Am I missing possible treatments?

[ringo]

Apparently, there are a lot of vets who are using a 2% cyclosporin solution in corn oil, just like what my human doctor has prescribed me. I checked with my vet, and he said they have a preparation which works faster and stronger than the ointment. Also they have the tacrolimus eyedrops, also compounded. That is not yet recommended for humans, but is stronger than cyclosporine and helps tremendously dogs that are not responding to cyclosporine. I hope that helps!

Regards,

[~Lin]

bump, no one explained how warm compresses help? What is it that they do to improve dry eye?

[odydnas]

Many times dry eye symptoms can be caused by a clogging of the meibomian glands. Meibomian glands release oil with every blink to stabilize the tear film. This oil can get thickened, cloggin the meibomian glands, so without the release of this oil, the tear film is no longer stable, causing dry eye symptoms. Clogging of the MGs are common with age, but docs don't really know why some people have severe symptoms and some people have none at all. Warm compresses followed by an eyelid massage (I don't know how that works on dogs) are supposed to melt down the thickened meibum, to allow the oil to flow freely. Many people do warm compresses 2-4 times a day.

Very simply, there are 3 layers to the tear film: a watery layer, an oil layer, and a mucus layer. When one of them gets disrupted, the whole tear film and its delicate balance is messed up. Warm compresses hope to restore some of the oily layer to the tear film.

I don't know if the vet knows how to check the eyelids for clogged glands or perform a Tear Break Up Time (TBUT) test, which shows how fast tears evaporate. For humans, a normal TBUT is 10+, altho many doctors don't put too much emphasis on one TBUT reading because it fluctuates from hour to hour.

If you do decide to do a warm compress, make sure it is warm and not hot. You do not want to accidentally burn the eyelids, or worse, burn her eyes.

I hope that helps!

[~Lin]

Would a warm wet washcloth be good enough for a warm compress? I was thinking having 2 washcloths and a container of hot water, and swap them since it would probably cool down fast. 10 minutes twice a day is recommended?

[ringo]

I would not recommend hot compress for everybody with dry eye. For one thing, when there is inflammation hot compress may dilute the oil in the meiboian glands but at the expense of aggravating the existing inflammation,so the relief from the hot compress is very short lived. It needs to be done every day, sometimes twie, and it provides little temporary relief, with more subsequent inflammation.

It is a well known fact that one does NOT put heat on inflamed sites in the body.

I would much prefer, if any compress, to be icy cold. That brings the inflammation down.

[RobLIC]

Ringo's comments, above, summarize one of the greatest debates in this community - and among dozens of doctors in the U.S.

The simple truth is that warm compresses do melt meibum AND can aggravate preexisting inflammation. It's a question of which is the lesser of two evils, and the AAO has been saying for years that moist heat, followed by massage and expression, is the way to go here.

I've come to think of it this way: For whatever reason, our MGs have swollen up and are producing thick lipids. In response, blood vessels have to do more "heavy lifting" to get around and themselves become dilated, which we recognize as inflammation. Reduce the junk causing that inflammation (i.e. by melting it) and the blood vessels may become less dilated on their own. That's the argument in favor of moist heat.

The good news is, no reason you can't be doing both. You just have to find what works for you ... or Fido.

[odydnas]

I agree, it is a very controversial topic. Especially for those suffering from ocular rosacea - lots of inflammation (no heat!) along with MGD (needs heat!). So what are we to do? I remember Dr. Latkany had advised that in those situations, where the inflammation is out of control, any additional heat would be bad and one should stick to cold compresses (but not too cold). However, if the inflammation is overly terrible, there is no reason that one couldn't do both warm and cool compresses. The warm compresses first, followed by cool compresses to reduce the inflammation.

Personally, warm compresses alone with a washcloth or rice baggy is too irritating for me, but moderate wet heat from a warm shower followed by a cool compress gives me much temporary relief.

[ringo]

Dear RobLic,

Just a small note on what you said-- heat dilates the blood vessels in the eyelids, and that makes them less functional. Especially if this is combined with rubbing abd massaging the eyelid, it can get real terrible.

