Tacrolimus

[patrick]

Hi,

Wanted to share my experience here. Curious about your opinions.
Yesterday i went to my opthalmologist for a regular yearly check up.
I got confirmed what i already suspected. Things have gotten much worse than before.
I have mgd an till this point only very slightly aqueous deficient.
Yesterday it turned out my schirmers have plummeted considerably. Used to be around 10 mm and has been decreasing over time and now i have 1mm in both eyes. This is severe dry eye. And it sure feels like it to. My eyes drive me crazy!
I could see my opth was somewhat shocked about in what direction my eyecondition is hedding at this point.
Never had what is called 'punctata' but now i have them in both eyes. Like small scratches on my corneas.

My opth said i now qualify for the most aggressive approach for dry eye she has in her toolbox. Its like all or nothing it seems. I could read her face and she is WORRIED..


We of course discussed the steroids and cyclosporin route,but she is not very enthousiastic about these drugs. She finds especially cyclosporin not very effective in most cases.
I am now on a 3 months course of 100 mg doxy per day. An antibiotic ointment for the same period. Also daily.
And a drug i had not heard about before. Tacrolimus.unfortunately i Forgot how long and how often and in which grade.
I have to go pick up the prescription next monday. I hope the people there can explain how it is used.
I read this tacrolimus is often used in the veterinary world to treat dry eye and it seems a lot more potent than cyclosporin and about as effective as a grade 2 steroid. To my understanding Without a lot of the side effects that steroids have.

Anyone here who has experience with this rather new drug? It is approved here for humans. But stillnot in north america yet. Not sure about that though.

Patrick..

[PotatoCakes]

I don't know a lot about Tacromilus, except what I found online, but, it seems to me that trying cyclosporin would be a much better first step than a drug that is used under strict supervision for organ transplants http://www.nlm.nih.gov/medlineplus/d...s/a601117.html

I understand your doctor's hesitation; it doesn't work for a lot of people but wouldn't it be better to try that before jumping to the end of the line, with something that has so many risks?

What else have you tried? Scleral lenses, punctal plugs, serum drops, Evoxac (used for Sjogren's / dry mouth but some doctors think it increases tear production too). At the very least, I'd make sure you tried everything before becoming a human guinea pig with a drug that seems pretty high risk...

[patrick]

Hi,

Thanks for your reply!
Yes,i've tried a lot of different treatment options. Without much succes i have to say.
I have been struggling with this since approximately 2008. Till now i do eyelid hygiene,massage,warm compresses and taking fish oil.
I've had a 6 weeks course of doxy (which did nothing) and some years ago i got a short course of steroids. This worked wonders. After two days of use all my symptoms disappeared completely. Unfortunately a week after stopping with the steroids the symptoms returned.
In the course of time my symptoms have become much worse and also the clinical signs are much more present than in the early days.
So,i must say that this condition for me is a progressive one. I read it several times in different articles. And i don't want to sound pessimistic,but it is a condition that gets worse if you do not intervene aggressively in the early stages. Unfortunately most of the clinicians do not make the right diagnosis and put you on the right treatment right away,because they don't see enough clinical signs and they think the pain you describe is partly between your ears or so.
That is what happened to me. I've seen a lot of opthalmologists and especially in the first few years i always got dismissed with the words; its not all that bad. Try to take it easy and not think about it too much. Yeah right.

As for the tacrolimus. I've tried reading about it on the internet,but i cannot find very much about it. The link you posted (thanks for that) also does not fully describe the action when it is used topically. It describes much more what it does,and what the side effects can be when used systematically. I admit it is quite nasty stuff, but on the other hand so is cyclosporine when you take it systematically.
As far as i understand the action of cyclosporine and tacrolimus when used topically is somewhat similar. They're immume suppressants. Both drugs are used for conjunctivitis sicca in animals and from what i understand from the veterinarian articles i read the tacrolimus is a lot more potent than cyclosporine.
Another reason my opth prescribed the tacrolumus is that cyclosporine (0,05%) was never approved here for the use in humans. It failed to prove effective enough.
But,you are right it is pretty scary to be put on a drug that is potentially dangerous. However at this point i am willing to try anything. Under the right professional supervision of course.

I discussed the option of sclerals with my opth to. She says that it is something we definitely can look into ,but not for now.
She wants to try to improve the tearfilm first and if really everything fails we can try sclerals. My opth considers sclerals as the absolute end of the line in treating dry eye...

