Ocular Immune Privilege and Defense by Dr. Akshita Aggarwal, June 3, 8:00 PM IST

Añadido: 2026-06-06

[00:00:05]Hi Daudi. Hello sir. We are live please.

[00:00:09]I Okay, we are live.

[00:00:11]>> Okay.

[00:00:12]>> Good evening everybody.

[00:00:16]>> I welcome you all to today's focus online session. Uh today is episode number 69. Currently we're running in the physiology module. Uh today we have Dr. Dr. Asha Agarbal, associate consultant from center forite I hospital Delhi uh to talk on ocular immune privilege and defense. Welcome Dr. Axita.

[00:00:36]>> Thank you Dr. Pratika.

[00:00:38]>> To moderate today's session we have Dr. Tanya Jen. Ma'am is a consultant at vidual retina ubiitis and RO team at Dr. Shra's charity eye hospital New Delhi.

[00:00:49]Uh she has done a DNB from Sadguru Netra Chikitalia Chitra and her VR fellowship from Dr. Shov charity hospital New Delhi after which she did a advanced training uh that's diploma in uvitis at Stanford University USA. Uh ma'am has 60 plus publications in peer-reviewed journals to her name. She's been a speaker at national and international conferences.

[00:01:10]Uh she has been a winner of many award including HShan trophy by Delhi athanic society. She has been involved in clinical trials and fellow training program as well. Ma'am has been an exassociate editor of Delhi Journal of Thalmology. Uh she holds a membership in prestigious journals like AAO IIS, MRCS, VR SI, AIOS, DOS and MPSOS. Welcome ma'am. Over to you for the introduction of our chairperson Dr. Mod Ja and uh our speaker.

[00:01:45]>> Hello. Thank you Dr. Pritika and welcome everyone to uh the I focus online session. Uh it's my absolute pleasure to introduce Dr. Mudagi sir. Sir sir need no introduction but just uh I'm going to introduce him. Sir was trained at BGMC Ahmedabad and following which he did his vitto retina fellowship from LBPI. He's the head uh of the uh vital retina diseases center at LB Prasad Hyderabad. Sir is uh very famously known for all his uvia work and also his great work with fibbrin glue and retinal diseases. He has many uh publications in many peer-reviewed journals and he has been a recipient of many honors and awards from the uh ASRS and u retina. He has also won the best innovation of the year from VRSI for his work on fibrin glue and cresing award uh in arro for his excellent retina surgeries. Welcome sir and it's always a pleasure and privilege to hear you talk and explain such uh difficult concepts beautifully and uh uh for the speaker tonight is Dr. Axita.

[00:03:04]Dr. Axita is uh from MAMI her MB her undergraduation and UCMS uh she has done her uh residency. She's also completed her ICU and done her fellowship in VTO Retina uh at LVP Hyderabad. She's currently working in as an associate consultant at CFS New Delhi. She has numerous publications and presentations in both national and international conferences and has won awards for her video and paper presentations at DOSS.

[00:03:36]So she is also interested in research and is also a clinical reader in some clinical trials. So hello Dr. Axita and uh we're excited to learn about ocular physiology from you today.

[00:03:52]>> Uh thank you Dr. Tanya. So I'll start sharing my slides. I hope my slides are visible. Uh firstly I would like to thank I focus for the opportunity and uh today I'll be discussing about the ocular immune privilege and defense.

[00:04:10]So we'll be discussing about blood ocular barriers, the ocular surface defense mechanisms, the immune privilege of the eye, the anterior chamber associated immune deviation and control of inflammation. These will be then followed by the clinical application of this immune privilege of the eye uh in respect to uvitis patterns the sympathetic ofia the corial graph survival and role of steroids and imunom modulators.

[00:04:44]So going back to history, Peter Mawavar was the first one who uh showed us how the immune privilege is working and he also won a prize in nobble in physiology or medicine in 1960.

[00:04:59]Stalin also uh elaborated about the mechanism of the immune privilege. So what exactly is immune privilege? It is basically the tolerance of the foreign antigens to preserve vision without having a destructive immune response. So basically uh whenever there is a severe inflammation, there will be scarring, there will be fibrosis. These will in turn lead to the disruption of transparency and hence will have an impact on the vision.

