 Hi, it's Monday. Yeah, good morning. What's good about it? I'm going to talk about electroretinograms, and if I get far enough about electroocular grams also today. Beginning around 1800, they started to realize that their electricity was involved in all physiological function. And the first was the Galvanes famous frog experiment. And as far as all of the electrophysiologies, actually the electroretinogram was discerned into its separate parts the earliest. So that by the middle of the 19th century on 1908, they knew that there were three waves, the A, B, and the C waves that made up the electroretinogram. I'm going to talk about the multifocals later. Whenever you have your photo taken with a flash of light, there's an electrical discharge in your eye that looks similar to this. And the first wave, the A wave, is generated in the layer of rods and cones. And the B wave is an accumulation of everything going on in the mid-retina. The main contributors are, let's just jump through these. If you look at this cartoon of the retina, the A wave is generated by the layer of rods and cones. The B wave is everything in the mid-retina, mainly the on bipolar cells, the on bipolar cells, and the Mueller cells, which are physically the biggest. But everything in the mid-retina contributes to it. So the horizontal cells, the American cells, also contribute. So if you mess with any of these with, say, chemicals that affect their transmitters, you will affect the makeup of the electroretinogram. That's why the electroretinogram is quite sensitive to metabolic disorders. There are different kinds of contacts used. I use, generally, the Burian-type contact lens, which is this nasty thing that looks like this, that all of you that are rotated through neuro or beads have probably seen. But there are other types of disposables. Disposables are becoming more common in use. There are countries, including Great Britain, that don't allow contact lenses to be reused. That dates back to the break out of Croix-Fell Yacht disease in the late 1990s. So they have to use disposables. The disposable that I use commonly is called a DTL. And if you look, finally, there's a silver thread between these two white dots that goes in the lower lid. It's a very thin thread as thin as a hair. It's actually five strands, and it's as thin as a hair. A roll about this big is 10 miles. I sometimes use this one when I'm testing an infant in the OR that has an eye too small for my smallest speculum contact. I sometimes use this one. It's called the Arden Goldfoil. It's a piece of cassette tape with gold foil on one side. If you've got an eye even smaller than what this will go in, or a case of trauma where the eye is so swollen shut, all you can do is crack it open a little bit. Those are the three most common disposables used. Until about 30 years ago, the mode of stimulation was a strobe flash, usually the strobe flash that's been used in EEG for the last 50 years. When I learned ERGs, a strobe flash like this was on an articulated arm. And the patient laid on an examining table, and you placed it a certain distance above their face. And there was an attachment to the front that you could add filters for different colors. Now Gansfels are used. The original Gansfels were similar to this. Gansfels is a German word that means whole field. Similar to this, it looks like a field machine. And you all know how much most patients like visual field testing. I've had patients come to my door and stop and say, no. I had that already. I'm not doing that again. The field machines such as this one had at the top a tray system of filters that when you selected a color, a tray slid in front of a strobe lamp. The modern ones that produce their flashes by LEDs like a television. And this is the one that I use. Because of the retina being duplex, both night and day receptors, by using dark adaptation, light adaptation, and different colors of filters, you can pretty much separate rod and cone function. Photopic, secret doctor word for in the light, scotopic, secret doctor word for in the dark. By changing light adaptation, the stimulus rate, stimulus intensity, and color, you can really separate rod and cone function. Let's go over each of these. This is obvious, light versus dark, which is related to the intensity. Cones are fast and really sensitive in a light situation, but poor in a dark situation. And a rod is three logs, a 1,000-fold more sensitive. This rate question is the cones can also recover quickly, whereas rods can't. Under no condition can a rod recover and refire at even 20 per second. Its upper limit is about 18 per second as fast as a rod can go. Comes out of the old neural-realtory refractory period, like how fast can a neuron refire? Well, a rod can only refire at the fastest about 18 per second. Cones can easily refire in a normal person up to 70, 100 per second. Worldwide, 30 hertz is the common speed used. So if you use a flickering light of 30 per second and you get a nice following, which I'll show you, that tells you that as a group, the cones are healthy. And then stimulus color, they have different peak sensitivities. The peak sensitivity of all three cones together is this tennis ball yellow. Tennis ball yellow is not an accident. They chose tennis ball yellow. It's the color that the human system can see best in the light. The peak for rods is 510 nanometers. These colors are approximately correct. In the days when you use filters, this red, red 26 and 47 blue is Kodak makes a series of cellulose filters that are calibrated for the wavelengths that they will pass through them and their numbered system. So red 26 is a filter that cuts off. The lowest it goes is about 580 nanometers. So if you use a dim red, you'll just nick the cones. If you use a dim blue, you'll just nick the rods. By using these colors, after a person is dark adapted, you can separate the cones. How else can you separate the cones? 