Oh,i forgot to mention; i also have permanent lower plugs. Still my schirmers are only 1 mm...

Patrick..

[PotatoCakes]

Have you tried serum drops? They repaired the damage to my eyes. Unfortunately, they don't help produce tears but they've improved my life dramatically. Sadly, plugs didn't help me. I do believe this is a progressive disease. I began my dry eye journey in my 20s, now in my 40s, I produce virtually no tears. I wish you luck with the Tacromilus, let us know how it works for you.

[peter56]

Hello Patrick,
before addressing the MGD issues, your watery-mucin tear film layer has to be restored.
A severe tearfilm disorder does always cause severe ocular surface inflammations-keratoconjunctivitis-sicca.
In the anterior stroma of the Cornea, there are a few hundred very very thin nerves.
These nerves to belong to the tears Reflex arc and are Controlling the watery tears production.
Even a mild inflammation can put these nerves out of action.
Then the tear glands to only tearing after very intensive Stimulation or no more at all.
Tacrolimus like Cyclosporine are t-cell Inhibitors to suppress the inflammations.
Tacrolimus eye Drops are only available in Japan-Talymus and very low dosed Drops from Leiters-Sacramento.
Tacrolimus drops-ointment is 8-10 more efficient per dose than CyA, but Tacrolimus drops will only become
available here in Europe late next year.

I don`t think that Tacrolimus-Tabs-Prograf will help. Prograf does have a lot of adverse side effects.
It is impossible to get the necessary concentrations in the corneal stroma by systemic Tracrolimus.

That is only possible by applying the Cyclosporine drops from Germany.
These Drops can be ordered from:

Neue Apotheke - Tuebingen
Europaplatz 2/1
D-72072 Tuebingen

The prescription may be for example:

6 x 2,5ml Ciclosporin-Liposomen-AT - 1%

Since this pharmacy does deliver the drops here to Switzerland or Austria, they may also deliver to the NL.
Simply try it, sending the prescription to this pharmacy. They will include the invoice to the parcel.

Late this year, Novaliq in Heidelberg will introduce thair CyclAsol-CyA Drops on the market.
Next year another German pharma comp will Launch more powerful CyA Drops.
Some US ophthalm do apply Naltrexone Drops to heal the corneal nerves.

It is most difficult to suppress the inflammations, while there are permanent irritations on your ocular surfaces.

In order to stop the inflammation, you may have to wear sclerals for several months only.

The Visserlenzen are expensive - 1500 Euro for one.

But there is another comp MISA, that does also make and fit small and large Diameter sclerals in Arnhem.

http://www.microlens.eu/eu/scleral-general

I don't know the Prices of these sclerals.

Peter

[patrick]

Hello potatocakes and peter,

Thanks for your replies. I really appreciate it!
Unfortunately i am a bit out of 'screentime' for today,but i will of course make a longer reply tomorrow.

What i do want to mention now Peter,is that to my understanding the prescription i got for the tacrolimus is an eyedrop and not tablets.not sure though.
I was at the pharmacie yesterday to pick up all the things the opth had prescribed me,but i could not get it any sooner than tomorrow (wednesday). When i gave the prescription to the lady behind the desk she of course read it and then she immediately called out for her supervisor who told me to come back in two days. I guess that's a sign that this is something a little bit out of the ordinairy here.
So now i am very curious what it will be. Tablets or drops.
I am not very keen on taking this stuff systematically . For all the obvious reasons.

[patrick]

Went to the pharmacie yesterday and for whatever reason my prescription still was not ready.
Something went wrong and i didn't bother to ask what exactly.
The lady behind the desk asked me to come back tomorrow in the afternoon. ( That's today,thursday).
So,i will go there again this afternoon. That will be the third time i go there to try to pick up my prescription drugs.

Peter, i couldn't resist asking her if the tacrolimus are tablets or is a drop. She answered that its an ointment.
So,that means its administered topically. I'm glad for that of course. If i would have been given the tablets i'd probably have refused it.

Potatocakes, i also think that using the serum drops while i am on all these anti inflammatory drugs is a really good idea.
It gives the corneal nerves a better chance to heal properly. it's just a very valuable addition to the treatment.
However, i am a bit reluctant to ask for it at this moment. I don't want to annoy this opthalmologist who is really doing her best to try to help me. i find it quite difficult to point out that she,with all the knowledge she has,is forgetting an important part of the package.


