Lecture: How to Avoid Misdiagnosis of Orbit and Periocular Disease: Learning from Atypical Presentations

During this live case-based interactive webinar, we will examine how to avoid misdiagnosis of orbital and periocular disease for an optimal patient outcome. We will learn from cases that presented as common conditions such as orbital cellulitis, eyelid infection, or nasolacrimal duct obstruction, but when examined closely give us evidence of atypical presentation of a common condition. To distinguish what is atypical, we will compare and contrast two cases for each presentation of common misdiagnosis.

Lecturer: Dr. Vivian Yin, Ophthalmologist, Vancouver, British Columbia, Canada

Transcript

[Vivian] Hi, everyone. Thank you so much for joining us today. I am speaking to you from Vancouver, Canada. My name is Vivian Yin, I am a clinical associate professor at the University of British Columbia in Vancouver, Canada. And today we’re going to talk a little bit about case base presentation on atypical presentation of what may be common conditions that you will see in oculoplastic and orbit. And how to spot the things that will clue you in on something more than what meets the eye or what the referral was initially for. So let’s get right into it.

We’re going to look at a couple of common conditions. The first one we’ll go through is orbital cellulitis, and when an orbital cellulitis may not be so simple and straightforward. Then, of course, I think it doesn’t matter if you’re an oculoplastic surgeon or general ophthalmologist, blepharitis and ectropion and tearing are all common conditions we see in our patients. We’ll talk about a few cases of how these presented as common condition but in the end was something more than that and how can you spot that.

This first case is a 34-year-old male who was referred for orbital cellulitis. He tells you that there’s been a bump in the medial canthus for the past month, it’s not really tender, it’s not really red. And no history of any dental abscesses or recent dental surgery. He has, however, been admitted for a colonoscopy in his 20s, so roughly ten years ago. But no genetic testing, just had some polyps removed. Otherwise he’s a very healthy young man, no risk factor for any immunocompromise or HIV.

And this is where you see him after being treated in a community hospital on IV broad spectrum antibiotics. So he was initially on vancomycin plus ceftriaxone for two days, didn’t respond. So they switched him to daptomycin, a little bit more fungal coverage and ceftriaxone and presents with this type of an imaging. The first thing you look at, you know the obvious abnormality, of course, is in the left inferior medial orbit. So there’s massive, infiltrative, ill-defined grey matter. You’ll probably notice that it’s pushing and indenting the globe superolaterally. And when you look around it, though, you’ll notice that there’s some thickening of turbinates and nasal mucosa, so this is your inferior turbinate, I’m not sure if you can see my pointer or not. But you can see adjacent to it, there’s some soft grey tissue mass. But it does go pretty far posterior, traveling between the inferior rectus and the medial rectus.

At this point, recognizing that this is referring for an orbital cellulitis, presumably failed medical therapy, and you’re seeing this patient for consideration of incision and drainage of this mass. When you look at the CT, what do you think is missing on the CT that will clue you in that when you’re counseling this patient for surgery that what would you like to do in addition to draining the abscess, so to speak? What is missing?

I’ll give you guys a few seconds to fill that in. Think about what normally you would expect of a routine orbital cellulitis. What is the most common thing that should be there that you didn’t really see in this case?

It’s interesting that I think the majority of people picked all of the above because those are all symptoms of orbital cellulitis. Definitely you can get heterogeneity of mass, so usually if it’s an abscess you should see some more hypodense matters in the center and more hyperdense around the surrounding. Sinus opacity is definitely high on the list as orbital cellulitis needs a source. And the more common source is our paranasal sinuses. Although in adult hematological spread can happen, it’s still the minority. Fat stranding and mucosal thickening are both signs of inflammatory conditions. So it could either be cellulitis, meaning driven by an organism, or it could be idiopathic inflammation or any of the other inflammatory conditions of the orbit. But the most telltale sign is actually sinus opacity. Because you need to have a source of your infection. And if you don’t have a source, then you really have to think hard about even if this was still a cellulitis, where is the organism coming from, are we dealing with an immunocompromised patient? Are we dealing with one of the weird bugs which some of you have mentioned in the presubmitted question about parasites or even referring physician or any thought about fungal but also atypical bacterium?

This was actually a diffuse large B cell lymphoma. The lack of sinusitis and the mass being very solid. And you’ll know that as soon as you go into the orbit as well, intraoperatively, that it was a completely firm, solid mass. With not really any fluid or pus we need to drain. So that, at the time, would have indicated to you the need for a biopsy. And I’m showing you this about how diffuse large B cell lymphoma is really not a surgical disease. This is a medical disease. So these images on the small full face are PET CT scans. These are very useful to try to highlight hyperactivity in a tissue and cancerous cells or inflammatory cells are usually quite active so they come out really, really bright.

So this is him at baseline, you can see the hyperactivity despite us debulking this a little bit during the time of surgery. Both to get tissue but also to give him some relief of the pressure of the globe. You can see how infiltrated this mass is that actually goes quite back into the apex. And this is three months later after four cycles of RCHOP, which is one of the most standard chemotherapy. And how it almost completely melt away and there’s no longer that hyperactivity. Extraocular muscle do highlight a little bit, so that’s what you’re seeing here, this is actually nonresidual disease.

Let’s move onto the next orbital cellulitis. Also a young individual, 26-year-old female. I’m showing you two cases of young individuals, but by no mean am I trying to imply that you have to have an increase and extra suspicion that an orbital cellulitis in a young individual is not orbital cellulitis. Not at all. It just happens that these two cases all happen to be young individual. The same principles apply, it doesn’t matter if this is a 20, 30 year old or if this is an 80 or 90 year old, the principles are still the same, the things you need to look for are still the same.

