advice on cyclosporin?

[mrunicorn]

I’m new to the forum, hence I’m posting here. But my wife, known to some of you here as ‘unicorn’, has been suffering for some time, hence what I’m afraid is a long post to try to summarise! We’ve had recent consultations which raise some questions about treatments such as Restasis/ cyclosporine that it would be great to get others’ advice and opinions on.

My wife has been suffering from dry eye symptoms for more than 18 months. She has had numerous consultations with opthalmologists (although it has so far proved impossible to see her actual ‘official’ consultant, which is frustrating since he has published clinical research on dry eye treatments and diagnosis and is obviously an interested specialist—somehow even when he has ‘clinics’ in the hospital he is never actually there. Does anyone understand the NHS?).

She has tried many products without much success and usually with significant sensitivity to ingredients. Steroids resulted in large increase in eye pressure and so are not possible. Symptoms vary over time, but typically worsen over the course of a day from morning until night. Day to day severity also varies. Conditions such as dry air (from central heating) and stress make things worse although there is still a lot of variability and unpredictability. She also suffers from rosacea although it isn’t clear how this is related to the eye situation. We have a diet high in fish, vegetables etc, lactose-free, and relatively low in gluten and sugar although not zero. My wife tried a histamine-free diet for a while but this did not change anything (and was not easy, tends to rule out fish!)

Consultations result in a diagnosis of ‘mild’ dry eye typically, based on visual inspections, although this doesn’t match the severity of the experience and its effect on our lives. A vision research unit at a nearby university was good enough to carry out some substantial diagnostic tests, seemingly far beyond what you are likely to get as part of a consultation. If I can gather anything consistent from various consultations, it is that the problems are probably to do with inflammation.

There is the complication of what appear to be cysts on the inside of the eyelid, although in the last consultation the registrar felt these were not actually cysts, just ‘follicles’. In any case the effect is the same, of increased irritation and inflammation.

In the most recent consultation, two doctors (one a consultant although not officially my wife’s consultant, one the registrar for my wife’s consultant) openly disagreed about potential treatment. The consultant effectively ‘pulled rank’ somewhat, although the registrar had spent significantly more time discussing the symptoms and examining the eyes and seemed to be thinking harder and trying to treat the patient as a person rather than a statistic. The registrar described the symptoms as ‘allergic eye disease’. He recommended Occusan and said that while Restasis (cyclosporine) was a potential treatment as anti-inflammatory, he felt the likelihood of sensitivity meant it should be more of a ‘last resort’. The consultant seemed to think it was Restasis or nothing, if I am interpreting her rather short and terse advice correctly.

The registrar felt strongly that viral swabs should be taken to check for presence of viruses and seemed surprised that this had not been done already. The consultant dismissed the possibility of viral presence and at first refused to consider swabs. We had to insist rather strongly that this should be done, if only to rule out what is certainly an unlikely possibility.

Finally we left with prescriptions for Occusan and Restasis and the instruction to come back in 4 months.

Occusan turns out to be another preparation of sodium hyaluronate, which my wife has been trying in the form of hyabak already without long-lasting success (a slight easing of irritation for a few minutes but nothing more). It’s possible that occusan could be different in terms of molecular weight, which would change the viscosity and perhaps the ‘lifetime’ of the drop in the eye, but as far as I can see the molecular weight in most of these preps is unlikely to vary strongly. There may be other components in the different products too.

So I would be especially interested to know if anyone has experienced noticeable differences between these or other similar products, whether in effects on symptoms or just how the drops behave/how long their effects continue after application. It would be nice to understand the differences and why there are so many possibly identical products being recommended. My wife needs to decide whether it is worth trying this latest version given her history of sensitivity and the possibility that using all these various products is only making the inflammation steadily worse!

