Dry eye exam in patient suspected for ocular graft-versus-host disease results in an unexpected finding

Kaleb Abbott, OD, MS, of the University of Colorado School of Medicine, shares an engaging case about a patient who was suspected of having ocular graft-versus-host disease but the root of the problem was something completely different. Watch the video to learn more.

Kaleb Abbott, OD, MS:

My name is Kaleb Abbott. I’m an optometrist and Assistant Professor at the University of Colorado School of Medicine where I practice in our Dry Eye Clinic and our Center for Ocular Inflammation. Today, I’ll be sharing a case of how we are able to successfully diagnose obstructive sleep apnea via a dry eye examination.

We had a 78-year-old white male who presented to our clinic. He was 6-foot-1 and 185 pounds, so relatively slender individual, but he was actually referred from hematology to evaluate for ocular graft-versus-host disease. He had myelodysplastic syndromes, which is a condition that affects the blood. It’s a certain blood disorder that requires a bone marrow transplant. He had a bone marrow transplant, an allogeneic one, so a bone marrow transplant from another individual, and that was 4 years earlier, and then 7 months later, he went on to develop graft-versus-host disease.

Graft-versus-host disease is a complication from an allogeneic bone marrow transplant that can occur after a stem cell transplant where the donor’s immune cells, ie the graft, actually attacks the recipient’s body, ie the host, which is why it’s called graft-versus-host disease. It can attack really anywhere throughout the entire body, including the eyes. If it does attack the eyes, typically it’s affecting the lacrimal glands first.

He was coming into our clinic from hematology because he was having severe eye irritation, foreign body sensation. It was worse when he blinked his eyes and he actually came into clinic and he was wearing a contact lens and he said he had to wear this contact lens all the time for the comfort of his eyes. He said if he had the soft contacts out of his eyes, his eyes hurt horribly and he had to put the contact lens in the eye, which is kind of an unusual complaint because typically a contact lens would dry out the eyes, it would make the eyes feel a little bit worse, but in his case it made the eyes feel much better.

That already kind of raised some suspicions that this might not be a normal case. He was using artificial tears every 5 minutes. He was using serum drops made from his own blood at the concentration of 25% and moxifloxacin twice a day. He actually kept these contact lenses in his eyes 24/7. He was prescribed moxifloxacin to use to prevent an infection.

He was using fluoromethylone a light steroid every now and then, whenever his eyes were really uncomfortable, and then Restasis once or twice a day. When we did our examination with him, he had 99% loss of his meibomian glands and a completely unmeasurable lipid layer thickness. When I went to express his glands, he had zero glands secreting in either eye. His tear breakup time was approximately 2 seconds. We were actually unable to do other tests with him. We couldn’t do Schirmer’s, or tear osmolarity, or anything like that just because his eyes were so uncomfortable that he wanted to keep the contacts and as long as possible before taking them out for the examination.

Then when we did slit lamp exam with him, we saw mild conjunctiva aclasis in both eyes, but it was actually worse superiorly underneath the lid. He had mild corneal staining centrally and inferiorly, but 2-plus corneal staining kind of superiorly right at the top. Then he also had one plus superior bulbar staining. With Lissamine green, he was having staining of these superior bulbar conjunctiva.

Now, anytime we see superior corneal staining and we see superior bulbar staining, that should really raise our level of suspicion for a friction-related ocular surface disease. Something where the eye lid, when it’s going to blink over the eye, it’s causing friction and is rubbing on the eye. That’s typically the point that you’ll see the friction ends up causing the most damage to the ocular surface. This kind of lines up with the fact that he was saying he had to wear a contact lens all the time because the contact lens is going to reduce the friction between the eye lid and the ocular surface.

The next thing that we wanted to do in our examination was try to figure out where is this friction coming from? What is happening here and is it friction because it sure seems like it. We checked things like lid wiper epithelial, but we didn’t really see any of that. Typically for that, you would put in the Lissamine green and then you would see staining kind of in the lid wiper area, kind of right at that line of marks where you’d see a normally a really thin line, but you’d see a lot thicker of a line that’s present there on the superior eyelid. But what we did find was when we went to go check for floppy eye lid syndrome… We would tug kind of right here and we would tug kind of upward and laterally and he had kind of mild to moderate floppy eye lid syndrome.

Whenever we pulled there, you could easily see the palpebral conjunctiva underneath that upper eyelid because typically it should be kind of nice and tight. It should be fairly taut. You pull on it exposes some of the bulbar conjunctiva, but you shouldn’t really be able to easily avert the eyelid and see the palpebral conjunctiva kind of underneath that eyelid.

