sign of ocular GVHD.

(09:34): I remember early in my career, I would wonder why their eyes suddenly got so dry. How did their eyes change from apparently normal before transplant to significantly dry after transplant? What happened? I could not find a good answer in the literature, so I started asking Dana-Farber, my wonderful collaborator, for their cooperation. I asked them to send their patients to see me very early after transplant. I wanted to see them before they started to complain of dry eyes, to be able to assess what was happening early on. Even if they weren’t noticing any changes, I wanted to see these patients to ask them about their eyes.

(10:28): Then, I noticed some patients reporting that they had never experienced any prior problems with their eyes, and suddenly their eyes were becoming very watery or wet. Typically, they were small changes that they wouldn’t even report to their transplant doctors, and I would have to listen closely and ask specific questions.  

(10:55): Some small changes include extremely crusted lashes in the morning, or significantly increased discharge and tearing. These would be the only symptoms, and the patients wouldn’t even think to report them. Oftentimes, they assumed it was conjunctivitis, or reported their symptoms to an ophthalmologist, or simply overlooked it because they had other issues they were more worried about. Because of this, their transplant doctors were never made aware of these issues.

(11:46): I started hearing more and more of these stories, and I started noticing bumps under the upper eyelids. When I would flip the upper lid, I could see pretty raw bumps, or perhaps some sort of film.

(12:05): As you can see in these pictures, I would even see these very patchy, little sticky spots without any distinctive form or shape to them. The tissue there was just raw; it was eroded and oftentimes it was on the upper eyelid. At this point in time, they usually had no other complaints, other than possibly some discharge. Then, after a few weeks, I would begin to see fibrosis – or scarring – occurring in the same place.

(12:47): I started looking at these cases closely. I saw over 200 patients in a 12-month span, reviewed every single case, and found that 19 of these patients actually had these lesions that you saw in the previous slides. I turned my focus to them because I wanted to see what had happened.

(13:13): Age, sex, and diagnosis had no effect or correlation with these symptoms. In this table, you can see the symptom onsets are all over the place.  

(13:37): However, what I found in common among all of them – except for one who couldn't provide any history – is that each patient had experienced an immunogenic event – an event that had triggered an immune system response – within about one month prior to the onset of symptoms.

(13:54): What were those immunogenic events? Many of them were tapering their immunosuppression medications, such as discontinuing Tacrolimus or oral steroids. A lot of them had received a vaccination. These were COVID vaccinations, some were the nine-month and even twelve-month post-transplant vaccine bundles. There was one patient whose onset was shortly after a donor lymphocyte infusion. All of these events can boost and activate the immune system.

(14:32): Now, I had noticed a trend – symptoms of ocular GVHD happened when the immune system was activated. You would have eyes that were seemingly fine. Then we would start to see erosive lesions under the lid, and with or without treatment, these erosions eventually will scar.  

(14:57): The difference I've seen so far is that, if I treat the lesions early and aggressively, there is less scarring. If they are left untreated, severe scarring can occur, and even lead to deformity of the lids – meaning the lids turn in or stick out.

(15:14): This graph displays the most common symptoms and how they change overtime. At onset, most patients complain of discharge or crusting, and not so much dryness. Six months later, they would no longer have crusting or discharge, but their eyes would be a lot drier.

(15:36): The numbers in this graph do not total one hundred percent because some of these cases are recurrent, meaning they already had dryness and fibrosis, and then they had another immunogenic event occur. When that happens, they can have another attack of erosion, then another round of fibrosis, and their tear production goes down even further due to significant scarring.

(16:02): To summarize, I was able to identify what happened and why. There's an immune attack, the attack damages some of the tissue in the eye, decreases tear production, and causes scarring. As a result, the patient develops very dry eyes.

(16:23): Patients don’t know to associate these changes with graft-versus-host disease, so there is often a delay between the moment they notice their tears decrease to the moment they report these changes. I think this is worth noting, because people need to know what to look for early in order to prevent the scarring. If it has already happened, we need to treat it quickly in order to prevent further damage.

