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Comparative Toxicity of Preservatives in Ophthalmic Solutions

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  • Comparative Toxicity of Preservatives in Ophthalmic Solutions

    http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum
    J Ocul Pharmacol Ther. 2009 Apr;25(2):113-9.

    Comparative toxicity of preservatives on immortalized corneal and conjunctival epithelial cells.
    Epstein SP, Ahdoot M, Marcus E, Asbell PA.

    Department of Ophthalmology, Mount Sinai Medical Center, New York, NY 10029-6574, USA. seth.epstein@mssm.edu

    PURPOSE: Nearly all eye drops contain preservatives to decrease contamination. Nonpreservatives such as disodium-ethylene diamine tetra-acetate (EDTA) and phosphate-buffered saline are also regularly added as buffering agents. These components can add to the toxicity of eye drops and cause ocular surface disease. To evaluate the potential toxicity of these common components and their comparative effects on the ocular surface, a tissue culture model utilizing immortalized corneal and conjunctival epithelial cells was utilized.

    METHODS: Immortalized human conjunctival and corneal epithelial cells were grown. At confluency, medium was replaced with 100 microL of varying concentrations of preservatives: benzalkonium chloride (BAK), methyl paraben (MP), sodium perborate (SP), chlorobutanol (Cbl), and stabilized thimerosal (Thi); varying concentrations of buffer: EDTA; media (viable control); and formalin (dead control). After 1 h, solutions were replaced with 150 microL of MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazonium bromide). After 4 h, solutions decanted, 100 microL of acid isopropanol added, and the optical density determined at 572 nm to evaluate cell viability.

    RESULTS: Conjunctival and corneal cell toxicity was seen with all preservatives. Depending upon concentration, BAK exhibited from 56% to 89% toxicity. In comparison, Cbl exhibited from 50% to 86%, MP from 30% to 76%, SP from 23% to 59%, and Thi from 70% to 95%. EDTA with minimal toxicity (from 6% to 59%) was indistinguishable from SP.

    CONCLUSIONS: Generally, the order of decreasing toxicity at the most commonly used concentrations: Thi (0.0025%) > BAK (0.025%) > Cbl (0.25%) > MP (0.01%) > SP (0.0025%) approximately EDTA (0.01%). Even at low concentration, these agents will cause some degree of ocular tissue damage.

    PMID: 19284328 [PubMed - in process]

  • #2
    A presentation at ARVO stated similar findings. The excuse docs give for not being more forceful with patients is: "patient wants the cheapest eye drop." I think patients deserve to know what's bad for their eyes. then if they choose they can continue to use a product that doesn't help. But the doctor should inform the patient.

    Comment


    • #3
      Originally posted by Scout View Post
      Even at low concentration, these agents will cause some degree of ocular tissue damage.

      PMID: 19284328 [PubMed - in process]
      And we don't need that (tissue damage), do we?
      Another good reason to sign this online petition:
      http://associationgeniris.free.fr/in...joomlapetition

      Everyone may sign as said elsewhere.

      Comment


      • #4
        Very informative Scout -thanks !
        However it leaves me ,and everyone else using Dr Holly's drops with a problem
        They are preserved - I quote from Clinitas ultra 3 - polyquaternium 42 and disodium edetate
        I understand that these are minimally damaging and also have anti microbal qualities which is good
        I DO hope so as i intend to use them indefinately
        Anyone any comments or better still reassurance that they are OK ???

        Comment


        • #5
          I think I can answer my own questions ----

          I looked up the question i asked Dr Holly back in October about EDTA and my concerns about it
          I did not realize he had replied in January
          His reply was very reassuring You can look it up under Q and Answers Dr Holly
          Basically he says it is harmless - a chelating agent which helps enhance the preservative which is polyquaternium in clinitas

          Then i looked up his answer to Rebeccas question on the differece between polyquaternium and polixetonium (basically the same preservative )
          THAT was very reassuring (you can read the whole thing if you put polyquaternium into the search box - that will get you Rebeccas question )
          He says amounst other things that polixetonium (polyquaternium) is - a highly effective anti-microbal that does'nt damage the ocular surface or tear film with long term use
          It is used as a contact lens disinfectant to facilitate wetting of the surface to make it more comfortable
          Well thats good enough for me !

          I hope this reassures the other worried users of Dr Holly's drops It has reassured me and i do intend to use it indefinately

          Comment


          • #6
            Originally posted by Scout View Post
            EDTA with minimal toxicity (from 6% to 59%) was indistinguishable from SP.

            CONCLUSIONS: Generally, the order of decreasing toxicity at the most commonly used concentrations: Thi (0.0025%) > BAK (0.025%) > Cbl (0.25%) > MP (0.01%) > SP (0.0025%) approximately EDTA (0.01%). Even at low concentration, these agents will cause some degree of ocular tissue damage.

            PMID: 19284328 [PubMed - in process]

            Minimal toxicity doesn't mean none. I prefer to use preservative free vials in any case. But obviously if you compare other preservatives with BAK then you'll find it's always much much worse.
            http://preservative.free.fr/English/consequences-per-preservative.htm
            http://preservative.free.fr/English/...servatives.htm

            You'll find some references to EDTA. Maybe we could start by banning BAK...
            don't forget to sign our petition.

