Lecture: Anterior Segment OCT for Ocular Surface Tumors

DR NARIANI: A very good morning, good afternoon, good evening to each and every one of you. I want to thank each of you for taking time out of your busy schedules to be with us today. And a very hearty thanks to the Cybersight team, Dr. Hunter Cherwek, Lawrence, Larry, and many more who have made this possible. Cybersight is an ideal platform for ophthalmologists, optometrists, technical teams, and many more all over the world. And to my understanding, 1300 registrations or so have come in for this lecture. With a total of 133 countries. And it’s just such an honor to be invited to give you the lecture today, titled Anterior Segment OCT for Ocular Surface Tumors. I have no relevant financial disclosures. Today we will start off with a few interactive multiple choice questions. Dive into the principles of anterior segment OCT, understand how to interpret a normal cornea, and distinguish this from ocular surface tumors and lesions. And finally, end on a look into the future. Future advancements in the realm of ocular surface imaging. So question number one for everyone: Which of the following represent or represents ocular surface squamous neoplasia or OSSN on anterior segment OCT “optical biopsy”? So you will be seeing on your screens the poll, A, B, C, D, and we’ll give you some time to go ahead and plug in your answers there. OSSN “optical biopsy”. Great. So we have a mix across the board. And I love that about this question. I’m so happy that there is that mix. Because we’re gonna go through the same question. And I want you to all remember what you answered right now, so that we can then go ahead and leave the suspense to the end of the lecture. To go through this. And one more question for all of you. Number two. And this is a look into the future. But very important to start to get a handle on this. On OCT angiography, which of the following is true regarding OSSN vessel area density? Or VAD? I’ll give you a few moments to take a look at the answer choices and plug in your best guess. Great. So we do have a leader of D. However, again, this is also across the board, and I love that, about that. That just goes to show that we have the gamut. And we’re gonna go through this question as well. At the end. Great. So let’s get started. I want to focus in on anterior segment OCT principles. Now, OCT of the anterior segment was initially introduced in 1994, using 830 nanometer wavelength of light. It had sectioning capabilities similar to that of confocal microscopy. But with better depth resolution. OCTs, however, have now evolved over time to include wavelengths ranging from 400 to 2500 nanometers. This technology of anterior segment OCT utilizes a Michelson interferometer, which creates an infrared reference beam of light, against which multiple other beams of light are measured. As they return from various ocular surface and ocular tissues at large. These reflected light beams are then collected by the device to create an interference pattern over the surface of this structure that is imaged. Now, today we’re gonna focus on anterior segment OCT as it relates in its utility for the analysis of ocular surface tumors, and of course, as an addendum to that, would be the ocular surface lesions. However, OCT of the anterior segment has shown great promise in identifying various other diseases, such as dry eyes, keratoconus, corneal dystrophies, endothelial graft assessments, intraoperatively, as well as postoperatively. And here’s a beautiful example of an anterior segment OCT where you can see a DSEK graft that is detached in the postoperative period. Now, anterior segment OCT has also shown great utility in the field of glaucoma. Allowing for acquisition of highly reproducible iridocorneal angle measurements. As compared with ultrasound biomicroscopy or UBM. And this image on the right visibly exemplifies closed iridocorneal angle. No two anterior segment OCT imaging platforms are the same. I want to emphasize that. Initial platforms were time domain devices, in which a reference mirror moved in a linear fashion over the eye to generate multiple A scans. Axial resolution, however, was limited by the speed of A scan acquisition. The transition from spectral domain — from time domain over to spectral domain or Fourier domain devices has permitted faster scanning speeds and higher axial resolution. Images due to the employment of spectrometers, high speed cameras, and broadband light sources, to allow for simultaneous capturing of all A scans. While newer domain platforms have offered higher axial resolutions, they are limited in their overall depth of penetration of tissues, as compared with time domain OCT, as well as UBM. Rapidly obtained images can range from axial resolutions in the range of 5 to 7 microns. That is considered high resolution. And you can see that in purple here on your screen. Whereas ultrahigh resolution involves axial resolutions of less than 5 microns. More recently, commercially available swept source OCTs, like the ones shown in green, have emerged that can acquire up to 100,000 A scans per minute. High resolution and ultrahigh resolution scans on OCT and of the anterior segment has allowed for a beautiful detail, increasing detail, as the technology gets better and better. And I want to take you through what is normal. Okay? To understand the depth in which we’re going to talk about this topic, it’s important to understand what normal is. You know, with MRIs and CTs, we have a radiologist