Restasis: Worse Before Better?

[Guest]

Dear Rebecca,

...my point is that this concern should not be overrated or used to deny people a cure ... If the people in charge of approving treatments and medications were so overconcerned with safety, 90 percent of the medications on the market should be banned, including the LASIK procedure...

Very Expensive Drugs for rheumatoid arthritis and similar conditions caused tuberculosis, lymphomas and SJS in clinical trials and post-marketing experience but nevertheless are widely prescribed. I do not think that this shows a very high concern for drug safety. The explanation being that in many patients the benefits outweigh the risks. Why does this logic never apply to dry eye treatments?

You raise some interesting points Ringo. For example, for rheumatoid arthritis treatment, there does indeed seem to be a higher threshold for tolerating adverse effects in drugs used to treat this compared to dry eye. I think this is because most health care professionals/regulatory bodies see RA as a severely debilitating disease, and therefore believe the benefits of those drugs outweigh the risks.

In the case of dry eye, most people assume that it is no big deal. The debilitating effects of severe dry eye are grossly underestimated, therefore regulatory bodies will not tolerate much in the way of risk in the drugs that are approved for treatment. (This is just my assumption...)

In addition, because dry eye treatments typically are instilled into the EYE (no kidding, right?? heehee), I think regulatory bodies are extra paranoid in that they would not want to risk any potential damage to sight. (and rightly so - as bad as dry eye is, my one consolation is that at least I can see!)

Lastly, because we live in such a lawsuit-happy society, drug companies and regulatory bodies will tend to be extra cautious... Can you imagine if they approved a dry eye drug that ended up causing some other debillitating side effect (Ex. cancer) - someone would eventually sue the drug company, and a jury would probably side with the plaintiff because the jury would see dry eye as "no big deal" and therefore see the drug company as irresponsible to market a dry eye drug with ANY potential serious side effect.

It's a tough question... how much risk would we want to accept in a treatment for severe dry eye? And, if a more risky treatment were approved, will patients be adequately informed of the potential risks so that they can make an informed decision as to whether or not they wish to take on those risks?? As those of us who have had Lasik know, patients are often NOT fully informed of what the risks are.

Regarding the approval of 0.2% cyclosporine for animal dry eye - I think this higher strength would be tolerated by regulator for animals for the following reasons:
1) As much as us pet owners love our animals, to many people, they are "just" animals, and therefore more risk is acceptable in their eyes.

2) Most pets do not live nearly as long as humans, therefore there will be less concern with long term adverse effects.

As you may be aware, when cyclosporine is taken by mouth, there are major side effects (cancer anyone??). So far, they do not believe that topical cyclosporine eye drops cause cancer... but has anyone studied people who have used this med for DECADES?? I hope decades of use would not show any problems, but nobody knows, because no-one has used this drop for that long yet.

I will be starting Restasis myself in a week or so (I'm waiting for the pharmacy to get it in stock)... because I am desperate for relief, I will use it, even though I fear the long-term effects that might turn up later... I feel like I'm taking a gamble, and hope that I'll come out a winner... I'm hoping that since "it's the dose that makes the poison", this low dose in the drops is too low to cause any major problems decades from now.

Regarding whether or not it would be profitable for a drug company to find a cure for dry eye - I think the profit potential would be enormous. They would charge a heck of a lot more for a dry eye cure than they do for those artificial tears... plus, they could market the med to every person suffering from age-related dry eye... plus all of us refractive surgery folks (this number will only grow as time goes on), plus all the other usual dry eye patients (ocular rosacea, auto-immune diseases, blepharitis etc. etc....).

Anyhow... that's my 2 cents

Wow... this turned into a WAY longer ramble than I thought it would!

[ringo]

Hi Saag,

Completely agree that the debilitating effects of severe dry eye are grossly underestimated. And that being a reason for reluctance in accepting any risks with drug safety, however there are many eye drugs, including some routinely prescribed for dry eye that have serious side effects and can be even sight threatening.

While the substances I was referring to have never been shown to produce such effects through eye use.Yes, cyclosporine can cause cancer when taken intravenously in huge doses for long periods of time (for example in graft versus host disease).

But the drug has been shown, in a variety of concentrations for eye use (ranging from 0.05 to 0.5) to virtually have zero accumulation in the body (no traces of it in plasma, etc.)

Also, it has been shown to have no increased risks realted to developing eye viral or fungal or bacterial infections, or raising IOP-- while these are proven risks with even the mildest steroid drop. So it is much safer than other existing eye drugs....and in no way sight threatening.

