February 12, 2025 • 30 mins
As preservative-free eye drops become more common, one has to wonder why it is so important to reduce our use of preservatives. What kind of toxicity do preservatives wreak on the eye? And without preservatives, are eye drops still as effective and resistant to infection? Especially in the realms of dry eye and glaucoma, how have preservative free drops started to change the landscape, and what can we expect moving forward? Denmark's Dr. Miriam Kolko joins the podcast.
This episode is sponsored by Thea Pharma Canada - https://www.theapharma.ca
Become a supporter of this podcast: https://www.spreaker.com/podcast/blind-spot-the-eye-doctor-s-podcast--5819306/support.
This episode is sponsored by Thea Pharma Canada - https://www.theapharma.ca
Become a supporter of this podcast: https://www.spreaker.com/podcast/blind-spot-the-eye-doctor-s-podcast--5819306/support.
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Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Speaker 1 (00:11):
Hey everybody, I'm Zaio Medni can Welcome to blind Spot.
This episode is sponsored by THEA Pharma Canada. THEA Pharma
Canada is the Canadian subsidiary of THEA, Europe's leading pioneering
and innovative eye health brand. Founded in nineteen ninety four
by Henri Chibra. With five generations of history, the Chabrat
family has been dedicated to I care for more than
(00:32):
one hundred and fifty years. Their commitment to improving lives
is born of their pioneering spirit. They continue to lead
the worldwide preservative free movement in I care. They've created
innovative delivery systems and they focused on making products accessible
and cost effective for patients. They live this mission every
day because everyone should have the same opportunities to see
the world through healthy eyes. Thank you THEO Pharma Canada
(00:54):
for supporting this podcast. For many years, it was the
status quo that preservatives were part of the eye drops
that patients put in their eyes, But over the last
several years that has changed as a preservative free movement
has grown. So why did we use preservatives? And how
toxic are preservatives for our eyes? How important is it
(01:15):
to transition from preservative based eye drops to preservative free
eye drops.
Speaker 2 (01:19):
What are the.
Speaker 1 (01:20):
Benefits and what are some of the challenges in changing
to preservative free medications. To discuss this topic, I'm joined
by doctor Miriamkalco. Doctor Colco is professor at the University
of Copenhagen. She's also a chief physician and glaucoma specialist
at the Copenhagen University Hospital. She's President of the Danish
Glaucoma Society and holds several board positions including member of
the main board of Fight for Site Denmark, Danish Glaucoma Society,
(01:43):
carln Nikolain Larsen Foundation, and Marite and La Fontaine Foundation.
In twenty twenty one, Professor Colco was named one of
the one hundred most influential female ophomologists in the world
and top point one two percent of scholars writing about glaucoma.
At the University of Copenhagen, Professor Colco is part of
the Leader team as head of Section. In addition, she
is heading her research group I Translational Research Unit. The
(02:05):
research concerns translational and clinical research and seeks to improve
the understanding and management of glaucoma She's received almost eight
million euros in funding. Is co chair of the Neuroprotection
SIG in the European Glackhoma Society and member of the
European Glaucoma Society Membership and National Society Committee.
Speaker 2 (02:22):
She's one of the few.
Speaker 1 (02:22):
Clinician scientists worldwide that bridge between a clinical career with
medical and surgical treatments of site threatening diseases and research
that seek to improve I health. All right, doctor Cole,
welcome to the podcast. Thank you so much for joining me.
I'm self conscious because I know that I did not
pronounce your name right there.
Speaker 2 (02:38):
How do you do you pronounce your name correctly? Tell
me again?
Speaker 3 (02:42):
I I don't know an English but I would say Culco.
So I think that was actually pretty good what you did.
Speaker 2 (02:47):
Okay, we'll go. We'll go with that. Thank you so
much for joining me.
Speaker 1 (02:52):
We're gonna be talking about preservatives today, and this really
fits in the scheme of what blind spots about, kind
of looking at something that we think we know about,
which is a general paradigm, the status quo of what
we've been doing, and for a long time, preservatives were
a part of that status quo.
Speaker 2 (03:09):
All the drops we used were preservative based over.
Speaker 1 (03:13):
The last I don't know how many, fifteen twenty years,
there's certainly been a movement that's increasing in its intensity,
moving towards preservative free and we're going to talk about
that today. Before we do that, though, I want to
have a better understanding of preservatives in general. Why did
we use them for so long? What's the benefits of preservatives?
(03:34):
And as I say that, I realize on the surface
it's a basic question because they preserve drops, But why
have preservatives been a mainstay for so long? What do
they do that's positive?
Speaker 3 (03:47):
Well, certainly they kill bacteria, and that's also a good
reason for actually having had preservatives so long. So fifty
years ago the eye drops were produced with preservatives so
that we did and get infection using eye drops. So
in that sense, it's been very reasonable to actually add
preservatives into the eye drops. They do still kill bacteria,
(04:09):
so in that sense they are pretty effective. However, they
also kill all the cells, and that's what we're going
to talk about today. I assume, yeah.
Speaker 1 (04:20):
In addition to killing bacteria, does it also just allow
drops once you open a bottle with traditional bottles. Before
we get into some of the newer dispensing bottles. Would
it allow an eye drop bottle to last longer by
having preservatives once you've opened it?
Speaker 3 (04:35):
Well, not really actually, when we look at the market
today and the choices that we have, so the duration
of the eye drops are not really affected by preservatives
because that there has been so much development. However, you
could say that preservatives in some way will stabilize the
active compound. So it can be tricky to produce or
(04:56):
develop a preservative free option, but so you could say
the preservatives they prevent a bacterial growth, they can, and
so in certain cases actually stabilize the active component, the
active drug. And then there has been a discussion about
the penetration of the active drog is that better when
you use preservatives, And no matter whether this might be
(05:20):
true in a way that it can break down cell
membrane and thereby introduce more drug into the deep a
lying tissues, we have not seen any clinical relevant differences
in the efficacy in preservative free and preserved eye drops.
Speaker 1 (05:34):
So in the past it sounds like these are more
important things. But as we'll get to you, as the preservative
free drops and delivery systems have gotten better, those problems
have somewhat been negated to an extent where those benefits
don't necessarily stack up to what they used to be.
Speaker 3 (05:52):
Yes or no. So in fact, it is important to
understand that preservatives can stabilize the active component. Means that
if you have a preservative free option and you then
get a generic option, you really need to test the
efficacy because it might rely on the preservatives. So I'm
(06:13):
definitely not arguing that we should use preservatives in any way.
