April 15, 2025 • 32 mins
With the arrival of Eyezirgan (commercial available topical ganciclovir), we now have a more readily accessible preservative-free option for treatment of HSV. So why is Eyezirgan a potentially important new player on the market? How does one decide between oral or topical treatments for HSV, and is there a longer-term role for antivirals in the treatment of Zoster, in addition to just HSV? Dr. Parwez Hossain 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 XAEO Mednik and welcome to another episode
of Blindspot. 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 Schibre. With five generations of history,
the Chubret family has been dedicated to I care for
(00:32):
more than 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 eye care.
They've created innovative delivery systems. They've 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. So thank you THEO
(00:54):
Pharmer Canada for supporting Blindspot. Herpes simplex and Herpe's zaster
virus can at time be very challenging to treat in
the eye. In some ways, it's extra challenging because there's
multiple ways to treat these viruses and the inflammation that
they induce. Typically oral antivirals such as a cyclovier and
valet cyclovier have been used to treat HSV. However, in
(01:15):
the past there were topical options such as trifloriding, commercially
known as viropatic. Those options, however, at least in Canada
and in the United States, went by the wayside several
years ago, but more recently a newer option is available
top themologists and optometrists topical gan cycle beer or commercially
known as isergan. So how does one go about making
(01:37):
the decision of when to use oral antivirals versus topical antivirals?
What are the advantages and disadvantages of each? I'm joined
today by doctor Parvez Hussein. Doctor Hossein is the Professor
and King James, the fourth Professor in Ophthalmology within the
Faculty of Medicine at the University of Southampton. He also
served as a consultant of Theolmbic Surgeon at University Hospital Southampton.
(01:58):
He's a clinical scientist focusing on corny in ocular surface disease.
He qualified in medicine from Aberdeen University and trained in
ophthalmology at Aberdeen Nottingham Chester in Miami. His clinician scientist
career started as a Welcome Trust clinical Research Fellow at
Aberdeen University. He started for his PhD in Immunology and
Biomedical Physics and Engineering to investigate the mechanisms of T
(02:19):
cell traffic in ocular inflammation. In his awarded PhD thesis,
he established a novel method for in vivo tracking of
immune cells and the retina and choroid, showing the early
interactions of lymphocytes with an inflamed and vascular endothelium. All right,
doctor parvezjus say, and welcome to the podcast. Thank you
so much for joining me.
Speaker 2 (02:38):
Thank you Zille.
Speaker 3 (02:39):
You are joining me.
Speaker 1 (02:40):
From across the pond, as we say, and you just
gave me a bit of a good history lesson on
where you're from. And I like my British history. And
we're going to be chatting also about HSV today.
Speaker 2 (02:50):
Some things don't change, doesn't matter how far you're away,
so HSB as well as it. So that's a good connection.
Speaker 1 (02:56):
So in terms of the history, I guess the history
that I kind of cited the introduction there was that
most of us are used to treating HSV and we'll
talk about zoster a little bit later, but most of
us are used to treating HSV historically with antivirals, whether
it's a cyclovier or valtrex. Now I know that in
Canada and in the US there was an option to
treat topically with trifluoridine, which was commercially known as viroptic
(03:18):
a while ago, but that was continued several years ago.
Before we get into topical gant cyclovia, which is commercially
known as isergan, I just want to talk a little
bit about the history of trifluoridine or viroptic and why
that went off the market.
Speaker 2 (03:33):
Yeah, I mean it's not I mean you have to
take it from my perspective. In the UK TFT three
drops that were available very over a long time ago,
we become totally obsolete. Now the reason why they were
taken off and I have to go back to the
nineteen nineties in the UK, there was this head study
(03:56):
Apetic eye Disease study, which looked at the effect of
anti virals and its effect on controlling herpetic carotitis, and
clearly there was a role for anti virals, particularly of
a cyclo bear but I think TFT three was in that.
But one drug company managed to manufacture a cyclo beer
(04:16):
as an eye ownment, and they and that took off
because of disease of application and the fact that it
was applied locally to the eye where the dendritic ulcer
might be in the cornea, and it had less toxicity
than TFT three. So one of the problems was the
epithelial toxicity on the cornea of using that agent. And
(04:40):
I'm still surprised to see that those available in North America,
although it has it's got its own merits, of course,
but in the UK, when a cycle of beer was
introduced as an eye ownment, then TFT three effectively became obsolete,
and the toxicity difference is between the two agents became
(05:01):
very proud. So because in the UK we're used to
using topical treatment, that's why topical treatments there are here
have been very popular. So of course there's been a
bit of a transition from that to taking systemic treatment,
which you can talk about a bit later on. But
the main reason why tftcree wasn't so popular is because
of its effect on the cornea cleared the virus, but
(05:23):
it also caused a lot of damage and collateral damage
on the surface of the eye.
Speaker 3 (05:28):
Yeah, that was my impression.
Speaker 1 (05:29):
I recall that when we were treating it in residency
with the trifluoridine or TFT as you're calling it, we
were taught that it is quite toxic, so only to
use it for limited periods, and that's why a lot
of my mentors suggested at the time that we use
oils instead. You mentioned a cyclovir eye ointment there. I've
heard of that used in North America, but not super commonly.
Is that Is that something that's still commonly used in
(05:51):
the UK?
Speaker 2 (05:53):
Yeah, I mean it's still commonly used. It was a
dominant form of treatment, so a lot of the drug
supply depends upon the manufacturer where they're willing to make it,
and so the main manufacturer decided to disinvest in it,
and then then it became generic and then it's trying
to find and manufacturer make it. So it's still available
in the UK. It's still used, but because of supply availabilities,
(06:17):
then people look around for other anti viral agents that
might be available to use topically to the eye. So
it's still widely used when it's available, and that currently
as can see, it is available over the last few years,
but there was a patch where there are problems trying
to find a manufacturer to make it, and we regular
(06:38):
face this problem in the UK. I'm sure this must
be a problem in North America where certain drugs are
supply lines become limited and optimologists then have to start
looking at alternatives to treat their patients, so that shifts
the usage rather than the side effects per se. They
need a treatment that bet she works, So that's that's
(07:00):
why there's been ups and downs with acyclvi topical YE treatments.
Speaker 1 (07:05):
And that transitions well into topical cycle. Isergan is the
commercial name now. I have used topical gan cyclovia in
the past over several years when I didn't have another
topical option, but it needed to be formulated at a
compounding pharmacy, so that really limited my use of it.
And now that isergan is commercially available and easy for
patients to buy, it's kind of re emerged on the
(07:27):
scene as a new option for a topical therapy as
opposed to just having our oral therapies. So with isergan
now being more easily commercially available, how has that factored
into your practice and how has that kind of bypassed
some of the challenges with other topical treatments that there
have been.
Speaker 2 (07:44):
Yeah, I think to be fair. Really, the supply lines
of drugs, you know when they get when they become difficult.
For example, when we've had to say cycle of a
topical treatment supply shortage, then then other other agents have
stepped in. So gan cyclob in the UK and Europe
came in just at about the right time when a
(08:06):
cyclo where it wasn't available so easily, and so that's
taken in and people then you know, conditions start using it.
The frequencies are same, the clinical effect is maybe it's
better in some ways, but when people try to use
it realize, oh, this is quite useful, this works well,
and perhaps is maybe it has associated with less toxicity.
(08:30):
But so people get used to it and they realize
that it does actually work as it says on the
tin as it were, so they so that you get
a massive uptake. And obviously it depends on the supply
lines are available in the pharmacy. So if the pharmacy
has it, then you tend to write it out. And
the tolerances are quite good and the treatment effectiveness appears
to be similar to a cyclo bear and so that's
(08:53):
why it's taken off. And while you know a cycle
of there's a competitive product, it's being the issue of
who's being able to manufacture and sufficient volume so that
actually can be used. So it's less about apps. A
clinical effectiveness is the supply effectiveness and supply lines and recruitment.