            Comment


            • #7
              I wish i did not know about those experiments posted by Z351!

              Why would someone as intellegent and respected as Dr Holly include anything in his drops that would harm the eye surface?

              What is someone like myself supposed to do - --
              I have finally found an effective eye drop that gives me relief and now i am told it could be harmful to my eyes ????

              Who do i believe ?
              Dr Holly or these researchers ?

              Any comments gratefully recieved

              Comment


              • #8
                I think I read somewhere that as long as you don't do more than 4 drops a day of it you are fine. (bak that is)

                Also if you think about it, if it is in steroids then it will likely be negated from the healing iniated by the steroids.
                Which is it? Is it what you know or who you know? Or is it how well you convey what you know to who you know it to?

                -Tim

                Comment


                • #9
                  what's the source of information

                  Check your sources (i've read that many times on industry websites and the opposite from the research). If it's the industry saying that then maybe you shouldn't trust them. from what I've read BAK is bad news from drop ONE, of course drop two if worse, and so on.

                  "Depending upon concentration, BAK exhibited from 56% to 89% toxicity."

                  And it all depends on the state or your cornea and individual aspects (healing etc). I react to the first drop. Stella's doctor is probably the only person who may give competent advice knowing the state of her corneal surface, etc.

                  Remember that BAK is a detergent so it destroys the lipid layer from drop one.

                  Comment


                  • #10
                    I have re-read the discusion and comments on polixetonium/polyquternium-42
                    as found in Dr Holly's drops and realize to my relief that Dr Holly says polixetonium/polyquaternium-42 is "not to be confused with Alcons polyquaternium -1"So to come back to these researchers - It is probably polyquaternium - 1 they are talking about

                    Another name for polixitonium according to Cindy, is Busan 1507

                    It is very confusing for the unscientific lay person

                    As for BAK --- I would'nt let it anywhere near my eyes !

                    Comment


                    • #11
                      Additional info

                      Hi Stella if you want to perfect your knowledge on preservative synomyms, here's a page for you, but Cindy's right:

                      http://preservative.free.fr/English/...n-eyedrops.htm

                      I asked the guy who knows more about this within Keratos, and he told me that:
                      - regarding the 4 daily dose even the industry "sends conflicting messages, have a look at the comparative study done by Allergan after seven days of use: http://preservative.free.fr/Images/N...comparison.jpg. Obviously damage is proportionnal to dosage, frequency and individual factors but it starts with the first drop.".

                      I you want to look for yourself, there are also listed studies on EDTA on the same site but there are "no studies on polexitonium to support innocuity or eventual danger".

                      On EDTA, a researcher, Dr Dhouailly, that support Keratos and the ban has sent us "a letter regarding her experience with EDTA but the English letter was not uploaded yet. I'll keep you posted."

                      As a friend of mine usually says: "with dry eyes, either you become your own expert or miraculasly get better... or you're *******".

                      My advice is then become the expert

                      Comment


                      • #12
                        I use to think bak was bad too.

                        I was just as paranoid as you but truthfully it is not as bad as advertised. Those other preservatives are bad too but as long as you limit your use to say 3 a day you should be fine.
                        Last edited by clairvoyant; 13-May-2009, 19:43.
                        Which is it? Is it what you know or who you know? Or is it how well you convey what you know to who you know it to?

                        -Tim

                        Comment


                        • #13
                          Z 351
                          As a dedicated member of Keratos , i appreciate that your prime concern is a campaign to get rid of ALL preservatives in eye drops -- and that would help us all on this site , however i do think you should be careful not to alarm those of us who are very vulnerable 'cos of our DES over issues we do not properly understand because we are not scientists in this field
                          After all it is not as though we have any choice in many instances -----
                          In my case if Dr Holly's drops were to come on the market unpreserved - of course i would rather use those - until that happens i have no choice but to use the preserved drops, and hope and pray they will do no damage

                          Comment


                          • #14
                            Originally posted by stella View Post
                            Z 351
                            As a dedicated member of Keratos , i appreciate that your prime concern is a campaign to get rid of ALL preservatives in eye drops -- and that would help us all on this site , however i do think you should be careful not to alarm those of us who are very vulnerable 'cos of our DES over issues we do not properly understand because we are not scientists in this field
                            After all it is not as though we have any choice in many instances -----
                            In my case if Dr Holly's drops were to come on the market unpreserved - of course i would rather use those - until that happens i have no choice but to use the preserved drops, and hope and pray they will do no damage
                            MGD: you don't know how someone else's cornea really is... so how can you be sure it'll be fine using BAK 3 times a day?

                            Stella: My ONLY purpose is to inform everyone and find a way to have non-preserved options for all of us. I have nothing to gain from alarming for the sake of alarming but there's a thin line between sharing what worries you because of what you read about it and possibly alarming people as a side-effect; Besides, Is not knowing something so reassuring?

                            Consider my posts as general considerations on this issue and avoid reading them if need be, but I feel these opinions have the right to be expressed in such a forum, don't they?
                            I never told anyone to change his treatment, nor indicated anyone what do to (use this, this is fine and this isn't).

                            Comment


                            • #15
                              I accept your explanation and reasoning

                              I have already signed the petition to get rid of preservatives in eye drops and do hope it will put pressure on the drug companies concerned
                              Keep up the good work
                              Stella

                              Comment

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