I think that we should use preservative free options whenever
it's possible, But there is something to consider when you
consider activity and how stable the active drug is.
Speaker 1 (06:31):
Before we get into preservative free, I want to understand
a little bit more about the toxicity and the issues
that preservatives did cause that led to this preservative free movement.
First of all, what are some of the most common preservatives?
I know back is one that is I commonly heard
when I was in residency, But it's been a while
since residency, and I'm sure listeners don't necessarily even know
(06:53):
what these preservatives are and how many are really common
in the preservative based drops we use.
Speaker 3 (06:59):
Yeah, so when we talk about preservative free drops, I mean,
for my case, I have been mostly focusing on antiglo
coomatist drugs or eye drops, but also artificial tears that
we can talk a little bit about. If we start
out with the anti glocomatis eye drops, which are the
major treatment for glocoma patients, then the bentyl conin chloride
(07:23):
or back as you say, is the far most commonly
used preservative, but there are other preservatives that are actually
having less toxicity compared to bentyl conin chloride, And one
to mention could be polyquot which is actually also in
quite a few of our eye drops.
Speaker 1 (07:41):
And give me a little bit more scope you alluded
to it before about just what they are doing negatively,
Is it ocular surface that we're really concerned about when
we're thinking about the damage that can be wreaked by
these preservatives.
Speaker 3 (07:55):
Obviously the ocular surface is a major issue, and let's
let's start there. But unfortunately it's not only the ocula surface.
It's also been shown that the preservatives are penetrating to
deeplyning tissues such as the tubacular messwork, and accumulation in
a turbacular messwork may cause fibrosis and actually a lesser
(08:18):
degree of filtration of the aquis humor, so there are
many other issues to consider. Also, it's been shown to
accumulate as far back in the iris in the retina,
but the ocula surface is right at the spot of
introducing the preservatives, so obviously we see a lot of
side effects on the oculo surface. So yes, let's definitely
(08:40):
focus on that, but not forgetting that it's not only
the ocula surface that we should actually be worried about.
Speaker 2 (08:48):
The irony. Of course, there is a lot of these drops.
Speaker 1 (08:50):
Especially you're a glaucoma specialist, You're saying a lot of
these drops that are used to treat glaucoma could actually
be to an extent making it harder to treat glaucoma.
If there's two s beecular meshwork damage being induced by
these very drugs that are supposed to in stiltration or
reduce the pressure. In terms of the ocular surface, walk
me through that. How does it damage the ocular surface?
(09:12):
Is it simply and I don't want to say simply
to diminish it, because I'm a corny specialist and I
see dryness a lot. But is it simply dryness or
is it also the risk of limbal stem cell disease?
What's really going on and what is the concern with
the ocular surface.
Speaker 3 (09:28):
Well, I think that it's it's both. So we are
dealing with a toxin. And if we start with benzel
coniu chloride, it's quite toxic. And if you are looking
at the bottles with benzel conium chloride that people would
use in a laboratory for experimental research, then it will
say this is dangerous and if you if you get
it into or near the eye, you need to wash
(09:49):
you out carefully. Right, So this is a toxin in
first place, and it's been shown in various pre clinical
studies that that benzilconium chloride is actually killing OLKLOS surface
cells such as the epithelial cells, the goblet cells in particular.
So my research group have worked very much with the
goblet cells, so they killed the OClO surface cells. And
(10:14):
if we think about the goblet cells, they're very important
in producing mucin, which is a highly important component of
the tear film. So it might also affect the mypomean glands,
so it might also affect the lipid component and the
til film. So in general, the toxicity based on the use,
(10:35):
the chronic use of pensyl conia and chloride may actually
kill cells and glands that are essential for a good
tear film.
Speaker 1 (10:46):
That's a really good explanation of it. A typical paradigm
I've used when I speak to patients, and maybe this
is wrong, and I have a feeling.
Speaker 2 (10:54):
It probably is.
Speaker 1 (10:55):
Is I see the people because preservative free artificial tiers
are more expensive, and they say, what should I use?
I say, you know what, if you're only using it
three four times a day, I'm okay with you using
preservative based medication. It's cheaper, it might be a little
bit easier for you to access. And I'm not so
concerned as you say that, though I realize, well, I
(11:17):
could be doing some damage with those preservative based tiers,
because even if they're not using it so much and
they're not putting so much preservative in their eye, I
don't know exactly what that balance is between you're getting
good artificial tier in, but you're also getting preservative in.
Speaker 2 (11:32):
How do you look at artificial tiers in that way?
Speaker 1 (11:34):
And I will qualify what I just said by if
I see they're already on a bunch of other glauckhoma drops,
some of which might have preservatives I'll certainly be more
incentivized to say, let's definitely stay away from preservatives in
your artificial tiers, because you could just be.
Speaker 2 (11:49):
Compounding the problem.
Speaker 1 (11:50):
But in someone with just run of the mill dry eye,
how important is it to say, yeah, even if you're
just using it three four times a day, it should
be preservative free.
Speaker 3 (12:00):
Well, first of all, I would never ever ever argue
that it's okay to use preservative containing artificial tears in
patients that are having ouglar surface issues, even not once
a day, So I think three to four times is
a lot. Having said that, it is also depending on
what preservative. So some preservatives, for instance, bensal cornium chloride
(12:24):
is very toxic, whereas public quad has been shown to
be less toxic. So there is differences in the different preservatives.
Now I would not use the preservative in any way
in any circumstance, But again there's also a matter of
how high concentration of the preservative is actually in the
artificial tiers. So some have very low concentration and others
(12:48):
they have much higher concentration, and the toxicity of the
preservatives that's concentration dependent. So the more eye drops you use,
so the more times you use it a day, the
higher concentration you have of the preservative, the worst it
is for the okolo surface. But honestly, I have no
idea why it's even allowed to put a preservative in
(13:13):
a treatment that's going to treat the oculo surface. And
then paradoxically, you're actually, you know, you're creating a lot
of issues and trouble by using this preservative. That is
a paradox and I would not recommend that in any way.
And actually, we do have a paper that was just
accepted in ACTA that that everybody should should read that
(13:34):
it's actually stating what preservatives are in the in the
artificial tears, and and why is it that we should
actually care for our patients and not using artificial tears
with preservatives.