That's actually the main issue there. But saying that, the
(09:15):
preparation and the way that it handles, the way you
can instill it in the eye is quite favorable, and
so that's why it's so popular.
Speaker 1 (09:27):
One of the big benefits that's touted for isergan is
that it's preserved and free. And when I hear that,
obviously I think great. We know that preservative free is important.
We've done an episode recently on that. But I think
it's important to be clear that just because something's preservative free,
it doesn't mean that it's not toxic to the cornea,
especially important when we're dealing with treating a corneal disease. Right,
(09:49):
is it correct to say that it's much better to
use preservative free, but that doesn't mean that gan cycle
ofvia itself ceases to be toxic to the cornea. The
gan cyclovir ingredient can still cause cornial toxicity, albeit it's
much better when it is preservative free.
Speaker 2 (10:04):
I mean the problem with anti viratopical antiviral treatments too.
On the whole, they are somewhat toxic to the corneal epithelium.
Of course, when you're taking any medication more than four
times a day, then the preservatives do become significant. So
having less preservative in it does help and reduces the
(10:27):
level of toxicity. But you see this with a cycle
of organicyclo via. They if they used it quite regularly
and overused it for several weeks that five times a day,
then you will see a mild kerotopathy and spicating. The
problem is for the untrained eye, when you're dealing with
(10:47):
a dendritic type lesion or a petic involvement of the cornea,
some of the patterns of the spks that you might
see can get confused and somebody might confuse that with
latent bio activity. So the less toxicity you have, the better.
My impression is probably vigan as we call it a
(11:07):
gancycle it in the UK. It is probably less less
toxic on the eye then perhaps some of the other products.
But you still can get SPK, but the fact that
there's less preservative and it means at least that's less
likely to be a component within of the SPK that's
(11:28):
been induced, So some of it is from the drug
itself directly. So sorry, I'm not giving you a clear answer,
but there is an advantage obviously with having it preserved fee.
It means it probably doesn't sting so much, it may
not irritate the eye so much. You're most likely to
get a toxic reaction per se from the preservative, So
(11:49):
that level of ambiguity that or confusion you get later
on when the patient's been treated chronically with a drug
is less of an issue. And so there has its advantage,
and that's why it's probably one of the other fact
is why it's a popular product because of that.
Speaker 3 (12:06):
I think those are some very important points.
Speaker 1 (12:08):
One is that toxicity can make it challenging to discern
what is true disease, what's an actual dendrite or resolving
dendrite or epithelial regeneration line or versus toxicity. And the
other point you make there, which is important to remember
is that for all drops, even if they are preserved
a free that's super important, but that doesn't mean they're
devoid of causing toxicity.
Speaker 2 (12:29):
Well like glaucoma. Colleagues will say, there's a bleach called
domestos in that you clean the floor with. So this
is my latest drop is preservadive free domestos. So that
means you can have a floor cleaner which is preservative free,
but it's still that can damage your eyes. So don't
forget the big picture is quiet agent. The active agent
(12:54):
can be quite toxic, but it applies to all drye
drops to that extent. You know, some one, some are more.
But if we actually think about antiviral eye drops, so
one of the challenges is that actually they deal with
the purine since this pathway, so they are going to
affect cell cycle changes within the cell with any cell,
and you tend to get a bit. You get damage
(13:16):
from the surface from all of them. And I think
the extreme example is the TFT drops. That's probably the
extreme example of a of those anti virals. And as
we go to a cycler and gancycle, we see the
kinder type of domestos of your eye. But not to
say it is domestos, but it's much kinder on the
(13:36):
eye and that's why you can see the take up
of those medications are so high in places out of
UK and in Europe where it's used very widely, so
people are aware of that toxicity. And then there's the
argument of using oral treatment. You know, we were going
to discuss that versus topical treatment. So that's a relative advantage.
(13:59):
You don't have to worry the toxicity on the eye,
but then you're left with the toxicity or vessel of
the body to worry about. That. That's a different matter.
Speaker 1 (14:06):
Yeah, So let's talk about that, because I do find
it sometimes a bit challenging to decide when am I
going to use oral something like a cyclovia or valley
cyclovier as opposed to something topical like gance cyclovier. In
my mind, I think if it's just a dendrite, not
to minimize the significance of a dendrite, but if it's
confined to the epithelium, I might be more likely to
use the topical gan cyclovia because I'll say, you.
Speaker 3 (14:27):
Know what, there's not much else I need to treat.
Speaker 1 (14:29):
It's not that the gan cyclovia isn't going to penetrate
at all into the eye, but it's going to be
most effective on the superficial aspect of the cornea, whereas
if I've got other stuff going on, and also based
on the heads trial that has been done in the past,
then I might be more inclined if there's an iritis,
for example, something deeper in the eye. At that point
to go oral, what helps guide your decision when you're
(14:50):
making that choice, I.
Speaker 2 (14:52):
Mean the way I look at it exactly the same
as what you've cited there, because what you have to
look at is where is the viral latency of where
is it most active. So if you're seeing a dendrite,
then clearly the virus is laden in their epithelium, and
so if you're applying an antiviral ointment directly topically to
(15:12):
the eye, you'll be hitting it ahead on. So that
makes a lot of sense. That also applies to latency
as well, because if you think about the viral and
you know the whole pathway we're talking about the opthalmic
divisionals or trigeneral novid it depends where you starts off
from the ganglion all the way up to the cordial
epithelian and the nerves and the cornea and the virus
(15:33):
can be at any point, but if it's predominantly at
the tip at the corneal epithetium or corneal sub epithel there,
then perhaps a topical treatment will be very effective. But
if it's latencies deeper down in the trigeminal ganglion, then
you may want to think we consider whether systemic treatment
(15:53):
would be useful in that case, especially one that will
help cross the blood brain barrier. And if you're thinking
about latency that's in the iris or the uveal tract,
then again systemic treatment would be your best choice. And
so so that's the way to think about it. Think
about the anatomy where the virus is, where can you
(16:14):
see it active? So if it's active in the corneal epithemium,
it means most of the virus particles are there and
that's where you've got to target it. But it is
also very frequent to see virus all over the place
and you may want to use both. So quite a
lot of patients that we have are on both treatments.
They are on topical gang cycle of BEA and on
(16:36):
systemic valel cycle of here and it's very very frequent.
If you're more office based, or if you're like saying
an optometrist, as it's got prescribing rights, they're rather reluctant
to give oral treatment. They probably don't have the prescribing
rights to go to oral treatment. So you know, it
depends on your registration and your own locality. So you'd
be more comfortable using topical treatment, and that's perfectly fine.
(16:59):
I mean in primary I care, for example, a lot
of conditions are uncomfortable using systemic therapies and they're worried
what the side effects could be, and so you're more
inclined to then give topical treatment in that situation. But
if you're possible with based practitioner, and you'd have a
little bit more latitude and be able to use systemic medication,
(17:20):
maybe more comfortable using it. So things also that level
as well, depends on the actual condition and what they
feel comfortable using. But sometimes you can get effective control
of the cornell activity with high dosages of systemic anti virals.
But then if you're going to go to that line
of things, then you have to then worry about the
(17:41):
side effects, so and you may have to take it
for a long time and then patients will have keepen
asking you or is he going to damage my liver
or kidneys? And certainly with valid cycling, but you have
to be very careful in elderly patients because because it
affects I mean, this is the way to think about it.
It can create confusion for patients with low grades of
(18:01):
in high grades of dementia. So if you start giving
regular valor cyclovia, you could make their dementia somewhat worse.
So you have to be careful what you use. But
sometimes you can argue that it's easier to administer the
treatment because you can mix it up in their food
and give the tablet, whereas harder they give topical treatment
(18:23):
on those sort of patients. But that's something to think about,
you know. That's another angle and things that we come across. So, yeah,
the logic of using it depends where you see most
predominant activities, So topical treatment that you can see directly
in the eye, deeper in the eye, maybe you're thinking
about systemic treatments. Combination of both might also be sensible
as well. And if you want to do prophile axis
(18:45):
of antiviral reactivation, then perhaps you're better off taking systemic
treatment because of the latency with it might be resident
in the trigeminal ganglion and perhaps the topical treatment has
got no way near nowhere near where that activity might be.
