Q&A with Dr. Tim Stout about Inherited retinal diseases (IRD) and the importance of genetic testing.
So Dr Stout thank you for being with us
today.
I'm wondering if you can please tell us
you know who you are and what you do?
Hi Tiff, so i'm a vitro retinal
specialist.
I specialize in pediatric retina as well
as
inherited retinal diseases, that's what I
do on the clinical side.
I run a laboratory which looks at the
development of gene therapy tools
and stem cell therapy tools for
inherited rental diseases
and I'm chairman of the ophthalmology
department at baylor college of medicine
here in Houston Texas. And can you tell
us today
what are inherited retinal diseases?
Right, inherited retinal diseases are a
collection of
generally genetically defined
diseases
that affect the retina's ability to
work.
The retina is that part of the eye that
gathers the light
and converts light information into
electrical signals
which is what the brain can understand.
And then all those electrical signals go
back to the brain
through the optic nerve and the brain
sorts it all out.
So the retina is like the film in the
camera.
It's the part of the eye that
senses
and and starts the process of light.
And as it turns out it takes a lot of
moving parts to do that,
over 300 moving parts.
And each of those moving parts is
encoded, those moving parts are proteins,
and each of those moving parts are
encoded by your genes.
So that whole process of converting
light information to electrical
information requires 300 different
moving parts.
and so if you have a problem in one of
those moving parts
it's going to affect your vision.
Now there's a big spectrum
between what affects your vision means.
Sometimes it can be so mild that your
vision is essentially normal your entire
life
and then you start to lose some
peripheral vision in your 60s or 70s.
Sometimes it can be so severe that you
can't see light
from day of life one. So there's a wide
spectrum in there
of problems with these moving parts that
cause your retina to not work so well.
So can you give us some examples of
an inherited retinal disease and some of
the primary symptoms?
So maybe Leber congenital amaurosis, RP,
retinitis pigmentosa or Usher syndrome.
So for this let's talk a little bit of
more complexity of the retina
there are two different kinds of cells
that gather the light and start the
whole process
you have rods and cones and they're
different from each other
rods are generally good for vision under
low lighting situations so when it gets
really really dim
like you're walking into a dark room
you're using your rods.
Cones are good for your highly accurate
vision
and that's good for color vision. And you
can have
some diseases that affect rods some
diseases that affect cones
some diseases that affect both.
So for example if you had a
cone-mediated disease
you might not be able to see colors well
you might have reduced central acuity
but your peripheral vision might be just
fine,
for some period of time. if you had a rod
mediated disease
you would probably not be able to see
well when things got dim and because the
rods and the cones
aren't evenly distributed around the
entire retina,
cones are more central and rods are more
peripheral,
if you had a rod mediated disease you
might have problems with your peripheral
vision,
and if you had a cone-mediated disease
you'd have a problem with your vision
right in the middle.
So Leber congenital amaurosis is one of
those diseases that affects both rods
and cones.
So those are typically children who are
born
with poor vision within the first couple
of years of life.
They have trouble seeing colors and they
have trouble
when it gets dim. Somebody with retinitis
pigmentosa for example
that's typically it starts off as a rod
problem.
So those patients are going to lose
peripheral vision
and those patients are going to be
initially picked up because they can't
see well in the dark.
A different disease one that you didn't
mention that's called Stargardt's
disease
is a cone-mediated disease and so that's
going to be a patient who
sometime in their early teens loses the
ability to see color
and starts to lose their central vision.
That make sense? Absolutely, well so maybe
just a follow-on question.
What is genetic testing and why is it
important when we're talking about
inherited retinal diseases?
So all of these moving parts, all of
these 300 proteins
they are encoded by our genes.
So our genes are the blueprint for what
allows every cell to make the moving
parts that they need.
And there are some moving parts that are
common to every cell your, retina cell
needs it, your liver cells need it,
your brain cells need it. There are some
of these moving parts that are very very
cell specific.
You have some proteins that are only
expressed in cones
and no place else in your body. So for us
if we get somebody in clinic who has a
problem seeing.
I can ask some questions and find out
whether it's rod or
cone or both but there are dozens or
hundreds of genes that can cause that
so the only way that i can figure out
exactly which gene is responsible,
is by going into the blueprint and
sequencing
hundreds of genes to figure out which is
the one that has the problem.
So which programs are available Tim for
for some of these patients?
You mean for getting genetic testing?
Yes.
So one is something that's funded
by the Foundation Fighting Blindness,
and ProQR, and it's
called My Retina Tracker and it's a
very ingenious
research database that will
involve sequencing of genes,
registering that change in a database,
that's a private database it's not
it's not publicly accessible, and then
counseling the patient. And this is a
really important part. Counseling the
patient
on the significance of those those
genetic changes.
There's another company called Spark,
which has partnered with a company
called
Invitae and they have a testing panel as
well
they don't have the same database that
My Retina Tracker has
but but they will sequence these genes
and just like My Retina Tracker it's
free to the patient.
You've kind of touched on this but why
should a patient
want a genetic test and and then
how can they participate in a program
like My Retina Tracker?
So Tiff I like to think that
there are four good reasons to get your
your genetic testing done. Number one it
precludes a misdiagnosis.