This was a young lady who initially complained that she had some eyelid swelling. She went to a walk-in clinic to see a GP, or a general practitioner, and was given some moxifloxacin drops. Two days later she got a little worse, so she went back and amoxicillin orally was added for five days. Still no response, so then was changed to Keflex for five days and still was continuing to worsen. Otherwise she’s been healthy up until this point. And when you examine her, you see globe displacement, you see proptosis, there’s some mild erythema but much more edema than erythema, so three to four plus edema. Almost like a very faint pink swellings, I apologize, I don’t have a clinical photo of her. And she had some restriction in abduction, but that’s it. The rest of the ocular exam was normal, no optic neuropathy. Nothing else to indicate to you what is going on.

Of course, you smartly order a scan, just to see what’s going on and this is what you see. This scan, at presentation, shows you the classic things that you would expect of an orbital cellulitis. Looks like an abscess, there’s, as I mentioned earlier, the hyperdense surrounding tissue with a hypodense central cavity. Even more prominent here, really makes you think this is an abscess and a cellulitis. However, we talked a little bit earlier about how if there is an abscess, especially ones that are against an ethmoidal air cell, you would expect that in order for this abscess to have formed from a source from the ethmoids, you have to have ethmoidal infection. But these ethmoids and these sinuses are pristine and perfectly clear. Makes you take pause what is really going on.

And this is her after drainage. So we did go in and drain and there was fluid in the cavity so you can see the cavity, especially this view in the corona view, it really deflated or shrunken. But she still wasn’t improved and that’s why we got another scan. Culture was all negative, even though you cultured fluid, as well as swabs. And 36 hours later she wasn’t improving clinically. We repeated the scan and this is what the scan looked like. She doesn’t really look worse. But you still seeing just massive amounts of what I usually keep as simple and call “fluffy stuff” that’s going on that is indistinguishable from any other surrounding orbital tissue. There’s definitely lots of inflammation going on, there’s fat stranding. At this point, though, you really have to think about what else could this be?

We went in again after she did not respond to the incision and draining, nor did she respond to broad spectrum coverage, and took biopsy of the tissue that was still remaining and this turned out to be an embryonal rhabdomyosarcoma. The lesson for this case is really sometimes things can have certain feature that may lead you to think that is classic for an orbital cellulitis. But if one of the key feature is not there, which in this particular case I’m stressing the importance of looking for sinus opacity. Not that those other signs are not part of the diagnosis of orbital cellulitis, but more sinus opacity is very, very important, probably the most important thing to look for on an orbital cellulitis diagnosis. This particular patient, because of the embryonal feature of it, had a standard regiment of five agent chemotherapy. It shrank significantly, as she’s clinically back to baseline, but you can still see there’s a residual mass sort of indistinguishable from the medial rectus. Maybe even directly involving the medial rectus. So as a sidebar, in cases like this, the next step after four cycles of this would be to proceed with adding radiation to this. So she’s now getting combined radiation and chemotherapy to try to shrink the rest of this.

Now the question in your mind is sometimes your medical oncologist may push you to say well can you cut out the rest? And a lot of time in the orbit the answer is almost universally no. Because the morbidity of cutting out the rest of this would have been too significant for the patient, she basically will have a globe that does not function normally and be suffering from intractable diplopia which in adults is not something most patients can tolerate.

Switching gear a little bit, it’s not uncommon that sometimes people will tell you they got an incidental mass that was found, now that we’re doing more neuro imaging for other causes. This is just a case to highlight that this is a 67-year-old male who was scanned because he was complaining about a frontal headache that wouldn’t go away after many, many months. The community hospital ordered a CT scan for the patient and noticed this infiltrative mass in the left apex of the orbit. And you can see it quite involved all the way to the almost the optic nerve and the superior orbital fissure, that’s what you’re seeing here. Patient was referred to you as incidental mass of the orbital apex. And usually when we get this type of referral, we think about benign lesions. So this must be inflammatory because the patient had no symptom and there was nothing else going on, he’s otherwise healthy. But if you look carefully there’s a couple of things that will clue you in that this might be something more than just benign inflammatory syndrome.

One of which is this subtle bone destruction. You’ll notice where my pointer is that the cribriform plate, which is this horizontal line right here, this is your sphenoid sinus, is slightly starting to get thinned out on the left side. Whereas the right side is still intact. This is bone erosion. And wherever you see bone erosion there’s one of two things that can happen. One is cancer, until proven otherwise. And the second one is one of these nasty infection such as mucor and the ones where you really want to treat early and aggressively to try to save the patient’s life. However, the patient, as I mentioned to you, had no symptom. In the event that the patient has no symptom, no orbit or ocular sign and presents simply with this, then cancer moves a little bit higher on the list of differential.

The other thing to look at on the axial scan, that’s why I’m showing you this particular cut, the superior orbital fissure, is you can see a subtle enhancement into the brain. If you look very, very carefully you can see an outline right here. This mass, not only is it intraocular, it’s actually starting to creep into this space for the brain, so intracranial extension. Whether this is inflammatory, secondary to this mass, or this is actual direct cancer extension, you wouldn’t know on a CT. So you would need to order an MRI to better delineate that. But these are the two telltale sign that there’s something more. And, of course, when you biopsy this patient and you find out that he actually has follicular lymphoma and this is actually lymphoma.