[00:05:36]So the um immune privilege sites of the eye include anterior chamber. So the anterior chamber uh the arrow is not correct. The anterior chamber is having aquis humor. Aquis humor is basically a avascular intraocular tissue. It basically is protected by the blood aquequis barrier which limits the immune cell entry and there will be anterior chamber associated immune deviation system also that induces the systemic tolerance. We will be discussing about this in the subsequent slides. Uh we have cornea which is partially immuno privileged site because the central cornea doesn't have the lymphatics. Also there is lack of blood vessels in the central cornea. Normally there are low MHC expressions. The corial endothelial cells also express fast lyan. These lians are important to induce the epoptosis of activated T- cells. We also have subretinal space which is basically a potential space between the retina and the RP. it is having the immune uh limited immune surveillance because of the presence of the blood retinal barrier. Again, we'll be discussing about these barriers in the subsequent slides. This enables the survival of both [clears throat] grafts as well as the antigens in this potential sub retinal space. Then we have retrus cavity. It is a avascular gel-like structure. It has low protein content.

[00:07:17]It also has different immunosuppressor factors like PGF beta 2, alpha, MSH, VIP and sumostat. Again we'll be discussing about these in details in subsequent slides. Uh the vitus gel is also important uh because it limits the uh trafficking of the immune cells from anterior to the posterior segment.

[00:07:42]The another important site that is there is the lens protein. So basically lens protein is sequestered from the immune system because it is surrounded by a lens capsule which is avascular and also it is uh protecting the lens from the direct exposure to the immune cells as well as the antibodies that are there in the system.

[00:08:08]So how exactly the u I and immune privilege site because we have different mechanisms working in place which are protecting the eye from the immune response and the immune system. We have anatomical uh mechanisms. This include the blood ocular barriers. There is also absence of lymphatic drainage in the eye.

[00:08:32]We another thing that is there the mechanism that is there in the uh important in immune privilege is the cellular mechanism. Apart from these two mechanisms we have different soluble imunosuppressive factors in both aus as well as the vitrus humor. All these are very important for the immune privilege of the eye. So the anatomical barrier that is there that is the blood ocular barrier. we have two different types that is the blood aquis barrier and the blood retinal barrier.

[00:09:03]So blood aqueas barrier is basically uh formed by the tight junctions that are there in between the non-pigmented celary epithelia. Then pigmented celary epithelium the endothelial cells of the iris vessels are another important uh structure which are part of blood at barrier. The inner wall of endothelium of the Schlim's canal also forms the blood aquas barrier. So uh the function of this blood aquis barrier is to control the passage of the solutes into the anterior chamber. This maintains the immune privilege of the anterior segment allowing the active transport of important molecules like escorbate by the serial epithelium.

[00:09:52]Whenever there is a breakdown of the blood aquas barrier which can happen either because of uvitis some amount of inflammation exposure or foreign antigen either through surgery or uh following trauma or it can also happen whenever the patient is using some amount of uh some anti-gloma medications like prostaglandates.

[00:10:16]So the clinical signs that will be there uh indicating us that the blood aquest barrier has been disrupted is the presence of protein in the anterior chamber which we commonly called as flare. Then there can be cells in the anterior chamber. There will be altered aquest dynamics.

[00:10:36]So go now going to the posterior segment. The blood retinal barrier protects the posterior segment. So it also consists of two types. There can be inner uh blood retinal barrier and there is an outer blood retinal barrier. The inner blood retinal barrier is basically formed by the tight junctions that are there between the retinal capillary endothelial cells that are there. Uh along with that there is reinforcement from the foot processes of the molar cells which are surrounding uh the blood endothelial cells and also the parasites that are there.

[00:11:15]The outer blood retinal barrier is formed by the tight junctions between the retinal pigment epithelium. And this outer blood retinal barrier acts as a bridge or a barrier between the neural retina from the underlying varascular coroidal circulation.