(16:48): I advise that physicians should be strategic about making immunogenic treatment changes, and should try to separate immunogenic events as much as possible. For example, I think anybody who's having a donor lymphocyte infusion or tapering off immunosuppression should have their eyes examined within a month and ensure these changes be made separately. I also often advise our Dana-Farber colleagues not to give a vaccination on the day they discontinue tacrolimus. They need to strategically space these immunologic events out as much as possible.  

(17:12): I still need prospective clinical trials to prove these hypotheses, but I do want to share this with you because a lot of people do not know about this.

(17:25): Now we’ll talk about what we can do when the eyes are already dry. In this picture, you can see tiny spots of surface damage illuminated by the green staining. There are thousands of them, and they cause irritation to the eyes.

(17:47): When the surface of the eye gets dry, not only are there tiny spots of surface damage, but sometimes it can also grow filaments. These filaments are extensions of the epithelium layer – the surface layer – of cells and grow out in a long string, rather than growing flat as they are supposed to.

(18:13): They look like a dot or a ball of mucus on scans, but they are attached to the eye, so every time you blink over those balls, it pulls on the cornea. It's very painful and causes severe light sensitivity. This is a common occurrence when someone's eye surface is very dry and inflamed.

(18:36): Important oil glands on the inside of the lids are damaged as well.  Oil glands help produce an essential component of the tear film that acts as a natural barrier to prevent evaporation from the ocular surface. The black and white photo shows these white glands, which are the meibomian glands, or oil glands. When these glands are dead, even if you are able to produce a lot of tears or put in a lot of lubrication, the eye will still suffer because that natural barrier is gone.

(19:13): On the right side, these colored pictures show the conjunctival scars. These pictures were originally shown in a paper previously published, with no specific mention of where these conjunctival scars came from. I think I've just answered the question. If you want to read that paper, you can download the slides. https://www.sciencedirect.com/science/article/abs/pii/S1542012417300332  

(19:40): When the surface of the eye is that dry, and the oil and tear productions are deficient, the surface can break down because healing is severely compromised. Erosion can occur, and in just days, the cornea can actually melt.

(20:06): In the picture, you can see a purple circle in an otherwise perfect-looking cornea. This is just a pinpoint sized-hole, but that pupil is actually getting dragged out towards the outer part of the eye because the fluid inside the eye is leaking. If this happens, I have to put a patch on the cornea, and sew up the hole.  

(20:31): In this next picture, you can see the patch that was placed. I was able to repair the hole, and for a short time after surgery, things looked good. However, new erosions and new melting can and will occur.

(20:48): In the picture on the left, you can see the little round patch is still fine and intact, but the area above it is starting to melt. This new melting is highlighted in green in the middle picture, and I had to sew a bigger patch onto that green hole.  

(21:12): Unless we fundamentally change the issues of inflammation, the dryness and lack of nutrition in the eye will continue to cause damage, no matter how much we attempt to repair and fix it. Therefore, my goal is to prevent my patients from getting to that point, because once this level of damage has occurred, it will always be a significant problem.

(21:40): Now that you've seen what graft-versus-host disease in the eye looks like, let’s discuss what we can do about it. First, we want to understand the problem. Second, we want to avoid preventable damage to the eyes. Third, we want to invest in maintaining the health of the eyes, and this takes a big commitment on your part.

(22:08): We alluded to all this earlier but I want to do a quick review here. The inflammation caused by the immune system's attack can damage the tear and oil glands, leading to surface damage. When tear production and oil production decrease, there's very little natural defense in the eye to prevent it from disintegrating and melting.

(22:39): I am frequently asked if ocular graft-versus-host disease can go away. The issue is, it’s the adopted immune system that is causing this graft-versus-host disease, and we need to keep that adopted immune system in the body. If we get rid of it, then we lose the defense mechanism against the cancer or initial disease.  

