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**teddy1324** · 30-May-2016, 18:25

Hello, Jaybo. As you already know, we have both developed permanently dry eyes from Roaccutane. It is clear that you would rather communicate through this site only, and so I'll write some more of my thoughts here. This is more or less what I wanted to discuss with you over the phone. You can see how paradoxical trying to work out a diagnosis is.

Firstly, when I found myself in your position months after finishing roaccutane, my tests were similarly inconclusive, and to this day they remain so. However, it took over a year for my cornea to start showing signs of staining: I remember with irritation how Moorfields ophthalmologists used to comment exasperatedly that my corneas looked 'pristine.' Years later, when I developed serious staining, The Dry Eye Centre informed me that while my meibomian gland function was not perfect, the severity of their dysfunction could not alone explain my symptoms. At times my schirmers scores have been very low - around 2-3 - but at times they have been as high as 15-16, while at others been displayed a score anywhere in between. Many ophthalmologists regard the test as so inconsistent as to be worthless, and some studies I have read have accordingly demonstrated that the test is very poor - bordering on useless - in distinguishing those who have dry eyes from those who don't. My own experience of wildly varying results led me agree that the test is generally inconclusive. While I have said to you in the past that I am convinced that the problem is solely lacrimal, there at times, like now, where I begin to doubt my own prognosis. Here are some of the puzzling reasons why I feel it is impossible to tell exactly what has gone wrong:

Firstly, this article http://archderm.jamanetwork.com/arti...icleid=1148708 demonstrates that no patients of the 14,648 studied showed any long term lacrimal gland dysfunction from their course of roaccutane. You and I would have to be very, very rare specimens to have suffered permanent lacrimal gland dysfunction from a drug which is known to have no documented effect on them. Secondly, it makes no sense physiologically; the purpose of roaccutane is to permanently (which explains why whatever it accidentally did to us is also permanent) shrink the size of the oil producing sebaceous glands in the skin. The meibomian glands are very closely related to the sebaceous glands, and transient meibomian gland dysfunction is a well documented side effect of isotretinoin. That is why roaccutane is given to control extreme cases of blepharitis: the drug reduces the flow of oil from the meibomian glands, thereby easing symptoms.

This should lead us to the natural conclusion that we have suffered severe meibomian gland dysfunction, as I concluded for the first year or two after I finished my course. But, then, as I have mentioned, the dry eye centre's assessment led me to doubt this obvious verdict. I have even more reason to doubt it now; after taking oil supplements, receiving thorough gland expression and a having a course of IPL treatment, my tear break up time rocketed from sub-normal levels up to around 16 seconds, which indicates very healthy meibomian gland function and a strong tear film. I figured at this stage that my problem was by process of elimination lacrimal. However, a very well respected corneal specialist who I saw about a corneal erosion named Melanie Corbett told me she thought that despite my high break-up times, my meibomian glands looked too 'pristine' to be ruled out as the suspects; it was her professional opinion that my meibomian glands were the principal cause of my issues.

On the balance of this evidence alone, it might be safe to assume that the issue lies with my meibomian glands rather than with my lacrimal glands. But then, there are two more compelling pieces of evidence to suggest that it is my lacrimal glands which are dysfunctional after all. Firstly, I have suffered a dry mouth as well as dry eyes. Just as the sebaceous glands and the meibomian glands are closely linked, so too are the salivary and lacrimal glands. There is always a correlation between the dryness of my mouth and the dryness of my eyes - the drier my mouth, the drier my eyes. The is most noticeable overnight, which is when my mouth becomes bone dry. While I sleep, my eyes are also at their driest; I often wake to find them stuck to my eyelids, feeling just as dessicated as my mouth. Secondly, and closely linked to this connection between my eyes and mouth, is what happens when I start eating food. Eating food induces salivation and eases my dry mouth, but it is also the only time of day that I experience complete relief from my dry eyes. Strangely, is only when eating food that I feel my eyes produce natural tears, just as my mouth begins producing more saliva than usual. My eyes feel incredible for about 10-15 minutes every time I eat due to the amount of tears they produce while chewing food. This relief would suggest that the problem is lacrimal after all, but if this is the case, it also suggests that my lacrimal glands are very much capable of producing loads of nourishing, healthy tears, they just, for some reason related to roaccutane, choose not to. It is all very confusing and paradoxical: and so it is hardly surprising that every expert has a different opinion.