[00:11:34]The uh result that we find clinically in cases where there is disruption of a blood retinal barrier is the retinal edema. Along with that there will be lipid exudation. So the clinical conditions in which there is disruption of the blood retinal barrier is the posterior ubiitis and different types of retinopathies like diabetic hypertensive retinopathies commonly.

[00:12:01]So apart from that the immunoppressive micro environment that is helping in maintaining the immune privilege of the eye include the cellular mechanism which is basically formed by the endothelial fast liant which induces the apoptosis of tea cells. Then we have the RT cells which are forming the barrier. Along with that it also secretes imunosuppressive factors. So apart from that we have celery and the iris pigment epithelium which also protect pro provides the blood aquequis barrier and there will be cytoine production by them. We uh have key soluble immunosuppressive factors that are there in the aquis and the vitrus humor. The key soluble factors are TGF beta2. So it is an important immunosuppressive cytoine which is present in the vitrus humor. We also have alpha MSH which is have which is having the anti-inflammatory signaling uh pathway uh mediator. We have VIP and summatin which promotes immune deviation. Then the complement uh mediated injury is protected by the suppressants like CD46 and CD55.

[00:13:19]So these uh both soluble imunosuppressive factors as well as the key cellular mechanisms are very important and clinically it is important for the high corial graft survival uh because of the avascular bed and also the graft is able to survive because there are and we don't need HLA matching before coral transplants.

[00:13:46]So whenever uh the there is severe trauma infection or surgery there will be disruption of this immunosuppressor micro environment these will lead to the abolishing or there will be disruption of the immune privilege of the eye leading to inflammation.

[00:14:04]So now coming on to anterior chamber associated immune deviation. This is an important defense mechanism u that is seen in cases where there is an exposure to a foreign antigen in the acquisum.

[00:14:19]These will prevent severe ocular damage uh in the anterior segment and hence prevent uh the uh scarring or the uh disruption in the transparency of the uh vision. So the uh there will be moderate inflammation leading to the exposure of foreign antigens uh to the aqua humor.

[00:14:40]This will lead to increase in TNF alpha.

[00:14:43]There will be increase in MS MCP1 in the aquasum. These will then stimulate the recruitment of monocytes that is F480 plus. These will home in the iris tissue then further migrating to thymus and sple. in thymus and spleen. They will then cause the induction of the regulatory tea cells. These regulatory tea cells are an important component of suppression of the T- cell mediated immune response. So whenever the T- cell im mediated immunity or the cell mediated immunity is disrupted, this will protect us from the intense inflammation and immune response to the foreign antigen that was exposed in the aquas humor. thus protecting the eye from the ocular damage.

[00:15:34]The immune defense of the uh eye um so it can be broadly divided into parameological or the non-specific defenses which include the normal ocular flora that are anatomical barriers as we discussed. Then there is a mucous layer which is produced by the conjunctal goblet cells. Then we have antimicrobial factors that are present in the clear film. Apart from that we also have uh natural killer cells that are there. Uh the imunological or the specific defenses that are there are the conjunctiva associated lymphoid tissue langanger hen cells and also there are secrettory imunoglobilin A.

[00:16:19]So tier film and uh its antimicrobial defense. So the tearf is composed of three different layers. So all the three different layers have three different uh properties which are important for the uh defense mechanism against the foreign antigens. So the lipid layer which is secreted by the mibonian glands is important to prevent the evaporation of the tar film. It also helps in maintaining the tar film stability and provides antimicrobial fatty acids. Then the aquis layer that is produced by the accessory and the main lacrimmal glands washes away the debris. They are important to provide nutrients and also to deliver their antimicrobial proteins.

[00:17:03]Then this is followed by the mucin layer that is the goblet layer. These are important to stabilize the tear film.

[00:17:10]These are important to trap the pathogens and facilitate the epithelial adhesion. So lacrimmal gland also produces in IgA via plasma cells. It secretes defensing and growth factors for the epithelial repair. It is also uh helpful in production of different antimicrobial factors and lipo. So the different antimicrobial components that are there in the clear fill uh include lysosyme. So lysosyme is produced by the lacrimmal gland. It helps to degrade the bacterial cell walls. The lactopherin is there which is again secreted by the lacrimmal gland. It is having a bacteratic action uh by ironulation.

