Lecture: Uveitis: Paradigm-shifting Notes

DR El-LATIF: Okay. Good evening, everybody. It’s a very nice opportunity to meet you today. I’m Eiman Abd El-Latif, and I’m an associate professor of uveitis and ocular inflammation at Alexandria University in Egypt. We will discuss the paradigm shifting notes, including a stepwise approach to the methodology of diagnosing uveitis. We all know that uveitis patients are quite an underprivileged sector of the ophthalmic patients. You know? The effect of surgery, cataract surgery, and all these subjects, have had a much better luck in improvement and technology advancement than the ocular inflammation. This is my WhatsApp number, just in case the duration of the webinar does not afford all your questions. I would be more than happy to answer you and to assist. The approach we shall present you to achieve the correct and precise etiologic diagnosis in case of ocular inflammation is a clinical approach. Uveitis is a clinical skill. Some clinical muscles that you train with time. It does not need sophisticated technology or unnecessary lab investigations or imaging. I shall begin the presentation with a case, a clinical case, and then from this case, we shall come out with a few lessons that we use as figures to build up your clinical experience. This is a real patient, by the way. He’s a 42-year-old man. Was admitted in the gastrointestinal unit for resection and anastomosis. He had an obstruction and underwent a major surgery for resection and anastomosis of the intestine. He had no previous ocular problem whatsoever. No disease, no surgery. And then he complained of acute painless drop of vision in the left eye. One more time. Acute painless loss of vision in the left eye. They called in the ophthalmologist. In order to see what this gentleman was suffering from. And the ophthalmologist found inflammation in the anterior segment with hypopyon. That is to say, pus in the anterior chamber. And the posterior segment showed a similar degree of inflammation. The vitreous was turbid. Was infiltrated with inflammatory cells. And the red reflex was dim, and the fundus detail almost invisible. The initial diagnosis, that the ophthalmologist thought of, was left endogenous endophthalmitis. And in part, in part, misdiagnosis. Why? Because this was a healthy — otherwise healthy — middle aged man who had a problem with his GIT and underwent a major surgery, and the ophthalmologist thought that the flora or the bacteria in the intestine had access to the bloodstream and traveled to the eye and caused the endophthalmitis. Because he had no previous eye disease or eye surgery. And indeed, he was preparing the patient for intravitreal injections of antibiotics and vitrectomy and so forth. And then… He consulted me about this patient. And this was the case after evaluation. After referral to me. I conduct myself a detailed systemic evaluation for every patient. By myself. My hands. But for the sake of time, I’ll show you the evident relevant signs in this patient. He had sublingual — what do we mean by sublingual? Ulcers on the undersurface of the tongue. And scrotal ulcers. This patient did not suffer from endogenous endophthalmitis. He had Behcet’s disease. And so the intravitreal injection of antibiotics and the vitrectomy would have only made things worse. Because this is a uveitis due to a disturbance in the immune system. And you would operate on it while still active. And you might probably end with a flare of the ocular inflammation, postoperative, post-intervention. I hope that I will be able to break the ice between you as an ophthalmologist, as a general ophthalmologist, I mean, you might be a wonderful ophthalmologist, but let me teach you some basic notes, so if there are among our audience some general or young ophthalmologists, maybe we can succeed in breaking the ice between them and between this tough subject known as uveitis. The systemic signs, if you will use them as criteria or clues for diagnosing the cause of uveitis, you have to be competent at estimating the significance of every particular sign in the diagnosis of several diseases. For example… Oral ulcers. Many ophthalmologists — and I’m speaking from experience, because for 17 years, I’ve been a referral for patients from different countries. Many ophthalmologists think that if the patient has uveitis and oral ulcers, this is a case of Behcet’s disease. And this is a practice we need to change. Oral ulcers, for example, as one of hundreds of systemic manifestations, is a double edged sword. As much as it can help you with diagnosing the cause of uveitis and providing better service to your patient, as much as it can harm you if you are not competent enough in dealing with this particular sign… Oral ulcers are a diagnostic feature in Behcet’s disease and a diagnostic feature in systemic lupus and it can occur with many viruses, with many medications, with leukemia. So please, I’m speaking to colleagues, to my sons and daughters. I’m speaking right from my heart. Never ever ask the patient: Do you have