As rare sufferers of this debilitating side effect, this leaves us feeling confused and totally undermines any confidence in medicine to help us - they don't, in reality, know any better than us, despite the fact that practitioners of medicine in another field got us into this mess. I suppose that a definite diagnosis would not even be of much use; treatment of any kind of dry eye is pathetic and rudimentary, revolving mostly around artificial tear substitutes even when a prognosis is possible. It feels almost unbelievable that dry eye treatment is this primitive when one considers what medicine is capable of in other fields.. It feels surreal, as though this is some twisted practical joke. Do let me know what you think of this conundrum. I would be interested to know if you report any similar experiences. If you are unsure, wait and see how your eyes feel the next time you eat a meal. It's been four years, and I can't tell to this day whether the issue is lacrimal or meibomian gland dysfunction. It's interesting that you are having the same issue pinning down a definite cause.

**Jaybo** · 31-May-2016, 09:39

Hi Teddy, I'm sorry to say that reading your posts gets me down, because it's painfully familiar. I'm still at the point where I don't want to accept that it could be the sole cause for what is going on, as it will imply that there is no answer at present and thus a potential lifetime under these circumstances. Eating is the only time that I too, feel complete comfort. However, that is reported to be true among a lot of dry eye sufferers. It certainly doesn't help that I am being expressly told that I don't have dry eyes, yet the discomfort is painfully real and more than is tolerable. I have to be honest, and I'm sorry to admit it, but I fear the fate you are currently suffering. It has been 8 months for me so far, since the sudden onset of my eye issues (5 weeks after stopping the course of roaccutane). The reason I have been unsure that our experiences are exactly the same are that; your description was that you were unable to leave the house without copious amounts of lacrilube and also had an incredibly low schirmers score. I can't say that's the same for me (I know schirmers is very unreliable, but I have little else to go on other than my dry eye centre visit which I have reported on here). I also don't have the typical problems with wind and keeping my eyes open in general, that you'd associate with mgd. I also didn't experience the same severity whilst taking the drug (my eyes watered a lot, and were very sensitive, but the pain that started 5 weeks after stopping was very much different). I really do apologise if I have overlooked anything, as these discomforts are all so horribly subjective.

I'm also experiencing issues with my joints and stomach, which, if I remember correctly, you haven't experienced. This has led me to the requirement for having a lot of tests run prior to accepting that this is all down to roaccutane (although if something has been instigated, I certainly would put a portion of the blame down to the drug). What is frightening is that, even if nothing is found, I will still have little confidence as, from what I've read, many of the potential culprits, including sjogren's which you have mentioned before, can take years to be diagnosed and often be missed. This is less than comforting in my search for answers.

A few theories I have that I'm happy to share. My thoughts fire backwards and forwards on a daily basis, so my apologies if any sound crazy, but our situation is crazy and thus may even benefit from a crazy idea:

You mention that your eyes may be capable of producing adequate tears but choose not to. Could this be a nerve damage issue, so the signal is never sent? Perhaps the longstanding dryness/inflammation could cause this.

I'm sure you are aware of the possible causation of a vitamin a deficiency as a result of overloading receptors with synthetic vitamin a. I read a study that showed that the joints of mice that were subjected to a vitamin deficient diet, on inspection, appeared to be perfectly normal, however, they were in fact keratinised (replaced with similar tissue to scar tissue) and thus did not function correctly. On resumption of a balanced diet, the joints began working correctly again. I wonder if there is anything to be taken from this in relation to the eyes, I don't think the study looked at the eyes of the mice. I have been taking multivitamins lately (that include vitamin a) and at times, have felt an improvement. (I have however, heard things about roaccutane patients already being in a state of hypervitaminosis a, anyway, so it may even be making the situation worse. I can't tell as of yet, my eyes felt better but my joints feel much worse, though there could be a lot of reasons of late that this could be attributed to).