The drug companies do not seem to be worried about being sued for the existing eye medications with very serious side effects....

Regarding cyclopsorine 0.2 being approved for animals-- i agree with what you mentioned,
but in the human clinical trials the only reason for not having 0.2 % manufactured was not related to safety-- the reason mentioned was that in humans both 0.05 and 0.2 produced identical efficacy on dry eye. This, according to my experience is grossly not true. According to the animal trials nothing below 0.2% showed any improvement; only probably slowed down deterioration.

I myself would prefer to use that and have dramatic improvement without any clinical proof of adverse effects rather than just cope on much more dangerous bunch of NSAIDs and steroids and antibiotics with proven serious side effects and god knows what else I have been prescribed, as my case was really severe (i lost my job and was hospitalized).

Regarding the profit from a dry eye cure-- you mentioned people will have to use it for decades....actually i meant a drug resolving the problem and thus not having to use anything any more. I do not think that would be more profitable than the current situation. Moreover, since the substances that can resolve dry eye in many of its forms are already well known, researched and even tried in clinical trials (and of course widely used for animals), they are not breakthrough new formula treatments, just like restasis wasn't. So charging huge amounts of money for them would not be justifiable.

Actually the best formula for profit is something like restasis, expensive and at the same time- just one fourth of the minimum dose that actually works, so you are hooked for life, as you said; not only on restasis, but on all other dry eye products, as you still need them with this low efficiency dose.So now you have all these patients you mentioned hooked for life on a ton of dry eye products plus restasis:every person suffering from age-related dry eye... plus all of us refractive surgery folks (this number will only grow as time goes on), plus all the other usual dry eye patients (ocular rosacea, auto-immune diseases, blepharitis etc. etc....), without anyone of them actually getting much better.

Since I started to use cyclosporine 0.2 i gradually stopped everything else ( I was using about 8 to 10 different medications into the eye and by mouth, including restasis).

Now I am spending around 20 times less money and effort, plus getting 100 times more comfort and actually not having dry eye most of the time.
Especially at night and in the morning when it was worst. I was actually waking up to apply ointments and drops just to get a bit of sleep. Now I sleep all the way and wake up with very comfortable eyes.

No swelling of the cornea or eyelids, no redness, so much less filaments its incredible, no burning, no pain, total resistance to air conditioning and computer use.

Clinical research has shown a few substances to be much more effective and rapid in action than cyclosporine in treating dry eye. Imagine all these patients dropping all their medications and getting so much better they hardly use anything. I do not see this as profitable for anybody except the patients, not even for the company that actually markets the cure drug, especially in the long term.

But because like you mentioned noone views dry eye as a debilitating disease (like rheumathoid arthritis for ex), noone would consider it worth losing their huge profits over resolving a simple "annoying irritation" like dry eye.

I have similar thoughts regarding treatments of other chronic diseases and flu medications and vaccines but this is another subject. Stem cell research for instance is being hindered in so many ways based on "ethical issues" by conservatives who hardly have any ethical dilemmas regarding so many appalling practices around the world that bring them huge money; when the real concern about stem cell treatments is that they will be a final solution to so many diseases whose current treatments for life generate enormous profits. Diabetes is only one of numerous examples of chronic diseases that can be cured by stem cell treatment.

I am just expressing thoughts-- i might very well be wrong and pharmaceuticals and drug approving authorities might be working primarily for the patients interests....it is just getting harder and harder to believe that, given the enormous scientific progress and research available and the lack of actual imrpovement for chronic disease sufferers.

It is also very hard to believe , given that the same conservatives who are concerend with patients interests, "safety" and other idealistic issues like "ethical" dilemmas, are the ones who are fighting against universally accessible healthcare and insisting on keeping health a commodity for the priviliged. How many people with chronic diseases have gone bankrupt because of healthcare bills?how many have been denied insurance because of existing chronic disease? how many have been given expensive treatments that actually trigger chronic disease without being briefed on the risks involved? how many pipeline breakthrough medications are being delayed for obscure reasons?

All that does not give me much trust into the people in charge concerned primarily with drug safety and patients' interests. Again, that is only my opinion and I hope I am wrong in suspecting health caretakers of putting profits before patients welfare.

[Guest]

I had to leave work early today, the eyes were bothering me way too much to make it through to 4:30... the right eye was getting the brown mucus like strands stuck on the cornea and it hurt like hell. Once I'm away from work and off the computer I feel so much better, not normal but much better... its always such a relief to get off work and away from the computer.