30 hertz flicker following helps you separate the cones. These are typical traces. They are not accurate vertically. This is a single flash in the light of white flash. It's very fast. Usually peaks about 30 milliseconds. This is a really bright white flash in the dark. This is to scale, this would be four, five times or more larger in amplitude than this. This is a dim blue response. This is the dim red response. This B component of the dim blue and the dim red are contributions from the rods. This little BX here is this response just being tickled a little bit by the red dim red flash. I do these in the order of dim blue after dark adaptation. And then dim red. If this red one looks just like the blue one and you don't see this little bump here, I'll say to the patient, how's your color vision? Because if this goes away, so the waveform is just like this, it probably tells you right while you're still in the dark that they have cone issues. Which you verify later with the single flash photopic response and 30 hertz flicker. Two traces of 30 hertz flicker in a normal person. Superimposed, let me go back a couple. Superimposed on the ascending limb, particularly visible in white flashes, on the ascending limb are oscillatory potentials. Which you can filter out mathematically by changing the lower band pass on them. These are most sensitive to vascular disorders. For instance, if you caught a patient with diabetic retinopathy at just the right phase, all of their ERGs might be normal. But these would be gone. If you, what? Oh, it's a loop system in the mid retina that is an interaction. I'd have to check this, look it up. Is I think it's the amocrine cells. And it's a cycling loop within the mid retina. Development of the ERG, a full term infant usually has an ERG that just looks like ours. They can be a little bit reduced in amplitude, but you don't routinely see it. Anesthetic effects, whenever we do exams under anesthesia, it's important you work with the anesthesiologist so that you have a very light level. Anesthesia depth can reduce the amplitude of B waves as much as 50%, although A waves are pretty much immune and peak implicit times are pretty much immune. But when I'm working in the OR, when you're in cases with Hoffman or Dries or somebody, you'll hear me say to them, as soon as you're happy, after they get the lines in, as light as you're comfortable. In the OR, now I use these goggles that have LEDs inside of them and then control from the computer a few feet away, which are flashing. And underneath the goggles are usually the speculum contacts. That's what the LEDs look like inside the goggles. Very few things extinguish an ERG. That is give you a completely flat ERG. This is the whole list. Complete retinal dysfunction, total retinal detachment. Labor's congenital lamerosis are really severe retinitis pigmentosa. Everything else, all of the hundreds and hundreds and hundreds of other, just hundreds and hundreds of things that affect the ERG. Everything else, it's graded. They've got some ERG. The question is, how big is it? How fast is it? How slow is it? There are diseases that particular disorders affect more than others. Those that affect the B wave are on this list. This was interesting and found here years ago. We had the opportunity to follow a person from no symptoms to deceased in only four or five months with CJD. And their first complaint was a little bit of blurry vision and came into neuroclinic. And so followed her with ERGs. I've tested a handful, five, six individuals with CJD, but never from the beginning. Usually they're already hospitalized before I test them. There are about 25 chemicals in the retina that might affect retinal physiology. An unusual example that the men in the audience will get with is that until a few years ago, whenever TERT procedures were done, glycine was the irrigating solution. Glycine's an inhibitor in the mid-retin affecting amicron and bipolar cells. Typically, TERT procedures are done under a spinal block. And occasionally, a patient will say in the operating room where it's so bright you can hardly look at the ceiling, will say, why'd you turn the lights off? If the TERT procedure would take a long time and they would dig into the vascular bed too much, the glycine would be absorbed to get into the system. When it reached the eye, it was like throwing a switch and shutting off the eye. We followed some patients by getting patients that they thought there would be a long procedure and found that in a normal individual, this is the top 2, 30 Hertz flicker and a B-wave flash. And then what goes away because the amicron cells and the bipolar are in the loop you asked about, it eliminates the