I intend also to have some more detailed thyroid testing done, in case there is an issue there, as that is capable of causing a lot of the issues that I have experienced.

Over all, I wonder whether our issue is in fact to do with the third element of tear constitution; mucin. I know that people report dry mucous membranes after accutane, and I know that the inside of my nose generally feels different to how it felt before, often it is very dry (other times not so much). I just wonder whether the synthetic vitamin A overload has caused this effect. Has it turned it off permanently through altered gene expression? I have no idea. Is it a case of a latent vitamin a deficiency that has remained? I have no idea. Is it a case of longstanding hypervitaminosis? Again, I have no idea. The symptoms of hypervitaminosis and also hypovitaminosis A seem to cross over.I once read about a woman who still had high vitamin a levels, years after ceasing high consumption. I also notice that some women report longstanding vaginal dryness after roaccutane, there's possibly a connection here also in terms of mucin production. I should add that this was another symptom noted in the mice I mentioned earlier, another symptom that faded after the cessation of the limited diet. A crazy part of me is wondering whether the normally mucous producing cells on the underside of my eyelids and eyes, have become keratinised or something, whilst looking patent, as per the study on the mice, resulting in our tears having nothing to combine with or properly adhere. This could explain the oral dryness also as it may simply be that, although saliva is present, there is limited mucin for it to adhere to, or to protect the mouth overnight when salivation is minimalised. if it is used to having a constant layer of mucin, retaining moisture etc, it could explain the way my mouth feels. I worry that this is also what is happening in my joints as I have a crunching sensation in every joint now, inclusive of my jaw and sternum, which I had never even looked fully into the anatomy of until I head the sound of crushing freshly laid snow, emanating from the centre of my chest. This keratinisation could also resemble what is going on in my mouth, as the odd thing is that, during the day, I generally have enough saliva, and can even conjure saliva without having any stimulus, however the sensation on my tongue is one of dryness, even through the saliva that is present my tongue feels rough and dry, and sometimes feels as though it is burning of its own accord. It truly is strange.

I echo your thoughts on the field of dry eyes, it is thoroughly awful and painfully lacking. Everytime I mention dry eyes or dry mouth and hear of tear or saliva substitutes, I feel a rage build up inside because, to me, it seems so lazy. It isn't looking at the cause of the issue, but aims to placate a symptom of something that may be going on. That something may even be as simple as a vitamin deficiency. It's truly ridiculous and likewise, feels like a horrible joke.

**savino** · 31-May-2016, 10:07

...........

**teddy1324** · 31-May-2016, 12:52

Hi Jaybo,

I recall your position at around the 8 month mark. I wanted to believe I could find a permanent solution, and it is only recently that I have resigned myself to this for the foreseeable future. Rest assured, we will not suffer from this for the rest of our lives; we are both young, and medicine will catch up within our lifetimes. I hope this happens sooner rather than later.

I would like to clarify a few things about my symptoms. Firstly, they fluctuate, and this is important. At times over the years I have found walking around and exposing my eyes to natural air/wind has caused them immense discomfort, though I was never entirely sure what the cause of this was. At other times, I was able to walk around without irritation. It is only over the last few days that I finally have an answer. I had two theories: either it was the sensation of evaporating tears (described by users of this forum as a cooling, stinging 'menthol' type sensation), or pain arising, not from tear evaporation, but from extreme sensitivity due to stained corneas. I am now certain it is the latter: I have spent the last 4 weeks at my girlfriend's house, spending every single day predominantly inside, keeping my eyes constantly lubricated in order to test this theory. My thinking was as follows: If I got no improvement in my symptoms after taking such exhaustive and meticulous care to keep my eyes lubricated at all time, that would suggest that the discomfort arose from an evaporative disorder. But if my intensive regime resulted in the cessation of sensitivity to outside air, then I knew that the pain arose from staining in my corneas, as in keeping them constantly lubricated, I would be allowing them a chance to heal any damage that might be causing pain. I did this because I am about to suck it up and look to start my career, but before I do, I need to learn everything I can about the specificities of my condition, so I am best equipped to manage it as possible.

