 Morning everybody. We're going to go ahead and get started. Thank you Jeff So this morning We have a presentation on the ocular surface by Dr. Michael Duffin from the Moran Eye Center and That should be the only presentation Welcome Good morning. Good to be with you this morning What I'd like to talk about is the ocular surface, but near the topic to talking mostly about dry eye disease practical approach and treatment to that My wife and I were missionaries in Panama between 2004 and 2007 We noticed down there our eyes didn't give us any trouble at all But we came back to Salt Lake City a few years ago all of a sudden at least my eyes began to burn and sting a lot And I started thinking you know, I haven't paid a lot of attention with my dry eye patients to Humidification and control of the environment and I started paying more attention to that and found that it actually did work a little bit This is us a few years ago in the Sun Bloss Islands 95% humidity and more like a hundred percent humidity and 95 degrees all year round Dry eye disease as all of you know is a very prevalent condition and about five million adults in this country have a preponderance of women The cost of dry eye disease is significant was estimated in a recent study Published a few months ago in the cornea journal that the cost to the patient direct cost with co-pay and Coinsurance was about eight hundred dollars a year. Then if you look at the total cost What insurance companies pay the government pays and even lost to employers approaching 11 or $12,000 a year So the financial burden is significant No matter what specialty or subspecialty we happen to be in in ophthalmology We're finding that it's more important now that we used to realize before to pay attention to the ocular surface particularly with refractive surgeons premium Iowals But ocular plastic surgeons of course have to pay a lot of attention to the ocular surface with blink abnormalities retina surgeons with neurotrophic carotopathy with diabetics and Certainly glaucoma specialists with the amount of topical medications and preservatives that are placed on the eye We all know that it's a multifactorial problem with pharmacology neurology Allergy immunology Blepharitis infections trauma all kinds of different factors can have an effect on the ocular surface and dry eye I've come to realize especially after coming to Salt Lake Where it's much drier than even in the desert where I practice in Southern, California That I was really quite weak in my approach to dry disease and my patients in California One of the weaknesses I had was taking an incomplete history not really talking to the patient about their lifestyle Failure really to look at the whole patient Maybe not noticing their face that they had rosacea or looking at their hands to see that they had rheumatoid arthritis Sometimes we have the weakness of just approaching everybody that says my eyes burn and sting and giving them artificial tears instead of looking at some other modalities that may be more helpful and Failure to address the basic cause of dry eye and not educating our patients correctly in 1946 Eugene Wolfe put forth the the theory of the three separate layers of the tear film the lipid the aqueous and the mucous layer and later in 1965 alers noted that these three separate layers actually worked in unison When a pressure was placed on the lower eyelid it seemed the tear film seemed to move on block a few years ago and in Australia Ivan share coined the term dachroon Which emphasized the integrated body of the tear film and here's a an illustration from his paper which shows Interpalpebral tear film and the retropalpebral tear film which Probably does not contain much of any lipid concentration Here on the on the right in this diagram. We see the corneal epithelium In immediately adjacent to the corneal epithelium. We have a glycol calyx, which is a slippery layer of glycol proteins that Decrease the friction when we blink That's secreted by the corneal epithelial cells then immediately to the left of that We have the mucin layer the aqueous layer and then the lipid layer here to the left What we've learned in recent years is that the aqueous and the mucin layer are not completely separate It's actually called the muco aqueous layer now because the mucin Molecules are interspersed in the aqueous layer with a concentration that decreases as we go toward the external tear film Steven Flugfelder and others have popularized the notion of the lacrimal functional unit recognizing that the tear glands don't act in an isolated manner, but are Linked together with the neural network and the ocular surface to work together as is a unit And this will have an effect as we'll see both in the pathology as well as the normal physiology of the tear film There's been a lot of different terms that have that have been used in the literature to describe dry eye disease One of the terms that was popularized I believe by the Delphi panel a few years ago was dysfunctional tear syndrome Which doesn't use the term dry eye that terminology is not really caught on because dry Eye the term dry eye is so ingrained in the literature But the rationale for using dysfunctional tears syndrome is to recognize that not all tear film abnormalities are dry eye But as we read the recent literature the most common term is either dry eye disease or dry eye syndrome currently in the literature There have been several attempts to define and classify dry eye One of the main ones a few years ago, which was published in corny in 2006 was the Delphi panel now a Delphi panel is simply a consensus of experts. There are 17 External disease experts who are brought together to try to classify and define what dry eye is And they concluded that the terms