 Well, thank you very much all for being here. I'm really delighted to be able to talk to you today. Yeah, I know ophthalmology is like a little bit separate than a lot of other Medical fields, so I'm really excited that everybody's here and interested I'm going to be talking to you today about dry eye disease and ocular surface disease that tried to bend it a little bit more towards systemic association so that you can hopefully It'll help you in your practice I am Like like Sam said, I am a cornea specialist University of Maryland downtown as well as in the redwood clinic as well as I see patients in owing's mills So thank you very much Okay So the objective today, I'm going to find dry eye disease We're going to go over some tests that we use for diagnosis of dry eye disease and uh systemic diseases that are associated with dry eye disease as well as some treatments So this is more an outline of the talk the anatomy We're going to go through the definition of dry eye disease tests And then we're going to talk about these diseases as well as inflammatory dry eye disease and treatments So the ocular surface um really involves Uh the tear film the lacrimal gland the congenitiva both epithelium and goblet cells the cornea the clear part of the eye Including which has both epithelium The corneal epithelium is really uh the most involved area of the cornea the eyelids including mybomian glands and the immune system Both innate and adaptive immune systems are involved So going over the normal tear film. There are really three major components to the normal tear film There's the lipid layer and the aqueous and mucin layers um and these uh So the lipid layer is from the mybomian glands the aqueous and mucin layers are from the lacrimal gland and goblet cells respectively And we're going to go into a little bit more detail on those Um, so mybomian glands are involved in lipid secretion the lipid layer Helps to prevent evaporation of the of the um tears as well as smooth the optical surface um and stabilize the tear film um and uh It's pretty important for um Maintaining a good ocular surface Um the mybomian gland dysfunction is the number one cause of dry eyes Um as far as aqueous secretion that's from the lacrimal glands. They secrete um Most of the proteins found in the tear film the basal tear secretion is from the grant glands of kraus and wolf feeding Which you can see Here um and that are accessory glands and reflex tearing is from the main lacrimal gland um and finally the mucin layer um mucin 5ac is from the goblet cells and they're also membrane bound mucin um and uh And it allows it prevents bacterial adhesion and also helps with lubrication So in order to study any disease, it's really important to have a uh a definition that everybody can agree on so the T faus dues the um to came up with a Clear definition of dry eye disease and what's interesting here that we're going to highlight and come back to a few times during this talk is that um dry eye is a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film accompanied by ocular symptoms um and tear film instability and hyper osmolarity ocular surface inflammation and damage and neurosensory abnormalities play etiologic roles and what's really important with this is that um There are a number of different components to this definition that really um will help determine both what tests we run as well as How to define dry eye disease clinically So the etiology of dry eye disease can be broken down into a number of different ways I'm going to go through a few here. Um, but as far as uh dry eye you can have um both aqueous deficient as well as um evaporative dry eye and the reality is that this is more of a Spectrum as opposed to total separation of these patients, but it's helpful to think about it in this way So if you go down towards uh aqueous tear production deficiency, you have shogrens and non shogrens So shogrens, we have primary and secondary which we'll go into in a little bit more detail in a moment But non shogrens can be um aqueous tear deficiency can be due to lacrimal gland dysfunction, lacrimal obstruction, cicatricial changes to the eyelids and neurotrophic Components and then if you go towards evaporative loss That's due to the mybomian gland dysfunction exposure or can be caused by contact lenses or a problem with blinking or environmental factors Oh, this slide got a little bit funny, but um, so another way to think about dry eye disease is based on the The cause so if you think about it about immune mediated versus inflammatory versus neurosensory and anatomical changes So immune mediated cause can affect the lacrimal gland causing aqueous tear deficiency or problems with the mucin layer Causing a lipid layer abnormalities inflammatory changes can lead to decreased lacrimal gland secretion and hyperosmolarity And evaporative dry eye and mucin bomian gland dysfunction Can also fit into inflammatory causes Neurotrophic keratitis is important for