oral ulcers? The patient says yes. Then you are a case of Behcet’s disease — I’ve seen this practice for hundreds of times. This is very harmful. For every sign to be counted as a diagnostic sign of a specific disease, it has to fulfill some… For example, the typical oral ulcer of Behcet’s disease is this ulcer. By the way, this is the real patient’s photos. This is this ulcer. The arrow I was pointing to is the typical Behcet’s disease oral ulcer. It is called sublingual, parafrenular. What is the frenulum? The frenulum is this fold of mucous membrane joining the undersurface of the tongue to the floor of the mouth. And this is a classic site for Behcet’s disease oral ulcers. Very rarely does Behcet’s disease cause ulcers on the dorsum of the tongue. The classic site is the ventral surface of the tongue. Lingual parafrenula. Ulcers on the eyelid are also supportive of Behcet’s disease. Ulcers on the tonsillar bed are very suggestive of Behcet’s disease. And so on. The list goes on. I’ll just stop here for a minute to elaborate on the importance of understanding every single detail related to every systemic sign. If you choose to examine the patient systemically, yourself. However… Let’s assume that you did not find those systemic manifestations. Of Behcet’s disease in this patient. Who suffered acute loss of vision in the left eye, while being admitted in the gastrointestinal ward. Is it possible that his initial diagnosis of left endogenous endophthalmitis is still correct? Very rare. It’s clinically impossible. I mean, theoretically, anything can happen. Anything can happen. But clinically, it’s very difficult to find a case of left endogenous endophthalmitis. Why? The mainstay, the core, the cornerstone of diagnosing the etiology of uveitis is a constant known as pattern recognition. It is not the more lab investigations you do (audio drop) then you have the diagnosis. No, on the contrary. They might be misleading. Pattern recognition means: That every single cause of uveitis synthesizes. Tailors. Formulates a specific combination of the different signs of uveitis. It has its specific cells, specific proteins, specific synechiae, specific keratic precipitate. Have you ever wondered why, in a patient with uveitis, you get exclusive or inclusive synechiae, and in a third patient, you get focal synechiae, and in another, you get no synechiae? Like Fuch’s syndrome? Ever wondered why? Ever wondered why one uveitis patient has round KPs, another one has (inaudible) KPs, another has no KPs? Ever wonder why some come at the pupillary border whereas others come mid-iris? Every single sign needs its own webinar to be covered. Today this webinar… And I’m looking forward to giving you… Other webinars down the road. But for the time restriction, today’s webinar is about one very important pillar in the pattern recognition of uveitis. (audio drop) What do we mean by the laterality? Well, half the work, half the job, half the way to diagnose the case of uveitis, to determine its exact etiology, is to classify properly, according to the laterality. And don’t get too intimidated by this long list of signs. I hope that at the end of following webinars with Cybersight, I will be able to share with you a grand table I’ve made myself summarizing all the cases I’ve seen for the previous 16 or 17 years, to facilitate reaching the diagnosis for you. I’ll give it as a gift. However, in order to navigate properly through this table, you have to understand: What do we mean by each single sign, and how do we comment on it? The most important part of this lecture is the laterality comment. How to comment on the case of uveitis regardless the laterality. Unilateral uveitis means unilateral disease. One eye has uveitis. Whether active or inactive. And the other eye has no uveitis. Neither active nor inactive. One is the master eye, the main one. Unilateral uveitis is unilateral what? Unilateral disease. One eye has uveitis, whether active or not, and the other eye does not have uveitis, whether active or not. However, bilateral uveitis is the opposite. Bilateral uveitis is not bilateral disease. It is bilateral simultaneous activity. So in bilateral uveitis, the patient has bilateral uveitis, simultaneously active at the same time. And this is a common mistake, a common clinical pitfall, because I see patients. Some of the patients refer to my clinic, my center, with one eye suffering from uveitis, in an active state. And the other eye suffering from uveitis in an inactive state, and he was told and he was sent with a letter that it was a bilateral uveitis. This gets us to the third classification. Alternating uveitis. Alternating uveitis means bilateral disease, but one eye is active and the other eye is not active. So one more time. If one eye has uveitis and the other one does not have uveitis, this is unilateral. If both eyes have uveitis, and both eyes are active simultaneously, this is bilateral uveitis. If both eyes have uveitis with one eye active and one eye inactive, this is alternating uveitis. We further classify