Speaker 1 (13:48):
That's really really important and that's going to guide the
way I treat treat dryness. And my naivete is on
display on this podcast, So I feel a bit naive
that I've done that.
Speaker 2 (14:00):
I think though a lot of people could probably relate.
Speaker 1 (14:02):
To that in the sense that a lot of the
samples we get are the ones that contain preservatives. They're
the easiest ones that we get, and sometimes for practical
reasons we do that, but based on what you're saying,
that's a really really strong argument, especially given the research
you've done, even for the ones that have lower concentration
or lower potency of the preservatives. I think one of
(14:24):
the challenges is most of us don't really know which
ones those are right. So I could say, well, I'm
going to use the ones that have less preservatives, but
I think the reality is the general ophthalmologist doesn't really know,
and it's tough to parse that out.
Speaker 3 (14:39):
And that's actually why it's so important that we give
this overview. Obviously, this overview is from the Scandinavian countries,
but I think that it relates very well to the
rest of the world. Just to be aware of the
paradox in treating a patient for a disease then perhaps
even making the disease worse. Now, again, the concentration and
(15:03):
the subtype of preservative is very important to consider. Also,
then you can say the cost for the patient is
obviously a huge issue, and I fully recognize that, but
I think that's policy, and that means that we need
to argue and speak up loud and actually tell the
(15:23):
politicians that this is not okay for the sake of
the patients. We need to get We need to get
to the stage where it's actually illegal to put preservatives
in artificial tears. It does not make sense.
Speaker 1 (15:36):
Talk to me a bit about another issue. Cost is one.
The other that I think is changing, which you'll talk about,
is the delivery system. So there's a lot of preservative
free medications that I use, either for dry eye or
for glaucoma, that come in these vials, and obviously it's
important because they're preservative free, but it's a little bit waste.
(16:00):
Well to an extent, patients don't always like using the
vials as opposed to having a bottle that they bring.
They throw them out at the end of the day,
and it can be a little bit challenging for patients.
Talk to me about how that's changing, because there are
new bottle delivery systems where you can get a preservative
free glaucoma drop or artificial tier where we're not reliant
(16:20):
on these perhaps more cumbersome vials.
Speaker 3 (16:23):
So you're fully fully correct saying that that we have
these one time vials. We can call them that or units,
and that's kind of been the first step in paving
the way to preservative free options. And here you can
argue some about climate and the use of plastic and
how difficult it is for the individual person using these,
(16:46):
and some would prefer it, some would not prefer it.
But the good news is that the filters in the
bottles are improving so much so we actually have quite
a few options where the preservative free options are come
in in bottles and not in the one, one time
use files. So I think we will see a huge
(17:07):
development in that direction where it's not about single use
viles or bottles. You can choose both, and some would
prefer one, some would prefer the other.
Speaker 1 (17:18):
Has there been any and I think you described this
earlier saying we don't have to be concerned about it.
But with those new bottles with the filters, is there
any evidence that infection risk is higher without the preservatives
in those bottles?
Speaker 3 (17:33):
I think that one should always be cautious, but in
my case, I haven't seen any any cases with the
infection due to the use of a preservative free bottle.
But but you should always be cautious. But I think
that it's proven that there are safe I mean even so,
and again, if you if you use preservatives, there are
(17:53):
so many other, so many other challenges that it's not
in the in the ideal world, you would not use.
I mean, the eye drop is not good for the
okolo surface in any way. So if you are a
glaucoma patient and you use anti glocoma medication, it's not
only the preservative, it's also the active component. It's also
the other inactive ingredients in the vehicle that can actually
(18:15):
affect the okalo surface. So the okyla surface simply is
not fond of the eye drop in itself. But why
would we make it even worse by adding a preservative
when it's not needed? And we the infection. Infection is
al wait, always something that you need to be careful about,
but in my in my opinion, it's not. It's not
(18:39):
an issue that is actually going to prevent us from
using preservative free options because there's so much damaged by
the preservatives in themselves.
Speaker 1 (18:50):
And in terms of the effectiveness of the glaucoma drops,
the potency of them, no.
Speaker 2 (18:55):
Drop off there.
Speaker 1 (18:56):
And as I say that, I realized maybe even if
there is a little bit of a drop off, a
five ten percent drop off, maybe that's even worth it. Frankly,
if you're not putting preservatives in the eyes, and it
means you might need a second agent to get a
little more effect if that means you.
Speaker 2 (19:10):
Don't have to use preservatives.
Speaker 1 (19:12):
But from your experience and the research you've done, is
there any significant drop off and effectiveness or with the
current models that we've got of these let me repeat that,
or with these current mechanisms of installation, is the effectiveness
pretty on parer?
Speaker 3 (19:28):
So when systematic reviews have been done also by my
group among others, it has not shown any efficacy difference
between preserved and non preserved eye drops. However, having said
that again, I think it's very important to understand the
generics as well. I don't know the rules are different
from country to country, but in Denmark and I have
(19:52):
I think that it's actually also the case in many
other countries. You can tell me about Canada, but there
are very very few regulations when you introduce a generic
eye drop. So there are so many steps that you
need to go through to introduce a brand name eye drop.
But then when it's off patent, a lot of competitors
can introduce the generic eye drops. And I'm not against
(20:14):
that because obviously it's good for the cost for the patients,
but with so few regulations, we are not even testing
efficacy and side effects. So I think what is very
important now is when we start introducing preservative free options,
there might be some matters that are not have not
(20:36):
been been tested enough. So here efficacy can be an issue.
Here the side effects can actually be an issue. So
I think it's very important for the patients to understand
that if they get a generic eye drop, it may
actually not be the same as the original brand name drug.
And I think that's up to us to actually explain
to the patients, not saying that the generics are not okay,
(21:00):
just saying that the regulations are not very very strong
so that we actually don't always know.
Speaker 1 (21:07):
And what you're saying is applying to generics that are
both preservative based and preservative free generic.
Speaker 3 (21:13):
Yes, and we will see more and more preservative free
options that are also generic, as we do see now
with the preserved options. And it comes down to bottle design,
It comes down to the vehicle. So the only regulation
in Denmark, for instance, is that it has to be
the same active component within twenty percent. It has to
(21:33):
be the same administration form. So an eye drop needs
to be an eye drop, it cannot be a tablet,
and then the bio equivalence needs to be the same.
But it's not that important for the majority of eye drops.