Now to the Restasis. Picking up the product from the hospital pharmacy we discovered that it is made by Allergan and is an unlicensed treatment in the UK (which we sort of knew already). Concentration is 0.05%, preservative free. I think it is oil-based, which is not ideal because of the well-known low tolerance of oils in the eye. We are aware that there may be a 0.06% water-based prep recently developed through Moorfields. (Interestingly, the registrar in the hospital didn’t know about this but proceeded to google it in front of us.) I’ve read a bit of the research literature (I’m a physicist/chemical engineer so can more or less handle discussions of hydrophobicity, emulsions, colloids etc) and the challenge for cyclosporine seems to be the low solubility in water, which means you can’t easily get to therapeutic concentrations in the eye—you can’t ordinarily get enough of the molecule into water to make it effective.

From scouring the Moorfields website it seems the ‘water-based’ prep is in the form of a ‘polyaphron dispersion’. This means the active ingredient itself is in oil droplets dispersed in an external water phase, prepared in such a way as to make what is sometimes called a ‘biliquid foam’. This is different to a normal emulsion in that it requires less stabilising surfactant to keep the oil in the water (normally oil and water don’t mix, of course, this is why mustard helps make a stable vinaigrette). This is good for eyes because surfactants are generally not desirable molecules to have lying around… There will still be oil present, however, so ‘water-based’ isn’t as simple as it sounds. (All of this is partly guesswork too as of course they don’t reveal the actual ingredients or structure.)

But enough of the lecture. What we would be interested to know from others is what experience people have had with the Allergan/oil-based Restasis, and if anyone has tried the new water-based Moorfields (0.06%) version or has any idea how it could be obtained? Does anyone know if it can be prescribed through a consultant? Or through a pharmacy?

Our GP has said she cannot prescribe the Allergan product as it is unlicensed and will not be accepted by Primary Care: we will need to go back to the hospital to get more. Which is important, because they only gave us enough for 20 days, despite setting the next appointment in 4 months!

Moreover, the guidance on the Restasis box is to use twice a day (and discard unused vial immediately); whereas the prescription was TID (3 times a day).
So we are pretty confused as to how to proceed! It would be great to hear opinions on whether to use the product once, twice, three times a day, etc… And whether its positive benefits outweigh its potential negative effects (burning, stinging…) Same goes for the Moorfields version, if anyone has managed to get hold of some…

Finally given the slow and not very comprehensible workings of the NHS so far, we are thinking it would be an idea to find a private specialist. Does anyone have any recommendations in the UK? We’re in central Scotland but would be willing to travel if we could get useful consultation—it’s just you need to know you’re going to be talking to someone knowledgeable and concerned, which without recommendations is pretty difficult to be sure of…

Any advice/informed opinions gratefully received!

[bookwoman]

I am also new to the forum and have ATD, MGD, severe allergies and sensitivities, ocular rosacea and corneal neuropathy. I have been wearing PROSE lenses since August and they are a wonder! Nonetheless, I still use a lot of other treatments including Restasis. Like your wife, I am highly sensitive to the ingredients in gels, drops and ointments and I tolerate Restasis well. I have found it helpful for reducing inflammation and increasing tear production. I won't say that it doesn't sting because it truly does but this passes after a bit. I just use the regular Restasis out of the box. Before PROSE lenses I used it 4 times a day but now I only use it twice a day. It took about 2 months before I noticed more tear production.

I hope this helps!

[No tears in ATL]

Bumping this since I would like very much like to hear others' responses. I feel as though I am in the same situation as your wife. I'm super sensitive to Restasis with lots of underlying inflammation and almost every lubricating drop out there seems to make things worse. I've asked my own doctors about compounded Restasis that was not in any type of oil carrier and they don't seem to know either. Of course, I'm in the U.S., where our FDA seems to be the last on the bandwagon with things...

[NotADryEye]

Whatever your wife tries, she can always try it in one eye only first. If she is able to tolerate it, then she can proceed with the other eye. I've found that it is better to have only one really bad eye at a time. If both are bad and burning you somehow can't get away from the pain and it is maddening.

Restasis only helps about 15% of patients who use it. It is an important statistic to keep in mind. Some, like me and NTinATL can't tolerate it at all. My pain was so bad I reported to the FDA (I'm in the US).