alternating uveitis into two categories. For example… If the patient has had ten attacks, ten bouts of uveitis activity, five in the right eye and five in the left eye, this classification is equal alternating uveitis. Alternating means that half the attacks are in each eye. However, a large sector of patients get most of their attacks in one eye, and the other eye has only had two attacks. This is not equal alternating uveitis. This is uveitis preferring one eye. In every specialty or domain of ophthalmology, there’s no major difference between the right eye and the left eye. For example, right cataract and left cataract. What’s the major difference in the diagnosis or treatment, except maybe that the nose might make (inaudible) if projected forward? Nothing else. Nothing major. Between the right and the left eye, except in ocular inflammation. Huge differences exist between right uveitis and left uveitis. This is because… The right eye might be similar to the left eye in anatomy. However, the neck, the chest, and the abdomen, this is what we call the torso, is asymmetrical around the midline. Your neck, chest, and abdomen are not the same on both sides of the body. And this is where most causes of uveitis arise. That’s why some causes of uveitis affect only the right eye. And some causes of uveitis affect only the left eye. And it’s quite pitiful that some patients come to me with piles and piles of investigations and labs, looking for a cause of uveitis that simply does not affect this particular eye. I cannot overemphasize the importance of the accurate classification of each patient, and in referring him to the proper group, to the proper category. I work in Alexandria, in Egypt. If I lose my keys in Egypt, I come to the US to look for my keys. And everybody is helpful and supportive and cooperative and leaves his work and comes to help me and assist me and look for my keys… They will not find it. They will never find the cause of uveitis if we are looking in the wrong direction. So concerning the laterality, we further classify the unilateral uveitis into a right and left. And we further classify the alternating uveitis, preferring one eye into alternating, preferring right eye, and alternating preferring the left eye. So according to the laterality, which is one of several diagnosis-defining features for every case of uveitis, this is the official name. Diagnosis defining features. These are the features that make you find the diagnosis. According to the laterality. Any patient in uveitis, however young or old, male or female, is either right or left or bilateral or equal alternating or alternating preferring right eye or alternating preferring the left eye. There are six possibilities. Nothing more, nothing less. Back to our gentleman. He had Behcet’s disease that caused him the hypopyon and the vitreous infiltration. Our question was: Why was the initial diagnosis of left endogenous endophthalmitis incorrect? This is because if it were a case of left endogenous endophthalmitis, then the culprit, the contaminant, the microbe, would be in the left ventricle. And the left ventricle contracts to push the blood up the ascending aorta. Then the arch. Then the descending thoracic, descending abdominal, then the iliac, and so on. By the way, to be a good uveitologist, you have to be a perfect anatomy specialist. Anatomy, physiology, ophthalmology — these things are must-dos. And must-knows in the field of uveitis. Anyway… This is what I’ve just been talking to you about. The anatomy of the neck, chest, and abdomen is different between the right and left side. And this hugely influences the involvement of each of the right and the left eye with the uveitis, and this is something we have to understand. The blood supply to the right eye arises first. From the arch of the aorta. And the brachiocephalic artery, which divides to become the right subclavian and the right common carotid of the head and neck, the right common carotid further subdivides into the right external carotid for the face and scalp and the right internal carotid for the brain and the right eye. Which gives the ophthalmic, and so on. About 3 centimeters in the average sized adult male arises the blood supply to the left eye, as the left common carotid, which divides into internal and external, and so on. So if this were a case of left endogenous endophthalmitis, and the left ventricle was full of the organism that is going to affect the eye, it is against logic that the organism would skip the right eye, the blood supply of which arises first, and is more in line with the pumping action of the left ventricle, and affect only the left eye, whose blood supply arises more distally. And at the perpendicular angle, this angle is about 90 degrees, very difficult for the blood to get to it. And so the references, the literature, has always and for years taught us that in endogenous bacterial endophthalmitis, the right eye is affected much more commonly than the left, because of the more proximal and direct — means in line with the