Speaker 3 (19:00):
You read my mind there.
Speaker 1 (19:01):
My next question was going to be, so we know
that it does stay dormant in the ganglion, and in
those situations a topical treatment isn't going to penetrate that ganglion. Obviously,
So in those situations, if you've decided to go for
long term prophile axis, because you don't always decide to
Usually you wait if somebody's had a recurrence or two.
But in the situation where you do decide to go
(19:22):
for long term prophile axis, are you more likely to
go for oral as opposed to topical because we know
that the oral is systemic and can actually get to
that ganglion where the virus is hiding out and laying dormant.
Speaker 2 (19:35):
Yeah, yeah, yeah, So that's certainly. In my practice we
use a lot of oil treatment. But you don't remember
that my practice is based predominant in a tertiary in
it in a coordinal service. There so most of the
easy stuff has already been done, So all the topical
treatments already been tried, and patients have quite often on
their fourth or fifth or sixth attack and they want
(19:58):
more X but help to control their attack. So the
topic treatments already been tried and they were onto systemic
therapies and usually the treatment that I tend to use
is or palicyclo bear and we would try to trade
the dose accordingly to see whether we can reduce the
number of attacks. And many other patients are on the
treatment for you know, several months, even several years to
(20:21):
control these attacks. And every time you have an attack
of a petticaretitis, then the inflammation and the net scarring
that occurs, it brings down your vision and it may
not recover back to the level that was before. So
you really want to be able to control that virus,
hold it in its place, stop it from traveling down
(20:42):
the trigeminal nerve and activating locally in the cornea. So
that's the strategy for those patients, and having used it
for the last fifteen years, I can say that that
can be a very effective strategy. But sometimes you see latency,
not necessarily in the trigeneral gangling. It's somewhat further down,
(21:04):
closer to the cornea, and for some patients they probably
do also need topical treatment as well. And it is
quite defined where that. You know, we can't see where
the virus is precisely latent. We you know, we can
see historological studies showing that it is latent in the
trigeneral gaming, but the latencies in theory could be I
(21:26):
missed anywhere. Really, But if it is more latent in
let's say, in the corn illos, Remember the cornillinas are
quite a dense structure. You know, we can't we don't
see them on the slit land, but if you do comevocal,
you'll see a lot of them, and the virus may
be latent in that region. And for that reason, then
perhaps in certain cases the topical treatment would be more
(21:48):
effective at controlling it, or combined with systemic treatment would
be very effective way of controlling in the virus so
that it doesn't reactivate. So, you know, this is what
I'm trying to think. Think about the anatomy. Then you
can then think about your treat and choices and the presentations.
But generally speaking, systemic treatment work really well in long
term control when the whole disease has been settled down
(22:09):
and it reduces recurrences and you're less likely for a
patient to turn up to the emergency department with the
generative form lesion on their cornea.
Speaker 3 (22:18):
That's very practical.
Speaker 1 (22:20):
I naively perhaps didn't realize that it could lie dormant
in the cornea itself. I thought when we spoke about
dormancy and latency of HSV, it was always in the ganglion.
So that's really really helpful to hear the pathy of
physiologic correlation to what we can sometimes be seeing.
Speaker 2 (22:34):
Yeah, I mean it's not the majority of the cases,
but you find that, and I found in that situation,
adding in topical treatment solves the problem and you don't
need the full dose of five times a day of gancyclopa.
You're talking about twice a day or once a day
even of topical treatment. But it just holds it there.
And that's the way I've understood it, and that's what
(22:56):
the patterns I've noticed over the years. But the majority,
as you said, you know, that is what happens. You know,
oral treatment will control most of the patients, but you know,
maybe nine patients out of ten will be like that,
but you'll get one that has got still genderity formulations
in the corneat despite regular doses of oral valence cyclobar
even at the higher doses, and still not getting anywhere.
(23:18):
And then you have to start thinking what's happening here?
And so that's one approach of thinking about it.
Speaker 1 (23:24):
I think it's helpful to review some dosing because it's
very practical obviously for practitioners who are prescribing these drugs.
I know, the regimen for topical gain cycle of her
eyeser again would initially be five times a day until
the dendrite is gone, and then you can slowly taper
it from there. In terms of topical prophylaxis, though you're
saying you would potentially use that in some cases keep
(23:44):
somebody on that once daily for several months.
Speaker 2 (23:47):
Yeah, I mean the topical. If you want to do prophylaxis,
then you can do that. But then the problem is
a compliance and the amount of irritation. It's crazy for
the eye. So sometimes that isn't approach. It depends on
their ability how comfortable are using systemic treatments. But systemic
treatments have the advantage and don't irritate the eye and
you don't have that confusion of coexisting OOCLA surfaces these
(24:11):
like dry disease and things like that, which confound the
whole thing. So personally, I mean, I don't use it
as a prophylactic agent, but you can do it that
way if you're stuck and you don't have oral treatment,
or you're worried about the oral treatment, if you're worried
about someone's got renal or payment or opathic impairment, or
they've got dementia, and you're worried that the medication is
(24:31):
going to cause confusion, then you're going to have to
use a topical treatment. That's the only way out. And
so you've got it, so there's still a role for it,
and one size doesn't fit all. So that's the thing
to remember. You have to then, and these issues do
come in because if you think about this, a lot
of patients get reactivation of pedict disease when they're heavily
(24:54):
eminie supressed. And with so many patients, especially in the
center their work are having very fancy fema therapy on
qology therapy and heavily even as suppressed, but all sorts
of fancy drugs at coming out these days then is
not surprising They've got reactivation of a pedic disease. And
then you're going to be adding in oral treatment, which
is going to confuse the picture more. And then your
(25:15):
general physicians are going to feel, hey, wait, these optimologies
are giving you this, all these tablets at this dosage,
and your kidney's are already going and your liver's going.
I mean, optimology is going to add more insult to injury.
So there were You've got your topical treatment there to
save you. So you have to you have to be
he is a very pragmatic approach to solve the problem
(25:36):
for sure.
Speaker 1 (25:37):
In terms of the doses for the oral medications, just
to review the prophylactic doses, is it correct that vallet
cyclovia would be approximately one gram once daily, any cyclavia
would be four hundred milligrams twice daily for the prophylactic
road roughly.
Speaker 2 (25:52):
I mean actually valast cycle but I give you five
hundred milligrams spice to day says one gram daily active there, yes,
four hundred. The problem actually, one of the problems with
a cyclobe and you know, is it's half life that
you've got a real problem with the half life of
a cyclo bear because as soon as you take the
medication then it gets it suffers from first past metabolism
(26:13):
in the liver. So the actual therapeutic level of a
cyclo BEA in the circulation is relatively low, whereas valor
cycle bear. The way to think about it, the va
l is your first master metabolism that gets knocked off
for the liver and you're left with all of the
A cycle of Bear in the systemic circulation. So and
(26:33):
a good thing about that. We also know that a
cycle of Bear in its form in the serum crosses
the blood brain barrier really well. And the blood brain
barrier and the blood ocular barriers have a very similar
mechanism and they cross over very well. So they are
very very good drugs that much lower doses frequency are
controlling the viral activity. And so when we're talking about
(26:55):
petic eye disease in general, certainly for my practice, we
miss exclusively used by the cyclo bear because of the
dosing frequency and the therapeutic effect. And five hundred bad
or one grammars you use in North America, that's quite
a good dose to use and it's very effective at
controlling the condition. Now if it is more severe than
(27:18):
you can also escalate up to two grams in a
day and without much sort of side effect profile that
I've seen. But you know, again you have to be
careful in patients who've got any dimension and so on.