Also, your wife was diagnosed with mild dry eye, but can you tell us with any more specificity about the diagnosis? Dry eye is a catch-all term whereas aqueous deficiency or evaporative dry eye mean something more specific. Did the doctors tell you anything else?

The different opinions - a universal problem. You were witness to it in person. So many of us had to go from doctor to doctor before we find accurate diagnosis and help.

When confusion reigns, because they tell you one thing but you are faced with another, call for clarification. They owe you that.

If you can contact littlemermaid, she posts quite a bit on DEZ and seems to know who the good doctors are in London, maybe she can guide you toward better care.

[mrunicorn]

Also, your wife was diagnosed with mild dry eye, but can you tell us with any more specificity about the diagnosis? Dry eye is a catch-all term whereas aqueous deficiency or evaporative dry eye mean something more specific. Did the doctors tell you anything else?


.

Thanks! Here are some more details of various diagnoses/measurements so far--although I feel like the doctors are more or less throwing every possible idea at it until something sticks!
In the latest consultation the registrar said it was more like allergic eye disease not dry eye. However he dismissed allergy testing as not useful, likely to result in false positives or false negatives and just confuse. Meanwhile the consultant he brought in said evaporative dry eye - which is more consistent from previous people we've talked to. Clinical signs are mild MGD, diagnostic tests showed tbut 4s schirmers test 8mm corneal staining grade 1. The
cysts/follicles on inside upper eyelid are due to chronic irritation/inflammation according to registrar. Punctal plugs inappropriate according to registrar.
My wife is reluctant to start cyclosporin without more support and clearer diagnosis. But your advice is very gratefully received!

[mrunicorn]

I am also new to the forum and have ATD, MGD, severe allergies and sensitivities, ocular rosacea and corneal neuropathy. I have been wearing PROSE lenses since August and they are a wonder! Nonetheless, I still use a lot of other treatments including Restasis. Like your wife, I am highly sensitive to the ingredients in gels, drops and ointments and I tolerate Restasis well. I have found it helpful for reducing inflammation and increasing tear production. I won't say that it doesn't sting because it truly does but this passes after a bit. I just use the regular Restasis out of the box. Before PROSE lenses I used it 4 times a day but now I only use it twice a day. It took about 2 months before I noticed more tear production.

I hope this helps!

It does... thanks for your very swift reply!

[littlemermaid]

She has had numerous consultations with opthalmologists (although it has so far proved impossible to see her actual ‘official’ consultant, which is frustrating since he has published clinical research on dry eye treatments and diagnosis and is obviously an interested specialist—somehow even when he has ‘clinics’ in the hospital he is never actually there

I think I would write to him and ask for at least one appointment since he is the responsible consultant and she has been suffering so long and the treatment is uncertain. I've never understood this 'covering the clinic' business myself. I like the sound of your Registrar though. It must be difficult for them.

http://www.dryeyezone.com/talk/showt...t=cyclosporine Here's a thread on Moorfields Pharmaceuticals. Easy to contact Customer Services.

On paying for meds, if anyone wishes to join me, I am lobbying NHS Trust Pharmacy services to allow us to buy prescription drugs and eyedrops through them which are not covered by NHS at a fair price nearer the negotiated NHS rate (ours is interested and the CCG is very happy). Mainly so a hospital-standard Pharmacist is coordinating and checking our meds and keeping an eye on the docs for contraindications. This does, of course, open the floodgates for co-pay or no-pay

I haven't managed to get a Private prescription in an NHS consultation but if anyone has, please let us know.

[bookwoman]

I completely agree with NotADryEye about trying things in one eye first. Does your wife seem to have seasonal/pet mold allergies or just to products that she has tried to use in her eyes?

Why do you think that the plugs were set aside as an option? Dry eye considered too mild?

Also, you mentioned Rosacea is in the mix. Has anyone mentioned using doxycycline for your wife?

