Lecturer: Dr. Somasheila Murthy, MD, L.V. Prasad Eye Institute, India
This Live Lecture covers the clinical features, classification, differential diagnosis, investigations and management strategy in scleritis.
Hello. A very good morning or afternoon. Or night, as it may be. My name is Dr. Somasheila Murthy, and I am speaking to you from India, from a city called Hyderabad in Central India. I’m the Head of Corneal Services at the LV Prasad Eye Institute in Hyderabad, in India, and I also am a consultant in the uveitis service. Today I’m going to talk to you about scleritis, which includes episcleritis, and share with you the diagnosis and management of scleritis. Over to the PowerPoint now. So this is interactive, so I think that you have used this medium before, so please feel free to send in questions, or you could also pop up by — I think you can show your photograph and try to ask questions in between, if you like. And we have Gunala Djali, who is taping us, from Cybersight, Orbis, and he will be coordinating the interactive part. So let’s go on to the presentation. My plan to present to you is, first of all, an overview of episcleritis and scleritis, followed by classification. I’ll talk about the clinical features. And I’m going to take you through a few case examples. Then we’ll go on to investigations, and then finally to a few management guidelines. It’s quite a long list, but let’s see how much we can cover in the time that I have. Just to remind all of us, we know that scleritis is an inflammation which has a very characteristic clinical picture. It’s extremely painful, it’s slow and insidious, and it can actually destroy the tissues, locally. And the problem for us is that it can also be associated with serious sight-threatening or vision-threatening ocular disease, as well as life-threatening systemic disease. So it not only involves the sclera. Sometimes it might spill over to the cornea, episclera, as well as to the uveal tissue. What is the extent of the problem? Fortunately the disease itself is rare, but we do see it at tertiary care centers, and I’m sure many of you must have seen cases. The problem is more confounded or very important when you see patients with necrotizing scleritis, because remember that these patients could have systemic disease. And although the disease itself is rare, but if you have a patient with this problem, the patient could well be having a disease that can be potentially life-threatening. And I’ll explain to you by and by. So it has been noticed in various studies that up to 40 or even 57% of patients with scleritis might end up having an underlying systemic disease. These are various diseases, which are called connective tissue diseases, or vasculitic diseases. That would be about 30% to 48%. Another 5% to 10% present to us with what looks like scleritis, but the etiology would be infectious. And a small percentage of these patients can also have systemic disease, but less life-threatening. For example, atopy, gout, or rosacea. So whenever I see a patient who may have scleritis walk into the clinic, how do I manage the patient? For that, I ask myself the following questions. So the first question I want to look at is: Does the patient have episcleritis, which is different, or the patient has scleritis, or is it a masquerade, meaning it’s neither scleritis nor episcleritis, but probably something else? Maybe an infection. Supposing I think yes, this is scleritis, I want to right away classify whether it is necrotizing scleritis versus a non-necrotizing scleritis, and also I want to immediately look at whether — could it be an infection or not? Once I sort of have in my mind what kind of scleritis I’m dealing with, I also try to think about which investigations are necessary, and then what is the management strategy for these patients, once I know what kind of scleritis I’m dealing with. So let’s talk a little bit about episcleritis. So you know that episcleritis is inflammation of the episcleral tissue. That is, the tissue which is the Tenon’s or the blood vessels getting inflamed in the areas above the episcleral plexus. Characteristically, the patient may not have systemic connective tissue diseases, as compared to the evil twin that is scleritis. These patients usually — or those patients should not have a complaint of pain. In fact, many patients with episcleritis actually come to the clinic because their relatives or family members noted that their eye is extremely red, and they themselves may just have had some discomfort or some tenderness. And also, when you examine them, even though the lesion itself might look very angry — for example, in the photograph that you see here, it’s a very angry-looking lesion — but the vessels here will blanch almost completely when you use phenylephrine, or when you use dilating drops in the clinic. So here is a patient who has a diffuse… A nodular recurrent episcleritis. Comes to the clinic. And if you’re not very sure if this is episcleritis versus scleritis, you can dilate. When you dilate the pupil with phenylephrine, you’ll notice that just about most — almost all of the vessels simply disappear or blanch. So this is a patient who has episcleritis. What about scleritis? On the other hand, this is a deeper inflammation. More ominous inflammation. And so in the clinic, you’ll see that the hue or the appearance is not bright red, but it is more violaceous or deeper red. So coming back to episcleritis, what is its importance? One third of patients with episcleritis may have certain systemic conditions or diseases. Luckily, these are not as common. One third includes diseases such as rheumatoid arthritis. I’ve seen many patients with episcleritis who actually have ischemic bowel disease, and a few patients with SLE, relapsing polychondritis, erythema nodosum, and so on. But these are very rare. Often we see patients with less ominous or less significant conditions. For