So the bio equivalence is the concentration in the blot,
but not too much actually enters into the blot, mostly
(21:53):
for beta bloggers, but not for many of the other
active components. Not totally true, but it's not that important
with bioequivalents when you speak about topical treatments as eye drops,
so that's it. Nothing else, no efficacy, no side effects.
So in Denmark actually, and that's something I'd like to
share with you because I think this is so important,
(22:15):
we actually have talked to the politicians because until twenty
twenty three there were no regulations in Denmark either for
the preservatives. That meant that we did not have to
use the same preservative in a generic eye drop as
you did in the original brand name. So we had
eye drops that were toxic to the oukla surface when
(22:37):
you used the generic, but not when you use the
brand the original brand name. I drop that together with
the patient Organization's fight socide Denark, the Danish Glocoma Association,
also the Danish Glocoma Society. We went together with our
research and we actually had a law changed so that
now it's not now you cannot subsidize another preservative in
(23:01):
a generic eye drop if the original brand name does
not have it. So we don't have mental CORNI implore
right now in generic variants where it's not in the
original brand name. And I think that's a good story.
That means that we need to speak up. Also with
the artificial tis we should not just accept that they
come with preservatives because that's not good for our patients.
Speaker 1 (23:23):
It's really well, that's that's that's so interesting because again
a lot of us I just think, don't don't know,
you know, we get a letter back from the pharmacy,
we don't have this available, and kind of a lot
of our first reaction is to say, okay, sure, then
go with the generic. That's okay, probably because we assume
to some extent that there are more regulations that are
(23:46):
saying you have to be pretty similar to the brand
name that's undergone the more rigorous studies. But it seems
like that's not the case, and we need to be
more on guard with that. For preservative based and non
preservative based medications.
Speaker 3 (24:00):
Right, So actually in Denmark get a generic eyedrop. It's
called a copy eyedrop like a copy, so it's like, yes,
a copy would be the same, but in reality it's not,
or at least you don't know if it is. So
I think that's a huge challenge and I think that
for the sake of the patients, we should actually be
concerned about this. This is not I mean, one thing
(24:22):
would be if you start a treatment for two weeks,
and in fact, now I think that perhaps some of
our antibiotic eye drops they could contain pensulconium chloride because
we want to get rid of the bacteria. And so
maybe in those short term use, if you want to
get rid of an infection, it's fine. But for chronic use,
(24:43):
in chronic exposure to a toxin to the OKLA surface
is like it does not make sense. And also then
people will ask me, but why are you so, why
are you so concerned about this? And I would go like,
can you explain me one good reason to put a
(25:03):
toxin into an eye drop for chronic use when it's
not needed?
Speaker 2 (25:09):
And that's the and that's the crux there.
Speaker 1 (25:11):
When it's not needed because in the past it was
needed because there were these other options, But now there
are the these other options. I'm glad you mentioned antibiotics there,
because it wasn't on my radar. I was more so
thinking in this talk about glaucoma drops.
Speaker 2 (25:23):
And artificial tears.
Speaker 1 (25:24):
But the antibiotics one is a good example, because, as
you said, that's not long term, and there is a
difference between chronicity and acute use of a medication. How
would you put steroid in that in that spectrum? People,
For example, steroids are used more, are used longer after
cataract surgery than an antibiotic. Obviously, some patients are on
(25:45):
long term steroid, even if it's just once a day
for corneal transplants. Do you have concern about that to
the same degree that you do about these other drops
we've been speaking about.
Speaker 3 (25:55):
I would still use a preservative free option, but I'm
not as concerned again with treatments that are not lasting,
like for the rest of the patient's life, perhaps like
chronic use. But again I don't see why would you
use a preserved option if there is a preservative free
if it's a steroid. I mean, the only reason to
(26:19):
maybe go into an argument about it may be okay
is for the antibiotics, because it does definitely kill everything
it sees.
Speaker 1 (26:29):
So the last question I have is where is this
preservative free movement going? And what I mean by that
is obviously it's growing, that's where it's going. But there
are certain medications, at least in Canada, in glaucoma, for example,
where it is just seems like prostaglandins for example, There's
a lot of preservative free options that are out there
(26:49):
for carbonic anhydrates inhibitors, though for alpha agonists I don't
see that as readily available in terms of the brand names.
Is that, first of all, maybe that's just the Canadian
American problem and you're not seeing that in Europe.
Speaker 2 (27:02):
Is that something that we're going to see change?
Speaker 1 (27:04):
So it's a little bit easier for us to prescribe
those medications where patients can more readily access them at
an affordable price.
Speaker 3 (27:12):
Unfortunately, when it comes to development of new drugs in general,
it's also about economy. I mean, we have stories in
Denmark where we actually had a preservative free option and
it went off market because it wasn't it you know,
it didn't pay off for the company, which is devastating
for the sake of the patients. As concerns carbon androthrais inhibitus,
(27:34):
we do have preservative preservative free options here and it
may very well come to Canada, I would say alpha
two agonists. Actually, I'm just sending a patient to Portugal
where they actually have a preservative free option. We don't
have it in Denmark. I'm trying to argue why why
would we not have it since it's available, But again
(27:55):
it's then it gets to be policy and money again.
And I think that we we as optomologist, as physicians,
we need to be advocating the best for our patients
and and always just looking into what's the best for
the patients. I'm also sometimes people are asking me, is
it just because you're collaborating with the industry that are
(28:17):
making preservative free options, And I'm like, no, I would
collaborate with anybody, but I will always tell what I
think is best for the patients. And and so no
matter what industry, I think it's important that we tell
the industry what is best for the patients because in fact,
although they need to think about the business, they also
(28:41):
want the best for the patients obviously, So I think
it's it's a you know, it's a win win to
to to to collaborate and to express what is the
route we need to take to actually have better patient care.
Speaker 1 (28:56):
Well, Professor Miriam Colco, I am so grateful that you've
join this podcast and your passion really shines through so boldly,
and I have zero doubt you.
Speaker 2 (29:05):
Are completely authentic.
Speaker 1 (29:06):
And this is not related to the work you do,
and well, it's related to the work you do in
the area, but it's not incentivized by the work you
do in the area. And I think that's very clear
that you just believe there is a better option. Why
would we not use that option and advocate for our patients.
You've done a great job at explaining why we used
to use preservatives, why we no longer have to use preservatives,
the damaged preservatives can cost, and that we don't need
(29:29):
to be worried about increased risks of infection reduced potency.