A couple of things to really look out for when you’re thinking about orbital cellulitis that may not be orbital cellulitis, the number one thing, is of course, the lack of sinus opacity. The second most important thing is when there’s lack of response to appropriate and broad spectrum antibiotic. Now, it’s very important to talk about appropriate antibiotic choices. In the Cybersight archive there was a lecture I’d given last year on treatment of orbital inflammatory diseases and in there you’ll find the recommended antibiotic regimens for adults and pediatric orbital cellulitis. If you’re wondering what is appropriate broad spectrum, definitely look that up.

The other thing you have to keep in mind is there are significant regional variation, mostly with antibiotic resistance. So also contact your local infectious disease personnel, ask them what is the most recent antibiotic use spectrum that they recommend. They’re always usually tracking that and will be able to tell you that. The third thing to keep in mind is that if it truly is a cellulitis, there has to be inflammatory signs. Now a lot of other things can produce inflammatory signs as well, and I believe there was a question about that. How do you distinguish true inflammatory diseases from other diseases that may masquerade as inflammatory disease?

One is, we’ve already talked about, which is cancer. And I would say, for cancer, usually the inflammatory signs are there but they are very mild. With someone who has, let’s say, EOM restriction or significant globe displacement or even worse, optic neuropathy and yet they have just faint pink and just some swelling. Not a red hot eye that just looks uncomfortable, then you should be thinking about this might be something more because it’s not really in keeping with things.

I put bone destruction in gray because there are some cellulitis that can cause bone destruction. So it’s not that cellulitis cannot cause bone destruction, but more if you do see bone destruction and you have the above three things in addition to it, then you have to think about something other than cellulitis.

And of course, take tissue in addition to your usual culture and swabs. And there was actually a recent study I remember reading, that came out a couple of months ago, that talked about what is the best way to culture orbital cellulitis. And I think the key take home points of that study was the best culture to take is actually directly from the abscess. If the patient has orbital cellulitis and you take a conjunctival swab, it’s actually not as diagnostic as getting the abscess fluid. When possible if there is an abscess, try to get the abscess fluid if they’re not responding to antibiotic. And of course at the same time when you go in to get that also take some tissue in case you’re dealing with something other than a cellulitis.

Okay, let’s switch gear a little bit and move on to our spectrum of blepharitis. This is a 67-year-old female who’s been given a diagnosis and been treating for rosacea blepharitis. She said she’s been getting some foreign body sensation in this left eye for about seven years now. The community doctors have put her on doxycycline appropriately if she was having recalcitrant blepharitis. And she gets Tobradex ointment twice a day when she gets a flare up. But sometimes she has to use it for up to six weeks as these flare up tend to stick around for a lot longer. Her past medical history was non significant and she’s otherwise healthy.

So looking at her picture here, have a close look at her blepharitis and try to figure out is there anything in this picture that is out of keeping of what you would suspect of a blepharitis? I’ll give you a second to look at that.

Sorry about that. If you look very, very carefully, you’ll notice that, I will actually argue that her blepharitis is not that bad. But if you look and follow her lid margin all the way over, you’ll notice that the eyelid margin is sectorially different right here, compared to this part. There’s some thickening, there’s a little bit of erythema here. And then there’s some irregularity to the mucocutaneous junction.

When you take a biopsy of this, this is what you actually find. Lots of blue cells, in a serpiginous or infiltrative pattern. And under high mag, you’ll start to see the basophilic cells that infiltrates throughout. These atypical, funny looking cells, big nuclei. So this is actually an infiltrative basal cell carcinoma. So she’s been misdiagnosed or this basal cell has been growing without being mistreated as a blepharitis.

And when you look a little closer at her, you’ll notice that the erythema on the papules side of the conjunctiva, actually comes further medial. And then you start to notice there is some caruncle edema here in erythema and even the plica seems inflamed and congested.

You smartly organize a CT scan to see what else is going on and you’ll notice this mass along the entire medial orbit, little hard to tell apart from the medial rectus, but the medial rectus is right here so it’s pushing the medial rectus up and laterally. And when you do a frozen section and follow this mass all the way back, you realize that this is actually a much bigger mass and resection than you anticipated. We have to look for subtle signs, sometimes these things are sneaky and it doesn’t necessarily present with a mass, so to speak, but you have to look for those telltale signs that are giving you a hint that something’s not right.

Another patient who’s been suffering from blepharitis for a while, now this is a much older patient. This is a 93-year-old woman with blepharitis and she says that she’s had foreign body sensation and burning for now three years on the right side. Also healthy, otherwise, no other health issues. And probably one of the healthiest 93-year-old you’ll ever see.

I mentioned to you that it’s the right side that she complains about. If you look very carefully at her clinical photo now, you’ll notice a similar appearance as the last lady. When you look at the lid margin, you’ll notice there’s some faint erythema, but really nothing too shocking. But this kind of subtle thickening to the lid margin. Especially when you compare to the other side, you’ll see how the other side of lid margin looks a lot thinner. And sure, there’s some erythema or some injection, but it’s really not like night and day. And the other thing to remember with blepharitis, is that sure, it can be asymmetric between the two sides, but it shouldn’t be completely unilateral. This eyelid looks completely normal and just have a pure unilateral blepharitis is not normal and you should be thinking about something else.

What would you like to do on the exam at this point for this lady? Would you like to evert the eyelid? Would you like to do an intraocular pressure? Would you like a Schrimer test? Do you want to know the extraocular motility or none of the above? So I’ll give you a couple of seconds to answer that.