This had me thinking, well, this sure seems like a classic example of floppy eye lid syndrome associated with obstructive sleep apnea. The second thought that I had was that this is absolutely not consistent with ocular graft-versus-host syndrome. Typically, with ocular graft-versus-host syndrome, you see really, really low Schirmer’s see diffuse corneal staining pattern. It’s very, very severe desiccation all over the cornea, lots of glycemic green staining throughout the entire bulbar conjunctiva. We didn’t really see any of that, and even though we couldn’t measure Schemer’s, his tiramisus height was relatively normal.

It much more aligned with obstructive sleep apnea. However, he did not have a diagnosis of obstructive sleep apnea. But one thing we know is high doctors is that if you find floppy eyelid syndrome that is highly specific for obstructive sleep apnea. Almost all the time that you find this and you refer a patient for polysomnography, they have it done. They’ll almost always end up being diagnosed with obstructive sleep apnea.

I started asking him some questions about his sleep. I said, do you snore? He said, yes. I said, do you ever wake up gasping for air in the middle of the night? He said yes, which I was surprised, most of the times I asked patients for this they don’t say that. I asked him if he had any daytime fatigue. He said yes, and then any morning headaches, he also said yes.

He kind of hit every single classic sign and symptom for obstructive sleep apnea, with the exception that he did not meet the classic phenotype for obstructive sleep apnea. Typically, these are older men like he was, he’s 78 years old, but he was not overweight. He’s 6-foot-1, 185 pounds, so relatively slender. He was not a smoker or anything like that, so he didn’t really have other risk factors for it. But still everything that we were finding screamed obstructive sleep apnea and floppy eyelid syndrome.

The plan… He came in with a pretty robust regimen and we can’t really change a whole lot because if he’s going to wear a bandage contact lens all the time, there’s not a lot of prescription drops you can put in the eyes if there’s a bandage contact lens in there all the time. We said well continue getting the bandage contact lens replaced every 2 to 3 weeks, continue the moxifloxacin, let’s start Optase Intense, a nice thick drop with hyaluronic acid in it to kind of lubricate and also aid with frictional relief from the eyelid blinking over the globe. It’ll kind of work well with those contacts.

Let’s add Tyrvaya, the nasal spray, to try to boost tear secretions. That is not a drop that you put in the eye, so it’s something that we could do that is not a drop, which you can’t really use with contact lenses. We said use that 2 to 3 times a day, space it out at least 4 to 6 hours, and then we’re going to keep the rest of the plan the same. Keep doing the serum drops your 6 to 8 times a day, keep doing the serum drop as needed. Of course, we educated him on risks with the serum drop, cataracts progressing, intraocular pressure spikes, infection risk, especially since you’re using the bandage contact lens, although he was also using moxifloxacin, which kind of mitigates that risk a little bit. But then the biggest thing that we said that we wanted to do was we really wanted to have him get polysomnography because we do know if you have obstructive sleep apnea, it can cause way more than just floppy eyelid syndrome.

This can dramatically impact the systemic of individuals. This can also impact the retinal health and the optic nerve health in these individuals. It’s really important to diagnose this. I said, we’re going to refer you for polysomnography. I went ahead and put in those orders, and then when I put in those orders, it also automatically referred the patient to a pulmonologist to interpret the findings from the polysomnography.

He had the polysomnography done about a month later, a sleep study, and this confirms severe sleep apnea. I mean very, very bad sleep apnea. He was immediately started on CPAP therapy. At this point now we’re still following him because there is evidence that shows that if you have obstructive sleep apnea and floppy eyelid syndrome and you treat it with CPAP therapy, there is evidence that it can improve the clinical outcomes of floppy eyelid syndrome.

Now, we’re giving it time and we’re going to see is this actually going to improve his floppy eyelid syndrome and maybe aid him with some of the friction-related ocular surface disease.

Also coordinated with his outside optometrist who he’d seen at one of our satellite locations saying we really need to be watching this patient carefully for glaucoma and retinal pathology as well. We do know that that’s very tied in with obstructive sleep apnea.

In the end, we didn’t necessarily help his eyes that much, but we gave him an answer as to why he was having a severe, severe discomfort that improves whenever he wore contact lenses. We also helped rule out ocular graft-versus-host disease, which is a really important thing to do, and something that the hematologist really want to understand is the graft versus host. Is the fact that you had that bone marrow transplant, is the transplant actually attacking the eyes? This is important for them to know so that they can adjust their systemic therapy, and then we’re hopefully going to help him in the future reduce his risk of systemic and ocular complications related to obstructive sleep apnea.