Metastases to the Eye

Podcast Transcript

Dale Shepard, MD, PhD: Cancer Advances, a Cleveland Clinic podcast for medical professionals, exploring the latest innovative research and clinical advances in the field of oncology. Thank you for joining us for another episode of Cancer Advances. I'm your host, Dr. Dale Shepard, a medical oncologist here at Cleveland Clinic overseeing our Taussig phase one and Cleveland Clinic sarcoma programs. Today, I'm happy to be joined by Dr. Arun Singh, Director of the Department of Ophthalmic Oncology here at Cleveland Clinic. He's here today to talk to us about metastases to the eye. So, welcome back to the podcast.

Arun D. Singh, MD: Thank you so much for having me.

Dale Shepard, MD, PhD: So, remind us again a little bit about your role here at Cleveland Clinic.

Arun D. Singh, MD: Well, I run the Ophthalmic Oncology Service. It's a unique kind of practice, limited to tumors and tumor related conditions of the eye. Most of them are primary tumors, but of course, we see secondary tumors and metastasis, conjunctiva, eyelid, orbit, uvea, retina, children, adults, all kinds.

Dale Shepard, MD, PhD: Excellent. So, we're going to talk about metastases to the eye. So, we have a number of people that might be listening from different backgrounds. Tell us a little bit about how common metastases of cancers are to the eye.

Arun D. Singh, MD: Well, I would say overall they're uncommon, but they do happen. Again, nowadays, patients are living longer even when they get diagnosed with cancer. And they're trying multiple therapies, first line, second line. And as they go through multiple lines of therapy, they're also more likely to get Mets in other places. And therefore, if you live long with cancer, you'll get met and then some of them also happen in the eye. So, I would say, overall, its a rising incidence, but we don't have any hard numbers.

Dale Shepard, MD, PhD: So, similar to how we've seen an increase in brain metastases and things like that?

Arun D. Singh, MD: I would say it'll mimic that to some extent, yeah.

Dale Shepard, MD, PhD: So, when we think about metastases to the eye, tell us a little bit about where that typically occurs. The eye is a complex structure. I think most people just see it as those who are not in ophthalmology to say the eye but tell us a little bit more detail about what usually happens with eye metastasis.

Arun D. Singh, MD: So, you can think about the eyeball and the socket or the orbit around it. And I would say, the most common site is the globe itself or the inside the eye, the lining of the eye, I would say uvea. The Uveal layer of the eye is the most common site. Retina and the vitreous inside are rare. And the second most common site would be the orbit. You can have orbital muscles, orbital space, orbital bones, and they all can get met, lacrimal gland, for example. So, nothing is spared, but most common in the eyeball itself.

Dale Shepard, MD, PhD: And so, when we think about eye metastases, what types of cancers do you see being most common that you see in your practice? Who's most likely to show up in your clinic?

Arun D. Singh, MD: So, to some extent it mimics the frequency of cancers in the general population. We see the most common cancers are breast cancer and lung cancer, so those are the ones that we see the most. Then also, really, colon cancers from the GI. Rare would-be skin melanoma, for example. Those really typically don't come to the eye. But most uncommon would-be sarcomas. The sarcomas, very rare in the eye. Mostly carcinomas, which are epithelial tumors, and among them adenocarcinomas more than squamous carcinomas.

Dale Shepard, MD, PhD: Got you.

Arun D. Singh, MD: It depends upon the type of cancer. But if you look, go by the site, a breast, a lung, colon, prostate, skin, are the top ones.

Dale Shepard, MD, PhD: And so, what would be the most common symptom that would lead someone to show up in clinic with a concern about eye metastasis?

Arun D. Singh, MD: Well, there's no specific symptom as such that you have this and therefore you have a met. Is that non-specific? Usually, it'll be visual, some kind of visual distortion, shadow in the vision or just loss of vision. And that's when this in the eye itself. And when it's in the orbit, then you can have things like double vision or difficulty in moving the eye, or the eye is more prominent, along those lines. And rarely can it mimic inflammation. The eye is red, painful and not responding to the treatment, and then you find that it is a metastasis that's masquerading like an inflammation.

Dale Shepard, MD, PhD: And I guess that becomes confusing sometimes, because some of our therapies will cause blurry vision or they'll cause changes in visual acuity, or even some of our targeted therapies will cause distortion and vision. At what point should oncologists be considering having someone seen by an ophthalmologist?

Arun D. Singh, MD: I think if the patient is aware enough to complain, the eye should be examined. Like you said, rightly said, some of them are drug induced minors. And some of them can be more significant, like retinopathies with the new targeted drugs, but they can be significant. But uveitis or inflammation that we see with immune therapies can be blinding. And in such cases, you have to either cut down the dose of the immune therapy or hold back certain cycles, or cover with steroids, or just change, or find an alternative. So, those are important issues. One thing is to make the patient live long, but what if they go blind in the process? How does that help the quality of life? So, I would say to pay attention.

And the other thing very common really is the use of steroids. And all of these chemotherapy steroids are being used in the background to cut down nausea, et cetera. And they can cause cataracts. They can cause focusing problems and some dryness issues related to chemotherapy. So, some of them can be non-specific, but nevertheless, if patient is complaining, I think they should be checked.

Dale Shepard, MD, PhD: So, as oncologists, are we paying enough attention to symptoms and are we sending to see you at the proper time? Do you normally see patients coming in later than you would've liked to have seen them?

