steroid resistance?

[poppy]

Docs and patients, is there such a thing as steroid resistance?

I know that some patients have found steroids don't help their symptoms, that's not really what I'm referring to.

Docs have always told me I have tons of inflammation, keratitis, conjunctivitis, blepharitis, and always give me steroids.

What I'm finding is that I need more and more and stronger steroids which still barely manage to keep things under control. At the moment I am using scary amounts of steroids, and have been using steroids every day for about 9 months. I consider this abnormal, if my diagnosis of rosacea bleph/mgd is correct - occasional use of mild steroids should surely keep things under control in most patients.

I'm one of those patients whose symptoms are always less than their signs, so when my eyes start to feel even mildy bad from past experience I know that the doc will see lots of inflammation, and other bad stuff happening, and give me steroids and then be surprised when the steroids don't change my signs nearly as much as they should.

Is it that some individuals are steroid resistant despite having inflammation that SHOULD be responding to steroids, or do I just have so much inflammation and ever worsening dry eye that topical steroids can only help so much? Or is it more likely that I have a condition in which steroids shouldn't in fact be being used, and the steroids are actually making the underlying condition worse (even though they keep my symptoms bearable and help my signs somewhat)?

BTW, if you are thinking I should lay off the steroids for a while to see if my eyes will improve, I've tried that and things get really, really bad. I can't work or drive or do things. I'm not willing to try this again without a good alternative treatment, even tapering slowly has a bad result.

[LVNatalie]

Hi Poppy,
This isn't going to help you, BUT I can empthasize.
I've only been on steroids for a little over a week now (for severe inflammation in my left eye), however they do not help at all.
I started with Lotemax, but was switched to Prednisolone Acetate. I have also been wondering how it could have NO effect at all on my inflammation and severe redness.
Looking forward to your responses.
-N

[hirentherock]

I dont know what reasons are there for eyes to not respond to steroid.
But one thing is sure...the more you will be dependent on them,the more it will make u need them.

Tapering the dose with proper planning is must.I feel very much soothing when i use loteflam(lotemax type brand).When i feel too much burnbing etc i used them in un organized manner.Didnt taper it off properly etc.It resulted eyes to produce less tears for some time.Then 0.1% cyclosporine use made me ok.

My doctor suggests me to be less dependent on them simple cause it does not cure the underlying decease.It works as temporary soother.
Yes, if doctor is advising for the reasons more than the soothing effect, or to control the things, its must.

But please be careful about prolonged use.Thats a piece of advise.

[Ahmed]

Hi Poppy,

What is more likely is that the level of your inflammation is not the same. EG your eyes maybe more inflammed now than previously, so it appears as if the steroid is having less of an effect.

Im not sure of your diagnosis or treatment, but you mention roscea /bleph. Doxycycline + maxitrol ointment for 6 weeks is common. It would be unusual to have been using steroids for 9 months with no improvement of symptoms, if it was an inflammatory condition.

regards

Ahmed.

[littlemermaid]

Ahmed's right. We can't improve LM's rosacea MGD on steroid alone without oral antibiotics or topical antibacterials, even with no lid margin infection. Interestingly, a tiny maintenance dose like 2/week topical will do it. Obviously this doesn't touch bacteria so there must be some other benefit action. I don't like Maxitrol though because it has trashed the surface in some cases (FDA), something milder would be better, you have no infection and plenty of steroid. The protocols in the US inc oral antibiotics pulse therapy, as we know. Any chance of another try on your doxycycline? http://www.dryeyezone.com/talk/showt...-presentations

Also, although we are in chronic use of steroid, we have been down to 2/week in the past by improving the MGs. Also we are currently attempting to use Cyclosporine in addition as a steroid-sparing agent. Yes, it's tinkering about looking for improvement, but for sure, an experienced and knowledgeable cornea surface specialist to work with is a huge relief. Are we sure your dude is up to speed on management? What about a nice trip to Sydney.