[00:17:57]Then we have secrettory imunoglobilin A which is secreted by the plasma cells.

[00:18:04]It also prevents the microbial adhesion.

[00:18:08]The complement system works by oxinization and lis. Then there is beta which is having and which is basically a antimicrobial peptide which is secreted by the cornal epithelium.

[00:18:21]Then uh the uh conjunctiva associated lymphoid tissue is a part of mucosa associated lymphoid tissue of the body.

[00:18:29]It is a diffuse lymphoid tissue in the conjunctiva. It has both follicular and interfolicular area. So B cells are located in the follicular area area sorry and T cells are located in the interfolicular area. So whenever there is an exposure of antigen to the conjunctiva associated lymphoid tissue there will be stimulation of the lymphocytes which will travel to the regional lymph nodes from there they travel through thoros thoracic duct into the bloodstream.

[00:19:00]So whenever these um um lymphocytes activated lymphocytes are exposed in the bloodstream they reach the uh lerimmal gland. There they stimulate in the form of plasma cells they stimulate the secrettory component of the lrimmal gland uh which will then induce the production of the secrettory imunoglobulin A and also they stimulate the T- cell response in the conjunctiva.

[00:19:26]This is very important in maintaining the balance between the tolerance to the commensils and also the defense against the environmental agents which are important.

[00:19:39]So uh how our body reacts there are two different types of uh inflammatory response in the eye. It can be either acute response uh which is mostly physiological. It is generally controlled and self-limited response. In this there is vascular change, cell migration. There is pathogen clearance and resolution because of the presence of pro-resolving [clears throat] mediators like lipoxins, resolins and protectants.

[00:20:10]So uh this if there is a continuous antigen exposure either in the form of infection or because of auto antigens can lead to chronic inflammation which is pathological.

[00:20:22]So in the chronic inflammation there will be failure of the regulatory mechanisms. The TH7 and TH1 responses are important in the autoimmune ukitis.

[00:20:34]there will be breakdown of the anterior chamber associated immune deviation mechanism.

[00:20:40]So whenever there is chronic inflammation that is the pathological response that is happening in the eye there will be different uh risks that are involved to it. So whenever there is chronic inflammation there is a risk of development of neovascularization of either cornea or retina or iris leading to the um uh scarring and in chronic phases there can be fibrosis in terms of there will be cycotic membrane leading to hypoteninal membrane formation also.

[00:21:17]So now uh moving on to the clinical applications uh basically applying the knowledge of a cular immunology to the clinical practice. So uh the first thing is the uvitis pattern recognition. So whenever there is an immune trigger either through infection or trauma or autoimmune there will be breakdown of the ocular immune privilege. These will in turn lead to a very characteristic uviatic pattern which will help us to know the probable ideology and thus a targeted management.

[00:21:53]So [snorts] uh for example when we have anterior uritis so we will have clinically cells there will be flare in anterior chamber there will be keratic precipitates. So it usually happens because of the breakdown of the blood aquis barrier.

[00:22:09]So intermediate uvitis in this we clinically will have ubiitis there will be snowballs there will be snow banking the uh response will be because of the immune cell infiltration into the vitrius cavity the posterior uvitis has koiditis retinitis vasculitis these will be there because of the uh in response to or as a uh will lead to breakdown of retinal barrier and there will be an of the extensive failure of the immune regulation.

[00:22:48]So whenever we clinically see that there is a granulomatus anterior ukiis in the form of mutton fat kps iris nodules it usually indicate that there is a chronic cell mediated immune response which we commonly see uh indicate and uh point towards the granulomatus ukitis that is sarcoidosis tuberculosis and VKC. So the non-granulomatus recurrent anterior uvitis indicates that there is a disregulated adaptive immunity which is commonly seen in HLA B27 vasculitis. There will be aggressive immune mediated vascular inflammation and uh it usually points towards tuberculosis or bashes.

