Comparative Toxicity of Preservatives in Ophthalmic Solutions

[Z351]

Also read some other crap that it can cause scar tissue in your eye, not sure I'm buying that one. Ah, jk im sure anything is possible.

http://cme.medscape.com/viewarticle/574777

Tha's not crap, I know that for a fact after a BAK induced ulcer!!!
And were at least two within Keratos to have this experience (since you don't trust studies).
I did use BAK for a long long time (10 years maybe, but small doses, maybe 2 months a year, do not exactly). In Portugal, there are very few or none preservative free drops whereas in France you do have more choice. Thanks to the people of Keratos I've been "travelling" to get better treatment.

It sounds like you are using a lot of BAK, anyway, wouldn't cyclosporin make sense to control part of the inflammation?
would'nt a non preserved steroid be better?
Isn't there preservative free cortisone in the US?

My advice: Don't drop the medications but do discuss this with your doc or another one and check for unpreserved options. So no on the spot paranoia but look ahead for alternatives.

[clairvoyant]

Yea, I'm backing off the BAK for a while cause I used a lot of that OmniPred over the last month. Then all the other drops too... cause like I'll totally douse my eye with the omni pred like 2 or 3 drops each eye then wait a few mins and drop some more lol. So I was probably doing like 12 drops a day some days and probably upward of 6 as I tapered down. I haven't done this blind though, I was in the doctors office a month ago and a week ago. They said cornea looked great a week ago but admitedly that foreign body I just expierenced yesterday has me a lil worried!

My eyes feel fine today since I didn't use any BAK drops before bed last night. Just gonna use azasite and restasis till I see my doctor again.

Here is the article I promised. Also did you notice in that CME article that they said the damage reveresed after stopping the BAK?

http://www.revophth.com/index.asp?page=1_97.htm

Is your ulcer chronic or did it go away?

[Scout]

MGD: I read your article, written in 2002. Even this article makes the point clear that those of us with dry eye syndrome are much more sensitive to the effects of BAK and anyone who is on more than one medication containing BAK is more sensitive to the toxic effects.

• Benzalkonium chloride. BAK is a quaternary ammonium compound that’s often used in conjunction with disodium EDTA. It’s a chemical detergent preservative that’s chemically stable, doesn’t degrade easily, even at high temperatures, and is very effective and fast-acting against many microorganisms. BAK acts upon microorganisms by altering cell membrane permeability and lysing cytoplasmic contents. It’s also been shown to increase the corneal penetration of some drugs by causing a separation of the epithelium.

BAK has been the gold standard of preservatives for years, and is the most common antimicrobial preservative currently used in topical multiuse ophthalmic solutions. Reports have shown that BAK can accumulate in ocular tissue, however, and can cause different types of cell death with frequent dosing.

It’s thought that patients at greatest risk for BAK-induced adverse effects are those suffering from dry-eye syndrome. Because of the lack of natural tears in these patients, the BAK in each eye drop is not as diluted as it would be in a patient with normal tear formation. This may damage the corneal epithelium, contributing to ocular surface disease. These patients may also overdose (use more than six drops per day), which increases the likelihood of BAK-induced adverse effects.

In my case, the effects of long-term use of an allergy drop with BAK did eventually improve. But it took close to a year (I had used the allergy drop with BAK for over two years).

[clairvoyant]

At concentrations and dosing used clinically, however, BAK doesn’t appear to have significant adverse effects unless its frequency of use exceeds four to six times daily.4 This becomes a concern when patients use other drops on top of chronic medications, such as glaucoma drops. It’s important to recall that preservatives themselves are bactericidal.

Additionally, patients with soft contact lenses must remove their lenses for 5 minutes to prevent the absorption of the medication into the lens.5

Clearly, BAK is a wonderful, safe preservative, since it’s been used for years. It’s important to note, however, that we need to be careful with its use in patients who are using several medications, are overdosing or have a history of severe corneal damage.

[clairvoyant]

Just as I said, 4-6 per day.

[Z351]

At concentrations and dosing used clinically, however, BAK doesn’t appear to have significant adverse effects unless its frequency of use exceeds four to six times daily.4 This becomes a concern when patients use other drops on top of chronic medications, such as glaucoma drops. It’s important to recall that preservatives themselves are bactericidal.