The eversion of the eyelid, what you’re looking at, is basically the palpebral conjunctiva. Great. Excellent. I’m glad that my hints worked. At this point you definitely want to evert the eyelid and have a look at what’s going on. So this is what you see on eversion. Lots and lots of thickening, irregular thickening of the conjunctiva. At first glance you may think this is a papillary reaction but it really isn’t. It’s not, you can see a hint of white to it. And you can see an edge here that goes all the way up and this part is completely thickened and plaquoid like. This was actually a sebaceous cell carcinoma that was missed and she had basically diffuse involvement onto even the parts of the superior fornix and wrapped around onto the lateral lower lid as well.

She chose to proceed with external beam radiation, which because these are not super radiosensitive, those tend to be a little high and it can cause this type of skin necrosis. That if you’re just patient it does heal over time. And you can see how now it’s completely smoothed out. Of course, radiation causes significant damage to normal tissue as well. So even though you’ve treated the cancer and the cancer is completely gone, she has madarosis, she has loss of pigmentation and these effect, quite a few of them are actually permanent and life long.

She’s very happy because she did not want surgery, so this was her choice to proceed with radiation. She felt like she was 93, she wasn’t going to live that long anyway and she just wanted to make sure that this at least doesn’t spread and cause her to have metastasis or lose the eye completely.

There’s a question from Rhyme about the lymphoma case. Sorry, I didn’t see it earlier. The biopsy, what Rhyme is referring to was that last case I showed of the infiltrative mass of the orbital apex that was incidental, so to speak. And he or she is wondering whether the biopsy was done through the orbit or the sinus. Thank you for the question, Rhyme. That’s a great question, so it was actually done through the sinus. As you can see a sinus access instead of trying to access the orbital apex was such a confined space and so close to the nerve would have been easier. So I had to ask one of my ENT colleague to biopsy through the sinus. Very good point. Sometimes in the orbital apex a biopsy is easily accessible through the sinus, even if it’s on the other side, sometimes I will still do the biopsy through the sinus approach rather than through the orbit. Especially when you’re not sure what the diagnosis is.

That were the two cases of blepharitis that ended up being something more. This is along the same spectrum. It’s not a blepharitis, but I sort of think of chalazion as going along with a blepharitis or untreated blepharitis. This was a 64-year-old African American female who had a chalazion that just won’t go away. She says that she’s been scraped initially and then had an I+D, but still was having some foreign body sensation that she used the word scraping. But really just discomfort and ocular surface irritation. She thought the doctors couldn’t do anything anymore so she waited six months and it’s just getting worse and she feels like now there’s multiple chalazion, multiple growth. She finds the eye to be tearing and itchy and just uncomfortable.

She does have some past medical history, she has some hypertension and asthma, she’s morbidly obese. She also has eczema, arthritis and some reflux that are all managed medically.

If you look a little bit closer at her, this is what you see. And at first glance, you can think, well, she’s had I+D in the past, and she’s an African American female, which they do have a tendency to hypopigment with inflammatory lesions. And this could almost look like a pyogenic granuloma on top of a previous excision site. And you see that sometimes with chronic chalazion that they get these little pyogenic granuloma forming at the site of where the chalazion used to be, even if the chalazion is not quite there anymore.

But the things to really pay attention to is the mucocutaneous junction. And this is the point where it goes from non-keratinized to keratinized, or start to become keratinized. And this junction is actually one of the most telltale signs about whether there’s something more going on, some destruction of normal cell junctions or cell territories. Even though this, sure, I would buy that, that that might be a pyogenic granuloma. But the stuff that is surrounding it, sorry, trying to get my pointer to show up again. The strand that’s surrounding it, this stuff, is what concerns me. This almost looked like blurring of margin between what should be squamous, non-stratified squamous to some of the keratinized squamous cells. And you can see, same thing over here, this breakage of that nice angle you’re supposed to have of the lower lid margin.

But this actually, well, I guess I’ve already given you the answer, but this is not something you want to treat as if it’s just a chalazion. And instead of continuing with standard treatment for what you would expect, a chalazion with Tobradex and warm compresses. You probably want to investigate a little further. So we had organized a CT scan. And this is what the CT scan show. I’ll give you a minute to have a look at this on your own first, and then I will walk you through it.

While you’re looking at this, Ace has asked, how do you diagnose sebaceous cell carcinoma in that patient that we just saw? When clinically you are suspicious that there’s something a little bit more, you do a biopsy. It’s hard to biopsy over the conjunctiva over the tarsus, you can, but it’s just a little bit more viable. In diffuse enlargement like that, the easiest spot to biopsy is right at the superior edge of tarsus. When the conjunctiva from the tarsal edge meets the superior fornix, that’s an area that’s easy for you to biopsy.

In terms of when, I think Amaruta is trying to ask about for cases of blepharitis that are atypical, when do you biopsy an atypical blepharitis? And I will say my index of suspicion for biopsy blepharitis that just don’t respond to treatment at all is pretty low. A lid margin biopsy or taking a small piece of the lid margin or even conjunctiva, those heal really, really well. So really you can’t argue with not doing a biopsy. Usually what I would biopsy is anyone who I put on treatment for blepharitis who comes back a month later and they’re just zero improvement. You don’t see any decrease in that thickness, you don’t see any decrease in the injections, or the quote/unquote papillary reaction when it’s really just conjunctival thickening. And, of course, there’s also some that you know it’s not. For that sebaceous cell carcinoma case that I showed you with a diffuse thickening, that, I think, once you’ve seen it once now, you know that that is not blepharitis. I think the next time you see that you’ll know that that is not blepharitis and you’ll still need to do a biopsy in order to prove your suspicion. But you’ll probably not even treat that with conservative management for a month at all.