[00:23:39]When we see there is a focal retininoidis adjacent to a scar we immediately think about to oxoplasmosis it usually indicates that there is a localized infectious immune response that is happening. Whenever there is necrotising retinitis it indicates that there is a failure of immune containment of the viral infection to because of the herpes infection.

[00:24:08]Whenever we see there is a bilateral panubitis with serrus retinal detachment, it usually indicates that there is an autoimmune response against the melanocy antigens uh which we commonly see either in VKH or in sympathetic of depending on the history.

[00:24:25][snorts] So whenever there is granulumatus scaratic precipitates with vitritis we think of saridosis or tuberculosis. Whenever there is unilateral iris atrophy with high intraocular pressure, it indicates that there is a herpes infection or a viral ideiology. Whenever there is bilateral granular matter span uvitis it indicates VKH or sympathetic of the recurrent when uh we are asking about history and there is a positive history of recurrent oral ulcers and clinically we see there is intense inflammation panovitis with hypoponit it point towards specials then whenever there is acute anterior unilateral uritis with fibrant we suspect HLA B27 Seven.

[00:25:14]So sympathetic of uh is an important and very uh important example of basically uh compromise to the ocular immune privilege. In this there is a bilateral granulomatus panuvitis following penetrating trauma or injury to one eye that would be the exciting eye which will be followed by a delayed hyper sensitivity reaction in the fellow eye that is the sympathizing eye.

[00:25:42]So basically what is happening in this is the exposure of these uh sequestered uvial antigens that is melanocy associated and retinal s antigen. There will be breach in the immune privilege because of the breach in the blood aquis and the blood retinal barrier. Then um there will be a basically T- cell mediated autoimmune response in both the eyes. It can happen between 2 weeks to decades typically happening between 3 months to one year. uh there will be diffuse granulomatus inflammation of the uvial tract predominantly it is CD4 T cells and the lympho uh sorry macrofage infiltration in this the characteristics are the denfukes modules which are the uh aggregates of the lymphoid cells it is there found between the brooks membrane and the retinal pigment epithelium uh then as we discussed the coin cornal graft survival. Uh they are a perfect example how without HLA matching we are able to have good coral grafts and successful coral grafts that also uh is because of the avascular recipient bed that is there in the central cornea with limited antigen presenting cells. Uh there is also absence of lymphatics in the central cornea. Endothelium has fast lians which deletes the uh activated T- cells. Then there are low MSC expression centrally along with the presence of anterior chamber associated immune deviation uh that we discussed. [snorts] So when uh we should suspect these are the high risktolastes or where uh basically there these are the eyes where the immune privilege has been lost. So those eyes include when there is vascularization reaching the central cornea that is the deep or the stomal vessels. Whenever there was a previous rejection before whenever we are doing graphs in a large um whenever there are larger grafts that is the uh edge or the bed is reaching till the limbbus where we have different immune rea where we can have immune response and the chemical burns. So where again the limal cells are hampered or are affected leading to the higher risk of graft rejection. So the along with these factors whenever there is an active inflammation that is the blood aquis barrier is already compromised that is another condition where the catlastes become a high risk.

[00:28:24]So uh now coming on to the treatment mostly it is the uh decrease of the inflammation that is happening. So corticosteroids are the first line of therapy. So the mechanism how the corticosteroids work are by decreasing the luccoyte migration. They [snorts] also are important to stabilize the blood aquequis barrier as well as the blood retinal barrier. They reduce the inflammatory cytoines by reducing the transcription of these cytoines. They also uh reduce the cellular or the vascular permeabil permeability by stabilizing the vascular uh vessels. Then these corticosteroids can be given in different routes. Uh it can be given as topical corticosteroids in anterior ubiitis. then perocular subpenance or the intravitral form uh in systemic where corticosteroids can be given in panuvitis or sympathetic of so immunom modulators are basically steroid sparing uh they alter the immune response to reduce the pathological inflammation uh while preserving the overall immune function. The uh indication are the chronic ubiitis whenever there is bilateral disease whenever we have recurrent disease and whenever there is uh steroid intolerance. We have different classes of immunom modulators like uh we have mythtotric that is most commonly used or aathopre and microfenolate. So these three are the anti metabolites. Then we have cycllosporin and tacrolyus that are calcinurine inhibitors. We have biologics also that is NTNF uh infleximab adalimab and the other molecules.