Arun D. Singh, MD: No, they come. I think in the clinic system, people I think tuned in. And many times, like you said, they just need new glasses, or they happen to have a cataract that they didn't realize they had, or their diabetes went out of control because of something else. So, it's not necessarily all cancer related, but something else in their therapy has tipped the balance of something or the other.

Dale Shepard, MD, PhD: And so, when you think about imaging, how are these usually diagnosed?

Arun D. Singh, MD: Usually, by examination. So, it'll be rare for some of the Mets to show up, say on the scans, CT scans or the MRI, because the eye is too small for many of these imaging modalities, except the orbit. But in the eyeball, itself, we examine them directly with our lenses. We can see the retina; we can see the tumors under the retina. That's the best and the most sensitive way of noticing them. And based on what we find, we order special imaging. We have eye ultrasounds, we have eye OCT, we have other imaging dedicated to the eye, which is magnified and so much better than the regular MRI, for example.

Dale Shepard, MD, PhD: And typically, what would be the role of a biopsy to confirm metastasis?

Arun D. Singh, MD: So, if the patient has cancer, say breast cancer, just to talk about it. And as for the patient is concerned that all the recent testing has indicated there's no metastasis, she's under control, breast was the only place and everything else was clear, and then she gets blurred vision. So, that is the first time you're trying to say that now she has a metastatic disease. In a case that, biopsy is necessary. You have to show the tumor has gone from beyond where it is, at least at one site away from the main tumor. If it's a well-known case of metastases, they have Mets in the lung, brain, wherever, and they now have blurred vision, and the clinical findings can be corroboratory, and you do not need a biopsy for that. So, it just depends on the clinical setting.

Dale Shepard, MD, PhD: And then from a treatment standpoint, how are these usually treated?

Arun D. Singh, MD: So, the first line treatment is that we will assess what patient has been on already. And if they're getting Mets on the treatment that they're on, obviously they're failing the chemotherapy that they're on or immunotherapy that they're on. So, then the question is to explore second line treatments or alternatives, which are usually less effective and more toxic. So, the likelihood of response also goes down. So, based upon patients' overall status and the expected lifespan and other things of that nature, we would first work within the spectrum of their primary therapy. And if that's not effective or available, or nothing else is possible, then we talk about radiation therapy. And it can be external, like the typical radiation or it can be more specialized, like brachytherapy.

Dale Shepard, MD, PhD: And talk to us about, if you think about systemic therapies in terms of the eye and access of systemic therapies to the eye, tell us a little bit about how effective most of our therapies are.

Arun D. Singh, MD: That's a very important question. I would say the circulation of the eye, or the metastases happens mostly in the uveal layer of which has circulation like the rest of the body. So, if you have intravenous chemotherapy, it'll get access to the tumor in the choroid or the uvea for sure. And so, it's not restricted by blood brain barrier as it might be, for example, in the brain. So, the eye is an extension of the brain, but the uvea has a different circulation, so there is no restriction from that perspective.

Dale Shepard, MD, PhD: Are there any new therapies that might be particularly important for eye metastases or anything that looks promising in the future? Or does it really focus primarily on systemic therapies that access the eye?

Arun D. Singh, MD: So, most of it is systemic therapies, because the Mets can be multiple and multifocal. So, it's not just one area. There could be two or three spots in the right eye, two or three in the left eye. So, that makes it a little challenging to go after each little spot. And what you're seeing, there's obviously more than what you're seeing, so we have to keep that in mind as well. But for some particular tumors, such as carcinoid and other tumors for which we don't have good effective chemotherapies, we obviously get into more in terms of laser therapies, special kind of treatments which are laser-based specifically for the eye.

Dale Shepard, MD, PhD: And I guess the question would be, these are uncommon, if somebody might be listening out in the community, how important is it for them to be seen by someone that is more experienced seeing these eye metastases?

Arun D. Singh, MD: So, I tell them it's important that first the diagnosis be established correctly and rapidly without unnecessary and harmful tests. So, there's going to be a delay. And that delay obviously doesn't lead to a good outcome. And when it comes to chemotherapy, that can be done in community, that's usually not an issue. We always work with the oncologists, we call them, talk to them and figure all those things out. When it comes to radiation, I encourage them to come to main campus, I have to say, because these are tissues or organs to be treated, and many oncologists, radiation may not be familiar with it. So, we encourage them to come here perhaps with better-quality treatment.

Dale Shepard, MD, PhD: Excellent. Anything else that you think people need to know about eye metastases?

Arun D. Singh, MD: I think in the metastasis business, some of it is palliative, and I guess most of it is, and it's all about quality of life. And I would say vision is way up there in quality of life. If you can't see what's in front of you, I'm not so sure how meaningful life can be. And being an ophthalmologist, maybe I'm biased a bit, but I think this is important. And the other thing, and this is very significant, people may have a tumor in the liver or lung that they don't feel or see. But if the vision is blurry, as long as you're alive and blinking, you are seeing that manifestation of the tumor. There's a constant reminder to you that something is wrong with you. So, they somehow disproportionately sometime fixate on the symptoms and that's just the way human psychology is. And we have to be mindful of that or be respectful. And I think it's important to take care of it. If you think about the quality of life, it's all this business is about.

Dale Shepard, MD, PhD: Well, this is a rare, but important topic. And I appreciate you being with us today.

Arun D. Singh, MD: Well, thank you so much for highlighting it.

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