So so the preference actually iscle. The only reason why
we didn't use it, let's say ten years was the cost,
because it was more expensive than using a cyclo bear.
(27:40):
And now people would hold our tie holder. I can say, sorry,
you know, you're not allowed to prescribe it. You know,
acyclo bear is a lot cheaper, So then we have
to then really give four hundred bad but actually you
have to give it even more than that sometimes, you know,
four times a day, if one hundred four times a
day to get a good strong effect, especially if you're
worried about a Ubia tic type chain DAKI, right, so
(28:01):
you might have to use it a high dose and
the effectiveness of twice a day valid Cyclova. I think
it's superior, BUTS and I think there's a lot of
studies showing that. I mean, if I look at the literature,
we've done some review papers on this, and it is
it has gone marginally superior effect. But I think what
is clear is if dosing is much more superior in
(28:22):
terms of what to take a tablet twice a day.
And the other thing is that both drugs are very
safe to take.
Speaker 1 (28:29):
I want to transition to disaster briefly, because typically the
recommendation for disaster was that we would use or a
valid cyclovir or a cyclovier if caught within the first
three days, in order to prevent post trapedic neuralgia and
potentially even the acute disease burden. Now you could also
use it outside that three day window. That three day
window was based on an initial study that only really
(28:50):
looked at trialing it in the first three days. But
there isn't evidence that it doesn't work if you take
it outside of the three days, And I don't really
see the downside to adding it in because maybe it
will reduce the incidence of post trapedic neuralgia. All that
is to say, though, is that newer evidence has come
out in the Z's trial, which we're going to be
doing an episode on at some point in the future,
(29:10):
newer evidence has come out that the viral aspect of
recurrent zaster is stronger than we initially thought. The traditional
thinking was that outside of the initial period of getting
shingles in the v one distribution, that when you had recurrences,
it was mostly an inflammatory reaction that was causing the
damage and reading havoc on the eye, not necessarily the
virus itself, but anecdotes such as seeing a pseudodendrite in
(29:34):
recurrent episodes, which we know represents active virus, and that
seeing some of these antivirals in recurrent cases did help
is part of what prompted the z's trial. That's a
long way of saying, what's your current role, if any,
for using anti virals in recurrent HZ right.
Speaker 2 (29:49):
You're asking you very look, I'm a very sopheating heavy person, Matt.
For us, we would be using antivirals very very regularly,
very frequently, more than what would be sort of generally
would be in the guidelines perhaps, So you're right, I mean,
definitely what we notice if you think, you know, as
(30:10):
you know you're in practice in the in the first
few days, if you don't give the anti virals, it's
so many patients miss that opportunity and they have really
troublesome disease. So if you get them in the early stages,
and that's going to be fantastic for the patient. But
the people who get recurrences of perhaps may have missed
the boat. There's still a role for it, and that's
always kept them on anti virus for quite long time,
(30:31):
and especially people who have pseudodendrites. I mean the pseudodendrites.
You know, it's still a dendrite. But I don't know
why it's called pseudodendrite. I mean, it means it is
a dendrite, but it's called active viris on the eye. Yeah,
I mean, but you know, I mean, are they active viruses?
Actually they VIZV. It's interesting because you know, we often
(30:55):
will do PCR on patients who've got dendritic legions. I
need to be surprised you do get vz V recovered
from some of these patients. So you know, this is
well outside that sort of you know, that window of
the first few days. So invariably, certainly in our corneral service,
we will be putting them on to both systemic anti
(31:16):
virus and they've got studio and that's topical treatment as
well to ensure the virus is kept at bay. Because
that virus is causing all sorts of havoc and the work.
The last thing you want is someone who's got intractable
neuralgia post to petic neuralgia. It's a very difficult thing
to treat, or a recurrent uv ititis, herpheesoster uviitis or retinitis.
(31:42):
So we're worried about that, and we know that people
can get that that's very severe reaction later on, and
as corneial specialists, we're less likely to even look at
the retina and they're presenting our firm and you know,
one of the criticism from our uvitist colleagues and we
don't look at the back of the ironer. So so
there will be on all antivirals until somebody tells us
(32:04):
to stop it. So that's usually what tends to happen,
and they're on it for weeks and weeks and weeks.
I mean, you know, you might think we're sort of
a little bit sort of loose on this, but and
also when they've got Cornell involvement, especially pseudodendrots as opposed
to inflammatory features, they will be on topical anti virals
(32:27):
as well, because to sad extent, it's quite a devastating disease.
You know, if you get the loster, you're really really
going to have a hard time. And the people that
have the hardest time of the people who are treated
late and inadequately, and that is the problem. And you're
going to be stuck with these patients for years. So
you've got to be quite aggressive, and you've goo be
(32:51):
also quite consistent with your approach. You've got to give
them quite regular treatment, and you must cover all the possibilities.
And that's my about it. And it's very interesting that
you've got all that information that's coming out from studies
suggesting that the virus is actually still sort of burning
around and hanging around, because that is the clinical impression.
Speaker 1 (33:12):
And I don't want to be held to my word there.
I'm not fully up to date on the results from
the Z's trial. I don't have all the insider knowledge
or haven't read all the studies yet, but I do
know that one reason the Zed's trial was done was
because people kind of did have this hunch that the
virus might be more active than we were initially giving
credence to.
Speaker 3 (33:30):
So it seems like your approach probably is not.
Speaker 1 (33:32):
Or fully aggressive, not that you need me to tell
you that, but it probably is quite prudent, and the
paradigm does seem to be shifting more towards the use
of antivirals in recurrent cases of h s ZO.
Speaker 2 (33:44):
You know, we've seen evidence, and again it's not like
a proper study, but clinical evidence of patients who've got
the pseudotendrins with PCR samples. They've got positive VSV on
PCR from samples Jesus are swabs off the court me
on apithelium and they come back a few days later
positively And this is outside that sort of normal window
that you would get their treatment. So I think that
(34:05):
is the whole view is hopefully changing about it. But
that's how we've been taking it, and it's welcoming that
other people are thinking are the same. I think the
most important thing to take home really is the first
few days is really important. You have to get in
there and treat them adequately with a sufficient dose to
make sure those blisters don't form, and those blisters in
(34:26):
the I don't form and the effects on the I
don't form. So that's really important. And perhaps the other
thing to think about is whether you know people as
a society, they should be vaccinated at the right time
to reduce anything happening. But that's that's probably another separate
story about their out You can go on about this.
Speaker 3 (34:43):
Well, doctor is saying, do you have any final thoughts
on this topic.
Speaker 1 (34:45):
You've done such an incredible job of explaining the path
of physiology really of each of these diseases and then
correlating that with how we could make a decision on
whether to use oral anti virals or the new kid
on the block topical anti virals with against.
Speaker 2 (35:00):
I mean, I've just given my views about these things
that we have written a few review articles on this.
What's worth very welcoming is that the disease doesn't change
whether you're on this side of the pond on the
other side of the pond, Okay, So it's exactly the
same thing, and the thought process are exactly the same.
So that's why we're welcoming. Everybody's doing exactly the same thing.
(35:21):
And I think one of the taking mentions some people
who might be thinking that they're slightly overtreating them. Perhaps
I've got them on their anti virals for a bit
longer then should be the normal guidelines. They've always been
feeling whether they're doing a disservice for the patients. Now,
I've had patients for over fifteen years on systemic anti
(35:43):
virals and it's very rare for someone to get a
damage to their kidneys or the or the liver from it.
And we've also had patients with on topical treatment, sometimes
quite regularly for a very long time. And at least
even if you do get a bit of irritation or
SPK on the surface of the corner, it doesn't cause
(36:06):
any long lasting damage and as soon as you reduce
it to or go away. So I think at the
end of the day, use your common sense, see what
is appropriate, think about the condition, and if you're in doubt,
then there's no harm in using antiviral therapy and it's
not as dangerous. It's probably more dangerous to leave it
(36:26):
alone and be active than to treat it. So that's
my view about it.