that we've used in the past and still use aqueous Deficiency dry eye and evaporative dry eye really inadequate because they seem to imply there's two separate categories When really they're not most of our patients have a combination of evaporative and aqueous deficient dry eye most cases of significant dry eye will have an inflammatory basis Diagnostic tests such as the Schermer test have limitations and they proposed a stage classification which will help to direct treatment a year or two after that the in the ocular surface journal the The dry eye workshop study the do's study was published and in this study a definition was put forward stating that dry eyes a multifactorial disease Consisting of symptoms visual disturbance instability of the tear film and Then they use two terms one is increased osmolarity hyper osmolarity and inflammation which Help us to understand the pathophysiology of dry eye syndrome There are many anatomic and physiologic Factors that impact dry eye whether it be decreased blinking ectropion decrease in aqueous tear production my bomean gland health corneal epithelial health Neurotrophic keratopathy and immune system In addition to these factors, there are many other factors such as age gender hormonal changes Pharmacology vitamin a deficiency, etc. That Many of these will take their effect through a common pathway to destabilize the tear film causing hyper osmolarity damage to the ocular surface and discomfort We're all aware of many lifestyle Factors that affect dry eye. There's actually a syndrome called computer eye syndrome And it's amazing how many patients will see today that they ask him how many hours a day do you spend on the computer? They'll say eight ten sometimes twelve hours on the computer And it's been shown in several studies that that has an effect in exacerbating the symptoms long commutes in the car Especially if people have the vent directed toward their face Airplane flights and other environmental recreational and occupational Factors and perhaps even diet may play a role as we'll see in a minute. There are many clinical tests for dry eye I don't do the Schurmer test near as much as I used to in the past. It doesn't correlate It's not as reproducible. It doesn't correlate with the symptoms is not as helpful as other tests such as The tear breakup time or corneal epithelial staining so generally In a busy clinic, it's very helpful to put a drop of fluorescein in the eye Technically if a person is doing research, they should quantify the volume and the concentration of fluorescein Maybe 50 microliters of 2% fluorescein, but in practice it is not really that practical to do So a little drop of fluorescein in the eye and one can check epithelial staining although it's best to wait Three or four minutes if you can do that because sometimes epithelial staining will not be present within 10 or 15 seconds But might show up after a minute or two or even four or five minutes We can also check the tear meniscus with the fluorescein stain and then of course check tear breakup time Other tests such as tear osmolarity and impression cytology are primarily reserved for research applications So vital dye staining besides fluorescein we have rose bengal and lysamine green Fluorescene will stain of course corneal epithelial defects and defects in the tight junctions Whereas rose bengal and lysamine green both will stain Devitalized epithelial cells even though there are no defects and also areas where the mucin layer is deficient Rose bengal will sting quite a bit. Lysamine green stings a little bit less than that and Rose bengal and lysamine green are better for staining conjunctiva Here we see lysamine green here on the lower right. Whereas the fluorescein is better for staining the corneal epithelium A study by a Korean group in this month's issue of cornea Reported their results and actually combining lysamine green with topical fluorescein to stain both at the same time Their conclusions were not really that surprising These are not photos from the study, but they saw both corneal epithelial staining as well as conjunctival staining and concluded that Symptoms were better correlated with conjunctival staining for some reason Whereas corneal staining correlated better with the tear breakup time The tear breakup time Consists of simply putting fluorescein in the eye Asking the patient to blink a few times and then having using the cobalt blue filter having them Stare straight ahead without blinking and checking to see how long it takes to see the fluorescein layer Begin to break up this presumably is due to the lipid layer the outer lipid layer becoming disrupted which allows the muco aqueous layer to begin to evaporate now the the Patients generally will blink every few seconds, maybe every five to ten seconds if the tear breakup time is Sooner than the the blink rate then there's a problem with the evaporation leading to symptoms If the breakup time is longer than the Inner blink interval then there shouldn't be as much problem Irradiator light reflex can also be seen at the slit lamp. Here's a photo Post-lasic patient sewing some epithelial changes, which are quite common, especially in the lower cornea after lasik I don't know if this instrument is available yet. Does anybody know if the hyper The the tear lab instrument for measuring osmolarity is available Did they okay I haven't I haven't seen it yet But I believe it cost about $6,000 and the kit is about 40 or $50 for measuring the osmolarity of the tear and this Holds a lot of promise because it could be a very good marker for helping with dry eye studies with with new medications and clinical trials They're coming Coming forward to help us to better evaluate the efficacy of medications Yes Yeah, well basically if