example, atopy, rosacea, or it could be an infectious cause, like herpes simplex or syphilis. And certain drugs are also known to cause episcleritis. So I’m trying to look for a poll question here, but I’m missing it. Okay. Coming to the examination of a patient with scleritis, whenever it’s a patient with scleritis, we have to be extremely cautious not to examine the patient directly on the slit lamp. So if this is a patient who complains of severe pain and red eye, there is some amount of lid edema, and we have already dilated the pupil, so you can see this is the inflammation despite dilation. You can see that a lot of vessels are very angry-looking. So if you see the patient in daylight or under torchlight examination, you’ll see the extent of the problem. So there is a lot of congestion. A deep red color that is appearing in the eye. The patient looks to the left and also looks to the right, and the patient looks down, and then the patient looks up. So these findings would be missed if you just directly place the patient on the slit lamp. So it’s very important to examine the patient in daylight or torchlight. Look at the hue of the scleral tissue. You can also have even more severe cases where it’s very obvious that there’s scleritis. So you’ll have scleral thinning, there will be a large nodule like this, sometimes you might even have staphyloma formation, and even uveal exposure, in extreme cases. This is an examination of a patient who has a nodular scleritis, and you can see that the slit lamp beam becomes sort of thinner and splits over here at the highest part of the nodule. But it’s displaced forward. So you may also remember that in our textbooks, we used to talk about red-free illumination. Actually, this is a very useful test. So when you look at this patient who has a diffuse anterior scleritis, lots of dilated vessels which are very irregular, capillaries, and so on, and there’s a lot of area which has less such vessels. When you apply the red-free filter, you’ll actually notice very easily that this is an area where there are no capillaries at all. So this is an area of ischemia or an ischemic previous episode. So this patient definitely has had previous episodes, and these findings can be picked up with the help of the red-free light, which will pick up capillary vessel dropout. The next plan we had was to talk about the classification of scleritis. So this is Watson’s classification. It still holds extremely good. It talks about scleritis as being classified as whether it’s infective versus non-infective. When you talk about infective, you look at: Is it anterior scleritis or posterior scleritis? When you talk about anterior scleritis, you look at diffuse, nodular, and necrotizing scleritis. And when you talk about necrotizing scleritis, the two entities that you think of is with inflammation and without inflammation. However, when you say that it’s without inflammation, remember that at the molecular level, there is still inflammation going on. Coming to case examples of these various entities which we classified. So this is a patient with diffuse anterior scleritis. Very angry-looking appearance. This patient has extreme pain. There are dilated vessels in all the quadrants, as well as — when you ask the patient to look up, you’ll notice that there is some amount of thinning, attesting previous episodes, and the corneal periphery, the limbus, shows whitening, which suggests that there could be some inflammation into the cornea as well. And also there are these small areas of breakdown of the tissue, which is attestive of an ischemic process. So this is a case of severe anterior scleritis. This is a case of nodular scleritis. There’s a large nodule in this area. Another patient where there’s a small ischemic process going on, which is even better picked up in the red-free illumination. These patients can often have systemic disease. The example you’ll see here is of a patient who has deformities of the hand. This is an elderly male patient. And this is a younger female patient, in her 40s, who gives history of joint inflammation. So both these patients have rheumatoid arthritis of varying severity and stage. And both of these patients could show a scleral malacia perforans kind of picture, which means that they could have a very slow chronic smoldering kind of scleritis, which could lead to staphyloma formation in this situation. Coming to another entity in classification. That is posterior scleritis. So posterior scleritis is the clinical situation where the patient actually doesn’t — when you examine the patient, you will not be able to see anything from the anterior segment point of view. The eye may look reasonably quiet. However, the patient would complain of severe, severe pain, and the patient would also say that the eye movements are painful. So when you have a patient like that, and you examine the retina, you see that you might see a lesion which you may mistake as choroiditis sometimes. You may see some disc edema, and if you do angiography for this disc, you will see that initially there’s blot fluorescences, followed by staining and pooling in the late stages. So you must suspect a case of… You must suspect posterior scleritis in this situation, especially correlating with the history of severe pain. So scleritis patients will always have severe pain. When you do a B scan for them, you can either see — you can see of course that there’s scleral thickening, but you’ll also see the classic T-sign. So this is the retinal image on B scan, and you can image the choroid as well, and this is the fluid in the sub-Tenon’s space. So this is the sclera, and in this case, there is fluid, which is known as the T-sign. So this is fluid in the subscleral space. It’s called T-sign, which is classic of posterior scleritis. So earlier I mentioned that you can have patients who have necrotizing scleritis or patients who have systemic disease. Here