pumping action of the heart — arterial blood flow than the left eye. So for the diagnosis of uveitis, our system that we want to convey to you is that it is a clinical diagnosis. It is a mental exercise. It is a pattern recognition. And that every case has a cause. And you have to exert every possible effort to reach this cause. Because if you give treatment without determining the cause, most likely this patient will eventually be misdiagnosed. The remaining part of the lecture I’ll give you another example of uveitis, and how to reach the cause using the laterality. And then I’ll be more than happy to answer your questions. Because I’m not copying and pasting some text. This is not my way of teaching. I’m trying to give you my experience to make you think better and serve these patients better. Every single disease has its own cells, own flare, own KPs, on, on, on. And own laterality. So laterality-wise, endogenous endophthalmitis is either right or bilateral. Very difficult to be only on the left. We’ve explained why. And it’s very important to me, when I teach a piece of information, that I give you the rationale. I give you why this piece of information is correct and is crucial. I always love to link the academic base with the clinical top. Now to another example. Let’s talk about ankylosing spondylitis. From the curricula of the undergraduate teaching in the different faculties and universities, across the world, we’ve all learned that the classic symptoms of ankylosing spondylitis are alternating buttock pain. Let me stand up. Focus on this symptom. I’ve just had a man a few weeks ago. He is not diagnosed with ankylosing spondylitis. So he has not yet received treatment for ankylosing spondylitis. And he is narrating the classic history. Let’s listen together to his complaint. He says: For two months, I woke up, every day, throughout two months, with right hip pain. He means sacroiliac joint pain. But he doesn’t know the specific anatomic notation of that term. So he says: For two months, I wake up every morning with severe hip pain. On the right side. I limp. And then… After these two months… The right hip is very normal. It’s painless. And the pain shifted to the left hip. And again, for two months, he wakes up with severe pain on the left side. And he cannot bear weight on it. This is the classic ankylosing spondylitis complaint in an untreated patient. It is called alternating buttock pain, due to alternating sacroiliitis. It so happens also that uveitis in ankylosing spondylitis, laterality-wise, is either unilateral or alternating. In the cases that have not received treatment from ophthalmologists, it’s very difficult to find a case of simultaneous bilateral uveitis. I mean, is it a coincidence? That sacroileitis in ankylosing spondylitis is laterally alternating, and uveitis in ankylosing spondylitis is unilateral or alternating? It’s not a coincidence. Let’s understand it together. For the second time today, I’ll try to bridge the gap. Between the academic sciences and the clinicians. Because I do appreciate that ophthalmologists are clinicians and surgeons, and they are not very much obsessed with the academic sciences. Unlike me. I just adore the academic sciences. And one of my obsessions in life is a juicy subject known as immunology. I just love it. I cannot help loving it. So without entering into too many complicated slides and theories and maps… I’ll try to explain to you the immunologic basis of uveitis in ankylosing spondylitis patients, because this is crucial. This is not a fantasy. This is not a luxury. This is crucial to saving these patients. In a story-like form. And as a liability release, what I’m going to say right now is not very much academic. It is oversimplified. Because if I stick to every single academic detail, you will not probably bear with me the tough explanation of this part. So in an oversimplification, your immune system has two wings. One arm is the innate system. Your innate system is the army that guards your borders. The body borders. The skin, the mucosa. And so on. One more time. The immune system — immaculate and meticulous organization. It has two wings. One wing is known as the innate system. The innate system is a non-specific system. It’s an army. Guarding your borders. Any attack is brutally aborted. Your innate system recognizes a foreign intruder. Without a question, it attacks it. The innate system is made of several types, mainly the neutrophils and the macrophages. The neutrophil is a blind killer. Again, the neutrophil is a blind killer. This x is a foreign agent, this x is an intruder, this x will be killed. I don’t care what his name is. I won’t ask what his name is. The other wing is the specific system. The delayed system. The specific system… It has to interview the foreign intruder first. So what is your name? My name is staph aureus. Okay, Mr. Staph aureus. We’ll form some antibodies against you. So we’ll form an anti-staph aureus antibody. And so on. So the specific system has to interview you, and give you some tea, some