the patient symptomatic I think it's perfectly reasonable to treat to treat them anyway You treat them at least with artificial tears and see That certainly wouldn't hurt anything You know if if you if you know really why do the test? I told I totally agree very expensive tests And really what's it going to add? You know is it in the in the final analysis were basically going to treat symptoms and signs anyway And probably not pay a lot of attention to whatever that osmol out so I think primarily this probably will help in as a research tool to To help in research studies because it can be a marker for because it's well It's well accepted generally accepted that hyper osmolarity is correlated with the pathology and in dry disease We all know that dry a disease can affect the visual acuity this hasn't always been well understood the reason most likely is because the the differences in their refractive indices between air and The liquid of the tears is greatest of that Transition interface that it is in any other Transition interface in the ocular system There are also studies showing opaque corneal epithelial cells by confocal microscopy and other pathology That could occur certainly when you look at a Light reflex such as this here below. It's it's easy to see why visual acuity could be affected a Study a couple of years ago in the ocular surface journal by an optometrist I Addressed the correlation or lack of correlation sometimes between signs and symptoms He concluded that generally there's a positive relationship between the amount of the severity of the signs and the severity of the symptoms But the association is always is not always that strong And he found that higher correlations actually exist among questionnaires than among objective tests What causes symptoms in dry eye? Most likely it's due to irritation or stimulation of corneal nerves either due to the cytokines hyperosmolarity pH changes or or trauma And we've all seen patients that come in with symptoms, but we don't see anything wrong on the examination or Have Significant signs on the examination but not really complaining very much the former here on the left symptoms without signs It can be a little perplexing. We wonder if we just have a complaining patient, but it may be a just a hypersensitive eye There was a study by Belmonti that Postulated that in some cases there may be a micro neuroma or something wrong with one or more nerves that could be causing some pain In the absence of any visible symptoms on the ocular surface The a scenario of signs without symptoms is more dangerous In our situation because if you have somebody with neurotrophic keratopathy, they can have significant problems even corneal melts Impending perforations with very little symptoms may not even come to see us. So it's always important to Take a careful look at the ocular surface, especially before surgery Even if a person is not complaining of dry eye symptoms There's several entities that can masquerade is dry disease with similar symptoms such as blepharitis particularly posterior blepharitis and conjunctival Colases which I know that I have not paid much attention to in the past and probably still miss a lot of cases Most of our older patients will have redundant conjunctiva especially in the lateral portion just over the above the lower eyelid and The symptom the main symptom of conjunctiva chelases is a burning or a stinging sensation of fleeting Stinging sensation when they blink so during the blink mechanism if it stings then and after when they're not blinking It doesn't sting that could be conjunctiva chelases is probably due to the redundant kind of type of being Moved across the ocular surface especially with a deficient ocular tear film which will cause friction and Simulation of corneal nerves this can be treated generally pretty well with Artificial tears some people have used procedures such as caudary Conjunctival resections to tighten the conjunctiva with some good results So as we look at the pathophysiology of dry eye what was actually happening on the ocular surface What is the cause hyperosmolarity is the main driving force that leads to activation of various? inflammatory cytokines That in turn will cause goblet cell reduction Loss of mucin on the ocular surface and epithelial damage and apoptosis This will destabilize the tear film which in turn exacerbates the tear hyperosmolarity leaving leading to a vicious cycle these core mechanisms are Driving force this Diagram taken from the Dew's report are a driving force that will stimulate the nerves and initially in the early stages Increase the reflex drive to the lacrimal gland increasing aqueous production However with the passage of time nerve injury can occur in chronic dry eye Which will lead to a reflex block which decreases aqueous production? and That will lead to worsening of the hyperosmolarity now Also as we look at the eyelids with my bomean gland dysfunction Decrease film lipid film layer from my bomean gland dysfunction which leads to increased evaporation especially with environmental changes dry air and low humidity which will lead to high evaporation and increased hyperosmolarity and Other factors we see here on the periphery surgery the aging process Low androgens which accounts for the fact that the predominant The majority of people that have dry eye are women and other factors systemic drugs such as antihistamines Estrogen replacement and postmenopausal women and other factors which will exacerbate this condition So we see a disruption of the mucin layer here with goblet cell loss Decrease in the aqueous layer by reflex block of the lacrimal gland and decrease in the lipid layer from my bomean gland dysfunction Which are the pathophysiologic? elements that drive the dry