Again, interestingly, the benefit for rosacea is not dose dependent, 40mg works as well as higher dose. Maybe have a chat about this Effective and evidence-based management strategies for rosacea: summary of a Cochrane systematic review E.J. van Zuuren, S.F. Kramer, B.R. Carter, M.A. Graber, Z. Fedorowicz British Journal of Dermatology Volume 165, Issue 4, pages 760–781, October 2011

[poppy]

Hi Poppy,

What is more likely is that the level of your inflammation is not the same. EG your eyes maybe more inflammed now than previously, so it appears as if the steroid is having less of an effect.

Im not sure of your diagnosis or treatment, but you mention roscea /bleph. Doxycycline + maxitrol ointment for 6 weeks is common. It would be unusual to have been using steroids for 9 months with no improvement of symptoms, if it was an inflammatory condition.

regards

Ahmed.

Thanks for your reply Ahmed. I didn't mean to say that the steroids have no effect on my symptoms - they do keep away my very worst symptom - disabling photophobia - but only if I use high doses constantly. And they do improve my signs somewhat, however, the docs still rate my eyes as severe and they just won't improve any further (they do get worse if I taper though).

[Ahmed]

Ahmed's right. We can't improve LM's rosacea MGD on steroid alone without oral antibiotics or topical antibacterials, even with no lid margin infection. Interestingly, a tiny maintenance dose like 2/week topical will do it. Obviously this doesn't touch bacteria so there must be some other benefit action. I don't like Maxitrol though because it has trashed the surface in some cases (FDA), something milder would be better, you have no infection and plenty of steroid. The protocols in the US inc oral antibiotics pulse therapy, as we know. Any chance of another try on your doxycycline? http://www.dryeyezone.com/talk/showt...-presentations

Also, although we are in chronic use of steroid, we have been down to 2/week in the past by improving the MGs. Also we are currently attempting to use Cyclosporine in addition as a steroid-sparing agent. Yes, it's tinkering about looking for improvement, but for sure, an experienced and knowledgeable cornea surface specialist to work with is a huge relief. Are we sure your dude is up to speed on management? What about a nice trip to Sydney.

Again, interestingly, the benefit for rosacea is not dose dependent, 40mg works as well as higher dose. Maybe have a chat about this Effective and evidence-based management strategies for rosacea: summary of a Cochrane systematic review E.J. van Zuuren, S.F. Kramer, B.R. Carter, M.A. Graber, Z. Fedorowicz British Journal of Dermatology Volume 165, Issue 4, pages 760–781, October 2011

I find maxitrol effective, the best way is to place a small amount on a clean finger and rub it into the lid margin before bed.

Im not sure of maxitrol "trashing" corneas, however as it contains dexymethasone, it can stimulate viruses on the cornea, such as the herpes virus which could already be there dormant, this can be a serious problem.

regards

Ahmed.

[littlemermaid]

'Eye drops may make matters worse - sometimes this is a toxic effect of the drug, such as Maxitrol. Avoid 'Maxitrol' drops after cataract surgery if you have dry eyes or conjunctival disease. It can cause very severe corneal problems (Midland Ophth Meeting, 2005).' Don't know what these guys experienced with this. It's north Birmingham, Heart of England NHS http://www.goodhope.org.uk/departmen...0dry%20eye.htm

I had an FDA ref but I've lost it (dexamethosone can leave phosphate sediment in sub-epithelial layers particularly where there is surface damage; also, for us, preservative free is very important). It's standard for people without surface damage who aren't in chronic use and aren't sensitive. Just concerned about chronic or frequent use in rosacea as LM and Poppy. We used a course of Maxitrol to no effect so happy to hear you've got healing with this, Ahmed. In the long term, we're much happier with the theory of this subantimicrobial dose therapy and had remission of MGD for 2m to the point of clear meibom on 2/week chloramphenicol + 2/week FML until the skin flared up and the glands clogged again.