is one such patient. She’s a 35-year-old lady who presented to us with severe pain in the eye, a recent onset lesion, which looked necrotic and ischemic, like this, and also the peripheral cornea showed ulceration, as well as involvement of the peripheral cornea and ciliary processes. So we were a little confused, because of the appearance of this lesion. We were not sure whether we were dealing with an infectious process — in fact, we took scrapings from this lesion, which turned out — microbiology showed that there was no infection. And eventually we worked up this patient for systemic causes, and the patient had a positive S-ANCA, and then we diagnosed the patient to have Wegener’s granulomatosis. So patients who can present with scleritis, with necrotizing scleritis, as well as a peripheral ulcerative keratitis, have a very high chance, almost 75% chance, of systemic disease association. So when you have patients coming in with a peripheral ulcerative keratitis, make sure you thoroughly investigate these patients, even if the systemic investigations turn out to be negative. The patient still has a chance of, later on in life, coming back to us with manifestations systemically. So we have to treat these patients with aggressive immunosuppression. Coming to another patient who I have been following up almost for 14 years now — she first came to me in 2003. She was a 37-year-old housewife at that point. And she had history of severe redness, watering, and pain in both eyes since one year. She had undergone cataract surgery two years ago. And when I asked her about systemic symptoms or associations, the only thing she had was a history of dysuria for 10 years. Examination showed that her vision was good. She had 20/20 vision. However, when we examined the external part of the eye, we saw that there were a lot of dilated and very angry-looking vessels in all the quadrants in that part of the sclera, as well as there were these small pinpoint infiltrates onto the cornea. So we labeled this patient as having scleritis with peripheral corneal infiltrates, and we began investigating this patient to look for systemic etiology. So we did complete blood count. ESR was elevated, but x-ray test and Mantoux test was normal. Antinuclear antibody testing was done, rheumatoid arthritis factors, as well as CRP, and we also tried to rule out HIV and VDRL, because we knew we would be putting this patient on immunosuppressants. So subsequently, we also got P and C-ANCA. That is antineutrophilic antibodies done for this patient. And all of these tests were negative. We also did an extensive panel, which included ASO, anti ds-DNA, SS-A, SS-B, et cetera. So the patient received treatment with oral steroids. Because she needed prolonged immunosuppression, we also added oral methotrexate to the treatment. The patient also was pulsed with cyclophosphamide because of the severity of the disease, as well as with intravenous methylprednisolone. However, despite our management, though she would get better again, she would come back very frequently. So in September, 2004, which is about — more than a year later — she had gotten better initially. She came back again with relapse, and in the same year, she also suddenly developed vasculitis of the nasal cartilage, and she developed the saddle-form deformity of the nasal cartilage. And this is the year following that, in which she had the saddle-form deformity, where she showed that despite the medical management, there is still a relentless kind of process going. So based on the triad — the patient also developed significant joint pain — so based on the triad of joint pain, the cartilage involvement, that is the nasal septum, and the history of scleritis, the final diagnosis for this patient became relapsing polychondritis. So there are a couple of questions asked by Frank Albert. Those patients without any systemic issue — what about those patients without any systemic issue? And the second question is: What are methotrexate treatment guidelines do we usually use? So for the answer to the question about those patients without any systemic issue, and what do we do for them, we will still thoroughly investigate these patients. These patients will still require oral steroids, as well as immunomodulators. The guidelines for using methotrexate generally include all patients of scleritis who are not improving, or who need prolonged immunosuppression, so we introduce steroid-sparing agents. And that’s a reason to use methotrexate. It’s a very good drug. I’ll come to it a little bit later on in the presentation. I just thought I’ll discuss one more case. This is about a 68-year-old lady. She presented to us in the year 2014, and she gave complaints of redness, pain, and watering in the right eye since ten days. Now, in contrast to the previous patient, this patient actually had a systemic diagnosis first. So the patient — the ocular picture that I have here shows that the patient had severe necrotizing scleritis. This is where the patient is looking down, so it’s the superior part of the sclera. There is some melting going on over here, as well as the peripheral cornea is also involved. And there is a quite significant thinning in this area. So the couple of other questions — George asked: What is the dosage of steroids and methotrexate, and how long do you use them? The other question that he has also asked us, or somebody else asked: Is necrotic scleritis usually associated with systemic disease? So I’ll come again to the dose of immunosuppressants. Necrotic scleritis — yes, necrotizing scleritis we would like to call it, actually — is often associated with systemic disease. So it can be — the patient can either present to us with the disease, or the patient can actually come down the line and present to us with characteristic features of the systemic disease. We’ve seen patients like that. Or this case that I’m describing to you just