eye disease pathology My bomean gland dysfunction is not necessarily synonymous with posterior blepharitis, but it consists of hyperviscous secretions in the my bomean glands Leading to an inadequate tear lipid layer and bacterial lipases can act on the discretions the waxes and esters to Convert them to triglycerides and fatty acids which will lead to a Suponification process and little micro bubbles or froth that we can see along the eyelid margin and that is considered to be Pathognomonic when we see that froth at the slit lamp on the eyelid margin Pathognomonic of bacterial growth that perhaps some antibiotic ointment on the eyelid margin and I might be beneficial An article last year in cornea entitled non obvious obstructive my bomean gland dysfunction presented several cases where There was no obvious inflammation. There was no obvious whitish secretions from the my bomean gland orifices and one our initial inspection might say well the eyelids look fine There's no posterior blepharitis the only way to diagnose this non obvious mgd would be to try to express The my bome from the glands and if one tries to do that They could see that the glands at least some of the glands are obstructed and that can lead to the same problems of decreased lipid layer and evaporative dry eye So even though we probably don't generally at least I don't routinely try to express sometimes at the slit lamp We can certainly put some digital pressure on the on the eyelids just to see what happens With the myvim at the orifice to see if there is obstruction The treatment for my bomean gland dysfunction is well known starting with warm compresses The warm compresses probably should be kept on the eye for at least four or five minutes to really be effective It's not the one or two minutes. It's not sufficient If you really talk to your patients about this compliance is probably very low most people I mean, I don't know how many of you have tried to do warm compresses It's not the easiest thing or funnest thing to do you're tired want to go to bed and putting warm compress on your eye People probably don't do this as much as we would hope they would but following the warm compress I live massage and expression of the the secretions Lid margin hygiene is needed antibiotic application We've talked about now oral doxycycline can probably be used in doses lower than what we've been accustomed to in the past For example, 100 milligrams BID a maximal dose is is often not needed In fact even 20 to 50 milligrams of doxycycline a day or BID Can be a very good maintenance dose for many patients We'll talk in just a minute about the possible benefit of dietary omega-3 supplements Topical asus site and also my bomean gland probing We can teach our patients how to digitally massage the my bomean gland that the eyelids after hot compresses To help express some of the secretions and then clean them off with an ice scrub pad or with the washcloth itself in the office we can express the my bomean glands secretions such as this and This is a picture showing them a strata paddle, which is just an instrument that can be used to do the same thing And then tear science has produced this instrument. I'm not sure if this is available yet, but it's called lipoflow Where if you look here at this diagram I'm not sure I'd want to have one of these put in my eye, but Good luck trying to talk your patients into the volunteering for this But the internal aspect that goes again There's a corneal protector and then an internal warmer that heats up the adjacent to the my bomean glands heats up the the glands And then a an eye cup on the outside that puts external pressure on the Eyelids expressing both the upper and lower eyelid at the same time Now the question comes comes up. Does it really do any good to try to express my bomean glands this? article from last month's issue of cornea by RC and aga They did baseline studies of tear evaporation rates, and then they looked at evaporation rates both in a relatively dry and a relatively relatively humid environment and Looked at it at about six minutes 12 minutes and 24 minutes, and they found that the tear evaporation rates did decrease at the six and twelve twelve minute marks, but 24 minutes there is really no Change at all in the evaporation rate. So from this study anyway, there's not we wouldn't expect a lasting effect By expressing my bomean glands in the office One of the reasons for that is that if you have a completely occluded gland which many of our older patients do Expressing is not going to do a bit of good for that. So that leads us to Steve Maskin's Procedure that he presented at Arvo two and a half years ago my bomean duct probing which seemed rather barbaric at the time Who would want to have little needles or probes stuck into their eyelids 20 times? But his results were really very good have been reproduced by others at least anecdotally The rationale behind probing the ducts is that they can be obstructed there can be obstruction of the orifices by surface Metaplasia there can be fibrotic destruction and my bome plugs within the glands themselves And these probes are currently available through Ryan medical Maskin published his studies a year ago in cornea 25 patients were treated Just about all of them reported immediate improvement in the symptoms and all of them had symptomatic relief at four weeks and This seemed to the symptomatic relief seemed to last with 80% of them within Within a year for a year. So this Actually going in and probing the gland can be much more longer longer lasting than the expression No, no, yeah, and that probably would be a little difficult to I see a sham probing just being Going through the procedure. We're not actually probing. Yeah. He did. I don't think he did