Speaker 3 (36:31):
I think that's very stage advice.
Speaker 1 (36:32):
And doctor Prevez, who's saying, thank you so so much
for joining me on blind Spot, Okay, thank you very much.
Hey everybody, I'm XAEO Mednik and welcome to another episode
of Blindspot. 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 Schibre. With five generations of history,
the Chubret family has been dedicated to I care for
(00:32):
more than 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 eye care.
They've created innovative delivery systems. They've 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. So thank you THEO
(00:54):
Pharmer Canada for supporting Blindspot. Herpes simplex and Herpe's zaster
virus can at time be very challenging to treat in
the eye. In some ways, it's extra challenging because there's
multiple ways to treat these viruses and the inflammation that
they induce. Typically oral antivirals such as a cyclovier and
valet cyclovier have been used to treat HSV. However, in
(01:15):
the past there were topical options such as trifloriding, commercially
known as viropatic. Those options, however, at least in Canada
and in the United States, went by the wayside several
years ago, but more recently a newer option is available
top themologists and optometrists topical gan cycle beer or commercially
known as isergan. So how does one go about making
(01:37):
the decision of when to use oral antivirals versus topical antivirals?
What are the advantages and disadvantages of each? I'm joined
today by doctor Parvez Hussein. Doctor Hossein is the Professor
and King James, the fourth Professor in Ophthalmology within the
Faculty of Medicine at the University of Southampton. He also
served as a consultant of Theolmbic Surgeon at University Hospital Southampton.
(01:58):
He's a clinical scientist focusing on corny in ocular surface disease.
He qualified in medicine from Aberdeen University and trained in
ophthalmology at Aberdeen Nottingham Chester in Miami. His clinician scientist
career started as a Welcome Trust clinical Research Fellow at
Aberdeen University. He started for his PhD in Immunology and
Biomedical Physics and Engineering to investigate the mechanisms of T
(02:19):
cell traffic in ocular inflammation. In his awarded PhD thesis,
he established a novel method for in vivo tracking of
immune cells and the retina and choroid, showing the early
interactions of lymphocytes with an inflamed and vascular endothelium. All right,
doctor parvezjus say, and welcome to the podcast. Thank you
so much for joining me.
Speaker 2 (02:38):
Thank you Zille.
Speaker 3 (02:39):
You are joining me.
Speaker 1 (02:40):
From across the pond, as we say, and you just
gave me a bit of a good history lesson on
where you're from. And I like my British history. And
we're going to be chatting also about HSV today.
Speaker 2 (02:50):
Some things don't change, doesn't matter how far you're away,
so HSB as well as it. So that's a good connection.
Speaker 1 (02:56):
So in terms of the history, I guess the history
that I kind of cited the introduction there was that
most of us are used to treating HSV and we'll
talk about zoster a little bit later, but most of
us are used to treating HSV historically with antivirals, whether
it's a cyclovier or valtrex. Now I know that in
Canada and in the US there was an option to
treat topically with trifluoridine, which was commercially known as viroptic
(03:18):
a while ago, but that was continued several years ago.
Before we get into topical gant cyclovia, which is commercially
known as isergan, I just want to talk a little
bit about the history of trifluoridine or viroptic and why
that went off the market.
Speaker 2 (03:33):
Yeah, I mean it's not I mean you have to
take it from my perspective. In the UK TFT three
drops that were available very over a long time ago,
we become totally obsolete. Now the reason why they were
taken off and I have to go back to the
nineteen nineties in the UK, there was this head study
(03:56):
Apetic eye Disease study, which looked at the effect of
anti virals and its effect on controlling herpetic carotitis, and
clearly there was a role for anti virals, particularly of
a cyclo bear but I think TFT three was in that.
But one drug company managed to manufacture a cyclo beer
(04:16):
as an eye ownment, and they and that took off
because of disease of application and the fact that it
was applied locally to the eye where the dendritic ulcer
might be in the cornea, and it had less toxicity
than TFT three. So one of the problems was the
epithelial toxicity on the cornea of using that agent. And
(04:40):
I'm still surprised to see that those available in North America,
although it has it's got its own merits, of course,
but in the UK, when a cycle of beer was
introduced as an eye ownment, then TFT three effectively became obsolete,
and the toxicity difference is between the two agents became
(05:01):
very proud. So because in the UK we're used to
using topical treatment, that's why topical treatments there are here
have been very popular. So of course there's been a
bit of a transition from that to taking systemic treatment,
which you can talk about a bit later on. But
the main reason why tftcree wasn't so popular is because
of its effect on the cornea cleared the virus, but
(05:23):
it also caused a lot of damage and collateral damage
on the surface of the eye.
Speaker 3 (05:28):
Yeah, that was my impression.
Speaker 1 (05:29):
I recall that when we were treating it in residency
with the trifluoridine or TFT as you're calling it, we
were taught that it is quite toxic, so only to
use it for limited periods, and that's why a lot
of my mentors suggested at the time that we use
oils instead. You mentioned a cyclovir eye ointment there. I've
heard of that used in North America, but not super commonly.
Is that Is that something that's still commonly used in
(05:51):
the UK?
Speaker 2 (05:53):
Yeah, I mean it's still commonly used. It was a
dominant form of treatment, so a lot of the drug
supply depends upon the manufacturer where they're willing to make it,
and so the main manufacturer decided to disinvest in it,
and then then it became generic and then it's trying
to find and manufacturer make it. So it's still available
in the UK. It's still used, but because of supply availabilities,
(06:17):
then people look around for other anti viral agents that
might be available to use topically to the eye. So
it's still widely used when it's available, and that currently
as can see, it is available over the last few years,
but there was a patch where there are problems trying
to find a manufacturer to make it, and we regular
(06:38):
face this problem in the UK. I'm sure this must
be a problem in North America where certain drugs are
supply lines become limited and optimologists then have to start
looking at alternatives to treat their patients, so that shifts
the usage rather than the side effects per se. They
need a treatment that bet she works, So that's that's
(07:00):
why there's been ups and downs with acyclvi topical YE treatments.
Speaker 1 (07:05):
And that transitions well into topical cycle. Isergan is the
commercial name now. I have used topical gan cyclovia in
the past over several years when I didn't have another
topical option, but it needed to be formulated at a
compounding pharmacy, so that really limited my use of it.
And now that isergan is commercially available and easy for
patients to buy, it's kind of re emerged on the
(07:27):
scene as a new option for a topical therapy as
opposed to just having our oral therapies. So with isergan
now being more easily commercially available, how has that factored
into your practice and how has that kind of bypassed
some of the challenges with other topical treatments that there
have been.
Speaker 2 (07:44):
Yeah, I think to be fair. Really, the supply lines
of drugs, you know when they get when they become difficult.
For example, when we've had to say cycle of a
topical treatment supply shortage, then then other other agents have
stepped in. So gan cyclob in the UK and Europe
came in just at about the right time when a
(08:06):
cyclo where it wasn't available so easily, and so that's
taken in and people then you know, conditions start using it.
The frequencies are same, the clinical effect is maybe it's
better in some ways, but when people try to use
it realize, oh, this is quite useful, this works well,
and perhaps is maybe it has associated with less toxicity.
(08:30):
But so people get used to it and they realize
that it does actually work as it says on the
tin as it were, so they so that you get
a massive uptake. And obviously it depends on the supply
lines are available in the pharmacy. So if the pharmacy
has it, then you tend to write it out. And
the tolerances are quite good and the treatment effectiveness appears
to be similar to a cyclo bear and so that's
(08:53):
why it's taken off. And while you know a cycle
of there's a competitive product, it's being the issue of
who's being able to manufacture and sufficient volume so that
actually can be used. So it's less about apps. A
clinical effectiveness is the supply effectiveness and supply lines and recruitment.
That's actually the main issue there. But saying that, the
(09:15):
preparation and the way that it handles, the way you
can instill it in the eye is quite favorable, and
so that's why it's so popular.