to read our scans. For us, and interpret. But for all of us who are in cornea and ocular oncology fields, we are the ones assessing our own AS OCTs and determining what’s tumor and what’s not. So it’s very important to understand the normal. Over here, you can appreciate the thin tear film is thin and hyperreflective. The epithelium right below it, with the dashed red arrow, is a representation of what is normal epithelium. Which is thin and hyporeflective. You can also appreciate the level of the corneal stroma and the thickness and its consistency. And then here the hyperreflective corneal endothelium. So I can’t emphasize enough these two last images for us, as that is the basis of what we’re going to do. And it’s all about pattern recognition, my friends. Both normal — and this is an example of normal cornea and normal conjunctiva down below. And pattern recognition as it relates to abnormal pathologies. And this slide really sums it up. Here are your classic anterior segment OCT patterns for various corneal pathologies. Benign and malignant. So let’s go through it step by step. The first step… When you see something that looks abnormal on your anterior segment OCT is to identify whether it is located in the epithelial layer or the subepithelial layer. And it’s always helpful to look at various cuts in your anterior segment OCT. The differential of the image lesion that you take can be broadened, based on whether it’s epithelial or subepithelial. Now, OSSN, as you can see on the table in the leftmost column, or I should say the second to leftmost column, is located in the epithelium. It’s a disease of the epithelium. Whereas the other five lesions noted there are primarily subepithelial. They are pathologies located in your subepithelial layer. OSSN has the classic thickened hyperreflective epithelium, with an abrupt transition between normal and abnormal tissue. Now, those are your buzzwords. So I’m gonna repeat it. OSSN has classically thickened hyperreflective epithelium with an abrupt transition between normal and abnormal tissue. This is key. Now, you know — okay, it’s not an epithelial lesion predominantly — then you’re looking most commonly — would be to distinguish OSSN from the following five lesions, which would be conjunctival lymphoma, conjunctival amyloidosis, though rare, important to distinguish from all the others, conjunctival melanoma, conjunctival nevus or nevi, and pterygium. Or pterygia. Now, when we look at the next column after OSSN, conjunctival lymphoma, conjunctival lymphoma and amyloidosis both are hyporeflective. And two ways to distinguish these two are by their borders and their infiltrating material. In conjunctival lymphoma, all the cells are monomorphic. They’re the same. They’re dark. The appearance, thus, is homogeneous. And here in conjunctival lymphoma, the conjunctiva almost looks like a pseudocapsule. So another thing to keep in mind there. Conjunctival amyloidosis, as mentioned, is very rare. But it is good to know its distinguishing features. You will see lines in the subepithelial space, and those lines are very suggestive and classic for amyloidosis. We have discrete, smooth borders with stippled monomorphic infiltrates in your lymphoma, versus in amyloidosis, they are irregular, diffuse borders, with hyperreflective linear material. Conjunctival melanoma and pterygia will both be hyperreflective, though pterygia will have a very different appearance. And would be fibrillary in nature. And unlike conjunctival melanomas, a question has come up about this — when, you know, already prior to the lecture, from a number of audience participants. So one of the questions that came up was conjunctival melanoma versus conjunctival nevus. And that’s a great question. Unlike melanomas, conjunctival nevis will have cysts, tell tale of its chronicity. These cysts are generally in the subepithelial space. Yes. However, for children, many times, you may see these cysts in the junction as well. Now, it is important in the pterygia to remember that the epithelium is normal in thickness, but can oftentimes be hyperreflective. Why is this important? Clinically, when you’re looking at a patient in your clinic, and you’re assessing a pterygium, and wondering if there’s foci in there of OSSN as well, if you see thickening, that’s abnormal. If you see hyperreflectivity consistent with normal actinic changes, then you can rest assured that it’s a pterygium. Here is a beautiful flow diagram from a review handbook that I highly recommend those who are very passionate about this field and want to really understand the principles of it. Review, and I’ve kept the title of that review handbook there for you. By Carol Karp out of Bascom Palmer. This is a good way to understand — when you’re talking about epithelium, is it hyperreflective, subepithelial hyporeflective — versus hyporeflective epithelium, is it thickened, yes, or no, and accordingly, understand what it is you’re looking for. So your practice is… Keeping this up, by your anterior segment OCT, I think, will be a great tool for all of us. In addition to anterior segment OCT being an excellent diagnostic modality, AS OCT can also be used to monitor the progress of topical chemotherapy agents, such as mitomycin C, 5-fluorouracil, and interferon α2b. So here is an example of a 69-year-old male, with the classic pattern of — on AS OCT — in the top right, thickened hyperreflective epithelium, with abrupt transition between normal and abnormal tissue. After four cycles of 5-fluorouracil, there