coffee, some cookies, and then forms the antibodies and so on. This is the delayed system. This is the specific system. Let’s put aside the innate system for a while and let’s meet the specific system. The specific system has two major wings. One wing is the B lymphocyte system. The B lymphocyte does not enter into battle by itself. The B lymphocyte with a sword and a gun — no. It forms antibodies with the plasma cells. I mean… So a series of steps. It forms antibodies. And the antibodies go and make war. I don’t do war myself. The other wing of the specific system is known as the T-cell system. The T-lymphocyte system. The T-lymphocyte system is the commanders. The T-lymphocyte fights by itself. I fight myself. I either kill or get killed. I fight myself. I send no messengers. I fight myself. So it’s called the cell mediated system. Cell mediated means that the cell fights by its own body. The other one, the cell system, is called antibody mediated immunity. It sends antibodies to do battle. It doesn’t do battle itself. So far so good? So the immune system, two wings. To recap — innate system, put it aside for the moment. Specific system, further encompasses the B-cell system and the T-cell system. The B-cell system forms antibodies to fight. The T-cell system fights by itself. For ankylosing spondylitis, put aside the B-cell system for the moment. And let’s sit for a couple of minutes with the T-cell system. We’ve all learned that (audio drop) I’ll stand up again. The parts of the immunology that I adore — explain. Every cell in the immune system has a name tag. Has a badge. For communication and many other purposes. Your T-cell system is a very big system. A huge system. A subset of T-lymphocytes have a name tag called CD4. What is CD? CD stands for cluster differentiation. What is a cluster? A cluster is a group. So this CD4, it’s a molecule, a glycoprotein, that helps identify the cells into clusters. Into groups. So… A subset of T-lymphocytes, for example, the T-helper cells, have a badge. Have a name tag known as CD4. Cluster differentiating molecule number 4. Another subset of T-lymphocytes has a different name tag, known as CD8. So it is cluster differentiating molecule number 8. Number 8. Like the cytotoxic T-cell, the T-cell that kills the virus-infected cells and the malignant cells. Let me give you a hint. The T-lymphocytes that are CD4 positive are CD8 negative. So if you are a T-lymphocyte that carries the CD4 badge, the CD4 ID, you cannot put on the CD8 ID. And if you’ve put on the CD8 ID, you cannot put on the CD4 ID. Again… The T-helper cell is a CD4 positive, CD8 negative T-lymphocyte. And the T cytotoxic is a CD8 positive, CD4 negative T-lymphocyte. A small subset of T-lymphocytes do not carry neither the CD4 nor the CD8 identification molecules. So this small subset of T-lymphocytes is known as double negative. So what do we mean by a double negative T-cell? It is negative to the CD4, negative to the CD8. It doesn’t carry any name tags. No. It carries one name tag known as the CD3. The CD3 is present on all T-lymphocytes. It is known as the pan-T-cell marker, the pan-T-cell identifier. So let’s recap. The T-helper is CD3 positive. CD4 positive. CD8 negative. This is its full name. My full name is Eiman Abd El-Latif. This is the full name of the cell. The T cytotoxic is CD3 positive, CD8 positive, CD4 negative. However, a small subset of the T-cells carry neither the CD4 nor the CD8 molecules. They are still CD3 positive, because these are T-cells. These double negative T-cells are one of five extremely powerful, extremely powerful weapons of your immune system. To the extent that to date the jury is still out, the literature is still divided, whether this cell is the savior of your immune system or the villain of the immune system. In single language, the double negative cell is a very powerful weapon. If healthy, it can save a failing immune system. However, if inappropriately activated, if unhealthy, it can destroy a healthy immune system. It’s very powerful. Its effect is massive. In many universities, in many undergraduate curricula, the undergraduate students study the T-helper cells and the T cytotoxic cells, but doesn’t study the double negative cells. In my opinion, this is due to its small number. However… This is totally against the way your immune system (audio drop). The immune system deliberately limits the number of its aggressive and powerful weapons. So we might think that the double negative cells are few in the body. So it’s not important to teach them. But the immune system thinks that the double negative cells are very powerful. So I have to make the number much lower than the less aggressive entities in my organization. What is the significance of this story to the ankylosing spondylitis sacroileitis and uveitis? Ankylosing spondylitis is one of a long list of diseases that result principally from inappropriate activation of the double negative cells. So I have to be aware of this before I assume that I’m a very competent uveitologist and I can handle everything