that That's a good. I I've been doing this in a few cases over the last year and I've noticed that We do one eye first and every patient except for one that I've done Immediately notices an improvement, but a lot of that could be placebo effect also So it's really hard to tell hard to I think might be a little hard to do do a control But I don't he didn't do that in this particular study This is a video in bypassing the two millimeter probe through the orifice You may need a fine router movement to find the opening especially in setting of orifice metaplasia if Epithelium has grown across the orifice the probe may still be able to pierce through if not in top Galactica may be used to de-epithelize the orifice if the orifice is scarred You may be able to penetrate by cutting the tip with a barred Parker blade Cut it on an angle to achieve a more pointed tip Be sure to visualize the gland before attempting to penetrate an orifice to avoid the completely atrophic non-existent gland So the first patient I did with this last year He had probably 75% of his glands. I couldn't even enter they were there It is a very advanced case and either because of surface metaplasia or fibrosis within the gland and maybe my Inexperience, I just couldn't get in most of the glands and he didn't notice any improvement But subsequent patients have I've only done three or four, but they've all noticed some symptomatic improvement and every single one of them is noticed improvement On the treated eye versus the control was the eye that wasn't treated, but of course that could be placebo The these probes come in two four and six millimeter lengths and generally the two millimeter is sufficient to Relieve the symptoms and what's what's happened before? Anecdotally in going to meetings and talking to people across the country. There's several Ophthalmologists that are doing this at the present time. I'm not aware of any other published study yet Maybe somebody else is but time will tell whether this is really beneficial or not Theoretically it does make sense if obstruction is a problem and expression is not really relieving the my bomeans The my bome obstruction then perhaps probing probing will be helpful Here's another video from Steve mask and showing a different approach Penetrating the orifice of the two millimeter use the four or six millimeter depending upon the length of the gland to achieve complete Patency of the ductal highway you may encounter resistance Respecting the length of the gland will prevent extending the probe too far Therefore if you obtain resistance, you may be up against a fibrotic band Check to ensure that you are colinear to the gland and then provide additional force to pop through the introductory scar It will give way similar to popping through a thin lacquer more punctile scar from thermal quarry At times you will notice a drop of heme at the orifice this may occur as you pass through a fibrotic neovascular scar or simply a Neovascular membrane Here's an example of a plug of my bum Freed up from behind a neovascular membrane Notice the my bum being released and here into the probe and a drop of heme at the orifice At times a trace amount of perilangular subconcentival heme may be noticed from opening a membrane Maskin describes a popping Popping sensation which which he could feel when he introduces these probes which I've noticed also in fact My technician that helps me do these at Rocky AJ even he can feel the popping sensation when I'm going through there He's holding the eyelid for me with his finger and I can actually feel the resistance as we're going through with the with the probes so Just an idea that may be beneficial for the future but remains to be Seen whether it is whether it's going to be helpful. I Yes There there isn't yeah, there is a code for a not it's a non-reimbursed code that's used I think it's a v code and Apparently at the Medicare carriers if they get enough of these v codes will eventually decide to so what we currently do I charge I think 250 or 275 per eye being both upper and lower eyelid It takes about a half hour to 40 minutes to do both eyelids and and just have the patient If they want to they need to pay for it cash pay up front As far as anesthetic mask and does this with topical lidocaine gel generally I found that about half my patients Will tolerate that although there is some pain involved and the other half require a block of the eyelid with some Xylokane to tolerate the procedure This is a study reported by Flugfelder's group at Arvo a couple of years ago Let's say a laboratory study with cultured corneal epithelial cells showing Apparently showing that topical Azithromycin or incubation with azithromycin Maybe beneficial in decreasing inflammation on the ocular surface they found that When these epithelial cells were incubated with My probe my microbial components inflammatory mediators were released However, when they added a zithromycin that blocked the release of inflammatory mediators Here are two clinical studies one by Gary folks and the other by Jody Luke's studying patients in The past few years with topical Azocyte drops and as you know many people are using these as an off-label treatment of posterior blepharitis In folks study He measured both the transition temperature of my bum, which is essentially the melting point and notice that that Decrease making it easier for the my them to melt and flow out when Azocyte was used for one month He also noticed a difference in the lipid pattern approaching that of of my women an increase in the tear film breakup time which seems to Imply that Azocyte might help with the my bone flow and might help with evaporative dry eye Jody Luke's found essentially the same thing mostly focusing though on symptomatology