Right? There are other things that can be
going wrong
that can cause similar symptoms that may
very well be treatable you know there
are inflammatory conditions of the eye
that you can treat if you treat with
steroids or if you treat with
with other kinds of medicines so you
don't want to assume that somebody has
disease A
and you start treating them for disease
A when truthfully
they have retinitis pigmentosa or
stargardt's or some other disease like
that
so number one it it prevents
misdiagnosis
number two not in all cases
but in many cases it allows me
to interact with the patient or the
parents
to describe what's likely to be the
tempo of the disease
you've got this problem in this gene it
will get worse over the next five years
or it's going to get worse over the next
20 years and that has a lot to do with
their family planning and their
their career planning
the third thing is
as you may know now that we understand
the genetic basis of a lot of these
diseases
we're starting to test and actually have
one commercially available drug
for treating these diseases and i can do
surgery
on children who have lieber's congenital
amaurosis
as a consequence of RPE65 deficiency
i can do surgery on those patients give
them a virus
that virus infects the cells and in many
many cases it reverses the disease
process
something that was unheard of 10 years
ago
so it could very well be that the
identification of your mutation
might make you amenable to a surgical
intervention
and then the last reason which is
is an important reason that people don't
think about that often is
it allows us to get an idea of
which genes cause problems
in the United States or elsewhere and
what's the frequency of that kind of
genetic change
because that can help the development
that can help
drive interest from biotech companies
in coming up with a change if there is a
gene that has
you know 10 000 people that are affected
well for a small biotech company that
might be more attractive as a target
than one gene in which there are two
patients in the world that have
been found to have the problem so for
all four of those reasons i think
getting
your genes tested is a smart thing to do
so how do patients get access to genetic
testing or more specifically
um my rep the my retina tracker well i'm
going to answer that
in the pre-Covid world and the
post-Covid world
so in the pre-Covid world typically
what happened
was a patient would go to their eye
provider
often times it was an optometrist the
optometrist or a
comprehensive ophthalmologist and the
optometrist or ophthalmologist would say
you know i think you've got a problem
with your retina
i'm not really sure what it is you need
to see a retina person or you need to
see a pediatric ophthalmologist
the pediatric ophthalmologist would then
say well this kind of looks like it may
be an inherited rental disease so i'll
send you to an inherited rental disease
specialist
the inherited rental disease
specialist
most of us are pretty facile with
my retina tracker and so in that
situation we would say you know we
here's here's a program that we think
may benefit you and it's
and it's free so it's it's a
pretty compelling argument
the post-Covid world you know one of the
silver linings if there are any silver
linings to this catastrophe
is that we have i won't say introduced
and i won't really say
reintroduced because we didn't use it a
lot before but the whole concept of
telemedicine
has exploded and we've become very
good at it
a couple of days ago i had a
telemedicine consult from
somebody from tennessee who had an
inherited rental disease i asked the
questions
i obviously i couldn't examine them at
some point
everybody with a potential inherited retina
disease needs to have an examination
but i was able to counsel them on what i
thought might be going on
and i was able to say i can have a kit
mailed to you to your home you can
spit into the tube because we know that
DNA
is present in spit you can mail it back
to the company and the DNA testing can
take place that way
and then i can hook you up with a
telegenetic consult
where the significance of all this is
explained to you
so i don't think we're ever going to
go back to the way it was completely
but it but i guess we still have a
lot of the potential for this to carry on
during the in the new Covid reality
so when a patient gets their results and
you kind of touched on this
what should they do with those results
and you also mentioned research
and then also you know clinical trials
so what does that conversation look like
once they get their results so
often times i talk to them about what
specific gene is
is problematic and i speak to them about you know number one what the
gene is
often times i'll talk about what the gene
does why it's an important part of
those 300 moving parts
then i'll talk a little bit if i can
about
what this means for them long term how
rapid is this likely to be
sometimes the answer is very slow
sometimes the answer is quick
and sometimes the answer is i don't
really know
and then often times what we'll do is
we'll go to a website
clinicaltrials.gov and we will look to
see this is a public
government-sponsored website we will
look to see if there are clinical trials
who's doing the clinical trial is it
interventional or just observational are
we just looking at the patients
or are we treating them what's the
rationale behind the treatment
and how do we get patients enrolled in
in those clinical trials
so it's counseling as well as it's
explaining
its counseling and it's looking for
treatment options
can you just summarize for us
the importance of genetic testing i.e
the my retina tracker and the
impact that it has had on your practice
and on patient care we keep a list of
all we have a database of all the
patients that we've seen and we know
what their
specific change is so when this
RPE65 drug became available
i was able to go through our list and
say oh you know what this person
had RPE65 and we get them on the phone
and say hey guess what
we've got a treatment for you now so
it's
there we've gone from having one
clinical trial for one disease
to probably now there are 15 to 20
different clinical trials for a variety
of different diseases
and we've got 300 to go so we got we
have a lot more to go
but you know it's it's easier for me to
go back and say
hi mrs jones i think you've got a
problem that may have a treatment
why don't you come back to see me well
thank you so much for your time today
we really appreciate it and
appreciate your service to patients
my pleasure tiff thanks

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