Speaker 1 (09:27):
One of the big benefits that's touted for isergan is
that it's preserved and free. And when I hear that,
obviously I think great. We know that preservative free is important.
We've done an episode recently on that. But I think
it's important to be clear that just because something's preservative free,
it doesn't mean that it's not toxic to the cornea,
especially important when we're dealing with treating a corneal disease. Right,
(09:49):
is it correct to say that it's much better to
use preservative free, but that doesn't mean that gan cycle
ofvia itself ceases to be toxic to the cornea. The
gan cyclovir ingredient can still cause cornial toxicity, albeit it's
much better when it is preservative free.
Speaker 2 (10:04):
I mean the problem with anti viratopical antiviral treatments too.
On the whole, they are somewhat toxic to the corneal epithelium.
Of course, when you're taking any medication more than four
times a day, then the preservatives do become significant. So
having less preservative in it does help and reduces the
(10:27):
level of toxicity. But you see this with a cycle
of organicyclo via. They if they used it quite regularly
and overused it for several weeks that five times a day,
then you will see a mild kerotopathy and spicating. The
problem is for the untrained eye, when you're dealing with
(10:47):
a dendritic type lesion or a petic involvement of the cornea,
some of the patterns of the spks that you might
see can get confused and somebody might confuse that with
latent bio activity. So the less toxicity you have, the better.
My impression is probably vigan as we call it a
(11:07):
gancycle it in the UK. It is probably less less
toxic on the eye then perhaps some of the other products.
But you still can get SPK, but the fact that
there's less preservative and it means at least that's less
likely to be a component within of the SPK that's
(11:28):
been induced, So some of it is from the drug
itself directly. So sorry, I'm not giving you a clear answer,
but there is an advantage obviously with having it preserved fee.
It means it probably doesn't sting so much, it may
not irritate the eye so much. You're most likely to
get a toxic reaction per se from the preservative, So
(11:49):
that level of ambiguity that or confusion you get later
on when the patient's been treated chronically with a drug
is less of an issue. And so there has its advantage,
and that's why it's probably one of the other fact
is why it's a popular product because of that.
Speaker 3 (12:06):
I think those are some very important points.
Speaker 1 (12:08):
One is that toxicity can make it challenging to discern
what is true disease, what's an actual dendrite or resolving
dendrite or epithelial regeneration line or versus toxicity. And the
other point you make there, which is important to remember
is that for all drops, even if they are preserved
a free that's super important, but that doesn't mean they're
devoid of causing toxicity.
Speaker 2 (12:29):
Well like glaucoma. Colleagues will say, there's a bleach called
domestos in that you clean the floor with. So this
is my latest drop is preservadive free domestos. So that
means you can have a floor cleaner which is preservative free,
but it's still that can damage your eyes. So don't
forget the big picture is quiet agent. The active agent
(12:54):
can be quite toxic, but it applies to all drye
drops to that extent. You know, some one, some are more.
But if we actually think about antiviral eye drops, so
one of the challenges is that actually they deal with
the purine since this pathway, so they are going to
affect cell cycle changes within the cell with any cell,
and you tend to get a bit. You get damage
(13:16):
from the surface from all of them. And I think
the extreme example is the TFT drops. That's probably the
extreme example of a of those anti virals. And as
we go to a cycler and gancycle, we see the
kinder type of domestos of your eye. But not to
say it is domestos, but it's much kinder on the
(13:36):
eye and that's why you can see the take up
of those medications are so high in places out of
UK and in Europe where it's used very widely, so
people are aware of that toxicity. And then there's the
argument of using oral treatment. You know, we were going
to discuss that versus topical treatment. So that's a relative advantage.
(13:59):
You don't have to worry the toxicity on the eye,
but then you're left with the toxicity or vessel of
the body to worry about. That. That's a different matter.
Speaker 1 (14:06):
Yeah, So let's talk about that, because I do find
it sometimes a bit challenging to decide when am I
going to use oral something like a cyclovia or valley
cyclovier as opposed to something topical like gance cyclovier. In
my mind, I think if it's just a dendrite, not
to minimize the significance of a dendrite, but if it's
confined to the epithelium, I might be more likely to
use the topical gan cyclovia because I'll say, you.
Speaker 3 (14:27):
Know what, there's not much else I need to treat.
Speaker 1 (14:29):
It's not that the gan cyclovia isn't going to penetrate
at all into the eye, but it's going to be
most effective on the superficial aspect of the cornea, whereas
if I've got other stuff going on, and also based
on the heads trial that has been done in the past,
then I might be more inclined if there's an iritis,
for example, something deeper in the eye. At that point
to go oral, what helps guide your decision when you're
(14:50):
making that choice, I.
Speaker 2 (14:52):
Mean the way I look at it exactly the same
as what you've cited there, because what you have to
look at is where is the viral latency of where
is it most active. So if you're seeing a dendrite,
then clearly the virus is laden in their epithelium, and
so if you're applying an antiviral ointment directly topically to
(15:12):
the eye, you'll be hitting it ahead on. So that
makes a lot of sense. That also applies to latency
as well, because if you think about the viral and
you know the whole pathway we're talking about the opthalmic
divisionals or trigeneral novid it depends where you starts off
from the ganglion all the way up to the cordial
epithelian and the nerves and the cornea and the virus
(15:33):
can be at any point, but if it's predominantly at
the tip at the corneal epithetium or corneal sub epithel there,
then perhaps a topical treatment will be very effective. But
if it's latencies deeper down in the trigeminal ganglion, then
you may want to think we consider whether systemic treatment
(15:53):
would be useful in that case, especially one that will
help cross the blood brain barrier. And if you're thinking
about latency that's in the iris or the uveal tract,
then again systemic treatment would be your best choice. And
so so that's the way to think about it. Think
about the anatomy where the virus is, where can you
(16:14):
see it active? So if it's active in the corneal epithemium,
it means most of the virus particles are there and
that's where you've got to target it. But it is
also very frequent to see virus all over the place
and you may want to use both. So quite a
lot of patients that we have are on both treatments.
They are on topical gang cycle of BEA and on
(16:36):
systemic valel cycle of here and it's very very frequent.
If you're more office based, or if you're like saying
an optometrist, as it's got prescribing rights, they're rather reluctant
to give oral treatment. They probably don't have the prescribing
rights to go to oral treatment. So you know, it
depends on your registration and your own locality. So you'd
be more comfortable using topical treatment, and that's perfectly fine.
(16:59):
I mean in primary I care, for example, a lot
of conditions are uncomfortable using systemic therapies and they're worried
what the side effects could be, and so you're more
inclined to then give topical treatment in that situation. But
if you're possible with based practitioner, and you'd have a
little bit more latitude and be able to use systemic medication,
(17:20):
maybe more comfortable using it. So things also that level
as well, depends on the actual condition and what they
feel comfortable using. But sometimes you can get effective control
of the cornell activity with high dosages of systemic anti virals.
But then if you're going to go to that line
of things, then you have to then worry about the
(17:41):
side effects, so and you may have to take it
for a long time and then patients will have keepen
asking you or is he going to damage my liver
or kidneys? And certainly with valid cycling, but you have
to be very careful in elderly patients because because it
affects I mean, this is the way to think about it.
It can create confusion for patients with low grades of
(18:01):
in high grades of dementia. So if you start giving
regular valor cyclovia, you could make their dementia somewhat worse.
So you have to be careful what you use. But
sometimes you can argue that it's easier to administer the
treatment because you can mix it up in their food
and give the tablet, whereas harder they give topical treatment
(18:23):
on those sort of patients. But that's something to think about,
you know. That's another angle and things that we come across. So, yeah,
the logic of using it depends where you see most
predominant activities, So topical treatment that you can see directly
in the eye, deeper in the eye, maybe you're thinking
about systemic treatments. Combination of both might also be sensible
as well. And if you want to do prophile axis
(18:45):
of antiviral reactivation, then perhaps you're better off taking systemic
treatment because of the latency with it might be resident
in the trigeminal ganglion and perhaps the topical treatment has
got no way near nowhere near where that activity might be.