now. This patient has already had a diagnosis of systemic disease that started first, and then the patient has come to us with the ocular disease. So this — coming back to the case, this is a patient who had granulomatosis with polyangiitis. That was earlier known as Wegener’s granulomatosis, but the name has been changed now. It is called granulomatosis with polyangiitis. So she’s a known case of that. And also her RA factor was positive. Which sometimes can happen in cases of Wegener’s or GPA. She also unfortunately had pulmonary Koch’s, and she was a known hypertensive. She was already using oral steroids and antitubercular therapy, and she had already received recently two doses of intravenous cyclophosphamide for GPA, as well as methylprednisolone. However, when she developed pulmonary Koch’s, they had stopped the immunosuppression. So when she came to us, she had the following lab parameters with her, which included a positive C-ANCA test with her, RA factor was elevated, sputum was positive for AFB, ESR was very elevated, so just about all the tests were positive and abnormal for her. So at this point, we couldn’t do much except for watch her ocular findings and hope that she gets better. Because we have a patient who has pulmonary tuberculosis, as well as a patient who needs oral immunosuppression. So you have to wait until the tuberculosis is well taken care of, so the bacteria are killed with the antitubercular treatment, and only after that you can take care of the patient for immunosuppression. So we waited on this patient. Luckily for us, the tuberculosis got controlled, and the patient could be restarted on oral steroids, and this time she was on methotrexate, as well as pulse cyclophosphamide. The patient followed up with us on a regular basis. Subsequently, since she couldn’t tolerate methotrexate, for some reason, she was started on azathioprine, which is another medication that we use commonly. And down the line, again, the patient developed another problem. She turned out to have pulmonary aspergillosis, and we had to add voriconazole to the treatment for this patient. So when she was under methotrexate, in fact her C-ANCA became negative. So it was a very good sign. But again, we had to stop azathioprine for a while when the patient developed a fungal infection of the lungs, and she had to be on voriconazole for a while. So since then, the patient got much better, and is currently doing well. So I’ll show you the clinical photographs of this patient. This is when she first came to us with a known diagnosis for several years of GPA, and now showing scleritis and melt. This is when we managed the patient initially, conservatively, and then after that, we added oral steroids, methotrexate, and then azathioprine. So that’s showing some resolution with staphyloma formation. And this is the most recent follow-up. So this entire area does show staphylomatous change, but the patient is stable, condition is good, and her vision was 20/50. She has an early cataract. So the patient is doing well on a minimum dose of immunosuppression at this point. So I’m looking at the questions again, because I’m switching gears next to infectious scleritis. So looking at the questions again, I think that… Yeah. Frank has asked: What are the other masquerades for pain on eye movement? A very good question, Frank. The other masquerades would be a myositis, which is inflammation of the extraocular muscles, perhaps, and Tolosa-Hunt syndrome, where there’s pain — just generally pain, not just on movements. Carotid cavernous fistula. So these would be cases that we need to look at. The second case that did not improve, Frank — actually, it really… Everything was done right for the second case. We conservatively managed the patient. So the idea of presenting the second case, which was a patient who had a known case of GPA, which presented to us with scleritis, is that we don’t need to rush and do something drastic like a patch graft, or we can withhold the oral immunosuppressants for a short time, if the patient has another concurrent infection in the body, and the patient will improve. As long as we keep the patient on close follow-up. So coming to another entity altogether, which is about infectious scleritis, I thought it was important to cover this topic, because infectious scleritis is something we see a lot of in this part of the world. Perhaps areas where agriculture and patients working with their hands physically in the farm is very common. So these patients can have a history of injury to the eye, and multiple organisms can lead to infectious scleritis. So it can be — bacteria is actually the commonest. It can be fungi, which is probably the most notorious, because of the vegetative matter injury. It can be various viruses, especially herpes simplex. It can be parasites like acanthamoeba, as well as parasites such as toxoplasma and toxocara. So I’m coming to another question asked by Savin Sahu, who asked that if the patient develops scleral thinning, but has reduced congestion and inflammatory features during the course of management with oral or topical steroids, is it a good or a bad sign? I think that if the congestion and inflammatory features have gone down, scleral thinning is a natural consequence of having scleritis. So that is a given. And you will have scleral thinning. So I would consider this as a good sign. So for me, the patient’s symptomatology would kind of guide me, guide my therapy, and I would probably use treatment based on how the patient is improving, in terms of the symptoms and the signs. I would look at — definitely increased in the amount of congestion and the inflammatory features. So I’m trying to come to another very interesting case, which is sort of an infectious cause of keratitis or sclerokeratitis. So this is a 35-year-old man. It says 35, but he actually looks much older in this picture, as you can see here. And this patient