There’s a lot of question about the sebaceous case. I’ll leave the question about reconstruction, Reynaldo, to the end. I’ll come back to that. I’ll come back to some of the more detailed question about treatment of lymphoma a little bit later.

Coming back to this case, you notice that just walking you through this, you’ll notice on the right side. I showed you a CT coronal slice through the area of the lacrimal system. Let’s look at the normal side first. This is your lacrimal sac, here’s your inferior turbinate. So the sac duct junction will come out somewhere around here. Because the mucosa of that area’s rather thin, sometimes you don’t see any gray matter around it, you just see a tapering off. That’s what the normal sac and duct look like. And when you look at the other side, you’ll notice that the sac is distended and enlarged. And there’s significant mucosal thickening of this nasolacrimal duct.

When you look at it on the other side as well, you’ll notice that the normal sac feels a little thin and there’s more emptiness or sag in the middle of it. Whereas on the other side you don’t see a lumen as well, the lumen just looks like a sliver right here. Then there’s a lot more thickening of this sac mucosa. This actually was a squamous cell in situ that’s completely involved the lacrimal drainage system, originating from the eyelid, of course, and then traveling down the sac. And this is your canaliculus, so this is the lumen of the canaliculus. And you can see this profound thickening of the wall of the canaliculus.

Another view to try to really show you how this, usually this is only a couple cell layer thick. So this is way thicker with a lot of lack of differentiation and keratinization to the surface of the mucosa. And this just can show you in comparison, on to the conjunctival surface, these large blob of cells that comes all the way out to the mucosal surface. Not these, these are just mucin. But these large cells that come all the way up without losing it’s extracellular matrix which is what it’s supposed to do once it reaches the surface. That kind of transition of normal cell pattern is completely lost. A lot of cellularity which you’re not supposed to see with normal conjunctival mucosa.

In this case with squamous cell carcinoma involving the lacrimal system, unfortunately in order to completely remove it, you could do radiation alone. Because squamous cell is sensitive to radiation. However, in order to do that, you would have had to radiate a good portion of the globe. And in this particular case, you would have probably caused a sectorial retinopathy. Because she was relatively young, and relatively healthy, healthy enough to undergo significant surgery, she chose for a curative intent with complete removal of the lacrimal sac, complete removal of the nasolacrimal duct, removal of all the ethmoid around that area to insure that there’s no extra luminal spread. And then with topical Adjuvant chemotherapy with 5FU and Interferon.

This is what she looked like after the surgery. On the surface, it actually didn’t look like much because most of the surgery was done conjunctival and then into the removal of the nasolacrimal duct as well as the ethmoid. So you can do that actually quite easily with split thickness of the eyelid. So you’ll notice when I pull the eyelid down that there is the edge of completely reconstructive eyelid. And when you split it like that, and then detach the eyelid from the medial campus tendon in order to reach your lacrimal sac, you can actually access the medial orbit in that fashion without performing your standard orbitotomy fashions. This was also done in conjunction with ENT, so this way you can dual access visualization. So you can see up the nose, know where your mucosa cuts are at the same time.

A couple of things to think about for atypical blepharitis is think about lid margin thickening. It’s useful to us that the lid margin has a very characteristic appearance with a square edge at the mucocutaneous junction. When the eyelid thickens, it’s quite noticeable. And then if you lose the mucocutaneous junction where that non-keratinized to keratinized mucosa happen, that’s also a very, very telltale sign of something going on. You’ll notice in the future, now that I mention this, look at your blepharitis patient. And you notice that despite the rounding of the angle, they still maintain that mucocutaneous junction. You can pinpoint or draw a line of where keratinization occur. Practice and train your eye to spot that and when you start losing that, that’s when you know something more is going on.

And then look for the palpebral conjunctival thickening. You can’t chalk everything up to just mix reaction or papillary reaction. Actually look at the conjunctiva with a slit lamp and look for how that thickening appearance that you can see. And that is more telling of something more going on rather than just blepharitis or chronic chalazion.

The other thing is to look for madarosis. Now madarosis doesn’t always happen. So the sebaceous cell case, you didn’t see any madarosis. You saw some madarosis with the squamous cell case that I just showed you. Madarosis is useful, it’s in gray because it’s useful if it’s there. It has good, positive predictive value. But if it’s not there, it doesn’t rule out the fact that there might be something more. You have to still look for the other signs.

I’ll pause there and see if there’s any question because I think I may have gone over that a little quick. So please feel free to go ahead and type in your question if there was anything that was unclear that you would like me to go through.

And there is a couple more cases I would like to go through, but I’m also watching the time because I want to make sure that I answer your questions and not run out of time at the end. So I’ll go forward, slowly, but if you have any question about the last three cases I presented, the two blepharitis cases, and the chalazion case, feel free to put them in the question.

Would these slides be available after the session? Yes. So all of Cybersight’s lectures are recorded and they are posted on the Cybersight website for you to access afterwards. And I believe Lawrence will actually be emailing it to all the participant who’s registered today.

How do I manage post operative epiphora in cases like this? Azel, I’m guessing you’re talking about the lady that I had a complete removal of lacrimal sac and nasolacrimal duct. Interestingly, she actually had, I’ll show you some subsequent cases. She actually did not have any tearing. We get, as in human, after a certain age we all get a touch of dry eye. The loss of the lacrimal system is not a guarantee that patients are going to have epiphora. I would say it’s about 50/50. 50% of the patient, even if you remove the entire lacrimal drainage system, they have zero symptom of epiphora and that was the case in this particular patient, the African American. I’ll show you the next couple of cases talks a little bit more about lacrimal drainage systems, so that’s a great segway. Where there are ways that you can still recreate a drainage system the works without a sac, without a proper sac in these lacrimal duct. Let’s go onto those lacrimal cases.