This heat treatments were a very popular doctor's recommendation for a long time in te past; but now almost all doctors recognize heat is NOT good for your eye, especially when it is inflamed. Because blocked meiboian glands cause dry eye and dry eye inflammation, putting heat on them will not resolve the problem-- it has already been compunded by the consequences of this blockage.

Making the dry eye inflammation worse by exposing the eye to heat (especiall in rosacea cases which are the main cause for dysfunctional meiboian glands) will make the glands less and less functional, and the blood vessels surroundig them as well.

I used to put cold compresses which really decreased the swelling and buring and pain (for about half an hour), but then Igave it up. It is like pushing a big rock up a steep hill. It will never reach the top this way.

It is widely concluded from contemporary research that dry eye plus dysfunctional meiboian glands are the result of immune disorder affecting the eye surface and adnexa. It is a kind of autoimmune inflammation going on, which makes both the tear glands and the other glands in the eye less functional due to interference of the inflammatory molecules and cells with the nerve signalling process.

I assure you that putting heat on that regularly is going to progressively deteriorate the condition, albeit any sort of temporary relief. My doctor has advised me never to go to saunas, hot baths, put any hot water near my eyes and even face, or go to tanning beds-- basically anything that heat my eyes.

Unfortunately I live in a hot climate, and that hurts but I can't help it. Living in a cold climate has the downside of living with central heating and stuff, which may be even worsethan the natural heat.

To sum it up-- I believe hot compresses to inflamed eyes are a treatment that belongs to the past, which reflects very well the lack of understanding doctors had (and many still ave) about what they call corneal surface and adnexa disease.

Actually I myself got much worse because of doctors prescribing me oral antihistamines and topical antibiotics for 6 months and whitening eyedrops in the beginning of my dry eye . I wish I had never listened to them, but I did not know any better. I tred to put hot compresses but it really inflamed the edges of my eyelids, so I to stop it.

I would wish people would stop putting heat no their eyes-- but some truly believe it is helping them. I think IPL treatment heat works differently and do believe it is preferable to putting heat compresses directly on the eyelids.

Anyhow-- everyone has the choice to make, and I have chosen to fight inflammation instead of aggravating it. I know I sound like I am trying to convince those using the hot compresses to stop. I apologize I do not mean to confuse anyone, it is up to them and their doctors what treatment optios they will choose, but to me the reasons for sopiing doing something like that are overwhelming andy benefits it might have.

[RobLIC]

Hi, Ringo.

That's not a small note

I get skeptical when I read statements on this board such as "now almost all doctors recognize heat is not good for your eye." That's patently untrue, at least in New York City, Boston, and the places around the U.S. where I've consulted with an assortment of doctors. Things still seem to run about 4-to-1 in favor of recommending heat. Dr. Latkany is a respected exception here. He advocates for cold.

When meibum impacts a gland and is not somehow forced out, the pain, as I can tell you know first hand, can be excruciating. I firmly believe we're still talking about heat as the lesser of two evils, because that stuff has just GOT to get out of there.

Important to note, as well, that many of us have ended up at this destination via wildly different roads: rosacea, refractive surgery, Sjogren's etc etc. Personally, I'm a refractive surgery problem child. I think that if I was a rosacea patient, I'd be a lot less comfortable with the idea of heat before an expression, for exactly the reasons you suggest.

You've stated, "It is widely concluded from contemporary research that dry eye plus dysfunctional meibomian glands are the result of immune disorder affecting the eye surface and adnexa." Again, I have to think of that in a more tempered fashion, because while it may be true in some cases, and the cases of many others, the data just doesn't exist to make that a universal truth.

I just think we, again, need to recognize that not everyone's the same and different things work for different people.

I am a little surprised and sorry to hear that a doctor actually prescribed you an antihistamine at one point. As much as I love me some Nyquil and anti-depressants and all the good sleeping pills, they're all trashed - as should be any medicines that are remotely associated with "drying" qualities.

