Welcome to the Mayo Clinic
ophthalmology podcast,
a weekly podcast on
all things ophthalmology brought
to you by Mayo Clinic.
I'm your host, Dr. Andrea to
Lee and I'm Dr. Eric Bolton.
We're here to bring you the
latest and greatest in
ophthalmology medicine and more.
Today we're joined by Dr. John Chen,
a professor of neural ophthalmology
and Neurology here at Mayo Clinic.
We're talking all things papilledema,
how to tell papilledema and conditions like I
H versus other more
atypical causes of papilledema.
We're also talking about the role
of AI artificial intelligence,
looking at the optic nerve, finally,
we'll test it on astronauts and conditions
their optic nerves may
suffer while they're in space.
John Chen is an MD, PhD,
and professor of ophthalmology and
Neurology here at the Mayo Clinic
in Rochester, Minnesota.
He serves as president of
the Minnesota Academy of Ophthalmology,
chairman of the Upper
Midwest neuro ophthalmology group,
and is an editorial board member
of neuro ophthalmology.
We frequently see his editorials
on neuro ophthalmology through EO.
Additionally, John Chen was
just awarded in R0 R1 for his work
with invest to work to investigate
structural changes in eyes with papilledema.
Welcome Dr. Chen.
Well, thanks for having me.
I'm excited to be here.
We're excited to have you
we're talking papilledema today.
And whenever I think of papilledema,
I immediately think of I
h idiopathic intracranial hypertension.
So could you just quickly take us
through the traditional papilledema we
see with IH versus
other more atypical types of papilledema?
No, absolutely.
So in a scenario when you have
a patient with Bilateral swollen optic nerves
within tech vision,
that's typically going to be papilledema
from race intracranial pressure.
I think the first thing you have to do
is determine is it truly
papilledema because some patients
can come in with nerves that look
elevated from optic disc drusen
are other causes and that pseudo papilledema.
So that's my first branch is
this papilledema is this pseudo papilledema.
Once you determine it's papel edema,
then you've gotta go and truly
investigate to make
sure it's truly idiopathic
intracranial hypertension.
So entails getting an MRI and MMRV.
And if that's normal other
than indirect sensor race pressure,
then you proceed with a lumbar puncture
to confirm you've got
an elevated opening pressure,
makes sure that fluid shows
no signs of infection or inflammation.
Then you can make your diagnosis
of idiopathic intracranial hypertension.
Of course, some of these other causes
of race pressure may have
neurologic deficits other than just division.
So if they've got problems with
balance or weakness in the arm,
obviously you're not thinking this is gonna
be idiopathic intracranial hypertension.
But sometimes you don't know.
We had a patient a month ago
who was a female in her 30s,
who came in with headaches,
bilateral swan optic nerves,
look like it was gonna
be idiopathic intracranial hypertension,
got an MRI and there was a massive tumor.
They're causing mid-line shift
and that was a mass that was doing that.
So just looking at a patient
alone isn't enough.
You really have to do that imaging
to make sure everything looks okay.
The lumbar puncture to
make sure there's no signs
of inflammation or other things like that.
When such patients come in and they're
complicated and I think
most of us is ophthalmologists can
recognize or something
potentially more going on.
It's so critical to stop
and think about what you're referring
to as other signs and symptoms to
help us in diagnostically.
You bring in a phenomenal skill set,
not just as an ophthalmologist,
but also as a neurologist.
So help the rest of us in terms of giving us
a quick and dirty list
of things we should do.
That would be a neurological examination in
our eye clinics to help us evaluate patients.
Well, that's great. I think
a lot of it's going to come from the history.
And so oftentimes with patients,
I'll just rattle off
some symptoms to see if they have any.
Say Do you have any numbness,
tingling, weakness, imbalance?
I just kinda router that off but
almost every patient I see.
And so
that's that's one thing that's helpful.
I just see them
walk in the room because you know,
you're looking for problems with
imbalanced ataxia,
prompts in coordination,
you can see that in their gait.
Then if they do say
they have problems with coordination,
just a simple knows to finger kind of tests
to look for kind of
crude problems with coordination.
I can list some of the main things I do.
The great thing about being at
the Mayo Clinic is we
have some phenomenon neurologists.
And so I often
refer our patients to our colleagues in
neurology if they have
any of these symptoms or
any of these signs of any deficits.
And so it's great to have colleagues
that have expertise beyond what we have.
And again,
it's good to build those
relationships no matter where you are.
There's been a lot of talk
about AI and grading
disc edema and how
that's kinda the new frontier.
What do you see with the role of
AI in terms of
how we look at the optic nerve,
how we grade disk edema, and how would
that fit into your practice?
Artificial intelligence is pretty
amazing and I do think
it's going to be having a large impact.
We actually had a collaborative study
with Dan Emilia in Singapore.
And he's got this amazing set
up to look at AI
for looking at swollen
optic nervous versus not swollen up in nurse.
And so, yes, this train
algorithm to
differentiate Pepperdine
from pseudo papilledema.