Speaker 3 (19:00):
You read my mind there.
Speaker 1 (19:01):
My next question was going to be, so we know
that it does stay dormant in the ganglion, and in
those situations a topical treatment isn't going to penetrate that ganglion. Obviously,
So in those situations, if you've decided to go for
long term prophile axis, because you don't always decide to
Usually you wait if somebody's had a recurrence or two.
But in the situation where you do decide to go
(19:22):
for long term prophile axis, are you more likely to
go for oral as opposed to topical because we know
that the oral is systemic and can actually get to
that ganglion where the virus is hiding out and laying dormant.
Speaker 2 (19:35):
Yeah, yeah, yeah, So that's certainly. In my practice we
use a lot of oil treatment. But you don't remember
that my practice is based predominant in a tertiary in
it in a coordinal service. There so most of the
easy stuff has already been done, So all the topical
treatments already been tried, and patients have quite often on
their fourth or fifth or sixth attack and they want
(19:58):
more X but help to control their attack. So the
topic treatments already been tried and they were onto systemic
therapies and usually the treatment that I tend to use
is or palicyclo bear and we would try to trade
the dose accordingly to see whether we can reduce the
number of attacks. And many other patients are on the
treatment for you know, several months, even several years to
(20:21):
control these attacks. And every time you have an attack
of a petticaretitis, then the inflammation and the net scarring
that occurs, it brings down your vision and it may
not recover back to the level that was before. So
you really want to be able to control that virus,
hold it in its place, stop it from traveling down
(20:42):
the trigeminal nerve and activating locally in the cornea. So
that's the strategy for those patients, and having used it
for the last fifteen years, I can say that that
can be a very effective strategy. But sometimes you see latency,
not necessarily in the trigeneral gangling. It's somewhat further down,
(21:04):
closer to the cornea, and for some patients they probably
do also need topical treatment as well. And it is
quite defined where that. You know, we can't see where
the virus is precisely latent. We you know, we can
see historological studies showing that it is latent in the
trigeneral gaming, but the latencies in theory could be I
(21:26):
missed anywhere. Really, But if it is more latent in
let's say, in the corn illos, Remember the cornillinas are
quite a dense structure. You know, we can't we don't
see them on the slit land, but if you do comevocal,
you'll see a lot of them, and the virus may
be latent in that region. And for that reason, then
perhaps in certain cases the topical treatment would be more
(21:48):
effective at controlling it, or combined with systemic treatment would
be very effective way of controlling in the virus so
that it doesn't reactivate. So, you know, this is what
I'm trying to think. Think about the anatomy. Then you
can then think about your treat and choices and the presentations.
But generally speaking, systemic treatment work really well in long
term control when the whole disease has been settled down
(22:09):
and it reduces recurrences and you're less likely for a
patient to turn up to the emergency department with the
generative form lesion on their cornea.
Speaker 3 (22:18):
That's very practical.
Speaker 1 (22:20):
I naively perhaps didn't realize that it could lie dormant
in the cornea itself. I thought when we spoke about
dormancy and latency of HSV, it was always in the ganglion.
So that's really really helpful to hear the pathy of
physiologic correlation to what we can sometimes be seeing.
Speaker 2 (22:34):
Yeah, I mean it's not the majority of the cases,
but you find that, and I found in that situation,
adding in topical treatment solves the problem and you don't
need the full dose of five times a day of gancyclopa.
You're talking about twice a day or once a day
even of topical treatment. But it just holds it there.
And that's the way I've understood it, and that's what
(22:56):
the patterns I've noticed over the years. But the majority,
as you said, you know, that is what happens. You know,
oral treatment will control most of the patients, but you know,
maybe nine patients out of ten will be like that,
but you'll get one that has got still genderity formulations
in the corneat despite regular doses of oral valence cyclobar
even at the higher doses, and still not getting anywhere.
(23:18):
And then you have to start thinking what's happening here?
And so that's one approach of thinking about it.
Speaker 1 (23:24):
I think it's helpful to review some dosing because it's
very practical obviously for practitioners who are prescribing these drugs.
I know, the regimen for topical gain cycle of her
eyeser again would initially be five times a day until
the dendrite is gone, and then you can slowly taper
it from there. In terms of topical prophylaxis, though you're
saying you would potentially use that in some cases keep
(23:44):
somebody on that once daily for several months.
Speaker 2 (23:47):
Yeah, I mean the topical. If you want to do prophylaxis,
then you can do that. But then the problem is
a compliance and the amount of irritation. It's crazy for
the eye. So sometimes that isn't approach. It depends on
their ability how comfortable are using systemic treatments. But systemic
treatments have the advantage and don't irritate the eye and
you don't have that confusion of coexisting OOCLA surfaces these
(24:11):
like dry disease and things like that, which confound the
whole thing. So personally, I mean, I don't use it
as a prophylactic agent, but you can do it that
way if you're stuck and you don't have oral treatment,
or you're worried about the oral treatment, if you're worried
about someone's got renal or payment or opathic impairment, or
they've got dementia, and you're worried that the medication is
(24:31):
going to cause confusion, then you're going to have to
use a topical treatment. That's the only way out. And
so you've got it, so there's still a role for it,
and one size doesn't fit all. So that's the thing
to remember. You have to then, and these issues do
come in because if you think about this, a lot
of patients get reactivation of pedict disease when they're heavily
(24:54):
eminie supressed. And with so many patients, especially in the
center their work are having very fancy fema therapy on
qology therapy and heavily even as suppressed, but all sorts
of fancy drugs at coming out these days then is
not surprising They've got reactivation of a pedic disease. And
then you're going to be adding in oral treatment, which
is going to confuse the picture more. And then your
(25:15):
general physicians are going to feel, hey, wait, these optimologies
are giving you this, all these tablets at this dosage,
and your kidney's are already going and your liver's going.
I mean, optimology is going to add more insult to injury.
So there were You've got your topical treatment there to
save you. So you have to you have to be
he is a very pragmatic approach to solve the problem
(25:36):
for sure.
Speaker 1 (25:37):
In terms of the doses for the oral medications, just
to review the prophylactic doses, is it correct that vallet
cyclovia would be approximately one gram once daily, any cyclavia
would be four hundred milligrams twice daily for the prophylactic
road roughly.
Speaker 2 (25:52):
I mean actually valast cycle but I give you five
hundred milligrams spice to day says one gram daily active there, yes,
four hundred. The problem actually, one of the problems with
a cyclobe and you know, is it's half life that
you've got a real problem with the half life of
a cyclo bear because as soon as you take the
medication then it gets it suffers from first past metabolism
(26:13):
in the liver. So the actual therapeutic level of a
cyclo BEA in the circulation is relatively low, whereas valor
cycle bear. The way to think about it, the va
l is your first master metabolism that gets knocked off
for the liver and you're left with all of the
A cycle of Bear in the systemic circulation. So and
(26:33):
a good thing about that. We also know that a
cycle of Bear in its form in the serum crosses
the blood brain barrier really well. And the blood brain
barrier and the blood ocular barriers have a very similar
mechanism and they cross over very well. So they are
very very good drugs that much lower doses frequency are
controlling the viral activity. And so when we're talking about
(26:55):
petic eye disease in general, certainly for my practice, we
miss exclusively used by the cyclo bear because of the
dosing frequency and the therapeutic effect. And five hundred bad
or one grammars you use in North America, that's quite
a good dose to use and it's very effective at
controlling the condition. Now if it is more severe than
(27:18):
you can also escalate up to two grams in a
day and without much sort of side effect profile that
I've seen. But you know, again you have to be
careful in patients who've got any dimension and so on.
So so the preference actually iscle. The only reason why
we didn't use it, let's say ten years was the cost,
because it was more expensive than using a cyclo bear.