Update;
just picked up the prescripted tacrolimus.
Its two 4 gram tubes with 0,03 grade tacrolimus ointment.
3 times per day one drop. Not sure for how long initially. I guess its a 3 months course.

Patrick..

[peter56]

Hello Patrick,
so is your TAC ointment a compounded one?
sometimes pharmacies do refill the TAC Protopic 0.03 Skin creame into smaller tubes.
Other pharmacies do simply dissolve the TAC powder in castor or olive oil. These formulations do burn somewhat and
don't penetrating the cornea very deep. But I do hope, that the TAC ointment does suppress the Inflammation in your
corneal nerves, so that they will control the watery tear glands again.
Long time or intensive ocular survace Inflammation does destroy these nerves irriversiblely.
Without the watery-mucin layer, the people have to wear sclerals or dropping every few minutes.

In order to protect the ocular surface-Cornea from mechanical irritations, it may be neccessary wearing bandage or
scleral lenses for some months!
Procornea in the NL does make beside sclerals also bandage lenses.

Did you try Hylo Protect eye drops to improve the lipid layer?
Some patients here are claiming that Hylo Protect are the best lipid drops they have tried.
Hylo Protect should be avaiable all over western Europe.

http://www.ursapharm.de/en/home

That is the same german comp that does also make hylo Comod and Hylo Gel.
Here many patients do fill thair sclerals with 50% saline and 50% Hylo-Comod or Hylo-Gel.

Peter

[patrick]

Hello peter,

Thanks for your reply and interest!
Yes,the hospital pharmacy has compounded the ointment. Don't know if this is just the skin cream in a smaller tube or an ointment specifically made for opthalmic use. To me it seems like its a paraffin based ointment. It surely is not a drop.

The drops i got for rewetting the corneas is hylo gel for daytime and visidic carbogel for nighttime (unidose).
Is hylo protect any different than hylo gel? Aren't they somewhat similar? They both contain hyaluronic acid as active ingredient.

In short this is the regimen i have to follow the next three months;

- 3 weeks per month 100mg of doxycycline 1x per day.
- 1 week per month i have to apply fucithalmic 10 mg antibiotic ointment 2x per day. (Unidose).
- 3 months i have to apply tacrolimus 0,03% ointment 3x per day.

I have all of it at home for over a week now and i haven't started using it because i think you have raised a really good point that in order to suppress the inflamation properly i have to do all i can to avoid mechanical irritations.
Do you suggest the use of bandage lenses for 3 months is necessary before i start with these medicines?
In that case i will have go back to my opthalmologist and ask if she wants to prescribe them to me,because i guess its impossible to just go to a contact lens specialist and buy a bunch of them.

Patrick..

[peter56]

Hello Patrick,
the therapies your doc does recommend are well suited, but don't address the complete system that is in disorder.

Most importent is the optimal order or successions of therapies and a good timing.
Unfortunately it is not possible combining the TAC ointment with a protective bandage lens wearing.
It should be possible removing the lens at evening and then applying 3 times TAC until morning. In the morning rinsing the eyes and then
reinserting the lenses.
I do fear that without the lenses, the corneal nerves will not Regenerate.

It is a matter of fact, that only protective soft lenses or sclerals do support the healing process of the corneas.

The B&L PureVision one month lenses are somewhat thicker than standard lenses and thus are well suited.
Other Bandage lenses are available from Procornea-NL, Hydro-Baby lens from Cantor-Nissel-UK,
Orbit-CH etc.

While wearing soft lenses and a low schirmer, it is neccessary dropping every 15-20 min.
Hylo-Gel, Vidisic, Hylo-Comod are OK for doing that.
Here we do have patients that still do have sufficient watery tears and they do wear soft lenses for years now.

The Hylo-Protect drops should improve-complete the lipid layer.

The double suger of the Thealoz-Duo drops from Theapharma should protect the epithelial from drying out and cell death.

Later on you may also try the Eloisin drops from Spain to increase the aqueous tears production.

You also have to check the success of these therapies.

So please watch:
Are coming tears while yawning,
while Peeling onions,
while crying - better suited for female patients, but...
nasal stimulation etc.
If you do think that the corneal nerves are working somewhat better, you may try pillocarpine-Evoxac tabl to stimulate
all glands.