This was a 67-year-old gentleman who presented with ectropion. Specifically cicatricial ectropion. He tells you that he’s had some nasal polyp removed by an ENT colleague in town. The pathology all showed inverted papilloma but the most recent one, after the surgery, because they also combined it with a standard DCR, because of how much surgery he’s had. And he has some tearing, et cetera. So they decided to do a little bit more polyp removal but also do a DCR through an externo approach at the same time. And then since then he’s had this cicatricial ectropion that’s happened. And he’s bothered by the lid and some of these bumpiness he still feels from the scarring on the nasal sidewall. Healthy individual otherwise no other medical history.

When you do a scan of this, this is what you see. You’ll notice significant infiltrated mass of the nasal cavity, all the way into almost the septum, indiscrimatory from the septal mucosa. On the coronal scan, it almost gives you the sense that’s it’s even pushing into the orbit. And then, of course, envelopes the entire nasolacrimal system. On the other side, I’m showing you once again a scan right through the sac. On the right side you’ll see there’s the sac, here’s the inferior turbinate, so we’re one slice forward from where the nasolacrimal duct is. So if I had clicked one more slice back, you would have seen the nasolacrimal duct.

This was a case, oops, I’m sorry. This was a case of a recurrent inverted papilloma that has transformed to squamous cell. Going back to the previous image, how could you tell that this is more than cicatricial ectropion? Two things. One is the history. The fact that a standard external DCR can cause this degree of ectropion. Sure? Sometimes it can happen in some individuals rarely. However, that should have made you think that there might be something more going on. So even if you do decide, okay, you did a scan and the CT scan was normal. I would still caution you to take a biopsy at the time of fixing this ectropion. When you remove the scar, send off the scar.

I’ve even been burned by cases where I was fixing an ectropion of someone else’s cancer reconstruction and all I saw was scar and nothing more. I’m in the practice of sending off anything I cut out. When I sent off some scar, I was totally not suspicious of anything and it ended up coming back as a recurrence of the basal cell.

Whenever the patient have had prior surgery and they respond in a way that is out of the ordinary. You all have seen and done external DCR. To have an external DCR scar like this is not normal in respective of the previous surgeon’s experience level. When something is this profound it should clue you in that something more is going on. And of course, the history of inverted papilloma should have clued you in that is there something more going on? Is this potentially a transformation?

Just looking at some of the questions here. There was a question about recurrent chalazion by Kubra. What if you have a recurrent chalazion, you biopsy it and it still shows just chalazion and then it recurred again with an abscess. The abscess designed and reserved with topical antibiotic, any other signs of malignancy? What’s the next step, biopsy again? Kubra, I think you already answered your own question. People who are prone to getting chalazion are going to get multiple chalazion. It’s not just the fact that someone with a chalazion got another chalazion is enough to think that there’s something more. But rather that is there something about this chalazion that doesn’t quite feel normal?

For example, if you have a chalazion that recurred, the most common type that I see when a chalazion is misdiagnosed, is someone says that they drained it and there wasn’t much that drained out. Or they drained it and that there was, what’s the word I’m looking for, a thicker material that came out instead of liquid pus. You know that after chalazion has been chronic, there are two way that they can present as. They either presents with just a nodular very, very firm scar. Or they will present with granulation tissue. Almost like cottage cheese, it’s clumpy, it’s grey-white, translucent. Anything outside of those two, you should think about something else is going on. So it’s a combination of when you biopsy it, what did it look like and is it really exactly the same spot? If it’s really, exactly the same spot, then I would say yes, you should biopsy it again. And really talk to your pathologist about looking for other things. Sebaceous carcinoma is very hard to diagnose, even for pathologists. I would definitely say talk to your pathologist and make sure that they specifically look for sebaceous. And sometimes they’ll do some special stains and something even immunostains in order to really find it.

Also about eyelid mucocutaneous junction. Sometimes you’ll see a small transparent vascular bridge of tissue on the lower lid margin at the mucocutaneous, should I worry? One of the things with blepharitis, that it can cause, is that blepharitis does increase to adjuntasia at the lid margin. If you just see a vast vessel that goes from palpebral edge, cross over on towards the lashes in a vertical pattern, and it crosses that mucocutaneous junction, that’s okay. That is more likely to be just inflammatory changes induced by chronic blepharitis than anything. But if you see it’s more loss of the kerontinazation or that transition point between keratinization and non-keratinized mucosa that you have to worry about.

Looking at the time I’m going to go through the last case, because I think there are some points I want you to learn from this last case. And then we’ll come back to the questions.

This is a 37-year-old female with nasolacrimal duct obstruction or referred to you as nasolacrimal duct obstruction. She said she’s been having some intermittent tearing for the past two years. And progressively in the past year things have gotten worse to the point where she has now gotten some medial canthus swelling at times. Otherwise healthy. And when you palpate and examine her, you do feel sort of a sac distention or a soft palpable mass of the medial canthus. When you probe and irrigate her she’s 100% patent, there’s no mucus regurgitation or anything. When you do her CT scan, this is the part that I think most radiologists are not great at commenting either, so I really want you guys to see this part. Which is how to look at the lacrimal sac system on CT scan.