(27:40):
And now people would hold our tie holder. I can say, sorry,
you know, you're not allowed to prescribe it. You know,
acyclo bear is a lot cheaper, So then we have
to then really give four hundred bad but actually you
have to give it even more than that sometimes, you know,
four times a day, if one hundred four times a
day to get a good strong effect, especially if you're
worried about a Ubia tic type chain DAKI, right, so
(28:01):
you might have to use it a high dose and
the effectiveness of twice a day valid Cyclova. I think
it's superior, BUTS and I think there's a lot of
studies showing that. I mean, if I look at the literature,
we've done some review papers on this, and it is
it has gone marginally superior effect. But I think what
is clear is if dosing is much more superior in
(28:22):
terms of what to take a tablet twice a day.
And the other thing is that both drugs are very
safe to take.
Speaker 1 (28:29):
I want to transition to disaster briefly, because typically the
recommendation for disaster was that we would use or a
valid cyclovir or a cyclovier if caught within the first
three days, in order to prevent post trapedic neuralgia and
potentially even the acute disease burden. Now you could also
use it outside that three day window. That three day
window was based on an initial study that only really
(28:50):
looked at trialing it in the first three days. But
there isn't evidence that it doesn't work if you take
it outside of the three days, And I don't really
see the downside to adding it in because maybe it
will reduce the incidence of post trapedic neuralgia. All that
is to say, though, is that newer evidence has come
out in the Z's trial, which we're going to be
doing an episode on at some point in the future,
(29:10):
newer evidence has come out that the viral aspect of
recurrent zaster is stronger than we initially thought. The traditional
thinking was that outside of the initial period of getting
shingles in the v one distribution, that when you had recurrences,
it was mostly an inflammatory reaction that was causing the
damage and reading havoc on the eye, not necessarily the
virus itself, but anecdotes such as seeing a pseudodendrite in
(29:34):
recurrent episodes, which we know represents active virus, and that
seeing some of these antivirals in recurrent cases did help
is part of what prompted the z's trial. That's a
long way of saying, what's your current role, if any,
for using anti virals in recurrent HZ right.
Speaker 2 (29:49):
You're asking you very look, I'm a very sopheating heavy person, Matt.
For us, we would be using antivirals very very regularly,
very frequently, more than what would be sort of generally
would be in the guidelines perhaps, So you're right, I mean,
definitely what we notice if you think, you know, as
(30:10):
you know you're in practice in the in the first
few days, if you don't give the anti virals, it's
so many patients miss that opportunity and they have really
troublesome disease. So if you get them in the early stages,
and that's going to be fantastic for the patient. But
the people who get recurrences of perhaps may have missed
the boat. There's still a role for it, and that's
always kept them on anti virus for quite long time,
(30:31):
and especially people who have pseudodendrites. I mean the pseudodendrites.
You know, it's still a dendrite. But I don't know
why it's called pseudodendrite. I mean, it means it is
a dendrite, but it's called active viris on the eye. Yeah,
I mean, but you know, I mean, are they active viruses?
Actually they VIZV. It's interesting because you know, we often
(30:55):
will do PCR on patients who've got dendritic legions. I
need to be surprised you do get vz V recovered
from some of these patients. So you know, this is
well outside that sort of you know, that window of
the first few days. So invariably, certainly in our corneral service,
we will be putting them on to both systemic anti
(31:16):
virus and they've got studio and that's topical treatment as
well to ensure the virus is kept at bay. Because
that virus is causing all sorts of havoc and the work.
The last thing you want is someone who's got intractable
neuralgia post to petic neuralgia. It's a very difficult thing
to treat, or a recurrent uv ititis, herpheesoster uviitis or retinitis.
(31:42):
So we're worried about that, and we know that people
can get that that's very severe reaction later on, and
as corneial specialists, we're less likely to even look at
the retina and they're presenting our firm and you know,
one of the criticism from our uvitist colleagues and we
don't look at the back of the ironer. So so
there will be on all antivirals until somebody tells us
(32:04):
to stop it. So that's usually what tends to happen,
and they're on it for weeks and weeks and weeks.
I mean, you know, you might think we're sort of
a little bit sort of loose on this, but and
also when they've got Cornell involvement, especially pseudodendrots as opposed
to inflammatory features, they will be on topical anti virals
(32:27):
as well, because to sad extent, it's quite a devastating disease.
You know, if you get the loster, you're really really
going to have a hard time. And the people that
have the hardest time of the people who are treated
late and inadequately, and that is the problem. And you're
going to be stuck with these patients for years. So
you've got to be quite aggressive, and you've goo be
(32:51):
also quite consistent with your approach. You've got to give
them quite regular treatment, and you must cover all the possibilities.
And that's my about it. And it's very interesting that
you've got all that information that's coming out from studies
suggesting that the virus is actually still sort of burning
around and hanging around, because that is the clinical impression.
Speaker 1 (33:12):
And I don't want to be held to my word there.
I'm not fully up to date on the results from
the Z's trial. I don't have all the insider knowledge
or haven't read all the studies yet, but I do
know that one reason the Zed's trial was done was
because people kind of did have this hunch that the
virus might be more active than we were initially giving
credence to.
Speaker 3 (33:30):
So it seems like your approach probably is not.
Speaker 1 (33:32):
Or fully aggressive, not that you need me to tell
you that, but it probably is quite prudent, and the
paradigm does seem to be shifting more towards the use
of antivirals in recurrent cases of h s ZO.
Speaker 2 (33:44):
You know, we've seen evidence, and again it's not like
a proper study, but clinical evidence of patients who've got
the pseudotendrins with PCR samples. They've got positive VSV on
PCR from samples Jesus are swabs off the court me
on apithelium and they come back a few days later
positively And this is outside that sort of normal window
that you would get their treatment. So I think that
(34:05):
is the whole view is hopefully changing about it. But
that's how we've been taking it, and it's welcoming that
other people are thinking are the same. I think the
most important thing to take home really is the first
few days is really important. You have to get in
there and treat them adequately with a sufficient dose to
make sure those blisters don't form, and those blisters in
(34:26):
the I don't form and the effects on the I
don't form. So that's really important. And perhaps the other
thing to think about is whether you know people as
a society, they should be vaccinated at the right time
to reduce anything happening. But that's that's probably another separate
story about their out You can go on about this.
Speaker 3 (34:43):
Well, doctor is saying, do you have any final thoughts
on this topic.
Speaker 1 (34:45):
You've done such an incredible job of explaining the path
of physiology really of each of these diseases and then
correlating that with how we could make a decision on
whether to use oral anti virals or the new kid
on the block topical anti virals with against.
Speaker 2 (35:00):
I mean, I've just given my views about these things
that we have written a few review articles on this.
What's worth very welcoming is that the disease doesn't change
whether you're on this side of the pond on the
other side of the pond, Okay, So it's exactly the
same thing, and the thought process are exactly the same.
So that's why we're welcoming. Everybody's doing exactly the same thing.
(35:21):
And I think one of the taking mentions some people
who might be thinking that they're slightly overtreating them. Perhaps
I've got them on their anti virals for a bit
longer then should be the normal guidelines. They've always been
feeling whether they're doing a disservice for the patients. Now,
I've had patients for over fifteen years on systemic anti
(35:43):
virals and it's very rare for someone to get a
damage to their kidneys or the or the liver from it.
And we've also had patients with on topical treatment, sometimes
quite regularly for a very long time. And at least
even if you do get a bit of irritation or
SPK on the surface of the corner, it doesn't cause
(36:06):
any long lasting damage and as soon as you reduce
it to or go away. So I think at the
end of the day, use your common sense, see what
is appropriate, think about the condition, and if you're in doubt,
then there's no harm in using antiviral therapy and it's
not as dangerous. It's probably more dangerous to leave it
(36:26):
alone and be active than to treat it. So that's
my view about it.
Speaker 3 (36:31):
I think that's very stage advice.
Speaker 1 (36:32):
And doctor Prevez, who's saying, thank you so so much
for joining me on blind Spot, Okay, thank you very much.
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