00:00
Let's think about how this is going on in kind of a pathophysiologic way looking at the
structures. So, the macula is indicated up above, so that is where we are in the retina and
truly that is the highest density of photoreceptors right in that area. Those photoreceptors,
those nerves that are going to be collecting the light impulses and then sending it out
through the optic nerve are sitting on a layer of retinal pigmented epithelium that sits on a
basement membrane that we call, in this case, Bruch's membrane. Because Bruch got their
first before basement got their and so he called it Bruch's membrane. Below that is the
choroid and below that is the sclera. So that's kind of the general visual 3-dimensional
representation of what we're going to be looking at. So, this is what it looks like histologically,
I think it's a beautiful structure. Up above those little tiny nuclei that you're seeing are all
parts of the rods and cones there in the retina of the patient at the macula. Below that,
those single layers of cells that have kind of a dark brown speckled pigment, those are retinal
pigmented epithelial cells. And they sit on Bruch's membrane, that's the bright red line that's
coming all the way across and labeled Bruch's membrane. And then below that is the choroid.
01:27
Here we've identified it as the choriocapillaris because there is a lot of vasculature and that's
going to be providing the necessary nutrition, oxygenation, etc. for the retinal pigmented
epithelial cells as well as the overlying rods and cones. So that's what it looks like and that's
normal. Okay. Let's make it abnormal in some way. So in AMD, whether it's wet or dry at this
point, in AMD we get a deposition of protein and lipids beginning in Bruch's membrane. And
again, why we get the deposition we don't entirely understand and why do some patients
get and not others. But we begin to see a deposition in that membrane, and that's the
membrane that's right below the retinal pigmented epithelial cells that you see identified
there. So, we'll begin to get that there. Those deposition, it's proteins and lipids, they are
oxidized lipids, there are some complement proteins in there, there are variety of other things.
02:28
They will induce an inflammatory response coming from the choroid. So, the immune system
recognizes goes "Hey, those aren't supposed to be there" and they will induce an inflammatory
response. Not always a good thing in a small area like this. With inflammation, we get
increased vascular permeability and vasodilation in the choroid and we'll get more and more
and more accumulation. So, once it get started and once it's underway, it's a little bit of a
snowball effect and gradually we can appreciate nodular deposits. And you see them in the
bottom panel with a little asterisk, the star associated with them, these are drusen, a German
word meaning droplet. And the drusen are the kind of the really recognizable manifestations
of these early depositions in Bruch's membrane. Now, they also contain protein and lipid
and they're pro inflammatory, they are in many ways helping their manifestation of the
inflammation but also continuing to drive in a circular fashion the inflammation. With the
inflammatory infiltrates and probably because of free radical damage sometimes associated
with the drusen, we get retinal pigmented epithelial cell dysfunction, and they begin to
separate themselves from Bruch's membrane. So that's dry AMD in a nutshell. That's dry AMD
and that is what is giving us that progressive degenerative loss of visual acuity in that area.
04:12
On the other hand, wet AMD is just building on this, it's only 10% of the population, it's not
entirely different in terms of the pathophysiology except in a subset of patients. They will
also, as part of the inflammatory response, develop neovascularization. The inflammation will
drive vascular endothelial growth factor production which will drive new blood vessels
sprouting coming in to the retinal pigmented epithelium from the choroid. Now, those new
blood vessels are leaky, they will hemorrhage, they will have much greater amount of
exudate, that sort of stuff. So that's the difference between wet and dry AMD, but it all
starts in exactly the same way. This is just an example of what that looks like. So, the choroid
is below, the retinal pigmented epithelium is above with the retina on top of that. And we
have new ingrowth of blood vessels and we have clearly hemorrhage. And so this will give
us the wet AMD kind of phenotype. What does it look like on fundoscopic examination? So
dry AMD is going to be mainly associated with drusen and the drusen look a little bit like
cotton wool spots except they're different. Cotton wool spots, remember our little
microinfarcts, the drusen there are these kind of lipid protein depositions that we can see is
discrete little things, they're much more broadly distributed in typical cotton wool spots.
05:35
And they're going to be predominantly in the macula because we're getting macular
degeneration. On the other hand in wet AMD, there are drusen that are behind there but it's
going to be kind of definitely overridden, much more impressive hemorrhage that's associated
with that and there will also be neovascularization in earlier stage before the hemorrhage.
05:58
How does it present, signs and symptoms? So macular degeneration is very gradual onset,
it is not something that happens overnight. So it kind of sneaks up on you and it will be
asymptomatic in most cases. But when it starts becoming symptomatic you find that you will
often have bilateral, painless, central visual distortion or loss and so the example there in the
bottom panel is very much what it looks like. You can see kind of sort of the faces, but you
can't recognize a lot of people. You may even have scotomas, little blind spots that are
there. There will be difficulty with night vision because you have lost rods so you have
difficulty with low light situations and it takes a long time for you to adapt. So you have to
really open up your pupils and collect a lot of light, it takes time to go to get used to be in a
low light level. The scotomas will be blind spots in the visual field and again this is going to be
right in the middle of your central visual field. You'll have reading difficulty because again
the macula is how we read the written word; you cannot make out faces, so the example
that you see here the 2 little kids, you can see that there is somebody there holding some
balls but you have no idea who. And you can get distortion of those straight lines and that's
seen a little bit on the fence behind these kids so metamorphopsia. Okay, and with that
we've talked about changes that occur in the vasculature of the eye that can cause
blindness, but also a very common entity that we don't completely understand, macular
degeneration. Hope you enjoyed it.