okay. So ankylosing spondylitis is one of a long list of diseases that result from inappropriate activation of the double negative cells. Why are the typical signs of ankylosing spondylitis never bilateral? Why are they unilateral or alternating? Why is uveitis and ankylosing spondylitis unilateral or alternating? This is the second mechanism by which your immune system checks, limits the powerful responses of the double negative cell. We have just mentioned the first mechanism, which is limiting the number. The second mechanism is unique to the double negative cell. And to date, the mechanism I’m going to share with you in a moment has not been described for any other weapon in your body. Exclusive to the double negative cell. Exclusive. It is called intrinsic negative feedback. The immune system is aware of the mighty responses of the double negative cells. So it gave them an order. If you get activated on one half of the patient’s body, you send negative feedback, impulses, or orders to inhibit any possible activation of your colleagues on the other side of the body. That’s why the dentist — I’ve just shared his story for you — said for two months, suffering from severe, crippling, handicapping right buttock pain, then without any diagnosis, without any treatment, the right side is very fine. Quite normal. And the left side became activated. What happened is that when the left double negative cells became inappropriately activated, they inhibited the right sided cells. That is why uveitis in ankylosing spondylitis is typically what? Unilateral or alternating. And if I have a word with you tonight, one on one, just me and you, never ever put a uveitis as a poem, to go and vomit it on the exam paper. This is no good. This is not the way to serving this sector of patients. You have to understand every single sign and pathophysiology to the core. Anyway… The third point we want to study is why is the uvea involved in every disease? I mean, ankylosing spondylitis targets what? It targets the sacroiliac joints, the tendon Achilles, the plantar fascia, the enthesis. What do we mean by enthesis? The attachment of the tendons to the bones. The uvea. The digits. And so on. Why is the uvea involved in this disease? What does the uvea have to do with the tendon Achilles and the sacroiliac joints? Why? This is the third mechanism by which your wise immune system who knows well the strength and weaknesses of each individual, working under its patronage, this is the third mechanism by which your wise immune system restricts your double negative cells. It does not allow this serious cell to flow unlimited in the bloodstream. It limits it to certain foci. Certain islands. Certain locations. Certain homes. So the double negative cell is not freely mobile in your bloodstream like the neutrophil and such naive cells. No. The double negative cell is a very strong weapon. It lives in foci, in homes. It so happens that the homes, the huts, the tents where the double negative cells are restricted are the sacroiliac joint, the tendon Achilles, the plantar fascia, the enthesis, and the uvea. So what is the pathophysiology? In my masters exams, I always explain to my postgraduate students every sign to the core. I never copy and paste text. And when I come to examine them, I always discuss: Why is the uvea involved in ankylosing spondylitis? It is because the uvea is one of the foci where the double negative cell lives. I’ve given you today two examples of the importance of the laterality, as a diagnosis-defining pattern for each case of uveitis. Please do not assume the uveitis is idiopathic without going through all the right knowledge and right thinking, because this patient who is assumed to be idiopathic is not, and is given empirical treatment, and just follows up… Takes empirical treatment, and it recurs and so on. And loses his vision and maybe his life. If not now, then later. I’ve come to the end of my topic today. I will welcome all your questions. But just in case the next webinar we arrange with Cybersight might not be very near, if you are interested in listening to a simplified explanation on uveitis, you will find some of my lectures on the YouTube. Just look by uveitis made easy. They are free for everybody. We do our best to spread knowledge without any financial interest. And this is my WhatsApp, if you have any questions. And if you have any questions at the moment, I’ll be happy to discuss them after opening the Q and A. We have received a number of questions on the Q and A of the webinar. I will read them aloud one by one, and we will answer them together. And then I’m more than ready for any help or any assistance I can give. The first question that comes from one of our colleagues that attended the webinar: Usually endogenous endophthalmitis is unilateral or bilateral? I’ll concentrate on this question. It’s a very good question. Endogenous endophthalmitis is either bilateral or one-sided, but it’s very difficult to find it isolated left side. Shall we type the answer, or is it enough to say it?