was clinical resolution in that OSSN. Here is a patient of mine. Another question that was brought up prior to the lecture was: How do you assess… You know, CIN and sebaceous or squamous, I should say, CIN, OSSN, epithelial versus just… Versus squamous cell, that’s invasive? So here is an example for you of a patient of mine with invasive squamous cell carcinoma. On anterior segment OCT, I’ve been able to actually create an anterior segment montage, and you know in the retina field how much we love our retinal montage to be able to identify the different locations. This is not something that has been published yet, but something that we do hope to publish in the near future, is this idea that we can create, on every slice and every corner of the lesion that is in question, a cross sectional aspect. So it’s not just depth. But it’s also location-based, and be able to create a protocol that will help us assess these patients. And not only that, but also be able to help identify your surgical margins. Because a number of times what you see there is not actually where your surgical margins are. And if you’re able to, on anterior segment, be able to put together a montage of images, you will be able to identify more accurately your surgical margins, should you need to go in for surgery. So the clinical pearls here… Use “optical biopsy” with anterior segment high resolution or ultrahigh resolution to differentiate ocular surface squamous neoplasia from other ocular surface lesions. During medical therapy, use anterior segment high resolution or ultrahigh resolution OCT to monitor progress. I keep repeating this. High resolution or ultrahigh resolution. That’s very important. Because in some parts of the world, where I am in India, we don’t always have access to high resolutions or ultrahigh resolutions in every center. And that really skews whether you can use your anterior segment modality to accurately identify and diagnose and monitor lesions. So it’s very important, if you’re getting into this field or looking for a new machine out there, to really focus on your high resolution or ultrahigh resolution OCT for anterior segment, should there not be a financial constraint. And finally, use anterior segment OCT to identify surgical margins and plan your surgical excision accordingly. A quick look into the future, as it’s very important that we actually start to identify what it is that we are going to be moving forward from anterior segment OCT, like we know now, with swept source OCT, and ultrahigh resolution OCT, being sort of the leaders, when it comes to ocular surface imaging. So too now has been this concept in the past few years of OCT angiography. And this is a beautiful paper out of Ocular Surface, back in 2020. And identifying vascular network patterns. OCT angiography is a rapid, non-invasive imaging modality that can detect vessel network via motion contrast imaging of the red blood cells across sequential B scans. Okay? And so this paper highlights the novel use of OCT angiography for OSSN. Now, going into this, I really want to focus in on the beautiful answers that you all have come up with. And I’m going to pause here again, because I think it’s a really good time for us to replay that poll. Now that we’ve gone through some of the concepts. And let’s talk about it. So question number one, again. Which of the following represents ocular surface squamous neoplasia on AS OCT “optical biopsy”? And let’s give everyone about 30 seconds or more to really evaluate each of these lesions. And it takes some time. So I want us to give time to really analyze each of these lesions, now that we know what we know. And then we will go ahead and answer this question. Okay. Super. So let’s analyze. Okay? The leader was B. And that was 42%. So it wasn’t a landslide. Followed by C. And that, my friends, is the right answer. C is the correct answer here. Okay? So C is OSSN. So let’s talk about that. Right? When we’re looking at the three lesions, we have to focus on the epithelial layer. If we’re thinking… Is this an ocular surface squamous neoplasia? Then we identify that if it has any pathology in the epithelial layer, that topmost layer, which should be hyperreflective and thin, then it should completely alert us to… Hey, could this be OSSN? When we look at C, we can appreciate that that epithelial layer — you can see the thickness on one side and the normal on the other, so you can appreciate that there is thickened hyperreflectivity in that epithelium with an abrupt transition. Do we see that abrupt transition between the abnormal on the left side of your screen in C to the normal on the right? There’s an abrupt lesion. Like, you can almost draw it. And I wish I did. But you can see that that epithelium has an abrupt transition. So that lesion that has the star asterisk in it, that is OSSN. Now, we’re not done here. Because if this is OSSN, what are A, B, and D? And if you would like, you’re welcome to put that in the chat box. What do you think A is? I’m gonna give a minute or less. To everyone. I want to just see what you think A is. Based on what we’ve gone through in today’s lecture. And now that you’ve thought about A, what do you think B is? And D?

>> So Dr. Nariani, we have some responses in the Q and A. If you want to open that up, you can…

DR NARIANI: Oh, perfect. Would you be able to read that for me, Lawrence? Because I’m not able to open it up on my screen.

>> Sure. So someone said A would be melanoma, B is lymphoma, B could be pterygium, D, amyloidosis.