The maestro is telling me that in some paed rosacea cases they are not maintaining improvement without this small antibacterial dose, nobody knows quite how this works. (Maybe the hypersensitive inflammation is partly an immunology over-reaction to normal flora/fauna which could be why eg topical/oral metronidazole/antibiotics, demodex control, anti-fungal+zinc/tea-tree shampoo, antibac control, and rebalance of the gut bacteria helps sometimes. Lipid metabolism/homeostasis also needs adjusting, ie the dietary oils, to achieve meibom with better fatty acids and less enzymes around the eyes to react to. Also flora/fauna goes into overgrowth where there is sebaceous overreaction, and the antimicrobial skin barrier functions are struggling/dysfunctional. Also high GI foods enable the inappropriate inflammation response with an insulin/hormone spike somehow (she tested this with an illegal sip of hot red wine punch at Xmas, OMG instant spectacular red face + red eye surfaces - no I did not give it to her as an experiment...) or maybe feed the bugs with fats/sugars. There is also an inflammatory response to environmental and contact allergens and chemicals, also enabled by histamine. Also heat, esp while sleeping. It should be noted topical antimicrobials, topical steroid and other insults have also triggered rosacea in some people, but help manage it in others where the skin restores. Also correcting vit/mineral deficiencies improves it. Even stress/cortisol kicks off vascular inflammatory response. This is why we are looking for a rebalance of the immune system ie health. We're also into beeswax/manuka honey moisturisers currently to support the skin barrier, brings instant calm, adjunct to daily topical antibacs. TBH I'm listening to spmcc on this since I haven't found a derm we can have a conversation with about rosacea yet, still looking. Not just a pair of eyeballs indeed. We also get major flareup during the normal cold virus, and bright red dry nose from sun exposure, which kinda confirms all this. Hope the detail helps. Lots of people are looking at what's happened to the immunology switches now, so there's plenty hope if it helps to know that, PubMed 'rosacea'.)

So that's the point of low-dose doxycycline and protective face skin treatment and eliminating chemicals and allergens and eating healthy + oils and any environmental protection/punctal plugs to retain moisture on the eye surface we can manage. And, crucially, the emotional support of sympathetic, current, docs to work with on our self-management and feedback with regular eye exam, if this can be found.

This is a spiral back to improvement with different anti-inflammatory factors to deal with, however nebulous they sound. We reduce steroids to 2/wk in remission but back on 3 or 4/day in flareup, then taper again. Can't do it without improving the other factors and looking for rosacea triggers. With separate steroid + antibacterial we can adjust and taper according to flareups. We are introducing daily cyclosporine as a steroid-sparing agent although we think we can't manage on cyclosporine alone yet unless better tearing returns. This is the 'benefit' of being able to correlate obvious rosacea flares with eye symptoms and share with people relatively asymptomatic on the skin.

Still doesn't answer your original question about steroid resistance.

Poppy, are you still using FML or does it have to be Prednisolone?

[poppy]

Poppy, are you still using FML or does it have to be Prednisolone?

Thanks LM, I'm trying pred forte at the moment. If I use FML I end up having to use it more than 4x a day, and I think the BAK ends up irritating my eyes.

[spmcc]

I'm trying pred forte at the moment. If I use FML I end up having to use it more than 4x a day, and I think the BAK ends up irritating my eyes.

Poppy,

We seem very similar. I was once addicted to my Pred Forte (which, btw, contains BAK as a preservative).

Anyway, this may or may not be helpful to you, but I have been kind of obsessing over Dr. Scheffer Tseng's article in Cornea Oct 2011 (see pubmed http://www.ncbi.nlm.nih.gov/pubmed/21912234). ** PM me with your email address if you want the full-text pdf.

He suggests 4 steps for treatment of dry eye. They are (in bastardized form):

(1) eliminate all inflammatory, infectious, allergic, and toxic insults;
(2) correct diseases that impede and interfere with tear spread and capacity;
(3) create delayed tear clearance by punctual occlusion; and
(4) treat lipid-deficient dry eye after sufficient aqueous tears have been conserved.

As I look back on 16 years of dry eye, I see that I used to focus on Step 4. I did this because I was told over and over I have MGD. Now I see, in hindsight, that I was doing things (e.g., using drops with BAK, hot compresses) that messed with Step 1. I also (somewhat) neglected Step 2 which for me is to get my rosacea under better control.

