Diabetic Retinopathy: Classification and Pathophysiology

00:00 Welcome back. So we have moved from the front of the eye and now we're at the back of the eye looking at pathologies that influence that part of the ophthalmologic anatomy.

00:12 This is retinopathies today. We're going to start first with diabetic retinopathy. You seen this kind of image of the eye over and over again. This one looks pretty bad, looks pretty different. You should have been able to pick up on a couple of things. So, just to get you used to the nomenclature of what we're going to be seeing on fundoscopic exam, but also an understanding part of the pathophysiology we'll do some terms. So, a hard exudate.

00:39 This is actually going to be a deposition of protein and lipid that has a very demarcated discrete area of yellow that we can see on fundoscopic exam. Cotton wool spots in comparison are little tiny areas that will look pale and that's actually because those are microinfarcts. We'll have areas of neovascularization so kind of a poof of capillary new growth and we may even see larger vessels, that's neovascularization. Those vessels are immature and they will tend to bleed, so there will be associated hemorrhage. And, ultimately if we get a lot of neovascularization with new vessels that leak, we can actually get areas of scar formation and reorganization and when that scar does its usual thing in terms of retracting, we can pull the retina away from its underlying choroid and get a retinal detachment. Okay, so these are the kind of things we're going to be looking for in diabetic retinopathy. Interestingly, we will see them also in the retinopathy of prematurity and hypertensive retinopathy. So, diseases of the retina such as diabetic retinopathy are those in individuals who have longstanding diabetes mellitus. Eventually, 90% of patients with poorly controlled type 1 diabetes, the autoimmune form of diabetes. And relative about a quarter of patients with the type 2 obesity associated insulin-resistant type diabetes will develop diabetic retinopathy. And worldwide it's responsible for significant amount of blindness, 5%. Diabetic retinopathy is kind of broadly classified in 2 different forms, nonproliferative and then obviously proliferative. Nonproliferative is most common and the proliferation that we are referring to has to do with the vasculature. And we'll talk about how diabetes causes neovascularization. But, diabetic retinopathy then is nonproliferative, we'll have microaneurysms, blood vessels develop focal dilation that's because the associated pericytes, modified smooth muscle cells that are around capillaries are very prone to diabetic injury and will die. And if those little pericytes around the capillaries die, then there's nothing to maintain normal tone and we will get kind of a globoid dilation or microaneurysm. There will be capillary leakage. So leakage because of abnormal capillaries due to the diabetes and the endothelium in diabetic patients will be particularly prone to leakage. This will give us our hard exudates. Remember those are the protein and lipid depositions, give us a bright yellow little plaque. You can have retinal and macular edema. Again, this is related to the diabetic-induced endothelial cell dysfunction. So that the microvasculature is increasingly leaky and so you have a substantial amount of edema. And that edema will actually clearly modify the way that light goes through and the way that the nerves talk to one another and send their signals out the optic disc. We'll get exudates. So, in addition to hemorrhage, we will have those hard exudates that we've talked about, but will get cotton wool spots that are little tiny areas of microinfarction where the blood vessels have actually completely thrombosed or become occluded. Macular edema, part and parcel of that same edema that we talked about previously and we'll get intraretinal hemorrhages because the vessels are immature and are very prone to hemorrhaging. Now we haven't really had any significant new blood vessel formation, but in the proliferative form of diabetic retinopathy we do. And so everything that you saw above is exceedingly increased because we now are making lots of brand new immature blood vessels and days will be seen in and around the disc and in and around the retina. We will see a lot of hemorrhage both within and around the retina, but also right into the vitreous chamber and as a result of having that hemorrhage organization scarring, we'll get fibrosis and as the scar contracts we will get retinal detachment. Okay, so proliferative, nonproliferative having to do with whether blood vessels are just damaged because of diabetes or whether we're getting new blood vessels. Let's look at this in a slightly different way. So, the drawing on the right shows you the sclera, the choroid, and the retina. The choroid is going to be revascularized as you see there and the retina will have some degree of vascularization as well. Microvascular disease is due to hyperglycemia, that persistent longstanding elevation in glucose levels causes nonenzymatic glycation of cells and of extravascular tissues and that will lead to the microvascular disease. Because of the changes in the endothelium, we will have chronic ischemia of the retina. So all those little areas of bleeding, all those little areas of microinfarct, all those extensive exudates, all those things will lead to a retina that becomes starved for an adequate blood supply. As a result, we will get the tissues in that area, the fibroblast, the smooth muscle cells, the endothelial cells, etc. where we will see an increase in the release of vascular endothelial growth factor.

06:38 That's the appropriate response to chronic ischemia. Whenever we become hypoxic anywhere in the body we want to have new blood vessels that come in and provide better perfusion.

06:50 When we get now this increased VEGF production, vascular endothelial growth factor, now we're going to get neovascularization, those new blood vessels are immature. They leak like crazy so we will get exudates. They rupture like crazy because they're delicate and fragile and they are not well formed yet so they will have hemorrhage, and again as we organize the hemorrhage we will get scarring and retinal detachment. Okay, so those are the things that will explain the pathophysiology of the diabetic retinopathy.