Additionally, patients with soft contact lenses must remove their lenses for 5 minutes to prevent the absorption of the medication into the lens.5

Clearly, BAK is a wonderful, safe preservative, since it’s been used for years. It’s important to note, however, that we need to be careful with its use in patients who are using several medications, are overdosing or have a history of severe corneal damage.

Just a small excerpts from your study:

"Reports have shown that BAK can accumulate in ocular tissue, however, and can cause different types of cell death with frequent dosing.

It’s thought that patients at greatest risk for BAK-induced adverse effects are those suffering from dry-eye syndrome. Because of the lack of natural tears in these patients, the BAK in each eye drop is not as diluted as it would be in a patient with normal tear formation. This may damage the corneal epithelium, contributing to ocular surface disease. These patients may also overdose (use more than six drops per day), which increases the likelihood of BAK-induced adverse effects.

Another French study, this one from 1999, investigated the action of BAK on epithelial conjunctival cells in vitro. Cell exposure to 0.1% and 0.05% BAK induced cell lysis immediately after treatment. All cells treated with 0.01% BAK died within 24 hours. The study’s results suggest that BAK induces cell growth arrest and death at a concentration as low as 0.0001 percent.3

Reports have shown that BAK can accumulate in ocular tissue, however, and can cause different types of cell death with frequent dosing.

It’s thought that patients at greatest risk for BAK-induced adverse effects are those suffering from dry-eye syndrome. Because of the lack of natural tears in these patients, the BAK in each eye drop is not as diluted as it would be in a patient with normal tear formation. This may damage the corneal epithelium, contributing to ocular surface disease. These patients may also overdose (use more than six drops per day), which increases the likelihood of BAK-induced adverse effects.

Another French study, this one from 1999, investigated the action of BAK on epithelial conjunctival cells in vitro. Cell exposure to 0.1% and 0.05% BAK induced cell lysis immediately after treatment. All cells treated with 0.01% BAK died within 24 hours. The study’s results suggest that BAK induces cell growth arrest and death at a concentration as low as 0.0001 percent.3"

your wonderful preservatives has caused me to have dry eyes and some central visual loss due to that ulcer that wouldn't heal (3 months, it eventually heal but nothing's the same after that, it's still fragile).

May i insist on:
"The study’s results suggest that BAK induces cell growth arrest and death at a concentration as low as 0.0001 percent."
So your cornea may be fine but this might not me the case for ever nor for everyone. We're not equal in terms of corneal healing/health.
It is a concern for DE and allergy sufferers (my case at the beginning, now both thanks to BAK).
Preservatives are bactericidal, sure, but the best way to avoid bacteria is still single use vials or specific containers that cannot be contaminated. So I hope you understand that I want those options for me, for you and all of us!

I had no history of corneal damage before I had the damage so how are you planning to prevent that problem? (I just don't mean that just for you but for anyone using BAK). Don't you think this might be a problem?

Look at those pictures they tell a lot

Remember that there are alternatives - single use vials or specific containers - for BAK and that's what we want.

When did your BAK escalade start, because it sounds like you're using a lot of drops a day?

[clairvoyant]

I've had dry eyes for like 4 years now. I was first put on alrex right when it started. Used a couple of bottles of that way back then. Then less than a year ago I started using pataday and azasite. And I probably used some lotemax peroidically. Used durazol for no reason though =o- that one I regret. That didn't have BAK though.

Then just recently 2 bottles of omni pred and some azasite/pataday. Oh and some xibrom. Think I am ok with the bak though cause it was used with steroids for the most part so it probably didn't have a chance to do any damage.

Maybe some are real sensitive to this but consider this- I fully trust both doctors who indicated to me that the BAK is fine. They are both experts in dry eye. I don't know about either of your situation's but maybe you are limiting your treatment because of this preservative?

If you have an ulcer from it though, you probably have to stay away from it but who knows. If you know you can't use it cause you have a really good doctor then you know. But I am pretty sure I am not to that point yet.

[Z351]

But I am pretty sure I am not to that point yet.

The questions remain: where does that point start?
wouldn't non preserved drops be better for everyone (including you)?
Most doctors supporting our petition are DE experts as well.

Keep you eyes open!

[clairvoyant]

I signed the petition. Sucks pataday has BAK and those other drops.

[Blinks]

Hi All,
Does anyone know of (or use) a Pataday equivalent without the cell damaging BAK preservative?
Not sure if it's equivalent but I've read about Catacrom preservative free single use vials by Moorfields but it doesn't appear to be available in the US. Thanks for any suggestions.
Blinks