[00:30:20]Thank you.

[00:30:26][clears throat] >> Uh thank you. Thank you so much Dr. Axita. This was a very detailed and comprehensive review of ocular defenses and ocular privilege. Uh we do have a few questions in the chat box but before we start let's have some you know uh remarks from uh Dr. Mudjit sir please.

[00:30:47]>> Yeah. All right. First of all Axita very nicely covered. I think you have very adequately summarize most of the points and I think it becomes very important for us to understand the immune mechanisms that come to play in the eye.

[00:31:00]The reason is that it's got different ramifications not only in terms of understanding the corial pathologies but also what's happening in vasesopathies. Like if you understand what happens to outer and inner retinal barriers then you can understand what's happening in terms of inflammation when the inner retinal barriers get broken down you get lipid exodations which become very important in lot of diabetic retinopathy and vascularies. Same holds true for outer retinal barrier changes and lot of inflammations that happen over there.

[00:31:29]The fact that you have got an immune privilege side in the eye helps you understand why a cornal graph survive so well and why the large graphs or eyes where there's a vascularization are the ones which tend to fail because once there is vascularization that starts seeping in then the eye gets exposed to more of immune mechanisms and more of these immune agents and that's why these graph fail. So once you understand the fact that you are dealing with an immune privileged site you start understanding the reasons for graph failures. you start understanding and appreciating why and what are the factors that you have to look for in prognostication.

[00:32:04]So eyes which have got a past history of inflammation, eyes where you have got limal blood vessels which are growing over eyes with ocular surface inflammation. These are the eyes where the graphs tend to fail and the reason is because the immune privilege of the eye is lost because of the vascularization and the changes that have happened. So a lot of times people do not give that much of a weightage in understanding the immune mechanisms which are there inside the eye but once you understand them you are able to clinically correlate them and that becomes important like uh Axita showed very nicely what happens in sympathetic and T- cell mediated response. So obviously your immunosuppression that you need to use in these eyes will be the ones which help in taking care of that. Lymphas on the other hand have got a lot of times of B cell mediated response and so you need to take care of those in that sense. So it becomes important to understand the various mechanism they come to play over here for you to start correlating them clinically.

[00:32:59]>> Right. And sir also it is very important in guiding what future therapies will come out.

[00:33:05]>> Yeah.

[00:33:06]>> Come you know because if we don't understand the basics where all these problems are happening then that is actually the seat of all the innovation.

[00:33:15]>> Exactly.

[00:33:15]>> That is happening.

[00:33:17]>> Right. So we have a couple of questions in the chat box. One is uh could you please explain the mechanism associated with anterior chamber associated immune deviation?

[00:33:30]>> I think Axita has very nicely explained it. Axita if you can go back and open the slide again. That slide very nicely summed up. Maybe you can just answer it and then me and Tanya can chip in later on. Just open that.

[00:33:39]>> Yeah. Right. So basically uh what is happening in the anterior chamber associated immune deviation is that whenever there is an exposure of aquisum to a foreign antigen there will be increase of cytoines like TNF alpha and MCP1 in the anterior chamber which will then stimulate the recruitment of the monocytes. These will travel to thymus and spleen where basically they will cause an induction of a regulatory tea cells and will cause a suppression of the cell mediated immunity. So whenever there is a suppression of this cell mediated immunity that is the uh going to cause more of inflammation there will be protection of the ocular damage that will be there.

[00:34:22]>> Yeah t just a question these lectures are freely available now for people to go back again and >> right sir. Right. Right.

[00:34:31]>> They will be available on YouTube.

[00:34:33]>> Anybody who is listening to us today, I think this is a very nice lecture and maybe it and this is something which you should listen to again and again for you to get it deeply embedded into your head. Immune mechanisms are not something which are easy. The reason being that we do not you routinely use them in our clinics. They are not something that come in play whenever you are examining a patient clinically. But understanding them becomes important for you like what Tanya said to not only understand what's happening but also to help in evolution of future therapeutics.