came with a history of symptoms for the past one month. When we examined him, we saw that this was this rather large scleral nodule, and right away, we thought that this didn’t look — because he didn’t have the characteristic pain also, and the patient looked malnourished. We thought this is very likely to be an infectious etiology. And because the scleral nodule is communicating with the anterior chamber, there is also hypotony. The patient is looking in the straight view. You can see some thickening of the pupil, and this area of the cornea, showing edema, and cystic formation. So there was communication from that scleral nodule into that anterior chamber. So we decided to seal that communication with the help of a patch graft and excise this lesion for a microbiological diagnosis. So the patient looks older for age than his 35 years. He shows very dry, scaly skin. And in addition to that, he shows dry palms and feet. The patient also has thickened ear lobule, as well as loss of the lateral one third of the eyelashes. So basically what we’re looking at is a patient of Hansen’s disease. We excised the lesion, and this is the histopathology of this lesion. It shows that it’s really teeming with histiocytic cells and multinucleated cells. We fixed this problem by putting a patch graft with sclera in this case. When we did special staining for the histopathological sections, we could see that it was teeming with leprae bacilli. So this was a patient who had Hansen’s disease, and it was systemically spread, in fact, to the eye as well, causing a scleral nodule, so it was kind of mimicking scleritis or nodular scleritis. And the patient did well, the eye did well, after the patch graft, and the patient was put on anti-lepra treatment, though he had some issues. He had discontinued it. In terms of compliance, he was not good, but he was sort of convinced to start the treatment again. So we’re moving on to our questions. There is a question from George. There aren’t any bad questions. He says that I hope this isn’t a bad question, but patients suffering from glaucoma and getting prostaglandin analogs — would this (inaudible) the proinflammatory factors (inaudible)? This is a question that we’re often asked, so I’m guessing if the patient is, say, on Latanoprost or one of the other PG analogs, and they’re controlling the glaucoma… I would say that now the usage of PG analogs is reasonably high. We have not seen too many cases of increased inflammation. So I would continue… I would either ask my glaucoma colleagues to suggest an alternative, or if there isn’t any, then I would continue the PG analog and take my chances, and continue the antiinflammatory medication for the patient. But if the same patient doesn’t improve, then I will assume that the PG analog is contributing to the lack of resolution of the condition, and I would really look to changing that particular antiglaucoma medication. I hope that answers your question. I’m going to describe one more unusual case, because we have so many unusual cases coming to us, being in a tertiary care center. So one more question that (inaudible) has asked us: How to differentiate clinically between infective and non-infective scleritis. It’s a really important question. I think I’ll be coming to that. Before that, let me finish up with this case, and this also answers part of your question. So this is a 14-year-old girl. So she came with a history of recurrent redness and pain for the past one year. And she had more such pain since the past 4 days, for some reason. And she was consulting many other doctors for the past one year, when she was diagnosed as nodular scleritis, she was treated with oral steroids, topical medication. But when she came to us, since the pain was very mild, and the lesion certainly looked very necrotic, plaque-like, and the surrounding conjunctiva looked very chemosed, it did not give the look of a nodular scleritis. We had a high suspicion of an infective etiology. And this is an ultrasound via microscopy. We wanted to do that, because this mass lesion looked very flat. We wanted to make sure it was not invading the sclera. So this shows the cut through the boggy area of the conjunctiva, and its extent. It’s a little difficult to see. The plaque becomes very thin. The sclera becomes very thin. So an ultrasound biomicroscope — it kind of helps us, when we’re doing a surgery, to sort of differentiate, to identify what level of the sclera is the lesion involving. We went ahead, we did excision biopsy, and though we could not really identify mycobacterium from the tissue specimens, we couldn’t really — not in the previous case, where it was teeming with leprae bacilli — but in this case, we saw the classical Langerhans giant cell, and inflammatory background. So this patient was diagnosed to have a tubercular granuloma of the eye, which is not infrequent, and the patient was started on anti-COX therapy. For tubercular scleritis. And the patient’s condition completely resolved. Then we used antitubercular therapy for this patient. One more question from Lila Moman is: Does dengue virus produce sclerokeratitis and perforation? Lila, it’s quite possible. I haven’t seen sclerokeratitis following dengue virus, but we have several viral etiologies, and the commonest being herpes simplex. If I have a patient with herpes zoster, for example, who recently had herpes zoster ophthalmicus, and then come to us with scleritis — so I have seen there can be very severe scleritis, and they can have perforation also. Herpes simplex sclerokeratitis — again, the patient can have extremely severe pain, and one of the problems is that we cannot differentiate between immune-mediated versus viral etiology, unless we see any corneal involvement, which sometimes may not be present. So the viral component drives the inflammation, and unless you use antivirals, the patient doesn’t get better. But in the case of dengue