oscillatory potentials on the ascending limb and the 30 Hertz flicker goes away too. And then a few hours later, they recover from that. These individuals, all that I tested, did not lose their sight. They just were affected physiologically. There was one that did lose their sight, and I didn't get to testing because they were too busy saving his life from hyponatremia. The first application of electroretinograms was clinically back in the late 40s and early 50s was to confirm retinitis pigmentosa and to quantify how far they were in the disorder. As you all know, retinitis pigmentosa is quite variable. I think I've got a couple of fundus photos here. In addition to being quite variable in just apparent ocular fundus appearance, they're also quite variable in the expression because there are so many mitigating factors. As you know, I don't even know what, does anybody know what the number is yet? The lowest now, the lowest I don't know. Years ago, it was 80 or something, but it's probably well in the hundreds. These are the RGs you get, scotopic blue, dim flash blue, dim flash red, bright white, all in the dark, and then light adapted, 30 Hertz flicker, and photopic white. Retinitis pigmentosa is obliterated. The rod response is obliterated. You get a little bit of a BX response surviving because the dim red does, quote, tickle the cones. You get a little remnant of a bright white flash, and you have more functioning flicker and single flash because these are cones. This person I picked on purpose, this is not what they're all like. If you catch a person just at the right stage, this might be what you see when they've still got some cone physiology. But if you don't catch them till later, everything could be flat, or labor's congenital amaurosis, all the responses will look like this. Some of the severe X-linked inherited males, all of the responses will look like this even before their school age. This was a young woman about 20 years old that was early in the expression. There are no absolutes, everything. I mean, you can get clinical expression that when they get the gene, find out that it's not the disease it looks like. In addition, there are about 50 disorders that have retinitis pigmentosa as part of them. Some of those that we see here relatively commonly like ushers. Usher's syndrome makes up over 20% of people with retinitis pigmentosa. It's a really high number. That's based on a study by Jerry Fishman of 400 and something, over 400, I think it was 429, consecutive retinitis pigmentosin patients in Chicago. 22% were ushers. You see these NART patients in neuro, and then just saw one in clinic last week, the Lawrence Moon Bardae beetle. And to see several of those a year during exams under anesthesia at primary. You remember Lawrence Moon, extra digits, hypogonads, usually overweight, not developmentally delayed. This is a Lawrence Moon, regardless of what retinitis pigmentosa is attached to among the 45 or 50 and known syndromes that have it as a part of it, the expression variability is the same. This was an interesting case that came up just a couple of years ago. No, this is the excellent carrier state. Excellent female carriers can have a slight effect in their electroretinograms. Full field ERGs are the best way to detect cone dystrophies, not multifocal. Multifocal, every disease that affects the cones or the macular area looks the same with a multifocal. AMD, cone dystrophy, starguards, anything. So it's not good for separating cone dystrophies. What's good is the full field ERG, using the three things I mentioned, the appearance of the BX wave on the dim red, the 30 hertz flicker following, and the photopic single flash response. Most cone dystrophy fundi are unremarkable. This one does have a little bit of pigment, but you can't count on fundus appearance to help you that much with cone dystrophy diagnosis. Here's a cone dystrophy. Just the opposite of retinitis pigmentosa. B wave responses in the dark are good. They're just slower. Why are they slower? If you pull the cones out, it's going to make the time to these peaks slower. These top half are normal, except the BX wave isn't there. The 30 hertz flicker, though, in the classic case, you get no 30 hertz flicker and no response to a single flash of white light in the light. No absolutes. I see patients every month that have cone dystrophy and the responses are there. They're just attenuated in amplitude and slower in their speeds. Anything that messes with the vasculature will affect the electroretinogram. Central retinal artery occlusion. Cherry red spot, fairly white, not a classic, but fairly white fundus, because it's devoid of much of the blood that gives the redness to the ocular fundus. Here's a central retinal artery occlusion response. ERGs, in general, will be graded depending on what the severity of the expression. That's the point that you're doing them for. The reason you're doing them will give you a graded response of how severe the expression is in that individual. Central retinal vein occlusion. Ophthalmic artery occlusion, of course, can just obliterate everything. And as I just mentioned, it will reflect the degree of the ischemia. That's true also in retinitis pigmentosa. When you have sector retinitis pigmentosa, the electroretinogram will reduce, depending upon the