And then a group of us sent in
photographs of
optic nerves to have papilledema,
some that have ischemic optic
rapidly, some that are normal,
and some that are drusen and
tested this algorithm essentially blindly.
So essentially it was trained
on these other photographs and we set
them 1,500 photos that
it had never seen before.
And essentially it was 90% accurate in
being able to detect
papilledema versus non papilledema.
Unbelievable. So it's just going
to revolutionize the way
of being able to pick things up.
And then what's exciting beyond that is we
then sent to the
best interrupt modest in the US.
Valerie abuse and Nancy Newman
sent them the Singapore to
challenge the AI computer.
It was sort of like the chest
versus chess master computer.
And the results were striking.
Essentially, they were about the same.
And the time it took the AI to do
the analysis was 25 s
and our experts that took over an hour.
And this was the best of the best and still
ended up with about 90% accuracy
based on the funnest photos.
And then we've got a future study looking at
AI versus non or up the monstrous.
So ophthalmologist,
neurologists, optometrists,
ER physicians, and essentially ai is,
is, is beating them.
So I see AI potentially being in the ER.
So if we've got a fun as camera in the ER,
patient comes in with headaches,
blurred vision.
Take a non mydriatic,
non-duality picture of the fundus photo.
And then just run it through the eye.
And the eye is going to be all pickup,
papilledema and alert.
What's, what's important or not.
So I think it's exciting.
It's right around the corner.
And I think will
revolutionize the way we care
for these patients and avoid
missing patients that could
have significant problems.
It's such a condition that
pattern recognition of
subtleties are so valuable.
So it's wonderful to think about
some of these tools helping us
because most of us look at
a swollen optic nerve getting nervous.
Because we don't have the expertise and
pattern recognition built up
like neuro ophthalmologists do.
So you make a diagnosis of IH
based on your own expertise
and our teamwork and or AI.
Tell us just over
the last ten years what's changed in
the classic paradigms or treatment of
i h for a patient,
then you want to diagnose?
Yeah. Actually a lot.
We've known about for a long time,
but some things have changed.
We've always treated with acetazolamide
and clinically we knew it worked.
But in 2014, we actually had
a randomized clinical trial showing that
acetazolamide is superior than diet alone.
And not only lead to
faster recovery of the papilledema,
but also actually ended up
with better visual outcomes.
So it's really nice to have
that clinical trial data showing
that things that we've done
for awhile does work.
And so it just
proves that these treatments are effective.
It allowed us to know what dose we can go to.
Patients allowed patients can tolerate a
size 2,000 mg twice a day,
so 4,000 mg of acetazolamide a day.
And again, outcomes were excellent.
The other large shift
is there has been in terms of surgery,
traditionally, we've reserved surgery
for vision threatening disease and
our options were optic nerve sheath
fenestration and a VP shunt.
Over the past five years or so,
there has been a little bit more exploration
of another surgery
called venous sinus stenting.
So patients with IH typically
have stenosis or squishing
of their transverse venous sinus.
And with this surgery, endovascular surgery,
they were able to put in
a stent to open up that stenosis
and allows the blood
to essentially escape the brain.
And it has been working very, very well.
We've done about 100 cases of
venous sinus stenting at the Mayo Clinic.
And essentially, I don't think there's
really been any patient who
had normal II H who
did not respond in terms of
the demon grade to
the venous sinus stenting
and complications rates are quite low.
So I think that's been
a large paradigm shift
is how much more venous sinus stenting we're
doing compared to a VP shunt and some of
these other surgical options.
Again, it's still remains.
Medical disease.
But if you need surgery,
it's nice to have that extra treatment.
And then most recently
this has done actually the UK,
they did a randomized clinical
trial comparing
bariatric surgery to weight-loss
alone in its response in patients with IH.
And this was just published in the summer.
And they found that patients
who underwent bariatric surgery,
of course, had more weight loss,
but they also had lower
intracranial pressure,
faster resolution of papilledema.
Obviously you're not going to do that in
a patient who comes in with fulminant.
Ih, he's gonna be blind in a week.
That's going to take time.
But it's nice to know that that is an option.
We know weight-loss works and
bariatric surgery certainly helps with that.
So a lot of a lot of new treatments,
new data, and I'm
sure in the future we'll probably have
randomized data on
venous sinus stenting as well.
But I am very
confident that it's going to work.
Yeah, it's amazing. The new treatment options
that we can offer our patients is terrific.
This is clearly a passion
of yours and my research interests of yours.
You actually just got an R1.
Congratulations,
looking at structural changes
in the eyes with papilledema,
can you tell us about
your research and your R1?
Yeah, of course it's,
I find papillary move very fascinating.
One of
the most fascinating things is the fact
that it's so variable.
You'll see a patient who's got
an opening pressure of 35, which is high.
And they've got great for papilledema.
You'll see another patient who
has an opening pressure of 50,
which is two times normal and
they've got grade one papilledema.
So why is there
not a direct correlation between
how much pressure you have
in your head and the amount of swelling.
And even rare,
sometimes we'll see a patient with
papilledema in one eye and none in the other.
And obviously again, the
pressure is high everywhere
in the brain and yet one nerve is 11 is not.