I'm sorry to hear that you're having such a rough time with the Restasis Aaron... it's got to be tough having to use the computer all day at work while trying to cope with dry eyes. Hopefully things will improve in a major way for you SOON! Keep us posted!

[Guest]

Hi Saag,

Again, that is only my opinion and I hope I am wrong in suspecting health caretakers of putting profits before patients welfare.

Well, there's good and bad in everything right? It sucks when we suspect that the bad is effecting us personally... and reading about what you've gone through with your eyes (it sounds horrendous... seriously, just awefull!), I can only imagine your frustration, since it sounds like in your situation you would have considered much of the risk in the treatments you've researched as an acceptable trade-off for relief from the condition you were in!

[ringo]

Thank you SAAG,

it is so nice when someone like you shows so much understanding that a person who is suffering can be quite willing to trade off "long term potential" and "remotely probable" risks for obtaining some long-sought relief and actually returning back to at least being partially functional.

Dry eye affected my life in so many ways-- it damaged my professional life, my personal relationships, made me clinically depressed and at some point made it virtually impossible for m to perform the most elementary daily tasks, with noone really being able to understand what pain i am going through.

In my case, i had to be prescribed drugs that can have immediate serious adverse effects, for ex. steroids causing significant intraocular pressure rise which actually happened to me but was reduced with dosage adjustment; the adverse effects of NSAIDs on the compromised cornea of dry eye; the preservatives in all of these; the nasty side effects of the pilocarpine tablets; the doxy side effects; etc etc. , i experienced it all. The only thing that seems to produce no adverse effects is the cyclosporine 0.2%. And like i said, it was not manufactured for humans for the only reason that it was supposed to have the same efficacy as the lower concentrations.

So I always feel frustrated when the issue of some unproven very long term side effects from this drug always gets raised over and above the great benefits it has.I have only been using it for a month now.... i can't even start being concenred with some long-term no clinical evidence adverse effects. I am much more concenred about my intraocular pressure being measured every couple of weeks coz of steroids and the integrity of my cornea checked at the same rate coz of NSAIDs and BAK; or my fertility being affected by pilocarpine tablets, not to mention the excessive dehydration it causes, just for the sake of producing a little amount of extra tears.

So you can see the real and immediate threat to my eyes is presented by very well approved and widely used drugs, not by cyclosporine 0.2%.

Thank you for your understanding and support

[Aaron77]

Ringo, not enough eye strength to read everything that was said here but could it be that its simply the optimune delivery vehicle thats helping your eyes and not the cyclosporin? My eyes are killing me since starting Restasis, they burn bad. Not going to make it much longer, hopefully the opthamologist has something to improve my situation next time I see him otherwise I'm going to have to be declared reading disabled.

[ringo]

Dear Aaron,

when I started the Restasis it was burning me awfully, doctor said it is because the vehicle castor oil burns especially inflamed eyes. He gave me Akular which is NSAID drop to put in around 5-10 min befor instilling the restasis. It helped, but Akular itself was burning, though it was only transitory for a few seconds.I could not feel the restasis after putting the Akular.

Doctor said for those who have too much pain from the Akular itself there is weak steroids like Lotemax or FML to help with the burning in the initial phase of Restasis (6 weeks).

I am sure that what is helping me now with optimmune is the higher concentration of cyclosporine and the fact that, as the vehicle is an ointment, it stays long on the eye, especially at night.

Hope that helped. Please do not give up on the cyclosporine, whether in restasis or optimmune. If you can't tolerate either, a compounding pharmacy can dissolve it for you in oil (like corn oil) as a vehicle. This does not hurt the eyes at all and is much cheaper than restasis or optimmune.

After all,cyclosporine is the only drug proven clinically to target the clinical signs of dryness and the dryness inflammatory cascade (by inflammatory cascade I mean the cycle of inflammatory cells activation involved in inflammation caused by dryness). In my experience, it was extremely hard to cope with my treatment regimen, but perseverance paid off.

I wish I can be of more help. Please let me know how you are doing.Wishing you success,

[Aaron77]

Saw the opthamologist on thursday, in addition to the Restasis he gave me a prescription for doxy 100mg/d, erthromycin, FML drops for 3 weeks and stressed the importance of warm compresses.

[ringo]

Dear Aaron,

Thank you for the update. I think that the regimen you are prescribed will help, I was prescribed the same in addition to a few other things and it did work to some extent, I mean after a certain time (for me it was more than 3 weeks), I felt much better than what i was initially. And initially I was in an extremely bad condition.