neurosensory changes and anatomically you can have post surgical sensory denervation and abnormal blink So, um, I think this is my personal favorite way of thinking about it sort of combines both So if a patient comes into your clinic with dry eye disease, you can be asymptomatic or symptomatic So the classic patient is a symptomatic patient who comes in with symptoms of Tearing and discomfort and a dry gritty feeling or decreased vision And and on exam you see clinical signs of ocular surface disease or dry eye disease and I'll go into Bit more details of that in a moment And then you treat it with again, we're going to talk about in more detail But what's interesting here is to think about those patients that come in that are asymptomatic and then on exam you see changes that are consistent with dry eye disease and That can either be due to just early changes that the patient's not symptomatic from yet and you can think about doing a preventative therapy or treatment for those patients or The patients can have a neurotrophic component and have four corneal sensation And those patients are really ones that you want to focus on treating And want to treat pretty aggressively because they run the risk of of perforation As far as symptomatic patients you can have no signs And those are patients that we would call uh sign symptom disconnect And it's it's a little bit of a discussion whether or not you treat it or just observe it because it's a little bit harder To treat because you don't really have an end point exactly for those patients And then there's this other component that involves neuropathic pain And those you treat like any other neuropathic pain in the body and you can either Refer for pain management or trigavapentin or an ssri so the pathophysiological mechanism of dry eye is Pretty well studied, but it's also really complicated and we're not going to go into these details today, but To break it down a bit for you here the The mechanism of dry eye is this cyclical Problem where it leads one issue Can lead to the other and you have to kind of break the cycle So you if you have A patient with environmental factors or medications or contact lens issues Which causes irritation and then they develop inflammation due to the irritation Which then causes deficiency of the tears and then you get more irritation and it just It continues in this path and it doesn't really matter where you come into it You end up with all The problems which goes back to my point originally about that this is really a spectrum Even though we think about it a little bit separately Um So the underlying pathophysiology of dry eye disease to simplify it is just a combination of evaporative loss of the tear film And aqueous deficiency leading to damage of the ocular surface So um dry eye disease has a number of risk factors including um older age Women are at increased have more dry eye disease than men hormonal changes abnormal corneal innervation Vitamin deficiency contact lens use infection or a history of ophthalmic surgery The symptoms that patients complain of are dryness irritation far far and body sensation light sensitivity or itching And these patients are Have been shown to be more associated with patients with anxiety and depression um, and then uh, this affects five million americans over the age of 50 And two-thirds of them are women. So it affects a lot of people And again the diagnosis and management we're going to go into more detail on but the the way that I like to think about it Is the four main categories of dry eye disease the inflammatory immunologic anatomical and nerve sensory The symptoms there's a wide range of symptoms. You can have mild irritation that is minimally Problematic to the patient a significant decline in vision and even perforation of the cornea So um So to go into the clinical exam So the history and symptoms are probably the most Are very crucial to deciding what's under having a better idea of what's going on and what's really bothering the patient um, you also do a thorough slit lamp exam and It's paying special focus to the cornea the conjunctiva and the eyelids And then there are a number of clinical tests Some of them are standard in most clinics and some are a little more Novel so you look at you can look at tear breakup time ocular redness ocular surface staining Shermers is a measurement of tear fluid production or tears. Um, and a fluorescein clearance test you can also have You can measure the tear fluid osmolarity, which is important because that's part of the definition of dry eye disease And some newer test is uh inflama dry or mmp9 Which is a measurement of um inflammation in the eye on the surface of the eye, excuse me Um, and you can also measure uh, have my boming gland imaging, which is a nice way to look at the uh The structures of the my boming glands So tear breakup time. Um, what you do for this is you place fluorescein in the eye. Um using either fluorescein strip or um But you do