(23:16): Ideally, we would be able to develop a system that would train the new immune system to know what to fight, and what to leave be. We are still working on that. The slow tapering of immunosuppression medications seem to be working pretty well. And there is a lot of research being done within the transplant community to find combinations of treatments, conditioning regimens, and post-transplant care to try to enhance and train the new immune system that one is getting. We are learning how to manage it, but we still don’t have it completely figured out and under control.

(23:50): Once you have GVHD, there will always be a risk of having it. That said, I have seen a lot of patients where, after many years, the activity of the GVHD seems to die down. We really don’t have any definitive answers regarding when and how we might be able to completely get rid of graft-versus-host disease.

(24:19): There are things we can be mindful to avoid to help prevent exacerbation of oGVHD, and some techniques we can utilize to help manage symptoms. The number one most harmful behavior we can stop is touching your fingers to your eyes. Everybody who comes through my clinic knows this, because I spend a lot of time talking to my patients and showing them why they shouldn't be rubbing their eyes. If they follow that advice, they often notice a difference. Be careful not to scratch your eyes; you don't want to irritate an already very fragile surface.

(25:01): Do not use preservative-containing medication on your eyes. Do not use Clear Eyes, Visine, Naphcon-A, anti-allergy drops, and most over-the-counter medication. If they are not labeled ‘preservative-free’, then they contain preservatives, which is a big irritant to the surface as well.

(25:24): Do not stare at your screen for too long, and ensure you take breaks during screen usage. When we stare at any type of screen, we blink 75% less. Blinking is important to distribute whatever tear film you have. If you do need to use screens for a significant amount of time, makes sure you use eyedrops so that the surface doesn’t get too dry.

(25:44): Be very careful with makeup and makeup removal. If those chemicals spill into the eyes, they can be very harmful. Those organic solvents can significantly damage the surface, particularly in cases of ocular GVHD.

(26:00): Notice if your eyes start producing any discharge, and be mindful of whether it's just a little bit of normal sleep-crusting, or something more. If you just have a cold or pneumonia, then it’s probably not GVHD. If you have copious amounts of mucus coming out, then it’s most likely not bacterial conjunctivitis, and is something you need to tell your provider about. Antibiotic drops probably will not help. Do not use Visine. Use warm water to try to clean it up, and tell your provider.  

(26:34): You should also try to modify and control your environment to keep it moist. Use humidifiers, point air vents away from your face, and wear sunglasses, or goggles. Within the past few years, even Amazon now stocks ‘moisture chambers’ or ‘moisture goggles’ that can be worn to help with dry eyes.  

(27:10): Warm compresses are also very effective, and are really nice for the oil glands. There are multiple varieties of microwavable masks. I would recommend putting a moist face cloth between your eyelid skin and any microwavable bead mask, because it's a little gentler to the skin and to your eyes.

(27:41): If tears are not being made, we want to ensure we are using preservative-free lubricant to keep our eyes wet. There are many brands that make bottles of preservative-free tears. The phrase ‘preservative free’ must be stated on the box. Typically, the bottle caps look a little funny, and they have a relatively big head. A traditional eyedrop body with a completely open end is not typically preservative-free.

(28:41): You want to instill only one drop at a time into each eye. The eye can hold about half a drop, so one drop in each eye is enough lubrication. There's no need to do more unless you are flushing something out. Using the drops more frequently will be more effective and productive. Using one drop, and then an hour or two later using another drop, is better than a lot of drops at once.

(29:11): At night, you can try one of the thicker preservative-free lubricant ointments shown on this screen. They don't work for everybody; some people find them very helpful, and some people don't. Since these are over the counter and readily available, I highly recommend everybody try them.

(29:32): If these conservative, over the counter management options aren’t working, we have pharmaceutical options to help us make more tears as well. For example, cyclosporine (Restasis) or lifitegrast (Xiidra) are good choices. If you have at least 50% of your tear glands functioning, these products can help stimulate the production of more tears. For patients who are so dry that they are not making any tears – like when you cut onions you want to cry, but no tears come out – Restasis or Xiidra probably won’t work.

(30:11): Oral medication – such as oral pilocarpine (Salagen) or cevimeline (Evoxac) are frequently prescribed by our oral GVHD colleagues to stimulate saliva glands to treat dry mouth. If they work for your mouth, chances are they're going to work for your eyes as well, so I always welcome the use of these oral medications.