Treating one group with a zithromycin and warm compresses and the other just with warm compresses alone symptoms were better when the Azocyte was used another approach the common approach with dry eyes of courses with to use artificial tears and it makes sense to Target our use with artificial tears depending on the particular need for example if someone Seems to have a deficient lipid layer with a short breakup time We might want to use a lipid containing products such as refresh and Dura or products such as sustained balance which is formulated for Unstable tear film If we're looking to replenish the aqueous layer products such as their tissue refresh might be good for glaucoma patients and other patients that have significant inflammation on the surface of their eye Reducing the preservative load by using preservative free or disappearing preservatives such as found in theratheers and gentile or Refresh would be good if we want to try to reduce osmolarity Theratheers aqua tears and hypoteers will do that We should keep in mind though that hypoteers has benzalconium as a preservative one of the few tears that do so It's probably not a good idea to use too much of that because benzalconium is not good for the ocular surface There's several different techniques also that have been Explained in the literature one is saturation dosing where an individual if they're using Preservative free artificial tears that may have about six or eight drops in it Put a drop in each eye and instead of throwing it away wait a couple minutes and do it again And wait maybe five minutes and do it again till the vial is gone Putting several drops in each eye over a five or ten minute period and that should help to may help to decrease the frequency That the person needs to put the tears in during the day Combo dosing is something I've used with several of my patients and some of them will notice the benefit If you have somebody that's used finding they need to use artificial tears every hour ask them instead to use cysteine gel or theratheers liquid gel Initially and then about 30 seconds later chasing it with the regular artificial tear like cysteine ultra or theratheers Regular theratheers and that will help to clear the vision that's caused by the the gel and Many patients can go from every hour to maybe every three or four hours instead and save some time Then preventative maintenance rather than waiting until eight o'clock at night when you've been on the computer for several hours And your eyes are stinging using the idrots before they begin to cause symptoms Many years ago the thought of using steroids for dry eye was considered not a good idea But now the days it is accepted if it's used judicially a lot of max is a good drop But rather costly and even fml is really quite expensive. There was a study recently. I forget where I think it was last year Looking at very dilute a topical dexamethasone instead of 0.1% using 0.01% Dexamethasone and that seemed to relieve symptoms if used even twice a day What about restasis Topical cyclosporine of course is gained a lot of popularity. It's the only medication. It's been approved by the FDA for use in dry eye It's an immunomodulator that acts by Suppressing the expression of inflammatory markers and also reducing the number of activated telemphasis this action is primarily in the lacrimal gland and the Oculosurface so even though it's applied to the oculosurface one of its main actions is remotely at the lacrimal gland because of the telemphaside action, so it increases aqueous production and increases goblet cell population and In Perry's study a few years ago Recommended that perhaps we should consider using it a more mild to moderate cases as opposed to the severe cases because it seemed to be More efficacious The problem is that most treatments are probably going to be more efficacious have used in the milder cases and one of the concerns I have with Restasis is that it costs a lot. I mean this is the Walmart cost in Salt Lake City just a few days ago $135 and Somebody has to pay for that it is a good medication But somebody has to pay for it and and the cost actually will go up to even 180 $190 per One month supply, but restasis I can be very great beneficial especially if we're dealing with a An inflammatory component to dry such as Shogun syndrome But not all experts in the field agree that it doesn't a good in fact most patients that I ask who are on restasis the majority I ask them do you think it's helping you and most of them really can't tell me and that doesn't mean it's not helping it just means that the Pathology is so complicated. There's so many factors. We really can't control for all of them In fact when the study was done to approve restasis. It didn't The FDA study restasis did not meet the primary efficacy guidelines for approval They'd only met one secondary efficacy guideline, which is increasing the Schumer test and also Improving symptoms in a subset of the patient. So just barely squeak by But it's the only medication that has been approved today In the past I didn't pay a lot of attention to Humidity but once I moved to Salt Lake. I got a little humidity gauge I was wondering why my eyes were bothering me so much And so I measured the humidity and found that it was really only about 20% inside So I got humidifiers from my house and found That I needed to put one on the furnace as well as in the room in order to get the humidity up to a Reasonable level of 45% This is a chart showing the water holding capacity of air and this is something we don't learn in medical school But it's something we probably all ought to be aware of If you look at air at zero degrees Fahrenheit cold outside air in the winter here in Salt Lake It holds very little water If you bring