it without anesthetic And then you have a patient blink and then you evaluate them for the dry spot. Can you see my cursor at all? Okay, so um what you see here is what and the patient blinks for the first time they open their eyes and you see Kind of diffuse green and then here you can see the breakup time where there are spots that aren't covered in that same green um so uh The normal tear breakup time is anything greater than 10 seconds if it's less than um, you would want to think about dry eye disease So to back up a little bit and talk about ocular surface staining and ophthalmology We use three different stains. We use fluorescein most commonly But we also can use rose bengal and listening green So fluorescein um stains areas of missing epithelium. The epithelium is the surface of the cornea It shows epithelial defects or erosions And uh, it has the ability to permeate inside the cell as well It's used For to evaluate the corneal epithelium as well as to look for tear breakup time. That's the the stain that we use Um, you also have rose bengal and listening green and they they basically do the same thing They both stain live epithelial cells that have lost their mucin um, but um Uh rose bengal is a little bit more painful and a little bit more um Irritating to the patient. So I tend to stick to listening green. Um, but they're both available Um, both rose bengal and listening green are much Better at staining the conjunctiva or the white part of the eye. So that's um, definitely an important part to note Uh, fluorescein really doesn't stain the conjunctiva as well Um, so briefly to go into how we use these staining. Um, so if you see superior staining So what you see here is that um the hazy part is where there would be staining so Often there's actual epithelial defects or changes that are not Diffuse although you can't get diffuse changes which is associated with viral conjunctivitis and toxicity or very severe dry eye But often where the staining is most prominent can really help you Think about the differential diagnosis on these patients. So superior staining you want to think about super limbic keratitis or vernal conjunctivitis or floppy eyelids or Contact lens induced limbal stem cell deficiency. You can see it with that As well as a foreign body under the upper eyelid If you see interpal peeperal or between the eyelids, which you can see here That's more consistent with dry eye exposure and our trophic changes inferior staining is more consistent with uh, blepharitis or other forms of dry eye disease and This is a particular Staining which is at three and nine o'clock and that's associated with the tight contact lens Which is interesting. So shirmers is another test that we use. So shirmers is uh, you use these, um Strips in the outer one third of the lower eyelid Patient closes their eyes for five minutes and then you get a measurement of the Tears that are produced and less than five millimeters on the strip is uh, is very It's pretty specific for dry eye disease. Um, it's not as sensitive, but it is a very useful test Without anesthesia, you're measuring both the basal and reflexes tearing but with anesthesia. You're only measuring the basal tears um, oculosurfritz disease index score is a measurement of uh, is a questionnaire that's used for, um Uh Measure to measure the symptoms that patients are having for dry eye disease and what you can see Um, it's at this this oculosurfritz disease index there has been very well validated. There are many Different questionnaires. This is probably my favorite. It's relatively easy and fast and um, you get a good idea of how the patients symptoms are affecting their daily lives And it's only 12 questions, which is nice um, so these are a couple more tests more, um less standard, uh, universally but um tear lab osmolarity um, is uh, an important test because again, it's part of the um It's part of the definition of dry eye disease, but it's not necessary in order to diagnose dry eye disease mmp9 is in flama dry. It's a point of care test in the clinic that is able to um Let us know if there's inflammation on the ocular surface. Um, that's one of my personal favorites And then there's conjugal impression cytology, which is really more of a um, uh Really hasn't found a clear place in the clinic, but is still used for research So, um to switch gears a little bit and talk about systemic diseases associated with dry eye disease um And the first one is definitely chogren's syndrome um, so this affects women more than females more than males with a 10 to 1 ratio um primary chogrens is no other associated autoimmune diseases secondary chogrens is with rheumatoid arthritis lupus or other autoimmune diseases um in order to diagnose it you do a thorough history including symptoms of dryness elsewhere including in the mouth And then ocular signs you do charmers is very helpful. Um, and uh, there's usually a lot of staining these patients You can also do auto antibody tests