With respect to joints, while I don't experience and joint pain, I do hear cracking sounds that are very odd for a 21 year old; for instance, if I were to bend down to tie my shoe laces, I hear several cracking sounds from my legs. My ankles often crack too; it is as though I am an old man! My dry mouth has got worse over the last year. For the first three years or so after finishing roaccutane, I rarely noticed that they were severely dry during the day - it was only upon waking that I was aware that they must have been bone dry over night, along with my eyes. I too considered the nerve damage theory: if both of our eyes are clearly capable of producing tears, as we both agree they do when we eat, then it would suggest some gene alteration or signal failure from the eyes to the lacrimal gland. It is also worth considering that the relief resulting from the influx of tears we get while eating would suggest that we are aqueous deficient: if we already had normal tear production to begin with, a sudden increase in tear production would make no difference to us, as we never had a problem with quantity to begin with. I suspect a lot of people on this board report similar comfort when eating from this increase in lacrimation, but that is not altogether surprising when you consider how many people have suffered LASIK-induced nerve damage.

When it comes to Mucin production, things get more complicated, as even less is known about eye mucins and their role in eye lubrication than is known about oil and tears.I am taking oral pilocarpine, however, which is proven to increase Mucin production in the eyes, rather than tears. I can't say it has made any difference to my eyes, but it does cause me to salivate uncontrollably. Do you also have very dry lips?

**Jaybo** · 01-Jun-2016, 09:22

Thanks Savino, I'd be interested to read what you have to say.

Teddy, congratulations on the decision to start your career. I wish you the best of luck.

My lips fluctuate, but they are no longer anything like they were whilst on the drug. Much of the time I don't notice much dryness at all, and find myself constantly checking to see how they feel, but I certainly don't feel that they require lip balm at all any longer, even at their worst they only feel a little dry.

My eyes do feel sensitive, but on the whole, since my post a few weeks ago, there has been an improvement. As I mentioned, there had been improvement previous to that, when I experienced around a week of minimal comfort. Looking back, I worry that it may have been an increase in mucin production due to me having a cold of some sort that never really came to full force, but rather remained mild for a long period. I know you mention that when we eat, the comfort suggests a lacrimal deficiency, but it may be that the excess tears are enough to compensate for the missing mucin? I really don't know.

The reason for the improvement in the past few weeks since my eyes took a real dive, is difficult to answer for. the only thing I have been doing differently has been the daily high doses of multi vitamins. I've added these on top of some others that I was taking (vit D as it's hard to overdose on, K, Calcium, MSM, Glucosimine and Chondroitin for my joints). I actually stopped the Fish oils a while back but may start them again soon. Unfortunately, the multivitamins that I have been taking have a lot in them, so it's difficult to know what, if any, is making the difference.

I take it you have tried vitamin supplements?

Whatever has happened has definitely reduced the burning to almost zero, it is just an ongoing scratchiness and night time dryness that remains. I will also state that, since around February, I haven't been using any drops nor lubricants during the day. I also stopped using the vitapos eye ointment at night and felt an improvement. On the whole, this has helped give me a more stable discomfort as opposed to the wildly changing sensations involved with applying drops regularly and using the ointment at night. In the last week or so, I have been putting a few drops of theratears eye drops in before bed, which may or may not be contributing to their current state. What I can say however, is that if I compare the way they feel right as I type this message, to how they felt throughout November, December, January, February and March, they do feel an awful lot more comfortable. Though I may have gotten use to a certain amount of discomfort, back in December/January I felt as though I was trapped in a constant state of panic with them, where every lid closure felt like it was scratching the surface of my eyeball creating constant discomfort. I could also barely sleep without the eye ointment. These sensations are milder, though I hesitate to get carried away, the discomfort is still a horrible part of my life.

**dryeyedad** · 04-Jun-2016, 22:36

I recently read an article that talks about an unrelated injury causing nerve problems that make you feel like you have dry eyes, even though your tear metrics should not lead to that level of pain. The article is, Ocular neuropathic pain by Perry Rosenthal and David Borsook. Here is the intro...