We always need to be worried about those things in general,
as you said, and be vigilant, but there shouldn't necessarily
be a heightened risk in these preservative free medications have
come out. So I am so so thankful for your
impassioned plea to people, and I know myself I'm going
to start using a lot more preservative free.
Speaker 2 (29:50):
So thank you so so much for joining.
Speaker 3 (29:52):
Me, thank you so much for invitding me, and thank.
Speaker 1 (29:55):
You everybody for listening to another episode of blind Spot.
Speaker 2 (29:58):
Have a great day, stistist
Hey everybody, I'm Zaio Medni can Welcome to blind Spot.
This episode is sponsored by THEA Pharma Canada. THEA Pharma
Canada is the Canadian subsidiary of THEA, Europe's leading pioneering
and innovative eye health brand. Founded in nineteen ninety four
by Henri Chibra. With five generations of history, the Chabrat
family has been dedicated to I care for more than
(00:32):
one hundred and fifty years. Their commitment to improving lives
is born of their pioneering spirit. They continue to lead
the worldwide preservative free movement in I care. They've created
innovative delivery systems and they focused on making products accessible
and cost effective for patients. They live this mission every
day because everyone should have the same opportunities to see
the world through healthy eyes. Thank you THEO Pharma Canada
(00:54):
for supporting this podcast. For many years, it was the
status quo that preservatives were part of the eye drops
that patients put in their eyes, But over the last
several years that has changed as a preservative free movement
has grown. So why did we use preservatives? And how
toxic are preservatives for our eyes? How important is it
(01:15):
to transition from preservative based eye drops to preservative free
eye drops.
Speaker 2 (01:19):
What are the.
Speaker 1 (01:20):
Benefits and what are some of the challenges in changing
to preservative free medications. To discuss this topic, I'm joined
by doctor Miriamkalco. Doctor Colco is professor at the University
of Copenhagen. She's also a chief physician and glaucoma specialist
at the Copenhagen University Hospital. She's President of the Danish
Glaucoma Society and holds several board positions including member of
the main board of Fight for Site Denmark, Danish Glaucoma Society,
(01:43):
carln Nikolain Larsen Foundation, and Marite and La Fontaine Foundation.
In twenty twenty one, Professor Colco was named one of
the one hundred most influential female ophomologists in the world
and top point one two percent of scholars writing about glaucoma.
At the University of Copenhagen, Professor Colco is part of
the Leader team as head of Section. In addition, she
is heading her research group I Translational Research Unit. The
(02:05):
research concerns translational and clinical research and seeks to improve
the understanding and management of glaucoma She's received almost eight
million euros in funding. Is co chair of the Neuroprotection
SIG in the European Glackhoma Society and member of the
European Glaucoma Society Membership and National Society Committee.
Speaker 2 (02:22):
She's one of the few.
Speaker 1 (02:22):
Clinician scientists worldwide that bridge between a clinical career with
medical and surgical treatments of site threatening diseases and research
that seek to improve I health. All right, doctor Cole,
welcome to the podcast. Thank you so much for joining me.
I'm self conscious because I know that I did not
pronounce your name right there.
Speaker 2 (02:38):
How do you do you pronounce your name correctly? Tell
me again?
Speaker 3 (02:42):
I I don't know an English but I would say Culco.
So I think that was actually pretty good what you did.
Speaker 2 (02:47):
Okay, we'll go. We'll go with that. Thank you so
much for joining me.
Speaker 1 (02:52):
We're gonna be talking about preservatives today, and this really
fits in the scheme of what blind spots about, kind
of looking at something that we think we know about,
which is a general paradigm, the status quo of what
we've been doing, and for a long time, preservatives were
a part of that status quo.
Speaker 2 (03:09):
All the drops we used were preservative based over.
Speaker 1 (03:13):
The last I don't know how many, fifteen twenty years,
there's certainly been a movement that's increasing in its intensity,
moving towards preservative free and we're going to talk about
that today. Before we do that, though, I want to
have a better understanding of preservatives in general. Why did
we use them for so long? What's the benefits of preservatives?
(03:34):
And as I say that, I realize on the surface
it's a basic question because they preserve drops, But why
have preservatives been a mainstay for so long? What do
they do that's positive?
Speaker 3 (03:47):
Well, certainly they kill bacteria, and that's also a good
reason for actually having had preservatives so long. So fifty
years ago the eye drops were produced with preservatives so
that we did and get infection using eye drops. So
in that sense, it's been very reasonable to actually add
preservatives into the eye drops. They do still kill bacteria,
(04:09):
so in that sense they are pretty effective. However, they
also kill all the cells, and that's what we're going
to talk about today. I assume, yeah.
Speaker 1 (04:20):
In addition to killing bacteria, does it also just allow
drops once you open a bottle with traditional bottles. Before
we get into some of the newer dispensing bottles. Would
it allow an eye drop bottle to last longer by
having preservatives once you've opened it?
Speaker 3 (04:35):
Well, not really actually, when we look at the market
today and the choices that we have, so the duration
of the eye drops are not really affected by preservatives
because that there has been so much development. However, you
could say that preservatives in some way will stabilize the
active compound. So it can be tricky to produce or
(04:56):
develop a preservative free option, but so you could say
the preservatives they prevent a bacterial growth, they can, and
so in certain cases actually stabilize the active component, the
active drug. And then there has been a discussion about
the penetration of the active drog is that better when
you use preservatives, And no matter whether this might be
(05:20):
true in a way that it can break down cell
membrane and thereby introduce more drug into the deep a
lying tissues, we have not seen any clinical relevant differences
in the efficacy in preservative free and preserved eye drops.
Speaker 1 (05:34):
So in the past it sounds like these are more
important things. But as we'll get to you, as the preservative
free drops and delivery systems have gotten better, those problems
have somewhat been negated to an extent where those benefits
don't necessarily stack up to what they used to be.
Speaker 3 (05:52):
Yes or no. So in fact, it is important to
understand that preservatives can stabilize the active component. Means that
if you have a preservative free option and you then
get a generic option, you really need to test the
efficacy because it might rely on the preservatives. So I'm
(06:13):
definitely not arguing that we should use preservatives in any way.
I think that we should use preservative free options whenever
it's possible, But there is something to consider when you
consider activity and how stable the active drug is.
Speaker 1 (06:31):
Before we get into preservative free, I want to understand
a little bit more about the toxicity and the issues
that preservatives did cause that led to this preservative free movement.
First of all, what are some of the most common preservatives?