and we tend to refer these patients to rheumatology for further work up Uh ocular complications include filamentary keratitis, which you can see here. It's these deposits On the surface of the eye. These are actually attached to the cornea and they have this windshield wiper type of process which Causes further irritation Um, and then you can also get an infection microbial keratitis or a sterile ulcerative keratitis Which you can see here where there's thinning and melting of the cornea And that can lead to perforation So these we want to treat with both topical and systemic immunosuppression and punctile occlusion can sometimes help um neurotrophic keratitis is I guess less of a systemic uh problem, but um, you get uh decreased Corneal sensation and it can be caused by a number of different problems like a herpetic infection diabetes history of surgery um retinal surgery or prp or laser uh retinal changes can also cause uh decrease corneal sensation um history of lasik Also topical medications. So patients that are particularly on glaucoma medications can have this problem or any other topical medications that they've been on long term Or damage to uh cranial nerve five um and then treatment for these is um particularly important because the patient is not going to have as much symptoms um to to help dictate um any uh To give you an idea of what's going on. Um, so they can be pretty far progressed and um, not be aware So the treatments include uh non-preservative artificial tears serum tears punctile occlusion bandage contact lens can be used Or lateral tarsography, which is closing the eyelid And scleral lenses can also help these patients Um blufferitis is a is an important other cause of dry eye disease. So it's chronic inflammation of the eyelid margin There's anterior and posterior types of blufferitis anterior is associated with staff uh Staffed cockle inflammation um as well as uh posterior blufferitis is more focused on the mybomian gland dysfunction You can have both seborrheic, which is a hyper secretary um Blufferitis or hyposecretory blufferitis, which is mybomian gland plugging or loss of glands Often you get both an anterior and posterior picture here So to go into a little bit more detail on this so staff blufferitis It's really an immune response to the staff toxins So it can cause marginal keratitis, which is inflammation of the um it which causes uh an infiltrate on the cornea So it looks like small corneal ulcers on the periphery of the cornea You can also get flictenials And you get mattering of the eyelids or crusting, which you can see here um Or loss of lashes and this is really important to treat with lid hygiene as well as topical antibiotics and in the right patient You also need to treat with topical steroids because um You it's the inflammatory or immune response that you're trying to quiet down um But I would highly recommend making sure that the patient is being seen by somebody who's able to measure the um Measure the intraocular pressure if you're going to start a topical steroid because the pressure can go up um, so hyper secretary mybomian gland disease, um, you get these greasy lashes Um, it can be associated with cyborrheic dermatitis elsewhere in the body Um, and it also can occur with other types of mybomian glands This you treat just like any other cyborrheic dermatitis with selenium containing shampoos So it is a different treatment Um, so to go into mybomian gland disease in a little bit more detail here Um, these pictures are helpful actually. Um, you get uh symptoms of burning watering or blurring of vision Especially with reading you can also get light sensitivity in these patients Um, you get uh inflammation of the mybomian glands and blockage of the mybomian glands, which you can see here um, and you get this increased blood vessel growth the telangiectasia um, foamy tear film Which I don't show here and then you get these peripheral corneal ulcers Which are these white spots in the periphery of the eye. You can see them here as well Um, and you get rapid tear breakup time in these patients This is best treated with lid hygiene. So warm compresses and, uh, lid scrubs, which is simply baby shampoo on Uh, a clean washcloth or you can use over-the-counter like ocusoft lid scrubs or some other type of, uh, lid wipes Um, you can treat this with antibiotic ointments like erythromycin ointment Or azithromycin or you can also use a combination of steroids and antibiotics like toberdex or maxetrol And, uh, systemic treatment is with doxycycline. You start off at 50 milligrams twice a day And then you can go down to once a day, but that's a long-term therapy For at least three months And that has both bacterial and anti-inflammatory components So rosacea keratitis is associated with my bone gland disease and blepharitis, but what this is Was a patient that I saw with among the most severe rosacea Um, uh, blepharitis that I'd encountered. He actually had multiple perforations But