Thanks ... Rob K.

[~Lin]

How do you determine if the meiboian glands are involved/impacted?

[ringo]

Hi, Ringo.



You've stated, "It is widely concluded from contemporary research that dry eye plus dysfunctional meibomian glands are the result of immune disorder affecting the eye surface and adnexa." Again, I have to think of that in a more tempered fashion, because while it may be true in some cases, and the cases of many others, the data just doesn't exist to make that a universal truth.

Thanks ... Rob K.

Dear Lic,

Thank you for your response. And by the way only a small portion of it was a note to you

I would like to metion that regardless of the reason for dry eye-- whether it is idiopathic, or the rsult of rosacea or other autoimmune inflammatory disorders, or Computer Vision Syndrome,or brought on by surgery that actually damaged the nerves on the cornea-- once there is inadequate lubrication of the eye surface for a significant period of time, an inflammatory process starts-- the so-called dry eye inflammatory cascade-- which is self perpetuating (very very sadly).

That is why it is called autoimmune-- because the dryness triggers this inflammatory cascade, and inflammation in turn disrupts the nerve signalling to the tear glands, which causes more dryness, and in turn more inflammation, etc. This is already a medical fact, well researched and documented.

As to the pain from the meiboian glands, I know how it feels. Nothing helped me more with that than doxycycline, cyclosporine, steroids, NAC-- in general all types of medications directed at suppressing the unnecessary immune activity going on in the eyes. Somke f the medications like doxycyline disarm only certain substances-- like metaloproteinase involved in the inflammatory cascade. Cyclosporine also only targets certain type of lymphocytes, the so called effector lymphocytes, whose response in dry eye is shown to be erratic and self-perpetuating. For one thing, the immune cells triggering the dry eye inflammation just don't die like they are supposed to with normal inflammation. In normal inflammation after the source of the inflammation is attacked, the immune cells involved disappear. In dry eye the process is a vicious slf-perpetuating cycle, which needs medication to be disrupted.

And even with the available medications,even with the aggressive ones, it takes months of persistent treatment to achieve a significant disruption of the inflammation cycle. If anti-inflammatory treatment is stopped, the situation deteriorates quickly back to square zero, back where one started fighting it. So really, as of now, there is no medication that can permanently resolve this catch 22 situation with dry eye.

Most researchers believe that restoring the nerve signalling system in dry eye is the permanent answer via instilling the right hormones to de- and re-regulate it.The antiinflammatory therapy is not the answer, but it is the best solution we have currently.

Looking forward to any comments you might have. We are all looking for solutions.

Thanks,
Dani

[Rebecca Petris]

Hi Dani,

I love your thoughtful and detailed contributions.

But I strongly disagree with some of what you're saying about heat.

In my opinion (and... to readers... anything anyone posts here is opinion - so we all need to remember to say so now and then) the true picture of dry eye, lids, inflammation and heat is very complex and not conducive to sweeping generalizations. There is a wide spectrum of inflammatory dry eye and lid margin disease and a wide spectrum of responses to treatment - and thus a similarly wide range of medical opinions and studies on the topic.

When you say things like "almost all doctors recognize heat is NOT good for your eye", um, where are you getting this? I would say the opposite.

I also have to say we have to be very careful in drawing the line between sharing opinions and giving advice. "I assure you that putting heat on that regularly is going to progressively deteriorate the condition", is way over the line. How do you know? Have you examined their eyes? I sell warm and cold compresses, and I find myself whenever I'm on the phone with a customer pressing to find out their diagnosis and whether their doctor has recommended it before I place the order, because I could not presume to suppose I know what's good for them. I am sure I don't do as good a job as I should of avoiding giving advice inappropriately, but I really try, because any of us no matter how well informed could inadvertently mislead others simply by speaking too authoritatively on something we have a strong opinion about.