fever, even antivirals, generally, which antivirals would you use? You don’t have an effective one. So the answer is that I wouldn’t be surprised to see such a case. It is possible. So coming to another… And remember when I said that you can have a patient who has either scleritis, or it could be episcleritis, or it could be something else? So what is that something else? The something else is a masquerade. When we talk about a masquerade, you eventually think about a tumor. So these are extremely rare, but we had at least five cases, to my knowledge, in our setup, where the initial diagnosis, either from the referral doctor or by our group itself was scleritis or scleritis with peripheral ulcerative keratitis. Only when the disease worsened did we realize that we’re dealing with something else. So here is a young male patient, about 25 years old, who presented with initially what we thought was a necrotizing scleritis, with peripheral ulcerative keratitis. In fact, you can see here he has a perforation in the iris tissue over here. So we worked up the patient for the usual immune-mediated disorders, all of which were negative, and we started the patient on immunosuppressants, including steroids. But instead of getting better, the patient worsened. And subsequent visits, the patient came back with this large nodular lesion, and subsequently, the patient also had extension of the thinning, as well as more uveal show. And this is another — so the patient was lost to follow-up, and came back a few months later. Suddenly there was a dramatic change. There was a large perforation with uveal tissue prolapsing from the cornea, showing a lot of edema, and there is extremely keratic-looking, white-looking plaque-like lesion over here. So this patient only was — no light perception. So the patient was advised to undergo evisceration. The evisceration specimen that you can see on this slide actually showed classic features of ocular surface squamous neoplasia, which is now invasive, because it had invaded the eye. This is a classic squamous (inaudible). So this patient, who initially presented as what we thought was scleritis with UK, ulcerative keratitis, actually turned out to be OSSN. That was a clear cut masquerade, and this can happen sometimes. So coming back to the question, Sabin asked: What are the chances of developing staphyloma in cases with scleral thinning after treatment for scleritis? How can we prevent such staphyloma formation? So if the patient has necrotizing scleritis, if we cannot adequately immunosuppress the patient, and it’s really hard to tell you what is adequate immunosuppression, so the patient should have no symptoms, the patient should clinically look very quiet, so that is probably adequate immunosuppression. Then the chances of developing staphyloma are less. But the same patient typically may get lost to follow-up and may come back later, and then when they come back the second time, we always see that there’s scleral thinning and staphyloma formation. So prevention of staphyloma formation is simply by aggressive and adequate immunosuppression. So I keep talking about — we investigated this patient, and so on. So what are these investigations? Lab investigations — when should we do them? Do we do them for episcleritis at all? So most of the time, when the patient comes with episcleritis, we know that it’s an innocuous condition. It’s usually self-limiting, or it does not need oral medication. So most of the time with episcleritis, we do not investigate. And also because we have done it in the past and we’ve seen that it doesn’t really reveal anything. We don’t get much positivity. So for episcleritis, we don’t do it, unless the patient has episcleritis which is not improving, or the patient has a recurrent disease. Now, all scleritis needs investigation. So whether it’s unilateral or bilateral, I believe it needs investigation. And if it’s necrotizing, of course we have to investigate, because as I mentioned earlier, these patients can have a systemic — severe or a very sight-threatening immune disorder, immune dysfunction. And of course, in patients who may have scleral infection, for example, say I have a patient who says that there was history of injury in the eye, but the clinical picture looks like scleritis, but my clinical suspicion would be more towards infection. When I suspect infection, I would go for a different set of investigations in these patients. So it is very useful to kind of do a screening evaluation, especially if the money — which usually is limited for our patients, is very limited, and many of these investigations are expensive. So our screening panel typically involves doing a routine blood count, to look at the lymphocytes, do a sed rate or erythrocyte sedimentation rate, and to do a C-reactive protein assay. So this would tell us — these are acute phase reactants. This would let us know that it’s probably immune-mediated, and how high is the CRP will help us in monitoring therapy. So the second very important set of investigations include rheumatoid factor testing, because patients who may not have rheumatoid arthritis at this point, but they could have an RA factor positivity — they could present with scleritis. Same with ANCA, which is a very good test. It has a very high sensitivity and specificity to diagnose Wegener’s granulomatosis. So a serum ANCA test is extremely important for all cases of scleritis, because a patient who has ANCA positivity means that the patient can have vasculitis, either systemic or peripheral vasculitis, any time in their lifetime, and these can be grave diseases, in terms of morbidity and mortality. The other investigations include an ANA, which is a kind of very sort of broad investigation, used to think about SLE. We also want to start the patient on immunosuppressants for that reason. We try to rule out syphilis, and we also do a PPD and x-ray test to rule out concurrent