(30:32): There are different mechanisms and procedures to help maintain eye lubrication as well. We have structures in the inner corner of each eye to collect any excessive fluid, which then drains into your nose and into your throat. We can use different mechanisms to close them.

(31:00): The picture on the left shows a dissolvable plug, and the middle picture shows a permanent plug. Basically, both close the drain. I often tell my patients that this is a plumbing issue; if you don't have a lot of water coming in, we need to close the drain to keep the water in the sink.

(31:21): The last picture shows a procedure call ‘punctal cautery’. This uses cauterization to seal the drains into your nose and throat. Even though it works the same as a permanent silicone plug, it seems to work better, although I do not know exactly why that is. Punctal cautery is a procedure that's easily done in the office.

(32:03): We also want to control the inflammation in the eyes. Systemic immunosuppression agents – not just tacrolimus or prednisone – are commonly used. I have seen belumosudil (Rezurock), ruxolitinib (Jakafi), and extracorporeal photopheresis (ECP) used to get the fluid back into your eyes.

(32:45): Work with your transplant providers to get all the systemic possibilities taken care of. And, as I mentioned at the beginning of the talk, monitor carefully for oGVHD during immunosuppression tapering.

(33:04): Steroids can be used in the eyes as well, but only for a time and should eventually be tapered off. Consider the preservative-free versions. It's a little cumbersome to get, but if someone needs to be on topical steroids for more than a couple of weeks, I would highly recommend using the preservative-free version.

(33:37): Serum tears are also very good choice. Serum tears are made in a laboratory using the patient’s own blood to make higher concentrated tears. Now there are more and more providers producing these, and I would recommend a concentration of 40% or higher. Usually, we would be getting similar benefits and nutrition through our tears or oil secretions, but when both aren’t working, you can get them from your blood. Serum tears can fix a lot of problems, and can even restore the nerve endings, and some of the tear and oil functions.

(34:25): The therapeutic scleral lens is another lifesaver. These are not soft or hard contact lenses as they work differently and are used differently. They must be custom-made by a professional. If you cannot tolerate wearing soft contact lenses because your eyes are too dry, therapeutic scleral lenses might be a good choice. Basically, a therapeutic scleral lens is a bath of fluid that hovers over the cornea, so your cornea is bathed in fluid while you’re wearing them. They are very comfortable, and can help restore vision in most cases as well.

(35:12): My goal is to avoid any form of surgical interventions with my patients for multiple reasons. First, corneal patches and transplants are not curative, and they don’t tend to survive well afterwards. I sometimes use an amniotic membrane to rescue a failing cornea, but that's a short-term solution that doesn't provide a long-term benefit.

(35:41): I recommend avoiding any cosmetic surgery of the lids or the eyes, and Lasik is absolutely not an option. Many will develop cataracts after a transplant, and that greatly impacts vision, so cataract surgery is appropriate and recommended. It should be done early, and post-operative care should be more extensive and different than the general population.

(36:10): Glaucoma surgeries are not ideal, but if they have a mild stage of glaucoma and are needing a lot of eye drops, I refer my patients to get the procedure done as those eyedrops can be pretty toxic. Laser surgery – such as Selective Laser Trabeculoplasty (SLT) – is very effective in lowering intraocular pressure and decreasing the need for eye drops, so it is another good choice for patients with oGVHD.

(36:46): Although we’ve talked about many different treatments, none of them are FDA-approved specifically for ocular graft-versus-host disease yet. A lot of research is ongoing, but are still needing human trials. I encourage you to participate and spread awareness of the importance of clinical trials, so that we can eventually find a clinical trial for you.

(37:23): Summary. I have met so many patients going through this enormous journey of transplant and then graft-versus-host disease. I have learned so much from them. I have seen so much strength, have felt their resilience, and have felt that bond and support from family and friends. There is still so much overwhelm, and issues like oGVHD can be very difficult and discouraging.