proportion of the retina involved in the retinitis pigmentosa. Yes? The what potential? You mean the osteothelic curie potentials? No, not necessarily. They will be depressed, but it won't quantitate it as well as the full field response. Again, in cases of detachment, the ERG amplitudes are usually reduced proportional to the amount of the retina involved in the detachment. You can't get, when there's a detachment that's recent and it's a detached retina just floating in the vitreous, it will stay functional for a period of time. It could be functional for weeks that you would get an ERG. Flecked retina diseases usually have normal ERGs until later stages. If you wanted to put it in years like how a person gets at least into their 30s or 40s, and then it will start to come down. But at the age that most are diagnosed, the electroretinogram will be normal. Some stargarts. Diseases that mimic the changes in the retina, such as scarring from rubella, usually have normal ERGs. Also, some stages of syphilis will have normal ERGs, especially inherited congenital form. So you can get some pretty nasty looking retinas, but depending upon the etiology of the abnormality, they could have normal ERGs. Riccardi syndrome. Usually, monocular, terrible ERGs on that side. Full field ERGs, well, they were the only way until less than 20 years ago to detect pathology from toxicity from drugs. And some can be used. Chloroquine used to be the only method. Full field ERG is not that sensitive. The test of choice is the multifocal electroretinogram. Unfortunately, it's still the most commonly used drug in most of the world for malaria and arthritis, lupus, strogens disease, and dermatological inflammations. In late stages of chloroquine toxicity, you get this ring scatoma, or ring of parents. And you can see abnormalities in the full field ERGs. This is from 30 years ago when chloroquine was the drug of choice, even in the United States. Some other effects can be a dephyrus oxamine toxicity. Using the treatment of liver disease can be toxic to the retina. Unfortunately, most of them aren't sent to me. There was a guy, a doctor that retired from here a couple of years ago, that paid attention and would send people that were to it. I don't see him anymore. So the people getting it aren't being followed for their possible retinal problems here anyway. Just abnormalities. Steroid toxicity, this was an unusual one. This was an ENT procedure where they injected a steroid into the upper nasal area and got the ophthalmic artery on one side. So there's the side, normal eye, reduced in amplitude on the other eye. I didn't mean to do that. This is the patient I thought was going to come up earlier, a mystery patient a couple of years ago, coincident with cataract surgery. He lost his vision. This is not uncommon, but in this case, there was a reason for it. His acuity dropped from 2025 to 2050, both eyes, and had poor night vision. It's one of my few catches in history, because he'd already been worked up and worked up and they couldn't figure out why. I quizzed him more about his history and his ERG has a peculiar, let's see if I've got it here. This is his electroretinogram. No dim flash, nothing, nothing. This was like a, this first part is like, all of these are like the ERG of a labor's congenital lamerosis. And using the dim white, really poor. But the really bright white flash in the dark, he had no B wave, but had this little BX, which tells you that his cones are working. This is almost a singular kind of a response that would give you this. And then no oscillatory potentials, but he has cone physiology, which with his acuity drop, you would expect that not to be good. Drum roll please. Vitamin A deficiency. So when I saw his ERG, he had already been through his internist and Dr. Olson and cats at sending for an ERG. And I asked cats if they had a vitamin A level on him and they said no. His vitamin A level was 0.002. What had happened was at the same time as he had the cataract surgery, he had seen a science report on NBC News, which CBS News that I'd seen also. And it was a guy saying that if you eat well, you don't need to take vitamins. And he saw that and he quit taking his multiple vitamin. And so coincident with it, he was not supplementing himself with vitamin A at all. And he had had a procedure where he only had 130 centimeters of bowel remaining. So you see this abnormality in people with liver disease. The worst case scenario was, we saw a fellow earlier, we knew what the problem was. He was on the liver transplant list and he had had most of his small bowel resected. Also some of the people that have the, I don't know the term, the weight reduction surgery. Yeah, that can have this too. But I've never seen one myself. I've seen it in the literature as all. So he was put on vitamin A for, this is 30 days later. Every, here's his B ways. Remember these first three were completely flat lines. And the only thing that had happened to his cone responses where they were slow. This is another good example of how sensitive the retina is to the chemicals and transmitters that are in it. So any disorder, any metabolic disorder that even touches on the retina can affect the electro retina gram. So it's back to it. This first one, talcretinopathy, really rare. It's talcretinopathy, what's