Preservatives in Eye Drops
Chat Highlights
August 7, 2002

Norma Devine, Editor

On Wednesday, August 7, 2002, Dr. Rick Wilson, a glaucoma specialist at Wills, and the glaucoma chat group discussed "Preservatives in Eye Drops."

Moderator:  Doctor Rick, what's in glaucoma eye drops besides the actual medicine?

Dr. Rick Wilson:  There are three parts to most drops.  One part is the medicine.  One part is the solution the medication is dissolved in, called the vehicle.  Most times the vehicle is an artificial tear drop solution.  The third part is a preservative to prevent the solution from becoming contaminated.  It is usually a chemical that is hard on bacteria.

Moderator:  Why do some drops have preservatives and others do not?  

Dr. Rick Wilson:  The only drops that do not contain preservatives are the ones in the daily dose packs, the small plastic dropperettes.  Some drops, like GenTeal, have a preservative that evaporates as soon as the drops hit the cornea and so are not as toxic as drops that have preservatives that stay around. 

P:  Are there disadvantages to drops with preservatives?

Dr. Rick Wilson:  Chronic use of drops with preservatives causes ocular surface toxicity and mild changes to the cornea and the conjunctiva.  That is why patients who have never used glaucoma eye drops do much better, on average, after glaucoma surgery than patients who have been on drops.  

P:  If one patient has never used glaucoma eye drops, another one has used them for five weeks, and a third one has used them five years, which patient has the best chance for a successful trabeculectomy?

Dr. Rick Wilson:  The more often and longer glaucoma drops are used, the less likely a trabeculectomy will be effective.  Now, with the use of mitomycin C, most often we can overcome that additional risk and still get a good effect.

P:  Are the preservatives the most likely cause of eye irritation and discomfort? 

Dr. Rick Wilson:  No.  The predominant cause would be an allergy to the medicine in the drop. However, individuals who are allergic to many different kinds of drops are often allergic to benzalkonium chloride (BAK), the most common preservative.  The concentration of BAK is important in causing toxicity.  Xalatan has 0.02% BAK, whereas Lumigan has 0.005% BAK, which is weaker than most.

P:  Today my glaucoma doctor said he stopped prescribing Lumigan because of the large percentage of his patients who could not tolerate the eye inflammation.  Have you had that experience?  

Dr. Rick Wilson:  Yes, I have had that experience.  I usually start with one of the other, less irritating prostaglandins, and if they don't give enough effect, I may try Lumigan.  That way the incremental increase in redness is not as noticeable to the patient.

P:  Do patients' eyes sometimes become more sensitive to the preservatives after prolonged use?  I did not have any redness at first, but now, after six months, my eyes are red and I notice an unpleasant burning sensation.

Dr. Rick Wilson:  Yes, it is possible to become allergic to a medication, even if you have been taking it for years.

P:  Then the side effects listed for glaucoma eye drops are caused by the medication itself, not the preservative?

Dr. Rick Wilson:  Yes, except for the possibility of allergy to the preservative, and the redness and irritation that the preservative can cause in some people.  The pH acidity/alkalinity of the drop is also important.  The closer the pH is to the physiologic pH,  the less problem it poses to the ocular surface.  Trusopt (5.6%) has the lowest pH, which is why it stings slightly more than some of the other drops.

P:  Is enough really known about the safety of the preservative Purite?  Some of us in this group had more side effects with Alphagan P than with the original Alphagan.  That is consistent with the results of clinical trials.  Only allergic conjunctivitis, narrowly defined, was less with Purite, at a statistically significant level. The only other ophthalmic trial I could find concerned Refresh Tears, and that trial  lasted only four weeks.  So what do we really know, I wonder?

Dr. Rick Wilson:  The other change with Alphagan P was that the strength of the solution was reduced from 0.2% to 0.15%.  That reduced allergies to the medication, and only minimally changed the effectiveness.

P:  I take it from your answer that you are satisfied with the safety of Purite, given what is known about it now.  Is that correct?

Dr. Rick Wilson:  I have not seen quite as many allergic reactions with it as I did with the regular Alphagan.  I don't know how much research was done before the FDA approval.

P:  Why do some drops still need to be refrigerated even though they have preservatives in them?

Dr. Rick Wilson:  Xalatan used to have a chemical that prevented the medication from leaking through the bottle.  It used to need to be refrigerated after opening to keep that chemical in solution with the medication.

P:  Is it no longer necessary to refrigerate Xalatan?

Dr. Rick Wilson:  That is what the sales representative tells me. [Editor's note:  According to Pharmacia, "Store unopened bottles of Xalatan under refrigeration at 36 to 46 degrees F. (2 to 8 degrees C).  Once opened, the 2.5 mL container may be stored at room temperature up to 77 degrees F (25 degrees C) for 6 weeks."]

P:  Why aren't more drops packaged in daily doses, or even weekly doses, so toxic preservatives are not needed?

Dr. Rick Wilson:  Because of the cost.  Timolol by Merck and pilocarpine by Alcon are packaged that way for those who are willing to pay, or need to pay, the extra money for all that individual packaging.

P:  What is the shelf life of drops after they have been opened?

Dr. Rick Wilson:  I discourage my patients from using drops for more than six weeks, because of the risk that they have become contaminated or lost their effectiveness.  It is not uncommon for the tip of the dropper to touch the eyelashes and the bacteria that grow on them.  After patients feel one drop hit the eye, they stop squeezing the bottle and a drop coming out of the bottle may be sucked back into the bottle.

P:  I have noticed an increase in eye irritation the closer I get to the sixth week of using Xalatan.

Dr. Rick Wilson:  Perhaps that is caused by a change in the concentration of the medication or more concentrated preservatives at the end of the medication's life.

P:  Would it help to shake the bottle before using the drops to prevent that possible concentration?

Dr. Rick Wilson:  No.   The concentration may come from one component of the drop evaporating faster than the others, causing concentration of the remaining components.

P:  You indicated that the preservative of choice was usually hard on bacteria.  Are there bacteria that reside naturally in the eye?  I realize that the main purpose of the preservative is to maintain the integrity of the medication.

Dr. Rick Wilson:  Yes, there are bacteria that live in the nooks and crannies of your eyes, as well as on the lashes and the many glands along the length of your eyelids.

P:  So is this medication hard on the natural bacteria of the eye?  Could it cause an imbalance of natural bacteria and perhaps explain some of the reactions to the eye drops?

Dr. Rick Wilson:  In the short term it might, but the bacteria soon get used to the preservative and repopulate the eye with bacteria that are more tolerant of the BAK or other preservative.

P:  What is the risk associated with bacteria getting into the drops?  Could the bacteria cause an eye infection or just reduce the effectiveness of the drops?

Dr. Rick Wilson:  It could cause an eye infection, especially if you have dry eyes or a corneal scratch (such as from using contact lenses), and break down the natural barrier into the eye.

P:  Many of us glaucoma patients seem to suffer from blepharitis.  Do you have any idea why that would be?

Dr. Rick Wilson:  I think maybe the medications or the preservatives may cause mild allergy or toxicity, which can close down the openings to the oil glands on the lid margins, which then get infected.  At least, that's my theory.

End of highlights for August 7, 2002.

On August 14, Dr. Wilson discussed "Second Opinions" in the Chat room. Click here for highlights of that meeting.

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