I think I'm not alone in getting into a cycle that actually makes things worse. Maybe going back to Step 1 and examining EVERYTHING being put in the eyes, on the skin, in the mouth is a place to start?

I don't know if this info will help you, but I thought it might.

Good luck,
Sheila

[poppy]

Poppy,

We seem very similar. I was once addicted to my Pred Forte (which, btw, contains BAK as a preservative).

Thanks for your reply. I know the pred forte has bak too, but I guess that because I should need to use it less per day than a weaker steroid, it's easier for my eyes to cope with. How long were you using the pred forte and did you end up with any complications? How exactly did you manage to get off the steroids? To me, I can't imagine ever being able to go off them. I think that if such a powerful anti-inflammatory drug can't get my eyes under control properly, what good is any other treatments going to do.

[spmcc]

How long were you using the pred forte and did you end up with any complications? How exactly did you manage to get off the steroids?

I used Pred Forte from Fall 2002 until around 2008 (I still have Lotemax for dire emergencies). Luckily, I am not a steroid responder (i.e, my IOPs never increased greatly... but that doesn't mean that one day I won't get glaucoma or cataracts from steroid use).

I improved when I started wearing moisture chambers 24/7. I also had all four puncta sealed. Both those treatments meant that I didn't have to use drops - which in hindsight I realize never helped much in the short-term (esp OTC) or long-term (because they ended up causing more trouble).

(NOTE: I still use 1-2 drops in each eye prior to sealing my eyes at night. I stick with PF saline, Muro drops, or Systane Balance).

I know it's difficult. Where is the Betty Ford Clinic for Pred Forte users?!?!

[poppy]

I used Pred Forte from Fall 2002 until around 2008 (I still have Lotemax for dire emergencies). Luckily, I am not a steroid responder (i.e, my IOPs never increased greatly... but that doesn't mean that one day I won't get glaucoma or cataracts from steroid use).

That's good to hear that you were able to use steroids for so long without any side effects so far. Did you use the pred forte every day x 4 or did you have breaks? I am using it every day about 5 or 6 times.

[spmcc]

That's good to hear that you were able to use steroids for so long without any side effects so far. Did you use the pred forte every day x 4 or did you have breaks? I am using it every day about 5 or 6 times.

True, I have not had an side effects from steroids - yet.

You should check with your doctor about that amount of use. It sounds very high to me, and seems that it is NOT working for you.

[littlemermaid]

seems that it is NOT working for you.

I'm just wondering if Mr Happy has come up with a useful routine for poor Poppy instead of just blitzing with steroid. He's only just got round to trying plugs.

LM was originally booted out by the county hospital service serially discharged and written off chronic to self-medicate 3/day FML (also 2 previous 6wk tapering courses starting Prednisolone 4/day) like this with no other treatment advice, re-presenting again and again with SPK and red eye, mis/undiagnosed. Tear film and MGs not examined. Still not happy about this, this is why I'm an internet junky now. The MGD was not addressed. Now it is, we manage fine and life is full and very good.

The difference between that approach and someone who's current-ish and good at ongoing skilful surface disease management (like we have now from various people) is astounding. http://www.osnsupersite.com/edulab/default.aspx (may have to register, which is fine) On OSNSupersite, in the Education section, are current CME units on controlling inflammation and dry eye treatment options from members of our beloved Tear Film & Ocular Surface Society. http://www.tearfilm.org/. OSNSupersite is wonderful (also on surgery and post-surgery management, obviously), deeply grateful for public access.*

Useful measures seem small but they are very significant, like an improving mix of tapering eye drops (steroid, antibacterial, immunomodulator, tear film support + hypersensitivity, environmental, diet oils, warm/cold compress, hygiene, soothing derm in our case).

Poppy, Is there a problem to presenting quickly at Sydney Eye Clinic to see an inflammation specialist since this is uncontrolled (prob listed under uveitis)? They might also have ocular immunologists. Might get access to eg loteprednol.

*Ha. I just clicked on the TFOS blog App and got a message from my protection, 'Whoa! Are you sure you want to go there? This site has exhibited some risky behaviours'