(38:04): I've learned from you to appreciate life and to appreciate what we have. I want each of you to cherish that inner strength, and feel empowered to speak up, as you know your body best. Tell your doctors about any changes right away, because only then can we know you need something and help you.

(38:38): When you are inpatient, you can request an inpatient ophthalmology consult. When you are outpatient, you can ask for a referral to a more experienced eye doctor who is familiar with oGVHD. You can discuss systemic treatment options with your bone marrow transplant team in coordination with your eye doctors.

(39:21): I am very grateful for Dana-Farber’s bone marrow transplant service, because we collaborate and work together so well. Despite all that, everything comes down to you. If you know that ocular GVHD is not just dry eyes and that it can happen early on, you might be able to advocate for yourself and get treatment much earlier.

(40:01): I hope to eventually create a structure that provides patient-centered care, with all needed services fully collaborating together and with the patient to create a better, more efficient experience. I want to raise awareness about this, so I wrote this review last year published in Transplantation and Cellular Therapy (TCT), on the right side of the screen. You can download this paper at https://www.astctjournal.org/action/showPdf?pii=S2666-6367%2824%2900493-7.  

(41:17): This review was written for you, the patient. It is for you, for your family and your physicians. Share it with your physicians and I hope they will read it and invest the time and effort to learn more about providing better, more cohesive care for you.

(41:48): I want to thank Dana-Farber, and I want to thank BMT InfoNet and Sue Stewart for giving me the opportunity to talk with you. I'm happy to take questions now.

Question and Answer

(42:02): [Susan Stewart]: Thank you, Dr. Luo, that was a great presentation with lots of information. We've got a lot of questions lined up, but we'll try to answer as many as possible.  

(42:21): Is it common to not be able to cry? Her transplant was in August 2024, and she noticed dryness around March 2025.

(42:32): [Dr. Zhonghui Katie Luo]: Yes, unfortunately, I hear that quite often. And the experiences and stories I hear from patients about this issue shows how emotionally complex this can be. Unfortunately, this is very, very common – when all of the tear glands are scarred, no tears will be produced. This can be a pretty stressful thing to experience.

(43:11): [Susan Stewart]: How effective are serum tears?

(43:16): [Dr. Zhonghui Katie Luo]: Serum tears are very effective. If you compare serum tears to preservative-free artificial tears, the difference is that serum tears are more than just moisture or lubricant. Serum tears have growth factors, cytokines, and everything that's flowing in our own body. That provides nutrition to the surface of the eyes.

(43:46): There are many studies – typically done in the general dry eye population, but some that included graft-versus-host disease patients – where solid evidence was found that serum tears can promote the nerve plexus under the cornea to grow again. The nerves provide a lot of supporting factors to the health of the cornea as well.

(44:11): In my own anecdotal experience, people on serum tears do see results, but it happens very slowly. You're not going to see a difference in a single month – I put my patients on serum tears for years. Over time, you'll notice the eyes are more comfortable and less inflamed. I do recommend serum tears.  

(44:50): [Susan Stewart]: A woman who's 10 years out from transplant had no problems with her eyes until she had cataract surgery and now she can't focus. Could this be related to GVHD?

(45:06): [Dr. Zhonghui Katie Luo]: Yes, this is quite common. What happens in post-transplant patients is that previous treatments decrease tear production and depletes some of the oils, it’s just not always noticeable or recognized

(46:03): Now you add cataract surgery, which by itself is traumatic. We cut into your cornea in at least two places to make the incision, and make it even more traumatic because generally you are instructed to take three different eye drops a day for a month – each with preservatives in it – after the procedure.

(46:36): I have seen otherwise stable corneas completely deteriorate after that. We really need surgeons to understand how to treat these eyes differently when performing cataract surgery.

(47:03): Normal eyes can take a little bit of abuse from the post-operative drops, but post-transplant patients cannot. I only put my patients on preservative-free prednisone post-op. I do not put them on any other drops other than lubrication of their own serum tears. It's really important.