infection, such as latent or overt tuberculosis. So all scleritis needs to be investigated. The commonest one that we have is a diffuse anterior scleritis. It is the commonest. And necrotizing scleritis may have seropositivity for these investigations that I mentioned earlier. And so antiCCCP testing is another test that is more useful now, because rheumatoid arthritis can be diagnosed either with positive RA factor or by positive antiCCCP antibodies. Some investigators like to do HLA panels. So we do B27 and other HLAs. And in case of viral suspicion, you might want to take scrapings from the ocular fluids and send them for virology. So in my mind, if I would divide the investigations, I would divide them as those important for management of the patient, because it will start immunosuppression, those important for etiology, in terms of what is the underlying cause of the scleritis, which includes this, as well as local investigations, which include scrapings from the tissue, ultrasound, potentially, or a B scan for posterior scleritis, and impression cytology. For example, in the patients that we presume (inaudible), and also biopsy in patients where you are suspecting an infectious etiology or a viral etiology, or a mass. So I’m going to sort of rush through treatment in a very simplistic way. As follows. Although the textbooks do talk about… Sorry. Yeah. The textbooks do talk about using non-steroidal agents or NSAIDs as line one therapy, but for us — it may be because many of the patients that come to us are referred, or they may be more severe, but on a personal level, I’ve never had success with using oral and topical non-steroidal agents alone. Usually my first line of therapy for me is actually using systemic steroids, for whatever kind of scleritis. Depending on the severity, it could be diffuse anterior scleritis, or it could be necrotizing scleritis. If it’s necrotizing, then I know that I’m looking at a very long-term kind of immunosuppression. So in necrotizing scleritis, I would use systemic steroids, as well as also start the patient on an immunomodulator. In the case of anterior scleritis, I might just use systemic steroids for 2 to 3 months in tapering doses. And hope that the patient does well and does not have a recurrence. And in case the patient is doing well, I will maintain on non-steroidal agents for a few more months, and then stop therapy altogether. In the case of more severe scleritis, or in the case where there is failure with systemic steroids alone, I would use immunomodulators. This includes methotrexate, cyclosporine for very severe cases of necrotizing scleritis. For example, patients who have Wegener’s or relapsing polychondritis. Also, cyclosporine is a very good drug that we can use. Unfortunately for us, it’s pretty expensive. So generally methotrexate is the cheapest, followed by azathioprine is the cheapest, and both are safe. So we generally end up using methotrexate as first and azathioprine as second, for the less severe cases, and cyclophosphamide for the very severe cases. Now, what happens if our patient still has either not enough control, or the patient still has repeated recurrences, or say it’s a pediatric patient. In which case, we go to line four, which are the use of the biological agents. We have had experience with the use of infliximab, etanercept, and rituximab. Especially rituximab. Because all of these drugs are very expensive, which is the main current disadvantage for the users. But we have generics, which are made locally, in India. And that has brought down the drug cost to almost one third of the international drug available. So rituximab works pretty well. Especially for the patients who have Wegener’s granulomatosis, or those patients who have a chronic, relentless kind of a course, or those patients where you can’t use oral steroids, or even when you’re using oral steroids, and immunosuppressants — so you need something even more. And that’s when you use biological agents. We’ll go on to one more question. So Frank has asked: What is the definition of therapeutic failure? The definition of therapeutic failure is that we start the patient on medication, and the patient doesn’t improve. So that’s the easiest definition I can think of. Or we start the patient on a particular agent — for example, non-steroidal. The patient gets better for a few days, and then again shows a relapse very early on. To me, that too is a therapeutic failure. A little bit about surgical management. So I showed you a couple of cases — one case, at least, where we have to do patch graft. Another case where we did excision biopsy. So when you have to take a patient for patch graft, you have to make sure that the primary disease itself is quiet. So otherwise, like this case here, this is a patient who had a scleral melt following SINS. That is surgically induced necrotizing scleritis. After surgery done here. So the patient underwent a patch graft, but the patient was not adequately systemically immunosuppressed. So very soon after the patch graft, within the month, you can see that there’s a very ischemic scleral patch, and in fact, this tissue began to undergo melt. There was melt of the scleral patch also. The other tissue that we can use to sort of tectonically support the area of scleral thinning includes multilayered amniotic membrane, we can use fascia and periosteum, but before surgery, also, or intraoperatively, as well as postoperatively, we have to use adequate immunosuppression for these patients. Otherwise, whatever agent we use, the inflammation will set in, and it will be a therapeutic — it will be a surgical failure in this case. So, coming to conclusions, I think the take-home message from today’s lecture is that we need to differentiate what is episcleritis versus scleritis, and if it is scleritis, we need to look at whether it’s infectious versus non-infectious. And also, if it is scleritis, you have to remember that, if it’s a necrotizing variant, there’s quite a high possibility that it’s a systemic vasculitic disease, life-threatening disease, and we need to immunosuppress these patients for the long term. The top two conditions that I have mentioned include Wegener’s granulomatosis, and another condition, polyarthritis nodosa. These patients absolutely need cyclophosphamide, as well as oral steroids, for long term, or maybe biological agents. And if I take a patient for any kind of surgical intervention related to the scleritis, then we have to make sure that the patient is adequately immunosuppressed. Otherwise our surgical therapy is going to fail. So I have kind of come to the end of the actual lecture, so that we have time for questions. It’s 45 minutes. So… Any questions for me? Can we go to the poll questions?>> There are no poll questions in this.