[00:35:04]>> Right?

[00:35:06]Uh another thing I think the question which we already talked about is how might future imunotherapies target ocular inflammation while preserving vision. So I think the understanding the physiology behind uh ocular inflammation especially in uvitis is the cornerstone for any of the future developing therapies. If we know what are the factors which are associated with you know all this kind of inflammation happening that is when we find and today is the era of finding targeted therapy so that there is least damage to the uh associated ocular structures.

[00:35:48]>> Exactly. any anything else >> like if you look for ititis or for uvitis lot of monoconal antibodies are coming into play and mapab has become such an important part of our armament >> similarly for recalcit and non-dissolving sclerit started using ritosimab why are we using ritos a cd20 antibbody the reason is because now you know what is the immune mechanism behind it so unless and until you know that your future potential therapeutics will not evolve >> right Even jack inhibitors are coming up very much in vogue nowadays. We are uh in fact we are having a trial where we are comparing to fatisinib with methotate and combination therapy for HLA B27 associated uvitis and we have very good results where patients are doing very well with these jack inhibitors. So >> of course it it is very exciting but uh the future always holds your it will take you back to the basics and understanding these basics is very important.

[00:36:54]>> Yeah. So I think that's a very valid point because unless and until you know what has happened you cannot build upon something new lot of work in VF is going on people are trying to re look at tyrosin kynise inhibitors in terms of taking care of AMD as well as DME because now you know the tyrosin kynise is a molecule that works over there helps in complement activation. So once you know that then you can start targeting those specific proteins going forward >> right uh no more questions from my side anything else Dr. Uh ma'am there is one question we just received.

[00:37:32]>> Okay.

[00:37:33]>> Uh what are the I mean how does a failure of ocular immune privilege lead to macular edma?

[00:37:40]>> All right. Again I think that is something that was shown by Axita in one of our slides. But what is a failure of the mechanisms you get those inflammatory cytoines lead to m cell dysfunction lead to changes in the internal of the eye and then you start getting cy maladema which starts developing over here that can happen even after a pseudo macular what we used to call a urin gas syndrome also has got melody happening over here. We have just undergone a catact surgery. There is inflammation that is happening. Lot of uvitis has got a breakdown of the blood retinal barriers. So when and now that white ultra wide field fluorosine angography has come. We have started seeing how many of these eyes have got an extensive pervascular leakage like what you earlier used to associate only with batchets. So there's a breakdown of the blood retinal barrier. Inflammatory cytoines start coming into play and then that leads to cytoma.

[00:38:38]>> Yes. And to add to this ultra wide field actually after we started doing these angographies I realized that how much we were under treating the patient before.

[00:38:48]>> Yeah.

[00:38:49]>> You know stopping steroids when there is actually inflammation or not giving adequate amunosuppression. So these uh so all these advances actually help us to treat the patient better.

[00:39:00]>> Yes.

[00:39:06]So Katika, Tanya, if there's nothing else, maybe we can wrap up.

[00:39:10]>> Yes. Yes sir. That's that's all the questions from audience side as well. So uh so just a reminder uh for the audience. Uh so we have a physical eye focus coming up. Uh that's from July 5th through 12th in Hyderabad. uh where we'll be covering both the dactic session from July 6th to 11 and hands-on sessions uh on July 5th and July 12th.

[00:39:34]Uh so uh registration is limited to 300 candidates. So hurry up, >> right? So thank you Kika, thanks for having us. Thanks Tanya for such a great motion and a thank you. That was a really nice lecture and maybe it will be good if people can revisit and listen to it again.

[00:39:52]>> Thank you.

[00:39:52]>> Thank you so much sir. Thank you sir.

[00:39:54]Thank you for >> Thank you everybody. Thank you everybody.

[00:39:56]>> Thank you. Thank you.

[00:39:57]>> Bye. Good night everyone. Take care.

[00:39:59]>> Good night.

[00:40:00]>> Good night everybody.

[00:40:01]>> Bye.