I know back is one that is I commonly heard
when I was in residency, But it's been a while
since residency, and I'm sure listeners don't necessarily even know
(06:53):
what these preservatives are and how many are really common
in the preservative based drops we use.
Speaker 3 (06:59):
Yeah, so when we talk about preservative free drops, I mean,
for my case, I have been mostly focusing on antiglo
coomatist drugs or eye drops, but also artificial tears that
we can talk a little bit about. If we start
out with the anti glocomatis eye drops, which are the
major treatment for glocoma patients, then the bentyl conin chloride
(07:23):
or back as you say, is the far most commonly
used preservative, but there are other preservatives that are actually
having less toxicity compared to bentyl conin chloride, And one
to mention could be polyquot which is actually also in
quite a few of our eye drops.
Speaker 1 (07:41):
And give me a little bit more scope you alluded
to it before about just what they are doing negatively,
Is it ocular surface that we're really concerned about when
we're thinking about the damage that can be wreaked by
these preservatives.
Speaker 3 (07:55):
Obviously the ocular surface is a major issue, and let's
let's start there. But unfortunately it's not only the ocula surface.
It's also been shown that the preservatives are penetrating to
deeplyning tissues such as the tubacular messwork, and accumulation in
a turbacular messwork may cause fibrosis and actually a lesser
(08:18):
degree of filtration of the aquis humor, so there are
many other issues to consider. Also, it's been shown to
accumulate as far back in the iris in the retina,
but the ocula surface is right at the spot of
introducing the preservatives, so obviously we see a lot of
side effects on the oculo surface. So yes, let's definitely
(08:40):
focus on that, but not forgetting that it's not only
the ocula surface that we should actually be worried about.
Speaker 2 (08:48):
The irony. Of course, there is a lot of these drops.
Speaker 1 (08:50):
Especially you're a glaucoma specialist, You're saying a lot of
these drops that are used to treat glaucoma could actually
be to an extent making it harder to treat glaucoma.
If there's two s beecular meshwork damage being induced by
these very drugs that are supposed to in stiltration or
reduce the pressure. In terms of the ocular surface, walk
me through that. How does it damage the ocular surface?
(09:12):
Is it simply and I don't want to say simply
to diminish it, because I'm a corny specialist and I
see dryness a lot. But is it simply dryness or
is it also the risk of limbal stem cell disease?
What's really going on and what is the concern with
the ocular surface.
Speaker 3 (09:28):
Well, I think that it's it's both. So we are
dealing with a toxin. And if we start with benzel
coniu chloride, it's quite toxic. And if you are looking
at the bottles with benzel conium chloride that people would
use in a laboratory for experimental research, then it will
say this is dangerous and if you if you get
it into or near the eye, you need to wash
(09:49):
you out carefully. Right, So this is a toxin in
first place, and it's been shown in various pre clinical
studies that that benzilconium chloride is actually killing OLKLOS surface
cells such as the epithelial cells, the goblet cells in particular.
So my research group have worked very much with the
goblet cells, so they killed the OClO surface cells. And
(10:14):
if we think about the goblet cells, they're very important
in producing mucin, which is a highly important component of
the tear film. So it might also affect the mypomean glands,
so it might also affect the lipid component and the
til film. So in general, the toxicity based on the use,
(10:35):
the chronic use of pensyl conia and chloride may actually
kill cells and glands that are essential for a good
tear film.
Speaker 1 (10:46):
That's a really good explanation of it. A typical paradigm
I've used when I speak to patients, and maybe this
is wrong, and I have a feeling.
Speaker 2 (10:54):
It probably is.
Speaker 1 (10:55):
Is I see the people because preservative free artificial tiers
are more expensive, and they say, what should I use?
I say, you know what, if you're only using it
three four times a day, I'm okay with you using
preservative based medication. It's cheaper, it might be a little
bit easier for you to access. And I'm not so
concerned as you say that, though I realize, well, I
(11:17):
could be doing some damage with those preservative based tiers,
because even if they're not using it so much and
they're not putting so much preservative in their eye, I
don't know exactly what that balance is between you're getting
good artificial tier in, but you're also getting preservative in.
Speaker 2 (11:32):
How do you look at artificial tiers in that way?
Speaker 1 (11:34):
And I will qualify what I just said by if
I see they're already on a bunch of other glauckhoma drops,
some of which might have preservatives I'll certainly be more
incentivized to say, let's definitely stay away from preservatives in
your artificial tiers, because you could just be.
Speaker 2 (11:49):
Compounding the problem.
Speaker 1 (11:50):
But in someone with just run of the mill dry eye,
how important is it to say, yeah, even if you're
just using it three four times a day, it should
be preservative free.
Speaker 3 (12:00):
Well, first of all, I would never ever ever argue
that it's okay to use preservative containing artificial tears in
patients that are having ouglar surface issues, even not once
a day, So I think three to four times is
a lot. Having said that, it is also depending on
what preservative. So some preservatives, for instance, bensal cornium chloride
(12:24):
is very toxic, whereas public quad has been shown to
be less toxic. So there is differences in the different preservatives.
Now I would not use the preservative in any way
in any circumstance, But again there's also a matter of
how high concentration of the preservative is actually in the
artificial tiers. So some have very low concentration and others
(12:48):
they have much higher concentration, and the toxicity of the
preservatives that's concentration dependent. So the more eye drops you use,
so the more times you use it a day, the
higher concentration you have of the preservative, the worst it
is for the okolo surface. But honestly, I have no
idea why it's even allowed to put a preservative in
(13:13):
a treatment that's going to treat the oculo surface. And
then paradoxically, you're actually, you know, you're creating a lot
of issues and trouble by using this preservative. That is
a paradox and I would not recommend that in any way.
And actually, we do have a paper that was just
accepted in ACTA that that everybody should should read that
(13:34):
it's actually stating what preservatives are in the in the
artificial tears, and and why is it that we should
actually care for our patients and not using artificial tears
with preservatives.
Speaker 1 (13:48):
That's really really important and that's going to guide the
way I treat treat dryness. And my naivete is on
display on this podcast, So I feel a bit naive
that I've done that.
Speaker 2 (14:00):
I think though a lot of people could probably relate.
Speaker 1 (14:02):
To that in the sense that a lot of the
samples we get are the ones that contain preservatives. They're
the easiest ones that we get, and sometimes for practical
reasons we do that, but based on what you're saying,
that's a really really strong argument, especially given the research
you've done, even for the ones that have lower concentration
or lower potency of the preservatives. I think one of
(14:24):
the challenges is most of us don't really know which
ones those are right. So I could say, well, I'm
going to use the ones that have less preservatives, but
I think the reality is the general ophthalmologist doesn't really know,
and it's tough to parse that out.