DR MURTHY: There are no poll questions? Can I play poll questions from my end, or not?
>> Yeah, you can play it. They may not be able to answer, but you can play them.
DR MURTHY: I’ll just wait for any more questions. Because if I can’t get the answers for the poll questions, then it’s not that much fun, I think. So I’m just waiting for any more questions. Yeah. So there are some questions here. Frank, thank you for thanking me for the useful lecture. And yes, I think some of the nodules on the sclera can be infections. But of course it depends on where you’re practicing. It depends on which part of the world you are from. Depends on that. Because you may not see too many infections in the part that you are practicing in. And you may see some places — they see more viral disease. And in some areas, it could be purely a lot of prevalence of immune-mediated diseases. So it depends on that. Sabhin asked me that if a patient develops scleral thinning, but reduced congestion and inflammation features during the postmanagement… I’ve answered that question, sorry. So what is the NSAID of choice? Oral NSAID… You can use any NSAID. I typically tend to use indomethacin sustained release medication, oral medication, because — and of course, you have to ensure that the patient knows that it can cause severe gastritis and ulcers, and so on. It has a lot of side effects. That’s a typical choice. Certain other doctors like to use naproxen. Certain other doctors like to use Bufferin or a combination. But all the NSAIDs have a side effect of gastritis, and we need to keep that in mind. So I don’t think it’s really which one you use. But it’s just which one the patient can tolerate. Another question is from Anil, who says that: Is there any sign characteristic of TB scleritis? When to suspect? So that’s a very good question. This is really a difficult question to answer, in the sense that TB scleritis — we assume that it’s going to be sort of a nodular scleritis, because of the way that the bacteria always mounts a granulomatous inflammation. So, first of all, you think it’s going to be nodular. And if I have a patient who has a very highly elevated Mantoux, and in these cases, I would treat the patient for tuberculosis anyway, and if that nodule totally disappears without really using oral steroids, I would assume backwards. I would assume that this was probably a tubercular-related etiology. So that is difficult. I could do a tissue biopsy. I could biopsy the tissue and look at the cytopathology, which would be a more scientific way of doing it, if I have access to good histopathology. And the other sign for tuberculosis scleritis is the case that I pointed out. You’ll have this ischemic or this white-looking sort of a lesion, very dry-looking, and you usually have to biopsy to see what’s happening in it. A couple of other questions. (inaudible) said that they have a patient who was critically ill, in the ICU, with dengue fever, and the cornea and the sclera just melted. Exactly, yeah. So I have heard of dengue fever causing severe such conditions of the eye. Panophthalmitis, and so on, but sometimes it can also be secondary bacteremia. So we have to really check if it’s a virus or if it’s a secondary bacterial panophthalmitis, endophthalmitis, or chondritis. George has asked: How thin does the sclera have to be to go for patch graft to prevent rupture? So yeah. That’s a good question, George. The reason I’m having this question is because the scleral tissue can tolerate a lot, in the sense that, although it can look very thin, but once the scleral tissue undergoes healing, it’s reasonably tectonically good. And it’s very difficult to apply a patch graft on a sclera which is otherwise — the pedicle was intact. And really, we can just wait and watch. We’ve had patients followed for years. They don’t come with spontaneous rupture. None of them do. So you have to keep the scleritis under control. So if the eye is quiet, the patient is asymptomatic, and even if the patient has a staphyloma which has formed from previous scleritis, I wouldn’t do a patch graft on these patients. I would just wait on them. So I think it’s great. Everybody, I hope you got some good management points from the questions that I asked you. And we have another ten minutes of the allotted time. So if there are any more questions, I would be happy to answer. Thank you, Lila. Thanks, everyone, for saying thank you. You’re welcome, Doctor. I’m glad you logged in and listened to the lecture. Thank you, George. Nice chatting with you, as well as Frank and Lila, and everybody else, and (inaudible), who asked the questions. Thank you very much. So I guess if there aren’t any other questions, we can wrap up. You’re welcome, Frank. Thank you so much for listening in. So thank you, everyone. Thanks for listening in, and thanks to Cybersight for organizing this. If there are no other questions, we will ask Cybersight to help us all out, and I hope that you enjoyed this, and I hope you log into more of Cybersight lectures. Thank you, Johnny, for all your help.