[mrunicorn]

two 3-month courses of doxycycline, 40mg and 100mg/day, and there was no improvement. No seasonal allergies, very basic allergy testing came back negative (including pets, pollen, mites etc). More like sensitivity perhaps, although there is an infinite number of things that could generate allergy! My wife has had rhinitis ('vasomotor or non-allergic' rhinitis, according to previous doctors) for a long time but never affected eyes before.
The registrar reckoned that plugs would result in constant tears 'running down your face'.
Not sure my wife has ever tried the one-eye-at-a-time trick! might be worth a go...

[littlemermaid]

Has the rhinitis ever been swabbed for bugs? or has she used a nasal steroid? http://www.dryeyezone.com/talk/showt...ighlight=sinus This thread has experience on how sinus and eye inflammation can be linked.

The registrar reckoned that plugs would result in constant tears 'running down your face'.

Is that his experience? We had improvement with lower plugs only. The upper tear drains still worked - you can test this by blowing your nose after fluorescein has been put onto eye surface for eye exam. Cool trick.

Recommend PubMed and registering for access to Medscape, if you haven't discovered these. NHS website - Clinical Knowledge Summaries and Clinical Guidelines - are pretty good these days too.

Some Ophthalmologists call the 'rosacea' version of allergy or sensitivity, 'type IV hypersensitivity' if you want to Google.

[mrunicorn]

Didn't really talk about the plugs much, they seemed to be dismissed quickly. Not sure, as ever, whether such comments are based on direct experience!

Viral swabs were done at the last consultancy, which at least might rule this out. I think the nasal steroids might be a risk because of the very extreme eye pressure reaction to steroid drops.

Thanks for the sinusitis link, some interesting things in the research literature that are worth looking at. Will report when I've digested some of it!

[NotADryEye]

Thanks! Here are some more details of various diagnoses/measurements so far--although I feel like the doctors are more or less throwing every possible idea at it until something sticks!
In the latest consultation the registrar said it was more like allergic eye disease not dry eye. However he dismissed allergy testing as not useful, likely to result in false positives or false negatives and just confuse. Meanwhile the consultant he brought in said evaporative dry eye - which is more consistent from previous people we've talked to. Clinical signs are mild MGD, diagnostic tests showed tbut 4s schirmers test 8mm corneal staining grade 1. The
cysts/follicles on inside upper eyelid are due to chronic irritation/inflammation according to registrar. Punctal plugs inappropriate according to registrar.
My wife is reluctant to start cyclosporin without more support and clearer diagnosis. But your advice is very gratefully received!

So many of us have had to deal with the same confusion and varying diagnoses. The thing is, they may not all be wrong. They may only be partially correct however. The propensity is to have numerous co-morbidities. When you finally seem to be getting somewhere, your faith in medicine will be restored. Until then, it is important to not give up hope.

Allergy testing is not all that useful because only some relatively narrow subset of allergens is ever tested. They will never be able to test for everything. With pollens they only test for common ones even though there can be all sorts of plants in your area producing pollens from anywhere in the world. And that's just pollens. No doubt, they don't test for allergies to demodex mites, but they do test for allergies to dust mites. Again, not so useful if you are allergic to demodex. And then there is the difference between allergies and sensitivities. Allergies can kill you. Allergists know about and treat these. But if your wife is just sensitive, which causes her no end of discomfort but doesn't kill her, then the allergists won't be able to help.

4 Schirmer's is low. Have we already asked about autoimmune conditions like Sjogren's or Hashimoto's thyroiditis?

Mild mgd can still be a lot of different things. It is like saying you have minor swelling. Is it obstructive mgd? Is there a bacterial component? Demodex? Sensitivities to food? A poor Omega 6 to Omega 3 ratio? All of the above? What did they say about the meibum? Probably it is not clear because later you tell us she was on Doxy. The course may not have been long enough. I'm on it daily, 20mg.

Rhinitis - sometimes it is best to seek care from a naturopath. They might suggest bee pollen, local of course. Easy, inexpensive and actually quite healthy, full of nutrients, if she can take the sugar, starting with 1/2 tsp per day for 1 week, then 1 tsp for a few more weeks. But always best to chase down each of these threads. Anyone might help just 10%. But 5 things helping 10% is 50%.

