The choroid in aging and disease

Published on October 31, 2016   28 min
0:00
Good day, my name is Robert Mullins, and I'm a professor of Ophthalmology and Visual Sciences at the University of Iowa. Today we're going to talk about the changes that occur in the choroid in aging and in macular disease.
0:15
The choroid has some normal physiological changes that occur during aging that are differentiated from those that occur in diseases, like macular degeneration. Some of the same events that occur during normal aging, however, can occur to a more profound extent in diseases, like age-related macular degeneration or AMD.
0:36
Age-related macular degeneration is a common form of blindness that affects millions in the Western world. And as its name implies, it is an age-related disease. It's normally not seen in individuals under the age of 55 or 60. It affects the macular specific region of the retina that's responsible for visual acuity. The macula itself is about only the size of a button on one's shirt, but in spite of the fact that it's a small portion of the retina, it's responsible for most of our daily vision. And it's a degenerative disease in which the photoreceptor cells will eventually succumb to loss through one of several mechanisms. We don't completely understand the pathogenesis of this disease. We do know that there are different phenotypes or what might be considered stages including early AMD, neovascular AMD, and atrophic AMD. And these stages are characterized by structural feature called drusen.
1:35
The next few slides will compare the fundus appearance on the left, with the histological appearance on the right, of different disease types in AMD. And I should say that the sections are not collected from the same photograph in each case, as the fundus picture. However, they do give a good comparison of what the histology looks like in each case. First is a normal eye, you can see the retinal circulation. The collateral circulation is masked largely by the RPE. And histologically, the ganglion cell layer, the inner nuclear layer, the outer nuclear layer are present. The RPE is present as a continuous layer, and the choriocapillaris, you can see as these white openings that correspond to healthy viable choriocapillaris vessels.
2:22
Early age-related macular degeneration is characterized by the presence of drusen, which appear on clinical examination as these white spots. Histologically, drusen occur between the choroid and the RPE. And you can see these two large, sort of out of place, pink hemispheres that are present in the early AMD eye on the right. In this case these drusen are pressing into the photoreceptor layer. The photoreceptors themselves are shorter where drusen are present. And this is the histological appearance of early AMD. Early AMD is itself not characterized by severe vision loss. There's some subtle physiological defects that can be detected, but having only early AMD is not a severe problem. Unfortunately, some patients progress beyond early AMD.
3:13
One form of advanced AMD is called geographic atrophy, shown here. And in this case, if you look at the fundus picture on the left, we can see into the deeper choroidal vessels. Now the choriocapillaris is badly degenerated as we'll see in an eye like this. Some of the deeper vessels are still filled but the loss of the retina pigment epithelium allows a unique window into the deeper choroid. And histologically, in this side, you see loss of photoreceptor cells, the inner and outer segments are completely missing, the RPE is disheveled, the choriocapillaris is thinned, and there's this thick pink layer underneath the RPE of basal deposits.
3:57
The other extreme form of advanced AMD is the development of neovascularization. And you can see what this looks like in a patient fundus photograph on the left and histological appearance of these extra vessels that have grown into the retina. And again you can see that the normal architecture of the photoreceptor, inner and outer segments, is completely lost. And there is no vision in this portion of the retina.
4:23
So our laboratory has been interested in understanding the vascular changes in the choroid that occur in aging and in AMD. And for this talk, I'm going to split this into structural changes that include choroidal thinning and vascular dropout or loss of endothelial cells of the choriocapillaris; as well as some of the molecular changes that include, formation membrane attack complex, C-reactive protein, and changes in gene expression.
4:55
So until quite recently, the presence of the RPE barrier in imaging the posterior pole of the eye was really an insurmountable obstacle for many studies, and the choroid had been largely neglected. And recently, with the development of the enhanced depth imaging OCT methodology, it's possible to quantify choroidal changes. And so the number of publications that have been listed describing choroidal thickness has greatly increased over the last several years.
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The choroid in aging and disease

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