Just saying we have to keep in mind we are all so individual - as are our doctors. There are a ton of doctors across the country and world using heat for MGD very successfully, and there is solid medical evidence backing it up - not just patients who "think" it's helping them as you suggest. (Incidentally, I'm one of the successes, and I'm thankful the doctor that recommended it to me is clinically savvy about heat.) I think many, perhaps most recognize that heat can aggravate inflammation; some, hopefully more and more, recognize when it might be inappropriate and know what the alternatives are.

[Rebecca Petris]

p.s.

I'm struggling a bit to understand you on the inflammatory and autoimmune thing - still trying to digest your posts. Are you saying that all inflammatory dry eye conditions (mg-related or no) are essentially autoimmune?

[ringo]

reply to Rebecca with many thanks

Dear Rebecca,

I am taking this information from various textbooks on ophthalmology which I have been reading ina library, including their electronic database. Tha is why it s hard for me to keep a bibliography of what I ahve read.

But basically, to summarize, medical science defines dry eye, Keratoconjuctivitis sicca (KCS) as a chronic inflammatory disease notably characterized by the deficient production of the aqueous portion of the tear film (quantitative disorder) or the inadequate production of the lipid layer which leads to evaporative (qualitative disorder) or combination of the two.the disease causes damage to the corneal and conjuctval surface and varies in severity.

The corneal-conjuctival inflammation is mainly characterized by T-cell infiltration in the lacrimal glands (meiboian glands as well),and responds to immunosuppressive therapy with different agents, the only one of which approved for ophthalmic use in humans being cyclosporine A and various steroid preparations.

The pathogenesis of idiopathic KCS in humans has been established as follows--

epithelial cells of the conjuctiva regularly secrete antigens or cellular proteins. In normal states, these antigens are recognized by antigen-presenting cells and then presented to effector lymphocytes on the ocular surface. In parallel, regulatory lymphocytes which are also present block the action of effector lymphocytes, thus preventing the development of an inflammatory state and maintaining local immunohomeostasis.

This pathway is regulated by androgens which are responsible for the regulation of the production of transforming growth factor beta (TGF-beta), whose function is to reduce local prolactin concentration.Conditions such as senility and other idiopathic factors may reduce the production of androgen hormones, leading to changes in conjuctival homeostasis due to reduced production of TGF_beta and increased prolactin concentration in conjuctival epithelial cells. This alters local antigen detection, favoring the effector lymphocyte pathway and thus triggering local inflammation.

after the effector lymphocytes are activated they start an inflammatory cascade which involves many molecules and other cells and substances, like cytokines, TNF-alpha, etc. Various proinflammatory cytokines that may cause cellular destruction, including interleukin 1 (IL-1), interleukin 6 (IL-6), interleukin 8 (IL-8), TGF-beta, TNF-alpha, and RANTES, are altered in patients with KCS. IL-1 beta and TNF-alpha, which are present in the tears of patients with KCS, cause the release of opioids that bind to opioid receptors on neural membranes and inhibit neurotransmitter release through NF-K b production. IL-2 also binds to the delta opioid receptor and inhibits cAMP production and neuronal function. This loss of neuronal function diminishes normal neuronal tone, leading to sensory isolation of the lacrimal gland and eventual atrophy.

Proinflammatory neurotransmitters, such as substance P and calcitonin gene related peptide (CGRP), are released, which recruit and activate local lymphocytes. Substance P also acts via the NF-AT and NF-K b signaling pathway leading to ICAM-1 and VCAM-1 expression, adhesions molecules that promote lymphocyte homing and chemotaxis to sites of inflammation. Cyclosporin A is an NK-1 and NK-2 receptor inhibitor that can downregulate these signaling molecules and is a prominent addition to the therapeutic armamentarium for dry eye, being used to treat both aqueous tear deficiency and meibomian gland dysfunction. It has been shown to improve the goblet cell counts and to reduce the numbers of inflammatory cells and cytokines in the conjunctiva.