that from? Cocaine cut with talc. So it's physically can't pass through the microcapillaries from snorting cocaine with this cut with talc. This is a normal on the left and that particular patient on the right. That was pre-multifocal. So probably the multifocal would have shown it better. I've never seen another one since then. Not one's been sent to me anyway in the last 20 years. Retinoschesis, this is something that's sometimes a question. You all know what retinoschesis is. What's it do to the ERG? You know what it does to the retina? What should it do to the ERG? It'll obliterate the B wave because it's splitting into the retina, interferes with the physical transmission of the electro retina gram from the layer of rods and cones to the ganglion cells. Right, in fact, and I'm glad you brought that up. Because this is a whole, the full field ERG is a full field response. If you have just a little bit of the separation, it's not enough to affect it. In fact, we had an exam under anesthesia with Dr. Hartnett in the last couple of months in the OR. And obvious schesis, they did OCT as part of the exam too, but it was so limited to just a little bit of the foveal area and not enough in general that it could affect the ERG. It takes about 20% of the retina, whatever the disorder is, it takes about 20% of the retina to be involved to for it to affect the electro retina. So that's a great question. What about the... Yeah. That's still not the same. You know, I would agree with you that that sounds logically, but I've never seen a patient that that's been specified to me. But it is true. You can't just have a little bit or area that you will get it. But in the classic where you've got much of the retina involved, you get a super normal A. Why is it's not really a super normal A in that the rods and cones are making a bigger one, but when you have a B wave that's normal, the B wave will cut it off earlier in its generation. So this is a very dramatic one. Although a real one that I tested years ago, usually the B wave will come back about to baseline, but in the normal individual, the B wave should be about double the size of the A wave. Congenital and stationary night blindness also can give you the same looking electro retina gram or the B wave, but it's a completely different reason. It's a transmission issue. It's a transmission issue in between the photoreceptor and bipolar cells in the mid retina, producing the no B wave. But if you just look at the electro retina gram, they're different kinds. This is, today the term is, they say classic. I don't know why, I like the specificity. But in the literature, they don't say the real disease, they say classic. No B wave, poor acuity myopia, so that this is the kind of response you get. No B wave, just a little BX from the cones, no B wave, and then attenuated because the 30 Hertz flicker is just a chain of B waves, but it's from the cones, which are less sensitive to this abnormality. The other form, what do they call it? They call that one classic, they call this. I can't remember what they now call this instead of the real name, which is rigs. This is the detailed issue of what's going on in the Congenital stationary night blindness. Other forms of night blindness. I included this one, because it's such a great photo. It's not from here, it's from somebody else. I learned about it, it was in, I think it was in Jim Gilman's library, and he told me where he got it, and I got permission to use it. Agucchi's disease, I've never seen an Agucchi's disease. Agucchi's disease is the disease that has this rust-colored fundus like this, and the dark adaptation takes hours, again, like this, and what happens is over the period of hours, this changes to the normal color of a fundus. I have not personally seen one. These are the low side known as of last year, so I haven't searched the literature recently, but there's a lot of gene locations for Congenital stationary night blindness. Inherited in all forms. Okay, what happens when you get a foreign body in the eye? The effect of a foreign body in the eye is graded much like the abnormality that you would see in vascular issues or in the varied expression of retinitis pigmentosa. How are we doing on time? Oh, really, okay, I'll just finish next week. So you get a graded response. Multifocal electrorentinograms are wonderful. I consider them the magic of electrophysiology. Typically, the patient looks at a stimulus like this that I tried to show all of you when you float through neuro. These are different projectors, mine's similar to this. It's a miniature display inside. This is the pattern the patient views. They view this for 30 seconds at a time. And then if they need a break, it stops and I have to push the mouse before it goes on to the next 30 seconds. They view this 30 seconds at a time for a total of four minutes. When these land on the retina, they stimulate in the adult eye about one square millimeter of retina. You end up with a color print out of a map that areas that are dark blue or black indicate reduced areas of B wave amplitudes. Bird shot, rare, you'll see a whirl of it because of Shakur and Vitaly. The best way to follow bird shot choreoretinopathy is the full field electrorentinogram. Okay, I'll continue next week and I'll remember and be here on time.