(47:24): [Susan Stewart]: Do you think intense pulsed light (IPL) treatments are effective for regrowing oil gland tubes damaged or destroyed from GVHD?

(47:39): [Dr. Zhonghui Katie Luo]: There are no GVHD-specific studies done, but I have anecdotal experience. In my experience, it depends on how involved the oil glands are. For example, in some patients the oil glands are inflamed and pretty blocked up. If I push on the glands, and I can still spread some oil – even if it’s very thick – I can know that the oil glands are not dead. I think IPL can work for those eyes.

(48:45): Can it cure the glands? Maybe not, but it can improve the health of those glands by decreasing inflammation in the local tissue. Once the oil starts flowing – even if only 30% – that's going to help the surface tremendously.

(49:04): On the other hand, there are plenty of eyes that I have seen – typically in people many years out from transplant – where the oil glands have nothing in them. There's not even inflammation, they are dead. For those eyes, IPL would not help at all.

(49:30): [Susan Stewart]: For people who don't know what IPL is, can you explain what that is?

(49:35): [Dr. Zhonghui Katie Luo]: IPL is ‘intensive pulsating light treatment’. It is a new group of small device treatments for patients with dry eyes. A lot of them target the meibomian glands, or oil glands. They're new on the market and are not yet insurance-approved. It’s an out-of-pocket expense for the patient, and many big academic centers don’t have access to IPL because the billing is tricky.  

(50:18): If you look at the publications, you can see the efficacy of these treatments. I refer some of my patients out to get IPL treatments, and I see some who have already been treated elsewhere with this machine. In those cases, I definitely did see an improvement and it decreased local inflammation.  

(50:50): [Susan Stewart]: I heard that butyrate might be important in eye health including intraocular bacterial infections and ocular surface inflammation. Is long-term supplementation of butyrate recommended to prevent ocular GVHD?

(51:18): [Dr. Zhonghui Katie Luo]: I'm not familiar with that data. I don't know if there's any clinical trial to say one way or the other.  

(51:28): [Susan Stewart]: Does GVHD of the eye always affect both eyes or can it affect one at a time?

(51:36): [Dr. Zhonghui Katie Luo]: It definitely can affect both eyes asymmetrically, and it can affect just one eye, but that is rare. It's more likely that one eye is more affected than the other. I have a theory that this is because there is more fibrosis or scarring in one eye than the other eye for whatever reason.

(52:00): [Susan Stewart]: Post-chemo, when my eyelashes grew back, they grew back in bent, so they scratch my eyes and my prosthetic replacement of the ocular surface ecosystem (PROSE) lenses. What is a common protocol for this issue?

(52:12): [Dr. Zhonghui Katie Luo]: Depending on the cause, there are two possibilities. One possibility is that the lid position is fine but the lashes grew back in the wrong place or pointing in the wrong direction. To treat that, you can see an oculoplastic surgeon. They can use selective treatment to target single follicles to get rid of individual lashes. If those lashes are hurting you, you need to get rid of the follicles, otherwise they'll keep growing.

(52:42): The second possibility is that sometimes the scarring and fibrosis can cause the lid to turn. If the lids have turned inward, it is pretty hard to treat because that would involve lid surgery to correct it.  

(53:03): Having surgery on the lids is not always ideal – particularly if the inflammation is still occurring – so wearing PROSE is good protection because they are hard lenses. The lashes can poke on PROSE and it's not going to hurt you. For someone in a position where they are not ready to have surgery, I would say definitely consider PROSE as they will protect your cornea.

(53:29): [Susan Stewart]: Have you seen any benefit from the use of 1% progesterone cream to the forehead for dry eyes?

(53:41): I actually did a clinical trial for this in 2019 and published a paper. https://www.sciencedirect.com/science/article/pii/S2666636721006746  

(53:48): Using 1% progesterone cream on the forehead showed an overwhelmingly positive benefit. That company is still in preparation for a phase three trial; it has not started yet because of the pandemic and a lot of obstacles. I personally look forward to further clinical trials, and hopefully it will eventually be approved.