that into your furnace and heat it up to room temperature It will hold 16 times as much water Now what that means is you can take this cold outside air even if it's 100% humidity Relative of course to the temperature Bring it into this into the house heat it up if you don't add water to the air You're going to end up with less than 10% humidity now in practice if you get a Hygrometer and measure the humidity here It'll generally be in the wintertime about 20 to 25 percent indoors in a commercial environment in the summer time It's more like 35 percent, but that's one of the reasons why our patients will complain of dry eye because the air is just very dry Which will increase evaporation the other factor is that we live in a relatively high elevation here and of course with higher elevation the vapor pressure is Is increased relative to the atmospheric pressure which will increase evaporation also So here's some photos just showing the room humidifiers and furnace humidifiers and Hygrometers which are inexpensive and I have a lot of my patients Buy one of these because otherwise it's really hard to tell whether the humidifier is doing any good now taking a turn to talk about dietary supplementation with Omega fatty acids the rationale behind taking Omega-3 or omega-6 fatty acids are the following There has been a study showing that it may change my bomean gland oils and the tissue levels are Inversely related to the severity of dry eye disease, but most importantly the long chain Omega-3s are Anti-inflammatory and they tend to block the gene transcription of pro-inflammatory cytokines Which related to the pathogenesis of chogren syndrome? So if we look at the metabolic cascade with omega-3s and omega-6s Flaxseed oil is about 50% alpha linolytic acid which is not Which is not anti-inflammatory okay, our bodies do not Metabolize alpha linolytic acid to icosapentanoic and docosahexanoic acid very well Only about 5% of that goes to icosapentanoic and less than 1% to DHA in our bodies So taking flaxseed oil is not going to do a whole lot for anti-inflammation compared to fish oil Fish oil is much higher in EPA and DHA the Omega-6s Will produce both anti-inflammatory DGLA as well as pro-inflammatory Arachidonic acid and so they're not as good as the Omega-3s The potential clinical benefit of essential fatty acids are to number one try to restore the lipid layer of the tear film and block the inflammatory cytokines now here is a Here's a summary of Recent studies that were that were done some are clinical studies some one is an epidemiologic study and others are animal studies that look at either systemic or topical Omega-6s and Omega-3s one of the problems with these studies is that most of them used either Just Omega-6s or a combination of Omega-6s and Omega-3s But in spite of which are not as anti-inflammatory as Omega-3s Nevertheless, they still most of them found some symptomatic relief We talked about this before that the fish oil is actually preferred over plant sources because there's more anti-inflammatory Effect in EPA and DHA than there is on the Omega-6 side Now, I think this will hold true for use of these products with macular degeneration as well as cardiovascular disease If you tell your patient just to go to the store and buy some fish oil, what are they going to buy? they probably should have some guidance because Generally, if they go to most stores a 1,000 milligram capsule of fish oil will have about 300 milligrams of totally EPA DHA But some products have much less than that even close to 100 milligrams and others will have Almost 700 milligrams of course, Levesa, which is the prescription medication will have has the most but it's also very expensive Thorne research is a company up in Idaho, which sells a high quality fish oil only online It's more expensive than the Costco variety What I recommend for most of my patients is to go to Costco and get the 1200 milligram and tarot coated Which has almost 700 milligrams of EPA DHA and the cost of that is even less than Walmart It's very very low cost. It's the cheapest available and is readily available for our patients So that is a good buy for And they make their fish oil out of Small fish so the PCB and mercury contamination is probably pretty low Now a couple of clinical studies. This is one that was published a few months ago in cornea Oral omega-3 supplementation using fish oil They gave a total of just one fish oil capsule per day, but it contained 750 milligrams of DHA and EPA and they found That there was no difference in the mybom composition or the tear evaporation rate So the effect of this oral fish oil didn't seem to be affecting the mybomian gland Mybom composition or the tear lipid layer the best they could tell what it did affect was the tear production and Another study published just this month in in cornea using plant Omega-3s Also found no difference in mybom composition So Wrapping this up additional therapies include punctal plugs one thing about punctal plugs if we use them We probably should not place them in the presence of ocular inflammation because of the ocular surface and the lid margins are inflamed We're also making the eye retain these inflammatory Mediators and debris from the inflammation along with the tears. So it's best to treat the inflammation first and then place the plugs I actually take more plugs out nowadays than I put in for that reason patients coming in with symptoms And sometimes they do better without the plugs lack research have been Reintroduced but are rather expensive and not not always tolerated secretogogs such as oral Sevemaline can be used Just as a cholinergic agonist, but that also stimulates the GI system and and sweat glands Autologous serum moisture chamber spectacles and others The