um, the he was obviously treated systemically, but you get progressive corneal thinning and, uh, And risk of infection You want to treat these patients with both steroids and long-term rastasis as well as doxycycline is probably the key here That's systemic doxycycline Other causes of um, blepharitis is demodex, which is, um, these small mites that you can get on the eyelids Um, and, uh, as well as contact dermatitis, which is usually caused by, um, other eye drops So my personal favorite of these diseases is, um, ocular graft versus host disease. Um, So I have a, uh, um, a number of ocular GVHD patients Um, so this affects, uh, 40 to 60 percent of all patients who undergo allotransplants are, um, develop GVHD of those 60 to 90 percent with, um, will develop ocular, uh, changes The, uh, ocular GVHD is usually during the chronic phase from six to 18 months after transplant Um, and they get pan ocular surface disease. Um, and all of the ocular surface structures that we've discussed are involved And it's, it's a robust inflammatory cause Um, and this can cause, uh, corneal blindness or in a significant decline in their quality of life And again, this affects all, uh, components of the ocular surface from the lids to the lacrimal glands to the congenitiva and the corneal lens It's, um, can be really detrimental to these patients. Um, and it's also fascinating disease from, uh, Uh, uh, to study because we actually have, we know when it's, uh, gonna start because we are involved in causing it So there's a special diagnostic criteria for these patients including corneal staining Um, congenitival injection, a Shermer's test and ocular surface disease index and we've gone through all of these tests Uh, previously and then, uh There's, uh, you, you kind of add all of them up and then depending on whether or not they have a diagnosis a confirmed diagnosis Of systemic graft versus disease elsewhere in the body. Um, you can diagnose them with either probable or definite ocular graft versus host disease So, um, what options do we have available for treating dry eye disease? Um, there's Four basic principles that I like to think about one is you can replace the moisture You can treat the mybomian gland disease You can prevent loss of the, um, tears and you can control the inflammation depending on the cause of the dry eye disease So to replace the moisture you want to think about preservative free artificial tears or regular artificial tears um, uh Tier gels ointment, um or serum tears For mybomian gland disease you want to think about warm compresses, erythromycin ointment, doxycycline systemically And you can also think about intense pulse light, which we'll go into in a bit More detail, um, and then, uh to prevent loss of the tear fluid film You want to you can use soft contact lenses or scleral contact lenses, which are larger contact lenses that are hard and go Instead of sitting on the cornea they sit on the white part of the eye and Vault above the cornea and therefore continue to lubricate the surface You can also use moisture chamber goggles or environmental changes like humidifiers changing the height of your computer screen um, not Sitting near or sleeping with a fan They're a number of different, uh possibilities And then you also want to control the inflammation if it's present So you do that with top glee with steroids Tachrylimus cyclosporin like rostasis or sequa or systemically with systemic steroids systemic Tachrylimus rotoxymabermicofenylate and again, that's depending on the um, the cause the underlying cause of the dry eye disease as well as the patient symptoms So to go into a little bit more detail so the way that for, uh Dry eye most forms of dry eye disease the way that you want to think about it It is in a stepwise approach um, so one, uh important thing is to educate the patient and explain to them why they're having their symptoms or how uh, how they're What how dry eye disease occurs? And then you can talk about modifications to their environment removing fans, lowering computer screen increasing humidifier use um, they're dietary modifications Um, or you can if they're on other medications both systemic or topical you can Determine if you can stop or change some of them for topical medications You can use preservative free formulations as possible. That definitely helps a number of patients And then lubrication with artificial tears And then lid hygiene and warm compresses are sort of the baseline where we start Um A step further would you be using preservative free? artificial tears if they have demodex you can think about tea tree oil you can If they're non inflammatory causes of dry eye disease you can think about punctile occlusion Um overnight you can use ointment. Um, although during the day that would cause blurring of their vision Or moisture chambers. You can also think about lipoflow or intense pulse light therapy And then there are some prescription medications that we can use like topical