These cytokines, in addition to inhibiting neural function, may also convert androgens into estrogens, resulting in meibomian gland dysfunction, as discussed above. An increased rate of apoptosis is also seen in conjunctival and lacrimal acinar cells, perhaps due to the cytokine cascade. Elevated levels of tissue-degrading enzymes called matrix metalloproteinases (MMPs) are also present in the epithelial cells. The latter can be deactivated with doxycyline or other tetracyclines that chelate substnces needed for the production of the enzymes.

There may be many reasons for the onset of dryness in the eye. But whatever the reason (for example surgery like LASIK disrupts the nerve signalling so in that case the inflammation starts after the neural isolation of the lacrimal gland), the inflammatory cascade that is involved is autoimmune and self-perpetuating in essence. Some new treatments may be developed involving stimulating the Nerve Growth Factor on the ocular surface to compensate the initial surgery damage or subsequent inflammatory damage of the corneal nerves.

For now,treatment goes as follows: after doctors establish that eyelid hygiene, artificial tears,and removal of exacerbating factors is not enough to maintain the patient, they go on to add anti-inflammatory therapy which starts with topical steroids and NSAIDS and immunosuppressants like cyclosporine(which is also a potent lacrimostimulant) and tetracyclines, moisture chambers and secretagogues like pilocarpine(which is a substitute for the neurotransmitter acetylcholine which stimulates the lacrimal glands to excrete tears; that also keeps them functional), punctal occlusion. In more severe cases that do not imrove on the latter therapy, the immunosuppressants are taken by mouth or intravenously.

Antiinflammatory therapy with lacrimostimulation is essential in the halting of the progression of the disease especially when it comes to corneal surface damage which is not only measured by staining and erosions; it is the loss of goblet cells and neural desensitization and isolation of the lacrimal glands.

However, as we all know,antiinflammatory therapy cannot remain the mainstay of dry eye treatment in the future, as it only controls the progress of the disease without curing it. The answer will most probably be a combination of hormone and nerve growth factor therapies with stem cell therapy. But that seems to be feasible in hte far future indeed. For now what doctors can do is firefight the consequences of an activated inflammatory cascade.

Doctors started me on antiinflammatories after my eyes were totally devastated-- I had developed filamentary keratitis (mucous strings and plaques set deep in the surface of th cornea that severely damage the corneal surface), prominent corneal oedema, severe erosions and ulcers, episcleritis, severe inflammation, etc. That is when they decided that I need something more than artificial tears an lid hygiene. It was too late. Now I have to live with the irreversible complications of this disease. If antiinflammatry therapy was started earlier, I would have been much better.

Oh, I forgot to mention for everyone-- never take sulfonamide antibiotics-- they are a direct cause of dry eye-- T cells respond to haptens generated by oxidative metabolites derived from these substances. So there you have another cause of dry eye. But whatever the cause is, it always involves an element of self-perpetuating inflammation and subsequent neural isolation of the lacrimal glands.

regarding heat compresses-- I can accept warm compresses, but about hot ones I don't know. All the processes I described above are intensified by heat and slowed down by cold. That patients get temporary symptomatic relief from the hot compress may be one thing, but the long-term impact on the actual underlying disease does not seem to be very good.I am not giving advice against using hot compresses.It is upt to every individual and how they feel to use or not to use something. There is hardly any medication for dry eye anyway, that does not have various degrees of potentially dangerous side effects.

And in the end,dear Rebecca, I would like to thank you for giving me the opportunity to share my experience on this wonderful forum, and for all your efforts that have helped ease so much suffering, including mine.

P.S. I posted an edited version of this post in a separate thread as I thought other dry eye patients might have the same questions as you regarding my not very well explained statements in previous posts.The post is better organized and a bit more systematic and understandabe I think. It is such a complicated subject that it never comes right from the first draft. If you like you might have a look at that one as well.

Please let me know your thoughts on my post. I truly appreciate your feedback.

Respectfully,
Dani

[littlemermaid]

References

Ringo! Like your posts - but please include proper sciency references (books, journals, articles) and links for us to follow up because aetiologies are all different. Thanks for your interesting inflammation reading (pathology grads help!), altho' so far warm compress is heaven for littlemermaid's MGs we are struggling with rosacea