[mrunicorn]

Agree about the allergies, not really a direction we want to go in if it can be avoided because as you say there's an infinity of possible allergens and possible levels of response.

I'm looking into Sjogrens and Hashimoto's... We've tried various diet-based things without any visible improvement, similar to the doxy, but it was all worth trying. My wife takes enough omega 3 to heat a small town but I'm sure that has many advantages even if it isn't the answer.

Interesting about the bee pollen, I'll look into it. My wife has suffered the rhinitis for many years, at varying severity, so not obvious it is linked to the eye problem, but worth investigating.

thanks also for the encouragement--despite some difficult times we are keeping going, often thanks to these posts!

[littlemermaid]

I think the nasal steroids might be a risk because of the very extreme eye pressure reaction to steroid drops.

No, quite right. I'm wondering if she used nasal steroids or oral antihistamines for sinuses, and this might have brought on the eye trouble. I would not use inhaled steroid, and I do remember how her eye pressure was raised high after dexamethasone eyedrops (member Unicorn) Also a worry that Ophthalmology were not tracking her, and she only knew because she wisely got a high street Optometrist IOP check after starting, so good to have that professional backup.

My d. got periorificial rosacea after using the topical steroid hydrocortisone in Clotrimazole around the hairline for Tinea versicolor when she came back from camp (PubMed 'child steroid rosacea'). Concentration doesn't seem to matter if you are a rosacea-genotype responder. This formulation is now withdrawn. This can be a side effect even of asthma steroid inhalers. Obviously these are immune suppressants and the body has to reregulate after intervention with steroid (the reason for a steroid-tapering regime). In the literature, there are accounts of periorificial immunity changes like this with or without rash (eyes, nose, mouth, ears, even anus). Obviously the immune defence is specialised there against invaders. Just a line of enquiry. I'm trying to find a doc to help me think through how cyclosporine would readjust the immune system.

We are doing so well at the moment ~ please feel that once the regime is tweaked, her eyes will be so much more comfortable. Lots of good management ideas here, which are beyond what the NHS can offer. I think she was saying she has lubricant drops she is comfortable with? We've got members who are suffering on chemical eyedrops who are doing well on autologous serum, for example. Scleral lenses are getting easier to source even in UK. There are plenty of options for wraparound sunglasses and night protection to help keep the eye surface moist and support healing (Dryeyezone). We adjust different factors and it feels like a spiral of improvement rather than worsening.

Paediatric, our ophthalmologist feels that using lots of prescription eyedrops can make things worse for 'rosacea' types and he doesn't like courses of steroid eyedrops unless unavoidable, which it sometimes has been. In terms of allowing the immune system to reregulate itself, that sounds right to me. Obviously we fix anything that's a problem though.

Some people can't metabolise flaxseed oil and use fish oils. It was suggested in Rheumatology to stick with rebalancing the diet but eat good non-inflammatory oils and oily fish.

Might be worth looking again at side effects of any oral meds, inc 'natural' supplements, anti-anxiety, hormonal. So glad that you've found Dryeyetalk.

[bookwoman]

Plugs really helped me be able to tolerate other drops, gels and ointments. My Schirmers are 1 and 3 and I was ready to faint from the pain and was not sleeping for more than 2 hours at a time before I got plugs. Once things calmed down a bit we added serum tears and Restasis and I find serum tears very soothing. They compound them at various percentages but if your wife is hypersensitive to all artificial tears, perhaps they would consider 100% serum. I use 50%. Has she tried this option? Maybe she could try one plug in one eye, if she got the type that are easily removed if she has excessive tearing.

Is the pain severe enough to consider systemic pain management meds?

For me scleral lenses were the magic bullet, and I was able to try a pair of PROSE lenses for about 3 hours before we had to commit to any more treatment. I don't know how this would work in the UK. Would your wife consider trying these?