(54:24): [Susan Stewart]: Do you find GVHD occurrence and severity related to whether the donor is related, or how good the match is, or whether the donor and the host were different genders?

(54:37): [Dr. Zhonghui Katie Luo]: This is an ongoing area of research that bone marrow transplant services have spent many decades trying to figure out. There are some general trends for GVHD including how well matched they are and what chemo regimen they receive prior to transplant. However, I don't think we have data as specific regarding what affects the eyes more.

(55:23): [Susan Stewart]: Will using flax oil as a supplement help with dry eyes?

(55:34): [Dr. Zhonghui Katie Luo]: Flaxseed oil is utilized for the omega-three supplementation. Omega-three oil can help the meibomian glands produce better quality oil, but I’m not aware of any specific study that compares flaxseed oil with other omega-three supplements to see if helps the eyes.

(56:21): [Susan Stewart]: My eyes really feel good with serum tears, but I can't get the film to go away. It makes daily function difficult. What would you suggest?

(56:34): [Dr. Zhonghui Katie Luo]: It really depends on what the film is. For example, film can come from a pretty thick strand of mucus. If you blink and it comes into the center of your cornea, then it’s mucus. It also could be an overall hazy quality of the cornea epithelium. Regardless of serum tears, that is a difficult situation and it can make the vision blurry. I’m sorry, but to answer that question more thoroughly, I’d need to know more specifics.

(57:43): [Susan Stewart]: Will I have to use serum tears for the rest of my life?

(57:51): [Dr. Zhonghui Katie Luo]: That is a difficult question to answer. Not all my patients stay on serum tears forever. But there are other elements also being managed. What is the systemic immunosuppression situation? What's a systemic GVHD situation? Have punctal plugs or cautery been tried? Are they wearing PROSE already?

(58:16): There's no black or white answer. However, if serum tears are helping you, and you are using a high concentration, stick with it and perhaps one day you can stop using it.

(58:38): [Susan Stewart]: I'm dealing with an autoimmune disease diagnosis of iritis uveitis. Is there any relationship between these problems and chronic GVHD?

(58:53): [Dr. Zhonghui Katie Luo]: I would say ocular GVHD tends to affect the surface of the eye – like the white part of the eye, the lids, or cornea. It has been reported to go inside and cause uveitis, but it sounds like the incidence is pretty rare. It might be possible that it's almost like a form of oGVHD – perhaps the transplanted immune system somehow identified the target inside the eye instead of outside the eye in your particular case. In that sense, it would be considered oGVHD. It could also be like an acquired autoimmune attack, but either way, it’s not very common.  

(59:54): [Susan Stewart]: 70 days post-transplant, I developed thick tears that cannot be cleared away by blinking. Is this GVHD? Is this the mucus that you mentioned in your talk?

(01:00:07): [Dr. Zhonghui Katie Luo]: The challenge is that it could possibly be both. If you wake up in the morning and the lids are consistently crusted shut, there is a chance this is some sort of flare-up. Like I showed in the early pictures, there could be erosion inside your eyelids and the sloughing of tissue is causing that thick discharge. It is possible, but you need an eye exam to know one way or the other. Go to your eye doctor and have the doctor flip the upper lids to take a look. Only by flipping the upper lids can one see it.

(01:00:50): [Susan Stewart]: I'm five and a half years post-allo-transplant, using Restasis twice a day, along with autologous serum tears, preservative-free tears, and collagen plugs. I only had one millimeter of tears on a Schirmer test. I suspect I'm too far gone with scarring and meibomian gland dysfunction to experience any benefit from Restasis. How do I know if that's true and whether I should continue or stop using Restasis?

(01:01:25): [Dr. Zhonghui Katie Luo]: Stop using it for six weeks straight and see what happens. Then restart it for another six weeks straight and see what happens. You'll get a clear answer.

(01:01:34): [Susan Stewart]: Thank you very much, Dr. Luo, for a very clear and interesting presentation. I want to thank the viewers as well, and the audience who submitted a lot of excellent questions. Please contact us at BMT InfoNet if we can help you in any way. 

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