Speaker 3 (14:39):
And that's actually why it's so important that we give
this overview. Obviously, this overview is from the Scandinavian countries,
but I think that it relates very well to the
rest of the world. Just to be aware of the
paradox in treating a patient for a disease then perhaps
even making the disease worse. Now, again, the concentration and
(15:03):
the subtype of preservative is very important to consider. Also,
then you can say the cost for the patient is
obviously a huge issue, and I fully recognize that, but
I think that's policy, and that means that we need
to argue and speak up loud and actually tell the
(15:23):
politicians that this is not okay for the sake of
the patients. We need to get We need to get
to the stage where it's actually illegal to put preservatives
in artificial tears. It does not make sense.
Speaker 1 (15:36):
Talk to me a bit about another issue. Cost is one.
The other that I think is changing, which you'll talk about,
is the delivery system. So there's a lot of preservative
free medications that I use, either for dry eye or
for glaucoma, that come in these vials, and obviously it's
important because they're preservative free, but it's a little bit waste.
(16:00):
Well to an extent, patients don't always like using the
vials as opposed to having a bottle that they bring.
They throw them out at the end of the day,
and it can be a little bit challenging for patients.
Talk to me about how that's changing, because there are
new bottle delivery systems where you can get a preservative
free glaucoma drop or artificial tier where we're not reliant
(16:20):
on these perhaps more cumbersome vials.
Speaker 3 (16:23):
So you're fully fully correct saying that that we have
these one time vials. We can call them that or units,
and that's kind of been the first step in paving
the way to preservative free options. And here you can
argue some about climate and the use of plastic and
how difficult it is for the individual person using these,
(16:46):
and some would prefer it, some would not prefer it.
But the good news is that the filters in the
bottles are improving so much so we actually have quite
a few options where the preservative free options are come
in in bottles and not in the one, one time
use files. So I think we will see a huge
(17:07):
development in that direction where it's not about single use
viles or bottles. You can choose both, and some would
prefer one, some would prefer the other.
Speaker 1 (17:18):
Has there been any and I think you described this
earlier saying we don't have to be concerned about it.
But with those new bottles with the filters, is there
any evidence that infection risk is higher without the preservatives
in those bottles?
Speaker 3 (17:33):
I think that one should always be cautious, but in
my case, I haven't seen any any cases with the
infection due to the use of a preservative free bottle.
But but you should always be cautious. But I think
that it's proven that there are safe I mean even so,
and again, if you if you use preservatives, there are
(17:53):
so many other, so many other challenges that it's not
in the in the ideal world, you would not use.
I mean, the eye drop is not good for the
okolo surface in any way. So if you are a
glaucoma patient and you use anti glocoma medication, it's not
only the preservative, it's also the active component. It's also
the other inactive ingredients in the vehicle that can actually
(18:15):
affect the okalo surface. So the okyla surface simply is
not fond of the eye drop in itself. But why
would we make it even worse by adding a preservative
when it's not needed? And we the infection. Infection is
al wait, always something that you need to be careful about,
but in my in my opinion, it's not. It's not
(18:39):
an issue that is actually going to prevent us from
using preservative free options because there's so much damaged by
the preservatives in themselves.
Speaker 1 (18:50):
And in terms of the effectiveness of the glaucoma drops,
the potency of them, no.
Speaker 2 (18:55):
Drop off there.
Speaker 1 (18:56):
And as I say that, I realized maybe even if
there is a little bit of a drop off, a
five ten percent drop off, maybe that's even worth it. Frankly,
if you're not putting preservatives in the eyes, and it
means you might need a second agent to get a
little more effect if that means you.
Speaker 2 (19:10):
Don't have to use preservatives.
Speaker 1 (19:12):
But from your experience and the research you've done, is
there any significant drop off and effectiveness or with the
current models that we've got of these let me repeat that,
or with these current mechanisms of installation, is the effectiveness
pretty on parer?
Speaker 3 (19:28):
So when systematic reviews have been done also by my
group among others, it has not shown any efficacy difference
between preserved and non preserved eye drops. However, having said
that again, I think it's very important to understand the
generics as well. I don't know the rules are different
from country to country, but in Denmark and I have
(19:52):
I think that it's actually also the case in many
other countries. You can tell me about Canada, but there
are very very few regulations when you introduce a generic
eye drop. So there are so many steps that you
need to go through to introduce a brand name eye drop.
But then when it's off patent, a lot of competitors
can introduce the generic eye drops. And I'm not against
(20:14):
that because obviously it's good for the cost for the patients,
but with so few regulations, we are not even testing
efficacy and side effects. So I think what is very
important now is when we start introducing preservative free options,
there might be some matters that are not have not
(20:36):
been been tested enough. So here efficacy can be an issue.
Here the side effects can actually be an issue. So
I think it's very important for the patients to understand
that if they get a generic eye drop, it may
actually not be the same as the original brand name drug.
And I think that's up to us to actually explain
to the patients, not saying that the generics are not okay,
(21:00):
just saying that the regulations are not very very strong
so that we actually don't always know.
Speaker 1 (21:07):
And what you're saying is applying to generics that are
both preservative based and preservative free generic.
Speaker 3 (21:13):
Yes, and we will see more and more preservative free
options that are also generic, as we do see now
with the preserved options. And it comes down to bottle design,
It comes down to the vehicle. So the only regulation
in Denmark, for instance, is that it has to be
the same active component within twenty percent. It has to
(21:33):
be the same administration form. So an eye drop needs
to be an eye drop, it cannot be a tablet,
and then the bio equivalence needs to be the same.
But it's not that important for the majority of eye drops.
So the bio equivalence is the concentration in the blot,
but not too much actually enters into the blot, mostly
(21:53):
for beta bloggers, but not for many of the other
active components. Not totally true, but it's not that important
with bioequivalents when you speak about topical treatments as eye drops,
so that's it. Nothing else, no efficacy, no side effects.