So there has to be
something that either predisposes and I
oedema or something that
prevents the pathogen from happening.
In one of our theories is that there may be
structural differences within the eye itself.
And so in collaboration
with damaging and sit,
we're using this technology
caught ultrasound, elasto graphy.
So essentially it's an ultrasound
that we typically see.
But on top of that we have
something called a shaker that actually
just gently vibrates the eye
and moves it a little bit.
And then with the, what it does is it causes
little waves of propagation through the eye.
And depending on how fast the tissue moves,
you can actually determine how stiff it
is using ultrasound unless telegraphy.
And what we did is we measured
the posterior sclera of eyes.
This was a mini grant
through the Mayo Clinic ultrasound team.
And we found that
the posterior sclera was actually stiffer
and eyes with papilledema
compared to normal controls.
And an eyes with unilateral papilledema.
The eye width, the Pepperdine with
stiffer than the other eye.
So they almost had an internal control.
So essentially there's two theories
in terms of what might be going on.
One is you've got a stiff posterior sclera.
And we can't measure the landmark Barbosa
where
the actual pressure is being transmitted.
But if you've got a stiff posterior sclera,
you can see that there's
less flexibility there.
So all that pressure
is getting transmitted to
the laminar Kubota and then you've
got two more swollen optic nerve.
And then if you had a softer post
your sclera pretty much if you've got
pressure going in the back of the eye,
the entire area can move up and that
may kind of protect you. So that's stiffer.
Sclera may predispose you to papilledema.
The other option is that what we're measuring
is there's more pressure
getting to the eye with more papilledema.
And that's why it's different because
everything's just kinda pressing on the eye.
I think both of
those explanations will be helpful.
One, we could potentially predict
which eyes are predisposed to papilledema.
Or two, we can
actually detect that there's pressure
getting to the eye so we can help
differentiate papilledema
from pseudo papilledema.
So with the R1, we've got funding now to
enroll about 50 to 100 patients
with IH to confirm or finding.
And also what's great is burned get
baseline measurements
while there's papilledema,
we're going to treat them medically
or surgically if they need it.
And when the papilledema has gone,
we're going to remeasure those
exact same eyes and
see what happens to that stiffness.
And then we'll be able to answer.
Is this secondary depression
we're getting transmitted the eye?
Or is this that predisposition
that allows that to devote more papilledema.
That's fascinating, kind of a chicken
or an egg situation.
But I think both answers are
gonna be helpful clinically.
Yeah, I really like it.
And you're also looking into
structural changes in the optic nerve
in astronauts or types
of changes that we see in space flight?
Yes. Yes, absolutely.
So it's really fascinating.
So astronauts when they go to space,
will actually develop, some of
them will develop papilledema quarter false.
It will look like our terrestrial IH,
but these are not your demographics of IH.
Ih is going to be typically females.
90% are gonna be obese or overweight.
Are astronauts, are
the fittest men and women we've got.
And yet they develop these
structural changes that look like I
H. And it's gonna be
from the microgravity essentially.
On Earth, we've got
gravity pulling that blood back
down to our heart in
microgravity that doesn't exist.
So that's how I think they
developed a papilledema NIH.
We've been collaborating with
a group in nasa,
Scott Smith and Sierra Resort.
And they're using, what they found is that
astronauts to dip develop
more papilledema tend to have a polymorphism,
polymorphism in
the one-carbon metabolism pathway.
And so what we're
doing now is we're looking at our patients
with II H to see if
they may potentially have
those polymorphisms as well.
Because that may be a shared phenotype
that predisposes to papel edema.
They're also in Germany.
There's this amazing cohort.
We're trying to come up with some kind of
on Earth I guess,
mechanism of mimicking papilledema and space.
So in Germany they have normal,
healthy volunteers that lie six
degrees head down for a month at a time.
And actually within one or two weeks,
they start developing
Pavlo edema in Colorado folates.
So that's our terrestrial model
of spaceflight,
is people just six degrees head down.
And Scott Smith and zeros where it looked
at the ones that
didn't more papilledema and they
had the same polymorphisms in there.
And so we're now going to extend ultrasound,
the last geography to see if we can predict
and help predict which of
the astronauts that might develop edema.
Or some of these patients that
are six degrees head down.
They're looking at the one-carbon
metabolism pathways to
see if we could potentially
alter this by diet.
We're looking at OCT or CT
angiography in both astronauts and these,
these healthy volunteers in Germany.
So it's exciting to
try and be able to get this sorted out.
This is important because we think that
there's more papilledema the
longer you're out in space.
So if we do want to send
our astronauts to Mars,
we've gotta get this figured
out because less than when I do,
it's ever astronauts
unable to see why they're
piloting these
incredibly intricate space shuttles.
It's fascinating. Well, thank
you so much for the tour.
Both locally, nationally, globally and outer
space through optic or
swollen optic nerves and papilledema.
Of course, happy to be here.
Thanks so much. Wonderful.
Thanks everyone.
You can find all episodes of
the Mayo Clinic ophthalmology
podcast on our website.
Thank you for listening and we definitely
look forward to sharing more next week.