Our corneal pain system is unique in its principal
role of protecting, sustaining and restoring the
optical tear layer without which our vision would
be non-functional. To meet this existential need,
the human dry eye alarm evolved into the most
powerful, sensitive and complex pain system in the
body, incorporating sensors that are unusually vulnerable
to being exposed to the noxious environment.
Like other damaged nociceptive systems, it is
capable of failing and becoming a disease in its
own right known as neuropathic pain.1 Indeed, the
features of corneal nerves associated with pain parallel
the well-defined properties of somatic neuropathic
pain defined as ongoing pain as a direct
consequence of a lesion or disease affecting the
somatosensory system. Nevertheless, a recent
PubMed search (http://www.ncbi.nlm.nih.gov/
pubmed) using key words cornea, neuropathic, pain
came up empty except for references to herpes
zoster. Here we provide an overview of disorders
of the corneal pain system in the context of neuropathic
pain as it relates to dry eye disease (DED)
and other disorders affecting the corneal sensory
system characterised by otherwise inadequately
explained chronic pain.
WHAT IS DRY EYE DISEASE?
Although the definition of DED is ambiguous and
often contradictory, its most consistent clinical
feature is chronic dry eye-like pain (DELP).
Dry eye symptoms
DELP is a unique type of corneal pain that we associate
with excessive tear film evaporation. Unlike
pain experienced elsewhere in the body, that of dry
eye is characterised by its sensitivity to environmental
evaporative factors in being exacerbated by circumstances
that promote tear film evaporation and
are mitigated by those that suppress it. Thus, in addition
to mechanisms commonly associated with
neuropathic pain, specialised corneal nociceptors
tuned to tear film evaporation have been shown to
play a central role in generating chronic sensations
of dry eye (see below). Moreover, we believe that it
is appropriate to distinguish them from symptoms
caused by the mechanical consequences of dry
ocular surfaces such as scratchy or foreign body-like
and others such as burning when they are not highly
sensitive to tear evaporation. The reasons for our
arbitrary decision to highlight symptoms associated
with evaporation of the pre-corneal tear layer will
become apparent below.
Although patients with chronic corneal evaporative
symptoms as a group have lower tear metrics
than those who are asymptomatic,2 the weak
relationship between DELP and tear metrics3 4 questions
the assumption of a direct causal relationship.
Moreover, the validity of highlighting Meibomian
gland dysfunction (MGD) to explain the disparity
between signs and symptoms has been challenged by
the recent report of its similarly weak relationship
with dry eye symptoms.5 On the other hand, dry eye
symptoms are keyed to the sensitivity of specialised
evaporation-sensitive (cold) receptors located in
afferent corneal nerve terminals6 known as TRPM8
channels that in murine models are responsive to
cooling7 and the presence of hyperosmotic tears,8
and others described as innocuous cold afferents.9 It
should be noted that different results have been
obtained on the effects of hyperosmolality6 8 that
may reflect differences in the experimental set-up or
others that can alter the responsivity of the coldsensitive
afferents (including genetic background).
Hypertonicity and increased rate of cooling at the
corneal surface that occurs with evaporative thinning
of the overlying tear film drive the nociceptive
activity that sustains basal tear secretion.9�11 When
thinning of the tear layer exceeds certain programmed
thresholds, the escalating activity of these
nerves triggers the release of fresh tears that normally
restores the tear film thickness, thereby silencing
the dry eye alarm. However, if the tearing
response is inadequate, the escalating alarm activity
breaches conscious levels and triggers the maximum

release of available tears. Notably, damaged nociceptors in other
body parts usually demonstrate enhanced activity to cold typical
of many neuropathic conditions.12

**Carlos 80** · 20-Jul-2016, 01:17

Check out conjunctivochalasis as to why you experience pain. Ask your eye doctors about it.

**Klee** · 20-Jul-2016, 02:10

Hi,my tests for dryness are all normal. I have posterior mgd. The doctor said anyone who has mgd is considered to have dry eye because of the gland issues. Mgd can also caus all symptoms of dry eye as the oil is compromised.

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