It’s the right side that is the side of interest. So here is your lacrimal sac. You don’t really see mucosal thickening. So just like the previous case I was highlighting to you, that when the mucosal is not thickened, it’s something hard to find where it is. But you sort of see this indentation here, so this is where the sac fossa is. She’s slightly tilted and that’s why you’re not seeing it on the other side. But on the axial scan you can see, once again, there’s the start of the nasolacrimal duct on the one side. The other side she’s tilted so that little spot is where the nasolacrimal duct is. When you start to travel downwards, you start to see the nasolacrimal duct is actually losing it’s lumen again even though the sac itself is normal. And on the other side there’s the nasolacrimal duct right there. Once again it’s okay for it to have different caliber. But at the same time, this degree of asymmetry and with this mucosal thickening is questionable.

And the other thing with nasolacrimal duct is if you are able to flush anything through, they should not have a form at the extension of the sac. It’s a combination of the fact that she tells you that she has almost the story of a sac distention with dacryocystitis, or chronic dacryocystitis. Yet when you probe her and irrigate her, she’s patent. There’s lumen, even though slightly collapsed, the lumen is still there. Which tells you the reason of this brain matter compressing on the lumen is not a scarring but rather something is going on with that mucosa.

This was actually a follicular lymphoma of the nasolacrimal system. And how do we know that? Because I did a dacryocystectomy in order to find out what was going on. So we went in by external DCR approach thinking that if the sac was normal then we would proceed with a standard DCR for her to try to eliminate her tearing. But the honest truth, is my suspicion was high enough that as soon as we had a look at the sac, the sac mucosa on direct inspection was also abnormal. We took the entire sac out, and then sent that for pathological analysis and it came back as follicular lymphoma.

You do not have to take the nasolacrimal duct in these cases, because lymphoma are so radiosensitive. You’ll notice that previously with the sebaceous cell, the patient had 66 Gray. With follicular lymphoma you can do down to almost less than half the dosage, so these are not toxic to the eye. So she only had 26 Gray with complete resolution.

Earlier someone asked about how do you treat a peripheral after removal of the sac? You can actually proceed with a standard DCR. Because you have the canaliculus still perfectly intact, and you have your nasal mucosa that is normal. In cases like this, you can actually do a standard DCR and the canaliculus mucosa and the nasal mucosa will actually basically connect with each other and form your osteotomy. And these are actually quite successful and the patient had patent drainage. You do have to wait though, until the effect of radiation completely subside before you proceed with this, otherwise you’re going to have an increased failure rate from scarring. And my standard usually is wait one year after radiation. She had her DCR about 16 months later and completely no symptom of tearing and very happy with the result. That addresses one of your questions.

I’m just looking at the time. I’m going to wrap up and then I will come back to some of your questions. We may not be able to get to all of them. But there should be a way for you to reach me through Cybersight and Lawrence can help you guys with that.

We summarized earlier about some of the atypical presentation of cellulitis but atypical presentation of lacrimal drainage system is to look for lacrimal sac distention without any pus or mucus that comes out, which gives you the indication of lacrocysitis. If there’s patency on irrigation with sac distention, that should really clue you in that something more is going on.

Be suspicious of any cicatricial changes that occur after repeated surgeries. Even if it’s repeated surgery for non cancerous condition. Just think about excessive scarring that is out of keeping of what you would expect. We know that there’s scarring that occurs but when it’s much more profound than what you would expect, you should think is there something more going on?

Pay close attention to what I call lid micro structure which is the perfect angle of the mucocutaneous junction, that keratinization change that you’re supposed to see. And when you see these micro structure being destructed in chronic blepharitis, think about proceeding with a biopsy instead of keep treating it with your standard blepharitis package deal.

In cellulitis we talked about how if there’s minimal inflammatory signs, lack of sinusitis or response to appropriate broad spectrum antibiotic, you should really be thinking about is there something more with this cellulitis? Do I need to dig a little bit further, potentially with a tissue biopsy?

I’ll come back to some of these questions. I’m really happy to see so many questions from the participants. It tells me that this is an interesting topic to you. Let me go back and see some of these questions that was asked earlier.

There was a question from Reynaldo that I promised to come back and answer about reconstruction of the eyelid in that sebaceous eyelid case. When it’s that profound, your only good alternative becomes a Cutler-Beard. When you’re going to lose or anticipate losing the entire upper lid, you could try, there are patients that I have tried non Cutler-Beard by using a combination of flaps. If this is an elderly patient who is one eyed and you really cannot use a Cutler-Beard flap, you can try to use a tarsus replacement. AlloDerm is a great option, if you don’t have access to AlloDerm for tarsal replacement you can also use sclera. I think most places has eye bank. And sometimes if the eye bank may not realize that after the harvest a cornea, the sclera is actually very useful for oculoplastic surgeons. So you can talk to your local eye bank and ask them to keep the sclera for you and you can use that for your tarsal replacement.

And then for the skin and muscle, you’ll need to bring in a vascular flap. And if you don’t want to use a Cutler-Beard as your vascular flap, sometimes you can use forehead skin. So you can do a swinging pedicle flap from the forehead skin down. It’s cosmetically not as good looking as a Cutler-Beard, and that’s why I say Cutler-Beard is still my go-to. But if it’s a patient that you really just want to protect the globe and has a functional eyelid, that becomes an option for you.

