In my last post I mentioned some imaging techniques that have revolutionized what we know about diabetic retinopathy. These imaging techniques have the wonderfully weird names of optical coherence tomography, fundus photography, and fluorescein angiography. Optical coherence tomography (OCT) is pretty complicated but basically it uses the physics of how light bounces around to get a real-time image of the eye at a resolution of somewhere between 1 and 10 microns. Since a capillary is about 40 microns in diameter this technique is quite suitable for looking at the blood vessels within the eye. The technique is similar in concept to the way in which ultrasound images are generated – just with a much higher resolution. The limitation of the technique is that we can only analyze light waves that have penetrated just a few millimeters into a biological tissue. This is fine for the retina but would not work for imaging a fetus where we need those better penetrating low resolution sound waves to do the work. The patient has a light beam of very specific wavelength focused onto a section of the retina and the light that bounces off of the retina hits a special detector that can begin to deconvolute all of the various wave lengths ultimately allowing a computer to use the information to construct a 3 dimensional image of that small region of retinal tissue.
Fundus is a Latin word meaning the bottom of something. When applied to the eye it means the back of the eye so ultimately fundus photography means taking pictures of the retina and all of the other structures back there. (Doctors do love their Latin) A fundus camera is basically a microscope with a bunch of lenses that allows the clinician to see an image of the retina. It is relatively low resolution but this can be good because it allows the clinician to see the entire retina while OCT can only focus on very small bits of the retina. Also it does not involve the intense computational requirements of OCT. the physician can get an immediate read on what is happening in the patient’s eye without having to wait a couple of days. Now, we can make things even better by somehow making the blood vessels stand out in high contrast. What better way than to inject into the patient a safe fluorescent compound that makes the blood glow for a short period of time. One such dye is fluorescein and when doctors use fluorescein with a fundus camera they cannot resist giving it yet a new and complicated name: fluorescein angiography. (Angiography is the act of visualizing blood vessels).
Using these imaging tools, we have learned a lot about the eye both in healthy individuals and in patients with diabetes. I mentioned some of what we have learned in my previous post. The problem, though, is that once we see the changes in the retina characteristic of diabetic retinopathy it is too late. The disease has set in and now we are playing catch up. It is true what they say – an ounce of prevention is worth a pound of cure. It is especially frustrating given what we have learned in studying animal models of diabetes.
You can create diabetes in a rat in a couple of ways. We use the drug; streptozotocin. It damages the pancreatic beta cells and virtually overnight the rats develop full blown diabetes. Now, we know that these animals will develop diabetic retinopathy. It is a consequence of their carefully controlled genetics and the method by which diabetes arose. Interestingly, there are several drugs which, if given immediately and consistently to the animal, will block the development of diabetic retinopathy. So, in a sense we have a cure for this problem. However, these drugs are not without side effects and they will be expensive. The National Eye Institute estimates that about 40% of diabetes patients will experience some form of retinopathy but only 8% will have a vision threatening version of the disease. We cannot give drugs to millions of people who really do not need them. We need a way to figure out who are most likely to be part of that 8% and treat them. Translating this into research lingo – we need to find a biomarker.
I’ll talk about that in a subsequent post.