erythromycin ointment Or an antibiotic and steroid combination Or you can do A short course of a low potency steroid like lotamax Or you can also use anti inflammatory medications like levidograst Or Doxycycline systemically um If that's uh, not sufficient then you can think about um, autologous serum tears, um, which is where we take the You do a blood draw it gets processed and spun down to serum It's mixed with preservative free artificial tears and it really helps to um Uh certain patients that can make a big difference in the in um improving the ocular surface And then you can also talk about therapeutic contact lens. These are not for uh vision changes necessarily They're more for the surface. So again the scleral lenses or even soft contact lenses can help If all of that's not helpful, then you can think about a longer course of steroids amniotic membrane graft You can surgically or more permanently have punctal occlusion or A tarsaur or fee or closing the eyelid Which actually can make a a huge difference and you can really make Big strides forward in the right patient And then um Cyclosporin is rostasis or sequa And that's more helpful in patients with inflammation Or although patients with severe tear film insufficiency Usually can't tolerate it as well, especially at the beginning. They have lots of burning And it takes a couple of months to work. So you want to start the steroids at the same time that you start rostasis Or cyclosporin And kind of taper them appropriately as it starts to kick in There was a question About tea tree oil. I think in the right patient population That's really helpful, but um, that's more for treatment of demodex as opposed to Just in general Dry eye disease patients. So it needs to be targeted appropriately when it's appropriate. It can have really nice results And again the refractory dry eye disease you want to think about the serum tears, which I really like in scleral contact lenses um, so scleral contact lenses um They sit so this is a patient wearing a scleral contact lens and what you can see is the edge of the Of the hard lens and you can tell from the um The light beam slip beam that you can um that the that it's kind of vaulted over the cornea um, and it causes Pretty marked uh improvement in corneal staining and the ocular surface. So you can see here is outside The the space that the contact lens sits and you can almost see where the contact lens is sitting and how Much of improvement they have prior to starting scleral scleral contact lenses as a patient had diffuse staining um Even though you can see pretty remarkable results of scleral lenses. They're definitely not Without their uh drawbacks. They're harder to use They need patients need to be trained how to use them access to scleral lenses is a little bit challenging um, and uh, some patients still, uh Don't necessarily just can't tolerate them But when you really have no other options, they're great, especially in really severe dry eye cases graft versus host disease patients do remarkably well with these as well as choker and SJS patients So lipoflow and uh intense pulse light it's um Basically just warms the my botanical glands and then massages them and then helps to excrete the um The sebum, um, but patients can really uh show some nice results from them um, the neuropathic component to dry eye disease is actually very interesting um, it's it's more challenging to treat because um, you don't necessarily See it as much on exam, but um things that we can use to treat it is autologous serum tears Contact lenses like I talked about you can use systemic therapy with tricyclics calcium channel blockers And gabapentin also lifestyle changes can have a big effect on these patients improving sleep exercise hydration Um can really make a difference So just to review the four principles of management and really in most patients We do a combination of all of these and want to address the various components You want to replace the moisture treat the my botanical gland disease prevent loss of the tear film with lenses or moisture chambers? um and controlled inflammation So, um in conclusion dry eye disease is a complex disease The patient's history is really important for identifying the underlying etiology which allows you to treat it more appropriately um and to target the treatment for the underlying cause and not all dry eye diseases the same or should be treated the same depending on the severity or the cause um or in some cases if there's um Uh more of a cause due to inflammation You obviously don't want to wait until you've you've gone down your list to get to anti inflammatory medications You want to start that sooner so um This slide basically puts together all of this. So you want to ask the question um if you think it's dry eye disease you look at risk factors diagnostic testing Um that we went through classify them and then it's a spectrum. So you want to treat it depending on um all the different components