In terms of treatment in lymphoma, you don’t treat it surgically because it is such an infiltrative mass. You will end up accidentally cutting into normal tissue and that’s the reason why radiation is much more effective and they’re very, very exquisitely radiosensitive. I showed you earlier that for follicular lymphoma sometimes you’ll go up to as high as 26. Literature, and also my own personal experience, is that sometimes with MALT lymphoma which is the most common type we see, they will respond to as low as four Grays or eight Grays. Two sessions of four Grays will be enough for these patients. And these are such low dosage that you really have almost no side effect whatsoever, not even dry eyes. That’s the reason why lymphoma we tend to say, just leave it to radiation.

The question about should we at least debulk it or not? That I think is case to case. If this was a massive mass in the orbit, the patient is extremely uncomfortable like the first patient I showed you with a young gentleman with the diffuse large B cell lymphoma. I did debulk, I debulk for the purpose of giving him temporary relief. Knowing that that is not the definitive treatment and that is just to give him relief until he’s set up for radiation from that globe pressure.

What about if patient is not going to come back for long term follow up for radiation treatments? Eden has asked. You will not get rid of the disease by debulking it. That’s the bottom line. I have seen patients with conjunctival MALT lymphoma who other surgeons in the community keep debulking and debulking and debulking. You will end up causing more harm to the patient by trying to do that than just trying to talk the patient into getting radiation. When the radiation is given in such low dosage, even if the patient can’t stay in town for long durations, you need just two sessions. So two days of four Gray each and that will elicit a response way more effectively than trying to debulk. So definitely I still think it is much better to treat with radiation then it is to try to debulk in temperise cases.

I remember seeing earlier, someone asking about what if you don’t have access to radiation? Donna G asked about if you don’t have access to radiation for sebaceous cell carcinoma, would you perform an exenteration? That’s a great question. It depends on whether you think that the globe is not salvageable or not. And yes, there is some variation in terms of what people’s comfort level is in terms of the degree of surgery they feel comfortable doing. For me, I can lose three quarters of the limbal stem cells and still maintain viability of that globe. But I would say it depends on in your hands, do you think you can still maintain the globe’s health without an exenteration? And if you think you cannot, then yes, unfortunately exenteration, a lid sparing exenteration becomes your only choice.

In the case of lymphoma, if you don’t have access to radiation, what is your backup plan? I would say the backup plan is still chemotherapy and not surgery. Once again, lymphomas are exquisitely sensitive to treatment, both radiation and chemotherapy. So if you’re in a place where you don’t have easy access to radiotherapy, and you have to treat the patient, then I would say even low dose chemotherapy with standard platinum-based chemotherapy at very, very low dose would respond. I would still say try to avoid cutting into these. You will end up with more long term issues than you so choose.

Usama mentioned that from her experience, external DCR can cause that level of ectropion if the lacrimal sac flap is pulled more tightly. Any comment on this? Yes, I agree with you, Usama, that I do actually suture my lacrimal sac flap in my standard external DCR. I have not personally had ectropion as a result of that. And I think it depends on where you sew your flap. This is a little bit of a tangent now, but you don’t want to sew your flap to the orbicularis. You want to sew your flap to the periosteum of your interior lacrimal sac. I do cut back my interior lacrimal sac flap because that gives you a little better visualization of the sac. But I don’t cut it back as far as what some of the old school mechanism of external DCR does. I’m not going to go into too too much details of technique of DCR. I believe there is a Cybersight lecture on DCR and there might even be some videos.

There’s a question about how long do you leave the silicone tube in the post endo DCR woman with the follicular lymphoma and radiation afterwards? Surprisingly, you don’t actually need to leave it in for that much longer. One of the things with tubes, that I find, is you actually don’t want to leave it in too long and then you start to get a foreign body reaction which then promotes scarring. My range is anywhere between six week and three months. The one thing I do is I irrigate them before I remove the tube. If I can irrigate easily, then it means the tube can definitely come out. If I irrigate at the first follow up, which is usually around three to four weeks, and I start to feel some early stricture already. Then what I would do is actually give them a little bit more topical steroid and then reirrigate in another three to four weeks and if it’s a little bit flowing a little bit better, then remove the tube at that point. So you actually don’t need to leave it in much longer than that and you can remove the stent.

We’ve gone a little bit over time, but I still see that there’s a lot of questions going on. What I’m going to do is actually encourage you to go onto the Cybersight website. Some of the question about Graves’ disease, I know there was some interest around that from the early populated questions. There’s actually great lectures on thyroid eye disease on the Cybersight site.

And then there was a question about, there was a couple of questions about lacrimal gland lesions. I didn’t go into that because there’s actually an entire lecture that we did a couple of years ago now on Cybersight that talks specifically just about lacrimal gland tumors and everything you want to know about them. It’s specifically answering that questions, DP, you had about bone remodeling versus bone destruction, versus hyperostosis. So definitely have a look at those lectures and you may find your questions in there. If not, engage on the Cybersight website and you can always reach out to me through the website or other faculty that are equally talented.

Thank you, everyone, and I hope you guys enjoyed the lecture and I hope I answered as many of your questions as I could. I hope to see you guys in the future on another lecture.

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May 10, 2021

Last Updated: September 12, 2022

6 thoughts on “Lecture: How to Avoid Misdiagnosis of Orbit and Periocular Disease: Learning from Atypical Presentations”

  1. Congratulations !
    Comprehensive with good examples and treatment strategies !
    Could you make an webinar about Neurofybromatosis and succes rate cosmetically please .

    Reply
    • Dear Dr. Ashraf – thank you for your question. Yes, we have a free service where you can present difficult cases for advice from an expert. You can read more about Cybersight Consult here:

      https://cybersight.org/consultation/

      Any eye health professional can create a free account and submit cases for consultation with international expert volunteers. We hope you find this service helpful!

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