Obviously your eyes - glands do only tearing, after very intensive stimulation.
So the therapeutic objective should be that your eyes are tearing from the natural corneal stimulation.

Only if you do have a permanent schirmer of >=7-8mm, it is possible addressing the Meibomian GD!
Without a good watery-gel layer, even the best lipid layer is useless.

[patrick]

Hello peter,

I decided to leave the plan of using bandage lenses during the treatment of tacrolimus ointment.
Its sort of undoable i guess.
Instead i want to try to apply drops every 30 mns religiously in order to keep the corneas from drying out too much. I also planned to wear moisture retaining glasses as much as i can during the treatment. Hopefully these measures will keep the eyes as moist as possible to give the corneal nerves a chance to heal a bit.

I do not have the hylo protect drops,but i will order them to give them a try. I do have the hylo parin drops. Containing heparine. It is supposed to support the healing of damaged corneas as well. You know these drops?

Started with the tacrolimus ointment yesterday and i was astonished about how it hurts,stings and burns! After applying it for the second time that day i couldn't do anything anymore,but sit and wait till it would subside a bit. Which it didn't. So i went to bed. It even burns today after a good night of sleep (8 hours).
I was told it would hurt the first few days and that the pain would disappear after about a week of use or so. I can only hope that the stinging is not caused by benzalkonium chloride. I hope the pharmasist wasn't stupid enough to use this as the preservative in the ointment. Can't check that. It is compounded and there is no list of ingredients on the tube. I didn't get a list with instructions for the user as well. It is non existent.

My observation at this point is that my eyes tear very easily when they get stimulated by various stimulants.I work regularly under cars lying on my back and for some reason i very often have tears running down my cheek when doing that. I find that strange. Although i am told once that it could be caused by the lack of lipids on the tearfilm. If they,re too watery they don't stick properly to the corneas. Don't know if that is true though.

I'd be very interested in trying the thealoz-duo and eloisin drops,but at this moment i am using so many eye drops that i sometimes think i am overdoing it at bit. If that is even possible of course.
You think i should try these drops right now or maybe wait with them and try them later? I can also stop using the drops i currently use and replace them with the drops you recommend. To be honest it is a bit confusing. I am so determined to do the right thing here. I feel there is just no room for error anymore.

Again,thanks for reading! I appreciate it very highly..

[patrick]

Hello,

Went to my ophthalmologist a couple of days ago to assess my 3 months course with tacrolimus ointment.
To make a long story short,it didn't work.
My eyes were checked at the slitlamp and tbut was measured with a dye. as always. My tearlayer starts breaking almost instantly. Which surprised the oph a bit,because none of my glands are clogged and upon expression liquid meibum comes out. Production low maybe?
A schirmer test was not conducted. I know this test is notoriously unreliable,but how has the oph seen that aqueous part of my tears has not improved? a schirmertest was done before the 3 months course,so to me it seems only logical to also do one afterwards. Isn't it a usage to use parameters in science? Guess not in ophthalmology. I guess she had seen enough at the slitlamp. I really don't know.
There is not much room for asking many questions. As these doctors always seem to be in a hurry.

On the other hand this doctor is not dismissive at all. She wants to try a few other options,because she is fully aware that my eye condition is quite serious.
She wants me to try what she calls 'dog's' eyedrops for 3 months. What? Yes,cyclosporin. It is really unknown here and only approved for veterinary use. I know of restasis for a long time already of course,but again no time to tell her that. She commanded the hospital pharmacy to order the drops in the usa. We'll see.
She also wants me to make an appointment with a dermatologist. She recognised a particular skintype i have and she thinks it is suspicious. ( i have dry skin) mainly on hands and feet. Okay. I"ll go there and hear what the dermatologist has to say about the matter.
Last but not least i need to go to a scleral lens fitter and have an exploratory conversation. Luckily we have a very reputable sleral lens fitter here in the netherlands. My appointment is in two weeks. Very curious about what they can offer me.

If there is something to report i'll make an update here on these boards of course...

Oh,i forgot to mention. The 100mg doxy tablets daily and fucithalmic anti biotic ointment 2x daily has been extended with another 3 months.

[Gerri55455]

[QUOTE=Tacrolimus eye Drops are only available in Japan-Talymus and very low dosed Drops from Leiters-Sacramento.[/QUOTE]

Does someone know a doctor who can prescribe this in the upper Mid-West?

Thanks!