So in Denmark actually, and that's something I'd like to
share with you because I think this is so important,
(22:15):
we actually have talked to the politicians because until twenty
twenty three there were no regulations in Denmark either for
the preservatives. That meant that we did not have to
use the same preservative in a generic eye drop as
you did in the original brand name. So we had
eye drops that were toxic to the oukla surface when
(22:37):
you used the generic, but not when you use the
brand the original brand name. I drop that together with
the patient Organization's fight socide Denark, the Danish Glocoma Association,
also the Danish Glocoma Society. We went together with our
research and we actually had a law changed so that
now it's not now you cannot subsidize another preservative in
(23:01):
a generic eye drop if the original brand name does
not have it. So we don't have mental CORNI implore
right now in generic variants where it's not in the
original brand name. And I think that's a good story.
That means that we need to speak up. Also with
the artificial tis we should not just accept that they
come with preservatives because that's not good for our patients.
Speaker 1 (23:23):
It's really well, that's that's that's so interesting because again
a lot of us I just think, don't don't know,
you know, we get a letter back from the pharmacy,
we don't have this available, and kind of a lot
of our first reaction is to say, okay, sure, then
go with the generic. That's okay, probably because we assume
to some extent that there are more regulations that are
(23:46):
saying you have to be pretty similar to the brand
name that's undergone the more rigorous studies. But it seems
like that's not the case, and we need to be
more on guard with that. For preservative based and non
preservative based medications.
Speaker 3 (24:00):
Right, So actually in Denmark get a generic eyedrop. It's
called a copy eyedrop like a copy, so it's like, yes,
a copy would be the same, but in reality it's not,
or at least you don't know if it is. So
I think that's a huge challenge and I think that
for the sake of the patients, we should actually be
concerned about this. This is not I mean, one thing
(24:22):
would be if you start a treatment for two weeks,
and in fact, now I think that perhaps some of
our antibiotic eye drops they could contain pensulconium chloride because
we want to get rid of the bacteria. And so
maybe in those short term use, if you want to
get rid of an infection, it's fine. But for chronic use,
(24:43):
in chronic exposure to a toxin to the OKLA surface
is like it does not make sense. And also then
people will ask me, but why are you so, why
are you so concerned about this? And I would go like,
can you explain me one good reason to put a
(25:03):
toxin into an eye drop for chronic use when it's
not needed?
Speaker 2 (25:09):
And that's the and that's the crux there.
Speaker 1 (25:11):
When it's not needed because in the past it was
needed because there were these other options, But now there
are the these other options. I'm glad you mentioned antibiotics there,
because it wasn't on my radar. I was more so
thinking in this talk about glaucoma drops.
Speaker 2 (25:23):
And artificial tears.
Speaker 1 (25:24):
But the antibiotics one is a good example, because, as
you said, that's not long term, and there is a
difference between chronicity and acute use of a medication. How
would you put steroid in that in that spectrum? People,
For example, steroids are used more, are used longer after
cataract surgery than an antibiotic. Obviously, some patients are on
(25:45):
long term steroid, even if it's just once a day
for corneal transplants. Do you have concern about that to
the same degree that you do about these other drops
we've been speaking about.
Speaker 3 (25:55):
I would still use a preservative free option, but I'm
not as concerned again with treatments that are not lasting,
like for the rest of the patient's life, perhaps like
chronic use. But again I don't see why would you
use a preserved option if there is a preservative free
if it's a steroid. I mean, the only reason to
(26:19):
maybe go into an argument about it may be okay
is for the antibiotics, because it does definitely kill everything
it sees.
Speaker 1 (26:29):
So the last question I have is where is this
preservative free movement going? And what I mean by that
is obviously it's growing, that's where it's going. But there
are certain medications, at least in Canada, in glaucoma, for example,
where it is just seems like prostaglandins for example, There's
a lot of preservative free options that are out there
(26:49):
for carbonic anhydrates inhibitors, though for alpha agonists I don't
see that as readily available in terms of the brand names.
Is that, first of all, maybe that's just the Canadian
American problem and you're not seeing that in Europe.
Speaker 2 (27:02):
Is that something that we're going to see change?
Speaker 1 (27:04):
So it's a little bit easier for us to prescribe
those medications where patients can more readily access them at
an affordable price.
Speaker 3 (27:12):
Unfortunately, when it comes to development of new drugs in general,
it's also about economy. I mean, we have stories in
Denmark where we actually had a preservative free option and
it went off market because it wasn't it you know,
it didn't pay off for the company, which is devastating
for the sake of the patients. As concerns carbon androthrais inhibitus,
(27:34):
we do have preservative preservative free options here and it
may very well come to Canada, I would say alpha
two agonists. Actually, I'm just sending a patient to Portugal
where they actually have a preservative free option. We don't
have it in Denmark. I'm trying to argue why why
would we not have it since it's available, But again
(27:55):
it's then it gets to be policy and money again.
And I think that we we as optomologist, as physicians,
we need to be advocating the best for our patients
and and always just looking into what's the best for
the patients. I'm also sometimes people are asking me, is
it just because you're collaborating with the industry that are
(28:17):
making preservative free options, And I'm like, no, I would
collaborate with anybody, but I will always tell what I
think is best for the patients. And and so no
matter what industry, I think it's important that we tell
the industry what is best for the patients because in fact,
although they need to think about the business, they also
(28:41):
want the best for the patients obviously, So I think
it's it's a you know, it's a win win to
to to to collaborate and to express what is the
route we need to take to actually have better patient care.
Speaker 1 (28:56):
Well, Professor Miriam Colco, I am so grateful that you've
join this podcast and your passion really shines through so boldly,
and I have zero doubt you.
Speaker 2 (29:05):
Are completely authentic.
Speaker 1 (29:06):
And this is not related to the work you do,
and well, it's related to the work you do in
the area, but it's not incentivized by the work you
do in the area. And I think that's very clear
that you just believe there is a better option. Why
would we not use that option and advocate for our patients.
You've done a great job at explaining why we used
to use preservatives, why we no longer have to use preservatives,
the damaged preservatives can cost, and that we don't need
(29:29):
to be worried about increased risks of infection reduced potency.
We always need to be worried about those things in general,
as you said, and be vigilant, but there shouldn't necessarily
be a heightened risk in these preservative free medications have
come out. So I am so so thankful for your
impassioned plea to people, and I know myself I'm going
to start using a lot more preservative free.
Speaker 2 (29:50):
So thank you so so much for joining.
Speaker 3 (29:52):
Me, thank you so much for invitding me, and thank.
Speaker 1 (29:55):
You everybody for listening to another episode of blind Spot.
Speaker 2 (29:58):
Have a great day, stistist
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