Also, the combination of FML and doxycycline was given to me because of the erosions I had. Do you also have erosions? If you do, these medicatoins and the ointment can cure them.

I am still on the cyclosporine ointment and every day things are getting better at a rapid pace ( i mean rapid compared to all else I have tried). Like today is better than yesterday, and actually it is the best day I have had in more than 4 years. I managed to watch the movie Case 39 in a strongly air conditioned hall without putting a single artificial tear drop. Just a couple of months ago going to the cinema was like a death sentence to me. I can hardly believe this development and thank God for the relief.

Just wanted to thank you again for mentioning this medication.It truly changed my life.


since there is a serious inflammation involved in dry eye, unfortunately any real relief or treatment cannot be achieved without targeting the inflammation element of the disease.So there is no escape from the steroids and the immunosuppressants... i am trying to think like-- ok , so i am like all these people with chronic diseases who are hooked on serious medications. I am still trying to come to terms with it.

Please let us know how you are doing on your new medications. I hope they will work for you and you won't need to turn to "unusual" therapy like I did

[Aaron77]

Saw the opthamologist on thursday, in addition to the Restasis he gave me a prescription for doxy 100mg/d, erthromycin, FML drops for 3 weeks and stressed the importance of warm compresses.

My eyes feel worse since starting the FML, much harder to sit in front of a computer and the vision gets blurry much faster.

[Guest]

Aaron, I wonder if you should consider going off work for a month or two... would you qualify for EI benefits?

I was just thinking that perhaps if you were able to be home, in a humidity-controlled environment, without having to stare at a computer all day, it might give the Restasis and FML etc. a better chance at working.

Having to dry your eyes out every day looking at the computer at work surely must be decreasing the chances of any treatments helping, right?

I was posting on Dr. Trattler's forum, and he mentioned something about Restasis not working very well if you have a lot of inflammation that is poorly controlled... maybe this is your problem? and therefore maybe going off work (if you can) would help get you over this hump.

[Aaron77]

Aaron, I wonder if you should consider going off work for a month or two... would you qualify for EI benefits?

I was just thinking that perhaps if you were able to be home, in a humidity-controlled environment, without having to stare at a computer all day, it might give the Restasis and FML etc. a better chance at working.

Having to dry your eyes out every day looking at the computer at work surely must be decreasing the chances of any treatments helping, right?

I was posting on Dr. Trattler's forum, and he mentioned something about Restasis not working very well if you have a lot of inflammation that is poorly controlled... maybe this is your problem? and therefore maybe going off work (if you can) would help get you over this hump.

Already took over half a year off. Not back at my old job which would require some intense reading, if I take any more time off my company will probably cut me loose for good.

My opthamologist tells me there's no inflammation in my eyes and that my eyes don't look overly dry. Why treat the inflammation if there is none there?

[Aaron77]

Funny thing, when my eyes seem to burn the most my nose also starts to burn.

Opthamologist also said I have minor signs of rosacea, but only after I asked him about a possible connection.

[mylittlem]

Arron,

I understand entirely your position. I too have been out of work and there is no longer any chance of returning. In addition I share the experience of being told the inflammation and glands don't look bad, but there is no explanation for the constant pain and discomfort. How could a person be totallly unable to work yet be told "... things don't look too bad..." ?? I truly don't believe the doctors understand this condition and worse still the medical community does not seem to believe that this most certainly can be disabling.

[Guest]

Already took over half a year off. Not back at my old job which would require some intense reading, if I take any more time off my company will probably cut me loose for good.

My opthamologist tells me there's no inflammation in my eyes and that my eyes don't look overly dry. Why treat the inflammation if there is none there?

Does the Restasis seem to bother your eyes less on your days off (ie. when not on the comp?) Mind you, 2 days away from the comp may not be enough recovery time to notice a difference... but I thought it was worth asking...

Regarding your company cutting you loose for good if you take any more time off... perhaps this is naive of me, but, if you went on EI for disability reasons (I certainly think the severity of your dry eye, combined with the requirements of your job to use the comp, would qualify you!), your company cannot legally cut you loose, correct? Would your doc agree to recommend you take some time off for medical reasons?? Maybe you've already looked into this...

If there is ANY chance that you could get your life back by taking some time out to just concentrate on the Restasis/FML drops/other treatments without stressing your eyes by being on the comp all day... it is SO worth considering...

Worst case scenario, if your job DID cut you loose, could you survive it financially? Would you be able to get another comparable job in your field if you needed to?

Anyhow, one way or another, you'll get through this! Hang in there!