moisture chamber spectacles I found to be really good These are advertised seven eyes and why the X are advertised in the motorcycle Magazines for people are outdoor enthusiasts and riding ATVs etc. Quite helpful for those sports and some of our patients these can be purchased with Clear or even prescription lenses for use of our dry eye patients I find these to be quite helpful especially with lagothalamus and patients with eyelid abnormalities and neurotrophic care top of thing These will cost one or two hundred dollars You can also go down to Walmart and get something almost as good with shooting glasses They cost about four ninety seven about five bucks and protect the eyes really quite well from draft and may even increase the humidity So in summary, I've presented a practical clinical approach in approaching dry disease taking a good history Considering lifestyle activities focus the examination using fluorescein to examine the breakup time effectively educating the patient Keeping an eye on compliance because they often don't really comply with what we asked them to do These are some environmental and lifestyle factors that can have an effect Smoking sleeping with pets overhead fans swimming and cycling long hours on the computer I use a handout that I developed for my patients that I After I explained to them once or twice what I like them to do Check off on the handout and give them in printed form so they can take home and digest it And I think this will help compliance. It also gives them information where they can buy Hygrometers and get humidifiers On the horizon they're coming up with some next-generation lubricants To reconstitute the mucin and lipid layer new medications in office measurement of tear cytokines in the current dry eye research is focused on mucin secretogogs Mucomimetics and immunomodulators similar to cyclosporin and others that can help with the inflammatory problem One of the main problems with these studies is that it's very difficult to pass FDA scrutiny and It's impossible ready to control all the different variables one of the challenges with the FDA approval is that It's impossible to control the variables the efficacy endpoints are Relatively strict and because of all the variables for example, how are you going to control? What a person eats so the relative humidity in their home or how much time they spend on the computer or drive in their car Or other lifestyle factors and even the seasonal variations here in Salt Lake City the relative humidity Changing from season to season as the study progresses You really can't control for all those things so these that those who are designing the studies are looking for different endpoints and different environmental conditions that can test the Efficacy of the medications in a more rapid way So in summary, we've looked at the pathogenesis with the core mechanisms the effect on the lacrimal gland and and the eyelid and learned that Inflammation is a key element in dry disease hyperosmolarity and instability of the tear film or principal forces Aqueous deficiency is often immune mediated Understanding the history and lifestyle can be very helpful a patient can have minimal symptoms and significant signs Which means that we need to always examine the patient even if they're not complaining and Punctal plugs if they use should be used after controlling inflammation Corticosteroids are allowed and if used wisely can be tolerated and helpful to improve inflammation over a few days or weeks Topical cyclosporinate can be very beneficial Lephoritis needs to be controlled Lower doses of doxycycline are often effective Dietary supplements may or may not play a role in the future the initial studies are not conclusive, but it need to be substantiated, but It appears that possibly oral ingestion of omega-3s may be beneficial particularly fish oil high in EPA and DHA We can decrease economic burden by focusing on the causes of Dry disease and not being too quick to write a prescription The ocular surface should be examined and managed pre-op particularly with refractive surgery and cataract surgery and Obtaining FDA approval for new medications is incredibly difficult Which is one of the reasons why we've had only one approved medication in the last several years any comments or questions Yeah, so the question is how do I select patients to probe? As with any other treatment it probably would be more effective if we didn't wait till the end stage But generally what I'll do is I'll take the patients that I've Treated with pretty much everything else that they will tolerate for example We have them on artificial tears preservative free Beyond doxycycline warm compresses massage lead lead hygiene and maybe even a trite asa site And it just didn't seem to help and they're still having a lot of symptoms Then if I look at the my bomean glands and try to express them and notice that there's some obstruction Those are the patients that all tend to do so it's kind of a last resort with me right now simply because they have to pay More money for it and it takes some time and it's not not my favorite procedure to do but it has helped the patients I've been really quite impressed I had one patient that I I checked his tear break at time before the procedure. It was it was four seconds And then I hadn't come back a week later was 10 seconds and he was saying wow I really feel a whole lot better and I had that that that sign is significant just one patient, but It seems to be beneficial Jeff. I haven't know That would be That would be nice to have those particularly for the patients that are not able to blink and having significant cornea problems Short of doing a tarsorophy on them. Bala. Thank you. Is that DHE is that topical or systemic topical? Thank you