DR NARIANI: Super. Well, we have a brilliant audience out there. Okay? So A was indeed a melanoma. It was an amelanotic melanoma. But of course, we cannot tell whether it’s amelanotic or not. But it’s important to identify that… Yes, this A is a melanoma. Okay? Great job, guys. B is a conjunctival lymphoma. Remember the monomorphic cells. Remember the homogeneity in lymphoma. And D being conjunctival amyloidosis with that sort of stringy appearance. Okay? And that is what is classically seen here. Super, guys. Very, very good. Going to our final question. Question number two. We’re gonna play this again. As a poll. On OCT angiography, which of the following is true regarding OSSN vessel area density? Now, we’ve not gone through this in great detail in the lecture, but I just want to identify and put some thoughts into this, and make sure we are on the same page with this. So let’s give everyone a poll for this question. Super. So the answer that was before, that everyone predominantly answered, or I should say around the same… I think it was 42%… Answered D and here were saying 45% D… The actual answer is C. Okay? The vessel area density was highest within the tumor. Which makes sense. Right? A tumor being vascular. We want to identify that they found the most within the tumor. Secondly, followed by the adjacent subepithelial tissue within… Underneath the conjunctival component. Okay? So I think this is a very important concept, but why am I bringing this up here? Well, we actually had a course called ocular tumors during the COVID time. Myself, Carol Shields, Carol Karp, Santo Swanaver, and others. And one of the things that was identified when we talked about OCT angiography for ocular surface tumors… This was back in 2020… Was this concept that it’s not easy to do. It’s a look in the future of what could potentially be useful in identifying OSSN cases. However, the patients have to be very still. Whereas with anterior segment OCT, we really have a lot more freedom and flexibility, but here patients have to be very, very still. And it’s very much technically dependent. Technician dependent, user dependent, as compared to anterior segment OCT. There is a beautiful paper out of Ocular Surface, in 2020, on this topic. Identifying 15 OSSN patients. And there the vessel area density within the conjunctival component was significantly higher than the corneal component. The vessel area density under the conjunctival tumor was significantly higher than the corneal component. And the vessel area density was highest in the tumor, followed by the adjacent subepithelial tissue. And here is some en face beautiful imaging that show the image on the top left is your clinical photographs, followed by your anterior segment imaging, in B and C. And when you look into the images of E, F, G, and H, you can identify where there is more activity going on. But again, it’s a very user-dependent modality. And it still takes time, I believe, for us to go ahead and use this as a standard of therapy. I’m sorry. In terms of standard of diagnosis. Of OSSN and other ocular surface tumors. I think the baseline imaging, nowadays, ’til date, is anterior segment OCT. And the ideal would be ultrahigh resolution. This is a beautiful image of an OSSN and showing… On OCT angiography clinically, in A, B, showing its beautiful OCT angiography with the florid intratumoral thin vascular channels, within the loops. And I think it’s just a beautiful way to just show and demonstrate what we could be assessing in the future. I’ve put together a few reading materials that can really help, in terms of understanding this topic more. And one of them was put out with Carol Karp, Gargi Vora, Melissa Daluvoy, and myself, out of the Manual of Cataract Surgery. And like I said, there is this course that we had put out back in 2020, which is free. It’s on YouTube. And available for everyone to review. Regarding not only ocular surface tumors and anterior segment OCT, but the gamut of ocular tumors. And I encourage everyone to take a look at that, in their spare time. I am always available. So if anyone has questions or comments or anything that I can be of help with… Because one of the things that… I think the most important thing that I can relate in this talk today, if you take nothing else, is that we are the radiologists for the corn and in the field of ocular oncology. The more normal you see, the better you are. It’s like a first year radiology resident. Right? We see normal, normal, normal. And then we start to understand what abnormal is. The more normal we see, the better we understand what abnormal is. So I would encourage you, as an exercise, if you have anterior segment OCT accessible in your practice, wherever you are in the world, to go ahead and take images of whatever you’re seeing. It could be just a random corneal lesion, a Salzmann’s nodule, a pterygium, what have you. But go ahead and practice visualizing it and seeing them. And interpreting them. Because as you do interpret what is benign, you start to understand — this is more malignant. And start to use it as a tool to monitor the progress of topical chemotherapy, as well as surgical margins. And in your postoperative scenarios, make sure to use it as an ideal tool for monitoring for any recurrence. Or remnants that may have settled in. So I thank everyone for their time. I’m going to stop my screen share. And I am just going to take a look at the questions that have come in. Oh, beautiful. Okay. I think all of the questions that have come in is basically exactly that. Discussing and identifying the answers to some of the questions that we’ve had. And I think that’s beautiful. So I want to thank everyone for their kind attention. Like I said, this is the basis of what you’re gonna do in clinical practice. So I am always ready and available to help you, if you see any scans that you want to run by me. Send it on WhatsApp. Send it on email. I get a number of those. So you’re always welcome to do so at any time. I thank you for your kind attention.