>> You can give a verbal answer. That would be perfect.

DR El-LATIF: Okay. Thank you very much. The next question: From one of our colleagues… I think diagnosing a case of Behcet’s syndrome as an endogenous endophthalmitis is just because of improper history taking. It does not require too much philosophy to differentiate between both. Yes, an excellent question, dear colleague. However, sometimes, especially at the beginning of their clinical career, some common pitfalls and some common mistakes are made by our junior colleagues. So we try to always deliver our experience to the following generations. The third question, from one of our colleagues: Why left endophthalmitis — why the left eye — because it’s LE. So I think he means the left eye. Why the left eye is involved less than the right eye? As the left carotid artery come direct from aorta, but right carotid after branch with subclavian. It’s an excellent question, dear. But it is… I mean, the fact, anatomical fact, is that the right common carotid is in line with the pumping action of the heart. And it arises more proximally from the arch of the aorta. However, the left common carotid arises more distally, about 3 to 4 centimeters distal to the origin of the right arterial supply. And almost at a right angle. So that’s why, as we showed together, the text, the literature always teaches us that the right artery is vulnerable to endogenous endophthalmitis. The left — because of this arrangement of its arterial supply. The next question: Are there other examples of double negative CD3 disease as ophthalmology or general medicine? An excellent question. I have to greet you for this excellent question. Because this is one of the fields I love examining. Yes. There is a long list of diseases. And we will ask for the permission of Cybersight to arrange another webinar. And we will focus it on the double negative T-cell diseases in the eye and in general medicine and what concerns ophthalmologists. Which will take about… An hour and a half or something to cover. We will take their permission. And they are very supportive and very cooperative. And we will arrange this with them. Do you have medical references for your comments? Yes, sure. We do have, as I’ve put one, and every single comment or piece of explanation does have its relevant references. More than one for each comment. The third one is… Thank you very much, an excellent presentation. You’re most welcome, dear. It’s always a pleasure to work with Cybersight. And to work with you. And it is my pleasure. Thank you so much for your decent comment. Thank you so much.

>> All right. Thank you, Dr. Eiman. That seems like all of the questions for now. So… Oh, it looks like there’s one more question. And then we can end the session.

DR El-LATIF: Oh, okay. There is another colleague who says how about in situs inversus. Well, my dear colleague, this is a question that I have been asked in all the different countries I’ve taught in. It’s an excellent comment and an excellent question, which pops to the mind of several of my attendees in the Gulf and some European countries I’ve taught in. However, I have not encountered a case of situs inversus with endogenous endophthalmitis. So maybe when I meet a case like that, I will… I will be able to reply to this question. But as you know… I have to speak from experience. So… Theoretically, yes. It might differ. But I haven’t met this case yet. Maybe we will meet one day in person. And I will tell you about my experience. The next question… Well, the coming comments are all letters of thank you. Thank you so much. Thank you, professor. Very lovely comments that I do appreciate. I’m very happy that you liked the lecture. I’ve enjoyed my time with you. And I really hope we will organize another webinar, Cybersight. They are very supportive and very (audio drop) organization that helps with knowledge and clinical experience all over the world. I appreciate them personally and I have learned a lot with them. So… I’m really flattered with all your kind comments and thank yous. I am the one who is grateful for enjoying this time with you. You have made my day, all of you.

>> Great. Thank you so much, doctor. And thank you, everyone, for joining. Have a great night.

DR El-LATIF: Thank you very much.